Investigating non-inferiority of internet-delivered versus face-to-face cognitive behavioural therapy for insomnia (CBT-I): a randomised controlled trial (iSleep well).

BACKGROUND: Insomnia is a highly prevalent disorder associated with numerous adverse health outcomes. Cognitive behavioural therapy for insomnia (CBT-I) is recommended as first-line treatment by clinical guidelines but is accessible to only a minority of patients suffering from insomnia. Internet-delivered CBT-I (iCBT-I) could contribute to the widespread dissemination of this first-line treatment. As there is insufficient evidence regarding non-inferiority, this study directly aims to compare therapist-guided internet-delivered versus face-to-face CBT-I in terms of insomnia severity post-treatment. Furthermore, a health-economic evaluation will be conducted, and potential benefits and disadvantages of therapist-guided iCBT-I will be examined. METHODS: This study protocol describes a randomised controlled two-arm parallel-group non-inferiority trial comparing therapist-guided iCBT-I with face-to-face CBT-I in routine clinical care. A total of 422 patients with insomnia disorder will be randomised and treated at 16 study centres throughout Germany. Outcomes will be assessed at baseline, 10 weeks after randomisation (post), and 6 months after randomisation (follow-up). The primary outcome is insomnia severity measured using the Insomnia Severity Index. Secondary outcomes include depression-related symptoms, quality of life, fatigue, physical activity, daylight exposure, adverse events related to treatment, and a health-economic evaluation. Finally, potential moderator variables and several descriptive and exploratory outcomes will be assessed (e.g. benefits and disadvantages of internet-delivered treatment). DISCUSSION: The widespread implementation of CBT-I is a significant healthcare challenge. The non-inferiority of therapist-guided iCBT-I versus face-to-face CBT-I will be investigated in an adequately powered sample in routine clinical care, with the same therapeutic content and same level of therapist qualifications provided with both interventions. If this trial demonstrates the non-inferiority of therapist-guided iCBT-I, healthcare providers may be more confident recommending this treatment to their patients, contributing to the wider dissemination of CBT-I. TRIAL REGISTRATION: Trial registration number in the German Clinical Trials Register: DRKS00028153 ( https://drks.de/search/de/trial/DRKS00028153 ). Registered on 16th May 2023.

Correlation between carotid intima-media thickness and patient outcomes in coronary artery disease in central South Africa.

OBJECTIVES: Carotid intima-medial thickness (CIMT) is a non-invasive tool used to detect atherosclerosis and diagnose cardiovascular disease. This study aimed to determine whether pre-operative CIMT measurements correlated with intra- and postoperative outcomes in patients with acute coronary syndrome (ACS) undergoing coronary artery bypass graft (CABG) surgery. METHODS: This retrospective, analytical cohort included 89 patients diagnosed with ACS who received CABG surgery. Patients were divided into two cohorts: group 1: normal CIMT < 0.07 cm and group 2: abnormal CIMT ≥ 0.07 cm. B-mode ultrasound was used to measure the CIMT in all patients. Pre-, intra- and postoperative data and complications were recorded for each patient. RESULTS: The study included 77 (86.5%) males and 12 (13.5%) females. Pre-operative mean body mass index was significantly higher (p = 0.03) in group 2 than in group 1. Group 2 had a significantly increased incidence of diabetes (p = 0.008) and hypertension (p = 0.009), and increased NT-proBNP levels (p = 0.02). Intra- and postoperative outcomes between the groups were comparable, with no significant differences. CONCLUSION: The study showed no correlation between abnormal CIMT and increased adverse intra- and postoperative patient outcomes. Therefore, the results of this study show CIMT should not be considered a tool to predict adverse events in patients undergoing CABG surgery.

Outcomes of single-ventricle physiology in central South Africa.

INTRODUCTION: Single-ventricle physiology is a critical cardiac condition requiring early diagnosis and intervention. The objectives of this study were to report on the management and outcomes of patients diagnosed with single-ventricle physiology in central South Africa. METHODS: This study was a retrospective, observational analysis of patients presenting with single-ventricle physiology at the Universitas Academic Hospital in central South Africa between November 1997 and June 2021. RESULTS: Patients were referred from the Free State (54%) and Northern Cape (29%) provinces and Lesotho. One hundred and fifty-four patients presented with single-ventricle physiology: 114 received interventions and 40 were not eligible for intervention. Patients presented for the first time at a median age of 34.5 days, with patients from nearby districts presenting within a few days of birth. However, patients from outlying areas presented much later. Eighty-seven patients received systemic-to-pulmonary artery shunting or pulmonary artery banding. Sixty-three patients proceeded to bidirectional Glenn procedures, and 30 patients (26%) had full palliation to Fontan. Twenty-one patients died after stage 1, six after the Glenn procedure and two after the Fontan procedure. Overall, 34 (29.8%) patients were lost to follow up. CONCLUSION: Patients in our study presented late and follow up of these patients was a challenge. The highest mortality rate occurs during the first stage of palliation. Outcomes from this study are comparable to other sub-Saharan studies.

Development of a simple standardized scoring system for assessing large vessel vasculitis by 18F-FDG PET-CT and differentiation from atherosclerosis.

PURPOSE: This study is to develop a structured approach to distinguishing large-artery vasculitis from atherosclerosis using 18-fluorodeoxyglucose positron emission tomography combined with low-dose computed tomography (FDG PET/CT). METHODS: FDG PET/CT images of 60 patients were evaluated, 30 having biopsy-proven giant cell arteritis (GCA; the most common form of large-artery vasculitis), and 30 with severe atherosclerosis. Images were evaluated by 12 nuclear medicine physicians using 5 criteria: FDG uptake pattern (intensity, distribution, circularity), the degree of calcification, and co-localization of calcifications with FDG-uptake. Criteria that passed agreement, and reliability tests were subsequently analysed for accuracy using receiver operator curve (ROC) analyses. Criteria that showed discriminative ability were then combined in a multi-component scoring system. Both initial and final 'gestalt' conclusion were also reported by observers before and after detailed examination of the images. RESULTS: Agreement and reliability analyses disqualified 3 of the 5 criteria, leaving only FDG uptake intensity compared to liver uptake and arterial wall calcification for potential use in a scoring system. ROC analysis showed an area under the curve (AUC) of 0.90 (95%CI 0.87-0.92) for FDG uptake intensity. Degree of calcification showed poor discriminative ability on its own (AUC of 0.62; 95%CI 0.58-0.66). When combining presence of calcification with FDG uptake intensity into a 6-tiered scoring system, the AUC remained similar at 0.91 (95%CI 0.88-0.93). After exclusion of cases with arterial prostheses, the AUC increased to 0.93 (95%CI 0.91-0.95). The accuracy of the 'gestalt' conclusion was initially 89% (95%CI 86-91%) and increased to 93% (95%CI 91-95%) after detailed image examination. CONCLUSION: Standardised assessment of arterial wall FDG uptake intensity, preferably combined with assessment of arterial calcifications into a scoring method, enables accurate, but not perfect, distinction between large artery vasculitis and atherosclerosis.

Extending the Hoyle-State Paradigm to

Carbon burning is a key step in the evolution of massive stars, Type 1a supernovae and superbursts in x-ray binary systems. Determining the ^{12}C+^{12}C fusion cross section at relevant energies by extrapolation of direct measurements is challenging due to resonances at and below the Coulomb barrier. A study of the ^{24}Mg(α,α^{'})^{24}Mg reaction has identified several 0^{+} states in ^{24}Mg, close to the ^{12}C+^{12}C threshold, which predominantly decay to ^{20}Ne(ground state)+α. These states were not observed in ^{20}Ne(α,α_{0})^{20}Ne resonance scattering suggesting that they may have a dominant ^{12}C+^{12}C cluster structure. Given the very low angular momentum associated with sub-barrier fusion, these states may play a decisive role in ^{12}C+^{12}C fusion in analogy to the Hoyle state in helium burning. We present estimates of updated ^{12}C+^{12}C fusion reaction rates.

Advantages of decellularized bovine pericardial scaffolds compared to glutaraldehyde fixed bovine pericardial patches demonstrated in a 180-day implant ovine study.

Glutaraldehyde (GA)-fixed bovine pericardial patches remain the cardiovascular industry standard despite reports of degradation, thickening, inflammation, calcification and lack of tissue remodelling. Decellularization provides the opportunity to attenuate some of these immune-mediated processes. This study compared the mechanical and morphological integrity of bovine pericardium that is GA-fixated (Glycar® patches) or decellularized (BPS), using a proprietary protocol, following implantation in an ovine model. The impact of the processing methods on tissue strength and morphology was assessed prior to implantation. Pericardial patches were then implanted in the descending aorta and main pulmonary artery of juvenile sheep (n = 6 per group) for 180 days, and clinically evaluated using echocardiography. At explanation, patches were evaluated for strength, calcification and biological interaction. Histology demonstrated a wave-like appearance of well-separated collagen fibers for BPS scaffolds that provided pore sizes adequate to promote fibroblast infiltration. The collagen of the Glycar® patches showed loss of collagen fiber integrity, making the collagen densely compacted, contributing to insignificant recipient cell infiltration. The clinical performance of both groups was excellent, and echocardiography confirmed the absence of aneurysm formation, calcification and degeneration. Explanted Glycar® patches demonstrated cells in abundance within the fibrous encapsulation that separated the implant from the host tissue. More importantly, the fibrous encapsulation also contributed to patch thickening of both the explanted aorta and pulmonary patches. The decellularized pericardial scaffolds demonstrated recellularization, resistance to calcification, re-endothelialization and adequate strength after 180-day implantation. The proprietary decellularization protocol produced pericardial scaffolds that could be considered as an alternative to GA-fixed pericardial patches.

Upregulation of miR-3195, miR-3687 and miR-4417 is associated with castration-resistant prostate cancer.

PURPOSE: Prostate cancer (PCa) is a leading cause of cancer-related death. Upon androgen-deprivation therapy, the disease may progress further to castration-resistant PCa (CRPC) with a poor prognosis. MicroRNAs (miRNAs) are small non-coding RNAs, which play crucial roles in gene regulation. The aim of our study is to find CRPC-associated miRNAs and to evaluate their functional role. METHODS: In this study, 23 benign prostatic hyperplasia (BPH), 76 primary PCa, and 35 CRPC specimens were included. Total RNA extracted from tissue sections was used for miRNA profiling on the Affymetrix GSC 3000 platform. Subsequently, stem-loop RT-qPCR analysis was performed to validate the expression levels of selected miRNAs. PCa cell lines were transfected with miRNA mimics or inhibitors to evaluate the effects on cell proliferation, cell migration and cell invasion. RESULTS: In our profiling study, several miRNAs were found to be deregulated in CRPC compared to primary PCa tissue, of which miR-205 (- 4.5-fold; p = 0.0009), miR-92b (- 3.1 fold; p < 0.0001) were downregulated and miR-3195 (5.6-fold; p < 0.0001), miR-3687 (8.7-fold; p = 0.0006) and miR-4417 (5.0-fold; p = 0.0005) were most upregulated. While KLK3, miR-21 and miR-141 expression levels in androgen-treated VCaP and LNCaP cells were increased, the expression levels of miR-3687 and miR-4417 were reduced. None of the miRNAs were androgen-regulated in the AR-negative PC3 cell line. Overexpression of miR-3687 reduced cell migration and cell invasion, whilst miR-3195 enhanced cell migration. CONCLUSION: We have identified several novel deregulated miRNAs in CRPC tissue, including two microRNAs that are potentially involved in tumor invasion. Our data support the hypothesized involvement of miRNAs in PCa tumorigenesis and progression to CRPC. The applicability of these miRNAs as novel biomarkers for CRPC remains to be further investigated.

The sequential effects of a multifactorial detergent based decellularization process on bovine pericardium.

Decellularization is a promising method for obtaining extracellular matrix scaffolds (ECM) to be used as replacement material in reconstructive procedures. The effectiveness of decellularization and the alterations to the ECM vary, depending on several factors, including the tissue source, composition and density. With an optimized decellularization process, decellularized scaffolds can preserve the spatial and temporal ECM microenvironment, which play an integral role in modulating cell migration, proliferation and differentiation. The exploration of a variety of decellularization protocols has led to mixed outcomes and comparisons between decellularization protocols could not attribute these differences to any single step in a multiple-step process. This study aimed to characterize the effects of each step of a multifactorial decellularization method on the scaffold structure and mechanical integrity of bovine pericardium. Each step of the decellularization process and the effect on the tissue was assessed using hematoxylin and eosin staining, electron microscopy, total protein, ECM protein and triglyceride quantification. The biomechanical properties were assessed using uniaxial tensile strength testing. Cell lysis occurred mainly during the detergent and alcohol steps. Collagen structural damage occurred during the detergent and alcohol steps, with no significant decreased in collagen concentration. No significant damage to elastin could be shown throughout the process, however glycosaminoglycans were significantly removed by detergent treatment. Triglycerides were removed mostly by the alcohol treatment. The strength of the pericardium decreased somewhat after each step of the protocol. It is important to characterize each decellularization protocol with regards to the decellularization efficiency and the effect on the ECM proteins structure and function to accurately evaluatein vivooutcomes.

Outcome determinants of urethroplasty in the management of inflammatory anterior urethral strictures.

BACKGROUND: Limited data are available on outcomes of the surgical management of inflammatory urethral strictures secondary to infection, a major cause of stricture. Several shortcomings that need to be addressed have been identified in the past. OBJECTIVE: To determine the impact of stricture length, position and degree of obliterative urethral lumen on the surgical outcomes of corrective procedures for inflammatory anterior urethral strictures. METHODS: This retrospective analysis used the records of patients who presented with proven infective anterior urethral strictures at an academic hospital from 2007 to 2010. All patients were followed up after 48 months. Urethroplasty outcomes were analysed according to stricture location and length and effect of urethral obliteration. RESULTS: The median age of the 174 patients in the study was 47 (range 21 - 86) years. Anastomotic urethroplasty was successful in 59/99 (59.6%) patients. Augmented anastomotic urethroplasty was successful in 11/15 (73.3%) patients. Dorsal onlay buccal mucosa graft urethroplasty was successful in 23/32 (71.9%) patients, significantly higher than in 2/9 (22.2%) patients who underwent ventral onlay buccal mucosa graft urethroplasty (p=0.017; hazard ratio 3.4; 95% confidence interval 1.29 - 9.40). The one-stage circular pedicled penile skin-flap urethroplasty was successful in 1/12 (8.3%) patients. Two-stage urethroplasty was successful in 5/7 (71.4%) patients. A primary component analysis of the 73 failed procedures showed that stricture length was the main contributor to failure (eigenvalue 1.79; 45%). CONCLUSIONS: Urethroplasty remains a challenge in inflammatory urethral strictures, where stricture length was the main reason for treatment failure.

Freehand-SPECT con 99mTc-HDP como herramienta para guiar la biopsia percutánea de lesiones esqueléticas detectadas en la gammagrafía ósea / Freehand-SPECT with 99mTc-HDP as tool to guide percutaneous biopsy of skeletal lesions detected on bone scintigraphy

OBJETIVOS: Determinar la factibilidad de la freehand-SPECT en la identificación de lesiones óseas con captación de 99mTc-HDP evaluando los datos generados mediante la utilización de sistemas de navegación con realidad aumentada y virtual. MATERIAL Y MÉTODOS: Se generaron 21 imágenes 3D utilizando freehand-SPECT con una gammacámara manual en 20 pacientes referidos para gammagrafía ósea con 99mTc-HDP. Las imágenes freehand-SPECT y las gammagrafías fueron comparadas y se analizó el grado de concordancia. Además, se evaluó la factibilidad de navegación hacia las lesiones óseas hipercaptantes. RESULTADOS: En el 86% de los casos freehand-SPECT mostró una buena concordancia con las imágenes correspondientes de la gammagrafía ósea. En lesiones con una señal lesión/fondo de>1,36 freehand-SPECT pudo automáticamente proporcionar puntos de referencia segmentados con finalidad de navegación. En el 14% de los casos (índice lesión/fondo: valor promedio 1,82, rango 1,0-3,4) las imágenes freehand-SPECT mostraron concordancia intermedia debido a que estaban localizadas en regiones anatómicas difíciles o asociadas con una gammagrafía ósea negativa y fueron consideradas como no apropiadas para la navegación dirigida. CONCLUSIÓN: En este estudio piloto, se encontró un 86% de los casos apropiados para propósitos de navegación con una buena concordancia entre freehand-SPECT y la gammagrafía ósea. Un índice lesión/fondo de 1,36 o más facilitó la navegación con freehand-SPECT. La alta calidad de las imágenes generadas con freehand-SPECT potencialmente asegura una exitosa estrategia de navegación para biopsias óseas guiadas

PURPUSE: To assess the feasibility of using freehand Single Photon Emission Computed Tomography (freehandSPECT) for the identification of technetium-99m-hydroxydiphosphonate (99mTc-HDP) positive bone lesions and to evaluate the possibility of using these imaging data-sets for augmented- and virtual-reality based navigation approaches. MATERIAL AND METHODS: In 20 consecutive patients referred for scintigraphy with 99mTc-HDP, 21 three-dimensional freehandSPECT-images were generated using a handheld gamma camera. Concordance of the two different data sets was ranked. Furthermore, feasibility of segmenting the hotspot of tracer accumulation for navigation purposes was assessed. RESULTS: In 86% of the cases freehandSPECT images showed good concordance with the corresponding part of the scintigraphic images. In lesions with a signal to background ratio (SBR) >1.36, freehandSPECT provided an automatically segmented reference point for navigation purposes. In 14% of the cases (average SBR 1.82, range 1.0-3.4) freehandSPECT images showed intermediate concordance due to difficult anatomical area or negative bone scintigraphy and could not be used as navigation targets. CONCLUSION: In this pilot study, in 86% of the cases freehandSPECT demonstrated good concordance with traditional scintigraphy. A lesion with a SBR of 1.36 or more was suitable for navigation. These high-quality freehandSPECT images supported the future exploration navigation strategies, e. g. guided needle biopsies

Freehand-SPECT with 99mTc-HDP as tool to guide percutaneous biopsy of skeletal lesions detected on bone scintigraphy. / Freehand-SPECT con 99mTc-HDP como herramienta para guiar la biopsia percutánea de lesiones esqueléticas detectadas en la gammagrafía ósea.

PURPOSE: To assess the feasibility of using freehand Single Photon Emission Computed Tomography (freehandSPECT) for the identification of technetium-99m-hydroxydiphosphonate (99mTc-HDP) positive bone lesions and to evaluate the possibility of using these imaging data-sets for augmented- and virtual-reality based navigation approaches. MATERIAL AND METHODS: In 20 consecutive patients referred for scintigraphy with 99mTc-HDP, 21 three-dimensional freehandSPECT-images were generated using a handheld gamma camera. Concordance of the two different data sets was ranked. Furthermore, feasibility of segmenting the hotspot of tracer accumulation for navigation purposes was assessed. RESULTS: In 86% of the cases freehandSPECT images showed good concordance with the corresponding part of the scintigraphic images. In lesions with a signal to background ratio (SBR) >1.36, freehandSPECT provided an automatically segmented reference point for navigation purposes. In 14% of the cases (average SBR 1.82, range 1.0-3.4) freehandSPECT images showed intermediate concordance due to difficult anatomical area or negative bone scintigraphy and could not be used as navigation targets. CONCLUSION: In this pilot study, in 86% of the cases freehandSPECT demonstrated good concordance with traditional scintigraphy. A lesion with a SBR of 1.36 or more was suitable for navigation. These high-quality freehandSPECT images supported the future exploration navigation strategies, e.g. guided needle biopsies.

Recognizing critically ill children with a modified pediatric early warning score at the emergency department, a feasibility study.

Pediatric Early Warning Scores were developed to monitor clinical deterioration of children admitted to the hospital. Pediatric Early Warning Scores could also be useful in the Emergency Department to quickly identify critically ill patients so treatment can be started without delay. To determine if a newly designed, fast, and easy to use Modified Pediatric Early Warning Score can identify critically ill children in the Emergency Department. We conducted a retrospective observational study in the Emergency Department of an urban district hospital in Rotterdam, the Netherlands. Patients < 16 years attending the Emergency Department with an internal medical problem were included. Immediate intensive care unit admission was used as a measure for critically ill children. During the study period 2980 children attended the Emergency Department, ten (0.4%) of them required immediate intensive care unit admission. The Modified Pediatric Early Warning Score can identify critically ill children in the general pediatric Emergency Department population (area under the ROC curve 0.82). A sensitivity of 80% and specificity of 85% show potential to rule out critical illness in children visiting the Emergency Department when these results are validated in a larger population. A model containing both the Modified Pediatric Early Warning Score and the Manchester Triage System did not perform significantly better than the Manchester Triage System alone but did show a positive tendency in favor of the model containing the Modified Pediatric Early Warning Score and Manchester Triage System, area under the ROC curve 0.89 [95% CI 0.77-1.00] versus area under the ROC curve 0.82 [95% CI 0.68-0.95].Conclusions: In this feasibility study, the Modified Pediatric Early Warning Score could be a fast and easy to use tool to identify critically ill children in the general pediatric Emergency Department population. The effectiveness of the Modified Pediatric Early Warning Score may be optimized if combined with triage systems such as the Manchester Triage System. A larger prospective study is needed to confirm our results. What is known: • Pediatric Early Warning Scores can identify children who are in need for immediate intensive care unit admission at the Emergency Department. • Pediatric Early Warning Scores can be time-consuming, contain subjective parameters or parameters which are difficult to obtain in a reliable and standardized method. What is new: • We introduce a simplified, manageable and smartly designed Pediatric Early Warning Score on a pocket card based on an existing and previously investigated Pediatric Early Warning Score. • In this feasibility study the diagnostic performance of the Modified Pediatric Early Warning Score to predict immediate intensive care unit admission in the Emergency Department is in line with the original Pediatric Early Warning Scores but has to be validated on a larger scale.

Value and potential limitations of vertebral fracture assessment (VFA) compared to conventional spine radiography: experience from a fracture liaison service (FLS) and a meta-analysis.

We evaluated the value of VFA in the identification of vertebral fractures using a retrospective study and a meta-analysis. Performance of VFA was adequate in the meta-analysis although this was not demonstrated in our centre. We recommend checking the performance of VFA tools before exclusively relying on this tool. INTRODUCTION: Vertebral fractures are traditionally diagnosed using conventional radiographs of the spine. Vertebral fracture assessment (VFA) has been advocated as an alternative tool in the diagnosis of these fractures. METHODS: We conducted a retrospective study as well as a systematic review and a meta-analysis to evaluate the performance of VFA compared to conventional spinal radiography in patients who had sustained a fracture and thus at risk for osteoporosis. A risk of bias analysis was also performed. RESULTS: The diagnostic study included 542 patients (25% male) with fractures. The sensitivity of low-radiation VFA to detect a patient with a vertebral fracture ≥ Genant grade 2 was 0.77 and its specificity 0.80. Two hundred ninety-seven (55%) patients had ≥1 and 135(25%) ≥3 unevaluable vertebrae. The systematic review identified 16 studies including a total of 3238 subjects (19% male) with a mean age range of 45 to 74 years. Seven studies had a low risk of bias and 9 had an intermediate risk, mainly due to not consecutively including patients. The pooled sensitivity of VFA to detect a patient with a vertebral fracture ≥Genant grade 2 was 0.84 (95% CI, 0.72-0.92) and specificity 0.90 (95% CI, 0.84-0.94). CONCLUSIONS: Our findings from the meta-analysis suggest an adequate performance of VFA for the detection of vertebral fractures. However, we could not demonstrate these findings in our center, especially the specificity. Our data advocate caution with exclusively relying on VFA in the assessment of vertebral fractures without identifying performance and potential limitations of the technique.

[Child maltreatment: long-term economic consequences and implications]. / Kindermishandeling: economische gevolgen op lange termijn1.

BACKGROUND: Child maltreatment occurs frequently. This has detrimental effects later in life on mental health and is linked to considerable costs due to health care use and sick leave. Self-mastery, however, is a factor that may well mitigated the effects of child maltreatment .
AIM: To quantify the long-term costs of child abuse and to test the hypothesis that self-mastery can modify the after-effects of maltreatment .
METHOD: Data were obtained from a psychiatric cohort study (n=5618). The risk factors were emotional neglect and mental, physical and sexual abuse before the age of 16.
RESULTS: When individuals are about 39 years old, the various forms of maltreatment to which they were subjected as children are associated with substantially higher health care costs and frequent absenteeism. Higher levels of self-mastery achieved in childhood were indeed associated with lower costs in adulthood.
CONCLUSION: Child maltreatment costs the Netherlands millions of euros annually because it leads to higher health care costs and more frequent sick leave. Active steps to curb child abuse are of both financial and economic significance. More training in self-mastery could perhaps be helpful, but further research is needed in this area.

[Prognostic modelling and proactive intervention in psychosis: efficacy and cost-effectiveness]. / Prognostisch modelleren en proactieve interventie bij psychose: effectiviteit en kosteneffectiviteit.

BACKGROUND: Diagnoses have heterogeneous outcomes, varying from good to extremely poor. There is a need to single out an ultra-high-risk group of individuals who have illnesses that might well end unfavourably or who might later develop serious psychopathology.
AIM: To devise a screening instrument that can identify a group of individuals who run a very high risk of developing a first-episode psychosis, and to create a type of intervention that can modify the course of the illness.
METHOD: We developed a short screening instrument (PQ-16) and were able to ascertain its predictive value. We also tested an intervention that could influence risk factors and deal with emerging symptoms thereby achieving a better outcome for the patient.
RESULTS: We developed a two-step detection instrument with a positive predictive value of 44%. The intervention, involving cognitive behavioural therapy for ultra-high-risk patients, was effective and led to a risk reduction of about 50%. Using the ultra-high-risk group of patients, we were able to model three prognostic profiles, each carrying a 4%, 13%, and 70% risk of subsequently developing psychosis. The intervention was cost-effective, reducing the financial burden on the health care services and on society as a whole.
CONCLUSION: Prognostic modelling and proactive intervention can achieve improvements in health at lower costs.

[Online self-help for persons with suicidal intentions: budget impact analysis]. / Onlinehulp bij suïcidale gedachten: budgetimpactanalyse.

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Development of a stage-dependent prognostic model to predict psychosis in ultra-high-risk patients seeking treatment for co-morbid psychiatric disorders.

BACKGROUND: Current ultra-high-risk (UHR) criteria appear insufficient to predict imminent onset of first-episode psychosis, as a meta-analysis showed that about 20% of patients have a psychotic outcome after 2 years. Therefore, we aimed to develop a stage-dependent predictive model in UHR individuals who were seeking help for co-morbid disorders. METHOD: Baseline data on symptomatology, and environmental and psychological factors of 185 UHR patients (aged 14-35 years) participating in the Dutch Early Detection and Intervention Evaluation study were analysed with Cox proportional hazard analyses. RESULTS: At 18 months, the overall transition rate was 17.3%. The final predictor model included five variables: observed blunted affect [hazard ratio (HR) 3.39, 95% confidence interval (CI) 1.56-7.35, p < 0.001], subjective complaints of impaired motor function (HR 5.88, 95% CI 1.21-6.10, p = 0.02), beliefs about social marginalization (HR 2.76, 95% CI 1.14-6.72, p = 0.03), decline in social functioning (HR 1.10, 95% CI 1.01-1.17, p = 0.03), and distress associated with suspiciousness (HR 1.02, 95% CI 1.00-1.03, p = 0.01). The positive predictive value of the model was 80.0%. The resulting prognostic index stratified the general risk into three risk classes with significantly different survival curves. In the highest risk class, transition to psychosis emerged on average ⩾8 months earlier than in the lowest risk class. CONCLUSIONS: Predicting a first-episode psychosis in help-seeking UHR patients was improved using a stage-dependent prognostic model including negative psychotic symptoms (observed flattened affect, subjective impaired motor functioning), impaired social functioning and distress associated with suspiciousness. Treatment intensity may be stratified and personalized using the risk stratification.

Metacognitive training for schizophrenia spectrum patients: a meta-analysis on outcome studies.

BACKGROUND: Metacognitive training (MCT) for schizophrenia spectrum is widely implemented. It is timely to systematically review the literature and to conduct a meta-analysis. METHOD: Eligible studies were selected from several sources (databases and expert suggestions). Criteria included comparative studies with a MCT condition measuring positive symptoms and/or delusions and/or data-gathering bias. Three meta-analyses were conducted on data gathering (three studies; 219 participants), delusions (seven studies; 500 participants) and positive symptoms (nine studies; 436 participants). Hedges' g is reported as the effect size of interest. Statistical power was sufficient to detect small to moderate effects. RESULTS: All analyses yielded small non-significant effect sizes (0.26 for positive symptoms; 0.22 for delusions; 0.31 for data-gathering bias). Corrections for publication bias further reduced the effect sizes to 0.21 for positive symptoms and to 0.03 for delusions. In blinded studies, the corrected effect sizes were 0.22 for positive symptoms and 0.03 for delusions. In studies using proper intention-to-treat statistics the effect sizes were 0.10 for positive symptoms and -0.02 for delusions. The moderate to high heterogeneity in most analyses suggests that processes other than MCT alone have an impact on the results. CONCLUSIONS: The studies so far do not support a positive effect for MCT on positive symptoms, delusions and data gathering. The methodology of most studies was poor and sensitivity analyses to control for methodological flaws reduced the effect sizes considerably. More rigorous research would be helpful in order to create enough statistical power to detect small effect sizes and to reduce heterogeneity. Limitations and strengths are discussed.