Experiences and Attitudes of Genome Investigators Regarding Return of Individual Genetic Test Results

Purpose Whether and how to return individual genetic results to study participants is among the most contentious policy issues in contemporary genomic research. Methods: We surveyed corresponding authors of genome-wide association studies (GWAS), identified through the National Human Genome Research Institute's Catalog of Published GWAS, to describe the experiences and attitudes of these stakeholders. Results: Of 357 corresponding authors, 200 (56%) responded. One hundred twenty-six (63%) had been responsible for primary data and sample collection, whereas 74 (37%) had performed secondary analyses. Only 7 (4%) had returned individual results within their index GWAS. Most (69%) believed that return of results to individual participants was warranted under at least some circumstances. Most respondents identified a desire to benefit participants's health (63%) and respect for participants's; desires for information (57%) as major motivations for returning results. Most also identified uncertain clinical utility (76%), the possibility that participants will misunderstand results (74%), the potential for emotional harm (61%), the need to ensure access to trained clinicians (59%), and the potential for loss of confidentiality (51%) as major barriers to return. Conclusion: Investigators have limited experience returning individual results from genome-scale research, yet most are motivated to do so in at least some circumstances

Are Meaningful Use Stage 2 certified EHRs ready for interoperability? Findings from the SMART C-CDA Collaborative

Background and objective Upgrades to electronic health record (EHR) systems scheduled to be introduced in the USA in 2014 will advance document interoperability between care providers. Specifically, the second stage of the federal incentive program for EHR adoption, known as Meaningful Use, requires use of the Consolidated Clinical Document Architecture (C-CDA) for document exchange. In an effort to examine and improve C-CDA based exchange, the SMART (Substitutable Medical Applications and Reusable Technology) C-CDA Collaborative brought together a group of certified EHR and other health information technology vendors. Materials and methods We examined the machine-readable content of collected samples for semantic correctness and consistency. This included parsing with the open-source BlueButton.js tool, testing with a validator used in EHR certification, scoring with an automated open-source tool, and manual inspection. We also conducted group and individual review sessions with participating vendors to understand their interpretation of C-CDA specifications and requirements. Results: We contacted 107 health information technology organizations and collected 91 C-CDA sample documents from 21 distinct technologies. Manual and automated document inspection led to 615 observations of errors and data expression variation across represented technologies. Based upon our analysis and vendor discussions, we identified 11 specific areas that represent relevant barriers to the interoperability of C-CDA documents. Conclusions: We identified errors and permissible heterogeneity in C-CDA documents that will limit semantic interoperability. Our findings also point to several practical opportunities to improve C-CDA document quality and exchange in the coming years

Hormonal intervention for the treatment of veterans with COVID-19 requiring hospitalization (HITCH): a multicenter, phase 2 randomized controlled trial of best supportive care vs best supportive care plus degarelix: study protocol for a randomized controlled trial

Background Therapeutic targeting of host-cell factors required for SARS-CoV-2 entry is an alternative strategy to ameliorate COVID-19 severity. SARS-CoV-2 entry into lung epithelium requires the TMPRSS2 cell surface protease. Pre-clinical and correlative data in humans suggest that anti-androgenic therapies can reduce the expression of TMPRSS2 on lung epithelium. Accordingly, we hypothesize that therapeutic targeting of androgen receptor signaling via degarelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, will suppress COVID-19 infection and ameliorate symptom severity. Methods This is a randomized phase 2, placebo-controlled, double-blind clinical trial in 198 patients to compare efficacy of degarelix plus best supportive care versus placebo plus best supportive care on improving the clinical outcomes of male Veterans who have been hospitalized due to COVID-19. Enrolled patients must have documented infection with SARS-CoV-2 based on a positive reverse transcriptase polymerase chain reaction result performed on a nasopharyngeal swab and have a severity of illness of level 3–5 (hospitalized but not requiring invasive mechanical ventilation). Patients stratified by age, history of hypertension, and severity are centrally randomized 2:1 (degarelix: placebo). The composite primary endpoint is mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at 15 after randomization. Important secondary endpoints include time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a normal temperature, and the maximum severity of COVID-19 illness. Exploratory analyses aim to assess the association of cytokines, viral load, and various comorbidities with outcome. In addition, TMPRSS2 expression in target tissue and development of anti-viral antibodies will also be investigated. Discussion In this trial, we repurpose the FDA approved LHRH antagonist degarelix, commonly used for prostate cancer, to suppress TMPRSS2, a host cell surface protease required for SARS-CoV-2 cell entry. The objective is to determine if temporary androgen suppression with a single dose of degarelix improves the clinical outcomes of patients hospitalized due to COVID-19. Trial registration ClinicalTrials.gov NCT04397718. Registered on May 21, 202

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Lessons learned from dental patient safety case reports.

BackgroundErrors are commonplace in health care, including dentistry. It is imperative for dental professionals to intercept errors before they lead to an adverse event and to mitigate their effects when an adverse event occurs. This requires a systematic approach at both the profession level, encapsulated in the Agency for Healthcare Research and Quality's patient safety initiative framework, as well as at the practice level, in which crew resource management is a tested paradigm. Supporting patient safety at both the profession and dental practice levels relies on understanding the types and causes of errors, which have not been well studied.MethodsThe authors performed a retrospective review of dental adverse events reported in the literature. Electronic bibliographic databases were searched, and data were extracted on background characteristics, incident description, case characteristics, clinic setting where adverse event originated, phase of patient care that adverse event was detected, proximal cause, type of patient harm, degree of harm, and recovery actions.ResultsThe authors identified 182 publications (containing 270 cases) through their search. Delayed treatment, unnecessary treatment, or disease progression after misdiagnosis was the largest type of harm reported. Of the reviewed cases, 24.4% of those patients involved in an adverse event experienced permanent harm. One of every 10 case reports reviewed (11.1%) reported that the adverse event resulted in the death of the affected patient.ConclusionsPublished case reports provide a window into understanding the nature and extent of dental adverse events; however, the overall dearth of publications on adverse events in the dental literature points to the need for more study.Practical implicationsSiloed and incomplete contributions to dentistry's understanding of adverse events in the dental office are threats to dental patients' safety. Publishing more, and more comprehensive, case reports on adverse events is recommended for dental practitioners

Measuring up: Implementing a dental quality measure in the electronic health record context.

BackgroundQuality improvement requires using quality measures that can be implemented in a valid manner. Using guidelines set forth by the Meaningful Use portion of the Health Information Technology for Economic and Clinical Health Act, the authors assessed the feasibility and performance of an automated electronic Meaningful Use dental clinical quality measure to determine the percentage of children who received fluoride varnish.MethodsThe authors defined how to implement the automated measure queries in a dental electronic health record. Within records identified through automated query, the authors manually reviewed a subsample to assess the performance of the query.ResultsThe automated query results revealed that 71.0% of patients had fluoride varnish compared with the manual chart review results that indicated 77.6% of patients had fluoride varnish. The automated quality measure performance results indicated 90.5% sensitivity, 90.8% specificity, 96.9% positive predictive value, and 75.2% negative predictive value.ConclusionsThe authors' findings support the feasibility of using automated dental quality measure queries in the context of sufficient structured data. Information noted only in free text rather than in structured data would require using natural language processing approaches to effectively query electronic health records.Practical implicationsTo participate in self-directed quality improvement, dental clinicians must embrace the accountability era. Commitment to quality will require enhanced documentation to support near-term automated calculation of quality measures

Adoption of dental innovations: The case of a standardized dental diagnostic terminology.

BackgroundStandardized dental diagnostic terminologies (SDDxTs) were introduced decades ago. Their use has been on the rise, accompanying the adoption of electronic health records (EHRs). One of the most broadly used terminologies is the Dental Diagnostic System (DDS). Our aim was to assess the adoption of SDDxTs by US dental schools by using the Rogers diffusion of innovations framework, focusing on the DDS.MethodsThe authors electronically surveyed clinic deans in all US dental schools (n = 61) to determine use of an EHR and SDDxT, perceived barriers to adoption of an SDDxT, and the effect of implementing an SDDxT on clinical productivity.ResultsThe response rate was 57%. Of the 35 responses, 91% reported using an EHR to document patient care, with 84% using axiUm; 41% used the DDS. Fifty-four percent of those who did not use an SDDxT had considered adopting the DDS, but 38% had not, citing barriers such as complexity and compatibility.ConclusionsAdoption of an SDDxT, particularly the DDS, is on the rise. Nevertheless, a large number of institutions are in the Rogers late majority and laggards categories with respect to adoption. Several factors may discourage adoption, including the inability to try out the terminology on a small scale, poor usability within the EHR, the fact that it would be a cultural shift in practice, and a perception of unclear benefits. However, the consolidation of the DDS and American Dental Association terminology efforts stands to encourage adoption.Practical implicationsThe successful adoption of dental innovation depends not only on the intrinsic merit of the innovation, as some useful innovations do not achieve widespread traction. As such, it is important for health care providers to understand how to disseminate their ideas in order to ensure traction and widespread adoption

The dangers of dental devices as reported in the Food and Drug Administration Manufacturer and User Facility Device Experience Database.

BackgroundThe authors conducted a study to determine the frequency and type of adverse events (AEs) associated with dental devices reported to the Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) database.MethodsThe authors downloaded and reviewed the dental device-related AEs reported to MAUDE from January 1, 1996, through December 31,2011.ResultsMAUDE received a total of 1,978,056 reports between January 1, 1996, and December 31, 2011. Among these reports, 28,046 (1.4%) AE reports were associated with dental devices. Within the dental AE reports that had event type information, 17,261 reported injuries, 7,777 reported device malfunctions, and 66 reported deaths. Among the 66 entries classified as death reports, 52 reported a death in the description; the remaining were either misclassified or lacked sufficient information in the report to determine whether a death had occurred. Of the dental device-associated AEs, 53.5% pertained to endosseous implants.ConclusionsA plethora of devices are used in dental care. To achieve Element 1 of Agency for Healthcare Research and Quality's Patient Safety Initiative, clinicians and researchers must be able to monitor the safety of dental devices. Although MAUDE was identified by the authors as essentially the sole source of this valuable information on adverse events, their investigations led them to conclude that MAUDE had substantial limitations that prevent it from being the broad-based patient safety sentinel the profession requires.Practical implicationsAs potential contributors to MAUDE, dental care teams play a key role in improving the profession's access to information about the safety of dental devices