Pulmonary embolism in menopausal hormone therapy: a population-based register study.

OBJECTIVE: Oral but not transdermal menopausal hormone therapy (MHT) increases the risk of venous thromboembolism. There is no evidence regarding the risk of the serious complication pulmonary embolism (PE). The aim was to investigate the risk of PE in women using MHT depending on administration route, type of progestin and treatment duration. METHOD: The population-based case-control study covered 1,771,253 women aged 40-69 years, during 2006-2015. Diagnoses of PE (n = 13,974) and drug dispensations were received from national validated registers. RESULTS: Current MHT users had a higher risk of PE than non-users (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.05-1.26). First ever users had the highest risk (OR 2.07, 95% CI 1.23-3.50). Transdermal administration was not associated with increased risk of PE. The OR was slightly but non-significantly higher with estrogen combined with medroxyprogesterone acetate than with norethisterone acetate. DISCUSSION: The risk of PE was significantly increased in users of oral but not transdermal MHT, with the highest risk in first ever users of oral estrogen combined with medroxyprogesterone acetate. The risk was considerably lower in women with recurrent treatment, probably because of the healthy user effect. CONCLUSION: PE was most common close to initiation of oral treatment. Transdermal MHT did not increase the risk of PE.

Overlapping expression of serotonin transporters and neurokinin-1 receptors in posttraumatic stress disorder: a multi-tracer PET study.

The brain serotonergic system is colocalized and interacts with the neuropeptidergic substance P/neurokinin-1 (SP/NK1) system. Both these neurochemical systems have independently been implicated in stress and anxiety, but interactions between them might be crucial for human anxiety conditions. Here, we examined the serotonin and substance P/neurokinin-1 (SP/NK1) systems individually as well as their overlapping expression in 16 patients with posttraumatic stress disorder (PTSD) and 16 healthy controls. Participants were imaged with the highly selective radiotracers [(11)C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB) and [(11)C]GR205171 assessing serotonin transporter (SERT) and NK1 receptor availability, respectively. Voxel-wise analyses in the amygdala, our a priori-defined region of interest, revealed increased number of NK1 receptors, but not SERT in the PTSD group. Symptom severity, as indexed by the Clinician-administered PTSD Scale, was negatively related to SERT availability in the amygdala, and NK1 receptor levels moderated this relationship. Exploratory, voxel-wise whole-brain analyses revealed increased SERT availability in the precentral gyrus and posterior cingulate cortex of PTSD patients. Patients, relative to controls, displayed lower degree of overlapping expression between SERT and NK1 receptors in the putamen, thalamus, insula and lateral orbitofrontal gyrus, lower overlap being associated with higher PTSD symptom severity. Expression overlap also explained more of the symptomatology than did either system individually, underscoring the importance of taking interactions between the neurochemical systems into account. Thus, our results suggest that aberrant serotonergic-SP/NK1 couplings contribute to the pathophysiology of PTSD and, consequently, that normalization of these couplings may be therapeutically important.

Genetic variations of NLRP1: susceptibility in psoriasis.

BACKGROUND: NACHT, LRR and PYD domain-containing protein (NLRP)1 is part of the inflammasome multiprotein complex involved in the production of interleukin (IL)-1ß and IL-18, two cytokines strongly implicated in psoriasis pathogenesis. Genetic variations in NLRP1 are associated with a predisposition for chronic inflammatory conditions. OBJECTIVES: The aim of the study was to investigate the role of genetic variation in the NLRP1 inflammasome in psoriasis susceptibility. MATERIAL AND METHODS: Four haplotype-tagging single-nucleotide polymorphisms (SNPs) (rs6502867, rs8079034, rs878329 and rs12150220) were investigated by TaqMan allelic discrimination in a patient sample comprising 1847 individuals from 478 families and 802 healthy controls. RESULTS: Using the transmission disequilibrium test, a significant increase in the transmission of the NLRP1 rs8079034C and rs878329C alleles to patients with psoriasis was demonstrated (P = 0·006 and P = 0·033, respectively). Furthermore, homozygosity for the rs878329C allele correlated with a younger age of onset. We also observed an increase in the expression of NLRP1 mRNA in the peripheral blood cells of patients with psoriasis. This was accompanied by a higher level of circulating IL-18 and appeared to be associated with the rs878329C allele. CONCLUSIONS: Our data support the involvement of NLRP1 and the NLRP1 inflammasome in psoriasis susceptibility and further support the role of innate immunity in psoriasis.

What determines immediate use of invasive ventilation in patients with COPD?

BACKGROUND: The choice between non-invasive ventilation (NIV) and invasive ventilation in patients with an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) may be irrational. The aim of this study was to examine those patient characteristics, and circumstances deemed important in the choice made between NIV and invasive ventilation in the intensive care unit (ICU). METHODS: We first examined 95 admissions of AECOPD patients on nine ICUs and identified variables associated with invasive ventilation. Thereafter, a questionnaire was sent to ICU personnel to study the relative importance of different factors with a possible influence on the decision to use invasive ventilation at once. RESULTS: Univariable analysis showed that increasing age [odds ratio (OR) 1.06 per year] and increasing body mass index (BMI) (OR 1.11 per kg/m(2) ) were associated with immediate invasive ventilation, while there was no such association with arterial blood gases or breath rate. BMI was the only factor that remained associated with immediate invasive ventilation in the multivariable analysis [OR 1.12 (95% confidence interval 1.03-1.23) kg/m(2) ]. Ranking of responses to the questionnaire showed that consciousness, respiratory symptoms and blood gases were powerful factors determining invasive ventilation, whereas high BMI and age were ranked low. Non-patient-related factors were also deemed important (physician in charge, presence of guidelines, ICU workload). CONCLUSION: Factors other than those deemed most important in guidelines appear to have an inappropriate influence on the choice between NIV and immediate intubation in AECOPD in the ICU. These factors must be identified to further increase the appropriate use of NIV.

In type 2 diabetes, randomisation to advice to follow a low-carbohydrate diet transiently improves glycaemic control compared with advice to follow a low-fat diet producing a similar weight loss.

AIMS/HYPOTHESIS: The study aimed to compare the effects of a 2 year intervention with a low-fat diet (LFD) or a low-carbohydrate diet (LCD), based on four group meetings to achieve compliance. METHODS: This was a prospective randomised parallel trial involving 61 adults with type 2 diabetes consecutively recruited in primary care and randomised by drawing ballots. Patients that did not speak Swedish could not be recruited. The primary outcomes in this non-blinded study were weight and HbA(1c). Patients on the LFD aimed for 55-60 energy per cent (E%) and those on LCD for 20 E% from carbohydrate. RESULTS: The mean BMI and HbA(1c) of the participants were 32.7 ± 5.4 kg/m(2) and 57.0 ± 9.2 mmol/mol, respectively. No patients were lost to follow-up. Weight loss did not differ between groups and was maximal at 6 months: LFD -3.99 ± 4.1 kg (n=31); LCD -4.31 ± 3.6 kg (n=30); p < 0.001 within groups. At 24 months, patients on the LFD had lost -2.97 ± 4.9 kg and those on LCD -2.34 ± 5.1 kg compared with baseline (p = 0.002 and p = 0.020 within groups, respectively). HbA(1c) fell in the LCD group only (LCD at 6 months -4.8 ± 8.3 mmol/mol, p = 0.004, at 12 months -2.2 ± 7.7 mmol/mol, p = 0.12; LFD at 6 months -0.9 ± 8.8 mmol/mol, p = 0.56). At 6 months, HDL-cholesterol had increased with the LCD (from 1.13 ± 0.33 mmol/l to 1.25 ± 0.47 mmol/l, p = 0.018) while LDL-cholesterol did not differ between groups. Insulin doses were reduced in the LCD group (0 months, LCD 42 ± 65 E, LFD 39 ± 51 E; 6 months, LCD 30 ± 47 E, LFD 38 ± 48 E; p = 0.046 for between-group change). CONCLUSIONS/INTERPRETATION: Weight changes did not differ between the diet groups, while insulin doses were reduced significantly more with the LCD at 6 months, when compliance was good. Thus, aiming for 20% of energy intake from carbohydrates is safe with respect to cardiovascular risk compared with the traditional LFD and this approach could constitute a treatment alternative. TRIAL REGISTRATION: ClinicalTrials.gov NCT01005498 FUNDING: University Hospital of Linköping Research Funds, Linköping University, the County Council of Östergötland, and the Diabetes Research Centre of Linköping University.

Impact of stress coping capacity on recovery from abdominal hysterectomy in a fast-track programme: a prospective longitudinal study.

OBJECTIVE: To evaluate the effect of stress coping capacity in combination with mode of anaesthesia on postoperative recovery in fast-track abdominal hysterectomy. DESIGN: Prospective longitudinal study. SETTING: Five hospitals in the south-east of Sweden. POPULATION: A cohort of 162 women undergoing fast-track abdominal hysterectomy for benign conditions. METHODS: Self-administered questionnaires, the Stress Coping Inventory (SCI) and the Swedish Postoperative Symptom Questionnaire (SPSQ), and clinical information were collected prospectively. Stress coping capacity was categorised as high or low according to the summed score of the SCI. Comparisons of effect variables were adjusted using a propensity score-matching model. MAIN OUTCOME MEASURES: Associations between stress coping capacity and hospital stay, sick leave, use of analgesic and self-reported postoperative symptoms. RESULTS: Women with high stress coping capacity had a significantly shorter sick leave, experienced postoperative symptoms significantly less often, and with lower intensity, than women with low stress coping capacity. With the exception of symptom intensity, these findings were related to having had the operation under spinal anaesthesia as opposed to general anaesthesia. Hospital stay, use of analgesics and abdominal pain were not related to stress coping capacity. CONCLUSIONS: In patients for whom spinal anaesthesia was applied, high stress coping seems to be a quality that helps patients manage the burden of surgery. It is desirable for the individual, as well as for the healthcare system, to enhance recovery by using intervention programmes designed to improve or manage stress coping, particularly for individuals with low stress coping capacity. This recommendation merits further investigation.

Genetic influences on central and peripheral nervous system activity during fear conditioning.

Fear conditioning is an evolutionarily conserved type of learning serving as a model for the acquisition of situationally induced anxiety. Brain function supporting fear conditioning may be genetically influenced, which in part could explain genetic susceptibility for anxiety following stress exposure. Using a classical twin design and functional magnetic resonance imaging, we evaluated genetic influences (h2) on brain activity and standard autonomic measures during fear conditioning. We found an additive genetic influence on mean brain activation (h2 = 0.34) and autonomic responses (h2 = 0.24) during fear learning. The experiment also allowed estimation of the genetic influence on brain activation during safety learning (h2 = 0.55). The mean safety, but not fear, related brain activation was genetically correlated with autonomic responses. We conclude that fear and safety learning processes, both involved in anxiety development, are moderately genetically influenced as expressed both in the brain and the body.

To continue or discontinue aspirin in the perioperative period: a randomized, controlled clinical trial.

BACKGROUND: Major adverse cardiac events (MACEs) are a common cause of death after non-cardiac surgery. Despite evidence for the benefit of aspirin for secondary prevention, it is often discontinued in the perioperative period due to the risk of bleeding. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in order to compare the effect of low-dose aspirin with that of placebo on myocardial damage, cardiovascular, and bleeding complications in high-risk patients undergoing non-cardiac surgery. Aspirin (75 mg) or placebo was given 7 days before surgery and continued until the third postoperative day. Patients were followed up for 30 days after surgery. RESULTS: A total of 220 patients were enrolled, 109 patients received aspirin and 111 received placebo. Four patients (3.7%) in the aspirin group and 10 patients (9.0%) in the placebo group had elevated troponin T levels in the postoperative period (P=0.10). Twelve patients (5.4%) had an MACE during the first 30 postoperative days. Two of these patients (1.8%) were in the aspirin group and 10 patients (9.0%) were in the placebo group (P=0.02). Treatment with aspirin resulted in a 7.2% absolute risk reduction [95% confidence interval (CI), 1.3-13%] for postoperative MACE. The relative risk reduction was 80% (95% CI, 9.2-95%). Numbers needed to treat were 14 (95% CI, 7.6-78). No significant differences in bleeding complications were seen between the two groups. CONCLUSIONS: In high-risk patients undergoing non-cardiac surgery, perioperative aspirin reduced the risk of MACE without increasing bleeding complications. However, the study was not powered to evaluate bleeding complications.

Long-term effect of the ICU-diary concept on quality of life after critical illness.

BACKGROUND: Critically ill patients often spend time in the intensive care unit (ICU) either unconscious or sedated. On recovery, they are often in a state of confusion with memory loss that may be associated with a longstanding reduction in health-related quality of life (QoL). We hypothesised that the ICU-diary concept could improve their QoL by filling in their memory gaps. METHODS: A non-randomised, prospective study in a non-academic eight-bedded general ICU. A group of patients (n=38) were selected to receive the ICU-diary concept (keeping a diary with photos while on the ICU plus a follow-up meeting) when a long and complicated course was expected. Health-related QoL at 6, 12, 24 and 36 months was compared with a group that did not receive the ICU-diary (n=224). The Medical Outcomes Study 36-Item Short-Form (SF-36) was used to measure health-related QoL. Multiple regression models adjusted for age, sex, illness severity, pre-existing disease and diagnostic category was used to analyse the effects of the ICU-diary concept at 6 months, and changes over time were analysed using repeated measures MANOVA. RESULTS: Crude and adjusted scores for two dimensions of SF-36 (general health and vitality) and the physical component summary score were significantly higher at 6 months in the ICU-diary group (P<0.05) and some of the effects remained during the 3-year follow-up period (P<0.05). CONCLUSION: The ICU-diary concept was associated with improved health-related QoL during the 3-year follow-up period after a critical illness. The effect of this intervention needs to be confirmed in a larger randomised study.

N-terminal fragment of pro-B-type natriuretic peptide is a predictor of cardiac events in high-risk patients undergoing acute hip fracture surgery.

BACKGROUND: The aim of this investigation was to assess the incidence of elevated N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) and its relation to outcome defined as perioperative adverse cardiac events and all-cause mortality in high-risk patients undergoing non-elective surgery for hip fracture. METHODS: A cohort of patients with hip fractures were extracted from a prospective observational study of high-risk patients (ASA class III or IV) undergoing emergency surgery. NT-proBNP and troponin I were measured before operation. An NT-proBNP > or = 3984 ng litre(-1) was set as the cut-off level for significance. Perioperative adverse cardiac events and 30 day and 3 month mortality were recorded. RESULTS: Sixty-nine subjects were included. Thirty-four subjects (49%) had an NT-proBNP > or = 3984 ng litre(-1) before surgery. Thirty-four subjects (49%) had a perioperative adverse cardiac event. Of these, 22 subjects (65%) had NT-proBNP above the diagnostic threshold compared with 12 subjects (34%) who had an NT-proBNP below the diagnostic threshold (P=0.01). Preoperative NT-proBNP > or = 3984 ng litre(-1) [odds ratio (OR) 3.0; 95% confidence interval (CI) 1.0-8.9] and congestive heart failure (OR 3.0; 95% CI 1.0-9.0) were independent predictors of perioperative adverse cardiac events. A total of eight subjects (12%) died within 30 days after operation. CONCLUSIONS: There is a high incidence of elevated NT-proBNP in subjects undergoing non-elective hip fracture surgery. Preoperative NT-proBNP is a valuable predictor of cardiac complications in the perioperative period.

Predictors of cardiac events in high-risk patients undergoing emergency surgery.

BACKGROUND: The aim of this study was to determine the incidence of myocardial damage and left ventricular myocardial dysfunction and their influence on outcome in high-risk patients undergoing non-elective surgery. METHODS: In this prospective observational study, 211 patients with American Society of Anesthesiologists classification III or IV undergoing emergent or urgent surgery were included. Troponin I (TnI) was measured pre-operatively, 12 and 48 h post-operatively. Pre-operative N-terminal fragment of B-type natriuretic peptide (NT-proBNP), as a marker for left ventricular systolic dysfunction, was analyzed. The diagnostic thresholds were set to TnI >0.06 microg/l and NT-proBNP >1800 pg/ml, respectively. Post-operative major adverse cardiac events (MACE), 30-day and 3-months mortality were recorded. RESULTS: Elevated TnI levels were detected in 33% of the patients post-operatively. A TnI elevation increased the risk of MACE (35% vs. 3% in patients with normal TnI levels, P<0.001) and 30-day mortality (23% vs. 7%, P=0.003). Increased concentrations of NT-proBNP were seen in 59% of the patients. Elevated NT-proBNP was an independent predictor of myocardial damage post-operatively, odds ratio, 6.2 [95% confidence interval (CI) 2.1-18.0] and resulted in an increased risk of MACE (21% vs. 2.5% in patients with NT-proBNP < or = 1800 pg/ml, P<0.001). CONCLUSION: Myocardial damage is common in a high-risk population undergoing unscheduled surgery. These results suggest a close correlation between myocardial damage in the post-operative period and increased concentration of NT-proBNP before surgery. The combinations of TnI and NT-proBNP are reliable markers for monitoring patients at risk in the peri-operative period as well as useful tools in our risk assessment pre-operatively in emergency surgery.

The health promoting conversations intervention for families with a critically ill relative: A pilot study.

BACKGROUND: After intensive care unit treatment, patients often have prolonged impairments that affect their physical, cognitive and mental health. Family members can face overwhelming and emotionally challenging situations and their concerns and needs must be addressed. OBJECTIVE: We investigated the outcomes of pilot randomised control trial, a nurse-led family intervention, Health Promoting Conversations, which focused on family functioning and wellbeing in families with a critically ill member. STUDY DESIGN: This randomised controlled pilot study used a pre-test, post-test design with intervention and control groups to investigate the outcomes of the nurse-led intervention in 17 families. OUTCOME MEASURES: The Health Promoting Conversations intervention was evaluated using validated instruments that measure family functioning and family wellbeing: the General Functioning sub-scale from the McMaster Family Assessment Device; the Family Sense of Coherence, the Herth Hope Index, and the Medical Outcome Short-Form Health Survey. Descriptive and analytical statistical methods were used to analyse the data. RESULTS: After 12 months, the intervention group reported better family functioning than the control group. The intervention group also had better social functioning and mental health after 12 months. CONCLUSION: This intervention may improve family wellbeing by improving family function, reducing stress, and promoting better mental health.

Symptoms in peri- and postmenopausal women in relation to testosterone concentrations: data from The Women's Health in the Lund Area (WHILA) study.

OBJECTIVES: The aim of this study was to investigate possible associations between androgen concentrations in perimenopausal women and symptoms that may be associated with low androgen concentrations in the blood. METHODS: All women born in the period 1935-1945 and living in a defined geographic area in Sweden (n = 10 766) were invited to a screening program that included physical and laboratory examinations and a questionnaire. Three groups were identified: premenopausal women, women on hormone replacement therapy (HRT) and postmenopausal women without HRT. Concentrations of testosterone, androstendione, sex hormone binding globulin and estradiol were measured. Waist-hip ratio, body mass index and free testosterone index (FTI) were calculated. RESULTS: A total of 6908 women participated. The women on HRT had lower testosterone and FTI and were less satisfied with mood and energy (p < 0.05). Women with hot flushes had higher testosterone and FTI and women reporting coldness had lower concentrations (p < 0.05). Sexual well-being was not correlated to testosterone or FTI (p > 0.05). CONCLUSIONS: Lower testosterone concentrations were associated with lower quality of life in perimenopausal women but not to sexual well-being. There must be factors other than decrements in sex hormones that contribute to the emergence of some perimenopausal symptoms.

Low risk of melanoma in patients with atopic dermatitis.

BACKGROUND: There is a possible association between atopy and cancer based on the concept of atopic diseases as a hyper-reactive state of the immune system. Melanoma is an immunogenic tumour, and since patients with atopic dermatitis (AD) are subjected to local and systemic immunosuppressives, it would be expected to find an influence of AD on the melanoma risk. There is a positive correlation between the number of naevi and melanoma risk, and children and adults with AD have fewer naevi than controls although many patients receive ultraviolet treatment. OBJECTIVE: This study aims to investigate the melanoma risk in a retrospective cohort of AD patients compared with the population. STUDY DESIGN: 6280 AD patients born 1935-1979 visited five Dermatology clinics during 1986-2004. Mean follow-up time was 36.7 years (SD 6.9) corresponding to 230 742 person-years at risk. The cohort file was linked to the National Cancer register. RESULTS: Six AD patients with melanoma were identified, and the Poisson regression analysis adjusted for age group, sex and year resulted in an incidence rate ratio of 0.49 (95% confidence interval: 0.27-1.35, P = 0.08) for the AD group compared with the total population in the region. CONCLUSION: A low risk to develop melanoma was found in AD patients. However, the results must be interpreted with caution since the small number of expected cases of melanoma makes the risk estimate sensitive to chance effects. We hypothesize that formation of naevi and progression to melanoma is counteracted by the inflammatory process in the skin of AD patients.

Deaths caused by injury among people of working age (18-64) are decreasing, while those among older people (64+) are increasing.

BACKGROUND: Injury is an important cause of death in all age groups worldwide, and contributes to many losses of human and economic resources. Currently, we know a few data about mortality from injury, particularly among the working population. The aim of the present study was to examine death from injury over a period of 14 years (1999-2012) using the Swedish Cause of Death Registry (CDR) and the National Patient Registry, which have complete national coverage. METHOD: CDR was used to identify injury-related deaths among adults (18 years or over) during the years 1999-2012. ICD-10 diagnoses from V01 to X39 were included. The significance of changes over time was analyzed by linear regression. RESULTS: The incidence of prehospital death decreased significantly (coefficient -0.22, r 2 = 0.30; p = 0.041) during the study period, while that of deaths in hospital increased significantly (coefficient 0.20, r 2 = 0.75; p < 0.001). Mortality/100,000 person-years in the working age group (18-64 years) decreased significantly (coefficient -0.40, r 2 = 0.37; p = 0.020), mainly as a result of decrease in traffic-related deaths (coefficient -0.34, r 2 = 0.85; p < 0.001). The incidence of deaths from injury among elderly (65 years and older) patients increased because of the increase in falls (coefficient 1.71, r 2 = 0.84; p < 0.001) and poisoning (coefficient 0.13, r 2 = 0.69; p < 0.001). CONCLUSION: The epidemiology of injury in Sweden has changed during recent years in that mortality from injury has declined in the working age group and increased among those people 64 years old and over.

Diffusion tensor imaging and tractography of the white matter in normal aging: The rate-of-change differs between segments within tracts.

Knowledge concerning the normal aging of cerebral white matter will improve our understanding of abnormal changes in neurodegenerative diseases. The microstructural basis of white matter maturation and aging can be investigated using diffusion tensor imaging (DTI). Generally, diffusion anisotropy increases during childhood and adolescence followed by a decline in middle age. However, this process is subject to spatial variations between tracts. The aim of this study was to investigate to what extent age-related variations also occur within tracts. DTI parameters were compared between segments of two white matter tracts, the cingulate bundle (CB) and the inferior fronto-occipital fasciculus (IFO), in 257 healthy individuals between 13 and 84years of age. Segments of the CB and the IFO were extracted and parameters for each segment were averaged across the hemispheres. The data was analysed as a function of age. Results show that age-related changes differ both between and within individual tracts. Different age trajectories were observed in all segments of the analysed tracts for all DTI parameters. In conclusion, aging does not affect white matter tracts uniformly but is regionally specific; both between and within white matter tracts.

Increased neurokinin-1 receptor availability in the amygdala in social anxiety disorder: a positron emission tomography study with [11C]GR205171.

The neurokinin-1 (NK1) receptor is abundantly expressed in the fear circuitry of the brain, including the amygdala, where it modulates stress and anxiety. Despite its proposed involvement in psychopathology, only a few studies of NK1 receptor availability in human subjects with anxiety disorders exist. Here, we compared NK1 receptor availability in patients with social anxiety disorder (SAD; n = 17) and healthy controls (n = 17) using positron emission tomography and the radiotracer [11C]GR205171. The Patlak Graphical plot using a cerebellar reference region was used to model the influx parameter, Ki measuring NK1 receptor availability. Voxel-wise statistical parametric mapping analyses revealed increased NK1 receptor availability specifically in the right amygdala in SAD patients relative to controls. Thus, we demonstrate that exaggerated social anxiety is related to enhanced NK1 receptor availability in the amygdala. This finding supports the contribution of NK1 receptors not only in animal models of stress and anxiety but also in humans with anxiety disorders.