Reporting adherence, validity and physical activity measures of wearable activity trackers in medical research: A systematic review.

BACKGROUND: Wearable activity trackers are gaining traction in medical research, providing both real-time and remote monitoring of physical fitness. Activity trackers offer an excellent source of personalized physical activity data from patients, as well as healthy individuals, that would provide insights into healthcare analytics and user-feedback on health status. In addition, these activity trackers would also allow researchers to monitor symptom severity and assist clinicians in providing their patients a more holistic care. Despite the promise of wearable device technology, there is still a lack of standardization in the medical literature regarding the analysis and reporting of adherence, validity and physical activity data generated by these activity trackers. OBJECTIVE: We performed a systematic review to identify the activity tracker-derived measures and evaluate the relations of reported adherence, validity, and physical activity types across currently available literature. METHODS: The searches were performed using Pubmed and Embase databases. Studies enrolling at least 1,000 human subjects regardless of health or disease status, using activity trackers of any brand used to track step count, distance, heart rate, energy expenditure or activity intensity, were included. Studies have been published between 2009 to March 2021, with editorials, systematic reviews, meta-analysis, grey literature, validation studies, study protocols and studies using smartphone trackers being excluded. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: A total of 27 studies met the eligibility criteria and were included in the review, with a total of 514,418 and 1,186,530 subjects recruited in observational and interventional studies, respectively. Apart from ActiGraph (n = 11, 41%), Fitbit (n = 4, 15%) and Axivity (n = 3, 11%) were found to be the most commonly used activity trackers in both types of studies. The wear duration of activity trackers ranged from 1 day to 59 months, with 1 week being the most common length (n = 16, 59%). The most frequently collected physical activity measure was activity intensity (n = 21, 78%), followed by step count (n = 9, 33%) and energy expenditure (n = 2, 7%). Most studies defined a valid day as wear-time of at least 10 h within 1 day (n = 10, 37%), and a valid interval as a week with at least 3 valid days (n = 8, 30%). CONCLUSIONS: This systematic review reveals the diverse analysis and reporting of activity tracker data in the medical literature. Future studies will need to evaluate the feasibility on adopting minimum reporting thresholds of data generated by wearable activity trackers.

Extracellular Vesicle Proteome of Breast Cancer Patients with and Without Cognitive Impairment Following Anthracycline-based Chemotherapy: An Exploratory Study.

Cognitive impairment due to cancer and its therapy is a major concern among cancer patients and survivors. Extracellular vesicle (EVs) composition altered by cancer and chemotherapy may affect neurological processes such as neuroplasticity, potentially impacting the cognitive abilities of cancer patients and survivors. We investigated the EV proteome of breast cancer patients with and without cognitive impairment following anthracycline-based chemotherapy from longitudinally collected plasma. EVs were cup-shaped and positive for Flotillin-1 and TSG-101. We identified 517 differentially expressed EV proteins between the cognitive impaired and non-impaired groups during and post-chemotherapy. The observed decreased expression of p2X purinoceptor, cofilin-1, ADAM 10, and dynamin-1 in the plasma EVs of the cognitive impaired group may suggest alterations in the mechanisms underlying synaptic plasticity. The reduced expression of tight junction proteins among cognitive-impaired patients may imply weakening of the blood-brain barrier. These EV protein signatures may serve as a fingerprint that underscores the mechanisms underlying cognitive impairment in cancer patients and survivors.

A study protocol for HEalth-Related quality of life-intervention in survivors of Breast and other cancers experiencing cancer-related fatigue using TraditionAL Chinese Medicine: the HERBAL trial.

BACKGROUND: Cancer-related fatigue (CRF) is a debilitating condition which commonly affects cancer survivors. The management of CRF remains a challenge due to the lack of effective pharmacological interventions. Traditional Chinese medicine (TCM) could be a potential therapeutic option for CRF. The modified Xiang Bei Yang Rong Tang (XBYRT) is a TCM herbal decoction, formulated to improve fatigue symptoms in cancer survivors. This clinical trial aims to evaluate the efficacy and safety of XBYRT in improving CRF and quality of life (QOL) of cancer survivors. METHODS: This is a single centre, randomized, double-blind, placebo-controlled, parallel trial. Eighty cancer survivors will be recruited and randomized to receive the XBYRT or placebo decoction, in a ratio of 1:1. Participants will consume the XBYRT/placebo decoction daily for 8 weeks and undergo assessments at baseline and 4, 8 and 10 weeks after baseline. The participants will be assessed for patient-reported outcomes (PRO), blood biomarkers and adverse events at each time point. The primary outcome is the overall health and QOL status, at 8 weeks follow-up. The secondary outcomes are the effects of XBYRT on fatigue levels, cancer-related cognitive impairment and QOL, as assessed by PRO. The incidence of adverse events and the effects of the XBYRT decoction on blood biomarkers associated with CRF will also be evaluated. DISCUSSION: Efficacy and safety outcomes from this trial will provide important clinical data to guide future large-scale randomized controlled trials, and the evaluation of the objective blood biomarkers can help to delineate the biological mechanisms of CRF. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT04104113 . Registered on 26 September 2019.

Advances and future directions in the use of mobile health in supportive cancer care: proceedings of the 2019 MASCC Annual Meeting symposium.

PURPOSE: The role of mobile health (mHealth) technology in cancer care has evolved alongside the rapid development in digital technology. Its use can come with significant potential benefits; however, such use may also be associated with risks. This paper summarizes the latest developments around mHealth use in cancer care presented by a panel of experts at the 2019 Annual Meeting of the Multinational Association of Supportive Care in Cancer. METHODS: Through lectures, case studies, and panel discussions, speakers and participants (including cancer specialist doctors, nurses, and allied health professionals) evaluated current and emerging mHealth methods for supportive care in cancer survivorship. Focus areas and special considerations were agreed upon by consensus. RESULTS: Three focus areas for the use of mHealth in cancer care were identified: activation and support of self-management, exercise oncology, and enablement of survivorship care delivery. In addition to these focus areas, two special considerations were highlighted: technology-enhanced supportive cancer care for disparate populations, and ethical considerations relevant to the use of technology in supportive care. CONCLUSION: mHealth has the potential to revolutionize and transform cancer care delivery. Future research should guide further advances in the use of technology in supportive cancer care and carefully explore the safety, efficacy, cost-effectiveness, and implementation of interventions delivered through mHealth platforms.

Minimal clinically important difference of the EORTC QLQ-CIPN20 for worsening peripheral neuropathy in patients receiving neurotoxic chemotherapy.

CONTEXT/OBJECTIVES: This is the first study to determine the minimal clinically important difference (MCID) of the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (EORTC QLQ-CIPN20), a validated instrument designed to elicit cancer patients' experience of symptoms and functional limitations related to chemotherapy-induced peripheral neuropathy. METHODS: Cancer patients receiving neurotoxic chemotherapy completed EORTC QLQ-CIPN20 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX] at baseline, second cycle of chemotherapy (T2, n = 287), and 12 months after chemotherapy (T3, n = 191). Anchor-based approach used the validated FACT/GOG-NTX neurotoxicity (Ntx) subscale to identify optimal MCID cutoff for deterioration. Distribution-based approach used one-third standard deviation (SD), half SD, and one standard error of measurement of the total EORTC QLQ-CIPN20 score. RESULTS: There was a moderate correlation between the change scores of the Ntx subscale and sensory and motor subscales of QLQ-CIPN20 (T2: r = - 0.722, p < 0.001 and r = - 0.518, p < 0.001, respectively; T3: r = - 0.699; p < 0.001 and r = - 0.523, p < 0.001, respectively). The correlation between the change scores of the Ntx subscale and the QLQ-CIPN20 autonomic subscale was poor (T2: r = - 0.354, p < 0.001; T3: r = 0.286, p < 0.001). Based on the MCID derived using distribution-based method, the MCID for the QLQ-CIPN20 sensory subscale was 2.5-5.9 (6.9% to 16.4% of the subdomain score) and for motor subscale was 2.6-5.0 (8.1%-15.6% of the subdomain score). CONCLUSION: The MCID for the EORTC QLQ-CIPN20 established using distribution-based approaches was 2.5-5.9 for the sensory subscale and 2.6-5.0 for the motor subscale. When noted in assessments even with small change in scores, clinicians can be alerted for appropriate intervention.

Effects of bilobalide, ginkgolide B and picrotoxinin on GABAA receptor modulation by structurally diverse positive modulators.

Anxiolytics and anticonvulsants generally positively modulate the action of GABA, whereas many convulsants (including the chloride channel blocker picrotoxinin) negatively modulate the action of GABA on GABAA receptors. Like picrotoxinin, bilobalide and ginkgolide B, active constituents of Ginkgo biloba, have been shown to negatively modulate the action of GABA at α1ß2γ2L GABAA receptors. However, unlike picrotoxinin, bilobalide and ginkgolide B are not known to cause convulsions. We have assessed the action of bilobalide, ginkgolide B and picrotoxinin on a range of GABAA modulators (etomidate, loreclezole, propofol, thiopentone sodium, diazepam, and allopregnanolone), using two-electrode voltage clamp electrophysiology at recombinant α1ß2γ2L GABAA receptors expressed in Xenopus oocytes. The results indicate that bilobalide and ginkgolide B differ from picrotoxinin in their ability to inhibit the actions of a range of these structurally diverse GABAA positive modulators consistent with these modulators acting on a multiplicity of active sites associated with GABAA receptors. In the presence GABA, ginkgolide B was more potent than bilobalide in inhibiting the GABA-potentiating effect of propofol, equipotent against loreclezole and allopregnanolone, and less potent against etomidate, diazepam, and thiopentone sodium. This indicates that in comparison to picrotoxinin, bilobalide and ginkgolide B differ in their effects on the different modulators.

EGFR-Co-Mutated Advanced NSCLC and Response to EGFR Tyrosine Kinase Inhibitors.

OBJECTIVES: The evolution of EGFR tyrosine kinase inhibitors (TKIs) has changed the landscape of disease for a subset of patients with NSCLC. Most patients with an EGFR mutation respond to these drugs; however, a proportion show limited or no tumor response. We explored the impact of co-mutation (double or multiple mutation), compared with a single mutation, of the EGFR gene on response to TKIs in a series of patients with metastatic NSCLC. METHODS: We retrospectively analyzed the mutation profiles of nonsquamous NSCLC tested at Royal Prince Alfred Hospital between 2012 and 2015 by MassArray using the OncoCarta v1.0 panel. Patients with metastatic disease whose tumors had sensitizing EGFR mutation(s) were included. The primary end point was progression-free survival (PFS). We used the Kaplan-Meier method for PFS and overall survival; the log rank test was used to compare groups with and without co-mutation. Multivariable analysis was done for PFS; response rate was assessed using chi-square and logistic regression analysis. RESULTS: A total of 62 patients were included, and of these, eight (12.9%) had a co-mutation. The median PFS and overall survival times were 11.5 and 26.3 months, respectively. Patients with EGFR co-mutation had a significantly shorter median PFS than those with a single mutation (5.7 months versus 12.3 months, p = 0.02). The response rate to TKIs was significantly worse in those with co-mutation compared with in those without co-mutation (38% versus 89%, p < 0.001). CONCLUSIONS: Taking into account the small number of patients in this study, PFS in patients with EGFR co-mutation appeared significantly shorter, and response rate significantly lower, than in patients with a single mutation. Data from multipanel testing may identify subgroups of patients who are likely to respond poorly to standard treatment. Clarification of these subgroups may improve patient care.

GABAA receptor cysteinyl mutants and the ginkgo terpenoid lactones bilobalide and ginkgolides.

The terpenoid lactones from Ginkgo biloba, bilobalide and ginkgolides, have been shown to act as negative modulators at α1ß2γ2L GABAA receptors. They have structural features similar to those of the chloride channel blocker picrotoxinin. Unlike picrotoxinin, however they are not known to produce convulsant effects. Using two-electrode voltage clamp electrophysiology, this study compared the effect of mutation of 2', 6' and 15' pore facing M2 domain residues to cysteine on the action of picrotoxinin, bilobalide and ginkgolides at α1ß2γ2L GABAA receptors expressed in Xenopus oocytes. Picrotoxinin was affected by mutation differently from the ginkgo terpenoid lactones. Although some of these compounds were affected by the mutation at same position and/or subunit, the changes in their potency were found to be dissimilar. The results suggest that the intracellular pore binding site for picrotoxinin, bilobalide, ginkgolide A, ginkgolide B and ginkgolide C is comprised of 2'ß-6'ß6'γ, 2'α2'ß-6'α6'ß, 2'α2'ß2'γ-6'ß6'γ, 2'α, 2'ß2'γ-6'ß and 2'α2'ß, respectively. Unlike bilobalide and ginkgolides, the inhibitory action of picrotoxinin was not affected by mutations at 15' position. It is proposed that 15'α15'ß, 15'ß, 15'α15'ß and 15'α15'ß15'γ forms an extracellular pore binding site for bilobalide, ginkgolide A, ginkgolide B and ginkgolide C, respectively. The lack of convulsant effects of bilobalide, and ginkgolide A and B may be associated in part with their different binding locations within the chloride channel.

The suitability of small biopsy and cytology specimens for EGFR and other mutation testing in non-small cell lung cancer.

BACKGROUND: Patients with advanced non-small cell lung cancer (NSCLC) benefit from treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) when their tumor harbors an activating EGFR mutation. As the majority of NSCLC patients present with advanced disease, cytology and small biopsy specimens are frequently the only tissue available for mutation testing, but can pose challenges due to low tumor content. We aim to better define the suitability of these specimens for mutation testing. METHODS: NSCLC cases referred to our institution for mutation testing over a 15-month period were retrospectively reviewed. Specimens were tested for mutations including EGFR, KRAS, and BRAF, using a multiplex PCR assay (OncoCarta Panel v1.0) and analyzed on the Agena Bioscience MassARRAY platform. RESULTS: A total of 146 specimens were tested, comprising 53 (36.3%) resection specimens (including 28 lung resection specimens), 55 (37.7%) small biopsy specimens and 38 (26%) cytology specimens. Of 142 cases with sufficient DNA for mutation testing, EGFR mutations were detected in 31 specimens (21.8%), KRAS mutations in 31 specimens (21.8%) and BRAF mutations in three specimens (2.1%). There was no significant difference in the EGFR mutation rate between lung resection (10 of 28 cases; 35.7%), small biopsy (9 of 53 cases; 17%), and cytology specimens (8 of 36 cases; 22.2%). CONCLUSIONS: Our results support the utility of small biopsy and cytology specimens for mutation testing. Careful evaluation of the adequacy of small specimens is required to minimize the risk of false negative or positive results.

BRAF mutations in non-small cell lung cancer.

BACKGROUND: BRAF is a proto-oncogene encoding a serine/threonine protein kinase which promotes cell proliferation and survival. BRAF mutations are commonly seen in melanoma and papillary thyroid carcinoma. We aimed to investigate the prevalence and clinicopathological features of BRAF mutations in non-small cell lung cancer (NSCLC) cases submitted for routine mutation testing at our institution. METHODS: Mutation analysis for BRAF, EGFR and KRAS was performed using Sequenom MassARRAY platform with OncoCarta panel v1.0. Pathological features were reviewed and immunohistochemistry for BRAF V600E was also performed. RESULTS: Seven out of 273 cases (2.6%) had BRAF mutations (three males and four females, median age 70 years, all smokers), with six adenocarcinomas and one NSCLC, not otherwise specified (NOS). All had wild-type EGFR and KRAS. The identified BRAF mutations were V600E (4/7, 58%), K601N, L597Q and G469V. BRAF V600E immunohistochemistry was positive in two cases with V600E and negative in one case with K601N (tissue available in three cases only). No significant difference in age or gender was found (BRAF mutant vs. wild-type). CONCLUSIONS: BRAF mutations occur in a small proportion of NSCLC that lack other driver mutations. The clinicopathological profile differs from that of EGFR mutant tumours. The potential benefits of BRAF-inhibitors should be investigated.

Patterns of DNA mutations and ALK rearrangement in resected node negative lung adenocarcinoma.

BACKGROUND: Many studies have examined specific mutations in patients with resected lung adenocarcinoma across heterogeneous stages, comprising predominantly advanced/metastatic disease, but there is little data regarding the mutation profile of patients with early stage node negative disease. The aim of this study was to identify patterns of mutations in early stage node negative lung adenocarcinoma. METHODS: A total of 204 patients who underwent resection for stage IB (sixth Ed American Joint Committee on Cancer) lung adenocarcinoma and received no neoadjuvant or adjuvant treatments were identified. Tumors were genotyped using the OncoCarta v1.0 kit (Sequenom, San Diego, CA) on the Sequenom MassARRAY platform. Fluorescence in situ hybridization for ALK rearrangement was also performed. RESULTS: A total of 110 (54%) patients' tumors harbored at least one mutation. KRAS, EGFR, PIK3CA, ALK, PDGFRA, AKT1, BRAF, FGFR1, and HRAS mutations were detected in tumors from 77 (37.7%), 29 (14.2%), 9 (4.4%), 2 (1%), 2 (1%), 1 (0.5%), 1 (0.5%), 1 (0.5%), and 1 (0.5%) patients respectively. Synchronous mutations (either comutations or double mutations) were identified in 18 (8.8%) patients. KRAS and PIK3CA mutations were associated with poorly differentiated tumors (p = 0.03; p = 0.02), whereas EGFR mutations were associated with well-differentiated tumors (p = 0.001). Five tumours contained EGFR mutations (one T790M and four exon 20 insertions), which are associated with resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs). CONCLUSIONS: Diverse patterns of mutations are seen in resected node-negative lung adenocarcinoma including an unexpectedly low rate of ALK rearrangement, EGFR mutations associated with resistance to EGFR-TKIs and a high rate of synchronous mutations. These data may influence the design of future adjuvant targeted therapy trials.

SeqVis: visualization of compositional heterogeneity in large alignments of nucleotides.

UNLABELLED: Most phylogenetic methods assume that the sequences evolved under homogeneous, stationary and reversible conditions. Compositional heterogeneity in data intended for studies of phylogeny suggests that the data did not evolve under these conditions. SeqVis, a Java application for analysis of nucleotide content, reads sequence alignments in several formats and plots the nucleotide content in a tetrahedron. Once plotted, outliers can be identified, thus allowing for decisions on the applicability of the data for phylogenetic analysis. AVAILABILITY: http://www.bio.usyd.edu.au/jermiin/programs.htm.