Introduction:The increasing financial burden associated with diabetes treatment presents a challenge to healthcare systems worldwide. Recently, clinical guidelines have focussed on patients with type 2 diabetes (T2D) and established cardiovascular disease (CVD) and recommend a sodium-glucose co-transporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist as second-line treatment after metformin or independently of baseline glycated haemogloblin A1c (HbA1c). In Danish clinical guidelines, empagliflozin and liraglutide are highlighted owing to their positive impact on mortality. Thus, this study aimed to assess the cost-effectiveness of empagliflozin plus standard of care (SoC) versus liraglutide plus SoC in Danish patients with T2D and established CVD using a lifetime and 5-year horizon. Methods: The IQVIA Core Diabetes Model (CDM) was calibrated to reproduce the clinical event rates observed in the cardiovascular outcome trial EMPA-REG OUTCOME. Network meta-analysis provided the relative risks for cardiovascular outcomes with empagliflozin versus liraglutide. Microvascular outcomes were predicted by standard CDM risk equations. The relative treatment effect was assumed for 9 years after which treatment was switched to basalbolus therapy. The CDM was populated with Danish costs of events and drug costs at pricelevel 2019. Discounting of 4% was applied. Results: Over a lifetime horizon, CDM projected 9.858 and 9.667 life years, 6.162 and 5.976 quality-adjusted life years (QALY) and DKK 478,026 (€64,079) and DKK 500,025 (€67,027) in total costs for empagliflozin plus SoC and liraglutide plus SoC, respectively. For a 5-year horizon, the results were 4.189 and 4.140 life years, 2.746 and 2.655 QALY, as well as DKK 123,413 (€16,543) and DKK 161,783 (€21,687), respectively. Empagliflozin was the

Aim: To evaluate the cost–effectiveness of oral semaglutide+metformin versus empagliflozin+metformin in people with Type 2 diabetes uncontrolled on msetformin alone. Materials and methods: The IQVIA Core Diabetes Model was populated with efficacy data from a head-to-head study between oral semaglutide+metformin and empagliflozin+metformin. Danish costs and quality-of-life data were sourced from literature. Price per day was Danish Krone (DKK) 25.53 for oral semaglutide and DKK11.40 for empagliflozin. Discounting was fixed at 4%. Scenario and sensitivity analyses were performed. Results: Over a lifetime, Core Diabetes Model projected 8.78 and 8.75 quality-adjusted life-years and a total cost of DKK 447,633 and DKK 387,786, thereby generating an incremental cost–effectiveness ratio of DKK 1,930,548 for oral semaglutide+metformin versus empagliflozin+metformin. Scenario and sensitivity analyses showed the robustness of the outcomes. Duration of treatment with oral semaglutide is the key driver of the analyses. Conclusion: Oral semaglutide+metformin seems not cost effective versus empagliflozin+metformin in patients uncontrolled on metformin in Denmark.

Pulmonary embolism (PE) is a common, ubiquitous, and potentially lethal disease. As symptoms and clinical findings are notoriously nonspecific, diagnostic imaging is essential to avoid undertreatment as well as overtreatment. Controversies remain regarding first-line imaging in suspected PE. The two main contemporary contenders are ventilation/perfusion scintigraphy with single-photon emission computed tomography (V/Q SPECT) with or without additional low-dose CT (SPECT/CT) and CT angiography (CTA). We present our results from a systematic review and meta-analysis of the diagnostic performances of these modalities: V/Q SPECT, V/Q SPECT/CT, and CTA are all viable options, but we consider V/Q SPECT/CT to be superior in most clinical settings with better overall diagnostic performance, that is, pooled sensitivities (97.6 vs. 82.0%), specificities (95.9 vs. 94.9%), positive predictive values (93.0 vs. 93.8%), negative predictive values (98.6 vs. 84.7%), and accuracies (96.5 vs. 88.6%). We further address some of the ongoing controversies regarding the various modalities, that is, radiation exposure, the issues of subsegmental PE, nondiagnostic studies, and various challenges in specific patient populations.

BackgroundOn April 1, 2015, Odense University Hospital (OUH) began a new diagnostic strategy, wherein all malignant melanoma (MM) patients in the Region of Southern Denmark with a positive sentinel lymph node biopsy (SLNB) underwent FDG-PET/CT preoperatively prior to lymph node dissection (LND). The purpose of this study is to determine FDG-PET/CT’s efficacy in finding distant metastasis in the first year after the implementation of this new strategy, and to what extent these findings influence subsequent diagnostic testing and treatment in this patient group. We conducted a retrospective multicenter cohort study which included all patients with MM from all hospitals in the Region of Southern Denmark from April 1, 2015 to April 1, 2016 found to be SLNB-positive who subsequently underwent FDG-PET/CT. Patient information was acquired from the Danish Melanoma Database and was cross-referenced with OUH’s patient records. The data was analyzed for a number of parameters including FDG-PET/CT findings and treatment strategy. Median follow-up time was 7 months.ResultsA total of 47 patients were eligible from the first year of this new diagnostic strategy. One patient was excluded due to undergoing LND prior to FDG-PET/CT. Thus, 46 patients were included in this study. Ultimately, preoperative FDG-PET/CT neither uncovered any distant metastases nor led to any alterations in treatment strategy in this patient group.ConclusionsSurprisingly, this new diagnostic strategy did not find any MM metastases or uncover anything else of relevance. FDG-PET/CT did, however, provide false positive findings in 13 % (6/46) of these patients. These scans triggered additional, predominantly invasive, procedures, which did not ultimately have an impact on the therapeutic strategy. Thus, these findings indicate a need for re-evaluation of this new diagnostic strategy as well as the necessity for further clinical trials evaluating FDG-PET/CT’s utility in this clinical setting.

Purpose: Venous thromboembolism (VTE) is common; deep venous thrombosis (DVT) and pulmonary embolism (PE) are the most common presentations. VTE may arise in the entire venous bed and the diagnosis may be difficult. VTE is a dynamic disease, inflammation is key, and FDG-PET/CT has been proposed, e.g. to detect thrombi in any anatomic location, to differentiate acute from chronic VTE, and to differentiate bland VTE from tumor thrombosis. The aim of this systematic review was to assess if the potential uses of 18 F-Fluorodeoxyglucose positron emission tomography/computer tomography (FDG-PET/CT) in VTE are described and documented in the literature. Methods: PubMed and Embase databases were searched. Duplicates and papers in other languages than English and Scandinavian were removed. Remaining papers were screened by title and abstract. Eligible papers were assessed in full-text. Results: The master search yielded 3,897 hits, 316 papers were eligible for full-text assessment. Ten papers were included; six on diagnostic performance of PET/CT in VTE, and four on the ability of PET/CT to differentiate bland VTE from tumor thrombosis. Three papers were prospective, seven were retrospective. Conclusion: If applied early, FDG-PET/CT may have a role in diagnosing DVT, but not PE, to discriminate acute from chronic VTE, and to demonstrate recurrent VTE. FDG-PET/CT is by some considered adept in differentiating bland VTE from tumor thrombosis, but we find this controversial due to FDG avidity in bland VTE. FDG-PET/CT may be feasible when screening for occult malignancy. However, in all mentioned areas, available literature is too sparse and too heterogeneous to allow firm conclusions.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases characterized by systemic inflammation in small- to medium-sized blood vessels. Although immunosuppressive therapy has greatly improved the prognosis for these patients, there are still significant comorbidities, such as cancer and infection, associated with AAV. These comorbidities are often indistinguishable from an underlying AAV disease relapse, and create a clinical conundrum, as these conditions are normally contraindications for immunosuppressive treatment. Thus, it is important to be able to rule out these comorbidities before initiation of immunosuppressive treatment. We examined 18F-fluoro-deoxy-glucose positron emission tomography combined with computed tomography (FDG-PET/CT)'s value in ruling out cancer or infection in patients with AAV.Data were obtained retrospectively for a clinically based cohort of AAV patients who underwent FDG-PET/CT during 2009 to 2014 owing to a suspicion of cancer, infection, or both cancer and infection indistinguishable from disease relapse. FDG-PET/CT conclusions were compared to the final diagnoses after follow-up analysis (mean 43 months).A total of 19 patients were included who underwent a total of 26 scans. The results of FDG-PET/CT outcome compared to final diagnosis were: 9 true positives, 3 false positives, 13 true negatives, and 1 false negative. The diagnostic probabilities for FDG-PET/CT with respect to overall comorbidity (i.e., cancer or infection) were: sensitivity 90% ( 95% confidence interval [CI] 60%–98%), specificity 81% ( 95% CI 57%–93%), positive predictive value 75% (95% CI 47%–91%), negative predictive value 93% (95% CI 68%–99%), and accuracy 84% (95% CI 66%–94%).FDG-PET/CT had a high negative predictive value and ruled out the comorbidities correctly in all but one case of urinary tract infection, a well-known limitation. Our study showed FGD-PET/CT's promise as an effective tool for ruling out cancer or infection in patients with AAV albeit in a limited population.

While the free vascularised double-barrel fibula flap has been traditionally used in the reconstruction of defects in the long bones of the lower extremities, the advantages of this type of graft can also be seen in the treatment of adjacent radial and ulnar non-unions of the forearm. The main advantage of the double-barrel fibula flap in treatment of antebrachial non-unions is that it allows for the simultaneous anatomical reconstruction of the radius and the ulna while maximising forearm functionality. In contrast to other procedures, this tailored graft also helps preserve pronation and supination of the forearm. In this article, we chronicle a case in which a microvascular osteomyocutaneous double-barrel fibula flap was used to concurrently reconstruct the radius and ulna of a patient with a severe antebrachial non-union.

Thank you for the opportunity to reply to the correspondence from Drs. Bajc and Grüning.1 We thank the authors for their interest in our recent article, 2 and as the title implies, controversies remain central in pulmonary embolism (PE) imaging and as such we acknowledge and welcome every opinion. Regardless of type, the literature selection in a review is always debatable. Our systematic review was based on rather strict inclusion and exclusion criteria, for example, all patients should be subjected to ventilation/perfusion (V/Q) scan, computed tomography angiography (CTA), and followup. Those studies mentioned by Bajc and Grüning 1 were not included in our analysis, 2 as they did not meet our criteria per se. In the study by Bajc et al, 3 the diagnosis was based on single-photon emission computed tomography (SPECT) and follow-up, but not CTA in the bulk of patients. However, we do acknowledge that a selected subset of 152 patients had both modalities performed and could have been included in our meta-analysis, 2 but the study was excluded in the initial screening as this subset was not explicit from the abstract. In the study by van Strijen et al, 4 only planar scintigraphy was employed; patients with a normal perfusion scintigraphy (47%) did not undergo further evaluation, and conventional pulmonary angiography was an integral part of the gold standard. In the study by Grüning et al, 5 most diagnosis was based on V/Q SPECT, as less than 10% of included patients underwent CTA. Nonetheless, although not included in our meta-analysis, we acknowledge the quality of these studies on their own accord and they present important results and relevant findings. We agree that the choice of interpretation criteria may impact the results, and we addressed this in our discussion 2 of differences in the two perfusion-only studies by Bajc et al 3 and Gutte et al, 6 respectively. Clearly, this may also be the case in combined V/Q scans, but nonetheless, the specificity and false-positive rate improved with the addition of lowdose CT, and as described by the authors, the reasons for false-positive findings on V/Q SPECT were interlobar fissures and parenchymal infiltrates, readily visible on V/Q SPECT/CT but not necessarily recognizable by different interpretation criteria. We agree that caution is advised whenever ionizing radiation is employed medically, a subject we also covered as one of the major concerns with the use of CTA. We should stress that the CT we advocate is not full-dose, contrastenhanced CTA in addition to V/Q SPECT but low-dose scans without contrast. Thus, in our opinion, the additional radiation dose of less than 1 mSv is more than justifiable,