Catheter ablation for atrial fibrillation in elderly patients: an updated meta-analysis of comparative studies.

BACKGROUND: Age is a relevant risk factor for the development of atrial fibrillation (AF) and is associated with increased recurrence rates in the setting of rhythm-control. Catheter ablation is increasingly advocated in elderly despite conflicting data regarding its efficacy and safety in this patient cohort. Therefore, we aimed to analyze currently available evidence regarding catheter ablation for AF in patients ≥75 years compared to younger patients. METHODS: We performed a systematic literature search and meta-analysis on efficacy and safety of catheter ablation in patients ≥75 years with AF. Primary efficacy and safety endpoints were: first recurrence of atrial arrhythmia following first-time ablation and occurrence of death, stroke, or any procedure-related complication. Secondary outcomes included procedure and fluoroscopy time. RESULTS: We identified 301 potentially relevant studies of which 39 underwent detailed analysis. A total of 19 studies (MINORS score ≥13) reporting on 108,419 patients (101,844 <75 years, 6,575 ≥75 years) undergoing first-time catheter ablation for AF were included. Risk of arrhythmia recurrence following catheter ablation (39% vs. 32%; RR [95% CI] 1.24 [1.09-1.41]; P=0.001) and occurrence of safety endpoints (10.8% vs. 8.5%; RR [95% CI] 1.64 [1.53-1.76], P<0.00001) were significantly higher in patients ≥ 75 years compared to younger patients. There was no difference concerning procedure (P=0.33) or fluoroscopy time (P=0.91) between younger and elderly patients. CONCLUSION: In patients ≥75 years of age catheter ablation for AF has higher risk of arrhythmia recurrence and is associated with an increased risk of procedure-related complications and safety endpoint occurrence compared to younger patients.

Changes in modifiable risk factors in women at increased risk for breast and ovarian cancer during the COVID-19 pandemic.

Background: Modifiable lifestyle factors exert a substantial influence on the development of various diseases. The COVID-19 pandemic necessitated the implementation of containment measures to mitigate the viral spread, which affected the maintenance of healthy habits. Methods: Changes in lifestyle factors (e.g. physical activity, nutrition, smoking, drinking alcohol) within a cohort of German women at increased risk of breast cancer (BC) or ovarian cancer (OC) were evaluated through an anonymous web-based survey. The self-reported assessment of mental health was conducted using the PHQ-4 questionnaire. This tool combines two items from the Patient Health Questionnaire for Depression (PHQ-2) and two queries from the Generalized Anxiety Disorder Scale (GAD-2). Potential predictors of lifestyle changes were determined via multiple logistic regression analysis. A heuristic model was employed to project potential long-term consequences on BC incidence. Results: During the pandemic, 41.6 % of respondents reported reduced engagement in physical activity (PA), whereas 14.3 % reported increased engagement in PA. A score ≥5 on the PHQ-2 scale emerged as an independent risk factor for reduced PA (OR 12.719; 95 % CI 1.089-148.549; p = 0.043). By the heuristic approach, we projected an increase of BC by 3384 cases in Germany by 2030, which is attributable to the alterations in PA patterns during the pandemic. Discussion: Impaired mental health during the pandemic constituted a risk factor for unfavorable changes in PA. Consequently, a surge in BC may arise due to decreased engagement in PA. Healthcare professionals must remain aware of the potential risk factors that facilitate adverse alterations in modifiable risk factors caused by pandemic-related contingency measures or similar future events.

Pulmonary Vein Isolation or Pace and Ablate in Elderly Patients With Persistent Atrial Fibrillation (ABLATE Versus PACE)-Rationale, Methods, and Design.

Age is a major risk-factor for atrial fibrillation (AF) and associated hospitalisations. With increasing emphasis on rhythm control, pulmonary vein isolation (PVI) is often suggested, even to elderly patients (≥ 75 years of age). Efficacy of PVI aiming at rhythm control is limited in persistent AF. Pacemaker implantation with atrioventricular node (AVN) ablation may represent a reasonable alternative, with the aim of controlling symptoms and improving quality of life in elderly patients. In this investigator-initiated, randomised, multicentre trial, we test the hypothesis that pacemaker implantation and AVN ablation provides superior symptom control over PVI in elderly patients with symptomatic persistent AF, without any increase in adverse event profile. In the ABLATE Versus PACE (NCT04906668) prospective open-label superiority trial, 196 elderly patients with normal ejection fraction and symptomatic persistent AF despite guideline-indicated medical therapy will be randomised to either cryoballoon PVI (ABLATE) or dual-chamber pacemaker implantation with subsequent AVN ablation (PACE), and followed for a minimum of 12 months. The primary efficacy outcome is a composite end point of rehospitalisation for atrial arrhythmia or cardiac decompensation/heart failure, (outpatient) electrical cardioversion, or upgrade to cardiac resynchronisation therapy owing to worsening of left ventricular ejection fraction to ≤ 35%. Secondary end points include death from any cause, stroke, quality of life, and procedure-related complications. Sample size is designed to achieve 80% power for the primary end point (2-tailed alpha of 5%). ABLATE Versus PACE will determine whether pacemaker implantation and AVN ablation can improve symptom-control in elderly patients with persistent AF over PVI without increasing safety end points.

Real-world data on polysomnography- and patient-reported outcomes in hypoglossal nerve stimulation and auto-titrating positive airway pressure therapy for obstructive sleep apnea.

BACKGROUND: Few data are available comparing first-line positive airway pressure (PAP) therapy of obstructive sleep apnea (OSA), especially auto-adjusting PAP (aPAP), with second-line hypoglossal nerve stimulation (HGNS) therapy. The aim of this study was to directly compare these therapeutic options by standard polysomnography (PSG)-related parameters and patient-reported outcomes in comparable groups. METHODS: 20 patients (aged 57.30 ± 8.56 years; 6 female) were included in the HGNS and 35 patients (aged 56.83 ± 9.20 years; 9 female) were included in the aPAP group. In both groups participants had to fit the current guideline criteria for HGNS treatment. Groups were compared by analysis of covariance (ANCOVA) using inverse propensity score weighting. RESULTS: Propensity scores did not differ between groups. Pre-therapeutic AHI (HGNS: 40.22 ± 12.78/h; aPAP: 39.23 ± 12.33/h) and ODI (HGNS: 37.9 ± 14.7/h, aPAP: 34.58 ± 14.74/h) were comparable between the groups. After 413.6 ± 116.66 days (HGNS) and 162.09 ± 140.58 days (aPAP) of treatment AHI (HGNS: 30.22 ± 17.65/h, aPAP group: 4.71 ± 3.42/h; p < 0.001) was significantly higher in the HGNS group compared to the aPAP group. However, epworth sleepiness scale (ESS) was post-interventionally significantly lower in the HGNS group compared to the aPAP group (pretherapeutic: HGNS: 13.32 ± 5.81 points, aPAP: 9.09 ± 4.71 points; posttherapeutic: HGNS: 7.17 ± 5.06 points; aPAP: 8.38 ± 5.41 points; p < 0.01). CONCLUSION: These are novel real-world data. More research on the key parameters regarding titration of the HGNS neurostimulation parameter tuning and on the impact of factors influencing HGNS adherence is needed.

Angiotensin Receptor-Neprilysin Inhibitor Is Associated With Improved Cardiac Autonomic Function in Heart Failure.

BACKGROUND: Heart failure with reduced ejection fraction is associated with potentially deleterious imbalance of the cardiac autonomic nervous system. Sacubitril/valsartan (angiotensin receptor-neprilysin inhibitor [ARNI]) reduces cardiovascular mortality and hospitalization for heart failure with reduced ejection fraction. Whether ARNI affects the cardiac autonomic nervous system has not been studied. METHODS AND RESULTS: This investigator-initiated, prospective, single-center cohort study compared heart rate (HR) variability, HR, deceleration capacity, and periodic repolarization dynamics as noninvasive measures of the cardiac autonomic nervous system before and after initiation of ARNI therapy. Patients underwent standardized 12-lead Holter-ECG, echocardiography and laboratory testing before and 3 months after start of therapy. End points were changes in HR variability (SD of normal-to-normal intervals, mean square of differences between consecutive R-R intervals), HR, deceleration capacity, and periodic repolarization dynamics as well as ventricular function and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Of 63 patients with heart failure with reduced ejection fraction enrolled, 48 (76.2%) patients were still on ARNI at follow-up. SD of normal-to-normal intervals increased from 25 to 36 milliseconds (P<0.001), mean square of differences between consecutive R-R intervals increased from 12 to 19 milliseconds (P<0.001), HR decreased from 73±9 bpm to 67±4 bpm, (P<0.001), and deceleration capacity increased from 2.1 to 4.4 milliseconds (P<0.001). A trend for periodic repolarization dynamics reduction was observed (5.6 deg2 versus 4.7 deg2, P=0.09). Autonomic changes were accompanied by increased left ventricular ejection fraction (29±6% versus 40±8%, P<0.001) and reduced NT-proBNP (3548 versus 685 ng/L, P<0.001). Correlation analysis showed a significant relationship between volume-unloading (as evidenced by NT-proBNP reduction) and autonomic improvement. CONCLUSIONS: Three months of ARNI therapy resulted in a significant increase in cardiac parasympathetic tone. The improvement in autonomic properties may be mediated by "volume unloading" and likely contributes to the beneficial effects of ARNI in heart failure with reduced ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04587947.

Study draft: "UVC-You Will See" study: longer vs. shorter umbilical venous catheter (UVC) dwell time (6-10 vs. 1-5 days) in very premature infants with birth weight < 1250 g and/or gestational age < 30 weeks.

BACKGROUND: Umbilical venous catheters (UVCs) are often used in preterm infants. Their use is associated with complications (infections, clot formation, organ injury). Very preterm infants with acquired bloodstream infection are at a higher risk for death and important morbidities (e.g., adverse neurodevelopmental outcomes). It is standard clinical practice to remove UVCs in the first days of life. Replacement of intravenous access is often performed using percutaneously inserted central catheters (PICCs). It is unclear whether serial central line use affects the rates of catheter-related complications. METHODS: A multicenter randomized controlled trial (random group assignment) was performed in 562 very premature (gestational age < 30 weeks) and/or very low birth weight infants (< 1250 g) requiring an UVC for administration of parenteral nutrition and/or drugs. Group allocation was random. HYPOTHESIS: A UVC dwell time of 6-10 days (281 infants) is not associated with an increased rate of central venous catheter (UVC, PICC)-related complications compared to 1-5 days (281 infants), and a longer UVC dwell time will significantly reduce the number of painful, invasive procedures associated with the need for vascular access as well as radiation exposure, use of antibiotics, and medical costs. PRIMARY OUTCOME PARAMETER: The number of catheter-related bloodstream infections and/or catheter-related thromboses and/or catheter-associated organ injuries related to the use of UVC/PICC was the primary outcome. CONCLUSION: Extending the UVC dwell time may significantly reduce the number of painful invasive procedures, with the potential to positively impact not only long-term pain perception but also important social competencies (attention, learning, and behavior). Thus, the "UVC-You Will See" study has the potential to substantially change current neonatal intensive care practice.

Comparative Retrospective Assessment of the Effectiveness and Risk Factors of Fluoroquinolones, Cephalosporines, and Selective Antibiotic Prophylaxis for Transrectal Prostate Biopsy.

INTRODUCTION: Despite increasing resistance of enterobacteria against fluoroquinolones (FLU), they are still widely used during transrectal prostate biopsy (TRPB). This study was designed to analyse infectious complications and risk factors between FLU, cephalosporines (CEPH) and selective other antibiotics (O-AB) used during TRPB. METHODS: 664 patients were included retrospectively (152 FLU, 452 CEPH and 60 O-AB). Infectious complications were defined as fever >38.0°C, the in-house definition of complicated urinary tract infection (cUTI) (if all applied: fever >38.0°C, leucocytosis >11.000/µL and positive urine dipstick) or postinterventional bacteriuria. Hospitalisation rate, duration and comorbidities were also assessed. χ2 and Fisher's exact test were used for group comparison. Multivariate regression analysis assessed the association of comorbidities with infectious complications. RESULTS: FLU and CEPH were indifferent regarding infectious complications, however in the O-AB group significantly more common compared to FLU and CEPH (11.6, 13.3, 25%, p < 0.05). Duration of hospital stay in CEPH was significantly shorter compared to FLU and O-AB (4.1 vs. 6.3 vs. 8.2 days, p < 0.05). Arterial hypertension showed increased association with fever (OR 6.002 (1.178; 30.597) p = 0.031) and cUTI (OR 6.006 (1.207; 29.891) p = 0.029). CONCLUSION: Infectious complications were low and indifferent between FLU and CEPH but significantly more frequent in O-AB. Arterial hypertension was significantly associated with postinterventional fever and cUTI.

Early postnatal high-dose fat-soluble enteral vitamin A supplementation for moderate or severe bronchopulmonary dysplasia or death in extremely low birthweight infants (NeoVitaA): a multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial.

BACKGROUND: Vitamin A plays a key role in lung development, but there is no consensus regarding the optimal vitamin A dose and administration route in extremely low birthweight (ELBW) infants. We aimed to assess whether early postnatal additional high-dose fat-soluble enteral vitamin A supplementation versus placebo would lower the rate of moderate or severe bronchopulmonary dysplasia or death in ELBW infants receiving recommended basic enteral vitamin A supplementation. METHODS: This prospective, multicentre, randomised, parallel-group, double-blind, placebo-controlled, investigator-initiated phase 3 trial conducted at 29 neonatal intensive care units in Austria and Germany assessed early high-dose enteral vitamin A supplementation (5000 international units [IU]/kg per day) or placebo (peanut oil) for 28 days in ELBW infants. Eligible infants had a birthweight of more than 400 g and less than 1000 g; gestational age at birth of 32+0 weeks postmenstrual age or younger; and the need for mechanical ventilation, non-invasive respiratory support, or supplemental oxygen within the first 72 h of postnatal age after admission to the neonatal intensive care unit. Participants were randomly assigned by block randomisation with variable block sizes (two and four). All participants received basic vitamin A supplementation (1000 IU/kg per day). The composite primary endpoint was moderate or severe bronchopulmonary dysplasia or death at 36 weeks postmenstrual age, analysed in the intention-to-treat population. This trial was registered with EudraCT, 2013-001998-24. FINDINGS: Between March 2, 2015, and Feb 27, 2022, 3066 infants were screened for eligibility at the participating centres. 915 infants were included and randomly assigned to the high-dose vitamin A group (n=449) or the control group (n=466). Mean gestational age was 26·5 weeks (SD 2·0) and mean birthweight was 765 g (162). Moderate or severe bronchopulmonary dysplasia or death occurred in 171 (38%) of 449 infants in the high-dose vitamin A group versus 178 (38%) of 466 infants in the control group (adjusted odds ratio 0·99, 95% CI 0·73-1·55). The number of participants with at least one adverse event was similar between groups (256 [57%] of 449 in the high-dose vitamin A group and 281 [60%] of 466 in the control group). Serum retinol concentrations at baseline, at the end of intervention, and at 36 weeks postmenstrual age were similar in the two groups. INTERPRETATION: Early postnatal high-dose fat-soluble enteral vitamin A supplementation in ELBW infants was safe, but did not change the rate of moderate or severe bronchopulmonary dysplasia or death and did not substantially increase serum retinol concentrations. FUNDING: Deutsche Forschungsgemeinschaft and European Clinical Research Infrastructures Network (ECRIN).

Individualized center-based analysis of urinary and sexual functional outcome after radical prostatectomy based on the prostate cancer outcome study: a post hoc pathway to patient outcome measurement analysis for quality improvement.

PURPOSE: We evaluate differences of patient-reported outcome measurements (PROM) based urinary continence and sexual function 12 months after radical prostatectomy (RPE) based on perioperative, surgical, and patient-specific characteristics in a large European academic urology center. MATERIALS AND METHODS: All men enrolled in the Prostate Cancer Outcome Study (PCO) study who were treated with RPE between 2017 and 2021 completed EPIC-26 information surveys before and 12 months after RPE. Survey data were linked to clinical data of our institution. Logistic regression analyses were performed to examine the correlation between individual surgeons, patient characteristics, patient clinical data, and their urinary continence and sexual function. RESULTS: In total, data of 429 men were analyzed: unstratified mean (SD) EPIC-26 domain score for urinary function decreased from 93.3 (0.7) to 60.4 (1.5) one year after RPE, respectively for sexual function from 64.95 (1.6) to 23.24 (1.1). Patients with preoperative adequate urinary function (EPIC-26 score > 80) reported significantly different mean urinary function scores between 53.35 (28.88) and 66.25 (25.15), p= 0.001, stratified by surgeons experience. On binary logistic regression analyses, only nerve sparing techniques (OR: 1,83, 95% CI: 1.01;3.21; p = 0.045) and low body mass index (OR: 0.91, CI: 0.85;0.99, p= 0.032) predicted adequate postoperative urinary function. CONCLUSIONS: The results show how using provider-specific data from a larger cohort study enables to develop institution-specific analysis for functional outcomes after RPE. These models can be used for internal quality improvement as well as enhanced and provider-specific patient communication and shared decision making.

Proximal humeral fractures in children - controversies in decision making.

BACKGROUND: Proximal humeral fractures in children are rare and usually treated non-operatively, especially in children younger than ten. The decision between operative and non-operative treatment is mostly based on age and fracture angulation. In the current literature, diverging recommendations regarding fracture angulation that is still tolerable for non-operative treatment can be found. Besides, there is no consensus on how fracture angulation should be determined. This study aimed to determine whether leading experts in pediatric trauma surgery in Germany showed agreement concerning the measurement of fracture angulation, deciding between operative and non-operative treatment, and choosing a treatment modality. METHODS: Twenty radiographs showing a proximal humeral fracture and the patient's age were assessed twice by twenty-two senior members of the "Section of Pediatric Traumatology of the German Association for Trauma Surgery". Experts determined the fracture angulation and chose between several operative and non-operative treatment modalities. The mean of individual standard deviations was calculated to estimate the accuracy of single measurements for fracture angulation. Besides Intra-Class Correlation and Fleiss' Kappa coefficients were determined. RESULTS: For fracture angulation, experts showed moderate (ICC = 0.60) interobserver and excellent (ICC = 0.90) intraobserver agreement. For the treatment decision, there was fair (Kappa = 0.38) interobserver and substantial (Kappa = 0.77) intraobserver agreement. Finally, experts preferred ESIN over K-wires for operative and a Gilchrist over a Cuff/Collar for non-operative treatment. CONCLUSIONS: Firstly, there is a need for consensus among experts on how fracture angulation in PHFs in children should be reliably determined. Our data indicate that choosing one method everybody agrees to use could be more helpful than using the most sophisticated. However, the overall importance of fracture angulation should also be critically discussed. Finally, experts should agree on treatment algorithms that could translate into guidelines to standardize the care and perform reliable outcome studies. LEVEL OF EVIDENCE: III.

Bright Light Therapy as Add-On to Inpatient Treatment in Youth With Moderate to Severe Depression: A Randomized Clinical Trial.

Importance: Major depressive disorder is one of the most common mental disorders among adolescents, entailing severe, long-term psychosocial impairment and a high risk of chronicity. In view of the large number of patients requiring treatment, along with insufficient treatment responses with small effect sizes, innovative adjunctive treatment strategies are urgently needed. Objective: To investigate whether the effect of adolescent psychiatric inpatient treatment as usual for major depressive disorder can be enhanced by simultaneous use of morning bright light therapy. Design, Setting, and Participants: This was a double-blind, placebo-controlled randomized parallel-group trial with enrollment between March 2018 and November 2020 and follow-up completed in May 2021. The study took place among inpatients at 4 university hospitals for child and adolescent psychiatry across Germany. Of 248 eligible youth aged 12 to 18 years fulfilling ICD-10 criteria for major depressive disorder, 227 were randomized to bright light therapy (n = 116) or placebo red light (n = 111); 151 participants completed the study. Interventions: Up to 20 sessions of either morning bright light therapy with an intensity of 10 000 lux or placebo red light (100 lux) in addition to multimodal inpatient treatment as usual over 4 weeks. Main Outcomes and Measures: The primary outcome was the change in Beck Depression Inventory-II (BDI-II) score from baseline to posttreatment in the intention-to-treat sample. Results: Among the 224 patients included in the intention-to-treat analyses (192 girls and 32 boys; mean [SD] age, 15.5 [1.4] years), the mean (SD) BDI-II score at baseline was 37.3 (8.7). BDI-II scores were significantly reduced after 4 weeks (postassessment) by a mean of -7.5 (95% CI, -9.0 to -6.0; Hedges g = 0.71). Bright light therapy had no impact on this change (no significant group × time effect). Loss to follow-up was 31% (n = 69) at 16 weeks and 49% (n = 110) at 28 weeks. There were 10 serious adverse events throughout the whole trial, which were not considered related to study treatment. Conclusions and Relevance: The findings in this study did not indicate superiority of bright light therapy over placebo red light therapy in a large sample of adolescent inpatients with moderate or severe major depressive disorder. Both groups benefited equally from treatment as usual, showing relevant symptom reduction. Trial Registration: German Clinical Trials Register: DRKS00013188.

Pulmonary Vein Isolation in Elderly Patients ≥ 75 Years: A Propensity Score-Matched Analysis With Focus on Differences Among Atrial Fibrillation Types.

BACKGROUND: Age is a major risk factor for development of atrial fibrillation (AF) and associated with increased recurrence rates in the setting of rhythm control. Current data tend to support catheter ablation in elderly patients, but uncertainties exist regarding efficacy and safety of ablation in elderly patients. METHODS: This was a prospective single-centre observational study with propensity score matching (PSM) to investigate the influence of age on efficacy and safety of cryoballoon ablation (CBA) stratified by age (< 75 years vs ≥ 75 years) and AF phenotype (paroxysmal vs persistent). Primary efficacy endpoint was recurrence of atrial arrhythmia after a 90-day blanking period. Safety endpoints were death, stroke, or procedure-associated complications. RESULTS: Consecutive patients (n = 953) underwent CBA for first-time AF ablation. Median follow-up was 18 months. By means of PSM, 268 matches were formed. At 1 year, primary efficacy endpoint occurred in 22.4% of young vs 33.2% of elderly patients, including both AF phenotypes (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.47-0.90; P = 0.01). AF relapse occurred in 19.7% of young vs 28.5% of elderly patients with paroxysmal (HR, 0.63; 95% CI, 0.40-0.99; P = 0.046) compared with 25.9% (30 of 116, young) vs 38.8% (45 of 116, elderly) patients with persistent AF (HR, 0.62; 95% CI, 0.39-0.97; P = 0.038). No difference was observed regarding the incidence of safety endpoints between young and elderly patients (P = 0.38). CONCLUSIONS: CBA is associated with higher recurrence rates in elderly (≥ 75 years) than in younger patients, with highest recurrence rates in elderly patients with persistent AF.

Development and evaluation of an internet- and mobile-based intervention for individualized return to work planning after inpatient rehabilitation - Study protocol for a randomized-controlled-trial.

Background: Following discharge, it is crucial for patients to transfer intentions and action plans from inpatient rehabilitation into everyday life. This ensures their reintegration into social and working life and prevents economic costs due to sick leave or reduced earning capacity pension. However, most established aftercare programs do not specifically address occupational problems or challenges during occupational measures such as graded return to work. The aim of this study is to evaluate the efficacy of the low-threshold online self-help intervention marena (Meine Arbeitsbezogene Reha-Nachsorge - My Work-related Rehabilitation Aftercare) to support return to work. Methods: A two-arm randomized-controlled-trial (RCT) will be conducted. A total of N = 400 rehabilitation inpatients across different indication areas (psychosomatic, orthopedic, or cardiologic) aged 18 to 65 years with a planned return to work after medical rehabilitation, have a heightened social-medical risk and private internet access and are insured with the German Pension insurance or statutory health insurance, will be recruited in four medical and psychosomatic clinics in Germany. Participants will be allocated to either the intervention (IG) or the control group (CG). In a stepped-care model, participants of the IG will receive access to the non-guided internet- and mobile-based intervention marena (IG subgroup 1) or marena in combination with GSA-Online plus (IG subgroup 2), a guided psychodynamic internet-based intervention that has proven effective in two trials regarding occupational and health objectives. Based on a priori defined indication criteria, clinic staff will recommend either IG subgroup 1 or IG subgroup 2. The CG will receive optimized treatment as usual with access to a survey feature within marena. The primary outcome will be work status after 6 months (T2) and 12 months (T4). The endpoint at 12 months (T4) after discharge from inpatient rehabilitation will be considered as secondary endpoint. Work status is defined as positive if the participant is working and has ≤ 6 weeks of sick leave at T2 and ≤ 12 weeks of sick leave at T4. Secondary outcomes include successful completion of graded return to work, successful application for benefits for participation in working life, current work ability, social-medical risk, subjective prognosis of future employment, quality of life, somatic symptoms, coping, social support, depression, anxiety, and psychosocial stress. Discussion: This study will contribute to the evidence concerning efficacy of online aftercare interventions. If proven efficacious, marena could provide an individualized and adaptable self-help approach to promote return to work following inpatient rehabilitation.

ERASURE: early autologous blood pleurodesis for postoperative air leaks-a randomized, controlled trial comparing prophylactic autologous blood pleurodesis versus standard watch and wait treatment for postoperative air leaks following thoracoscopic anatomic lung resections.

BACKGROUND: The prolonged air leak is probably the most common complication following lung resections. Around 10-20% of the patients who undergo a lung resection will eventually develop a prolonged air leak. The definition of a prolonged air leak varies between an air leak, which is evident after the fifth, seventh or even tenth postoperative day to every air leak that prolongs the hospital stay. However, the postoperative hospital stay following a thoracoscopic lobectomy can be as short as 2 days, making the above definitions sound outdated. The treatment of these air leaks is also very versatile. One of the broadly accepted treatment options is the autologous blood pleurodesis or "blood patch". The purpose of this trial is to investigate the impact of a prophylactic autologous blood pleurodesis on reducing the duration of the postoperative air leak and therefore prevent the air leak from becoming prolonged. METHODS: Patients undergoing an elective thoracoscopic anatomic lung resection for primary lung cancer or metastatic disease will be eligible for recruitment. Patients with an air leak of > 100 ml/min within 6 h prior to the morning round on the second postoperative day will be eligible for inclusion in the study and randomization. Patients will be randomized to either blood pleurodesis or watchful waiting. The primary endpoint is the time to drain removal measured in full days. The trial ends on the seventh postoperative day. DISCUSSION: The early autologous blood pleurodesis could lead to a faster cessation of the air leak and therefore to a faster removal of the drain. A faster removal of the drain would relieve the patient from all the well-known drain-associated complications (longer hospital stay, stronger postoperative pain, risk of drain-associated infection, etc.). From the economical point of view, faster drain removal would reduce the hospital costs as well as the costs associated with the care of a patient with a chest drain in an outpatient setting. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00030810. 27 December 2022.

Development and validation of a multivariable risk prediction model for hepatic steatosis in patients with HIV infection.

OBJECTIVE: Early detection of hepatic steatosis in people with HIV (PWH) could prevent progression and inflammation. The aim was to develop and validate a multivariable risk prediction model for hepatic steatosis in German PWH. DESIGN: In this cohort study, 282 PWH were prospectively enrolled, and hepatic steatosis was defined via controlled attenuation parameter (CAP; ≥275 dB/m) using vibration-controlled transient elastography. METHODS: Three multivariable logistic regression models were conducted. Missing values were imputed with multiple imputation. Cut-offs were derived based on Youden-Indices. Performance was assessed via discriminatory and calibrative ability and accuracy via Brier Skill Score. Sensitivity, specificity, and predictive values were calculated. Internal validation was performed via bootstrapping. RESULTS: The prevalence of hepatic steatosis was 35.3% (100/282). Univariate analyses revealed associations with age, waist circumference, BMI, hypertension, hyperlipidemia and gamma-gt. In multivariable analyses, male sex [odds ratio (OR) 2.07, 95% confidence interval (CI) 1.42-3.00, P  = 0.001] and BMI (OR 1.27, 95% CI 1.18-1.36, P  < 0.001) were identified as independent predictors of hepatic steatosis. The naive and optimism-corrected c -statistic of 79% showed a good discriminatory ability, the calibration was well with a slight tendency for overestimation for predicted probabilities above 70%. At the cutoff of 1.95, the specificity was 71% and the negative-predictive value 82.3%. Twenty-seven percent of the 282 patients would be misclassified, 17% as false positives and 10% as false negatives. CONCLUSION: The developed prediction model contributes to the lack of validated noninvasive tools to predict hepatic steatosis in people with HIV. Future studies should include more candidate predictors and externally validate the model.

Recruitment of Patients With Cancer for a Clinical Trial Evaluating a Web-Based Psycho-Oncological Intervention: Secondary Analysis of a Diversified Recruitment Strategy in a Randomized Controlled Trial.

BACKGROUND: Participant recruitment poses challenges in psycho-oncological intervention research, such as psycho-oncological web-based intervention studies. Strict consecutive recruitment in clinical settings provides important methodological benefits but is often associated with low response rates and reduced practicability and ecological validity. In addition to preexisting recruitment barriers, the protective measures owing to the COVID-19 pandemic restricted recruitment activities in the clinical setting since March 2020. OBJECTIVE: This study aims to outline the recruitment strategy for a randomized controlled trial evaluating the unguided emotion-based psycho-oncological online self-help (epos), which combined traditional and web-based recruitment. METHODS: We developed a combined recruitment strategy including traditional (eg, recruitment in clinics, medical practices, cancer counseling centers, and newspapers) and web-based recruitment (Instagram, Facebook, and web pages). Recruitment was conducted between May 2020 and September 2021. Eligible participants for this study were adult patients with any type of cancer who were currently receiving treatment or in posttreatment care. They were also required to have a good command of the German language and access to a device suitable for web-based interventions, such as a laptop or computer. RESULTS: We analyzed data from 304 participants who were enrolled in a 17-month recruitment period using various recruitment strategies. Web-based and traditional recruitment strategies led to comparable numbers of participants (151/304, 49.7% vs 153/304, 50.3%). However, web-based recruitment required much less effort. Regardless of the recruitment strategy, the total sample did not accurately represent patients with cancer currently undergoing treatment for major types of cancer in terms of various sociodemographic characteristics, including but not limited to sex and age. However, among the web-recruited study participants, the proportion of female participants was even higher (P<.001), the mean age was lower (P=.005), private internet use was higher (on weekdays: P=.007; on weekends: P=.02), and the number of those who were currently under treatment was higher (P=.048). Other demographic and medical characteristics revealed no significant differences between the groups. The majority of participants registered as self-referred (236/296, 79.7%) instead of having followed the recommendation of or study invitation from a health care professional. CONCLUSIONS: The combined recruitment strategy helped overcome general and COVID-19-specific recruitment barriers and provided the targeted participant number. Social media recruitment was the most efficient individual recruitment strategy for participant enrollment. Differences in some demographic and medical characteristics emerged, which should be considered in future analyses. Implications and recommendations for social media recruitment based on personal experiences are presented. TRIAL REGISTRATION: German Clinical Trials Register DRKS00021144; https://drks.de/search/en/trial/DRKS00021144. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1016/j.invent.2021.100410.

A Novel Tool for Collaborative and Blinded Orthopedic Image Analysis.

Image analysis plays a central role in orthopedics and research but comes with many challenges, including anonymization, bias, and achieving efficient analyses using multiple independent observers. Appropriate software is still lacking. Tyche is a free online tool that displays images in a random order without showing any metadata. Additionally, when using Tyche, observers can store results in the same window, and the final results are immediately visible to the project manager. In this study, we compared results from Tyche with those from a validated tool. One hundred pelvic radiographs were analyzed separately by five orthopedic surgeons using both Tyche and the validated software. Common orthopedic measurement modalities and scores were determined. The methods were compared using intra-class correlations and Fleiss' kappa coefficients as well as Bland-Altman plots. Significant correlations ranging from r = 0.17 (Kallgren and Lawrence Score) to r = 0.99 (area measurements) were calculated for inter- and intraobserver agreements between the two tools for all measurements. The Bland-Altman plots indicated the non-inferiority of either tool. The images were analyzed significantly faster when Tyche was used. We conclude that Tyche is a valid tool for use in orthopedic image analysis. Tyche could be utilized for determining inter- and intraobserver agreements, in multicenter studies and for score validations.

Change in Splenic Volume as a Surrogate Marker for Immunotherapy Response in Patients with Advanced Urothelial and Renal Cell Carcinoma-Evaluation of a Novel Approach of Fully Automated Artificial Intelligence Based Splenic Segmentation.

BACKGROUND: In the treatment of advanced urothelial (aUC) and renal cell carcinoma (aRCC), biomarkers such as PD-1 and PD-L1 are not robust prognostic markers for immunotherapy (IO) response. Previously, a significant association between IO and a change in splenic volume (SV) was described for several tumour entities. To the best of our knowledge, this study presents the first correlation of SV to IO in aUC and aRCC. METHODS: All patients with aUC (05/2017-10/2021) and aRCC (01/2012-05/2022) treated with IO at our academic centre were included. SV was measured at baseline, 3 and 9 months after initiation of IO using an in-house developed convolutional neural network-based spleen segmentation method. Uni- and multivariate Cox regression models for overall survival (OS) and progression-free survival (PFS) were used. RESULTS: In total, 35 patients with aUC and 30 patients with aRCC were included in the analysis. Lower SV at the three-month follow-up was significantly associated with improved OS in the aRCC group. CONCLUSIONS: We describe a new, innovative artificial intelligence-based approach of a radiological surrogate marker for IO response in aUC and aRCC which presents a promising new predictive imaging marker. The data presented implicate improved OS with lower follow-up SV in patients with aRCC.

Refocusing of Attention on Positive Events Using Monitoring-Based Feedback and Microinterventions for Patients With Chronic Musculoskeletal Pain in the PerPAIN Randomized Controlled Trial: Protocol for a Microrandomized Trial.

BACKGROUND: Chronic musculoskeletal pain (CMSP) affects between 13% and 47% of the population, with a global growth rate of 20.3% within the last 15 years, suggesting that there is a high need for effective treatments. Pain diaries have long been a common tool in nonpharmacological pain treatment for monitoring and providing feedback on patients' symptoms in daily life. More recently, positive refocusing techniques have come to be used, promoting pain-free episodes and positive outcomes rather than focusing on managing the pain. OBJECTIVE: This study aims to evaluate the feasibility (ie, acceptability, intervention adherence, and fidelity) and initial signals of efficacy of the PerPAIN app, an ecological momentary intervention for patients with CMSP. The app comprises digitalized monitoring using the experience sampling method (ESM) and feedback. In addition, the patients receive 3 microinterventions targeted at refocusing of attention on positive events. METHODS: In a microrandomized trial, we will recruit 35 patients with CMSP who will be offered the app for 12 weeks. Participants will be prompted to fill out 4 ESM monitoring questionnaires a day assessing information on their current context and the proximal outcome variables: absence of pain, positive mood, and subjective activity. Participants will be randomized daily and weekly to receive no feedback, verbal feedback, or visual feedback on proximal outcomes assessed by the ESM. In addition, the app will encourage participants to complete 3 microinterventions based on positive psychology and cognitive behavioral therapy techniques. These microinterventions are prompts to report joyful moments and everyday successes or to plan pleasant activities. After familiarizing themselves with each microintervention individually, participants will be randomized daily to receive 1 of the 3 exercises or none. We will assess whether the 2 feedback types and the 3 microinterventions increase proximal outcomes at the following time point. The microrandomized trial is part of the PerPAIN randomized controlled trial (German Clinical Trials Register DRKS00022792) investigating a personalized treatment approach to enhance treatment outcomes in CMSP. RESULTS: Approval was granted by the Ethics Committee II of the University of Heidelberg on August 4, 2020. Recruitment for the microrandomized trial began in May 2021 and is ongoing at the time of submission. By October 10, 2022, a total of 24 participants had been enrolled in the microrandomized trial. CONCLUSIONS: This trial will provide evidence on the feasibility of the PerPAIN app and the initial signals of efficacy of the different intervention components. In the next step, the intervention would need to be further refined and investigated in a definitive trial. This ecological momentary intervention presents a potential method for offering low-level accessible treatment to a wide range of people, which could have substantial implications for public health by reducing disease burden of chronic pain in the population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43376.

Cryoballoon pulmonary vein isolation for atrial fibrillation in obese patients: A non-inferiority analysis.

Background: Patients with obesity are at higher risk of developing atrial fibrillation (AF) and benefit from radiofrequency ablation. Potentially, cryoballoon ablation (CBA) may be equally effective and safe in such patients. Methods: We conducted a prospective, single-center study to investigate whether CBA for pulmonary vein isolation is as effective and safe in obese patients as it is in non-obese controls. Primary efficacy endpoint was recurrence of AF, atrial flutter or atrial tachycardia after a 90-day blanking period. Safety endpoints were death, stroke or procedure-associated complications. Conduction of a subgroup analysis regarding the impact of additional diabetes was predefined in case the primary efficacy endpoint was met. The study was event driven and powered for noninferiority. Results: A total of 949 patients underwent CBA (251 obese with mean body-mass-index 33.5 ± 3 kg/m2 and 698 non-obese with mean body-mass-index 25.3 ± 3 kg/m2) during a 5-year recruitment period. Median follow-up was 15 months. The primary efficacy endpoint occurred in 78/251 obese and 247/698 non-obese patients (12-months Kaplan-Meier event-rate estimates, hazard ratio 0.79; 95% confidence interval [CI], 0.58 to 1.07; log-rank P = 0.0002 for noninferiority). No differences were observed in safety end point occurrence (P = 0.78). The occurrence of primary efficacy end point was found to be unaffected by the presence of diabetes in the prespecified subgroup analysis (log-rank P = 0.57). Conclusion: CBA is effective and safe in obese and DM patients. Weighing the high cardiovascular risk of obese patients against a reduction of cardiovascular events by early rhythm control, CBA should be offered to this patient population.