RiskScape: A Data Visualization and Aggregation Platform for Public Health Surveillance Using Routine Electronic Health Record Data.

Automated analysis of electronic health record (EHR) data is a complementary tool for public health surveillance. Analyzing and presenting these data, however, demands new methods of data communication optimized to the detail, flexibility, and timeliness of EHR data.RiskScape is an open-source, interactive, Web-based, user-friendly data aggregation and visualization platform for public health surveillance using EHR data. RiskScape displays near-real-time surveillance data and enables clinical practices and health departments to review, analyze, map, and trend aggregate data on chronic conditions and infectious diseases. Data presentations include heat maps of prevalence by zip code, time series with statistics for trends, and care cascades for conditions such as HIV and HCV. The platform's flexibility enables it to be modified to incorporate new conditions quickly-such as COVID-19.The Massachusetts Department of Public Health (MDPH) uses RiskScape to monitor conditions of interest using data that are updated monthly from clinical practice groups that cover approximately 20% of the state population. RiskScape serves an essential role in demonstrating need and burden for MDPH's applications for funding, particularly through the identification of inequitably burdened populations.

More Screening or More Disease? Gonorrhea Testing and Positivity Patterns Among Men in 3 Large Clinical Practices in Massachusetts, 2010-2017.

BACKGROUND: Gonorrhea diagnosis rates in the United States increased by 75% during 2009-2017, predominantly in men. It is unclear whether the increase among men is being driven by more screening, an increase in the prevalence of disease, or both. We sought to evaluate changes in gonorrhea testing patterns and positivity among men in Massachusetts. METHODS: The analysis included men (aged ≥15 years) who received care during 2010-2017 in 3 clinical practice groups. We calculated annual percentages of men with ≥1 gonorrhea test and men with ≥1 positive result, among men tested. Log-binomial regression models were used to examine trends in these outcomes. We adjusted for clinical and demographic characteristics that may influence the predilection to test and probability of gonorrhea disease. RESULTS: On average, 306 348 men had clinical encounters each year. There was a significant increase in men with ≥1 gonorrhea test from 2010 (3.1%) to 2017 (6.4%; adjusted annual risk ratio, 1.12; 95% confidence interval, 1.12-1.13). There was a significant, albeit lesser, increase in the percentage of tested men with ≥1 positive result (1.0% in 2010 to 1.5% in 2017; adjusted annual risk ratio, 1.07; 95% confidence interval, 1.04-1.09). CONCLUSIONS: We estimated significant increases in the annual percentages of men with ≥1 gonorrhea test and men with ≥1 positive gonorrhea test result between 2010 and 2017. These results suggest that observed increases in gonorrhea rates could be explained by both increases in screening and the prevalence of gonorrhea.

State and Local Chronic Disease Surveillance Using Electronic Health Record Systems.

OBJECTIVES: To assess the feasibility of chronic disease surveillance using distributed analysis of electronic health records and to compare results with Behavioral Risk Factor Surveillance System (BRFSS) state and small-area estimates. METHODS: We queried the electronic health records of 3 independent Massachusetts-based practice groups using a distributed analysis tool called MDPHnet to measure the prevalence of diabetes, asthma, smoking, hypertension, and obesity in adults for the state and 13 cities. We adjusted observed rates for age, gender, and race/ethnicity relative to census data and compared them with BRFSS state and small-area estimates. RESULTS: The MDPHnet population under surveillance included 1 073 545 adults (21.8% of the state adult population). MDPHnet and BRFSS state-level estimates were similar: 9.4% versus 9.7% for diabetes, 10.0% versus 12.0% for asthma, 13.5% versus 14.7% for smoking, 26.3% versus 29.6% for hypertension, and 22.8% versus 23.8% for obesity. Correlation coefficients for MDPHnet versus BRFSS small-area estimates ranged from 0.890 for diabetes to 0.646 for obesity. CONCLUSIONS: Chronic disease surveillance using electronic health record data is feasible and generates estimates comparable with BRFSS state and small-area estimates.

Audiological characteristics of children with congenital unilateral hearing loss: insights into Age of reliable behavioural audiogram acquisition and change of hearing loss.

Objectives: The aims of this study were to report the audiological characteristics of children with congenital unilateral hearing loss (UHL), examine the age at which the first reliable behavioural audiograms can be obtained, and investigate hearing changes from diagnosis at birth to the first reliable behavioural audiogram. Method: This study included a sample of 91 children who were diagnosed with UHL via newborn hearing screening and had reliable behavioural audiograms before 7 years of age. Information about diagnosis, audiological characteristics and etiology were extracted from clinical reports. Regression analysis was used to explore the potential reasons influencing the age at which first reliable behavioural audiograms were obtained. Correlation and ANOVA analyses were conducted to examine changes in hearing at octave frequencies between 0.5 and 4 kHz. The proportions of hearing loss change, as well as the clinical characteristics of children with and without progressive hearing loss, were described according to two adopted definitions: Definition 1: criterion (1): a decrease in 10 dB or greater at two or more adjacent frequencies between 0.5 and 4 kHz, or criterion (2): a decrease in 15 dB or greater at one octave frequency in the same frequency range. Definition 2: a change of ≥20 dB in the average of pure-tone thresholds at 0.5, 1, and 2 kHz. Results: The study revealed that 48 children (52.7% of the sample of 91 children) had their first reliable behavioural audiogram by 3 years of age. The mean age at the first reliable behavioural audiogram was 3.0 years (SD 1.4; IQR: 1.8, 4.1). We found a significant association between children's behaviour and the presence or absence of ongoing middle ear issues in relation to the delay in obtaining a reliable behavioural audiogram. When comparing the hearing thresholds at diagnosis with the first reliable behavioural audiogram across different frequencies, it was observed that the majority of children experienced deterioration rather than improvement in the initial impaired ear at each frequency. Notably, there were more instances of hearing changes (either deterioration or improvement), in the 500 Hz and 1,000 Hz frequency ranges compared to the 2,000 Hz and 4,000 Hz ranges. Seventy-eight percent (n = 71) of children had hearing deterioration between the diagnosis and the first behavioural audiogram at one or more frequencies between 0.5 and 4 kHz, with a high proportion of them (52 out of the 71, 73.2%) developing severe to profound hearing loss. When using the averaged three frequency thresholds (i.e., definition 2), only 26.4% of children (n = 24) in the sample were identified as having hearing deterioration. Applying definition 2 therefore underestimates the proportion of children that experienced hearing changes. The study also reported diverse characteristics of children with or without hearing deterioration. Conclusion: The finding that 78% of children diagnosed with UHL at birth had a decrease in hearing loss between the hearing levels at first diagnosis and their first behavioural audiogram highlights the importance of monitoring hearing threshold levels after diagnosis, so that appropriate intervention can be implemented in a timely manner. For clinical management, deterioration of 15 dB at one or more frequencies that does not recover warrants action.

SARS-CoV-2 antibody seroprevalence after the first wave among workers at a community healthcare system in the Greater Boston area.

SARS-CoV-2 antibody seroprevalence among health-care workers (HCW) can assess past exposure and possible immunity, which varies across different regions, populations and times. We investigated the seroprevalence among HCW in Massachusetts (a region suffering high COVID-19 mortality) at the end of first wave of the SARS-CoV-2 pandemic. All HCW at Cambridge Health Alliance were invited to participate in this cross-sectional survey in June 2020. Those who volunteered, consented and provided a blood sample were included. Dried blood specimens from finger-prick sampling collected either at home by each HCW or onsite by the study team were analyzed for anti-SARS-CoV-2 IgM and IgG to the virus' receptor binding domain, using an enzyme-linked immunosorbent assay. IgM and IgG antibody abundance were categorized based on the number of standard deviations above the cross-reacting levels found in existing, pre-pandemic blood samples previously obtained by the Ragon Institute and analyzed by the Broad Institute (Cambridge, MA). Seroprevalence estimates were made based on 'positive' IgM or IgG using 'low' (>6 SD), 'medium' (>4.5 SD), and 'high' prevalence cutoffs (>3 SD).A total of 433 out of 5,204 eligible HCWs consented and provided samples. Participating HCWs had a lower cumulative incidence (from the start of the pandemic up to the bloodspot collections) of SARS-CoV-2 RT-PCR positivity (1.85%) compared to non-participants (3.29%). The low, medium, and high seroprevalence estimates were 8.1%, 11.3%, and 14.5%, respectively. The weighted estimates based on past PCR positivity were 13.9%, 19.4%, and 24.9%, respectively, for the entire healthcare system population after accounting for participation bias.

Preventing Catheter-Associated Urinary Tract Infections in the Pediatric Intensive Care Unit.

BACKGROUND: Catheter-associated urinary tract infections are common health care-associated infections and have been associated with increased mortality, morbidity, length of stay, and cost. Prevention strategies are grouped into bundles focused on reducing unnecessary catheter use and promptly removing urinary catheters. Before intervention in the study institution, no urinary catheters were unnecessarily used and compliance with the catheter-associated urinary tract infection bundle was 84%. OBJECTIVE: To increase bundle compliance by using targeted rounds specifically focused on eliminating dependent loops in drainage tubing and ensuring appropriate catheter use to reduce the incidence of catheter-associated urinary tract infections. METHODS: A multidisciplinary team was formed to identify misperceptions, highlight best practices, and eliminate barriers to success over 1 year in a single pediatric intensive care unit. The team completed a quality improvement project of daily targeted rounding for patients with an indwelling urinary catheter. The goals were to assess appropriateness of catheterization, increase bundle compliance, and decrease catheter-associated urinary tract infection risk. Targeted rounds were conducted in addition to the medical team rounds. RESULTS: Bundle compliance supported by targeted rounding increased from 84% to 93% and helped reduce the overall catheter-associated urinary tract infection rate from 2.7 infections per 1000 catheter-days at baseline to 0. This change was sustained for 1 year. CONCLUSION: Targeted rounding for pediatric patients with an indwelling urinary catheter is an effective and sustainable strategy to reduce catheter-associated urinary tract infections. The ease of implementation for this intervention lends itself to generalizability to other patient populations.

Temporal Patterns in Chlamydia Repeat Testing in Massachusetts.

INTRODUCTION: National guidelines recommend test-of-cure for pregnant women and test-of-reinfection for all patients with chlamydia infections in order to interrupt transmission and prevent adverse sequelae for patients, partners, and newborns. Little is known about retesting and positivity rates, and whether they are changing over time, particularly in private sector practices. METHODS: Electronic health record data on patients with chlamydia tests were extracted from three independent clinical practice groups serving ≅20% of the Massachusetts population. Records were extracted using the Electronic medical record Support for Public Health platform (esphealth.org). These data were analyzed for temporal trends in annual repeat testing rates by using generalized estimating equations after index positive chlamydia tests between 2010 and 2015 and for differences in intervals to first repeat tests among pregnant females, non-pregnant females, and males. Data extraction and analysis were performed during calendar years 2017 and 2018. RESULTS: An index positive C. trachomatis result was identified for 972 pregnant female cases, 10,309 non-pregnant female cases, and 4,973 male cases. Test-of-cure 3-5 weeks after an index positive test occurred in 37% of pregnant females. Test-of-reinfection 8-16 weeks after an index positive test occurred in 39% of pregnant females, 18% of non-pregnant females, and 9% of males. There were no significant increases in test-of-cure or test-of-reinfection rates from 2010 to 2015. Among cases with repeat tests, 16% of pregnant females, 15% of non-pregnant females, and 16% of males had positive results. CONCLUSIONS: Chlamydia test-of-cure and test-of-reinfection rates are low, with no evidence of improvement over time. There are substantial opportunities to improve adherence to chlamydia repeat testing recommendations.

Impact of a Safety Huddle-Based Intervention on Monitor Alarm Rates in Low-Acuity Pediatric Intensive Care Unit Patients.

BACKGROUND: Physiologic monitors generate high rates of alarms in the pediatric intensive care unit (PICU), yet few are actionable. OBJECTIVE: To determine the association between a huddle-based intervention focused on reducing unnecessary alarms and the change in individual patients' alarm rates in the 24 hours after huddles. DESIGN: Quasi-experimental study with concurrent and historical controls. SETTING: A 55-bed PICU. PARTICIPANTS: Three hundred low-acuity patients with more than 40 alarms during the 4 hours preceding a safety huddle in the PICU between April 1, 2015, and October 31, 2015. INTERVENTION: Structured safety huddle review and discussion of alarm causes and possible monitor parameter adjustments to reduce unnecessary alarms. MAIN MEASUREMENTS: Rate of priority alarms per 24 hours occurring for intervention patients as compared with concurrent and historical controls. Balancing measures included unexpected changes in patient acuity and code blue events. RESULTS: Clinicians adjusted alarm parameters in the 5 hours following the huddles in 42% of intervention patients compared with 24% of control patients (𝑃 = .002). The estimate of the effect of the intervention adjusted for age and sex compared with concurrent controls was a reduction of 116 priority alarms (95% confidence interval, 37-194) per 24 hours (𝑃 = .004). There were no unexpected changes in patient acuity or code blue events related to the intervention. CONCLUSIONS: Integrating a data-driven monitor alarm discussion into safety huddles was a safe and effective approach to reducing alarms in low-acuity, highalarm PICU patients.

Dual-energy digital subtraction chest radiography: technical considerations.

In the evaluation of asbestos-related pulmonary and pleural abnormalities, conventional chest radiography has been shown to have a low sensitivity for the detection of lung nodules and subtle interstitial disease. Pleural plaques may simulate pulmonary nodules, and interstitial processes can be masked by adjacent pleural abnormalities. Dual-energy digital subtraction chest radiography may enable investigators to characterize asbestos-related pulmonary and pleural abnormalities with greater accuracy. "Soft-tissue" images, designed to remove pleural calcifications, may allow for better evaluation of the lung parenchyma. "Bone" images, designed to remove soft-tissue structures, may enhance the detection of pleural calcifications. In this pictorial essay we illustrate the methods, technical considerations, and limitations of dual-energy digital subtraction chest radiography performed with global subtraction weighting factors.

Carbon Nanotubes: Solution for the Therapeutic Delivery of siRNA?

Carbon nanotubes have many unique physical and chemical properties that are being widely explored for potential applications in biomedicine especially as transporters of drugs, proteins, DNA and RNA into cells. Specifically, single-walled carbon nanotubes (SWCNT) have been shown to deliver siRNA to tumors in vivo. The low toxicity, the excellent membrane penetration ability, the protection afforded against blood breakdown of the siRNA payload and the good biological activity seen in vivo suggests that SWCNT may become universal transfection vehicles for siRNA and other RNAs for therapeutic applications. This paper will introduce a short review of a number of therapeutic applications for carbon nanotubes and provide recent data suggesting SWCNT are an excellent option for the delivery of siRNA clinically.

Mouse let-7 miRNA populations exhibit RNA editing that is constrained in the 5'-seed/ cleavage/anchor regions and stabilize predicted mmu-let-7a:mRNA duplexes.

Massively parallel sequencing of millions of < 30-nt RNAs expressed in mouse ovary, embryonic pancreas (E14.5), and insulin-secreting beta-cells (betaTC-3) reveals that approximately 50% of the mature miRNAs representing mostly the mmu-let-7 family display internal insertion/deletions and substitutions when compared to precursor miRNA and the mouse genome reference sequences. Approximately, 12%-20% of species associated with mmu-let-7 populations exhibit sequence discrepancies that are dramatically reduced in nucleotides 3-7 (5'-seed) and 10-15 (cleavage and anchor sites). This observation is inconsistent with sequencing error and leads us to propose that the changes arise predominantly from post-transcriptional RNA-editing activity operating on miRNA:target mRNA complexes. Internal nucleotide modifications are most enriched at the ninth nucleotide position. A common ninth base edit of U-to-G results in a significant increase in stability of down-regulated let-7a targets in inhibin-deficient mice (Inha-/-). An excess of U-insertions (14.8%) over U-deletions (1.5%) and the presence of cleaved intermediates suggest that a mammalian TUTase (terminal uridylyl transferase) mediated dUTP-dependent U-insertion/U-deletion cycle may be a possible mechanism. We speculate that mRNA target site-directed editing of mmu-let-7a duplex-bulges stabilizes "loose" miRNA:mRNA target associations and functions to expand the target repertoire and/or enhance mRNA decay over translational repression. Our results also demonstrate that the systematic study of sequence variation within specific RNA classes in a given cell type from millions of sequences generated by next-generation sequencing (NGS) technologies ("intranomics") can be used broadly to infer functional constraints on specific parts of completely uncharacterized RNAs.

Novel microRNA candidates and miRNA-mRNA pairs in embryonic stem (ES) cells.

BACKGROUND: MicroRNAS (miRNAS: a class of short non-coding RNAs) are emerging as important agents of post transcriptional gene regulation and integral components of gene networks. MiRNAs have been strongly linked to stem cells, which have a remarkable dual role in development. They can either continuously replenish themselves (self-renewal), or differentiate into cells that execute a limited number of specific actions (pluripotence). METHODOLOGY/PRINCIPAL FINDINGS: In order to identify novel miRNAs from narrow windows of development we carried out an in silico search for micro-conserved elements (MCE) in adult tissue progenitor transcript sequences. A plethora of previously unknown miRNA candidates were revealed including 545 small RNAs that are enriched in embryonic stem (ES) cells over adult cells. Approximately 20% of these novel candidates are down-regulated in ES (Dicer(-/-)) ES cells that are impaired in miRNA maturation. The ES-enriched miRNA candidates exhibit distinct and opposite expression trends from mmu-mirs (an abundant class in adult tissues) during retinoic acid (RA)-induced ES cell differentiation. Significant perturbation of trends is found in both miRNAs and novel candidates in ES (GCNF(-/-)) cells, which display loss of repression of pluripotence genes upon differentiation. CONCLUSION/SIGNIFICANCE: Combining expression profile information with miRNA target prediction, we identified miRNA-mRNA pairs that correlate with ES cell pluripotence and differentiation. Perturbation of these pairs in the ES (GCNF(-/-)) mutant suggests a role for miRNAs in the core regulatory networks underlying ES cell self-renewal, pluripotence and differentiation.