Gabriel Granåsen

High dose and long-term statin therapy accelerate coronary artery calcification

BACKGROUND In randomized clinical trials statins and placebo treated patients showed the same degree of coronary artery calcium (CAC) progression. We reanalyzed data from two clinical trials to further investigate the time and dose dependent effects of statins on CAC. Additionally, we investigated whether CAC progression was associated with incident cardiovascular events. METHODS AND RESULTS Data were pooled from two clinical trials: St. Francis Heart Study (SFHS) (419 and 432 patients treated with placebo and 20 mg atorvastatin daily, respectively) and EBEAT Study (164 and 179 patients respectively treated with 10 mg and 80 mg atorvastatin daily). CAC scores were assessed at baseline, 2 years and 4-6 years in SFHS; in EBEAT they were measured at baseline and 12 months. After a short-term follow-up (12 to 24 months) placebo and low dose atorvastatin showed a similar CAC increase, although 80 mg/daily atorvastatin increased CAC an additional 12-14% over placebo (p<0.001). In the long-term, atorvastatin caused a greater progression of CAC compared to placebo (additional 1.1%, p=0.04). In SFHS 42 cardiovascular events occurred after the second CT scan. The baseline and progression of CAC were greater in patients with events. However, only baseline CAC and family history of premature cardiovascular disease but not CAC progression were independent predictors of events. CONCLUSIONS Despite a greater CAC increase with high dose and long-term statin therapy, events did not occur more frequently in statin treated patients. This suggests that CAC growth under treatment with statins represents plaque repair rather than continuing plaque expansion.

Parastomal hernia after ileal conduit with a prophylactic mesh: a 10 year consecutive case series

Abstract Objective. There are no data on the frequency of parastomal hernia (PSH) after ileal conduit with a prophylactic mesh. The primary objective of this study was to determine the prevalence of PSH. Secondary objectives were to elaborate whether age, gender, body mass index (BMI), previous laparotomy or diabetes influenced the outcome; and to find any mesh-related complications. Materials and methods. In a single centre during 2003-2012, a large-pore, lightweight mesh was placed in a sublay position in 114 consecutive patients with ileal conduits. Preoperative and postoperative patient data were retrospectively collected and cross-sectional follow-up was conducted. During the predefined clinical examination a PSH was defined as any protrusion in the vicinity of the ostomy with the patient straining in both an erect and a supine position. Results.Fifty-eight patients (24 women and 34 men, mean age 69 years) had follow-up examinations after a mean of 35 months (median 32 months). Bladder cancer was the most common cause for surgery. Eight patients (14%) had a PSH. Age, gender, BMI, previous laparotomy and diabetes did not affect the outcome. No mesh-related complications occurred among the 114 patients with a prophylactic mesh. Conclusions. The prevalence of PSH after ileal conduit with a prophylactic mesh corresponded to that of colostomies with a prophylactic mesh. A prophylactic mesh did not seem to be associated with complications. The degree to which a prophylactic mesh may reduce the rate of PSH after an ileal conduit should be established in randomized trials.

Pennation angle dependency in skeletal muscle tissue doppler strain in dynamic contractions.

Tissue velocity imaging (TVI) is a Doppler based ultrasound technique that can be used to study regional deformation in skeletal muscle tissue. The aim of this study was to develop a biomechanical model to describe the TVI strains dependency on the pennation angle. We demonstrate its impact as the subsequent strain measurement error using dynamic elbow contractions from the medial and the lateral part of biceps brachii at two different loadings; 5% and 25% of maximum voluntary contraction (MVC). The estimated pennation angles were on average about 4° in extended position and increased to a maximal of 13° in flexed elbow position. The corresponding relative angular error spread from around 7% up to around 40%. To accurately apply TVI on skeletal muscles, the error due to angle changes should be compensated for. As a suggestion, this could be done according to the presented model.

The natural history of coronary calcification : a meta-analysis from St Francis and EBEAT trials

BACKGROUND AND AIM Coronary artery calcium score (CACs) is an established quantitative tool for assessing subclinical atherosclerosis. The aim of this study was to assess in a meta-analysis model the natural history and reproducibility of CACs measurements obtained from St Francis and EBEAT trials. METHODS We analysed data from 649 individuals: 443 on placebo with 2 year follow-up from St Francis trial (Study A) and 209 on 10 mg atorvastatin with 1 year follow-up of EBEAT trial (Study B). Total CACs and that in the left coronary artery (LCA) branches, left main stem (LMS), left anterior descending (LAD), left circumflex (Cx) and right coronary artery (RCA) were analysed. In view of the wide CACs spectrum, data were logarithmically transformed before the analyses and mixed model analysis was used to evaluate the change of CACs over time. RESULTS The overall agreement between the two measurements was fairly good, showing a small but significant increase in CAC: 68% of the group as a whole presented an increase in CACs, 23% of the cohort had negligible change in CACs of <10% irrespective of the baseline CACs; and the remaining 10% showed a fall in CACs. Both studies showed similar patterns. The analysis of individual coronary arteries showed significantly higher variability of measurements in the RCA than in the LCA. Males had higher baseline CACs than females, but the rate of progression was not different between genders, irrespectively of age and baseline score. CONCLUSION The natural history of CACs was overtime progression in the majority of subjects, irrespective of gender. The higher variability in RCA measurements could be related to the low baseline CACs or exaggerated movement of the right side atrioventricular ring, whereas those for LCA branches are influenced by the branch allocation of the CACs. Large changes to and from zero, might be related to technical limitations.

Brain parenchymal fraction in healthy adults : a systematic review of the literature

Brain atrophy is an important feature of many neurodegenerative disorders. It can be described in terms of change in the brain parenchymal fraction (BPF). In order to interpret the BPF in disease, knowledge on the BPF in healthy individuals is required. The aim of this study was to establish a normal range of values for the BPF of healthy individuals via a systematic review of the literature. The databases PubMed and Scopus were searched and 95 articles, including a total of 9269 individuals, were identified including the required data. We present values of BPF from healthy individuals stratified by age and post-processing method. The mean BPF correlated with mean age and there were significant differences in age-adjusted mean BPF between methods. This study contributes to increased knowledge about BPF in healthy individuals, which may assist in the interpretation of BPF in the setting of disease. We highlight the differences between post-processing methods and the need for a consensus gold standard.

Can echocardiography and ECG discriminate hereditary transthyretin V30M amyloidosis from hypertrophic cardiomyopathy

Abstract Objective: Hereditary transthyretin (ATTR) amyloidosis with increased left ventricular wall thickness could easily be misdiagnosed by echocardiography as hypertrophic cardiomyopathy (HCM). Our aim was to create a diagnostic tool based on echocardiography and ECG that could optimise identification of ATTR amyloidosis. Methods: Data were analysed from 33 patients with biopsy proven ATTR amyloidosis and 30 patients with diagnosed HCM. Conventional features from ECG were acquired as well as two dimensional and Doppler echocardiography, speckle tracking derived strain and tissue characterisation analysis. Classification trees were used to select the most important variables for differentiation between ATTR amyloidosis and HCM. Results: The best classification was obtained using both ECG and echocardiographic features, where a QRS voltage >30 mm was diagnostic for HCM, whereas in patients with QRS voltage <30 mm, an interventricular septal/posterior wall thickness ratio (IVSt/PWt) >1.6 was consistent with HCM and a ratio <1.6 supported the diagnosis of ATTR amyloidosis. This classification presented both high sensitivity (0.939) and specificity (0.833). Conclusion: Our study proposes an easily interpretable classification method for the differentiation between HCM and increased left ventricular myocardial thickness due to ATTR amyloidosis. Our combined echocardiographic and ECG model could increase the ability to identify ATTR cardiac amyloidosis in clinical practice.

Coherent Derivation of Equations for Differential Spectroscopy and Spatially Resolved Spectroscopy: An Undergraduate Tutorial

ABSTRACT Near-infrared spectroscopy (NIRS) is a spectroscopic method that is frequently used in health care and sports medicine to monitor oxygenation parameters in biological tissue. This tutorial provides a coherent derivation of equations for differential spectroscopy and spatially resolved spectroscopy, from basic theories to implementable equations. The basic theories are applicable to any kind of tissue oximeter but mainly focus on continuous-wave instruments.

Polymorphisms in dopamine-associated genes and cognitive decline in Parkinson's disease

Cognitive decline is common in Parkinsons disease (PD), but the underlying mechanisms for this complication are incompletely understood. Genotypes affecting dopamine transmission may be of importance. This study investigates whether genotypes associated with reduced prefrontal dopaminergic tone and/or reduced dopamine D2‐receptor availability (Catechol‐O‐methyltransferase [COMT] Val158Met genotype and DRD2 C957T genotype) affect the development of cognitive deficits in PD.

The impact of adjusted work conditions and disease-modifying drugs on work ability in multiple sclerosis

Background: Multiple sclerosis (MS) is a neurological disorder that causes significantly reduced ability to work, and the Expanded Disability Status Scale (EDSS) is one of the main predictors for reduced work ability. Objectives: To investigate how work requirements, flexible work conditions and disease-modifying drugs (DMDs) influence the work ability in relation to different EDSS grades in two MS populations. Methods: Work ability was studied in two MS populations: one in the southern and one in the northern part of Sweden, both demographically similar. In the latter population, more active work-promoting interventions have been practised and second-generation DMDs have been widely used from the onset of disease for several years. Results: The proportion of MS patients who participated in the workforce or studied was significantly higher in the northern compared with the southern population (p < 0.001). The employees in the northern population had significantly lower requirements, greater adapted work conditions and were able to work more hours per week. Higher EDSS was associated with lower reduction in number of worked hours per week in the northern population (p = 0.042). Conclusion: Our data indicated that treatment strategy and adjusted work conditions have impact on work ability in MS.

PITX3 genotype and risk of dementia in Parkinson's disease : A population-based study

Dementia is a devastating manifestation of Parkinsons disease (PD). This study investigates whether a common polymorphism in the PITX3 gene (rs2281983), which is of importance for the function of dopaminergic neurons, affects the risk of developing dementia in PD and whether it affects dopamine transporter (DAT) uptake. We PITX3 genotyped 133 patients with new-onset, idiopathic PD, participating in a population-based study in Sweden. Patients were followed prospectively during 6-11years with extensive investigations, including neuropsychology and DAT-imaging with 123I FP-CIT. The primary outcome was the incidence of PD dementia (PDD), diagnosed according to published criteria, studied by the Kaplan-Meier method and Cox proportional hazards. Performance in individual cognitive domains, the incidence of visual hallucinations, disease progression and striatal DAT uptake on imaging was also investigated. PD patients carrying the PITX3 C allele had an increased risk of developing PDD (hazard ratio: 2.87, 95% CI: 1.42-5.81, p=0.003), compared to the PD patients homozygous for the T-allele. Furthermore, the PITX3 C allele carriers with PD had a poorer cognitive performance in the visuospatial domain (p<0.001) and a higher incidence of visual hallucinations. A trend towards a lower striatal DAT uptake in the PITX3 C allele carriers was suggested, but could not be confirmed. Our results show that a common polymorphism in the PITX3 gene affects the risk of developing PDD and visuospatial dysfunction in idiopathic PD. If validated, these findings can provide new insights into the neurobiology and genetics of non-motor symptoms in PD.