How subjective CT image quality assessment becomes surprisingly reliable: pairwise comparisons instead of Likert scale.

OBJECTIVES: The aim of this study is to improve the reliability of subjective IQ assessment using a pairwise comparison (PC) method instead of a Likert scale method in abdominal CT scans. METHODS: Abdominal CT scans (single-center) were retrospectively selected between September 2019 and February 2020 in a prior study. Sample variance in IQ was obtained by adding artificial noise using dedicated reconstruction software, including reconstructions with filtered backprojection and varying iterative reconstruction strengths. Two datasets (each n = 50) were composed with either higher or lower IQ variation with the 25 original scans being part of both datasets. Using in-house developed software, six observers (five radiologists, one resident) rated both datasets via both the PC method (forcing observers to choose preferred scans out of pairs of scans resulting in a ranking) and a 5-point Likert scale. The PC method was optimized using a sorting algorithm to minimize necessary comparisons. The inter- and intraobserver agreements were assessed for both methods with the intraclass correlation coefficient (ICC). RESULTS: Twenty-five patients (mean age 61 years ± 15.5; 56% men) were evaluated. The ICC for interobserver agreement for the high-variation dataset increased from 0.665 (95%CI 0.396-0.814) to 0.785 (95%CI 0.676-0.867) when the PC method was used instead of a Likert scale. For the low-variation dataset, the ICC increased from 0.276 (95%CI 0.034-0.500) to 0.562 (95%CI 0.337-0.729). Intraobserver agreement increased for four out of six observers. CONCLUSION: The PC method is more reliable for subjective IQ assessment indicated by improved inter- and intraobserver agreement. CLINICAL RELEVANCE STATEMENT: This study shows that the pairwise comparison method is a more reliable method for subjective image quality assessment. Improved reliability is of key importance for optimization studies, validation of automatic image quality assessment algorithms, and training of AI algorithms. KEY POINTS: • Subjective assessment of diagnostic image quality via Likert scale has limited reliability. • A pairwise comparison method improves the inter- and intraobserver agreement. • The pairwise comparison method is more reliable for CT optimization studies.

Optical coherence tomography for diagnosing recurrent or residual basal cell carcinoma after topical treatment: A diagnostic cohort study.

BACKGROUND: Recurrent/residual basal cell carcinoma (BCC) after topical treatment may not be visible during clinical and dermatoscopic examination (CDE). Optical coherence tomography (OCT) may detect these subclinical recurrences or residues. OBJECTIVE: To compare the diagnostic accuracy of CDE with that of CDE combined with OCT (CDE-OCT) for detecting recurrent/residual BCC after topical treatment of superficial BCC. METHODS: In this diagnostic cohort study, the suspicion level for recurrence or residue was recorded on a 5-point confidence scale. All patients with high suspicion of recurrence or residue based on CDE and/or CDE-OCT were referred for punch biopsy. Patients with a low suspicion on CDE and CDE-OCT were asked to (voluntarily) undergo a control biopsy. Histopathologic results of the biopsy were used for verification of CDE and CDE-OCT diagnoses (gold standard). RESULTS: This study included 100 patients. A histopathologic recurrent/residual BCC was found in 20 patients. For recurrence or residue detection, sensitivity was 100% (20 of 20) for CDE-OCT and 60% (12 of 20) for CDE (P = .005) and specificity was 95% for CDE-OCT and 96.3% for CDE (P = .317). The area under the curve for CDE-OCT (0.98) was significantly higher than that for CDE (0.77) (P = .001). LIMITATIONS: Results are based on 2 OCT assessors. CONCLUSION: Compared with CDE alone, CDE-OCT results in a significantly higher ability to detect recurrent/residual BCCs after topical treatment.

Screening for platelet function disorders with Multiplate and platelet function analyzer.

Light transmission aggregation (LTA) is the gold standard for the diagnosis of platelet function disorders (PFDs), but it is time-consuming and limited to specialized laboratories. Whole-blood impedance aggregometry (Multiplate) and platelet function analyzer (PFA) may be used as rapid screening tools to exclude PFDs. The aim of this study is to assess the diagnostic performance of Multiplate and PFA for PFDs, as detected by LTA.Data from preoperative patients, patients referred to the hematologist for bleeding evaluation, and patients with a diagnosed bleeding disorder were used. PFDs were defined as ≥2 abnormal LTA curves. Diagnostic performance of Multiplate and PFA for detecting PFDs was expressed as sensitivity and specificity. The ability of Multiplate agonists and PFA kits to detect corresponding LTA curve abnormalities was expressed as area under the receiver operating characteristic curve. Prevalence of PFDs was 16/335 (4.8%) in preoperative patients, 10/54 (18.5%) in referred patients, and 3/25 (12%) in patients with a diagnosed bleeding disorder. In preoperative and referred patients, the sensitivity of Multiplate and PFA for detecting mild PFDs varied between 0% and 40% and AUCs for detecting corresponding LTA curve abnormalities were close to 0.50. In patients with a diagnosed bleeding disorder, both assays could detect Glanzmann thrombasthenia (GT) with sensitivity of 100% and AUCs of 0.70-1.00. Multiplate and PFA cannot discriminate between preoperative and referred patients with and without mild PFDs, meaning that they cannot be used as screening tests to rule out mild PFDs in these populations. Both Multiplate and PFA can detect GT in previously diagnosed patients.

The Effect of Stenting on Venous Hypertension: Results Using a Treadmill Stress Test with Invasive Pressure Measurements in Patients with Iliofemoral Venous Obstruction.

OBJECTIVES: The primary aim was to investigate whether stenting of post-thrombotic iliofemoral obstruction reduces venous hypertension. The secondary aim was to establish whether improvement in haemodynamic parameters impacts on quality of life. METHODS: In this prospective observational study, 12 participants with unilateral post-thrombotic obstruction of the iliac and/or common femoral veins (CFVs) underwent a treadmill stress test with invasive pressure measurements in the CFVs and dorsal foot veins of both affected and non-affected limbs. This was performed the day before and 3 months after stenting the obstructed tract. Paired sample t-tests were used to compare the treatment effect and univariable linear regression analysis to determine the association with improvement in quality of life. RESULTS: Before treatment, CFV pressure increased 34.8 ± 23.1 mmHg during walking in affected limbs compared with 3.9 ± 5.8 mmHg in non-affected limbs. This pressure rise decreased to 22.3 ± 24.8 mmHg after 3 months follow up compared with a 4.0 ± 6.0 mmHg increase in non-affected limbs (-26.2 mmHg difference; 95% CI -41.2 to -11.3). No such effect was found in the dorsal foot veins. The VEINES-QOL increased 25.3 ± 11.3 points after stenting and was significantly associated with a decrease in CFV pressure rise during walking (regression coefficient 0.4; 95% CI 0.1-0.6). CONCLUSION: Stenting of post-thrombotic iliofemoral obstruction significantly reduces venous hypertension in the common femoral vein and correlates with an improvement in the quality of life. Larger studies with a broader range of degree of obstruction need be performed to assess whether pre-stenting pressure measurements can predict post stenting clinical success.

The Diagnostic Value of MR Imaging in Determining the Lymph Node Status of Patients with Non-Small Cell Lung Cancer: A Meta-Analysis.

Purpose To summarize existing evidence of thoracic magnetic resonance (MR) imaging in determining the nodal status of non-small cell lung cancer (NSCLC) with the aim of elucidating its diagnostic value on a per-patient basis (eg, in treatment decision making) and a per-node basis (eg, in target volume delineation for radiation therapy), with results of cytologic and/or histologic examination as the reference standard. Materials and Methods A systematic literature search for original diagnostic studies was performed in PubMed, Web of Science, Embase, and MEDLINE. The methodologic quality of each study was evaluated by using the Quality Assessment of Diagnostic Accuracy Studies 2, or QUADAS-2, tool. Hierarchic summary receiver operating characteristic curves were generated to estimate the diagnostic performance of MR imaging. Subgroup analyses, expressed as relative diagnostic odds ratios (DORs) (rDORs), were performed to evaluate whether publication year, methodologic quality, and/or method of evaluation (qualitative [ie, lesion size and/or morphology] vs quantitative [eg, apparent diffusion coefficients in diffusion-weighted images]) affected diagnostic performance. Results Twelve of 2551 initially identified studies were included in this meta-analysis (1122 patients; 4302 lymph nodes). On a per-patient basis, the pooled estimates of MR imaging for sensitivity, specificity, and DOR were 0.87 (95% confidence interval [CI]: 0.78, 0.92), 0.88 (95% CI: 0.77, 0.94), and 48.1 (95% CI: 23.4, 98.9), respectively. On a per-node basis, the respective measures were 0.88 (95% CI: 0.78, 0.94), 0.95 (95% CI: 0.87, 0.98), and 129.5 (95% CI: 49.3, 340.0). Subgroup analyses suggested greater diagnostic performance of quantitative evaluation on both a per-patient and per-node basis (rDOR = 2.76 [95% CI: 0.83, 9.10], P = .09 and rDOR = 7.25 [95% CI: 1.75, 30.09], P = .01, respectively). Conclusion This meta-analysis demonstrated high diagnostic performance of MR imaging in staging hilar and mediastinal lymph nodes in NSCLC on both a per-patient and per-node basis. (©) RSNA, 2016 Online supplemental material is available for this article.

Endovascular treatment of complex aortic aneurysms: prevalence of acute kidney injury and effect on long-term renal function.

OBJECTIVES: To analyse predictors for short- and long-term renal function changes after fenestrated and branched endovascular aortic repair (EVAR). METHODS: A total of 157 patients underwent fenestrated and branched EVAR. Procedural intra-arterial iodinated contrast volume was documented. Serum creatinine and estimated glomerular filtration rate (eGFR) at baseline, during 48 h following EVAR, at discharge and latest moment of follow-up were recorded. Development of post-EVAR acute kidney injury (AKI; according to AKIN criteria), and potential risk factors for renal failure were recorded. Multivariate regression analyses were used to identify independent risk factors for AKI and eGFR decrease during follow-up. RESULTS: Forty-three patients (28 %) developed post-EVAR AKI. Long procedure time and occlusion of accessory renal arteries were independent risk factors for development of AKI. (odds ratio (OR) 1.005 per minute, 95 % CI 1.001-1.01; p = 0.025 and OR 3.02, 95 % CI 1.19-8.16; p = 0.029). Post-EVAR AKI was associated with a significantly increased risk for eGFR decrease at discharge and latest follow-up (hazard ratio (HR) 3.47, 95 % CI 1.63-7.36, p = 0.001 and HR 3.01, 95 % CI 1.56-5.80; p = 0.001). Iodinated contrast volume was not an independent risk factor for AKI or eGFR decrease during follow-up. CONCLUSION: Development of post-EVAR AKI is an independent risk factor for long-term renal function decrease. KEY POINTS: • Longer procedure time is associated with an increased risk for AKI. • Renal perfusion defects on angiography are associated with increased risk for AKI. • Post-EVAR AKI is associated with higher probability for long-term eGFR decrease. • Iodinated contrast volume is not an independent risk factor for AKI. • Iodinated contrast volume is not an independent risk factor for long-term eGFR decrease.

Diagnostic Performance of Dedicated Axillary T2- and Diffusion-weighted MR Imaging for Nodal Staging in Breast Cancer.

PURPOSE: To evaluate the diagnostic performance of unenhanced axillary T2-weighted and diffusion-weighted (DW) magnetic resonance (MR) imaging for axillary nodal staging in patients with newly diagnosed breast cancer, with node-by-node and patient-by-patient validation. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Fifty women (mean age, 60 years; range, 22-80 years) underwent high-spatial-resolution axillary 3.0-T T2-weighted imaging without fat suppression and DW imaging (b = 0, 500, and 800 sec/mm(2)), followed by either sentinel lymph node biopsy (SLNB) or axillary lymph node dissection. Two radiologists independently scored each lymph node on a confidence level scale from 0 (benign) to 4 (malignant), first on T2-weighted MR images, then on DW MR images. Two researchers independently measured the mean apparent diffusion coefficient (ADC) of each lymph node. Diagnostic performance parameters were calculated on the basis of node-by-node and patient-by-patient validation. RESULTS: With respective node-by-node and patient-by-patient validation, T2-weighted MR imaging had a specificity of 93%-97% and 87%-95%, sensitivity of 32%-55% and 50%-67%, negative predictive value (NPV) of 88%-91% and 86%-89%, positive predictive value (PPV) of 60%-70% and 62%-75%, and area under the receiver operating characteristic curve (AUC) of 0.78 and 0.80-0.88, with good interobserver agreement (κ = 0.70). The addition of DW MR imaging resulted in lower specificity (59%-88% and 50%-84%), higher sensitivity (45%-64% and 75%-83%), comparable NPV (89% and 90%-91%), lower PPV (23%-42% and 34%-60%), and lower AUC (0.68-0.73 and 0.70-0.86). ADC measurement resulted in a specificity of 63%-64% and 61%-63%, sensitivity of 41% and 67%, NPV of 85% and 85%-86%, PPV of 18% and 35%-36%, and AUC of 0.54-0.58 and 0.69-0.74, respectively, with excellent interobserver agreement (intraclass correlation coefficient, 0.83). CONCLUSION: Dedicated high-spatial-resolution axillary T2-weighted MR imaging showed good specificity on the basis of node-by-node and patient-by-patient validation, with good interobserver agreement. However, its NPV is still insufficient to substitute it for SLNB for exclusion of axillary lymph node metastasis. DW MR imaging and ADC measurement were of no added value.

Quantification of Respiratory Movement of the Aorta and Side Branches.

PURPOSE: To assess and quantify the magnitude and direction of respiratory movement of the aorta and origins of its side branches. METHODS: A quantitative 3-dimensional (3D) subtraction analysis of computed tomography (CT) scans during inspiration and expiration was performed to determine the respiratory geometric movements of the aorta and side branches in 60 patients. During breath-hold expiration and inspiration, 1-mm-thick CT slices of the aorta were acquired in unenhanced and contrast-enhanced scans. The datasets were compared using dedicated multiplanar reformation image subtraction software to determine the change in position of relevant anatomic sections, including the ascending thoracic aorta (AA), the origins of the brachiocephalic artery (BA) and left subclavian artery (LSA), the descending thoracic aorta (DTA) at the level of the tenth thoracic vertebra, as well as the origins of the celiac trunk, superior mesenteric artery, and the renal arteries. RESULTS: Complex movement was visible during inspiration; the regions of interest in the thoracic aorta and side branches moved in the anterior, medial, and caudal directions compared with the expiration state. Mean 3D movement vectors (± standard deviation) were 8.9±3.6 mm (AA), 12.0±4.1 mm (BA), 11.1±3.9 mm (LSA), and 4.9±2.5 mm (DTA). Abdominal side branches moved in the caudal direction 1.3±1.1 mm. There was significantly less movement in the DTA compared to AA (p<0.001). The correlation coefficient between the extent of LSA movement and thoracic excursion was 0.78. CONCLUSION: The aorta and side branches undergo considerable respiratory movement. The results from this study provide an important contribution to understanding aortic dynamics.

Diagnosing intracranial aneurysms with MR angiography: systematic review and meta-analysis.

BACKGROUND AND PURPOSE: The aim of this study was to evaluate the sensitivity and specificity of MR angiography (MRA) in the diagnosis of ruptured and unruptured intracranial aneurysms. METHODS: A systematic search was performed on 4 electronic databases on relevant articles that were published from January 1998 to October 2013. Inclusion criteria were met by 12 studies that compared MRA with digital subtraction angiography as reference standard. Two independent reviewers evaluated the methodological quality of the studies. Data from eligible studies were extracted and used to construct 2×2 contingency tables on a per-aneurysm level. Pooled estimates of sensitivity and specificity were calculated for all studies and subgroups of studies. Heterogeneity was tested, and risk for publication bias was assessed. RESULTS: Included studies were of high methodological quality. Studies with larger sample size tended to have higher diagnostic performance. Most studies used time-of-flight MRA technique. Among the 960 patients assessed, 772 aneurysms were present. Heterogeneity with reference to sensitivity and specificity was moderate to high. Pooled sensitivity of MRA was 95% (95% confidence interval, 89%-98%), and pooled specificity was 89% (95% confidence interval, 80%-95%). False-negative and false-positive aneurysms detected on MRA were mainly located at the skull base and middle cerebral artery. Freehand 3-dimensional reconstructions performed by the radiologist significantly increased diagnostic performance. Studies performed on 3 Tesla showed a trend toward higher performance (P=0.054). CONCLUSIONS: Studies on diagnostic performance of MRA show high sensitivity with large variation in specificity in the detection of intracranial aneurysms.

Contrast-enhanced mammography versus conventional imaging in women recalled from breast cancer screening (RACER trial): a multicentre, open-label, randomised controlled clinical trial.

Background: Women recalled from breast cancer screening receive post-screening work-up in the hospital with conventional breast imaging. The RACER trial aimed to study whether contrast-enhanced mammography (CEM) as primary imaging instead of conventional imaging resulted in more accurate and efficient diagnostic work-up in recalled women. Methods: In this randomised, controlled trial (registered under NL6413/NTR6589) participants were allocated using deterministic minimisation to CEM or conventional imaging as a primary work-up tool in two general and two academic hospitals. Predefined patients' factors were reason for recall, BI-RADS score, and study centre. Primary outcomes were sensitivity and specificity. Secondary outcomes were the proportion of women needing supplemental examinations, and number of days until diagnosis. Findings: Between April, 2018, and September, 2021, 529 patients recalled from the Dutch screening program were randomised, 265 to conventional imaging and 264 to CEM. Three patients in the control arm had to be excluded from analysis due to a protocol breach. After the entire work-up, sensitivity was 98.0% (95% CI; 92.2-99.7%) in the intervention arm and 97.7% (91.8-99.6%) in the control arm (p = 1.0), and specificity was 75.6% (72.5-76.6%) and 75.4% (72.5-76.4%, p = 1.0), respectively. Based on only primary full-field digital mammography/digital breast tomosynthesis or CEM, final diagnosis was reached in 27.7% (73/264) in the intervention arm and 1.1% (3/262) in the control arm. The frequency of supplemental imaging was significantly higher in the control arm (p < 0.0001). Median time needed to reach final diagnosis was comparable: 1 day (control arm: IQR 0-4; intervention arm: IQR 0-3). Thirteen malignant occult lesions were detected using CEM, versus three using conventional imaging. No serious adverse events occurred. Interpretation: Diagnostic accuracy of CEM in the work-up of recalled women is comparable with conventional imaging. However, work-up with CEM as primary imaging is a more efficient pathway. Funding: ZonMw (grant number 843001801) and GE Healthcare.

Incremental value of cardiovascular magnetic resonance over echocardiography in the detection of acute and chronic myocardial infarction.

BACKGROUND: Although echocardiography is used as a first line imaging modality, its accuracy to detect acute and chronic myocardial infarction (MI) in relation to infarct characteristics as assessed with late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) is not well described. METHODS: One-hundred-forty-one echocardiograms performed in 88 first acute ST-elevation MI (STEMI) patients, 2 (IQR1-4) days (n = 61) and 102 (IQR92-112) days post-MI (n = 80), were pooled with echocardiograms of 36 healthy controls. 61 acute and 80 chronic echocardiograms were available for analysis (53 patients had both acute and chronic echocardiograms). Two experienced echocardiographers, blinded to clinical and CMR data, randomly evaluated all 177 echocardiograms for segmental wall motion abnormalities (SWMA). This was compared with LGE-CMR determined infarct characteristics, performed 104 ± 11 days post-MI. Enhancement on LGE-CMR matched the infarct-related artery territory in all patients (LAD 31%, LCx 12% and RCA 57%). RESULTS: The sensitivity of echocardiography to detect acute MI was 78.7% and 61.3% for chronic MI; specificity was 80.6%. Undetected MI were smaller, less transmural, and less extensive (6% [IQR3-12] vs. 15% [IQR9-24], 50 ± 14% vs. 61 ± 15%, 7 ± 3 vs. 9 ± 3 segments, p < 0.001 for all) and associated with higher left ventricular ejection fraction (LVEF) and non-anterior location as compared to detected MI (58 ± 5% vs. 46 ± 7%, p < 0.001 and 82% vs. 63%, p = 0.03). After multivariate analysis, LVEF and infarct size were the strongest independent predictors of detecting chronic MI (OR 0.78 [95%CI 0.68-0.88], p < 0.001 and OR 1.22 [95%CI0.99-1.51], p = 0.06, respectively). Increasing infarct transmurality was associated with increasing SWMA (p < 0.001). CONCLUSIONS: In patients presenting with STEMI, and thus a high likelihood of SWMA, the sensitivity of echocardiography to detect SWMA was higher in the acute than the chronic phase. Undetected MI were smaller, less extensive and less transmural, and associated with non-anterior localization and higher LVEF. Further work is needed to assess the diagnostic accuracy in patients with non-STEMI.

The performance of contrast-enhanced mammography and breast MRI in local preoperative staging of invasive lobular breast cancer.

PURPOSE: Breast MRI is considered the best modality for preoperative staging of invasive lobular carcinoma (ILC). However, contrast-enhanced mammography (CEM) shows comparable diagnostic performance to MRI, but evidence of CEM's accuracy in women diagnosed with ILC is scant. We aimed to retrospectively evaluate CEM and MRI accuracy in preoperative staging of ILC. METHODS: ILC cases diagnosed between 2013 and 2021 were collected. For both modalities, tumour diameter was extracted from the reports. Bland-Altman plots were used to assess discrepancies between size measurements according to imaging and histopathological findings. CEM and MRI's ability to detect multifocal/contralateral cancer was expressed as sensitivity, specificity, and diagnostic odds ratios (DORs). Pairwise comparison of women undergoing both CEM and MRI was not performed. RESULTS: 305 ILC-cases fulfilled preset inclusion criteria. Mean age was 63.7 years. Preoperative staging was performed using MRI or CEM in 266 (87.2%) and 77 (25.2%) cases, respectively. MRI and CEM overestimated tumour size by 1.5 and 2.1 mm, respectively. Sensitivity to detect multifocal disease was higher for MRI than for CEM (86% versus 78%), but specificity was lower for MRI (79% versus 92%). For detection of contralateral breast cancer, sensitivity for MRI was 96% versus 88% for CEM, and specificity was 92% and 99%, respectively. For both indications, DOR was higher for CEM, but differences were non-significant (p = 0.56 and p = 0.78). CONCLUSION: CEM and MRI overestimate ILC size with comparable systematic and random errors. MRI's higher sensitivity for detection of multifocal/contralateral cancers is accompanied by lower specificity, but discriminative ability for both modalities was non-significant.

BMI is not independently associated with coronary artery calcification in a large single-center CT cohort.

Objective: Obesity is associated with cardiovascular disease (CVD) and CVD mortality. However, previous reports showed a paradoxical protective effect in patients with known CVD referred as "obesity paradox". Therefore, the aim of the present study was to investigate the association of body mass index (BMI) with coronary artery calcification (CAC) in a large outpatient cardiac CT cohort. Methods: 4.079 patients who underwent cardiac CT between December 2007-May 2014 were analyzed. BMI and clinical risk factors (current smoking, diabetes mellitus type 2, family history, systolic blood pressure, lipid spectrum) were assessed. Missing values were imputed using multiple imputation. CAC extent was categorized as absent (0), mild (>0-100), moderate (>100-400) and severe (>400). Results: Multivariable multinomial logistic regression analysis, including all risk factors as independent variables, showed no association between BMI and CAC. Using absence of calcification as reference category, the odds ratios per unit increase in BMI were 1.01 for mild; 1.02 for moderate; and 1.00 for severe CAC (p-values ≥0.103). Conclusions: No statistically significant association was observed between BMI and CAC after adjustment for other risk factors.

Treatment of Actinic Keratosis: Does Effectiveness Depend on the Location?

This is a comment on a network meta-analysis that evaluated the ranking of treatments for actinic keratosis outside the head and neck. The results of a limited number of heterogeneous studies contrast with the results of studies in the head and neck area. The extent to which these results can be generalized to larger treatment fields or areas with extensive field cancerization is uncertain.

The impact of differences in EQ-5D and SF-6D utility scores on the acceptability of cost-utility ratios: results across five trial-based cost-utility studies.

OBJECTIVE: This article investigates whether differences in utility scores based on the EQ-5D and the SF-6D have impact on the incremental cost-utility ratios in five distinct patient groups. METHODS: We used five empirical data sets of trial-based cost-utility studies that included patients with different disease conditions and severity (musculoskeletal disease, cardiovascular pulmonary disease, and psychological disorders) to calculate differences in quality-adjusted life-years (QALYs) based on EQ-5D and SF-6D utility scores. We compared incremental QALYs, incremental cost-utility ratios, and the probability that the incremental cost-utility ratio was acceptable within and across the data sets. RESULTS: We observed small differences in incremental QALYs, but large differences in the incremental cost-utility ratios and in the probability that these ratios were acceptable at a given threshold, in the majority of the presented cost-utility analyses. More specifically, in the patient groups with relatively mild health conditions the probability of acceptance of the incremental cost-utility ratio was considerably larger when using the EQ-5D to estimate utility. While in the patient groups with worse health conditions the probability of acceptance of the incremental cost-utility ratio was considerably larger when using the SF-6D to estimate utility. CONCLUSIONS: Much of the appeal in using QALYs as measure of effectiveness in economic evaluations is in the comparability across conditions and interventions. The incomparability of the results of cost-utility analyses using different instruments to estimate a single index value for health severely undermines this aspect and reduces the credibility of the use of incremental cost-utility ratios for decision-making.

Assessment and determinants of whole blood and plasma fibrinolysis in patients with mild bleeding symptoms.

Enhanced clot lysis is associated with bleeding, but assessment of lysis capacity remains difficult. The plasma turbidity lysis and whole blood tissue Plasminogen Activator-Rotational Thromboelastometry (tPA-ROTEM) assays estimate fibrinolysis under more physiological conditions than clinically used assays. We hypothesized that these assays could find signs of enhanced lysis capacity in patients who report bleeding symptoms, but are not diagnosed with bleeding disorders. We also aimed to gain insight in determinants of the results of these lysis assays. Data from 240 patients with and 95 patients without self-reported bleeding symptoms were obtained, who were included in a study that primarily aimed to assess prevalence of haemostatic abnormalities in preoperative patients. ROTEM and turbidity assays were performed with rtPA. Blood counts, fibrinolysis and coagulation factor activities were determined. Data were analysed using multivariable linear regression models. Remarkably, patients reporting bleeding symptoms showed signs of significantly impaired lysis capacity in the tPA-ROTEM, but not in the turbidity lysis assay. In these patients, the tPA-ROTEM results depended on FII, FXII, plasminogen, α2-antiplasmin, PAI-1 and TAFI levels. The turbidity lysis results were significantly influenced by fibrinogen, α2-antiplasmin, PAI-1 and TAFI. In conclusion, the tPA-ROTEM and the turbidity lysis assay could not detect enhanced fibrinolytic capacity in patients with bleeding symptoms. This suggests that these symptoms are not caused by enhanced fibrinolytic activity. As both assays were sensitive to important determinants of fibrinolysis they may be able to detect a fibrinolytic imbalance, but this needs to be validated in patients with known hypo- or hyperfibrinolytic disorders.

Dose timing and patient compliance with two antibiotic treatment regimens for lower respiratory tract infections in primary care.

The objective of this study was to assess compliance with a 10-day treatment of antibiotics or placebo once-daily (OD) and three-times-daily (TD) for lower respiratory tract infections (LRTIs) using electronic monitoring, and to evaluate whether compliance depends on time since the start of treatment and weekday. Taking compliance, timing compliance, correct dosing compliance and mean interdose intervals were assessed using data from 155 LRTI patients who received either a 10-day treatment of amoxicillin TD and placebo OD or roxithromycin OD and placebo TD using a double-dummy technique. Compliance was assessed by electronic monitoring. Taking compliance was 98.0% for the OD regimen and 91.0% for the TD regimen. Correct dosing was 98.1% for the OD regimen and 91.1% for the TD regimen and timing compliance was 48.2% and 10.9%, respectively. The mean interdose interval before the first daily dose for the TD group was particularly prolonged to >13h. Correct dosing over time showed fewer patients with correct dosing compliance, reaching a low of 79% for the TD group towards the end of the 10-day treatment. Compliance was not influenced by weekday. This study adds important information to the limited evidence on compliance with antibiotics for LRTI, one of the most common reasons for consultation in primary care. Taking compliance was high for both regimens, yet timing compliance was poor. The prolonged mean interdose intervals provide striking new insights into understanding non-compliance with more-than-once-daily regimens. These findings require consideration when exploring ways to improve future compliance in short-term antibiotic treatment for respiratory tract infections.