Increased reaction times and reduced response preparation already starts at middle age

Generalized slowing characterizes aging and there is some evidence to suggest that this slowing already starts at midlife. This study aims to assess reaction time changes while performing a concurrent low-force and high-force motor task in young and middle-aged subjects. The high-force motor task is designed to induce muscle fatigue and thereby progressively increase the attentional demands. Twenty-five young (20-30 years, 12 males) and sixteen middle-aged (35-55 years, 9 males) adults performed an auditory two-choice reaction time task (CRT) with and without a concurrent low- or high-force motor task. The CRT required subjects to respond to two different stimuli that occurred with a probability of 70% or 30%. The motor task consisted of index finger abduction, at either 10% (10%-dual-task) or 30% (30%-dual-task) of maximal voluntary force. Cognitive task performance was measured as percentage of correct responses and reaction times.Middle-aged subjects responded slower on the frequent but more accurately on the infrequent stimuli of CRT than young subjects. Both young and middle-aged subjects showed increased errors and reaction times while performing under dual-task conditions and both outcome measures increased further under fatiguing conditions. Only under 30%-dual-task demands, an age-effect on dual-task performance was present. Both single- and dual-task conditions showed that already at mid-life response preparation is seriously declined and that subjects implement different strategies to perform a CRT task.<br/

Indicatoren voor de zorgtoewijzing bij persoonlijkheidsstoornissen: resultaten van een concept map analyse

Using the concept map method, this study revealed patient characteristics that are important for treatment selection decisions in patients with personality disorders. Concept mapping is a specific type of structured conceptualization process and describes the underlying structure of specific phenomena. The method uses qualitative and quantitative methods. In this study, we integrated a literature investigation with the opinions of 29 experts in the field of treatment allocation and/or personality disorders. Our goal was to reduce and describe the number of patient characteristics that are important for treatment allocation in personality disorders. The concept map procedure resulted in eight patient characteristics: (1) severity of symptoms, (2) severity of personality pathology, (3) ego-adaptive capacity, (4) motivation and capacity for a therapeutic alliance, (5) patient’s social system, (6) social demographic variables, (7) traumata, (8) treatment history and physical examination. This report describes in detail the concept mapping procedure and the outcomes are discussed

Stepping stones to improve cardio-oncological care

Cardio-oncology is a new subspecialty which focuses on cardiovascular side effects of anticancer therapy. Cardiovascular effects consist of arrhythmias, pericardial-, valvular- or coronary artery disease. The risk of cardiovascular effects is predominantly determined by the type of anticancer treatment. One of the most important side effects is myocardial damage, which can lead to an impaired cardiac function. This impaired cardiac function can eventually can lead to heart failure. This thesis describes methods for the establishment of specialized cardio-oncological care for patients at risk for cardiotoxic side effects due to anticancer treatment. One of the studies in this thesis describes the added value of specialized cardiac care for cancer patients. Two other studies focus on the cardiotoxic effects of a number of anticancer treatments. Another study describes the design of ONCOR, the Dutch Cardio-Oncology Registry. This registry collects data of patients who have received care at specialized cardio-oncology clinics. The ONCOR registry has been implemented in several Dutch hospitals and outcomes can be helpful in the improvement of cardio-oncology care. An important finding from the thesis is that the majority of patients with cancer therapy-induced myocardial damage do not experience cardiac complaints. This side-effect can therefore remain undetected in the absence of cardiac screening. Early identification can be beneficial, as one study found that patients with early identification of cardiac dysfunction showed better improvement of cardiac function after initiation of heart failure therapy

Stepping stones to improve cardio-oncological care

Cardio-oncology is a new subspecialty which focuses on cardiovascular side effects of anticancer therapy. Cardiovascular effects consist of arrhythmias, pericardial-, valvular- or coronary artery disease. The risk of cardiovascular effects is predominantly determined by the type of anticancer treatment. One of the most important side effects is myocardial damage, which can lead to an impaired cardiac function. This impaired cardiac function can eventually can lead to heart failure. This thesis describes methods for the establishment of specialized cardio-oncological care for patients at risk for cardiotoxic side effects due to anticancer treatment. One of the studies in this thesis describes the added value of specialized cardiac care for cancer patients. Two other studies focus on the cardiotoxic effects of a number of anticancer treatments. Another study describes the design of ONCOR, the Dutch Cardio-Oncology Registry. This registry collects data of patients who have received care at specialized cardio-oncology clinics. The ONCOR registry has been implemented in several Dutch hospitals and outcomes can be helpful in the improvement of cardio-oncology care. An important finding from the thesis is that the majority of patients with cancer therapy-induced myocardial damage do not experience cardiac complaints. This side-effect can therefore remain undetected in the absence of cardiac screening. Early identification can be beneficial, as one study found that patients with early identification of cardiac dysfunction showed better improvement of cardiac function after initiation of heart failure therapy

Early- and late anthracycline-induced cardiac dysfunction: echocardiographic characterization and response to heart failure therapy

BACKGROUND: Anthracycline-induced cardiac dysfunction (ACD) is a notorious side effect of anticancer treatment. It has been described as a phenomenon of a continuous progressive decline of cardiac function, eventually leading to dilated cardiomyopathy (DCM). This progressive nature suggests that patients with a delayed ACD diagnosis have greater compromise of cardiac function and more adverse remodeling, with a poor response to heart failure (HF) treatment. This study aimed to delineate the impact of a delayed ACD diagnosis on echocardiographic characteristics and response to HF treatment. METHODS AND RESULTS: From the population of our cardio-oncology outpatient clinic, 92 ACD patients were included in this study (age 51.6 ± 16.2 years, median cumulative anthracycline dose 329 [200-329] mg/m2), and a median follow-up of 25.0 [9.6-37.2] months after ACD diagnosis. Median time to ACD diagnosis for patients diagnosed early ( 1 year) was 4.0 vs. 47.7 months respectively. There were no echocardiographic differences between patients diagnosed early vs. late (LVEF 43.6 ± 4.9% vs. 43.0 ± 6.2% and iEDV 63.6 vs. 62.9 mL/m2). Eighty-three percent of patients presented with mild LV dysfunction and in 79% the LV was not dilated. Patients diagnosed early were more likely to have (partial) recovery of cardiac function upon HF treatment initiation (p = 0.015). CONCLUSIONS: In the setting of a cardio-oncology outpatient clinic, patients with ACD presented with a hypokinetic non-dilated cardiomyopathy, rather than typical DCM. Timing of ACD diagnosis did not impact HF disease severity. However, in patients receiving an early diagnosis, cardiac function was more likely to recover upon HF treatment

Cancer Therapy-Related Cardiac Dysfunction of Nonanthracycline Chemotherapeutics. What Is the Evidence?

Cancer therapy–related cardiac dysfunction (CTRCD) is one of the most concerning cardiovascular side effects of cancer treatment. Important reviews within the field of cardio-oncology have described various agents to be associated with a high risk of CTRCD, including mitomycin C, ifosfamide, vincristine, cyclophosphamide, and clofarabine. The aim of this study was to provide insight into the data on which these incidence rates are based. We observed that the reported cardiotoxicity of mitomycin C and ifosfamide is based on studies in which most patients received anthracyclines, complicating the interpretation of their association with CTRCD. The high incidence of vincristine-induced cardiotoxicity is based on an incorrect interpretation of a single study. Incidence rates of clofarabine remain uncertain due to a lack of cardiac screening in clinical trials. The administration of high-dose cyclophosphamide (>1.5 g/m2/day) is associated with a high incidence of CTRCD. Based on our findings, a critical re-evaluation of the cardiotoxicity of these agents is warranted

Cardiovascular adverse events in patients with non-Hodgkin lymphoma treated with first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP with rituximab (R-CHOP) : a systematic review and meta-analysis

Background: Patients treated for non-Hodgkin lymphoma are at risk of cardiovascular adverse events, with the risk of heart failure being particularly high. A regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone, with (R-CHOP) or without (CHOP) rituximab is the standard first-line treatment for aggressive non-Hodgkin lymphoma, and doxorubicin and cyclophosphamide are both associated with left ventricular dysfunction. The aim of this systematic review and meta-analysis was to evaluate the cardiovascular toxicity of this regimen. Methods: We systematically searched PubMed, EMBASE, and the Cochrane Library from database inception to June 3, 2019, for clinical trials and observational studies in adult patients with non-Hodgkin lymphoma (diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma, and non-Hodgkin lymphoma not otherwise specified) that received first-line treatment with R-CHOP or CHOP. Studies reporting on cardiovascular adverse events and treatment-related cardiovascular mortality were included. Abstracts and articles not written in English were excluded. The main outcomes were the proportion of patients with grade 3–4 cardiovascular adverse events and heart failure. Meta-analyses of one-sample proportions were done in all patients receiving CHOP or R-CHOP. Subgroup analyses on summary estimates were done to determine the effect of number of CHOP or R-CHOP cycles, cycle interval, age, and sex. Findings: Of 2314 identified entries, 137 studies (21 211 patients) published between April, 1984, and June, 2019 were eligible (9541 patients treated with CHOP, 11 293 patients treated with R-CHOP, 377 both regimens used in the study; median follow-up 39·0 months [IQR 25·5–52·8]). From the included studies, 85 subgroups were treated with CHOP, 76 with R-CHOP, and in four studies both CHOP and R-CHOP were used without a subdivision in separate groups. The pooled proportion for grade 3–4 cardiovascular adverse events, based on 77 studies (n=14 351 patients), was 2·35% (95% CI 1·81–2·93; heterogeneity test Q=326·21; τ 2=0·0042; I 2=71·40%; p<0·0001). For heart failure, the pooled proportion, based on 38 studies (n=5936 patients), was 4·62% (2·25–7·65; heterogeneity test Q=527·33; τ 2=0·0384; I 2=95·05%; p<0·0001), with a significant increase in reported heart failure from 1·64% (95% CI 0·82–2·65) to 11·72% (3·00–24·53) when cardiac function was evaluated post-chemotherapy (p=0·017). 53 (39%) of 137 studies were rated as having high risk of bias for incomplete outcome data and 54 (39%) for selective reporting. Interpretation: The considerable increase of reported heart failures with cardiac monitoring, indicates that this complication often remains undiagnosed in patients with non-Hodgkin lymphoma who received first-line R-CHOP or CHOP. Our findings are of importance to raise awareness of this complication among clinicians treating patients with non-Hodgkin lymphoma and stresses the need for cardiac monitoring during and after chemotherapy. Prompt initiation of treatment for heart failure in the presymptomatic phase can mitigate the progression to more advanced heart failure stages. Funding: None

Cardiovascular adverse events in patients with non-Hodgkin lymphoma treated with first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP with rituximab (R-CHOP) : a systematic review and meta-analysis

Background: Patients treated for non-Hodgkin lymphoma are at risk of cardiovascular adverse events, with the risk of heart failure being particularly high. A regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone, with (R-CHOP) or without (CHOP) rituximab is the standard first-line treatment for aggressive non-Hodgkin lymphoma, and doxorubicin and cyclophosphamide are both associated with left ventricular dysfunction. The aim of this systematic review and meta-analysis was to evaluate the cardiovascular toxicity of this regimen. Methods: We systematically searched PubMed, EMBASE, and the Cochrane Library from database inception to June 3, 2019, for clinical trials and observational studies in adult patients with non-Hodgkin lymphoma (diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma, and non-Hodgkin lymphoma not otherwise specified) that received first-line treatment with R-CHOP or CHOP. Studies reporting on cardiovascular adverse events and treatment-related cardiovascular mortality were included. Abstracts and articles not written in English were excluded. The main outcomes were the proportion of patients with grade 3–4 cardiovascular adverse events and heart failure. Meta-analyses of one-sample proportions were done in all patients receiving CHOP or R-CHOP. Subgroup analyses on summary estimates were done to determine the effect of number of CHOP or R-CHOP cycles, cycle interval, age, and sex. Findings: Of 2314 identified entries, 137 studies (21 211 patients) published between April, 1984, and June, 2019 were eligible (9541 patients treated with CHOP, 11 293 patients treated with R-CHOP, 377 both regimens used in the study; median follow-up 39·0 months [IQR 25·5–52·8]). From the included studies, 85 subgroups were treated with CHOP, 76 with R-CHOP, and in four studies both CHOP and R-CHOP were used without a subdivision in separate groups. The pooled proportion for grade 3–4 cardiovascular adverse events, based on 77 studies (n=14 351 patients), was 2·35% (95% CI 1·81–2·93; heterogeneity test Q=326·21; τ 2=0·0042; I 2=71·40%; p<0·0001). For heart failure, the pooled proportion, based on 38 studies (n=5936 patients), was 4·62% (2·25–7·65; heterogeneity test Q=527·33; τ 2=0·0384; I 2=95·05%; p<0·0001), with a significant increase in reported heart failure from 1·64% (95% CI 0·82–2·65) to 11·72% (3·00–24·53) when cardiac function was evaluated post-chemotherapy (p=0·017). 53 (39%) of 137 studies were rated as having high risk of bias for incomplete outcome data and 54 (39%) for selective reporting. Interpretation: The considerable increase of reported heart failures with cardiac monitoring, indicates that this complication often remains undiagnosed in patients with non-Hodgkin lymphoma who received first-line R-CHOP or CHOP. Our findings are of importance to raise awareness of this complication among clinicians treating patients with non-Hodgkin lymphoma and stresses the need for cardiac monitoring during and after chemotherapy. Prompt initiation of treatment for heart failure in the presymptomatic phase can mitigate the progression to more advanced heart failure stages. Funding: None

Sustainable Urban Mobility Plans: implementation process and indicators to evaluate effects on physical activity

BACKGROUND: Active mobility and public transport increase physical activity (PA) levels. With varying intensity and effectiveness, European cities implement Sustainable Urban Mobility Plans (SUMPs) to spur transport-related PA. Therefore, we aim to examine drivers and barriers to SUMP implementation and assess its influence on PA across European cities. METHODS: We screened policy reports to gain insights into SUMP implementation in one Danish, two German and two Polish cities. Further, we conducted semi-structured interviews with SUMP stakeholders in these cities to explore their experiences with SUMP implementation. Thematic analysis of interview transcripts was applied to identify similarities and differences across cities. To assess the effect of SUMP implementation on PA, we searched for data on indicators of transport-related PA. RESULTS: All investigated cities are committed to sustainable mobility. Nonetheless, complex institutional structures, the dominant role of motorized traffic as well as complex regional and local policy integration hamper SUMP implementation. Danish, German and Polish cities face different contexts in terms of financing, national guidelines and the prominence of sustainability as a policy objective. Each city adopts unique indicators for monitoring the effects of SUMPs on transport-related PA. The variety of indicators and limited data availability impede a comparative evaluation across cities. Constrained by this restriction, we identified motorization rate, modal split and public transport ridership as suitable indicators. CONCLUSIONS: Local idiosyncrasies need to be accounted for when assessing the implementation of SUMPs. Nonetheless, consistent indicators and data transparency are essential for comparing the effectiveness of SUMPs and their impact on PA.The PEN project is funded by the Joint Programming Initiative (JPI) ‘A Healthy Diet for a Healthy Life’, a research and innovation initiative of EU member states and associated countries. The funding agencies supporting this work are (in alphabetical order of participating countries): Germany: Federal Ministry of Education and Research (BMBF) (grant numbers: 01EA1818A (for Bremen); 01EA1818D (for Ulm)); Poland: The National Centre for Research and Development (NCBR) grant nr JFA PEN/I/PEN40/02/2019; The Netherlands: The Netherlands Organisation for Health Research and Development (ZonMw) (grant no. 529051020)