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Biomedical subjects

Erik Jørgensen

Publications and source records attributed to Erik Jørgensen.

At least 19 recordsLinked to original sources

[Therapy with stem cells for acute ischemic heart disease: myocardial regeneration?].

Treatment of ischemic heart disease with injections of bone-marrow-derived stem cells is a promising new modality. However, recent medium-sized placebo controlled trials in patients with acute myocardial infarction have not been conclusive regarding the treatment effect. This short review aims to elucidate some of the unresolved issues raised by the first clinical trials. These include long-term safety, tissue-distribution of infused cells, selecting the optimal cell type and number, timing of the treatment, and the mechanism of a potential treatment effect.

Clinical Trials as Topic↗

Circulating angiogenic cytokines and stem cells in patients with severe chronic ischemic heart disease--indicators of myocardial ischemic burden?

BACKGROUND: Angiogenic growth factors and stem cell therapies have demonstrated varying results in patients with chronic coronary artery disease. A reason could be that these mechanisms are already up-regulated due to reduced blood supply to the myocardium. The objective of this study was to examine if plasma concentrations of circulating stem cells and angiogenic cytokines in patients with severe stable chronic coronary artery disease were correlated to the clinical severity of the disease. METHODS: Fifty-four patients with severe coronary artery disease and reversible ischemia at stress myocardial perfusion scintigraphy were prospectively included. The severity of the disease was quantified by an exercise tolerance test, Canadian Cardiovascular Society angina classification, and Seattle Angina Pectoris Questionnaire. Fifteen persons without coronary artery disease served as control subjects. RESULTS: Plasma concentration of VEGF-A, FGF-2, SDF-1, and circulating CD34+ and CD34-/CD45- cells were similar in the two groups, but early stem cell markers (CD105, CD73, CD166) and endothelial markers (CD31, CD144, VEGFR2) were significantly different between patients and control subjects (p<0.005-0.001). Diabetic patients had higher concentration of SDF-1 (2528 vs. 2150 pg/ml, p=0.004). We found significant correlations between both VEGF-A, FGF-2, and CD34+ to disease severity, including degree of reversible ischemia, angina stability score, and exertional dyspnoea. CONCLUSIONS: Plasma concentrations of circulating stem cells and angiogenic cytokines have large inter-individual variations, which probably exclude them from being useful as indicators of myocardial ischemic burden.

Adult↗

Myocardial regeneration induced by granulocyte-colony-stimulating factor mobilization of stem cells in patients with acute or chronic ischaemic heart disease: a non-invasive alternative for clinical stem cell therapy?

Mobilization of stem cells into the peripheral circulation for myocardial regeneration using subcutaneous injections of granulocyte-colony-stimulating factor (G-CSF) has been tested in both patients with acute myocardial infarction (AMI) and patients with chronic myocardial ischaemia. G-CSF treatment seems to be safe and unblinded trials in patients with AMI were encouraging. However, larger double-blind placebo-controlled trials have not been able to demonstrate effect of G-CSF treatment. In patients with chronic myocardial ischaemia, small-unblinded G-CSF trials did not show effect on myocardial perfusion and function. In both patient populations, G-CSF did mobilize stem cells of known importance to myocardial regeneration, but there seemed to be a general lack of homing of the stem cells into the ischaemic myocardium. In AMI, factors of importance to homing of stem cells, stem cell derived factor-1, are maximally elevated in plasma 3 weeks after infarction, suggesting that this time point could be the optimal time for stem cell mobilization treatment. The known complex interaction of stem cells and cytokines for induction of vasculogenesis should be implemented in future clinical trials, to elucidate whether G-CSF mobilization of stem cells might be useful as a new regenerative treatment in patients with ischaemic heart disease.

Acute Disease↗

Intramyocardial injection of vascular endothelial growth factor-A165 plasmid followed by granulocyte-colony stimulating factor to induce angiogenesis in patients with severe chronic ischaemic heart disease.

AIMS: To assess the safety and effects of combined treatment with vascular endothelial growth factor-A(165) plasmid (VEGF-A(165)) and granulocyte- colony stimulating factor (G-CSF) mobilization of bone marrow stem cells in patients with severe chronic ischaemic heart disease (IHD). METHODS AND RESULTS: Sixteen patients with severe chronic IHD were treated with intramyocardial injections of VEGF-A(165) plasmid followed 1 week later by G-CSF (10 microg/kg/day for 6 days). Two control groups included (i) sixteen patients treated with intramyocardial injections of VEGF-A(165) plasmid and (ii) sixteen patients treated with intramyocardial injections of placebo. In the G-CSF group, circulating CD34+ stem cells increased almost 10-fold compared with the control groups (P<0.0001). After 3 months, there was no improvement in myocardial perfusion at single photon emission computerized tomography in the VEGF-A(165) and G-CSF treated group, and clinical symptoms were unchanged. There were no side effects to the gene and G-CSF therapy. CONCLUSION: Intramyocardial VEGF-A(165) gene transfer followed by bone marrow stem cell mobilization with G-CSF seemed safe. However, a significant increase in circulating stem cells did not lead to improved myocardial perfusion or clinical effects suggesting a neutral effect of the treatment. To improve homing of stem cells, higher doses of VEGF-A(165) and/or use of SDF-1 transfer might be considered.

Adolescent↗

[Telemedicine in the transmission of prehospitalisation ECGs of patients with suspected acute myocardial infarction].

INTRODUCTION: Time to reperfusion is critical to the outcome of patients with ST-elevation myocardial infarction (MI). Other studies have indicated that wireless transmission of prehospital ECGs can reduce the time to reperfusion. This study evaluated the effect on time to treatment using prehospitalisation ECG transmission to a cardiologist's handheld device in patients with acute chest pain, as well as the potential effect of direct transfer of patients to the closest appropriate cardiological facility. MATERIALS AND METHODS: During a one-year study period, prehospitalisation ECGs were transmitted for all patients with symptoms indicative of acute coronary syndrome. The ECGs were received on a handheld device by an attending cardiologist, and the patient was referred to PCI treatment if ST-elevation was found. RESULTS: 152 transmissions were registered; 27 of these patients underwent primary PCI treatment. 135 (89%) of the attempted transmissions were successful. Compared to historic controls, there was an increased on-scene time usage of 7 minutes, including transfer. The median time spent from arrival at the hospital to the start of invasive treatment was low, 22 minutes. Compared to historic controls, we found a total reduction in time spent of 72 minutes (p< 0.01). DISCUSSION: The results indicate that it is possible to minimize the time delay to primary PCI treatment by direct transfer through consultation and use of wireless transmission of prehospitalisation-acquired ECGs to a handheld device carried by an attending cardiologist.

Ambulances↗

Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: result of the double-blind, randomized, placebo-controlled stem cells in myocardial infarction (STEMMI) trial.

BACKGROUND: Phase 1 clinical trials of granulocyte-colony stimulating factor (G-CSF) treatment after myocardial infarction have indicated that G-CSF treatment is safe and may improve left ventricular function. This randomized, double-blind, placebo-controlled trial aimed to assess the efficacy of subcutaneous G-CSF injections on left ventricular function in patients with ST-elevation myocardial infarction. METHODS AND RESULTS: Seventy-eight patients (62 men; average age, 56 years) with ST-elevation myocardial infarction were included after successful primary percutaneous coronary stent intervention <12 hours after symptom onset. Patients were randomized to double-blind treatment with G-CSF (10 microg/kg of body weight) or placebo for 6 days. The primary end point was change in systolic wall thickening from baseline to 6 months determined by cardiac magnetic resonance imaging (MRI). An independent core laboratory analyzed all MRI examinations. Systolic wall thickening improved 17% in the infarct area in the G-CSF group and 17% in the placebo group (P=1.0). Comparable results were found in infarct border and noninfarcted myocardium. Left ventricular ejection fraction improved similarly in the 2 groups measured by both MRI (8.5 versus 8.0; P=0.9) and echocardiography (5.7 versus 3.7; P=0.7). The risk of severe clinical adverse events was not increased by G-CSF. In addition, in-stent late lumen loss and target vessel revascularization rate in the follow-up period were similar in the 2 groups. CONCLUSIONS: Bone marrow stem cell mobilization with subcutaneous G-CSF is safe but did not lead to further improvement in ventricular function after acute myocardial infarction compared with the recovery observed in the placebo group.

Adult↗

Sirolimus versus bare metal stent implantation in patients with total coronary occlusions: subgroup analysis of the Stenting Coronary Arteries in Non-Stress/Benestent Disease (SCANDSTENT) trial.

BACKGROUND: Coronary restenosis is more common in a total coronary occlusion (TCO) than other lesion types after implantation of bare metal stents (BMS). But whereas sirolimus-eluting stents (SES) have been shown to improve the outcomes in simple coronary artery lesions, data on their efficacy in complex coronary lesions are scarce. METHODS: We enrolled 127 patients with coronary artery disease and a TCO > or = 15 mm in length to have either SES or BMS implanted after successful recanalization. Outcome measures included the minimal lumen diameter, the late lumen loss, and angiographic restenosis (> 50% diameter stenosis) at 6 months follow-up and the occurrence of target vessel failure during a 7-month period. RESULTS: The patients were well matched in demographic and angiographic baseline characteristics, and 20% had diabetes. The reference vessel was 2.92 mm in mean, and the lesion length was 25.2 mm. At follow-up, patients who received SES had a minimal lumen diameter of 2.49 mm compared with 1.46 mm in those who received BMS (P = .015), 0% versus 38% developed restenosis (P < .001), lumen loss was -0.05 versus 0.99 mm (P < .001), and the target vessel failure rate 5% with SES versus 35% with BMS (P < .001). Stent thrombosis occurred in 1 patient in the BMS group. CONCLUSIONS: Implantation of SES is safe, and it markedly reduces angiographic restenosis and the occurrence of adverse events in patients with a TCO.

Aged↗

Comparison of sirolimus-eluting and bare metal stents in coronary bifurcation lesions: subgroup analysis of the Stenting Coronary Arteries in Non-Stress/Benestent Disease Trial (SCANDSTENT).

BACKGROUND: Sirolimus-eluting stent implantation improves the outcome in simple coronary artery lesions compared with bare metal stents, but there is limited evidence of their safety and efficacy when implanted in complex lesions like coronary bifurcations. METHODS: SCANDSTENT was a randomized controlled study comparing implantation of sirolimus-eluting stents with bare-metal stents in patients with complex coronary artery disease. This substudy evaluates the angiographic and clinical outcome of 126 patients with lesions located in a coronary bifurcation. RESULTS: The baseline characteristics of the patients were comparable: 15% had diabetes, and 1.7 stents were implanted per lesion. At follow-up, the minimum lumen diameter of the main branch was 2.35 mm in patients who received sirolimus-eluting stents compared with 1.68 mm in those who received bare-metal stents, and that of the side branch was 1.70 versus 1.19 mm (both P < .001). The late lumen loss in the main branch was 0.12 mm in the sirolimus-eluting stent group versus 0.99 mm in the bare-metal stent group and 0.03 versus 0.56 mm in the side branch (both P < .001). Thus, sirolimus-eluting stents reduced the restenosis rate from 28.3% to 4.9% in the main branch and from 43.4% to 14.8% in the side branches (both P < .001). Major adverse cardiac events occurred in 9% with sirolimus-eluting stents versus 28% with bare-metal stents (P = .01), and stent thrombosis was observed in 0% versus 9% (P = .02). CONCLUSION: Sirolimus-eluting stent implantation improves both the angiographic and clinical outcomes considerably compared with that of bare-metal stents in patients with stenoses located in coronary bifurcations.

Aged↗

The Stenting Coronary Arteries in Non-stress/benestent Disease (SCANDSTENT) trial.

OBJECTIVES: The purpose of the SCANDSTENT study was to evaluate the use of sirolimus-eluting stents (SES) in complex coronary lesions. BACKGROUND: The use of SES improves angiographic and clinical outcomes compared with bare-metal stents (BMS) in simple coronary artery lesions, but there is limited evidence of their safety and efficacy when implanted in complex lesions. METHODS: We randomly assigned 322 patients with symptomatic complex coronary artery disease to receive either SES or BMS. The lesions were occluded (36%), bifurcational (34%), ostial (22%), or angulated (8%) in morphology. The primary end point was the difference in minimal lumen diameter six months after stent implantation. RESULTS: The patients were well matched in terms of demographic and angiographic baseline characteristics; 18% had diabetes. The reference vessel diameter was 2.86 mm in mean, and the lesion length 18.0 mm. At follow-up, patients who received SES had a minimal lumen diameter of 2.48 mm compared with 1.65 mm in those who received BMS (p < 0.001), a diameter stenosis of 19.3% versus 43.8% (p < 0.001), and 2.0% versus 31.9% developed restenosis (p < 0.001). The rate of major adverse cardiac events was 4.3% with SES versus 29.3% with BMS (p < 0.001), and stent thrombosis was observed in 0.6% in the SES group versus 3.1% in the BMS group (p = 0.15). CONCLUSIONS: The use of SES markedly reduced restenosis and the occurrence of major adverse cardiac events in patients with complex coronary artery lesions without increasing the risk of stent thrombosis.

Aged↗

[Primary percutanous intervention in acute mycardial infarction. A comparison with the DANAMI-2 results].

INTRODUCTION: Several studies, including the DANAMI-2 trial, have shown that primary percutanous intervention (PCI) results in better survival, fewer reinfarctions and fewer cerebrovascular incidents than thrombolysis in the treatment of acute ST-elevation myocardial infarction (STEMI). The aim of this study was to follow the implementation of primary PCI as a routine treatment for patients with STEMI and to compare the results with those of DANAMI-2. MATERIALS AND METHODS: We performed a prospective analysis of 212 patients admitted to our department from 1 April 2002 to 31 December 2002 with STEMI. Acute coronary angiography and, if indicated, primary PCI were performed. RESULTS: At 30 days, the mortality rate was 6.6%, the reinfarction rate 1.4% and the rate of disabling stroke 1.4%. Combined endpoints were present in 8% of the patients. The results are in agreement with those from the DANAMI-2 trial. DISCUSSION: Primary PCI can be performed in daily clinical practice in accordance with the DANAMI-2 protocol. The results are in agreement with data from newly published meta-analyses.

Angioplasty, Balloon, Coronary↗

In-stent neo-intimal hyperplasia after stem cell mobilization by granulocyte-colony stimulating factor Preliminary intracoronary ultrasound results from a double-blind randomized placebo-controlled study of patients treated with percutaneous coronary intervention for ST-elevation myocardial infarction (STEMMI Trial).

OBJECTIVE: The influence of treatment with granulocyte-colony stimulating factor (G-CSF) on the development of in-stent intimal hyperplasia is not known. We aimed to study this phenomenon in patients who had stents implanted in the course of an acute ST-elevation infarction and successively were treated with G-CSF. METHOD: We performed angiography and intracoronary ultrasound follow-up after 5 months in 41 consecutive patients in the STEMMI trial, which is a randomized double-blind placebo-controlled study on the effect of G-CSF injections on the myocardial function following acute myocardial infarction in patients treated with primary percutaneous coronary stent implantation. The intracoronary ultrasound images were analyzed by a blinded and independent core laboratory. RESULTS: There were no differences in in-stent neo-intimal hyperplasia determined by intracoronary ultrasound between patients treated with G-CSF compared to patients treated with placebo. Neo-intimal hyperplasia per mm of stent was 1.87 (+/-1.41) and 1.89 (+/-1.39), respectively (p = 0.97). Angiographic in-segment restenosis (>50% diameter stenosis) was found in 28% of patients (24% in the G-CSF group and 33% in the placebo group; p = 0.55). CONCLUSION: G-CSF treatment following coronary stent implantation in primary PCI treated AMI patients does not increase in-stent restenosis excessively and it does not seem warranted to limit further study of effects of G-CSF for that reason.

Angioplasty, Balloon, Coronary↗

Effect of mobilization of bone marrow stem cells by granulocyte colony stimulating factor on clinical symptoms, left ventricular perfusion and function in patients with severe chronic ischemic heart disease.

OBJECTIVES: A phase I safety and efficacy study with granulocyte colony stimulating factor (G-CSF) mobilization of bone marrow stem cells to induce vasculogenesis in patients with severe ischemic heart disease (IHD) was conducted. DESIGN, PATIENTS AND RESULTS: 29 patients with IHD participated in the study. Thirteen patients were treated with G-CSF for 6 days and 16 patients served as controls. G-CSF treatment was without any serious adverse events. Four patients were "poor mobilizers" with a maximal increase in CD34+ cells to 5,000+/-700/mL blood (mean+/-S.D.) compared to 28,900+/-5,100/mL blood in "mobilizers". At the follow-up, G-CSF treated had improved in CCS classification, NTG consumption and angina attacks, but the controls only in CCS classification. No difference was seen between the two groups. The decline in NTG consumption tended to be significant in "mobilizers" compared to controls. Myocardial perfusion was unchanged at adenosine stress single photon emission computerized tomography (SPECT) or magnetic resonance images (MRI). Left ventricular ejection fraction decreased from 57% to 52% (p<0.01, MRI) and from 48% to 44% (p=0.07, SPECT) in G-CSF treated, but was unchanged measured with echocardiography. CONCLUSIONS: Treatment by G-CSF improved symptoms but not signs of myocardial ischemia in patients with severe IHD. The effects seemed related to mobilization of stem cells. An adverse effect on ejection fraction could not be excluded.

Aged↗

Direct intramyocardial plasmid vascular endothelial growth factor-A165 gene therapy in patients with stable severe angina pectoris A randomized double-blind placebo-controlled study: the Euroinject One trial.

OBJECTIVES: In the Euroinject One phase II randomized double-blind trial, therapeutic angiogenesis of percutaneous intramyocardial plasmid gene transfer of vascular endothelial growth factor (phVEGF-A(165)) on myocardial perfusion, left ventricular function, and clinical symptoms was assessed. BACKGROUND: Evidence for safety and treatment efficacy have been presented in phase I therapeutic angiogenesis trials. METHODS: Eighty "no-option" patients with severe stable ischemic heart disease, Canadian Cardiovascular Society functional class 3 to 4, were assigned randomly to receive, via the NOGA-MyoStar system (Cordis Corp., Miami Lakes, Florida), either 0.5 mg of phVEGF-A(165) (n = 40) or placebo plasmid (n = 40) in the myocardial region showing stress-induced myocardial perfusion defects on (99m)Tc sestamibi/tetrofosmin single-photon emission computed tomography. RESULTS: No differences among the groups were recorded at baseline with respect to clinical, perfusion, and wall motion characteristics. After three months, myocardial stress perfusion defects did not differ significantly between the VEGF gene transfer and placebo groups (38 +/- 3% and 44 +/- 2%, respectively). Similarly, semiquantitative analysis of the change in perfusion in the treated region of interest did not differ significantly between the two groups. Compared with placebo, VEGF gene transfer improved the local wall motion disturbances, assessed both by NOGA (p = 0.04) and contrast ventriculography (p = 0.03). Canadian Cardiovascular Society functional class classification of angina pectoris improved significantly in both groups but without difference between the groups. No phVEGF-A(165)-related adverse events were observed; however, NOGA procedure-related adverse events occurred in five patients. CONCLUSIONS: The VEGF gene transfer did not significantly improve stress-induced myocardial perfusion abnormalities compared with placebo; however, improved regional wall motion, as assessed both by NOGA and by ventriculography, may indicate a favorable anti-ischemic effect. This result should encourage more studies within the field. Transient VEGF overexpression seems to be safe.

Angina Pectoris↗

Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology.

In patients with stable CAD, PCI can be considered a valuable initial mode of revascularization in all patients with objective large ischaemia in the presence of almost every lesion subset, with only one exception: chronic total occlusions that cannot be crossed. In early studies, there was a small survival advantage with CABG surgery compared with PCI without stenting. The addition of stents and newer adjunctive medications improved the outcome for PCI. The decision to recommend PCI or CABG surgery will be guided by technical improvements in cardiology or surgery, local expertise, and patients' preference. However, until proved otherwise, PCI should be used only with reservation in diabetics with multi-vessel disease and in patients with unprotected left main stenosis. The use of drug-eluting stents might change this situation. Patients presenting with NSTE-ACS (UA or NSTEMI) have to be stratified first for their risk of acute thrombotic complications. A clear benefit from early angiography (<48 h) and, when needed, PCI or CABG surgery has been reported only in the high-risk groups. Deferral of intervention does not improve outcome. Routine stenting is recommended on the basis of the predictability of the result and its immediate safety. In patients with STEMI, primary PCI should be the treatment of choice in patients presenting in a hospital with PCI facility and an experienced team. Patients with contra-indications to thrombolysis should be immediately transferred for primary PCI, because this might be their only chance for quickly opening the coronary artery. In cardiogenic shock, emergency PCI for complete revascularization may be life-saving and should be considered at an early stage. Compared with thrombolysis, randomized trials that transferred the patients for primary PCI to a 'heart attack centre' observed a better clinical outcome, despite transport times leading to a significantly longer delay between randomization and start of the treatment. The superiority of primary PCI over thrombolysis seems to be especially clinically relevant for the time interval between 3 and 12 h after onset of chest pain or other symptoms on the basis of its superior preservation of myocardium. Furthermore, with increasing time to presentation, major-adverse-cardiac-event rates increase after thrombolysis, but appear to remain relatively stable after primary PCI. Within the first 3 h after onset of chest pain or other symptoms, both reperfusion strategies seem equally effective in reducing infarct size and mortality. Therefore, thrombolysis is still a viable alternative to primary PCI, if it can be delivered within 3 h after onset of chest pain or other symptoms. Primary PCI compared with thrombolysis significantly reduced stroke. Overall, we prefer primary PCI over thrombolysis in the first 3 h of chest pain to prevent stroke, and in patients presenting 3-12 h after the onset of chest pain, to salvage myocardium and also to prevent stroke. At the moment, there is no evidence to recommend facilitated PCI. Rescue PCI is recommended, if thrombolysis failed within 45-60 min after starting the administration. After successful thrombolysis, the use of routine coronary angiography within 24 h and PCI, if applicable, is recommended even in asymptomatic patients without demonstrable ischaemia to improve patients' outcome. If a PCI centre is not available within 24 h, patients who have received successful thrombolysis with evidence of spontaneous or inducible ischaemia before discharge should be referred to coronary angiography and revascularized accordingly--independent of 'maximal' medical therapy.

Angioplasty, Balloon, Coronary↗

Comparison of the left ventricular electromechanical map before percutaneous coronary stent revascularization and at one-month follow-up in patients with a recent ST elevation infarction.

The study aimed to evaluate the safety and potential of percutaneous transluminal electromechanical mapping (NOGA) in patients with regional myocardial wall dysfunction after a recent ST elevation myocardial infarction (STEMI). Regional myocardial wall dysfunction is a major cause of morbidity in survivors of ST elevation myocardial infarction. Fifteen males who recently had suffered a STEMI were studied prospectively with coronary angiography, ventriculography, and NOGA before and 1 month after percutaneous coronary intervention (PCI). The left ventricular angiographic ejection fraction increased from 50% +/- 11% before PCI to 56% +/- 10% at follow-up (P = 0.006). Qualitative analysis of the NOGA color map identified and outlined an area of regional wall dysfunction in all patients. Quantitative analysis of the NOGA maps showed improvements at follow-up after PCI in regional wall parameters of the infarct area (bipolar voltage: 1.7 +/- 1.4 mV before intervention, 2.2 +/- 1.6 mV at follow-up, P = 0.05; local shortening, a NOGA parameter on wall motion: 3.5% +/- 6.2% before, 7.4% +/- 5.8% at follow-up, P = 0.01), whereas there were no changes in the noninfarcted area (bipolar voltage: 2.7 +/- 2.5 mV before intervention, 2.8 +/- 2.6 mV at follow-up, P = 0.99; local shortening: 7.8% +/- 7.8% before, 8.2% +/- 7.8% at follow-up, P = 0.99). There were no complications to the NOGA procedures. In patients treated with PCI for a recent STEMI, NOGA might be considered used in the quantification of myocardial recovery and in the outlining of myocardial areas of incomplete or no recovery.

Adult↗

Diagnosing diagnostic tests: evaluating the assumptions underlying the estimation of sensitivity and specificity in the absence of a gold standard.

Latent class analysis to assess the sensitivity and specificity of a diagnostic test can be carried out under different assumptions. An often applied set of assumptions is known as the Hui-Walter paradigm, which essentially states that: (i) the population is divided into two or more populations in which two or more tests are evaluated under assumption that (ii) sensitivity and specificity of the tests are the same in all populations; and (iii) the tests are conditionally independent given the disease status. This study explores the implications of these assumptions. Through simulation studies, it is shown how the size of the difference between disease prevalences within the populations influences the precision of the estimates. It is also illustrated by a simulation study how a difference in a test sensitivity between populations may result in estimates that are biased towards the sensitivity of the test in the population with highest disease prevalence, since that population estimate is supported by most of the data. It is shown that the assumption of conditional independence between tests in general cannot be ignored in latent class models. Failure to impose conditional independence will result in a model that lacks identifiability in a way that cannot be handled by adding more tests or dividing the sample into more populations.

Animals↗