Mediational Analyses of the Effects of Social Behaviour and Network Therapy on Alcohol Use.

INTRODUCTION: Social behaviour and network therapy involves an active participation of the practitioner in recruiting a supportive network to change the client's alcohol use. Despite achieving beneficial effects on alcohol consumption, its possible mechanisms of change are a relatively under-studied topic compared to those of other alcohol treatment interventions. This study aimed to explore therapist skills through which social behaviour and network therapy may achieve effects on alcohol consumption in comparison with motivational enhancement therapy. METHODS: This study was secondary analysis of data from the UK Alcohol Treatment Trial, a multicentre, pragmatic, randomized controlled trial. The sample comprised 376 participants randomized to motivational enhancement therapy or social behaviour and network therapy. We used the UK Alcohol Treatment Trial Process Rating Scale to assess therapist skills. Outcomes drinks per drinking day and percentage of days abstinent were assessed 12 months after treatment initiation. Analyses were conducted in a simple mediation framework. RESULTS: Therapist skills score (combining frequency and quality) for involving others in behaviour change mediated social behaviour and network therapy effects on percentage of days abstinent (b = 0.06, 95% CI: 0.02; 0.10, p = 0.01). The frequency with which therapists acted as an active agent for change also mediated the effects of social behaviour and network therapy on percentage of days abstinent (b = 0.03, 95% CI: 0.003; 0.05, p = 0.03). The frequency with which the therapist stressed social support as a key factor in achieving change unexpectedly mediated an increase in drinks per drinking day (b = 0.10, 95% CI: 0.01; 0.18, p = 0.02). The two latter mediation effects were not sustained when quality was considered. All other indirect effects tested were non-significant. DISCUSSION/CONCLUSIONS: How social behaviour and network therapy exerts effects on alcohol outcomes is not yet well understood and in this study was not attributable to observed ratings of therapist treatment-specific skills. Therapist skill in planning the involvement of others during treatment, however, warrants further study. We suggest that the present findings should be regarded as hypothesis generating as it identifies specific targets for further investigation in alcohol treatment process studies.

Efficacy and Acceptance of Cognitive Behavioral Therapy in Adults with Chronic Fatigue Syndrome: A Meta-analysis.

BACKGROUND: The systematic aggregation of research on cognitive behavioral therapy (CBT) in chronic fatigue syndrome (CFS) needs an update. Although meta-analyses evaluating interventions typically focus on symptom reduction, they should also consider indicators of treatment acceptability, e.g., drop-out rates. METHODS: Randomized controlled trials (RCTs) investigating CBT in adults with CFS compared to inactive and non-specific control groups were included. First, efficacy was examined, considering fatigue, depression, anxiety, and perceived health. Secondly, drop-out rates through different trial stages were analyzed: Non-completion of all mandatory sessions, drop-out (primary study definition), treatment refusal (non-starters), and average of sessions completed. RESULT: We included 15 RCTs with 2015 participants. CBT was more effective than controls in fatigue (g = -0.52, 95%CI -0.69 to -0.35), perceived health, depression, and anxiety at post-treatment. At long-term follow-up the effects were maintained for fatigue and anxiety. Rates of non-completion (22%, 95%CI 3-71), drop-out (15%, 95%CI 9-25), and treatment refusal (7%, 95%CI 3-15) were relatively low, with a high average proportion of sessions completed. Total time of therapy moderated the effect on fatigue, while the number of sessions moderated the effect on perceived health. Fatigue severity influenced adherence. CONCLUSION: The results indicate that CBT for CFS is effective in reducing fatigue, fatigue related impairment, and severity of depression and anxiety. Conclusions on efficacy at follow-ups are still limited. However, adherence is high in CBT. The results may help to inform clinical practice. Future research should focus on examining the maintenance of effects, while also emphasizing the importance of treatment acceptance.

Cardiac and mortality outcome differences between methadone, buprenorphine and naltrexone prescriptions in patients with an opioid use disorder.

IMPORTANCE: More than 109,000 Americans died of drug overdose in 2022, with 81,231 overdose deaths involving opioids. Methadone, buprenorphine and naltrexone are the most widely used medications for opioid use disorders (MOUD) and the most effective intervention for preventing overdose deaths. However, there is a concern that methadone results in long QT syndrome, which increases the risk for fatal cardiac arrythmias. Currently few studies have systematically evaluated both the short-term and long-term differences in cardiac and mortality outcomes between MOUD. OBJECTIVES: To compare the risks of cardiac arrythmias, long QT syndrome and overall mortality between patients with opioid use disorders (OUD) who were prescribed methadone, buprenorphine or naltrexone. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study based on a multicenter and nationwide database of electronic health records (EHRs) in the United States. The study population was comprised of 144,141 patients who had medical encounters for OUD in 2016-2022, were prescribed MOUD within 1 month following a medical encounter for OUD diagnosis and had no diagnosis of cardiac arrythmias or long QT syndrome before any MOUD prescription. The study population was divided into three cohorts: (1) Methadone cohort (n = 40,938)-who were only prescribed methadone. (2) Buprenorphine cohort (n = 80,055)-who were only prescribed buprenorphine. (3) Naltrexone cohort (n = 5,738)-who were only prescribed naltrexone. EXPOSURES: methadone, buprenorphine, or naltrexone. MAIN OUTCOMES AND MEASURES: Cardiac arrythmias, long QT syndrome, and death. Hazard ratio (HR) and 95% confidence interval (CI) of outcomes at six different follow-up time frames (1-month, 3-month, 6-month, 1-year, 3-year, and 5-year) by comparing propensity-score matched cohorts using Kaplan-Meier survival analysis. RESULTS: Patients with OUD who were prescribed methadone had significantly higher risks of cardiac arrhythmias, long QT syndrome and death compared with propensity-score matched patients with OUD who were prescribed buprenorphine or naltrexone. For the 1-month follow-up, the overall risk for cardiac arrythmias was 1.03% in the Methadone cohort, higher than the 0.87% in the matched Buprenorphine cohort (HR: 1.20, 95% CI: 1.04-1.39); The overall risk for long QT syndrome was 0.35% in the Methadone cohort, higher than the 0.15% in the matched Buprenorphine cohort (HR: 2.40, 95% CI: 1.75-3.28); The overall mortality was 0.59% in the Methadone cohort, higher than the 0.41% in the matched Buprenorphine cohort (HR: 1.48, 95% CI: 1.21-1.81). The increased risk persisted for 5 years: cardiac arrhythmias (HR: 1.31, 95% CI: 1.23-1.38), long QT syndrome (HR: 3.14, 95% CI: 2.76-3.58), death (HR: 1.50, 95% CI: 1.41-1.59). CONCLUSIONS AND RELEVANCE: Methadone was associated with a significantly higher risk for cardiac and mortality outcomes than buprenorphine and naltrexone. These findings are relevant to the development of guidelines for medication selection when initiating MOUD treatment and inform future medication development for OUD that minimizes risks while maximizing benefits.

Substantial gaps in evaluation and treatment of patients with hepatitis B in the US.

BACKGROUND & AIMS: The occurrence of HBV-associated liver complications is reduced by antiviral therapy. However, prior studies using local institutional cohorts have suggested that evaluation and treatment are suboptimal. We aimed to determine the proportion of patients with chronic HBV infection who received adequate evaluation, were treatment eligible, and received antiviral treatment using a large, nationwide cohort. METHODS: This retrospective analysis utilized claims data of approximately 73 million enrollees across the US from Optum's de-identified Clinformatics® Data Mart Database, 2003-2019. Adults observed for ≥6 months before and after an index diagnosis of chronic HBV infection were identified via ICD-9/ICD-10 codes, with the diagnosis confirmed by positive HBsAg, HBeAg or HBV DNA PCR. RESULTS: We included 12,608 eligible patients in the study analysis (mean age 45.7 years, 52.1% male, 54.6% Asian, 18.1% Caucasian, 10.5% African American). About half of the cohort (n = 6,559, 52.3%) did not have a complete laboratory evaluation (defined as having HBeAg, HBV DNA, and ALT tests) and only 72.4% (n = 9,129) had an "adequate" evaluation (at least HBV DNA and ALT) during the entire study period. Of those with an adequate evaluation, 11.2% were treatment eligible by AASLD criteria and 13.9% by EASL criteria; 60.4% of AASLD eligible patients and 54.3% of EASL eligible patients received treatment within 12 months from becoming eligible. CONCLUSIONS: Half of patients with chronic HBV infection in the US with private insurance did not have a complete laboratory assessment. Over one-third of treatment-eligible patients did not receive antiviral therapy. Patients who visited a specialist had a higher chance of receiving adequate evaluation and treatment. Urgent intervention is needed to identify and address the barriers to optimal care. LAY SUMMARY: In this study, we used a national database that includes laboratory data in addition to medical and pharmacy claims data to assess the current real-world management of chronic HBV infection in the US. Among the 12,608 patients with chronic HBV infection included in our study, 52.3% never had a complete laboratory evaluation and only 73% had an adequate evaluation. Among those who were treatment eligible according to major society guidelines, only 60.4% and 54.3% received treatment within 12 months, respectively.

Potential clinical utility of liquid biopsy in early-stage non-small cell lung cancer.

BACKGROUND: Liquid biopsy has been widely researched for early diagnosis, prognostication and disease monitoring in lung cancer, but there is a need to investigate its clinical utility for early-stage non-small cell lung cancer (NSCLC). METHODS: We performed a meta-analysis and systematic review to evaluate diagnostic and prognostic values of liquid biopsy for early-stage NSCLC, regarding the common biomarkers, circulating tumor cells, circulating tumor DNA (ctDNA), methylation signatures, and microRNAs. Cochrane Library, PubMed, EMBASE databases, ClinicalTrials.gov, and reference lists were searched for eligible studies since inception to 17 May 2022. Sensitivity, specificity and area under the curve (AUC) were assessed for diagnostic values. Hazard ratio (HR) with a 95% confidence interval (CI) was extracted from the recurrence-free survival (RFS) and overall survival (OS) plots for prognostic analysis. Also, potential predictive values and treatment response evaluation were further investigated. RESULTS: In this meta-analysis, there were 34 studies eligible for diagnostic assessment and 21 for prognostic analysis. The estimated diagnostic values of biomarkers for early-stage NSCLC with AUCs ranged from 0.84 to 0.87. The factors TNM stage I, T1 stage, N0 stage, adenocarcinoma, young age, and nonsmoking contributed to a lower tumor burden, with a median cell-free DNA concentration of 8.64 ng/ml. For prognostic analysis, the presence of molecular residual disease (MRD) detection was a strong predictor of disease relapse (RFS, HR, 4.95; 95% CI, 3.06-8.02; p < 0.001) and inferior OS (HR, 3.93; 95% CI, 1.97-7.83; p < 0.001), with average lead time of 179 ± 74 days between molecular recurrence and radiographic progression. Predictive values analysis showed adjuvant therapy significantly benefited the RFS of MRD + patients (HR, 0.27; p < 0.001), while an opposite tendency was detected for MRD - patients (HR, 1.51; p = 0.19). For treatment response evaluation, a strong correlation between pathological response and ctDNA clearance was detected, and both were associated with longer survival after neoadjuvant therapy. CONCLUSIONS: In conclusion, our study indicated liquid biopsy could reliably facilitate more precision and effective management of early-stage NSCLC. Improvement of liquid biopsy techniques and detection approaches and platforms is still needed, and higher-quality trials are required to provide more rigorous evidence prior to their routine clinical application.

Psychopathology and health-related quality of life as patient-reported treatment outcomes: evaluation of concordance between the Brief Symptom Inventory (BSI) and the Short Form-36 (SF-36) in psychiatric outpatients.

PURPOSE: Treatment outcome for common psychiatric disorders, such as mood and anxiety disorders, is usually assessed by self-report measures regarding psychopathology [e.g., via Brief Symptom Inventory (BSI)]. However, health-related quality of life [as measured by the 36-item Short-Form Health Survey (SF-36)] may be a useful supplementary outcome domain for routine outcome monitoring (ROM). To date, the assessment of both outcomes has become fairly commonplace with severe mental illness, but this is not yet the case for common psychiatric disorders. The present study examined among outpatients with common psychiatric disorders whether aggregate assessments of change across treatment regarding psychopathology and health-related quality of life yield similar results and effect sizes. METHODS: We compared treatment outcome on the BSI and the SF-36 in a sample of 13,423 outpatients. The concordance of both instruments was assessed at various time points during treatment. RESULTS: Scores on both instruments were associated, but not so strongly to suggest they measure the same underlying construct. The SF-36 scales presented a varied picture of treatment outcome: understandably, patients changed more on the mental component scales than on physical component scales. Outcome according to the BSI was quite similar to outcome according to scales of the SF-36 that showed the largest change. CONCLUSIONS: Although (mental health) scores on both instruments are associated, adding the SF-36 in addition to the BSI in treatment evaluation research produces valuable information as the SF-36 measures a broader concept and contains physical/functional component scales, resulting in a more complete clinical picture of individual patients.

Establishment and evaluation of retroperitoneal liposarcoma patient-derived xenograft models: an ideal model for preclinical study.

Retroperitoneal liposarcoma (RLPS) is one of the most common subtypes of retroperitoneal soft tissue sarcomas. It is characterized by poor sensitivity to radiotherapy and chemotherapy and a low success rate of complete surgical resection. However, there are few reliable preclinical RLPS models for target discovery and therapy research. In this study, we aimed to establish RLPS patient-derived xenograft (PDX) models that are useful for biological research and preclinical drug trials. A total of 56 freshly resected RLPS tissues were subcutaneously transplanted into non-obese diabetic-severe combined immune deficient (NOD-SCID) mice, with subsequent xenotransplantation into second-generation mice. The tumor engraftment rate of first generation PDXs was 44.64%, and higher success rates were obtained from implantations of dedifferentiated, myxous, pleomorphic, high-grade liposarcomas and those with retroperitoneal organ infiltration. The first- and second- generation PDX models preserved the histopathological morphology, gene mutation profiles and MDM2 amplification of the primary tissues. PDX models can also provide the benefit of retaining original tumor biology and microenvironment characteristics, such as abnormal adipose differentiation, elevated Ki67 levels, high microvessel density, cancer-associated fibroblast presence, and tumor-associated macrophage infiltration. Overall survival (OS) and disease-free survival (DFS) of patients with successful first-generation PDX engraftment were significantly poorer than those with failed engraftment. Treatment with MDM2 inhibitor RG7112 significantly suppressed tumor growth of DDLPS PDX in mice. In conclusion, we successfully established RLPS PDX models that were histologically, genetically, and molecularly consistent with the original tissues. These models might provide opportunities for advancing RLPS tumor biology research, facilitating the development of novel drugs, particularly those targeting MDM2 amplification, adipose differentiation process, angiogenesis, cancer-associated fibroblasts, and so on.

A nationwide registry for recurrent urolithiasis in the upper urinary tract - The RECUR study protocol.

BACKGROUND: Urinary stone disease is a widespread disease with tremendous impact on those affected and on societies around the globe. Nevertheless, clinical and health care research in this area seem to lag far behind cardiovascular diseases or cancer. This may be due to the lack of an immediate deadly threat from the disease and therefore less public and professional interest. However, the patients suffer from recurring, sometimes intense pain and often must be treated in hospital. Long-term morbidity includes doubled rates of chronic kidney disease and arterial hypertension after at least one stone-related event. Observational studies, more specifically, registries and other electronic data sets have been proposed as a means of filling critical gaps in evidence. We propose a nationwide digital and fully automated registry as part of the German Ministry for Education and Research (BMBF) call for the "establishment of model registries". METHODS: RECUR builds on the technical infrastructure of Germany's Medical Informatics Initiative. Local data integration centres (DIC) of participating medical universities will collect pseudonymized and harmonized data from respective hospital information systems. In addition to their clinical data, participants will provide patient reported outcomes using a mobile patient app. Scientific data exploration includes queries and analysis of federated data from DICs of eleven participating sites. All primary patient data will remain at the participating sites at all times. With comprehensive data from this longitudinal registry, we will be able to describe the disease burden, to determine and validate risk factors, and to evaluate treatments. Implementation and operation of the RECUR registry will be funded by the BMBF for five years. Subsequently, the registry is to be continued by the German Society of Urology without significant costs for study personnel. DISCUSSION: The proposed registry will substantially improve the structural and procedural framework for patients with recurrent urolithiasis. This includes advanced diagnostic algorithms and treatment pathways. The registry will help us identify those patients who will most benefit from specific interventions to prevent recurrences. The RECUR study protocol and the registry's technical architecture including full digitalization and automation of almost all registry-associated proceedings can be transferred to future registries. TRIAL REGISTRATION: This study is registered at the German Clinical Trial Register (Deutsches Register Klinischer Studien), DRKS-ID DRKS00026923 , date of registration January, 11th 2022.

The Burden of Care in Nasoalveolar Molding Treatment in Cleft Patients.

Objectives This study, first in Hungary, examined the success of presurgical nasoalveolar molding (NAM) therapy in cleft patients from a caregiver's perspective and revealed factors that can cause inconvenience. Patients and Methods A survey-based study was performed using a 32-item questionnaire following NAM therapy. The survey was sent to families whose child underwent NAM therapy from 2010 until 2020 at the 1st Department of Paediatrics, Semmelweis University. The questions focused on four main parts: socioeconomic, origin of the cleft, difficulties of therapy, and self-assessment. Fifty-three families received the questionnaire, 17 of them completed it. Results The mean age was 5 ± 3.7 weeks when NAM therapy started. Fifty-eight percent of the patients were male and 42% female. Patients are living more than 60 km from the cleft center (59%). Patients had to make the journey between their residence and the cleft center ∼10 to 15 times. In most cases, NAM therapy was covered by health insurance (83%). The unilateral cleft and lip palate occurred 58%, while the bilateral were 42%. Thirty-five percent of the patients had an allergic reaction against the adhesive, and 35% were affected by wounds on their lips or noses. The way of feeding was variable. Seventeen percent of the parents were able to breastfeed. In all cases, parents were satisfied with the NAM therapy. Conclusions The present study highlighted the value of caregivers' role in NAM therapy. The burden of care is acceptable, caregivers have high compliance, and are determined to help the effectiveness of therapy. Limitations of this study include a single-institute data with a small number of cases.

[Concepts and assessment methods in lower urinary tract symptoms: From symptom score to Patient-Reported Outcomes and Outcomes (PRO)]. / Concepts et méthodes d'évaluation en pelvi périnéologie : du score de symptômes aux attentes et résultats rapportés par les patients (PRO).

INTRODUCTION: The evaluation of pelvic perineal treatments has changed significantly in recent years. Initially focused on the assessment of symptoms, quality of life or patient satisfaction, it has gradually turned to new concepts, such as Patient Reported Outcome (PRO) and Goal Attainment (GA). OBJECTIVE: To describe the different concepts and methods of assessment available, in recent years, in the context of urinary functional pathologies such as bladder overactivity or urinary incontinence. METHODS: We conducted a non-systematic literature review to identify the main questionnaires and tools available to evaluate treatment outcomes. Oncology and pediatrics questionnaire has been excluded. RESULTS: In functional pathology (overactive bladder or incontinence), the objective of treatment is to meet the expectations of patients and it is important to be able to assess the feelings of patients. In this context, new specific questionnaires have been developed to evaluate the PROs. For about ten years, these subjective criteria, are more and more widespread in the evaluation of treatments. A new field then appeared, namely Goal Attainment Scaling (GAS) and Self Appreciation Goal Attainment (SAGA), allowing to determine with the patient, the expected objectives of the treatment. CONCLUSION: These concepts of PRO and GAS open up a new domain in the evaluation of treatments, with a subjective view of the results. They deserve to be integrated into the usual, objective evaluations, in order to adapt the treatment of the patients, according to the real impact of the treatment.

Perfusion MRI in treatment evaluation of glioblastomas: Clinical relevance of current and future techniques.

Treatment evaluation of patients with glioblastomas is important to aid in clinical decisions. Conventional MRI with contrast is currently the standard method, but unable to differentiate tumor progression from treatment-related effects. Pseudoprogression appears as new enhancement, and thus mimics tumor progression on conventional MRI. Contrarily, a decrease in enhancement or edema on conventional MRI during antiangiogenic treatment can be due to pseudoresponse and is not necessarily reflective of a favorable outcome. Neovascularization is a hallmark of tumor progression but not for posttherapeutic effects. Perfusion-weighted MRI provides a plethora of additional parameters that can help to identify this neovascularization. This review shows that perfusion MRI aids to identify tumor progression, pseudoprogression, and pseudoresponse. The review provides an overview of the most applicable perfusion MRI methods and their limitations. Finally, future developments and remaining challenges of perfusion MRI in treatment evaluation in neuro-oncology are discussed. Level of Evidence: 3 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;49:11-22.

Lower urinary tract symptoms treatment constraints assessment (LUTS-TCA): a new tool for a global evaluation of neurogenic bladder treatments.

OBJECTIVES: To develop a new tool to assess constraints due to urinary treatments in neurological patients. MATERIALS AND METHODS: A prospective, monocentric study has been conducted from January to May 2017. Out-patients (multiple sclerosis, spinal cord injury, Parkinson disease) were included in a referral center if they had LUTS treatment for at least 3 months. To validate psychometric properties, we conducted a literature review, qualitative interviews, and discussion with a panel of six experts. Comprehension, acceptation, and pertinence were tested by a pilot study. A validation study, designed to calculate content validity, internal consistency reliability, and test-retest reliability [intraclass correlation coefficient (ICC)] has been conducted. The primary outcome was good psychometric properties defined with Cronbach's α > 0.7 and ICC > 0.7. RESULTS: Comprehension, acceptation, and pertinence were excellent. Validation study showed a perfect content validity (r2 = 1) and excellent internal consistency reliability (Cronbach' α = 0.90). Total score was between 0 (best score) to 66 (maximal constraints). Test-retest reliability calculated using ICC was 0.81. Time to fill questionnaire was 4 min 20 s. The final version was composed by 22 items. CONCLUSION: LUTS TCA is the first validated tool to assess constraints of urinary treatment and has excellent psychometric properties.

[Magnetic resonance imaging following cartilage repair of focal chondral lesions]. / Postoperative Bildgebung fokaler Knorpeldefekte mittels Magnetresonanztomographie.

BACKGROUND: Focal cartilage lesions are common pathologies of weight-bearing joints. Clinical presentation ranges from asymptomatic patients to severe, pain-related movement deficits. Moreover, focal chondral lesions are risk factors for the development of osteoarthritis. There are various treatment options involving both surgical and nonsurgical treatments. Musculoskeletal radiologists should be aware of the various surgical options as well as the postsurgical imaging characteristics to depict whether the encountered imaging findings reflect the normal postoperative course or are indicative of a treatment failure. OBJECTIVES: We aim to describe the most common surgical procedures for the repair of focal cartilage lesions and their typical postsurgical appearance on MRI studies. MATERIALS AND METHODS: The literature in PubMed was searched with the terms "focal articular cartilage lesions", "chondral lesions", "MOCART", "Microfracture", "Osteochondral Autograft Transfer", "mosaicplasty", "Osteochondral Allograft Transplantation", "OATS", "OCT", "Autologous Chondrocyte Implantation", "ACI", "Matrix-Assisted Chondrocyte Implantation", "Autologous Matrix-induced Chondrogenesis". RESULTS: Surgical methods for the treatment of focal cartilage lesions as well as the MR imaging features are explained.

Developing more efficient, effective, and disseminable treatments for eating disorders: an overview of the multiphase optimization strategy.

The present manuscript describes the multiphase optimization strategy (MOST) and its potential applications to treatments for eating disorders (EDs). The manuscript describes the three phases of MOST, discusses a hypothetical case example of how MOST could be applied to developing a disseminable ED treatment, and reviews the pros and cons of the MOST approach. Outcomes from treatments for EDs leave room for improvement. However, traditional methods of treatment development and evaluation (i.e., the treatment package approach) make it challenging to determine how best to improve ED treatments. For example, testing full treatment packages in open trials and RCTs without systematic testing of each component is inefficient (as it is unknown which components are effective), and often does not provide concrete future directions for optimization of the treatment. Much stands to be gained by optimizing treatments in the early stages before testing them in open trials or RCTs. MOST is an alternative, engineering-inspired research framework that is well-suited to address the issues of inefficiency associated with the treatment package approach. MOST entails identifying the most promising treatment components for inclusion in interventions, then eliminating or deemphasizing less efficacious/inert components. This strategy results in a treatment comprised of only effective components that can then be tested via RCT. Though the MOST approach has limitations, it has the potential to greatly benefit ED treatment research and is worthy of application in the field.

Post-treatment positron emission tomography-computed tomography is highly predictive of outcome in Plasmablastic lymphoma.

PURPOSE: Plasmablastic lymphoma (PBL) is a rare variant of diffuse large B cell lymphomas (DLBCL) clinically characterized by a poorer prognostic. Few clinical and imaging data are available and derived from pooled case reports and small series. The aim of the study was to evaluate the FDG avidity at baseline and the utility of 18-Fluorodeoxyglucose (FDG) positron-emission-tomography/computed-tomography (PET/CT) for staging and response assessment. METHODS: Patients with newly diagnosed PBL seen at Lymphoma Study Association centers during the period 2005-2015 were included if they underwent a PET/CT at staging and at the end of treatment (eotPET) and had received an anthracycline-based first line therapy. EotPET scans were analyzed using the 5-point-scale visual analysis in accordance with Lugano criteria. Patients were classified in complete metabolic response (CMR) or no-CMR including partial metabolic response (PMR), stable disease (SD) and progression disease (PD). EotPET results were assessed for the ability to predict event free survival (EFS) and overall survival (OS). RESULTS: Thirty-five PBL patients fulfilled the inclusion criteria. The median follow-up was 34 months (2.8-120 months). FDG avidity was found in all patients at diagnosis. Most patients (80%) achieved CMR, and 20% were no-CMR including 9% PMR, 6% SD, and 6% PD. A CMR after first line chemotherapy predicted higher EFS (p < 0.0001) and OS (p = 0.0006). CONCLUSIONS: This study confirmed the FDG avidity of PBL subtype and the usefulness of PET/CT scanning in restaging an aggressive lymphoma at the completion of chemotherapy. EotPET can predict outcomes following treatment in patients with PBL.

3X-Knee: A Novel Technology for 3D Preoperative Planning and Postoperative Evaluation of TKA Based on 2D X-Rays.

This chapter introduces a solution called "3X-knee" that can robustly derive 3D models of the lower extremity from 2D long leg standing X-ray radiographs for preoperative planning and postoperative treatment evaluation of total knee arthroplasty (TKA). There are three core components in 3X-knee technology: (1) a knee joint immobilization apparatus, (2) an X-ray image calibration phantom, and (3) a statistical shape model-based 2D-3D reconstruction algorithm. These three components are integrated in a systematic way in 3X-knee to derive 3D models of the complete lower extremity from 2D long leg standing X-ray radiographs acquired in weight-bearing position. More specifically, the knee joint immobilization apparatus will be used to rigidly fix the X-ray calibration phantom with respect to the underlying anatomy during the image acquisition. The calibration phantom then serves two purposes. For one side, the phantom will allow one to calibrate the projection parameters of any acquired X-ray image. For the other side, the phantom also allowsone to track positions of multiple X-ray images of the underlying anatomy without using any additional positional tracker, which is a prerequisite condition for the third component to compute patient-specific 3D models from 2D X-ray images and the associated statistical shape models. Validation studies conducted on both simulated X-ray images and on patients' X-ray data demonstrate the efficacy of the present solution.

Patient reported outcome measures (PROMs): examination of the psychometric properties of two measures for burden of symptoms and quality of life in patients with depression or anxiety.

INTRODUCTION: Patient-reported outcome measures (PROMs) for anxiety and depressive disorders are an important aspect of measurement-based care. AIM: The aim of the study was to perform a clinimetric analysis of two PROMs scales in patents with depression and anxiety. METHODS: Patients completed a 10-item version (SCL-10) of the Symptom Checklist to measure burden of symptoms and a brief 5-item version of World Health Organization Well-being scale (WHO-5) to measure quality of life. T-scores were used to standardize the SCL-10 and WHO-5 in terms of being in need of treatment. The coefficient of alpha and the coefficient of homogeneity were used to evaluate the internal consistency or scalability respectively of SCL-10 and WHO-5. Effect size statistics and Spearman correlation coefficients were used to measure the effect of gender and age, respectively. RESULTS: A total of 801 patients were recruited from two Danish mental health centers with anxiety or depression. The standardization of the SCL-10 and WHO-5 by T-scores indicated that a T-score of 65 corresponding to being moderately in need of treatment and a T-score of 75 to be severely in need of treatment. The coefficient of alpha and the coefficient of homogeneity were both found acceptable for SCL-10 and WHO-5. No gender or age factors were found being in operation. CONCLUSION: The results from the current study supported the use of the SCL-10 and WHO-5 as potential PROMs to capture symptom burden and quality of life within groups of people with anxiety or depression undergoing psychotherapy treatment.

[Therapy drop-out as a predictor of re-delinquency : Legal probation of substance addicted patients according to §64 of the German Legal Code]. / Therapieabbruch als Prädiktor erneuter Straftaten : Legalbewährung von Patienten nach Unterbringungen gemäß § 64 StGB.

BACKGROUND: Recidivism rates in substance-addicted patients placed in institutions according to §64 of the German legal code are approximately 50%, 3 years after discharge from inpatient treatment. The recidivism rates of patients with premature termination of inpatient treatment who had then been referred back to prison and were finally discharged into the community are unknown. RESEARCH QUESTION: Is premature termination of treatment a risk factor for recidivism? METHODS: Patients released from forensic treatment according to § 64 of the German legal code were followed up for violent and non-violent recidivism. Full data were acquired for Baden-Württemberg patients released in 2010 and 2011 with regular vs. premature termination of treatment. RESULTS: All measures revealed highly significant group differences: 48% of the patients discharged after subsequent prison sentences recidivated within the first year and 73% within 3 years after discharge. Among recidivists, the severity of offences was much higher (odds ratio > 3.8 each). Regularly discharged patients also re-offended to a remarkable extent (50%). DISCUSSION: Patients serving prison sentences after unsuccessful forensic treatment are a high-risk group for recidivism. Alternative concepts of clinical and legal treatment of this group should be developed.

A systematic review of the clinical presentation, treatment and relapse characteristics of human Plasmodium ovale malaria.

BACKGROUND: Despite increased efforts to control and ultimately eradicate human malaria, Plasmodium ovale malaria is for the most part outside the focus of research or public health programmes. Importantly, the understanding of P. ovale-nowadays regarded as the two distinct species P. ovale wallikeri and P. ovale curtisi-largely stems from case reports and case series lacking study designs providing high quality evidence. Consecutively, there is a lack of systematic evaluation of the clinical presentation, appropriate treatment and relapse characteristics of P. ovale malaria. The aim of this systematic review is to provide a systematic appraisal of the current evidence for severe manifestations, relapse characteristics and treatment options for human P. ovale malaria. METHODS AND RESULTS: This systematic review was performed according to the PRISMA guidelines and registered in the international prospective register for systematic reviews (PROSPERO 2016:CRD42016039214). P. ovale mono-infection was a strict inclusion criterion. Of 3454 articles identified by the literature search, 33 articles published between 1922 and 2015 met the inclusion criteria. These articles did not include randomized controlled trials. Five prospective uncontrolled clinical trials were performed on a total of 58 participants. P. ovale was sensitive to all tested drugs within the follow-up periods and on interpretable in vitro assays. Since its first description in 1922, only 18 relapsing cases of P. ovale with a total of 28 relapse events were identified in the scientific literature. There was however no molecular evidence for a causal relationship between dormant liver stages and subsequent relapses. A total of 22 severe cases of P. ovale malaria were published out of which five were fatal. Additionally, two cases of congenital P. ovale malaria were reported. CONCLUSIONS: Current knowledge of P. ovale malaria is based on small trials with minor impact, case reports and clinical observations. This systematic review highlights that P. ovale is capable of causing severe disease, severe congenital malaria and may even lead to death. Evidence for relapses in patients with P. ovale malaria adds up to only a handful of cases. Nearly 100 years after P. ovale's first description by Stephens the evidence for the clinical characteristics, relapse potential and optimal treatments for P. ovale malaria is still scarce.

Gait characterization in golden retriever muscular dystrophy dogs using linear discriminant analysis.

BACKGROUND: Accelerometric analysis of gait abnormalities in golden retriever muscular dystrophy (GRMD) dogs is of limited sensitivity, and produces highly complex data. The use of discriminant analysis may enable simpler and more sensitive evaluation of treatment benefits in this important preclinical model. METHODS: Accelerometry was performed twice monthly between the ages of 2 and 12 months on 8 healthy and 20 GRMD dogs. Seven accelerometric parameters were analysed using linear discriminant analysis (LDA). Manipulation of the dependent and independent variables produced three distinct models. The ability of each model to detect gait alterations and their pattern change with age was tested using a leave-one-out cross-validation approach. RESULTS: Selecting genotype (healthy or GRMD) as the dependent variable resulted in a model (Model 1) allowing a good discrimination between the gait phenotype of GRMD and healthy dogs. However, this model was not sufficiently representative of the disease progression. In Model 2, age in months was added as a supplementary dependent variable (GRMD_2 to GRMD_12 and Healthy_2 to Healthy_9.5), resulting in a high overall misclassification rate (83.2%). To improve accuracy, a third model (Model 3) was created in which age was also included as an explanatory variable. This resulted in an overall misclassification rate lower than 12%. Model 3 was evaluated using blinded data pertaining to 81 healthy and GRMD dogs. In all but one case, the model correctly matched gait phenotype to the actual genotype. Finally, we used Model 3 to reanalyse data from a previous study regarding the effects of immunosuppressive treatments on muscular dystrophy in GRMD dogs. Our model identified significant effect of immunosuppressive treatments on gait quality, corroborating the original findings, with the added advantages of direct statistical analysis with greater sensitivity and more comprehensible data representation. CONCLUSIONS: Gait analysis using LDA allows for improved analysis of accelerometry data by applying a decision-making analysis approach to the evaluation of preclinical treatment benefits in GRMD dogs.