Predicting the onset of psychosis in patients at clinical high risk: practical guide to probabilistic prognostic reasoning

Prediction of psychosis in patients at clinical high risk (CHR) has become a mainstream focus of clinical and research interest worldwide. When using CHR instruments for clinical purposes, the predicted outcome is but only a probability; and, consequently, any therapeutic action following the assessment is based on probabilistic prognostic reasoning. Yet, probabilistic reasoning makes considerable demands on the clinicians. We provide here a scholarly practical guide summarising the key concepts to support clinicians with probabilistic prognostic reasoning in the CHR state. We review risk or cumulative incidence of psychosis in, person-time rate of psychosis, Kaplan-Meier estimates of psychosis risk, measures of prognostic accuracy, sensitivity and specificity in receiver operator characteristic curves, positive and negative predictive values, Bayes’ theorem, likelihood ratios, potentials and limits of real-life applications of prognostic probabilistic reasoning in the CHR state. Understanding basic measures used for prognostic probabilistic reasoning is a prerequisite for successfully implementing the early detection and prevention of psychosis in clinical practice. Future refinement of these measures for CHR patients may actually influence risk management, especially as regards initiating or withholding treatment.

Final Results of a Prospective Evaluation of the Predictive Value of Interim Positron Emission Tomography in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP-14 (SAKK 38/07)

PURPOSE Our main objective was to prospectively determine the prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) after two cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone given every 14 days (R-CHOP-14) under standardized treatment and PET evaluation criteria. PATIENTS AND METHODS Patients with any stage of diffuse large B-cell lymphoma were treated with six cycles of R-CHOP-14 followed by two cycles of rituximab. PET/CT examinations were performed at baseline, after two cycles (and after four cycles if the patient was PET-positive after two cycles), and at the end of treatment. PET/CT examinations were evaluated locally and by central review. The primary end point was event-free survival at 2 years (2-year EFS). RESULTS Median age of the 138 evaluable patients was 58.5 years with a WHO performance status of 0, 1, or 2 in 56%, 36%, or 8% of the patients, respectively. By local assessment, 83 PET/CT scans (60%) were reported as positive and 55 (40%) as negative after two cycles of R-CHOP-14. Two-year EFS was significantly shorter for PET-positive compared with PET-negative patients (48% v 74%; P = .004). Overall survival at 2 years was not significantly different, with 88% for PET-positive versus 91% for PET-negative patients (P = .46). By using central review and the Deauville criteria, 2-year EFS was 41% versus 76% (P < .001) for patients who had interim PET/CT scans after two cycles of R-CHOP-14 and 24% versus 72% (P < .001) for patients who had PET/CT scans at the end of treatment. CONCLUSION Our results confirmed that an interim PET/CT scan has limited prognostic value in patients with diffuse large B-cell lymphoma homogeneously treated with six cycles of R-CHOP-14 in a large prospective trial. At this point, interim PET/CT scanning is not ready for clinical use to guide treatment decisions in individual patients.

Ultra-low-dose dual-source CT coronary angiography with high pitch: diagnostic yield of a volumetric planning scan and effects on dose reduction and imaging strategy

OBJECTIVE To evaluate the role of an ultra-low-dose dual-source CT coronary angiography (CTCA) scan with high pitch for delimiting the range of the subsequent standard CTCA scan. METHODS 30 patients with an indication for CTCA were prospectively examined using a two-scan dual-source CTCA protocol (2.0 × 64.0 × 0.6 mm; pitch, 3.4; rotation time of 280 ms; 100 kV): Scan 1 was acquired with one-fifth of the tube current suggested by the automatic exposure control software [CareDose 4D™ (Siemens Healthcare, Erlangen, Germany) using 100 kV and 370 mAs as a reference] with the scan length from the tracheal bifurcation to the diaphragmatic border. Scan 2 was acquired with standard tube current extending with reduced scan length based on Scan 1. Nine central coronary artery segments were analysed qualitatively on both scans. RESULTS Scan 2 (105.1 ± 10.1 mm) was significantly shorter than Scan 1 (127.0 ± 8.7 mm). Image quality scores were significantly better for Scan 2. However, in 5 of 6 (83%) patients with stenotic coronary artery disease, a stenosis was already detected in Scan 1 and in 13 of 24 (54%) patients with non-stenotic coronary arteries, a stenosis was already excluded by Scan 1. Using Scan 2 as reference, the positive- and negative-predictive value of Scan 1 was 83% (5 of 6 patients) and 100% (13 of 13 patients), respectively. CONCLUSION An ultra-low-dose CTCA planning scan enables a reliable scan length reduction of the following standard CTCA scan and allows for correct diagnosis in a substantial proportion of patients. ADVANCES IN KNOWLEDGE Further dose reductions are possible owing to a change in the individual patient's imaging strategy as a prior ultra-low-dose CTCA scan may already rule out the presence of a stenosis or may lead to a direct transferal to an invasive catheter procedure.

Towards an Earlier Diagnosis of Primary Ciliary Dyskinesia: Which Patients Should Undergo Detailed Diagnostic Testing?

Primary ciliary dyskinesia is a rare heterogeneous recessive genetic disorder of motile cilia, leading to chronic upper and lower respiratory symptoms. Prevalence is estimated at around 1:10,000, but many patients remain undiagnosed, while others receive the label incorrectly. Proper diagnosis is complicated by the fact that the key symptoms such as wet cough, chronic rhinitis and recurrent upper and lower respiratory infection, are common and nonspecific. There is no single gold standard test to diagnose PCD. Presently, the diagnosis is made by augmenting the medical history and physical examination with in patients with a compatible medical history following a demanding combination of tests including nasal nitric oxide, high- speed video microscopy, transmission electron microscopy, genetics, and ciliary culture. These tests are costly and need sophisticated equipment and experienced staff, restricting use to highly specialised centers. Therefore, it would be desirable to have a screening test for identifying those patients who should undergo detailed diagnostic testing. Three recent studies focused on potential screening tools: one paper assessed the validity of nasal nitric oxide for screening, and two studies developed new symptom-based screening tools. These simple tools are welcome, and hopefully remind physicians whom to refer for definitive testing. However, they have been developed in tertiary care settings, where 10 to 50% of tested patients have PCD. Sensitivity and specificity of the tools are reasonable, but positive and negative predictive values may be poor in primary or secondary care settings. While these studies take an important step forward towards an earlier diagnosis of PCD, more remains to be done before we have tools tailored to different health care settings.