bluuebunny/crossref_metadata_2025 huggingface dataset:
Superficial Fascia of the Cheek Shown in P45 Sheet Plastination
Authors: Hwang Kun , Sui Hong-Jin , Kim Hun
Published: November 2020

In this paper, the authors attempted to determine the extent of the superficial fascia of the cheek using P45 sheet plastination.

Three head and neck specimens were sliced in horizontal (46 slices), coronal (30 slices), and sagittal (29 slices) sections using P45 sheet plastination (special polyester resin corrosion-resistant method designed to preserve biological sectional specimens in situ). Through slicing, bleaching, dehydration, casting, forced impregnation, curing, cutting, and sanding the molds, P45 plastination sheets provided good light transmission, allowing the internal structures within the sheet to reveal clearly in their intact form.

P45 sheet plastination revealed that the superficial fascia in the cheek area is generally composed of 3 layers: a superficial fatty layer, a membranous layer, and a deep fatty layer. Anteriorly, the membranous layer of superficial fascia (MSF) extended to the posterior border of the zygomaticus major muscle, enveloping this muscle, and then to the lateral border of the orbicularis oculi muscle. Posteriorly, the MSF extended to the anterior border of the parotid gland, and then was continuous with the parotid fascia. Superiorly, the MSF extended to the line from the tragus to the alar base. Inferiorly, the MSF extended to the line from the mandibular angle to the mouth corner. Below this line, the SMAS continued to the upper border of the platysma muscle.

Our results using P45 plastination concorded well with Mitz's original drawing. We suggest that the results of the present study may be helpful for practicing surgeons to apply in subcutaneous dissection or sub-SMAS dissection in facelift procedures.
Effect of Cleft Palate Repair Timing on Inpatient Complication Rate: Review of a National Database
Authors: Bluher Andrew E. , Cunningham Tina D. , Reeves Travis D.
Published: November 2020

Objectives:

Timing of cleft palate repair is controversial. We aim to assess whether timing of cleft palate repair affects rates of inpatient complications, length of stay (LOS), and cost of stay.

Methods:

The Healthcare Cost and Utilization Project Kids’ Inpatient Database 2009 was queried for all admissions with a primary diagnosis of cleft palate during which cleft palate repair was performed as a primary procedure. Age 6 months or less was termed “early” repair, while age >6 months was termed “standard” repair. Patients age >3 years old, inpatient stays >30 days, and those stays in which a cleft lip repair was performed were excluded. Logistic regressions were used to model the probability of complications. Generalized linear models and a natural log link function were used for LOS and hospital charges, using SAS 9.4.

Results:

We included 223 early and 1482 standard repair patients. Early repairs were exclusively performed in urban hospitals (P < 0.001). Eighty-nine patients experienced a total of 100 complications, including respiratory failure (N = 53), airway obstruction (N = 18), and oropharyngeal hemorrhage (N = 13). We found no significant difference in complication rate or total hospital charges in the 2 groups. The earlier repair group had a slightly longer LOS (P = 0.048).

Conclusion:

Over 85% of United States cleft palate repairs are performed after 6 months of age. All early repairs were performed at urban hospitals, and had slightly longer LOS. There was a 5.1% overall complication rate. Available data revealed no significant difference in complication rates between early repair and standard repair groups.

Level of Evidence:

3b
Barbed Broach in the Maxillary Sinus: A Report of Unusual Complication in Craniofacial Area
Authors: Jamil Firas A.
Published: November 2020

The upper posterior teeth are usually in close relation to the maxillary sinus (MS). This proximity may lead to serious complications throughout different dental procedures. Early diagnosis and management play a significant role in preventing the sequelae of sinusitis and/or cysts. This article presented an extremely unusual case of barbed broach (BB) displacement into the MS, during endodontic treatment, together with the optimal surgical management. Searching the databases has revealed that it was be the first case reported in the literature. It seemed that the modified Caldwell-Luc approach used in this case was very safe, effective, and associated with minimal post-operative side effects.
Incidence and Outcomes of COVID-19 in Kidney and Liver Transplant Recipients With HIV: Report From the National HOPE in Action Consortium
Authors: Mehta Sapna A. , Rana Meenakshi M. , Motter Jennifer D. , Small Catherine B. , Pereira Marcus R. , Stosor Valentina , Elias Nahel , Haydel Brandy , Florman Sander , Odim Jonah , Morsheimer Megan , Robien Mark , Massie Allan B. , Brown Diane , Boyarsky Brian J. , Garonzik-Wang Jacqueline , Tobian Aaron A.R. , Werbel William A. , Segev Dorry L. , Durand Christine M. ,   on behalf of the HOPE in Action Investigators
Published: November 2020

Background.

Transplant recipients with HIV may have worse outcomes with coronavirus disease 2019 (COVID-19) due to impaired T-cell function coupled with immunosuppressive drugs. Alternatively, immunosuppression might reduce inflammatory complications and/or antiretrovirals could be protective.

Methods.

Prospective reporting of all cases of SARS-CoV-2 infection was required within the HOPE in Action Multicenter Consortium, a cohort of kidney and liver transplant recipients with HIV who have received organs from donors with and without HIV at 32 transplant centers in the United States.

Results.

Between March 20, 2020 and September 25, 2020, there were 11 COVID-19 cases among 291 kidney and liver recipients with HIV (4%). In those with COVID-19, median age was 59 y, 10 were male, 8 were kidney recipients, and 5 had donors with HIV. A higher proportion of recipients with COVID-19 compared with the overall HOPE in the Action cohort were Hispanic (55% versus 12%) and received transplants in New York City (73% versus 34%, P < 0.05). Most (10/11, 91%) were hospitalized. High-level oxygen support was required in 7 and intensive care in 5; 1 participant opted for palliative care instead of transfer to the intensive care unit. HIV RNA was undetectable in all. Median absolute lymphocyte count was 0.3 × 103 cells/μL. Median CD4 pre–COVID-19 was 298 cells/μL, declining to <200 cells/μl in 6/7 with measurements on admission. Treatment included high-dose steroids (n = 6), tocilizumab (n = 3), remdesivir (n = 2), and convalescent plasma (n = 2). Four patients (36%) died.

Conclusions.

Within a national prospective cohort of kidney and liver transplant recipients with HIV, we report high mortality from COVID-19.
Organ Donation and Transplantation During the COVID-19 Pandemic: A Summary of the Spanish Experience
Authors: Domínguez-Gil Beatriz , Fernández-Ruiz Mario , Hernández Domingo , Crespo Marta , Colmenero Jordi , Coll Elisabeth , Rubio Juan José
Published: November 2020

Background.

Spain has been amongst the countries most affected by the COVID-19 pandemic, which has posed significant challenges to the donation and transplantation program. Despite a dramatic decrease of donation and transplantation activities during the critical early weeks of the outbreak, the program has recovered and is learning to cope with COVID-19.

Methods.

We describe the 4 pillars upon which the Spanish donation and transplantation program has been rebuilt.

Results.

(1) Standards have been developed and progressively updated for the evaluation and selection of potential donors and recipients with regards to SARS-CoV-2 infection. (2) Spain has been actively generating evidence to assess the validity of our standards and to understand the natural history of the infection in transplant recipients. No case of donor-derived COVID-19 has been reported to date. COVID-19 has been more frequent and has had a more aggressive course in recipients of solid organ transplants than in the general population, but this seems largely explained by the demographics and comorbidity of transplant patients. (3) As a result of this evidence and experience, recommendations have been issued for the management of COVID-19 in solid organ transplant recipients and candidates on the waiting list. (4) Finally, concrete guidance has been issued for centers to manage the donation and transplantation programs in relation to a dynamic and heterogeneous epidemiologic scenario.

Conclusions.

The Spanish experience confronting the impact of COVID-19 upon donation and transplantation may help serve the needs of a broader community in other countries.
Increasing test specificity without impairing sensitivity - lessons learned from SARS-CoV-2 serology
Authors: Perkmann Thomas , Koller Thomas , Perkmann-Nagele Nicole , Ozsvar-Kozma Maria , Eyre David , Matthews Philippa , Bown Abbie , Stoesser Nicole , Breyer Marie-Kathrin , Breyer-Kohansal Robab , Burghuber Otto C , Hartl Slyvia , Aletaha Daniel , Sieghart Daniela , Quehenberger Peter , Marculescu Rodrig , Mucher Patrick , Radakovics Astrid , Klausberger Miriam , Duerkop Mark , Holzer Barba , Hartmann Boris , Strassl Robert , Leitner Gerda , Grebien Florian , Gerner Wilhelm , Grabherr Reingard , Wagner Oswald F , Binder Christoph J , Haslacher Helmuth
Published: November 2020

Background
Serological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity and specificity of test systems is often poor, leaving room for false positive and false negative results. However, conventional methods used to increase specificity decrease sensitivity and vice versa. Using SARS-CoV-2 serology as an example, we propose here a novel testing strategy: the "Sensitivity Improved Two-Test" or "SIT2" algorithm.
Methods
SIT2 involves confirmatory re-testing of samples with results falling in a predefined retesting-zone of an initial screening test, with adjusted cut-offs to increase sensitivity. We verified and compared the performance of SIT2 to single tests and orthogonal testing (OTA) in an Austrian cohort (1,117 negative, 64 post-COVID positive samples) and validated the algorithm in an independent British cohort (976 negatives, 536 positives).
Results
The specificity of SIT2 was superior to single tests and non-inferior to OTA. The sensitivity was maintained or even improved using SIT2 when compared to single tests or OTA. SIT2 allowed correct identification of infected individuals even when a live virus neutralization assay could not detect antibodies. Compared to single testing or OTA, SIT2 significantly reduced total test errors to 0.46% (0.24-0.65) or 1.60% (0.94-2.38) at both 5% or 20% seroprevalence.
Conclusion
For SARS-CoV-2 serology, SIT2 proved to be the best diagnostic choice at both 5% and 20% seroprevalence in all tested scenarios. It is an easy to apply algorithm and can potentially be helpful for the serology of other infectious diseases.
Medical Capacity Shortages Facilitated the Rapid Dissemination of COVID-19 in Wuhan, New York State, and Italy
Authors: Xu Yuehao , Zhang Cheng , Qian Lixian
Published: November 2020

During the coronavirus disease 2019 (COVID-19) outbreak, every public health system faced the potential challenge of medical capacity shortages. Infections without timely diagnosis or treatment may facilitate the stealth transmission and spread of the virus. Using infection and medical capacity information reported in Wuhan in China, New York State in the United States, and Italy, we developed a dynamic susceptible–exposed–infected–recovered (SEIR) model to estimate the impact of medical capacity shortages during the COVID-19 outbreak at the city, state, and country levels. After accounting for the effects of travel restrictions and control measures, we find that the number of infections in Wuhan could have been 39% lower than the actual number if the medical capacity were doubled in this city. Similarly, we find the less shortages in medical capacity in both New York state and Italy, the faster decline in the daily infection numbers and the fewer deaths. This study provides a method for estimating potential shortages and explains how they may dynamically facilitate disease spreading during future pandemics such as COVID-19.
Analytical assessment of Beckman Coulter Access anti-SARS-CoV-2 IgG immunoassay
Authors: Ruscio Maurizio , D’Agnolo Elisa , Belgrano Anna , Plebani Mario , Lippi Giuseppe
Published: November 2020

Background

The approach to diagnosing, treating and monitoring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies strongly on laboratory resources, with serological testing representing the mainstay for studying the onset, nature and persistence of humoral immune response. This study was aimed at evaluating the analytical performance of the novel Beckman Coulter anti-SARS-CoV-2 IgG chemiluminescent immunoassay.

Methods

This analytical assessment encompassed the calculation of intra-assay, inter-assay and total imprecision, linearity, limit of blank (LOB), limit of detection (LOD), functional sensitivity, and comparison of anti-SARS-CoV-2 antibodies values obtained on paired serum samples using DiaSorin Liaison SARS-CoV-2 S1/S2 IgG and Roche Elecsys Anti-SARS-CoV-2 total antibodies. Diagnostic performance was also tested against results of molecular testing on nasopharyngeal swabs, collected over the previous 4 months.

Results

Intra-assay, inter-assay and total imprecision of Beckman Coulter anti-SARS-CoV-2 IgG were between 4.3-4.8%, 2.3-3.9% and 4.9-6.2%, respectively. The linearity of the assay was excellent between 0.11-18.8 antibody titers. The LOB, LOD and functional sensitivity were 0.02, 0.02 and 0.05, respectively. The diagnostic accuracy (area under the curve; AUC) of Beckman Coulter anti-SARS-CoV-2 IgG compared to molecular testing was 0.87 (95% CI, 0.84-0.91; p<0.001) using manufacturer’s cut-off, and increased to 0.90 (95% CI, 0.86-0.94; p<0.001) with antibody titers. The AUC was non-significantly different from that of Roche Elecsys Anti-SARS-CoV-2, but was always higher than that of DiaSorin Liaison SARS-CoV-2 S1/S2 IgG. The correlation of Beckman Coulter Access SARS-CoV-2 IgG was 0.80 (95% CI, 0.75-0.84; p<0.001) with Roche Elecsys Anti-SARS-CoV-2 and 0.72 (95% CI, 0.66-0.77; p<0.001) with DiaSorin Liaison SARS-CoV-2 S1/S2 IgG, respectively.

Conclusions

The results of this analytical evaluation of Beckman Coulter Access anti-SARS-CoV-2 IgG suggests that this fully-automated chemiluminescent immunoassay represents a valuable resource for large and accurate seroprevalence surveys.
Tracking the Dynamics and Allocating Tests for COVID-19 in Real-Time: an Acceleration Index with an Application to French Age Groups and Départements*
Authors: Baunez Christelle , Degoulet Mickael , Luchini Stéphane , Pintus Patrick A. , Teschl Miriam
Published: November 2020

An acceleration index is proposed as a novel indicator to track the dynamics of the COVID-19 in real-time. Using French data on cases and tests for the period following the first lock-down - from May 13, 2020, onwards - our acceleration index shows that the ongoing pandemic resurgence can be dated to begin around July 7. It uncovers that the pandemic acceleration has been stronger than national average for the [59 − 68] and especially the 69 and older age groups since early September, the latter being associated with the strongest acceleration index, as of October 25. In contrast, acceleration among the [19 − 28] age group is the lowest and is about half that of the [69 − 78], as of October 25. In addition, we propose an algorithm to allocate tests among French départements, based on both the acceleration index and the feedback effect of testing. Our acceleration-based allocation differs from the actual distribution over French territories, which is population-based. We argue that both our acceleration index and our allocation algorithm are useful tools to guide public health policies as France enters a second lock-down period with indeterminate duration.

JEL Classification Numbers

I18; H12
Kinetics of viral load, immunological mediators and characterization of a SARS-CoV-2 isolate in mild COVID-19 patients during acute phase of infection
Authors: Anantharaj Anbalagan , Gujjar Sunil , Kumar Saurabh , Verma Nikhil , Wangchuk Jigme , Khan Naseem Ahmed , Panwar Aleksha , Kanakan Akshay , A Vivekanand , Vasudevan Janani Srinivasa , Das Asim , Pandey Anil Kumar , Pandey Rajesh , Medigeshi Guruprasad R.
Published: November 2020

Over 95% of the COVID-19 cases are mild-to-asymptomatic who contribute to disease transmission whereas most of the severe manifestations of the disease are observed in elderly and in patients with comorbidities and dysregulation of immune response has been implicated in severe clinical outcomes. However, it is unclear whether asymptomatic or mild infections are due to low viral load or lack of inflammation. We have measured the kinetics of SARS-CoV-2 viral load in the respiratory samples and serum markers of inflammation in hospitalized COVID-19 patients with mild symptoms. We observed a bi-phasic pattern of virus load which was eventually cleared in most patients at the time of discharge. Viral load in saliva samples from a subset of patients showed good correlation with nasopharyngeal samples. Serum interferon levels were downregulated during early stages of infection but peaked at later stages correlating with elevated levels of T-cell cytokines and other inflammatory mediators such as IL-6 and TNF- α which showed a bi-phasic pattern. The clinical recovery of patients correlated with decrease in viral load and increase in interferons and other cytokines which indicates an effective innate and adaptive immune function in mild infections. We further characterized one of the SARS-CoV-2 isolate by plaque purification and show that infection of lung epithelial cells (Calu-3) with this isolate led to cytopathic effect disrupting epithelial barrier function and tight junctions. Finally we showed that zinc was capable of inhibiting SARS-CoV-2 infection in this model suggesting a beneficial effect of zinc supplementation in COVID-19 infection.

IMPORTANCE

A majority of COVID-19 patients are asymptomatic or exhibit mild symptoms despite high viral loads suggesting a key role for the acute phase innate immune response in limiting the damage and clearing the virus. Therefore, it is important to understand the early phase response to SARS-CoV-2 infection in such patients to devise strategies for clinical management of the disease. Our study shows the kinetics of immune mediators in the serum samples collected from hospitalized COVID-19 patients with mild symptoms. We further characterize a virus isolate from one of these patients and demonstrate its effect on epithelial barrier functions and show that zinc was capable of inhibiting SARS-CoV-2 infection under these conditions. Our results suggest a key role for the innate immune responses in the early phase of infection in mitigating clinical symptoms, clearing the virus and recovery from illness and suggest an antiviral role for zinc in COVID-19 infection.
Epidemiological characteristics of deaths from COVID-19: an analysis at almost three months of the first confirmed case in Peru
Authors: Ramos Willy , Arrasco Juan , De La Cruz-Vargas Jhony A. , Ordóñez Luis , Vargas María , Seclén Yovana , Luna Miguel , Guerrero Nadia , Medina José , Sandoval Isabel , Solís Edith , Loayza Manuel
Published: November 2020

OBJECTIVE

To determine the epidemiological characteristics of deaths from COVID-19 in Peru from March 28 to May 21, 2020, 85 days after the report of the first confirmed case.

MATERIAL AND METHODS

Case series type study. Deaths from various sources were investigated, including the COVID-19 Epidemiological Surveillance and the National System of Deaths. Deaths that met the definition of a confirmed case and had a positive (reactive) result of RT-PCR or rapid test were considered for the analysis. From these sources, epidemiological variables were obtained and a time analysis was performed, defining as the pre-hospital time the time from the onset of symptoms to the date of hospitalization and hospital time from the date of hospitalization to the date of death.

RESULTS

3,244 confirmed deaths were included in the study. Deaths were more frequent in males (71.8%), elders (68.3%), residents of the department of Lima (41.8%), and others from the coast (37.7%). In 81.3% of cases, the death occurred in a public hospital, 16.0% died at home, shelter, penitentiary institution, public highway, or in transit to a hospital, and 31.1% had some comorbidity.

Statistical difference was observed in pre-hospital time according to age group (p <0.001) and gender (p = 0.037), being significantly higher in adults, elders, and women. There was a statistically significant difference in hospital time according to geographic area, showing a significantly shorter time in the departments of the coast (p <0.001) and Andean region (p = 0.014) compared to Lima. The cases that were seen in private clinics (p = 0.001) survived longer than those seen in public hospitals.

CONCLUSION

Deaths from COVID-19 occur mainly in male, elders, on the coast, with considerable deaths at home, in shelters, penitentiaries, public roads, or in transit to a hospital. Pre-hospital time is affected by age group and gender; while, hospital time is also influenced by the region of origin and the health care provider.
Multiplexed, quantitative serological profiling of COVID-19 from a drop of blood by a point-of-care test
Authors: Heggestad Jacob T. , Kinnamon David S. , Olson Lyra B. , Liu Jason , Kelly Garrett , Wall Simone A. , Fontes Cassio M. , Joh Daniel Y. , Hucknall Angus M. , Pieper Carl , Naqvi Ibtehaj A. , Chen Lingye , Que Loretta G. , Oguin Thomas , Nair Smita K. , Sullenger Bruce A. , Woods Christopher W. , Sempowski Gregory D. , Kraft Bryan D. , Chilkoti Ashutosh
Published: November 2020

Highly sensitive, specific, and point-of-care (POC) serological assays are an essential tool to manage the COVID-19 pandemic. Here, we report on a microfluidic, multiplexed POC test that can profile the antibody response against multiple SARS-CoV-2 antigens—Spike S1 (S1), Nucleocapsid (N), and the receptor binding domain (RBD)—simultaneously from a 60 µL drop of blood, plasma, or serum. We assessed the levels of anti-SARS-CoV-2 antibodies in plasma samples from 19 individuals (at multiple time points) with COVID-19 that required admission to the intensive care unit and from 10 healthy individuals. This POC assay shows good concordance with a live virus microneutralization assay, achieved high sensitivity (100%) and specificity (100%), and successfully tracked the longitudinal evolution of the antibody response in infected individuals. We also demonstrated that we can detect a chemokine, IP-10, on the same chip, which may provide prognostic insight into patient outcomes. Because our test requires minimal user intervention and is read by a handheld detector, it can be globally deployed in the fight against COVID-19 by democratizing access to laboratory quality tests.
COVID-19 isolation and containment strategies for ships: Lessons from the USS Theodore Roosevelt outbreak
Authors: Stoddard Madison , Johnson Kaitlyn , White Doug , Nolan Ryan , Hochberg Natasha , Chakravarty Arijit
Published: November 2020

The control of shipborne disease outbreaks represents a vexing but entirely predictable challenge at the start of any pandemic. Passenger ships, with large numbers of people confined in close quarters, can serve as incubators of disease, seeding the pandemic across the globe as infected passengers return home. Short-term steps taken by local authorities can exacerbate this problem, creating humanitarian crises and worsening the scale of the outbreak. In this work, we have undertaken a model-based examination of the USS Theodore Roosevelt outbreak to understand the dynamics of COVID-19 spread aboard the aircraft carrier. We have used a series of counterfactual “what-if” analyses to better understand the options available to public health authorities in such situations. The models suggest that rapid mass evacuation and widespread surveillance testing can be effective in these settings. Our results lead to a set of generalizable recommendations for disease control that are broadly applicable to the current COVID-19 crisis as well as to future pandemics.
Biological Perspective of Balur Therapy: A Network Pharmacology Study
Authors: Aristyani Sherry , Subagjo Saraswati , Rahayu Tintrim , Sumitro Sutiman Bambang
Published: November 2020

Balur is an integrative topical medication from Indonesia using herbal medicines:Moringa oleifera,Nicotiana tabacum, andCoffea arabica. Balur can be applied to treat various diseases including chronic diseases and autism because it performs to scavenge free radicals and release electron of heavy metals. However, the complexity of the balur mechanism as medical therapy needs a comprehensive understanding. Not only from a modern physics perspective but also from a biological perspective to explore the effect of active compounds on the human body. In this study, we proposed the computational study to understand balur therapy from a biological perspective though the molecular mechanism. Active compounds of 3 herbal medicines Balur were collected from Dr. Duke’s Phytochemical and Ethnobotanical Databases. Proteins target related to active compounds were obtained from SwissTargetPrediction and PharmMapper Server. Gene Ontology (GO) was conducted to verify the potential mechanism. Moreover, network analysis was conducted with Cytoscape. We found that the active compounds were contributed to the therapeutic effectiveness through a molecular mechanism. This study demonstrated the multi-compounds and multi-target of balur’s herbal medicines to treat disease.
Healthcare strain and intensive care during the COVID-19 outbreak in the Lombardy region: a retrospective observational study on 43,538 hospitalized patients
Authors: Trentini Filippo , Marziano Valentina , Guzzetta Giorgio , Tirani Marcello , Cereda Danilo , Poletti Piero , Piccarreta Raffaella , Barone Antonio , Preziosi Giuseppe , Arduini Fabio , Della Valle Petra Giulia , Zanella Alberto , Grosso Francesca , del Castillo Gabriele , Castrofino Ambra , Grasselli Giacomo , Melegaro Alessia , Piatti Alessandra , Andreassi Aida , Gramegna Maria , Ajelli Marco , Merler Stefano
Published: November 2020

Background

During the spring of 2020, the SARS-CoV-2 epidemic has caused significant resource strain in hospitals of Lombardy, Italy, with the demand for intensive care beds for COVID-19 patients exceeding the overall pre-crisis capacity. In this study, we evaluate the effect of healthcare strain on ICU admission and survival.

Methods

We used data on 43,538 patients admitted to a hospital in the region between February 20 and July 12, 2020, of which 3,993 (9.2%) were admitted to an ICU. We applied logistic regression to model the probability of being admitted to an ICU and the probability of survival among ICU patients. Negative binomial regressions were used to model the time between hospital and ICU admission and the length of stay in ICU.

Results

During the period of highest hospital strain (March 16 – April 22), individuals older than 70 years had a significantly lower probability of being admitted to an ICU and significantly longer times between hospital and ICU admission, indicating elective admission due to constrained resources. Healthcare strain did not have a clear effect on mortality, with the overall proportion of deaths declining from 52.1% (95%CI 49.8-54.5) for ICU patients admitted to the hospital before March 16, to 43.4% (95%CI 41.5-45.6) between March 16 and April 22, to 27.6% (95%CI 20.0-35.2) after April 22.

Conclusions

These data demonstrate and quantify the adoption of elective admission to ICUs during the peak phase of the SARS-CoV-2 epidemic in Lombardy. However, we show that for patients admitted to ICUs, clinical outcomes progressively improved despite the saturation of healthcare resources.
Increasing frequency of hospital admissions for retinal detachment and vitreo-retinal surgery in England 2000-2018
Authors: Madi Haifa A , Keller Johannes
Published: November 2020

Objectives

To analyse the changes in reported frequency of retinal detachment admissions and vitreo-retinal surgery procedures performed between 2000-2018 in England. To obtain information useful to contribute towards the planning of service delivery.

Methods

Analysis of England’s Hospital Episode Statistics from the Health and Social Care Information Centre and population data from the United Kingdom’s Office for National Statistics.

Results

Episodes of “retinal detachments with breaks” increased year on year from 3,447 (7.0/100M) in 2000 to 10,971 (19.7/100M) in 2018 (p<0.001), whereas records of “tractional retinal detachment” increased from 290 (0.6/100M) to 910 (1.6/100M) in the same period (p<0.0001). The number of reported pars plana vitrectomies irrespective of indication increased over fourfold from 5,761 to 26,900 (p<0.0001), while the number of scleral buckling records decreased by two thirds from 2,897 to 780 (p<0.0001). During the same period the population of England increased from 49.2 million-55.6 million, proportionally at a slower rate than that for recorded hospital episodes.

Conclusions

The frequency of admissions to hospital for surgically treated retinal detachment seems to have been increasing significantly since 2000. This effect is more marked in cases of rhegmatogenous retinal detachment. This may be partially explained by repeat surgery in cases of recurrent retinal detachment. Other possible explanations may be increased incidence of disease (due to increased rates of cataract surgery, increasing longevity and rates of myopia), improvements in patient access, and increased public awareness. It is possible that this observation is due in part to local changes in methodology of hospital coding.
Seroprevalence of Anti-SARS-CoV-2 Antibodies in a Cohort of New York City Metro Blood Donors using Multiple SARS-CoV-2 Serological Assays: Implications for Controlling the Epidemic and “Reopening”
Authors: Jin Daniel K. , Nesbitt Daniel. J. , Yang Jenny , Chen Haidee , Horowitz Julie , Jones Marcus , Vandergaast Rianna , Carey Timothy , Reiter Samantha , Russell Stephen J , Kyratsous Christos , Hooper Andrea , Hamilton Jennifer , Ferreira Manuel , Deng Sarah , Straus Donna , Baras Aris , Hillyer Christopher D. , Luchsinger Larry L.
Published: November 2020

Projections of the stage of the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) pandemic and local, regional and national public health policies designed to limit the spread of the epidemic as well as “reopen” cities and states, are best informed by serum neutralizing antibody titers measured by reproducible, high throughput, and statically credible antibody (Ab) assays. To date, a myriad of Ab tests, both available and authorized for emergency use by the FDA, has led to confusion rather than insight per se. The present study reports the results of a rapid, point-in-time 1,000-person cohort study using serial blood donors in the New York City metropolitan area (NYC) using multiple serological tests, including enzyme-linked immunosorbent assays (ELISAs) and high throughput serological assays (HTSAs). These were then tested and associated with assays for neutralizing Ab (NAb). Of the 1,000 NYC blood donor samples in late June and early July 2020, 12.1% and 10.9% were seropositive using the Ortho Total Ig and the Abbott IgG HTSA assays, respectively. These serological assays correlated with neutralization activity specific to SARS-CoV-2. The data reported herein suggest that seroconversion in this population occurred in approximately 1 in 8 blood donors from the beginning of the pandemic in NYC (considered March 1, 2020). These findings deviate with an earlier seroprevalence study in NYC showing 13.7% positivity. Collectively however, these data demonstrate that a low number of individuals have serologic evidence of infection during this “first wave” and suggest that the notion of “herd immunity” at rates of ∼60% or higher are not near. Furthermore, the data presented herein show that the nature of the Ab-based immunity is not invariably associated with the development of NAb. While the blood donor population may not mimic precisely the NYC population as a whole, rapid assessment of seroprevalence in this cohort and serial reassessment could aid public health decision making.
Engineering a Mobile Platform to Promote Sleep in the Pediatric Primary Care Setting
Authors: Mitchell Jonathan A. , Morales Knashawn H. , Williamson Ariel A. , Huffnagle Nicholas , Eck Casey , Jawahar Abigail , Juste Lionola , Fiks Alexander G. , Zemel Babette S. , Dinges David F.
Published: November 2020

Background

Pediatricians lack tools to support families at home for the promotion of childhood sleep. We are using the Multiphase Optimization Strategy (MOST) framework to guide the development of a mobile health platform for childhood sleep promotion.

Purpose

Under the preparation phase of the MOST framework, to demonstrate feasibility of a mobile health platform towards treating children with insufficient sleep.

Methods

Children aged 10-12y were enrolled (Study #1: N=30; Study #2: N=43). Participants wore a sleep tracker to measure sleep duration. Data were retrieved by a mobile health platform, programmed to send introductory messages during run-in (2 weeks) and goal achievement messages during intervention (7 weeks) periods. In study #1, participants were randomized to control, gain-framed incentive or loss-framed incentive arms. In study #2, participants were randomized to control, loss-framed incentive, normative feedback or loss-framed incentive plus normative feedback arms.

Results

In study #1, 1,514 nights of data were captured (69%) and sleep duration during the intervention was higher by an average of 21 (95% CI: -8, 51) and 34 (95% CI: 7, 61) minutes per night for the gain-framed and loss-framed arms, respectively, compared to controls. In study #2, 2,689 nights of data were captured (81%), with no major differences in average sleep duration between the control and the loss-framed or normative feedback arms.

Conclusion

We have developed and deployed a mobile health platform that can capture sleep data and remotely communicate with families. Promising candidate intervention components will be further investigated under the optimization phase of the MOST framework.
Validation of home oxygen saturations as a marker of clinical deterioration in patients with suspected COVID-19
Authors: Inada-Kim Matthew , Chmiel Francis P. , Boniface Michael J. , Pocock Helen , Black John J. M. , Deakin Charles D.
Published: November 2020

Background

The early identification of deterioration in suspected COVID-19 patients managed at home enables a more timely clinical intervention, which is likely to translate into improved outcomes. We undertook an analysis of COVID-19 patients conveyed by ambulance to hospital to investigate how oxygen saturation and measurements of other vital signs correlate to patient outcomes, to ascertain if clinical deterioration can be predicted with simple community physiological monitoring.

Methods

A retrospective analysis of routinely collected clinical data relating to patients conveyed to hospital by ambulance was undertaken. We used descriptive statistics and predictive analytics to investigate how vital signs, measured at home by ambulance staff from the South Central Ambulance Service, correlate to patient outcomes. Information on patient comorbidities was obtained by linking the recorded vital sign measurements to the patient’s electronic health record at the Hampshire Hospitals NHS Foundation Trust. ROC analysis was performed using cross-validation to evaluate, in a retrospective fashion, the efficacy of different variables in predicting patient outcomes.

Results

We identified 1,080 adults with a COVID-19 diagnosis who were conveyed by ambulance to either Basingstoke & North Hampshire Hospital or the Royal Hampshire County Hospital (Winchester) between March 1st and July 31st and whose diagnosis was clinically confirmed at hospital discharge. Vital signs measured by ambulance staff at first point of contact in the community correlated with patient short-term mortality or ICU admission. Oxygen saturations were the most predictive of mortality or ICU admission (AUROC 0.772 (95 % CI: 0.712-0.833)), followed by the NEWS2 score (AUROC 0.715 (95 % CI: 0.670-0.760), patient age (AUROC 0.690 (95 % CI: 0.642-0.737)), and respiration rate (AUROC 0.662 (95 % CI: 0.599-0.729)). Combining age with the NEWS2 score (AUROC 0.771 (95 % CI: 0.718-0.824)) or the measured oxygen saturation (AUROC 0.820 (95 % CI: 0.785-0.854)) increased the predictive ability but did not reach significance.

Conclusions

Initial oxygen saturation measurements (on air) for confirmed COVID-19 patients conveyed by ambulance correlated with short-term (30-day) patient mortality or ICU admission, AUROC: 0.772 (95% CI: 0.712-0.833). We found that even small deflections in oxygen saturations of 1-2% below 96% confer an increased mortality risk in those with confirmed COVID at their initial community assessments.
Longitudinal Physiological Data from a Wearable Device Identifies SARS-CoV-2 Infection and Symptoms and Predicts COVID-19 Diagnosis
Authors: Hirten Robert P. , Danieletto Matteo , Tomalin Lewis , Choi Katie Hyewon , Zweig Micol , Golden Eddye , Kaur Sparshdeep , Helmus Drew , Biello Anthony , Pyzik Renata , Nabeel Ismail , Charney Alexander , Glicksberg Benjamin , Levin Matthew , Reich David , Charney Dennis , Bottinger Erwin P , Keefer Laurie , Suarez-Farinas Mayte , Nadkarni Girish N. , Fayad Zahi A.
Published: November 2020

Background

Changes in autonomic nervous system function, characterized by heart rate variability (HRV), have been associated with and observed prior to the clinical identification of infection. We performed an evaluation of this metric collected by wearable devices, to identify and predict Coronavirus disease 2019 (COVID-19) and its related symptoms.

Methods

Health care workers in the Mount Sinai Health System were prospectively followed in an ongoing observational study using the custom Warrior Watch Study App which was downloaded to their smartphones. Participants wore an Apple Watch for the duration of the study measuring HRV throughout the follow up period. Survey’s assessing infection and symptom related questions were obtained daily.

Findings

Using a mixed-effect COSINOR model the mean amplitude of the circadian pattern of the standard deviation of the interbeat interval of normal sinus beats (SDNN), a HRV metric, differed between subjects with and without COVID-19 (p=0.006). The mean amplitude of this circadian pattern differed between individuals during the 7 days before and the 7 days after a COVID-19 diagnosis compared to this metric during uninfected time periods (p=0.01). Significant changes in the mean MESOR and amplitude of the circadian pattern of the SDNN was observed between the first day of reporting a COVID-19 related symptom compared to all other symptom free days (p=0.01).

Interpretation

Longitudinally collected HRV metrics from a commonly worn commercial wearable device (Apple Watch) can identify the diagnosis of COVID-19 and COVID-19 related symptoms. Prior to the diagnosis of COVID-19 by nasal PCR, significant changes in HRV were observed demonstrating its predictive ability to identify COVID-19 infection.

Funding

Support was provided by the Ehrenkranz Lab For Human Resilience, the BioMedical Engineering and Imaging Institute, The Hasso Plattner Institute for Digital Health at Mount Sinai, The Mount Sinai Clinical Intelligence Center and The Dr. Henry D. Janowitz Division of Gastroenterology.
Synchronization in Epidemic Growth and the Impossibility of Selective Containment
Authors: Budich Jan Carl , Bergholtz Emil J.
Published: November 2020

Containment, aiming to prevent the epidemic stage of community-spreading altogether, and mitigation, aiming to merely ‘flatten the curve’ of a wide-ranged outbreak, constitute two qualitatively different approaches to combating an epidemic through non-pharmaceutical interventions. Here, we study a simple model of epidemic dynamics separating the population into two groups, namely a low-risk group and a high-risk group, for which different strategies are pursued. Due to synchronization effects, we find that maintaining a slower epidemic growth behavior for the high-risk group is unstable against any finite coupling between the two groups. More precisely, the density of infected individuals in the two groups qualitatively evolves very similarly, apart from a small time delay and an overall scaling factor quantifying the coupling between the groups. Hence, selective containment of the epidemic in a targeted (high-risk) group is practically impossible whenever the surrounding society implements a mitigated community-spreading. We relate our general findings to the ongoing COVID-19 pandemic.
Unraveling the relationship of loneliness and isolation in schizophrenia: Polygenic dissection and causal inference
Authors: Andreu-Bernabeu A. , Díaz-Caneja C.M. , Costas J. , de Hoyos L. , Stella C. , Gurriarán X. , Alloza C. , Fañanás L. , Bobes J. , González Pinto A. , Crespo-Facorro B. , Martorell L. , Vilella E. , Muntane G. , Nacher J. , Molto M.D. , Aguilar E.J. , Parellada M. , Arango C. , González-Peñas J.
Published: November 2020

There is increasing recognition of the association between loneliness and social isolation (LNL-ISO) with schizophrenia. Here, we demonstrate significant LNL-ISO polygenic score prediction on schizophrenia in an independent case-control sample (N=3,488). We then dissect schizophrenia predisposing variation into subsets of variants based on their effect on LNL-ISO. Genetic variation with concordant effects in both phenotypes show significant SNP-based heritability enrichment, higher polygenic predictive ability in females and positive covariance with other mental disorders such as depression, anxiety, attention-deficit hyperactivity, alcohol use disorder, and autism. Conversely, genetic variation with discordant effects is only predictive in males and negatively correlated with those disorders. This correlation pattern is not observed for bipolar and obsessive-compulsive disorders. Mendelian randomization analyses demonstrate a plausible bi-directional causal relationship between LNL-ISO and schizophrenia, with a greater effect of LNL-ISO liability on schizophrenia. These results illustrate the genetic footprint of LNL-ISO on schizophrenia and suggest its role as a potential target for early intervention.
Trends in body mass index and blood pressure associations from 1989 to 2018: co-ordinated analysis of 145,399 participants
Authors: Bann David , Scholes Shaun , Hardy Rebecca , O’Neill Dara
Published: November 2020

Background

High body mass index (BMI) is an important contributor to higher blood pressure (BP) levels and its deleterious consequences. However, the strength of this association may be context-specific and differ across time due to increases in medication use or secular changes in body composition. Thus, we utilised two independent data sources to investigate if associations between BMI and systolic BP (SBP) in Britain changed from 1989-2018.

Methods

We used 23 repeated cross-sectional datasets—the Health Survey for England (HSE) at ≥25 years (1994–2018; N=126,742); and three British birth cohorts (born 1946, 1958, and 1970) with outcomes available at 43-46 years (N=18,657). Anthropometry and BP were measured using standard protocols. We used linear and quantile regression to investigate cross-sectional associations between BMI and SBP.

Results

In HSE, associations were weaker in subsequent years, and this trend was most pronounced amongst older adults—after accounting for sex, treatment and education, the mean difference in SBP per 1 kg/m2 increase in BMI amongst adults ≥55 years was 0.75mmHg (95% CI: 0.60, 0.90) in 1994, 0.66mmHg (0.46, 0.85) in 2003, and 0.53mmHg (0.35, 0.71) in 2018. In cohorts, BMI and SBP associations were of similar magnitude in 1958 and 1970 cohorts and weaker in the 1946 cohort. Quantile regression analyses suggested that associations between BMI and SBP were present both below and above the hypertension threshold.

Conclusion

The consequences of BMI may differ across time and by age —associations between BMI and SBP appear to have weakened in recent decades, particularly in older ages. Thus, at older ages, this weakening strength of association may partly offset the public health impacts of increases in obesity prevalence. However, BMI remains positively associated with SBP in all adult age groups, highlighting the potential adverse consequences of the ongoing obesity epidemic.
Mitochondrial DNA haplogroups and trajectories of cardiometabolic risk factors during childhood and adolescence: a prospective cohort study
Authors: O’Neill Kate N , Aubrey Emily , Howe Laura D , Stergiakouli Evie , Rodriguez Santiago , Kearney Patricia M , O’Keeffe Linda M
Published: November 2020

Background

Mitochondria are organelles responsible for converting glucose into energy. Mitochondrial DNA is exclusively maternally inherited by offspring. The role of mitochondrial DNA haplogroups in the aetiology of cardiometabolic disease risk is not well understood.

Methods

We examined the sex-specific association between European mitochondrial DNA haplogroups and trajectories of nine cardiometabolic risk factors from birth to 18 years in a prospective English birth cohort. Mitochondrial haplogroups were analysed according to common European haplogroups; H,U,J,T,K,V,W,I and X. Nine cardiometabolic risk factors measured over varying times from birth/mid-childhood to age 18 years included body mass index (BMI), fat mass and lean mass, systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, high-density lipoprotein cholesterol (HDL-c), non HDL-c and triglycerides. Fractional polynomial and linear spline multilevel models stratified by sex explored the sex-specific association between haplogroups and risk factor trajectories.

Results

Among 6,360-7,954 participants with 22,864-79,178 repeated measures per outcome, we found no strong evidence that haplogroups U,T,J,K and W were associated with trajectories of cardiometabolic risk factors across childhood and adolescence compared to haplogroup H. In females, haplogroup V was associated with 4.0% (95% CI: 1.4, 6.7) lower BMI at age 7 years and 9.3% (95% CI: 1.9, 16.7) lower fat mass at age 9, though differences did not persist at age 18. Haplogroup X was associated with 1.3kg (95% CI: 0.5, 2.2) lower lean mass and 16.4% (95% CI: 3.5, 29.3) lower fat mass at age 9; associations with lower lean mass persisted at 18 years whereas associations with fat mass did not. In males, haplogroup I was associated with 2.4% (95% CI: 0.2, 4.6) higher BMI at age 7; this difference widened to 5.1% (95% CI: 0.9,9.3) at 18 years.

Conclusion

Our study demonstrated some evidence of sex-specific associations between mitochondrial DNA haplogroups V, I and X and trajectories of adiposity during childhood and adolescence.