Time Trends in Incidence and Mortality of Acute Myocardial Infarction,and All-Cause Mortality following a Cardiovascular Prevention Program in Sweden

Background

In 1988, a cardiovascular prevention program which combined an individual and a population-based strategy was launched within primary health-care in Sollentuna, a municipality in Stockholm County. The aim of this study was to investigate time trends in the incidence of and mortality from acute myocardial infarction and all-cause mortality in Sollentuna compared with the rest of Stockholm County during a period of two decades following the implementation of a cardiovascular prevention program.

Materials and Methods

The average population in Sollentuna was 56,589 (49% men) and in Stockholm County (Sollentuna included) 1,795,504 (49% men) during the study period of 1987–2010. Cases of hospitalized acute myocardial infarction and death were obtained for the population of Sollentuna and the rest of Stockholm County using national registries of hospital discharges and deaths. Acute myocardial infarction incidence and mortality were estimated using the average population of Sollentuna and Stockholm in 1987–2010.

Results

During the observation period, the incidence of acute myocardial infarction decreased more in Sollentuna compared with the rest of Stockholm County in women (-22% vs. -7%; for difference in slope <0.05). There was a trend towards a greater decline in Sollentuna compared to the rest of Stockholm County in the incidence of acute myocardial infarction (in men), acute myocardial mortality, and all-cause mortality but the differences were not significant.

Conclusion

During a period of steep decline in acute myocardial infarction incidence and mortality in Stockholm County the municipality of Sollentuna showed a stronger trend in women possibly compatible with favorable influence of a cardiovascular prevention program.

Trial Registration

ClinicalTrials.gov NCT02212145     

Prevalence and Incidence of Diabetes in Stockholm County 1990-2010

Background

Diabetes is on the rise in the western world, but data from Scandinavia are inconsistent with indications of stable or even reverse trends. To shed new light on this issue, we investigated diabetes trends in Stockholm County 1990–2010, taking into account trends in risk factors and mortality.

Methods

We used data from a large population-based quadrennial public health survey conducted between 1990 and 2010 in Stockholm County (∼2.1 million inhabitants), supplemented with data from national registers. The age-standardized prevalence and incidence rates of diabetes and related risk factors 1990–2010 were estimated in adult inhabitants. We also modelled the influence of potential risk factors on the diabetes trends and estimated the life time risk of diabetes.

Results

The prevalence of diabetes was 4.6% (95% confidence interval (CI); 4.5–4.8%) in 2010 compared to 2.8% (95% CI; 2.3–3.5%) in 1990. Between 1990 and 2002 the prevalence rose annually by 3.8% (95% CI; 2.1–5.5). Incidence rates showed a similar pattern and rose by 3.0% (95% CI; 0.3–5.7%) annually 1990–2002. The rising incidence was mainly attributable to increasing prevalence of overweight/obesity, which rose by 46% during the observation period. In 2010, the lifetime risk of adult onset diabetes was 28% (95% CI; 26–31%) in men and 19% (95% CI; 17–21%) in women.

Conclusions

Diabetes rates have been increasing in Stockholm over the last decades, both in terms of incidence and prevalence, and this development is most likely the result of increasing overweight and obesity in the population.     

Autism spectrum disorders in the stockholm youth cohort: design, prevalence and validity

Objective

Reports of rising prevalence of autism spectrum disorders (ASD), along with their profound personal and societal burden, emphasize the need of methodologically sound studies to explore their causes and consequences. We here present the design of a large intergenerational resource for ASD research, along with population-based prevalence estimates of ASD and their diagnostic validity.

Method

The Stockholm Youth Cohort is a record-linkage study comprising all individuals aged 0–17 years, ever resident in Stockholm County in 2001–2007 (N = 589,114). ASD cases (N = 5,100) were identified using a multisource approach, involving registers covering all pathways to ASD diagnosis and care, and categorized according to co-morbid intellectual disability. Prospectively recorded information on potential determinants and consequences of ASD were retrieved from national and regional health and administrative registers. Case ascertainment was validated through case-note review, and cross validation with co-existing cases in a national twin study.

Results

The 2007 year prevalence of ASD in all children and young people was 11.5 per 1,000 (95% confidence interval 11.2–11.8), with a co-morbid intellectual disability recorded in 42.6% (41.0–44.2) of cases. We found 96.0% (92.0–98.4) of reviewed case-notes being consistent with a diagnosis of ASD, and confirmed ASD in 85.2% (66.2–95.8) of affected twins.

Conclusions

Findings from this contemporary study accords with recently reported prevalence estimates from Western countries at around 1%, based on valid case ascertainment. The Stockholm Youth Cohort, in light of the availability of extensive information from Sweden''s registers, constitutes an important resource for ASD research. On-going work, including collection of biological samples, will enrich the study further.     

Human papillomavirus (HPV) 16 E6 variants in tonsillar cancer in comparison to those in cervical cancer in Stockholm, Sweden

Background

Human papillomavirus (HPV), especially HPV16, is associated with the development of both cervical and tonsillar cancer and intratype variants in the amino acid sequence of the HPV16 E6 oncoprotein have been demonstrated to be associated with viral persistence and cancer lesions. For this reason the presence of HPV16 E6 variants in tonsillar squamous cell carcinoma (TSCC) in cervical cancer (CC), as well as in cervical samples (CS), were explored.

Methods

HPV16 E6 was sequenced in 108 TSCC and 52 CC samples from patients diagnosed 2000–2008 in the County of Stockholm, and in 51 CS from young women attending a youth health center in Stockholm.

Results

The rare E6 variant R10G was relatively frequent (19%) in TSCC, absent in CC and infrequent (4%) in CS, while the well-known L83V variant was common in TSCC (40%), CC (31%), and CS (29%). The difference for R10G was significant between TSCC and CC (p = 0.0003), as well as between TSCC and CS (p = 0.009). The HPV16 European phylogenetic lineage and its derivatives dominated in all samples (>90%).

Conclusion

The relatively high frequency of the R10G variant in TSCC, as compared to what has been found in CC both in the present study as well as in several other studies in different countries, may indicate a difference between TSCC and CC with regard to tumor induction and development. Alternatively, there could be differences with regard to the oral and cervical prevalence of this variant that need to be explored further.     

Plasmodesmenstudien

Ohne ZusammenfassungIn schwedischer Sprache wurde diese Untersuchung im Arkiv för Botanik, Bd. 5, Stockholm 1905, veröffentlicht.     

Prevalence,Pharmacological Treatment,and Control of Cardiometabolic Risk Factors among Older People in Central Stockholm: A Population-Based Study

Background

Cardiometabolic risk factors and related cardiovascular diseases represent major threats to healthy aging.

Objective

We aimed to estimate distribution, pharmacological treatment, and control of main cardiometabolic risk factors among older people.

Methods

This population-based study included 3363 participants (age≥60 years, 64.9% women) in the Swedish National study on Aging and Care in Kungsholmen, in central Stockholm, Sweden (2001-2004). Data on demographics, cardiometabolic risk factors (hypertension, obesity, diabetes, and high cholesterol), and medication use were collected through face-to-face interviews, clinical examinations, laboratory tests, and the inpatient register. Cardiometabolic risk factors were defined following the most commonly used criteria. Prevalence was standardized using local census data.

Results

The age- and sex-standardized prevalence of diabetes, obesity, high cholesterol, and hypertension was 9.5%, 12.8%, 49.7%, and 74.9%, respectively. The prevalence of hypertension and diabetes increased with age, whereas the prevalence of obesity and high cholesterol decreased with age. Forty-nine percent of older adults had two or more cardiometabolic risk factors; 9.8% had three or more. Overall, 55.5% of people with hypertension, 50.3% with diabetes, and 25.0% with high cholesterol received pharmacological treatment. Of those treated pharmacologically, 49.4%, 38.1%, and 85.5% reached therapeutic goals for hypertension (blood pressure<150/90 mmHg), diabetes (glycated haemoglobin<7%), and high cholesterol (total cholesterol<6.22 mmol/l), respectively.

Conclusions

Hypertension, high cholesterol, and clustering of cardiometabolic risk factors were common among older people in Stockholm, but pharmacological treatment and control of these major factors can be improved. Appropriate management of cardiometabolic profiles among older people may help improve cardiovascular health and achieve healthy aging.     

Asthmatics exhibit altered oxylipin profiles compared to healthy individuals after subway air exposure

Background

Asthma is a chronic inflammatory lung disease that causes significant morbidity and mortality worldwide. Air pollutants such as particulate matter (PM) and oxidants are important factors in causing exacerbations in asthmatics, and the source and composition of pollutants greatly affects pathological implications.

Objectives

This randomized crossover study investigated responses of the respiratory system to Stockholm subway air in asthmatics and healthy individuals. Eicosanoids and other oxylipins were quantified in the distal lung to provide a measure of shifts in lipid mediators in association with exposure to subway air relative to ambient air.

Methods

Sixty-four oxylipins representing the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic pathways were screened using liquid chromatography-tandem mass spectrometry (LC-MS/MS) of bronchoalveolar lavage (BAL)-fluid. Validations through immunocytochemistry staining of BAL-cells were performed for 15-LOX-1, COX-1, COX-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Multivariate statistics were employed to interrogate acquired oxylipin and immunocytochemistry data in combination with patient clinical information.

Results

Asthmatics and healthy individuals exhibited divergent oxylipin profiles following exposure to ambient and subway air. Significant changes were observed in 8 metabolites of linoleic- and α-linolenic acid synthesized via the 15-LOX pathway, and of the COX product prostaglandin E₂ (PGE₂). Oxylipin levels were increased in healthy individuals following exposure to subway air, whereas asthmatics evidenced decreases or no change.

Conclusions

Several of the altered oxylipins have known or suspected bronchoprotective or anti-inflammatory effects, suggesting a possible reduced anti-inflammatory response in asthmatics following exposure to subway air. These observations may have ramifications for sensitive subpopulations in urban areas.     

Targeted Routine Antenatal Anti-D Prophylaxis in the Prevention of RhD Immunisation - Outcome of a New Antenatal Screening and Prevention Program

Objective

To estimate the incidence of RhD immunisation after implementation of first trimester non-invasive fetal RHD screening to select only RhD negative women carrying RHD positive fetuses for routine antenatal anti-D prophylaxis (RAADP).

Materials and Methods

We present a population-based prospective observational cohort study with historic controls including all maternity care centres and delivery hospitals in the Stockholm region, Sweden. All RhD negative pregnant women were screened for fetal RHD genotype in the first trimester of pregnancy. Anti-D immunoglobulin (250–300 µg) was administered intramuscularly in gestational week 28–30 to participants with RHD positive fetuses. Main outcome measure was the incidence of RhD immunisation developing during or after pregnancy.

Results

During the study period 9380 RhD negative women gave birth in Stockholm. Non-invasive fetal RHD genotyping using cell-free fetal DNA in maternal plasma was performed in 8374 pregnancies of which 5104 (61%) were RHD positive and 3270 (39%) RHD negative. In 4590 pregnancies with an RHD positive test the women received antenatal anti-D prophylaxis. The incidence of RhD immunisation in the study cohort was 0.26 percent (24/9380) (95% CI 0.15–0.36%) compared to 0.46 percent (86/18546) (95% CI 0.37 to 0.56%) in the reference cohort. The risk ratio (RR) for sensitisation was 0.55 (95% CI 0.35 to 0.87) and the risk reduction was statistically significant (p = 0.009). The absolute risk difference was 0.20 percent, corresponding to a number needed to treat (NNT) of 500.

Conclusions

Using first trimester non-invasive antenatal screening for fetal RHD to target routine antenatal anti-D prophylaxis selectively to RhD negative women with RHD positive fetuses significantly reduces the incidence of new RhD immunisation. The risk reduction is comparable to that reported in studies evaluating the outcome of non selective RAADP to all RhD negative women. The cost-effectiveness of this targeted approach remains to be studied.     

Identifying Risk Factors for PTSD in Women Seeking Medical Help after Rape

Objectives

Rape has been found to be the trauma most commonly associated with Posttraumatic Stress Disorder (PTSD) among women. It is therefore important to be able to identify those women at greatest risk of developing PTSD. The aims of the present study were to analyze the PTSD prevalence six months after sexual assaults and identify the major risk factors for developing PTSD.

Methods

Participants were 317 female victims of rape who sought help at the Emergency Clinic for Raped Women at Stockholm South Hospital, Sweden. Baseline assessments of mental health were carried out and followed up after six months.

Results

Thirty-nine percent of the women had developed PTSD at the six month assessment, and 47% suffered from moderate or severe depression. The major risk factors for PTSD were having been sexually assaulted by more than one person, suffering from acute stress disorder (ASD) shortly after the assault, having been exposed to several acts during the assault, having been injured, having co-morbid depression, and having a history of more than two earlier traumas. Further, ASD on its own was found to be a poor predictor of PTSD because of the substantial ceiling effect after sexual assaults.

Conclusions

Development of PTSD is common in the aftermath of sexual assaults. Increased risk of developing PTSD is caused by a combination of victim vulnerability and the extent of the dramatic nature of the current assault. By identifying those women at greatest risk of developing PTSD appropriate therapeutic resources can be directed.     

The Validity of Self-Initiated,Event-Driven Infectious Disease Reporting in General Population Cohorts

Background

The 2009/2010 pandemic influenza highlighted the need for valid and timely incidence data. In 2007 we started the development of a passive surveillance scheme based on passive follow-up of representative general population cohorts. Cohort members are asked to spontaneously report all instances of colds and fevers as soon as they occur for up to 9 months. Suspecting that compliance might be poor, we aimed to assess the validity of self-initiated, event-driven outcome reporting over long periods.

Methods

During two 8 week periods in 2008 and 2009, 2376 and 2514 cohort members in Stockholm County were sent one-week recall questionnaires, which served as reference method.

Results

The questionnaires were completed by 88% and 86% of the cohort members. Whilst the false positive proportion (1–specificity) in the reporting was low (upper bound of the 95% confidence interval [CI] ≤2% in each season), the false negative proportion (failure to report, 1–sensitivity) was considerable (60% [95% CI 52%–67%] in each season). Still, the resulting epidemic curves for influenza-like illness compared well with those from existing General Practitioner-based sentinel surveillance in terms of shape, timing of peak, and year-to-year variation. This suggested that the error was fairly constant.

Conclusions

Passive long-term surveillance through self-initiated, event-driven outcome reporting underestimates incidence rates of common upper respiratory tract infections. However, because underreporting appears predictable, simple corrections could potentially restore validity.     

Body Mass Index Development from Birth to Early Adolescence; Effect of Perinatal Characteristics and Maternal Migration Background in a Swedish Cohort

Background

Well documented diversity in risk of developing overweight and obesity between children of immigrant and of native mothers, might be explained by different body mass index (BMI) development trajectories in relation to maternal and perinatal characteristics of offspring.

Objectives

To assess BMI development trajectories among children born to immigrant and to Swedish mothers from birth to adolescence in relation to perinatal characteristics.

Methods

A cohort of 2517 children born in Stockholm during 1994 to 1996 was followed with repeated measurement of height and weight at eleven time points until age 12 years. We estimated changes over time for BMI in relation to maternal and perinatal characteristics of offspring using mixed linear model analysis for repeated measure data.

Results

We observed a significant BMI change over time in children and time interaction with maternal migration status (P<0.0001). Estimated BMI over time adjusted for maternal and perinatal characteristics of offspring, showed slower BMI growth before age of 5, followed by an earlier plateau and steeper BMI growth after 5 years among children of immigrant mothers compared with children of Swedish mothers. These differences in BMI growth were more prominent among children with mothers from outside Europe.

Conclusion

Beside reinforcing early childhood as a crucial period in development of overweight, the observed slower BMI development at early childhood among children of immigrants followed by a steeper increase in BMI compared with children of Swedish mothers is important for further studies and for planning of preventive public health programs.     

Prevalence of Human Papillomavirus (HPV) in Oesophageal Squamous Cell Carcinoma in Relation to Anatomical Site of the Tumour

Background

The prevalence and role of human papillomavirus (HPV) in the aetiology of oesophageal squamous cell carcinoma is uncertain. Based on the presence of HPV in the oral cavity and its causal association with squamous cell carcinoma of the oropharynx, we hypothesised that HPV is more strongly associated with proximal than distal oesophageal squamous cell carcinoma.

Methods

A population-based study comparing HPV infection in relation to tumour site in patients diagnosed with oesophageal squamous cell carcinomas in the Stockholm County in 1999–2006. Multiplex polymerase chain reaction genotyping (PCR) with Luminex was conducted on pre-treatment endoscopic biopsies to identify type specify HPV. Carcinogenic activity of HPV was assessed by p16^INK4a expression. Multivariable logistic regression was used to calculate odds ratios and 95% confidence intervals.

Results

Among 204 patients, 20 (10%) had tumours harbouring HPV DNA, almost all (90%) of HPV high-risk type, mainly HPV16. Tumours containing HPV were not overrepresented in the upper compared to the middle or lower third of the oesophagus (odds ratio 0.6, 95% confidence interval 0.2–1.9). P16^INK4a expression was similarly common (24% and 16%) in the HPV-positive and HPV-negative groups.

Conclusion

This study found a limited presence of HPV in oesophageal squamous cell carcinoma of uncertain oncogenic relevance and did not demonstrate that HPV was more strongly associated with proximal than distal tumours.     

Incidence and Predictors of Multimorbidity in the Elderly: A Population-Based Longitudinal Study

Background

We aimed to calculate 3-year incidence of multimorbidity, defined as the development of two or more chronic diseases in a population of older people free from multimorbidity at baseline. Secondly, we aimed to identify predictors of incident multimorbidity amongst life-style related indicators, medical conditions and biomarkers.

Methods

Data were gathered from 418 participants in the first follow up of the Kungsholmen Project (Stockholm, Sweden, 1991–1993, 78+ years old) who were not affected by multimorbidity (149 had none disease and 269 one disease), including a social interview, a neuropsychological battery and a medical examination.

Results

After 3 years, 33.6% of participants who were without disease and 66.4% of those with one disease at baseline, developed multimorbidity: the incidence rate was 12.6 per 100 person-years (95% CI: 9.2–16.7) and 32.9 per 100 person-years (95% CI: 28.1–38.3), respectively. After adjustments, worse cognitive function (OR, 95% CI, for 1 point lower Mini-Mental State Examination: 1.22, 1.00–1.48) was associated with increased risk of multimorbidity among subjects with no disease at baseline. Higher age was the only predictor of multimorbidity in persons with one disease at baseline.

Conclusions

Multimorbidity has a high incidence at old age. Mental health-related symptoms are likely predictors of multimorbidity, suggesting a strong impact of mental disorders on the health of older people.     

Immigration,Transition into Adult Life and Social Adversity in Relation to Psychological Distress and Suicide Attempts among Young Adults

Background

The increasing incidence of mental health problems among young people is a major concern in many Western countries. The causal mechanisms underlying these trends are not well established, but factors influenced by current societal changes ought to be implicated. Such factors include immigration and social adversity as well as the timing of taking on adult social roles (e.g. gainful employment, parenthood and own housing tenure). We therefore examined relationships between these factors and the risks of psychological distress as well as suicide attempts in young adults, with a focus on gender differences.

Methods

We conducted a population-based study including 10,081 individuals aged 18–29, recruited in 2002 and 2006 in Stockholm, Sweden. Data were collected by record linkage and questionnaires.

Results

Non-European immigrants had an increased risk of distress, and female non-European immigrants had a markedly higher risk of suicide attempts. Both early parenthood (≤24 years) and not being a parent, being a student and the lack of own housing tenure were associated with distress, but only in women. In both sexes, financial strain was associated with the increased risk of distress and suicide attempts, while unemployment was only associated with distress.

Conclusions

Immigration from outside Europe and social adversity are associated with mental health problems in young adults, especially females. Postponed transition into adulthood is associated with poor mental health in young women. These factors are influenced by current societal changes, and may have contributed to the increasing incidence of mental health problems among young people in Western countries.     

Clinical Implications of Diffuse Excessive High Signal Intensity (DEHSI) on Neonatal MRI in School Age Children Born Extremely Preterm

Objective

Magnetic resonance imaging (MRI) of the brain carried out during the neonatal period shows that 55–80% of extremely preterm infants display white matter diffuse excessive high signal intensity (DEHSI). Our aim was to study differences in developmental outcome at the age of 6.5 years in children born extremely preterm with and without DEHSI.

Study Design

This was a prospective cohort study of 83 children who were born in Stockholm, Sweden, between 2004 and 2007, born at gestational age of < 27 weeks + 0 days and who underwent an MRI scan of their brain at term equivalent age. The outcome measures at 6.5 years included testing 66 children with the modified Touwen neurology examination, the Movement Assessment Battery for Children 2, the Wechsler Intelligence Scale for Children—Fourth Edition, Beery Visual-motor Integration test—Sixth Edition, and the Strengths and Difficulties Questionnaire. Group-wise comparisons were done between children with and without DEHSI using Student t-test, Mann Whitney U test, Chi square test and regression analysis.

Results

DEHSI was detected in 39 (59%) of the 66 children who were assessed at 6.5 years. The presence of DEHSI was not associated with mild neurological dysfunction, scores on M-ABC assessment, cognition, visual-motor integration, or behavior at 6.5 years.

Conclusion

The presence of qualitatively defined DEHSI on neonatal MRI did not prove to be a useful predictor of long-term impairment in children born extremely preterm.     

Is Drug Treatment for Dementia Followed Up in Primary Care? A Swedish Study of Dementia Clinics and Referring Primary Care Centres

Purpose

It is largely unknown how the medical treatment of patients diagnosed with dementia is followed up in primary care. Therefore, we studied patient medical records from two dementia clinics and from the referring primary care centres.

Methods

A retrospective study of 241 patients was conducted from April to October 2011 in north west Stockholm, Sweden. Over half (51.5%) of the patients had Alzheimer’s disease (AD), the remainder had mixed AD/vascular dementia (VaD). Eighty-four medical reports from primary care (35% of the study group) were analysed at follow-up 18 months after diagnosis.

Results

All four dementia drugs available on the Swedish market (three cholinesterase inhibitors [donepezil, rivastigmine and galantamine] and memantine) were prescribed at the two dementia clinics. The most commonly used dementia drug was galantamine. There were differences between the two dementia clinics in preference and combination of drugs and of treatment given to male and female patients. At follow-up, 84% were still on dementia medication. Drug use was followed up by the general practitioners (GPs) in two-thirds of the cases. Eighteen per cent of the GPs’ medical records made no reference to the patient’s dementia or treatment even though dementia drugs were included in the list of medications prescribed.

Conclusions

The results indicate that the Swedish guidelines for treatment of cognitive symptoms in AD are being followed in primary care. However, documentation of follow-up of drug treatment was sometimes insufficient, which calls for development of guidelines for complete medical records and medication lists.     

Respiratory Viruses in Hospitalized Children with Influenza-Like Illness during the H1n1 2009 Pandemic in Sweden

Background

The swine-origin influenza A(H1N1)pdm09 pandemic of 2009 had a slower spread in Europe than expected. The human rhinovirus (HRV) has been suggested to have delayed the pandemic through viral interference. The importance of co-infections over time during the pandemic and in terms of severity of the disease needs to be assessed.

Objective

The aim of this study was to investigate respiratory viruses and specifically the presence of co-infections with influenza A(H1N1)pdm09 (H1N1) in hospitalized children during the H1N1 pandemic. A secondary aim was to investigate if co-infections were associated with severity of disease.

Methods

A retrospective study was performed on 502 children with influenza-like illness admitted to inpatient care at a pediatric hospital in Stockholm, Sweden during the 6 months spanning the H1N1 pandemic in 2009. Respiratory samples were analyzed for a panel of 16 viruses by real-time polymerase chain reaction.

Results

One or more viruses were detected in 61.6% of the samples. Of these, 85.4% were single infections and 14.6% co-infections (2–4 viruses). The number of co-infections increased throughout the study period. H1N1 was found in 83 (16.5%) children and of these 12 (14.5%) were co-infections. HRV and H1N1 circulated to a large extent at the same time and 6.0% of the H1N1-positive children were also positive for HRV. There was no correlation between co-infections and severity of disease in children with H1N1.

Conclusions

Viral co-infections were relatively common in H1N1 infected hospitalized children and need to be considered when estimating morbidity attributed to H1N1. Population-based longitudinal studies with repeated sampling are needed to improve the understanding of the importance of co-infections and viral interference.     

No Myocardial Vulnerability to Mental Stress in Takotsubo Stress Cardiomyopathy

Objectives

Due to the frequent use of coronary angiography the awareness of Takotsubo stress cardiomyopathy (TSC) has increased although the exact pathophysiology of TSC is still largely unknown. Our objective was to investigate the effects of mental stress on myocardial function, heart rate variability (HRV) and salivary cortisol (SC) in TSC patients.

Design

This study is a case-control study and a sub-study of the Stockholm Myocardial Infarction with Normal Coronaries (SMINC) study.

Setting

Mental stress test was performed more than 6 months after the acute event in TSC patients and age- and sex-matched controls. Standard echocardiography and tissue Doppler imaging (TDI) - derived time-phases of cardiac cycle were recorded to calculate myocardial performance index (MPI) to assess ventricular function before and during mental stress. Holter-ECG recording was made to estimate HRV before, during and after mental stress. SC was measured at baseline, before and 20 minutes after mental stress.

Subjects

Twenty-two TSC patients and 22 sex-and age-matched controls were recruited from the SMINC-study and investigated with a mental stress test. All TSC patients had a previous normal cardiovascular magnetic resonance investigation.

Results

There were no significant differences at rest or during mental stress for left and right ventricular MPI or other standard diastolic variables between TSC patients and controls. HRV did not differ between TSC patients and controls. There was a trend towards less increase in SC after mental stress in TSC patients compared to controls.

Conclusion

Mental stress did not induce a significant difference in myocardial function or HRV response between TSC and controls. Moreover, no significant difference could be seen in SC response at baseline, during or after mental stress. This study indicates that myocardial vulnerability to mental stress does not persist in TSC patients.     

A Gamma-Knife-Enabled Mouse Model of Cerebral Single-Hemisphere Delayed Radiation Necrosis

Purpose

To develop a Gamma Knife-based mouse model of late time-to-onset, cerebral radiation necrosis (RN) with serial evaluation by magnetic resonance imaging (MRI) and histology.

Methods and Materials

Mice were irradiated with the Leksell Gamma Knife^® (GK) Perfexion^TM (Elekta AB; Stockholm, Sweden) with total single-hemispheric radiation doses (TRD) of 45- to 60-Gy, delivered in one to three fractions. RN was measured using T2-weighted MR images, while confirmation of tissue damage was assessed histologically by hematoxylin & eosin, trichrome, and PTAH staining.

Results

MRI measurements demonstrate that TRD is a more important determinant of both time-to-onset and progression of RN than fractionation. The development of RN is significantly slower in mice irradiated with 45-Gy than 50- or 60-Gy, where RN development is similar. Irradiated mouse brains demonstrate all of the pathologic features observed clinically in patients with confirmed RN. A semi-quantitative (0 to 3) histologic grading system, capturing both the extent and severity of injury, is described and illustrated. Tissue damage, as assessed by a histologic score, correlates well with total necrotic volume measured by MRI (correlation coefficient = 0.948, with p<0.0001), and with post-irradiation time (correlation coefficient = 0.508, with p<0.0001).

Conclusions

Following GK irradiation, mice develop late time-to-onset cerebral RN histology mirroring clinical observations. MR imaging provides reliable quantification of the necrotic volume that correlates well with histologic score. This mouse model of RN will provide a platform for mechanism of action studies, the identification of imaging biomarkers of RN, and the development of clinical studies for improved mitigation and neuroprotection.     

Is There an Association between Long-Term Sick Leave and Disability Pension and Unemployment beyond the Effect of Health Status? – A Cohort Study

Background

Studies have shown that long-term sick leave is a strong predictor of disability pension. However, few have aimed to disentangle the effect of sick leave and of health status.The objective of this study was to investigate whether there is an association between long-term sick leave and disability pension and unemployment, when taking health status into account.

Methods/Principal Findings

The study was based on the Stockholm Public Health Cohort, restricted to 13,027 employed individuals (45.9% men) aged 18–59 in 2002 and followed until 2007.Hazard ratios (HR) with 95% Confidence Interval (CI) were estimated by Cox regression models adjusting for socio-demographic factors and five measures of health status.Having been on long-term sick leave increased the risk of disability pension (HR 4.01; 95% CI 3.19–5.05) and long-term unemployment (HR 1.45; 95% CI 1.05–2.00), after adjustment for health status. The analyses of long-term sick leave due to specific illness showed that the increased risk for long-term unemployment was confined to the group on sick leave due to musculoskeletal (HR 1.70 95% CI 1.00–2.89) and mental illness (HR 1.80 95% CI 1.13–2.88) and further that there was an increased risk for short-term unemployment in the group on sick leave due to mental illness (HR1.57 95%CI 1.09–2.26).

Conclusions/Significance

Long-term sick leave increases the risks of both disability pension and unemployment even when taking health status into account. The results support the hypothesis that long-term sick leave may start a process of marginalization from the labor market.