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Tobacco dependence treatment initiated in the hospital emergency department (ED) is effective. However, trials typically use multicomponent interventions, making it difficult to distinguish specific components that are effective. In addition, interactions between components cannot be assessed. The Multiphase Optimization Strategy allows investigators to identify these effects.We conducted a full-factorial, 2Between February 2017 and May 2019, we enrolled 1,056 adult smokers visiting the ED. Odd ratios (95% confidence intervals) from the primary analysis of biochemically confirmed abstinence rates at 3 months for each intervention, versus control, were: brief negotiation interview, 1.8 (1.1, 2.8); nicotine replacement therapy, 2.1 (1.3, 3.2); quitline, 1.4 (0.9, 2.2); SmokefreeTXT, 1.1 (0.7, 1.7). There were no statistically significant interactions among components. Economic and qualitative analyses are in progress.The brief negotiation interview and nicotine replacement therapy were efficacious. This study is the first to identify components of ED-initiated tobacco dependence treatment that are individually effective. Future work will address the scalability of the brief negotiation interview and nicotine replacement therapy by offering provider-delivered brief negotiation interviews and nicotine replacement therapy prescriptions.

Background: The association between heart rate (HR) and pulmonary embolism (PE) outcomes has not been well studied. Furthermore, optimal cutoffs to identify low-risk and intermediate- to high-risk patients are not well known. Research Question: Does an association exist between baseline HR and PE outcome across the continuum of HR values? Study Design and Methods: The current study included 44,331 consecutive nonhypotensive patients with symptomatic PE from the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2021. Outcomes included 30-day all-cause and PE-specific mortality. We used hierarchical logistic regression to assess the association between admission HR and outcomes. Results: A positive relationship was found between admission HR and 30-day all-cause and PE-related mortality. Considering an HR of 80 to 99 beats/min as a reference, patients in the higher HR strata showed higher rates of all-cause death (adjusted OR, 1.5 for HR of 100-109 beats/min; adjusted OR, 1.7 for HR of 110-119 beats/min; adjusted OR, 1.9 for HR of 120-139 beats/min; and adjusted OR, 2.4 for HR of ≥ 140 beats/min). Patients in the lower strata of HR showed significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR, 0.6 for HR of 60-79 beats/min; and adjusted OR, 0.5 for HR of < 60 beats/min). The findings for 30-day PE-related mortality were similar. For identification of low-risk patients, a cutoff value of 80 beats/min (vs 110 beats/min) increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from 93.4% to 98.8%. For identification of intermediate- to high-risk patients, a cutoff value of 140 beats/min (vs 110 beats/min) increased the specificity of the Bova score from 93.2% to 98.0%. Interpretation: In nonhypotensive patients with acute symptomatic PE, a high HR portends an increased risk of all-cause and PE-related mortality. Modifying the HR cutoff in the sPESI and the Bova score improves prognostication of patients with PE.

The ability of ultraviolet radiation to suppress the immune system is thought to be central to both its beneficial (protection from autoimmunity) and detrimental (carcinogenic) effects. Previous work revealed a key role for lipids particularly platelet-activating factor and sphingosine-1-phosphate in mediating UV-induced immune suppression. We therefore hypothesized that there may be other UV-induced lipids that have immune regulatory roles. To assess this, mice were exposed to an immune suppressive dose of solar-simulated UV (8 J/cm2). Lipidomic analysis identified 6 lipids (2 acylcarnitines, 2 neutral lipids, and 2 phospholipids) with significantly increased levels in the skin-draining lymph nodes of UV-irradiated mice. Imaging mass spectrometry of the lipids in combination with imaging mass cytometry identification of lymph node cell subsets indicated a preferential location of UV-induced lipids to T cell areas. In vitro co-culture of skin-draining lymph node lipids with lymphocytes showed that lipids derived from UV-exposed mice have no effect on T cell activation but significantly inhibited T cell proliferation, indicating that the lipids play an immune regulatory role. These studies are important first steps in identifying novel lipids that contribute to UV-mediated immune suppression.

Background Orofacial clefts are characterized by a frequent occurrence of dental anomalies. Numerous studies demonstrate the high prevalence of dental aplasia, supernumerary teeth, and hypoplastic teeth in patients with cleft lip with/without cleft palate (CL/P), yet the therapeutic consequences are rarely discussed. This study explores prevalence, localization, and association between primary and secondary dentition in a large European collective and begins to evaluate the significance of dental anomalies in the therapeutic course of patients with CL/P. Methods The medical reports of 1070 patients with different entities of CL/P who presented to our clinic within a 15-year investigation period were evaluated retrospectively. Dental anomalies were classified into three different diagnostic groups: dental aplasia, supernumerary teeth and hypoplastic teeth. The statistical analyses included studies of the frequency and localization of dental anomalies in different cleft entities as well as of the association between primary and secondary dentition and the therapeutic consequences. Results Uni- or bilateral cleft lip and palate (CLP) (47.5%) occurred most frequently, followed by cleft palate only (CPO) (32.9%) and cleft lip with or without alveolus (CL ± A) (19.6%). Dental anomalies were found significantly more often on the side of the cleft. Aplastic permanent teeth were mostly found in patients with CLP (54.8%), while supernumerary permanent teeth occurred primarily in patients with CL ± A (21.7%). Patients with CPO presented dental aplasia but no patient with CPO showed supernumerary teeth. The occurrence of dental aplasia in the primary dentition significantly increases the probability of aplastic teeth in the permanent dentition. Dental anomalies, in particular dental aplasia, significantly increase patients’ need for subsequent orthodontic therapy and orthognathic surgery. Conclusion Dental aplasia and hypoplasia are common in patients with CL/P not only in the cleft area but in the whole dentition. In the event of dental aplasia in the primary dentition, the frequency of aplastic teeth in the permanent dentition is significantly higher. Additionally, the need for therapeutic interventions, especially concerning orthognathic surgery, seems to be significantly higher in patients with CL/P who are affected by dental anomalies. Clinicians should take this into account when creating long-term treatment plans.

Here we present a comprehensive mass cytometry analysis of peripheral innate lymphoid cell (ILC) subsets in relapsing/remitting MS (RRMS) patients prior to and after onset of cladribine tablets (CladT). ILC analysis was conducted on CyTOF data from peripheral blood mononuclear cells (PBMC) of MS patients before, 2 and 6 months after onset of CladT, and non-MS controls. Dimensionality reduction was used for immunophenotyping ILC subsets. CladT reduced all ILC subsets, except for CD56bright NK cells and ILC2. Furthermore, CD38+ NK cell and CCR6+ ILC3 were excluded from CladT-induced immune cell reductions. Post-CladT replenishment by immature ILC was noted by increased CD5+ ILC1 proportions at 2 months, and boosted CD38−CD56bright NK cell numbers at 6 months. CladT induce immune cell depletion among ILC but exclude CD56bright NK cells and ILC2 subsets, as well as CD38+ NK cell and CCR6+ ILC3 immunophenotypes. Post-CladT ILC expansions indicate ILC reconstitution towards a more tolerant immune system phenotype.

Multiple sclerosis (MS) is a chronic, demyelinating disease of the central nervous system (CNS) induced by immune dysregulation. Cladribine has been championed for its clinical efficacy with relatively minor side effects in treating MS. Although it is proposed that cladribine exerts an anti-migratory effect on lymphocytes at the blood–brain barrier (BBB) in addition to its lymphocyte-depleting and modulating effects, this has not been properly studied. Here, we aimed to determine if cladribine treatment influences trans-endothelial migration of T cell subsets across an inflamed BBB. Human brain endothelial cells stimulated with pro-inflammatory cytokines were used to mimic the BBB. Peripheral blood mononuclear cells were obtained from healthy controls, untreated and cladribine-treated MS patients. The trans-endothelial migration of CD4+ effector memory T (TEM) and CD8+ central memory T (TCM) cells was reduced in cladribine-treated MS patients. CD28 expression was decreased on both CD4+ TEM and CD8+ TCM cells, suggesting lowered peripheral activation of these cells thereby maintaining the integrity of the BBB. In addition, these cells have likely reconstituted following cladribine treatment, revealing a long-term anti-migratory effect. These results highlight new mechanisms by which cladribine acts to control MS pathogenesis.

PurposeSince 2012 fentanyl-detected fatal overdoses have risen from 4% of all fatal overdoses in Connecticut to 82% in 2019. We aimed to investigate the geographic and temporal trends in fentanyl-detected deaths in Connecticut during 2009-2019.MethodsData on the dates and locations of accidental/undetermined opioid-detected fatalities were obtained from Connecticut Office of the Chief Medical Examiner. Using a Bayesian space-time binomial model, we estimated spatiotemporal trends in the proportion of fentanyl-detected deaths.ResultsDuring 2009-2019, a total of 6,632 opioid deaths were identified. Among these, 3,234 (49%) were fentanyl-detected. The modeled spatial patterns suggested that opioid deaths in northeastern Connecticut had higher probability of being fentanyl-detected, while New Haven and its neighboring towns and the southwestern region of Connecticut, primarily Greenwich, had a lower risk. Model estimates also suggested fentanyl-detected deaths gradually overtook the preceding non-fentanyl opioid-detected deaths across Connecticut. The estimated temporal trend showed the probability of fentanyl involvement increased substantially since 2014.ConclusionOur findings suggest that geographic variation exists in the probability of fentanyl-detected deaths, and areas at heightened risk are identified. Further studies are warranted to explore potential factors contributing to the geographic heterogeneity and continuing dispersion of fentanyl-detected deaths in Connecticut.

Extracellular vesicles (EVs) are lipid-membrane enclosed nanoparticles that play significant roles in health and disease. EVs are abundant in body fluids and carry an array of molecules (proteins, lipids, nucleic acids and glycans) that reflect the identity and activity of their cell-of-origin. While the advent of high throughput omics technologies has allowed in-depth characterisation of EV compositions, how these molecular species are spatially distributed within EV structures is not well appreciated. This is particularly true of the EV surface where a plethora of molecules are reported to be both integral and peripherally associated to the EV membrane. This coronal layer or 'atmosphere' that surrounds the EV membrane contributes to a large, highly interactive and dynamic surface area that is responsible for facilitating EV interactions with the extracellular environment. The EV coronal layer harbours surface molecules that reflect the identity of parent cells, which is likely a highly valuable property in the context of diagnostic liquid biopsies. In this review, we describe the current understanding of the mechanical, electrostatic and molecular properties of the EV surface that offer significant biomarker potential and contribute to a highly dynamic interactome.

ObjectiveNeurofibromatosis type 1 (NF1) is a genetic disorder in which chronic pain commonly occurs. The study sought to understand the needs of individuals with NF1 and pain management experts when adapting a pain self-management mobile health application (app) for individuals with NF1.DesignWe conducted a series of online, audio-recorded focus groups that were then thematically analysed.SettingOnline focus groups with adults currently residing in the USA.ParticipantsTwo types of participants were included: individuals with NF1 (n=32 across six focus groups) and pain management experts (n=10 across three focus groups).ResultsSix themes across two levels were identified. The individual level included lifestyle, reasons for using the mobile app and concerns regarding its use. The app level included desired content, desired features and format considerations. Findings included recommendations to grant free access to the app and include a community support feature for individuals to relate and validate one another’s experience with pain from NF1. In addition, participants noted the importance of providing clear instructions on navigating the app, the use of an upbeat, hopeful tone and appropriate visuals.ConclusionsBoth participant groups endorsed the use of iCanCope (iCC) as an NF1 pain self-management mobile app. Differences between groups were noted, however. The NF1 group appeared interested in detailed and nuanced pain tracking capabilities; the expert group prioritised tracking information such as mood, nutrition and activity to identify potential associations with pain. In tailoring the existing iCC app for individuals with NF1, attention should be paid to creating a community support group feature and to tailoring content, features and format to potential users’ specific needs.

Venous thromboembolism (VTE) is a frequent complication in patients with cancer and a leading cause of morbidity and death. The objective of the RIETECAT study was to compare the long-term effectiveness and safety of enoxaparin versus dalteparin or tinzaparin for the secondary prevention of VTE in adults with active cancer. We used the data from the multicenter, multinational RIETE registry to compare the rates of VTE recurrences, major bleeding, or death over 6 months in patients with active cancer and acute VTE using full doses of enoxaparin versus dalteparin or tinzaparin, and a multivariable Cox proportional hazard model was used to analyze the primary end point. From January 2009 to June 2018, 4451 patients with active cancer received full doses of the study drugs: enoxaparin, 3526 patients; and dalteparin or tinzaparin, 925 (754 + 171) patients. There was limited difference in VTE recurrences (2.0% vs 2.5%) and mortality rate (19% vs 17%) between the enoxaparin and dalteparin or tinzaparin subgroups. However, there was a slight numerical increase in major bleeding (3.1% vs 1.9%). Propensity score matching confirmed that there were no differences in the risk for VTE recurrences (adjusted hazard ratio [aHR], 0.81; 95% confidence interval [CI], 0.48-1.38), major bleeding (aHR, 1.40; 95% CI, 0.80-2.46), or death (aHR, 1.07; 95% CI, 0.88-1.30) between subgroups. In RIETECAT, in patients with cancer and VTE receiving full-dose enoxaparin or dalteparin or tinzaparin, no statistically significant differences were observed regarding effectiveness and safety outcomes over a 6-month period.

Pleural mesothelioma, previously known as malignant pleural mesothelioma, is an aggressive and fatal cancer of the pleura, with one of the poorest survival rates. Pleural mesothelioma is in urgent clinical need for biomarkers to aid early diagnosis, improve prognostication, and stratify patients for treatment. Extracellular vesicles (EVs) have great potential as biomarkers; however, there are limited studies to date on their role in pleural mesothelioma. We conducted a comprehensive proteomic analysis on different EV populations derived from five pleural mesothelioma cell lines and an immortalized control cell line. We characterized three subtypes of EVs (10 K, 18 K, and 100 K), and identified a total of 4054 unique proteins. Major differences were found in the cargo between the three EV subtypes. We show that 10 K EVs were enriched in mitochondrial components and metabolic processes, while 18 K and 100 K EVs were enriched in endoplasmic reticulum stress. We found 46 new cancer-associated proteins for pleural mesothelioma, and the presence of mesothelin and PD-L1/PD-L2 enriched in 100 K and 10 K EV, respectively. We demonstrate that different EV populations derived from pleural mesothelioma cells have unique cancer-specific proteomes and carry oncogenic cargo, which could offer a novel means to extract biomarkers of interest for pleural mesothelioma from liquid biopsies.

Multiple sclerosis (MS) is a disease in which the immune system damages components of the central nervous system (CNS), leading to the destruction of myelin and the formation of demyelinating plaques. This often occurs in episodic “attacks” precipitated by the transmigration of leukocytes across the blood-brain barrier (BBB), and repeated episodes of demyelination lead to substantial losses of axons within and removed from plaques, ultimately leading to progressive neurological dysfunction. Within leukocyte populations, macrophages and T and B lymphocytes are the predominant effectors. Among current immunotherapies, oral cladribine’s impact on lymphocytes is well characterised, but little is known about its impact on other leukocytes such as monocytes and dendritic cells (DCs). The aim of this study was to determine the transmigratory ability of monocyte and DC subsets in healthy subjects and untreated and cladribine-treated relapse-remitting MS (RRMS) patients using a well-characterised model of the BBB. Peripheral blood mononuclear cells from subjects were added to an in vitro transmigration assay to assess cell migration. Our findings show that while prior treatment with oral cladribine inhibits the migration of intermediate monocytes, it has no impact on the transmigration of DC subsets. Overall, our data indicate a previously unrecognised role of cladribine on intermediate monocytes, known to accumulate in the brain active MS lesions.

The RIETE Investigators., [Background] The optimal therapy of patients with acute subsegmental pulmonary embolism (PE) is controversial., [Methods] We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) database to compare the rate of symptomatic PE recurrences during anticoagulation in patients with subsegmental, segmental, or more central PEs. [Results] Among 15 963 patients with a first episode of symptomatic PE, 834 (5.2%) had subsegmental PE, 3797 (24%) segmental, and 11 332 (71%) more central PE. Most patients in all subgroups received initial therapy with low‐molecular‐weight heparin, and then most switched to vitamin K antagonists. Median duration of therapy was 179, 185, and 204 days, respectively. During anticoagulation, 183 patients developed PE recurrences, 131 developed deep vein thrombosis (DVT), 543 bled, and 1718 died (fatal PE, 135). The rate of PE recurrences was twofold higher in patients with subsegmental PE than in those with segmental (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.16‐3.85) or more central PE (HR, 1.89; 95% CI, 1.12‐3.13). On multivariable analysis, patients with subsegmental PE had a higher risk for PE recurrences than those with central PE (adjusted HR, 1.75; 95% CI, 1.02‐3.03). After stratifying patients with subsegmental PE according to ultrasound imaging in the lower limbs, the rate of PE recurrences was similar in patients with DVT, in patients without DVT, and in those with no ultrasound imaging. [Conclusions] Our study reveals that the risk for PE recurrences in patients with segmental PE is not lower than in those with more central PE, thus suggesting that the risk of PE recurrences is not influenced by the anatomic location of PE.

Addressing patients’ religion and spirituality (R/S) needs has been associated with positive health outcomes. However, despite receiving extensive training in spiritual assessment and care, chaplaincy services are primarily confined to inpatient settings, with few studies occurring in outpatient settings. The study sought to understand mental health providers’ views about what shaped provider and patient motivation to engage in R/S discussions and seek referrals to chaplaincy services. We conducted five one-hour focus group sessions with a total of 38 staff members and thematically analyzed the resulting session and field notes. We identified four themes concerning provider knowledge and attitudes about R/S and chaplaincy services: Staff Information Needs, Staff Motivation to Discuss R/S and Refer, Patient Motivation to Use Chaplaincy Services, and Chaplain Accessibility. The study findings suggest that providers in outpatient substance use treatment clinics in the Veterans Health Administration are receptive to learning about R/S care and the possibility of expanding chaplaincy services. However, staff have misconceptions about the roles and responsibilities of chaplains. Attitudes about and experiences with R/S discussions varied. Trust and confidence in the benefits of chaplaincy services may be improved among both providers and patients by increasing chaplains’ accessibility and visibility within these outpatient settings.

Host-directed therapies (HDT) are rapidly advancing as a new and clinically relevant strategy to treat infectious disease. The application of HDT can be broadly used to (i) inhibit host factors essential for pathogen development, including host protein kinases, (ii) control detrimental immune signalling, resulting from excessive release of cytokines, chemokines and extracellular vesicles and (iii) strengthen host defence mechanisms, such as tight junctions in the endothelium. For malaria and other eukaryotic parasite-causing diseases, HDTs could provide a novel avenue to combat the growing resistance seen across all antimicrobials and provide protection against the severe forms of disease through modulation of the host immune response.

B cells play a major role in multiple sclerosis (MS), with many successful therapeutics capable of removing them from circulation. One such therapy, alemtuzumab, is thought to reset the immune system without the need for ongoing therapy in a proportion of patients. The exact cells contributing to disease pathogenesis and quiescence remain to be identified. We utilized mass cytometry to analyze B cells from the blood of patients with relapse-remitting MS (RRMS) before and after alemtuzumab treatment, and during relapse. A complementary RRMS cohort was analyzed by single-cell RNA sequencing. The R package "Spectre" was used to analyze these data, incorporating FlowSOM clustering, sparse partial least squares-discriminant analysis and permutational multivariate analysis of variance. Immunoglobulin (Ig)A

Zika virus (ZIKV) has recently emerged as an important human pathogen due to the strong evidence that it causes disease of the central nervous system, particularly microcephaly and Guillain–Barré syndrome. The pathogenesis of disease, including mechanisms of neuroinvasion, may include both invasion via the blood–brain barrier and via peripheral (including cranial) nerves. Cellular responses to infection are also poorly understood. This study characterizes the in vitro infection of laboratory-adapted ZIKV African MR766 and two Asian strains of (1) brain endothelial cells (hCMEC/D3 cell line) and (2) olfactory ensheathing cells (OECs) (the neuroglia populating cranial nerve I and the olfactory bulb; both human and mouse OEC lines) in comparison to kidney epithelial cells (Vero cells, in which ZIKV infection is well characterized). Readouts included infection kinetics, intracellular virus localization, viral persistence and cytokine responses. Although not as high as in Vero cells, viral titres exceeded 104 plaque-forming units (p.f.u.) ml−1 in the endothelial/neuroglial cell types, except hOECs. Despite these substantial titres, a relatively small proportion of neuroglial cells were primarily infected. Immunolabelling of infected cells revealed localization of the ZIKV envelope and NS3 proteins in the cytoplasm; NS3 staining overlapped with that of dsRNA replication intermediate and the endoplasmic reticulum (ER). Infected OECs and endothelial cells produced high levels of pro-inflammatory chemokines. Nevertheless, ZIKV was also able to establish persistent infection in hOEC and hCMEC/D3 cells. Taken together, these results provide basic insights into ZIKV infection of endothelial and neuroglial cells and will form the basis for further study of ZIKV disease mechanisms.

Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system that results in demyelination of axons, inefficient signal transmission and reduced muscular mobility. Recent findings suggest that B cells play a significant role in disease development and pathology. To further explore this, B cell profiles in peripheral blood from 28 treatment-naive patients with early MS were assessed using flow cytometry and compared to 17 healthy controls. Conventional and algorithm-based analysis revealed a significant increase in MS patients of IgA+ memory B cells (MBC) including CD27+, CD27- and Tbet+ subsets. Screening circulating B cells for markers associated with B cell function revealed a significantly decreased expression of the B cell activation factor receptor (BAFF-R) in MS patients compared to controls. In healthy controls, BAFF-R expression was inversely associated with abundance of differentiated MBC but this was not observed in MS. Instead in MS patients, decreased BAFF-R expression correlated with increased production of proinflammatory TNF following B cell stimulation. Finally, we demonstrated that reactivation of Epstein Barr Virus (EBV) in MS patients was associated with several phenotypic changes amongst MBCs, particularly increased expression of HLA-DR molecules and markers of a T-bet+ differentiation pathway in IgM+ MBCs. Together, these data suggest that the B cell compartment is dysregulated in MS regarding aberrant MBC homeostasis, driven by reduced BAFF-R expression and EBV reactivation. This study adds further insights into the contribution of B cells to the pathological mechanisms of MS, as well as the complex role of BAFF/BAFF-R signalling in MS.

Neurofibromatosis Type 1 (NF1) is a genetic disorder presenting with chronic pain symptoms that has limited treatment options for addressing the pain. The utilization of a mobile application allows for greater reach and scalability when using empirically valid psychosocial self-management treatments for pain. The iCanCope mobile application has been utilized in several different populations dealing with pain symptoms and has demonstrated initial effectiveness. To address the need for this population, we have customized the iCanCope mobile application for the NF1 population and included additional tailored features. We describe the rationale and design of a pilot randomized control study with a sample of 108 adults with NF1, in which two groups will receive access to the mobile application, of which one group will be incentivized to engage in the mobile application and the third group will treatment as usual over the course of 8-week period with a six-week follow-up. Outcomes will focus on the acceptability of the iCanCope-NF mobile application within the NF1 population and the impact of pain related activity on psychometric evaluations to determine if the contingency management will impact the engagement of mobile application, as well as to identify the participants' experiences in relationship to their treatment satisfaction and perceived support.

Multiple sclerosis (MS) is an immune-mediated inflammatory disease of the central nervous system that results in demyelination of axons, inefficient signal transmission and reduced muscular mobility. Recent findings suggest that B cells play a significant role in disease development and pathology. To further explore this, B cell profiles in peripheral blood from 28 treatment-naive patients with early MS were assessed using flow cytometry and compared to 17 healthy controls. Conventional and algorithm-based analysis revealed a significant increase in MS patients of IgA

BackgroundDuring the first months of the Sars-CoV-2 pandemic, antimalarial drugs were the central axis of the treatment of patients with acute respiratory infection. After that, several studies reported a risk of prolongation of corrected QT interval (QTc) at the electrocardiogram (ECG).Historically, these drugs, have been the common denominator in the treatment of patients with Systemic Lupus Erythematosus (SLE).ObjectivesTo analyze the possible relationship between the use of antimalarial drugs ant the electrocardiographic alterations in patients diagnosed with SLE.MethodsCross-sectional study in patients diagnosed with SLE (SLICC 2012). In all of them, we performed a 12-lead ECG at rest. We measured the QT interval: manually and automatically, ant its correction was made according to the Hodge formule (QTc).Results91 patients diagnosed with SLE were included in the study. Of the total of patients included in the study, 64 were in current treatment with an antimalarial drug, with a mean of 9.09 (5.73) years of treatment, and a mean cumulative dosage of 813.16 (436.12) gr.Of the patients on current treatment with antimalarial drugs, 4.69% had a prolonged QTc, compared to 3.7% of the patients without current treatment with these drugs.Table 1.NO antimalarialn= 27YES antimalarialn= 64Heart disease7 (25,93%)5 (7,81%)Cumulative dosage HCQ (gr)316,41 (457,28)813,16 (436,12)ECG disorders5 (18,52%)12 (18,75%)Structural disorders1 (3,7%)6 (9,38%)Electrical conduction disorders2 (7,41%)6 (9,38%)We analyzed the possible relationship between the QTc interval, the current treatment with antimalarial drugs, and the cumulated dosage of this medication. We corrected the lineal regression models by the years of disease evolution, the presence or absence of known heart disease, the women gender, and other treatments such as antiarrhythmics or beta-blockers.We found a statistically significant association between taking antimalarial drugs and the elongated QTc interval (p= 0,001). Nevertheless, in the multivariate analysis, we did not found a significant relationship between the ECG alterations and the treatment with antimalarial drugs.Figure 1.ConclusionIn our study, we did not observe a direct relationship between the intake of antimalarial drugs and the alteration of the corrected QT interval.ReferencesN/ADisclosure of InterestsNone declared

Background: Contact tracing is a core element of the public health response to emerging infectious diseases including COVID-19. Better understanding the implementation context of contact tracing for pandemics, including individual- and systems-level predictors of success, is critical to preparing for future epidemics.Methods: We carried out a prospective implementation study of an emergency volunteer contact tracing program established in New Haven, Connecticut between April 4 and May 19, 2020. We assessed the yield and timeliness of case and contact outreach in reference to CDC benchmarks, and identified individual and programmatic predictors of successful implementation using multivariable regression models. We synthesized our findings using the RE-AIM implementation framework.Results: Case investigators interviewed only 826 (48%) of 1,705 cases and were unable to reach 545 (32%) because of incomplete information and 334 (20%) who missed or declined repeated outreach calls. Contact notifiers reached just 687 (28%) of 2,437 reported contacts, and were unable to reach 1,597 (66%) with incomplete information and 153 (6%) who missed or declined repeated outreach calls. The median time-to-case-interview was 5 days and time-to-contact-notification 8 days. However, among notified contacts with complete time data, 457 (71%) were reached within 6 days of exposure. The least likely groups to be interviewed were elderly (adjusted relative risk, aRR 0.74, 95% CI 0.61–0.89, p = 0.012, vs. young adult) and Black/African-American cases (aRR 0.88, 95% CI 0.80–0.97, pairwise p = 0.01, vs. Hispanic/Latinx). However, ties between cases and their contacts strongly influenced contact notification success (Intraclass Correlation Coefficient (ICC) 0.60). Surging caseloads and high volunteer turnover (case investigator n = 144, median time from sign-up to retirement from program was 4 weeks) required the program to supplement the volunteer workforce with paid public health nurses.Conclusions: An emergency volunteer-run contact tracing program fell short of CDC benchmarks for time and yield, largely due to difficulty collecting the information required for outreach to cases and contacts. To improve uptake, contact tracing programs must professionalize the workforce; better integrate testing and tracing services; capitalize on positive social influences between cases and contacts; and address racial and age-related disparities through enhanced community engagement.

Opioid overdose and substance abuse treatment entry data suggest that injection drug use is increasing in nonurban locations. We sought to explore the prevalence and incidence of viral infections among people who inject drugs (PWID) residing in Fairfield and New Haven counties but outside of the six largest cities. A longitudinal cohort of PWID was assembled and incidence of HIV-1, hepatitis B virus, and hepatitis C virus infections was determined by annual antibody screening. Data on participants’ socioeconomic situation and risk behaviors were collected. We identified 11 new hepatitis C virus infections and calculated incidence at 9.03 cases per 100 person-years. Only one new HIV infection and one new hepatitis B virus infection were detected. Factors associated with seroconversion were assessed. Given the high incidence of HCV and lack of HBV vaccination coverage, prevention and treatment resources need to be targeted to this population.

Background Many have proposed the use of Bluetooth technology to help scale up contact tracing for COVID-19. However, much remains unknown about the accuracy of this technology in real-world settings, the attitudes of potential users, and the differences between delivery formats (mobile app vs carriable or wearable devices). Objective We pilot tested 2 separate Bluetooth contact tracing technologies on a university campus to evaluate their sensitivity and specificity, and to learn from the experiences of the participants. Methods We used a convergent mixed methods study design, and participants included graduate students and researchers working on a university campus during June and July 2020. We conducted separate 2-week pilot studies for each Bluetooth technology. The first was for a mobile phone app (“app pilot”), and the second was for a small electronic “tag” (“tag pilot”). Participants validated a list of Bluetooth-identified contacts daily and reported additional close contacts not identified by Bluetooth. We used these data to estimate sensitivity and specificity. Participants completed a postparticipation survey regarding appropriateness, usability, acceptability, and adherence, and provided additional feedback via free text. We used tests of proportions to evaluate differences in survey responses between participants from each pilot, paired t tests to measure differences between compatible survey questions, and qualitative analysis to evaluate the survey’s free-text responses. Results Among 25 participants in the app pilot, 53 contact interactions were identified by Bluetooth and an additional 61 by self-report. Among 17 participants in the tag pilot, 171 contact interactions were identified by Bluetooth and an additional 4 by self-report. The tag had significantly higher sensitivity compared with the app (46/49, 94% vs 35/61, 57%; P Conclusions Convenient and carriable Bluetooth technology may improve tracing efficiency while alleviating privacy concerns by shifting data collection away from personal devices. With accuracy comparable to, and in this case, superior to, mobile phone apps, such approaches may be suitable for workplace or school settings with the ability to purchase and maintain physical devices.

BACKGROUND Many have proposed the use of Bluetooth technology to help scale up contact tracing for COVID-19. However, much remains unknown about the accuracy of this technology in real-world settings, the attitudes of potential users, and the differences between delivery formats (mobile app vs carriable or wearable devices). OBJECTIVE We pilot tested 2 separate Bluetooth contact tracing technologies on a university campus to evaluate their sensitivity and specificity, and to learn from the experiences of the participants. METHODS We used a convergent mixed methods study design, and participants included graduate students and researchers working on a university campus during June and July 2020. We conducted separate 2-week pilot studies for each Bluetooth technology. The first was for a mobile phone app (“app pilot”), and the second was for a small electronic “tag” (“tag pilot”). Participants validated a list of Bluetooth-identified contacts daily and reported additional close contacts not identified by Bluetooth. We used these data to estimate sensitivity and specificity. Participants completed a postparticipation survey regarding appropriateness, usability, acceptability, and adherence, and provided additional feedback via free text. We used tests of proportions to evaluate differences in survey responses between participants from each pilot, paired t tests to measure differences between compatible survey questions, and qualitative analysis to evaluate the survey’s free-text responses. RESULTS Among 25 participants in the app pilot, 53 contact interactions were identified by Bluetooth and an additional 61 by self-report. Among 17 participants in the tag pilot, 171 contact interactions were identified by Bluetooth and an additional 4 by self-report. The tag had significantly higher sensitivity compared with the app (46/49, 94% vs 35/61, 57%; PP=.02). Most participants felt that Bluetooth contact tracing was appropriate on campus (26/32, 81%), while significantly fewer participants felt that using other technologies, such as GPS or Wi-Fi, was appropriate (17/31, 55%; P=.02). Most participants preferred technology developed and managed by the university rather than a third party (27/32, 84%) and preferred not to have tracing apps on their personal phones (21/32, 66%), due to “concerns with privacy.” There were no significant differences in self-reported adherence rates across pilots. CONCLUSIONS Convenient and carriable Bluetooth technology may improve tracing efficiency while alleviating privacy concerns by shifting data collection away from personal devices. With accuracy comparable to, and in this case, superior to, mobile phone apps, such approaches may be suitable for workplace or school settings with the ability to purchase and maintain physical devices.

Background: Fractures of the talus are a rare but challenging injury. This study sought to quantify the area of osseous exposure afforded by a posteromedial approach to the talus and medial malleolar osteotomy. Methods: Five fresh-frozen cadaveric lower extremities were dissected using a posteromedial approach and medial malleolar osteotomy respectively. Following exposure, the talar surfaces directedly visualized were marked and captured using a calibrated digital image. The digital images were then analyzed using ImageJ software (National Institutes of Health) to calculate the surface area of the exposure. Results: The average square area of talus exposed using the posteromedial approach was 9.70 cm2 (SD = 2.20, range 7.20-12.46). The average quantity of talar exposure expressed as a percentage was 9% (SD = 1.58, range 7.03-10.40). The average square area of talus exposed using a medial malleolar osteotomy was 14.32 cm2 (SD = 2.00, range 11.26-16.66). The average quantity of talar exposure expressed as a percentage was 12.94% (SD = 1.79, range 9.97-14.73). The posteromedial approach provided superior visualization of the posterior talus, whereas the medial malleolar osteotomy offered greater access to the medial body. Conclusion: The posteromedial approach and medial malleolar osteotomy allow for significant exposure of the talus, yielding 9.70 and 14.32 cm2, respectively. Given the differing portions of the talus exposed, surgeons may prefer to use the posteromedial approach for operative fixation of posterior process fractures and elect to use a medial malleolar osteotomy in cases requiring more extensive medial and distal exposure for neck or neck/body fractures. Level of Evidence: Level IV.