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Aims A strategy of systematic, early rhythm control (ERC) improves cardiovascular outcomes in patients with atrial fibrillation (AF). It is not known how this outcome-reducing effect is mediated. Methods and results Using the Early treatment of Atrial Fibrillation for Stroke prevention Trial (EAST—AFNET 4) data set, potential mediators of the effect of ERC were identified in the total study population at 12-month follow up and further interrogated by use of a four-way decomposition of the treatment effect in an exponential model predicting future primary outcome events. Fourteen potential mediators of ERC were identified at the 12-month visit. Of these, sinus rhythm at 12 months explained 81% of the treatment effect of ERC compared with usual care during the remainder of follow up (4.1 years). In patients not in sinus rhythm at 12 months, ERC did not reduce future cardiovascular outcomes (hazard ratio 0.94, 95% confidence interval 0.65–1.67). Inclusion of AF recurrence in the model only explained 31% of the treatment effect, and inclusion of systolic blood pressure at 12 months only 10%. There was no difference in outcomes in patients who underwent AF ablation compared with those who did not undergo AF ablation. Conclusion The effectiveness of early rhythm control is mediated by the presence of sinus rhythm at 12 months in the EAST-AFNET 4 trial. Clinicians implementing ERC should aim for rapid and sustained restoration of sinus rhythm in patients with recently diagnosed AF and cardiovascular comorbidities.

Background: The randomized EAST-AFNET4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial–Atrial Fibrillation Network) demonstrated that early rhythm control (ERC) reduces adverse cardiovascular outcomes in patients with recently diagnosed atrial fibrillation and stroke risk factors. The effectiveness and safety of ERC in patients with multiple cardiovascular comorbidities is not known. Methods: These prespecified subanalyses of EAST-AFNET4 compared the effectiveness and safety of ERC with usual care (UC) stratified into patients with higher (CHA 2 DS 2 -VASc score ≥4) and lower comorbidity burden. Sensitivity analyses ignored sex (CHA 2 DS 2 -VA score). Results: EAST-AFNET4 randomized 1093 patients with CHA 2 DS 2 -VASc score ≥4 (74.8±6.8 years, 61% female) and 1696 with CHA 2 DS 2 -VASc score 2 DS 2 -VASc score ≥4 (ERC, 127/549 patients with events; UC, 183/544 patients with events; hazard ratio [HR], 0.64 [0.51–0.81]; P < 0.001) but not in patients with CHA 2 DS 2 -VASc score P =0.56, P interaction =0.037). The primary safety outcome (death, stroke, or serious adverse events of rhythm control therapy) was not different between study groups in patients with CHA 2 DS 2 -VASc score ≥4 (ERC, 112/549 patients with events; UC, 132/544 patients with events; HR, 0.84 [0.65, 1.08]; P =0.175), but occurred more often in patients with CHA 2 DS 2 -VASc scores P =0.019, P interaction =0.008). Life-threatening events or death were not different between groups (CHA 2 DS 2 -VASc score ≥4, ERC, 84/549 patients with event, UC, 96/544 patients with event; CHA 2 DS 2 -VASc scores 2 DS 2 -VA score), the P interaction was not significant for the primary efficacy outcome ( P =0.25), but remained significant ( P =0.044) for the primary safety outcome. Conclusions: Patients with recently diagnosed atrial fibrillation and CHA 2 DS 2 -VASc score ≥4 should be considered for ERC to reduce cardiovascular outcomes, whereas those with fewer comorbidities may have less favorable outcomes with ERC. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01288352. URL: https://www.clinicaltrialsregister.eu ; Unique identifier: 2010-021258-20. URL: https://www.isrctn.com/ ; Unique identifier: ISRCTN04708680.

Background Type 2 diabetes mellitus (T2DM) is a major health problem in the western world. Despite a widespread implementation of integrated care programs there are still patients with poorly controlled T2DM. Shared goal setting within the process of Shared Decision Making (SDM) may increase patient’s compliance and adherence to treatment regimen. In our secondary analysis of the cluster-randomized controlled DEBATE trial, we investigated if patients with shared vs. non-shared HbA1c treatment goal, achieve their glycemic goals. Methods In a German primary care setting, we collected data before intervention at baseline, 6, 12 and 24 months. Patients with T2DM with an HbA1c ≥ 8.0% (64 mmol/mol) at the time of recruitment and complete data at baseline and after 24 months were eligible for the presented analyses. Using a generalized estimating equation analysis, we analysed the association between the achievement of HbA1c goals at 24 months based on their shared vs. non-shared status, age, sex, education, partner status, controlled for baseline HbA1c and insulin therapy. Results From N = 833 recruited patients at baseline, n = 547 (65.7%) from 105 General Practitioners (GPs) were analysed. 53.4% patients were male, 33.1% without a partner, 64.4% had a low educational level, mean age was 64.6 (SD 10.6), 60.7% took insulin at baseline, mean baseline HbA1c was 9.1 (SD 1.0). For 287 patients (52.5%), the GPs reported to use HbA1c as a shared goal, for 260 patients (47.5%) as a non-shared goal. 235 patients (43.0%) reached the HbA1c goal after two years, 312 patients (57.0%) missed it. Multivariable analysis shows that shared vs. non-shared HbA1c goal setting, age, sex, and education are not associated with the achievement of the HbA1c goal. However, patients living without a partner show a higher risk of missing the goal (p = .003; OR 1.89; 95% CI 1.25–2.86). Conclusions Shared goal setting with T2DM patients targeting on HbA1c-levels had no significant impact on goal achievement. It may be assumed, that shared goal setting on patient-related clinical outcomes within the process of SDM has not been fully captured yet. Trial registration The trial was registered at ISRCTN registry under the reference ISRCTN70713571.

Background: The QT interval is a well established marker for ventricular repolarization. As the QT interval is inversely regulated with the heart rate, several correction formula are established to calculate corrected QT intervals (QTc). In practical courses of physiology, medical students learn the correct measurement of the QT interval and its autonomous regulation. For this, students record and analyse ECGs under resting conditions and during/following a workout. However, little is known about teaching QT/QTc skills in students. In particular, it is not established whether untrained medical students can determine the length of the QT interval in rest and following an exercise with sufficient accuracy to allow discussion of its physiological regulation. Methods: A full cohort of 3rd year medical students (n=380) participated in a practical ECG course. In each course (20 students), ECGs of volunteers were recorded in small groups (2-4 students) under resting conditions and immediately following standardised physical exercise (squats and push-ups). Students calculated HR, QT intervals and QTc intervals using Bazett’s exponential correction. Automatically calculated QT intervals were retrieved from the ECG devices. Following the course, QT intervals of the same ECG passages were measured by experienced physiology teachers and expert clinical electrophysiologists. To compare effects of established QTc correction formulas, QTc was calculated for all retrieved intervals using Bazett, Framingham, Fridericia and Hodges. Data were analysed on the level of individual experiments and as pooled data of student groups. Results: In 117 experiments, students reported resting HRs of ~70 bpm and corresponding QT intervals of ~360 ms. Following exercise, students found an average increase of the HR by ~75% and a decrease of the QT interval by ~25%. Using pooled data sets of each course, the overall efficacy of the Bazett formula could well be demonstrated. Students HR data were highly concordant with the data generated by the automated ECG routines, the experienced physiologists and the clinical electrophysiologists. While average QT and QTc intervals were also comparable between the groups, the variance was substantially higher in students data than in the other groups, especially in the exercise ECGs. In the HR ranges generated in the course, QT correction by Fridericia and Framingham was more efficient than by Bazett and Hodges. Conclusions: Untrained students can determine QT intervals from ECGs recorded under resting conditions and following a workout with sufficient accuracy to demonstrate the autonomous regulation of this important (bio)marker on the level of individual data sets. Due to the high individual variance of the QTc, however, we recommend QTc correction based on data pooled within each student group to discuss the relevance of the QT correction formulas. The study was financed by institutional budget. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Aims The randomized, controlled EAST-AFNET 4 trial showed that early rhythm control (ERC) reduces the rate of a composite primary outcome (cardiovascular death, stroke, or hospitalization for worsening heart failure or acute coronary syndrome) by ∼20%. The current study examined the cost-effectiveness of ERC compared to usual care. Methods and results This within-trial cost-effectiveness analysis was based on data from the German subsample of the EAST-AFNET 4 trial (n = 1664/2789 patients). Over a 6-year time horizon and from a healthcare payer’s perspective, ERC was compared to usual care regarding costs (hospitalization and medication) and effects (time to primary outcome; years survived). Incremental cost-effectiveness ratios (ICERs) were calculated. Cost-effectiveness acceptability curves were constructed to visualize uncertainty. Early rhythm control was associated with higher costs [+€1924, 95% CI (−€399, €4246)], resulting in ICERs of €10 638 per additional year without a primary outcome and €22 536 per life year gained. The probability of ERC being cost-effective compared to usual care was ≥95% or ≥80% at a willingness-to-pay value of ≥€55 000 per additional year without a primary outcome or life year gained, respectively. Conclusion From a German healthcare payer’s perspective, health benefits of ERC may come at reasonable costs as indicated by the ICER point estimates. Taking statistical uncertainty into account, cost-effectiveness of ERC is highly probable at a willingness-to-pay value of ≥€55 000 per additional life year or year without a primary outcome. Future studies examining the cost-effectiveness of ERC in other countries, subgroups with higher benefit from rhythm control therapy, or cost-effectiveness of different modes of ERC are warranted.

Aims Clinical practice guidelines restrict rhythm control therapy to patients with symptomatic atrial fibrillation (AF). The EAST-AFNET 4 trial demonstrated that early, systematic rhythm control improves clinical outcomes compared to symptom-directed rhythm control. Methods and results This prespecified EAST-AFNET 4 analysis compared the effect of early rhythm control therapy in asymptomatic patients (EHRA score I) to symptomatic patients. Primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome, analyzed in a time-to-event analysis. At baseline, 801/2633 (30.4%) patients were asymptomatic [mean age 71.3 years, 37.5% women, mean CHA2DS2-VASc score 3.4, 169/801 (21.1%) heart failure]. Asymptomatic patients randomized to early rhythm control (395/801) received similar rhythm control therapies compared to symptomatic patients [e.g. AF ablation at 24 months: 75/395 (19.0%) in asymptomatic; 176/910 (19.3%) symptomatic patients, P = 0.672]. Anticoagulation and treatment of concomitant cardiovascular conditions was not different between symptomatic and asymptomatic patients. The primary outcome occurred in 79/395 asymptomatic patients randomized to early rhythm control and in 97/406 patients randomized to usual care (hazard ratio 0.76, 95% confidence interval [0.6; 1.03]), almost identical to symptomatic patients. At 24 months follow-up, change in symptom status was not different between randomized groups (P = 0.19). Conclusion The clinical benefit of early, systematic rhythm control was not different between asymptomatic and symptomatic patients in EAST-AFNET 4. These results call for a shared decision discussing the benefits of rhythm control therapy in all patients with recently diagnosed AF and concomitant cardiovascular conditions (EAST-AFNET 4; ISRCTN04708680; NCT01288352; EudraCT2010-021258-20).

AimTo evaluate the effects of a multimodal intervention (including exercise training, psychosocial interventions, nutrition coaching, smoking cessation program, medical care) on the health and long-term cardiovascular disease (CVD) mortality risk of company employees with pre-diabetes or diabetes mellitus (DM) at high CVD risk.MethodsIn the PreFord study, German company employees (n=4196) participated in a free-of-charge CVD mortality risk screening at their workplace. Based on their European Society of Cardiology – Systematic Coronary Risk Evaluation score (ESC-SCORE), they were subdivided into three risk groups. High-risk patients (ESC-SCORE≥5%) were randomly assigned to a 15-week lifestyle intervention or usual care control group. Data from patients with pre-DM/DM were analyzed intention-to-treat (ITT: n=110 versus n=96) and per protocol (PP: n=60 versus n=52).ResultsBody mass index, glycated hemoglobin, total cholesterol, low-density lipoprotein, triglyceride levels as well as systolic and diastolic blood pressure improved through the intervention (ITT, PP: pConclusionThe study demonstrates the feasibility of attracting employees with pre-DM/DM at high CVD mortality risk to participate in a multimodal lifestyle program following a free CVD mortality risk screening at their workplace. The lifestyle intervention used in the PreFord study shows high potential for improving health of company employees with pre-DM/DM in the long term. ISRCTN23536103.

Supplemental Digital Content is available in the text., Background: Even on optimal therapy, many patients with heart failure and atrial fibrillation experience cardiovascular complications. Additional treatments are needed to reduce these events, especially in patients with heart failure and preserved left ventricular ejection fraction. Methods: This prespecified subanalysis of the randomized EAST-AFNET4 trial (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) assessed the effect of systematic, early rhythm control therapy (ERC; using antiarrhythmic drugs or catheter ablation) compared with usual care (allowing rhythm control therapy to improve symptoms) on the 2 primary outcomes of the trial and on selected secondary outcomes in patients with heart failure, defined as heart failure symptoms New York Heart Association II to III or left ventricular ejection fraction [LVEF]

Objective Due to the increasing concerns about polypharmacy, there is a growing need for clinical recommendations for drug discontinuation. This requires studies investigating the process on several levels. This paper addresses the methodological problems of drug discontinuation trials (DDTs). To that end, we offer a new typology of research aims and corresponding methodological recommendations for trials evaluating drug discontinuation. Study Design and Setting Multi-stage development process, including literature search and expert panels. Results Clinical trials are only required in cases of scientific uncertainty. We identified three situations of uncertainty associated with drug discontinuation from which we derived three study types: 1) Uncertainty regarding the effectiveness and/or safety of a drug; 2) Uncertainty regarding the procedure of discontinuing a previously taken drug; 3) Uncertainty regarding the effectiveness of complex strategies used to discontinue one or more drugs. We developed specific methodological recommendations for each study type. Conclusion We offer a comprehensive definition of research aims, study designs, and methodological recommendations regarding DDTs. The typology we propose can help investigators clarify their research aims and study design. The type-specific methodological recommendation should improve the quality of future drug discontinuation trials.

Children of mentally ill parents represent a particularly vulnerable risk group for the development of mental illness. This study examines whether there is a predictive association between children’s psychiatric symptomatology and (1) the clinical diagnosis according to the International Statistical Classification of Diseases and Related Health Problems (ICD-10) of their mentally ill parent as well as (2) to families both parents showing psychiatric symptoms. The study is part of the multicenter controlled trial project “Children of Mentally Ill Parents” (CHIMPS). For this purpose, the psychiatric symptomatology of the mentally ill parent (N = 196) and his or her partner (N = 134) as well as the psychiatric symptomatology of their children aged 4 to 18 years (N = 290) was measured using clinical rated ICD-10-diagnosis, self-rated Brief Symptom Inventory (BSI), and Child Behavior Checklist (CBCL). Using multilevel analyses, the severity of the parental psychiatric symptomatology (BSI) was identified as a significant predictor of children’s psychiatric symptomatology (CBCL). Children of parents with a personality disorder (ICD-10) were not more affected than children of parents with another ICD-10-diagnosis. However, children with two parents showing psychiatric symptoms (CBCL) were significantly more affected than children with one mentally ill parent. The results of this study support the well-known view that parental mental illness is a risk factor for children’s psychiatric symptoms. Therefore, increased support, especially in high-risk families, both parents having psychiatric symptoms, is highly necessary and should be implemented in the future psychotherapeutic family care.

This study was conducted to determine the effect of hypothermic temperature control after in-hospital cardiac arrest (IHCA) on mortality and functional outcome as compared with normothermia.An investigator initiated, open-label, blinded-outcome-assessor, multicenter, randomized controlled trial comparing hypothermic temperature control (32-34°C) for 24 h with normothermia after IHCA in 11 hospitals in Germany. The primary endpoint was all-cause mortality after 180 days. Secondary end points included in-hospital mortality and favorable functional outcome using the Cerebral Performance Category scale after 180 days. A Cerebral Performance Category score of 1 or 2 was defined as a favorable functional outcome.A total of 1055 patients were screened for eligibility and 249 patients were randomized: 126 were assigned to hypothermic temperature control and 123 to normothermia. The mean age of the cohort was 72.6±10.4 years, 64% (152 of 236) were male, 73% (166 of 227) of cardiac arrests were witnessed, 25% (57 of 231) had an initial shockable rhythm, and time to return of spontaneous circulation was 16.4±10.5 minutes. Target temperature was reached within 4.2±2.8 hours after randomization in the hypothermic group and temperature was controlled for 48 hours at 37.0°±0.9°C in the normothermia group. Mortality by day 180 was 72.5% (87 of 120) in hypothermic temperature control arm, compared with 71.2% (84 of 118) in the normothermia group (relative risk, 1.03 [95% CI, 0.79-1.40];Hypothermic temperature control as compared with normothermia did not improve survival nor functional outcome at day 180 in patients presenting with coma after IHCA. The HACA in-hospital trial (Hypothermia After Cardiac Arrest in-hospital) was underpowered and may have failed to detect clinically important differences between hypothermic temperature control and normothermia.URL: https://www.gov; Unique Identifier: NCT00457431.

Patients with atrial fibrillation and a history of stroke are at high risk of recurrent stroke and cardiovascular complications. In the EAST-AFNET 4 trial we showed that a systematic strategy of early rhythm control was associated with a lower risk of cardiovascular outcomes than usual care in patients with atrial fibrillation diagnosed in the past 12 months. In this pre-specified subgroup analysis we aimed to assess whether a strategy of early rhythm control is safe and can prevent adverse cardiovascular outcomes compared with usual care in such patients.EAST-AFNET 4 was a randomised, open-label trial with blinded-outcome assessment done at 135 hospitals and secondary care practices in 11 European countries. Adults with early atrial fibrillation (ie, diagnosed ≤12 months before enrolment) were randomly assigned (1:1) to either early rhythm control or usual care, with stratification according to site and variable block lengths used for concealment. The first primary outcome was time to first occurrence of the composite of cardiovascular death, ischaemic or haemorrhagic stroke, or hospital admission with worsening of heart failure or acute coronary syndrome. The second primary outcome was the number of nights spent in hospital in 1 year. The primary safety outcome was the composite of any death, stroke, or serious adverse events related to rhythm-control therapy. Here we present the results of these outcomes in patients with a history of stroke. Analyses were done in the intention-to-treat population. EAST-AFNET 4 is registered with ClinicalTrials.gov (NCT01288352), EudraCT (2010-021258-20), and ISRCTN (ISRCTN04708680).Between July 28, 2011, and Dec 30, 2016, 2789 patients were randomly assigned in the EAST-AFNET 4 trial to either early rhythm control (n=1395) or usual care (n=1394). Of these patients, five had no information on history of stroke and were excluded from this subgroup analysis. 217 (8%) patients had a history of stroke, of whom 110 were assigned to early rhythm control and 107 to usual care. The median age of participants with a history of stroke was 72·0 years (IQR 66·0-76·0). 95 (44%) participants were female and 122 (56%) were male. During a median follow-up of 4·7 years (3·5-6·4) for patients with a history of stroke, a first primary outcome event occurred in 18 (16%) of 110 patients in the early rhythm-control group (3·7 per 100 person-years) and 33 (31%) of 107 in the usual care group (7·4 per 100 person-years; hazard ratio [HR] 0·52, 95% CI 0·29-0·93). The mean number of nights spent in hospital per year was 5·1 (SD 13·2) for patients with a history of stroke assigned to early rhythm control and 6·6 (10·1) for those assigned to usual care (incidence rate ratio 0·87, 95% CI 0·55-1·38). Among patients with a history of stroke, primary safety events occurred in 17 (15%) patients in the early rhythm-control group versus 30 (28%) in the usual care group.In this prespecified subgroup analysis in patients with recently diagnosed atrial fibrillation and a history of stroke, the effects of early rhythm control were consistent with the findings of the primary analysis. As the evidence from this subgroup analysis is considered supportive and exploratory, further research is needed to confirm the safety and efficacy of this approach in patients with a history of stroke.German Ministry of Education and Research, German Center for Cardiovascular Research (DZHK), Atrial Fibrillation Network (AFNET), European Heart Rhythm Association, St Jude Medical-Abbott, Sanofi, and the German Heart Foundation.

Aims Atrial fibrillation (AF) is associated with a high risk of cardiovascular and non-cardiovascular death, even on anticoagulation. It is controversial, which conditions—including concomitant diseases and AF itself—contribute to this mortality. To further clarify these questions, major determinants of long-term mortality and their contribution to death were quantified in an unselected cohort of AF patients. Methods and results We established a large nationwide registry comprising 8833 AF-patients with a median follow-up of 6.5 years (45 345 patient-years) and central adjudication of adverse events. Baseline characteristics of the patients were evaluated as predictors of mortality using Cox regression and C-indices for determination of predictive power. Annualized mortality was highest in the first year (6.2%) and remained high thereafter (5.2% in men and 5.5% in women). Thirty-eight percent of all deaths were cardiovascular, mainly due to heart failure or sudden death. Sex-specific age was the strongest predictor of mortality, followed by concomitant cardiovascular and non-cardiovascular conditions. These factors accounted for 25% of the total mortality beyond age and sex and for 84% of the mortality differences between AF types. Thus, the electrical phenotype of the disease at baseline contributed only marginally to prediction of mortality. Conclusion Mortality is high in AF patients and arises primarily from heart failure, peripheral artery disease, chronic obstructive lung disease, chronic kidney disease, and diabetes mellitus, which, therefore, should be targeted to lower mortality. Parameters related to the electrical manifestation of AF did not have an independent impact on long-term mortality in our representative cohort.

Background Cardiovascular morbidity and mortality are closely linked to chronic kidney disease (CKD). Sex-specific long-term outcome data of patients with coronary artery disease (CAD) and CKD are scarce. Methods In the prospective observational multicenter Coronary Artery Disease and REnal F ailure (CAD-REF) Registry, 773 (23.1%) women and 2,579 (76.9%) men with angiographically documented CAD and different stages of CKD were consecutively enrolled and followed for up to 8 years. Long-term outcome was evaluated using survival analysis and multivariable Cox-regression models. Results At enrollment, women were significantly older than men, and suffered from more comorbidities like CKD, hypertension, diabetes mellitus, and multivessel coronary disease. Regarding long-term mortality, no sex-specific differences were observed (Kaplan–Meier survival estimates: 69% in women vs. 69% in men, plog-rank = 0.7). Survival rates decreased from 89% for patients without CKD at enrollment to 72% for patients with CKD stages 1–2 at enrollment and 49% for patients with CKD stages 3–5 at enrollment (plog-rank Conclusions Sex differences in CAD patients mainly exist in the cardiovascular risk profile and the extent of CAD. Long-term mortality was not depended on sex or multivessel disease. More attention should be given to treatment of comorbidities such as CKD and peripheral artery disease being independent predictors of death. Clinical Trail Registration ClinicalTrials.gov Identifier: NCT00679419 Graphic abstract

Objectives This subanalysis of the CASTLE-AF (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF) trial aimed to address the association between atrial fibrillation (AF) recurrence, AF burden, and hard clinical outcomes in heart failure (HF) patients with AF. Background The CASTLE-AF trial demonstrated the benefit of CA compared to pharmacological treatment in decreasing mortality and CV hospitalizations in patients with AF and HFrEF. However, the impact of AF recurrence and AF burden after ablation on long-term treatment benefit remains unknown. Methods The CASTLE-AF protocol randomized 363 patients with coexisting HF and AF in a multicenter prospective controlled fashion to catheter ablation (n = 179) versus pharmacological therapy (n = 184). Two hundred eighty patients were included in this subanalysis (as-treated), 128 of them underwent ablation and 152 received pharmacological treatment. All patients had implanted dual chamber or biventricular implantable defibrillators with activated home monitoring capabilities. The individual AF burden was calculated as the percentage of the atrial arrhythmia time per day. Results AF burden at baseline was not predictive of the primary endpoint (p = 0.473) or all-cause mortality (p = 0.446). AF recurrence (defined as any episode >30 s) did not show any relationship with the primary endpoints of mortality and occurrence of HF, irrespective of the treatment arm. An AF burden below 50% after 6 months of catheter ablation, was associated with a significant decrease in primary composite outcome (hazard ratio [HR]: 0.33; 95% confidence interval [CI]: 0.15 to 0.71; p = 0.014) and all-cause mortality (HR: 0.23; 95% CI: 0.07 to 0.71; p = 0.031). The risk of the primary endpoint or mortality was directly related to a low ( Conclusions AF burden at 6 months was predictive of hard clinical outcomes in HF patients with AF. The first recurrent atrial tachyarrhythmia episode >30 s after ablation was not associated with improvement in mortality and hospitalization for HF. (Catheter Ablation vs. Standard Conventional Treatment in Patients With LV Dysfunction and AF [CASTLE-AF]; NCT00643188 )

Background Depression in older adults is becoming an increasing concern. As depressive symptoms change over time, it is important to understand the determinants of change in depressive symptoms. The aim of our study is to use a longitudinal study design to explore the predictors of change, remission and incident depression in older patients with multimorbidity. Methods Data from the MultiCare cohort study were used. The cohort studied 3,189 multimorbid general practice patients aged 65-85. Data were collected during personal interviews. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS-15). Predictors of change in depressive symptoms were determined using multivariate linear regression, while multivariate logistic regression was used to analyze predictors of remission and incident depression. Models included depressive symptoms at baseline and follow-up, socio-demographics and data on health status and social support. Results Overall, 2,746 participants with complete follow-up data were analyzed. Mean age was 74.2 years, 59.2% were female, and 11.3% were classified as depressed at baseline. Burden of multimorbidity and social support were statistically significant predictors in all regression analyses. Further predictors of change in depressive symptoms were: income, pain, nursing grade, self-rated health and self-efficacy. Limitations The sample size for prediction of remission limited statistical certainty. Assessment of depressive symptoms using GDS-15 differs from routine clinical diagnoses of depression. Conclusions Predictors of change in depressive symptoms in older multimorbid patients are similar to those predicting remission and incident depression, and do not seem to differ significantly from other older patient populations with depressive symptoms.

Introduction We aimed to compare the efficacy of cognitive-behavioral therapy (CBT) among children with functional abdominal pain with an attention control (AC), hypothesizing the superiority of CBT group intervention regarding pain intensity (primary outcome), pain duration and frequency (further primary outcomes), functional disability, and quality of life and coping strategies (key secondary outcomes). Methods We conducted a prospective, multicenter, randomized controlled efficacy trial (RCT) with 4 time points (before intervention, after intervention, 3-month follow-up, and 12-month follow-up). One hundred twenty-seven children aged 7-12 years were randomized to either the CBT (n = 63; 55.6% girls) or the AC (n = 64; 57.8% girls). Results Primary endpoint analysis of the logarithmized area under the pain intensity curve showed no significant difference between groups (mean reduction = 49.04%, 95% confidence interval [CI] -19.98%-78.36%). Treatment success rates were comparable (adjusted odds ratio = 0.53, 95% CI 0.21-1.34, number needed to treat = 16). However, time trend analyses over the course of 1 year revealed a significantly greater reduction in pain intensity (40.9%, 95% CI 2.7%-64.1%) and pain duration (43.6%, 95% CI 6.2%-66.1%) in the CBT compared with the AC, but not in pain frequency per day (1.2, 95% CI -2.7 to 5.2). In the long term, children in the CBT benefitted slightly more than those in the AC with respect to functional disability, quality of life, and coping strategies. Discussion Both interventions were effective, which underlines the role of time and attention for treatment efficacy. However, in the longer term, CBT yielded more favorable results.

Partners in families with a mentally ill parent often experience psychiatric symptoms themselves. Recent studies indicate that there might be overlaps in disorder-specific symptom areas between partners and spouses. This study aimed at examining associations in psychiatric symptoms and symptom coping in partners in families with a mentally ill parent, e.g., having a psychiatric diagnosis according to the International Classification of Diseases (ICD-10). Furthermore, a moderation of the psychiatric symptoms of the parent with a mental illness on the association in symptom coping was assumed. Families with at least one parent with a mental illness were recruited into the longitudinal “Children of Mentally Ill Parents” (CHIMPS) trial at seven clinical centers in Germany and Switzerland. In total, 139 families were included in the current study. Psychiatric symptoms were assessed using the Brief Symptom Inventory (BSI), Clinical Global Impression scale (CGI), Global Assessment of Functioning (GAF), and Patient Health Questionnaire (PHQ), while symptom coping strategies were measured using the Freiburger Fragebogen zur Krankheitsverarbeitung (FKV). Regression analyses have indicated an association in psychiatric symptoms between mentally ill parents and their partners concerning psychosocial functioning, somatic, and stress-related symptoms. Additionally, one symptom coping strategy of the partners was predicted by the same strategy of the parent with a mental illness. The results emphasize the importance of screening and providing support to parents burdened by the mental disorder of their partners, especially regarding the children in these partnerships.

Aims: Depression is a frequent comorbidity in patients with chronic heart failure (CHF). Telemonitoring has emerged as a novel option in CHF care. However, patients with depression have been excluded in most telemedicine studies. This pre-specified subgroup analysis of the Telemedical Interventional Monitoring in Heart Failure (TIM-HF) trial investigates the effect of telemonitoring on depressive symptoms over a period of 12 months. Methods and results: The TIM-HF study randomly assigned 710 patients with CHF to either usual care (UC) or a telemedical intervention (TM) using non-invasive devices for daily monitoring electrocardiogram, blood pressure and body weight. Depression was evaluated by the 9-item Patient Health Questionnaire (PHQ-9) with scores ���10 defining clinically relevant depressive symptoms. Mixed model repeated measures were performed to calculate changes in PHQ-9 score. Quality of life was measured by the Short Form-36. At baseline, 156 patients had a PHQ-9 score ���10 points (TM: 79, UC: 77) with a mean of 13.2 points indicating moderate depressiveness. Patients randomized to telemedicine showed an improvement of their PHQ-9 scores, whereas UC patients remained constant (P = 0.004). Quality of life parameters were improved in the TM group compared to UC. Adjustment was performed for follow-up, New York Heart Association class, medication, age, current living status, number of hospitalizations within the last 12 months and serum creatinine. In the study population without depression, the PHQ-9 score was similar at baseline and follow-up. Conclusion: Telemedical care improved depressive symptoms and had a positive influence on quality of life in patients with CHF and moderate depression.

BackgroundDespite improvements in the management of atrial fibrillation, patients with this condition remain at increased risk for cardiovascular complications. It is unclear whether early rhythm-control therapy can reduce this risk. MethodsIn this international, investigator-initiated, parallel-group, open, blinded-outcome-assessment trial, we randomly assigned patients who had early atrial fibrillation (diagnosed

Background: We aimed to analyze preferred and perceived levels of patients’ involvement in treatment decision-making in a representative sample of cancer patients.Material and Methods: We conducted...

Background: Catheter ablation for ventricular tachycardia (VT) reduces the recurrence of VT in patients with implantable cardioverter-defibrillators (ICDs). The appropriate timing of VT ablation and its effects on mortality and heart failure progression remain a matter of debate. In patients with life-threatening arrhythmias necessitating ICD implantation, we compared outcomes of preventive VT ablation (undertaken before ICD implantation to prevent ICD shocks for VT) and deferred ablation after 3 ICD shocks for VT. Methods: The BERLIN VT study (Preventive Ablation of Ventricular Tachycardia in Patients With Myocardial Infarction) was a prospective, open, parallel, randomized trial performed at 26 centers. Patients with stable ischemic cardiomyopathy, a left ventricular ejection fraction between 30% and 50%, and documented VT were randomly assigned 1:1 to a preventive or deferred ablation strategy. The primary outcome was a composite of all-cause death and unplanned hospitalization for either symptomatic ventricular arrhythmia or worsening heart failure. Secondary outcomes included sustained ventricular tachyarrhythmia and appropriate ICD therapy. We hypothesized that preventive ablation strategy would be superior to deferred ablation strategy in the intention-to-treat population. Results: During a mean follow-up of 396±284 days, the primary end point occurred in 25 (32.9%) of 76 patients in the preventive ablation group and 23 (27.7%) of 83 patients in the deferred ablation group (hazard ratio, 1.09 [95% CI, 0.62–1.92]; P =0.77). On the basis of prespecified criteria for interim analyses, the study was terminated early for futility. In the preventive versus deferred ablation group, 6 versus 2 patients died (7.9% versus 2.4%; P =0.18), 8 versus 2 patients were admitted for worsening heart failure (10.4% versus 2.3%; P =0.062), and 15 versus 21 patients were hospitalized for symptomatic ventricular arrhythmia (19.5% versus 25.3%; P =0.27). Among secondary outcomes, the proportions of patients with sustained ventricular tachyarrhythmia (39.7% versus 48.2%; P =0.050) and appropriate ICD therapy (34.2% versus 47.0%; P =0.020) were numerically reduced in the preventive ablation group. Conclusions: Preventive VT ablation before ICD implantation did not reduce mortality or hospitalization for arrhythmia or worsening heart failure during 1 year of follow-up compared with the deferred ablation strategy. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02501005.

Background Advances in genetic and pharmaceutical technology and pediatric care have enabled treatment options for an increasing number of rare diseases in affected children. However, as current treatment options are primarily of palliative nature, the Health-Related Quality of Life (HRQoL) and mental health of this impaired population and their siblings are of increasing importance. Among children and adolescents with rare diseases, those who are technology-dependent carry a high disease burden and are selected as the target population in our study. In a cross-sectional observational design, the children’s HRQoL was assessed with the DISABKIDS (DCGM-37) as well as KIDSCREEN-27, while mental health was assessed with the Strengths and Difficulties Questionnaire (SDQ) by both the affected children, their parents, and siblings. Results Results of the study sample were compared to normative data. Affected children scored significantly lower than the norm on almost all HRQoL subscales as reported by parent and child. From the parental perspective, more mental health subscales were significantly impaired compared to the child’s perspective. Siblings showed no impairment in HRQoL as well as significantly fewer behavioral problems and higher prosocial behavior regarding their mental health compared to the norm. Conclusion Children and adolescents with rare diseases seem particularly impaired in social and emotional aspects of HRQoL and mental health. Interventions may focus primarily on promoting social skills, fostering prosocial behavior and peer relationships.

Europace : the European journal of pacing, arrhythmias and cardiac electrophysiology euac062 (2022). doi:10.1093/europace/euac062, Published by Oxford Univ. Press, Oxford

This SERVE-HF (Treatment of Predominant Central Sleep Apnea by Adaptive Servo Ventilation in Patients With Heart Failure) sub study analysis evaluated polysomnography (PSG) data in patients with heart failure with reduced ejection fraction (HFrEF) and predominant central sleep apnea (CSA) randomised to guideline-based medical therapy, with or without adaptive servo ventilation (ASV). Patients underwent full overnight PSG at baseline and at 12 months. All PSG recordings were analysed by a core laboratory. Only data for patients with baseline and 3- or 12-month values were included. The sub study included 312 patients; the number with available PSG data differed for each variable (94–103 in the control group, 77–99 in the ASV group). After 12 months, baseline-adjusted respiratory measures were significantly better in the ASV group versus control. Although some between-group differences in sleep measures were seen at 12 months (e.g., better sleep efficiency in the ASV group), these were unlikely to be clinically significant. The number of periodic leg movements during sleep (PLMS) increased in the ASV group (p = 0.039). At 12 months, the respiratory arousal index was significantly lower in the ASV versus control group (p < 0.001), whilst the PLMS-related arousal index was significantly higher in the ASV group (p = 0.04 versus control). ASV attenuated the respiratory variables characterising sleep apnea in patients with HFrEF and predominant CSA in SERVE-HF. Sleep quality improvements during ASV therapy were small and unlikely to be clinically significant. The increase in PLMS and PLMS-related arousals during ASV warrants further investigation, particularly relating to their potential association with increased cardiovascular risk. in press

Background and ObjectivesIntravenous alteplase improves functional outcome after acute ischemic stroke. However, little is known about the effects on self-reported health-related quality of life (HRQoL).MethodsWAKE-UP was a multicenter, randomized, placebo-controlled trial of MRI-guided intravenous alteplase in stroke with unknown onset time. HRQoL was assessed using the EuroQol five-dimensional questionnaire (EQ-5D) at 90 days, comprising the EQ-5D index and the EQ visual analogue scale (VAS). Functional outcome was assessed by the modified Rankin Scale (mRS). We calculated the effect of treatment on EQ-5D index and EQ VAS using multiple linear regression models. Mediation analysis was performed on stroke survivors to explore the extent to which the effect of alteplase on HRQoL was mediated by functional outcome.ResultsAmong 490 stroke survivors, the EQ-5D index was available for 452 (92.2%), of whom 226 (50%) were assigned to treatment with alteplase and 226 (50%) to placebo. At 90 days, mean EQ-5D index was higher, reflecting a better health state, in patients randomized to treatment with alteplase than with placebo (0.75 vs 0.67) with an adjusted mean difference of 0.07 (95% CI 0.02–0.12,p= 0.005). In addition, mean EQ VAS was higher with alteplase than with placebo (72.6 vs 64.9), with an adjusted mean difference of 7.6 (95% CI 3.9–11.8,p< 0.001). Eighty-five percent of the total treatment effect of alteplase on the EQ-5D index was mediated using the mRS score while there was no significant direct effect. By contrast, the treatment effect on the EQ VAS was mainly through the direct pathway (60%), whereas 40% was mediated by the mRS.DiscussionAssessment of patient-reported outcome measures reveals a potential benefit of intravenous alteplase for HRQoL beyond improvement of functional outcome.Trial Registration InformationClinicalTrials.govnumber,NCT01525290; EudraCT number, 2011-005906-32.

To explore predictors of return to work in patients after acute coronary syndrome and coronary artery bypass grafting, taking into account cognitive performance, depression, physical capacity, and self-assessment of the occupational prognosis.Observational, prospective, bicentric.Postacute 3-week inpatient cardiac rehabilitation (CR).Patients (N=401)65 years of age (mean 54.5±6.3y), 80% men.Not applicable.Status of return to work (RTW) 6 months after discharge from CR.The regression model for RTW showed negative associations for depression (odds ratio 0.52 per SD, 95% confidence interval 0.36-0.76, P=.001), age (odds ratio 0.72, 95% confidence interval 0.52-1.00, P=.047), and in particular for a negative subjective occupational prognosis (expected incapacity for work odds ratio 0.19, 95% confidence interval 0.06-0.59, P=.004; unemployment odds ratio 0.08, 95% confidence interval 0.01-0.72, P=.024; retirement odds ratio 0.07, 95% confidence interval 0.01-0.067, P=.021). Positive predictors were employment before the cardiac event (odds ratio 9.66, 95% confidence interval 3.10-30.12, P.001), capacity to work (fit vs unfit) at discharge from CR (odds ratio 3.15, 95% confidence interval 1.35-7.35, P=.008), and maximum exercise capacity (odds ratio 1.49, 95% confidence interval 1.06-2.11, P=.022). Cognitive performance had no effect.The patient's perception and expectation regarding the occupational prognosis play a crucial role in predicting return to work 6 months after an acute cardiac event and CR. These findings highlight the importance of the multimodal approach, in particular psychosocial components, of CR.

Purpose: Health-related quality of life (HRQoL) can be reduced in parents with mental illness (mental illness) who face the dual demands of disabling symptoms and their impact on family, social, and occupational life. This study aimed at analyzing the influence of various factors on HRQoL in parents with mental illness.Method: Baseline data of the German randomized controlled multicenter project CHIMPS (children of parents with mental illness) was used for analyses. The final sample consisted of n = 208 parents with mental illness and n = 197 children and adolescents aged 8–18 years. HRQoL was assessed with the EQ-5D.Results: Parents with mental illness reported significantly lower global and specific HRQoL than the German reference population. They were least satisfied with aspects that relate to anxiety and depression followed by usual activities, pain and discomfort. Better global HRQoL was primarily associated with self-reported physical and mental health, as well as adaptive coping behavior. Associations with mobility, self-care, usual activity, pain and discomfort, anxiety and depression were analyzed and discussed.Conclusions: HRQoL in parents with mental illness is reduced. Clinical interventions should focus on the alleviation of mental health symptoms and probably somatic symptoms and promote adaptive coping skills.

In patients who have acute myocardial infarction with cardiogenic shock, early revascularization of the culprit artery by means of percutaneous coronary intervention (PCI) improves outcomes. However, the majority of patients with cardiogenic shock have multivessel disease, and whether PCI should be performed immediately for stenoses in nonculprit arteries is controversial.In this multicenter trial, we randomly assigned 706 patients who had multivessel disease, acute myocardial infarction, and cardiogenic shock to one of two initial revascularization strategies: either PCI of the culprit lesion only, with the option of staged revascularization of nonculprit lesions, or immediate multivessel PCI. The primary end point was a composite of death or severe renal failure leading to renal-replacement therapy within 30 days after randomization. Safety end points included bleeding and stroke.At 30 days, the composite primary end point of death or renal-replacement therapy had occurred in 158 of the 344 patients (45.9%) in the culprit-lesion-only PCI group and in 189 of the 341 patients (55.4%) in the multivessel PCI group (relative risk, 0.83; 95% confidence interval [CI], 0.71 to 0.96; P=0.01). The relative risk of death in the culprit-lesion-only PCI group as compared with the multivessel PCI group was 0.84 (95% CI, 0.72 to 0.98; P=0.03), and the relative risk of renal-replacement therapy was 0.71 (95% CI, 0.49 to 1.03; P=0.07). The time to hemodynamic stabilization, the risk of catecholamine therapy and the duration of such therapy, the levels of troponin T and creatine kinase, and the rates of bleeding and stroke did not differ significantly between the two groups.Among patients who had multivessel coronary artery disease and acute myocardial infarction with cardiogenic shock, the 30-day risk of a composite of death or severe renal failure leading to renal-replacement therapy was lower among those who initially underwent PCI of the culprit lesion only than among those who underwent immediate multivessel PCI. (Funded by the European Union 7th Framework Program and others; CULPRIT-SHOCK ClinicalTrials.gov number, NCT01927549 .).

Background Depression is one of the most disabling disorders worldwide, yet it often remains undetected. One promising approach to address both early detection and disease burden is depression screening followed by direct feedback to patients. Evidence suggests that individuals often seek information regarding mental health on the internet. Thus, internet-based screening with automated feedback has great potential to address individuals with undetected depression. Objectives To determine whether automated feedback after internet-based depression screening reduces depression severity as compared to no feedback. Methods The internet-based, observer-blinded DISCOVER RCT aims to recruit a total of 1074 individuals. Participants will be screened for depression using the Patient Health Questionnaire (PHQ-9). In case of a positive screening result (PHQ-9 ≥ 10), participants with undetected depression will be randomised into one of three balanced study arms to receive either (a) no feedback (control arm), (b) standard feedback, or (c) tailored feedback on their screening result. The tailored feedback version will be adapted to participants' characteristics, i.e. symptom profile, preferences, and demographic characteristics. The primary hypothesis is that feedback reduces depression severity six months after screening compared to no feedback. The secondary hypothesis is that tailored feedback is more efficacious compared to standard feedback. Further outcomes are depression care, help-seeking behaviour, health-related quality of life, anxiety, somatic symptom severity, intervention acceptance, illness beliefs, adverse events, and a health economic evaluation. Follow-ups will be conducted one month and six months after screening by self-report questionnaires and clinical interviews. According to a statistical analysis plan, the primary outcome will be analysed on an intention-to-treat basis applying multilevel modelling. Discussion The results of the DISCOVER RCT will inform about how automated feedback after internet-based screening could improve early detection and resolution of depression. Ways of dissemination and how the trial can contribute to an understanding of help-seeking behaviour processes will be discussed. If the results show that automated feedback after internet-based depression screening can reduce depression severity, the intervention could be easily implemented and might substantially reduce the disease burden of individuals with undetected depression. Ethical approval The study is approved by the Ethics Committee of the Hamburg Medical Association. Trial registration The trial was registered at ClinicalTrials.gov in November 2020 (identifier: NCT04633096)., Highlights • DISCOVER is an internet-based three-armed randomised controlled trial. • The efficacy of feedback after internet-based depression screening is unknown. • The feedback intervention was developed in a multistage process and is open-source. • DISCOVER tests a novel approach to detect depression early via internet.

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

Family functioning is often impaired in families with a parent with mental illness and is linked to child mental health. This study aims to gain a better understanding of family functioning in affected families by comparing ratings among family members and by analyzing associations with clinician-rated family functioning. The cross-sectional sample comprised 210 families with ratings of 207 patients, 139 partners, and 100 children. Parents with a mental illness as well as their partners and children completed the German version of the Family Assessment Measure (FAM). Clinician ratings were obtained by the Global Assessment of Relational Functioning Scale (GARF). We conducted several mixed models to compare ratings of family functioning while accounting for family cluster. Family dysfunction was consistently elevated compared to a normative sample. On several domains, parents with a mental illness perceived family functioning to be worse compared to their partners and children. Partners and children did not differ in their perceptions of family functioning. Ratings of family members were moderately associated with clinician ratings. We discuss the importance of multi-informant assessment of family functioning and the implementation of family-based interventions for families with a parent with mental illness.

Objective: While incidence rates of depression and anxiety disorders in the elderly have been comprehensively investigated, the incidence rates of other mental disorders have rarely been researched. The incidence rate and predictors of various mental disorders in the elderly were evaluated in different European and associated countries. Methods: A cross-sectional and longitudinal multi-centre survey of Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnoses was conducted in different European and associated countries (Germany, Italy, Spain, Switzerland, the United Kingdom and Israel) to collect data on the prevalence and incidence of mental disorders in the elderly. The sample size of the longitudinal wave was N = 2592 elderly. Results: The overall 1-year incidence rate for any mental disorder in the elderly is 8.65%. At 5.18%, any anxiety disorder had the highest incidence rate across all diagnostic groups. The incidence rate for any affective disorder was 2.97%. The lowest incidence rates were found for agoraphobia (1.37%) and panic disorder (1.30%). Risk factors for the development of any mental disorder were never having been married, no religious affiliation, a higher number of physical illnesses and a lower quality of life. Conclusion: In comparison to other studies, lower incidence rates for any affective disorder and middle-range incidence for any anxiety disorder were found. To the authors’ knowledge, no prior studies have reported 1-year incidence rates for somatoform disorder, bipolar disorder and substance misuse in community-dwelling elderly. These findings indicate the need to raise awareness of psychosocial problems in the elderly and to ensure adequate availability of mental health services.

The relevance of coping behavior for the individual's own mental health has been widely investigated. However, research on the association between coping of parents with a mental illness and their children's mental health is scarce. In the current study, we address the role of several parental coping strategies and their relation to child psychological symptoms. As part of the German randomized controlled multicenter study CHIMPS (children of mentally ill parents), parents with mental illness completed questionnaires on illness-related coping and child mental health symptoms. Children's diagnoses of a mental disorder were assessed with diagnostic interviews. The sample comprised n = 195 parents with mental illness and n = 290 children and adolescents aged 4–18 years. We conducted mixed models to investigate the associations of parental coping strategies with internalizing and externalizing symptoms as well as the diagnosis of a mental disorder in children controlling for sociodemographic factors and parental symptom severity. Parental coping characterized by religiosity and quest for meaning was significantly associated with fewer mental health symptoms and lower odds of a mental disorder in children, whereas a depressed processing style was related to increased internalizing problems in the children. Coping behavior in parents with mental illness is a relevant factor for the mental health of their children and should be considered in preventive interventions.

Aims Treatment patterns were compared between randomized groups in EAST-AFNET 4 to assess whether differences in anticoagulation, therapy of concomitant diseases, or intensity of care can explain the clinical benefit achieved with early rhythm control in EAST-AFNET 4. Methods and results Cardiovascular treatment patterns and number of visits were compared between randomized groups in EAST-AFNET 4. Oral anticoagulation was used in >90% of patients during follow-up without differences between randomized groups. There were no differences in treatment of concomitant conditions between groups. The type of rhythm control varied by country and centre. Over time, antiarrhythmic drugs were given to 1171/1395 (84%) patients in early therapy, and to 202/1394 (14%) in usual care. Atrial fibrillation (AF) ablation was performed in 340/1395 (24%) patients randomized to early therapy, and in 168/1394 (12%) patients randomized to usual care. 97% of rhythm control therapies were within class I and class III recommendations of AF guidelines. Patients randomized to early therapy transmitted 297 166 telemetric electrocardiograms (ECGs) to a core lab. In total, 97 978 abnormal ECGs were sent to study sites. The resulting difference between study visits was low (0.06 visits/patient/year), with slightly more visits in early therapy (usual care 0.39 visits/patient/year; early rhythm control 0.45 visits/patient/year, P Conclusion The clinical benefit of early, systematic rhythm control therapy was achieved using variable treatment patterns of antiarrhythmic drugs and AF ablation, applied within guideline recommendations.

Summary. Background: The study aimed to evaluate the outcomes of percutaneous transluminal angioplasty (PTA) in lower-extremity peripheral artery disease (PAD) patients. Patients and methods: A multi-centre, observational study was performed with 32 German and Austrian centres contributing data to the PTA registry. Data of 1,781 patients with lower-leg and pelvic PAD who were suitable for endovascular PTA treatment were contributed from participating centres. Data from 1,533 patients are reported here (1,055 male and 478 female). This study did not have exclusion criteria. Quality of life (QOL) questionnaire (EQ-5D) scores, Rutherford classification, mortality, patency rate and details of major adverse cardiovascular events were collected at 6-, 12-, 18-, and 24-month follow ups. Results: PTA with/without stenting achieved 90.3 %, 86.5 %, 82.7 %, and 71.9 % technical success (recanalisation achieving ≥ 70 % patency, no evidence of embolisation, recoiling or dissection) in iliac, femoral, popliteal, and below-the-knee arteries, respectively. Procedural/postprocedural complications occurred in 142 (9.3 %, 1 death) and 74 (4.8 %) patients. QOL, mobility, self-care, activity, and pain/discomfort scores improved (p

Objectives To examine the effectiveness of extensive social therapy intervention during inpatient multi-component cardiac rehabilitation (CR) on return to work and quality of life in patients with low probability of work resumption after an acute cardiac event. Methods Patients after acute cardiac event with negative subjective expectations about return to work or unemployment (n = 354) were included and randomized in clusters of 3-6 study participants. Clusters were randomized for social counseling and therapy led by a social worker, six sessions of 60 min each in 3 weeks, or control group (usual care: individual counseling meeting by request). The return to work (RTW) status and change in quality of life (QoL, short form 12: Physical and Mental Component Summary PCS and MCS) 12 months after discharge from inpatient CR were outcome measures. Results The regression model for RTW showed no impact of the intervention (OR 1.1, 95% CI 0.6-2.1, P = 0.79; n = 263). Predictors were unemployment prior to CR as well as higher anxiety values at discharge from CR. Likewise, QoL was not improved by social therapy (linear mixed model: Delta PCS 0.3, 95% CI - 1.9 to 2.5; P = 0.77; n = 177; Delta MCS 0.7, 95% CI - 1.9 to 3.3; P = 0.58; n = 215). Conclusions In comparison to usual care, an intensive program of social support for patients during inpatient cardiac rehabilitation after an acute cardiac event had no additional impact on either the rate of resuming work or quality of life.

Aims To evaluate the effectiveness and safety of cryoballoon ablation (CBA) compared with radiofrequency ablation (RFA) for symptomatic paroxysmal or drug-refractory persistent atrial fibrillation (AF). Methods and results Prospective cluster cohort study in experienced CBA and RFA centres. Primary endpoint was ‘atrial arrhythmia recurrence’, secondary endpoints were as follows: procedural results, safety, and clinical course. A total of 4189 patients were included: CBA 2329 (55.6%) and RFA 1860 (44.4%). Cryoballoon ablation population was younger, with fewer comorbidities. Procedure time was longer in the RFA group (P = 0.01). Radiation exposure was 2487 (CBA) and 1792 cGycm2 (RFA) (P Conclusions The primary endpoint did not differ between CBA and RFA. Cryoballoon ablation was completed rapidly; the radiation exposure was greater. Rehospitalization due to re-ablations and adverse events during follow-up were observed significantly less frequently after CBA than after RFA. Subgroup analysis suggested a lower risk of recurrence after CBA in paroxysmal AF. Trial Registration ClinicalTrials.gov (NCT01360008), https://clinicaltrials.gov/ct2/show/NCT01360008.

Die Versorgung psychischer Storungen stellt eine grose Herausforderung fur das deutsche Gesundheitssystem dar. Wenn Mehrfachdiagnosen vorliegen, leiden die Betroffenen unter einer besonders hohen Krankheitslast. Innovative Behandlungsmodelle fur eine integrierte und gestufte Versorgung (Collaborative Care und Stepped Care) sind bisher nur hinsichtlich ihrer Wirksamkeit fur singulare Storungsbilder untersucht worden. Das Projekt „Integrierte und gestufte Versorgung psychischer Erkrankungen durch Uberwindung sektoraler Behandlungsbarrieren“ (COMET), welches vom Hamburger Netzwerk fur Versorgungsforschung (HAM-NET) von 2017 bis 2020 durchgefuhrt wird, untersucht ein innovatives, leitlinienorientiertes Versorgungsmodell zur Verbesserung der Versorgung von Menschen mit psychischen Storungen unter Einbezug moglicher Komorbiditaten. Dieses neue Stepped- und Collaborative-Care-Modell fur Patienten der Primarversorgung, das Hausarzte, Psychiater und Psychotherapeuten sowie Kliniken vernetzt, wird im vorliegenden Beitrag vorgestellt. Zur Implementierung und Forderung des Modells wurden leitliniengerechte Behandlungspfade, ein tabletgestutztes Programm fur Screening, Diagnostik und leitliniengerechte Behandlungsempfehlungen sowie eine webbasierte Terminvergabeplattform entwickelt. Die aus dem Projekt gewonnenen Erkenntnisse zur Effektivitat und Effizienz des Modells konnen die Entscheidung, ob das Modell zukunftig in die Gesundheitsversorgung ubertragen wird, unterstutzen. Damit konnte ein entscheidender Fortschritt im Hinblick auf eine starker integrierte und sektorenubergreifende Versorgung von Patienten mit psychischen Storungen gelingen.

A commonly used approach to study the association between a time-varying biomarker, such as forced vital capacity (FVC), and a time-to-event outcome, such as new onset of chronic obstructive pulmonary disease (COPD), is to incorporate the biomarker as a time-dependent covariate in a Cox model. This approach, which is known as the time-dependent Cox model (TDCM), requires knowledge of the value of the time-varying biomarker at all time points at which the event of interest occurs [1]. However, in clinical studies, longitudinal biomarker measurements are taken intermittently during scheduled (and sometimes unscheduled) visits, meaning that imputation of missing values is required for those event times at which the biomarker is not observed. In practical application of the TDCM, this is achieved by carrying forward the most recent biomarker measurement. While the use of last observation carried forward (LOCF) is easy to understand and implement, the resulting step function (see fig. 1, panel C for an example) is unlikely to provide a good approximation of the true biomarker trajectory. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr. Chen has nothing to disclose. Conflict of interest: Dr. Postmus has nothing to disclose. Conflict of interest: Dr. Cowie has nothing to disclose. Conflict of interest: Dr. Woehrle has nothing to disclose. Conflict of interest: Dr. Wegscheider has nothing to disclose. Conflict of interest: Dr. Simonds has nothing to disclose. Conflict of interest: Dr. Boezen has nothing to disclose. Conflict of interest: Dr. Somers reports other from Steering Committee SERV HF, outside the submitted work. Conflict of interest: Dr. Teschler has nothing to disclose. Conflict of interest: Dr. Eulenburg has nothing to disclose.

Background: Children of mentally ill parents have a three to seven times higher risk of developing mental disorders compared to the general population. For this high-risk group, specialized prevention and intervention programs have already been developed. However, there has been insufficient sytematic evaluation to date. Moreover, effectiveness and the cost-effectiveness data of the respective programs until today is very scarce and at the same time constitutes the pre-condition for the program's implementation into regular health care.Methods: The study consists of a two-group randomized controlled multicenter trial conducted at seven study sites throughout Germany and Switzerland. Participants are families with mentally ill parents and their children aged from 3 to 19 years. The intervention comprises 6 to 8 semi-structured sessions over a period of about 6 months. Topics discussed in the intervention include parental mental illness, coping, family relations and social support. Families in the control condition will receive treatment as usual. The children's mental health, assessed using the K-SADS-PL by blinded external raters will constitute the primary efficacy outcome. Further outcomes will be assessed from the parents' as well as from the children's perspectives. Participants are investigated at baseline, 6, 12, and 18 months after baseline assessment. In addition to the assessment of various psychosocial outcomes, a comprehensive health-economic evaluation will be performed.Discussion: This paper describes the evaluation of a family-based intervention program for children of mentally ill parents (CHIMPs) in the regular health care system in Germany and Switzerland. A methodically sophisticated study design has been developed to reflect the complexity of the actual health care situation. This trial will contribute to the regular health care for the high-risk group of children of mentally ill parents.Clinical Trial Registration:www.ClinicalTrials.gov, identifier NCT02308462; German Clinical Trials Register: DRKS00006806.

Background Families of children with rare diseases (i.e., not more than 5 out of 10,000 people are affected) are often highly burdened with fears, insecurities and concerns regarding the affected child and its siblings. Although families caring for children with rare diseases are known to be at risk for mental disorders, the evaluation of special programs under high methodological standards has not been conducted so far. Moreover, the implementation of interventions for this group into regular care has not yet been accomplished in Germany. The efficacy and cost-effectiveness of a family-based intervention will be assessed. Methods/design The study is a 2x2 factorial randomized controlled multicenter trial conducted at 17 study centers throughout Germany. Participants are families with children and adolescents affected by a rare disease aged 0 to 21 years. Families in the face-to-face intervention CARE-FAM, online intervention WEP-CARE or the combination of both will be treated over a period of roughly 6 months. Topics discussed in the interventions include coping, family relations, and social support. Families in the control condition will receive treatment as usual. The primary efficacy outcome is parental mental health, measured by the Structured Clinical Interview for DSM-IV (SCID-I) by blinded external raters. Further outcomes will be assessed from the parents’ as well as the children’s perspective. Participants are investigated at baseline, 6, 12 and 18 months after randomization. In addition to the assessment of various psychosocial outcomes, a comprehensive health-economic evaluation will be performed. Discussion This paper describes the implementation and evaluation of two family-based intervention programs for Children Affected by Rare Disease and their Family’s Network (CARE-FAM-NET) in German standard care. A methodologically challenging study design is used to reflect the complexity of the actual medical care situation. This trial could be an important contribution to the improvement of care for this highly burdened group. Trial registration German Clinical Trials Register: DRKS00015859 (registered 18 December 2018) and ClinicalTrials.gov: NCT04339465 (registered 8 April 2020). Protocol Version: 15 August 2020 (Version 6.1). Trial status: Recruitment started on 1 January 2019 and will be completed on 31 March 2021.

Background/Purpose The interaction between the risk of arrhythmic death and a competing non-arrhythmic risk of death in patients suitable for implantable cardioverter defibrillator (ICD) implantation is not well understood. Commonly, identification of subpopulations with the largest benefit of ICD implantation has been performed by separate risk models for the outcomes death and appropriate shock therapy. The interrelation between the outcomes was not sufficiently studied. Methods Data were derived from the safety population of the multinational, prospectively randomized NORDIC ICD trial (N=1067) with real-word patients implanted with a single, dual or triple chamber ICD for primary or secondary prevention. Since all outcome adjudication was performed by an independent Clinical Event Committee supported by full telemonitoring data transmission, a high validity of ICD interventions could be achieved. To investigate the impact of baseline characteristics on time to first appropriate shock, death without prior appropriate shock therapy and death after appropriate shock therapy, a multi-state Cox model was computed. Missing data have been multiply imputed before analysis. Results At 36 months follow-up, 86.4% of the patients were alive (7.8% after appropriate shock). 11.0% and 2.6% patients died without or after a foregoing appropriate shock, respectively. The primary randomization allocation showed no significant effect on the 3 outcome types. Higher age (per 5 years) and NYHA functional class (≥III vs. ≤II) were associated with an increased risk of death without appropriate shock (HR 1.31, 95% CI 1.14–1.50, p Conclusion The new multi-state model shows the interrelation between appropriate shocks and death, as well a remarkable variation of risk factors for the transitions. Specifically, the presence of higher age and NYHA functional class ≥III at baseline were strong prognostic factors for all-cause mortality without a foregoing shock therapy, but were not predictive for an appropriate shock therapy. In this all-comer study, a significant discriminator predictive for appropriate shock therapy, but not for death was an indication for secondary prevention of sudden cardiac death. Multi-state graph for NYHA class Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This work was supported by Biotronik SE & Co. KG (Berlin, Germany)

Background: Recent data demonstrate promising effects on left ventricular dysfunction and left ventricular ejection fraction (LVEF) improvement following ablation for atrial fibrillation (AF) in patients with heart failure. We sought to study the relationship between LVEF, New York Heart Association class on presentation, and the end points of mortality and heart failure admissions in the CASTLE-AF study (Catheter Ablation for Atrial Fibrillation With Heart Failure) population. Furthermore, predictors for LVEF improvement were examined. Methods: The CASTLE-AF patients with coexisting heart failure and AF (n=363) were randomized in a multicenter prospective controlled fashion to ablation (n=179) versus pharmacological therapy (n=184). Left ventricular function and New York Heart Association class were assessed at baseline (after randomization) and at each follow-up visit. Results: In the ablation arm, a significantly higher number of patients experienced an improvement in their LVEF to >35% at the end of the study (odds ratio, 2.17; P P =0.006), all-cause mortality (HR, 0.54; P =0.019), and cardiovascular hospitalizations (HR, 0.66; P =0.017). In the ablation group, New York Heart Association I/II patients at the time of treatment had the strongest improvement in clinical outcomes (primary end point: HR, 0.43; P P =0.001). Conclusions: Compared with pharmacological treatment, AF ablation was associated with a significant improvement in LVEF, independent from the severity of left ventricular dysfunction. AF ablation should be performed at early stages of the patient’s heart failure symptoms.