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Background: Nonprescription antibiotic use includes taking an antibiotic without medical guidance (eg, leftover antibiotics, antibiotics from friends or relatives, or antibiotics purchased without a prescription). Nonprescription use contributes to antimicrobial resistance, adverse drug reactions, interactions, and superinfections such as Clostridioides difficile colitis. Qualitative studies exploring perspectives regarding nonprescription use among Hispanic patients are lacking. We used the Kilbourne Framework for Advancing Health Disparities Research to identify factors influencing Hispanic patients’ nonprescription use and to organize our findings. Methods: Our study includes Hispanic primary-care clinic patients with different types of health coverage in the Houston metroplex who endorsed nonprescription use in a previous quantitative survey. Semistructured interviews explored the factors promoting nonprescription use in Hispanic adults. Interviews were conducted remotely, in English or Spanish, between May 2020 and October 2021. We used inductive coding and thematic analysis to identify the factors and motives for nonprescription use. Results: Of the 35 Hispanic participants surveyed, 69% were female and between the ages of 27 and 66. All participants had some form of healthcare coverage (eg, Medicare or private insurance, Medicaid, or the county financial assistance program). Participants reported obtaining antibiotics from their own leftover prescriptions and through trusted persons (eg, herbalists, pharmacists, friends/relatives, and others), buying them under the counter in US markets, and purchasing them without a prescription outside the United States. Thematic analysis revealed the factors contributing to nonprescription use (Fig. 1). Themes included beliefs that the ‘doctor visit was unnecessary,’ ‘limited direct access to healthcare’ in the United States (due to limited insurance coverage, high costs of the doctor’s visits and medications, and long clinic wait times), ‘more open indirect access to healthcare’ abroad and under the counter in the United States, and communication difficulties (eg, language barriers with clinicians, perceived staff rudeness, and gaps in health literacy). Figure 2 shows representative quotes across thematic domains. Participants expressed having confidence in medical recommendations from pharmacists and trusted community members in their social networks. Conclusions: Antibiotic stewardship interventions that include pharmacist-driven patient education regarding appropriate antibiotic use may decrease nonprescription antibiotic use in Hispanic communities. Additionally, improving access to care while addressing communication barriers and cultural competency in clinics may improve primary care delivery and reduce potentially unsafe antibiotic use.
There is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies in major depressive disorder (MDD).
In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10–20 mg daily for 8 weeks. Responders continued escitalopram while non-responders received adjunctive aripiprazole 2–10 mg daily for 8 weeks. Plasma levels of pro-inflammatory markers—C-reactive protein, interleukin (IL)-1β, IL-6, IL-17, interferon-gamma (IFN)-Γ, tumor necrosis factor (TNF)-α, and Chemokine C–C motif ligand-2 (CCL-2)—measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyzes to assess associations between inflammatory markers and treatment response.
Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16.
Higher pre-treatment levels of IFN-Γ and CCL-2 were associated with non-response to escitalopram. Increasing levels of these pro-inflammatory markers may be associated with non-response to adjunctive aripiprazole. These findings require validation in independent clinical populations.
Despite over a decade of both quantitative and qualitative studies, food insecurity among US college/university students remains a pervasive problem within higher education. The purpose of this perspective piece was to highlight research gaps in the area of college food insecurity and provide rationale for the research community to focus on these gaps going forward. A group of food insecurity researchers from a variety of higher education institutions across the United States identified five thematic areas of research gaps: screening and estimates of food insecurity; longitudinal changes in food insecurity; impact of food insecurity on broader health and academic outcomes; evaluation of impact, sustainability and cost effectiveness of existing programmes and initiatives; and state and federal policies and programmes. Within these thematic areas, nineteen specific research gaps were identified that have limited or no peer-reviewed, published research. These research gaps result in a limited understanding of the magnitude, severity and persistence of college food insecurity, the negative short- and long-term impacts of food insecurity on health, academic performance and overall college experience, and effective solutions and policies to prevent or meaningfully address food insecurity among college students. Research in these identified priority areas may help accelerate action and interdisciplinary collaboration to alleviate food insecurity among college students and play a critical role in informing the development or refinement of programmes and services that better support college student food security needs.
Approved therapeutics for bipolar depression are associated with a range of undesirable side effects. Lumateperone (LUMA), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA-approved for the treatment of schizophrenia and depressive episodes associated with bipolar I or bipolar II disorder. The efficacy of LUMA in bipolar depression was previously established in two Phase 3 trials, as monotherapy (NCT03249376) and as adjunctive to lithium or valproate (NCT02600507).
A recent Phase 3 multi-center trial, Study 401 (NCT02600494) investigated the efficacy and safety of LUMA in bipolar depression and comprised a 6-week, randomized, double-blind, placebo-controlled period and a 6-month open-label extension (OLE) period. Here, we report the results of the OLE period, examining long-term safety.
Patients, aged 18–75 years, with a clinical diagnosis of bipolar I or II disorder who were experiencing a major depressive episode (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score ≥20 and a Clinical Global Impression Scale-Bipolar Version, Severity [CGI-BP-S] score ≥4) were eligible for Study 401. Patients who completed the double-blind study were eligible for direct rollover into the OLE or were re-screened if completing the double-blind period prior to the initiation of the OLE. During the OLE, LUMA 42 mg was administered once-daily in the evening for 25 weeks.
The primary objective was safety and tolerability of LUMA as measured by incidences of adverse events (AEs) and changes in laboratory parameters, cardiometabolic measurements, electrocardiogram (ECG), and vital signs. The secondary objective was improvement/maintenance of symptoms of depression as measured MADRS and CGI-BP-S Total scores.
A total of 127 patients were enrolled in the OLE, with 74 (58.3%) completing the study. Treatment-emergent AEs (TEAEs) occurred in 73 patients (57.5%) with 54 (42.5%) experiencing a drug-related TEAE. TEAEs that occurred in ≥5% of patients were headache, dry mouth, dizziness, nausea, somnolence, anxiety, and irritability. Most TEAEs were mild or moderate in severity. Extrapyramidal-symptom-related TEAEs were rare. Most patients who had normal metabolic laboratory values at baseline remained normal during the treatment period. Mean changes in blood pressure, pulse rate, ECG, and body morphology were minimal. Symptoms of depression improved as measured by the mean change from baseline to Day 175 in MADRS Total score (−8.9) and CGI-BP-S Total score (−2.3).
In patients with bipolar depression, long-term LUMA treatment was generally well tolerated with low risk of extrapyramidal symptoms, weight gain, and cardiometabolic effects. These data further support the safety, tolerability, and effectiveness of LUMA in patients with bipolar depression.
Exposure to aerosol spray generated by high-speed handpieces (HSHs) and ultrasonic scalers poses a significant health risk to oral health practitioners from airborne pathogens. Aerosol generation varies with different HSH designs, but to date, no study has measured this.
Materials and methods:
We measured and compared aerosol generation by (1) dental HSHs with 3 different coolant port designs and (2) ultrasonic scalers with no suction, low-volume evacuation (LVE) or high-volume evacuation (HVE). Measurements used a particle counter placed near the operator’s face in a single-chair, mechanically ventilated dental surgery. Volume concentrations of aerosol, totaled across a 0.3–25-µm size range, were compared for each test condition.
HSH drilling and scaling produced significantly high aerosol levels (P < .001) with total volume concentrations 4.73×108µm3/m3 and 4.18×107µm3/m3, respectively. For scaling, mean volume of aerosol was highest with no suction followed by LVE and HVE (P < .001). We detected a negative correlation with both LVE and HVE, indicating that scaling with suction improved operator safety. For drilling, simulated cavity preparation with a 1-port HSH generated the most aerosol (P < .01), followed by a 4-port HSH. Independent of the number of cooling ports, lack of suction caused higher aerosol volume (1.98×107 µm3/m3) whereas HVE significantly reduced volume to −4.47×105 µm3/m3.
High concentrations of dental aerosol found during HSH cavity preparation or ultrasonic scaling present a risk of infection, confirming the advice to use respiratory PPE. HVE and LVE both effectively reduced aerosol generation during scaling, whereas the new aerosol-reducing ‘no air’ function was highly effective and can be recommended for HSH drilling.
Deficits in visuospatial attention, known as neglect, are common following brain injury, but underdiagnosed and poorly treated, resulting in long-term cognitive disability. In clinical settings, neglect is often assessed using simple pen-and-paper tests. While convenient, these cannot characterise the full spectrum of neglect. This protocol reports a research programme that compares traditional neglect assessments with a novel virtual reality attention assessment platform: The Attention Atlas (AA).
The AA was codesigned by researchers and clinicians to meet the clinical need for improved neglect assessment. The AA uses a visual search paradigm to map the attended space in three dimensions and seeks to identify the optimal parameters that best distinguish neglect from non-neglect, and the spectrum of neglect, by providing near-time feedback to clinicians on system-level behavioural performance. A series of experiments will address procedural, scientific, patient, and clinical feasibility domains.
Analyses focuses on descriptive measures of reaction time, accuracy data for target localisation, and histogram-based raycast attentional mapping analysis; which measures the individual’s orientation in space, and inter- and intra-individual variation of visuospatial attention. We will compare neglect and control data using parametric between-subjects analyses. We present example individual-level results produced in near-time during visual search.
The development and validation of the AA is part of a new generation of translational neuroscience that exploits the latest advances in technology and brain science, including technology repurposed from the consumer gaming market. This approach to rehabilitation has the potential for highly accurate, highly engaging, personalised care.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Background: In November 2020, bamlanivimab received emergency use authorization (EUA) to treat patients with early, mild-to-moderate COVID-19 who are at high risk of progression. Montefiore Medical Center serves an economically underserved community of >1.4 million residents in the Bronx, New York. Montefiore’s antimicrobial stewardship team (AST) developed a multidisciplinary treatment pathway for patients meeting EUA criteria: (1) outpatients and hospital associates and (2) acute-care patients (EDs or inpatient). Methods: The Montefiore AST established a centralized process for screening high-risk COVID-19 patients 7 days a week. Referrals were sent by e-mail from occupational health, primary care practices, specialty practices, emergency departments, and urgent care centers. Patients were screened in real time and were treated in the ED or a newly established infusion center within 24 hours. After infusion, all patients received phone calls from nurses and had an infectious diseases televisit. Demographics, clinical symptoms, subsequent ED visit or hospital admission, and timing from infusion to ED or hospitalization were obtained from the electronic health record. Results: In total, 281 high-risk patients (median age, 62 years; 57% female) received bamlanivimab at the infusion center or in the acute-care setting between December 2, 2020, and January 27, 2021 (Table 1). The number of treated patients increased weekly (Figure 1). Also, 62% were Hispanic or black, and 96% met EUA criteria. Furthermore, 51 (18%) were referred from occupational health, 205 (73%) were referred from the community, and 25 (9%) were inpatients (https://www.fda.gov/media/143605/download). All patients were successfully infused without adverse reactions. In addition, 23 patients (8.2%) were hospitalized and 6 (2.1%) visited EDs within 30 days of treatment. The average number of days between symptom onset and infusion was 4.9. The median age of admitted versus nonadmitted patients was 68 years versus 61.5 years (P = .07). Conclusions: An AST-coordinated bamlanivimab treatment program successfully treated multiple high-risk COVID-19 patients and potentially reduced hospitalizations. However, the effort, personnel, and resources required are significant. Dedicated hospital investment is necessary for maximal success.
Despite the fact that social deficits among individuals with autism spectrum disorder (ASD) are lifelong and impact many aspects of personal functioning, evidence-based programs for social skills training were not available until recently. The Program for the Education and Enrichment of Relational Skills (PEERS®) has been shown to effectively improve social skills for adolescents on the spectrum across different social cultures. However, the effectiveness for young adults beyond North America has yet to be examined. This study aimed to investigate the effectiveness of the PEERS intervention in Taiwanese young adults with ASD, and examine its durability and clinical correlates.
We recruited 82 cognitively-able young adults with ASD, randomized to the PEERS treatment or treatment-as-usual.
Following treatment, significant improvement was found in aspects of social deficits, autism severity, social interaction anxiety, empathy, and social skills knowledge either by self-report or coach-report. Additionally, communicative behaviors rated by observers improved throughout the sessions, showing a trend toward more appropriate eye contact, gestures, facial expression during conversation, and appropriate maintenance of conversation and reciprocity. Most effects maintained at 3-month and 6-month follow-ups. The improvement of social deficits was positively correlated with baseline severity, while gains in social skills knowledge were positively correlated with IQ. The improvement of social deficits, autism severity, and empathy were positively correlated with each other.
Overall, the PEERS intervention appears to effectively improve social functioning in Taiwanese young adults with ASD. Improvement of social response and knowledge may be predicted by baseline severity and intelligence respectively.
The coronavirus disease 2019 (COVID-19) pandemic has resulted in shortages of personal protective equipment (PPE), underscoring the urgent need for simple, efficient, and inexpensive methods to decontaminate masks and respirators exposed to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). We hypothesized that methylene blue (MB) photochemical treatment, which has various clinical applications, could decontaminate PPE contaminated with coronavirus.
The 2 arms of the study included (1) PPE inoculation with coronaviruses followed by MB with light (MBL) decontamination treatment and (2) PPE treatment with MBL for 5 cycles of decontamination to determine maintenance of PPE performance.
MBL treatment was used to inactivate coronaviruses on 3 N95 filtering facepiece respirator (FFR) and 2 medical mask models. We inoculated FFR and medical mask materials with 3 coronaviruses, including SARS-CoV-2, and we treated them with 10 µM MB and exposed them to 50,000 lux of white light or 12,500 lux of red light for 30 minutes. In parallel, integrity was assessed after 5 cycles of decontamination using multiple US and international test methods, and the process was compared with the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method.
Overall, MBL robustly and consistently inactivated all 3 coronaviruses with 99.8% to >99.9% virus inactivation across all FFRs and medical masks tested. FFR and medical mask integrity was maintained after 5 cycles of MBL treatment, whereas 1 FFR model failed after 5 cycles of VHP+O3.
MBL treatment decontaminated respirators and masks by inactivating 3 tested coronaviruses without compromising integrity through 5 cycles of decontamination. MBL decontamination is effective, is low cost, and does not require specialized equipment, making it applicable in low- to high-resource settings.
Approved treatments for bipolar depression are limited and associated with a spectrum of undesirable side effects. Lumateperone (lumateperone tosylate, ITI−007), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA-approved for the treatment of schizophrenia. Lumateperone is currently being investigated for the treatment of bipolar depression (major depressive episodes [MDE] associated with bipolar I and bipolar II disorder). This Phase 3 randomized, double-blind, parallel-group, placebo-controlled multinational study (NCT03249376) investigated the efficacy and safety of lumateperone in patients with bipolar I or bipolar II disorder experiencing a MDE.
Patients (18 75 years) with a clinical diagnosis of bipolar I or bipolar II disorder who were experiencing a MDE (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score =20 and a Clinical Global Impression Scale-Bipolar Version-Severity [CGI-BP-S] score =4 at screening and baseline) were randomized to lumateperone 42mg or placebo for 6 weeks. The primary and key secondary efficacy endpoints were change from baseline to Day 43 in MADRS total score and CGI-BP-S scores, respectively. Secondary efficacy outcomes included response (MADRS improvement = 50%) and remission (MADRS total score =12) at Day 43. Safety assessments included treatment emergent adverse events, laboratory parameters, vital signs, extrapyramidal symptoms (EPS), and suicidality.
In this study, 377 patients received treatment (placebo, n=189; lumateperone 42mg, n=188) and 333 completed treatment. Patients in the lumateperone 42-mg group had significantly greater mean improvement on MADRS total score change from baseline to Day 43 compared with placebo (least squares mean difference [LSMD]=-4.6; 95% confidence interval [CI]=-6.34, −2.83; effect size vs placebo [ES]=-0.56; P<.0001). Lumateperone treatment was associated with significant MADRS improvement in both patients with bipolar I (LSMD=-4.0; 95% CI=-5.92, −1.99; ES=-0.49; P<.0001) and bipolar II (LSMD=-7.0; 95% CI=-10.92, −3.16; ES=-0.81; P=.0004). The lumateperone 42-mg group also had significantly greater mean improvement in CGI-BP-S total score compared with placebo (LSMD=-0.9; 95% CI=-1.37, −0.51; ES=-0.46; P<.001). Lumateperone compared with placebo had significantly greater MADRS response rate (51.1% vs 36.7%; odds ratio=2.98; P<.001) and remission rates (P=.02) at Day 43. Lumateperone treatment was well tolerated, with minimal risk of EPS, metabolic, and prolactin side effects.
Lumateperone 42 mg significantly improved depression symptoms in both patients with bipolar I and bipolar II depression. Lumateperone was generally well tolerated. These results suggest that lumateperone 42 mg may be a promising new treatment for bipolar depression associated with bipolar I or bipolar II disorder.
We performed secondary analyses of a postdischarge decolonization trial of MRSA carriers that reduced MRSA infection and hospitalization by 30%. Hospitalized MRSA infection was associated with 7.9 days of non-MRSA antibiotics and CDI in 3.9%. Preventing MRSA infection and associated hospitalization may reduce antibiotic use and CDI incidence.
Background: Greater than 10% of hospitalized MRSA carriers experience serious MRSA infection in the year following discharge. Prevention opportunities have primarily focused on hospital stays; however postdischarge interventions have the potential to reduce morbidity, mortality and healthcare costs. The CLEAR trial found a 30% hazard reduction in postdischarge MRSA infections among patients who had inpatient MRSA cultures and were given postdischarge decolonization (5 days twice-a-month for 6 months) relative to hygiene education alone. We conducted a cost analysis of the CLEAR intervention to quantify the economic implications and understand the value of adopting this MRSA decolonization strategy. Methods: We constructed a decision model to estimate the one-year healthcare utilization and costs associated with postdischarge decolonization relative to hygiene education. Trial results for MRSA infection risk and downstream outcomes (including outpatient and emergency room visits, hospitalizations, related nursing home stays, and postdischarge antibiotics) were used to parameterize the model. Other medical care and prescription drug costs were based on Medicare Fee Schedules, Red Book and the literature. Patient out-of-pocket costs and time costs associated with subsequent infections were from a survey of trial participants experiencing infection (n=405). All costs were reported in 2019 US dollars. The analysis was conducted using healthcare system and societal perspectives. Sensitivity analyses were conducted on key parameters. Results: Among a hypothetical cohort of 1,000 hospitalized MRSA carriers, we estimated that a postdischarge decolonization intervention versus hygiene education would result in at least 36 fewer subsequent MRSA infections (130 vs 93 of 1,000, respectively) and >40 fewer MRSA-attributable healthcare events including 32 hospitalizations and 6 postdischarge nursing home visits over the course of a year. Assuming an intervention cost of $185 per individual, the program would result in an overall cost savings of $469,000 per 1,000 MRSA carriers undergoing decolonization. This translates to an overall savings of $13,200 per infection averted and $9,000 per infection averted from the healthcare system perspective. Even assuming a lower infection rate or a less effective intervention (15% reduction in infections vs 30% in the CLEAR trial), or a more expensive (up to $653 per patient) intervention, a decolonization program would still result in cost-savings for society, the healthcare system and patients. Conclusions: In addition to health benefits of preventing infections, postdischarge decolonization of MRSA carriers yields substantial savings to society and the healthcare system. Future recommendations for reducing postdischarge MRSA-related disease among MRSA carriers should consider routine decolonization at hospital discharge.
Funding: This study was supported by a grant from the AHRQ Healthcare-Associated Infections Program (R01HS019388) and by the University of California Irvine Institute for Clinical and Translational Science, which was funded by a grant from the NIH Clinical and Translational Sciences Award program (UL1 TR000153).
Disclosures: Dr. Huang reports conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker (Sage Products), Mölnlycke, 3M, Clorox, Xttrium Laboratories, and Medline. Ms. Singh reports conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker (Sage Products), 3M, Clorox, Xttrium Laboratories, and Medline. Dr. Rashid, conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker(Sage Products), Clorox, and Medline. Dr. McKinnell reports receiving grant support to his institution from Melinta Therapeutics, and fees for serving as a research investigator from Lightship, conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker (Sage Products), 3M, Clorox, Xttrium Laboratories and Medline, and serving as cofounder of Expert Stewardship. Dr. Miller reports receiving grant support from Gilead Sciences, Merck, Abbott, Cepheid, Genentech, Atox Bio, and Paratek Pharmaceuticals, grant support and fees for serving on an advisory board from Achaogen and grant support, consulting fees, and fees for serving on an advisory board from Tetraphase and conducting clinical studies in which participating nursing homes and hospitals received donated products from Stryker (Sage Products), 3M, Clorox, Xttrium Laboratories, and Medline.
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for the largest number of invasive infections due to a multidrug-resistant pathogen. Approximately 10% of hospitalized carriers will experience invasive MRSA disease in the year following discharge incurring antibiotic therapy beyond focused treatment of MRSA. Objective: We aimed to quantify the extent of non-MRSA empiric antibiotics incurred by MRSA infections and further assess the risk of Clostridioides difficile Infection (CDI) as a result of treatment of MRSA infection. Methods: The CLEAR Trial was a postdischarge randomized controlled trial of 2,121 MRSA carriers comparing MRSA education alone to education plus repeated decolonization that demonstrated a 30% reduction in MRSA infection and a 17% reduction in all-cause infection attributable to decolonization in the year following hospital discharge (Huang SS, NEJM 2019). We included all hospitalization outcomes due to MRSA infection in the CLEAR Trial with detailed medication administration records to quantify unintended consequences of MRSA infection related to empiric non-MRSA antibiotic use and resultant CDI. Full-text medical records were reviewed with a standardized abstraction form to collect inpatient administered antibiotics and hospital-associated CDI. Results: In total,154 hospitalizations due to MRSA infection with a mean length-of-stay of 10.6 days were identified. During 25 hospitalizations (16.2%), patients received only anti-MRSA antibiotics. During the remaining 129 (83.8%) hospitalizations, patients received a mean of 1.6 distinct non-MRSA antibiotics totaling a mean of 6.6 days of therapy (DOT). Empiric non-MRSA therapy was given for 3.2 DOT before MRSA culture results became available and was continued for an additional 3.4 DOT afterward. Among all 849 non-MRSA DOT, the most common were due to piperacillin-tazobactam (293 DOT, 34.5%), levofloxacin (105 DOT, 12.4%), and metronidazole (93 DOT, 11.0%). Across all 154 hospitalizations, a mean of 5.5 non-MRSA DOT was calculated per MRSA hospitalization, with 6 CDI cases (3.9%) as a direct sequelae of empiric non-MRSA antibiotics provided for MRSA infection. Conclusions: Hospitalization for MRSA infection results in extensive non-MRSA empiric antibiotic therapy both before and after MRSA culture results are known. This antibiotic use is associated with a 3.9% risk of CDI that exceeds the national risk of acquiring CDI (3.2 per 1,000 admissions) by 12-fold during any hospital stay (Barrett ML, AHRQ 2018). The CLEAR Trial findings that postdischarge decolonization reduces MRSA infection and hospitalization by 30% suggests that decolonization may also reduce non-MRSA antibiotic use and CDI in this population.
Background: New York City is a gateway for emerging pathogens and global threats. In 2013, faculty from Montefiore Medical Center and Memorial Sloan Kettering developed a free half-day workshop for postgraduate trainees in antimicrobial stewardship (AS), infection prevention (IP), hospital epidemiology, and public health. This annual workshop, sponsored by the Infectious Diseases Society of New York (IDSNY), incorporates case studies and expert panel discussions on timely topics such as Ebola, Candida auris, Clostridiodes difficile, measles, nosocomial influenza, drug shortages, and AS/IP “big data.” Methods: From 2013 through 2017, the workshop involved 10–15 interactive AS/IP cases with audience response questions and panel discussions. In 2018–2019, based on feedback, the format was revised to emphasize breakout sessions in which participants actively practiced AS/IP tools, (eg, medication utilization evaluations, epidemiologic curves, and performance improvement devices). Examples of 2018–2019 cases are shown in Figure 1. A pre- and postseminar paper survey was conducted yearly to understand baseline training in AS/IP, desire for future AS/IP careers, and self-reported effectiveness of the workshop. Results: Initially, the primary audience was NYC ID fellows. From 2018 onward, we opened enrollment to pharmacy residents. Approximately 45 NYC ID fellows were eligible for the course each year. Results from 2013 to 2016 surveys were reported previously (Fig. 2). There were 32 attendees in 2018, 42 in 2019. The survey response rate was 88% in 2018 and 95% in 2019, with 68 (92%) total participants. Most participants had received previous training in IP (82%) and AS (94%) (Fig. 3). Most participants reported that the program was a good supplement to their ID training (98%) and that case studies were an effective means of learning IP (100%) and AS (98%). Furthermore, 92% stated they would like additional AS/IP training, and many since 2013 have requested a full-day course. Self-reported interest in future involvement in AS/IP increased after the workshop: IP, 68%–83% (P =.04) and AS, 88%–91% (P = .61). Conclusions: Most trainees reported satisfaction with the workshop and case-study learning method; interest in future AS/IP careers increased after the seminar. We intend to explore Funding: to expand to a full-day program for all NYC postgraduate trainees and AS/IP junior faculty. As such, we hope to obtain the endorsement of professional societies such as SHEA. This workshop could address a crucial educational gap in AS/IP postgraduate training and help sustain our future workforce.
An individual’s view of self is a constant interplay between one’s self-referent cognitions, emotions, motivations, and the social world (Hoyle, Kernis, Leary, & Baldwin, 1999). Both gender and culture are important forces that shape what an individual experiences and how such experiences are interpreted, which in turn influence one’s conception of the self. This chapter aims to discuss two important questions on the selfhood and self-construal of women: How does women’s self-definition differ from that of men? To what extent does culture affect women’s self-definition?
Patent ductus arteriosus closure is traditionally performed by thoracotomy approach. Video-assisted thoracoscopic surgery is a less frequently utilised alternative. We sought to compare elective surgical outcomes between the two methods via a single-centre retrospective cohort analysis.
All patients >3.2 kg undergoing surgical patent ductus arteriosus ligation at a single institution from 2000 to 2018 were retrospectively reviewed. Propensity matching for age, weight, diuretic usage, and preterm status was conducted to adjust for differences in baseline patient characteristics. Outcome measures included operative time, hospitalisation duration, post-operative complications, and re-operation.
A total of 173 patients were included, 127 thoracoscopy and 46 thoracotomy. In the unmatched cohorts, no significant difference in closure success was found (94% thoracoscopy versus 100% thoracotomy, p = 0.192). Although median operative time was longer for thoracoscopy (87 versus 56 minutes, p < 0.001), hospitalisation duration was shorter (1.05 versus 2.41 days, p < 0.001), as was ICU stay (0.00 versus 0.75 days, p < 0.001). There were no significant differences in re-operation or complication rates, except chest tube placement (11% thoracoscopy versus 50% thoracotomy, p < 0.001). After matching (69 thoracoscopy versus 20 thoracotomy), these differences persisted, including median operative time (81 versus 56 minutes, p = 0.007; thoracoscopy versus thoracotomy), hospitalisation duration (1.25 versus 2.27 days, p < 0.001), and chest tube placement (17% versus 60%, p < 0.001). There remained no significant difference in complications or re-operations.
Thoracoscopic ligation was associated with shorter ICU and hospital stays and less frequent chest tube placement, but longer operative times. Other risks, including bleeding, chylothorax, and recurrent laryngeal nerve injury, were similar.
OBJECTIVES/GOALS: Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatologic disease childhood and a cause of pain and potential disability. JIA has a strong genetic component and no known cure. The goal of this study is to evaluate allele-dependent effects of a novel JIA risk variant at 1q24.3. METHODS/STUDY POPULATION: JIA patients meeting criteria for the two most common disease subtypes (oligoarticular and RF neg polyarthritis) were genotyped using the Immunochip, an Illumina array with dense coverage of the HLA region and 186 other loci previously reported in autoimmune diseases. Phase I association findings (Hinks, 2013) and Phase II analysis (unpublished) of an expanded cohort (4,271 JIA and 14,390 controls) identified new risk loci, including rs78037977 at 1q24.3. We prioritized rs78037977 and predicted possible impacted mechanisms based on Bayesian predictions of attributable risk, the surrounding chromatin landscape, and transcription factor binding data. A luciferase reporter assay was used to assess allele-dependent enhancer activity. RESULTS/ANTICIPATED RESULTS: rs78037977 is located between FASLG and TNFSF18 at chromosome 1q24.3 is associated with JIA (p = 6.3x10−09), and explains 94% of the posterior probability at this locus; no other SNPs in linkage disequilibrium (r2>0.6). The chromatin landscape around rs78037977 contains H3K4Me1 and H3K27Ac marks, which are indicative of enhancer activity. Further, >160 transcription factors have chromatin immunoprecipitation followed by sequencing (ChIP-seq) peaks overlapping rs78037977 in various cellular contexts. In luciferase reporter assays, the region around rs78037977 containing the reference A allele had ~2-fold increased enhancer activity compared to the non-reference allele. DISCUSSION/SIGNIFICANCE OF IMPACT: This work provides in vitro evidence to support allele-dependent enhancer activity of a novel JIA-risk variant at 1q24.3. Our ongoing work investigates the effect of the DNA-containing region of rs78037977 on gene expression and differential transcription factor binding at rs78037977.
Diet has direct and indirect effects on health through inflammation and the gut microbiome. We investigated total dietary inflammatory potential via the literature-derived index (Dietary Inflammatory Index (DII®)) with gut microbiota diversity, composition and function. In cancer-free patient volunteers initially approached at colonoscopy and healthy volunteers recruited from the medical centre community, we assessed 16S ribosomal DNA in all subjects who provided dietary assessments and stool samples (n 101) and the gut metagenome in a subset of patients with residual fasting blood samples (n 34). Associations of energy-adjusted DII scores with microbial diversity and composition were examined using linear regression, permutational multivariate ANOVA and linear discriminant analysis. Spearman correlation was used to evaluate associations of species and pathways with DII and circulating inflammatory markers. Across DII levels, α- and β-diversity did not significantly differ; however, Ruminococcus torques, Eubacterium nodatum, Acidaminococcus intestini and Clostridium leptum were more abundant in the most pro-inflammatory diet group, while Akkermansia muciniphila was enriched in the most anti-inflammatory diet group. With adjustment for age and BMI, R. torques, E. nodatum and A. intestini remained significantly associated with a more pro-inflammatory diet. In the metagenomic and fasting blood subset, A. intestini was correlated with circulating plasminogen activator inhibitor-1, a pro-inflammatory marker (rho = 0·40), but no associations remained significant upon correction for multiple testing. An index reflecting overall inflammatory potential of the diet was associated with specific microbes, but not overall diversity of the gut microbiome in our study. Findings from this preliminary study warrant further research in larger samples and prospective cohorts.