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BACKGROUND: Open calcaneal fractures are devastating, high-energy injuries frequently occurring in multiply-injured patients. Unsatisfactory outcomes with significant complications rates are frequently reported. Our purpose was to assess outcomes of delayed ORIF for open calcaneal fractures with medial hindfoot wounds and limited posterior facet comminution. MATERIALS AND METHODS: Following acute management of the open fractures, seven patients were determined to have stable medial hindfoot wounds and posterior facet comminution of three or fewer fracture fragments. The average age was 32.5 years. These patients were treated with operative management with a plate-and-screw construct using the extensile lateral approach. RAND-36 Item Health, AOFAS Ankle-Hindfoot Survey, and physical examinations were undertaken to access outcomes. RESULTS: All open calcaneal injuries were initially treated with irrigation and debridement, intravenous antibiotics, and plaster immobilization. Definitive fixation was performed at an average of 11.7 days. Six of seven patients were multiply injured. Prior to injury, five were employed on a full-time basis. Four returned to their original or a comparable job. The results of the RAND-36 Item Health Survey and the AOFAS Ankle-Hindfoot scores were 56.7 and 71, respectively. There were no postoperative infections. No patients required additional operative hindfoot procedures. Five continued to use tobacco products. None reported chronic narcotic usage. CONCLUSION: Aggressive treatment of select open calcaneal fractures with delayed ORIF produced satisfactory functional results. Most patients were able to return to gainful employment. There were no infections or wound complications. [ABSTRACT FROM AUTHOR]

The study objectives were to compare local public health professionals' bioterrorism risk perceptions, the extent of bioterrorism preparedness training, and to describe preferred methods for delivery of preparedness education in the United States. National needs assessments were conducted via a mailed survey to 3,074 local public health departments in October 2000 and November 2001. Compared to a survey conducted in October 2000, the perceived risk of a bioterrorism attack in the United States increased dramatically after September 11 (p < 0.0001); however, 57% of respondents believed one was unlikely to occur within their own community. Public health professionals perceive their own communities to be at low risk for a bioterrorism event. Ongoing, updated, standardized bioterrorism preparedness education is needed. [ABSTRACT FROM AUTHOR]

The primary evaluation and management of 47 consecutive patients with 48 open calcaneal fractures was retrospectively analyzed. The fractures were treated over a 7-year period. Forty-two fractures resulted from blunt trauma, and 6 followed penetrating trauma. The predominant mechanism of injury was a motor vehicle accident. Initial treatment consisted of emergent irrigation and debridement of the open wound with intravenous antibiotic prophylaxis. Most patients underwent a second debridement. More than two thirds of the wounds were >5 cm in length, degloving-type injuries, associated with a significant neurovascular deficit and/or required a free-tissue transfer. Internal fixation of the os calcis was undertaken in 40% of patients. In addition, >40% of patients sustained concomitant foot and ankle fractures. Two patients underwent below-the-knee amputations as primary treatment. Five patients required a free-tissue transfer. Complications included two infections and one below-the-knee amputation. Two deaths occurred due to unrelated causes. Treatment standards for the optimal management of open calcaneal fractures remain controversial. A better understanding of this complex injury will help determine suitable treatment strategies. [ABSTRACT FROM AUTHOR]

Loneliness, an emerging public health problem, is higher among people living with HIV and is associated with negative health outcomes. Black/African Americans have a high burden of HIV, and little is known about the characteristics of loneliness among Black adults living with HIV; therefore, this study sought to understand the sociodemographic and psychosocial correlates of Black adults living with HIV who are lonely and the implications of loneliness for their health outcomes. A sample of 304 Black adults living with HIV (73.8% sexual minority men) in Los Angeles County, CA, USA, completed the survey items assessing sociodemographic and psychosocial characteristics, social determinants of health, health outcomes, and loneliness. Antiretroviral therapy (ART) adherence was assessed electronically with the medication event monitoring system. Bivariate linear regressions analysis showed higher loneliness scores among those with higher levels of internalized HIV stigma, depression, unmet needs, and discrimination related to HIV serostatus, race, and sexual orientation. In addition, participants who were married or living with a partner, had stable housing, and reported receiving more social support had lower levels of loneliness. In multivariable regression models controlling for correlates of loneliness, loneliness was found to be a significant independent predictor of worse general physical health, worse general mental health, and greater depression. Loneliness was marginally associated with lower ART adherence. Findings suggest that Black adults living with HIV, who experience multiple intersectional stigmas, require targeted interventions and resources., (© 2023. The Author(s).)

Objectives: Black Americans have been disproportionally affected by the HIV epidemic, and experience significant disparities in sleep health, mental health, and physical health domains. Using longitudinal data from a sample of Black adults with HIV, the current study examined the associations between stigma and mental and physical health outcomes and how sleep disturbance may play a mediating role., Methods: Data were drawn from a recent randomized controlled trial. Questionnaires were used to examine internalized and anticipated HIV stigma, perceived discrimination (enacted stigma) based on multiple social identities (i.e., HIV-serostatus, race, sexual orientation), sleep disturbance, mental health problems (depressive and posttraumatic stress disorder [PTSD] symptoms), and mental and physical health-related quality of life (HRQOL) at baseline, 7-month follow-up, and 13-month follow-up assessments. Linear mixed modeling was used to examine main effects of stigma on health outcomes; causal mediation analysis was used to estimate indirect paths through sleep disturbance., Results: Internalized and anticipated HIV stigma and multiple discrimination were associated with more sleep disturbance, more depressive and PTSD symptoms, and poorer mental and physical HRQOL. Results also indicated significant indirect paths (i.e., mediation) through greater sleep disturbance between HIV-related stigma and discrimination and mental health and health-related quality of life., Conclusions: Results support that sleep disturbance is a mediating pathway through which different forms of stigmas impact health outcomes. Sleep may be an intervention target to help improve mental and physical well-being and reduce health disparities among racial and ethnic minority people with HIV., (© 2024. The Author(s).)

Black sexual minority men (SMM) are disproportionately impacted by HIV in the United States. Intimate partner violence (IPV), substance use, and depression are associated with HIV risk behavior such as condomless sex. In this study, we assessed cross-sectional associations between multiple types of IPV victimization and condomless sex with serodiscordant partners. We then evaluated the mediating roles of mental health and substance use, in a sample of 213 Black SMM living with HIV. We used validated scales to assess IPV victimization, depression, post-traumatic stress symptoms, general mental health, and substance use. All independent variables (IPV type) that had at least a marginal ( p  < .10) association with the dependent variable (condomless sex with a serodiscordant partner) and any potential mediator were included in mediation models. Mediator role was determined based on a statistically significant outcome ( p  < .05) in the mediation model. Physical assault, injury-inducing IPV, and sexual coercion were each positively correlated with condomless sex. Depression, overall mental health, and substance use were associated with physical assault and injury-inducing IPV, and depression was associated with sexual coercion IPV. Both physical assault and injury-inducing IPV were associated with overall mental health, but none of the mental health and substance use measures mediated the associations between IPV and condomless sex. Findings suggest that HIV prevention efforts for Black SMM may need to incorporate IPV screening and prevention services. Further research is needed to understand the psychosocial pathways by which physical forms of IPV relate to condom use., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Exposure to discrimination has been linked to lower HIV antiretroviral therapy (ART) adherence and poor HIV care outcomes among Black Americans. Coping has been shown to mitigate the harmful effects of discrimination on health behaviors, but the use of cultural relevant Africultural coping strategies is understudied as a moderator of the association between intersectional discrimination and ART adherence among Black Americans. We used adjusted logistic regression to test whether Africultural coping strategies (cognitive/emotional debriefing; collective; spiritual-centered; ritual-centered) moderated associations between multiple forms of discrimination (HIV, sexual orientation, race) and good ART adherence (minimum of 75% or 85% of prescribed doses taken, as measured by electronic monitoring in separate analyses) among 92 sexual minority Black Americans living with HIV. Mean adherence was 66.5% in month 8 after baseline (36% ≥ 85% adherence; 49% ≥ 75% adherence). Ritual-centered coping moderated the relationship between each of the three types of discrimination at baseline and good ART adherence in month 8 (regardless of the minimum threshold for good adherence); when use of ritual coping was low, the association between discrimination and adherence was statistically significant. The other three coping scales each moderated the association between racial discrimination and good ART adherence (defined by the 75% threshold); cognitive/emotional debriefing was also a moderator for both HIV- and race-related discrimination at the 85% adherence threshold. These findings support the benefits of Africultural coping, particularly ritual-centered coping, to help sexual minority Black Americans manage stressors associated with discrimination and to adhere well to ART., (© 2023. The Author(s).)

It has become apparent that beer (both alcoholic and nonalcoholic) contains appreciable amounts of non-starch polysaccharides, a broad subgroup of dietary fiber. It is worth noting that the occurrence of non-starch polysaccharides in alcoholic beer does not imply this should be consumed as a source of nutrition. But the popularity of nonalcoholic beer is growing, and the lessons learnt from non-starch polysaccharides in brewing can be largely translated to nonalcoholic beer. For context, we briefly review the origins of dietary fiber, its importance within the human diet and the significance of water-soluble dietary fiber in beverages. We review the relationship between non-starch polysaccharides and brewing, giving focus to the techniques used to quantify non-starch polysaccharides in beer, how they affect the physicochemical properties of beer and their influence on the brewing process. The content of non-starch polysaccharides in both regular and low/nonalcoholic beer ranges between 0.5 - 4.0 g/L and are predominantly composed of arabinoxylans and β-glucans. The process of malting, wort production and filtration significantly affect the soluble non-starch polysaccharide content in the final beer. Beer viscosity and turbidity are strongly associated with the content of non-starch polysaccharides.

The current study examined the prevalence and typology of unmet needs and the association between unmet needs and HIV antiretroviral therapy (ART) medication adherence among a sample of Black people living with HIV(PLHIV) (N = 304) in Los Angeles, CA. We found a high prevalence of unmet needs, with 32% of participants reporting having two or more unmet needs. The most common unmet needs category was basic benefits needs (35%), followed by subsistence needs (33%), and health needs (27%). Significant correlates of unmet needs included food insecurity, history of homelessness, and history of incarceration. A greater number of unmet needs and any unmet basic benefits needs were each significantly associated with lower odds of HIV ART medication adherence. These findings provide further evidence linking the social determinants of health and social disenfranchisement to ART medication adherence among Black PLHIV., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: We sought to develop an evidence-based tool to risk stratify patients diagnosed with seasonal influenza in the emergency department (ED)., Methods: We performed a single-center retrospective cohort study of all adult patients diagnosed with influenza in a large tertiary care ED between 2008 and 2018. We evaluated demographics, triage vital signs, chest x-ray and laboratory results obtained in the ED. We used univariate and multivariate statistics to examine the composite primary outcome of death or need for intubation. We validated our findings in patients diagnosed between 2018 and 2020., Results: We collected data from 3128 subjects; 2196 in the derivation cohort and 932 in the validation cohort. Medical comorbidities, multifocal opacities or pleural effusion on chest radiography, older age, elevated respiratory rate, hypoxia, elevated blood urea nitrogen, blood glucose, blood lactate, and red blood cell distribution width were factors associated with intubation or death. We developed the Predicting Intubation in seasonal Influenza Patients diagnosed in the ED (PIIPED) risk-stratification tool from these factors. The PIIPED tool predicted intubation or death with an area under the receiver operating characteristic curve (AUC) of 0.899 in the derivation cohort and 0.895 in the validation cohort. A version of the tool including only factors available at ED triage, before laboratory or radiographic evaluation, exhibited AUC of 0.852 in the derivation cohort and 0.823 in the validation cohort., Conclusion: Clinical findings during an ED visit predict severe outcomes in patients with seasonal influenza. The PIIPED risk stratification tool shows promise but requires prospective validation., Competing Interests: The authors declare no financial conflicts related to this work., (© 2023 The Authors. JACEP Open published by Wiley Periodicals LLC on behalf of American College of Emergency Physicians.)

In 2020, the authors published work examining disparities in clerkship grading and found students who identify as White were more likely to receive honors grades compared with students from races/ethnicities traditionally underrepresented in medicine. Through a quality improvement approach, the authors identified the following 6 areas where improvements could mitigate grading disparities and, therefore, put processes in place to: ensure equitable access to examination preparation resources, change student assessment, develop medical student curriculum interventions, improve the learning environment, change house staff and faculty recruitment and retention practices, and provide ongoing program evaluation and continuous quality improvement processes to monitor for success. While the authors cannot yet be sure that they have achieved their goal of promoting equity in grading, they believe this evidence-based, multipronged intervention is a clear step in the right direction and encourage other schools to consider a similar approach to tackling this critically important problem at their own institutions., (Copyright © 2023 by the Association of American Medical Colleges.)

Structural inequities have led to HIV disparities, including relatively low antiretroviral therapy adherence and viral suppression rates among Black Americans living with HIV. We conducted a randomized controlled trial of Rise, a community-based culturally congruent adherence intervention, from January 2018 to December 2021 with 166 (85 intervention, 81 control) Black adults living with HIV in Los Angeles County, California [M (SD) = 49.0 (12.2) years-old; 76% male]. The intervention included one-on-one counseling sessions using basic Motivational Interviewing style to problem solve about adherence, as well as referrals to address unmet needs for social determinants of health (e.g., housing services, food assistance). Assessments included electronically monitored adherence; HIV viral load; and baseline, 7-month follow-up, and 13-month follow-up surveys of sociodemographic characteristics, HIV stigma, medical mistrust, and HIV-serostatus disclosure. Repeated-measures intention-to-treat regressions indicated that Rise led to significantly (two-fold) higher adherence likelihood, lower HIV stigmatizing beliefs, and reduced HIV-related medical mistrust. Effects on HIV viral suppression, internalized stigma, and disclosure were non-significant. Moreover, Rise was cost-effective based on established standards: The estimated cost per person to reach optimal adherence was $335 per 10% increase in adherence. Interventions like Rise, that are culturally tailored to the needs of Black populations, may be optimal for Black Americans living with HIV (ClinicalTrials.gov #NCT03331978)., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The earth is rapidly warming, driven by increasing atmospheric carbon dioxide and other gases that result primarily from fossil fuel combustion. In addition to causing arctic ice melting and extreme weather events, climatologic factors are linked strongly to the transmission of many infectious diseases. Changes in the prevalence of infectious diseases not only reflect the impacts of temperature, humidity, and other weather-related phenomena on pathogens, vectors, and animal hosts but are also part of a complex of social and environmental factors that will be affected by climate change, including land use, migration, and vector control. Vector- and waterborne diseases and coccidioidomycosis are all likely to be affected by a warming planet; there is also potential for climate-driven impacts on emerging infectious diseases and antimicrobial resistance. Additional resources for surveillance and public health activities are urgently needed, as well as systematic education of clinicians on the health impacts of climate change., Competing Interests: Potential conflicts of interest. R. H. reports serving as a part-time consultant for the Medical Society Consortium for Climate and Health. P. J. E. reports payment for expert testimony for the Andrews Law Group, Tampa, FL. R. C. L. reports grants from the Centers for Disease Control and Prevention (CDC; U01-CK000633), royalties for chapters from UpToDate, providing editorial services for the CDC Foundation, and is a board member for Greater Boston Physicians for Social Responsibility. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Perceived discrimination and medical mistrust are contributors to HIV inequities. The current study examined whether medical mistrust mediated the associations between perceived discrimination and adherence to antiretroviral therapy (ART) as well as care engagement in a sample of 304 Black adults living with HIV. Perceived discrimination and medical mistrust were measured using validated scales; ART adherence was electronically monitored for a month; care engagement was determined by medical record data. Results support significant total indirect effects from perceived discrimination (due to HIV-serostatus, race, sexual orientation) to ART adherence through three types of medical mistrust (towards healthcare organizations, one's physician, and HIV-specific mistrust). The total indirect effects were also significant for care engagement and were largely driven by mistrust towards one's own physician. Findings suggest interventions at the provider or healthcare organization levels should address medical mistrust to improve the health and well-being of Black Americans living with HIV., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: There are no antiviral therapies for parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV., Methods: Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to room air (RTRA), normalization of vital signs for at least 24 hours, and survival up to day 45 from enrollment., Results: A total of 111 patients were randomized to DAS181 (n = 74) or placebo (n = 37). CSS was achieved by 45.0% DAS181-treated patients in the SO stratum compared with 31.0% for placebo (P = .15), whereas patients on MV had no benefit from DAS181. The proportion of patients achieving RTRA was numerically higher for SO stratum DAS181 patients (51.7%) compared with placebo (34.5%) at day 28 (P = .17). In a post hoc analysis of solid organ transplant, hematopoietic cell transplantation within 1 year, or chemotherapy within 1 year, more SO stratum patients achieved RTRA on DAS181 (51.8%) compared with placebo (15.8%) by day 28 (P = .012)., Conclusions: The primary endpoint was not met, but post hoc analysis of the RTRA component suggests DAS181 may have clinical activity in improving oxygenation in select severely immunocompromised patients with PIV LRTI who are not on mechanical ventilation. Clinical Trials Registration. NCT01644877., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in young children and the elderly. Protective immunity is not generated after repeated infections, but vaccination may hopefully prove effective., Methods: This phase 2 clinical study investigated a multivalent RSV vaccine (MVA-BN-RSV) designed to induce broad antibody and cellular immune responses by encoding RSV surface proteins F, G (for both A and B subtypes), and internal antigens (M2, N). This study evaluated the immune response in adults aged ≥55 years to identify the optimal MVA-BN-RSV dose and vaccination schedule., Results: A single dose increased the levels of neutralizing (plaque reduction neutralization test to RSV A and B) and total (IgG and IgA ELISA) antibodies (1.6 to 3.4-fold increase from baseline) and induced a broad Th1-biased cellular immune response (interferon-γ ELISPOT) to all 5 vaccine inserts (5.4 to 9.7-fold increases). Antibody responses remained above baseline for 6 months. A 12-month booster dose elicited a booster effect in antibody and T-cell responses (up to 2.8-fold from preboost levels). No drug-related serious adverse events were reported., Conclusions: MVA-BN-RSV induces a broad immune response that persists at least 6 months and can be boosted at 12 months, without significant safety findings., Clinical Trials Registration: NCT02873286., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The COVID-19 pandemic disrupted medical education worldwide, leading medical students to organize response initiatives. This paper summarizes the Washington University Medical Student COVID-19 Response (WUMS-CR) and shares lessons to guide future initiatives. We used a three-principle framework of community needs assessment, faculty mentorship, and partnership with pre-existing organizations to address needs in St. Louis, including contact tracing and childcare. In total, over 12,000 h were volunteered across 15+ projects. Overall, student response initiatives should use appropriate frameworks to guide projects and should capitalize on volunteer participation, speed and flexibility, and the diversity of student interests and skills for maximal impact., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© International Association of Medical Science Educators 2021.)

Background: Medical mistrust, a result of systemic racism, is prevalent among Black Americans and may play a role in COVID-19 inequities. In a convenience sample of HIV-positive Black Americans, we examined associations of COVID-19-related medical mistrust with COVID-19 vaccine and COVID-19 treatment hesitancy and negative impacts of COVID-19 on antiretroviral therapy (ART) adherence., Methods: Participants were 101 HIV-positive Black Americans (age: M = 50.3 years; SD = 11.5; 86% cisgender men; 77% sexual minority) enrolled in a randomized controlled trial of a community-based ART adherence intervention in Los Angeles County, CA. From May to July 2020, participants completed telephone interviews on negative COVID-19 impacts, general COVID-19 mistrust (eg, about the government withholding information), COVID-19 vaccine and treatment hesitancy, and trust in COVID-19 information sources. Adherence was monitored electronically with the Medication Event Monitoring System., Results: Nearly all participants (97%) endorsed at least one general COVID-19 mistrust belief, and more than half endorsed at least one COVID-19 vaccine or treatment hesitancy belief. Social service and health care providers were the most trusted sources. Greater COVID-19 mistrust was related to greater vaccine and treatment hesitancy [b (SE) = 0.85 (0.14), P < 0.0001 and b (SE) = 0.88 (0.14), P < 0.0001, respectively]. Participants experiencing more negative COVID-19 impacts showed lower ART adherence, assessed among a subset of 49 participants [b (SE) = -5.19 (2.08), P = 0.02]., Discussion: To prevent widening health inequities, health care providers should engage with communities to tailor strategies to overcome mistrust and deliver evidence-based information, to encourage COVID-19 vaccine and treatment uptake., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

In 2018, in response to a news story featuring the Icahn School of Medicine's decision to eliminate its chapter of Alpha Omega Alpha (AOA) due to perceived racial inequities, students at Washington University School of Medicine in St. Louis (WUSM) brought similar concerns to leadership. WUSM leadership evaluated whether students' race, ethnicity, and gender were associated with their receipt of honors in the 6 core clerkships, key determinants of AOA selection. In preliminary analysis of the school's data, statistically significant racial and ethnic disparities were associated with receipt of honors in each clerkship. Leaders shared these findings with the WUSM community along with a clear message that such discrepancies are unacceptable to the school. An effort to further analyze what lay behind the findings as well as to identify steps to resolve the problem was launched. Using a quality improvement framework, data from focus groups and student surveys were analyzed and 2 overarching themes emerged. Students perceived that both assessment and the learning environment impacted racial/ethnic disparities in clerkship grades. In multivariable logistic regression models, shelf exam scores (a part of student assessment) were found to be associated with receipt of honors in each clerkship; in some (but not all) clerkships, shelf exam scores attenuated the effect of race/ethnicity on receipt of honors, so that when the shelf scores were added to the model, the race/ethnicity effect was no longer significant. This case study describes WUSM's process to understand and address bias in clerkship grading and AOA nomination so that other medical schools might benefit from what has been learned.

Background: A number of psychological assessment tools have been developed to describe various dimensions of gender. Some of these tools are restricted to a binary gender concept and are inflexible in reflecting how a young person's gender may change and develop over time. Most are text questionnaires which require a good level of literacy., Aims: This study aimed to evaluate a newly developed pictorial tool that facilitates a conversation about gender between a child or adolescent (aged 11-18) and their clinician, enabling a diverse understanding and expression of gender identity., Methods: The Perth Gender Picture (PGP) was co-created between clinicians and young clients between 2016 and 2018. In 2018, the measure was evaluated through a pilot study at the Gender Diversity Service at Perth Children's Hospital in Western Australia. After use of the PGP during a clinical consultation, clients were invited to fill in a feedback questionnaire about their experience of its use. Clinicians participated in unstructured interviews to give their feedback., Results: Most participants rated the PGP as easy to understand, acceptable and useful, and many stated that they found gender easier to describe with the picture rather than words. The results show positive uptake from clients, demonstrating feasible implementation with gender diverse young people., Discussion: This evaluation positions the PGP as a useful tool to facilitate conversations about gender identity between gender diverse children and adolescents and their clinicians, in a nonjudgmental and playful manner. It is well-suited to young people who may have limited literacy or difficulty with complex language. The PGP has potential for use in other age groups and non-clinical contexts., Competing Interests: The authors have no other conflicts of interest to declare., (© 2020 Crown Copyright in the Commonwealth of Australia. The Gender Diversity Service.)

Traditional replicating smallpox vaccines are associated with serious safety concerns in the general population and are contraindicated in immunocompromised individuals. However, this very population remains at greatest risk for severe complications following viral infections, making vaccine prevention particularly relevant. MVA-BN was developed as a non-replicating smallpox vaccine that is potentially safer for people who are immunocompromised. In this phase II trial, 3 MVA-BN dosing regimens were evaluated for safety, tolerability, and immunogenicity in persons with HIV (PWH) who had a history of AIDS. Following randomization, 87 participants who were predominately male and African American received either 2 standard doses on weeks 0 and 4 in the standard dose (SD) group (N = 27), 2 double-standard doses on the same schedule in the double dose (DD) group (N = 29), or 3 standard doses on weeks 0, 4 and 12 in the booster dose (BD) group (N = 31). No safety concerns were identified, and injection site pain was the most commonly reported solicited adverse event (AE) in all groups (66.7%), with no meaningful differences between groups. The incidence of severe (Grade 3) AEs was low across groups and no serious AEs or AEs of special interest considered related to study vaccine were reported. Doubling the standard MVA-BN dose had no significant effect on induction of neutralizing antibodies, with 100% seroconversion and comparable GMTs at week 6 in the SD and DD groups (78.9 and 100.3, respectively). A booster dose significantly increased peak neutralizing titers in the BD group (GMT: 281.1), which remained elevated at 12 months (GMT: 45.3) compared to the SD (GMT: 6.2) and DD (GMT: 10.6) groups. However, based on the immune response previously reported for healthy participants, a third dose (booster) does not appear necessary, even for immunocompromised participants. Clinical Trial Registry Number: NCT02038881., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors Heinz Weidenthaler, Darja Schmidt, Brigitte Koenen, Günter Silbernagl, and Katrin Nopora are employees and stakeholders of Bavarian Nordic GmbH; Paul Chaplin is the company CEO. Drs. Edgar Turner Overton, Steven J. Lawrence, and Jack T. Stapleton were investigators for this study, which was funded by Bavarian Nordic. All authors attest they meet the ICMJE criteria for authorship., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Recent developments in human neuroimaging make it possible to non-invasively measure neural activity from different cortical layers. This can potentially reveal not only which brain areas are engaged by a task, but also how. Specifically, bottom-up and top-down responses are associated with distinct laminar profiles. Here, we measured lamina-resolved fMRI responses during a visual task designed to induce concurrent bottom-up and top-down modulations via orthogonal manipulations of stimulus contrast and feature-based attention. BOLD responses were modulated by both stimulus contrast (bottom-up) and by engaging feature-based attention (top-down). Crucially, these effects operated at different cortical depths: Bottom-up modulations were strongest in the middle cortical layer and weaker in deep and superficial layers, while top-down modulations were strongest in the superficial layers. As such, we demonstrate that laminar activity profiles can discriminate between concurrent top-down and bottom-up processing, and are diagnostic of how a brain region is activated., Competing Interests: SL, DN No competing interests declared, Fd Reviewing editor, eLife, (© 2019, Lawrence et al.)

There is limited knowledge on the yield of performing multiplex nucleic acid testing (NAT) on multiple lower respiratory tract specimens from a single patient with a single instance of infection. We evaluated the performance characteristics of multiplex NAT assays performed concurrently on bronchoalveolar lavage (BAL) and bronchial wash (BW) specimens to detect respiratory pathogens. A retrospective study of admitted patients from March 2013 through December 2016 was performed. Individual performance characteristics of BAL and BW specimens were compared to positive results from either set of specimens. Only contemporaneous BAL and BW specimens (received by the laboratory within 4 h of each other) were included. The final cohort included 170 patients, with 184 contemporaneous BAL and BW specimens submitted for multiplex NAT (median age, 58 years; 62% male). Of the patients with positive NAT results, 38 of 40 BW specimens tested positive (overall percent agreement with combined testing, 98.9%; 95% confidence interval [CI], 95.5 to 98.9%), and 34 of 40 BAL specimens tested positive (overall percent agreement with combined testing, 96.7%; 95% CI, 93.0 to 96.7%). Assays performed on BW specimens identified 4 additional specimens and had a higher positive percent agreement (95.0%) with combined testing results compared to those performed on BAL specimens (85.0%). There was exact concordance in 174 specimens (94.6%; negative and positive for respiratory pathogens, 144 and 34 specimens, respectively). We observed high concordance (95%) between multiplex NAT results from contemporaneous BAL and BW specimens. Performance characteristics of BW specimen testing were equivalent to those of BAL specimen testing. The benefit of performing additional testing should be carefully considered against the potential complications and health care costs., (Copyright © 2018 American Society for Microbiology.)

Background: Modified Vaccinia Ankara (MVA) is a live, viral vaccine under advanced development as a non-replicating smallpox vaccine. A randomised, double-blind, placebo-controlled phase III clinical trial was conducted to demonstrate the humoral immunogenic equivalence of three consecutively manufactured MVA production lots, and to confirm the safety and tolerability of MVA focusing on cardiac readouts., Methods: The trial was conducted at 34 sites in the US. Vaccinia-naïve adults aged 18-40 years were randomly allocated to one of four groups using a 1:1:1:1 randomization scheme. Subjects received either two MVA injections from three consecutive lots (Groups 1-3), or two placebo injections (Group 4), four weeks apart. Everyone except personnel involved in vaccine handling and administration was blinded to treatment. Safety assessment focused on cardiac monitoring throughout the trial. Vaccinia-specific antibody titers were measured using a Plaque Reduction Neutralization Test (PRNT) and an Enzyme-Linked Immunosorbent Assay (ELISA). The primary immunogenicity endpoint was Geometric Mean Titers (GMTs) after two MVA vaccinations measured by PRNT at trial visit 4. This trial is registered with ClinicalTrials.gov, number NCT01144637., Results: Between March 2013 and May 2014, 4005 subjects were enrolled and received at least one injection of MVA (n = 3003) or placebo (n = 1002). The three MVA lots induced equivalent antibody titers two weeks after the second vaccination, with seroconversion rates of 99·8% (PRNT) and 99·7% (ELISA). Overall, 180 (6·0%) subjects receiving MVA and 29 (2·9%) subjects in the placebo group reported at least one unsolicited Adverse Event (AE) that was considered trial-related. Vaccination was well tolerated without significant safety concerns, particularly regarding cardiac assessment., Conclusions: The neutralizing and total antibody titers induced by each of the three lots were equivalent. No significant safety concerns emerged in this healthy trial population, especially regarding cardiac safety, thus confirming the excellent safety and tolerability profile of MVA., Trial Registration: ClinicalTrials.gov NCT01144637.

Background: Immunocompromised patients can experience significant morbidity and occasional mortality from complications associated with herpes zoster (HZ), but live attenuated HZ vaccine is contraindicated for these patients. Inactivated zoster vaccine (ZV IN ) is in development for prevention of HZ in immunocompromised patients. However, there are limited data in the literature regarding the effect of anti-CD20 monoclonal antibodies on vaccine-related cell-mediated immune response. This study evaluated safety and immunogenicity of ZV IN in patients with hematologic malignancies (HM) receiving anti-CD20 monoclonal antibodies (alone or in combination chemotherapy regimens) and not likely to undergo hematopoietic cell transplant (HCT) (n=80)., Methods: This was an open-label, single-arm, multicenter Phase I study (NCT01460719) of a 4-dose ZV IN regimen (∼30days between doses) in patients ⩾18years old. Blood samples were collected prior to dose 1 and 28days Postdose 4 to measure varicella zoster virus (VZV)-specific T-cell responses using interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT). The primary hypothesis was that ZV IN would elicit significant VZV-specific immune responses at ∼28days Postdose 4, with a geometric fold rise (GMFR) >1.0. All vaccinated patients were evaluated for adverse events (AE) through 28days Postdose 4., Results: ZV IN elicited a statistically significant VZV-specific immune response measured by IFN-γ ELISPOT at 28days Postdose 4 (GMFR=4.34 [90% CI:3.01, 6.24], p-value<0.001), meeting the pre-specified success criterion. Overall, 85% (68/80) of patients reported ⩾1 AE, 44% (35/80) reported ⩾1 injection-site AE, and 74% (59/80) reported ⩾1 systemic AE. The majority of systemic AEs were non-serious and considered unrelated to vaccination by the investigator. Frequencies of AEs did not increase with subsequent doses of vaccine. No recipient of ZV IN had rash polymerase chain reaction (PCR) positive for VZV vaccine strain., Conclusions: In adults with HM receiving anti-CD20 monoclonal antibodies, ZV IN was well-tolerated and elicited statistically significant VZV-specific T-cell responses ∼28days Postdose 4. CLINICALTRIALS.GOV identifier: NCT01460719., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The use of T-cell replete haploidentical hematopoietic cell transplant (haplo-HCT) has increased substantially since the introduction of post-transplant cyclophosphamide (PTCy) regimens. Limited data exist concerning infectious complications of haplo-HCT utilizing mobilized peripheral blood (PB) hematopoietic cells., Methods: This retrospective cohort study included all adult patients at our institution undergoing PB haplo-HCT with PTCy between June 2009 and June 2015. Infections were microbiologically confirmed. Invasive fungal infections (IFI) classified as "proven" or "probable" by standard definitions were included., Results: In total, 104 patients were identified. Median follow-up was 218 days (range: 6-1576). A total of 322 episodes of infection were recorded. Eighty-nine percent of patients experienced at least one infection. Median time to first infection was 22 days. Patients experiencing at least one bacterial, viral, and IFI were 62%, 72%, and 6%, respectively. The majority (69%) of bacterial infections were caused by enteric organisms. Seven cases of Staphylococcus aureus infection were recorded, with one bacteremia case. Cytomegalovirus (CMV) viremia occurred in 54/71 (76%) at-risk patients at a median time of 24 days. Sixteen (15%) patients developed CMV disease. Nineteen percent (20/104) of patients developed BK polyomavirus-associated cystitis. Six (6%) patients experienced a total of seven IFI. Infection was the primary cause of death for 12% (6/51) of patients and was a secondary cause for 41%., Conclusion: In PB haplo-HCT patients, a high incidence of CMV viremia and disease was observed. Infections with enteric bacteria were common. Fungal and staphylococcal infections were uncommon. Further studies are needed to compare infectious complications in haplo-HCT with other transplant modalities., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Rationale: African Americans living with HIV are less likely to adhere to antiretroviral treatment (ART) compared to other racial/ethnic groups. Medical mistrust is thought to be a factor in this disparity., Objective: We examined (1) whether exposure to HIV conspiracy beliefs, a specific type of HIV-related mistrust (about the origins and treatment of HIV) in social networks is associated with ART nonadherence among African Americans living with HIV; and (2) the characteristics of individuals who discuss HIV-related mistrust in the social networks of African Americans living with HIV., Methods: At baseline and 6- and 12-months post-baseline, 175 African Americans living with HIV on ART completed egocentric social network assessments, from which we assessed the structure and composition of their personal networks (the social context immediately surrounding them). HIV-related mistrust was operationalized with an indicator of whether any social network member had expressed HIV conspiracy beliefs to the participant. Daily medication adherence was monitored electronically., Results: At baseline, 63% of participants agreed with at least one conspiracy belief, and 55% reported hearing at least one social network member ("alter") express conspiracy beliefs. In a multivariate linear repeated measures regression, expression of conspiracy beliefs by similar others in the network (in terms of age, gender, HIV status, sexual orientation, and race/ethnicity) was associated with ART nonadherence (i.e., percentage of prescribed doses taken). In a multivariate logistic regression, expression of conspiracy beliefs was more likely among social network members who were HIV-positive, who knew the participants' serostatus, and with whom participants interacted frequently, and less likely among more well-connected social network members., Conclusion: HIV-related mistrust in the network may be most influential when expressed by similar others who may be HIV-positive themselves., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Unlabelled: Representations in early visual areas are organized on the basis of retinotopy, but this organizational principle appears to lose prominence in the extrastriate cortex. Nevertheless, an extrastriate region, such as the shape-selective lateral occipital cortex (LO), must still base its activation on the responses from earlier retinotopic visual areas, implying that a transition from retinotopic to "functional" organizations should exist. We hypothesized that such a transition may lie in LO-1 or LO-2, two visual areas lying between retinotopically defined V3d and functionally defined LO. Using a rapid event-related fMRI paradigm, we measured neural similarity in 12 human participants between pairs of stimuli differing along dimensions of shape exemplar and shape complexity within both retinotopically and functionally defined visual areas. These neural similarity measures were then compared with low-level and more abstract (curvature-based) measures of stimulus similarity. We found that low-level, but not abstract, stimulus measures predicted V1-V3 responses, whereas the converse was true for LO, a double dissociation. Critically, abstract stimulus measures were most predictive of responses within LO-2, akin to LO, whereas both low-level and abstract measures were predictive for responses within LO-1, perhaps indicating a transitional point between those two organizational principles. Similar transitions to abstract representations were not observed in the more ventral stream passing through V4 and VO-1/2. The transition we observed in LO-1 and LO-2 demonstrates that a more "abstracted" representation, typically considered the preserve of "category-selective" extrastriate cortex, can nevertheless emerge in retinotopic regions., Significance Statement: Visual areas are typically identified either through retinotopy (e.g., V1-V3) or from functional selectivity [e.g., shape-selective lateral occipital complex (LOC)]. We combined these approaches to explore the nature of shape representations through the visual hierarchy. Two different representations emerged: the first reflected low-level shape properties (dependent on the spatial layout of the shape outline), whereas the second captured more abstract curvature-related shape features. Critically, early visual cortex represented low-level information but this diminished in the extrastriate cortex (LO-1/LO-2/LOC), in which the abstract representation emerged. Therefore, this work further elucidates the nature of shape representations in the LOC, provides insight into how those representations emerge from early retinotopic cortex, and crucially demonstrates that retinotopically tuned regions (LO-1/LO-2) are not necessarily constrained to retinotopic representations., (Copyright © 2016 Vernon et al.)

Individual radial frequency (RF) patterns are generated by modulating a circle's radius as a sinusoidal function of polar angle and have been shown to tap into global shape processing mechanisms. Composite RF patterns can reproduce the complex outlines of natural shapes and examining these stimuli may allow us to interrogate global shape mechanisms that are recruited in biologically relevant tasks. We present evidence for a global shape aftereffect in a composite RF pattern stimulus comprising two RF components. Manipulations of the shape, location, size and spatial frequency of the stimuli revealed that this aftereffect could only be explained by the attenuation of intermediate-level global shape mechanisms. The tuning of the aftereffect to test stimulus size also revealed two mechanisms underlying the aftereffect; one that was tuned to size and one that was invariant. Finally, we show that these shape mechanisms may encode some RF information. However, the RF encoding we found was not capable of explaining the full extent of the aftereffect, indicating that encoding of other shape features such as curvature are also important in global shape processing.

Background: The optimal treatment for respiratory syncytial virus (RSV) infection in adult immunocompromised patients is unknown. We assessed the management of RSV and other non-influenza respiratory viruses in Midwestern transplant centers., Methods: A survey assessing strategies for RSV and other non-influenza respiratory viral infections was sent to 13 centers., Results: Multiplex polymerase chain reaction assay was used for diagnosis in 11/12 centers. Eight of 12 centers used inhaled ribavirin (RBV) in some patient populations. Barriers included cost, safety, lack of evidence, and inconvenience. Six of 12 used intravenous immunoglobulin (IVIG), mostly in combination with RBV. Inhaled RBV was used more than oral, and in the post-stem cell transplant population, patients with lower respiratory tract infection (LRTI), graft-versus-host disease, and more recent transplantation were treated at higher rates. Ten centers had experience with lung transplant patients; all used either oral or inhaled RBV for LRTI, 6/10 treated upper respiratory tract infection (URTI). No center treated non-lung solid organ transplant (SOT) recipients with URTI; 7/11 would use oral or inhaled RBV in the same group with LRTI. Patients with hematologic malignancy without hematopoietic stem cell transplantation were treated with RBV at a similar frequency to non-lung SOT recipients. Three of 12 centers, in severe cases, treated parainfluenza and metapneumovirus, and 1/12 treated coronavirus., Conclusions: Treatment of RSV in immunocompromised patients varied greatly. While most centers treat LRTI, treatment of URTI was variable. No consensus was found regarding the use of oral versus inhaled RBV, or the use of IVIG. The presence of such heterogeneity demonstrates the need for further studies defining optimal treatment of RSV in immunocompromised hosts., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: A 40-year-old man with chronic myelogenous leukemia presented multiple times over a period of 3 years with episodes of confusion, wide-based gait and falls because of recurrent hydrocephalus despite repeated therapeutic lumbar punctures. These problems occurred in the context of persistent cerebrospinal fluid (CSF) pleocytosis and leptomeningeal enhancement. Extensive diagnostic workups and therapeutic trials had failed to identify a clinically plausible cause or produce any significant improvement in the CSF and neuroimaging abnormalities., Methods: We used high-throughput metagenomic shotgun sequencing to identify microbes in 2 CSF samples collected from the patient during his illness. These results were compared to sequence data from 1 CSF sample collected during treatment and 5 control CSF samples from other patients., Results: We found sequences representing 53% and 67% of the Propionibacterium acnes genome in 2 CSF samples collected from the patient during his illness. Directed antimicrobial therapy was administered for 6 weeks with resolution of CSF and neuroimaging abnormalities. Sequencing of a sample obtained during treatment demonstrated that the P. acnes levels were decreased to background levels. After insertion of a ventriculo-peritoneal shunt, the patient returned to baseline status., Conclusions: High-throughput metagenomic shotgun sequencing revealed P. acnes as the cause of chronic meningitis that had eluded conventional attempts at diagnosis. Treatment directed at this organism resulted in cure of the infection and clinical improvement., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

A fundamental feature of community-based participatory research (CBPR) is sharing findings with community members and engaging community partners in the dissemination process. To be truly collaborative, dissemination should involve community members in a two-way dialogue about new research findings. Yet little literature describes how to engage communities in dialogue about research findings, especially with historically marginalized communities where mistrust of researchers may exist because of past or present social injustices. Through a series of interactive community presentations on findings from a longitudinal study, we developed a process for community dissemination that involved several overlapping phases: planning, outreach, content development, interactive presentations, and follow-up. Through this process, we built on existing and new community relationships. Following each interactive presentation, the research team debriefed and reviewed notes to identify lessons learned from the process. Key themes included the importance of creating a flexible dissemination plan, tailoring presentations to each community group, establishing a point person to serve as a community liaison, and continuing dialogue with community members after the presentations. Core strategies for developing trust during dissemination included engaging community members at every step, reserving ample time for discussion during presentations, building rapport by sharing personal experiences, being receptive to and learning from criticism, and implementing input from community members. This process led to a deeper understanding of research findings and ensured that results reached community members who were invested in them.

Objective The aim of the present study was to develop a robust model that uses the concept of 'rehabilitation-sensitive' Diagnosis Related Groups (DRGs) in predicting demand for rehabilitation and geriatric evaluation and management (GEM) care following acute in-patient episodes provided in Australian hospitals. Methods The model was developed using statistical analyses of national datasets, informed by a panel of expert clinicians and jurisdictional advice. Logistic regression analysis was undertaken using acute in-patient data, published national hospital statistics and data from the Australasian Rehabilitation Outcomes Centre. Results The predictive model comprises tables of probabilities that patients will require rehabilitation or GEM care after an acute episode, with columns defined by age group and rows defined by grouped Australian Refined (AR)-DRGs. Conclusions The existing concept of rehabilitation-sensitive DRGs was revised and extended. When applied to national data, the model provided a conservative estimate of 83% of the activity actually provided. An example demonstrates the application of the model for service planning. What is known about the topic? Health service planning is core business for jurisdictions and local areas. With populations ageing and an acknowledgement of the underservicing of subacute care, it is timely to find improved methods of estimating demand for this type of care. Traditionally, age-sex standardised utilisation rates for individual DRGs have been applied to Australian Bureau of Statistics (ABS) population projections to predict the future need for subacute services. Improved predictions became possible when some AR-DRGs were designated 'rehabilitation-sensitive'. This improved methodology has been used in several Australian jurisdictions. What does this paper add? This paper presents a new tool, or model, to predict demand for rehabilitation and GEM services based on in-patient acute activity. In this model, the methodology based on rehabilitation-sensitive AR-DRGs has been extended by updating them to AR-DRG Version 7.0, quantifying the level of 'sensitivity' and incorporating the patient's age to improve the prediction of demand for subacute services. What are the implications for practitioners? The predictive model takes the form of tables of probabilities that patients will require rehabilitation or GEM care after an acute episode and can be applied to acute in-patient administrative datasets in any Australian jurisdiction or local area. The use of patient-level characteristics will enable service planners to improve their forecasting of demand for these services. Clinicians and jurisdictional representatives consulted during the project regarded the model favourably and believed that it was an improvement on currently available methods.

The objective of this study was to investigate the observation of daptomycin resistance in Corynebacterium striatum, both in vivo and in vitro. We describe a case of C. striatum bacteremia in a patient with a left ventricular assist device (LVAD); the initial isolate recovered was daptomycin susceptible with a minimum inhibitory concentration (MIC) of 0.125 μg/ml. Two months later, and after daptomycin therapy, the individual became bacteremic with an isolate of C. striatum with a daptomycin MIC of >256 μg/ml. To study the prevalence of daptomycin resistance in C. striatum, clinical isolates of C. striatum were grown in broth culture containing daptomycin to investigate the emergence of resistance to this antimicrobial. Molecular typing was used to evaluate serial isolates from the index patient and the clinical isolates of C. striatum we assayed. In vitro analysis of isolates from the index patient and 7 of 11 additional C. striatum isolates exhibited the emergence of high-level daptomycin resistance, despite initially demonstrating low MICs to this antimicrobial agent. This phenotype was persistent even after serial subculture in the absence of daptomycin. Together, these data demonstrate that caution should be taken when using daptomycin to treat high-inoculum infections and/or infections of indwelling medical devices with C. striatum. To our knowledge, this is the first report characterizing the emergence of daptomycin resistance in C. striatum.

We identified 22 cases of influenza infection among renal transplant recipients and matched them with 66 controls by influenza season to explore risk factors for influenza infection. Active cigarette smoking was associated with influenza infection in this population (adjusted odds ratio 13.1; 95% confidence interval 2.3-76; P = 0.004)., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)