Telemental Health for the Homeless Population: Lessons Learned when Leveraging Care.

PURPOSE OF REVIEW: The purpose of this paper is to review key lessons when using telehealth within the context of mental health and homelessness. We examine technological and bandwidth issues the homeless population might face when getting telehealth services, discuss clinical process adaption needed for working remotely, and highlight the lessons learned when leveraging mental health services to homeless patients across telehealth platforms. RECENT FINDINGS: Homelessness is associated with chronic, mental health disparities and access to mental health services is often less accessible among communities with unstable housing. Telehealth provides "OnDemand" treatment options while removing specific barriers found with in-person health care such as transportation, overwhelmed mental health facilities, i.e., appointment availability, and office hour limitations while reducing costs for both providers and patients. We provide two case examples to demonstrate successful delivery of telemental health services to homeless patients and review lessons learned when leveraging care.

Telemental Health and the Management of Psychosis.

PURPOSE OF REVIEW: The purpose of this paper is to review the application of telehealth in the assessment and treatment of psychotic illnesses. We present the contextual factors which make this approach to clinical care compelling, and review existing evidence about feasibility, acceptability, and effectiveness. RECENT FINDINGS: The use of telehealth with individuals that suffer from serious mental illness and psychosis has been demonstrated to be feasible and acceptable, with effectiveness that is comparable to in-person clinical care. Telehealth holds the additional promises of expanding access, connecting patients, families, and the general public to behavioral health resources, and reducing overall health care costs. We provide two case examples which demonstrate the successful use of technology for the delivery and coordination of effective patient care for individuals with psychotic illnesses.

An exploration of genetic counseling information needs and information-seeking behaviors.

Genetic counseling is a rapidly growing field with increasingly diverse practice settings. The growth of genomics and precision medicine across all medical specialties has been accompanied by corresponding growth in the amount of information available to genetic counselors. However, few published studies on genetic counseling information needs and seeking behaviors exist, and none look at information use across the profession. Meanwhile, a substantial body of research exists on this topic for other healthcare professionals, providing an evidence base supporting profession-tailored information-related services and resources. The purpose of this cross-sectional study was to explore genetic counseling information needs and seeking behaviors and to compare these needs and seeking behaviors across genetic counseling students and genetic counselors broadly, as well as to explore differences across various professional subgroups of genetic counselors. Genetic counselors and genetic counseling students were recruited via the National Society of Genetic Counselors and accredited genetic counseling programs to complete an online survey assessing information needs and seeking behaviors. Respondents were asked how often they used 70 different resources; whether 16 specific situations required additional information and how long it would take to get it and about specific barriers to obtaining that information. The results included a range of observations, including that GeneReviews and PubMed are frequently used resources across all respondents, that genetic counselors working 0-5 years are significantly more likely to need additional information when counseling patients from different cultural backgrounds than those working 6+ years, and that not having enough time is a common barrier to getting information across various situations. These results provide initial evidence to guide additional study on the efficient use and provision of information within the genetic counseling field.

Integrated genomic DNA/RNA profiling of hematologic malignancies in the clinical setting.

The spectrum of somatic alterations in hematologic malignancies includes substitutions, insertions/deletions (indels), copy number alterations (CNAs), and a wide range of gene fusions; no current clinically available single assay captures the different types of alterations. We developed a novel next-generation sequencing-based assay to identify all classes of genomic alterations using archived formalin-fixed paraffin-embedded blood and bone marrow samples with high accuracy in a clinically relevant time frame, which is performed in our Clinical Laboratory Improvement Amendments-certified College of American Pathologists-accredited laboratory. Targeted capture of DNA/RNA and next-generation sequencing reliably identifies substitutions, indels, CNAs, and gene fusions, with similar accuracy to lower-throughput assays that focus on specific genes and types of genomic alterations. Profiling of 3696 samples identified recurrent somatic alterations that impact diagnosis, prognosis, and therapy selection. This comprehensive genomic profiling approach has proved effective in detecting all types of genomic alterations, including fusion transcripts, which increases the ability to identify clinically relevant genomic alterations with therapeutic relevance.

Neoadjuvant radiotherapy for retroperitoneal sarcoma: A systematic review.

BACKGROUND AND OBJECTIVES: The multi-modal treatment of retroperitoneal sarcoma has seen increased use of neoadjuvant radiation. However, its effect on local recurrence and survival remain controversial. We aimed to synthesize and evaluate the literature. METHODS: The review was conducted according the recommendation of the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) group with pre-specified inclusion and exclusion criteria. RESULTS: Of 8,701 citations collected, 15 articles reported on 464 patients. The median age was 56 years (45-64). The predominant histological subtypes were liposarcoma (51.54%) and leiomyosarcoma (23.26%). Tumor differentiation composed of 37.1% well-, 12.8% moderate-, 46.0% poorly-, and 4.1% undifferentiated. Most studies featured external beam radiation therapy (EBRT) treatment regimen with some who included patients treated with IMRT instead. Median follow-up averaged 41.4 months (19-106 months). Median 5-year OS, PFS, and LRR rates were 58%, 71.5%, and 25%. Using the NCI CTCAE, toxicities from Grade 1 (Mild) through Grade 5 (death) were experienced by 18.8%, 10.2%, 16.3%, 0.7%, and 1.6% of patients. CONCLUSIONS: NART is a safe to use for RPS, but its effect toward survival and local control remains unclear. Without randomized control trials, common reporting criteria for pro- and retrospective studies are needed to allow comparison between studies. J. Surg. Oncol. 2016;113:628-634. © 2016 Wiley Periodicals, Inc.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: a systematic review and meta-analysis.

BACKGROUND: Due to the increased adoption of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), patients with malignant peritoneal mesothelioma (MPM) have seen improved outcomes. We aimed to evaluate and synthesize the recent published literature. METHODS: The review was conducted according to the recommendation of the Meta-Analysis of Observational Studies in Epidemiology group with prespecified inclusion and exclusion criteria. The DEALE method was used to combine mortality rates, and imputation techniques were used to calculate standard errors. Meta-regression techniques were used to synthesize data. Publication bias was assessed using funnel plots. RESULTS: Of 6,528 citations collected, 20 articles reporting on 1,047 patients were included in the analysis. The median age was 51 years (interquartile range 49-55), with 59 % (54-67) female. The median peritoneal carcinomatosis index score was 19 (16-23). Complete cytoreduction (CC0, 1) was performed in 67 % (46-93 %) of patients. Pooled estimates of survival yielded a 1-, 3- and 5-year survival of 84, 59, and 42 %, respectively. Patients receiving early postoperative intraperitoneal chemotherapy [EPIC] (44 %) and those receiving cisplatin intraperitoneal chemotherapy alone (48 %) or in combination (44 %) had an improved 5-year survival. CONCLUSIONS: While CRS + HIPEC has led to an improved survival for patients with MPM compared to historic data, heterogeneity of studies precludes generalizable inferences. EPIC chemotherapy and cisplatin chemoperfusion may infer survival benefit.

Identification of a chronic obstructive pulmonary disease genetic determinant that regulates HHIP.

Multiple intergenic single-nucleotide polymorphisms (SNPs) near hedgehog interacting protein (HHIP) on chromosome 4q31 have been strongly associated with pulmonary function levels and moderate-to-severe chronic obstructive pulmonary disease (COPD). However, whether the effects of variants in this region are related to HHIP or another gene has not been proven. We confirmed genetic association of SNPs in the 4q31 COPD genome-wide association study (GWAS) region in a Polish cohort containing severe COPD cases and healthy smoking controls (P = 0.001 to 0.002). We found that HHIP expression at both mRNA and protein levels is reduced in COPD lung tissues. We identified a genomic region located ∼85 kb upstream of HHIP which contains a subset of associated SNPs, interacts with the HHIP promoter through a chromatin loop and functions as an HHIP enhancer. The COPD risk haplotype of two SNPs within this enhancer region (rs6537296A and rs1542725C) was associated with statistically significant reductions in HHIP promoter activity. Moreover, rs1542725 demonstrates differential binding to the transcription factor Sp3; the COPD-associated allele exhibits increased Sp3 binding, which is consistent with Sp3's usual function as a transcriptional repressor. Thus, increased Sp3 binding at a functional SNP within the chromosome 4q31 COPD GWAS locus leads to reduced HHIP expression and increased susceptibility to COPD through distal transcriptional regulation. Together, our findings reveal one mechanism through which SNPs upstream of the HHIP gene modulate the expression of HHIP and functionally implicate reduced HHIP gene expression in the pathogenesis of COPD.

Evaluation of Telepsychiatry-Enabled Perinatal Integrated Care.

OBJECTIVE: The purpose of this article is to describe the implementation of the first known telepsychiatry-enabled model of perinatal integrated care and to report initial results following implementation. METHODS: Behavioral health screening data were collected from 712 patients at an urban women's clinic, and a more in-depth set of process and outcome measures, including treatment engagement, services utilized, and delivery and postpartum patient outcomes, was collected from 135 patients referred for behavioral health services. Using nationally published metrics to provide context, the authors applied a descriptive design to evaluate and conduct analyses of program outcomes. RESULTS: The telehealth-enabled integrated care model was successfully implemented within a specialty obstetrics practice. Identification and treatment of behavioral health issues exceeded nationally published rates. The model was also associated with positive indices related to birth weight and breastfeeding behavior. CONCLUSIONS: These initial results point to telepsychiatry as an effective tool for expanding perinatal integrated care and lay the foundation for further study and model refinement. The results also add to the growing body of evidence for the use of telepsychiatry-supported integrated care across diverse clinical settings and patient populations.

Clinical and analytical validation of FoundationOne Liquid CDx, a novel 324-Gene cfDNA-based comprehensive genomic profiling assay for cancers of solid tumor origin.

As availability of precision therapies expands, a well-validated circulating cell-free DNA (cfDNA)-based comprehensive genomic profiling assay has the potential to provide considerable value as a complement to tissue-based testing to ensure potentially life-extending therapies are administered to patients most likely to benefit. Additional data supporting the clinical validity of cfDNA-based testing is necessary to inform optimal use of these assays in the clinic. The FoundationOne®Liquid CDx assay is a pan-cancer cfDNA-based comprehensive genomic profiling assay that was recently approved by FDA. Validation studies included >7,500 tests and >30,000 unique variants across >300 genes and >30 cancer types. Clinical validity results across multiple tumor types are presented. Additionally, results demonstrated a 95% limit of detection of 0.40% variant allele fraction for select substitutions and insertions/deletions, 0.37% variant allele fraction for select rearrangements, 21.7% tumor fraction for copy number amplifications, and 30.4% TF for copy number losses. The limit of detection for microsatellite instability and blood tumor mutational burden were also determined. The false positive variant rate was 0.013% (approximately 1 in 8,000). Reproducibility of variant calling was 99.59%. In comparison with an orthogonal method, an overall positive percent agreement of 96.3% and negative percent agreement of >99.9% was observed. These study results demonstrate that FoundationOne Liquid CDx accurately and reproducibly detects the major types of genomic alterations in addition to complex biomarkers such as microsatellite instability, blood tumor mutational burden, and tumor fraction. Critically, clinical validity data is presented across multiple cancer types.

Analytical Validation of a Hybrid Capture-Based Next-Generation Sequencing Clinical Assay for Genomic Profiling of Cell-Free Circulating Tumor DNA.

Genomic profiling of circulating tumor DNA derived from cell-free DNA (cfDNA) in blood can provide a noninvasive method for detecting genomic biomarkers to guide clinical decision making for cancer patients. We developed a hybrid capture-based next-generation sequencing assay for genomic profiling of circulating tumor DNA from blood (FoundationACT). High-sequencing coverage and molecular barcode-based error detection enabled accurate detection of genomic alterations, including short variants (base substitutions, short insertions/deletions) and genomic re-arrangements at low allele frequencies (AFs), and copy number amplifications. Analytical validation was performed on 2666 reference alterations. The assay achieved >99% overall sensitivity (95% CI, 99.1%-99.4%) for short variants at AF >0.5%, >95% sensitivity (95% CI, 94.2%-95.7%) for AF 0.25% to 0.5%, and 70% sensitivity (95% CI, 68.2%-71.5%) for AF 0.125% to 0.25%. No false positives were detected in 62 samples from healthy volunteers. Genomic alterations detected by FoundationACT demonstrated high concordance with orthogonal assays run on the same clinical cfDNA samples. In 860 routine clinical FoundationACT cases, genomic alterations were detected in cfDNA at comparable frequencies to tissue; for the subset of cases with temporally matched tissue and blood samples, 75% of genomic alterations and 83% of short variant mutations detected in tissue were also detected in cfDNA. On the basis of analytical validation results, FoundationACT has been approved for use in our Clinical Laboratory Improvement Amendments-certified/College of American Pathologists-accredited/New York State-approved laboratory.

A high frequency of activating extracellular domain ERBB2 (HER2) mutation in micropapillary urothelial carcinoma.

PURPOSE: Micropapillary urothelial carcinoma (MPUC) is a rare and aggressive form of bladder cancer. We conducted genomic analyses [next-generation sequencing (NGS)] of MPUC and non-micropapillary urothelial bladder carcinomas (non-MPUC) to characterize the genomic landscape and identify targeted treatment options. EXPERIMENTAL DESIGN: DNA was extracted from 40 µm of formalin-fixed paraffin-embedded sections from 15 MPUC and 64 non-MPUC tumors. Sequencing (NGS) was performed on hybridization-captured, adaptor ligation-based libraries to high coverage for 3,230 exons of 182 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. The results were evaluated for all classes of genomic alteration. RESULTS: Mutations in the extracellular domain of ERBB2 were identified in 6 of 15 (40%) of MPUC: S310F (four cases), S310Y (one case), and R157W (one case). All six cases of MPUC with ERBB2 mutation were negative for ERBB2 amplification and Erbb2 overexpression. In contrast, 6 of 64 (9.4%) non-MPUC harbored an ERBB2 alteration, including base substitution (three cases), amplification (two cases), and gene fusion (one case), which is higher than the 2 of 159 (1.3%) protein-changing ERBB2 mutations reported for urinary tract cancer in COSMIC. The enrichment of ERBB2 alterations in MPUC compared with non-MPUC is significant both between this series (P < 0.0084) and for all types of urinary tract cancer in COSMIC (P < 0.001). CONCLUSIONS: NGS of MPUC revealed a high incidence of mutation in the extracellular domain of ERBB2, a gene for which there are five approved targeted therapies. NGS can identify genomic alteration, which inform treatment options for the majority of MPUC patients.

Clinical next-generation sequencing successfully applied to fine-needle aspirations of pulmonary and pancreatic neoplasms.

BACKGROUND: Next-generation sequencing was performed on pulmonary and pancreatic fine-needle aspirations (FNAs) and on paired FNAs and resected primary tumors from the same patient. METHODS: DNA was isolated in formalin-fixed, paraffin-embedded cell blocks from 16 pulmonary FNAs, 23 pancreatic FNAs, and 5 resected pancreatic primary tumors. Next-generation sequencing was performed for 4561 exons of 287 cancer-related genes and for 47 introns of 19 genes on indexed, adaptor-ligated, hybridization-captured libraries using a proprietary sequencing system (the Illumina HiSeq 2000). RESULTS: Genomic profiles were generated successfully from 16 of 16 (100%) pulmonary FNAs, which included 14 nonsmall cell lung cancers (NSCLCs) and 2 small cell lung cancers (SCLCs). The NSCLC group included 6 adenocarcinomas, 5 squamous cell carcinomas, and 3 NSCLCs not otherwise specified. Genomic profiles were successfully obtained from 23 of 23 (100%) pancreatic FNAs and from 5 of 5 (100%) matched pancreatic primary tumors, which included 17 ductal adenocarcinomas, 3 mucinous adenocarcinomas, 2 adenocarcinomas NOS, and 1 neuroendocrine tumor. Eighty-one genomic alterations were identified in the 16 pulmonary FNAs (average, 5.1 genomic alterations per patient); and the most common genomic alterations were TP53, RB1, SOX2, PIK3CA, and KRAS. Eighty-seven genomic alterations were identified in the 23 pancreatic tumor FNAs (average, 3.8 genomic alterations per patient); and the most common genomic alterations were KRAS, TP53, CDKN2A/B, SMAD4, and PTEN. Among the pancreatic tumors, there was 100% concordance of 20 genomic alterations that were identified in 5 patient-matched FNA and surgical primary tumor pairs. CONCLUSIONS: The authors were able to perform next-generation sequencing reliably on FNAs of pulmonary and pancreatic tumors, and the genomic alterations discovered correlated well with those identified in matched resected pancreatic tumors.

Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing.

As more clinically relevant cancer genes are identified, comprehensive diagnostic approaches are needed to match patients to therapies, raising the challenge of optimization and analytical validation of assays that interrogate millions of bases of cancer genomes altered by multiple mechanisms. Here we describe a test based on massively parallel DNA sequencing to characterize base substitutions, short insertions and deletions (indels), copy number alterations and selected fusions across 287 cancer-related genes from routine formalin-fixed and paraffin-embedded (FFPE) clinical specimens. We implemented a practical validation strategy with reference samples of pooled cell lines that model key determinants of accuracy, including mutant allele frequency, indel length and amplitude of copy change. Test sensitivity achieved was 95-99% across alteration types, with high specificity (positive predictive value >99%). We confirmed accuracy using 249 FFPE cancer specimens characterized by established assays. Application of the test to 2,221 clinical cases revealed clinically actionable alterations in 76% of tumors, three times the number of actionable alterations detected by current diagnostic tests.

Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies.

Applying a next-generation sequencing assay targeting 145 cancer-relevant genes in 40 colorectal cancer and 24 non-small cell lung cancer formalin-fixed paraffin-embedded tissue specimens identified at least one clinically relevant genomic alteration in 59% of the samples and revealed two gene fusions, C2orf44-ALK in a colorectal cancer sample and KIF5B-RET in a lung adenocarcinoma. Further screening of 561 lung adenocarcinomas identified 11 additional tumors with KIF5B-RET gene fusions (2.0%; 95% CI 0.8-3.1%). Cells expressing oncogenic KIF5B-RET are sensitive to multi-kinase inhibitors that inhibit RET.

Google Wave: Have CTSA-Minded Institutions Caught It?

BACKGROUND: Google Wave was touted as the next big communication tool-combining e-mail, social networking, and chat within a single "wave"-with the potential to create a new world for collaboration. Information professionals who are knowledgeable of this tool and its capabilities could become uniquely situated to use it, evaluate it, and teach it. This seemed especially true for those working within Clinical and Translational Science Award (CTSA)-minded institutions, given the promise of interdisciplinary collaboration between investigators and the potential for creating new authorship models. This case study on Google Wave users who are affiliated with CTSA-minded institutions, was designed for and presented at the Evidence-Based Scholarly Communication Conference held by the University of New Mexico Health Sciences Library and Information Center. It provides an early evidence based evaluation of Google Wave's potential. METHODS: Two "waves" were created. The first consisted of five survey questions designed to collect demographic data on the respondents' roles, a general impression of Wave, the specific tools within Wave that might be useful, and potential collaborators with whom the respondents might use Wave. The second wave was a private, guided discussion on Wave's collaboration potential. Individuals from CTSA-minded institutions were invited to participate with messages on Twitter, forums, blogs, and electronic mail lists, although there were difficulties reaching out to these institutions as a group. RESULTS: By the conclusion of the study, only a small number of people (n=11, with a viable n=9) had responded to the survey. Given this small result set, it made sense to group the responses by the respondents' roles (CTSA staff and researchers, support staff, medical librarian, or general public) and to treat them as individual cases. Most of the respondents were librarians and support staff who felt that Wave might have potential for collaboration; there were no CTSA researcher respondents. For the second part of the study, the discussion wave, only one participant explicitly expressed interest in joining. All were invited to join, but there was no participation in the discussion wave at the conclusion of the study. CONCLUSIONS: The results of this study implied that Google Wave was not on the forefront of CTSA-minded institutions' communication strategies. However, it was being used, and it did demonstrate new collaboration and authorship capabilities. Being generally aware of these capabilities may be useful to information professionals who seek to be current and informed regarding developing technology and to those interested in scholarly communication practices. In addition, the difficulties encountered during this case study in attempting to reach out to CTSA-minded institutions raised the question of how members currently communicate with each other as institutions and as individuals. There was a lesson learned in the usefulness of doing case-study research to evaluate new technologies; the cost in terms of time was relatively low, and knowledge about the technology itself was gained while establishing a base level of evidence to potentially build on in the future.