Scrybe: A Secure Audit Trail for Clinical Trial Data Fusion.

Clinical trials are a multi-billion dollar industry. One of the biggest challenges facing the clinical trial research community is satisfying Part 11 of Title 21 of the Code of Federal Regulations [7] and ISO 27789 [40]. These controls provide audit requirements that guarantee the reliability of the data contained in the electronic records. Context-aware smart devices and wearable IoT devices have become increasingly common in clinical trials. Electronic Data Capture (EDC) and Clinical Data Management Systems (CDMS) do not currently address the new challenges introduced using these devices. The healthcare digital threat landscape is continually evolving, and the prevalence of sensor fusion and wearable devices compounds the growing attack surface. We propose Scrybe, a permissioned blockchain, to store proof of clinical trial data provenance. We illustrate how Scrybe addresses each control and the limitations of the Ethereum-based blockchains. Finally, we provide a proof-of-concept integration with REDCap to show tamper resistance.

Radicalism: The asymmetric stances of radicals versus conventionals.

We study the conditions of propagation of an initial emergent practice qualified as extremist within a population adept at a practice perceived as moderate, whether political, societal, or religious. The extremist practice is carried by an initial ultraminority of radicals (R) dispersed among conventionals (C) who are the overwhelming majority in the community. Both R and C are followers, that is, agents who, while having arguments to legitimize their current practice, are likely to switch to the other practice if given more arguments during a debate. The issue being controversial, most C tend to avoid social confrontation with R about it. They maintain a neutral indifference, assuming it is none of their business. On the contrary, R aim to convince C through an expansion strategy to spread their practice as part of a collective agenda. However, aware of being followers, they implement an appropriate strategy to maximize their expansion and determine when to force a debate with C. The effect of this asymmetry between initiating or avoiding an update debate among followers is calculated using a weighted version of the Galam model of opinion dynamics. An underlying complex landscape is obtained as a function of the respective probabilities to engage in a local discussion by R and C. It discloses zones where R inexorably expand and zones where they get extinct. The results highlight the instrumental character of the above asymmetry in providing a decisive advantage to R against C. It also points to a barrier in R initial support to reach the extension zone. In parallel, the landscape reveals a path for C to counter R expansion, pushing them back into their extinction zone. It relies on the asymmetry of C being initially a large majority which puts the required involvement of C at a rather low level.

The remarkably frequent use of EQ-5D in non-economic research.

INTRODUCTION: EQ-5D is an instrument which has been utilized for a variety of purposes, including in health-economic appraisals as an input into quality-adjusted life year (QALY) calculations. Indeed, it is the most-widely applied instrument for health-economic appraisal worldwide, and is recommended for use in QALY calculations by many national Health Technology Assessment (HTA) agencies. There is also a growing body of evidence for its usefulness in a variety of settings other than economic appraisals, but such use has not been well-documented. This study addresses this issue and documents how EQ-5D has been applied in both the non-economic and economic contexts. METHODS: The PubMed database was searched using the terms 'EQ-5D', 'EQ-5D AND cost', and 'EQ-5D AND cost AND QALY' from 1 January 1980 to 31 December 2019. We concentrated on 2019 publications for more detailed analyses. All the data collected for 2019 were downloaded and collected in EndNote. For 2019 only, we classified economic and non-economic use based on the inclusion of 'cost'. We also checked by manual inspection whether the search terms were suitable in correctly identifying economic and non-economic use. Variants of the non-economic use of EQ-5D were classified as follows: (a) as a quality of life outcome measure; (b) as a tool for methodological research; (c) methodological issues of EQ-5D itself; (d) comparisons with other quality of life questionnaires; (e) mapping studies; (f) value sets; (g) alongside costs but no QALY calculated; and (h) other. RESULTS: The first publication found was from 1990. Up to and including 2019, 10,817 publications were identified, of which more than two in three did not contain any reference to costs or QALYs. In 2019, a total of 1409 manuscripts were identified, of which 239 were specifically for EQ-5D-5L.  Four hundred and seven (28.9%) included some form of 'costs' and 157 (11.1%) both 'costs' AND 'QALYs' terms. For EQ-5D-5L, the corresponding numbers were 104 (43.5%) and 29 (12.1%), respectively. After manually checking all the 1409 papers, three were duplicated records, which were omitted. In the remaining 1406 papers, only 40 (2.8%) contained the term 'cost', but not 'cost per QALY', and only 117 (8.3%) were identifiable as economic evaluations using the term 'cost per QALY'. Most non-economic use of EQ-5D was as a quality-of-life outcome measure (72.8%). Other applications were: as a tool for methodological research (6.7%); comparison studies (3.7%); EQ-5D methodological issues (3.5%); containing costs but not QALYs (2.8%); mapping (1.3%); value sets (0.4%); and other papers (0.4%). CONCLUSIONS: The majority of the studies retrieved, covering a wide variety of research areas, reported upon the non-economic use of EQ-5D. Despite being the most-used instrument worldwide for QALY calculations, economic appraisal accounted for only a small, but important, part of published use.

Impact of Statewide Prevention and Reduction of Clostridioides difficile (SPARC), a Maryland public health-academic collaborative: an evaluation of a quality improvement intervention.

To evaluate changes in Clostridioides difficile incidence rates for Maryland hospitals that participated in the Statewide Prevention and Reduction of C. difficile (SPARC) collaborative. Pre-post, difference-in-difference analysis of non-randomised intervention using four quarters of preintervention and six quarters of postintervention National Healthcare Safety Network data for SPARC hospitals (April 2017 to March 2020) and 10 quarters for control hospitals (October 2017 to March 2020). Mixed-effects negative binomial models were used to assess changes over time. Process evaluation using hospital intervention implementation plans, assessments and interviews with staff at eight SPARC hospitals. Maryland, USA. All Maryland acute care hospitals; 12 intervention and 36 control hospitals. Participation in SPARC, a public health-academic collaborative made available to Maryland hospitals, with staggered enrolment between June 2018 and August 2019. Hospitals with higher C. difficile rates were recruited via email and phone. SPARC included assessments, feedback reports and ongoing technical assistance. Primary outcomes were C. difficile incidence rate measured as the quarterly number of C. difficile infections per 10 000 patient-days (outcome measure) and SPARC intervention hospitals' experiences participating in the collaborative (process measures). SPARC invited 13 hospitals to participate in the intervention, with 92% (n=12) participating. The 36 hospitals that did not participate served as control hospitals. SPARC hospitals were associated with 45% greater C. difficile reduction as compared with control hospitals (incidence rate ratio=0.55, 95% CI 0.35 to 0.88, p=0.012). Key SPARC activities, including access to trusted external experts, technical assistance, multidisciplinary collaboration, an accountability structure, peer-to-peer learning opportunities and educational resources, were associated with hospitals reporting positive experiences with SPARC. SPARC intervention hospitals experienced 45% greater reduction in C. difficile rates than control hospitals. A public health-academic collaborative might help reduce C. difficile and other hospital-acquired infections in individual hospitals and at state or regional levels.

Rapid Assessment and Containment of Candida auris Transmission in Postacute Care Settings-Orange County, California, 2019.

BACKGROUND: Candida auris, a multidrug-resistant yeast, can spread rapidly in ventilator-capable skilled-nursing facilities (vSNFs) and long-term acute care hospitals (LTACHs). In 2018, a laboratory serving LTACHs in southern California began identifying species of Candida that were detected in urine specimens to enhance surveillance of C auris, and C auris was identified in February 2019 in a patient in an Orange County (OC), California, LTACH. Further investigation identified C auris at 3 associated facilities. OBJECTIVE: To assess the prevalence of C auris and infection prevention and control (IPC) practices in LTACHs and vSNFs in OC. DESIGN: Point prevalence surveys (PPSs), postdischarge testing for C auris detection, and assessments of IPC were done from March to October 2019. SETTING: All LTACHs (n = 3) and vSNFs (n = 14) serving adult patients in OC. PARTICIPANTS: Current or recent patients in LTACHs and vSNFs in OC. INTERVENTION: In facilities where C auris was detected, PPSs were repeated every 2 weeks. Ongoing IPC support was provided. MEASUREMENTS: Antifungal susceptibility testing and whole-genome sequencing to assess isolate relatedness. RESULTS: Initial PPSs at 17 facilities identified 44 additional patients with C auris in 3 (100%) LTACHs and 6 (43%) vSNFs, with the first bloodstream infection reported in May 2019. By October 2019, a total of 182 patients with C auris were identified by serial PPSs and discharge testing. Of 81 isolates that were sequenced, all were clade III and highly related. Assessments of IPC identified gaps in hand hygiene, transmission-based precautions, and environmental cleaning. The outbreak was contained to 2 facilities by October 2019. LIMITATION: Acute care hospitals were not assessed, and IPC improvements over time could not be rigorously evaluated. CONCLUSION: Enhanced laboratory surveillance and prompt investigation with IPC support enabled swift identification and containment of C auris. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Carbapenemase production among less-common Enterobacterales genera: 10 US sites, 2018.

BACKGROUND: Historically, United States' carbapenem-resistant Enterobacterales (CRE) surveillance and mechanism testing focused on three genera: Escherichia, Klebsiella, and Enterobacter (EsKE); however, other genera can harbour mobile carbapenemases associated with CRE spread. OBJECTIVES: From January through May 2018, we conducted a 10 state evaluation to assess the contribution of less common genera (LCG) to carbapenemase-producing (CP) CRE. METHODS: State public health laboratories (SPHLs) requested participating clinical laboratories submit all Enterobacterales from all specimen sources during the surveillance period that were resistant to any carbapenem (Morganellaceae required resistance to doripenem, ertapenem, or meropenem) or were CP based on phenotypic or genotypic testing at the clinical laboratory. SPHLs performed species identification, phenotypic carbapenemase production testing, and molecular testing for carbapenemases to identify CP-CRE. Isolates were categorized as CP if they demonstrated phenotypic carbapenemase production and ≥1 carbapenemase gene (bla KPC, bla NDM, bla VIM, bla IMP, or bla OXA-48-like) was detected. RESULTS: SPHLs tested 868 CRE isolates, 127 (14.6%) were from eight LCG. Overall, 195 (26.3%) EsKE isolates were CP-CRE, compared with 24 (18.9%) LCG isolates. LCG accounted for 24 (11.0%) of 219 CP-CRE identified. Citrobacter spp. was the most common CP-LCG; the proportion of Citrobacter that were CP (11/42, 26.2%) was similar to the proportion of EsKE that were CP (195/741, 26.3%). Five of 24 (20.8%) CP-LCG had a carbapenemase gene other than bla KPC. CONCLUSIONS: Participating sites would have missed approximately 1 in 10 CP-CRE if isolate submission had been limited to EsKE genera. Expanding mechanism testing to additional genera could improve detection and prevention efforts.

EQ-5D: a plea for accurate nomenclature.

Between 1987 and 1990, the EuroQol Group developed a 5-dimension health-related quality of life instrument, originally known as 'the EuroQol instrument', which since 1995 has been called the 'EQ-5D'. For several years, 'the EuroQol instrument' and 'EQ-5D' were both deployed in published materials. In order to standardise nomenclature, the EuroQol Group agreed in 2001 on a terminology glossary containing 12 items; this was recently revised and augmented to include 22 items and can be found on the Group's website ( www.euroqol.org ). Since 2009, EQ-5D has been available in three versions: EQ-5D-3L, EQ-5D-5L, and EQ-5D-Y, where 3L stands for three levels, 5L for five levels, and Y for youth. Yet, almost 20 years after the original glossary was published, the instrument and its components continue to be inaccurately named in published materials. Two surveys - of arthritis applications, and 82 recent publications - found a variety of terms used to describe the instrument. Despite the instrument being named 'EQ-5D' for 25 years, and the terms 'EQ-5D-3L' and 'EQ-5D-5L' being established for a decade, variations of 'the EuroQol instrument' continue to be used as descriptors. The EuroQol Group's website contains advice on how to use EQ-5D, including nomenclature, and potential users are urged to consult the site. Since standardising nomenclature is crucial in the compilation of systematic reviews, the EuroQol Group would like to emphasise that 'EQ-5D' is not an abbreviation and is the correct term to use when referring to the instrument in general. In the interests of accuracy and good practice, users of the EuroQol family of instruments should employ the standard EQ-5D nomenclature when reporting and discussing their findings.

Candida auris in a U.S. Patient with Carbapenemase-Producing Organisms and Recent Hospitalization in Kenya.

Candida auris is an emerging drug-resistant yeast that causes outbreaks in health care facilities; cases have been reported from approximately 30 countries. U.S. cases of C. auris are likely the result of importation from abroad followed by extensive local transmission in health care settings (1). Early detection of Candida auris is key to preventing its spread. C. auris frequently co-occurs with carbapenemase-producing organisms (CPOs), like carbapenem-resistant Enterobacteriaceae (CRE), organisms for which testing and public health response capacity substantially increased beginning in 2017. In September 2018, the Maryland Department of Health (MDH) was notified of a hospitalized resident with CPO infection and colonization and recent hospitalization in Kenya. In light of this history, the patient was screened for C. auris and found to be colonized. Public health responses to CPOs can aid in the early identification of C. auris. As part of CPO investigations, health departments should assess whether the patient has risk factors for C. auris and ensure that patients at risk are tested promptly.

Outbreak investigation of Pseudomonas aeruginosa infections in a neonatal intensive care unit.

A Pseudomonas aeruginosa outbreak was investigated in a neonatal intensive care unit that had experienced a prior similar outbreak. The 8 cases identified included 2 deaths. An investigation found the cause of the outbreak: tap water from contaminated hospital plumbing which was used for humidifier reservoirs, neonatal bathing, and nutritional preparation. Our findings reinforce a recent Centers for Medicare & Medicaid Services memo recommending increased attention to water management to improve awareness, identification, mitigation, and prevention of water-associated, health care-associated infections.

Completeness of HIV nucleotide sequence ascertainment and its potential impact on understanding HIV transmission - Maryland, 2011-2013.

HIV nucleotide sequences generated through routine drug resistance testing (DRT) and reported to Maryland's Molecular HIV Surveillance system are most effective for elucidating transmission patterns and identifying outbreaks if DRT is ordered promptly and sequences are reported completely. Among reported cases of HIV infection newly diagnosed during 2011-2013 in Maryland residents aged ≥13 years, we assessed sequence ascertainment completeness. To better understand which populations were most likely to have a sequence, we examined associations between sequence ascertainment and clinical and demographic characteristics. During 2011-2013, 4423 new HIV infection diagnoses were reported; sequences were ascertained for 1282 (29.0%). Among 3267 cases with complete data, odds for having a sequence ascertained were highest for cases in persons living inside Maryland's Central Region with initial CD4 counts ≤500 cells/mm3 (adjusted odds ratio [aOR] 2.4, 95% confidence interval [CI] 1.9-3.1). Sequence ascertainment did not vary significantly by patient age, sex, race/ethnicity or HIV transmission category. Educational interventions, policy changes and improved processes to increase timely DRT and subsequent sequence reporting with a focus on testing at entry to care, particularly for those with higher CD4 counts and those living outside the Central Region, might improve ascertainment completeness.

Positive verbal feedback about task performance is related with adaptive physiological responses: An experimental study of the effort-reward imbalance stress model.

Effort-reward imbalance in the workplace has been related with poor mental and physical health and a variety of negative organisational outcomes including increased rates of absenteeism, presentism, and job turnover, but the model has rarely been assessed using experimental designs. Female participants (N = 90) were randomly assigned to positive verbal feedback and no verbal feedback conditions. Within a simulated office environment, all participants were under time-pressure to successfully complete computer-based tasks in order to gain remuneration. Positive verbal feedback about task performance was provided to improve the aspect of 'esteem reward' (while keeping effort constant) using a mixed within-between subjects design. Psychological, behavioural (task performance), and physiological (heart rate variability, salivary alpha amylase) measures assessed the impact of the positive verbal feedback. Participants receiving the esteem manipulation did not self-report increased rewards, but performed moderately better on the task, and had more adaptive physiological reactivity in the high reward versus the standard condition. Similar to recent research our findings highlight the importance of concurrent assessments of both self-reports and physiological measures of stress, and suggest that positive verbal feedback about work performance can elicit adaptive physiological responses and may also positively influence task efficacy.

Multistate Outbreak of Burkholderia cepacia Complex Bloodstream Infections After Exposure to Contaminated Saline Flush Syringes: United States, 2016-2017.

BACKGROUND: Burkholderia cepacia complex (Bcc) has caused healthcare-associated outbreaks, often in association with contaminated products. The identification of 4 Bcc bloodstream infections in patients residing at a single skilled nursing facility (SNF) within 1 week led to an epidemiological investigation to identify additional cases and the outbreak source. METHODS: A case was initially defined via a blood culture yielding Bcc in a SNF resident receiving intravenous therapy after 1 August 2016. Multistate notifications were issued to identify additional cases. Public health authorities performed site visits at facilities with cases to conduct chart reviews and identify possible sources. Pulsed-field gel electrophoresis (PFGE) was performed on isolates from cases and suspect products. Facilities involved in manufacturing suspect products were inspected to assess possible root causes. RESULTS: An outbreak of 162 Bcc bloodstream infections across 59 nursing facilities in 5 states occurred during September 2016-January 2017. Isolates from patients and pre-filled saline flush syringes were closely related by PFGE, identifying contaminated flushes as the outbreak source and prompting a nationwide recall. Inspections of facilities at the saline flush manufacturer identified deficiencies that might have led to the failure to sterilize a specific case containing a partial lot of the product. CONCLUSIONS: Communication and coordination among key stakeholders, including healthcare facilities, public health authorities, and state and federal agencies, led to the rapid identification of an outbreak source and likely prevented many additional infections. Effective processes to ensure the sterilization of injectable products are essential to prevent similar outbreaks in the future.

EQ-5D and the EuroQol Group: Past, Present and Future.

Over the period 1987-1991 an inter-disciplinary five-country group developed the EuroQol instrument, a five-dimensional three-level generic measure subsequently termed the 'EQ-5D'. It was designed to measure and value health status. The salient features of its development and its consolidation and expansion are discussed. Initial expansion came, in particular, in the form of new language versions. Their development raised translation and semantic issues, experience with which helped feed into the design of two further instruments, the EQ-5D-5L and the youth version EQ-5D-Y. The expanded usage across clinical programmes, disease and condition areas, population surveys, patient-reported outcomes, and value sets is outlined. Valuation has been of continued relevance for the Group as this has allowed its instruments to be utilised as part of the economic appraisal of health programmes and their incorporation into health technology assessments. The future of the Group is considered in the context of: (1) its scientific strategy, (2) changes in the external environment affecting the demand for EQ-5D, and (3) a variety of issues it is facing in the context of the design of the instrument, its use in health technology assessment, and potential new uses for EQ-5D outside of clinical trials and technology appraisal.

Male-to-Female Sexual Transmission of Zika Virus-United States, January-April 2016.

We report on 9 cases of male-to-female sexual transmission of Zika virus in the United States occurring January-April 2016. This report summarizes new information about both timing of exposure and symptoms of sexually transmitted Zika virus disease, and results of semen testing for Zika virus from 2 male travelers.

Effects of simulated inflammation on the corrosion of 316L stainless steel.

Stainless steel alloys, including 316L, find use in orthopaedics, commonly as fracture fixation devices. Invasive procedures involved in the placement of these devices will provoke a local inflammatory response that produces hydrogen peroxide (H2O2) and an acidic environment surrounding the implant. This study assessed the influence of a simulated inflammatory response on the corrosion of 316L stainless steel. Samples were immersed in an electrolyte representing either normal or inflammatory physiological conditions. After 24h of exposure, electrochemical impedance spectroscopy (EIS) and inductively coupled plasma mass spectroscopy (ICPMS) were used to evaluate differences in corrosion behavior and ion release induced by the inflammatory conditions. Scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDX) were used to evaluate surface morphology and corrosion products formed on the sample surface. Inflammatory conditions, involving the presence of H2O2 and an acidic pH, significantly alter the corrosion processes of 316L stainless steel, promoting aggressive and localized corrosion. It is demonstrated that particular consideration should be given to 316L stainless steel implants with crevice susceptible areas (ex. screw-head/plate interface), as those areas may have an increased probability of rapid and aggressive corrosion when exposed to inflammatory conditions.

Likely Sexual Transmission of Zika Virus from a Man with No Symptoms of Infection - Maryland, 2016.

In June 2016, the Maryland Department of Health and Mental Hygiene (DHMH) was notified of a nonpregnant woman who sought treatment for a subjective fever and an itchy rash, which was described as maculopapular by her provider. Laboratory testing at the Maryland DHMH Laboratories Administration confirmed Zika virus infection. Case investigation revealed that the woman had not traveled to a region with ongoing transmission of Zika virus, but did have sexual contact with a male partner who had recently traveled to the Dominican Republic. The male partner reported exposure to mosquitoes while traveling, but no symptoms consistent with Zika virus infection either before or after returning to the United States. The woman reported no other sex partners during the 14 days before onset of her symptoms and no receipt of blood products or organ transplants.

Coping with the urge to smoke: A real-time analysis.

Successfully coping with the urge to smoke is important to achieve smoking cessation. Nicotine-dependent smokers (N = 123) were placed in a tempting setting in a laboratory, and the effectiveness of various coping strategies for resisting the urge to smoke were evaluated in real time. Latency (time between exposure to lit cigarettes and report of need to smoke) was the primary-dependent variable, and coping strategies listed by participants after the smoking encounter served as predictors. There was a small positive relationship between cognitive-specific strategies, such as using positive self-talk, and latency (r = .19, p < .05), whereas there was a small negative relationship between behavioral-general strategies, such as looking out the window, and latency (r = -.23, p < .01). Counseling approaches that include teaching cognitive-specific strategies may help individuals cope with the urge to smoke.

A normalized statistical metric space for hidden Markov models.

In this paper, we present a normalized statistical metric space for hidden Markov models (HMMs). HMMs are widely used to model real-world systems. Like graph matching, some previous approaches compare HMMs by evaluating the correspondence, or goodness of match, between every pair of states, concentrating on the structure of the models instead of the statistics of the process being observed. To remedy this, we present a new metric space that compares the statistics of HMMs within a given level of statistical significance. Compared with the Kullback-Leibler divergence, which is another widely used approach for measuring model similarity, our approach is a true metric, can always return an appropriate distance value, and provides a confidence measure on the metric value. Experimental results are given for a sample application, which quantify the similarity of HMMs of network traffic in the Tor anonymization system. This application is interesting since it considers models extracted from a system that is intentionally trying to obfuscate its internal workings. In the conclusion, we discuss applications in less-challenging domains, such as data mining.