Value of Engagement in Digital Health Technology Research: Evidence Across 6 Unique Cohort Studies.

BACKGROUND: Wearable digital health technologies and mobile apps (personal digital health technologies [DHTs]) hold great promise for transforming health research and care. However, engagement in personal DHT research is poor. OBJECTIVE: The objective of this paper is to describe how participant engagement techniques and different study designs affect participant adherence, retention, and overall engagement in research involving personal DHTs. METHODS: Quantitative and qualitative analysis of engagement factors are reported across 6 unique personal DHT research studies that adopted aspects of a participant-centric design. Study populations included (1) frontline health care workers; (2) a conception, pregnant, and postpartum population; (3) individuals with Crohn disease; (4) individuals with pancreatic cancer; (5) individuals with central nervous system tumors; and (6) families with a Li-Fraumeni syndrome affected member. All included studies involved the use of a study smartphone app that collected both daily and intermittent passive and active tasks, as well as using multiple wearable devices including smartwatches, smart rings, and smart scales. All studies included a variety of participant-centric engagement strategies centered on working with participants as co-designers and regular check-in phone calls to provide support over study participation. Overall retention, probability of staying in the study, and median adherence to study activities are reported. RESULTS: The median proportion of participants retained in the study across the 6 studies was 77.2% (IQR 72.6%-88%). The probability of staying in the study stayed above 80% for all studies during the first month of study participation and stayed above 50% for the entire active study period across all studies. Median adherence to study activities varied by study population. Severely ill cancer populations and postpartum mothers showed the lowest adherence to personal DHT research tasks, largely the result of physical, mental, and situational barriers. Except for the cancer and postpartum populations, median adherences for the Oura smart ring, Garmin, and Apple smartwatches were over 80% and 90%, respectively. Median adherence to the scheduled check-in calls was high across all but one cohort (50%, IQR 20%-75%: low-engagement cohort). Median adherence to study-related activities in this low-engagement cohort was lower than in all other included studies. CONCLUSIONS: Participant-centric engagement strategies aid in participant retention and maintain good adherence in some populations. Primary barriers to engagement were participant burden (task fatigue and inconvenience), physical, mental, and situational barriers (unable to complete tasks), and low perceived benefit (lack of understanding of the value of personal DHTs). More population-specific tailoring of personal DHT designs is needed so that these new tools can be perceived as personally valuable to the end user.

Assessment of the Effects of Occluding Pairs of Teeth on Oral Health-related Quality of Life among Dialysis Patients.

AIM: To determine oral health-related quality of life (OHRQoL) in hemodialysis patients and assess if location and distribution of teeth had perceived oral impacts. MATERIALS AND METHODS: Face-to-face interviews and oral examinations were conducted among 96 patients in southwest Florida. Sociodemographic data in addition to self-reported medical conditions were collected. OHRQoL was determined using the Geriatric Oral Health Assessment Index (GOHAI-12). Presence of decayed teeth, missing teeth, anterior occluding pairs (AOPs) and posterior occluding pairs (POPs), and community periodontal index were ascertained through oral examinations. RESULTS: Mean age was 64.81 ± 12.9 years. Mean number of teeth present was 20.12 ± 10.8. Nearly half (48%) of the participants had ≥1 decayed teeth. Among those examined for periodontal health, 86% had some form of periodontal disease. Mean AOP was 4.4 ± 2.3 and mean POP was 4.2 ± 3.1. Median GOHAI-12 score was 52. Limiting the kinds or amounts of food (p = 0.040), trouble biting or chewing (p = 0.010), feeling uncomfortable eating in front of people (p = 0.024), and pleased with looks (p = 0.038) were statistically significant for AOP groups. Only trouble biting or chewing (p = 0.044) and pleased with looks showed significant association with POP groups (p = 0.038). In adjusted regression analyses, participants with AOPs 0 to 2 had 86% lower odds of reporting GOHAI-12 scores above 40 (25th percentile) than the group with AOPs 3 to 6 (odds ratio = 0.14; 95% confidence interval = 0.04-0.58). CONCLUSION: The study highlights fewer AOP to have a larger effect than POP not only in the psychosocial dimension but also in the functional abilities. Lower GOHAI-12 scores were associated with AOP 2 or less than 2 in the study sample. CLINICAL SIGNIFICANCE: While treatment and management of oral health problems in dialysis patients are complicated by the presence of co-morbidities, age-related changes in the mouth, and issues of access to dental care, identification, repair, or replacement of strategically important teeth using the "shortened dental arch principle" to maintain oral function among hemodialysis patients are recommended.

Improving nutritional care: innovation and good practice.

AIMS: This paper presents examples of good practice in nutritional screening and care and identifies methods used to overcome contextual constraints and discusses the implications for nursing practice in hospitals. BACKGROUND: Nutritional screening is an important step in identifying those at risk of malnutrition, but does not produce improved nutritional care unless it results in a care plan that is acted on. The importance of nutrition and implications for clinical care make it imperative to improve practice. DESIGN: Qualitative investigation. METHODS: Between January 2011-February 2012, focus groups were held using a semi-structured discussion guide with nine groups of health professionals (n = 80) from one hospital: four with nurses, three with doctors and two with dietitians. Discussions were audio-recorded, transcribed and coded into themes and sub-themes, which were then depicted in a thematic map and illustrated with verbatim quotes. FINDINGS: Three strategies for sustaining effective nutritional practice emerged: establishing routines to ensure screening was undertaken; re-organizing aspects of care to promote good practice; developing innovative approaches. Issues to be addressed were the perceived disconnection between mandatory screening and the delivery of effective care, a requirement for nutrition education, organizational constraints of a large university hospital and the complexities of multidisciplinary working. CONCLUSION: Professionals seeking to improve nutritional care in hospitals need to understand the interaction of system and person to facilitate change. Nursing staff need to be able to exercise autonomy and the hospital system must offer enough flexibility to allow wards to organize nutritional screening and care in a way that meets the needs of individual patients.

Whole genome sequencing of phage resistant Bacillus anthracis mutants reveals an essential role for cell surface anchoring protein CsaB in phage AP50c adsorption.

BACKGROUND: Spontaneous Bacillus anthracis mutants resistant to infection by phage AP50c (AP50R) exhibit a mucoid colony phenotype and secrete an extracellular matrix. METHODS: Here we utilized a Roche/454-based whole genome sequencing approach to identify mutations that are candidates for conferring AP50c phage resistance, followed by genetic deletion and complementation studies to validate the whole genome sequence data and demonstrate that the implicated gene is necessary for AP50c phage infection. RESULTS: Using whole genome sequence data, we mapped the relevant mutations in six AP50R strains to csaB. Eleven additional spontaneous mutants, isolated in two different genetic backgrounds, were screened by PCR followed by Sanger sequencing of the csaB gene. In each spontaneous mutant, we found either a non-synonymous substitution, a nonsense mutation, or a frame-shift mutation caused by single nucleotide polymorphisms or a 5 base pair insertion in csaB. All together, 5 and 12 of the 17 spontaneous mutations are predicted to yield altered full length and truncated CsaB proteins respectively. As expected from these results, a targeted deletion or frame-shift mutations introduced into csaB in a different genetic background, in a strain not exposed to AP50c, resulted in a phage resistant phenotype. Also, substitution of a highly conserved histidine residue with an alanine residue (H270A) in CsaB resulted in phage resistance, suggesting that a functional CsaB is necessary for phage sensitivity. Conversely, introduction of the wild type allele of csaB in cis into the csaB deletion mutant by homologous recombination or supplying the wild type CsaB protein in trans from a plasmid restored phage sensitivity. The csaB mutants accumulated cell wall material and appeared to have a defective S-layer, whereas these phenotypes were reverted in the complemented strains. CONCLUSIONS: Taken together, these data suggest an essential role for csaB in AP50c phage infection, most likely in phage adsorption. (The whole genome sequences generated from this study have been submitted to GenBank under SRA project ID: SRA023659.1 and sample IDs: AP50 R1: SRS113675.1, AP50 R2: SRS113676.1, AP50 R3: SRS113728.1, AP50 R4: SRS113733.1, AP50 R6: SRS113734.1, JB220 Parent: SRS150209.1, JB220 Mutant: SRS150211.1).

Correction: An Alternative to the Light Touch Digital Health Remote Study: The Stress and Recovery in Frontline COVID-19 Health Care Workers Study.

[This corrects the article DOI: 10.2196/32165.].

PheMaDB: a solution for storage, retrieval, and analysis of high throughput phenotype data.

BACKGROUND: OmniLog™ phenotype microarrays (PMs) have the capability to measure and compare the growth responses of biological samples upon exposure to hundreds of growth conditions such as different metabolites and antibiotics over a time course of hours to days. In order to manage the large amount of data produced from the OmniLog™ instrument, PheMaDB (Phenotype Microarray DataBase), a web-based relational database, was designed. PheMaDB enables efficient storage, retrieval and rapid analysis of the OmniLog™ PM data. DESCRIPTION: PheMaDB allows the user to quickly identify records of interest for data analysis by filtering with a hierarchical ordering of Project, Strain, Phenotype, Replicate, and Temperature. PheMaDB then provides various statistical analysis options to identify specific growth pattern characteristics of the experimental strains, such as: outlier analysis, negative controls analysis (signal/background calibration), bar plots, pearson's correlation matrix, growth curve profile search, k-means clustering, and a heat map plot. This web-based database management system allows for both easy data sharing among multiple users and robust tools to phenotype organisms of interest. CONCLUSIONS: PheMaDB is an open source system standardized for OmniLog™ PM data. PheMaDB could facilitate the banking and sharing of phenotype data. The source code is available for download at http://phemadb.sourceforge.net.

An Alternative to the Light Touch Digital Health Remote Study: The Stress and Recovery in Frontline COVID-19 Health Care Workers Study.

BACKGROUND: Several app-based studies share similar characteristics of a light touch approach that recruit, enroll, and onboard via a smartphone app and attempt to minimize burden through low-friction active study tasks while emphasizing the collection of passive data with minimal human contact. However, engagement is a common challenge across these studies, reporting low retention and adherence. OBJECTIVE: This study aims to describe an alternative to a light touch digital health study that involved a participant-centric design including high friction app-based assessments, semicontinuous passive data from wearable sensors, and a digital engagement strategy centered on providing knowledge and support to participants. METHODS: The Stress and Recovery in Frontline COVID-19 Health Care Workers Study included US frontline health care workers followed between May and November 2020. The study comprised 3 main components: (1) active and passive assessments of stress and symptoms from a smartphone app, (2) objective measured assessments of acute stress from wearable sensors, and (3) a participant codriven engagement strategy that centered on providing knowledge and support to participants. The daily participant time commitment was an average of 10 to 15 minutes. Retention and adherence are described both quantitatively and qualitatively. RESULTS: A total of 365 participants enrolled and started the study, and 81.0% (n=297) of them completed the study for a total study duration of 4 months. Average wearable sensor use was 90.6% days of total study duration. App-based daily, weekly, and every other week surveys were completed on average 69.18%, 68.37%, and 72.86% of the time, respectively. CONCLUSIONS: This study found evidence for the feasibility and acceptability of a participant-centric digital health study approach that involved building trust with participants and providing support through regular phone check-ins. In addition to high retention and adherence, the collection of large volumes of objective measured data alongside contextual self-reported subjective data was able to be collected, which is often missing from light touch digital health studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT04713111; https://clinicaltrials.gov/ct2/show/NCT04713111.

Comprehensive Laboratory Evaluation of a Specific Lateral Flow Assay for the Presumptive Identification of Francisella tularensis in Suspicious White Powders and Aerosol Samples.

We conducted a comprehensive, multi-phase laboratory evaluation of the Tularemia BioThreat Alert® (BTA) test, a lateral flow assay (LFA) for the rapid detection of Francisella tularensis. The study, conducted at 2 sites, evaluated the limit of detection (LOD) of this assay using the virulent SchuS4 strain and the avirulent LVS strain of F. tularensis. In 6-phase evaluation (linear dynamic range and reproducibility, inclusivity, near-neighbor, environmental background, white powder, and environmental filter extract), 13 diverse strains of F. tularensis, 8 Francisella near neighbors, 61 environmental background organisms, 26 white powders, and a pooled aerosol extract were tested. In the 937 tests performed, the Tularemia BTA demonstrated an LOD of 107 to 108 cfu/mL, with a sensitivity of 100.00%, specificity of 98.08%, and accuracy of 98.84%. These performance data are important for accurate interpretation of qualitative results arising from screening suspicious white powders in the field.

Assessment of the Effect of Oral Health on Quality of Life and Oral-Health Indicators among ESRD Patients in Southwest Florida: A Pilot Study.

PURPOSE: To determine and compare OHRQoL (oral-health-related quality of life) using the Geriatric Oral Health Assessment Index (GOHAI-12) and Oral Health Impact Profile (OHIP-14) among patients receiving hemodialysis (HD). METHODS: Face-to-face interviews and intraoral examinations were conducted among 70 patients. Mann-Whitney U test and Kruskal-Wallis test were used to compare each item score with demographics and dental and overall health status. RESULTS: The mean number of years on dialysis was 4.7 ± 7.5 yrs; the mean number of teeth present was 19.7 ± 11.04; median values of OHRQoL using GOHAI-12 and OHIP-14 were 52 and 64. Within GOHAI-12, limiting food (p 0.043), uncomfortable eating in front of people (p 0.045), limiting contact with people (p 0.046), and eating without discomfort (p 0.011) were significantly associated with females. Being worried (p 0.040) and self-conscious (p 0.048) were significant for age groups ≤65 years. Prevented from speaking was associated with >20 teeth (p 0.016). Being worried about oral health was associated with number of years on dialysis (p 0.042). Within OHIP-14, speech was associated with number of teeth present (p 0.024). Total inability to function was significantly associated with race (p 0.018), number of teeth (p 0.028), and edentulousness (p 0.031). CONCLUSIONS: GOHAI-12 was more effective than OHIP-14 in assessing OHRQoL. However, most subjective experiences did not correlate with clinical findings. Systemic health issue like end-stage renal disease affecting QoL might have taken precedence over dental problems. Clinical assessments should be inherent in oral-health evaluation and there should be cooperation between nephrologists and dentists in promoting oral health and treating systemic conditions among HD patients.

Frequent Emergency Department Users: Focusing Solely On Medical Utilization Misses The Whole Person.

Frequent emergency department (ED) users often have complex behavioral health and social needs. However, policy makers often focus on this population's medical system use without examining its use of behavioral health and social services systems. To illuminate the wide-ranging needs of frequent ED users, we compared medical, mental health, substance use, and social services use among nonelderly nonfrequent, frequent, and superfrequent ED users in San Francisco County, California. We linked administrative data for fiscal years 2013-15 for beneficiaries of the county's Medicaid managed care plan to a county-level integrated data system. Compared to nonfrequent users, frequent users were disproportionately female, white or African American/black, and homeless. They had more comorbidities and annual outpatient mental health visits (11.93 versus 4.16), psychiatric admissions (0.73 versus 0.07), and sobering center visits (0.17 versus <0.01), as well as disproportionate use of housing and jail health services. Our findings point to the need for shared knowledge across domains, at the patient and population levels. Integrated data can serve as a systems improvement tool and help identify patients who might benefit from coordinated care management. To deliver whole-person care, policy makers should prioritize improvements in data sharing and the development of integrated medical, behavioral, and social care systems.

Comprehensive Laboratory Evaluation of a Lateral Flow Assay for the Detection of Yersinia pestis.

We conducted a comprehensive, multiphase laboratory evaluation of the Plague BioThreat Alert® (BTA) test, a lateral flow immunoassay (LFA), for the rapid detection of Yersinia pestis. The study was conducted in 7 phases at 2 sites to assess the performance of the LFA. The limit of detection (LOD) was determined using both a virulent and avirulent strain of Y. pestis, CO99-3015 (105 CFU/ml) and A1122 (104 CFU/ml), respectively. In the other phases, 18 Y. pestis strains, 20 phylogenetic near-neighbor strains, 61 environmental background microorganisms, 26 white powders, and a pooled aerosol sample were also tested. A total of 1,110 LFA test results were obtained, and their analysis indicates that this LFA had a sensitivity of 97.65% and specificity of 96.57%. These performance data are important for accurate interpretation of qualitative results arising from testing suspicious white powders and aerosol samples in the field. Any positive specimen in this assay is considered presumptive positive and should be referred to the Centers for Disease Control and Prevention Laboratory Response Network for additional testing, confirmation, and characterization for an appropriate public health response.

Comprehensive Laboratory Evaluation of a Highly Specific Lateral Flow Assay for the Presumptive Identification of Bacillus anthracis Spores in Suspicious White Powders and Environmental Samples.

We conducted a comprehensive, multiphase laboratory evaluation of the Anthrax BioThreat Alert(®) test strip, a lateral flow immunoassay (LFA) for the rapid detection of Bacillus anthracis spores. The study, conducted at 2 sites, evaluated this assay for the detection of spores from the Ames and Sterne strains of B. anthracis, as well as those from an additional 22 strains. Phylogenetic near neighbors, environmental background organisms, white powders, and environmental samples were also tested. The Anthrax LFA demonstrated a limit of detection of about 10(6) spores/mL (ca. 1.5 × 10(5) spores/assay). In this study, overall sensitivity of the LFA was 99.3%, and the specificity was 98.6%. The results indicated that the specificity, sensitivity, limit of detection, dynamic range, and repeatability of the assay support its use in the field for the purpose of qualitatively evaluating suspicious white powders and environmental samples for the presumptive presence of B. anthracis spores.

Scanning the landscape of genome architecture of non-O1 and non-O139 Vibrio cholerae by whole genome mapping reveals extensive population genetic diversity.

Historically, cholera outbreaks have been linked to V. cholerae O1 serogroup strains or its derivatives of the O37 and O139 serogroups. A genomic study on the 2010 Haiti cholera outbreak strains highlighted the putative role of non O1/non-O139 V. cholerae in causing cholera and the lack of genomic sequences of such strains from around the world. Here we address these gaps by scanning a global collection of V. cholerae strains as a first step towards understanding the population genetic diversity and epidemic potential of non O1/non-O139 strains. Whole Genome Mapping (Optical Mapping) based bar coding produces a high resolution, ordered restriction map, depicting a complete view of the unique chromosomal architecture of an organism. To assess the genomic diversity of non-O1/non-O139 V. cholerae, we applied a Whole Genome Mapping strategy on a well-defined and geographically and temporally diverse strain collection, the Sakazaki serogroup type strains. Whole Genome Map data on 91 of the 206 serogroup type strains support the hypothesis that V. cholerae has an unprecedented genetic and genomic structural diversity. Interestingly, we discovered chromosomal fusions in two unusual strains that possess a single chromosome instead of the two chromosomes usually found in V. cholerae. We also found pervasive chromosomal rearrangements such as duplications and indels in many strains. The majority of Vibrio genome sequences currently in public databases are unfinished draft sequences. The Whole Genome Mapping approach presented here enables rapid screening of large strain collections to capture genomic complexities that would not have been otherwise revealed by unfinished draft genome sequencing and thus aids in assembling and finishing draft sequences of complex genomes. Furthermore, Whole Genome Mapping allows for prediction of novel V. cholerae non-O1/non-O139 strains that may have the potential to cause future cholera outbreaks.

Genomic signatures of strain selection and enhancement in Bacillus atrophaeus var. globigii, a historical biowarfare simulant.

BACKGROUND: Despite the decades-long use of Bacillus atrophaeus var. globigii (BG) as a simulant for biological warfare (BW) agents, knowledge of its genome composition is limited. Furthermore, the ability to differentiate signatures of deliberate adaptation and selection from natural variation is lacking for most bacterial agents. We characterized a lineage of BGwith a long history of use as a simulant for BW operations, focusing on classical bacteriological markers, metabolic profiling and whole-genome shotgun sequencing (WGS). RESULTS: Archival strains and two "present day" type strains were compared to simulant strains on different laboratory media. Several of the samples produced multiple colony morphotypes that differed from that of an archival isolate. To trace the microevolutionary history of these isolates, we obtained WGS data for several archival and present-day strains and morphotypes. Bacillus-wide phylogenetic analysis identified B. subtilis as the nearest neighbor to B. atrophaeus. The genome of B. atrophaeus is, on average, 86% identical to B. subtilis on the nucleotide level. WGS of variants revealed that several strains were mixed but highly related populations and uncovered a progressive accumulation of mutations among the "military" isolates. Metabolic profiling and microscopic examination of bacterial cultures revealed enhanced growth of "military" isolates on lactate-containing media, and showed that the "military" strains exhibited a hypersporulating phenotype. CONCLUSIONS: Our analysis revealed the genomic and phenotypic signatures of strain adaptation and deliberate selection for traits that were desirable in a simulant organism. Together, these results demonstrate the power of whole-genome and modern systems-level approaches to characterize microbial lineages to develop and validate forensic markers for strain discrimination and reveal signatures of deliberate adaptation.

In vitro intracellular trafficking of virulence antigen during infection by Yersinia pestis.

Yersinia pestis, the causative agent of plague, encodes several essential virulence factors on a 70 kb plasmid, including the Yersinia outer proteins (Yops) and a multifunctional virulence antigen (V). V is uniquely able to inhibit the host immune response; aid in the expression, secretion, and injection of the cytotoxic Yops via a type III secretion system (T3SS)-dependent mechanism; be secreted extracellularly; and enter the host cell by a T3SS-independent mechanism, where its activity is unknown. To elucidate the intracellular trafficking and target(s) of V, time-course experiments were performed with macrophages (MPhis) infected with Y. pestis or Y. pseudotuberculosis at intervals from 5 min to 6 h. The trafficking pattern was discerned from results of parallel microscopy, immunoblotting, and flow cytometry experiments. The MPhis were incubated with fluorescent or gold conjugated primary or secondary anti-V (antibodies [Abs]) in conjunction with organelle-associated Abs or dyes. The samples were observed for co-localization by immuno-fluorescence and electron microscopy. For fractionation studies, uninfected and infected MPhis were lysed and subjected to density gradient centrifugation coupled with immunoblotting with Abs to V or to organelles. Samples were also analyzed by flow cytometry after lysis and dual-staining with anti-V and anti-organelle Abs. Our findings indicate a co-localization of V with (1) endosomal proteins between 10-45 min of infection, (2) lysosomal protein(s) between 1-2 h of infection, (3) mitochondrial proteins between 2.5-3 h infection, and (4) Golgi protein(s) between 4-6 h of infection. Further studies are being performed to determine the specific intracellular interactions and role in pathogenesis of intracellularly localized V.