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Implementation of Isopropyl Caps to Increase Intravenous Catheter Disinfection by Anesthesia ProvidersProblem: Blood stream infections are a significant cause of morbidity and mortality in post procedural patients. Intravenous catheters can become portals of entry for microbials without proper disinfection. A single infection can cost institutions up to 75000 dollars. In an endoscopy unit at an inner city academic medical center less than 10% of anesthesia providers reported disinfection of intravenous catheters between medication injections. The biggest barrier to disinfection was lack of time due to the dynamic working environment. Purpose: The purpose of this quality improvement project was to implement isopropyl caps by anesthesia providers in an endoscopy unit at an academic medical center and change intravenous tubing assembly practices by endoscopy nursing staff with utilization of closed lumen claves on open lumen stopcocks. Methods: This project was implemented over a 15-week period following education to endoscopy nurses (N=9), providers (N=14), and anesthesia technicians (N=2). Three endoscopy nursing champions were appointed to facilitate intravenous tubing assembly practices and encourage providers to utilize caps. Visual reminders were placed in the preprocedural areas and operating suites to remind providers and nurses about process changes. To track adherence a quality response code linked to a survey was laminated at each anesthesia workspace for providers to scan and complete each shift. Results: Following implementation strategies, at the end of week one 50% of providers were utilizing caps between medication injections and 37.5% of intravenous tubing sets were reported to have closed lumen claves. The median compliance by week 15 was 54% and 56% respectively. Conclusions: Implementation of caps decreases intravenous catheter disinfection time making it more feasible for anesthesia providers to utilize. Unit champions and visual reminders helped to change intravenous tubing assembly practices allowing caps to fit onto injection ports. Agreement of champions to continue the practice and interest of underclassmen students in project can help to achieve sustainability and further dissemination of this intervention.
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Implementing Chlorhexidine Skin Preparation to Improve Antimicrobial Skin Preparation for Neuraxial AnestheticsProblem: In a small community hospital, Povidone-Iodine (PVP-I) is the primary skin preparation for regional anesthetics despite evidence that chlorhexidine gluconate in alcohol (CHG-alcohol) is more effective at decreasing bacterial colonization on the skin and catheter tips. 35 knee and hip arthroplasty procedures with neuraxial anesthesia occur weekly. with 89% receiving PVP-I skin preparation due to CHG-alcohol unavailability. Purpose: This quality improvement initiative aimed to improve antimicrobial skin preparation by increasing the availability of CHG-alcohol for skin preparation in adults receiving neuraxial anesthesia for hip or knee surgeries. Methods: The project lead worked with site leaders to ensure adequate supply of CHG-alcohol for the anesthesia department and in the operating rooms. Staff were educated, and attendance and stocking data were collected via direct observation on week one. CHGalcohol use compliance was monitored weekly via chart review and EPIC-generated reports— staff received weekly updates. Adults receiving neuraxial anesthesia for total knee or total hip arthroplasty procedures were included; exclusions were a chlorhexidine allergy. Strategies included early adopters, change champions, collaboration, communication, and increased accountability and buy-in. Team members included the project lead, site sponsor, clinical site representative, anesthesia technicians, and anesthesia providers. Results: All 41 anesthesia providers received written education, and 38 attendees attended the in-person education sessions. CHG-alcohol supply was 100% available. 545 patients were included and three were excluded. After improving availability, CHG-alcohol use increased to a median compliance of 77% and averaged 77% compared to 11% pre-implementation. Conclusions: Findings suggest increased availability of CHG-alcohol improved compliance with CHG-alcohol skin preparation.
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Transitioning to Cue-Based Feeding by Implementing an Evidence-Based ProtocolProblem: In an urban 70-bed level IV Neonatal Intensive Care Unit, cue-based feeding scores were previously implemented into the electronic medical record without sufficient education, leading to a lack of documentation by nursing staff. In a random chart audit, only 4% (n=1) of eligible patients had feeding scores documented. As a result, premature infants were not provided developmentally appropriate care that could improve their feeding outcomes. Purpose: The purpose of this quality improvement initiative was to improve the documentation of feeding scores by implementing and evaluating an electronic medical record alert and cue-based feeding rounds to notify providers of cue-based feeding eligibility. Methods: An EMR alert was developed to identify patient eligibility, and cue-based feeding rounds were utilized to notify providers of patients who qualified for cue-based feeding. Eligibility criteria included patients who were 34 weeks corrected gestational age or older, on 4 liters Vapotherm or less, and with a diet order to oral feed. The intent of the alert was to trigger the provider to order feeding score documentation as well as to remind nurses of cue-based feeding assessment and documentation. Results: Forty six percent of staff completed cue-based feeding education (n=105), 100% of eligible patients were identified (N=137), and 27% (n=37) of orders were documented in the EMR. Sixty one percent of eligible patients (n=83) had feeding scores documented. Conclusions: Two hundred forty-two interdisciplinary providers participated in the project. One hundred thirty-seven patients were included in the project. Findings suggest that cue-based feeding rounds can be useful in identifying patients who are eligible for cue-based feeding and reminding staff to document feeding scores. Weekly staff reminders are helpful in identification of eligible infants and in documentation.
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Role of cellular effectors in the induction and maintenance of IgA responses leading to protective immunity against enteric bacterial pathogensThe mucosal immune system is a critical first line of defense to infectious diseases, as many pathogens enter the body through mucosal surfaces, disrupting the balanced interactions between mucosal cells, secretory molecules, and microbiota in this challenging microenvironment. The mucosal immune system comprises of a complex and integrated network that includes the gut-associated lymphoid tissues (GALT). One of its primary responses to microbes is the secretion of IgA, whose role in the mucosa is vital for preventing pathogen colonization, invasion and spread. The mechanisms involved in these key responses include neutralization of pathogens, immune exclusion, immune modulation, and cross-protection. The generation and maintenance of high affinity IgA responses require a delicate balance of multiple components, including B and T cell interactions, innate cells, the cytokine milieu (e.g., IL-21, IL-10, TGF-b), and other factors essential for intestinal homeostasis, including the gut microbiota. In this review, we will discuss the main cellular components (e.g., T cells, innate lymphoid cells, dendritic cells) in the gut microenvironment as mediators of important effector responses and as critical players in supporting B cells in eliciting and maintaining IgA production, particularly in the context of enteric infections and vaccination in humans. Understanding the mechanisms of humoral and cellular components in protection could guide and accelerate the development of more effective mucosal vaccines and therapeutic interventions to efficiently combat mucosal infections.
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Role of circulating T follicular helper subsets following Ty21a immunization and oral challenge with wild type S. Typhi in humansDespite decades of intense research, our understanding of the correlates of protection against Salmonella Typhi (S. Typhi) infection and disease remains incomplete. T follicular helper cells (TFH), an important link between cellular and humoral immunity, play an important role in the development and production of high affinity antibodies. While traditional TFH cells reside in germinal centers, circulating TFH (cTFH) (a memory subset of TFH) are present in blood. We used specimens from a typhoid controlled human infection model whereby participants were immunized with Ty21a live attenuated S. Typhi vaccine and then challenged with virulent S. Typhi. Some participants developed typhoid disease (TD) and some did not (NoTD), which allowed us to assess the association of cTFH subsets in the development and prevention of typhoid disease. Of note, the frequencies of cTFH were higher in NoTD than in TD participants, particularly 7 days after challenge. Furthermore, the frequencies of cTFH2 and cTFH17, but not cTFH1 subsets were higher in NoTD than TD participants. However, we observed that ex-vivo expression of activation and homing markers were higher in TD than in NoTD participants, particularly after challenge. Moreover, cTFH subsets produced higher levels of S. Typhi-specific responses (cytokines/chemokines) in both the immunization and challenge phases. Interestingly, unsupervised analysis revealed unique clusters with distinct signatures for each cTFH subset that may play a role in either the development or prevention of typhoid disease. Importantly, we observed associations between frequencies of defined cTFH subsets and anti-S. Typhi antibodies. Taken together, our results suggest that circulating TFH2 and TFH17 subsets might play an important role in the development or prevention of typhoid disease. The contribution of these clusters was found to be distinct in the immunization and/or challenge phases. These results have important implications for vaccines aimed at inducing longlived protective T cell and antibody responses.
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Changes in monocyte subsets in volunteers who received an oral wild-type Salmonella Typhi challenge and reached typhoid diagnosis criteriaAn oral Controlled Human Infection Model (CHIM) with wild-type S. Typhi was re-established allowing us to explore the development of immunity. In this model, ~55% of volunteers who received the challenge reached typhoid diagnosis criteria (TD), while ~45% did not (NoTD). Intestinal macrophages are one of the first lines of defense against enteric pathogens. Most organs have selfrenewing macrophages derived from tissue-resident progenitor cells seeded during the embryonic stage; however, the gut lacks these progenitors, and all intestinal macrophages are derived from circulating monocytes. After infecting gut-associated lymphoid tissues underlying microfold (M) cells, S. Typhi causes a primary bacteremia seeding organs of the reticuloendothelial system. Following days of incubation, a second bacteremia and clinical disease ensue. S. Typhi likely interacts with circulating monocytes or their progenitors in the bone marrow. We assessed changes in circulating monocytes after CHIM. The timepoints studied included 0 hours (pre-challenge) and days 1, 2, 4, 7, 9, 14, 21 and 28 after challenge. TD participants provided extra samples at the time of typhoid diagnosis, and 48-96 hours later (referred as ToD). We report changes in Classical Monocytes -CM-, Intermediate Monocytes -IM- and Non-classical Monocytes -NCM-. Changes in monocyte activation markers were identified only in TD participants and during ToD. CM and IM upregulated molecules related to interaction with bacterial antigens (TLR4, TLR5, CD36 and CD206). Of importance, CM and IM showed enhanced binding of S. Typhi. Upregulation of inflammatory molecules like TNF-a were detected, but mechanisms involved in limiting inflammation were also activated (CD163 and CD354 downregulation). CM upregulated molecules to interact/modulate cells of the adaptive immunity, including T cells (HLA-DR, CD274 and CD86) and B cells (CD257). Both CM and IM showed potential to migrate to the gut as integrin a4b7 was upregulated. Unsupervised analysis revealed 7 dynamic cell clusters. Five of these belonged to CM showing that this is the main population activated during ToD. Overall, we provide new insights into the changes that diverse circulating monocyte subsets undergo after typhoid diagnosis, which might be important to control this disease since these cells will ultimately become intestinal macrophages once they reach the gut.
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Mobilization of endocannabinoids by midbrain dopamine neurons is required for the encoding of reward predictionBrain levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) shape motivated behavior and nucleus accumbens (NAc) dopamine release. However, it is not clear whether mobilization of 2-AG specifically from midbrain dopamine neurons is necessary for dopaminergic responses to external stimuli predicting forthcoming reward. Here, we use a viral-genetic strategy to prevent the expression of the 2-AG-synthesizing enzyme diacylglycerol lipase α (DGLα) from ventral tegmental area (VTA) dopamine cells in adult mice. We find that DGLα deletion fromVTA dopamine neurons prevents depolarizationinduced suppression of excitation (DSE), a form of 2-AG-mediated synaptic plasticity, in dopamine neurons. DGLα deletion also decreases effortful, cuedriven reward-seeking but has no effect on non-cued or low-effort operant tasks and other behaviors. Moreover, dopamine recording in the NAc reveals that deletion of DGLα impairs the transfer of accumbal dopamine signaling from a reward to its earliest predictors. These results demonstrate that 2-AG mobilization from VTA dopamine neurons is a necessary step for the generation of dopamine-based predictive associations that are required to direct and energize reward-oriented behavior.
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Antidepressant treatment initiation among children and adolescents with acute versus long COVID: a large retrospective cohort studyBackground Child and adolescent antidepressant use increased post-pandemic, but it is unknown if this disproportionally affected those who develop post-acute sequelae of coronavirus disease 2019 (COVID) or long COVID. This study compared the risk of antidepressant initiation among children and adolescents with long COVID with those who had COVID but did not have evidence of long COVID. Methods Our retrospective cohort study of children and adolescents aged 3–17 years at the first evidence of COVID or long COVID from October 1, 2021 through April 4, 2022 was conducted within Komodo’s Healthcare Map™ database. The index date was the earliest date of a medical claim associated with a COVID (COVID comparators) or long COVID diagnosis (long COVID cases). The baseline period was six months before the index date. The outcome was antidepressant initiation within twelve months after the index date. Due to the large number of COVID relative to long COVID cases, COVID comparators were randomly selected with a ratio of 2 COVID to 1 long COVID. We used propensity score matching to control for confounding due to imbalances in the baseline covariates. Log-binomial models estimated the relative risk (RR) of antidepressant initiation in the propensity score matched sample. We conducted several sensitivity analyses to test the robustness of our findings to several assumptions. Results Our child and adolescent sample included 18 274 with COVID and 9137 with long COVID. Compared with those with COVID, a larger proportion of long COVID children and adolescents had psychiatric disorders, psychotropic use, medical comorbidities, were previously hospitalized, or visited the emergency department. In the propensity score-adjusted analysis, the long COVID group had a statistically significant higher risk of antidepressant initiation relative to the COVID comparator (adjusted-RR: 1.40, 95% CI = 1.20, 1.62). Our findings were robust across sensitivity analyses. Conclusions The increased risk of antidepressant initiation following long COVID warrants further study to better understand the underlying reasons for this higher risk. Emerging evidence of long COVID’s impact on child mental health has important implications for prevention and early interventions.
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Impact of the US Food and Drug Administration warning regarding increased risk of aortic aneurysms or aortic dissections on fluoroquinolone prescribing trendsBackground The US Food and Drug Administration (FDA) issued a warning in December 2018 regarding an increased risk of aortic aneurysms and aortic dissections associated with fluoroquinolone (FQ) use. This warning specifically targeted older adults and patients with conditions such as hypertension, Marfan syndrome, Ehlers-Danlos syndrome, atherosclerosis, peripheral vascular disease and history of aneurysms. Objective To evaluate the impact of the safety warning on prescribing trends of FQs in the targeted population. Methods This cross-sectional study with an interrupted time series (ITS) analysis (January 2018–December 2019) used a 25% random sample of IQVIA PharMetrics® Plus for Academics health plan claims database. The impact of the warning on FQ utilisation was quantified among the targeted population and a non-targeted population. Results From 2018 to 2019, both study populations saw a decrease in the year-over- year percent change of FQ prescriptions per 100 000 beneficiaries (−11%, from 14 227 to 12 662, targeted; −15%, from 5227 to 4446, non-targeted) and proportion of FQ use versus other antibiotics (from 15.6% to 13.8%, targeted; from 9.4% to 8%, non-targeted). In the targeted population, the ITS analysis did not show a significant trend change, a change in level or postwarning trend in the monthly rate of FQ prescriptions per 1000 beneficiaries. A positive trend change was observed in the non-targeted population (0.07, <0.01–0.13), but there were no significant changes in level or post-warning trend. Conclusion We did not find a change in FQ prescription rates after the warning. The utility of safety advisories as a primary tool for mitigating FQ use in high-risk populations should be revisited.
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County-level factors associated with a mismatch between opioid overdose mortality and availability of opioid treatment facilitiesOpioid overdose deaths in the United States remain a major public health crisis. Little is known about counties with high rates of opioid overdose mortality but low availability of opioid use disorder (OUD) treatment facilities. We sought to identify characteristics of United States (US) counties with high rates of opioid overdose mortality and low rates of opioid treatment facilities. Rates of overdose mortality from 3,130 US counties were compared with availability of opioid treatment facilities that prescribed or allowed medications for OUD (MOUD), from 2018- 2019. The outcome variable, “risk-availability mismatch” county, was a binary indicator of a high rate (above national average) of opioid overdose mortality with a low (below national average) rate of opioid treatment facilities. Covariates of interest included county-level sociodemographics and rates of insurance, unemployment, educational attainment, poverty, urbanicity, opioid prescribing, depression, heart disease, Gini index, and Theil index. Multilevel logistic regression, accounting for the clustering of counties within states, was used to determine associations with being a “risk-availability mismatch” county. Of 3,130 counties, 1,203 (38.4%) had high rates of opioid overdose mortality. A total of 1,098 counties (35.1%) lacked a publicly-available opioid treatment facility in 2019. In the adjusted model, counties with an additional 1% of: white residents (odds ratio, OR, 1.02; 95% CI, 1.01-1.03), unemployment (OR, 1.11; 95% CI, 1.05-1.19), and residents without insurance (OR, 1.04; 95% CI, 1.01-1.08) had increased odds of being a mismatch county. Counties that were metropolitan (versus non-metropolitan) had an increased odds of being a mismatch county (OR, 1.85; 95% CI, 1.45-2.38). Assessing mismatch between treatment availability and need provides useful information to characterize counties that require greater public health investment. Interventions to reduce overdose mortality are unlikely to be effective if they do not take into account diverse upstream factors, including sociodemographics, disease burden, and geographic context of communities.
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TasteThe 2024 Health Sciences and Human Services Calendar, Taste, features a selection of botanicals from the Historical Collections department. The calendar includes twelve edible botanicals as well as information on their medicinal and historical uses.
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HS/HSL Connective Issues 2023-2024University of Maryland, Baltimore. Health Sciences and Human Services Library, 2024
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Opioid use disorder in pregnancy: leveraging provider perceptions to inform comprehensive treatmentBackground: Medications for opioid use disorder (MOUD) are recommended with adjuvant behavioral therapies, counseling, and other services for comprehensive treatment of maternal opioid use disorder. Inadequate access to treatment, lack of prescribing providers and complex delivery models are among known barriers to care. Multidisciplinary provider input can be leveraged to comprehend factors that facilitate or inhibit treatment. The objective of this study is to explore provider perceptions of MOUD and factors critical to comprehensive treatment delivery to improve the care of pregnant women with opioid use disorder. Methods: A qualitative research approach was used to gather data from individual provider and group semistructured interviews. Providers (n = 12) responded to questions in several domains related to perceptions of MOUD, treatment delivery, access to resources, and challenges/barriers. Data were collected, transcribed, coded (by consensus) and emerging themes were analyzed using grounded theory methodology. Results: Emerging themes revealed persistent gaps in treatment and challenges in provider, health systems and patient factors. Providers perceived MOUD to be a “lifeline” to women. Conclusions: Inconsistencies in treatment provision, access and uptake can be improved by leveraging provider perceptions, direct experiences and recommendations for an integrated team-based, patient-centered approach to guide the care of pregnant women with opioid use disorder.
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Differential Actions of Muscarinic Receptor Subtypes in Gastric, Pancreatic, and Colon CancerCancers arising from gastrointestinal epithelial cells are common, aggressive, and difficult to treat. Progress in this area resulted from recognizing that the biological behavior of these cancers is highly dependent on bioactive molecules released by neurocrine, paracrine, and autocrine mechanisms within the tumor microenvironment. For many decades after its discovery as a neurotransmitter, acetylcholine was thought to be synthesized and released uniquely from neurons and considered the sole physiological ligand for muscarinic receptor subtypes, which were believed to have similar or redundant actions. In the intervening years, we learned this former dogma is not tenable. (1) Acetylcholine is not produced and released only by neurons. The cellular machinery required to synthesize and release acetylcholine is present in immune, cancer, and other cells, as well as in lower organisms (e.g., bacteria) that inhabit the gut. (2) Acetylcholine is not the sole physiological activator of muscarinic receptors. For example, selected bile acids can modulate muscarinic receptor function. (3) Muscarinic receptor subtypes anticipated to have overlapping functions based on similar G protein coupling and downstream signaling may have unexpectedly diverse actions. Here, we review the relevant research findings supporting these conclusions and discuss how the complexity of muscarinic receptor biology impacts health and disease, focusing on their role in the initiation and progression of gastric, pancreatic, and colon cancers.
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Successful Profiling of Plasmodium falciparum var Gene Expression in Clinical Samples via a Custom Capture Arrayvar genes encode Plasmodium falciparum erythrocyte membrane protein- 1 (PfEMP1) antigens. These highly diverse antigens are displayed on the surface of infected erythrocytes and play a critical role in immune evasion and sequestration of infected erythrocytes. Studies of var expression using non-leukocyte-depleted blood are challenging because of the predominance of host genetic material and lack of conserved var segments. Our goal was to enrich for parasite RNA, allowing de novo assembly of var genes and detection of expressed novel variants. We used two overall approaches: (i) enriching for total mRNA in the sequencing library preparations and (ii) enriching for parasite RNA with a custom capture array based on Roche’s SeqCap EZ enrichment system. The capture array was designed with probes based on the whole 3D7 reference genome and an additional .4,000 full-length var gene sequences from other P. falciparum strains. We tested each method on RNA samples from Malian children with severe or uncomplicated malaria infections. All reads mapping to the human genome were removed, the remaining reads were assembled de novo into transcripts, and from these, var-like transcripts were identified and annotated. The capture array produced the longest maximum length and largest numbers of var gene transcripts in each sample, particularly in samples with low parasitemia. Identifying the most-expressed var gene sequences in whole-blood clinical samples without the need for extensive processing or generating sample-specific reference genome data is critical for understanding the role of PfEMP1s in malaria pathogenesis.
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Malian adults maintain serologic responses to virulent PfEMP1s amid seasonal patterns of fluctuationPlasmodium falciparum erythrocyte membrane protein-1s (PfEMP1s), diverse malaria proteins expressed on the infected erythrocyte surface, play an important role in pathogenesis, mediating adhesion to host vascular endothelium. Antibodies to particular non-CD36-binding PfEMP1s are associated with protection against severe disease. We hypothesized that given lifelong P. falciparum exposure, Malian adults would have broad PfEMP1 serorecognition and high seroreactivity levels during follow-up, particularly to non-CD36-binding PfEMP1s such as those that attach to endothelial protein C receptor (EPCR) and intercellular adhesion molecule-1 (ICAM-1). Using a protein microarray, we determined serologic responses to 166 reference PfEMP1 fragments during a dry and subsequent malaria transmission season in Malian adults. Malian adult sera had PfEMP1 serologic responses throughout the year, with decreased reactivity to a small subset of PfEMP1 fragments during the dry season and increases in reactivity to a different subset of PfEMP1 fragments during the subsequent peak malaria transmission season, especially for intracellular PfEMP1 domains. For some individuals, PfEMP1 serologic responses increased after the dry season, suggesting antigenic switching during asymptomatic infection. Adults were more likely to experience variable serorecognition of CD36- binding PfEMP1s than non-CD36-binding PfEMP1s that bind EPCR or ICAM-1, which remained serorecognized throughout the year. Sustained seroreactivity to non-CD36-binding PfEMP1s throughout adulthood amid seasonal fluctuation patterns may reflect underlying protective severe malaria immunity and merits further investigation.
