Heart failure and promotion of physical activity before and after cardiac rehabilitation (HF-aPProACH):a study protocol

Abstract Aims Lifestyle changes, such as increasing physical activity (PA), are a cornerstone of treatment of patients with chronic heart failure (HF). However, improving PA in HF patients is challenging, and low participation rates for cardiac rehabilitation (CR) as well as relapse to low PA levels after CR are major issues. We designed a randomized controlled trial to investigate if PA monitoring with motivational feedback before and after centre‐based CR in HF patients with reduced ejection fraction (HFrEF) will lead to a clinically meaningful increase in physical fitness. Methods and results A randomized controlled trial will be conducted in a sample of 180 HFrEF patients (New York Heart Association Class II/III) who are referred to 12‐week standard CR. Patients will be randomized (2:1) to (1) standard of care (SoC) plus wearing a PA monitoring device (Fitbit Charge 3) with personalized step goals, feedback and motivation or (2) SoC only. The intervention lasts ±7 months: 4–5 weeks before CR, 12 weeks during CR and 12 weeks after CR. Measurements will take place at three time points. The primary endpoint is the change in the distance in 6‐min walking test (6MWT) over the entire study period. Other endpoints include step count, grip strength, quality of life and all‐cause mortality or hospitalization. Conclusions HF‐aPProACH will provide novel information on the effectiveness of remote PA stimulation and feedback before, during and after standard CR using a commercially available device to improve physical fitness in HFrEF patients

Population-based impact of COVID-19 on incidence, treatment, and survival of patients with pancreatic cancer

Background: The COVID-19 pandemic has put substantial strain on the healthcare system of which the effects are only partly elucidated. This study aimed to investigate the impact on pancreatic cancer care. Methods: All patients diagnosed with pancreatic cancer between 2017 and 2020 were selected from the Netherlands Cancer Registry. Patients diagnosed and/or treated in 2020 were compared to 2017–2019. Monthly incidence was calculated. Patient, tumor and treatment characteristics were analyzed and compared using Chi-squared tests. Survival data was analyzed using Kaplan–Meier and Log-rank tests. Results: In total, 11019 patients were assessed. The incidence in quarter (Q)2 of 2020 was comparable with that in Q2 of 2017–2019 (p = 0.804). However, the incidence increased in Q4 of 2020 (p = 0.031), mainly due to a higher incidence of metastatic disease (p = 0.010). Baseline characteristics, surgical resection (15% vs 16%; p = 0.466) and palliative systemic therapy rates (23% vs 24%; p = 0.183) were comparable. In 2020, more surgically treated patients received (neo)adjuvant treatment compared to 2017–2019 (73% vs 67%; p = 0.041). Median overall survival was comparable (3.8 vs 3.8 months; p = 0.065). Conclusion: This nationwide study found a minor impact of the COVID-19 pandemic on pancreatic cancer care and outcome. The Dutch health care system was apparently able to maintain essential care for patients with pancreatic cancer

Continuity of care for patients with de novo metastatic cancer during the COVID-19 pandemic:A population-based observational study

During the COVID-19 pandemic recommendations were made to adapt cancer care. This population-based study aimed to investigate possible differences between the treatment of patients with metastatic cancer before and during the pandemic by comparing the initial treatments in five COVID-19 periods (weeks 1–12 2020: pre-COVID-19, weeks 12–20 2020: 1st peak, weeks 21–41 2020: recovery, weeks 42–53 2020: 2nd peak, weeks 1–20 2021: prolonged 2nd peak) with reference data from 2017 to 2019. The proportion of patients receiving different treatment modalities (chemotherapy, hormonal therapy, immunotherapy or targeted therapy, radiotherapy primary tumor, resection primary tumor, resection metastases) within 6 weeks of diagnosis and the time between diagnosis and first treatment were compared by period. In total, 74,208 patients were included. Overall, patients were more likely to receive treatments in the COVID-19 periods than in previous years. This mainly holds for hormone therapy, immunotherapy or targeted therapy and resection of metastases. Lower odds were observed for resection of the primary tumor during the recovery period (OR 0.87; 95% CI 0.77–0.99) and for radiotherapy on the primary tumor during the prolonged 2nd peak (OR 0.84; 95% CI 0.72–0.98). The time from diagnosis to the start of first treatment was shorter, mainly during the 1st peak (average 5 days, p &lt;.001). These findings show that during the first 1.5 years of the COVID-19 pandemic, there were only minor changes in the initial treatment of metastatic cancer. Remarkably, time from diagnosis to first treatment was shorter. Overall, the results suggest continuity of care for patients with metastatic cancer during the pandemic.</p

Hearing loss in Pompe disease revisited: results from a study of 24 children

Little information is available regarding the auditory function in Pompe patients. Hearing loss has been reported in classic infantile patients, but it is still unknown whether central nervous system involvement interferes with auditory function and whether enzyme replacement therapy can improve hearing. Audi

A Multifactorial Approach for Surveillance of Shigella spp. and Entero-Invasive Escherichia coli Is Important for Detecting (Inter)national Clusters

Shigella spp. and entero-invasive Escherichia coli (EIEC) can cause mild diarrhea to dysentery. In Netherlands, although shigellosis is a notifiable disease, there is no laboratory surveillance for Shigella spp. and EIEC in place. Consequently, the population structure for circulating Shigella spp. and EIEC isolates is not known. This study describes the phenotypic and serological characteristics, the phenotypic and genetic antimicrobial resistance (AMR) profiles, the virulence gene profiles, the classic multi-locus sequence types (MLST) and core genome (cg)MLST types, and the epidemiology of 414 Shigella spp. and EIEC isolates collected during a cross-sectional study in Netherlands in 2016 and 2017. S. sonnei (56%), S. flexneri (25%), and EIEC (15%) were detected predominantly in Netherlands, of which the EIEC isolates were most diverse according to their phenotypical profile, O-types, MLST types, and cgMLST clades. Virulence gene profiling showed that none of the isolates harbored Shiga toxin genes. Most S. flexneri and EIEC isolates possessed nearly all virulence genes examined, while these genes were only detected in approximately half of the S. sonnei isolates, probably due to loss of the large invasion plasmid upon subculturing. Phenotypical resistance correlated well with the resistant genotype, except for the genes involved in resistance to aminoglycosides. A substantial part of the characterized isolates was resistant to antimicrobials advised for treatment, i.e., 73% was phenotypically resistant to co-trimoxazole and 19% to ciprofloxacin. AMR was particularly observed in isolates from male patients who had sex with men (MSM) or from patients that had traveled to Asia. Furthermore, isolates related to international clusters were also circulating in Netherlands. Travel-related isolates formed clusters with isolates from patients without travel history, indicating their emergence into the Dutch population. In conclusion, laboratory surveillance using whole genome sequencing as high-resolution typing technique and for genetic characterization of isolates complements the current epidemiological surveillance, as the latter is not sufficient to detect all (inter)national clusters, emphasizing the importance of multifactorial public health approaches

External validation and clinical utility assessment of PREDICT breast cancer prognostic model in young, systemic treatment-naïve women with node-negative breast cancer

Background: The validity of the PREDICT breast cancer prognostic model is unclear for young patients without adjuvant systemic treatment. This study aimed to validate PREDICT and assess its clinical utility in young women with node-negative breast cancer who did not receive systemic treatment. Methods: We selected all women from the Netherlands Cancer Registry who were diagnosed with node-negative breast cancer under age 40 between 1989 and 2000, a period when adjuvant systemic treatment was not standard practice for women with node-negative disease. We evaluated the calibration and discrimination of PREDICT using the observed/expected (O/E) mortality ratio, and the area under the receiver operating characteristic curve (AUC), respectively. Additionally, we compared the potential clinical utility of PREDICT for selectively administering chemotherapy to the chemotherapy-to-all strategy using decision curve analysis at predefined thresholds. Results: A total of 2264 women with a median age at diagnosis of 36 years were included. Of them, 71.2% had estrogen receptor (ER)-positive tumors and 44.0% had grade 3 tumors. Median tumor size was 16 mm. PREDICT v2.2 underestimated 10-year all-cause mortality by 33% in all women (O/E ratio:1.33, 95%CI:1.22–1.43). Model discrimination was moderate overall (AUC10-year:0.65, 95%CI:0.62–0.68), and poor for women with ER-negative tumors (AUC10-year:0.56, 95%CI:0.51–0.62). Compared to the chemotherapy-to-all strategy, PREDICT only showed a slightly higher net benefit in women with ER-positive tumors, but not in women with ER-negative tumors. Conclusions: PREDICT yields unreliable predictions for young women with node-negative breast cancer. Further model updates are needed before PREDICT can be routinely used in this patient subset.</p

A Meta-analysis of Attachment to Parents and Delinquency

To investigate the link between attachment to parents and delinquency, and the potential moderating effects of age and sex, 74 published and unpublished manuscripts (N = 55,537 participants) were subjected to a multilevel meta-analysis. A mean small to moderate effect size was found (r = 0.18). Poor attachment to parents was significantly linked to delinquency in boys and girls. Stronger effect sizes were found for attachment to mothers than attachment to fathers. In addition, stronger effect sizes were found if the child and the parent had the same sex compared to cross-sex pairs of children and parents. Age of the participants moderated the link between attachment and delinquency: larger effect sizes were found in younger than in older participants. It can be concluded that attachment is associated with juvenile delinquency. Attachment could therefore be a target for intervention to reduce or prevent future delinquent behavior in juveniles

Intraductal cisplatin treatment in a BRCA-associated breast cancer mouse model attenuates tumor development but leads to systemic tumors in aged female mice

BRCA deficiency predisposes to the development of invasive breast cancer. In BRCA mutation carriers this risk can increase up to 80%. Currently, bilateral prophylactic mastectomy and prophylactic bilateral salpingo-oophorectomy are the only preventive, albeit radical invasive strategies to prevent breast cancer in BRCA mutation carriers. An alternative non-invasive way to prevent BRCA1-associated breast cancer may be local prophylactic treatment via the nipple. Using a non-invasive intraductal (ID) preclinical intervention strategy, we explored the use of combined cisplatin and poly (ADP)-ribose polymerase 1 (PARP1) inhibition to prevent the development of hereditary breast cancer. We show that ID cisplatin and PARP-inhibition can successfully ablate mammary epithelial cells, and this approach attenuated tumor onset in a mouse model of Brca1-associated breast cancer from 153 to 239 days. Long-term carcinogenicity studies in 150 syngeneic wild-type mice demonstrated that tumor incidence was increased in the ID treated mammary glands by 6.3% due to systemic exposure to cisplatin. Although this was only evident in aged mice (median age = 649 days), we conclude that ID cisplatin treatment only presents a safe and feasible local prevention option if systemic exposure to the chemotherapy used can be avoided

Serious, Minor, and Non-Delinquents in Early Adolescence: The Impact of Cumulative Risk and Promotive Factors. The TRAILS Study

This study uses a social-ecological approach to the development of delinquency. The authors emphasize that a balance between eliminating risk and enhancing protection across domains is essential in reducing problems and promoting competence. The cumulative risk and promotive effects of temperament, family and school factors in preadolescence were examined on different groups of delinquents (based on self-report) in early adolescence. Data from the first two waves of the TRAILS study (N = 2,230) were used. The results provide evidence for a compensatory model that assumes main effects of risk and promotive factors on problem behavior. Accumulation of risks in preadolescence promoted being a serious delinquent in early adolescence, with the strongest effects for temperament. Accumulation of promotive effects decreased being a delinquent and supported being a non-delinquent. Furthermore, evidence is found for a counter-balancing effect of cumulative promotive and risk factors. Exposure to more promotive domains in the relative absence of risk domains decreased the percentage of serious delinquents. Our results did not support a protective model. Implications for prevention and intervention are discussed