[Show abstract][Hide abstract] ABSTRACT: Study Design Diagnostic accuracy study using a cross sectional design. Objectives To determine the inter-examiner reliability and the diagnostic accuracy in primary care of 1 existing weight-bearing meniscal test, the Thessaly test, 1 new weight-bearing test, the Deep Squat test, and 1 non-weight-bearing test, the Joint Line Tenderness test. Background Meniscal tears are difficult to detect in primary care. Although valuable in secondary care, weight-bearing physical examination tests require validation in primary care on unselected patients. Methods Between October 2009 and December 2013, 121 patients seen in primary care who were between 18 and 65 years old and were suspected to have internal derangement of the knee, which had existed less than 6 months, were included in the study. Diagnostic accuracy of the 3 meniscal tests was determined based on assessment with magnetic resonance imaging (MRI). The meniscal tests were performed by 3 trained physical therapists (PT) who were not informed about the patient history and MRI results. Each test was performed independently by 2 of the 3 trained PTs in alternating pairs. Results The Thessaly and Deep Squat tests had moderate level of inter-examiner reliability with Kappas of 0.54 and 0.46, respectively. The Joint Line Tenderness test had poor inter-examiner reliability and was therefore not assessed for diagnostic accuracy. Results are reported separately for both examiners, with the Thessaly test having a sensitivity of 66.7% (95% CI 53.0-78.0) and 51.2% (95% CI 36.8-65.4), specificity of 37.9% (95% CI 27.2-50.0) and 43.5% (95% CI 30.2-57.8), a positive likelihood ratio (LR+) of 1.07 (95% CI 0.82-1.41) and 0.91 (95% CI 0.62-1.33), and a negative likelihood ratio (LR-) of 0.88 (95% CI 0.54-1.45) and 1.12 (95% CI 0.72-1.76). Similarly, the Deep Squat test had a sensitivity of 74.5% (95% CI 61.1-84.5) and 76.7% (95% CI 62.3-86.9), a specificity of 42.4% (95% CI 31.2-54.4) and 36.2% (95% CI 24.0-50.5), a LR+ of 1.29 (95% CI 0.97-1.68) and 1.20 (95% CI 0.92-1.58), and a LR- of 0.60 (95% CI 0.35-1.04) and 0.64 (95% CI 0.33-1.25). Conclusion Although the Thessaly and Deep Squat tests have a moderate level of reliability neither test is sufficiently accurate to help in the diagnostic of meniscal tears in primary care. Future research should focus on other relevant patient variables instead of physical examination tests in the detection of meniscal tears. Level of Evidence Diagnosis, level 3b. J Orthop Sports Phys Ther, Epub 10 Jul 2015. doi:10.2519/jospt.2015.5712.
[Show abstract][Hide abstract] ABSTRACT: Different in-plane resolutions have been used for carotid 3T MRI. We compared the reproducibility, as well as the within- and between reader variability of high and routinely used spatial resolution in scans of patients with atherosclerotic carotid artery disease. Since no consensus exists about the optimal segmentation method, we analysed all imaging data using two different segmentation methods.
In 31 patient with carotid atherosclerosis a high (0.25 × 0.25 mm2; HR) and routinely used (0.50 × 0.50 mm2; LR) spatial resolution carotid MRI scan were performed within one month. A fully blinded closed and a simultaneously open segmentation were used to quantify the lipid rich necrotic core (LRNC), calcified and loose matrix (LM) plaque area and the fibrous cap (FC) thickness.
No significant differences were observed between scan-rescan reproducibility for HR versus LR measurements, nor did we find any significant difference between the within-reader and between-reader reproducibility. The same applies for differences between the open and closed reads. All intraclass correlation coefficients between scans and rescans for the LRNC, calcified and LM plaque area, as well as the FC thickness measurements with the open segmentation method were excellent (all above 0.75).
Increasing the spatial resolution at the expense of the contrast-to-noise ratio does not improve carotid plaque component scan-rescan reproducibility in patients with atherosclerotic carotid disease, nor does using a different segmentation method.
PLoS ONE 07/2015; 10(7):e0130878. DOI:10.1371/journal.pone.0130878 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Community-acquired pneumonia (CAP) accounts for a major proportion of intensive care unit (ICU) admissions for respiratory failure and sepsis. Diagnostic uncertainty complicates case management, which may delay appropriate cause-specific treatment.
We aimed to characterize the blood genomic response in patients with suspected CAP and identify a candidate biomarker for the rapid diagnosis of CAP upon ICU admission.
The study comprised two cohorts of consecutively enrolled patients treated for suspected CAP upon ICU admission. Patients were designated CAP (cases) and no-CAP patients (controls) by post-hoc assessment. The first (discovery) cohort (101 CAP and 33 no-CAP patients) was enrolled between January, 2011 and July, 2012; the second (validation) cohort (70 CAP and 30 no-CAP patients) between July, 2012 and June, 2013. Blood was collected within 24 hours of ICU admission.
Blood microarray analysis of CAP and no-CAP patients revealed shared and distinct gene expression patterns. A 78 gene signature was defined for CAP, from which a FAIM3:PLAC8 gene expression ratio was derived with area-under-curve of 0.845 (95% confidence interval 0.764-0.917), positive and negative predictive values of 83% and 81%, respectively. Robustness of the FAIM3:PLAC8 ratio was ascertained by quantitative polymerase chain reaction in the validation cohort. The FAIM3:PLAC8 ratio outperformed plasma procalcitonin, interleukins 8 and 6 in discriminating between CAP and no-CAP patients.
CAP and no-CAP patients presented shared and distinct blood genomic responses. We propose the FAIM3:PLAC8 ratio as a candidate biomarker to assist in the rapid diagnosis of CAP on ICU admission.
American Journal of Respiratory and Critical Care Medicine 06/2015; DOI:10.1164/rccm.201502-0355OC · 11.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In preclinical work and retrospective population studies, the anti-diabetic drug metformin has been associated with antineoplastic activity and decreased burden of many cancers, including pancreatic cancer. There is therefore interest in the hypothesis that this drug might be repurposed for indications in oncology. We aimed to assess the efficacy of the addition of metformin to a standard systemic therapy in patients with advanced pancreatic cancer, and provide the first report of a clinical trial with a survival endpoint of metformin for an oncological indication.
The Lancet Oncology 06/2015; 16(7). DOI:10.1016/S1470-2045(15)00027-3 · 24.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction: Patients with Marfan syndrome - caused by FBN1 mutations
- have an increased risk of life-threatening aortic complications. It has been
shown that losartan reduces aortic dilation rate in these patients. The response
to losartan treatment, however, was highly variable between individuals.
Here we investigate whether there is a difference in Losartan effectiveness
in genetically classified subgroups.
Methods: In this predefined sub-study of the COMPARE trial, we classified
FBN1 mutations into: 1) Dominant negative mutations leading to a mutated
fibrillin-1 protein incorporated in the extracellular matrix, 2) Haploinsufficient
mutations leading to decreased amount of normal fibrillin-1 protein.
The response to losartan therapy based on aortic root dilatation rate was
compared between the two groups.
Results: Baseline characteristics between treatment groups were similar.
Overall, losartan significantly reduced aortic root dilatation rate. However,
losartan only reduced aortic root dilatation rate in haploinsufficient patients
and not in dominant negative patients.
Conclusion: Marfan patients with haploinsufficient FBN1 mutations are
more responsive to losartan therapy with respect to inhibition of aortic root
dilatation rate compared to dominant negative patients. In order to predict
response on losartan therapy, mutation classification should be performed
for all Marfan patients. More research for novel treatment strategies is needed
in Marfan patients with a dominant negative FBN1 mutation.
European Society for Human Genetics, Glasgow UK; 06/2015
[Show abstract][Hide abstract] ABSTRACT: Small-study effects and time trends have been identified in meta-analyses of randomized trials. We evaluated whether these effects are also present in meta-analyses of diagnostic test accuracy studies.
A systematic search identified test accuracy meta-analyses published between May and September 2012. In each meta-analysis, the strength of the associations between estimated accuracy of the test (diagnostic odds ratio (DOR), sensitivity, and specificity) and sample size and between accuracy estimates and time since first publication were evaluated using meta-regression models. The regression coefficients over all meta-analyses were summarized using random effects meta-analysis.
Forty-six meta-analyses and their corresponding primary studies (N = 859) were included. There was a non-significant relative change in the DOR of 1.01 per 100 additional participants (95% CI 1.00 to 1.03; P = 0.07). In the subgroup of imaging studies, there was a relative increase in sensitivity of 1.13 per 100 additional diseased subjects (95% CI 1.05 to 1.22; P = 0.002). The relative change in DOR with time since first publication was 0.94 per 5 years (95% CI 0.80 to 1.10; P = 0.42). Sensitivity was lower in studies published later (relative change 0.89, 95% CI 0.80 to 0.99; P = 0.04).
Small-study effects and time trends do not seem to be as pronounced in meta-analyses of test accuracy studies as they are in meta-analyses of randomized trials. Small-study effects seem to be reversed in imaging, where larger studies tend to report higher sensitivity.
[Show abstract][Hide abstract] ABSTRACT: Although the ubiquitous detection of polybrominated diphenyl ether (PBDE) and organophosphate flame retardants (PFRs) in indoor dust have raised health concerns, only very few epidemiological studies have assessed their impact on human health. Inhalation of dust is an important exposure route of FRs, especially in children and can be hazardous for the respiratory health. Moreover, PFRs are structurally similar to organophosphate pesticides, which have been associated with allergic asthma. Thus, we investigated whether the concentrations of PFR and PBDEs in indoor dust are associated with development of childhood asthma. We selected 110 children who developed asthma at 4 or at 8 years old and 110 matched controls from a large prospective birth cohort (BAMSE-Barn, Allergy, Milieu Stockholm Epidemiology). We analysed the concentration of 7 PFRs and 21 PBDEs in dust collected around two months after birth from the mother's mattress. The abundance rank in dust was as follows: TBOEP>TPHP>mmp-TMPP>EHDPHP~TDCIPP>TCEP~TCIPP~BDE-209>BDE-99>BDE-47>BDE-153>BDE-183>BDE-100. There was no positive association between FRs in mattress dust and the development of childhood asthma. In contrast, mother's mattress dust collected of children who would develop asthma contained significant lower levels of TPHP and mmp-TMPP. This study provides data on a wide range of PFRs and PBDEs in dust samples and development of asthma in children. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Indoor Air 05/2015; DOI:10.1111/ina.12221 · 4.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AIMS: The identification of sex differences in the prognosis of adults with a secundum atrial septal defect (ASD2) could help tailor their clinical management, as it has in other cardiovascular diseases. We investigated whether disparity between the sexes exists in long-term outcome of adult ASD2 patients.
METHODS AND RESULTS: Patients with ASD2 classified as the primary defect were selected from the Dutch national registry of adult congenital heart disease. Survival stratified by sex was compared with a sex-matched general population. In a total of 2207 adult patients (mean age at inclusion 44.8 years, 33.0% male), 102 deaths occurred during a cumulative follow-up of 13 584 patient-years. Median survival was 79.7 years for men and 85.6 years for women with ASD2. Compared with the age- and sex-matched general population, survival was lower for male, but equal for female patients (P = 0.015 and 0.766, respectively). Logistic regression analyses showed that men had a higher risk of conduction disturbances (OR = 1.63; 95% CI, 1.22-2.17) supraventricular dysrhythmias (OR = 1.41; 1.12-1.77), cerebrovascular thromboembolic events (OR = 1.53; 1.10-2.12), and heart failure (OR = 1.91; 1.06-3.43).
CONCLUSION: In contrast to women, adult men with an ASD2 have worse survival than a sex-matched general population. Male patients also have a greater risk of morbidity during adult life. Sex disparity in survival and morbidity suggests the need for a sex-specific clinical approach towards these patients.
European Heart Journal 04/2015; DOI:10.1093/eurheartj/ehv097 · 14.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: seCundum atrial septal defeCt is assoCiated with reduCed survival in adult men Moderated Poster Contributions Congenital Heart Disease Moderated Poster Theater, Poster Hall B1 Saturday, March 14, 2015, 11:45 a.m.-11:55 a.m. Session Title: Congenital Heart Disease: Quality & Outcomes Abstract Category: 10. Congenital Heart Disease: Adult Background: We investigated whether gender disparity exists in long-term outcome of adult ASD2 patients, as this might call for a gender-specific approach toward these patients.
[Show abstract][Hide abstract] ABSTRACT: -It has been shown that losartan reduces aortic dilatation in patients with Marfan syndrome. However, treatment response is highly variable. This study investigates losartan effectiveness in genetically classified subgroups.
-In this predefined sub-study of COMPARE, Marfan patients were randomized to daily receive losartan 100mg or no losartan. Aortic root dimensions were measured by magnetic resonance imaging at baseline and after 3 years. FBN1 mutations were classified based on fibrillin-1 protein effect into 1) 'Haploinsufficiency', decreased amount of normal fibrillin-1, 2) 'Dominant negative', normal fibrillin-1 abundance with mutant fibrillin-1 incorporated in the matrix. A pathogenic FBN1 mutation was found in 117 patients, of whom 79 patients were positive for a dominant negative mutation (67.5%) and 38 for a mutation causing haploinsufficiency (32.5%). Baseline characteristics between treatment groups were similar. Overall, losartan significantly reduced aortic root dilatation rate (no losartan: 1.3±1.5mm/3years, n=59, versus losartan: 0.8±1.4mm/3years, n=58, p=0.009). However, losartan only reduced aortic root dilatation rate in haploinsufficient patients (no losartan: 1.8±1.5mm/3years, n=21, versus losartan 0.5±0.8mm/3years, n=17, p=0.001) and not in dominant negative patients (no losartan: 1.2±1.7mm/3years, n=38, versus losartan 0.8±1.3mm/3years, n=41, p=0.197).
-Marfan patients with haploinsufficient FBN1 mutations appear to be more responsive to losartan therapy for inhibition of aortic root dilatation rate compared to dominant negative patients. Additional treatment strategies are needed in Marfan patients with dominant negative FBN1 mutations.
-http://www.trialregister.nl/trialreg/index.asp; Unique Identifier: NTR1423.