Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data

OBJECTIVE: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. DESIGN: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. DATA SOURCES: Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. RESULTS: Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). CONCLUSIONS: In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002780

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: Meta-analysis of individual patient data

Objective To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. Design Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. Data sources Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. Eligibility criteria for selecting studies Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. Results Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). Conclusions In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. Systematic review registration PROSPERO CRD42012002780

Psychosocial functioning as a mediator between childhood trauma and symptom severity in patients with schizophrenia

Neumann E, Rixe J, Driessen M, Juckel G. Psychosocial functioning as a mediator between childhood trauma and symptom severity in patients with schizophrenia. Child Abuse &amp; Neglect. 2023;144: 106372.Background There is empirical evidence that childhood trauma is associated with symptom severity and psychosocial functioning in schizophrenia. Objective The present study aimed to further elucidate these associations by examining which subdomains of schizophrenic symptoms and psychosocial functioning are associated with childhood trauma. In addition, it should be tested whether the association between childhood trauma and schizophrenic symptoms is mediated by psychosocial functioning. Participants and Setting. Participants of this study were 253 inpatients of five psychiatric hospitals diagnosed with schizophrenia. Clinical interviews were conducted with these patients towards the end of therapy. Methods Childhood trauma was assessed with the Childhood Trauma Questionnaire (CTQ), a retrospective self-report scale. Schizophrenic symptoms were measured with the Positive and Negative Syndrome Scale (PANSS) and psychosocial functioning with the Personal and Social Performance Scale (PSP), two measures for ratings by experts. Results Most participants were affected by childhood trauma, with 91.7 % reporting at least one trauma. Childhood trauma showed small but significant correlations with positive symptoms and general psychopathology, and also with psychosocial functioning in the occupational and social area and in control over aggressive behavior. Psychosocial functioning was shown to mediate the association between childhood trauma and symptom severity, whereby full mediation was found with regard to positive symptoms and partial mediation with regard to general psychopathology. Conclusions The findings suggest that good psychosocial functioning mitigates the negative impact of childhood trauma on illness severity in schizophrenic patients. Therapeutic interventions that promote personal and social resources are therefore useful in the treatment of schizophrenia

Joint Crisis Plans and Crisis Cards in Inpatient Psychiatric Treatment

Rixe J, Neumann E, Möller J, et al. Joint Crisis Plans and Crisis Cards in Inpatient Psychiatric Treatment. Deutsches Ärzteblatt international . 2023;120(8):125-132.BACKGROUND: Joint Crisis Plans (JCP) and crisis cards (CC) are both instruments designed to improve the management of future psychiatric crisis situations, but they differ, for example, in terms of resource use, legal validity, and aims. International research findings for JCP are inconsistent.; METHODS: From January 2018 to December 2020, a single-blinded, two-armed multicenter RCT was carried out, with assessments at T0 (baseline) and T1 (18 months later). The patients included had schizophrenia or schizoaffective disorder and were aged between 18 and 62 years. The primary outcome was the cumulative duration of inpatient treatment (voluntary/involuntary), and coercive measures comprised the secondary outcome. Trial registration: DRKS00013985.; RESULTS: Of the 266 study participants, 157 completed the study. In the CC group 57.8% and in the JCP group 64.9% were admitted to psychiatric hospitals between the index treatment and T1 (p = 0.367); 8.4% of the CC group and 12.2% of the JPC group were admitted against their will (p = 0.441). The cumulative treatment duration was not significantly shorter (p = 0.631) in the JPC group (mean 42.43 days, SD = 48.60) than in the CC group (50.16 days, SD = 74.16). Thus, JPCs did not achieve the expected improvement with regard to the primary endpoint. There were also no relevant differences regarding the secondary endpoint. Major effects in favor of the JCP were observed, however, in patients' development of conficence in the treatment teams and in their active participation in the treatment procedure.; CONCLUSION: Although the study showed no superiority of JCP over CC with regard to the primary and secondary outcomes, JCP should be used more frequently in routine practice as an intervention to support a participative approach to treatment

Psychosocial functioning as a personal resource promoting a milder course of schizophrenia

Neumann E, Rixe J, Haussleiter IS, et al. Psychosocial functioning as a personal resource promoting a milder course of schizophrenia. Journal of Psychiatric Research . 2022;148:121-126.Schizophrenia has been shown repeatedly to be associated with a low level of psychosocial functioning. It is assumable that psychosocial functioning is related not only to current, but also to future symptom severity. To test this assumption, a follow-up study with two measurement time points with an interval of 18 months was conducted. In total, 154 inpatients from five psychiatric hospitals with a diagnosis of a schizophrenic disorder took part at both visits. Psychosocial functioning was measured with the Personal and Social Performance Scale (PSP scale) at baseline, and schizophrenic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at follow-up. Two PSP subscales, i.e. socially useful activities and control over disturbing and aggressive behavior, turned out to be significant predictors of symptom severity 18 months later. The findings reveal that personal resources in the occupational domain and in adequate interpersonal behavior can have a positive impact on the long-term course of schizophrenia

Individual patient data meta-analysis for the clinical assessment of coronary computed tomography angiography: protocol of the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT)

BACKGROUND: Coronary computed tomography angiography has become the foremost noninvasive imaging modality of the coronary arteries and is used as an alternative to the reference standard, conventional coronary angiography, for direct visualization and detection of coronary artery stenoses in patients with suspected coronary artery disease. Nevertheless, there is considerable debate regarding the optimal target population to maximize clinical performance and patient benefit. The most obvious indication for noninvasive coronary computed tomography angiography in patients with suspected coronary artery disease would be to reliably exclude significant stenosis and, thus, avoid unnecessary invasive conventional coronary angiography. To do this, a test should have, at clinically appropriate pretest likelihoods, minimal false-negative outcomes resulting in a high negative predictive value. However, little is known about the influence of patient characteristics on the clinical predictive values of coronary computed tomography angiography. Previous regular systematic reviews and meta-analyses had to rely on limited summary patient cohort data offered by primary studies. Performing an individual patient data meta-analysis will enable a much more detailed and powerful analysis and thus increase representativeness and generalizability of the results. The individual patient data is registered with the PROSPERO database (CoMe-CCT, CRD42012002780). METHODS: The analysis will include individual patient data from published and unpublished prospective diagnostic accuracy studies comparing coronary computed tomography angiography with conventional coronary angiography. These studies will be identified performing a systematic search in several electronic databases. Corresponding authors will be contacted and asked to provide obligatory and additional data. Risk factors, previous test results and symptoms of individual patients will be used to estimate the pretest likelihood of coronary artery disease. A bivariate random-effects model will be used to calculate pooled mean negative and positive predictive values as well as sensitivity and specificity. The primary outcome of interest will be positive and negative predictive values of coronary computed tomography angiography for the presence of coronary artery disease as a function of pretest likelihood of coronary artery disease, analyzed by meta-regression. As a secondary endpoint, factors that may influence the diagnostic performance and clinical value of computed tomography, such as heart rate and body mass index of patients, number of detector rows, and administration of beta blockade and nitroglycerin, will be investigated by integrating them as further covariates into the bivariate random-effects model. DISCUSSION: This collaborative individual patient data meta-analysis should provide answers to the pivotal question of which patients benefit most from noninvasive coronary computed tomography angiography and thus help to adequately select the right patients for this test

Applicability and accuracy of pretest probability calculations implemented in the NICE clinical guideline for decision making about imaging in patients with chest pain of recent onset.

OBJECTIVES: To analyse the implementation, applicability and accuracy of the pretest probability calculation provided by NICE clinical guideline 95 for decision making about imaging in patients with chest pain of recent onset. METHODS: The definitions for pretest probability calculation in the original Duke clinical score and the NICE guideline were compared. We also calculated the agreement and disagreement in pretest probability and the resulting imaging and management groups based on individual patient data from the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT). RESULTS: 4,673 individual patient data from the CoMe-CCT Consortium were analysed. Major differences in definitions in the Duke clinical score and NICE guideline were found for the predictors age and number of risk factors. Pretest probability calculation using guideline criteria was only possible for 30.8 % (1,439/4,673) of patients despite availability of all required data due to ambiguity in guideline definitions for risk factors and age groups. Agreement regarding patient management groups was found in only 70 % (366/523) of patients in whom pretest probability calculation was possible according to both models. CONCLUSIONS: Our results suggest that pretest probability calculation for clinical decision making about cardiac imaging as implemented in the NICE clinical guideline for patients has relevant limitations. KEY POINTS: • Duke clinical score is not implemented correctly in NICE guideline 95. • Pretest probability assessment in NICE guideline 95 is impossible for most patients. • Improved clinical decision making requires accurate pretest probability calculation. • These refinements are essential for appropriate use of cardiac CT