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The impact of preexposure prophylaxis uptake on sexual and injection-related behaviors among women who inject drugs is poorly understood. Over 24 weeks, preexposure prophylaxis uptake among women who inject drugs was associated with increased sharing of injection equipment but not syringes and no changes in condomless sex, providing limited evidence of risk compensation in this vulnerable population.

We performed a post hoc analysis of the Belimumab International Study in Lupus Nephritis (BLISS-LN), a Phase 3, multinational, double-blind, 104-week trial, in which 448 patients with lupus nephritis were randomized to receive intravenous belimumab 10 mg/kg or placebo with standard therapy (cyclophosphamide/azathioprine or mycophenolate mofetil). Add-on belimumab was found to be most effective in improving the primary efficacy kidney response and complete kidney response in patients with proliferative lupus nephritis and a baseline urine protein/creatinine ratio under 3 g/g. However, there was no observed improvement in the kidney response with belimumab treatment in patients with lupus nephritis and sub-epithelial deposits or with a baseline protein/creatinine ratio of 3 g/g or more. Belimumab significantly reduced the risk of kidney-related events or death and lupus nephritis flare in the overall population. Belimumab reduced the risk of a sustained 30% or 40% decline in estimated glomerular filtration rate (eGFR) versus standard treatment alone and attenuated the annual rate of eGFR decline in patients who remained on-study. Thus, our data suggest that the addition of belimumab to standard therapy could attenuate the risk of lupus nephritis flare and eGFR decline in a broad spectrum of patients with lupus nephritis.

Objective Enrollment of patients of Black African ancestry with systemic lupus erythematosus (SLE) in Phase 2 and 3 belimumab trials was not reflective of the racial distribution observed in the lupus population. This study assessed efficacy and safety of intravenous (IV) belimumab plus standard therapy in patients of self-identified black race. Methods EMBRACE (GSK Study BEL115471; NCT01632241): 52-week multicenter, double-blind (DB), placebo-controlled trial in adults of self-identified black race with active SLE, receiving monthly belimumab 10 mg/kg IV, or placebo, plus standard therapy. The optional 26-week open-label extension phase included patients who completed the DB phase. The primary endpoint was SLE Responder Index response rate at Week 52 with modified proteinuria scoring adapted from the SLEDAI-2K (SRI-S2K). Key secondary endpoints included: Week 52 SRI response rate, time to first severe flare, and reductions in prednisone dose. Results The modified intention-to-treat population comprised 448 patients (96.9% female; mean [standard deviation] age: 38.8 [11.42] years). The primary endpoint (SRI-S2K response rate at Week 52) was not achieved (belimumab 48.7%, placebo 41.6%; p=0.1068); however, numerical improvements favoring belimumab were observed, especially in patients with high baseline disease activity or renal manifestations. The safety profile of belimumab was generally consistent with previous SLE trials. Adverse events were the primary reason for DB phase withdrawals (belimumab 5.4%; placebo 6.7%). Conclusions The primary endpoint of this study was not achieved, but improvement with belimumab versus placebo was observed, suggesting that belimumab remains a suitable treatment option for SLE management in patients of Black African ancestry.

BACKGROUND In accordance with worldwide data, the Robert Koch Institute (RKI) has reported a constant increase of syphilis cases in Germany over the past decade. METHODS We analysed the data of all patients, referred to a Department of Ophthalmology in a tertiary referral centre in Dusseldorf, Germany between 2008 and 2019, who were tested for syphilis. The epidemiologic, demographic, clinical, diagnostic and therapeutic data were retrieved from the records and evaluated in a retrospective, descriptive, non-comparative study. RESULTS Syphilis serology was positive in 32/1840 (1.7%) patients, and was evenly distributed over this period. 26 (81.3%) were male, 19 (59.4%) belonged to a risk group. Ocular syphilis was the primary diagnosis for 29 patients (90.6%). The most frequent manifestation was uveitis (n = 20, 62.5%). By the end of therapy, 19 patients (59.4%) had an improved visual acuity. CONCLUSION The incidence of ocular syphilis cases has remained stable over the last decade.

New systems are often based on optimistic assumptions of how they will improve human performance. In the cognitive engineering tradition, these assumed benefits are regarded as hypotheses that need to be tested. An important element of a system user evaluation is to determine whether the hypothesized benefits are realized. Evaluation may also uncover unsupported aspects of performance or unanticipated side-effects of introducing the new technology that need to be addressed. We present a work-centered approach to user evaluation intended to meet these objectives, focusing specifically on design of tailored user-feedback questionnaires ( work-centered questionnaires) that are intended to be diagnostic of how specific system elements do, or do not, support work. We summarize two recent evaluation studies we have conducted that illustrate our approach and the diagnostic power of work-centered questionnaires. We discuss how the goals and approach of a work-centered evaluation differ from more traditional approaches to usability evaluation that emphasize the use of standardized questionnaires and broad assessments of usability.

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease affecting both adults and children. Belimumab is the only biologic approved for SLE, and the first in a class of drugs known as B-lymphocyte stimulator-specific inhibitors. The introduction of intravenous belimumab in 2011 was a major advance, being the first new therapy approved for SLE in over 50 years. As of April 2021, more than 7200 people with SLE have received belimumab in clinical studies, and it is approved in over 75 countries for the treatment of adults with SLE. A subcutaneous, self-injectable belimumab formulation was licensed in 2017 by both the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Belimumab was then approved for use in children in Europe, the USA and Japan in 2019, and China and Brazil in 2020. Recently, belimumab became the first FDA-approved drug for the treatment of adults with active lupus nephritis (LN), the most-common severe manifestation of SLE. Over the past 10 years, belimumab has established its position as a disease modifier in the SLE treatment paradigms. Robust evidence from randomised clinical studies and observational, real-world studies has demonstrated the tolerability and efficacy of belimumab for reducing disease activity and the risk of new, severe SLE flares. This enables patients to taper their glucocorticoid use, which limits damage accumulation. Significantly more patients with active LN met the criteria for renal responses and were at less risk of a renal-related event or death after receiving belimumab plus standard therapy, compared with standard therapy on top of mandatory steroid reduction. Ongoing clinical studies are evaluating belimumab’s effectiveness in various indications beyond SLE. Post-marketing and registry studies are gathering additional data on key areas such as pregnancy outcomes after belimumab exposure and belimumab co-administration with other biologics.

This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus‐based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue‐bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10–25% of patients laminin 332 is recognized. In 25–30% of MMP patients with anti‐laminin 332 reactivity, malignancies have been associated. As first‐line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first‐line regimens. Additional recommendations are given, tailored to treatment of single‐site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high‐quality randomized controlled trials.

There is a growing need for brief screening measures for HIV Associated Neurocognitive Disorders (HAND). We compared two commonly used measures (the Montreal Cognitive Assessment [MoCA] and the International HIV Dementia Scale [IHDS]) in their ability to identify asymptomatic HAND (i.e., asymptomatic neurocognitive impairment [ANI]). Participants included 74 Thai PLWH: 38 met Frascati criteria for ANI and 36 were cognitively normal (CN). Participants completed Thai language versions of the MoCA (MoCA-T) and IHDS, and a validated neurocognitive battery. We examined between-group differences for MoCA-T and IHDS total scores, and scale subcomponents. We also conducted receiver operating characteristic (ROC) analyses to determine the ability of the MoCA-T and IHDS to discriminate between CN and ANI groups, and compared their area under the curve (AUC) values. Results revealed lower MoCA-T total score, as well as the Visuospatial/Executive and Delayed Recall subtask scores, in the ANI relative to CN group. Groups did not differ on the IHDS. For ROC analyses, the MoCA-T, but not the IHDS, significantly differentiated the ANI from CN group, and there was a significant difference in AUC values between the MoCA-T (AUC = .71) and IHDS (AUC = .56). Sensitivity and specificity statistics were poor for both screening measures. These data indicate while the MoCA-T functions better than the IHDS in detecting Thai PLWH with ANI, the mildest form of HAND, neither cognitive screener, showed strong utility. Our findings reflect the limited efficacy of common screening measures in detecting subtler cognitive deficits among Thai PLWH, and highlight the need for better screening tools.

Objective To assess whether quantitative changes in the meniscus predict progression from early knee osteoarthritis (OA) to knee replacement (KR). Methods A nested case-control study was conducted among Osteoarthritis Initiative participants: all 35 case knees with baseline Kellgren/Lawrence (K/L) grade ≤2 that had KR between 36 and 60 months were matched 1:1 by age, sex, and baseline K/L grade to 35 control knees without subsequent KR. Quantitative 3-dimensional medial meniscus position and morphologic measures were determined from magnetic resonance imaging at the visit just before KR and 2 years before. Paired t-tests and case-control odds ratios (ORs, standardized per SD of change in controls) were used to compare changes between groups. Results Cases (52% women, age 65 ± 7 years, body mass index [BMI] 30 ± 4 kg/m2 , K/L grades 0/1/2: 5/8/22 participants, respectively) and controls (52% women, age 64 ± 7 years, BMI 30 ± 5 kg/m2 , K/L grades 0/1/2: 9/4/22 participants, respectively) were similar. Compared to control knees, KR case knees displayed longitudinal changes, specifically, a decrease in tibial plateau coverage, an increase in meniscal extrusion, and a decrease in meniscal width. The odds for KR increased with greater reduction in the percentage of tibial plateau coverage (OR 2.28 [95% CI confidence interval (95% CI) 1.43, 3.64]), a greater increase in maximal extrusion (OR 1.40 [95% CI 1.12, 1.75]), and a greater reduction of mean meniscal width (OR 2.01 [95% CI 1.23, 3.26]). The odds for KR increased with medial compartment cartilage thickness loss (OR 2.86 [95% CI 1.51, 5.41]) for comparison. Conclusion Quantitative measures of meniscal position and morphology are associated with subsequent KR in knees with rapidly progressing knee OA. These findings show that structural changes of the meniscus are related to an important clinical and economic outcome of knee OA.

BACKGROUND The emergency department plays a common and critical role in the treatment of postoperative patients. However, many quality improvement databases fail to record these interactions. As such, our understanding of the prevalence and etiology of postoperative emergency department visits in contemporary colorectal surgery is limited. Visits with potentially preventable etiologies represent a significant target for quality improvement, particularly in the current era of rapidly evolving postoperative and ambulatory care patterns. OBJECTIVE We aimed to characterize postoperative emergency department visits and identify factors associated with these visits for potential intervention. DESIGN This was a retrospective cohort study. SETTINGS The study was conducted at an academic medical center. PATIENTS Consecutive patients undergoing colectomy or proctectomy within the division of colorectal surgery at an academic medical center between 2014 and 2018 were included. MAIN OUTCOME MEASURES Frequency and indication for emergency department visits, as well as clinical and sociodemographic factors associated with emergency department visits in the postoperative period, were included measures. RESULTS From the 1763 individual operations, there were 207 emergency department visits from 199 patients (11%) within 30 days of discharge. Two thirds of emergency department visits led to readmission. Median (interquartile range) time to presentation was 8 days (4-16 d). Median time in the emergency department was 7.8 hours (6.0-10.1 h). One third of visits were identified as potentially preventable, most commonly for pain (17%) and stoma complications (excluding dehydration; 13%). A primary language other than English was associated with any postoperative emergency department visit risk ratio of 2.7 (95% CI, 1.3-5.3), as well as a preventable visit risk ratio of 3.6 (95% CI, 1.7-8.0). LIMITATIONS This was a single-center study and a retrospective review. CONCLUSIONS One third of emergency department visits after colorectal surgery are potentially preventable. Special attention should be directed toward those patients who do not speak English as a primary language. See Video Abstract at http://links.lww.com/DCR/B648. SE PUEDEN EVITAR LAS VISITAS AL SERVICIO DE URGENCIA DESPUS DE UNA CIRUGA COLORECTAL ANTECEDENTES:Las unidades de emergencia tienen un rol fundamental en el periodo posterior a una cirugia. Sin embargo muchos de los registros en las bases de datos de estas secciones no son de buena calidad. Por esto analizar la prevalencia y etiologia de las visitas postoperatorias en cirugia colorectal resulta ser bastante limitada. Para lograr una mejoria en la calidad es fundamental analizar las causas potencialmente evitables, especialmente al considerer la rapida evolucion de los parametros de medicion actuales.OBJETIVO:Nuestro objetivo es caracterizar las visitas postoperatorias al servicio de urgencias e identificar los factores asociados potencialmente evitables.DISENO:Estudio de cohorte retrospectivo.AJUSTE:Centro medico academico, 2014-2018.PACIENTES:Pacientes consecutivos sometidos a colectomia o proctectomia dentro de la division de cirugia colorrectal en un centro medico academico entre 2014 y 2018.PRINCIPALES MEDIDAS DE RESULTADO:Frecuencia e indicacion de las visitas al servicio de urgencias en el period postoperatorio: factores clinicos y sociodemograficos.RESULTADOS:De 1763 operaciones individuales, hubo 207 visitas al departamento de emergencias de 199 pacientes (11%) en los 30 dias posteriores al alta. Dos tercios de las visitas al servicio de urgencias dieron lugar a readmisiones. La mediana [rango intercuartilico] de tiempo hasta la presentacion fue de 8 [4-16] dias. La mediana de tiempo en el servicio de urgencias fue de 7,8 [6-10,1] horas. Un tercio de las visitas se identificaron como potencialmente evitables, mas comunmente dolor (17%) y complicaciones del estoma (excluida la deshidratacion) (13%). En los pacientes con poco manejo del ingles se asocio con una mayor frecuencia razon de visitas al departamento de emergencias posoperatorias [IC del 95%] 2,7 [1,3-5,3], asi como opetancialmente evitables con un RR de 3,6 [1,7-8,0].LIMITACIONES:Estudio de un solo centro y revision retrospectiva.CONCLUSION:Al menos un tercio de las visitas al servicio de urgencias despues de una cirugia colorrectal son potencialmente evitables. Se debe prestar especial atencion a los pacientes que no hablan ingles como idioma materno. Consulte Video Resumen en http://links.lww.com/DCR/B648.

Pre-exposure prophylaxis (PrEP) is a promising but underutilized HIV prevention strategy for Women who Inject Drugs (WWID). Stigma and disclosure concerns have been key barriers to PrEP use among women in PrEP efficacy trials. Social support has been found to buffer against some PrEP stigma, though these factors have been largely unexplored among WWID. Investigating how WWID disclose PrEP use is important given evidence that disclosure is associated with higher adherence. We aimed to identify the impact of stigma and support on PrEP disclosure within social networks of WWID participating in a PrEP demonstration project in Philadelphia, PA, USA. PrEP-using WWID ≥ 18 years completed social network surveys. Generalized estimating equations were used to account for the correlation of network structure. Thirty-nine WWID (i.e. egos) named an average of 9.5 ± 3.3 network members (i.e. alters), for a total sample of 371 unique relationships. Egos disclosed their PrEP use to an average of 4.0 alters (SD = 2.8). Related to PrEP stigma, participants had 0.4 times decreased odds of PrEP disclosure with alters who would disapprove of them taking PrEP (95% CI: 0.1–0.9). Related to support, participants had 2.5 times higher odds of disclosure among peers who could provide PrEP advice (95% CI: 1.0–6.0). Interventions that increase social support and decrease stigma are pivotal for increasing PrEP use disclosure among WWID.

Prior research has found that individuals with a pre-injury psychiatric history report greater difficulty with executive functioning after mild traumatic brain injury (mTBI). The present study examined self-rated executive functioning after the acute phase of recovery in individuals with mTBI having no prior psychiatric history. Participants included 59 individuals with mTBI and 27 healthy comparison subjects (HC). They completed the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) and Beck Depression Inventory-II. Participants had no prior history of psychiatric diagnosis based on semi-structured interview. In those with a valid BRIEF-A, the mTBI group (n = 54; days since injury: M = 465.04, SD = 146.92, range = 315–1144) endorsed poorer executive functioning than the HC group (n = 24) on several BRIEF-A scales. Only the Working Memory and Inhibit scales remained significant after adjusting for group differences in education and depression score, but they did not survive adjustment for multiple comparisons. The mean standardized scores for the mTBI group were well within normal limits across scales. Furthermore, there were no group differences on any BRIEF-A scales for percentage of participants with clinically elevated scores. Individuals with mTBI and no prior psychiatric history did not endorse significant executive dysfunction. Our findings support previous literature indicating that self-rated executive dysfunction in those with mTBI after the acute phase of recovery is likely due to factors other than brain injury, such as subclinical symptoms of depression.

It is clear, based on a deep scientific literature base, that genetic and genomic factors play significant roles in determining a wide range of sport and exercise characteristics including exercise endurance capacity, strength, daily physical activity levels, and trainability of both endurance and strength. Although the research field of exercise systems genetics has rapidly expanded over the past two decades, many researchers publishing in this field are not extensively trained in molecular biology or genomics techniques, sometimes creating gaps in generating high-quality and cutting-edge research for publication. As current or former Associate Editors for Medicine and Science in Sports and Exercise that have handled the majority of exercise genetics articles for Medicine and Science in Sports and Exercise in the past 15 yr, we have observed a large number of scientific manuscripts submitted for publication review that have exhibited significant flaws preventing their publication; flaws that often directly stem from a lack of knowledge regarding the "state-of-the-art" methods and accepted literature base that is rapidly changing as the field evolves. The purpose of this commentary is to provide researchers-especially those coming from a nongenetics background attempting to publish in the exercise system genetics area-with recommendations regarding best-practice research standards and data analysis in the field of exercise systems genetics, to strengthen the overall literature in this important and evolving field of research.

Introduction To guide future preexposure prophylaxis (PrEP) implementation for women who inject drugs (WWID), a population increasingly represented in new HIV cases in the United States, we present results from a demonstration project integrated within a syringe services program (SSP) in Philadelphia, PA. Methods WWID ≥18 years were educated about and offered 24 weeks of daily PrEP. Participants completed surveys and clinical assessments at baseline and at weeks 1, 3, 12, and 24. We used descriptive statistics to estimate feasibility/acceptability, engagement in the care cascade, HIV/sexually transmitted diseases (STI) and pregnancy, issues of safety/tolerability, and preferences/satisfaction with PrEP services. Multivariable logistic regression with generalized estimating equations was used to identify factors associated with PrEP uptake and retention. Results We recruited 136 WWID. Of those, 95 were included in the final sample, and 63 accepted a PrEP prescription at week 1. Uptake was associated with greater baseline frequency of SSP access [adjusted odds ratio (aOR) = 1.85; 95% confidence interval (CI): 1.24 to 2.77], inconsistent condom use (aOR = 3.38; 95% CI: 1.07 to 10.7), and experiencing sexual assault (aOR = 5.89; 95% CI: 1.02, 33.9). Of these 95, 42 (44.2%) were retained at week 24. Retention was higher among women who reported more frequent baseline SSP access (aOR = 1.46; 95% CI: 1.04 to 2.24). Self-reported adherence was high but discordant with urine-based quantification of tenofovir. Baseline STI prevalence was 17.9%; there were 2 HIV seroconversions and 1 pregnancy. Safety/tolerability issues were uncommon, and acceptability/satisfaction was high. Conclusions Integrating PrEP with SSP services is feasible and acceptable for WWID. This suggests that daily PrEP is a viable prevention tool for this vulnerable population.

Summary Background Belimumab is approved for the treatment of active systemic lupus erythematosus (SLE). Although clinical trials showed a favourable benefit–risk profile, numerical differences in the incidence of mortality and adverse events of special interest (AESIs) have been reported. We assessed the frequency of these events in patients with SLE receiving belimumab or placebo plus standard therapy. Methods BASE was a double-blind, randomised, placebo-controlled, phase 4 trial done in 33 countries. Adults with active SLE were randomly assigned (1:1) to receive intravenous belimumab (10 mg/kg) or placebo, plus standard therapy, for 48 weeks. The primary endpoints were incidences of all-cause mortality and AESIs during the on-treatment period (first-to-last study drug dose + 28 days). Safety analyses were done in the as-treated population (patients grouped by actual treatment received >50% of the time). This study was registered with ClinicalTrials.gov ( NCT01705977 ). Findings Between Nov 27, 2012, and July 28, 2017, we randomly assigned 4018 patients. The as-treated population included 2002 patients in the belimumab group versus 2001 in the placebo group. Ten (0·50%) patients in the belimumab group died versus eight (0·40%) in the placebo group (difference 0·10%, 95% CI −0·31 to 0·51). Incidences were similar in the belimumab and placebo groups for serious infections (75 [3·75%] of 2002 vs 82 [4·10%] of 2001; difference −0·35%, 95% CI −1·55 to 0·85), opportunistic infections and other infections of interest (36 [1·80%] vs 50 [2·50%]; −0·70%, −1·60 to 0·20), non-melanoma skin cancers (4 [0·20%] vs 3 [0·15%]; 0·05%, −0·21 to 0·31) and other malignancies (5 [0·25%] vs 5 [0·25%]; 0·00%, −0·31 to 0·31). A higher proportion of patients in the belimumab group than in the placebo group had infusion and hypersensitivity reactions (8 [0·40%] vs 2 [0·10%]; 0·30%, −0·01 to 0·61), serious depression (7 [0·35%] vs 1 [0·05%]; 0·30%, 0·02 to 0·58), treatment-emergent suicidality (28 [1·42%] of 1972 patients vs 23 [1·16%] of 1986; 0·26%, −0·44 to 0·96), and sponsor-adjudicated serious suicide or self-injury (15 [0·75%] of 1972 patients vs 5 [0·25%] of 1986; post hoc difference 0·50%, 0·06 to 0·94). Interpretation In line with previously published data, incidences of all-cause mortality and AESIs were similar in patients given belimumab and placebo, except for serious infusion or hypersensitivity reactions, serious depression, treatment-emergent suicidality, and sponsor-adjudicated serious suicide or self-injury events. Funding GSK.

Some women who inject drugs (WWID) would benefit from pre-exposure prophylaxis (PrEP), yet there are few studies of issues related to uptake in real-world settings. In this study, participants (n=95) were offered PrEP and responded to items measuring PrEP-related attitudes, norms, and perceived behavioral control based on the Theory of Planned Behavior. We tested associations with intention to initiate PrEP and uptake. Most WWID (88%) intended to initiate PrEP and 80% accepted a prescription. Compared to WWID who did not express PrEP intentions, those who did were less concerned about attitudinal and perceived behavioral control constructs such as temporary (75% vs. 36%, p=0.01) and long-term (63% vs. 27%, p=0.05) side effects, negative interactions with their birth control (93% vs. 38%, p

Objective: To determine where the current literature stands in regard to diet/exercise interventions on cognition in overweight or obese individuals. Data Source: A rapid review was conducted of English-language studies published in Medline from January 1965 to January 2020. Study Inclusion and Exclusion Criteria: Included studies were intervention studies lasting ≥12 weeks, with participants aged ≥65 years, with a body mass index ≥25 kg/m2 Data Extraction: Data extracted included study population, duration, intervention design, outcomes, and results. Data Synthesis: Outcomes were qualitatively measured due to paucity of RTC. Results: 1845 citations were identified, 31 full-text articles were reviewed, and 5 studies were included. Studies had usual care control groups and combined exercise/diet intervention groups with 31-3,526 participants randomized to each arm. Mean age of participants was 69.2-83.4 years. Studies reporting on cognitive changes showed marginally significant positive changes in cognition, and those that reported BMI indicated potential improvements in cognition. Conclusions: The number of interventions assessing the combined effects of both diet and exercise is low. Future studies should evaluate the impact of combined effects to ascertain whether cognitive decline may be reversed in older adults with a BMI ≥25 kg/m2.

Introduction Public health responses often lack the infrastructure to capture the impact of public health emergencies on pregnant women and infants, with limited mechanisms for linking pregnant women with their infants nationally to monitor long-term effects. In 2019, the Centers for Disease Control and Prevention (CDC), in close collaboration with state, local, and territorial health departments, began a five-year initiative to establish population-based mother-baby linked longitudinal surveillance, the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET).Objectives The objective of this report is to describe an expanded surveillance approach that leverages and modernizes existing surveillance systems to address the impact of emerging health threats during pregnancy on pregnant women and their infants.Methods Mother-baby pairs are identified prospectively during pregnancy and/or retrospectively after birth of the infant. All data are obtained from existing data sources (e.g., electronic medical records, vital statistics, laboratory reports, and health department investigations and case reporting).Results Variables were selected for inclusion to address key surveillance questions proposed by CDC and health department subject matter experts. General variables include maternal demographics and health history, pregnancy and infant outcomes, maternal and infant laboratory results, and child health outcomes up to the second birthday. Exposure-specific modular variables are included for hepatitis C, syphilis, and Coronavirus Disease 2019 (COVID-19). The system is structured into four relational datasets (maternal, pregnancy outcomes and birth, infant/child follow-up, and laboratory testing).Discussion SET-NET provides a population-based mother-baby linked longitudinal surveillance approach and has demonstrated rapid adaptation for use during COVID-19. This innovative approach leverages existing data sources and rapidly collects data to inform clinical guidance and practice. These data can help to reduce exposure risk and adverse outcomes among pregnant women and their infants, direct public health action, and strengthen public health systems.

Little is known about how social networks among women who inject drugs (WWID) can be leveraged to increase awareness about pre-exposure prophylaxis (PrEP). We tested the hypothesis that interpersonal characteristics influence willingness of WWID to communicate PrEP information with peers. Forty WWID ≥ 18 years completed social network surveys. Participants named on average 9.3 (SD = 3.3) network members, resulting in 375 unique relationships. WWID were willing to share PrEP information with 83% of network members. Participants had higher odds of willingness to share information within relationships when the network member was female, homeless and perceived to be at risk for HIV. Among relationships with family members and transactional sex clients, stronger emotional closeness was associated with higher odds of willingness to share information. Peer interventions where WWID share PrEP information with peers may be an efficient approach to increase PrEP awareness among this vulnerable population.

Nurses working in the hospital setting increasingly have become overburdened by managing alarms that, in many cases, provide low information value regarding patient health. The current trend, aided by disposable, wearable technologies, is to promote patient monitoring that does not require entering a patient's room. The development of telemetry alarms and middleware escalation devices adds to the continued growth of auditory, visual, and haptic alarms to the hospital environment but can fail to provide a more complete understanding of patient health. As we begin to innovate to both address alarm overload and improve patient management, perhaps using fundamentally different integration architectures, lessons from the aviation flight deck are worth considering. Commercial jet transport systems and their alarms have evolved slowly over many decades and have developed integration methods that account for operational context, provide multiple response protocol levels, and present a more integrated view of the airplane system state. We articulate three alarm system objectives: (1) supporting hazard management, (2) establishing context, and (3) supporting alarm prioritization. More generally, we present the case that alarm design in aviation can spur directions for innovation for telemetry monitoring systems in hospitals.

The National Academies Board on Human Systems Integration (BOHSI) has organized this session exploring the state of the art and research and design frontiers relating to the application of Artificial Intelligence (AI) technologies to Healthcare. Advances in AI, machine learning, and robotics promise to revolutionize access to and quality of healthcare. At the same time lessons learned from earlier applications of AI technologies suggest a need to carefully consider the user and use context and the need for effective human-machine teaming design to avoid brittle systems that fail to be used or worse that negatively impact patient safety. The Panel brings together prominent researchers from both the Human Factors and Computer Science and AI communities to discuss promising applications, challenges and short-falls and ways forward for achieving the promise of enhanced delivery of health care through application of AI technologies.

In a Philadelphia neighbourhood where opioid overdoses are frequent, neighbors used a smartphone app to request and give help for a victim of suspected overdose. A one-year study demonstrated the feasibility of this approach, which empowered the local community to save lives and even respond to overdoses faster than emergency medical services.

Background: There is an escalating worldwide population of thyroid cancer (TC) survivors. In addition to conventional metrics of quality of care, quality-of-life (QoL) assessment in TC patients is imperative. TC survivors face unique impediments to health-related quality of life (HRQoL), including thyroid-specific symptoms and exposure to disease-related stressors—including fear of recurrence and financial toxicity—over a prolonged survival period. Survey instruments currently used to assess HRQoL in TC survivors may be insufficient to accurately capture the burden of disease in this population. We aimed to identify the HRQoL instruments in the literature, which have been applied in the TC survivor population, and to present the psychometric properties of the scales and indexes that have been used. We hypothesized that few instruments have shown evidence of validity in this population. Summary: Of the 927 articles identified by search criteria, only 28 studies using 15 HRQoL instruments met inclusion criteria. Of the 15 HRQoL instruments identified, 9 were psychometric health status instruments and 6 were preference-based indexes, but none had been validated in the TC survivor population. While the majority of reviewed studies demonstrated impaired psychological and emotional well-being in TC survivors, these findings were not uniformly demonstrated across studies, and the longevity of the impact of TC on HRQoL was variably reported. Conclusions: Discrepancies in the literature regarding the impact of TC survivorship on HRQoL emphasize the challenges of accurately assessing patient perspectives, reinforcing the importance of using well-constructed instruments to measure patient-reported outcomes in the target population. Care providers involved in the treatment of TC survivors should be aware of longitudinal effects on HRQoL, especially pertaining to chronic psychological debilitation. Further development and rigorous validation of TC-specific instruments will allow for better data gathering and understanding of the barriers to achieving high long-term HRQoL in TC survivors throughout their long postsurvival course.

Little is known about differences in bystander behavior among people who use drugs, trained and untrained in opioid overdose prevention. We examined three types of recommended overdose response - a 911 call, rescue breathing/CPR, and naloxone administration-among Philadelphia-based, predominantly street-involved women with a history of illicit drug use. The study utilized a convergent mixed methods approach integrating data from 186 quantitative survey responses and 38 semi-structured qualitative interviews. Quantitative findings revealed that compared to untrained women, trained women were more likely to administer naloxone (32.9% vs. 5.2%) and use two recommended responses (20.0% vs. 9.5%). No significant differences were found between the two groups in calling 911 or using rescue breathing/CPR. Qualitative findings indicated that barriers to enacting recommended overdose response were either structural or situational and included the avoidance of police, inability to carry naloxone or phone due to unstable housing, and perceived lack of safety on the streets and when interacting with strangers. Our study demonstrated that overdose training improved the frequency of naloxone administration among this sample of predominantly street-involved women. Future efforts need to focus on avoiding intrusive policing, scaling-up naloxone refill sites, and providing secondary naloxone distribution via drug user networks.

Background The ODYSSEY CHOICE I study (NCT01926782) evaluated alirocumab 300 mg every 4 weeks (Q4W) in patients with hypercholesterolemia receiving maximally tolerated statin or no statin. Objective The objective of the study was to assess the relationship between alirocumab, proprotein convertase subtilisin/kexin type 9 (PCSK9), and low-density lipoprotein cholesterol (LDL-C) concentrations with the CHOICE I alirocumab dosing regimen. Methods This analysis included 803 patients (547 statin-treated, 256 without statin) who were randomized to alirocumab 300 mg Q4W, alirocumab 75 mg every 2 weeks (Q2W), or placebo. 300 mg Q4W and 75 mg Q2W doses were adjusted to 150 mg Q2W at Week 12 if Week 8 LDL-C was >70 or >100 mg/dL, depending on cardiovascular risk, or if LDL-C reduction was Results Most patients remained on 300 mg Q4W without dose adjustment as they achieved study-defined LDL-C goals at Week 8 (statin-treated: 80.7%; no statin: 85.3%). LDL-C was reduced by 60.5%–71.9% over Weeks 20–24 in patients on 300 mg Q4W and 57.2%–63.0% in patients with dose adjustment from 300 mg Q4W to 150 mg Q2W. Statin-treated patients had higher cardiovascular risk as well as higher free PCSK9 and lower alirocumab concentrations (vs no statin), suggesting increased target-mediated clearance. Regardless of statin status, the most common adverse events in alirocumab-treated patients were injection-site reaction and headache. Conclusions Data provide further insight on alirocumab's mode of action in terms of relationship between alirocumab, PCSK9, and LDL-C, and disease severity, and support the use of alirocumab 300 mg Q4W as an efficacious dosing regimen for clinically meaningful LDL-C reductions.

A qualitative egocentric social network approach was taken to explore motivations for pre-exposure prophylaxis (PrEP)-related communication between women who inject drugs and network members. Eligible participants were HIV-negative, 18 years or older, and participating in a PrEP demonstration project in Philadelphia, PA, USA. The study employed content analysis of in-depth interviews to identify themes related to contextual and relational factors impacting PrEP communication within networks. Participants ( n = 20) named on average three network members, resulting in a total of 57 unique relationships. PrEP conversations occurred within 30 of the 57 relationships, and motivations were to benefit others, to benefit themselves, and due to a sense of obligation. Some conversations also occurred when a peer unexpectedly found their pills. Taking a qualitative approach to network analysis provided a nuanced understanding of how interpersonal characteristics motivated PrEP conversations. Network interventions that facilitate information diffusion and social support may increase PrEP uptake and adherence among women who inject drugs.

To date, studies have found scattered and inconsistent use of existing opioid prescription support tools, such as Prescription Drug Monitoring Systems (PDMPs) and guidelines, and little research has been done to identify barriers for adopting them and better ways to support clinician decision making. This pilot study aims to better understand the flow, resources used, and challenges faced when prescribing opioid medications. The study will help shape research questions for a larger study geared towards informing future decision aid designs and considerations for clinicians in the emergency department (ED). Semi-structured interviews were conducted with a total of six emergency medicine physicians and nurses using an abbreviated variant of the Critical Decision Method. Discussions were focused around how participants made their decisions and what was difficult about them, in addition to whether current aids and tools are helpful. Common themes were identified from free-text notes in the following categories: cognitive and communication challenges, challenges with existing tools and databases, and decision-making strategies. Nurse responses were most commonly related to gaps in communication between physicians and patients and ensuring patient satisfaction. Physicians most commonly reported challenges with existing tools. While existing resources were said to be very helpful, several improvements were suggested by each group. By understanding these types of challenges and dynamics between physicians and nurses in the ED, we can better identify ways to improve the design of opioid prescription decision-making aids in the future.

ObjectivesThis ongoing Phase-2, randomised, placebo-controlled, double-blind study evaluated the efficacy, safety and pharmacokinetics of intravenous belimumab in childhood-onset systemic lupus erythematosus (cSLE).MethodsPatients (5 to 17 years) were randomised to belimumab 10 mg/kg intravenous or placebo every 4 weeks, plus standard SLE therapy. Primary endpoint: SLE Responder Index (SRI4) response rate (Week 52). Key major secondary endpoints: proportion of patients achieving the Paediatric Rheumatology International Trials Organisation/American College of Rheumatology (PRINTO/ACR) response using 50 and ‘30 alternative’ definitions (Week 52), and sustained response (Weeks 44 to 52) by SRI4 and Parent Global Assessment of well-being (Parent-global). Safety and pharmacokinetics were assessed. Study not powered for statistical testing.ResultsNinety-three patients were randomised (belimumab, n=53; placebo, n=40). At Week 52, there were numerically more SRI4 responders with belimumab versus placebo (52.8% vs 43.6%; OR 1.49 (95% CI 0.64 to 3.46)). PRINTO/ACR 30 alternative (52.8% vs 27.5%; OR 2.92 (95% CI 1.19 to 7.17)) and PRINTO/ACR 50 (60.4% vs 35.0%; OR 2.74 (95% CI 1.15 to 6.54)) responses were more frequent with belimumab than placebo, as were sustained responses for SRI4 (belimumab, 43.4%; placebo, 41.0%; OR 1.08 (95% CI 0.46 to 2.52)) and Parent-global (belimumab, 59.1%; placebo, 33.3%; OR 3.49 (95% CI 1.23 to 9.91)). Serious adverse events were reported in 17.0% of belimumab patients and 35.0% of placebo patients; one death occurred (placebo). Week-52, geometric mean (95% CI) belimumab trough concentration was 56.2 (45.2 to 69.8) µg/mL.ConclusionThe belimumab intravenous pharmacokinetics and benefit–risk profile in cSLE are consistent with adult belimumab studies and the 10 mg/kg every 4 weeks dose is appropriate.Trial registration numberNCT01649765.

The experiences of violence and overdose are highly prevalent among women who use illicit drugs. This study sought to ascertain whether multiple victimizations during adulthood increase the frequency of women’s overdose. The sample comprised 218 women recruited at Philadelphia harm reduction sites during 2016–2017. Victimization was assessed as exposure to 16 types of adulthood violence. Three measures were constructed for multiple victimizations: continuous and categorical polyvictimization, and predominant violence domain. Negative binomial regression estimated the incidence rate ratio (IRR) of lifetime overdoses from multiple victimizations. Lifetime history of opioid use (88.6%) and drug injection (79.5%) were common. Among overdose survivors (68.5%), the median of lifetime overdoses was 3. The majority of participants (58.7%) were victims of predominantly sexual violence, 26.1% experienced predominantly physical abuse/assault, and 3.7% were victims of predominantly verbal aggression/coercive control. Participants reported a mean of seven violence types; the higher-score category of polyvictimization (9–16 violence types) comprised 41.7% of the total sample. In multivariable models, one-unit increase in continuous polyvictimization was associated with 4% higher overdose rates (IRR: 1.04, 95% confidence interval [CI]: [1.00, 1.08]). Compared to women who were not victimized (11.5%), those in the higher-score category of polyvictimization (IRR: 2.01; 95% CI: [1.06, 3.80]) and exposed to predominantly sexual violence (IRR: 2.10, 95% CI: [1.13, 3.91]) were expected to have higher overdose rates. Polyvictimization and sexual violence amplified the risk of repeated overdose among drug-involved women. Female overdose survivors need to be screened for exposure to multiple forms of violence, especially sexual violence. Findings underscore the need to scale-up victimization support and overdose prevention services for disenfranchised women.

Objective The understanding of systemic lupus erythematosus (SLE) and lupus nephritis (LN) pathogenesis remains incomplete. This review assessed LN development in SLE, within-LN progression and progression to end-stage renal disease (ESRD). Methods A keyword-based literature search was conducted, and 26 publications were included. Results Overall, 7–31% of patients had LN at SLE diagnosis; 31–48% developed LN after SLE diagnosis, most within 5 years. Class IV was the most commonly found LN class and had the worst prognosis. Histological transformation occurred in 40–76% of patients, more frequently from non-proliferative rather than proliferative lesions. Cumulative 5- and 10-year ESRD incidences in patients with SLE were 3% and 4%, respectively, and 3–11% and 6–19%, respectively, in patients with SLE and LN. Conclusions Elevated serum creatinine was identified as a predictor of worsening disease state, and progression within LN classes and from SLE/LN to ESRD. This review highlights the substantial risk for developing LN and progressing to ESRD amongst patients with SLE.

Introduction and aims Young adults have the highest rates of drug use and contribute significantly to the growing population of medical cannabis patients (MCP). This study examined relationships between longitudinal patterns of illicit/prescription drug use/misuse and cannabis practices among young adult cannabis users. Design and methods In 2014-2015, 210 young adult MCP and 156 nonpatient users were recruited in Los Angeles and surveyed annually over four waves. The analytical sample was limited to completers of all four waves (n = 301). Distinct developmental trajectories of illicit drug use and prescription drug misuse were identified. Fixed effects regression analysis evaluated changes in cannabis practices by trajectory groups. Results Results supported two-trajectory solutions (high/low) for illicit drug use and prescription drug misuse. Decreases in use within all four trajectories occurred by wave 4. Low illicit drug use trajectory members were more likely to self-report medical cannabis use. Membership in both types of high-use trajectories was associated with use of concentrates and edibles. The prevalence of MCP, edibles use and cannabis days decreased significantly by wave 4. Discussion and conclusions While alternative cannabis forms use was associated with membership in high drug use trajectories, self-reported medical cannabis use (not MCP) was negatively associated with high illicit drug use trajectory membership. Reductions in the prevalence of MCP, cannabis days, edibles use and other drug use by wave 4 alongside stable levels of self-reported medical cannabis use might reflect the changing legal status of cannabis in California, maturing out phenomenon and safer patterns of cannabis use.

BACKGROUND: Motor deficits after stroke are a primary cause of long-term disability. The extent of functional recovery may be influenced by genetic polymorphisms. OBJECTIVES: Determine the effect of genetic polymorphisms for brain-derived neurotrophic factor (BDNF), catechol-O-methyltransferase (COMT), and apolipoprotein E (APOE) on walking speed, walking symmetry, and ankle motor control in individuals with chronic stroke. METHODS: 38 participants with chronic stroke were compared based upon genetic polymorphisms for BDNF (presence [MET group] or absence [VAL group] of a Met allele), COMT (presence [MET group] or absence [VAL group] of a Met allele), and APOE (presence [ε4+ group] of absence [ε4- group] of ε4 allele). Comfortable and maximal walking speed were measured with the 10-meter walk test. Gait spatiotemporal symmetry was measured with the GAITRite electronic mat; symmetry ratios were calculated for step length, step time, swing time, and stance time. Ankle motor control was measured as the accuracy of performing an ankle tracking task. RESULTS: No significant differences were detected (p≥0.11) between the BDNF, COMT, or APOE groups for any variables. CONCLUSIONS: In these preliminary findings, genetic polymorphisms for BDNF, COMT, and APOE do not appear to affect walking speed, walking symmetry, or ankle motor performance in chronic stroke.

Cirrhotic cardiomyopathy is a clinical syndrome in patients with liver cirrhosis characterized by blunted cardiac contractile responses to stress and/or heart rate-corrected QT (QTc) interval prolongation. Caveolin-3 (Cav-3) plays a critical role in cardiac protection and is an emerging therapeutic target for heart disease. We investigated the protective role of cardiac-specific overexpression (OE) of Cav-3 in cirrhotic cardiomyopathy. Biliary fibrosis was induced in male Cav-3 OE mice and transgene negative (TGneg) littermates by feeding a diet containing 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC; 0.1%) for 3 wk. Liver pathology and blood chemistries were assessed, and stress echocardiography, telemetry, and isolated heart perfusion studies to assess adrenergic responsiveness were performed. Cav-3 OE mice showed a similar degree of hyperdynamic contractility, pulmonary hypertension, and QTc interval prolongation as TGneg mice after 3 wk of DDC diet. Blunted systolic responses were shown in both DDC-fed Cav-3 OE and TGneg hearts after in vivo isoproterenol challenge. However, QTc interval prolongation after in vivo isoproterenol challenge was significantly less in DDC-fed Cav-3 OE hearts compared with DDC-fed TGneg hearts. In ex vivo perfused hearts, where circulatory factors are absent, isoproterenol challenge showed hearts from DDC-fed Cav-3 OE mice had better cardiac contractility and relaxation compared with DDC-fed TGneg hearts. Although Cav-3 OE in the heart did not prevent cardiac alterations in DDC-induced biliary fibrosis, cardiac expression of Cav-3 reduced QTc interval prolongation after adrenergic stimulation in cirrhosis. NEW & NOTEWORTHY Prevalence of cirrhotic cardiomyopathy is up to 50% in cirrhotic patients, and liver transplantation is the only treatment. However, cirrhotic cardiomyopathy is associated with perioperative morbidity and mortality after liver transplantation; therefore, management of cirrhotic cardiomyopathy is crucial for successful liver transplantation. This study shows cardiac myocyte specific overexpression of caveolin-3 (Cav-3) provides better cardiac contractile responses and less corrected QT prolongation during adrenergic stress in a cirrhotic cardiomyopathy model, suggesting beneficial effects of Cav-3 expression in cirrhotic cardiomyopathy.

Introduction Childhood-onset nephrotic syndrome has a variable clinical course. Improved predictive markers of long-term outcomes in children with nephrotic syndrome are needed. This study tests the association between baseline urinary epidermal growth factor (uEGF) excretion and longitudinal kidney function in children with nephrotic syndrome. Methods The study evaluated 191 participants younger than 18 years enrolled in the Nephrotic Syndrome Study Network, including 118 with their first clinically indicated kidney biopsy (68 minimal change disease; 50 focal segmental glomerulosclerosis) and 73 with incident nephrotic syndrome without a biopsy. uEGF was measured at baseline for all participants and normalized by the urine creatinine (Cr) concentration. Renal epidermal growth factor (EGF) mRNA was measured in the tubular compartment microdissected from kidney biopsy cores from a subset of patients. Linear mixed models were used to test if baseline uEGF/Cr and EGF mRNA expression were associated with change in estimated glomerular filtration rate (eGFR) over time. Results Higher uEGF/Cr at baseline was associated with slower eGFR decline during follow-up (median follow-up = 30 months). Halving of uEGF/Cr was associated with a decrease in eGFR slope of 2.0 ml/min per 1.73 m2 per year (P < 0.001) adjusted for age, race, diagnosis, baseline eGFR and proteinuria, and APOL1 genotype. In the biopsied subgroup, uEGF/Cr was correlated with EGF mRNA expression (r = 0.74; P < 0.001), but uEGF/Cr was retained over mRNA expression as the stronger predictor of eGFR slope after multivariable adjustment (decrease in eGFR slope of 1.7 ml/min per 1.73 m2 per year per log2 decrease in uEGF/Cr; P < 0.001). Conclusion uEGF/Cr may be a useful noninvasive biomarker that can assist in predicting the long-term course of kidney function in children with incident nephrotic syndrome., Graphical abstract

Dry eye disease (DED) is a multifactorial disease characterized by a disrupted tear film homeostasis and inflammation leading to visual impairments and pain in patients. Aqueous-deficient dry eye (ADDE) causes the most severe progressions and depends mainly on the loss of functional lacrimal gland (LG) tissue. Despite a high prevalence, therapies remain palliative. Therefore, it is of great interest to develop new approaches to curatively treat ADDE. Mesenchymal stem/stromal cells (MSC) have been shown to induce tissue regeneration and cease inflammation. Moreover, an increasing amount of MSC was found in the regenerating LG of mice. Therefore, this study investigated the therapeutic effect of MSC transplantation on damaged LGs using duct ligation induced ADDE in mice. Due to the transplantation of sex-mismatched and eGFP-expressing MSC, MSC could be identified and detected until day 21. MSC transplantation significantly improved LG regeneration, as the amount of vital acinar structures was significantly increased above the intrinsic regeneration capacity of control. Additionally, MSC transplantation modulated the immune reaction as macrophage infiltration was delayed and TNFα expression decreased, accompanied by an increased IL-6 expression. Thus, the application of MSC appears to be a promising therapeutic approach to induce LG regeneration in patients suffering from severe DED/ADDE.

Transplantation of organs from increased risk donors for infection transmission (IRDs) is increasing. These organs confer survival benefit to recipients. This study examined transplant center acceptance policies for IRD kidneys across United Network for Organ Sharing (UNOS) regions, based on transplant centers' annual responses to the Minimum Acceptance Criteria (MAC) for acceptance of IRD kidneys, and the association with national and regional IRD kidney utilization. De-identified MAC responses from all transplant centers in the United States from 2007-2019 were obtained. Implementation of MAC responses into practice was evaluated based on annual rates of recovery and transplantation of IRD kidneys, by MAC and UNOS region. Nationally, the number of transplant centers willing to accept IRD kidneys across all criteria increased from 22% in 2007 to 64% in 2019. Acceptance rates increased markedly from donors with intravenous drug use and other potential HIV exposures. However, significant heterogeneity exists in transplant center willingness to accept IRD kidneys, both regionally and between criteria. Trends towards increasing acceptance are strongly associated with higher rates of recovery and transplantation of IRD kidneys. Further research on provider- and center-based refusal to consider IRD kidneys for waitlisted patients is needed to improve utilization of this organ pool. This article is protected by copyright. All rights reserved.

Extracellular vesicles (EVs) play critical roles in many health and disease states, including ischemia, inflammation, and pain, which are major concerns in the perioperative period and in critically ill patients. EVs are functionally active, nanometer-sized, membrane-bound vesicles actively secreted by all cells. Cell signaling is essential to physiological and pathological processes, and EVs have recently emerged as key players in intercellular communication. Recent studies in EV biology have improved our mechanistic knowledge of the pathophysiological processes in perioperative and critical care patients. Studies also show promise in using EVs in novel diagnostic and therapeutic clinical applications. This review considers the current advances and gaps in knowledge of EVs in the areas of ischemia, inflammation, pain, and in organ systems that are most relevant to anesthesiology, perioperative medicine, critical care, and pain management. We expect the reader will better understand the relationship between EVs and perioperative and critical care pathophysiological states and their potential use as novel diagnostic and therapeutic modalities.

ObjectiveTo assess the efficacy and safety of belimumab in paediatric versus adult patients with systemic lupus erythematosus (SLE).MethodsWe performed across-study comparisons of patients with active SLE who received belimumab or placebo, plus standard therapy, in PLUTO (paediatric phase II) and BLISS-52, BLISS-76, BLISS-NEA and EMBRACE (adult phase III). Analysed efficacy data included Week 52 SLE Responder Index (SRI)-4 response rate (EMBRACE: SRI with modified Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) proteinuria scoring (SRI-S2K)); SRI-4 response rate (EMBRACE: SRI-S2K) according to baseline disease activity indicators (Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score; anti-dsDNA/C3/C4 levels); Week 52 SRI-6 response rate; and time to first severe flare (SELENA-SLEDAI Flare Index) over 52 weeks. Safety data were compared for all aforementioned studies along with adult LBSL02 (phase II) and BLISS-SC (phase III).ResultsSRI-4 response rates were similar across the paediatric and adult studies; more belimumab-treated patients achieved SRI-4 responses versus placebo (PLUTO: 52.8% vs 43.6%; BLISS-52: 57.6% vs 43.6%; BLISS-76: 43.2% vs 33.8%; BLISS-NEA: 53.8% vs 40.1%; EMBRACE: 48.7% vs 41.6%). Across all studies, SRI-4 response rates were generally greater in patients with baseline SELENA-SLEDAI scores ≥10 than in patients with baseline SELENA-SLEDAI scores ≤9. A similar proportion of belimumab-treated patients achieved SRI-6 across all studies (PLUTO: 41.2%; BLISS-52: 46.2%; BLISS-76: 33.1%; BLISS-NEA: 43.9%; EMBRACE: 37.5%). Belimumab reduced the risk of severe flare versus placebo in all studies. The incidence of adverse events was similar across all studies.ConclusionsThese analyses demonstrate consistent efficacy and safety of belimumab plus standard therapy across paediatric and adult patients with SLE.Trial registration numbersPLUTO (NCT01649765); BLISS-52 (NCT00424476); BLISS-76 (NCT00410384); BLISS-NEA (NCT01345253); EMBRACE (NCT01632241); BLISS-SC (NCT01484496); and LBSL02 (NCT00071487).

Introduction Wearable biosensors have the potential to monitor physiological change associated with opioid overdose among people who use drugs. Methods We enrolled 16 individuals who reported ≥4 daily opioid use events within the previous 30 day. Each was assigned a wearable biosensor that measured respiratory rate (RR) and actigraphy every 15 seconds for 5 days and also completed a daily interview assessing drug use. We describe the volume of RR data collected, how it varied by participant characteristics and drug use over time using repeated measures one-way ANOVA, episodes of acute respiratory depression (≤5 breaths/minute), and self-reported overdose experiences. Results We captured 1626.4 hours of RR data, an average of 21.7 daily hours/participant over follow-up. Individuals with longer injection careers and those engaging in polydrug use captured significantly fewer total hours of respiratory data over follow-up compared to those with shorter injections careers (94.7 vs. 119.9 hours, p = 0.04) and injecting fentanyl exclusively (98.7 vs. 119.5 hours, p = 0.008), respectively. There were 385 drug use events reported over follow-up. There were no episodes of acute respiratory depression which corresponded with participant reports of overdose experiences. Discussion Our preliminary findings suggest that using a wearable biosensor to monitor physiological changes associated with opioid use was feasible. However, more sensitive biosensors that facilitate triangulation of multiple physiological data points and larger studies of longer duration are needed.

Background Despite increased availability of take-home naloxone, many people who use opioids do so in unprotected contexts, with no other person who might administer naloxone present, increasing the likelihood that an overdose will result in death. Thus, there is a social nature to being “protected” from overdose mortality, which highlights the importance of identifying background factors that promote access to protective social networks among people who use opioids. Methods We used respondent-driven sampling to recruit adults residing in New York City who reported recent (past 3-day) nonmedical opioid use (n = 575). Participants completed a baseline assessment that included past 30-day measures of substance use, overdose experiences, and number of “protected” opioid use events, defined as involving naloxone and the presence of another person who could administer it, as well as measures of network characteristics and social support. We used modified Poisson regression with robust variance to estimate unadjusted and adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs). Results 66% of participants had ever been trained to administer naloxone, 18% had used it in the past three months, and 32% had experienced a recent overdose (past 30 days). During recent opioid use events, 64% reported never having naloxone and a person to administer present. This was more common among those: aged ≥ 50 years (PR: 1.18 (CI 1.03, 1.34); who identified as non-Hispanic Black (PR: 1.27 (CI 1.05, 1.53); experienced higher levels of stigma consciousness (PR: 1.13 (CI 1.00, 1.28); and with small social networks ( Conclusions Results show considerable gaps in naloxone protection among people who use opioids, with more vulnerable and historically disadvantaged subpopulations less likely to be protected. Larger social networks of people who use opioids may be an important resource to curtail overdose mortality, but more effort is needed to harness the protective aspects of social networks.

Coherent rendering is important for generating plausible Mixed Reality presentations of virtual objects within a user’s real-world environment. Besides photo-realistic rendering and correct lighting, visual coherence requires simulating the imaging system that is used to capture the real environment. While existing approaches either focus on a specific camera or a specific component of the imaging system, we introduce Neural Cameras, the first approach that jointly simulates all major components of an arbitrary modern camera using neural networks. Our system allows for adding new cameras to the framework by learning the visual properties from a database of images that has been captured using the physical camera. We present qualitative and quantitative results and discuss future direction for research that emerge from using Neural Cameras.

Background: Multiple reports have described neonatal SARS-CoV-2 infection, including likely in utero transmission and early postnatal infection. Most neonatal infections reported to date have been asymptomatic or mild disease; however, severe cases, including respiratory failure requiring intensive care unit admission, have been described.Objectives: To describe maternal, pregnancy and infant characteristics among neonates born to women with SARS-CoV-2 infection during pregnancy by neonatal SARS-CoV-2 testing results.Methods: Using aggregated data from the Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET) from March 29, 2020–August 6, 2021, we identified neonates who were: 1) born to women who were SARS-CoV-2 positive by RT-PCR at any time during their pregnancy, and 2) tested for SARS-CoV-2 by RT-PCR during the birth hospitalization. Results: Among 25,896 neonates of mothers with SARS-CoV-2-infection, 3,381 (13%) underwent PCR testing. One hundred thirty-six neonates (4%) were PCR-positive. Neonates testing positive were born to both symptomatic and asymptomatic women, and 95% were born to women with infection identified ≤ with 14 days of delivery.Conclusions: While perinatal SARS-CoV-2 infection was uncommon among neonates born to women with SARS-CoV-2 infection during pregnancy, nearly all cases of neonatal infection occurred in pregnant women infected around the time of delivery. These findings underline the need for infection prevention and control measures in delivery and outpatient pediatric settings, as well as counselling for persons who acquire COVID-19 during pregnancy about potential risk to their neonates. Moreover, pregnant people and those wanting to become pregnant should be vaccinated against COVID-19 in order to protect themselves and their infants.

Replicate previous research on Logical Memory Recognition (LM: Performance validity was psychometrically operationalized in a mixed clinical sample of 213 adults. Classification of the LM: LM: Critical item analysis enhances the classification accuracy of the optimal LM

OBJECTIVES HIV-associated neurocognitive disorders (HAND) remain prevalent in people living with HIV (PLWH) despite widespread use of combined antiretroviral therapy (ART). Vascular disease contributes to the pathogenesis of HAND, but traditional vascular risk factors do not fully explain the relation between vascular disease and HAND. A more direct measure of vascular dysfunction is needed. This cross-sectional study tested whether the cardio-ankle vascular index (CAVI), a novel method to assess arterial stiffness, is associated with HAND among PLWH. METHODS Participants included 75 non-diabetic adults with well-controlled HIV from an outpatient HIV clinic. We assessed the relation between CAVI and neurocognitive impairment (NCI). The latter was primarily characterized by the Frascati criteria and secondarily (post hoc) using the Global Deficit Score (GDS). Logistic regression models tested whether high CAVI (≥ 8) was independently associated with NCI when controlling for potential confounders. RESULTS Participants (Mage = 45.6 ± 8.3 years; 30.1% male) had few traditional cardiovascular disease (CVD) risk factors (hypertension, n = 7; dyslipidaemia, n = 34; body mass index ≥ 25 kg/m2 , n = 12; smoking history, n = 13; 2.2% mean 10-year risk of CVD or stroke). Twelve (16%) participants had high CAVI, which was independently associated with meeting Frascati criteria for NCI [n = 39, odds ratio (OR) = 7.6, p = 0.04], accounting for age, education, gender, income, CD4 nadir, recent CD4 and traditional CVD risk factors. High CAVI was also associated with NCI as reflected by higher GDS (OR = 17.4, p = 0.02). CONCLUSIONS Cardio-ankle vascular index is a promising measure of vascular dysfunction that may be independently associated with NCI in relatively healthy PLWH. Larger studies should test the utility of CAVI in predicting NCI/decline in PLWH.

ObjectiveTo assess the appropriateness of expanded serological activity eligibility criteria for belimumab use in the UK systemic lupus erythematosus (SLE) population (and possibly other countries), which includes patients with either anti-double-stranded DNA (anti-dsDNA) positivity or hypocomplementaemia rather than both criteria.MethodsThis post-hoc analysis used data from three randomised, double-blind, placebo-controlled phase III belimumab trials: BLISS-52 (BEL110752; NCT00424476), BLISS-76 (BEL110751; NCT00410384) and BLISS-SC (BEL112341; NCT01484496). Patients with SLE were stratified by high disease activity (HDA): HDA1, Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score ≥10, low complement and positive anti-dsDNA; and HDA2, SELENA-SLEDAI ≥10 and either low complement or positive anti-dsDNA.ResultsThis analysis included 660 HDA1 patients (n=396 on intravenous treatment; n=264 on subcutaneous treatment) and 969 HDA2 patients (n=532 on intravenous treatment; n=437 on subcutaneous treatment). Significant improvements were observed at week 52 with belimumab versus placebo, irrespective of subgroups or drug formulations, in SLE Responder Index (SRI) 4 response (OR (95% CI): HDA1 intravenous 2.7 (1.8 to 4.1); HDA2 intravenous 2.3 (1.61 to 3.26); HDA1 subcutaneous 2.2 (1.22 to 3.85); HDA2 subcutaneous 1.8 (1.17 to 2.74)); proportion of patients achieving ≥4-point reduction in SELENA-SLEDAI score (OR (95% CI): HDA1 intravenous 2.6 (1.7 to 3.9); HDA2 intravenous 2.1 (1.49 to 3.03); HDA1 subcutaneous 2.3 (1.30 to 4.14); HDA2 subcutaneous 1.9 (1.21 to 2.84)); patients with no worsening in Physician Global Assessment (OR (95% CI): HDA1 intravenous 2.0 (1.3 to 3.1); HDA2 intravenous 1.7 (1.17 to 2.45); HDA1 subcutaneous 2.3 (1.18 to 4.40); HDA2 subcutaneous 1.8 (1.11 to 2.92)); and risk of severe flares (HR (95% CI): HDA1 intravenous 0.6 (0.37 to 0.81); HDA2 intravenous 0.6 (0.43 to 0.86); HDA1 subcutaneous 0.52 (0.30 to 0.92); HDA2 subcutaneous 0.59 (0.37 to 0.94)).ConclusionBroadening the HDA population to include either low complement or positive anti-dsDNA, rather than both, would enable more UK patients to receive SLE treatment and experience improved clinical outcomes.

Introduction: The United States Centers for Disease Control and Prevention (CDC), through U.S. President's Emergency Plan for AIDS Relief (PEPFAR), supports a third of all people receiving HIV care globally. CDC works with local partners to improve methods to find, treat, and prevent HIV and tuberculosis. However, a shortage of trained medical professionals has impeded efforts to control the HIV epidemic in Sub-Saharan Africa and Asia. The Project Extension for Community Healthcare Outcomes (ECHOTM) model expands capacity to manage complex diseases, share knowledge, disseminate best practices, and build communities of practice. This manuscript describes a practical protocol for an evaluation framework and toolkit to assess ECHO implementation.Methods and Analysis: This mixed methods, developmental evaluation design uses an appreciative inquiry approach, and includes a survey, focus group discussion, semi-structured key informant interviews, and readiness assessments. In addition, ECHO session content will be objectively reviewed for accuracy, content validity, delivery, appropriateness, and consistency with current guidelines. Finally, we offer a mechanism to triangulate data sources to assess acceptability and feasibility of the evaluation framework and compendium of monitoring and evaluation tools.Expected impact of the study on public health: This protocol offers a unique approach to engage diverse group of stakeholders using an appreciative inquiry process to co-create a comprehensive evaluation framework and a compendium of assessment tools. This evaluation framework utilizes mixed methods (quantitative and qualitative data collection tools), was pilot tested in Tanzania, and has the potential for contextualized use in other countries who plan to evaluate their Project ECHO implementation.