Mobile health divide between clinicians and patients in cancer care: results from a cross-sectional international survey

Background: Mobile technologies are increasingly being used to manage chronic diseases, including cancer, with the promise of improving the efficiency and effectiveness of care. Among the myriad of mobile technologies in health care, we have seen an explosion of mobile apps. The rapid increase in digital health apps is not paralleled by a similar trend in usage statistics by clinicians and patients. Little is known about how much and in what ways mobile health (mHealth) apps are used by clinicians and patients for cancer care, what variables affect their use of mHealth, and what patients’ and clinicians’ expectations of mHealth apps are. Objective: This study aimed to describe the patient and clinician population that uses mHealth in cancer care and to provide recommendations to app developers and regulators to generally increase the use and efficacy of mHealth apps. Methods: Through a cross-sectional Web-based survey, we explored the current utilization rates of mHealth in cancer care and factors that explain the differences in utilization by patients and clinicians across the United States and 5 different countries in Europe. In addition, we conducted an international workshop with more than 100 stakeholders and a roundtable with key representatives of international organizations of clinicians and patients to solicit feedback on the survey results and develop insights into mHealth app development practices. Results: A total of 1033 patients and 1116 clinicians participated in the survey. The proportion of cancer patients using mHealth (294/1033, 28.46%) was far lower than that of clinicians (859/1116, 76.97%). Accounting for age and salary level, the marginal probabilities of use at means are still significantly different between the 2 groups and were 69.8% for clinicians and 38.7% for patients using the propensity score–based regression adjustment with weighting technique. Moreover, our analysis identified a gap between basic and advanced users, with a prevalent use for activities related to the automation of processes and the interaction with other individuals and a limited adoption for side-effect management and compliance monitoring in both groups. Conclusions: mHealth apps can provide access to clinical and economic data that are low cost, easy to access, and personalized. The benefits can go as far as increasing patients’ chances of overall survival. However, despite its potential, evidence on the actual use of mobile technologies in cancer care is not promising. If the promise of mHealth is to be fulfilled, clinician and patient usage rates will need to converge. Ideally, cancer apps should be designed in ways that strengthen the patient-physician relationship, ease physicians’ workload, be tested for validity and effectiveness, and fit the criteria for reimbursement

A unique RET EXON 11 (G691S) polymorphism in an Indian patient with a collision tumor of the thyroid

BACKGROUND: Collision tumors of the thyroid are rare, with occasional reports dealing with their genetic analysis. CASE PRESENTATION: A 59 year old lady presented with a neck mass, associated with hoarseness of voice of 5 years duration. Radiological examination revealed nodular masses in the left lobe of her thyroid, along with one in the isthmus, extending into the right lobe and associated with enlarged neck nodes. FNAC from the left thyroid showed features of medullary carcinoma. On total thyroidectomy, 2 distinct tumor nodules were identified in the left lobe with another in the isthmus, showing features of medullary carcinoma (MTC), papillary carcinoma and follicular variant of papillary carcinoma, respectively, accompanied with nodal metastasis. Subsequently, she underwent radioablation. RET gene analysis of the patient, her 2 daughters and a grandson revealed a unique G691S polymorphism on Exon 11. CONCLUSION: This unique case of a collision tumor of thyroid, including component of an MTC deals with the value of RET gene analysis and therapeutic implications in the index case and in family members

Rationale and design for the development of a novel nitroxyl donor in patients with acute heart failure

Hospitalisation for acute heart failure remains a major public health problem with high prevalence, morbidity, mortality, and cost. Prior attempts to develop new therapies for this condition have not been successful. Nitroxyl (HNO) plays a unique role in cardiovascular physiology by direct post‐translational modification of thiol residues on target proteins, specifically SERCA2a, phospholamban, the ryanodine receptor and myofilament proteins in cardiomyocytes. In animal models, these biological effects lead to vasodilatation, increased inotropy and lusitropy, but without tachyphylaxis, pro‐arrhythmia or evidence of increased myocardial oxygen demand. BMS‐986231 is an HNO donor being developed as a therapy for heart failure, and initial studies in patients with heart failure support the potential clinical value of these physiological effects. In this manuscript, we describe the ongoing phase II development programme for BMS‐986231, which consists of three related randomised placebo‐controlled clinical trials, StandUP‐AHF, StandUP‐Imaging and StandUP‐Kidney, which are designed to provide evidence of tolerability and efficacy as well as confirm the anticipated physiological effects in patients with heart failure with reduced ejection fraction. These studies will set the stage for the further study of BMS‐986231 in future phase III clinical trials

Evaluation of diffusion-weighted MRI and (18F) fluorothymidine-PET biomarkers for early response assessment in patients with operable non-small cell lung cancer treated with neoadjuvant chemotherapy

Objective: To correlate changes in the apparent diffusion coefficient (ADC) from diffusion-weighted (DW)-MRI and standardised uptake value (SUV) from fluorothymidine (18FLT)-PET/CT with histopathological estimates of response in patients with non-small cell lung cancer (NSCLC) treated with neoadjuvant chemotherapy and track longitudinal changes in these biomarkers in a multicentre, multivendor setting. Methods: 14 patients with operable NSCLC recruited to a prospective, multicentre imaging trial (EORTC-1217) were treated with platinum-based neoadjuvant chemotherapy. 13 patients had DW-MRI and FLT-PET/CT at baseline (10 had both), 12 were re-imaged at Day 14 (eight dual-modality) and nine after completing chemotherapy, immediately before surgery (six dual-modality). Surgical specimens (haematoxylin-eosin and Ki67 stained) estimated the percentage of residual viable tumour/necrosis and proliferation index. Results: Despite the small numbers,significant findings were possible. ADCmedian increased (p 30% reduction in unidimensional measurement pre-surgery), showed an increase at Day 14 in ADC75th centile and reduction in total lesion proliferation (SUVmean x proliferative volume) greater than established measurement variability. Change in imaging biomarkers did not correlate with histological response (residual viable tumour, necrosis). Conclusion: Changes in ADC and FLT-SUV following neoadjuvant chemotherapy in NSCLC were measurable by Day 14 and preceded changes in unidimensional size but did not correlate with histopathological response. However, the magnitude of the changes and their utility in predicting (non-) response (tumour size/clinical outcome) remains to be established. Advances in knowledge: During treatment, ADC increase precedes size reductions, but does not reflect histopathological necrosis

Mobile health divide between clinicians and patients in cancer care:Results from a cross-sectional international survey

Background: Mobile technologies are increasingly being used to manage chronic diseases, including cancer, with the promise of improving the efficiency and effectiveness of care. Among the myriad of mobile technologies in health care, we have seen an explosion of mobile apps. The rapid increase in digital health apps is not paralleled by a similar trend in usage statistics by clinicians and patients. Little is known about how much and in what ways mobile health (mHealth) apps are used by clinicians and patients for cancer care, what variables affect their use of mHealth, and what patients’ and clinicians’ expectations of mHealth apps are. Objective: This study aimed to describe the patient and clinician population that uses mHealth in cancer care and to provide recommendations to app developers and regulators to generally increase the use and efficacy of mHealth apps. Methods: Through a cross-sectional Web-based survey, we explored the current utilization rates of mHealth in cancer care and factors that explain the differences in utilization by patients and clinicians across the United States and 5 different countries in Europe. In addition, we conducted an international workshop with more than 100 stakeholders and a roundtable with key representatives of international organizations of clinicians and patients to solicit feedback on the survey results and develop insights into mHealth app development practices. Results: A total of 1033 patients and 1116 clinicians participated in the survey. The proportion of cancer patients using mHealth (294/1033, 28.46%) was far lower than that of clinicians (859/1116, 76.97%). Accounting for age and salary level, the marginal probabilities of use at means are still significantly different between the 2 groups and were 69.8% for clinicians and 38.7% for patients using the propensity score–based regression adjustment with weighting technique. Moreover, our analysis identified a gap between basic and advanced users, with a prevalent use for activities related to the automation of processes and the interaction with other individuals and a limited adoption for side-effect management and compliance monitoring in both groups. Conclusions: mHealth apps can provide access to clinical and economic data that are low cost, easy to access, and personalized. The benefits can go as far as increasing patients’ chances of overall survival. However, despite its potential, evidence on the actual use of mobile technologies in cancer care is not promising. If the promise of mHealth is to be fulfilled, clinician and patient usage rates will need to converge. Ideally, cancer apps should be designed in ways that strengthen the patient-physician relationship, ease physicians’ workload, be tested for validity and effectiveness, and fit the criteria for reimbursement

Effects of a Novel Nitroxyl Donor in Acute Heart Failure The STAND-UP AHF Study

Objectives: The primary objective was to identify well-tolerated doses of cimlanod in patients with acute heart failure (AHF). Secondary objectives were to identify signals of efficacy, including biomarkers, symptoms, and clinical events. Background: Nitroxyl (HNO) donors have vasodilator, inotropic and lusitropic effects. Bristol-Myers Squibb-986231 (cimlanod) is an HNO donor being developed for acute heart failure (AHF). Methods: This was a phase IIb, double-blind, randomized, placebo-controlled trial of 48-h treatment with cimlanod compared with placebo in patients with left ventricular ejection fraction ≤40% hospitalized for AHF. In part I, patients were randomized in a 1:1 ratio to escalating doses of cimlanod or matching placebo. In part II, patients were randomized in a 1:1:1 ratio to either of the 2 highest tolerated doses of cimlanod from part I or placebo. The primary endpoint was the rate of clinically relevant hypotension (systolic blood pressure <90 mm Hg or patients became symptomatic). Results: In part I (n = 100), clinically relevant hypotension was more common with cimlanod than placebo (20% vs. 8%; relative risk [RR]: 2.45; 95% confidence interval [CI]: 0.83 to 14.53). In part II (n = 222), the incidence of clinically relevant hypotension was 18% for placebo, 21% for cimlanod 6 μg/kg/min (RR: 1.15; 95% CI: 0.58 to 2.43), and 35% for cimlanod 12 μg/kg/min (RR: 1.9; 95% CI: 1.04 to 3.59). N-terminal pro–B-type natriuretic peptide and bilirubin decreased during infusion of cimlanod treatment compared with placebo, but these differences did not persist after treatment discontinuation. Conclusions: Cimlanod at a dose of 6 μg/kg/min was reasonably well-tolerated compared with placebo. Cimlanod reduced markers of congestion, but this did not persist beyond the treatment period. (Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure [STANDUP AHF]; NCT03016325

A Novel Unstable Duplication Upstream of HAS2 Predisposes to a Breed-Defining Skin Phenotype and a Periodic Fever Syndrome in Chinese Shar-Pei Dogs

Hereditary periodic fever syndromes are characterized by recurrent episodes of fever and inflammation with no known pathogenic or autoimmune cause. In humans, several genes have been implicated in this group of diseases, but the majority of cases remain unexplained. A similar periodic fever syndrome is relatively frequent in the Chinese Shar-Pei breed of dogs. In the western world, Shar-Pei have been strongly selected for a distinctive thick and heavily folded skin. In this study, a mutation affecting both these traits was identified. Using genome-wide SNP analysis of Shar-Pei and other breeds, the strongest signal of a breed-specific selective sweep was located on chromosome 13. The same region also harbored the strongest genome-wide association (GWA) signal for susceptibility to the periodic fever syndrome (praw = 2.3×10−6, pgenome = 0.01). Dense targeted resequencing revealed two partially overlapping duplications, 14.3 Kb and 16.1 Kb in size, unique to Shar-Pei and upstream of the Hyaluronic Acid Synthase 2 (HAS2) gene. HAS2 encodes the rate-limiting enzyme synthesizing hyaluronan (HA), a major component of the skin. HA is up-regulated and accumulates in the thickened skin of Shar-Pei. A high copy number of the 16.1 Kb duplication was associated with an increased expression of HAS2 as well as the periodic fever syndrome (p<0.0001). When fragmented, HA can act as a trigger of the innate immune system and stimulate sterile fever and inflammation. The strong selection for the skin phenotype therefore appears to enrich for a pleiotropic mutation predisposing these dogs to a periodic fever syndrome. The identification of HA as a major risk factor for this canine disease raises the potential of this glycosaminoglycan as a risk factor for human periodic fevers and as an important driver of chronic inflammation

Phase I clinical trial repurposing all-trans retinoic acid as a stromal targeting agent for pancreatic cancer

Abstract: Pre-clinical models have shown that targeting pancreatic stellate cells with all-trans-retinoic-acid (ATRA) reprograms pancreatic stroma to suppress pancreatic ductal adenocarcinoma (PDAC) growth. Here, in a phase Ib, dose escalation and expansion, trial for patients with advanced, unresectable PDAC (n = 27), ATRA is re-purposed as a stromal-targeting agent in combination with gemcitabine-nab-paclitaxel chemotherapy using a two-step adaptive continual re-assessment method trial design. The maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D, primary outcome) is the FDA/EMEA approved dose of gemcitabine-nab-paclitaxel along-with ATRA (45 mg/m2 orally, days 1–15/cycle). Dose limiting toxicity (DLT) is grade 4 thrombocytopenia (n = 2). Secondary outcomes show no detriment to ATRA pharmacokinetics.. Median overall survival for RP2D treated evaluable population, is 11.7 months (95%CI 8.6–15.7 m, n = 15, locally advanced (2) and metastatic (13)). Exploratory pharmacodynamics studies including changes in diffusion-weighted (DW)-MRI measured apparent diffusion coefficient after one cycle, and, modulation of cycle-specific serum pentraxin 3 levels over various cycles indicate stromal modulation. Baseline stromal-specific retinoid transport protein (FABP5, CRABP2) expression may be predicitve of response. Re-purposing ATRA as a stromal-targeting agent with gemcitabine-nab-paclitaxel is safe and tolerable. This combination will be evaluated in a phase II randomized controlled trial for locally advanced PDAC. Clinical trial numbers: EudraCT: 2015-002662-23; NCT03307148. Trial acronym: STARPAC