Tele-audiology: Implications and Practioners' Perceptions

Purpose: The purpose of this systematic review is to examine audiologists’ perceptions of tele-audiology and how tele-audiology is being implemented. Background: Telemedicine, and specifically tele-audiology, is a potential option to provide families and patients with hearing loss access to diagnostic and treatment services when there are access barriers. Tele-audiology originated from previous telemedicine programs dating back to the early 1960s and the utilization currently allows for hearing care practice to provide virtual care. It is important to consider how practitioners view this option for providing care and also to investigate how it is being implemented to determine which aspect of audiology telemedicine is best suited for. Methods/Proposed Methods: Article searches were performed in PubMed and CINAHL databases. Search criteria included articles published from June 2009 until January 2017 and any format other than case study designs. Reliability calculations were performed during the title/abstract review and the full text review. We ultimately decided to exclude any article not discussing tele-audiology practice in the United States during the full-text review. 16 articles were included for quality appraisal. Results/Anticipated Results: Tele-audiology is being implemented for various age populations and various diagnostic and intervention needs. The results suggest that most audiologists are comfortable with the technology needed to implement tele-audiology but not as many are in fact utilizing it in their practice. Discussion: Since tele-audiology practice is a relatively new service option, there needs to be more research performed in the United States about how many audiologists are utilizing it and to what extent. For those programs with established tele-audiology service options, the outlook is generally positive and these sites are using it for both diagnostic and intervention services. For those sites that have not yet started to implement tele-audiology, this may be useful for those patients where access to in-person care is not convenient. There was no financial or intellectual conflict of interest on behalf of any of the authors

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Estimating posttraumatic stress disorder severity in the presence of differential item functioning across populations, comorbidities, and interview measures: Introduction to Project Harmony

Multiple factor analytic and item response theory studies have shown that items/symptoms vary in their relative clinical weights in structured interview measures for posttraumatic stress disorder (PTSD). Despite these findings, the use of total scores, which treat symptoms as though they are equally weighted, predominates in practice, with the consequence of undermining the precision of clinical decision-making. We conducted an integrative data analysis (IDA) study to harmonize PTSD structured interview data (i.e., recoding of items to a common symptom metric) from 25 studies (total N = 2,568). We aimed to identify (a) measurement noninvariance/differential item functioning (MNI/DIF) across multiple populations, psychiatric comorbidities, and interview measures simultaneously and (b) differences in inferences regarding underlying PTSD severity between scale scores estimated using moderated nonlinear factor analysis (MNLFA) and a total score analog model (TSA). Several predictors of MNI/DIF impacted effect size differences in underlying severity across scale scoring methods. Notably, we observed MNI/DIF substantial enough to bias inferences on underlying PTSD severity for two groups: African Americans and incarcerated women. The findings highlight two issues raised elsewhere in the PTSD psychometrics literature: (a) bias in characterizing underlying PTSD severity and individual-level treatment outcomes when the psychometric model underlying total scores fails to fit the data and (b) higher latent severity scores, on average, when using DSM-5 (net of MNI/DIF) criteria, by which multiple factors (e.g., Criterion A discordance across DSM editions, changes to the number/type of symptom clusters, changes to the symptoms themselves) may have impacted severity scoring for some patients

Precision medicine for advanced pancreas cancer : the Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial

Purpose: Personalized medicine strategies using genomic profiling are particularly pertinent for pancreas cancer. The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial was initially designed to exploit results from genome sequencing of pancreatic cancer under the auspices of the International Cancer Genome Consortium (ICGC) in Australia. Sequencing revealed small subsets of patients with aberrations in their tumor genome that could be targeted with currently available therapies. Experimental Design: The pilot stage of the IMPaCT trial assessed the feasibility of acquiring suitable tumor specimens for molecular analysis and returning high-quality actionable genomic data within a clinically acceptable timeframe. We screened for three molecular targets: HER2 amplification; KRAS wild-type; and mutations in DNA damage repair pathways (BRCA1, BRCA2, PALB2, ATM). Results: Tumor biopsy and archived tumor samples were collected from 93 patients and 76 were screened. To date 22 candidate cases have been identified: 14 KRAS wild-type, 5 cases of HER2 amplification, 2 mutations in BRCA2, and 1 ATM mutation. Median time from consent to the return of validated results was 21.5 days. An inability to obtain a biopsy or insufficient tumor content in the available specimen were common reasons for patient exclusion from molecular analysis while deteriorating performance status prohibited a number of patients from proceeding in the study. Conclusions: Documenting the feasibility of acquiring and screening biospecimens for actionable molecular targets in real time will aid other groups embarking on similar trials. Key elements include the need to better prescreen patients, screen more patients, and offer more attractive clinical trial options.9 page(s

HNF4A and GATA6 loss reveals therapeutically actionable subtypes in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) can be divided into transcriptomic subtypes with two broad lineages referred to as classical (pancreatic) and squamous. We find that these two subtypes are driven by distinct metabolic phenotypes. Loss of genes that drive endodermal lineage specification, HNF4A and GATA6, switch metabolic profiles from classical (pancreatic) to predominantly squamous, with glycogen synthase kinase 3 beta (GSK3b) a key regulator of glycolysis. Pharmacological inhibition of GSK3b results in selective sensitivity in the squamous subtype; however, a subset of these squamous patient-derived cell lines (PDCLs) acquires rapid drug tolerance. Using chromatin accessibility maps, we demonstrate that the squamous subtype can be further classified using chromatin accessibility to predict responsiveness and tolerance to GSK3b inhibitors. Our findings demonstrate that distinct patterns of chromatin accessibility can be used to identify patient subgroups that are indistinguishable by gene expression profiles, highlighting the utility of chromatin-based biomarkers for patient selection in the treatment of PDAC

Endovascular Thrombectomy for Ischemic Stroke Increases Disability-Free Survival, Quality of Life, and Life Expectancy and Reduces Cost

BackgroundEndovascular thrombectomy improves functional outcome in large vessel occlusion ischemic stroke. We examined disability, quality of life, survival and acute care costs in the EXTEND-IA trial, which used CT-perfusion imaging selection.MethodsLarge vessel ischemic stroke patients with favorable CT-perfusion were randomized to endovascular thrombectomy after alteplase versus alteplase-only. Clinical outcome was prospectively measured using 90-day modified Rankin scale (mRS). Individual patient expected survival and net difference in Disability/Quality-adjusted life years (DALY/QALY) up to 15 years from stroke were modeled using age, sex, 90-day mRS, and utility scores. Level of care within the first 90 days was prospectively measured and used to estimate procedure and inpatient care costs (US$reference year 2014).ResultsThere were 70 patients, 35 in each arm, mean age 69, median NIHSS 15 (IQR 12–19). The median (IQR) disability-weighted utility score at 90 days was 0.65 (0.00–0.91) in the alteplase-only versus 0.91 (0.65–1.00) in the endovascular group (p = 0.005). Modeled life expectancy was greater in the endovascular versus alteplase-only group (median 15.6 versus 11.2 years, p = 0.02). The endovascular thrombectomy group had fewer simulated DALYs lost over 15 years [median (IQR) 5.5 (3.2–8.7) versus 8.9 (4.7–13.8), p = 0.02] and more QALY gained [median (IQR) 9.3 (4.2–13.1) versus 4.9 (0.3–8.5), p = 0.03]. Endovascular patients spent less time in hospital [median (IQR) 5 (3–11) days versus 8 (5–14) days, p = 0.04] and rehabilitation [median (IQR) 0 (0–28) versus 27 (0–65) days, p = 0.03]. The estimated inpatient costs in the first 90 days were less in the thrombectomy group (average US$15,689 versus US$30,569, p = 0.008) offsetting the costs of interhospital transport and the thrombectomy procedure (average US$10,515). The average saving per patient treated with thrombectomy was US$4,365.ConclusionThrombectomy patients with large vessel occlusion and salvageable tissue on CT-perfusion had reduced length of stay and overall costs to 90 days. There was evidence of clinically relevant improvement in long-term survival and quality of life.Clinical Trial Registrationhttp://www.ClinicalTrials.gov NCT01492725 (registered 20/11/2011)