The use and potential impact of digital health tools at the community level: results from a multi-country survey of community health workers.

BACKGROUND: Community health workers (CHWs) are increasingly viewed as a critical workforce to address health system strengthening and sustainable development goals. Optimizing and widening the capacity of this workforce through digital technology is currently underway, though there is skepticism regarding CHWs' willingness and optimism to engage in digital health. We sought to understand CHWs' perceptions on the use of digital health tools in their work. METHODS: We obtained survey data from 1,141 CHWs from 28 countries with complete study information. We conducted regression analyses to explore the relationship between CHWs' training and perceived barriers to digital health access with current use of digital devices/tools and belief in digital impact while adjusting for demographic factors. RESULTS: Most of the CHWs worked in Kenya (n = 502, 44%) followed by the Philippines (n = 308, 27%), Ghana (n = 107, 9.4%), and the United States (n = 70, 6.1%). There were significant, positive associations between digital tools training and digital device/tool use (Adjusted Odds Ratio (AOR) = 2.92, 95% CI = 2.09-4.13) and belief in digital impact (AORhigh impact = 3.03, 95% CI = 2.04-4.49). CHWs were significantly less likely to use digital devices for their work if they identified cost as a perceived barrier (AORmobile service cost = 0.68, 95% CI = 0.49-0.95; AORphone/device cost = 0.66, 95% CI = 0.47-0.92). CHWs who were optimistic about digital health, were early adopters of technology in their personal lives, and found great value in their work believed digital health helped them to have greater impact. Older age and greater tenure were associated with digital device/tool use and belief in digital impact, respectively. CONCLUSIONS: CHWs are not an obstacle to digital health adoption or use. CHWs believe that digital tools can help them have more impact in their communities regardless of perceived barriers. However, cost is a barrier to digital device/tool use; potential solutions to cost constraints of technological access will benefit from further exploration of reimbursement models. Digital health tools have the potential to increase CHW capacity and shape the future of community health work.

Pain Management and Education for Ambulatory Surgery: A Qualitative Study of Perioperative Nurses.

BACKGROUND: Ambulatory surgery presents unique challenges regarding adequate pain management and education. Studies have documented issues with transfer of information and patient comfort. Our objective was to explore perioperative nurses' perspectives of current practices and challenges with pain management and education. MATERIALS AND METHODS: We used a qualitative descriptive design and conducted four focus group interviews, with 24 total participants from two perioperative areas of an academic medical center, using a standardized script. Using qualitative analysis software, two investigators reviewed the data and coded major themes and subthemes. The consolidated criteria for reporting qualitative studies guidelines were followed for reporting the data. RESULTS: We identified four major themes impacting current perioperative pain management and education practices: communication among the perioperative care team, sources of nurses' frustrations in the perioperative setting, patient expectations for pain, and nurse-driven pain management and education. Nurses highlighted their work became easier with adequate information transfer and trust from physicians. Frustrations stemmed from surgeon, system, and patient factors. Nurses often use their clinical experience and judgment in managing patients throughout the perioperative period. Furthermore, nurses felt patients have limited pain education and stressed education throughout the surgical care pathway could improve overall care. CONCLUSIONS: Perioperative pain management, assessment, and education practices are inconsistent, incomplete, and sources of frustrations according to participants. Participant experiences highlight the need for improved and standardized models. Patient pain education should use a multidisciplinary approach, beginning at the point of surgery scheduling and continuing through postoperative follow-up.

Federated Networks for Distributed Analysis of Health Data.

Access to health data, important for population health planning, basic and clinical research and health industry utilization, remains problematic. Legislation intended to improve access to personal data across national borders has proven to be a double-edged sword, where complexity and implications from misinterpretations have paradoxically resulted in data becoming more siloed. As a result, the potential for development of health specific AI and clinical decision support tools built on real-world data have yet to be fully realized. In this perspective, we propose federated networks as a solution to enable access to diverse data sets and tackle known and emerging health problems. The perspective draws on experience from the World Economic Forum Breaking Barriers to Health Data project, the Personal Health Train and Vantage6 infrastructures, and industry insights. We first define the concept of federated networks in a healthcare context, present the value they can bring to multiple stakeholders, and discuss their establishment, operation and implementation. Challenges of federated networks in healthcare are highlighted, as well as the resulting need for and value of an independent orchestrator for their safe, sustainable and scalable implementation.

Post-Biopsy Pneumothorax Incidence in Patients Treated with Biosentry™ Plug Device.

INTRODUCTION: This study aimed to determine if the Biosentry™ Plug Device (BPD), a prophylactic sealant used to prevent pneumothorax after lung biopsies, reduced post-lung biopsy pneumothorax rates, and other complications compared to no device utilization. METHODS: This single institution, retrospective cohort study included patients who received a lung biopsy in the Department of Interventional Radiology from May 1, 2015 to August 31, 2017. Data such as sex, race, ethnicity, chronic obstructive pulmonary disease status, degree of lung bullae if present, smoking status, and use of BPD were recorded. Decisions to use BPD were based on operator preference. A chi squared analysis was used with a p value greater than 0.05 considered significant. RESULTS: The study included 521 patients who underwent a lung biopsy during the study timeframe. Of these, 74 (14.2%) received the BPD, while 447 (85.8%) did not. One-hundred ninety (36.4%) had a pneumothorax within one month of the lung biopsy. Of the total 190 that experienced pneumothorax, 36.7% of non-BPD biopsies resulted in pneumothorax, while 35.1% of BPD biopsies resulted in pneumothorax (p value = 0.7970; degrees of freedom = 1). CONCLUSIONS: These findings indicated that BPD may not reduce pneumothorax incidence nor limit the severity of complications in patients.

Src mutation induces acquired lapatinib resistance in ERBB2-amplified human gastroesophageal adenocarcinoma models.

ERBB2-directed therapy is now a routine component of therapy for ERBB2-amplified metastatic gastroesophageal adenocarcinomas. However, there is little knowledge of the mechanisms by which these tumors develop acquired resistance to ERBB2 inhibition. To investigate this question we sought to characterize cell line models of ERBB2-amplified gastroesophageal adenocarcinoma with acquired resistance to ERBB2 inhibition. We generated lapatinib-resistant (LR) subclones from an initially lapatinib-sensitive ERBB2-amplified esophageal adenocarcinoma cell line, OE19. We subsequently performed genomic characterization and functional analyses of resistant subclones with acquired lapatinib resistance. We identified a novel, acquired SrcE527K mutation in a subset of LR OE19 subclones. Cells with this mutant allele harbour increased Src phosphorylation. Genetic and pharmacologic inhibition of Src resensitized these subclones to lapatinib. Biochemically, Src mutations could activate both the phosphatidylinositol 3-kinase and mitogen activated protein kinase pathways in the lapatinib-treated LR OE19 cells. Ectopic expression of SrcE527K mutation also was sufficient to induce lapatinib resistance in drug-naïve cells. These results indicate that pathologic activation of Src is a potential mechanism of acquired resistance to ERBB2 inhibition in ERBB2-amplified gastroesophageal cancer. Although Src mutation has not been described in primary tumor samples, we propose that the Src hyperactivation should be investigated in the settings of acquired resistance to ERBB2 inhibition in esophageal and gastric adenocarcinoma.

Preexisting oncogenic events impact trastuzumab sensitivity in ERBB2-amplified gastroesophageal adenocarcinoma.

Patients with gastric and esophageal (GE) adenocarcinoma tumors in which the oncogene ERBB2 has been amplified are routinely treated with a combination of cytotoxic chemotherapy and the ERBB2-directed antibody trastuzumab; however, the addition of trastuzumab, even when tested in a selected biomarker-positive patient population, provides only modest survival gains. To investigate the potential reasons for the modest impact of ERBB2-directed therapies, we explored the hypothesis that secondary molecular features of ERBB2-amplified GE adenocarcinomas attenuate the impact of ERBB2 blockade. We analyzed genomic profiles of ERBB2-amplified GE adenocarcinomas and determined that the majority of ERBB2-amplified tumors harbor secondary oncogenic alterations that have the potential to be therapeutically targeted. These secondary events spanned genes involved in cell-cycle regulation as well as phosphatidylinositol-3 kinase and receptor tyrosine kinase signaling. Using ERBB2-amplified cell lines, we demonstrated that secondary oncogenic events could confer resistance to ERBB2-directed therapies. Moreover, this resistance could be overcome by targeting the secondary oncogene in conjunction with ERBB2-directed therapy. EGFR is commonly coamplified with ERBB2, and in the setting of ERBB2 amplification, higher EGFR expression appears to mark tumors with greater sensitivity to dual EGFR/ERBB2 kinase inhibitors. These data suggest that combination inhibitor strategies, guided by secondary events in ERBB2-amplified GE adenocarcinomas, should be evaluated in clinical trials.

SOX2 and p63 colocalize at genetic loci in squamous cell carcinomas.

The transcription factor SOX2 is an essential regulator of pluripotent stem cells and promotes development and maintenance of squamous epithelia. We previously reported that SOX2 is an oncogene and subject to highly recurrent genomic amplification in squamous cell carcinomas (SCCs). Here, we have further characterized the function of SOX2 in SCC. Using ChIP-seq analysis, we compared SOX2-regulated gene profiles in multiple SCC cell lines to ES cell profiles and determined that SOX2 binds to distinct genomic loci in SCCs. In SCCs, SOX2 preferentially interacts with the transcription factor p63, as opposed to the transcription factor OCT4, which is the preferred SOX2 binding partner in ES cells. SOX2 and p63 exhibited overlapping genomic occupancy at a large number of loci in SCCs; however, coordinate binding of SOX2 and p63 was absent in ES cells. We further demonstrated that SOX2 and p63 jointly regulate gene expression, including the oncogene ETV4, which was essential for SOX2-amplified SCC cell survival. Together, these findings demonstrate that the action of SOX2 in SCC differs substantially from its role in pluripotency. The identification of the SCC-associated interaction between SOX2 and p63 will enable deeper characterization the downstream targets of this interaction in SCC and normal squamous epithelial physiology.

Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity.

The incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With a 5-year survival rate of ~15%, the identification of new therapeutic targets for EAC is greatly important. We analyze the mutation spectra from whole-exome sequencing of 149 EAC tumor-normal pairs, 15 of which have also been subjected to whole-genome sequencing. We identify a mutational signature defined by a high prevalence of A>C transversions at AA dinucleotides. Statistical analysis of exome data identified 26 significantly mutated genes. Of these genes, five (TP53, CDKN2A, SMAD4, ARID1A and PIK3CA) have previously been implicated in EAC. The new significantly mutated genes include chromatin-modifying factors and candidate contributors SPG20, TLR4, ELMO1 and DOCK2. Functional analyses of EAC-derived mutations in ELMO1 identifies increased cellular invasion. Therefore, we suggest the potential activation of the RAC1 pathway as a contributor to EAC tumorigenesis.

Gastrointestinal adenocarcinomas of the esophagus, stomach, and colon exhibit distinct patterns of genome instability and oncogenesis.

A more detailed understanding of the somatic genetic events that drive gastrointestinal adenocarcinomas is necessary to improve diagnosis and therapy. Using data from high-density genomic profiling arrays, we conducted an analysis of somatic copy-number aberrations in 486 gastrointestinal adenocarcinomas including 296 esophageal and gastric cancers. Focal amplifications were substantially more prevalent in gastric/esophageal adenocarcinomas than colorectal tumors. We identified 64 regions of significant recurrent amplification and deletion, some shared and others unique to the adenocarcinoma types examined. Amplified genes were noted in 37% of gastric/esophageal tumors, including in therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, suggesting the potential use of genomic amplifications as biomarkers to guide therapy of gastric and esophageal cancers where targeted therapeutics have been less developed compared with colorectal cancers. Amplified loci implicated genes with known involvement in carcinogenesis but also pointed to regions harboring potentially novel cancer genes, including a recurrent deletion found in 15% of esophageal tumors where the Runt transcription factor subunit RUNX1 was implicated, including by functional experiments in tissue culture. Together, our results defined genomic features that were common and distinct to various gut-derived adenocarcinomas, potentially informing novel opportunities for targeted therapeutic interventions.