Examining adherence to activity monitoring devices to improve physical activity in adults with cardiovascular disease: A systematic review

Background Activity monitoring devices are currently being used to facilitate and monitor physical activity. No prior review has examined adherence to the use of activity monitoring devices amongst adults with cardiovascular disease. Methods Literature from June 2012 to October 2017 was evaluated to examine the extent of adherence to any activity monitoring device used to collect objective physical activity data. Randomized control trials comparing usual care against the use of an activity monitoring device, in a community intervention for adults from any cardiovascular diagnostic group, were included. A systematic search of databases and clinical trials registers was conducted using Joanna Briggs Institute methodology. Results Of 10 eligible studies, two studies reported pedometer use and eight accelerometer use. Six studies addressed the primary outcome. Mean adherence was 59.1% (range 39.6% to 85.7%) at last follow-up. Studies lacked equal representation by gender (28.6% female) and age (range 42 to 82 years). Conclusion This review indicates that current research on activity monitoring devices may be overstated due to the variability in adherence. Results showed that physical activity tracking in women and in young adults have been understudied

Oral Administration of GW788388, an Inhibitor of Transforming Growth Factor Beta Signaling, Prevents Heart Fibrosis in Chagas Disease

Cardiac damage and dysfunction are prominent features in patients with chronic Chagas disease, which is caused by infection with the protozoan parasite Trypanosoma cruzi (T. cruzi) and affects 10–12 million individuals in South and Central America. Our group previously reported that transforming growth factor beta (TGFß) is implicated in several regulatory aspects of T. cruzi invasion and growth and in host tissue fibrosis. In the present work, we evaluated the therapeutic action of an oral inhibitor of TGFß signaling (GW788388) administered during the acute phase of experimental Chagas disease. GW788388 treatment significantly reduced mortality and decreased parasitemia. Electrocardiography showed that GW788388 treatment was effective in protecting the cardiac conduction system, preserving gap junction plaque distribution and avoiding the development of cardiac fibrosis. Inhibition of TGFß signaling in vivo appears to potently decrease T. cruzi infection and to prevent heart damage in a preclinical mouse model. This suggests that this class of molecules may represent a new therapeutic tool for acute and chronic Chagas disease that warrants further pre-clinical exploration. Administration of TGFß inhibitors during chronic infection in mouse models should be further evaluated, and future clinical trials should be envisaged

Abnormal development of monoaminergic neurons is implicated in mood fluctuations and bipolar disorder

Subtle mood fluctuations are normal emotional experiences, whereas drastic mood swings can be a manifestation of bipolar disorder (BPD). Despite their importance for normal and pathological behavior, the mechanisms underlying endogenous mood instability are largely unknown. During embryogenesis, the transcription factor Otx2 orchestrates the genetic networks directing the specification of dopaminergic (DA) and serotonergic (5-HT) neurons. Here we behaviorally phenotyped mouse mutants overexpressing Otx2 in the hindbrain, resulting in an increased number of DA neurons and a decreased number of 5-HT neurons in both developing and mature animals. Over the course of 1 month, control animals exhibited stable locomotor activity in their home cages, whereas mutants showed extended periods of elevated or decreased activity relative to their individual average. Additional behavioral paradigms, testing for manic-and depressive-like behavior, demonstrated that mutants showed an increase in intra-individual fluctuations in locomotor activity, habituation, risk-taking behavioral parameters, social interaction, and hedonic-like behavior. Olanzapine, lithium, and carbamazepine ameliorated the behavioral alterations of the mutants, as did the mixed serotonin receptor agonist quipazine and the specific 5-HT 2C receptor agonist CP-809101. Testing the relevance of the genetic networks specifying monoaminergic neurons for BPD in humans, we applied an interval-based enrichment analysis tool for genome-wide association studies. We observed that the genes specifying DA and 5-HT neurons exhibit a significant level of aggregated association with BPD but not with schizophrenia or major depressive disorder. The results of our translational study suggest that aberrant development of monoaminergic neurons leads to mood fluctuations and may be associated with BPD

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Cardiotoxicity after cancer treatment: a process map of the patient treatment journey

Background/aim: Cardiotoxicity is a potential complication of anticancer therapy. While guidelines have been developed to assist practitioners, an effective, evidence based clinical pathway for the treatment of cardiotoxicity has not yet been developed. The aim of this study was to describe the journey of patients who developed cardiotoxicity through the healthcare system in order to establish baseline data to inform the development and implementation of a patient-centred, evidence-based clinical pathway.Methods: Mixed-methods design with quantitative and qualitative components using process mapping at 3 large medical centres in 2 states between 2010 and 2015.Results: Fifty (50) confirmed cases of cardiotoxicity were reviewed (39 medical record reviews, 7 medical record review and interviews\ua0and 4 internview only). The mean age at cancer diagnosis of this group was 53.3 years (range 6–89 years); 50% female; 30% breast cancer, 23% non-Hodgkin’s lymphoma; mean chemotherapy cycles 5.2 (median 6; range 1–18); 49 (89%) presented to chemotherapy with pre-existing cardiovascular risk factors; 39 (85%) had at least one modifiable risk factor and 11 (24%) had more than 4; 44 (96%) were diagnosed by echocardiogram and 27 (57%) were referred to a cardiologist (only 7 (15%) before chemotherapy). Post chemotherapy, 22 (48%) patients were referred to a multidisciplinary heart failure clinic; 8 (17%) to cardiac rehabilitation; 1 (2%) to cancer survivorship clinic and 10 (22%) to a palliative care service. There were 16 (34%) deaths during the timeframe of the study; 4 (25%) cardiac-related, 6 (38%) cancer-related, 4 (25%) due to sepsis and 2 (12%) other causes not recorded. The main concerns participants raised during the interviews were cancer professionals not discussing the potential for cardiotoxicity with them prior to treatment, nor risk modification strategies; a need for health education, particularly regarding risks for developing heart failure related to cancer treatment; and a lack of collaboration between oncologists and cardiologists.Conclusions: Our results demonstrate that the clinical management of cancer patients with cardiotoxicity was variable and fragmented and not patient centered. This audit establishes practice gaps that can be addressed through the design of an evidence-based clinical pathway for cancer patients with, or at risk, of cardiotoxicity

The Keeping on Track Study: Exploring the Activity Levels and Utilization of Healthcare Services of Acute Coronary Syndrome (ACS) Patients in the First 30-Days after Discharge from Hospital

The aim of this study was to investigate the impact of bedside discharge education on activity levels and healthcare utilization for patients with acute coronary syndrome (ACS) in the first 30 days post-discharge. Knowledge recall and objective activity and location data were collected by global positioning systems (GPS). Participants were asked to carry the tracking applications (apps) for 30–90 days. Eighteen participants were recruited (6 metropolitan 12 rural) 61% ST elevation myocardial infarction (STEMI), mean age 55 years, 83% male. Recall of discharge education included knowledge of diagnosis (recall = 100%), procedures (e.g., angiogram = 40%), and comorbidities (e.g., hypertension = 60%, diabetes = 100%). In the first 30 days post-discharge, median steps per day was 2506 (standard deviation (SD) ± 369) steps (one participant completed 10,000 steps), 62% visited a general practitioner (GP) 16% attended cardiac rehabilitation, 16% visited a cardiologist, 72% a pharmacist, 27% visited the emergency department for cardiac event, and 61% a pathology service (blood tests). Adherence to using the activity tracking apps was 87%. Managing Big Data from the GPS and physical activity tracking apps was a challenge with over 300,000 lines of raw data cleaned to 90,000 data points for analysis. This study was an example of the application of objective data from the real world to help understand post-ACS discharge patient activity. Rates of access to services in the first 30 days continue to be of concern