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ABSTRACT IMPACT: The potential to use vaginal pH as a low cost, non-invasive diagnostic test at the point of CIN2 diagnosis to predict worsening of cervical disease. OBJECTIVES/GOALS: We previously reported that persistence/progression of cervical intraepithelial neoplasia-2 (CIN2) was uncommon in women living with HIV (WLH) from the Women’s Interagency HIV Study (WIHS, now MWCCS). Here we examined additional factors that may influence CIN2 natural history. METHODS/STUDY POPULATION: A total of 337 samples from 94 WLH with a confirmed CIN2 diagnosis were obtained from the MWCCS. 42 cervicovaginal HPV types and 34 cervicovaginal cytokines/chemokines were measured at CIN2 diagnosis (94 samples) and 6-12 months prior to CIN2 diagnosis (79 samples). Covariates, including CD4 count and vaginal pH, were abstracted from core MWCCS visits. Logistic regression models were used to explore CIN2 regression (CIN1, normal) vs. persistence/progression (CIN2, CIN3). Log rank tests, Kaplan Meier method, and Cox regression modeling were used to determine CIN2 regression rates. RESULTS/ANTICIPATED RESULTS: The most prevalent HPV types were HPV54 (21.6%) and 53 (21.3%). 33 women (35.1%) had a subsequent CIN2/CIN3 diagnosis (median 12.5 years follow-up). Each additional hr-HPV type detected at the pre-CIN2 visit associated with increased odds of CIN2 persistence/progression (OR 2.27, 95% CI 1.15, 4.50). Higher vaginal pH (aOR 2.27, 95% CI 1.15, 4.50) and bacterial vaginosis (aOR 5.08, 95% CI 1.30, 19.94) at the CIN2 diagnosis visit associated with higher odds of CIN2 persistence/progression. Vaginal pH >4.5 at CIN2 diagnosis also associated with unadjusted time to CIN2 persistence/progression (log rank p=0.002) and a higher rate of CIN2 persistence/progression (adjusted hazard ratio [aHR] 3.37, 95% CI 1.26, 8.99). Cervicovaginal cytokine/chemokine levels were not associated with CIN2 persistence/progression. DISCUSSION/SIGNIFICANCE OF FINDINGS: We found relatively low prevalence of HPV16/18 in this cohort. Elevated vaginal pH at the time of CIN2 diagnosis may be a useful indicator of CIN2 persistence/progression and the rate of persistence/progression.
Amongst patients with CHD, the time of transition to adulthood is associated with lapses in care leading to significant morbidity. The purpose of this study was to identify differences in perceptions between parents and teens in regard to transition readiness.
Responses were collected from 175 teen–parent pairs via the validated CHD Transition Readiness survey and an information request checklist. The survey was distributed via an electronic tablet at a routine clinic visit.
Parents reported a perceived knowledge gap of 29.2% (the percentage of survey items in which a parent believes their teen does not know), compared to teens self-reporting an average of 25.9% of survey items in which they feel deficient (p = 0.01). Agreement was lowest for long-term medical needs, physical activities allowed, insurance, and education. In regard to self-management behaviours, agreement between parent and teen was slight to moderate (weighted κ statistic = 0.18 to 0.51). For self-efficacy, agreement ranged from slight to fair (weighted κ = 0.16 to 0.28). Teens were more likely to request information than their parents (79% versus 65% requesting at least one item) particularly in regard to pregnancy/contraception and insurance.
Parents and teens differ in several key perceptions regarding knowledge, behaviours, and feelings related to the management of heart disease. Specifically, parents perceive a higher knowledge deficit, teens perceive higher self-efficacy, and parents and teens agree that self-management is low.
Suicide prediction models have been formulated in a variety of ways and are heterogeneous in the strength of their predictions. Machine learning has been a proposed as a way of improving suicide predictions by incorporating more suicide risk factors.
To determine whether machine learning and the number of suicide risk factors included in suicide prediction models are associated with the strength of the resulting predictions.
Random-effect meta-analysis of exploratory suicide prediction models constructed by combining two or more suicide risk factors or using clinical judgement (Prospero Registration CRD42017059665). Studies were located by searching for papers indexed in PubMed before 15 August 2020 with the term suicid* in the title.
In total, 86 papers reported 102 suicide prediction models and included 20 210 411 people and 106 902 suicides. The pooled odds ratio was 7.7 (95% CI 6.7–8.8) with high between-study heterogeneity (I2 = 99.5). Machine learning was associated with a non-significantly higher odds ratio of 11.6 (95% CI 6.0–22.3) and clinical judgement with a non-significantly lower odds ratio of 4.7 (95% CI 2.1–10.9). Models including a larger number of suicide risk factors had a higher odds ratio when machine-learning studies were included (P = 0.02). Among non-machine-learning studies, suicide prediction models including fewer risk factors performed just as well as those including more risk factors.
Machine learning might have the potential to improve the performance of suicide prediction models by increasing the number of included suicide risk factors but its superiority over other methods is unproven.
OBJECTIVES/GOALS: The role of the vaginal microbiome (VM) in HIV disease progression is poorly understood. We examined VMs of HIV+ Elite Controllers (ECs) and HIV+ Long-Term Non-Progressors (LTNPs) compared to controls: HIV-positive antiretroviral (ARV) treated (HIV+ATs) and HIV-negative women in the Women’s Interagency HIV Study (DC/Chicago/Atlanta sites). METHODS/STUDY POPULATION: VMs were surveyed via both V3/V4 region of 16S rRNA gene amplicon sequencing and metagenomics sequencing in 67 women across 4 study groups: 1) LTNPs (CD4 >500 cells/mL for 5+ years without ARVs) (n = 7) and 2) ECs (HIV RNA <80 copies/mL for 2+ years without ARVs) (n = 8), matched with 3) HIV+ ATs (on ARVs for ≥1 year with CD4 increase ≥100 cells/mm3) (n = 34), and 4) HIV- women (n = 18). Metagenomes were characterized from specimens collected at two time points: 1) vaginal swabs collected 2016-2017 (n = 62) and 2) cervicovaginal lavage collected 2002-2016 (n = 35; DC/Chicago only). We used VIRGO (human vaginal non-redundant gene catalog), a newly developed referencing framework to comprehensively catalog VM gene content, taxonomy and functions. RESULTS/ANTICIPATED RESULTS: Women were 89% African American with a mean age of 46 years (SD 8.8). The most prevalent species were Gardnerella vaginalis (predominant in 34%), Lactobacillus iners (predominant in 21%), and L. crispatus (predominant in 14%). 90% of LTNP and 45% of EC samples were Lactobacillus-dominant vs. 28% of HIV- and 30% of HIV+ATs. L. crispatus and L. iners in ECs/LTNPs had significantly different gene content and greater gene richness vs. controls. G. vaginalis-predominant communities were found in 66% of HIV- and 68% of HIV+ATs, compared to 46% of EC and 0% of LTNP. The G. vaginalis strains present in EC/LTNP also showed significantly lower gene richness and different gene content vs. controls. DISCUSSION/SIGNIFICANCE OF IMPACT: These results suggest unique VM communities among EC/LTNP, and led us to hypothesize that differential regulation of vaginal immunity drives the observed differences. The similarity between VMs of HIV- and HIV+ATs warrants further study. Larger longitudinal VM studies are needed to assess associated functional pathways and understand the etiology of VM association with HIV progression. CONFLICT OF INTEREST DESCRIPTION: The authors have no conflicts of interest to disclose.
Older adults often collaborate with others to recreate past events and reminisce. In the current chapter, we discuss the patterns of gains and losses associated with social memory and aging specifically as they relate to research on collaborative remembering and social contagion. Within the collaborative remembering literatures, we focus on different methods of measuring group and individual memory performance and the role of partner familiarity. Within social contagion, we focus on age differences in susceptibility to socially suggested false memories and how perceptions of age influence the effects. Across literatures, there is some disagreement on precisely how and when collaboration benefits and/or disrupts older adults’ memories. However, there is strong agreement that collaboration influences memory and that social influence is an important contextual factor on older adults’ cognition.
Stop the Bleed (STB) is a national initiative that provides lifesaving hemorrhagic control education. In 2019, pharmacists were added as health-care personnel eligible to become STB instructors. This study was conducted to evaluate the efficacy of pharmacist-led STB trainings for school employees in South Texas.
Pharmacist-led STB trainings were provided to teachers and staff in Laredo, Texas. The 60-min trainings included a presentation followed by hands-on practice of tourniquet application, wound-packing, and direct pressure application. Training efficacy was assessed through anonymous pre- and postevent surveys, which evaluated changes in knowledge, comfort level, and willingness to assist in hemorrhage control interventions. Student volunteers (predominantly pharmacy and medical students) assisted in leading the hands-on portion, providing a unique interprofessional learning opportunity.
Participants with previous training (N = 98) were excluded, resulting in a final cohort of 437 (response rate 87.4%). Compared with baseline, comfort level using tourniquets (mean, 3.17/5 vs 4.20/5; P < 0.0001), opinion regarding tourniquet safety (2.59/3 vs 2.94/3; P < 0.0001), and knowledge regarding tourniquets (70.86/100 vs 75.84/100; P < 0.0001) and proper tourniquet placement (2.40/4 vs 3.15/4; P < 0.0001) significantly improved.
Pharmacist-led STB trainings are efficacious in increasing school worker knowledge and willingness to respond in an emergency hemorrhagic situation.
A priority focus on palliative and supportive care is helping the 43.5 million caregivers who care for individuals with serious illness. Lacking support may lead to caregiver distress and poorer care delivery to patients with serious illness. We examined the potential of instrumental support (assistance with material and task performance) to mitigate distress among caregivers.
We analyzed data from the nationally representative Health Information National Trends Survey (HINTS V2, 2018). Informal/family caregivers were identified in HINTS V2 if they indicated they were caring for or making healthcare decisions for another adult with a health problem. We used the PROMIS® instrumental support four-item short-form T-scores and the Patient Health Questionnaire (PHQ-4) for distress. We examined multivariable linear regression models for associations between distress and instrumental support, adjusted for sampling weights, socio-demographics, and caregiving variables (care recipient health condition(s), years caregiving (≥2), relationship to care recipient, and caregiver burden). We examined interactions between burden and instrumental support on caregiver distress level.
Our analyses included 311 caregivers (64.8% female, 64.9% non-Hispanic White). The unweighted mean instrumental support T-score was 50.4 (SD = 10.6, range = 29.3–63.3); weighted mean was 51.2 (SE = 1.00). Lower instrumental support (p < 0.01), younger caregiver age (p < 0.04), higher caregiving duration (p = 0.008), and caregiver unemployment (p = 0.006) were significantly associated with higher caregiver distress. Mean instrumental support scores by distress levels were 52.3 (within normal limits), 49.4 (mild), 48.9 (moderate), and 39.7 (severe). The association between instrumental support and distress did not differ by caregiver burden level.
Poor instrumental support is associated with high distress among caregivers, suggesting the need for palliative and supportive care interventions to help caregivers leverage instrumental support.
Duchenne muscular dystrophy is associated with progressive cardiorespiratory failure, including left ventricular dysfunction.
Methods and Results:
Males with probable or definite diagnosis of Duchenne muscular dystrophy, diagnosed between 1 January, 1982 and 31 December, 2011, were identified from the Muscular Dystrophy Surveillance Tracking and Research Network database. Two non-mutually exclusive groups were created: patients with ≥2 echocardiograms and non-invasive positive pressure ventilation-compliant patients with ≥1 recorded ejection fraction. Quantitative left ventricular dysfunction was defined as an ejection fraction <55%. Qualitative dysfunction was defined as mild, moderate, or severe. Progression of quantitative left ventricular dysfunction was modelled as a continuous time-varying outcome. Change in qualitative left ventricle function was assessed by the percentage of patients within each category at each age. Forty-one percent (n = 403) had ≥2 ejection fractions containing 998 qualitative assessments with a mean age at first echo of 10.8 ± 4.6 years, with an average first ejection fraction of 63.1 ± 12.6%. Mean age at first echo with an ejection fraction <55 was 15.2 ± 3.9 years. Thirty-five percent (140/403) were non-invasive positive pressure ventilation-compliant and had ejection fraction information. The estimated rate of decline in ejection fraction from first ejection fraction was 1.6% per year and initiation of non-invasive positive pressure ventilation did not change this rate.
In our cohort, we observed that left ventricle function in patients with Duchenne muscular dystrophy declined over time, independent of non-invasive positive pressure ventilation use. Future studies are needed to examine the impact of respiratory support on cardiac function.
Paramedics Providing Palliative Care at Home was launched in two provinces, including a new clinical practice guideline, database, and paramedic training. The aim of this study was to evaluate patient/family satisfaction and paramedic comfort and confidence.
In Part A, we gathered perspectives of patients/families via surveys mailed at enrolment and telephone interviews after an encounter. Responses were reported descriptively and by thematic analysis. In Part B, we surveyed paramedics online pre- and 18 months post-launch. Comfort and confidence were scored on a 4-point Likert scale, and attitudes on a 7-point Likert scale, reported as the median (interquartile range [IQR]); analysis with Wilcoxon ranked sum/thematic analysis of free text.
In Part A, 67/255 (30%) enrolment surveys were returned. Three themes emerged: fulfilling wishes, peace of mind, and feeling prepared for emergencies. In 18 post-encounter interviews, four themes emerged: 24/7 availability, paramedic professionalism and compassion, symptom relief, and a plea for program continuation. Thematic saturation was reached with little divergence. In Part B, 235/1255 (18.9%) pre- and 267 (21.3%) post-surveys were completed. Comfort with providing palliative care without transport improved post launch (p = < 0.001) as did confidence in palliative care without transport (p = < 0.001). Respondents strongly agreed that all paramedics should be able to provide basic palliative care.
After implementation of the multifaceted Paramedics Providing Palliative Care at Home Program, paramedics describe palliative care as important and rewarding. The program resulted in high patient/family satisfaction; simply registering provides peace of mind. After an encounter, families particularly noted the compassion and professionalism of the paramedics.
OBJECTIVES/SPECIFIC AIMS: Discrimination within the healthcare system and physician distrust have been associated with adverse clinical outcomes for people living with HIV; however, many studies do not link these variables to biological data. We hypothesize that perceived healthcare discrimination and physician distrust associates with higher longitudinal viremia among HIV-positive women. METHODS/STUDY POPULATION: A 2006 cross-sectional survey assessed healthcare-based discrimination and physician trust in 92 HIV-positive and 46 high-risk HIV-negative women from the Washington DC Women’s Interagency HIV Study (DC-WIHS). In addition, we identified HIV viral load trajectories and demographics from the HIV-positive women who contributed≥4 semi-annual visits from 1994 to 2015. Viral suppression was defined by assay detection limits (<80 to <20 copies/mL). Group-based probability trajectory analyses grouped women based on longitudinal viral load patterns, and identified 3 groups: sustained viremia (n=32) with low-viral suppression over time, intermittent viremia (n=27) with varying suppression over time, and non-viremia (n=33) with high-longitudinal viral suppression. Ordinal logistic regression models assessed trajectory group and discrimination variables, controlling for demographics, using stepwise selection with significance level of α=0.05. RESULTS/ANTICIPATED RESULTS: Most women were African American (60%), insured at the time of visit (89%) and nonsmokers (56%). While physician trust did not differ by HIV viral trajectory group, trust was lower among HIV-negative women compared with HIV-positive women (p=0.03). Over 1 in 5 HIV-positive women reported discrimination in the healthcare system based on HIV status (21.3%). Report of discrimination based on drug/alcohol use was higher among HIV-negative participants (19.2% vs. 6.5%, p=0.01). Among women with longitudinal sustained viremia, report of discrimination based on race ethnicity (29%, p=0.004) and sexual orientation (15.6%, p=0.008) were higher than within the nonviremic and intermittent trajectory groups. DISCUSSION/SIGNIFICANCE OF IMPACT: Physician trust did not associate with increased longitudinal viral suppression among HIV-positive women in Washington, DC. Lack of physician trust among high-risk HIV-negative women could have implications for uptake of prevention methods. Reports of discrimination vary between HIV-positive and HIV-negative women in the Washington, DC area. The findings of healthcare system distrust among HIV-negative women has implications outside the realm of HIV, as this lack of trust may impact risk for other disease states among similar populations of women.
Children with CHD and acquired heart disease have unique, high-risk physiology. They may have a higher risk of adverse tracheal-intubation-associated events, as compared with children with non-cardiac disease.
Materials and methods
We sought to evaluate the occurrence of adverse tracheal-intubation-associated events in children with cardiac disease compared to children with non-cardiac disease. A retrospective analysis of tracheal intubations from 38 international paediatric ICUs was performed using the National Emergency Airway Registry for Children (NEAR4KIDS) quality improvement registry. The primary outcome was the occurrence of any tracheal-intubation-associated event. Secondary outcomes included the occurrence of severe tracheal-intubation-associated events, multiple intubation attempts, and oxygen desaturation.
A total of 8851 intubations were reported between July, 2012 and March, 2016. Cardiac patients were younger, more likely to have haemodynamic instability, and less likely to have respiratory failure as an indication. The overall frequency of tracheal-intubation-associated events was not different (cardiac: 17% versus non-cardiac: 16%, p=0.13), nor was the rate of severe tracheal-intubation-associated events (cardiac: 7% versus non-cardiac: 6%, p=0.11). Tracheal-intubation-associated cardiac arrest occurred more often in cardiac patients (2.80 versus 1.28%; p<0.001), even after adjusting for patient and provider differences (adjusted odds ratio 1.79; p=0.03). Multiple intubation attempts occurred less often in cardiac patients (p=0.04), and oxygen desaturations occurred more often, even after excluding patients with cyanotic heart disease.
The overall incidence of adverse tracheal-intubation-associated events in cardiac patients was not different from that in non-cardiac patients. However, the presence of a cardiac diagnosis was associated with a higher occurrence of both tracheal-intubation-associated cardiac arrest and oxygen desaturation.
The Institute of Translational Health Sciences (ITHS) promotes and supports translational research collaboration between clinicians, communities, and investigators across the five-state Washington, Wyoming, Alaska, Montana, and Idaho (WWAMI) region. The ITHS has developed a collaborative regional clinical research network, the Northwest Participant & Clinical Interactions Network (NW PCI), involving 12 diverse clinical health systems and academic institutions.
This descriptive article details NW PCI’s development, infrastructure and governance, tools, characteristics, and initial outcomes.
Regional NW PCI sites are conducting largely industry-sponsored studies; they are interested in including more grant-funded research. Regional NW PCI sites had over 1,240 open studies involving over 6700 patients in 2016. NW PCI trials are largely industry-sponsored; NW PCI sites are interested in including more grant-funded research. In its first three years, the NW PCI Coordinating Center facilitated regional sites’ participation in 34 new grant and contract applications across diverse topics.
The NW PCI model supports the goals of the developing CTSA Trial Innovation Network by increasing access to cutting-edge research across the Northwestern U.S., by supporting investigators seeking diverse populations, including those with rare diseases, for their research studies, and by providing settings to test implementation and dissemination of effective interventions.
Training for the clinical research workforce does not sufficiently prepare workers for today’s scientific complexity; deficiencies may be ameliorated with training. The Enhancing Clinical Research Professionals’ Training and Qualifications developed competency standards for principal investigators and clinical research coordinators.
Clinical and Translational Science Awards representatives refined competency statements. Working groups developed assessments, identified training, and highlighted gaps.
Forty-eight competency statements in 8 domains were developed.
Training is primarily investigator focused with few programs for clinical research coordinators. Lack of training is felt in new technologies and data management. There are no standardized assessments of competence.
The translation of discoveries to drugs, devices, and behavioral interventions requires well-prepared study teams. Execution of clinical trials remains suboptimal due to varied quality in design, execution, analysis, and reporting. A critical impediment is inconsistent, or even absent, competency-based training for clinical trial personnel.
In 2014, the National Center for Advancing Translational Science (NCATS) funded the project, Enhancing Clinical Research Professionals’ Training and Qualifications (ECRPTQ), aimed at addressing this deficit. The goal was to ensure all personnel are competent to execute clinical trials. A phased structure was utilized.
This paper focuses on training recommendations in Good Clinical Practice (GCP). Leveraging input from all Clinical and Translational Science Award hubs, the following was recommended to NCATS: all investigators and study coordinators executing a clinical trial should understand GCP principles and undergo training every 3 years, with the training method meeting the minimum criteria identified by the International Conference on Harmonisation GCP.
We anticipate that industry sponsors will acknowledge such training, eliminating redundant training requests. We proposed metrics to be tracked that required further study. A separate task force was composed to define recommendations for metrics to be reported to NCATS.
To evaluate changes in outpatient fluoroquinolone (FQ) and nitrofurantoin (NFT) use and resistance among E. coli isolates after a change in institutional guidance to use NFT over FQs for acute uncomplicated cystitis.
We compared 2 time periods: January 2003–June 2007 when FQs were recommended as first-line therapy, and July 2007–December 2012, when NFT was recommended. The main outcomes were changes in FQ and NFT use and FQ- and NFT-resistant E. coli by time-series analysis.
Overall, 5,714 adults treated for acute cystitis and 11,367 outpatient E. coli isolates were included in the analysis. After the change in prescribing guidance, there was an immediate 26% (95% CI, 20%–32%) decrease in FQ use (P<.001), and a nonsignificant 6% (95% CI, −2% to 15%) increase in NFT use (P=.12); these changes were sustained over the postintervention period. Oral cephalosporin use also increased during the postintervention period. There was a significant decrease in FQ-resistant E. coli of −0.4% per quarter (95% CI, −0.6% to −0.1%; P=.004) between the pre- and postintervention periods; however, a change in the trend of NFT-resistant E. coli was not observed.
In an integrated healthcare system, a change in institutional guidance for acute uncomplicated cystitis was associated with a reduction in FQ use, which may have contributed to a stabilization in FQ-resistant E. coli. Increased nitrofurantoin use was not associated with a change in NFT resistance.