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OBJECTIVES/GOALS: Supported by the State of Alabama, the Alabama Genomic Health Initiative (AGHI) is aimed at preventing and treating common conditions with a genetic basis. This joint UAB Medicine-HudsonAlpha Institute for Biotechnology effort provides genomic testing, interpretation, and counseling free of charge to residents in each of Alabama’s 67 counties. METHODS/STUDY POPULATION: Launched in 2017, as a state-wide population cohort, AGHI (1.0) enrolled 6,331 Alabamians and returned individual risk of disease(s) related to the ACMG SF v2.0 medically actionable genes. In 2021, the cohort was expanded to include a primary care cohort. AGHI (2.0) has enrolled 750 primary care patients, returning individual risk of disease(s) related to the ACMG SF v3.1 gene list and pre-emptive pharmacogenetics (PGx) to guide medication therapy. Genotyping is done on the Illumina Global Diversity Array with Sanger sequencing to confirm likely pathogenic / pathogenic variants in medically actionable genes and CYP2D6 copy number variants using Taqman assays, resulting in a CLIA-grade report. Disease risk results are returned by genetic counselors and Pharmacogenetics results are returned by Pharmacists. RESULTS/ANTICIPATED RESULTS: We have engaged a statewide community (>7000 participants), returning 94 disease risk genetic reports and 500 PGx reports. Disease risk reports include increased predisposition to cancers (n=38), cardiac diseases (n=33), metabolic (n=12), other (n=11). 100% of participants harbor an actionable PGx variant, 70% are on medication with PGx guidance, 48% harbor PGx variants and are taking medications affected. In 10% of participants, pharmacists sent an active alert to the provider to consider/ recommend alternative medication. Most commonly impacted medications included antidepressants, NSAIDS, proton-pump inhibitors and tramadol. To enable the EMR integration of genomic information, we have developed an automated transfer of reports into the EMR with Genetics Reports and PGx reports viewable in Cerner. DISCUSSION/SIGNIFICANCE: We share our experience on pre-emptive implementation of genetic risk and pharmacogenetic actionability at a population and clinic level. Both patients and providers are actively engaged, providing feedback to refine the return of results. Real time alerts with guidance at the time of prescription are needed to ensure future actionability and value.
To provide comprehensive population-level estimates of the burden of healthcare-associated influenza.
Retrospective cross-sectional study.
US Influenza Hospitalization Surveillance Network (FluSurv-NET) during 2012–2013 through 2018–2019 influenza seasons.
Laboratory-confirmed influenza-related hospitalizations in an 8-county catchment area in Tennessee.
The incidence of healthcare-associated influenza was determined using the traditional definition (ie, positive influenza test after hospital day 3) in addition to often underrecognized cases associated with recent post-acute care facility admission or a recent acute care hospitalization for a noninfluenza illness in the preceding 7 days.
Among the 5,904 laboratory-confirmed influenza-related hospitalizations, 147 (2.5%) had traditionally defined healthcare-associated influenza. When we included patients with a positive influenza test obtained in the first 3 days of hospitalization and who were either transferred to the hospital directly from a post-acute care facility or who were recently discharged from an acute care facility for a noninfluenza illness in the preceding 7 days, we identified an additional 1,031 cases (17.5% of all influenza-related hospitalizations).
Including influenza cases associated with preadmission healthcare exposures with traditionally defined cases resulted in an 8-fold higher incidence of healthcare-associated influenza. These results emphasize the importance of capturing other healthcare exposures that may serve as the initial site of viral transmission to provide more comprehensive estimates of the burden of healthcare-associated influenza and to inform improved infection prevention strategies.
There have been a number of federal policies and guidance’s impacting diversity, equity, inclusion, and accessibility (DEI) in clinical research. While these are needed, they have not diminished the gaps related to clinical trial recruitment, research professional’s capacity for cultural competence, and clinical research professional role development. Mentoring and co-mentoring circles have traditionally been used in Medicine, but until now had not been used for workforce development of clinical research professionals (CRPs).
We designed a six-session, monthly co-mentoring circle to take place at two academic medical centers to pilot an interinstitutional co-mentoring circle centered on storytelling videos of Black Voices in Clinical Research. This provided a DEI framework for discussions on role experiences, cultural competence, and role progression.
Seven CRPs completed the DRC pilot. The participants positively evaluated the experience and made recommendations for future iterations. Discussion: Co-mentoring circles can be useful tools to connect CRPs across complex research medical centers and provide support that may have a positive impact on role satisfaction and retention.
This framework for developing co-mentoring circles can serve as a toolkit for future CRP co-mentoring circles within and across institutions for workforce development. The Black Voices in Clinical Research storytelling videos provide a rich foundation for future discussion on DEI issues for CRPs and collaborating with participants.
Background: Healthcare facilities have experienced many challenges during the COVID-19 pandemic, including limited personal protective equipment (PPE) supplies. Healthcare personnel (HCP) rely on PPE, vaccines, and other infection control measures to prevent SARS-CoV-2 infections. We describe PPE concerns reported by HCP who had close contact with COVID-19 patients in the workplace and tested positive for SARS-CoV-2. Method: The CDC collaborated with Emerging Infections Program (EIP) sites in 10 states to conduct surveillance for SARS-CoV-2 infections in HCP. EIP staff interviewed HCP with positive SARS-CoV-2 viral tests (ie, cases) to collect data on demographics, healthcare roles, exposures, PPE use, and concerns about their PPE use during COVID-19 patient care in the 14 days before the HCP’s SARS-CoV-2 positive test. PPE concerns were qualitatively coded as being related to supply (eg, low quality, shortages); use (eg, extended use, reuse, lack of fit test); or facility policy (eg, lack of guidance). We calculated and compared the percentages of cases reporting each concern type during the initial phase of the pandemic (April–May 2020), during the first US peak of daily COVID-19 cases (June–August 2020), and during the second US peak (September 2020–January 2021). We compared percentages using mid-P or Fisher exact tests (α = 0.05). Results: Among 1,998 HCP cases occurring during April 2020–January 2021 who had close contact with COVID-19 patients, 613 (30.7%) reported ≥1 PPE concern (Table 1). The percentage of cases reporting supply or use concerns was higher during the first peak period than the second peak period (supply concerns: 12.5% vs 7.5%; use concerns: 25.5% vs 18.2%; p Conclusions: Although lower percentages of HCP cases overall reported PPE concerns after the first US peak, our results highlight the importance of developing capacity to produce and distribute PPE during times of increased demand. The difference we observed among selected groups of cases may indicate that PPE access and use were more challenging for some, such as nonphysicians and nursing home HCP. These findings underscore the need to ensure that PPE is accessible and used correctly by HCP for whom use is recommended.
Background: Despite significant morbidity and mortality, estimates of the burden of healthcare-associated viral respiratory infections (HA-VRI) for noninfluenza infections are limited. Of the studies assessing the burden of respiratory syncytial virus (RSV), cases are typically classified as healthcare associated if a positive test result occurred after the first 3 days following admission, which may miss healthcare exposures prior to admission. Utilizing an expanded definition of healthcare-associated RSV, we assessed the estimates of disease prevalence. Methods: This study included laboratory-confirmed cases of RSV in adult and pediatric patients admitted to acute-care hospitals in a catchment area of 8 counties in Tennessee identified between October 1, 2016, and April 30, 2019. Surveillance information was abstracted from hospital and state laboratory databases, hospital infection control databases, reportable condition databases, and electronic health records as a part of the Influenza Hospitalization Surveillance Network by the Emerging Infections Program. Cases were defined as healthcare-associated RSV if laboratory confirmation of infection occurred (1) on or after hospital day 4 (ie, “traditional definition”) or (2) between hospital day 0 and 3 in patients transferred from a chronic care facility or with a recent discharge from another acute-care facility in the 7 days preceding the current index admission (ie, “enhanced definition”). The proportion of laboratory-confirmed RSV designated as HA-VRI using both the traditional definition as well as with the added enhanced definition were compared. Results: We identified 900 cases of RSV in hospitalized patients over the study period. Using the traditional definition for HA-VRI, only 41 (4.6%) were deemed healthcare associated. Adding the cases identified using the enhanced definition, an additional 12 cases (1.3%) were noted in patients transferred from a chronic care facility for the current acute-care admission and 17 cases (1.9%) were noted in patients with a prior acute-care admission in the preceding 7 days. Using our expanded definition, the total proportion of healthcare-associated RSV in this cohort was 69 (7.7%) of 900 compared to 13.1% of cases for influenza (Figure 1). Although the burden of HA-VRI due to RSV was less than that of influenza, when stratified by age, the rate increased to 11.7% for those aged 50–64 years and to 10.1% for those aged ≥65 years (Figure 2). Conclusions: RSV infections are often not included in estimates of HA-VRI, but the proportion of cases that are healthcare associated are substantial. Typical surveillance methods likely underestimate the burden of disease related to RSV, especially for those aged ≥50 years.
Background: Healthcare-associated transmission of influenza leads to significant morbidity, mortality, and cost. Most studies classify healthcare-associated viral respiratory infections (HA-VRI) as those with a positive test result after the first 3 days following admission, which does not account for healthcare exposures prior to admission. Utilizing an expanded definition of healthcare-associated influenza, we aimed to improve the estimates of disease prevalence on a population level. Methods: This study included laboratory-confirmed cases of influenza in adult and pediatric patients admitted to any acute-care hospital in a catchment area of 8 counties Tennessee identified between October 1, 2012, and April 30, 2019. Surveillance information was abstracted from hospital and state laboratory databases, hospital infection control practitioner databases, reportable condition databases, and electronic health records as a part of the Influenza Hospitalization Surveillance Network (FluSurv-NET) by the Centers for Disease Control and Prevention (CDC) Emerging Infections Program (EIP). Cases were defined as healthcare-associated influenza laboratory confirmation of infection occurred (1) on or after hospital day 4 (“traditional definition”), or (2) between hospital days 0 and 3 in patients transferred from a chronic care facility or with a recent discharge from another acute-care facility in the 7 days preceding the current index admission (ie, enhanced definition). The proportion of laboratory-confirmed influenza designated as HA-VRI using both the traditional definition as well as with the added enhanced definition were compared. Data were imported into Stata software for analysis. Results: We identified 5,904 cases of laboratory-confirmed influenza in hospitalized patients over the study period. Using the traditional definition for HA-VRI, only 147 (2.5%, seasonal range 1.3%–3.4%) were deemed healthcare associated (Figure 1). Adding the cases identified using the enhanced definition, an additional 317 (5.4%, range 2.3%–6.7%) cases were noted in patients transferred from a chronic care facility for the current acute-care admission and 336 cases (5.7%; range, 4.1%–7.4%) were noted in patients with a prior acute-care facility admission in the preceding 7 days. Using our expanded definition, the total proportion of healthcare-associated influenza in this cohort was 772 of 5,904 (13.1%; range, 10.6%–14.8%). Conclusion: HA-VRI due to influenza is an underrecognized infection in hospitalized patients. Limiting surveillance assessment of this important outcome to just those patients with a positive influenza test after hospital day 3 captured only 19% of possible healthcare-associated influenza infections across 7 influenza seasons. These results suggest that the traditionally used definitions of healthcare-associated influenza underestimate the true burden of cases.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
This monograph summarizes the proceedings of a roundtable meeting convened to discuss pseudobulbar affect (PBA). Two didactic lectures were presented, followed by a moderated discussion among 11 participants. Post-meeting manuscript development synthesized didactic- and discussion-based content and incorporated additional material from the neuroscience literature. A conceptual framework with which to distinguish between disorders of mood and affect is presented first, and disorders of affect regulation are then reviewed briefly. A detailed description of the most common of these disorders, PBA, is the focus of the remainder of the monograph. The prevalence, putative neuranatomic and neurochemical bases of PBA are reviewed, and current and emerging methods of evaluation and treatment of persons with PBA are discussed. The material presented in this monograph will help clinicians better recognize, diagnose, and treat PBA, and will form a foundation for understanding and interpreting future studies of this condition.
Emotional reactivity and expressivity in infants have been previously correlated with vagal tone. This study investigated vagal tone of 3- and 6-month-old infants of depressed mothers. Vagal tone did not differ for infants of depressed versus nondepressed mothers at 3 months, but lower vagal tone was noted in infants of depressed versus nondepressed mothers at 6 months. The developmental increase in vagal tone that occurred between 3 and 6 months for infants of nondepressed mothers did not occur for infants of depressed mothers. Correlation analyses suggested that higher vagal tone at 6 months was related to more vocalizations and more optimal neurological scores.
Collybia, as understood by Antonin & Noordeloos, comprises four species: C. racemosa, C. tuberosa, C. cirrhata and C. cookei.
Collybia tuberosa, C. cirrhata and C. cookei are morphologically similar and are primarily distinguished from each other by the
presence or absence and the colour of sclerotia. All four share a common and unique habitat. Phylogenetic reconstructions using
DNA sequences of the ribosomal ITS1–5.8S–ITS2 support four distinct clades, each corresponding to a morphological species, with
the C. tuberosa, C. cirrhata and C. cookei clades forming a larger group. Analyses of ribosomal Large Subunit DNA sequences
confirmed that Collybia tuberosa, C. cirrhata and C. cookei formed a monophyletic group. In both analyses, the C. racemosa sequence
was highly divergent from those of the other three species of the complex and we propose a separate genus name, Dendrocollybia,
for this species. Simple diagnostic RFLP patterns were identified for the four species and were used to validate morphological
designations and distributions.
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