bluuebunny/crossref_metadata_2025 huggingface dataset:
Migraine and menopause - a narrative review
Authors: Bernstein Carolyn , O’Neal Mary A.
Published: August 2020

Importance and objectives:

This narrative review addresses common clinical questions and concerns of both physicians and patients about migraine during and after the perimenopausal transition, specifically (1) How does the perimenopausal transition affect migraine prevalence and does this vary by migraine type? (2) Does the magnitude of stroke risk associated with migraine increase with hormone therapy (HT)?, and (3) What are best practices as regards migraine treatment in perimenopausal women?

Methods:

We searched PubMed from 2010 through the present. Search terms included migraine, menopause, and HT. Articles were included if they were in English and had full text availability. In addition, key references identified in the search articles were included.

Discussion and conclusion:

Many women are informed that their migraines will disappear postmenopause; there are some data to support this, but a specific time frame has not been evidenced. Stroke risk in women with migraine with aura is small in absolute terms, but important at the population level, because migraine is so prevalent. The risk becomes clinically important in the context of additional stroke risk factors, which increase with aging such as hypertension. Estrogen in combined hormonal contraception increases the risk of an ischemic stroke, however, the lower amount of estrogen in HT may not contribute to a meaningful increase in stroke risk. HT is a preventative sex-specific treatment for female migraineurs for the menopausal transition. Sex differences for other conventional treatments outside their use in menstrual and menstrually related migraine have not been studied specifically in the menopausal transition.

Video Summary:

http://links.lww.com/MENO/A636.
Clonal Hematopoiesis in Hospitalized Elderly Patients With COVID‐19
Authors: Hameister Erik , Stolz Sebastian M. , Fuhrer Yvonne , Thienemann Friedrich , Schaer Dominik J. , Nemeth Johannes , Schuepbach Reto A. , Goede Jeroen , Reinhart Sophie , Schmidt Adrian , Kahraman Abdullah , Schmid Mathias , Moch Holger , Zoche Martin , Manz Markus G. , Balabanov Stefan , Boettcher Steffen
Published: August 2020

Supplemental Digital Content is available in the text
A Pathophysiological Perspective on the SARS‐CoV‐2 Coagulopathy
Authors: Kusadasi Nuray , Sikma Maaike , Huisman Albert , Westerink Jan , Maas Coen , Schutgens Roger
Published: August 2020

Recent evidence is focusing on the presence of a hypercoagulable state with development of both venous and arterial thromboembolic complications in patients infected with SARS‐CoV‐2. The ongoing activation of coagulation related to the severity of the illness is further characterized by thrombotic microangiopathy and endotheliitis. These microangiopathic changes cannot be classified as classical disseminated intravascular coagulation (DIC). In this short review we describe the interaction between coagulation and inflammation with focus on the possible mechanisms that might be involved in SARS‐CoV‐2 infection associated coagulopathy in the critically ill.
Impact of dexamethasone intraocular suspension 9% on intraocular pressure after routine cataract surgery: post hoc analysis
Authors: Matossian Cynthia , Hovanesian John , Bacharach Jason , Paggiarino Dario , Patel Keyur
Published: August 2020

Purpose:

To characterize intraocular pressure (IOP) response after treatment with dexamethasone intraocular suspension 9% vs placebo (vehicle) injection or topical prednisolone acetate 1% and to identify factors associated with increased IOP after cataract surgery.

Setting:

Data were pooled from two multicenter phase 3 clinical trials of patients undergoing routine cataract surgery.

Design:

Randomized, double-blind study and open-label study.

Methods:

Subjects were randomized to treatment with dexamethasone intraocular suspension or placebo in the double-blind study 1 and to dexamethasone intraocular suspension or topical prednisolone acetate in the open-label study 2. Subjects who experienced 10 mm Hg or greater, 15 mm Hg or greater, or 20 mm Hg or greater postoperative IOP increase from baseline were stratified by baseline IOP. Univariate and multivariate logistic regression models of patient variables were applied to identify independent risk factors predictive of IOP elevation of 10 mm Hg or greater or 15 mm Hg or greater.

Results:

The study comprised 414 subjects. Dexamethasone intraocular suspension was associated with a slightly higher mean IOP at the first postoperative visit vs prednisolone (P < .05); however, mean IOP was not statistically different between the 2 groups by postoperative day 8 (P = .5006) or thereafter. Univariate analysis showed that both prednisolone and dexamethasone intraocular suspension increased risk for postoperative IOP elevation compared with placebo; however, there was no statistically significant increased risk with dexamethasone intraocular suspension vs prednisolone. Aside from antiinflammatory treatment, risk factors for postoperative IOP elevation by univariate and multivariate analyses were higher baseline IOP, high myopia, and, when defining IOP increase as 15 mm Hg or greater from baseline, male sex.

Conclusions:

Dexamethasone intraocular suspension was associated with IOP elevation patterns comparable with topical prednisolone. High myopia, higher baseline IOP, and male sex were significant predictors of postoperative IOP elevation in this cohort.
Measures of visual disturbance in patients receiving extended depth-of-focus or trifocal intraocular lenses
Authors: Kohnen Thomas , Suryakumar Rajaraman
Published: August 2020

The degree of visual disturbance associated with a particular model of intraocular lens (IOL) depends on several factors, including IOL optic, material, and mechanics. Characterization of visual disturbance profiles is paramount for informing clinical IOL selection. Although many studies evaluating presbyopia-correcting IOLs include subjective assessment of visual symptoms, the types of patient-reported outcome measures (PROMs) used to capture these outcomes are inconsistent across studies, complicating data contextualization. Furthermore, some tools produce more meaningful results than others. This review presents a discussion on the scientific literature published on the subjective and semiobjective (halo and glare simulator, light-distortion analyzer, vision monitor, and halometers) methods used to assess visual disturbances in patients implanted with trifocal or extended depth-of-focus IOLs, highlighting their advantages and limitations. It underscores the importance of between-study comparisons and the need for standardized PROMs in clinical IOL research to provide more accurate information for IOL selection.
Single subconjunctival injection formulation using sol-gel mesoporous silica as a controlled release system for drop-free post-cataract surgery care
Authors: Sun Yaoyao , Huffman Kristyn , Freeman William R. , Cheng Lingyun
Published: August 2020

Purpose:

To develop a mesoporous silica drug delivery system and target drop-free care after cataract surgery with a single subconjunctival injection.

Setting:

Laboratory.

Design:

Experimental animal study.

Methods:

Ketorolac was infiltration-loaded into sol-gel mesoporous silica particles encapsulated with poly(allylamine hydrochloride) and poly(sodium 4-styrenesulfonate) using a layer-by-layer adsorption technique (SG-Ket-LBL). The formulation was subjected to an in vitro and in vivo drug release study in addition to ocular toxicology evaluation.

Results:

Thermogravimetric analysis revealed that the drug loading efficiency was 4.4% for the SG-Ket-LBL particles. The in vivo safety study demonstrated that the formulation was well tolerated after subconjunctival injection and aqueous humor pharmacokinetics showed sustained therapeutic drug release for the targeted time window of 6 to 8 weeks.

Conclusions:

Findings indicated that sol-gel mesoporous silica could be used as a drug carrier for subconjunctival administration. The tested formulation, SG-Ket-LBL, provided therapeutic ketorolac for 6 to 8 weeks, which might be used for a single subconjunctival injection to replace nonsteroidal anti-inflammatory drug eyedrops after cataract surgery.
Explantation/exchange of the components of a new fluid-filled, modular, accommodating IOL
Authors: Kennedy Sean , Werner Liliana , Bontu Sneha , Jiang Bill , Kamae Kai , Ellis Nathan , Brady Daniel G. , Mamalis Nick
Published: August 2020

Purpose:

To evaluate the ease of replacement and capsular stability of a new fluid-filled, modular, accommodating intraocular lens (IOL) system composed of a monofocal base lens with a fluid lens clipped inside of it.

Setting:

John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA.

Design:

Experimental study.

Methods:

Five New Zealand rabbits underwent bilateral phacoemulsification with implantation of the test lens (Juvene, LensGen, Inc.) in both eyes (4 rabbits), or a control IOL in 1 eye (AcrySof, Alcon Laboratories, Inc.) and the test IOL in the other (1 rabbit). At 2 weeks, the 4 rabbits with bilateral Juvene IOLs had the clipped-in fluid lens exchanged for a new fluid lens in 1 eye, and the base and fluid lenses exchanged for a control lens in the contralateral eye. Slitlamp examinations were performed weekly for 4 weeks. The globes were enucleated and evaluated with ultrasound biomicroscopy, grossly from the posterior Miyake-Apple view, and histopathologically.

Results:

Explantation/exchange of the fluid lens was considered straightforward by the surgeon. Explantation of the base lens (4) was also safely performed, albeit more demanding, without any signs of damage to the capsular bag under clinical, ultrasound biomicroscopy, and pathological examination in the exchanged eyes. Less capsular bag opacification was observed with the Juvene lens system.

Conclusions:

Explantation/exchange of the fluid lens component, or both fluid and base lenses, of this new lens system can be safely accomplished if necessary, because of its modular design and the relative lack of postoperative capsular bag opacification associated with it.
Comparison of 2 swept-source optical coherence tomography–based biometry devices
Authors: Fişuş Andreea D. , Hirnschall Nino D. , Findl Oliver
Published: August 2020

Purpose:

To compare 2 swept-source optical coherence tomography (SS-OCT) biometers, IOLMaster 700 (biometer A), and ANTERION (biometer B).

Setting:

Department of Ophthalmology, Vienna Institute for Research in Ocular Surgery, Karl Landsteiner Institute, Hanusch Hospital, Vienna, Austria.

Design:

Retrospective study.

Method:

Biometric measurements of cataract patients performed between June and July 2019 were reviewed. Patients scheduled for cataract surgery were measured with both SS-OCT devices on the same day. The following biometry parameters were compared: keratometry, central corneal thickness, anterior chamber depth (ACD), lens thickness (LT), and axial length (AL).

Result:

In total, 389 eyes of 209 subjects were measured with both devices. The mean absolute difference between the keratometry data of the 2 devices was 0.04 ± 0.05 mm (7.80 ± 0.26 mm for biometer A and 7.82 ± 0.26 mm for biometer B; P < .0001) for the steep keratometry readings and 0.04 ± 0.04 mm (7.63 ± 0.26 mm and 7.65 ± 0.25 mm; P < .0001) for the flat keratometry readings. For ACD and LT, the mean absolute difference was 0.07 ± 0.04 mm and 0.07 ± 0.04 mm. The mean absolute difference for AL was 0.02 ± 0.03 mm (23.55 ± 1.18 mm for biometer A and 23.54 ± 1.18 mm for biometer B; P < .0001).

Conclusions:

Good agreement was found between the 2 devices, with a minor offset for ACD and LT measurements. Although differences were found to be small, the devices should not be used interchangeably.
Implementing a Heart Failure Transition Program to Reduce 30-Day Readmissions
Authors: Hinch Barbara K. , Staffileno Beth A.
Published: August 2020

Background:

Thirty-day readmissions for heart failure (HF) patients are often considered avoidable and linked to inadequate treatment and poor coordination of services and discharge plans.

Problem:

Lack of coordinated transitional care services and high 30-day readmissions prompted the interdisciplinary team to develop an HF Transition Program (HFTP).

Methods:

This quality improvement initiative used monthly trend data before and after HFTP implementation.

Interventions:

The American Heart Association Guidelines for HF Transitions served as a framework for developing the HFTP.

Results:

Over an 11-month period, 466 patients were enrolled into the HFTP, resulting in 18.2% (n = 82/450) 30-day cumulative readmission rate that is lower than the 21.9% national average. Sixteen patients did not code for HF after discharge. Heart Failure Transition Program calls to patients and families within the first week home were consistently high at 92.3% (430/466).

Conclusions:

These data show that care coordination and transitional care are important strategies to decrease 30-day HF readmissions.
Continuous Cloud-Based Early Warning Score Surveillance to Improve the Safety of Acutely Ill Hospitalized Patients
Authors: Morgan Christopher K. , Amspoker Amber B. , Howard Christopher , Razjouyan Javad , Siddique Muhammad , D'Avignon Seanna , Rosen Tracey , Herlihy James P. , Naik Aanand D.
Published: August 2020

Introduction:

This study sought to evaluate the impact of changes made to the process of continually screening hospitalized patients for decompensation.

Methods:

Patients admitted to hospital wards were screened using a cloud-based early warning score (modified National Early Warning Score [mNEWS]). Patient with mNEWS ≥7 triggered a structured response. Outcomes of this quality improvement study during the intervention period from February through August 2018 (1741 patients) were compared with a control population (1,610 patients) during the same months of 2017.

Results:

The intervention group improved the time to the first lactate order within 24 hours of mNEWS ≥7 (p < .001), the primary outcome, compared with the control group. There was no significant improvement in time to intensive care unit (ICU) transfer, ICU length of stay (LOS), or hospital mortality. Among patients with a lactate ordered within 24 hours, there was a 47% reduction of in-hospital mortality (odds ratio 0.53, 95% confidence interval 0.3–0.89, p = .02) and a 4.7 day reduction in hospital LOS (p < .001) for intervention versus control cohorts.

Conclusions:

Cloud-based electronic surveillance can result in earlier detection of clinical decompensation. This intervention resulted in lower hospital LOS and mortality among patients with early detection of and intervention for clinical decompensation.
Nurse Burnout Predicts Self-Reported Medication Administration Errors in Acute Care Hospitals
Authors: Montgomery Aoyjai P. , Azuero Andres , Baernholdt Marianne , Loan Lori A. , Miltner Rebecca S. , Qu Haiyan , Raju Dheeraj , Patrician Patricia A.
Published: August 2020

Background:

Every one out of 10 nurses reported suffering from high levels of burnout worldwide. It is unclear if burnout affects job performance, and in turn, impairs patient safety, including medication safety. The purpose of this study is to determine whether nurse burnout predicts self-reported medication administration errors (MAEs).

Methods:

A cross-sectional study using electronic surveys was conducted from July 2018 through January 2019, using the Copenhagen Burnout Inventory. Staff registered nurses (N = 928) in acute care Alabama hospitals (N = 42) were included in this study. Descriptive statistics, correlational, and multilevel mixed-modeling analyses were examined.

Results:

All burnout dimensions (Personal, Work-related, and Client-related Burnout) were significantly correlated with age (r = −0.17 to −0.21), years in nursing (r = −0.10 to −0.17), years of hospital work (r = −0.07 to −0.10), and work environment (r = −0.24 to −0.57). The average number of self-reported MAEs in the last 3 months was 2.13. Each burnout dimension was a statistically significant predictor of self-reported MAEs (p < .05).

Conclusions:

Nurse burnout is a significant factor in predicting MAEs. This study provides important baseline data for actionable interventions to improve nursing care delivery, and ultimately health care, for Alabamians.
Exploring the Association Between the Quality of HIV Care in Nursing Homes and Hospitalization
Authors: Olivieri-Mui Brianne , McGuire Jean , Griffith John , Cahill Sean , Briesacher Becky
Published: August 2020

Persons living with HIV/AIDS (PLWH) are living long enough to need age-related and HIV-related nursing home (NH) care. Nursing home quality of care has been associated with risk for hospitalization, but it is unknown if quality of HIV care in NHs affects hospitalization in this population. We assessed HIV care quality with four national measures adapted for the NH setting. We applied the measures to 2011–2013 Medicare claims linked to Minimum Data Set assessments of resident health, prescription dispensing data, and national reports of NH characteristics. Cox proportional hazards models calculated the risk of all-cause and HIV/AIDS-related hospitalization by HIV care compliance. We identified 1,246 PLWH in 201 NHs with 382 all-cause and 63 HIV/AIDS-related hospitalizations. Nursing home HIV care compliance varied from 24.9% to 64.7%. After regression adjustment, we could detect no difference in all-cause or HIV/AIDS-related hospitalizations by NH HIV care compliance. We postulate that the lack of association may be due to inappropriate HIV care quality measures that do not accurately represent NHs ability to care for PLWH. There is urgent need to create valid NH HIV care quality measures.
Hearing Disabilities and the Effectiveness of Rehabilitation in Different Age Groups
Authors: Jolink Casper , Lansbergen Simon E. , Dreschler Wouter A.
Published: August 2020

Objective:

To assess differences in hearing disabilities between different age groups and the effectiveness of rehabilitation with hearing aids.

Study Design:

Retrospective chart review.

Setting:

First line hearing aid dispensers.

Patients:

First-time hearing aid users divided in a younger group aged 18 to 65 years (119 subjects) and an elderly group aged 70 years and older (213 subjects).

Intervention(s):

Rehabilitative.

Main Outcome Measure(s):

Weighted pure tone averages (PTA) were calculated using the binaural impairment model. The patient-reported outcome measures (PROMs) Amsterdam Questionnaire for Auditory Disabilities (AVAB), and client oriented scale of improvement (COSI) were collected pre- and post-fitting. To analyze whether age group, weighted PTA, and type of auditory dimension influences AVAB, linear regression and two-way ANalysis Of VAriance models were used.

Results:

The weighted PTA of the young group was significantly lower than of the elderly group. In the regression model differences between age groups were found to be significant for pre-AVAB and for AVAB benefit. The two-way ANalysis Of VAriance showed that the effect of age on pre- and post-AVAB scores was not influenced by PTA or the type of auditory dimension.

Conclusions:

Younger first-time hearing aid users experience more auditory disabilities, despite better hearing levels than their elderly counterparts. Their disabilities are rehabilitated more effectively by hearing aids.
The Potential Added Value of Novel Hearing Therapeutics: An Early Health Economic Model for Hearing Loss
Authors: Mandavia Rishi , Horstink Yvette M. , Grutters Janneke P.C. , Landry Evie , May Carl , Rovers Maroeska , Schilder Anne G.M. , Scholte Mirre
Published: August 2020

Objective:

To construct an early health economic model to assess the potential added value of novel hearing therapeutics, compared with the current standard of care. We use idiopathic sudden sensorineural hearing loss (ISSNHL) as a case example, because it is a lead indication for several emerging hearing therapeutics.

Methods:

A decision analytic model was developed to assess the costs and effects of using novel hearing therapeutics for patients with ISSNHL. This was compared to the current standard of care. Input data were derived from literature searches and expert opinion. The study adopted a healthcare perspective of the UK National Health Service. Four analyses were conducted: 1) headroom, 2) scenario, 3) threshold, 4) sensitivity.

Results:

The decision analytic model showed that novel therapeutics for ISSNHL have potential value both in terms of improved patient outcomes, as well as incremental net monetary benefit (iNMB). The base case analysis revealed an iNMB of £39,032 for novel therapeutics compared with the current standard of care. Results of the threshold and scenario analysis revealed that age of treatment and severity of ISSNHL are major determinants of iNMB for novel therapeutics.

Conclusion:

This article describes the first health economic model for novel therapeutics for hearing loss; and shows that novel hearing therapeutics can be cost-effective under NICE's cost-effectiveness threshold, with considerable room for improvement in the current standard of care. Our model can be used to inform the development of cost-effective hearing therapeutics; and help decision makers decide which therapeutics represent value for money.
Age Estimation of Teenage Boys During Puberty
Authors: Pineau Jean-Claude
Published: August 2020

Background

Age estimation of a minor whose identity is unknown must be accurate enough to respond to judicial requests. The main objective of this study is to accurately determine a teenager's age from simple and reproducible criteria.

Samples and Methods

The first reference sample consists of 1720 measurements collected from 170 teenagers aged 11 to 16 years, over a period of 5 years. A second validation sample of 735 teenage boys aged 11 to 16 made it possible to verify the relevance of our estimates. The degree of maturation was determined using 4 pubertal stages: the stage below the age of puberty, the prepubescent stage, the parapubescent stage, and the pubescent stage.

For each pubertal stage, an optimization of the values of the age was carried out in order to reduce the differences between the estimated and the actual age at the different age groups.

Results

The mean differences between estimated age and actual age from these values were −0.06 ± 0.91 years for the reference group and −0.49 ± 0.73 years for validation group.

Conclusions

Our method of age estimation is simpler and accurate. It could be used routinely in a forensic frame to respond to judicial requests.
Impact of chemotherapy-induced enteric nervous system toxicity on gastrointestinal mucositis
Authors: McQuade Rachel M. , Al Thaalibi Maryam , Nurgali Kulmira
Published: August 2020

Purpose of review

Chemotherapy is a first-line treatment for many cancers; however, its use is hampered by a long list of side-effects. Gastrointestinal mucositis is a common and debilitating side-effect of anticancer therapy contributing to dose reductions, delays and cessation of treatment, greatly impacting clinical outcomes. The underlying pathophysiology of gastrointestinal mucositis is complex and likely involves several overlapping inflammatory, secretory and neural mechanisms, yet research investigating the role of innervation in gastrointestinal mucositis is scarce. This review provides an overview of the current literature surrounding chemotherapy-induced enteric neurotoxicity and discusses its implications on gastrointestinal mucositis.

Recent findings

Damage to the intrinsic nervous system of the gastrointestinal tract, the enteric nervous system (ENS), occurs following chemotherapeutic administration, leading to altered gastrointestinal functions. Chemotherapeutic drugs have various mechanisms of actions on the ENS. Oxidative stress, direct toxicity and inflammation have been identified as mechanisms involved in chemotherapy-induced ENS damage. Enteric neuroprotection has proven to be beneficial to reduce gastrointestinal dysfunction in animal models of oxaliplatin-induced enteric neuropathy.

Understanding of the ENS role in chemotherapy-induced mucositis requires further investigation and might lead to the development of more effective therapeutic interventions for prevention and treatment of chemotherapy-induced gastrointestinal side-effects.
Whole Care Home Testing for Covid-19 in a Local Authority Area in the United Kingdom
Authors: Starling Anna , White Eleanor , Showell Danny , Wyllie David , Kapadia Smita , Balakrishnan Ravi
Published: August 2020

Objectives

To describe the point prevalence of SARS-CoV-2 in care homes reporting low numbers of cases of COVID-19.

Design

A cross-sectional study of care homes, ascertaining perceived disease burden using interviews with care home managers and SARS-CoV-2 RNA detection in residents and staff using nose and throat swabbing.

Setting

15 Care homes in Essex, United Kingdom, all of which had reported either zero or one case of COVID-19 to the Health Protection Team.

Participants

912 residents and staff of care homes were tested. Residents were eligible to be tested regardless of symptoms.

Main outcome measure

Detection of SARS-CoV-2 in residents and staff.

Results

In the 15 care homes studied, SARS-CoV-2 was detected in 23 (5.2%) of 441 residents. Of these 23, 21/23 (91%) were asymptomatic as reported by the care home managers. SARS-CoV-2 was detected in 8/471 (1.7%) of staff. This differs from that in residents (p=0.003).

Conclusions

The study’s findings suggest that symptoms, as reported by care home managers, are an insensitive method of defining the extent of SARS-CoV-2 infection in nursing homes. Viral detection from residents is more common than from staff. Microbiological screening is a more sensitive method for defining the extent of SARS-CoV-2 in care homes than managerial reporting of resident symptoms.
The Impact of the COVID-19 Pandemic on Rabies Reemergence in Latin America: the case of Arequipa, Peru
Authors: Raynor Brinkley , Díaz Elvis W. , Shinnick Julianna , Zegarra Edith , Monroy Ynes , Mena Claudia , Castillo-Neyra Ricardo
Published: August 2020

Over the past decades, there has been tremendous progress towards eliminating canine rabies in Latin America. Major components of rabies prevention programs in Latin America leading to these successes have been constant and intense surveillance for rabid dogs and uninterrupted yearly mass dog vaccination campaigns. However, vital measures to control COVID-19 in Latin America have had the negative trade-off of jeopardizing these rabies elimination and prevention activities. In this paper, we aimed to assess the effect of interrupting canine rabies surveillance and mass dog vaccination campaigns on rabies trends. We built a deterministic compartment model of dog rabies dynamics parameterized for conditions found in Arequipa, Peru, where there is an ongoing dog rabies epidemic. Our model suggests that a decrease in canine vaccination coverage as well as decreased surveillance leading to an increased length of survival of infected dogs could lead to a sharp rise in canine rabies and, subsequently, human rabies risk. We examined our results over the best estimate of the basic reproductive number in Arequipa (R0 = 1.44) and a range of plausible values for R0 (1.36 - 2). The rising trend was consistent. It is very possible that COVID-19 will continue to challenge our public health departments in the short- and medium-term. Innovative strategies to conduct dog vaccination and rabies surveillance during these trying times should be considered to safeguard the achievements made in Latin America towards the elimination of dog-mediated human rabies.
Expanding COVID-19 symptom screening to retail, restaurants, and schools by preserving privacy using relaxed digital signatures
Authors: Jew Brandon , Korb Alexis , Lou Paul , Chiang Jeffrey N. , An Ulzee , Sahai Amit , Halperin Eran , Eskin Eleazar
Published: August 2020

Symptom screening is a widely deployed strategy to mitigate the COVID-19 pandemic and many public health authorities are mandating its use by employers for all employees in the workplace. While symptom screening has the benefit of reducing the number of infected individuals in the workplace, it raises some inherently difficult privacy issues as a traditional approach requires the employer to collect symptom data from each employee which is essentially medical information. In this paper, we describe a system to implement Cryptographic Anonymous Symptom Screening (CASS) which allows for individuals to perform COVID symptom screening anonymously while avoiding the privacy issues of traditional approaches. In the system, individuals report their symptoms without any identifying information and are issued a completion certificate. This certificate contains a cryptographic code which certifies that the certificate was obtained from the screener after reporting no symptoms. The codes can be verified using a cryptographic algorithm which is publicly available. A standard cryptography approach to implement such a system would be to use digital signatures. Unfortunately, standard digital signatures have some limitations for this application in that the signatures are often hundreds of characters long and if the signature contains the name of the individual, then there is also a risk of compromising privacy. In our approach, we develop and utilize a relaxed digital signature scheme to provide 16 character long codes and handle names using equivalence classes which helps preserve privacy. Both of these extensions technically compromise the security but in a way that is negligible for this application. Our system can either serve the function of standard symptom screening system approaches for employees, but can also extend symptom screening to non-employees such as visitors or customers. In this case, the system can be utilized in retail, restaurants and schools to ensure that everyone in the physical space, including employees, customers, visitors and students have performed symptom screening.
LamPORE: rapid, accurate and highly scalable molecular screening for SARS-CoV-2 infection, based on nanopore sequencing
Authors: James Phillip , Stoddart David , Harrington Eoghan D , Beaulaurier John , Ly Lynn , Reid Stuart W , Turner Daniel J , Juul Sissel
Published: August 2020

LamPORE™ is a rapid way of testing/screening large numbers of samples for the presence or absence of SARS-CoV-2, the virus causing COVID-19. It combines barcoded multi-target amplification, 15-minute barcoded library preparation and real-time nanopore sequencing. Starting with extracted RNA, results can be obtained from 12 samples in approximately an hour and from 96 samples in under 2 hours. High scalability is achieved by combinatorial barcoding. Performance characteristics are currently being established and regulatory clearance to market is underway.
Real-world Evidence of Diagnostic Testing and Treatment Patterns in U.S. Breast Cancer Patients with Implications for Treatment Biomarkers from RNA-sequencing Data
Authors: Fernandes Louis E. , Epstein Caroline G. , Bobe Alexandria M. , Bell Joshua S.K. , Stumpe Martin C. , Salazar Michael E. , Salahudeen Ameen A. , Pe Benito Ruth A. , McCarter Calvin , Leibowitz Benjamin D. , Kase Matthew , Igartua Catherine , Huether Robert , Hafez Ashraf , Beaubier Nike , Axelson Michael D. , Pegram Mark D. , Sammons Sarah L. , O’Shaughnessy Joyce A. , Palmer Gary A.
Published: August 2020

INTRODUCTION

We performed a retrospective analysis of longitudinal real-world data (RWD) from breast cancer patients to replicate results from clinical studies and demonstrate the feasibility of generating real-world evidence. We also assessed the value of transcriptome profiling as a complementary tool for determining molecular subtypes.

PATIENTS AND METHODS

De-identified, longitudinal data were analyzed after abstraction from U.S. breast cancer patient records structured and stored in the Tempus database. Demographics, clinical characteristics, molecular subtype, treatment history, and survival outcomes were assessed according to strict qualitative criteria. RNA sequencing and clinical data were used to predict molecular subtypes and signaling pathway enrichment.

RESULTS

The clinical abstraction cohort (n=4,000) mirrored U.S. breast cancer demographics and clinical characteristics indicating feasibility for RWE generation. Among HER2+ patients, 74.2% received anti-HER2 therapy, with ~70% starting within 3 months of a positive test result. Most non-treated patients were early stage. In this RWD set, 31.7% of patients with HER2+ IHC had discordant FISH results recorded. Among patients with multiple HER2 IHC results at diagnosis, 18.6% exhibited intra-test discordance. Through development of a whole-transcriptome model to predict IHC receptor status in the molecular sequenced cohort (n=400), molecular subtypes were resolved for all patients (n=36) with equivocal HER2 statuses from abstracted test results. Receptor-related signaling pathways were differentially enriched between clinical molecular subtypes.

CONCLUSION

RWD in the Tempus database mirrors the overall U.S. breast cancer population. These results suggest real-time, RWD analyses are feasible in a large, highly heterogeneous database. Furthermore, molecular data may aid deficiencies and discrepancies observed from breast cancer RWD.
COVID-19 mortality according to civilian records
Authors: Lovisolo Lisandro , Catalão Diego H. S. , Burgos Rodrigo B. , Grave Malú , Constantino-Teles Pamella , Cunha Americo
Published: August 2020

In this short report, we bring some data-driven analyses of COVID-19 mortality in Brazil. The impact of COVID-19 is evaluated by comparing the 2019 and 2020 civilian death records. There is evidence of a considerable excess of deaths since the pandemic started with respect to the previous year. In some states, it is clear that not all excess of deaths in 2020 is due to COVID-19, but to other respiratory causes that did not present the same prevalence in the previous year. Because of this unusual behavior of respiratory deaths, we may infer the evidence of a huge amount of under-reporting deaths due to the COVID-19. The data also shows that COVID-19 has produced an excess death in all ages besides people above 90 and below 10 years. In addition, when separates by sex, data indicate a larger increase in the deaths among males than females.
An Observational Study of COVID-19 from A Large Healthcare System in Northern New Jersey: Diagnosis, Clinical Characteristics, and Outcomes
Authors: Zhao Yanan , Cunningham Marcus H. , Mediavilla Jose R. , Park Steven , Fitzgerald Sean , Ahn Hee Sang , Li Xiangyang , Zhan Caixin , Hong Tao , Munk Gary , Chow Kar Fai , Perlin David S.
Published: August 2020

Background

New Jersey was an early epicenter for the COVID-19 pandemic in the United States, yet information on hospitalized COVID-19 patients from this area is scarce. This study aimed to provide data on demographics and clinical features of a hospitalized patient population who were confirmed with infection by our in-house (CDI) real-time reverse-transcription polymerase chain reaction (RT-PCR) test.

Methods

We included consecutive patients who were admitted to Hackensack Meridian Health system hospitals with laboratory-confirmed diagnoses of COVID-19 at Hackensack University Medical Center by the CDI virus test between March 12, 2020, and April 8, 2020. Clinical data and viral testing results were collected and analyzed for characteristics associated with outcomes, as well as the correlation with viral load.

Results

A total of 722 patients were included in the study, with a median age of 63 (interquartile range (IQR), 51-75) and 272 (37.7%) females. Mortality of this case series was 25.8%, with a statistically significant linear increase observed from age 40 to ≥80 by 10-year intervals. Viral load, as indicated by the cycle of threshold (Ct) values from the RT-PCR test, was significantly higher in the oldest patient group (≥80), and inversely correlated with survival.

Conclusions

This is the first report to describe the clinical characteristics and outcomes in a large hospitalized COVID-19 patient series from New Jersey. Findings from this study are valuable to the ongoing response of both nationwide healthcare networks and the medical research community.

We describe the diagnosis, clinical characteristics, and outcomes of a large hospitalized patient population in northern New Jersey during the early stages of the COVID-19 pandemic.
Considering indirect benefits is critical when evaluating SARS-CoV-2 vaccine candidates
Authors: Gallagher Molly E. , Sieben Andrew J. , Nelson Kristin N. , Kraay Alicia N. M. , Lopman Ben , Handel Andreas , Koelle Katia
Published: August 2020

Significant progress has already been made in development and testing of SARS-CoV-2 vaccines, and Phase III clinical trials have begun for 6 novel vaccine candidates to date. These Phase III trials seek to demonstrate direct benefits of a vaccine on vaccine recipients. However, vaccination is also known to bring about indirect benefits to a population through the reduction of virus circulation. The indirect effects of SARS-CoV-2 vaccination can play a key role in reducing case counts and COVID-19 deaths. To illustrate this point, we show through simulation that a vaccine with strong indirect effects has the potential to reduce SARS-CoV-2 circulation and COVID-19 deaths to a greater extent than an alternative vaccine with stronger direct effects but weaker indirect effects. Protection via indirect effects may be of particular importance in the context of this virus, because elderly individuals are at an elevated risk of death but are also less likely to be directly protected by vaccination due to immune senescence. We therefore encourage ongoing data collection and model development aimed at evaluating the indirect effects of forthcoming SARS-CoV-2 vaccines.
Characterization of SARS-CoV-2 ORF6 deletion variants detected in a nosocomial cluster during routine genomic surveillance, Lyon, France
Authors: Quéromès Grégory , Destras Grégory , Bal Antonin , Regue Hadrien , Burfin Gwendolyne , Brun Solenne , Fanget Rémi , Morfin Florence , Valette Martine , Lina Bruno , Frobert Emilie , Josset Laurence
Published: August 2020

Through routine genomic surveillance of the novel SARS-CoV-2 virus (n=229 whole genome sequences), 2 different frameshifting deletions were newly detected in the open reading frame (ORF) 6, starting at the same position (27267). While the 26-nucleotide deletion variant was only found in one sample in March 2020, the 34-nucleotide deletion variant was found within a single geriatric hospital unit in 5/9 patients sequenced and one health care worker with samples collected between April 2ndand 9th, 2020. Both the presence of the 34-nucleotide deletion variant limited to this unit and the clustering of the corresponding whole genome sequences by phylogeny analysis strongly suggested a nosocomial transmission between patients. Interestingly, prolonged viral excretion of the 34-nucleotide deletion variant was identified in a stool sample 14 days after initial diagnosis for one patient. Clinical data revealed no significant difference in disease severity between patients harboring the wild-type or the 34-nucleotide deletion variants. Thein vitroinfection of the two deletion variants on primate endothelial kidney cells (BGM) and human lung adenocarcinoma cells (Calu-3) yielded comparable replication kinetics with the wild-type strain. Furthermore, high viral loads were foundin vivoregardless of the presence or absence of the ORF6 deletion. Our study highlights the transmission and replication capacity of two newly described deletion variants in the same ORF6 region.

Importance

While the SARS-CoV-2 genome has remained relatively stable since its emergence in the human population, genomic deletions are an evolutionary pattern previously described for the related SARS-CoV. Real-time genomic monitoring of the circulating variants is paramount to detect strain prevalence and transmission dynamics. Given the role of ORF6 in interferon modulation, further characterization, such as mechanistic interactions and interferon monitoring in patients, is crucial in understanding the viral-host factors driving disease evolution.
K18-hACE2 Mice for Studies of COVID-19 Treatments and Pathogenesis Including Anosmia
Authors: Zheng Jian , Roy Wong Lok-Yin , Li Kun , Verma Abhishek K. , Ortiz Miguel , Wohlford-Lenane Christine , Leidinger Mariah R. , Knudson C. Michael , Meyerholz David K. , McCray Paul B. , Perlman Stanley
Published: August 2020

The ongoing COVID-19 pandemic is associated with substantial morbidity and mortality. While much has been learned in the first months of the pandemic, many features of COVID-19 pathogenesis remain to be determined. For example, anosmia is a common presentation and many patients with this finding show no or only minor respiratory signs. Studies in animals experimentally infected with SARS-CoV-2, the cause of COVID-19, provide opportunities to study aspects of the disease not easily investigated in human patients. COVID-19 severity ranges from asymptomatic to lethal. Most experimental infections provide insights into mild disease. Here, using K18-hACE2 mice that we originally developed for SARS studies, we show that infection with SARS-CoV-2 causes severe disease in the lung, and in some mice, the brain. Evidence of thrombosis and vasculitis was detected in mice with severe pneumonia. Further, we show that infusion of convalescent plasma (CP) from a recovered COVID-19 patient provided protection against lethal disease. Mice developed anosmia at early times after infection. Notably, while treatment with CP prevented significant clinical disease, it did not prevent anosmia. Thus K18-hACE2 mice provide a useful model for studying the pathological underpinnings of both mild and lethal COVID-19 and for assessing therapeutic interventions.
Worldwide tracing of mutations and the evolutionary dynamics of SARS-CoV-2
Authors: Zhou Zhong-Yin , Liu Hang , Zhang Yue-Dong , Wu Yin-Qiao , Peng Min-Sheng , Li Aimin , Irwin David M. , Li Haipeng , Lu Jian , Bao Yiming , Lu Xuemei , Liu Di , Zhang Ya-Ping
Published: August 2020

Understanding the mutational and evolutionary dynamics of SARS-CoV-2 is essential for treating COVID-19 and the development of a vaccine. Here, we analyzed publicly available 15,818 assembled SARS-CoV-2 genome sequences, along with 2,350 raw sequence datasets sampled worldwide. We investigated the distribution of inter-host single nucleotide polymorphisms (inter-host SNPs) and intra-host single nucleotide variations (iSNVs). Mutations have been observed at 35.6% (10,649/29,903) of the bases in the genome. The substitution rate in some protein coding regions is higher than the average in SARS-CoV-2 viruses, and the high substitution rate in some regions might be driven to escape immune recognition by diversifying selection. Both recurrent mutations and human-to-human transmission are mechanisms that generate fitness advantageous mutations. Furthermore, the frequency of three mutations (S protein, F400L; ORF3a protein, T164I; and ORF1a protein, Q6383H) has gradual increased over time on lineages, which provides new clues for the early detection of fitness advantageous mutations. Our study provides theoretical support for vaccine development and the optimization of treatment for COVID-19. We call researchers to submit raw sequence data to public databases.
SARS-CoV-2 neutralization and serology testing of COVID-19 convalescent plasma from donors with non-severe disease
Authors: Gniadek Thomas J. , Thiede Joshua M. , Matchett William E. , Gress Abigail R. , Pape Kathryn A. , Jenkins Marc K. , Menachery Vineet D. , Langlois Ryan A. , Bold Tyler D.
Published: August 2020

We determined the antigen binding activity of convalescent plasma units from 47 individuals with a history of non-severe COVID-19 using three clinical diagnostic serology assays (Beckman, DiaSorin, and Roche) with different SARS-CoV-2 targets. We compared these results with functional neutralization activity using a fluorescent reporter strain of SARS-CoV-2 in a microwell assay. This revealed positive correlations of varying strength (Spearman r = 0.37-0.52) between binding and neutralization. Donors age 48-75 had the highest neutralization activity. Units in the highest tertile of binding activity for each assay were enriched (75-82%) for those with the highest levels of neutralization.
Hydrogen Peroxide Levels in Freshly Brewed Coffee and the Effects of Storage
Authors: Uppu Sannihith N. , London Bianca K.
Published: August 2020

One of the world’s most consumed beverages, coffee has its origins as early as the 15thcentury Ethiopia. Although there are studies on caffeine and other components of coffee such as cafestol and kahweol, up until recently knowledge of the presence of hydrogen peroxide (H2O2) in coffee was confined to the scientific community and some informed public. It is a general belief that H2O2is formed only after long periods of storage or with certain roasting practices. The present study is focused on dispelling the myths of H2O2in coffee. We first measured H2O2in freshly brewed coffee from different companies using the ferrous oxidation-xylenol orange binding (FOX) assay. Following this, we examined the time-dependent accumulation of H2O2and its changes with temperature. Further, H2O2was estimated in coffee obtained from several local vendors. Contrary to the general belief that the accumulation of H2O2is an aging phenomenon of coffee, we found this toxicant even in freshly brewed coffee. This was true for all brands tested, and the H2O2content increased upon storage. The highest increase was seen in coffee stored on the hot plate compared to the ones kept at room temperature (22-25 °C) or in the cold (0-4 °C). The H2O2content of coffee from different vendors ranged between 0.29 and 0.82 mM, which is 5- to 20-fold higher than the typical H2O2concentrations at which significant cytotoxic effects have been reported for assay systems using the human Fanconi deficient (PD20 FANCD2−/−) fibroblasts and other cell types. Our findings are deemed to shine new light on the probable toxic effects of a commonly consumed beverage like coffee, and the time and temperature dependent variations of keeping. While there are documented benefits of consumption of coffee, the possible H2O2-medicated toxic effects are critical and should be considered. Future studies are warranted to delineate the contribution of H2O2in the healthy wellbeing of individuals who consume coffee extensively.
Input-output signal processing plasticity of vagal motorneurons in response to cardiac ischemic injury
Authors: Gorky Jonathan , Moss Alison , Balycheva Marina , Vadigepalli Rajanikanth , Schwaber James S.
Published: August 2020

Vagal stimulation is emerging as the next frontier in bioelectronic medicine to modulate peripheral organ health and treat disease. The neuronal molecular phenotypes in the dorsal motor nucleus of the vagus (DMV) remain largely unexplored, limiting the potential for harnessing the DMV plasticity for therapeutic interventions. We developed a mesoscale single cell transcriptomics data from hundreds of DMV neurons under homeostasis and following physiological perturbations. Our results revealed that homeostatic DMV neuronal states can be organized into distinguishable input-output signal processing units. Remote ischemic preconditioning induced a distinctive shift in the neuronal states towards diminishing the role of inhibitory inputs, with concomitant changes in regulatory microRNAs miR-218a and miR-495. Chronic cardiac ischemic injury resulted in a dramatic shift in DMV neuronal states suggestive of enhanced neurosecretory function. We propose a DMV molecular network mechanism that integrates combinatorial neurotransmitter inputs from multiple brain regions and humoral signals to modulate cardiac health.