Incidence of Venous Thromboembolism in Critically Ill Coronavirus Disease 2019 Patients Receiving Prophylactic Anticoagulation

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Objectives: One of the defining features of the novel coronavirus disease 2019 infection has been high rates of venous thromboses. The present study aimed to describe the prevalence of venous thromboembolism in critically ill patients receiving different regimens of prophylactic anticoagulation. Design: Single-center retrospective review using data from patients with confirmed severe acute respiratory syndrome coronavirus 2 requiring intubation. Setting: Tertiary-care center in Indianapolis, IN, United States. Patients: Patients hospitalized at international units Health Methodist Hospital with severe acute respiratory syndrome coronavirus 2 requiring intubation between March 23, 2020, and April 8, 2020, who underwent ultrasound evaluation for venous thrombosis. Interventions: None. Measurements and Main Results: A total of 45 patients were included. Nineteen of 45 patients (42.2%) were found to have deep venous thrombosis. Patients found to have deep venous thrombosis had no difference in time to intubation (p = 0.97) but underwent ultrasound earlier in their hospital course (p = 0.02). Sequential Organ Failure Assessment scores were similar between the groups on day of intubation and day of ultrasound (p = 0.44 and p = 0.07, respectively). d-dimers were markedly higher in patients with deep venous thrombosis, both for maximum value and value on day of ultrasound (p < 0.01 for both). Choice of prophylactic regimen was not related to presence of deep venous thrombosis (p = 0.35). Ultrasound evaluation is recommended if d-dimer is greater than 2,000 ng/mL (sensitivity 95%, specificity 46%) and empiric anticoagulation considered if d-dimer is greater than 5,500 ng/mL (sensitivity 53%, specificity 88%). Conclusions: Deep venous thrombosis is very common in critically ill patients with coronavirus disease 2019. There was no difference in incidence of deep venous thrombosis among different pharmacologic prophylaxis regimens, although our analysis is limited by small sample size. d-dimer values are elevated in the majority of these patients, but there may be thresholds at which screening ultrasound or even empiric systemic anticoagulation is indicated.Dr. Khan’s institution received funding from the National Institutes of Health. The remaining authors have disclosed that they do not have any potential conflicts of interest

Diets of the Barents Sea cod (Gadus morhua) from the 1930s to 2018

A new dataset on the diet of Atlantic cod in the Barents Sea from the 1930s to the present day has been compiled to produce one of the largest fish diet datasets available globally. Atlantic cod is one of the most ecologically and commercially important fish species in the North Atlantic. The stock in the Barents Sea is by far the largest, as a result of both successful management and favourable environmental conditions since the early 2000s. As a top predator, cod plays a key role in the Barents Sea ecosystem. The species has a broad diet consisting mainly of crustaceans and teleost fish, and both the amount and type of prey vary in space and time. The data – from Russia, Norway and the United Kingdom – represent quantitative stomach content records from more than 400 000 fish and qualitative data from 2.5 million fish. Many of the data are from joint collaborative surveys between Norway and Russia. The sampling was conducted throughout each year, allowing for seasonal, annual and decadal comparisons to be made. Visual analysis shows cod diets have changed considerably from the start of the dataset in the 1930s to the present day. There was a large proportion of herring in the diets in the 1930s, whereas in more recent decades capelin, invertebrates and other fish dominate. There are also significant interannual asynchronous fluctuations in prey, particularly capelin and euphausiids. Combining these datasets can help us understand how the environment and ecosystems are responding to climatic changes, and what influences the diet and prey switching of cod. Trends in temperature and variability indices can be tested against the occurrence of different prey items, and the effects of fishing pressure on cod and prey stocks on diet composition could be investigated. The dataset will also enable us to improve parametrization of food web models and to forecast how Barents Sea fisheries may respond in the future to management and to climate change. The Russian data are available through joint projects with the Polar Branch of the Russian Federal Research Institute of Fisheries and Oceanography (VNIRO).publishedVersio

The acceptability and usability of two HIV self‐test kits among men who have sex with men: a randomised crossover trial

Objectives: To compare the usability and acceptability of oral fluid- and blood-based HIV self-test kits among men who have sex with men in Australia. Design: Randomised crossover trial. Setting, participants: Gay, bisexual, and other men aged 18 years or older who have sex with men, who attended two metropolitan sexual health clinics in Sydney and Melbourne, 7 January – 10 December 2019. Main outcome measures: Ease of use of HIV self-test kits; preferred HIV self-test type; difficulties encountered during HIV self-testing. Results: 170 men were recruited (median age, 34 years; interquartile range, 29–43 years); 144 identified as gay (85%), 96 were born outside Australia (57%). Participants were more likely to report the oral fluid HIV self-test was easy to use than the blood-based self-test (oral fluid, 99%; blood, 86%; odds ratio [OR], 3.0; 95% confidence interval [CI], 1.4–6.6). The oral fluid test was preferred by 98 participants (58%; 95% CI, 50–65%), the blood-based test by 69 (41%; 95% CI, 33–48%). Difficulties with the oral fluid test kit identified by observing nurses included problems placing the buffer solution into the stand (40 of 170 participants, 24%) and not swabbing both gums (23 of 169, 14%); difficulties with the blood-based test kit included problems filling the device test channel (69 of 170, 41%) and squeezing the finger firmly enough to generate a blood drop (42 of 170, 25%). No participant received an invalid result with the oral fluid self-test; two of 162 participants (1%) received invalid results with the blood self-test. After adjusting for age, education level, and ethnic background, characteristics associated with higher odds of using HIV self-testing in the future were overseas birth (adjusted OR, 3.07; 95% CI, 1.42–6.64), and self-evaluated ease of use and confidence in using the kits. Conclusion: It is important to provide options for obtaining both oral fluid- and blood-based HIV self-tests. The usability and acceptability of both kits were high, but the ease of use and perceived accuracy influenced test kit preference

Molecular diagnosis of scabies using a novel probe-based polymerase chain reaction assay targeting high-copy number repetitive sequences in the Sarcoptes scabiei genome

Background The suboptimal sensitivity and specificity of available diagnostic methods for scabies hampers clinical management, trials of new therapies and epidemiologic studies. Additionally, parasitologic diagnosis by microscopic examination of skin scrapings requires sample collection with a sharp scalpel blade, causing discomfort to patients and difficulty in children. Polymerase chain reaction (PCR)-based diagnostic assays, combined with non-invasive sampling methods, represent an attractive approach. In this study, we aimed to develop a real-time probe-based PCR test for scabies, test a non-invasive sampling method and evaluate its diagnostic performance in two clinical settings. Methodology/Principal findings High copy-number repetitive DNA elements were identified in draft Sarcoptes scabiei genome sequences and used as assay targets for diagnostic PCR. Two suitable repetitive DNA sequences, a 375 base pair microsatellite (SSR5) and a 606 base pair long tandem repeat (SSR6), were identified. Diagnostic sensitivity and specificity were tested using relevant positive and negative control materials and compared to a published assay targeting the mitochondrial cox1 gene. Both assays were positive at a 1:100 dilution of DNA from a single mite; no amplification was observed in DNA from samples from 19 patients with other skin conditions nor from house dust, sheep or dog mites, head and body lice or from six common skin bacterial and fungal species. Moderate sensitivity of the assays was achieved in a pilot study, detecting 5/7 (71.4% [95% CI: 29.0% - 96.3%]) of clinically diagnosed untreated scabies patients). Greater sensitivity was observed in samples collected by FLOQ swabs compared to skin scrapings. Conclusions/Significance This newly developed qPCR assay, combined with the use of an alternative non-invasive swab sampling technique offers the possibility of enhanced diagnosis of scabies. Further studies will be required to better define the diagnostic performance of these tests

Aberrant brain responses to emotionally valent words is normalised after cognitive behavioural therapy in female depressed adolescents.

BACKGROUND: Depression in adolescence is debilitating with high recurrence in adulthood, yet its pathophysiological mechanism remains enigmatic. To examine the interaction between emotion, cognition and treatment, functional brain responses to sad and happy distractors in an affective go/no-go task were explored before and after Cognitive Behavioural Therapy (CBT) in depressed female adolescents, and healthy participants. METHODS: Eighty-two Depressed and 24 healthy female adolescents, aged 12-17 years, performed a functional magnetic resonance imaging (fMRI) affective go/no-go task at baseline. Participants were instructed to withhold their responses upon seeing happy or sad words. Among these participants, 13 patients had CBT over approximately 30 weeks. These participants and 20 matched controls then repeated the task. RESULTS: At baseline, increased activation in response to happy relative to neutral distractors was observed in the orbitofrontal cortex in depressed patients which was normalised after CBT. No significant group differences were found behaviourally or in brain activation in response to sad distractors. Improvements in symptoms (mean: 9.31, 95% CI: 5.35-13.27) were related at trend-level to activation changes in orbitofrontal cortex. LIMITATIONS: In the follow-up section, a limited number of post-CBT patients were recruited. CONCLUSIONS: To our knowledge, this is the first fMRI study addressing the effect of CBT in adolescent depression. Although a bias toward negative information is widely accepted as a hallmark of depression, aberrant brain hyperactivity to positive distractors was found and normalised after CBT. Research, assessment and treatment focused on positive stimuli could be a future consideration. Moreover, a pathophysiological mechanism distinct from adult depression may be suggested and awaits further exploration.The study was funded by the Medial Research Council (grant: G0802226). The IMPACT clinical trial was funded by the NHS Health Technology Assessment (HTA) Programme, Central Manchester and Manchester Children's University Hospitals NHS Trust, and the Cambridge and Peterborough Mental Health Trust. Additional support was provided by the jointly funded Medical Research Council/Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.jad.2015.09.00

The longer-term effects of access to HIV self-tests on HIV testing frequency in high-risk gay and bisexual men: follow-up data from a randomised controlled trial

Background: A wait-list randomised controlled trial in Australia (FORTH) in high-risk gay and bisexual men (GBM) showed access to free HIV self-tests (HIVSTs) doubled the frequency of HIV testing in year 1 to reach guideline recommended levels of 4 tests per year, compared to two tests per year in the standard-care arm (facility-based testing). In year 2, men in both arms had access to HIVSTs. We assessed if the effect was maintained for a further 12 months. Methods: Participants included GBM reporting condomless anal intercourse or > 5 male partners in the past 3 months. We included men who had completed at least one survey in both year 1 and 2 and calculated the mean tests per person, based on the validated self-report and clinic records. We used Poisson regression and random effects Poisson regression models to compare the overall testing frequency by study arm, year and testing modality (HIVST/facility-based test). Findings: Overall, 362 men completed at least one survey in year 1 and 343 in year 2. Among men in the intervention arm (access to HIVSTs in both years), the mean number of HIV tests in year 2 (3⋅7 overall, 2⋅3 facility-based tests, 1⋅4 HIVSTs) was lower compared to year 1 (4⋅1 overall, 1⋅7 facility-based tests, 2⋅4 HIVSTs) (RR:0⋅84, 95% CI:0⋅75-0⋅95, p=0⋅002), but higher than the standard-care arm in year 1 (2⋅0 overall, RR:1⋅71, 95% CI:1⋅48-1.97, p<0⋅001). Findings were not different when stratified by sociodemographic characteristics or recent high risk sexual history. Interpretation: In year 2, fewer HIVSTs were used on average compared to year 1, but access to free HIVSTs enabled more men to maintain higher HIV testing frequency, compared with facility-based testing only. HIV self-testing should be a key component of HIV testing and prevention strategies. Funding:: This work was supported by grant 568971 from the National Health and Medical Research Council of Australia

STEPWISE - STructured lifestyle Education for People WIth SchizophrEnia : a study protocol for a randomised controlled trial

BACKGROUND: People with schizophrenia are two to three times more likely to be overweight than the general population. The UK National Institute of Health and Care Excellence (NICE) recommends an annual physical health review with signposting to, or provision of, a lifestyle programme to address weight concerns and obesity. The purpose of this randomised controlled trial is to assess whether a group-based structured education programme can help people with schizophrenia to lose weight. METHODS: Design: a randomised controlled trial of a group-based structured education programme. SETTING: 10 UK community mental health trusts. PARTICIPANTS: 396 adults with schizophrenia, schizoaffective, or first-episode psychosis who are prescribed antipsychotic medication will be recruited. Participants will be overweight, obese or be concerned about their weight. INTERVENTION: participants will be randomised to either the intervention or treatment as usual (TAU). The intervention arm will receive TAU plus four 2.5-h weekly sessions of theory-based lifestyle structured group education, with maintenance contact every 2 weeks and 'booster' sessions every 3 months. All participants will receive standardised written information about healthy eating, physical activity, alcohol and smoking. OUTCOMES: the primary outcome is weight (kg) change at 1 year post randomisation. Secondary outcomes, which will be assessed at 3 and 12 months, include: the proportion of participants who maintained or reduced their weight; waist circumference; body mass index; objectively measured physical activity (wrist accelerometer); self-reported diet; blood pressure; fasting plasma glucose, lipid profile and HbA1c (baseline and 1 year only); health-related quality of life (EQ-5D-5L and RAND SF-36); (adapted) brief illness perception questionnaire; the Brief Psychiatric Rating Scale; the Client Service Receipt Inventory; medication use; smoking status; adverse events; depression symptoms (Patient Health Questionnaire-9); use of weight-loss programmes; and session feedback (intervention only). Outcome assessors will be blind to trial group allocation. Qualitative interviews with a subsample of facilitators and invention-arm participants will provide data on intervention feasibility and acceptability. Assessment of intervention fidelity will also be performed. DISCUSSION: The STEPWISE trial will provide evidence for the clinical and cost-effectiveness of a tailored intervention, which, if successful, could be implemented rapidly in the NHS. TRIAL REGISTRATION: ISRCTN19447796 , registered on 20 March 2014

Ecological Niche and Geographic Distribution of Human Monkeypox in Africa

Monkeypox virus, a zoonotic member of the genus Orthopoxviridae, can cause a severe, smallpox-like illness in humans. Monkeypox virus is thought to be endemic to forested areas of western and Central Africa. Considerably more is known about human monkeypox disease occurrence than about natural sylvatic cycles of this virus in non-human animal hosts. We use human monkeypox case data from Africa for 1970–2003 in an ecological niche modeling framework to construct predictive models of the ecological requirements and geographic distribution of monkeypox virus across West and Central Africa. Tests of internal predictive ability using different subsets of input data show the model to be highly robust and suggest that the distinct phylogenetic lineages of monkeypox in West Africa and Central Africa occupy similar ecological niches. High mean annual precipitation and low elevations were shown to be highly correlated with human monkeypox disease occurrence. The synthetic picture of the potential geographic distribution of human monkeypox in Africa resulting from this study should support ongoing epidemiologic and ecological studies, as well as help to guide public health intervention strategies to areas at highest risk for human monkeypox

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment