Plasma legumain in familial hypercholesterolemia: associations with statin use and cardiovascular risk markers.

Legumain is known to be regulated in atherosclerotic disease and may have both pro- and anti-atherogenic properties. The study aimed to explore legumain in individuals with familial hypercholesterolemia (FH), a population with increased cardiovascular risk. Plasma legumain was measured in 251 subjects with mostly genetically verified FH, of which 166 were adults (≥18 years) and 85 were children and young adults (<18 years) and compared to 96 normolipidemic healthy controls. Plasma legumain was significantly increased in the total FH population compared to controls (median 4.9 versus 3.3 pg/mL, respectively, p < 0.001), whereof adult subjects with FH using statins had higher levels compared to non-statin users (5.7 versus 3.9 pg/mL, respectively, p < 0.001). Children and young adults with FH (p = 0.67) did not have plasma legumain different from controls at the same age. Further, in FH subjects, legumain showed a positive association with apoB, and markers of inflammation and platelet activation (i.e. fibrinogen, NAP2 and RANTES). In the current study, we show that legumain is increased in adult subjects with FH using statins, whereas there was no difference in legumain among children and young adults with FH compared to controls. Legumain was further associated with cardiovascular risk markers in the FH population. However the role of legumain in regulation of cardiovascular risk in these individuals is still to be determined.

Physical Exercise and Serum BDNF Levels: Accounting for the Val66Met Polymorphism in Older Adults.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) expression, which can be measured in blood serum, has been found to increase with aerobic exercise. The link between BDNF level, physical exercise, and genetic status (Val66Met polymorphism) has not been well researched in older adults. OBJECTIVE: To investigate the possible link between BDNF expression, acute aerobic exercise, and the Val66Met polymorphism in older adults. METHOD: Twenty-three healthy older adults participated in one session of acute aerobic exercise. Their serum BDNF levels were measured both at baseline and post exercise. Saliva samples were collected to identify each individual's genetic status. RESULTS: At baseline, the individuals' mean serum BDNF level was 16.03 ng/mL (Val66Val = 15.89 ng/mL; Val66Met = 16.34 ng/mL); post exercise, the individuals' mean serum BDNF level was 16.81 ng/mL (Val66Val = 16.14 ng/mL; Val66Met = 18.34 ng/mL). CONCLUSION: One session of acute aerobic exercise significantly increased the individuals' mean serum BDNF level. Males had higher BDNF levels than females. There was a significant interaction between gender and BDNF expression post exercise and a significant between-group effect of gender. The Val66Met carriers had a more positive response to the acute aerobic exercise compared with the Val66Val carriers, although without a significant difference between the two groups.

Registered nurses' experience of care for adult patients with a temporary tracheostomy at general hospital wards. A phenomenological-hermeneutic explorative study.

BACKGROUND: Caring for adult patients with a temporary tracheostomy in general wards can be challenging and complex. Little research has explored registered nurses' experiences with caring for these groups of patients. OBJECTIVES: This study sought to interpret and describe registered nurses' lived experiences of caring for adult patients with a tracheostomy in general wards. RESEARCH DESIGN/METHODOLOGY: Six registered nurses were interviewed in this study. The interviews were analysed to gain comprehensive knowledge about caring for adult patients with a temporary tracheostomy. The interviews were transcribed, analysed, and interpreted by using Gadamers philosophical hermeneutics and Kvale and Brinkmann's three steps of understanding. SETTING: Three different wards medical, surgical, and neurological of a teaching hospital in Norway. FINDINGS: Three themes emerged from data analysis. These included experiencing clinically challenging patients, a lack of clinical support from the intensive care nurses, and a lack of professional confidence. CONCLUSION: This study highlighted the challenges surrounding the care of an adult patient with a tracheostomy in the general wards. Identifying these challenges would lead to further improvement in registered nurses' experiences and, in turn, in the quality of competent care for adult patients with a tracheostomy in the general ward. IMPLICATIONS FOR CLINICAL PRACTICE: Understanding the registered nurses' experiences will assist the head nurses in planning and providing relevant information and education to provide safe and holistic patient care. Adequate support from intensive care unit nurses and professional development are required to ensure high-quality care. This study recommends that healthcare managers focus on establishing step-down units to improve patient outcomes, especially for high-risk patients and to increase the competencies of registered nurses in caring for adult patients with a tracheostomy as a whole person.

No effect of omega-3 polyunsaturated fatty acid supplementation on inflammatory markers in familial hypercholesterolemia: a randomized crossover trial.

Individuals with familial hypercholesterolemia (FH) have increased cardiovascular risk despite lipid-lowering therapy, and additional therapy is warranted. Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplements have demonstrated an effect on cardiovascular endpoints in some clinical trials. Platelet-modifying and anti-inflammatory properties are among the proposed beneficial effects of n-3 PUFA. We investigated the effect of a high-dose n-3 PUFA supplement on platelet function and inflammatory markers in FH subjects. We performed a randomized, double-blind trial with a crossover design. Inclusion criteria were genetically verified heterozygous FH, stable disease, statin treatment >12 months, and age 18-75 years. Trial participants were allocated to two treatment periods in random order. The treatment periods (three months each) were separated by a three-month washout period. N-3 PUFA (1840 mg eicosapentaenoic acid and 1520 mg docosahexaenoic acid) and placebo (olive oil) were administered in four capsules daily. Endpoints were platelet function and inflammatory markers, assessed by platelet function analyzer, soluble markers P-selectin, vascular cell adhesion molecule (VCAM) and intercellular adhesion molecule (ICAM), 27 cytokines, and hematological parameters. Thirty-four heterozygous FH individuals completed the trial. No treatment effect (p = 0.93) from n-3 PUFA on the platelet function analyzer was found (2 s, 95% CI [-13, 6]). In our FH population, n-3 PUFA did not influence the levels of P-selectin (-2.0, 95% CI [-5.0, 2.0], p = 0.41), VCAM (0, 95% CI [-14.2, 14.2], p > 0.99), ICAM (-27.0, 95% CI [-70.1, 16.5]; p = 0.21), cytokine levels, or hematological parameters. In statin-treated FH individuals, high dose n-3 PUFA supplement did not affect platelet function and inflammatory markers.Trial registration number: EUDRACTNR 2012-000505-68; ClinicalTrials.gov NCT01813006HighlightsTrial studying the effect of omega-3 fatty acids supplements in familial hypercholesterolemia.High-dose omega-3 fatty acids supplements had no impact on platelet function.Cytokine levels were unchanged after three months of omega-3 fatty acid supplementation.No effect of omega-3 fatty acids on C-reactive protein was observed.

The risk of various types of cardiovascular diseases in mutation positive familial hypercholesterolemia; a review.

Familial hypercholesterolemia (FH) is a common, inherited disease characterized by high levels of low-density lipoprotein Cholesterol (LDL-C) from birth. Any diseases associated with increased LDL-C levels including atherosclerotic cardiovascular diseases (ASCVDs) would be expected to be overrepresented among FH patients. There are several clinical scoring systems aiming to diagnose FH, however; most individuals who meet the clinical criteria for a FH diagnosis do not have a mutation causing FH. In this review, we aim to summarize the literature on the risk for the various forms of ASCVD in subjects with a proven FH-mutation (FH+). We searched for studies on FH+ and cardiovascular diseases and also included our and other groups published papers on FH + on a wide range of cardiovascular and other diseases of the heart and vessels. FH + patients are at a markedly increased risk of a broad range of ASCVD. Acute myocardial infarction (AMI) is the most common in absolute numbers, but also aortic valve stenosis is by far associated with the highest excess risk. Per thousand patients, we observed 3.6 incident AMI per year compared to 1.9 incident aortic valve stenosis, however, standardized incidence ratio (SIR) for incident AMI was 2.3 compared to 7.9 for incident aortic valve stenosis. Further, occurrence of ischemic stroke seems not to be associated with increased risk in FH+. Clinicians should be aware of the excess risk of almost all kind of ASCVD in FH+, and the neutral risk of stroke need to be studied further in FH + patients.

[Physical activity has an acute effect on depression and anxiety syndromes]. / Fysisk aktivitet kan ha omedelbar effekt på depression och ångest.

Physical activity has a preventive and an acute effect on both depression and anxiety syndromes. The effect of just physical activity, usually 3 times/week for 8-12 weeks, is equal to treatment with psychotherapy or antidepressants for mild to moderate depression, according to several meta-analyses. Addition of physical exercise to psychotherapy has a significantly greater effect than psychotherapy alone. Few high-quality studies on anxiety syndromes have been performed regarding the treatment effect of physical activity. In anxiety syndromes, physical activity for 10-12 weeks has a better effect than no treatment. Yet, psychotherapy or pharmacological treatment has a better effect than physical exercise in panic disorder. The article describes a variety of positive physiological, neurobiological and psychological mechanisms of physical activity.

Self-Reported Measures Have a Stronger Association With Dizziness-Related Handicap Compared With Physical Tests in Persons With Persistent Dizziness.

Background: Associations between dizziness-related handicap and a variety of self-reported measures have been reported. However, research regarding associations between dizziness-related handicap and aspects of functioning that includes both physical tests and self-reported measures is scarce. Objective: The purpose of the study was to describe the variations in signs and symptoms in people with persistent dizziness using physical tests and self-reported outcomes across three severity levels of the Dizziness Handicap Inventory (DHI) and investigate their associations with the DHI. Method: Participants with persistent dizziness (n = 107) were included in this cross-sectional study. The participants underwent (1) physical tests (gait tests, grip strength, body flexibility, and movement-induced dizziness) and completed questionnaires regarding (2) psychological measures (Mobility Inventory of Agoraphobia, Body Sensation Questionnaire, Agoraphobic Cognitions Questionnaire, and Hospital Depression and Anxiety Questionnaire), and (3) fatigue, dizziness severity, and quality of life (Chalders Fatigue Scale, Vertigo Symptom Scale-Short Form, and EQ visual analog scale), in addition to the DHI. Data were presented by descriptive statistics for three DHI severity levels (mild, moderate, and severe). A multiple linear backward regression analysis was conducted for each group of measures in relation to the DHI total score, with additional analyses adjusting for age and sex. Based on these results, significant associations were tested in a final regression model. Results: With increasing severity levels of DHI, the participants demonstrated worse performance on most of the physical tests (preferred and fast gait velocity, dizziness intensity after head movements), presented with worse scores on the self-reported measures (avoidance behavior, fear of bodily sensation, fear of fear itself, psychological distress, fatigue, dizziness severity, quality of life). After adjusting for age and sex, significant associations were found between total DHI and avoidance behavior, psychological distress, dizziness severity, and quality of life, but not with any of the physical tests, explaining almost 56% of the variance of the DHI total score. Conclusion: There was a trend toward worse scores on physical tests and self-reported measurements with increasing DHI severity level. The DHI seems to be a valuable tool in relation to several self-reported outcomes; however, several signs and symptoms may not be detected by the DHI, and thus, a combination of outcomes should be utilized when examining patients with persistent dizziness.

Effect of N-3 Polyunsaturated Fatty Acids on Lipid Composition in Familial Hypercholesterolemia: A Randomized Crossover Trial.

Individuals with familial hypercholesterolemia (FH) have an increased risk of cardiovascular disease. Treatment is mainly low-density lipoprotein cholesterol (LDL-C) reduction. How omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplements affect lipoproteins in FH subjects is unknown. We hypothesized that a high-dose n-3 PUFA supplement would reduce atherogenic lipoproteins and influence the high-density lipoprotein cholesterol (HDL-C) function. We performed a randomized, double-blinded crossover study with 34 genetically verified FH individuals (18−75 years, clinically stable, statin treatment > 12 months). Treatment was 4 g n-3 PUFAs (1840 mg eicosapentaenoic acid and 1520 mg docosahexaenoic acid daily) or four capsules of olive oil for three months in a crossover design with a washout period of three months. The defined outcomes were changes in triglycerides, lipoproteins, lipoprotein subfractions, apolipoproteins, and HDL-C function. After treatment with n-3 PUFAs, total cholesterol, LDL-C, and triglycerides were reduced compared to placebo (p ≤ 0.01 for all). Total HDL-C levels were unchanged, but the subfraction of large HDL-C was higher (p ≤ 0.0001) after n-3 PUFAs than after placebo, and intermediate HDL-C and small HDL-C were reduced after n-3 PUFAs compared to placebo (p = 0.02 and p ≤ 0.001, respectively). No changes were found in apolipoproteins and HDL-C function. N-3 PUFAs supplements reduced atherogenic lipoproteins in FH subjects, leaving HDL-C function unaffected.

ICU nurses´ lived experience of caring for adult patients with a tracheostomy in ICU: a phenomenological-hermeneutic study.

BACKGROUND: The care of adult patients with a tracheostomy in intensive care unit is complex, challenging and requires skilled intensive care unit nurses. ICU nurses' live experience is scarcely known. This study aimed to describe the lived experience of intensive care unit nurses of caring for adult patients with a tracheostomy in intensive care unit. METHODS: This study employs a qualitative design. In-depth interviews were conducted with a purposive sampling of 6 intensive care unit nurses from a medical-surgical ICU of a university hospital in Norway who were interviewed. Data was analyzed and interpreted using a phenomenological-hermeneutic approach. This study was reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ). RESULTS: The interpretation yielded the following themes and subthemes: 1) theme: 'challenges of caring for patients with a tracheostomy' consisted of the sub-themes: 'difficult to communicate/interpret and understand the patient's different forms of expression', 'complicated professional assessments', 'caring with patience', and 'collaborating with patient regarding challenges. 2) theme: 'the satisfaction from providing care to patients with a tracheostomy' consisted of the sub-themes: 'working with intensive care patients is instructive' and 'importance to motivate'. CONCLUSIONS: ICU nurses experienced ambivalent feelings while caring for adult patients with a tracheostomy in ICU. They perceived caring as demanding owing to communication and collaboration at the same time, they experienced satisfaction while they strived to provide proper care and motivation. The identified challenges would lead to further improvement in nurses' experiences and, in turn, the quality-of-care for patients with a tracheostomy. Awareness of these challenges is crucial to understand the need for an effective communication strategy to improve the quality and safety of adult patients with tracheostomy in ICU.

Reduced gut microbial diversity in familial hypercholesterolemia with no effect of omega-3 polyunsaturated fatty acids intervention - a pilot trial.

Individuals with familial hypercholesterolemia (FH) undergo an aggressive treatment with cholesterol-lowering drugs to prevent coronary heart disease. Recent evidence suggests an interplay between the gut microbiota, blood lipid levels and lipid-lowering drugs, but this has yet to be studied in individuals with FH. The objective of the study was to characterize the gut microbiota of individuals with familial hypercholesterolemia and examine if effects of omega-3 polyunsaturated fatty acids (PUFAs) on blood lipids act through modification of the gut microbiome. The gut microbiota composition of individuals with FH (N = 21) and healthy controls (N = 144) was analyzed by extracting DNA from stool samples and sequencing of the V3-V4 region of the 16S rRNA gene. A subgroup (n = 15) of the participants received omega-3 polyunsaturated fatty acids (PUFAs) supplementation or placebo in a crossover manner, and the effect of PUFAs on the gut microbiota was also investigated. Individuals with FH had a different gut microbiota composition compared to healthy controls, characterized by reduced richness (p = .001) and reduction of several genera belonging to Clostridia and Coriobacteriia. Patients using ezetimibe in addition to statins appeared to have lower richness compared to those only using statins (p = .01). Intervention with omega-3 PUFAs had negligible impact on the microbiota composition. Positive effects on blood lipids after intervention with omega-3 PUFA were not associated with baseline gut microbiota composition or gut microbial changes during treatment. Further, patients with FH have an altered gut microbiota compared to healthy controls, possibly driven by the use of ezetimibe.

Transmural myocardial infarction with de Winter's sign on ECG. / Transmuralt hjerteinfarkt med de Winters tegn i EKG.

BACKGROUND: De Winter's sign represents a constellation of ECG changes including upward sloping ST depressions greater than 1 mm at the J-point, which end in tall, symmetrical T waves in the precordial leads and reciprocal ST elevation in aVR. The pattern is considered specific for acute occlusion of the LAD. CASE PRESENTATION: A previously healthy man in his forties was referred from urgent care with suspected non-ST-elevation myocardial infarction (NSTEMI) which presented with acute chest pain, ECG with ST depressions and positive troponin-T. Repeat ECG at the local hospital showed further changes, leading to echocardiogram which revealed pronounced cardiac hypokinesia both in the septum and apex. The patient was transferred to the closest interventional cardiology centre and underwent successful PCI. ECG findings were later interpreted as consistent with de Winter's sign. INTERPRETATION: This case illustrates the importance of recognising other ECG changes in addition to ST elevation as indicative of acute reperfusion therapy.

Relationship between Clinical Symptoms and Magnetic Resonance Imaging in Temporomandibular Disorder (TMD) Patients Utilizing the Piper MRI Diagnostic System.

Clinical problems of the temporomandibular joint (TMJ) and the masticatory musculature are both included in the term temporomandibular disorder (TMD). The purpose of the present study was to examine the pathology of the joints of patients diagnosed with TMD utilizing the dedicated Piper MRI-based classification, and to link these pathologies with various symptoms while considering their severity. In total, 64 patients with clinical TMD were examined. Symptoms were recorded using a questionnaire. The clinical examination included diagnosing the occlusion in centric relation, which was followed by a standardized MRI. It was confirmed that, although they occurred in a high percentage in all classes, muscle pain and occlusal interference are not indicators of TMJ damage. The results indicate that the progressive degradation of the TMJ, represented by qualification to the higher Piper classes, is associated with an increase in TMJ pain only up to a certain stage. For the highest Piper classes, the joint pain occurs in a smaller percentage of patients, but sounds are more frequent.

Loss of statin treatment years during pregnancy and breastfeeding periods in women with familial hypercholesterolemia.

BACKGROUND AND AIMS: Women with heterozygous familial hypercholesterolemia (FH) are recommended to initiate statin treatment at the same age as men (from 8 to 10 years of age). However, statins are contraindicated when pregnancy is planned, during pregnancy and breastfeeding. The aim of the study was to determine the duration of pregnancy-related off-statin periods and breastfeeding in FH women. METHODS: A cross-sectional study using an anonymous online self-administered questionnaire was conducted. Women with FH were recruited through Lipid Clinics in Norway and Netherlands and national FH patient organizations. RESULTS: 102 women with FH (n = 70 Norwegian and n = 32 Dutch) were included in the analysis. Total length of pregnancy-related off-statin periods was estimated for 80 women where data were available, and was median (min-max) 2.3 (0-14.2) years. Lost statin treatment time was estimated for 67 women where data were available, and was median (min-max) 18 (0-100)% at mean (SD) age of 31 (4.3) years at last pregnancy. More women breastfed in Norway (83%) and for longer time [8.5 [1-42] months] compared to the Netherlands [63%, p = 0.03; 3.6 (0-14) months, p < 0.001]. Eighty-six percent of the women reported need for more information on pregnancy and breastfeeding in relation to FH. CONCLUSIONS: Young FH women lose years of treatment when discontinuing statins in relation to pregnancy and breastfeeding periods and should be closely followed up to minimize the duration of these off-statin periods. Whether these periods of interrupted treatment increase the cardiovascular risk in FH women needs to be further elucidated.

High-Density Lipoprotein Subfractions: Much Ado about Nothing or Clinically Important?

High-density lipoproteins (HDL) are a heterogenous group of plasma molecules with a large variety in composition. There is a wide specter in lipid content and the number of different proteins that has been associated with HDL is approaching 100. Given this heterogeneity and the fact that the total amount of HDL is inversely related to the risk of coronary heart disease (CHD), there has been increasing interest in the function of specific HDL subgroups and in what way measuring and quantifying these subgroups could be of clinical importance in determining individual CHD risk. If certain subgroups appear to be more protective than others, it may also in the future be possible to pharmacologically increase beneficial and decrease harmful subgroups in order to reduce CHD risk. In this review we give a short historical perspective, summarize some of the recent clinical findings regarding HDL subclassifications and discuss why such classification may or may not be of clinical relevance.

Rifaximin or Saccharomyces boulardii in heart failure with reduced ejection fraction: Results from the randomized GutHeart trial.

BACKGROUND: The gut microbiota represents a potential treatment target in heart failure (HF) through microbial metabolites such as trimethylamine N-oxide (TMAO) and systemic inflammation. Treatment with the probiotic yeast Saccharomyces boulardii have been suggested to improve left ventricular ejection fraction (LVEF). METHODS: In a multicentre, prospective randomized open label, blinded end-point trial, we randomized patients with LVEF <40% and New York Heart Association functional class II or III, despite optimal medical therapy, to treatment (1:1:1) with the probiotic yeast Saccharomyces boulardii, the antibiotic rifaximin, or standard of care (SoC) only. The primary endpoint, the baseline-adjusted LVEF at three months, was assessed in an intention-to-treat analysis. FINDINGS: We enrolled a total of 151 patients. After three months' treatment, the LVEF did not differ significantly between the SoC arm and the rifaximin arm (mean difference was -1•2 percentage points; 95% CI -3•2 - 0•7; p=0•22) or between the SoC arm and the Saccharomyces boulardii arm (mean difference -0•2 percentage points; 95% CI -2•2 - 1•9; p=0•87). We observed no significant between-group differences in changes in microbiota diversity, TMAO, or C-reactive protein. INTERPRETATION: Three months' treatment with Saccharomyces boulardii or rifaximin on top of SoC had no significant effect on LVEF, microbiota diversity, or the measured biomarkers in our population with HF. FUNDING: The trial was funded by the Norwegian Association for Public Health, the Blix foundation, Stein Erik Hagen's Foundation for Clinical Heart Research, Ada og Hagbart Waages humanitære og veldedige stiftelse, Alfasigma, and Biocodex.

Physical exercise as an add-on treatment to cognitive behavioural therapy for anxiety: a systematic review.

BACKGROUND: Cognitive behavioural therapy (CBT) is currently the treatment of choice for most anxiety disorders. Yet, with recovery rates of approximately 50%, many patients fail to achieve complete remission. This has led to increased efforts to enhance treatment efficacy. Physical exercise (PE) has in recent years been advocated as means to augment the effects of CBT for anxiety disorders. PE appears to reduce anxiety through other mechanisms than CBT, some of which might also have the potential to augment the effects of psychological treatment. AIMS: The current review aimed to summarize and discuss the current research status on CBT augmented with PE for anxiety. METHOD: A systematic literature search was conducted in the databases PsychInfo, Medline and Web of Science to evaluate the potential augmentative effect of combining PE with CBT for anxiety disorders. These effects were intended to be evaluated in a meta-analysis, but findings from the few and diverse studies were better summarized in a systematic review. RESULTS: Eight articles were included in this review, of which two had no control group, while six had from two to four experimental arms. Six of the studies concluded in favour of benefits of add-on PE, while two studies found no added benefits of the combined interventions. CONCLUSIONS: The combination of PE and CBT appears feasible. Add-on PE seems to be more beneficial for clinical populations, when administered regularly several times per week, across several weeks. Future studies should investigate further how and for whom to best combine PE and CBT.

Subjects with familial hypercholesterolemia have lower aortic valve area and higher levels of inflammatory biomarkers.

BACKGROUND: Reduction of the aortic valve area (AVA) may lead to aortic valve stenosis with considerable impact on morbidity and mortality if not identified and treated. Lipoprotein (a) [Lp(a)] and also inflammatory biomarkers, including platelet derived biomarkers, have been considered risk factor for aortic stenosis; however, the association between Lp(a), inflammatory biomarkers and AVA among patients with familial hypercholesterolemia (FH) is not clear. OBJECTIVE: We aimed to investigate the relation between concentration of Lp(a), measurements of the aortic valve including velocities and valve area and circulating inflammatory biomarkers in adult FH subjects and controls. METHODS: In this cross-sectional study aortic valve measures were examined by cardiac ultrasound and inflammatory markers were analyzed in non-fasting blood samples. The study participants were 64 FH subjects with high (n = 29) or low (n = 35) Lp(a), and 14 healthy controls. RESULTS: Aortic valve peak velocity was higher (p = 0.02), and AVA was lower (p = 0.04) in the FH patients compared to controls; however, when performing multivariable linear regression, there were no significant differences. Furthermore, there were no significant differences between the high and low FH Lp(a) groups regarding the aortic valve. FH subjects had higher levels of platelet-derived markers CD40L, PF4, NAP2 and RANTES compared to controls (0.003 ≤ P ≤ 0.03). This result persisted after multiple linear regression. CONCLUSIONS: Middle-aged, intensively treated FH subjects have higher aortic valve velocity, lower AVA, and higher levels of the platelet-derived markers CD40L, PF4, NAP2 and RANTES compared to healthy control subjects. The aortic valve findings were not significant after multiple linear regression, whereas the higher levels of platelet-derived markers were maintained.

To make a run for IT - A feasibility study of ICBT combined with physical exercise for patients with panic disorder.

BACKGROUND: Guided Internet-based cognitive behavioural therapy (ICBT) is a recommended treatment for panic disorder promising to increase treatment availability, but there are some concerns regarding adherence, including adherence to the in vivo exposure given as home assignments. The aim of this study was to assess the feasibility of combining ICBT with physical exercise with the aim of improving adherence and treatment response to ICBT. METHOD: 12 participants were included via routine clinical practice to an open pre- post trial of feasibility using ICBT and an aerobe exercise protocol. We used a mixed model design investigating multiple areas of adherence, participants' experience and clinical outcome. RESULTS: 90.9% of the participants was considered completers in the ICBT program and the average adherence to the physical exercise was 93.1%. The experience of participating was summarized as "Hard work but worth it". Clinical outcomes effect sizes (d) ranged from 2.79 (panic severity) to .64 (Beck's anxiety index). CONCLUSION: The sum results on adherence, qualitative and quantitative data all suggest that augmenting ICBT with an aerobic exercise protocol is feasible. We conclude that further research is warranted.

Anti-inflammatory effects of non-statin low-density lipoprotein cholesterol-lowering drugs: an unused potential?

Objectives. Inflammatory responses are closely knit with low-density lipoprotein (LDL)-cholesterol in driving atherosclerosis. Even if LDL-cholesterol is causative to atherosclerotic diseases and LDL-cholesterol lowering reduces hard clinical endpoints, there is a residual risk for clinical events, possibly driven by inflammatory processes, in accordance with its role in autoimmune diseases. Design. As LDL-cholesterol treatment targets are reduced, the use of non-statin lipid-lowering drugs will probably increase. Atherosclerotic plaques evolve through lipid infiltration and modification in the intima, furthermore infiltration of cells including monocytes, macrophages, T-lymphocytes and neutrophils initiating inflammatory signaling. Here we briefly review inflammation in atherosclerosis and the effects of the non-statin lipid-lowering drugs on inflammation. The review is limited to the most common non-statin lipid lowering drugs, i.e. proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, bile acid sequestrants (BAS) and cholesterol absorption inhibitors. Results. PCSK9 inhibition is mostly studied together with statins and is associated with a reduction of pro-inflammatory cytokines. Furthermore, PCSK9 inhibitors seem to have an effect on monocyte migration trough CCR2. They also have an interaction with sirtuins, possibly offering a therapeutic target. BAS have several interesting effects on inflammation, including reduction of pro-inflammatory cytokines and a reduction of the number of infiltrating macrophages, however there are relatively few reports considering that these drugs have been on the market for decades. Ezetimibe also has effects on inflammation including reduction of pro-inflammatory cytokines and adhesion molecules, however these effects are usually accomplished in tandem with statins. Conclusion. This topic adds an interesting piece to the puzzle of atherosclerosis, indicating that PCSK9 inhibition, BAS and ezetimibe all affect thromboinflammation.