World Rabies Day - a decade of raising awareness

World Rabies Day was set up in 2007 to raise global awareness about rabies, to provide information on how to prevent the disease in at-risk communities and support advocacy for increased efforts in rabies control. It is held annually on September 28th, with events, media outreach and other initiatives carried out by individuals, professionals, organisations and governments from the local to the international level. The Global Alliance for Rabies Control coordinates World Rabies Day, amplifying the campaign's reach through the provision of a central event platform and resources to support events across the world, the promotion of messages through key rabies stakeholders, and the implementation of specific activities to highlight particular issues. Over the last decade, more than 1,700 registered events have been held across the world and shared with others in the global rabies community. Events in canine rabies endemic countries, particularly in Africa and Asia, have increased over time. Beyond the individual events, World Rabies Day has gained the support of governments and international agencies that recognise its value in supporting existing rabies control initiatives and advocating for improvements. As the rabies landscape has changed, World Rabies Day remains a general day of awareness but has also become an integral part of national, regional and global rabies elimination strategies. The global adoption of 2030 as the goal for the elimination of rabies as a public health threat has led to even greater opportunities for World Rabies Day to make a sustainable impact on rabies, by bringing the attention of policy makers and donors to the ongoing situation and elimination efforts in rabies-endemic countries

Retinoic Acid Differentially Regulates the Migration of Innate Lymphoid Cell Subsets to the Gut

SummaryDistinct groups of innate lymphoid cells (ILCs) such as ILC1, ILC2, and ILC3 populate the intestine, but how these ILCs develop tissue tropism for this organ is unclear. We report that prior to migration to the intestine ILCs first undergo a “switch” in their expression of homing receptors from lymphoid to gut homing receptors. This process is regulated by mucosal dendritic cells and the gut-specific tissue factor retinoic acid (RA). This change in homing receptors is required for long-term population and effector function of ILCs in the intestine. Only ILC1 and ILC3, but not ILC2, undergo the RA-dependent homing receptor switch in gut-associated lymphoid tissues. In contrast, ILC2 acquire gut homing receptors in a largely RA-independent manner during their development in the bone marrow and can migrate directly to the intestine. Thus, distinct programs regulate the migration of ILC subsets to the intestine for regulation of innate immunity

Exploring intentional medication non-adherence in patients with systemic lupus erythematosus: The role of physician-patient interactions

OBJECTIVE: Medication non-adherence contributes to worse health outcomes among SLE patients. The underlying mechanisms that drive medication non-adherence are poorly understood. The purpose of this study was to explore possible mechanisms of medication non-adherence by eliciting patient experiences. METHODS: Consented adult patients with ACR- or SLICC-classified SLE were recruited. Ten semi-structured interviews were conducted across six participants. Interviews were audio recorded, transcribed, and analysed using an iterative process. The findings were presented to an interactive public forum with SLE patients, family members and friends of patients, and health-care professionals to assess validity and for elaboration of the concepts developed. RESULTS: The following three interrelated themes emerged from the interviews. First, why do rheumatologists not know more about lupus or share what they do know with their patients? Second, why do I have to take so many drugs and why do the drugs not work? Third, if my rheumatologist cannot communicate with me, why should I follow the prescribed medication regimen? CONCLUSION: Our exploratory findings lay out a possible underlying logic by which patients might choose intentionally to engage with medication non-adherence behaviours. Patients suggested that poor communication with their rheumatologists along with a lack of validation of their symptoms contributed to them not valuing the recommendations of physicians. This also contributed to development of a cynical outlook and little belief that medication would improve their condition. Although further work is needed to validate these findings, our preliminary work suggests that interventions focusing on the development of communication skills among both patients and rheumatologists are necessary to reduce medication non-adherence

Development of a digital toolkit to improve quality of life of patients with systemic lupus erythematosus

OBJECTIVE: The purpose of this manuscript is to detail development and initial usability testing of an e-toolkit designed to provide skills and knowledge around self-management behaviors for individuals living with systemic lupus erythematosus. METHODS: Researchers worked with a steering committee of patients and providers to (1) develop a clickable prototype of an e-toolkit and (2) conduct alpha (individuals not affiliated with an academic clinic as patient or provider) and beta (individual patients with systemic lupus erythematosus as well as members of the clinic healthcare team and individuals who work in patient advocacy organizations) usability testing through semistructured interviews. RESULTS: During the review of the e-toolkit, the feedback provided by participants in both alpha and beta groups centered on two overarching themes: (1) improving user interface and materials and (2) integration of information and supports between toolkit and clinical personnel. CONCLUSION: Digital approaches that are tailored to individual symptom variation and integrated with a clinical system have the opportunity to enhance ongoing clinical care. These findings support movement toward integrated, team-based care models, tailored digital resources, and use of expanded virtual interaction options to ensure on-going engagement between healthcare providers and systemic lupus erythematosus patients

Mobile resistome of human gut and pathogen drives anthropogenic bloom of antibiotic resistance

BACKGROUND:The impact of human activities on the environmental resistome has been documented in many studies, but there remains the controversial question of whether the increased antibiotic resistance observed in anthropogenically impacted environments is just a result of contamination by resistant fecal microbes or is mediated by indigenous environmental organisms. Here, to determine exactly how anthropogenic influences shape the environmental resistome, we resolved the microbiome, resistome, and mobilome of the planktonic microbial communities along a single river, the Han, which spans a gradient of human activities. RESULTS:The bloom of antibiotic resistance genes (ARGs) was evident in the downstream regions and distinct successional dynamics of the river resistome occurred across the spatial continuum. We identified a number of widespread ARG sequences shared between the river, human gut, and pathogenic bacteria. These human-related ARGs were largely associated with mobile genetic elements rather than particular gut taxa and mainly responsible for anthropogenically driven bloom of the downstream river resistome. Furthermore, both sequence- and phenotype-based analyses revealed environmental relatives of clinically important proteobacteria as major carriers of these ARGs. CONCLUSIONS:Our results demonstrate a more nuanced view of the impact of anthropogenic activities on the river resistome: fecal contamination is present and allows the transmission of ARGs to the environmental resistome, but these mobile genes rather than resistant fecal bacteria proliferate in environmental relatives of their original hosts. Video abstract

Gambling and sexual behaviors in African-American adolescents

Objectives: Late adolescence represents a developmental risk period when many youth become involved in multiple forms of high-risk behaviors with adverse consequences. This study assessed the degree to which two such behaviors, adolescent sexual behaviors and gambling, were associated in a community-based sample with a large African-American presence. Study design: Data are derived from a cohort study. This study focuses on 427 African-American participants with complete information on gambling and sexual behaviors by age 18 (72% of original cohort). Gambling involvement and related problems were based on responses to the South Oaks Gambling Screen — Revised for Adolescents. Several questions assessed sexual behaviors, including age of initiation. Multivariable logistic regression models adjusted for demographics, intervention status, impulsivity, depressive and anxiety symptoms, and alcohol and illegal drug use. Results: Almost half of the sample (49%, n = 211) had gambled at least once before age 18. More gamblers than non-gamblers had initiated sexual intercourse by age 18 (aOR: 2.29 [1.16, 4.52]). Among those who had initiated sexual activity, more gamblers than non-gamblers with high impulsivity levels at age 13 (vs. low impulsivity levels) had become pregnant or had impregnated someone. Among those who had initiated sexual activity by age 18, more male gamblers had impregnated someone by age 18 as compared to female gamblers becoming pregnant. Conclusions: Gambling and sexual behaviors often co-occur among adolescents. Such findings prompt the need for the inclusion of gambling, an often overlooked risky behavior, in behavioral prevention/intervention programs targeting adolescents

Cervical Cancer in Women Aged 35 Years and Younger

AbstractPurposeAge has been evaluated as a prognostic factor in cervical cancer in both hospital- and population-based studies. Results regarding the relation of age and cervical cancer prognosis are conflicting. This study pursued a contemporary assessment of the association of extreme young age at the time of a cervical cancer diagnosis on survival.MethodsInstitutional review board approval was obtained, and retrospective data collection at 2 academic institutions was performed. Inclusion criteria involved women ≤35 years diagnosed with cervical cancer between 1990 and 2012. Data included demographic and prognostic information pertinent to survival and progression. Characteristics of very young (≤25 years) and young (>25–35 years) women were compared. Kaplan-Meier estimates, the log-rank test, and Cox proportional hazards modeling were used to assess the association of age, tumor histology, grade, stage, and parametrial involvement with progression-free survival (PFS) and overall survival (OS).FindingsIncident cases (n = 126) of cervical cancer in patients ≤35 years of age were identified of which complete clinical information was available for 114 women. Fifteen percent (17 of 114) were ≤25 years, with the remaining 85% (97 of 114) being 26 to 35 years of age. Race, smoking status, and marital status were comparable between the 2 groups. Squamous histology dominated overall (77 of 114; 68%) with adenocarcinoma contributing ~25% (30 of 114; 26%) of cases. The majority (96 of 114, 84%) had either stage 1A (31 of 114, 27%) or 1B (65 of 114, 57%) disease. A log-rank test revealed no evidence to infer a difference in either PFS or OS among the age groups (P = 0.511 and P = 0.340). In a univariate analysis, grade and stage significantly affected OS (P < 0.0001, P = 0.045), and stage significantly affected PFS (P < 0.0001). In multivariate modeling, presence of parametrial involvement and histologic cancer type significantly affected both PFS (P = 0.002, P = 0.001) and OS (P = 0.001, P = 0.001).ImplicationsTumor histology, parametrial involvement, and stage continue to be strong prognosticators for PFS and OS. Progression and survival outcomes are age independent in women with cervical cancer ≤35 years of age. Further study of a larger young cohort may potentially yield different outcomes

A Multicenter Observer Performance Study of 3D JPEG2000 Compression of Thin-Slice CT

The goal of this study was to determine the compression level at which 3D JPEG2000 compression of thin-slice CTs of the chest and abdomen–pelvis becomes visually perceptible. A secondary goal was to determine if residents in training and non-physicians are substantially different from experienced radiologists in their perception of compression-related changes. This study used multidetector computed tomography 3D datasets with 0.625–1-mm thickness slices of standard chest, abdomen, or pelvis, clipped to 12 bits. The Kakadu v5.2 JPEG2000 compression algorithm was used to compress and decompress the 80 examinations creating four sets of images: lossless, 1.5 bpp (8:1), 1 bpp (12:1), and 0.75 bpp (16:1). Two randomly selected slices from each examination were shown to observers using a flicker mode paradigm in which observers rapidly toggled between two images, the original and a compressed version, with the task of deciding whether differences between them could be detected. Six staff radiologists, four residents, and six PhDs experienced in medical imaging (from three institutions) served as observers. Overall, 77.46% of observers detected differences at 8:1, 94.75% at 12:1, and 98.59% at 16:1 compression levels. Across all compression levels, the staff radiologists noted differences 64.70% of the time, the resident’s detected differences 71.91% of the time, and the PhDs detected differences 69.95% of the time. Even mild compression is perceptible with current technology. The ability to detect differences does not equate to diagnostic differences, although perception of compression artifacts could affect diagnostic decision making and diagnostic workflow

Effect of Intravenous Golimumab on Fatigue and the Relationship with Clinical Response in Adults with Active Ankylosing Spondylitis in the Phase 3 GO-ALIVE Study

INTRODUCTION: We studied the effect of intravenous (IV)-golimumab on fatigue and the association of fatigue improvement with clinical response post hoc in adults with active ankylosing spondylitis (AS) in the GO-ALIVE trial. METHODS: Patients were randomized to IV-golimumab 2 mg/kg (N = 105) at week (W) 0, W4, then every 8 W (Q8W) or placebo (N = 103) at W0, W4, W12, crossover to IV-golimumab 2 mg/kg at W16, W20, then Q8W through W52. Fatigue measures included Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question #1 (fatigue; 0 [none], 10 [worst]; decrease indicates improvement) and 36-Item Short Form Health Survey (SF-36) vitality subscale (0 [worst], 100 [best]; increase indicates improvement). Minimum clinically important difference is ≥ 1 for BASDAI-fatigue and ≥ 5 for SF-36 vitality. GO-ALIVE primary endpoint was Assessment of SpondyloArthritis international Society ≥ 20% improvement criteria (ASAS20). Other clinical outcomes assessed included other ASAS responses, Ankylosing Spondylitis Disease Activity Score, and Bath Ankylosing Spondylitis Functional Index score. The distribution-based minimally important differences (MIDs) were determined for BASDAI-fatigue and SF-36 vitality. The relationship between improvement in fatigue and clinical outcomes was assessed via multivariable logistic regression. RESULTS: Mean changes in BASDAI-fatigue/SF-36 vitality scores were greater with IV-golimumab versus placebo at W16 (- 2.74/8.46 versus - 0.73/2.08, both nominal p ≤ 0.003); by W52 (after crossover), differences between groups narrowed (- 3.18/9.39 versus - 3.07/9.17). BASDAI-fatigue/SF-36 vitality MIDs were achieved by greater proportions of IV-golimumab-treated versus placebo-treated patients at W16 (75.2%/71.4% versus 42.7%/35.0%). A one-point/five-point improvement in BASDAI-fatigue/SF-36 vitality scores at W16 increased likelihood of achieving ASAS20 (odds ratios [95% confidence intervals]: 3.15 [2.21, 4.50] and 2.10 [1.62, 2.71], respectively) and ASAS40 (3.04 [2.15, 4.28] and 2.24 [1.68, 3.00], respectively) responses at W16; concurrent improvements and clinical response at W52 were consistent. A one-point/five-point improvement in BASDAI-fatigue/SF-36 vitality scores at W16 predicted increased likelihood of achieving ASAS20 (1.62 [1.35, 1.95] and 1.52 [1.25, 1.86], respectively) and ASAS40 (1.62 [1.37, 1.92] and 1.44 [1.20, 1.73], respectively) responses at W52. CONCLUSIONS: IV-golimumab provided important and sustained fatigue improvement in patients with AS that positively associated with achieving clinical response. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02186873