bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic Value of Coronary Computed Tomography Angiography–derived Morphologic and Quantitative Plaque Markers Using Semiautomated Plaque Software
Authors: Baumann Stefan , Kaeder Finja , Schoepf U. Joseph , Golden Joseph W. , Kryeziu Philipp , Tesche Christian , Renker Matthias , Jannsen Sonja , Weiss Christel , Hetjens Svetlana , Schoenberg Stefan O. , Borggrefe Martin , Akin Ibrahim , Lossnitzer Dirk , Overhoff Daniel
Published: April 2020

Purpose:

In this study, we analyzed the prognostic value of coronary computed tomography angiography–derived morphologic and quantitative plaque markers and plaque scores for major adverse cardiovascular events (MACEs).

Materials and Methods:

We analyzed the data of patients with suspected coronary artery disease (CAD). Various plaque markers were obtained using a semiautomated software prototype or derived from the results of the software analysis. Several risk scores were calculated, and follow-up data concerning MACE were collected from all patients.

Results:

A total of 131 patients (65±12 y, 73% male) were included in our study. MACE occurred in 11 patients within the follow-up period of 34±25 months.

CAD-Reporting and Data System score (odds ratio [OR]=11.62), SYNTAX score (SS) (OR=1.11), Leiden-risk score (OR=1.37), segment involvement score (OR=1.76), total plaque volume (OR=1.20), and percentage aggregated plaque volume (OR=1.32) were significant predictors for MACE (all P≤0.05). Moreover, the difference of the corrected coronary opacification (ΔCCO) correlated significantly with the occurrence of MACE (P<0.0001). The CAD-Reporting and Data System score, SS, and Leiden-risk score showed substantial sensitivity for predicting MACE (90.9%). The SS and Leiden-risk score displayed high specificities of 80.8% and 77.5%, respectively. These plaque markers and risk scores all provided high negative predictive value (>90%).

Conclusion:

The coronary computed tomography angiography–derived plaque markers of segment involvement score, total plaque volume, percentage aggregated plaque volume, and ΔCCO, and the risk scores exhibited predictive value for the occurrence of MACE and can likely aid in identifying patients at risk for future cardiac events.
Effects of the Enhanced Recovery Program on the Recovery and Stress Response in Patients With Cancer Undergoing Pancreatoduodenectomy
Authors: Kapritsou Maria , Papathanassoglou Elizabeth D. , Konstantinou Evangelos A. , Korkolis Dimitrios P. , Mpouzika Meropi , Kaklamanos Ioannis , Giannakopoulou Margarita
Published: April 2020

Aim the study was the comparison of enhanced recovery after surgery (ERAS) versus conventional care (CON) protocols in patients undergoing pancreatoduodenectomy with regard to pain intensity, emotional response (optimism/sadness/stress), and stress biomarker levels (adrenocorticotropopic hormone, cortisol). We conducted a prospective two-group randomized controlled study with repeated measures in 85 patients with cancer pancreatoduodenectomy. In the ERAS group (N = 44), the ERAS protocol was followed, compared with the CON group (N = 41). We assessed pain with the numeric rating scale and a behavioral scale (Critical Care Pain Observation Tool), emotional responses (numeric rating scale), and serum adrenocorticotropopic hormone and cortisol levels at three time points: T1, admission day; T2, day of surgery; and T3, discharge day (ERAS) or the fifth day of stay (CON). Data were analyzed by linear mixed modeling to account for repeated measurements. We observed decreased postoperative pain in ERAS patients after adjusting for confounders (p = .002) and a trend for less complications. No significant associations with stress/emotional responses were noted. Only age, but not protocol, appeared to have a significant effect on adrenocorticotropopic hormone levels despite a significant interaction with time toward increased adrenocorticotropopic hormone levels in the ERAS group. In conclusion, despite its fast track nature, ERAS is not associated with increased stress in patients undergoing pancreatoduodenectomy and is associated with decreased pain.
Risk Factors of Dysphagia Among Community-Dwelling Middle-Aged Women
Authors: Lee Young Hee , Jung Dukyoo , Yun Ok Jong , Lee Hyesoon , Lee Minkyung
Published: April 2020

This study aimed to characterize a population of middle-aged South Korean women at risk of developing dysphagia and to identify relevant risk factors. This study describes a cross-sectional survey. Data on the general characteristics of the participants, risk factors for dysphagia, depression, and dental pain were collected and analyzed using descriptive statistics and logistic regression analysis. Among the 247 participants, 80 (32.4%) were assigned to the dysphagia “risk” group. Logistic regression indicated that perceived health status, low body mass index, dental pain, and depression were significant risk factors for developing dysphagia. A greater proportion of individuals were classified as having depression in the dysphagia “risk” group. Depression and dental pain were recognized as dominant risk factors for dysphagia. This work provides a basic reference that can be useful for the development of a general health education program for the prevention of dysphagia in community-dwelling middle-aged women.
Gepants, calcitonin-gene-related peptide receptor antagonists: what could be their role in migraine treatment?
Authors: Moreno-Ajona David , Pérez-Rodríguez Abigail , Goadsby Peter J.
Published: April 2020

Purpose of review

Migraine is the second leading cause of years lived with disability after back pain. Poor tolerability, contraindications, drug–drug interactions and efficacy limited to a subpopulation make new approaches necessary for the acute and preventive treatment of migraine. The study of the calcitonin-gene-related peptide (CGRP) pathway over the last decades is a good example of translational medicine leading to directed therapies for patients.

Recent findings

After some of the first-generation CGRP receptor antagonists, gepants, were not fully developed because of hepatotoxicity, the second generation of gepants have shown efficacy, safety and tolerability in recent clinical trials.

Both rimegepant and ubrogepant have published positive randomized placebo-controlled clinical trials data. Vazegepant is the first intranasal gepant for the acute treatment of migraine and has announced a positive phase II/III study. Daily rimegepant use has preliminary data to suggest efficacy. Atogepant has shown efficacy in migraine prevention in a phase II/III study. Most importantly, hepatotoxicity has not been reported in specifically designed phase I studies or long-term extension studies, with rimegepant or ubrogepant, or in a preventive study with atogepant. Given the preventive effect, it seems likely that gepants will not lead to medication overuse headache. They will likely have no cardiovascular warnings. Because of the particular benefit gepants may represent for these groups of patients, specific studies in patients with medication overuse headache, as well as those with comorbid cardiovascular diseases, would be of considerable interest.
The window of opportunity for treatment of progressive multiple sclerosis
Authors: Sorensen Per Soelberg , Fox Robert J. , Comi Giancarlo
Published: April 2020

Purpose of review

Based on the knowledge of disease mechanisms in the progressive course of multiple sclerosis and the experience from randomized clinical trials, we assessed the timing of disease-modifying therapy in patients with progressive multiple sclerosis to define the optimal window of opportunity for treatment of progressive multiple sclerosis.

Recent findings

In progressive multiple sclerosis both small molecules that cross the blood--brain barrier (siponimod) and monoclonal antibodies (ocrelizumab) have shown therapeutic efficacy and have been approved for treatment of progressive multiple sclerosis. However, the majority of phase II and phase III trials in progressive forms of multiple sclerosis have been negative, probably owing to either late start of treatment or use of drugs that are ineffective for treatment of progressive multiple sclerosis.

Results from phase II and III trials suggest that the window of opportunity for treatment of progressive multiple sclerosis with anti-inflammatory drugs is predominantly in the early phase of the progressive disease course when patients have lower age, shorter duration of progressive multiple sclerosis, and more pronounced clinical and MRI inflammatory activity. Ongoing trials of neuroprotective drugs may widen the window of opportunity by expanding targeted pathophysiologies.
Neuroprotection of netrin-1 on neurological recovery via Wnt/β-catenin signaling pathway after spinal cord injury
Authors: Gao Kai , Niu Jianbing , Dang Xiaoqian
Published: April 2020

The neuroprotective effects of netrin-1 after spinal cord injury and its specific molecular mechanisms have not been elucidated. In our study, Western blot, transferase UTP nick end labeling staining and immunofluorescence staining first showed that netrin-1 significantly decreased the expression levels of caspase-3, caspase-9, transferase UTP nick end labeling-positive neurons, nuclear factor kappa-B, and tumor necrosis factor-α after spinal cord injury, which inhibited neuronal apoptosis and inflammatory response. Using Nissl and HE staining, we also found that netrin-1 significantly increased the number of Nissl bodies in the anterior horn of spinal cord and promoted the recovery of injured tissue after spinal cord injury, consequently providing a good microenvironment for recovery of motor function. Finally, the results of Basso, Beattie, and Bresnahan score further confirmed that netrin-1 promoted the recovery of neurological function after spinal cord injury. Furthermore, netrin-1 significantly promoted the expression of β-catenin and inhibited the expression of glycogen synthase kinase-3β, which activated Wnt/β-catenin signaling pathway after spinal cord injury. However, XAV939 inhibited Wnt/β-catenin signaling pathway, which significantly inhibited the regulatory effect of netrin-1 on apoptosis, inflammation, Nissl bodies, damaged tissues, and neuroprotection. These results demonstrate for the first time the correlation between netrin-1 and Wnt/β-catenin signaling pathway after spinal cord injury and show that netrin-1 exerts its neuroprotective effect by activating this signaling pathway after spinal cord injury.
New psychoactive substances in Australia: patterns and characteristics of use, adverse effects, and interventions to reduce harm
Authors: Sutherland Rachel , Allsop Steve , Peacock Amy
Published: April 2020

Purpose of review

To summarize the most recent peer-review literature on new psychoactive substances (NPS) within Australia.

Recent findings

NPS use among the general Australian population is low, yet more pervasive among specific subpopulations. There is considerable heterogeneity among people who use NPS, however, overall, they are not unique from those who use more established illicit drugs. NPS have been shown to be highly adulterated, used as contaminants, variable in dose, and changeable as to the specific substances available over time. Further, analyses of coroners’ cases highlight the importance of consumer understanding of NPS effects, particularly where they differ substantially to their more traditional illicit drug counterparts (e.g., synthetic vs. plant cannabinoids). One study posited that legislative approaches to NPS have been (partially) effective in reducing harms, and there are new systems being established to identify NPS-related health harms.

There have been few studies recently published on NPS in Australia (n = 17), however, findings mostly align with the international literature with respect to the rapidly changing nature of the NPS market, the use of NPS as adulterants, and associated harms. These themes highlight the need for proactive, novel approaches to rapidly identify, and respond to emerging drugs of concern.
Advances in prescription drug monitoring program research: a literature synthesis (June 2018 to December 2019)
Authors: Delcher Chris , Pauly Nathan , Moyo Patience
Published: April 2020

Purpose of review

Nearly every U.S. state operates a prescription drug monitoring program (PDMP) to monitor dispensing of controlled substances. These programs are often considered key policy levers in the ongoing polydrug epidemic. Recent years have seen rapid growth of peer-reviewed literature examining PDMP consultation and the impacts of these programs on diverse patient populations and health outcomes. This literature synthesis presents a review of studies published from June 2018 to December 2019 and provides relevant updates from the perspective of three researchers in this field.

Recent findings

The analyzed studies were primarily distributed across three overarching research focus areas: outcome evaluations (n = 29 studies), user surveys (n = 23), and surveillance (n = 22). Identified themes included growing awareness of the unintended consequences of PDMPs on access to opioids, effects on benzodiazepines and stimulant prescribing, challenges with workflow integration across multiple specialties, and new opportunities for applied data science.

There is a critical gap in existing PDMP literature assessing how these programs have impacted psychiatrists, their prescribing behaviors, and their patients. Although PDMPs have improved population-level monitoring of controlled substances from medical sources, their role in responding to a drug epidemic shifting to illicitly manufactured drugs is under scrutiny.
Partial unlock model for COVID-19 or similar pandemic averts medical and economic disaster
Authors: Shuler Robert L.
Published: April 2020

Data as of March 29, 2020 show that the “flattening” strategy for COVID-19 in the U.S. is working so well that a clean removal of social distancing (aka “unlock”) at any time in 2020 will produce a renewed catastrophe, overloading the healthcare system. Leaving the economy locked down for a long time is its own catastrophe. An SIR-type model with clear parameters suitable for public information, and both tracking and predictive capabilities which “learns” disease spread characteristics rapidly as policy changes, suggests that a solution to the problem is a partial unlock. Case load can be managed so as not to exceed critical resources such as ventilators, yet allow enough people to get sick that herd immunity develops and a full unlock can be achieved in as little as five weeks from beginning of implementation. The partial unlock could be for example 3 full working days per week. Given that not all areas or individuals will respond, and travel and public gatherings are still unlikely, the partial unlock might be 5 full working days per week. The model can be regionalized easily, and by expediting the resolution of the pandemic in the U.S. medical equipment and volunteers, many of them with already acquired immunity, can be made available to other countries.
Association of BCG vaccination policy and tuberculosis burden with incidence and mortality of COVID-19
Authors: Sala Giovanni , Chakraborti Rik , Ota Atsuhiko , Miyakawa Tsuyoshi
Published: April 2020

Background

Evidence suggests non-specific benefits of the tuberculosis vaccine bacillus Calmette-Guérin (BCG) against non-related infections. Recent studies propose such protection may extend to the novel COVID-19 as well. This is a contested hypothesis.

Methods

Our ecological study confronts this hypothesis. We examine the effects of BCG vaccination on countries’ COVID-19 (a) cases and deaths (per million) and (b) exponential growth factors over specific periods of the pandemic. Since the BCG vaccine was derived from Mycobacterium bovis, a bacterium causing tuberculosis in cattle, having suffered from tuberculosis also may exert a non-specific protection against the COVID-19 as well. Along with BCG vaccination, we test the effect of the prevalence of tuberculosis.

We employ multiple regression and principal component analysis (PCA) to control for potentially confounding variables (n= 16).

Results

BCG vaccination policy and incidence of tuberculosis is associated with a reduction in both COVID-19 cases and deaths, and the effects of these two variables are additive (≈ 5% to 15% of total unique variance explained). The study of exponential growth factors in the initial stages of the pandemic further shows that BCG vaccination exerts a significant effect (up to 35% of unique variance explained).

Conclusions

Overall, these findings corroborate the hypothesis that BCG vaccination and exposure to tuberculosis may induce a non-specific protection against the novel SARS-CoV-2 infection, even after accounting for a large number of confounding influences. However, given the potential public-health benefits, our results indicate that the hypothesis deserves further attention and should not be hastily dismissed.
Ultra-High-Resolution CT Follow-Up in Patients with Imported Early-Stage Coronavirus Disease 2019 (COVID-19) Related Pneumonia
Authors: Lin Yu , Lv Shaomao , Wang Jinan , Kang Jianghe , Zhang Youbin , Feng Zhipeng
Published: April 2020

Background

An ongoing outbreak of mystery pneumonia in Wuhan was caused by coronavirus disease 2019 (COVID-19). The infectious disease has spread globally and become a major threat to public health.

Purpose

We aim to investigate the ultra-high-resolution CT (UHR-CT) findings of imported COVID-19 related pneumonia from the initial diagnosis to early-phase follow-up.

Methods

This retrospective study included confirmed cases with early-stage COVID-19 related pneumonia imported from the epicenter. Initial and early-phase follow-up UHR-CT scans (within 5 days) were reviewed for characterizing the radiological findings. The normalized total volumes of ground-glass opacities (GGOs) and consolidations were calculated and compared during the radiological follow-up by artificial-intelligence-based methods.

Results

Eleven patients (3 males and 8 females, aged 32-74 years) with confirmed COVID-19 were evaluated. Subpleural GGOs with inter/intralobular septal thickening were typical imaging findings. Other diagnostic CT features included distinct margins (8/11, 73%), pleural retraction or thickening (7/11, 64%), intralesional vasodilatation (6/11, 55%). Normalized volumes of pulmonary GGOs (p=0.003) and consolidations (p=0.003) significantly increased during the CT follow-up.

Conclusions

The abnormalities of GGOs with peripleural distribution, consolidated areas, septal thickening, pleural involvement and intralesional vasodilatation on UHR-CT indicate the diagnosis of COVID-19. COVID-19 cases could manifest significantly progressed GGOs and consolidations with increased volume during the early-phase CT follow-up.
Using discrete Ricci curvatures to infer COVID-19 epidemic network fragility and systemic risk
Authors: de Souza Danillo Barros , da Cunha Jonatas T. S. , dos Santos Everlon Figueirôa , Correia Jailson B. , da Silva Hernande P. , de Lima Filho José Luiz , Albuquerque Jones , Santos Fernando A. N.
Published: April 2020

The damage of the novel Coronavirus disease (COVID-19) is reaching unprecedented scales. There are numerous classical epidemiology models trying to quantify epidemiology metrics. Usually, to forecast epidemics, classical approaches need parameter estimations, such as the contagion rate or the basic reproduction number. Here, we propose a data-driven, parameter-free, geometric approach to access the emergence of a pandemic state by studying the Forman-Ricci and Ollivier-Ricci network curvatures. Discrete Ollivier-Ricci curvature has been used successfully to forecast risk in financial networks and we suggest that those results can provide analogous results for COVID-19 epidemic time-series. We first compute both curvatures in a toy-model of epidemic time-series with delays, which allows us to create epidemic networks. By doing so, we are able to verify that the Ollivier-Ricci and Forman-Ricci curvatures can be a parameter-free estimate for identifying a pandemic state in the simulated epidemic. On this basis, we then compute both Forman-Ricci and Ollivier-Ricci curvatures for real epidemic networks built from COVID-19 epidemic time-series available at the World Health Organization (WHO). Both curvatures allow us to detect early warning signs of the emergence of the pandemic. The advantage of our method lies in providing an early geometrical data marker for the pandemic state, regardless of parameter estimation and stochastic modelling. This work opens the possibility of using discrete geometry to study epidemic networks.
Mass drug administration with azithromycin for trachoma elimination and the population structure of Streptococcus pneumoniae in the nasopharynx
Authors: Gladstone Rebecca A. , Bojang Ebrima , Hart John , Harding-Esch Emma M , Mabey David , Sillah Ansumana , Bailey Robin L. , Burr Sarah E. , Roca Anna , Bentley Stephen D. , Holland Martin J.
Published: April 2020

Background

Mass drug administration (MDA) with azithromycin for trachoma elimination reduces nasopharyngeal carriage ofStreptococcus pneumoniaein the short term. We evaluated S.pneumoniaecarried in the nasopharynx before and after a round of azithromycin MDA to determine whether MDA was associated with changes in pneumococcal population structure.

Methods

We analysed 514 pneumococcal isolates cultured from nasopharyngeal samples collected in Gambian villages that received MDA for trachoma elimination. The samples were collected during three cross-sectional surveys conducted before the third round of MDA (CSS-1) and at one (CSS-2) and six (CSS-3) months after MDA. Whole genome sequencing was conducted on randomly selected isolates. Bayesian Analysis of Population Structure (BAPS) was used to cluster related isolates by capturing variation in the core genome. Serotype and multi-locus sequence type were inferred from the genotype. The Antimicrobial Resistance Identification by Assembly (ARIBA) tool was used to identify macrolide resistance genes.

Results

Twenty-seven BAPS clusters were assigned. These consisted of 81 sequence types (STs), 15 of which were novel additions to pubMLST. Two BAPS clusters, BAPS20 (p-value<=0.016) and BAPS22 (p-value<=0.032) showed an increase in frequency at CSS-3 not associated with antimicrobial resistance. Macrolide resistance within BASP17 increased after treatment (p<0.05) and was carried on a mobile transposable element that also conferred resistance to tetracycline.

Conclusions

Limited changes in pneumococcal population structure were observed after the third round of MDA suggesting treatment had little effect on the circulating lineages. An increase in macrolide resistance within one BAPS highlights the need for antimicrobial resistance surveillance in treated villages.
The effect of including the Nordic Hamstring exercise on sprint and jump performance in athletes: protocol of a systematic review and meta-analyses
Authors: Krommes Kasper , Nielsen Mathias F. , Krohn Laura , Grønfeldt Birk M. , Thorborg Kristian , Hölmich Per , Ishøi Lasse
Published: April 2020

The Nordic Hamstring exercise reduces hamstring strain injuries in football and other sports, but the exercise is not well adopted in practice. Barriers from practitioners include fear of performance decrements, due to lack of specificity of the exercise with high speed running. However, in theory, increased eccentric hamstring strength could transfer to faster sprinting due to higher horizontal force production. Studies on the effect of the Nordic Hamstring exercise on performance have been conflicting and no synthesis of the evidence exists. We therefore pose the following question: does including the Nordic Hamstring exercise hamper sprint or jump performance in athletes? We will answer this question by performing a systematic review of the literature, critically appraise relevant studies, and GRADE the evidence across key outcomes and perform meta-analyses, meta-regression and subgroup analyses. In this protocol we outline the planned methods and procedures.

Progress report

Besides this protocol, our data extraction form and the process of data extraction has been piloted on 3 relevant studies, along with familiarization with the Risk of Bias 2.0 tool. We have also comprised a preliminary search strategy for PubMed.

Supplementary files

Data Extraction Form (.pdf)

Populated PRISMA-P checklist (.pdf)
Does a non-targeted publicly-funded health care voucher system for the elderly improve access to optometry services?
Authors: Sum Rita , Yap Maurice
Published: April 2020

Objective

To study how a non-targeted publicly-funded health care voucher system for the elderly impact on access to optometry services from the perspective of service users and service providers

Design

Cross-sectional study

Setting

19 elderly community centers

Participants

1176 people, aged 65 years or above, and 389 optometrists

Primary and secondary outcome measures

Usage characteristics of optometry services by eligible service users of the voucher scheme

Perspectives of eligible service users on access barriers to optometry services

Perspectives of service providers on voucher scheme

Results

In total, 1156 valid questionnaires were collected from a cohort of eligible service users. Results showed that 53.7% of subjects had used optometry services within the past 2 years, while 22% had not used optometry services before. Lack of familiarity with services provided, professional fees and prices of prescription spectacles were the main barriers to using optometry services. Of those subjects who had used the voucher for optometry service before, 80.4% had eye examination in the past 2 years, versus 64.1% among subjects who had not use health care voucher on the optometry service. “Insufficient voucher value” was a commonly quoted reason for not using the health care vouchers for optometry services. Over 80% of optometrists agreed that the voucher scheme improved the awareness of major eye conditions and enabled the elderly to have prescription spectacles when necessary.

Conclusion

The health care voucher for the elderly improved access to optometry services. Access could be improved further by promoting awareness optometry services, location of service providers, price transparency of professional services and prescription spectacles. Responses from optometry services providers are supportive of the view that the voucher scheme improved access to and utilization of preventive care services.

Article Summary

Strengths and limitations of this study

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High representativeness of community dwelling older population in Hong Kong.

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The mixed method approach provided a more in-depth investigation of the population.

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One limitation is the generalizability of the results with older people who are members in the community centers.
Fine adaptive control of precision grip without maximum pinch strength changes after median nerve mobilization
Authors: Dierick Frédéric , Brismée Jean-Michel , White Olivier , Bouché Anne-France , Périchon Céline , Filoni Nastasia , Barvaux Vincent , Buisseret Fabien
Published: April 2020

Fine dexterity critically depends on information conveyed by the median nerve. While the effects of its compression and vibration are well characterized, little is known about longitudinal tension and excursion. Using a force-sensitive manipulandum, a numeric dynamometer and Semmes-Weinstein monofilaments, we examined the adaptations of precision grip control, maximum pinch strength and fingertips pressure sensation threshold before and immediately after the application of longitudinal tension and excursion mobilizations applied on the median nerve. Grip (GF) and load (LF) forces applied by the thumb, index and major fingers were collected in 40 healthy young participants during three different grip precision tasks along the direction of gravity. For grip-lift-drop task, maximumGFandLFand their first time derivatives were computed. For up-down oscillations, means ofGFandLFand their variability were computed. For oscillations with up and down collisions, peaks ofGFandLF, time delay betweenGFpeak and contact, and values ofGFandLFat contact were collected. Our findings show that median nerve mobilizations induce significant fine adaptations of precision grip control in the three different tasks but mainly during grip-lift-drop and oscillations with collisions. Fingertips pressure sensation thresholds at index and thumb were significantly reduced after the mobilizations. No significant changes were observed for maximum pinch strength. We conclude that precision grip adaptations observed after median mobilizations could be partly explained by changes in cutaneous median-nerve mechanoreceptive afferents from the thumb and index fingertips.
COVID19-Tracker: A shiny app to perform comprehensive data visualisation for SARS-CoV-2 epidemic in Spain
Authors: Tobías Aurelio , Valls Joan , Satorra Pau , Tebé Cristian
Published: April 2020

Data visualization is an essential tool for exploring and communicating findings in medical research, especially in epidemiological surveillance. The COVID19-Tracker web application systematically produces daily updated data visualization and analysis of the SARS-CoV-2 epidemic in Spain. It collects automatically daily data on COVID-19 diagnosed cases, and mortality from February 24th, 2020 onwards. Several analyses have been developed to visualize data trends and estimating short-term projections; to estimate the case fatality rate; to assess the effect of the lockdown measures on the trends of incident data; to estimate infection time and the basic reproduction number; and to analyse the excess of mortality. The application may help for a better understanding of the SARS-CoV-2 epidemic data in Spain.
Glucocorticoids inhibit type I IFN beta signaling and the upregulation of CD73 in human lung
Authors: Jalkanen Juho , Pettilä Ville , Karvonen Matti , Huttunen Teppo , Mandelin Jami , Jalkanen Markku , Malmberg Markus , Elima Kati , Bellingan Geoff , Ranieri V. Marco , Hollmen Maija , Jalkanen Sirpa
Published: April 2020

Purpose

Glucocorticoids are widely used to treat acute respiratory distress syndrome (ARDS) despite its use is highly controversial based on randomized controlled trials and meta-analyses. As type I interferons (IFNs) are our first line of defense against severe viral respiratory infections, we explored whether glucocorticoids interfere with IFN signaling and whether their use associates to outcome of IFN beta treatment of ARDS.

Methods

We performed a propensity-matched post-hoc-analysis using data from the recent randomized INTEREST-trial comparing IFN beta-1a to placebo in ARDS patients. Based on the results of these analyses we utilized human lung tissue and human pulmonary endothelial cell cultures to investigate the effect of hydrocortisone on IFN nuclear signaling and the protein transcription of CD73, a molecule responsible for vascular integrity.

Results

We found that hydrocortisone reduces the production, and prevents the nuclear translocation of IRF9, that is required for IFN beta-dependent signaling of multiple IFN-induced genes. In addition, hydrocortisone inhibits IFN beta-dependent upregulation of CD73 in human lung tissue. Additionally, we found that use of glucocorticoids with IFN beta-1a was independently associated with increased mortality (OR 5.4, 95% CI 2.1–13.9, P< 0.001) in the INTEREST-trial.

Conclusions

Glucocorticoids inhibit type I IFN beta signaling and the upregulation of CD73 in human lung. This provides the mechanistic basis for the harmful association of glucocorticoids in IFN beta treated patients in the INTEREST-trial. Most importantly, it strongly speaks against the use of glucocorticoids in viral-induced ARDS such as in the current corona virus pandemia.

Take home message

Glucocorticoids inhibit type I interferon beta signaling and the upregulation of CD73 that is a key molecule preventing vascular leakage and harmful leukocyte infiltration into the lungs. This work provides the mechanistic basis for the need to avoid glucocorticoids in viral-induced ARDS, in which endogenous interferon is needed to combat the infection and its consequences.
Perceived vulnerability to COVID-19 infection from event attendance: Results from Louisiana, USA, two weeks preceding the national emergency declaration
Authors: Li Ran , Yang Bingcheng , Penn Jerrod , Houghtaling Bailey , Chen Juan , Prinyawiwatkul Witoon , Roe Brian E. , Qi Danyi
Published: April 2020

In response to the mounting threat of COVID-19, we added questions to an ongoing food preference study held at Louisiana State University from March 3-12 of 2020. We asked 356 participants: (1) In your opinion, how likely is it that the spread of COVID-19 (the coronavirus) will cause a public health crisis in the United States? (2) How concerned are you that you will contract COVID-19 by attending events on campus? Participants’ estimates of an impending national health crisis increased significantly during the study’s second week (March 9-12) while concern about personally contracting COVID-19 from attending campus events increased only marginally during the study’s final days. We find those expressing a higher likelihood of an impending national crisis were more concerned about contracting COVID-19 by attending campus events, suggesting a possible transmission from perceptions of national-level events to perceived personal vulnerability via local exposure. However, about 30% of participants perceived that COVID-19 would likely cause a public health crisis yet did not express concern about contracting COVID-19 from event attendance. These participants were significantly more likely to be younger students who agreed to participate in response to recruitment using same day flyer distribution. Women expressed a higher likelihood of an emerging national health crisis, although they were not more concerned than men that attending campus events would result in virus contraction. Other groups (e.g., white, students younger than 25, highest income group) displayed similar concern about a national-level crisis, yet were significantly less concerned about contracting COVID-19 from attending campus events than others. Also, participants randomly assigned to information emphasizing the national impacts of food waste expressed significantly greater concern of contracting COVID-19 by attending campus events. These results provide some initial insight about how people perceived national and personal risks in the early stages of the COVID-19 crisis in Louisiana.
Fear avoidance beliefs limit lumbar spine flexion during object lifting in pain-free adults
Authors: Knechtle D , Schmid S , Suter M , Riner F , Moschini G , Senteler M , Schweinhardt P , Meier ML
Published: April 2020

There is a long-held belief that physical activities such as lifting with a flexed spine is generally harmful for the back and can cause low back pain (LBP), potentially nurturing fear avoidance beliefs underlying pain-related fear. In chronic LBP patients, pain-related fear has been shown to be associated with reduced lumbar range of motion during lifting, indicating distinct and probably protective psychomotor responses to pain. However, despite short term beneficial effects for tissue health, recent evidence suggests that maintaining a protective trunk movement strategy may also pose a risk for (persistent) LBP due to possible pro-nociceptive consequences of altered spinal kinematics, reflected by increased loading on lumbar tissues and persistent muscle tension. Yet, it is unknown if similar psychomotor interactions already exist in pain-free individuals which would yield potential insights into how a person might react when they experience LBP. Therefore, the aim of this study is to test the impact of pain-related fear on spinal kinematics in a healthy cohort of pain-free adults without a history of chronic pain. The study subjects (N=57) filled out several pain-related fear questionnaires and were asked to perform a lifting task (5kg-box). High-resolution spinal kinematics were assessed using an optical motion capturing system. Time-sensitive analyses were performed based on statistical parametric mapping. The results demonstrated time-specific and negative relationships between self-report measures of pain-related fear and lumbar spine flexion angles during lifting, yielding important implications regarding unfavorable psychomotor interactions that might become relevant in a future LBP incident.
FREQUENCY OF INFECTION AFTER CEREBROSPINAL FLUID SHUNTING PROCEDURES
Authors: Ramooz Kashif , Yaqoob Eesha , Akhtar Nadeem , Mehmood Fraz , Javed Saad
Published: April 2020

Hydrocephalus is routinely treated by surgical procedures. Cerebrospinal fluid shunt placement is a critical therapeutic intervention for hydrocephalus.CSF shunting has multiple complications among which infection is very common. The major cause of morbidity and mortality in patients with CSF shunts is theinfection of the central nervous system (CNS).It can lead to prolonged hospital stay, increase the number of operative procedures 03 times more than then none infected cases and has twice the fatality rate. Study of such type of complication will help the patients to improve their health and also improve our sterilization techniques and reduce burden of hospital and patients expenditures. The objective of the study was to determine the frequency of infection after cerebrospinal fluid shunting procedures.Case series study was used as study design.Study was conducted from 10-2010 to 10-06-2011.One hundred and forty four patients with both genders of all age groups undergoing cerebrospinal fluid shunting, meeting inclusion and exclusion criteria, were selected for the present study after informed consent of patient or guardian and approval by the hospital ethical committee. Follow up was ensured by taking the telephonic contact and address of patient.Total no of patients were 144 among which, 89 were males and 55 were females. Age distribution was from 01 month to 75 years with the mean age of 15.280 and standard deviation was ± 20.450. Post-operative infection was present in 20(13.9%) patients.

Author’s approval

All the authors have seen the manuscript and approved it.

Declaration of interest

None

Conflict/Competing of Interest

None.

Disclosure of Funding

None.

Ethical Approval

Attached
A Contribution to the Mathematical Modeling of the Corona/COVID-19 Pandemic
Authors: Bärwolff Günter
Published: April 2020

The responsible estimation of parameters is a main issue of mathematical pandemic models. Especially a good choice of β as the number of others that one infected person encounters per unit time (per day) influences the adequateness of the results of the model. For the example of the actual COVID-19 pandemic some aspects of the parameter choice will be discussed. Because of the incompatibility of the data of the Johns-Hopkins-University [3] to the data of the German Robert-Koch-Institut we use the COVID-19 data of the European Centre for Disease Prevention and Control [2] (ECDC) as a base for the parameter estimation. Two different mathematical methods for the data analysis will be discussed in this paper and possible sources of trouble will be shown.

Parameters for several countries like UK, USA, Italy, Spain, Germany and China will be estimated and used in W. O. Kermack and A. G. McKendrick’s SIR model[1]. Strategies for the commencing and ending of social and economic shutdown measures are discussed.

The numerical solution of the ordinary differential equation system of the modified SIR model is being done with a Runge-Kutta integration method of fourth order [4].

At the end the applicability of the SIR model could be shown. Suggestions about appropriate points in time at which to commence with lockdown measures based on the acceleration rate of infections conclude the paper. This paper is an improved sequel of [5].
Case fatality rate in COVID-19: a systematic review and meta-analysis
Authors: Kahathuduwa Chanaka , Dhanasekara Chathurika , Chin Shao-Hua
Published: April 2020

Background

Estimating the prevalence of severe or critical illness and case fatality of COVID-19 outbreak in December, 2019 remains a challenge due to biases associated with surveillance, data synthesis and reporting. We aimed to address this limitation in a systematic review and meta-analysis and to examine the clinical, biochemical and radiological risk factors in a meta-regression.

Methods

PRISMA guidelines were followed. PubMed, Scopus and Web of Science were searched using pre-specified keywords on March 07, 2020. Peer-reviewed empirical studies examining rates of severe illness, critical illness and case fatality among COVID-19 patients were examined. Numerators and denominators to compute the prevalence rates and risk factors were extracted. Random-effects meta-analyses were performed. Results were corrected for publication bias. Meta-regression analyses examined the moderator effects of potential risk factors.

Results

The meta-analysis included 29 studies representing 2,090 individuals. Pooled rates of severe illness, critical illness and case fatality among COVID-19 patients were 15%, 5% and 0.8% respectively. Adjusting for potential underreporting and publication bias, increased these estimates to 26%, 16% and 7.4% respectively. Increasing age and elevated LDH consistently predicted severe / critical disease and case fatality. Hypertension; fever and dyspnea at presentation; and elevated CRP predicted increased severity.

Conclusions

Risk factors that emerged in our analyses predicting severity and case fatality should inform clinicians to define endophenotypes possessing a greater risk. Estimated case fatality rate of 7.4% after correcting for publication bias underscores the importance of strict adherence to preventive measures, case detection, surveillance and reporting.
Iterative community-driven development of a SARS-CoV-2 tissue simulator
Authors: Getz Michael , Wang Yafei , An Gary , Asthana Maansi , Becker Andrew , Cockrell Chase , Collier Nicholson , Craig Morgan , Davis Courtney L. , Faeder James R. , Ford Versypt Ashlee N. , Mapder Tarunendu , Gianlupi Juliano F. , Glazier James A. , Hamis Sara , Heiland Randy , Hillen Thomas , Hou Dennis , Islam Mohammad Aminul , Jenner Adrianne L. , Kurtoglu Furkan , Larkin Caroline I. , Liu Bing , Macfarlane Fiona , Maygrundter Pablo , Morel Penelope A , Narayanan Aarthi , Ozik Jonathan , Pienaar Elsje , Rangamani Padmini , Saglam Ali Sinan , Shoemaker Jason Edward , Smith Amber M. , Weaver Jordan J.A. , Macklin Paul
Published: April 2020

The 2019 novel coronavirus, SARS-CoV-2, is a pathogen of critical significance to international public health. Knowledge of the interplay between molecular-scale virus-receptor interactions, single-cell viral replication, intracellular-scale viral transport, and emergent tissue-scale viral propagation is limited. Moreover, little is known about immune system-virus-tissue interactions and how these can result in low-level (asymptomatic) infections in some cases and acute respiratory distress syndrome (ARDS) in others, particularly with respect to presentation in different age groups or pre-existing inflammatory risk factors. Given the nonlinear interactions within and among each of these processes, multiscale simulation models can shed light on the emergent dynamics that lead to divergent outcomes, identify actionable “choke points” for pharmacologic interventions, screen potential therapies, and identify potential biomarkers that differentiate patient outcomes. Given the complexity of the problem and the acute need for an actionable model to guide therapy discovery and optimization, we introduce and iteratively refine a prototype of a multiscale model of SARS-CoV-2 dynamics in lung tissue. The first prototype model was built and shared internationally as open source code and an online interactive model in under 12 hours, and community domain expertise is driving regular refinements. In a sustained community effort, this consortium is integrating data and expertise across virology, immunology, mathematical biology, quantitative systems physiology, cloud and high performance computing, and other domains to accelerate our response to this critical threat to international health. More broadly, this effort is creating a reusable, modular framework for studying viral replication and immune response in tissues, which can also potentially be adapted to related problems in immunology and immunotherapy.
LY6E Restricts the Entry of Human Coronaviruses, including the currently pandemic SARS-CoV-2
Authors: Zhao Xuesen , Zheng Shuangli , Chen Danying , Zheng Mei , Li Xinglin , Li Guoli , Lin Hanxin , Chang Jinhong , Zeng Hui , Guo Ju-Tao
Published: April 2020

C3A is a sub-clone of human hepatoblastoma HepG2 cell line with the strong contact inhibition of growth. We fortuitously found that C3A was more susceptible to human coronavirus HCoV-OC43 infection than HepG2, which was attributed to the increased efficiency of virus entry into C3A cells. In an effort to search for the host cellular protein(s) mediating the differential susceptibility of the two cell lines to HCoV-OC43 infection, we found that ADAP2, GILT and LY6E, three cellular proteins with known activity of interfering virus entry, expressed at significantly higher levels in HepG2 cells. Functional analyses revealed that ectopic expression of LY6E, but not GILT or ADAP2, in HEK 293 cells inhibited the entry of HCoV-OC43. While overexpression of LY6E in C3A and A549 cells efficiently inhibited the infection of HCoV-OC43, knockdown of LY6E expression in HepG2 significantly increased its susceptibility to HCoV-OC43 infection. Moreover, we found that LY6E also efficiently restricted the entry mediated by the envelope spike proteins of other human coronaviruses, including the currently pandemic SARS-CoV-2. Interestingly, overexpression of serine protease TMPRSS2 or amphotericin treatment significantly neutralized the IFITM3 restriction of human coronavirus entry, but did not compromise the effect of LY6E on the entry of human coronaviruses. The work reported herein thus demonstrates that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesisviaa distinct mechanism.

Importance

Virus entry into host cells is one of the key determinants of host range and cell tropism and is subjected to the control by host innate and adaptive immune responses. In the last decade, several interferon inducible cellular proteins, including IFITMs, GILT, ADAP2, 25CH and LY6E, had been identified to modulate the infectious entry of a variety of viruses. Particularly, LY6E was recently identified as host factors to facilitate the entry of several human pathogenic viruses, including human immunodeficiency virus, influenza A virus and yellow fever virus. Identification of LY6E as a potent restriction factor of coronaviruses expands the biological function of LY6E and sheds new light on the immunopathogenesis of human coronavirus infection.
Analytical Validation of a COVID-19 qRT-PCR Detection Assay Using a 384-well Format and Three Extraction Methods
Authors: Nelson Andrew C. , Auch Benjamin , Schomaker Matthew , Gohl Daryl M. , Grady Patrick , Johnson Darrell , Kincaid Robyn , Karnuth Kylene E. , Daniel Jerry , Fiege Jessica K. , Fay Elizabeth J. , Bold Tyler , Langlois Ryan A. , Beckman Kenneth B. , Yohe Sophia
Published: April 2020

The COVID-19 global pandemic is an unprecedented health emergency. Insufficient access to testing has hampered effective public health interventions and patient care management in a number of countries. Furthermore, the availability of regulatory-cleared reagents has challenged widespread implementation of testing. We rapidly developed a qRT-PCR SARS-CoV-2 detection assay using a 384-well format and tested its analytic performance across multiple nucleic acid extraction kits. Our data shows robust analytic accuracy on residual clinical biospecimens. Limit of detection sensitivity and specificity was confirmed with currently available commercial reagents. Our methods and results provide valuable information for other high-complexity laboratories seeking to develop effective, local, laboratory-developed procedures with high-throughput capability to detect SARS-CoV-2.