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Central retinal artery occlusion (CRAO; retinal stroke or eye stroke) is an under-recognized, disabling form of acute ischemic stroke which causes severe visual loss in one eye. The classical risk factor for CRAO is ipsilateral carotid stenosis; however, nearly half of patients with CRAO do not have high-grade carotid stenosis, suggesting that other cardiovascular risk factors may exist for CRAO. Specifically, prior studies have suggested that cardioembolism, driven by underlying atrial fibrillation, may predispose patients to CRAO. We describe the design of an observational, population-based study in this protocol. We evaluate two specific objectives: 1) To determine if atrial fibrillation is an independent risk factor for CRAO after adjusting for medical and cardiovascular risk; 2) To determine if use of oral anticoagulation can modify the risk of CRAO for patients with atrial fibrillation. This protocol lays out our strategy for cohort definition, case and control definition, comorbidity ascertainment, and statistical methods.

Introduction Parkinson’s prevalence is growing, and more people are being impacted by the condition than ever before. Self-management has been proposed as one way to enable people living with the condition to improve or maintain their quality of life and wellbeing whilst living at home. Aim To explore the views and experiences of how people living with Parkinson’s self-manage their condition and identify areas needed to be incorporated into self-management resources or interventions. Method Twenty people with Parkinson’s from across London and Hertfordshire, UK took part in semi-structured interviews on self-management. Interviews were transcribed and analysed using thematic analysis to identify themes. Results Three main themes were identified: (1) Management of physical symptoms, which included engaging in physical activities, adapting their lifestyles, managing medication and using e-health resources; (2) Management of emotional impact, which involved using a range of cognitive and practical strategies, and seeking talking therapies and medication; and (3) barriers to self-management such as accessing accurate information, experiencing stigma towards their condition which impacted their self-esteem and identity, in turn impacting on their ability to self-manage. Conclusion Holistic and person-centred self-management programmes or interventions should be developed incorporating components such as medication and emotional support, individualised planning of exercise regimes, and accessible, timely and accurate information. Furthermore, more public health knowledge on Parkinson’s is needed to help reduce stigma.

Central retinal artery occlusion (CRAO; retinal stroke or eye stroke) is an under-recognized, disabling form of acute ischemic stroke which causes severe visual loss in one eye. The classical risk factor for CRAO is ipsilateral carotid stenosis; however, nearly half of patients with CRAO do not have high-grade carotid stenosis, suggesting that other cardiovascular risk factors may exist for CRAO. Specifically, prior studies have suggested that cardioembolism, driven by underlying atrial fibrillation, may predispose patients to CRAO. We describe the design of an observational, population-based study in this protocol. We evaluate two specific objectives: 1) To determine if atrial fibrillation is an independent risk factor for CRAO after adjusting for medical and cardiovascular risk; 2) To determine if use of oral anticoagulation can modify the risk of CRAO for patients with atrial fibrillation. This protocol lays out our strategy for cohort definition, case and control definition, comorbidity ascertainment, and statistical methods. [ABSTRACT FROM AUTHOR]

Maternal group B streptococcal (GBS) vaccines under development hold promise to prevent GBS disease in young infants. Sub-Saharan Africa has the highest estimated disease burden, although data on incidence and circulating strains are limited. We described invasive bacterial disease (IBD) trends among infants

When traversing through an aperture, such as a doorway, people characteristically deviate towards the right. This rightward deviation can be explained by a rightward attentional bias which leads to rightward bisections in far space. It is also possible, however, that left or right driving practices affect the deviation. To explore this possibility, Australian (left-side drivers) and Swiss (right-side drivers) participants (n = 36 & 34) walked through the middle of an aperture. To control for the sway of the body, participants started with either their left or right foot. Sway had a significant effect on participants' position in the doorway and the amount of sway was greater for Australians-perhaps due to national differences in gait. There was a significant rightward deviation for the Swiss, but not for the Australians. It is suggested that driving practices have a small additive effect on rightward attentional biases whereby the bias is increased for people who drive on the right and reduced in people who drive on the left.

The ability to mentalize has been marked as an important cognitive mechanism enabling belief in supernatural agents. In five studies we cross-culturally investigated the relationship between mentalizing and belief in supernatural agents with large sample sizes (over 67,000 participants in total) and different operationalizations of mentalizing. The relative importance of mentalizing for endorsing supernatural beliefs was directly compared with credibility enhancing displays-the extent to which people observed credible religious acts during their upbringing. We also compared autistic with neurotypical adolescents. The empathy quotient and the autism-spectrum quotient were not predictive of belief in supernatural agents in all countries (i.e., The Netherlands, Switzerland and the United States), although we did observe a curvilinear effect in the United States. We further observed a strong influence of credibility enhancing displays on belief in supernatural agents. These findings highlight the importance of cultural learning for acquiring supernatural beliefs and ask for reconsiderations of the importance of mentalizing.

Data on neonatal group B streptococcal (GBS) invasive disease burden are needed to refine prevention policies. Differences in surveillance methods and investigating for cases can lead to varying disease burden estimates. We compared the findings of laboratory-based passive surveillance for GBS disease across South Africa, and for one of the provinces compared this to a real-time, systematic, clinical surveillance in a population-defined region in Johannesburg, Soweto. Passive surveillance identified a total of 799 early-onset disease (EOD,

Studies indicated that people behave less responsibly after exposure to information containing deterministic statements as compared to free will statements or neutral statements. Thus, deterministic primes should lead to enhanced risk-taking behavior. We tested this prediction in two studies with healthy participants. In experiment 1, we tested 144 students (24 men) in the laboratory using the Iowa Gambling Task. In experiment 2, we tested 274 participants (104 men) online using the Balloon Analogue Risk Task. In the Iowa Gambling Task, the free will priming condition resulted in more risky decisions than both the deterministic and neutral priming conditions. We observed no priming effects on risk-taking behavior in the Balloon Analogue Risk Task. To explain these unpredicted findings, we consider the somatic marker hypothesis, a gain frequency approach as well as attention to gains and / or inattention to losses. In addition, we highlight the necessity to consider both pro free will and deterministic priming conditions in future studies. Importantly, our and previous results indicate that the effects of pro free will and deterministic priming do not oppose each other on a frequently assumed continuum.

Household air pollution (HAP) from biomass fuel burning is linked to poor health outcomes. Improved biomass cookstoves (ICS) have the potential to improve HAP.A pre-/post- intervention study assessed the impact of six ICS on indoor air quality and acceptability of ICS to local users in rural Western Kenya.We measured mean personal and kitchen level concentrations of particulate matter

Identification of etiology remains a significant challenge in the diagnosis of infectious diseases, particularly in resource-poor settings. Viral, bacterial, and fungal pathogens, as well as parasites, play a role for many syndromes, and optimizing a single diagnostic system to detect a range of pathogens is challenging. The TaqMan Array Card (TAC) is a multiple-pathogen detection method that has previously been identified as a valuable technique for determining etiology of infections and holds promise for expanded use in clinical microbiology laboratories and surveillance studies. We selected TAC for use in the Aetiology of Neonatal Infection in South Asia (ANISA) study for identifying etiologies of severe disease in neonates in Bangladesh, India, and Pakistan. Here we report optimization of TAC to improve pathogen detection and overcome technical challenges associated with use of this technology in a large-scale surveillance study. Specifically, we increased the number of assay replicates, implemented a more robust RT-qPCR enzyme formulation, and adopted a more efficient method for extraction of total nucleic acid from blood specimens. We also report the development and analytical validation of ten new assays for use in the ANISA study. Based on these data, we revised the study-specific TACs for detection of 22 pathogens in NP/OP swabs and 12 pathogens in blood specimens as well as two control reactions (internal positive control and human nucleic acid control) for each specimen type. The cumulative improvements realized through these optimization studies will benefit ANISA and perhaps other studies utilizing multiple-pathogen detection approaches. These lessons may also contribute to the expansion of TAC technology to the clinical setting.

To determine the maximum tolerated dose (MTD) and safety, and explore efficacy and biomarkers of vandetanib with cetuximab and irinotecan in second-line metastatic colorectal cancer.Vandetanib (an orally bioavailable VEGFR-2 and EGFR tyrosine kinases inhibitor) was combined at 100 mg, 200 mg, or 300 mg daily with standard dosed cetuximab and irinotecan (3+3 dose-escalation design). Ten patients were treated at the MTD and plasma angiogenesis biomarkers (VEGF, PlGF, bFGF, sVEGFR1, sVEGFR2, IL-1β, IL-6, IL-8, TNF-α, SDF1α) were measured before and after treatment.Twenty-seven patients were enrolled at 4 dose levels and the MTD. Two dose-limiting toxicities (grade 3 QTc prolongation and diarrhea) were detected at 300 mg of vandetanib with cetuximab and irinotecan resulting in 200 mg being the MTD. Seven percent of patients had a partial response, 59% stable disease and 34% progressed. Median progression-free survival was 3.6 months (95% CI, 3.2-5.6) and median overall survival was 10.5 months (95% CI, 5.1-20.7). Toxicities were fairly manageable with grade 3 or 4 diarrhea being most prominent (30%). Vandetanib and cetuximab treatment induced a sustained increase in plasma PlGF and a transient decrease in plasma sVEGFR1, but no changes in plasma VEGF and sVEGFR2.Vandetanib can be safely combined with cetuximab and irinotecan for metastatic colorectal cancer. Exploratory biomarker analyses suggest differential effects on certain plasma biomarkers for VEGFR inhibition when combined with EGFR blockade and a potential correlation between baseline sVEGFR1 and response. However, while the primary endpoint was safety, the observed efficacy raises concern for moving forward with this combination.Clinicaltrials.gov NCT00436072.

Serotype-specific polysaccharide based group B streptococcus (GBS) vaccines are being developed. An understanding of the serotype epidemiology associated with maternal colonization and invasive disease in infants is necessary to determine the potential coverage of serotype-specific GBS vaccines.Colonizing GBS isolates were identified by vaginal swabbing of mothers during active labor and from skin of their newborns post-delivery. Invasive GBS isolates from infants were identified through laboratory-based surveillance. GBS serotyping was done by latex agglutination. Serologically non-typeable isolates were typed by a serotype-specific PCR method. The invasive potential of GBS serotypes associated with sepsis within seven days of birth was evaluated in association to maternal colonizing serotypes.GBS was identified in 289 (52.4%) newborns born to 551 women with GBS-vaginal colonization and from 113 (5.6%) newborns born to 2,010 mothers in whom GBS was not cultured from vaginal swabs. The serotype distribution among vaginal-colonizing isolates was as follows: III (37.3%), Ia (30.1%), and II (11.3%), V (10.2%), Ib (6.7%) and IV (3.7%). There were no significant differences in serotype distribution between vaginal and newborn colonizing isolates (P = 0.77). Serotype distribution of invasive GBS isolates were significantly different to that of colonizing isolates (P

BackgroundThe COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments.MethodsElectronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined.ResultsNeither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events.ConclusionAdministration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.

IntroductionThe carotid web is a compelling potential mechanism of embolic ischemic stroke. In this study, we aim to determine the prevalence of ipsilateral carotid web in a cohort of ischemic stroke patients and to perform a systematic review and meta-analysis of similar cohorts.Patients & methodsWe performed a retrospective, observational, cohort study of acute ischemic stroke patients admitted to a comprehensive stroke center from June 2012 to September 2017. Carotid web was defined on computed tomography angiography (CTA) as a thin shelf of non-calcified tissue immediately distal to the carotid bifurcation. We described the prevalence of carotid artery webs in our cohort, then performed a systematic review and meta-analysis of similar cohorts in the published literature.ResultsWe identified 1,435 potentially eligible patients of whom 879 met criteria for inclusion in our analysis. An ipsilateral carotid web was detected in 4 out of 879 (0.45%) patients, of which 4/4 (1.6%) were in 244 patients with cryptogenic stroke and 3/4 were in 66 (4.5%) patients DiscussionCarotid webs are more common in young patients with cryptogenic stroke than in other stroke subtypes. Future studies concerning the diagnosis and secondary prevention of stroke associated with carotid web should focus on this population.

BackgroundGlobally, over 400,000 neonatal deaths in 2015 were attributed to sepsis, however, the incidence and etiologies of these infections are largely unknown in low-middle income countries. We aimed to determine incidence and etiology of community-acquired early-onset (MethodsThis was a prospective observational study, in which we conducted a surveillance for pathogens using a combination of blood culture and a polymerase chain reaction (PCR)-based test. Blood culture was performed on all neonates with suspected EOS. Among the subset fulfilling criteria for protocol-defined EOS, blood and nasopharyngeal (NP) respiratory swabs were tested by quantitative real-time reverse-transcriptase PCR using a Taqman Array Card (TAC) with 15 bacterial and 12 viral targets. Blood and NP samples from 312 healthy newborns were also tested by TAC to estimate background positivity rates. We used variant latent-class methods to attribute etiologies and calculate pathogen-specific proportions and incidence rates.ResultsWe enrolled 2,624 neonates with suspected EOS and from these 1,231 newborns met criteria for protocol-defined EOS (incidence- 39.3/1,000 live-births). Using the partially latent-class modelling, only 26.7% cases with protocol-defined EOS had attributable etiology, and the largest pathogen proportion were Ureaplasma spp. (5.4%; 95%CI: 3.6-8.0) and group B Streptococcus (GBS) (4.8%; 95%CI: 4.1-5.8), and no etiology was attributable for 73.3% of cases. Blood cultures were positive in 99/1,231 (8.0%) with protocol-defined EOS (incidence- 3.2/1,000 live-births). Leading pathogens on blood culture included GBS (35%) and viridans streptococci (24%). Ureaplasma spp. was the most common organism identified on TAC among cases with protocol-defined EOS.ConclusionUsing a combination of blood culture and a PCR-based test the common pathogens isolated in neonates with sepsis were Ureaplasma spp. and GBS. Despite documenting higher rates of protocol-defined EOS and using a combination of tests, the etiology for EOS remains elusive.

Detection of clusters of Legionnaires' disease, a leading waterborne cause of pneumonia, is challenging. Clusters vary in size and scope, are associated with a diverse range of aerosol-producing devices, including exposures such as whirlpool spas and hotel water systems typically associated with travel, and can occur without an easily identified exposure source. Recently, jurisdictions have begun to use SaTScan spatio-temporal analysis software prospectively as part of routine cluster surveillance. We used data collected by the Active Bacterial Core surveillance platform to assess the ability of SaTScan to detect Legionnaires' disease clusters. We found that SaTScan analysis using traditional surveillance data and geocoded residential addresses was unable to detect many common Legionnaires' disease cluster types, such as those associated with travel or a prolonged time between cases. Additionally, signals from an analysis designed to simulate a real-time search for clusters did not align with clusters identified by traditional surveillance methods or a retrospective SaTScan analysis. A geospatial analysis platform better tailored to the unique characteristics of Legionnaires' disease epidemiology would improve cluster detection and decrease time to public health action.

AimTo explore experiences of health services and unmet care needs by people with late-stage Parkinson's in England.MethodTen participants, at Hoehn and Yahr stage 4 or 5, were interviewed using semi-structured open-ended questions. Data were analysed using qualitative thematic analysis.FindingsParticipants reported that whilst under the treatment of specialist hospitals, the majority of care provision had shifted into the community, often because hospital-based services were felt to be difficult to access and have limited benefit to them. When using health-care services, participants frequently experienced having to 'fit-in' to service structures that did not always accommodate their complex needs. Despite high levels of disability, participants expressed their desire to maintain their identity, normality of interests and activities in their lives, including remaining in their own homes. This was facilitated by bespoke care and equipment, and positive relationships with care providers. Knowledge on disease management was a key factor in their perceived ability to remain in control. Family caregivers had a central role in facilitating care at home. There was uncertainty about and little planning for the future, and moving to a residential nursing home was perceived an undesirable but potentially necessary option for future care.ConclusionUnmet care needs identified by people with late stage Parkinson's in England include greater flexibility of healthcare structures and bespoke service provision, to accommodate their individual complex needs. Support in their own homes and positive relationships with healthcare providers help People with Parkinson's (PwP) to maintain a degree of normality and identity, and provision of information help them maintain some control. There is a need for more informed discussions on future care planning for this specific population.