title: EMR is superior to rectal suction biopsy for analysis of enteric ganglia in constipation and dysmotility.

text: BACKGROUND AND AIMS Patients with chronic constipation or motility disorders may be referred for rectal suction biopsy (RSB) to rule out Hirschsprung's disease (HD). RSB may not be successful beyond infancy because of the increased thickness of the rectal mucosa. EMR could improve the diagnostic yield for HD when compared with traditional RSB because larger and deeper samples are acquired for analysis. METHODS In this prospective, single-center study, patients referred for RSB were offered enrollment for concurrent EMR. Specimens were analyzed pathologically for size, submucosal ganglionic tissue, and acetylcholinesterase or calretinin staining. Biopsy results were compared with transit studies, anorectal manometry, and constipation severity through validated questionnaires. RESULTS Seventeen patients (2 male, 15 female; mean age, 35.8 years; range, 22-61 years) were enrolled in the study from 2008 to 2014. All patients underwent anorectal manometry (88% with anorectal dysfunction, 68% with outlet obstruction) and transit studies (41% with delayed transit). There were no reports of adverse events from the RSB and EMR procedures. The RSB sample volumes were significantly lower than the EMR sample volumes (0.023 cm3 vs 0.26 cm3, P = .001). There was diagnostic tissue for submucosal visualization by RSB in 53% (9/17) of cases compared with 100% (17/17) with EMR (P = .003). No cases of HD were diagnosed by RSB; one patient had rare ganglions observed by EMR. CONCLUSIONS EMR provides greater tissue volume and can improve the characterization of ganglion cells in rectal tissue compared with RSB in patients with moderate to severe constipation with suspected HD.


title: Nutrition Modulation of Cardiotoxicity and Anticancer Efficacy Related to Doxorubicin Chemotherapy by Glutamine and ω-3 Polyunsaturated Fatty Acids.

text: BACKGROUND Doxorubicin (DOX) has been one of the most effective antitumor agents against a broad spectrum of malignancies. However, DOX-induced cardiotoxicity forms the major cumulative dose-limiting factor. Glutamine and ω-3 polyunsaturated fatty acids (PUFAs) are putatively cardioprotective during various stresses and/or have potential chemosensitizing effects during cancer chemotherapy. METHODS Antitumor activity and cardiotoxicity of DOX treatment were evaluated simultaneously in a MatBIII mammary adenocarcinoma tumor-bearing rat model treated with DOX (cumulative dose 12 mg/kg). Single or combined treatment of parenteral glutamine (0.35 g/kg) and ω-3 PUFAs (0.19 g/kg eicosapentaenoic acid and 0.18 g/kg docosahexaenoic acid) was administered every other day, starting 6 days before chemotherapy initiation until the end of study (day 50). RESULTS Glutamine alone significantly prevented DOX-related deterioration of cardiac function, reduced serum cardiac troponin I levels, and diminished cardiac lipid peroxidation while not affecting tumor inhibition kinetics. Single ω-3 PUFA treatment significantly enhanced antitumor activity of DOX associated with intensified tumoral oxidative stress and enhanced tumoral DOX concentration while not potentiating cardiac dysfunction or increasing cardiac oxidative stress. Intriguingly, providing glutamine and ω-3 PUFAs together did not consistently confer a greater benefit; conversely, individual benefits on cardiotoxicity and chemosensitization were mostly attenuated or completely lost when combined. CONCLUSIONS Our data demonstrate an interesting differentiality or even dichotomy in the response of tumor and host to single parenteral glutamine and ω-3 PUFA treatments. The intriguing glutamine × ω-3 PUFA interaction observed draws into question the common assumption that there are additive benefits of combinations of nutrients that are beneficial on an individual basis.


Post-Transplant Hepatic Artery Pseudoaneurysm Treated with the Pipeline Flow-Diverting Stent.


title: The antidepressive effects of exercise: a meta-analysis of randomized trials.

text: Several meta-analyses examining the effects of exercise on depression have been criticized for including studies of poor methodological integrity. More recent meta-analyses addressed the most common criticism by including only randomized control trials; however, these analyses suffer from incomplete literature searches and lack of moderating variable analyses. Using a more extensive search procedure, the current meta-analysis examines the effects of exercise on depressive symptoms in 58 randomized trials (n = 2982). An overall effect size of -0.80 indicates participants in the exercise treatment had significantly lower depression scores than those receiving the control treatment. This frac34; SD advantage represents level 1, Grade A evidence for the effects of exercise upon depression. Analysis of moderating variables examined the influence of population characteristics, exercise characteristics and methodological characteristics. Examination of clinical significance in 16 trials with clinically depressed patients found 9 of 16 exercise treatment groups were classified as 'recovered' at post-treatment, with another three groups classified as 'improved'. Analysis showed dropout rates for the exercise treatment were similar to those found in psychotherapeutic and drug interventions.


title: [Study on assessing early epidemiological parameters of coronavirus disease epidemic in China].

text: Objective: To study the early dynamics of the epidemic of coronavirus disease (COVID-19) in China from 15 to 31 January, 2020, and estimate the corresponding epidemiological parameters (incubation period, generation interval and basic reproduction number) of the epidemic. Methods: By means of Weibull, Gamma and Lognormal distributions methods, we estimated the probability distribution of the incubation period and generation interval data obtained from the reported COVID-19 cases. Moreover, the AIC criterion was used to determine the optimal distribution. Considering the epidemic is ongoing, the exponential growth model was used to fit the incidence data of COVID-19 from 10 to 31 January, 2020, and exponential growth method, maximum likelihood method and SEIR model were used to estimate the basic reproduction number. Results: Early COVID-19 cases kept an increase in exponential growth manner before 26 January, 2020, then the increase trend became slower. The average incubation period was 5.01 (95%CI: 4.31-5.69) days; the average generation interval was 6.03 (95%CI: 5.20-6.91) days. The basic reproduction number was estimated to be 3.74 (95%CI: 3.63-3.87), 3.16 (95%CI: 2.90-3.43), and 3.91 (95%CI: 3.71-4.11) by three methods, respectively. Conclusions: The Gamma distribution fits both the generation interval and incubation period best, and the mean value of generation interval is 1.02 day longer than that of incubation period. The relatively high basic reproduction number indicates that the epidemic is still serious; Based on our analysis, the turning point of the epidemic would be seen on 26 January, the growth rate would be lower afterwards.


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title: Ventral colporectopexy for overt rectal prolapse and obstructed defaecation syndrome: a systematic review.

text: AIM Laparoscopic ventral rectopexy (VR) with the use of prosthesis has been advocated for both overt rectal prolapse (ORP) and obstructed defaecation syndrome (ODS). The present study reviews the short-term and functional results of laparoscopic VR. METHOD A search was performed of MEDLINE, EMBASE, Ovid and Cochrane databases on all studies reporting on VR for ORP, ODS and other anatomical abnormalities of the pelvic floor from 2004 until February 2013. No language restrictions were made. All studies on VR were reviewed systematically. The main outcomes were intra-operative complications, conversion, procedure duration, short-term mortality and morbidity, length of stay, recurrence of ORP, recurrence of anatomical disorder, faecal incontinence and constipation, quality of life (QoL) score and patient satisfaction. Quality assessment and data extraction were performed independently by three observers. RESULTS Twenty-three studies including 1460 patients were eligible for analysis. The conversion rate ranged from 0 to 14.3%. No mortality was reported. The immediate postoperative morbidity rate was 8.6%. Length of stay ranged from 1 to 7 days. A significant improvement in constipation and incontinence symptoms was observed in the postoperative period for both ORP and ODS (chi-square test, P < 0.0001). CONCLUSION Laparoscopic VR is a safe and effective procedure for ORP and ODS. Longer follow-up is required, and studies comparing VR with standard rectopexy and stapled transanal rectal resection are not yet available.


title: Aging veterans' mental health and well-being in the context of COVID-19: The importance of social ties during physical distancing.

text: Prior wartime trauma likely acts as a double-edged sword that promotes both aging veterans' vulnerability and resilience in the context of the current COVID-19 pandemic. During this stressful time, aging veterans may benefit from having an array of socially supportive network ties. We therefore suggest that clinicians working with veterans encourage veterans to (a) create or sustain positive social connections while maintaining physical distance and (b) call upon coping strategies that helped them manage past difficulties. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Effectiveness of isolation, testing, contact tracing, and physical distancing on reducing transmission of SARS-CoV-2 in different settings: a mathematical modelling study.

text: BACKGROUND The isolation of symptomatic cases and tracing of contacts has been used as an early COVID-19 containment measure in many countries, with additional physical distancing measures also introduced as outbreaks have grown. To maintain control of infection while also reducing disruption to populations, there is a need to understand what combination of measures-including novel digital tracing approaches and less intensive physical distancing-might be required to reduce transmission. We aimed to estimate the reduction in transmission under different control measures across settings and how many contacts would be quarantined per day in different strategies for a given level of symptomatic case incidence. METHODS For this mathematical modelling study, we used a model of individual-level transmission stratified by setting (household, work, school, or other) based on BBC Pandemic data from 40 162 UK participants. We simulated the effect of a range of different testing, isolation, tracing, and physical distancing scenarios. Under optimistic but plausible assumptions, we estimated reduction in the effective reproduction number and the number of contacts that would be newly quarantined each day under different strategies. RESULTS We estimated that combined isolation and tracing strategies would reduce transmission more than mass testing or self-isolation alone: mean transmission reduction of 2% for mass random testing of 5% of the population each week, 29% for self-isolation alone of symptomatic cases within the household, 35% for self-isolation alone outside the household, 37% for self-isolation plus household quarantine, 64% for self-isolation and household quarantine with the addition of manual contact tracing of all contacts, 57% with the addition of manual tracing of acquaintances only, and 47% with the addition of app-based tracing only. If limits were placed on gatherings outside of home, school, or work, then manual contact tracing of acquaintances alone could have an effect on transmission reduction similar to that of detailed contact tracing. In a scenario where 1000 new symptomatic cases that met the definition to trigger contact tracing occurred per day, we estimated that, in most contact tracing strategies, 15 000-41 000 contacts would be newly quarantined each day. INTERPRETATION Consistent with previous modelling studies and country-specific COVID-19 responses to date, our analysis estimated that a high proportion of cases would need to self-isolate and a high proportion of their contacts to be successfully traced to ensure an effective reproduction number lower than 1 in the absence of other measures. If combined with moderate physical distancing measures, self-isolation and contact tracing would be more likely to achieve control of severe acute respiratory syndrome coronavirus 2 transmission. FUNDING Wellcome Trust, UK Engineering and Physical Sciences Research Council, European Commission, Royal Society, Medical Research Council.


title: COVID-19 and venous thromboembolism: current insights and prophylactic strategies.

text: The rapidly increasing number of studies on the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) indicate that this viral agent can cause the coronavirus disease 2019 (COVID-19), a syndrome with a wide spectrum of clinical presentations, ranging from a mild disease with flu-like symptoms to a life-threatening condition that requires specialized management at Intensive Care Units (ICU). Critical patients with COVID-19 have a high risk of thromboembolic complications, as expressed by a Padua prediction score always ≥4. Moreover, a number of clinical factors may increase the risk of major bleedings in these patients during ICU stay. Overall, literature data suggest that SARS-CoV-2 infection can rapidly develop into a severe condition with renal, pulmonary and hepatic complications, potentially increasing both thrombotic and haemorrhagic risk. Failure of prevention and interventional strategies for the haemostatic imbalance of severe COVID-19 patients may dramatically impact their prognosis. The role of thromboprophylaxis in this clinical setting is discussed. Key messagesSevere patients with the coronavirus disease 2019 (COVID-19) have a high risk of thromboembolic complications, as expressed by a Padua prediction score always ≥4.A number of clinical factors may also increase the risk of major bleedings in this clinical setting.A patient-tailored strategy with a case-by-case approach is needed when prescribing prophylactic anticoagulation to severe COVID-19 patients.


title: Long-term follow-up of neoplastic pancreatic cysts without high-risk stigmata: how often do we change treatment strategy because of malignant transformation?

text: UNLABELLED * OBJECTIVE Patients with potentially premalignant neoplastic pancreatic cysts without high-risk stigmata usually enter a surveillance program. Data on outcomes of such surveillance programs are scarce. We aimed to evaluate the resection rate and malignancy rate during follow-up. MATERIAL AND METHODS From our prospective database (2006-2015) of patients with pancreatic cysts, we analyzed patients with pancreatic cysts without high-risk stigmata with at least six months follow-up. RESULTS In total, 146 patients were followed for a median of 29 months (IQR 13.5-50 months). In 124 patients (84.9%), no changes in clinical or imaging characteristics occurred during follow-up. Thirteen patients (8.9%) developed an indication for surgery after a median follow-up of 25 months (IQR 12-42 months). Two patients did not undergo surgery because of comorbidity, 11 patients (7.5%) underwent resection. Indications for surgery were symptoms (n = 2), development of a pancreatic mass (n = 1), a new nodule (n = 2), thickened cyst wall (n = 1), pancreatic duct dilation (n = 3), and/or suspicion of mucinous cystic neoplasm (MCN) (n = 3). Postoperative histology showed one pancreatic malignancy not originating from the cyst, three mixed type-intraductal papillary mucinous neoplasm (IPMN), one side branch-IPMN, two MCN, one neuroendocrine tumor, one serous cystadenoma, one inflammatory cyst, and one lymphangioma. The highest grade of cyst dysplasia was borderline dysplasia. CONCLUSIONS Most neoplastic pancreatic cysts without high-risk stigmata at initial presentation show no substantial change during 1-4-year follow-up. Only 7.5% of patients underwent surgery and less than 1% of patients developed pancreatic malignancy. This indicates that additional markers are needed to tailor treatment of pancreatic cysts.


title: Sedentary Behavior and Body Weight and Composition in Adults: A Systematic Review and Meta-analysis of Prospective Studies.

text: BACKGROUND The cumulative effect of too much sedentary behavior may contribute to weight gain and obesity. OBJECTIVE The aim of this study was to conduct a systematic review and meta-analysis of prospective cohorts and randomized controlled studies to determine the association between sedentary behavior and body weight and obesity in adults. DATA SOURCES AND STUDY SELECTION Relevant studies were identified from searches of the MEDLINE, Embase, AMED and PubMed databases up to May 2017, and by manual searches of in-text citations. Studies that evaluated the association in adults between sedentary behavior and body weight or obesity, while controlling for physical activity, were included. Overall, 31 publications met the eligibility criteria, including 23 prospective cohort studies with data that could be extracted for a quantitative meta-analysis, and a single randomized controlled trial. RESULTS There were no significant associations between sedentary behavior and any measure of body weight or obesity, with the exception of waist circumference. For the latter outcome, over a 5-year follow-up period, each 1 h per day increase-from baseline to follow-up-in sedentary behavior was associated with a 0.02 mm [95% confidence interval (CI) 0.01-0.04; p = 0.001) increase in waist circumference. The odds ratio of becoming overweight or obese was 1.33 (95% CI 1.11-1.60; p = 0.001) in the highest compared with lowest categories of sedentary behavior. CONCLUSIONS Meta-analysis of data from prospective cohort studies showed small, inconsistent and non-significant associations between sedentary behavior and body weight.


title: Influence of a combined CT/C-arm system on periprocedural workflow and procedure times in mechanical thrombectomy.

text: OBJECTIVE To achieve the fastest possible workflow in ischaemic stroke, we developed a CT/C-arm system, which allows imaging and endovascular treatment on the same patient table. METHODS This prospective, monocentric trial was conducted between October 2014 and August 2016. Patients received stroke imaging and mechanical thrombectomy under general anaesthesia (GA) or conscious sedation (CS) using our combined setup comprising a CT-scanner and a mobile C-arm X-ray device. Primary endpoint was time between stroke imaging and groin puncture. We compared periprocedural workflow and procedure times with the literature and a matched patient cohort treated with a biplane angiographic system before installation of the CT/C-arm system. RESULTS In 50 patients with acute ischaemic stroke due to large-vessel occlusion in the anterior circulation, comparable recanalization rates were achieved by using the CT/C-arm setup (TICI2b-3:CT/C-arm-GA: 85.7%; CT/C-arm-CS: 90.9%; Angiosuite: 78.6%; p = 0.269) without increasing periprocedural complications. Elimination of patient transport resulted in a significant reduction of the time between stroke imaging and groin puncture: median, min (IQR): CT/C-arm-GA: 43 (35-52); CT/C-arm-CS: 39 (28-49); Angiosuite: 64 (48-74); p < 0.0001. CONCLUSION The combined CT/C-arm system allows comparable recanalization rates as a biplane angiographic system and accelerates the start of the endovascular stroke treatment. KEY POINTS • The CT/C-arm setup reduces median time from stroke imaging to groin puncture. • Mechanical thrombectomy using a C-arm device is feasible without increasing peri-interventional complications. • The CT/C-arm setup might be a valuable fallback solution for emergency procedures. • The CT/C-arm setup allows immediate control CT images during and after treatment.


title: Use of perfusion imaging and other imaging techniques to assess risks/benefits of acute stroke interventions.

text: The advent of multimodal neuroimaging has provided acute stroke care providers with an armamentarium of sophisticated imaging options to utilize for guidance in clinical decision-making and management of acute ischemic stroke patients. Here, we propose a framework and potential algorithm-based methodology for imaging modality selection and utilization for the purpose of achieving optimal stroke clinical care. We first review imaging options that may best inform decision-making regarding revascularization eligibility, with a focus on the imaging modalities that best identify critical inclusion and exclusion criteria. Next, we review imaging methods that may guide the successful achievement of revascularization once it has been deemed desirable and feasible. Further, we review imaging modalities that may best assist in both the noninterventional care of acute stroke as well as the identification of stroke-mimics. Finally, we review imaging techniques under current investigation that show promise to improve future acute stroke management.


title: Mesh-related complications in paraoesophageal repair: a systematic review.

text: BACKGROUND Paraoesophageal hernias (PEH) have a high recurrence rate, prompting surgeons to consider the use of mesh reinforcement of the hiatus. The risks and benefits of mesh augmentation in PEH repair are debated. Mesh-related complications including migration and erosion are considered in this publication. DESIGN A systematic literature review of articles published between 1970 and 2019 in Medline, OVID, Embase, and Springer database was conducted, identifying case reports, case series and observational studies of PEH repair reporting mesh-related complications. RESULTS Thirty-five case reports/series of 74 patients and 20 observational studies reporting 75 of 4200 patients with mesh complications have been included. The incidence of mesh-related erosions in this study is 0.035%. PTFE, ePTFE, composite and synthetic meshes were frequently associated with mesh erosion requiring intervention. Complete erosions are often managed endoscopically while partial erosions may require surgery and resection of the oesophagus and/or stomach. CONCLUSIONS Mesh-related complication is rare with dysphagia a common presenting feature. Mesh erosion is associated with synthetic mesh more frequently in the reported literature. A mesh registry with long-term longitudinal data would help in understanding the true incidence of mesh-related complications.


title: Imaging heterogeneity of peptide delivery and binding in solid tumors using SPECT imaging and MRI.

text: BACKGROUND As model system, a solid-tumor patient-derived xenograft (PDX) model characterized by high peptide receptor expression and histological tissue homogeneity was used to study radiopeptide targeting. In this solid-tumor model, high tumor uptake of targeting peptides was expected. However, in vivo SPECT images showed substantial heterogeneous radioactivity accumulation despite homogenous receptor distribution in the tumor xenografts as assessed by in vitro autoradiography. We hypothesized that delivery of peptide to the tumor cells is dictated by adequate local tumor perfusion. To study this relationship, sequential SPECT/CT and MRI were performed to assess the role of vascular functionality in radiopeptide accumulation. METHODS High-resolution SPECT and dynamic contrast-enhanced (DCE)-MRI were acquired in six mice bearing PC295 PDX tumors expressing the gastrin-releasing peptide (GRP) receptor. Two hours prior to SPECT imaging, animals received 25 MBq (111)In(DOTA-(βAla)2-JMV594) (25 pmol). Images were acquired using multipinhole SPECT/CT. Directly after SPECT imaging, MR images were acquired on a 7.0-T dedicated animal scanner. DCE-MR images were quantified using semi-quantitative and quantitative models. The DCE-MR and SPECT images were spatially aligned to compute the correlations between radioactivity and DCE-MRI-derived parameters over the tumor. RESULTS Whereas histology, in vitro autoradiography, and multiple-weighted MRI scans all showed homogenous tissue characteristics, both SPECT and DCE-MRI showed heterogeneous distribution patterns throughout the tumor. The average Spearman's correlation coefficient between SPECT and DCE-MRI ranged from 0.57 to 0.63 for the "exchange-related" DCE-MRI perfusion parameters. CONCLUSIONS A positive correlation was shown between exchange-related DCE-MRI perfusion parameters and the amount of radioactivity accumulated as measured by SPECT, demonstrating that vascular function was an important aspect of radiopeptide distribution in solid tumors. The combined use of SPECT and MRI added crucial information on the perfusion efficiency versus radiopeptide uptake in solid tumors and showed that functional tumor characteristics varied locally even when the tissue appeared homogenous on current standard assessment techniques.


title: Contrast Agent Enhanced Multimodal Photoacoustic Microscopy and Optical Coherence Tomography for Imaging of Rabbit Choroidal and Retinal Vessels in vivo.

text: Multimodal imaging with photoacoustic microscopy (PAM) and optical coherence tomography (OCT) can be an effective method to evaluate the choroidal and retinal microvasculature. To improve the efficiency for visualizing capillaries, colloidal gold nanoparticles (AuNPs) have been applied as a multimodal contrast agent for both OCT and PAM imaging by taking advantage of the strong optical scattering and the strong optical absorption of AuNPs due to their surface plasmon resonance. Ultra-pure AuNPs were fabricated by femtosecond laser ablation, capped with polyethylene glycol (PEG), and administered to 13 New Zealand white rabbits and 3 Dutch Belted pigmented rabbits. The synthesized PEG-AuNPs (20.0 ± 1.5 nm) were demonstrated to be excellent contrast agents for PAM and OCT, and do not demonstrate cytotoxicity to bovine retinal endothelial cells in cell studies. The image signal from the retinal and choroidal vessels in living rabbits was enhanced by up to 82% for PAM and up to 45% for OCT, respectively, by the administered PEG-AuNPs, which enables detection of individual blood vessels by both imaging modalities. The biodistribution study demonstrated the AuNP accumulated primarily in the liver and spleen. Histology and TUNEL staining did not indicate cell injury or death in the lung, liver, kidney, spleen, heart, or eyes up to seven days after AuNP administration. PEG-AuNPs offer an efficient and safe contrast agent for multimodal ocular imaging to achieve improved characterization of microvasculature.


title: Endovascular treatment of posterior circulation aneurysms.

text: Endovascular techniques are well suited for the treatment of posterior circulation aneurysms. This review describes the endovascular management of these aneurysms and discusses relevant technical advances.


title: A randomized comparison of laparoscopic, magnetically anchored, and flexible endoscopic cameras in performance and workload between laparoscopic and single-incision surgery.

text: BACKGROUND This study aimed to evaluate the surgeon performance and workload of a next-generation magnetically anchored camera compared with laparoscopic and flexible endoscopic imaging systems for laparoscopic and single-site laparoscopy (SSL) settings. METHODS The cameras included a 5-mm 30° laparoscope (LAP), a magnetically anchored (MAGS) camera, and a flexible endoscope (ENDO). The three camera systems were evaluated using standardized optical characteristic tests. Each system was used in random order for visualization during performance of a standardized suturing task by four surgeons. Each participant performed three to five consecutive repetitions as a surgeon and also served as a camera driver for other surgeons. Ex vivo testing was conducted in a laparoscopic multiport and SSL layout using a box trainer. In vivo testing was performed only in the multiport configuration and used a previously validated live porcine Nissen model. RESULTS Optical testing showed superior resolution for MAGS at 5 and 10 cm compared with LAP or ENDO. The field of view ranged from 39 to 99°. The depth of focus was almost three times greater for MAGS (6-270 mm) than for LAP (2-88 mm) or ENDO (1-93 mm). Both ex vivo and in vivo multiport combined surgeon performance was significantly better for LAP than for ENDO, but no significant differences were detected for MAGS. For multiport testing, workload ratings were significantly less ex vivo for LAP and MAGS than for ENDO and less in vivo for LAP than for MAGS or ENDO. For ex vivo SSL, no significant performance differences were detected, but camera drivers rated the workload significantly less for MAGS than for LAP or ENDO. CONCLUSION The data suggest that the improved imaging element of the next-generation MAGS camera has optical and performance characteristics that meet or exceed those of the LAP or ENDO systems and that the MAGS camera may be especially useful for SSL. Further refinements of the MAGS camera are encouraged.


title: Flavonoids isolated from loquat (Eriobotrya japonica) leaves inhibit oxidative stress and inflammation induced by cigarette smoke in COPD mice: the role of TRPV1 signaling pathways.

text: Chronic obstructive pulmonary disease (COPD) is a chronic, progressive lung disease with few successful treatments, and is strongly associated with cigarette smoking (CS). Since the novel coronavirus has spread worldwide seriously, there is growing concern that patients who have chronic respiratory conditions like COPD can easily be infected and are more prone to having severe illness and even mortality because of lung dysfunction. Loquat leaves have long been used as an important material for both pharmaceutical and functional applications in the treatment of lung disease in Asia, especially in China and Japan. Total flavonoids (TF), the main active components derived from loquat leaves, showed remarkable anti-inflammatory and antioxidant activities. However, their protective activity against CS-induced COPD airway inflammation and oxidative stress and its underlying mechanism still remain not well-understood. The present study uses a CS-induced mouse model to estimate the morphological changes in lung tissue. The results demonstrated that TF suppressed the histological changes in the lungs of CS-challenged mice, as evidenced by reduced generation of pro-inflammatory cytokines including interleukin 6 (IL-6), IL-1β, tumor necrosis factor α (TNF-α), nitric oxide (NO), and inducible nitric oxide synthase (iNOS) and diminished the protein expression of transient receptor potential vanilloid 1 (TRPV1). Moreover, TF also inhibited phosphorylation of IKK, IκB and NFκB and increased p-Akt. Interestingly, TF could inhibit CS-induced oxidative stress in the lungs of COPD mice. TF treatment significantly inhibited the level of malondialdehyde (MDA) and increased the activity of superoxide dismutase (SOD). In addition, TF markedly downregulated TRPV1 and cytochrome P450 2E1 (CYP2E1) and upregulated the expression of SOD-2, while the p-JNK level was observed to be inhibited in COPD mice. Taken together, our findings showed that the protective effect and putative mechanism of the action of TF resulted in the inhibition of inflammation and oxidative stress through the regulation of TRPV1 and the related signal pathway in lung tissues. It suggested that TF derived from loquat leaves could be considered to be an alternative or a new functional material and used for the treatment of CS-induced COPD.


title: The surgical treatment of fibroids for infertility.

text: Uterine fibroids are a major gynecologic disorder among women and commonly found in the infertile couple. Although numerous surgical techniques exist to destroy or remove these tumors, the role of such surgical procedures in the infertile woman has been heavily debated. The primary reason for this is a lack of evidence of a cause-and-effect relationship between fibroids and subfertility. However, review of the evidence suggests that submucous myomas and possibly intramural myomas both serve to decrease female fertility. A second reason for caution is concern over the impact of surgical treatment on fertility enhancement. For submucous myomas, hysteroscopic myomectomy has proven capable of increasing fertility rates, although this statement may not apply to type 2 submucous myomas. No evidence currently exists for a beneficial effect on fertility of surgical intervention for intramural or subserous fibroids. More randomized treatment trials are clearly needed to clarify the role of myomectomy and other procedures in the infertile woman with type 2 submucous and intramural myomas.


title: Automated versus non-automated weaning for reducing the duration of mechanical ventilation for critically ill adults and children: a cochrane systematic review and meta-analysis.

text: INTRODUCTION Automated weaning systems may improve adaptation of mechanical support for a patient's ventilatory needs and facilitate systematic and early recognition of their ability to breathe spontaneously and the potential for discontinuation of ventilation. Our objective was to compare mechanical ventilator weaning duration for critically ill adults and children when managed with automated systems versus non-automated strategies. Secondary objectives were to determine differences in duration of ventilation, intensive care unit (ICU) and hospital length of stay (LOS), mortality, and adverse events. METHODS Electronic databases were searched to 30 September 2013 without language restrictions. We also searched conference proceedings; trial registration websites; and article reference lists. Two authors independently extracted data and assessed risk of bias. We combined data using random-effects modelling. RESULTS We identified 21 eligible trials totalling 1,676 participants. Pooled data from 16 trials indicated that automated systems reduced the geometric mean weaning duration by 30% (95% confidence interval (CI) 13% to 45%), with substantial heterogeneity (I(2) = 87%, P <0.00001). Reduced weaning duration was found with mixed or medical ICU populations (42%, 95% CI 10% to 63%) and Smartcare/PS (28%, 95% CI 7% to 49%) but not with surgical populations or using other systems. Automated systems reduced ventilation duration with no heterogeneity (10%, 95% CI 3% to 16%) and ICU LOS (8%, 95% CI 0% to 15%). There was no strong evidence of effect on mortality, hospital LOS, reintubation, self-extubation and non-invasive ventilation following extubation. Automated systems reduced prolonged mechanical ventilation and tracheostomy. Overall quality of evidence was high. CONCLUSIONS Automated systems may reduce weaning and ventilation duration and ICU stay. Due to substantial trial heterogeneity an adequately powered, high quality, multi-centre randomized controlled trial is needed.


Effectiveness of Fertility Awareness-Based Methods for Pregnancy Prevention: A Systematic Review: Correction.


title: Medical overuse in the Iranian healthcare system: a systematic scoping review and practical recommendations for decreasing medical overuse during unexpected COVID-19 pandemic opportunity

text: Background: Overuse of medical care is a major problem across health systems as well as in Iran. By our knowledge, this is the first scoping review in which medical overuse in the Iranian healthcare system was investigated. Objective: To perform an inclusive search for original studies that report medical overuse in the Iranian healthcare system. Methods: A systematic search of the literature conducted in bibliographic databases including PubMed, Embase, Scopus, Web of Sciences, Cochrane and Scientific Information Database using a comprehensive search strategy without time limit until the end of 2018, accomplished by reference tracking, author contacting and expert consultation to identify studies on the overuse of medical care. Results: We reviewed 4124 published articles based on predetermined inclusion criteria. The authors consensus included a total of 40 articles. Of these, 31 were in English and 9 in Farsi, published between 19975-2018. The result categorized into two distinct clinical areas: treatment (17 articles), and diagnostic (23 articles) services. Almost all of the studies only described the magnitude of unnecessary overuse. Unnecessary overuse of Antibiotics, MRI and CT-scan were the most reported topics. The ranges of their overuse proportion were as follows; Antibiotic (31 to 97%); MRI (33 to 88%), and CT-scan (19 to 50%). Conclusions: Our review showed, even so, the magnitude of unnecessary overuse of medical services is high but there are only a few interventional studies in clinical and administrative level for finding effective methods for decreasing these unnecessary services. Researchers should be encouraged to conducting interventional studies. We suggest the ministry of health to use the golden opportunity of COVID-19 epidemic for designing Iran national policy and action plan for controlling and preventing unnecessary health care services and including a section for Interventional Research in the action plan.


title: Effects of pre-existing morbidities on occurrence of death among COVID-19 disease patients: A systematic review and meta-analysis

text: Abstract Background: Coronavirus disease 2019 (COVID-19), most hectic pandemic of the era, is increasing exponentially and taking thousands of lives, worldwide. Objective: This study aimed to assess the prevalence of pre-existing morbidities among COVID-19 infected patients and their mortality risks against each type of pre-existing morbidity categories. Design: Systematic review and meta-analysis Data sources: Medline, Web of Science, Scopus, and CINAHL databases were searched using the following keywords: (COVID-19 or 2019-nCoV or Coronavirus or SARS-CoV-2) AND (Comorbidity or Morbidity) AND (Mortality or Death or Died) up to May 01, 2020. Further searches were conducted using the reference list of the selected studies, renowned pre-print servers (e.g., medRxiv, bioRixv, SSRN), and relevant journal websites. Eligibility criteria: Studies written in the English language included if those were conducted among COVID-19 patients with and without comorbidities and presented survivor vs. non-survivor counts or hazard/odds of deaths or survivors against types of pre-existing morbidities. Methods: Comorbidities reported in the selected studies were grouped into eight categories. The pooled likelihoods of deaths in each category were estimated using a fixed or random-effect model, based on the heterogeneity assessment. Publication bias was assessed by visual inspection of the funnel plot asymmetry and Egger regression test. Trim and Fill method was used if there any publication bias was found. Results: A total of 42 studies included in this study comprised of 39,398 samples. The most common pre-existing morbidities in COVID-19 infected patients were hypertension (36.5%), cardiovascular disease (11.9%), and diabetes (22.0%). The higher likelihood of deaths was found among COVID-19 patients who had pre-existing cardiovascular system diseases (OR: 3.32, 95% CI: 2.79-3.95), immune and metabolic disorders (OR: 2.39, 95% CI: 2.00-2.85), respiratory diseases (OR: 2.02, 95% CI: 1.80-2.26), cerebrovascular system diseases (OR: 4.12, 95% CI: 3.04-5.58), any types of cancers (OR: 2.22, 95% CI: 1.63-3.03), renal (OR: 3.02, 95% CI: 2.60-3.52), and liver system diseases (OR: 1.44, 95% CI: 1.21-1.71). Conclusions: This study provides evidence of a higher likelihood of deaths among COVID-19 patients against morbidity categories. These findings could potentially help healthcare providers to sort out the most endangered COVID-19 patients by comorbidities, take precautionary measures during hospitalization, assess susceptibility to death, and prioritize their treatment, which could potentially reduce the number of fatalities in COVID-19 disease.


title: The Effectiveness of Targeted Quarantine for Minimising Impact of COVID-19

text: We model the extent to which age targeted quarantine can be used to reduce ICU admissions caused by novel coronavirus COVID-19. Using demographic data from New Zealand, we demonstrate that lowering the age threshold for quarantine to 50 years of age reduces ICU admissions drastically, and show that for sufficiently strict isolation protocols, isolating one third of the countries population for a total of 6 months is sufficient to avoid overwhelming ICU capacity throughout the entire course of the epidemic. Similar results are expected to hold for other countries, though some minor adaption will be required based on local age demographics and hospital facilities.


title: What has the covid-19 pandemic taught us about adopting preventive measures?/ ¿lo que la pandemia covid-19 nos enseñó sobre la adopción de las medidas preventivas?/ O que a pandemia da covid-19 tem nos ensinado sobre adoção de medidas de precaução?

text: ABSTRACT Objective: to analyze the COVID-19 pandemic and what we have (re)learned from the world experience of adopting prevention measures recommended by the World Health Organization as well as the epidemiological overview in the world, in Latin America and in Brazil. Results: the World Health Organization has pointed out that the path to reduce the speed of circulation of the virus, control and decrease in the number of cases and deaths resulting from this pandemic can only be accomplished with mass adoption of fundamental measures that include hand hygiene, alcohol gel use, cough etiquette, cleaning surfaces, avoiding agglomerations and social distancing. The epidemiological curve of the disease clearly shows the devastating proportions in Italy, Spain and the United States, surpassing China in death records, due to the delay in adopting the aforementioned measures. In Brazil, the rapid progression in relation to the world and Latin America points to an important increase in the number of cases. Conclusion: this is possibly the most serious pandemic in recent human history, and its course can be influenced by the rigor in adopting individual and collective behavioral measures.


title: A Heuristic Model for Spreading of COVID 19 in Singapore

text: This paper presents a simple heuristic model for COVID 19 spreading. The model is based on a propagation unit of time. The state of the epidemic at the end of the time unit is then related to that at the start through recurrence relationships. By propagating these relationships over the required number of time units, a projection can be made over time. The model is readily implemented on a spreadsheet and is therefore potentially widely accessible. It can serve as a useful tool for scenario planning and forecasting not just for an entire population, but also for a specific community within a population.


title: Social distancing prevents infections, but it can have unintended consequences

text: In response to the coronavirus pandemic, public health officials are asking us to do something that does not come naturally to our very social species: Stay away from each other Such social distancing—avoiding large gatherings and close contact with others—is crucial for slowing the spread of the virus and preventing our health care system from getting overwhelmed But it won’t be easy


title: A consensus Covid-19 immune signature combines immuno-protection with discrete sepsis-like traits associated with poor prognosis

text: Person-to-person transmission of SARS-CoV-2 virus has triggered a global emergency because of its potential to cause life-threatening Covid-19 disease. By comparison to pauci-symptomatic virus clearance by most individuals, Covid-19 has been proposed to reflect insufficient and/or pathologically exaggerated immune responses. Here we identify a consensus peripheral blood immune signature across 63 hospital-treated Covid-19 patients who were otherwise highly heterogeneous. The core signature conspicuously blended adaptive B cell responses typical of virus infection or vaccination with discrete traits hitherto associated with sepsis, including monocyte and dendritic cell dampening, and hyperactivation and depletion of discrete T cell subsets. This blending of immuno-protective and immuno-pathogenic potentials was exemplified by near-universal CXCL10/IP10 upregulation, as occurred in SARS1 and MERS. Moreover, specific parameters including CXCL10/IP10 over-expression, T cell proliferation, and basophil and plasmacytoid dendritic cell depletion correlated, often prognostically, with Covid-19 progression, collectively composing a resource to inform SARS-CoV-2 pathobiology and risk-based patient stratification.


title: Quantitative PCR for cannabis flower containing SARs-CoV-2

text: In January of 2020, COVID-19 became a worldwide pandemic. As many industries shutdown to comply with social distancing measures, the cannabis industry was deemed an essential business in most U.S. jurisdictions. Cannabis is manually farmed, trimmed and packaged. Employees and trimmers in cannabis grows have been reported to test qPCR positive for SARs-CoV-2 and as a result cannabis flower can be a potential inhaled SARs-CoV-2 fomite. Many of the comorbidities described in COVID-19 are also qualifying conditions for medical cannabis access. Bat guano has been identified as a rich source for novel coronavirus discovery and it is also a common fertilizer in the cannabis field. To better assess cannabis fomite risk we developed a SARs-CoV-2 quantitative PCR assay optimized to operate with a hemp flower background matrix. This assay was utilized to estimate the stability of gamma irradiated SARs-CoV-2 as a hemp flower fomite.


docid: ptnmtvzj

title: Effectiveness and safety of antiviral or antibody treatments for coronavirus: A rapid review

text: Background: To identify safe and effective medical countermeasures (e.g., antivirals/antibodies) to address the current outbreak of a novel coronavirus (COVID-19) Methods: Comprehensive literature searches were developed by an experienced librarian for MEDLINE, EMBASE, the Cochrane Library, and biorxiv.org/medrxiv.org; additional searches for ongoing trials and unpublished studies were conducted in clinicaltrials.gov and the Global Infectious Diseases and Epidemiology Network (GIDEON). Title/abstract and full-text screening, data abstraction, and risk of bias appraisal were carried out by single reviewers. Results: 54 studies were included in the review: three controlled trials, 10 cohort studies, seven retrospective medical record/database studies, and 34 case reports or series. These studies included patients with severe acute respiratory syndrome (SARs, n=33), middle east respiratory syndrome (MERS, n=16), COVID-19 (n=3), and unspecified coronavirus (n=2). The most common treatment was ribavirin (n=41), followed by oseltamivir (n=10) and the combination of lopinavir/ritonavir (n=7). Additional therapies included broad spectrum antibiotics (n=30), steroids (n=39) or various interferons (n=12). No eligible studies examining monoclonal antibodies for COVID-19 were identified. One trial found that ribavirin prophylactic treatment statistically significantly reduced risk of MERS infection in people who had been exposed to the virus. Of the 21 studies reporting rates of ICU admission in hospitalized SARS or MERS patients, none reported statistically significant results in favour of or against antiviral therapies. Of the 40 studies reporting mortality rates in hospitalized SARS or MERS patients, one cohort study (MERS) and one retrospective study (SARS) found a statistically significant increase in the mortality rate for patients treated with ribavirin. Eighteen studies reported potential drug-related adverse effects including gastrointestinal symptoms, anemia, and altered liver function in patients receiving ribavirin. Conclusion: The current evidence for the effectiveness and safety of antiviral therapies for coronavirus is inconclusive and suffers from a lack of well-designed prospective trials or observational studies, preventing any treatment recommendations from being made. However, it is clear that the existing body of evidence is weighted heavily towards ribavirin (41/54 studies), which has not shown conclusive evidence of effectiveness and may cause harmful adverse events so future investigations may consider focusing on other candidates for antiviral therapy.


title: Estimate number of individuals infected with the 2019-novel coronavirus in South Korea due to the influx of international students from countries with virus risk: a simulation study

text: Background: In March 2020, overall, 37,000 international students from the country at risk of the 2019-novel coronavirus (COVID-19) infection will arrive in Seoul, South Korea. Individuals from the country at risk of COVID-19 infection have been included in a home-quarantine program, but the efficacy of the program is uncertain. Methods: To estimate the possible number of infected individuals within the large influx of international students, we used a deterministic compartmental model for epidemic and perform a simulation-based search of different rates of compliance with home-quarantine. Results: Under the home-quarantine program, the total number of the infected individuals would reach 24-53 from March 17-March 20, 50-86 from March 18-March 16, and 234-343 from March 4-March 23 with the arrival of 0.1%, 0.2%, and 1% of pre-infectious individuals, in Seoul, South Korea, respectively. Our findings indicated when incoming international students showed strict compliance with quarantine, epidemics were less likely to occur in Seoul, South Korea. Conclusion: To mitigate possible epidemics, additional efforts to improve the compliance of home-quarantine are warranted along with other containment policies.


title: ACE inhibitors, AT1 receptor blockers and COVID-19: clinical epidemiology evidences for a continuation of treatments. The ACER-COVID study

text: Aims: The question of interactions between the renin angiotensin aldosterone system drugs and the incidence and prognosis of COVID-19 infection has been raised by the medical community. We hypothesised that if patients treated with ACE inhibitors (ACEI) or AT1 receptor blockers (ARB) were more prone to SARS-CoV2 infection and had a worse prognosis than untreated patients, the prevalence of consumption of these drugs would be higher in patients with COVID-19 compared to the general population. Methods and results: We used a clinical epidemiology approach based on the estimation of standardised prevalence ratio (SPR) of consumption of ACEI and ARB in four groups of patients (including 187 COVID-19 positive) with increasing severity referred to the University hospital of Lille and in three French reference samples (the exhaustive North population (n=1,569,968), a representative sample of the French population (n=414,046), a random sample of Lille area (n=1,584)). The SPRs of ACEI and ARB did not differ as the severity of the COVID-19 patients increased, being similar to the regular consumption of these drugs in the North of France population with the same non-significant increase for both treatment (1.17 [0.83-1.67]). A statistically significant increase in the SPR of ARB (1.56 [1.02-2.39]) was observed in intensive care unit patients only. After stratification on obesity, this increase was limited to the high risk subgroup of obese patients. Conclusions: Our results strongly support the recommendation that ACEI and ARB should be continued in the population and in COVID-19 positive patients, reinforcing the position of several scientific societies.


title: YouTube as an information source during the Coronavirus disease (COVID-19) pandemic

text: Bakcground: YouTube is an important online source of information. And its viewing numbers tend to increase exponentially in extraordinary situations. Our aim in this study was to evaluate the contents of the most frequently viewed YouTube videos during the COVID-19 pandemic. Method: In this study, contents of the most frequently viewed Turkish and English videos regarding COVID-19 pandemics are examined and scored with modified DISCERN, MICI and VPI. Results: The mean DISCERN score of Turkish videos is similar to English videos (2.55 and 2.43 respectively). Total MICI score tends to be higher in Turkish videos. 86.9% of all 168 videos and 65.2% of all 23 misleading videos were released by news channels. Average view counts, view ratios, and VPIs of misleading videos are higher than the useful videos. Conclusions: Since there is not a peer-review system on YouTube, it is very important for the content of videos that are released through news channels to be accurate because the important messages can be spread among people in society through them. Especially some Turkish videos included many different rumors and faulty statements. During the extraordinary situations such as the pandemics, the videos of official health authorities and international institutions should be more visible in YouTube. Keywords: SARS-CoV-2, DISCERN, MICI, Video Power Index


title: COVID-19 screening strategies that permit the safe re-opening of college campuses

text: Importance: The COVID-19 pandemic poses an existential threat to many US residential colleges: either they open their doors to students in September or they risk serious financial consequences. Objective: To define SARS-CoV-2 screening performance standards that would permit the safe return of students to campus for the Fall 2020 semester. Design: Decision and cost-effectiveness analysis linked to a compartmental epidemic model to evaluate campus screening using tests of varying frequency (daily-weekly), sensitivity (70%-99%), specificity (98%-99.7%), and cost ($10-$50/test). Reproductive numbers Rt = {1.5, 2.5, 3.5} defined three epidemic scenarios, with additional infections imported via exogenous shocks. We generally adhered to US government guidance for parameterization data. Participants: A hypothetical cohort of 5000 college-age, uninfected students. Main Outcome(s) and Measure(s): Cumulative tests, infections, and costs; daily isolation dormitory census; incremental cost-effectiveness; and budget impact. All measured over an 80-day, abbreviated semester. Results: With Rt = 2.5, daily screening with a 70% sensitive, 98% specific test produces 85 cumulative student infections and isolation dormitory daily census averaging 108 (88% false positives). Screening every 2 (7) days nets 135 (3662) cumulative infections and daily isolation census 66 (252) with 73% (4%) false positives. Across all scenarios, test frequency exerts more influence on outcomes than test sensitivity. Cost-effectiveness analysis selects screening every {2, 1, 7} days with a 70% sensitive test as the preferred strategy for Rt = {2.5, 3.5, 1.5}, implying a screening cost of {$470, $920, $120} per student per semester. Conclusions & Relevance: Rapid, inexpensive and frequently conducted screening (even if only 70% sensitive) would be cost-effective and produce a modest number of COVID-19 infections. While the optimal screening frequency hinges on the success of behavioral interventions to reduce the base severity of transmission (Rt), this could permit the safe return of student to campus.


title: Pollen Explains Flu-Like and COVID-19 Seasonality

text: Current models for flu-like epidemics insufficiently explain multi-cycle seasonality. Meteorological factors alone do not predict seasonality, given substantial climate differences between countries that are subject to flu-like epidemics or COVID-19. Pollen is documented to be antiviral and allergenic, play a role in immuno-activation, and seems to create a bio-aerosol lowering the reproduction number of flu-like viruses. Therefore, we hypothesize that pollen may explain the seasonality of flu-like epidemics including COVID-19. We tested the Pollen-Flu Seasonality Theory for 2016-2020 flu-like seasons, including COVID-19, in The Netherlands with its 17 million inhabitants. We combined changes in flu-like incidence per 100K/Dutch citizens (code: ILI) with weekly pollen counts and meteorological data for the same period. Finally, a discrete, predictive model is tested using pollen and meteorological threshold values displaying inhibitory effects on flu-like incidence. We found a highly significant inverse association of r(224)= -.38 between pollen and changes in flu-like incidence corrected for incubation period, confirming our expectations for the 2019/2020 COVID-19 season. We found that our predictive model has the highest inverse correlation with changes in flu-like incidence of r(222) = -.48 (p < .001) when pollen thresholds of 610 total pollen grains/m3 per week, 120 allergenic pollen grains/m3 per week, and a solar radiation threshold of 510 J/cm2 are passed. The passing of at least the pollen thresholds, preludes the beginning and end of flu-like seasons. Solar radiation is a supportive factor, temperature makes no difference, and relative humidity associates even with flu-like incidence increases. We conclude that pollen is a predictor for the inverse seasonality of flu-like epidemics including COVID-19, and solar radiation is a co-inhibitor. The observed seasonality of COVID-19 during Spring, suggests that COVID-19 may revive in The Netherlands after week 33, the start being preceded by the relative absence of pollen, and follows standard pollen-flu seasonality patterns.


docid: ngsstnpr

title: Dynamic Modeling to Identify Mitigation Strategies for Covid-19 Pandemic

text: Relevant pandemic-spread scenario simulations provide guiding principles for containment and mitigation policy developments. Here we devise a simple model to predict the effectiveness of different mitigation strategies. The model consists of a set of simple differential equations considering the population size, reported and unreported infections, reported and unreported recoveries and the number of Covid-19-inflicted deaths. For simplification, we assume that Covid-19 survivors are immune (e.g. mutations are not considered) and that the virus can only be passed on by persons with undetected infections. While the latter assumption is a simplification (it is neglected that e.g. hospital staff may be infected by detected patients with symptoms), it was introduced here to keep the model as simple as possible. Moreover, the current version of the model does not account for age-dependent differences in the death rates, but considers higher mortality rates due to temporary shortage of intensive care units. Some of the model parameters have been fitted to the reported cases outside of China1 from January 22 to March 12 of the 2020 Covid-19 pandemic. The other parameters were chosen in a plausible range to the best of our knowledge. We compared infection rates, the total number of people getting infected and the number of deaths in six different scenarios. Social distancing or increased testing can contain or drastically reduce the infections and the predicted number of deaths when compared to a situation without mitigation. We find that mass-testing alone and subsequent isolation of detected cases can be an effective mitigation strategy, alone and in combination with social distancing. However, unless one assumes that the virus can be globally defeated by reducing the number of infected persons to zero, testing must be upheld, albeit at reduced intensity, to prevent subsequent waves of infection. The model suggests that testing strategies can be equally effective as social distancing, though at much lower economical costs. We discuss how our mathematical model may help to devise an optimal mix of mitigation strategies against the Covid-19 pandemic. The website corona-lab.ch provides an interactive simulation tool based on the presented model.


title: Plasma Metabolomic and Lipidomic Alterations Associated with COVID-19

text: The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. COVID-19 is marked by its rapid progression from mild to severe conditions, particularly in the absence of adequate medical care. However, the physiological changes associated with COVID-19 are barely understood. In this study, we performed untargeted metabolomic and lipidomic analyses of plasma from a cohort of COVID-19 patients who had experienced different symptoms. We found the metabolite and lipid alterations exhibit apparent correlation with the course of disease in these COVID-19 patients, indicating that the development of COVID-19 affected patient metabolism. Moreover, many of the metabolite and lipid alterations, particularly ones associated with hepatic functions, have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about blood biomarkers associated with COVID-19 and potential therapeutic targets, and presents important resource for further studies of COVID-19 pathogenesis.


title: Deep Learning and Holt-Trend Algorithms for predicting COVID-19 pandemic

text: According to WHO, more than one million individuals are infected with COVID-19, and around 20000 people have died because of this infectious disease around the world. In addition, COVID-19 epidemic poses serious public health threat to the world where people with little or no pre-existing human immunity can be more vulnerable to the effects of the effects of the coronavirus. Thus, developing surveillance systems for predicting COVID-19 pandemic in an early stage saves millions of lives. In this study, the deep learning algorithm and Holt-trend model is proposed to predict coronavirus. The Long-Short Term Memory (LSTM ) algorithm and Holt-trend were applied to predict confirmed numbers and death cases. The real time data have been collected from the World Health Organization (WHO) . In the proposed research, we have considered three countries to test the proposed model namely Saudi Arabia, Spain and Italy. The results suggest that the LSTM models showed better performance in predicting the cases of coronavirus patients. Standard measure performance MSE, RMSE, Mean error and correlation are employed to estimate the results of the proposed models. The empirical results of the LSTM by using correlation metric are 99.94%, 99.94% and 99.91 to predict number of confirmed cases on COVID-19 in three countries. Regarding the prediction results of LSTM model to predict the number of death on COVID-19 are 99.86%, 98.876% and 99.16 with respect to the Saudi Arabia, Italy and Spain respectively. Similarly the experimented results of Holt-Trend to predict the number of confirmed cases on COVID-19 by using correlation metrics are 99.06%, 99.96% and 99.94, whereas the results of Holt-Trend to predict the number of death cases are 99.80%, 99.96 and 99.94 with respect to the Saudi Arabia, Italy and Spain respectively. The empirical results indicate the efficient performance of the presented model in predicting the number of confirmed and death cases of COVID-19 in these countries. Such findings provide better insights about the future of COVID-19 in general. The results were obtained by applying the time series models which needs to be considered for the sake of saving the lives of many people.


title: Risk Management of COVID-19 by Universities in China Short-term Forecasts of the COVID-19 Epidemic in Guangdong and Zhejiang, China: February 13–23, 2020

text: The rapid spread of new coronaviruses throughout China and the world in 2019–2020 has had a great impact on China’s economic and social development As the backbone of Chinese society, Chinese universities have made significant contributions to emergency risk management Such contributions have been made primarily in the following areas: alumni resource collection, medical rescue and emergency management, mental health maintenance, control of staff mobility, and innovation in online education models Through the support of these methods, Chinese universities have played a positive role in the prevention and control of the epidemic situation However, they also face the problems of alumni’s economic development difficulties, the risk of deadly infection to medical rescue teams and health workers, infection of teachers and students, and the unsatisfactory application of information technology in resolving the crisis In response to these risks and emergency problems, we propose some corresponding solutions for public dissemination, including issues related to medical security, emergency research, professional assistance, positive communication, and hierarchical information-based teaching The ongoing COVID-19 epidemic continues to spread within and outside of China, despite several social distancing measures implemented by the Chinese government Limited epidemiological data are available, and recent changes in case definition and reporting further complicate our understanding of the impact of the epidemic, particularly in the epidemic’s epicenter Here we use previously validated phenomenological models to generate short-term forecasts of cumulative reported cases in Guangdong and Zhejiang, China Using daily reported cumulative case data up until 13 February 2020 from the National Health Commission of China, we report 5- and 10-day ahead forecasts of cumulative case reports Specifically, we generate forecasts using a generalized logistic growth model, the Richards growth model, and a sub-epidemic wave model, which have each been previously used to forecast outbreaks due to different infectious diseases Forecasts from each of the models suggest the outbreaks may be nearing extinction in both Guangdong and Zhejiang;however, the sub-epidemic model predictions also include the potential for further sustained transmission, particularly in Zhejiang Our 10-day forecasts across the three models predict an additional 65–81 cases (upper bounds: 169–507) in Guangdong and an additional 44–354 (upper bounds: 141–875) cases in Zhejiang by February 23, 2020 In the best-case scenario, current data suggest that transmission in both provinces is slowing down


title: COVID-19; Systematic and literature review of transmission, case definitions, clinical management and clinical trials.

text: Background: SARS-CoV-2, the viral agent responsible for coronavirus disease 2019 (COVID-19) was identified in Wuhan, China at the end of December 2019. It rapidly spread to the rest of the world, and was declared a Public Health Emergency of International Concern on the 30th of January 2020. Our understanding of the virus, it is clinical manifestations and treatment options continues to evolve at an unparalleled pace. Objective: This review sought to summarise the key literature regarding transmission, case definitions, clinical management and trials, and performed a systematic review of reported clinical data on COVID-19. Synthesis methods: Two reviewers selected all the literature independently, and extracted information according to pre-defined topics. Results: COVID-19 is pandemic with ~4 million cases and 270,000 deaths in 210 countries as of 8 May 2020. Our review of reports showed that SARS-CoV-2 was mainly transmitted via inhalation of respiratory droplets containing the virus and had an incubation period of four to six days. The commonly reported symptoms were fever (80%) and cough (60%) across the spectrum of clinical disease - mild, moderate, severe and critical. Categorization of these cases for home care or hospital management need to be well defined considering the age of the patient and the presence of underlying co-morbidities. The case definitions we reviewed varied among affected countries, which could have contributed to the differences observed in the mean case fatality rates among continents: Oceania (1%), Asia (3%), Africa (4%), South America (5%), North America (6%) and Europe (10%). Asymptomatic cases, which constituted an estimated 80% of COVID-19 cases are a huge threat to control efforts. Conclusion: The presence of fever and cough may be sufficient to warrant a COVID-19 testing but using these symptoms in isolation will miss a proportion of cases. A clear definition of a COVID-19 case is important for managing, treating and tracking clinical illness. While several treatments are in development or in clinical trials for COVID-19, home care of mild/moderate cases and hospital care for severe and critical cases remain the recommended management for the disease. Quarantine measures and social distancing can help control the spread of SARS-CoV-2.


title: SSnet - Secondary Structure based End-to-End Learning model for Protein-Ligand Interaction Prediction

text: Computational prediction of bioactivity has become a critical aspect of modern drug discovery as it mitigates the cost, time, and resources required to find and screen new compounds. Deep Neural Networks (DNN) have recently shown excellent performance in modeling Protein-Ligand Interaction (PLI). However, DNNs are only effective when physically sound descriptions of ligands and proteins are fed into the neural network for processing. Furthermore, previous research has not incorporated the secondary structure of proteins in a meaningful manner. In this work, we developed a DNN framework that utilizes the secondary structure information of proteins which is extracted as the curvature and torsion of the protein backbone to predict PLI. We demonstrate how our model outperforms previous machine and non-machine learning models on four major datasets: humans, C.elegans, DUD-E, and BindingDB. Visualization of the intermerdiate layers of our model shows a potential latent space for proteins which extracts important information about the bioactivity. We further investigate the inner workings of our model by visualizing the most important aspects in a protein that the model finds influential. We observed that our model learns important information about possible locations where a ligand would bind including binding sites, allosteric sites and cryptic sites, regardless of the conformation used. This work opens the door to the exploration of secondary structure based deep learning in general, which is not just confined to protein-ligand interactions.


title: Real-Time Outlier Detection and Bayesian Classification using Incremental Computations for Efficient and Scalable Stream Analytics for IoT for Manufacturing

text: Abstract As the manufacturing industry progresses towards the Internet of Things (IoT) and Cyber-Physical Systems (CPS), current methods of historical data analytics face difficulties in addressing the new challenges which follow Industry 4.0. Industry 4.0 and IoT technologies facilitate the acquisition of ubiquitous data from machine tools and processes. However, these technologies also lead to the generation of a large number of data that are complex to be analyzed. Due to the streaming nature of the IoT systems, however, stream analytics could be used to extract features as the data are generated and published, which can prevent the need to store the data and perform advanced analytics that require high performance computing. This manuscript aims at demonstrating how traditional historical methods can be modified to be used as stream analytics tools for IoT data streams. Since data analytics is a wide domain, this paper has only focused on the two light-weighted methods that have been popular in the industry: Statistical Process Control Chart (SPCC), and Bayesian classification. This paper has defined, tested, and evaluated the accuracy and latency of the novel variation of these methods. It is concluded that by modifying the traditional methods and defining incremental solutions, methods such as Real-Time Dynamic Statistical Process Control Chart (RTDSPCC) and Incremental Gaussian Naïve Bayes (IGNB) can be formed that are highly beneficial for IoT applications as they are highly scalable, require minimal storage, and can update the models in real-time.


title: Optimal size of sample pooling for RNA pool testing: an avant-garde for scaling up SARS CoV 2 testing

text: Introduction-Timely diagnosis is essential for the containment of the disease and breaks in the chain of transmission of SARS-CoV-2. The present situation demands countries to scale up their testing and design innovative strategies to conserve diagnostic kits and reagents. The pooling of samples saves time, manpower, and most importantly diagnostic kits and reagents. In the present study, we tried to define the pool size that could be applied with acceptable confidence for testing. Material and methods- We used repeatedly tested positive clinical sample elutes having different levels of SARS CoV 2 RNA and negative sample elutes to prepare seven series of 11 pools each, having pool sizes ranging from 2 to 48 samples to estimate the optimal pool size. Each pool had one positive sample elute in different compositions. All the pools were tested by SARS CoV 2 RT-qPCR. Results- Out of the 77 pools, only 53 (68.8%) were found positive. The sensitivity of pools of 2 to 48 samples was decreased from 100% (95% CL; 98.4-100) to 41.41% (95% CL; 34.9-48.1). The maximum size of the pool with acceptable sensitivity (>95%) was found to be of 6 samples. For the pool size of 6 samples, the sensitivity was 97.8% and the efficiency of pooling was 0.38. Conclusion- The pooling of samples is a practical way for scaling up testing and ultimately containing the further spread of the COVID-19 pandemic.


title: Combined prophylactic and therapeutic use maximizes hydroxychloroquine anti-SARS-CoV-2 effects in vitro

text: While the SARS-CoV-2 pandemic is hardly hitting the world, it is of extreme importance that significant in vitro observations guide the quick set up of clinical trials. In this study, we evidence that the anti-SARS-CoV2 activity of a clinically achievable hydroxychloroquine concentration is maximized only when administered before and after the infection of Vero E6 cells. This strongly suggests that only a combined prophylactic and therapeutic use of hydroxychloroquine may be effective in limiting viral replication in patients.


title: Mathematical Modeling and Simulation of SIR Model for COVID-2019 Epidemic Outbreak: A Case Study of India

text: The present study discusses the spread of COVID-2019 epidemic of India and its end by using SIR model. Here we have discussed about the spread of COVID-2019 epidemic in great detail using Euler method. The Euler method is a method of solution of ordinary differential equations. The SIR model has the combination of three ordinary differential equations. In this study, we have used the data of COVID-2019 Outbreak of India on 8th May, 2020. In this data, we have used 135710 susceptible cases, 54340 infectious cases and 1830 reward or removed cases for the initial level of experimental purpose. Data about a wide variety of infectious diseases has been analyzed with the help of SIR model. Therefore, this model has already been well tested for infectious diseases. Using the data on the number of COVID-2019 outbreak cases in India, the results obtained from the analysis and simulation of the proposed model show that the COVID-2019 epidemic cases increase for some time and thereafter this outbreak will decrease. The results obtained from the SIR model also suggest that the Euler method can be used to predict transmission and prevent the COVID-2019 epidemic in India. Finally, from this study, we have found that the outbreak of COVID-2019 epidemic in India will be at its peak on 25 May 2020 and after that it will work slowly and on the verge of ending in the first or second week of August 2020.


title: Multicenter comparison of the Cobas 6800 system with the RealStar RT-PCR kit for the detection of SARS-CoV-2

text: Background RT-PCR testing is crucial in the diagnostic of SARS-CoV-2 infection. The use of reliable and comparable PCR assays is a cornerstone to allow use of different PCR assays depending on the local equipment. In this work, we provide a comparison of the Cobas® (Roche) and the RealStar® assay (Altona). Methods Assessment of the two assays was performed prospectively in three reference Parisians hospitals, using 170 clinical samples. They were tested with the Cobas® assay, selected to obtain a distribution of cycle threshold (Ct) as large as possible, and tested with the RealStar assay with three largely available extraction platforms: QIAsymphony (Qiagen), MagNAPure (Roche) and NucliSENS-easyMag (BioMérieux). Results Overall, the agreement (positive for at least one gene) was 76%. This rate differed considerably depending on the Cobas Ct values for gene E: below 35 (n = 91), the concordance was 99%. Regarding the positive Ct values, linear regression analysis showed a determination correlation (R2) of 0.88 and the Deming regression line revealed a strong correlation with a slope of 1.023 and an intercept of -3.9. Bland-Altman analysis showed that the mean difference (Cobas® minus RealStar®) was + 3.3 Ct, with a SD of + 2.3 Ct. Conclusions In this comparison, both RealStar® and Cobas® assays provided comparable qualitative results and a high correlation when both tests were positive. Discrepancies exist after 35 Ct and varied depending on the extraction system used for the RealStar® assay, probably due to a low viral load close to the detection limit of both assays.


docid: dnppshnv

title: Role of RNA Guanine Quadruplexes in Favoring the Dimerization of SARS Unique Domain in Coronaviruses

text: Coronaviruses may produce severe acute respiratory syndrome (SARS). As a matter of fact, a new SARS-type virus, SARS-CoV-2, is responsible of a global pandemic in 2020 with unprecedented sanitary and economic consequences for most countries. In the present contribution we study, by all-atom equilibrium and enhanced sampling molecular dynamics simulations, the interaction between the SARS Unique Domain and RNA guanine quadruplexes, a process involved in eluding the defensive response of the host thus favoring viral infection of human cells. Our results evidence two stable binding modes involving an interaction site spanning either the protein dimer interface or only one monomer. The free energy profile unequivocally points to the dimer mode as the thermodynamically favored one. The effect of these binding modes in stabilizing the protein dimer was also assessed, being related to its biological role in assisting SARS viruses to bypass the host protective response. This work also constitutes a first step of the possible rational design of efficient therapeutic agents aiming at perturbing the interaction between SARS Unique Domain and guanine quadruplexes, hence enhancing the host defenses against the virus. TOC GRAPHICS


title: Tracheostomy and personal protective equipment (PPE) in the midst of the COVID-19 pandemic

text: The primary aim was to review the guidelines published by Otolaryngology Societies for performing tracheostomies in the COVID-19 pandemic. A secondary aim was to briefly review the literature for the effectiveness of surgical masks, N-95 and FFP-3 respirators, and power air purifying respirators (PAPRs) in reducing transmission of respiratory viral infections to health care workers while performing tracheostomy. Recommendations are mainly derived from clinical case series/retrospective observational studies from the SARS 2003/2004 outbreaks or experimental evidence for effectiveness for N-95/FFP-3 respirators and PAPRs. Differences do occur due to lack of evidence for COVID-19 as to whether N-95 and FFP-3 respirators are sufficient, or PAPRs should be recommended for tracheostomy. We would recommend adopting a conservative (protective) approach for HCWs teams performing tracheostomies, by routinely utilizing additional PPE such as PAPRs. Recommendations for the timing of tracheostomy also varied, however, almost all recommend a period of delay. The optimum duration of which is still unclear.


docid: sszpzeor

title: Electroconvulsive therapy during a highly contagious respiratory pandemic - A framework during COVID-19

text: Necessary procedures during the COVID-19 pandemic include electroconvulsive therapy (ECT). Providing ECT has been considered an essential service during COVID-19 in the Singapore healthcare system, not least to contribute to disease control within a society in part due to the nature of the ECT patient population. There is limited evidence-based scientific information available regarding a procedural framework for ECT during a respiratory pandemic, when much attention in the healthcare system is focused on different areas of clinical care. This article attempts to describe such a framework for ECT procedures acknowledging limited solid scientific evidence at this time and being mindful of future changes to these suggestions as testing, immunization, and treatment options develop. This approach can be adopted in whole or in part to assist practitioners to protect the patient and themselves during the procedure.


title: The effect of inter-city travel restrictions on geographical spread of COVID-19: Evidence from Wuhan, China

text: Background: To contain the spread of COVID-19, a cordon sanitaire was put in place in Wuhan prior to the Lunar New Year, on 23 January 2020, restricting travel to other parts of China. We assess the efficacy of the cordon sanitaire to delay the introduction and onset of local transmission of COVID-19 in other major cities in mainland China. Methods: We estimated the number of infected travellers from Wuhan to other major cities in mainland China from November 2019 to March 2020 using previously estimated COVID-19 prevalence in Wuhan and publicly available mobility data. We focused on Beijing, Chongqing, Hangzhou, and Shenzhen as four representative major cities to identify the potential independent contribution of the cordon sanitaire and holiday travel. To do this, we simulated outbreaks generated by infected arrivals in these destination cities using stochastic branching processes. We also modelled the effect of the cordon sanitaire in combination with reduced transmissibility scenarios representing the effect of local non-pharmaceutical interventions. Findings: In the four cities, given the potentially high prevalence of COVID-19 in Wuhan between Dec 2019 and early Jan 2020, local transmission may have been seeded as early as 2 - 8 January 2020. By the time the cordon sanitaire was imposed, simulated case counts were likely in the hundreds. The cordon sanitaire alone did not substantially affect the epidemic progression in these cities, although it may have had some effect in smaller cities. Interpretation: Our results indicate that the cordon sanitaire may not have prevented COVID-19 spread in major Chinese cities; local non-pharmaceutical interventions were likely more important for this.


ICER releases pricing models for potential COVID-19 treatments


title: An Evaluation of Mathematical Models for the Outbreak of COVID-19

text: Mathematical modelling performs a vital part in estimating and controlling the recent outbreak of novel coronavirus (COVID-19) In this epidemic, most countries impose severe intervention measures to contain the spread of COVID-19 The policymakers are forced to make difficult decisions in order to leverage between health and economic development How and when to make clinical and public health decisions in the epidemic situation is a challenging question The most appropriate solution is based on scientific evidence, which is mainly depending upon data and models So one of the most critical problems during this crisis is whether we can develop reliable epidemiological models to forecast the evolution of the virus and estimate the effectiveness of various intervention measures and their impacts on the economy There are numerous types of mathematical models for epidemiological diseases In this paper, we present some critical reviews on mathematical models for the outbreak of COVID-19 Some elementary models are presented as an initial formulation for an epidemic We give some basic concepts, notations, and foundation for epidemiological modelling More related works are also introduced and evaluated by considering more epidemiological features such as disease tendency, latent effects, susceptibility, basic reproduction numbers, asymptomatic infections, herd immunity, and impact of the interventions


docid: wozwpvpq

title: Quantifying antibody kinetics and RNA shedding during early-phase SARS-CoV-2 infection

text: Our ability to understand and mitigate the spread of SARS-CoV-2 depends largely on antibody and viral RNA data that provide information about past exposure and shedding. Five months into the outbreak there is an impressive number of studies reporting antibody kinetics and RNA shedding dynamics, but extensive variation in detection assays, study group demographics, and laboratory protocols has presented a challenge for inferring the true biological patterns. Here, we combine existing data on SARS-CoV-2 IgG, IgM and RNA kinetics using a formal quantitative approach that enables integration of 3,214 data points from 516 individuals, published in 22 studies. This allows us to determine the mean values and distributions of IgG and IgM seroconversion times and titer kinetics, and to characterize how antibody and RNA detection probabilities change during the early phase of infection. We observe extensive variation in antibody response patterns and RNA detection patterns, explained by both individual heterogeneity and protocol differences such as targeted antigen and sample type. These results provide a robust reference for clinical management of individual patients, and a foundation for the mathematical models and serological surveys that underpin public health policies.


title: Causally Associations of Blood Lipids Levels with COVID-19 Risk: Mendelian Randomization Study

text: Background: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). It has been found that coronary artery disease (CAD) is a comorbid condition for COVID-19. As the risk factors of CAD, whether blood lipids levels are causally related to increasing susceptibility and severity of COVID-19 is still unknown. Design: We performed two-sample Mendelian Randomization (MR) analyses to explore whether dyslipidemia, low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), triglyceride (TG) and total cholesterol (TC) were causally related to COVID-19 risk and severity. The GWAS summary data of blood lipids involving in 188,578 individuals and dyslipidemia in a total of 53,991 individuals were used as exposures, respectively. Two COVID-19 GWASs including 1,221 infected patients and 1,610 severe patients defined as respiratory failure were employed as outcomes. Based on the MR estimates, we further carried out gene-based and gene-set analysis to explain the potential mechanism for causal effect. Results: The MR results showed that dyslipidemia was casually associated with the susceptibility of COVID-19 and induced 27% higher odds for COVID-19 infection (MR-IVW OR = 1.27, 95% CI: 1.08 to 1.49, p-value = 3.18 x 10-3). Moreover, the increasing level of blood TC will raise 14 % higher odds for the susceptibility of COVID-19 (MR-IVW OR = 1.14, 95% CI: 1.04 to 1.25, p-value = 5.07 x 10-3). Gene-based analysis identified that ABO gene was associated with TC and the gene-set analysis found that immune processes were involved in the risk effect of TC. Conclusions: We obtained three conclusions: 1) Dyslipidemia is casually associated with the susceptibility of COVID-19; 2) TC is a risk factor for the susceptibility of COVID-19; 3) The different susceptibility of COVID-19 in specific blood group may be partly explained by the TC concentration in diverse ABO blood groups.


Epitope finding in 2019 novel coronavirus (2019-nCoV): The first world report


title: Rapid, Large-Scale, and Effective Detection of COVID-19 Via Non-Adaptive Testing

text: Pooling of samples can increase lab capacity when using Polymerase chain reaction (PCR) to detect infections such as COVID-However, pool testing is typically performed via an adaptive testing strategy which requires a feedback loop in the lab and at least two PCR runs to confirm positive results. This can cost precious time. We discuss a non-adaptive testing method where each sample is distributed in a prescribed manner over several pools, and which yields reliable results after one round of testing. More precisely, assuming knowledge about the overall infection incidence rate, we calculate explicit error bounds on the number of false positives which scale very favourably with pool size and sample multiplicity. This allows for hugely streamlined PCR testing and cuts in detection times for a large-scale testing scenario. A viable consequence of this method could be real-time screening of entire communities, frontline healthcare workers and international flight passengers, for example, using the PCR machines currently in operation.


title: Early Evidence of Disparities in COVID-19 Testing in US Cities

text: We explored the emergence of disparities in COVID-19 testing and outcomes in NYC and Philadelphia, two large US cities at two different stages of the epidemic. We used zip code-level data from the NYC Department of Health and Mental Hygiene and the Philadelphia Department of Public Health. We linked this data to a deprivation index calculated using 2014-2018 American Community Survey data. We have documented a dynamic situation regarding disparities in COVID-19 testing in two US cities. There are wide disparities in testing availability for the most deprived neighborhoods in Philadelphia, a city early in the epidemic, while these disparities seemingly dissipated in NYC, a city with more widespread testing later in the epidemic. However, we consistently see a very strong positive correlation with the % of tests that are positive in both cities, and this disparity is widening over time.


title: Estimating number of global importations of COVID-19 from Wuhan, risk of transmission outside mainland China and COVID-19 introduction index between countries outside mainland China

text: Background The emergence of a novel coronavirus (SARS-CoV-2) in Wuhan, China in early December 2019 has caused widespread transmission within the country, with over 1,000 deaths reported to date. Other countries have since reported coronavirus disease 2019 (COVID-19) importation from China, with some experiencing local transmission and even case importation from countries outside China. We aim to estimate the number of cases imported from Wuhan to each country or territory outside mainland China, and with these estimates assess the risk of onward local transmission and the relative potential of case importation between countries outside China. Methods We used the reported number of cases imported from Wuhan and flight data to generate an uncertainty distribution for the estimated number of imported cases from Wuhan to each location outside mainland China. This uncertainty was propagated to quantify the local outbreak risk using a branching process model. A COVID-19 introduction index was derived for each pair of donor and recipient countries, accounting for the local outbreak risk in the donor country and the between-country connectivity. Results We identified 13 countries or territories outside mainland China that may have under-detected COVID-19 importation from Wuhan, such as Thailand and Indonesia. In addition, 16 countries had a local outbreak risk estimate exceeding 50%, including four outside Asia. The COVID-19 introduction index highlights potential locations outside mainland China from which cases may be imported to each recipient country. Conclusions As SARS-CoV-2 continues to spread globally, more epicentres may emerge outside China. Hence, it is important for countries to remain alert for the possibilities of viral introduction from other countries outside China, even before local transmission in a source country becomes known.


title: Epidemiological, socio-demographic and clinical features of the early phase of the COVID-19 epidemic in Ecuador

text: Abstract Background: The SARS-CoV-2 virus has spread all over the world infecting more than 3,585,936 people from over 210 countries and caused more than 245,803 deaths worldwide. We report the first epidemiological, socio-demographic, and clinical findings for the first 9,468 confirmed COVID-19 cases in Ecuador. Methods: We conducted a descriptive cross-sectional analysis of 9,468 COVID-19 confirmed cases in Ecuador from 27 February to 18 April 2020. The overall incidence, mortality, and case fatality rate was computed according to the entire population at risk living in a canton or a province. Disability adjusted life years, attack and crude mortality rates as well as relative risk and odds ratios were computed as an outcome. Results: Since the first case reported in Ecuador on 27 Feb 2020, at least 9,468 positive COVID-19 cases of which 474 deaths were officially registered over a 54-day period. Men accounted for 55.40% (n = 5, 247) of the overall cases with an incidence rate of 60.5 per 100,000 while women accounted for 44.60 % (n = 4, 221) representing 47.2 per 100,000. The mortality rate per canton showed that cantons with a lower attack rate had higher mortality rates. Coastal cantons have a lower attack rate than the highlands and living above >2,500 m seems to be linked with a lower risk of dying (RR: 0.63 [CI 95% 0.50 - 0.79]). Fatigue was reported in 53.2% of the patients, followed by headache (43%), dry cough (41.7%), ageusia (37.1%) and anosmia (36.1%). Conclusion: This study is the first of its kind in Ecuador. The results of this analysis show that men are at higher risk of dying from COVID-19 than women, which increases as with age and the presence of comorbidities. Areas with better testing capabilities reported lower CFR% and mortality, additionally cantons located above 2,500 m have lower attack and mortality rates although the risk of dying is greater among highlanders. Keywords: COVID-19; SARS-CoV-2; Ecuador; Epidemiology; Latin America


title: Methods of An Open-Label Proof-Of-Concept Trial of Intravenous Valproic Acid for Severe COVID-19

text: Background: Coronavirus disease 2019 (COVID-19) is the systemic entity caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may cause death through severe atypical pneumonia and acute lung injury. Valproic acid (VPA) has shown anti-inflammatory activity and mild intrinsic antiviral effect. These properties warrant the study of VPA as a possible active treatment in persons with severe COVID-19. Methods: Consecutive adult patients needing invasive mechanical ventilation (IMV) will be given intravenous (i.v.) VPA at a starting dose of 20 mg/kg/day and up to 60/kg/day (in 60 min i.v. infusions in 250 mL normal saline) as needed to reach plasma VPA concentrations of 50-100 mcg/mL (measured every 72 h). These patients will be followed-up for 10 days for the primary outcome and for a further period of 30 days after treatment completion for the secondary outcome of recurrence. The primary study outcome is the reduction in the case fatality rate of at least 50% after 10 days of treatment (as compared with natural history). Secondary outcomes are the reduction of length of stay (LOS) of at least 50%, as well as COVID-19 recurrence at 30-day follow-up. The most important safety outcomes are acute liver failure, acute pancreatitis, and thrombocytopenia. Conclusion: Although long-term adverse effects and even pro-inflammatory consequences have been reported with the chronic use of VPA, given the urgent need for a drug against COVID-19 to shorten the high mortality and LOS, the study of VPA is justified from a scientific standpoint.


title: Statistical Inference for Coronavirus Infected Patients in Wuhan

text: Importance: The new coronavirus outbreak has seriously affected the quality of life in China. Wuhan is the disaster area, where the number of cases has increased rapidly. However, the current measures of infected patients in Wuhan are still underestimated. Objective: To estimate the overall infected patients in Wuhan from several sampled data. The correct estimated infected patients can be helpful for the government to arrange the needed beds in hospital wards to meet the actual needs. Design: We proposed to use the sampling survey to estimate the overall infected patients in Wuhan. The sampling survey is a kind of non-comprehensive survey. It selected some units from all the survey objects to carry out the survey and made the estimation and inference to all the survey objects. Sampling surveys can obtain information that reflects the overall situation, although it is not a comprehensive survey. Setting: We estimated the overall infection rate in Wenzhou city, which has a better data collection system. Simultaneously, another different samples of Wuhan tourists to Singapore will be used to validate the infection rate in Wenzhou city. Combined these two samples, we give the estimation of the number of infected patients in Wuhan and other prefecture-level cities in Hubei Province. Participants: The number of people who returned from Wuhan to Wenzhou was selected from the daily notification of the pneumonia epidemic caused by a new coronavirus infection in the city. Exposures for observational studies: The daily rate of the pneumonia epidemic caused by the new coronavirus infection in Wenzhou City. The numerator is the number of people diagnosed and whether each person diagnosed had a history of living in Wuhan. The denominator is the total number of people returning to Wenzhou from Wuhan. Based on this rate, it is reasonable to predict the number of the infected patients.


title: Projektion der COVID-19-Epidemie in Deutschland

text: The authors model the evolution of the number of confi rmed cases of COVID-19 in Germany. Their theoretical framework builds on a continuous time Markov chain with four physical states: healthy, sick, recovered or asymptomatic infected, and dead. Their quantitative solution matches the number of sick individuals based on the most recent fi gures with the share of sick individuals following from infection rates and sickness probabilities. They employ this framework to study the expected peak of the number of sick individuals in a scenario without public regulation of social contacts. They also study the impact of public regulations. For all scenarios, they report the expected end of the COVID-19 epidemic.