•Fully automated detection of perivascular spaces on 7T MRI.•Good correlation with manual assessments of perivascular spaces.•Quantitative measurements of PVS characteristics: density, length, and ...tortuosity.
Perivascular spaces (PVS) are believed to be involved in brain waste disposal. PVS are associated with cerebral small vessel disease. At higher field strengths more PVS can be observed, challenging manual assessment. We developed a method to automatically detect and quantify PVS.
A machine learning approach identified PVS in an automatically positioned ROI in the centrum semiovale (CSO), based on -resolution T2-weighted TSE scans. Next, 3D PVS tracking was performed in 50 subjects (mean age 62.9 years (range 27–78), 19 male), and quantitative measures were extracted. Maps of PVS density, length, and tortuosity were created. Manual PVS annotations were available to train and validate the automatic method.
Good correlation was found between the automatic and manual PVS count: ICC (absolute/consistency) is 0.64/0.75, and Dice similarity coefficient (DSC) is 0.61. The automatic method counts fewer PVS than the manual count, because it ignores the smallest PVS (length <2 mm). For 20 subjects manual PVS annotations of a second observer were available. Compared with the correlation between the automatic and manual PVS, higher inter-observer ICC was observed (0.85/0.88), but DSC was lower (0.49 in 4 persons). Longer PVS are observed posterior in the CSO compared with anterior in the CSO. Higher PVS tortuosity are observed in the center of the CSO compared with the periphery of the CSO.
Our fully automatic method can detect PVS in a 2D slab in the CSO, and extract quantitative PVS parameters by performing 3D tracking. This method enables automated quantitative analysis of PVS.
This study aimed to determine the effects of estetrol (E4) on hemostasis, lipids, carbohydrate metabolism and bone turnover in postmenopausal women.
This study was a multicenter, randomized, ...double-blind placebo-controlled phase 2 trial. Participants (n = 180, age 43-64 years) received E4 2.5 mg, 5 mg, 10 mg and 15 mg or placebo once daily for 12 weeks. Changes from baseline at week 12 were evaluated versus placebo for hemostasis parameters, sex hormone binding globulin (SHBG), lipids, carbohydrate metabolism and bone markers.
Changes for hemostasis parameters were minimal with a small increase only in the normalized activated protein C sensitivity ratio in the E4 15 mg group versus placebo. SHBG increased in the E4 5 mg, 10 mg and 15 mg groups versus placebo. High-density lipoprotein cholesterol increased in all E4 groups; changes were not consistent for other lipids. Significant decreases versus placebo were seen for insulin resistance (E4 10 mg group), hemoglobin A1c (E4 15 mg group) and type 1 collagen C-terminal telopeptide (E4 10 mg and 15 mg groups). Small decreases in osteocalcin in the E4 5 mg, 10 mg and 15 mg groups were significant versus the increase observed in placebo.
E4 had limited impact on hemostasis and potentially beneficial effects on lipids, carbohydrate metabolism and bone turnover.
Purpose
Traditionally, total thyroidectomy has been advocated for patients with tumors larger than 1 cm. However, according to the ATA and NCCN guidelines (2015, USA), patients with tumors up to 4 cm ...are now eligible for lobectomy. A rationale for adhering to total thyroidectomy might be the presence of contralateral carcinomas. The purpose of this study was to describe the characteristics of contralateral carcinomas in patients with differentiated thyroid cancer (DTC) larger than 1 cm.
Methods
A retrospective study was performed including patients from 17 centers in 5 countries. Adults diagnosed with DTC stage T1b-T3 N0-1a M0 who all underwent a total thyroidectomy were included. The primary endpoint was the presence of a contralateral carcinoma.
Results
A total of 1313 patients were included, of whom 426 (32 %) had a contralateral carcinoma. The contralateral carcinomas consisted of 288 (67 %) papillary thyroid carcinomas (PTC), 124 (30 %) follicular variant of a papillary thyroid carcinoma (FvPTC), 5 (1 %) follicular thyroid carcinomas (FTC), and 3 (1 %) Hürthle cell carcinomas (HTC). Ipsilateral multifocality was strongly associated with the presence of contralateral carcinomas (OR 2.62). Of all contralateral carcinomas, 82 % were ≤10 mm and of those 99 % were PTC or FvPTC. Even if the primary tumor was a FTC or HTC, the contralateral carcinoma was (Fv)PTC in 92 % of cases.
Conclusions
This international multicenter study performed on patients with DTC larger than 1 cm shows that contralateral carcinomas occur in one third of patients and, independently of primary tumor subtype, predominantly consist of microPTC.
Wearing-off symptoms during natalizumab treatment in multiple sclerosis are characterized by an increase of MS-related symptoms prior to natalizumab administration. The influence of extended interval ...dosing (EID) on wearing-off symptoms are important to consider, as this might cause hesitancy in initiating or continuing EID.
Participants of the NEXT-MS trial, in which treatment intervals are adjusted based on drug concentrations, were divided into two groups: an extended group containing participants with at least one week of additional interval extension, and a group with a fixed interval during the trial (range 4–7 weeks). Changes in the occurrence, frequency, onset, and severity of wearing-off symptoms were evaluated.
255 participants were included (extended group n = 171, fixed group n = 84). The odds on occurrence of wearing-off symptoms in the extended group did not increase after extending the treatment interval. Additional analyses for frequency, onset, and severity of wearing-off symptoms showed no changes over time. Mean decrease in natalizumab drug concentration did not influence the frequency of wearing-off symptoms.
Wearing-off symptoms were not reinforced by further extending the natalizumab interval. Wearing-off symptoms might increase in a minority of patients after EID, although our data support the view that wearing-off symptoms appear to be unrelated to the decrease in natalizumab trough drug concentrations.
•Many natalizumab treated MS patients experience wearing-off symptoms.•Extension of natalizumab treatment intervals does not increase wearing-off symptoms.•Wearing-off symptoms are not related to natalizumab drug concentrations.
We aimed to systematically compare patients with major depressive disorder from three different treatment settings (a primary care outpatient, a secondary care outpatient and one inpatient sample), ...with regard to metabolic syndrome (MetSyn) prevalences, individual MetSyn components and related metabolic variables.
The outpatient samples were drawn from the ongoing Netherlands Study of Depression and Anxiety (302 primary care and 445 secondary care outpatients). The inpatient sample (n=80) was recruited from five Dutch mental health hospitals. The assessments of MetSyn and related variables waist circumference (WC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, glucose, systolic and diastolic blood pressure (SBP, DBP), body mass index (BMI), waist-hip ratio (WHR), LDL and total cholesterol (TC) were compared using analysis of (co)variance and regression analysis, whereas medication analyses examined the extent to which clinical differences (e.g., depression severity or medication use) mediated the observed metabolic differences across setting.
MetSyn prevalences (26% primary, 24% secondary care and 28% inpatients) did not significantly differ (P=.71). WC, BMI, LDL cholesterol, glucose and DBP were not significantly different across settings. However, WHR, TC and triglyceride levels were higher in inpatients than in both outpatients groups, while HDL cholesterol levels and SBP were lower. There was some mediating role for tricyclic and non-selective serotonin-reuptake inhibitor antidepressant use, but overall, the mediating role of clinical differences was limited.
Although overall MetSyn prevalences did not differ, patterns of individual MetSyn-related variables differed more markedly across depressed inpatients and outpatients. Inpatients showed more adverse WHR and serum lipid profiles, while SBP levels were lower.
The prevalence of severe refractory asthma Hekking, Pieter-Paul W., MD; Wener, Reinier R., MD; Amelink, Marijke, MD ...
Journal of allergy and clinical immunology,
04/2015, Letnik:
135, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Background Severe asthma is characterized by difficulty to achieve disease control despite high-intensity treatment. However, prevalence figures of severe asthma are lacking, whereas longstanding ...estimates vary between 5% and 10% of all asthmatic patients. Knowing the exact prevalence of severe refractory asthma as opposed to difficult-to-control asthma is important for clinical decision making, drug development, and reimbursement policies by health authorities. Objective We sought to estimate the prevalence of severe refractory asthma as defined by the Innovative Medicine Initiative consensus. Methods Adult patients with a prescription for high-intensity treatment (high-dose inhaled corticosteroids and long-acting β2 -agonists or medium- to high-dose inhaled corticosteroids combined with oral corticosteroids and long-acting β2 -agonists) were extracted from 65 Dutch pharmacy databases, representing 3% of the population (500,500 inhabitants). Questionnaires were sent to 5,002 patients, of which 2,312 were analyzed. The diagnosis of asthma and degree of asthma control were derived from questionnaires to identify patients with difficult-to-control asthma. Inhalation technique was assessed in a random sample of 60 adherent patients (prescription filling, ≥80%). Patients with difficult-to-control asthma, adherence to treatment, and a correct inhalation technique were qualified as having severe refractory asthma. Results were mirrored to the Dutch population. Results Of asthmatic adults, 3.6% (95% CI, 3.0% to 4.1%) qualified for a diagnosis of severe refractory asthma, representing 10.4 patients per 10,000 inhabitants. Conclusion The prevalence of severe refractory asthma might be lower than estimated by expert opinion. This implies that currently recognized severe asthma subphenotypes could meet the criteria of rare diseases.
To investigate the association between depression and anxiety symptoms and the metabolic syndrome (MetSyn), using a dimensional approach. The association between depression and anxiety, on the one ...hand, and the MetSyn as a cluster or its individual components, on the other hand, is equivocal. The categorical nature of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition might partly explain the inconsistent findings.
In 2,433 Netherlands Study of Depression and Anxiety participants (mean age, 42.3 years; 33.1% male), three symptoms dimensions-lack of positive affect (PA, depression specific); negative affect (NA, aspecific); and somatic arousal (SA, anxiety specific)-were assessed by a shortened adaptation of the Mood and Anxiety Symptom Questionnaire. The association between symptom dimensions and MetSyn components (waist circumference, triglycerides, high-density lipoprotein cholesterol, glucose, and mean blood pressure) was analyzed, using linear regression analysis.
The occurrence rate of the MetSyn was 20.1% (n = 490). SA, but not PA and NA, was strongly associated with four out of five MetSyn components, especially waist circumference, triglycerides, and blood pressure (β = 0.046, p = .01; β = 0.077, p < .001; and β = 0.069, p < .001, respectively), and with the total number of MetSyn components (β = 0.098, p < .001).
Our results demonstrate a strong association of most of the MetSyn components with the SA dimension, but not with the NA and PA scales.
CONTEXT Association between obesity and depression has repeatedly been established. For treatment and prevention purposes, it is important to acquire more insight into their longitudinal interaction. ...OBJECTIVE To conduct a systematic review and meta-analysis on the longitudinal relationship between depression, overweight, and obesity and to identify possible influencing factors. DATA SOURCES Studies were found using PubMed, PsycINFO, and EMBASE databases and selected on several criteria. STUDY SELECTION Studies examining the longitudinal bidirectional relation between depression and overweight (body mass index 25-29.99) or obesity (body mass index ≥30) were selected. DATA EXTRACTION Unadjusted and adjusted odds ratios (ORs) were extracted or provided by the authors. DATA SYNTHESIS Overall, unadjusted ORs were calculated and subgroup analyses were performed for the 15 included studies (N = 58 745) to estimate the effect of possible moderators (sex, age, depression severity). Obesity at baseline increased the risk of onset of depression at follow-up (unadjusted OR, 1.55; 95% confidence interval CI, 1.22-1.98; P < .001). This association was more pronounced among Americans than among Europeans (P = .05) and for depressive disorder than for depressive symptoms (P = .05). Overweight increased the risk of onset of depression at follow-up (unadjusted OR, 1.27; 95% CI, 1.07-1.51; P < .01). This association was statistically significant among adults (aged 20-59 years and ≥60 years) but not among younger persons (aged <20 years). Baseline depression (symptoms and disorder) was not predictive of overweight over time. However, depression increased the odds for developing obesity (OR, 1.58; 95% CI, 1.33-1.87; P < .001). Subgroup analyses did not reveal specific moderators of the association. CONCLUSIONS This meta-analysis confirms a reciprocal link between depression and obesity. Obesity was found to increase the risk of depression, most pronounced among Americans and for clinically diagnosed depression. In addition, depression was found to be predictive of developing obesity.Arch Gen Psychiatry. 2010;67(3):220-229-->
Context:
Stimulation of thermogenesis in brown adipose tissue (BAT) is a potential target to treat obesity. We earlier demonstrated that BAT activity is relatively low in obese subjects. It is ...unknown whether BAT can be recruited in adult humans.
Objective:
To study the dynamics of BAT, we observed BAT activity in morbidly obese subjects before and after weight loss induced by bariatric surgery.
Design:
This was an observational prospective cohort study.
Setting:
The study was conducted at a referral center.
Patients:
Ten morbidly obese subjects eligible for laparoscopic adjustable gastric banding surgery were studied before and 1 yr after bariatric surgery.
Main Outcome Measure:
The main outcome measure was BAT activity, as determined after acute cold stimulation using 18F-fluorodeoxyglucose positron emission tomography and computed tomography.
Results:
Before surgery, only two of 10 subjects showed active BAT. One year after surgery, the number of subjects with active BAT was increased to five. After weight loss, BAT-positive subjects had significantly higher nonshivering thermogenesis compared with BAT-negative subjects (P < 0.05).
Conclusions:
The results show that in humans BAT can be recruited in the regions in which it was also reported in lean subjects before. These results for the first time show recruitment of BAT in humans and may open the door for BAT-targeted treatments of obesity.
PDF
