bluuebunny/crossref_metadata_2025 huggingface dataset:
How Do Children Die in PICUs Nowadays? A Multicenter Study From Spain*
Authors: Agra-Tuñas Carme , Rodriguez-Ruiz Emilio , Rodríguez Merino Elva ,   on behalf of the MOdos de Morir en UCI Pediátrica-2 (MOMUCIP-2) study group of the Spanish Society of Paediatric Intensive Care (SECIP)
Published: April 2020

Objectives:

To describe how children currently die in Spanish PICUs, their epidemiologic characteristics and clinical diagnoses.

Design:

Prospective multicenter observational study.

Setting:

Eighteen PICUs participating in the MOdos de Morir en UCI Pediátrica-2 (MOMUCI-2) study in Spain.

Patients:

Children 1 to 16 years old who died in PICU during 2017 and 2018.

Interventions:

None.

Measurements and Main Results:

During the 2-year study period, 250 deaths were recorded. Seventy-three children (29.3%) were younger than 1 year, 131 (52.6%) were between 1 and 12 years old, and 45 (18.1%) were older than 12. One-hundred eighty patients (72%) suffered from an underlying chronic disease, 54 (21.6%) had been admitted to PICU in the past 6 months, and 71 (28.4%) were severely disabled upon admission. Deaths occurred more frequently on the afternoon-night shift (62%) after a median PICU length of stay of 3 days (1–12 d). Nearly half of the patients died (48.8%) after life-sustaining treatment limitation, 71 died (28.4%) despite receiving life-sustaining therapies and cardiopulmonary resuscitation, and 57 (22.8%) were declared brain dead. The most frequent type of life-sustaining treatment limitation was the withdrawal of mechanical ventilation (20.8%), followed by noninitiation of cardiopulmonary resuscitation (18%) and withdrawal of vasoactive drugs (13.7%). Life-sustaining treatment limitation was significantly more frequent in patients with an underlying neurologic-neuromuscular disease, respiratory disease as the cause of admission, a previous admission to PICU in the past 6 months, and severe disability. Multivariate analyses indicated that life-sustaining treatment limitation, chronicity, and poor Pediatric Cerebral Performance Category score were closely related.

Conclusions:

Currently, nearly half of the deaths in Spanish PICUs occur after the withdrawal of life-sustaining treatments. These children are more likely to have had previous admissions to the PICU, be severely disabled or to suffer from chronic diseases. Healthcare professionals who treat critically ill children ought to be aware of this situation and should therefore be prepared and trained to provide the best end-of-life care possible.
Generating Subcounty Health Data Products: Methods and Recommendations From a Multistate Pilot Initiative
Authors: Nguyen Trang Q. , Michaels Isaac H. , Bustamante-Zamora Dulce , Waterman Brian , Nagasako Elna , Li Yunshu , Givens Marjory L. , Gennuso Keith
Published: April 2020

Background:

County Health Rankings & Roadmaps (CHR&R) makes data on health determinants and outcomes available at the county level, but health data at subcounty levels are needed. Three pilot projects in California, Missouri, and New York explored multiple approaches for defining measures and producing data at subcounty geographic and demographic levels based on the CHR&R model. This article summarizes the collective technical and implementation considerations from the projects, challenges inherent in analyzing subcounty health data, and lessons learned to inform future subcounty health data projects.

Methods:

The research teams used 12 data sources to produce 40 subcounty measures that replicate or approximate county-level measures from the CHR&R model. Using varying technical methods, the pilot projects followed similar stages: (1) conceptual development of data sources and measures; (2) analysis and presentation of small-area and subpopulation measures for public health, health care, and lay audiences; and (3) positioning the subcounty data initiatives for growth and sustainability. Unique technical considerations, such as degree of data suppression or data stability, arose during the project implementation. A compendium of technical resources, including samples of automated programs for analyzing and reporting subcounty data, was also developed.

Results:

The teams summarized the common themes shared by all projects as well as unique technical considerations arising during the project implementation. Furthermore, technical challenges and implementation challenges involved in subcounty data analyses are discussed. Lessons learned and proposed recommendations for prospective analysts of subcounty data are provided on the basis of project experiences, successes, and challenges.

Conclusions:

This multistate pilot project offers 3 successful approaches for creating and disseminating subcounty data products to communities. Subcounty data often are more difficult to obtain than county-level data and require additional considerations such as estimate stability, validating accuracy, and protecting individual confidentiality. We encourage future projects to further refine techniques for addressing these critical considerations.
Managing Close Contacts of COVID-19 Confirmed Cases in Metropolitan Areas in China
Authors: Ding Jing , Tuan Wen-Jan , Temte Jonathan L.
Published: April 2020

The novel coronavirus (COVID-19) outbreak has rapidly spread across the world. As medical systems continue to develop vaccines and treatments, it is crucial for the public health community to establish nonpharmaceutical interventions (NPIs) that can effectively mitigate the rate of SARS-Coronavirus-2 (SARS-CoV-2) spread across highly populated residential areas, especially among individuals who have close contact with confirmed cases. A community-driven preparedness strategy has been implemented in metropolitan areas in China. The Chinese Center for Disease Control and Prevention (CCDC) has required that all COVID-19 confirmed cases be recorded and documented in a national notifiable disease surveillance system (NDSS). After receiving reports of newly confirmed cases, an epidemiological services team at the CCDC or trained medical professionals at local clinical facilities start a case-contact investigation. A task force performs home visits to infected individuals. Persons under investigation (PUIs) can stay in designated quarantine facilities for 14 days or in special circumstances can be quarantined at home. This community-based approach involved all stakeholders including local public health departments, public safety authorities, neighborhood councils, and community health centers.
Adapting to the Coronavirus Disease 2019 Pandemic in New York City
Authors: Escalon Miguel X. , Herrera Joseph
Published: April 2020

The coronavirus disease 2019 has and continues to overwhelm the medical establishment in New York City. It has moved faster and had rates of mortality higher than what were initially forecast. All departments within large hospital systems have had to learn lessons and adapt in real time to the crisis. We share our experience and what we have learned as it pertains to this pandemic and hope that it aides, guides, and influences other departments of physical medicine and rehabilitation regarding their potential roles and areas of growth during this time.
Prehabilitation May Help Mitigate an Increase in COVID-19 Peripandemic Surgical Morbidity and Mortality
Authors: Silver Julie K.
Published: April 2020

As physicians specializing in rehabilitation medicine consider sequelae from the novel coronavirus pandemic that began in 2019, one issue that should be top of mind is the physiologic effect that large-scale social distancing had on the health of patients in general but, more specifically, on preoperative patients who had their surgeries delayed or will have newly scheduled procedures during the peripandemic period. Predictably, as the virus becomes less prevalent, there will be a tremendous motivation to move forward with scheduling operations from both patient care and institutional perspectives. However, one can anticipate a pandemic-related increase in surgical morbidity and mortality above prepandemic levels, particularly in older or medically frail patients even
if they did not have a novel coronavirus (i.e., COVID-19) infection. Therefore, now is the time to consider for patients awaiting surgery a wider adoption of prehabilitation—physical and psychological assessments that establish a baseline functional level, identify impairments, and provide interventions that promote physical and psychological health to reduce the incidence and/or severity of future impairments.
Practical Considerations for Implementing Virtual Care in Physical Medicine and Rehabilitation
Authors: McIntyre McKyla , Robinson Lawrence R. , Mayo Amanda
Published: April 2020

This article outlines a practical approach to quickly implementing virtual care for physiatrists. This skill is relevant not only during times of a pandemic, when face to face care is impossible, but is also valuable when caring for patients who have physical, financial, logistic, or other challenges to on-site care. Key themes covered in this article include selecting appropriate virtual care platforms, consenting patients for virtual care and conducting successful virtual visits. It also reviews strategies for performing virtual physical examinations and engaging learners in virtual care.
Improving the Compliance of Intraoperative Antibiotic Redosing: A Quality Improvement Initiative
Authors: LeRiger Michelle M. , Phipps Amber R. , Norton Bridget M. , Spitznagel Rachel A.
Published: April 2020

Introduction:

At Children’s Hospital and Medical Center in Omaha, Nebraska, the intraoperative antibiotic redosing guidelines and the time frame considered compliant for redosing were unclear. This lack of clarity plus an ill-defined process for ensuring intraoperative antibiotic redosing resulted in a compliance rate of 11%. The organization’s surgical site infection (SSI) rate was 3.19%, above the national benchmark of 1.87%. The primary project goal was to increase intraoperative antibiotic redosing compliance. The secondary project goal was to decrease SSIs.

Methods:

With recommendations from the Infectious Disease Society of America, we developed new organizational redosing guidelines, as well as a new antibiotic-specific reminder alert in the electronic medical record. Implementation of the new guidelines and processes occurred after providing education to the anesthesiologists, surgeons, and circulating nurses. Monthly evaluation of data allowed for quick recognition of oversights followed by the initiation of process updates.

Results:

Data showed that the initial compliance rate for the intraoperative redosing of antibiotics was 11%. Following interventions, compliance has reached and sustained an average of 99%. Survey results show that provider knowledge of the guidelines and process has improved. Though not directly related, the National Surgical Quality Improvement Program observed that the SSI rate decreased from 3.19% in 2014 to 2.3% in 2018.

Conclusions:

This project demonstrates that comprehensive education along with antibiotic-specific electronic medical record alerts significantly increased the compliance of intraoperative antibiotic redosing at Children’s Hospital & Medical Center. Continuous education and monthly updates sustained results for over 40 months.
Association Among Glucocorticoid Receptor Sensitivity, Fatigue, and Inflammation in Patients With Head and Neck Cancer
Authors: Xiao Canhua , Eldridge Ronald C. , Beitler Jonathan J. , Higgins Kristin A. , Chico Cynthia E. , Felger Jennifer C. , Wommack Evanthia C. , Knobf Tish , Saba Nabil F. , Shin Dong M. , Bruner Deborah W. , Miller Andrew H.
Published: April 2020

Objective

Fatigued cancer patients often have high peripheral inflammation; however, the biological mechanisms of this association remain unclear. We examined whether decreased sensitivity of immune cells to the anti-inflammatory effects of glucocorticoids may contribute to inflammation and fatigue in head and neck cancer (HNC) patients during treatment.

Methods

HNC patients without distant metastasis and with curative intent (n = 77) were studied 1 week before intensity-modulated radiotherapy (IMRT) and 1 month after IMRT. At each time point, fatigue was measured by the Multidimensional Fatigue Inventory-20 along with plasma inflammation markers and glucocorticoid receptor (GR) sensitivity as determined by in vitro dexamethasone suppression of lipopolysaccharide-induced interleukin 6. Linear regression models were used.

Results

In contrast to our hypothesis, GR sensitivity increased during treatment; however, increased fatigue was associated with a lesser increase in GR sensitivity from baseline to 1 month after IMRT (unstandardized estimate = 4.07, p = .02). This effect was more prominent in human papillomavirus–unrelated HNCs (unstandardized estimate = 8.22, p = .002). Lower increases in GR sensitivity were also associated with increased inflammation at 1 month after IMRT as represented by C-reactive protein, interleukin 6, and tumor necrosis factor α. Addition of inflammation markers to models of GR sensitivity predicting fatigue indicated that these inflammation markers were stronger predictors of fatigue than GR sensitivity.

Conclusions

Lower increases in GR sensitivity during HNC treatment were significantly predictive of increased fatigue and inflammation markers. Inflammation markers in turn predicted fatigue above and beyond levels of GR sensitivity. Our findings indicate that HNC patients with cancer-related fatigue may exhibit a decreased capacity for glucocorticoids to regulate inflammatory processes, as evidenced by a lower increase in GR sensitivity. Larger studies are necessary to verify the findings.
Reinventing Extremity Amputation in the Era of Functional Limb Restoration
Authors: Herr Hugh M. , Clites Tyler R. , Srinivasan Shriya , Talbot Simon G. , Dumanian Gregory A. , Cederna Paul S. , Carty Matthew J.
Published: April 2020

Background:

Recent progress in biomechatronics and vascularized composite allotransplantation have occurred in the absence of congruent advancements in the surgical approaches generally utilized for limb amputation. Consideration of these advances, as well as of both novel and time-honored reconstructive surgical techniques, argues for a fundamental reframing of the way in which amputation procedures should be performed.

Methods:

We review sentinel developments in external prosthetic limb technology and limb transplantation, in addition to standard and emerging reconstructive surgical techniques relevant to limb modification, and then propose a new paradigm for limb amputation.

Results:

An approach to limb amputation based on the availability of native tissues is proposed, with the intent of maximizing limb function, limiting neuropathic pain, restoring limb perception/proprioception and mitigating limb atrophy.

Conclusions:

We propose a reinvention of the manner in which limb amputations are performed, framed in the context of time-tested reconstructive techniques, as well as novel, state-of-the-art surgical procedures. Implementation of the proposed techniques in the acute setting has the potential to elevate advanced limb replacement strategies to a clinical solution that perhaps exceeds what is possible through traditional surgical approaches to limb salvage. We therefore argue that amputation, performed with the intent of optimizing the residuum for interaction with either a bionic or a transplanted limb, should be viewed not as a surgical failure, but as an alternative form of limb reconstruction.
New therapeutic strategies for combatting gastrointestinal toxicity
Authors: Sylvester Cyan L. , Anderson Paul H. , Stringer Andrea M.
Published: April 2020

Purpose of review

An overwhelming majority of chemotherapy agents are known to cause gastrointestinal mucositis, an unwanted side effect of cancer treatment, for which no effective treatment currently exists. The pathological processes underlying the development of gastrointestinal mucositis are many and varied, with multiple pathways thought to be involved in initiation of inflammation and apoptosis. Physiological and or biochemical-based deficiencies, such as vitamin D deficiency and gut microbiome density and population, are also thought to have an impact on mucositis severity.

Recent findings

Recent studies investigating inflammatory pathways, such as cytokines and apoptotic markers, do show that interleukin-blocking proteins alleviate symptoms of gastrointestinal mucositis. However, the effectiveness of these treatments varies depending on the type of anticancer agent administered, meaning blocking compounds may be limited in their application. Targeting the host's gut microbiome in preventing dysbiosis is also thought to be a potential avenue for exploration. The use of probiotic gut bacteria (i.e. Lactobacillus spp.), while beneficial in preventing chemotherapy radiotherapy-induced diarrhoea, does not seem to alleviate the physiological damage caused by gastrointestinal mucositis. Vitamin D has been widely shown to have a host of anti-inflammatory and immunomodulatory effects in the intestine, as well as anticancer properties and therefore, may reduce severity of gastrointestinal mucositis.

While anti-inflammatory and antiapoptotic agents have shown promise in animal models of gastrointestinal mucositis, there is still no singular mechanism allowing for the development of a therapeutic drug to prevent or cure gastrointestinal injury. A greater insight into the exact mechanistic actions of both probiotics and vitamin D might reveal how to improve their use as therapeutic treatments for gastrointestinal mucositis.
Vaginal Energy-Based Devices
Authors: Alshiek Jonia , Garcia Bobby , Minassian Vatche , Iglesia Cheryl B. , Clark Amanda , Sokol Eric R. , Murphy Miles , Malik Shazia A. , Tran Alexis , Shobeiri S. Abbas
Published: April 2020

This clinical consensus statement on vaginal energy-based devices (EBDs) reflects statements drafted by content experts from the American Urogynecologic Society’s EBD writing group. The American Urogynecologic Society's EBD writing group used a modified Delphi process to assess statements that were evaluated for consensus after a structured literature search. A total of 40 statements were assessed and divided into 5 categories: (1) patient criteria, (2) health care provider criteria, (3) efficacy, (4) safety, and (5) treatment considerations. Of the 40 statements that were assessed, 28 reached consensus and the remaining 12 did not. Lack of evidence was among the main reasons that vulvovaginal EBD treatment statements did not reach consensus.
The effect of emergency medical system transport time on in route clinical decline in a rural system
Authors: Kai Taylor R. , Broady Marlene J. , Davenport Daniel L. , Bernard Andrew C.
Published: April 2020

BACKGROUND

The emergency medical system (EMS) Field Triage Decision Scheme (FTDS) exists to direct certain injured patients to high-level care facilities. In rural states, this may require long transport durations, with uncertainty about the effects on clinical decline. We investigate adherence to the FTDS and the effect of transport duration on clinical decline in helicopter emergency medical system (HEMS) and ground emergency medical system (GEMS) transport in the Commonwealth of Kentucky.

METHODS

This institutional review board–approved study retrospectively analyzed deidentified data from the 2017 National EMS Information System for Kentucky. Patients were classified using step 1 FTDS criteria (respiratory rate [RR], <10 or >29 breaths per minute; systolic blood pressure (SBP), <90 mm Hg; or Glasgow Coma Scale [GCS] score, <14 points), by mode of transport (HEMS or GEMS), and by arrival at an appropriate center (levels I–III trauma center). Clinical decline was defined in both groups as an in route decrease in GCS of 2 points or greater, a SBP decrease of 1 SD or greater into or within the low range, an RR increase of 1 SD or greater into or within the high range, or an RR decrease of 1 SD or greater into or within the low range.

RESULTS

Almost half (46.3%) of step 1 patients were transported to an inappropriate center; the most common reason recorded was “closest facility” (57.8%). The percent of step 1 patients who declined in route increased with prehospital time in both HEMS and GEMS (p < 0.001). Overall, 12.2% of step 1 patients declined during transport, most commonly because of decreasing GCS (median change, −5 points; interquartile range, −3 to −9, in GCS declining patients). Helicopter EMS patients were more likely to meet step 1 criteria at the scene (29.9% vs. 5.8% GEMS, p < 0.001) and to decline (27.8% vs. 6.1% GEMS, p < 0.001).

CONCLUSION

This study demonstrates that, in a rural state, injured patients meeting FTDS step 1 criteria reach levels I to III trauma centers only about half the time. The FTDS step 1 criteria identified patients at higher risk of further prehospital clinical decline. Rather than decline after 1 hour, these data show that an increasing proportion of patients experience clinical decline throughout prehospital transport.

LEVEL OF EVIDENCE

Therapeutic, Level IV.
Use of multiple potency assays to evaluate human mesenchymal stromal cells
Authors: Christy Barbara A. , Herzig Maryanne C. , Delavan Christopher P. , Abaasah Isaac , Cantu Carolina , Salgado Christi , Lovelace Sarah , Garcia Laurynn , Jensen Katherine , Montgomery Robbie , Cap Andrew P. , Bynum James A.
Published: April 2020

BACKGROUND

There is broad interest in the use of cell therapies and cell products for treatment of a variety of diseases and problems. Of interest to the military, cellular therapies have the potential to confer tremendous benefit for treatment of both acute and chronic injuries. Although many different cell therapy products are currently under investigation, mesenchymal stromal cells (MSCs) are good candidates, based on their ability to respond to inflammation, limit vascular permeability, and modulate immune responses to injury. Although a large number of clinical trials utilize MSCs or their products, there is no firm consensus defining the characteristics and activities of a good MSC product. Here, we test multiple human MSCs in several assays designed to test potency, to determine if functionally relevant differences between MSCs can be defined using in vitro assays, allowing identification of superior MSC products for preclinical or clinical testing.

METHODS

Human MSCs derived from several tissue sources (adipose, bone marrow, umbilical cord) were evaluated for their ability to respond to inflammatory signaling by upregulating indoleamine-2,3-dioxygenase and TSG6, suppress lymphocyte proliferation, alter the polarization of macrophages, and affect tube formation by endothelial cells.

RESULTS

All MSCs tested displayed activity in the functional assays utilized, but differences in potency were observed in each assay.

CONCLUSION

The indoleamine-2,3-dioxygenase enzyme activity assay represents a simple way to screen multiple samples. The mixed lymphocyte reaction and monocyte assays used to test interactions between MSCs and immune cells are more involved but give direct information on immunomodulation potential. The endothelial cell tube formation assay is relatively simple to perform but a large number of images must be generated and analyzed. However, it tests a functional activity other than immunomodulation and, therefore, adds another facet to MSC evaluation.
Evaluation of Immediate Interference After Intervention With Double Tasks in Elderly Individuals
Authors: Pessoa Raynara Maritsa Cavalcante , Davi Gisele Kariny de Souza , Marinho Maria de Fátima Duarte , de Araújo Joyce Freitas , Alves Maria Tatiane de Sousa , Brito Ilze Louize da Silva , Lima Núbia Maria Freire Vieira
Published: April 2020

This study investigated the immediate effects of an intervention with dual tasks on balance in elderly individuals. Eight tests and an evaluation on a force platform were used. The subjects were divided into 2 groups; one was subjected to an intervention proposal with double tasks and the other with simple tasks. After the intervention, the double-task group maintained its performance in the tests and showed improvement in the cognitive performance of some activities during posturography. The simple-task group required more time for simple and motor Timed Up and Go tests, and there was no increase in cognitive performance or postural control.
Benzodiazepine exposure in subjects with incident Alzheimer’s disease and related syndromes in France: a longitudinal study 2011–2017
Authors: Poncet Mathilde , Gardette Virginie , Couret Anaïs , Renoux Axel , Lapeyre-Mestre Maryse , Gallini Adeline
Published: April 2020

Benzodiazepines are commonly used for behavioral and psychiatric symptoms of dementia, despite their numerous adverse effects and the lack of evidence regarding their efficacy in this context. We studied longitudinal benzodiazepines exposure in incident cases of Alzheimer’s disease and related syndromes (ADRS) in France. We used a cohort of incident ADRS patients identified in 2012 within the national health data system. Benzodiazepines exposure was measured 1 year before, to 5 years after ADRS identification. Quarterly benzodiazepines prevalence and incidence were computed. We identified factors associated with long half-life benzodiazepines initiation. A total of 106 508 subjects were included. Quarterly benzodiazepines prevalence was stable (around 25%) but we saw an important decrease in long half-life benzodiazepines compensated by an increase in short half-life benzodiazepines. In most benzodiazepine initiations, the first episode lasted less than 3 months. Factors associated with initiating a long half-life benzodiazepine were young age, male gender, no registration with ADRS as a long-term disease, having consulted an ADRS specialist, antipsychotic reimbursement before the index date, no admission in nursing home. Prevalence of benzodiazepines use remains high in subjects with ADRS despite guidelines for their avoidance. However, indicators regarding benzodiazepine initiations (duration, benzodiazepine type) suggest some caution in their use.
Microbial gas vesicles as nanotechnology tools: exploiting intracellular organelles for translational utility in biotechnology, medicine and the environment
Authors: Hill Amy M. , Salmond George P. C.
Published: April 2020

A range of bacteria and archaea produce gas vesicles as a means to facilitate flotation. These gas vesicles have been purified from a number of species and their applications in biotechnology and medicine are reviewed here.

Halobacterium

sp. NRC-1 gas vesicles have been engineered to display antigens from eukaryotic, bacterial and viral pathogens. The ability of these recombinant nanoparticles to generate an immune response has been quantified both in vitro and in vivo. These gas vesicles, along with those purified from Anabaena flos-aquae and

Bacillus megaterium

, have been developed as an acoustic reporter system. This system utilizes the ability of gas vesicles to retain gas within a stable, rigid structure to produce contrast upon exposure to ultrasound. The susceptibility of gas vesicles to collapse when exposed to excess pressure has also been proposed as a biocontrol mechanism to disperse cyanobacterial blooms, providing an environmental function for these structures.
Effects of parity on the age at menopause and menopausal syndrome: a cross-sectional study in Northwest China
Authors: Sun Xiaoyan , Li Weiguo , Zhang Rui , Wang Lirong , Shen Xiping , Lu Yongbin , An Junxia , Wang Liyan , Wang Yiqing , Luo Xiaorong , Zhu Haiying , Zhang Xuehong
Published: April 2020

Objective

This study evaluated the relationship between the number of births and the age at menopause and menopausal syndrome among Chinese women in Gansu.

Methods

A cross-sectional study was conducted by a local university from March to November in 2016. A total of 7236 women aged 40–55 years met study eligibility criteria. The modified KMI was used to assess the menopausal syndrome. Cox regression was applied to estimate HR and 95% CI of the relationship between parity and age at menopause. Logistic regression was performed to calculate OR and CI of the effects of birth times on the menopausal syndrome.

Outcome measure

The relationship between the parity and the age at menopause and menopausal syndrome in mid-life northwest Chinese women was analyzed.

Results

The mean age at menopause was 47.91 ± 3.31 years. The relationships between parity and age at menopause were not significant by applying Cox regression (P = 0.488). Women with nulliparity and more births (3 and ≥4) seemed to have higher risks of moderate and severe menopausal syndrome. In addition, the potential beneficial effects of 1 or 2 births on menopausal syndrome were still observed by applying the multivariable logistic regression analysis, particularly in urogenital symptoms.

Conclusions

No obvious relationship was found between parity and age at menopause among Chinese women in Gansu. Women with nulliparity and more births appeared to be at the increased risk of menopause syndrome compared with women with 1 and 2 births. The underlying mechanisms were not assessed and deserved further investigation.

Highlight

. The mean age at menopause was lower among Chinese women in Gansu than developed countries and regions.

. There is no obvious relationship between parity and age at menopause.

. Women with nulliparity and more births (3 and ≥4) appeared to be at the increased risk of menopause syndrome, particularly in urogenital symptoms.
Detection of SARS-CoV-2 RNA by direct RT-qPCR on nasopharyngeal specimens without extraction of viral RNA
Authors: Hasan Mohammad Rubayet , Mirza Faheem , Al-Hail Hamad , Sundararaju Sathyavathi , Xaba Thabisile , Iqbal Muhammad , Alhussain Hashim , Yassine Hadi Mohamad , Lopez Andres Perez , Tang Patrick
Published: April 2020

To circumvent the limited availability of RNA extraction reagents, we aimed to develop a protocol for direct RT-qPCR to detect SARS-CoV-2 in nasopharyngeal swabs without RNA extraction. Nasopharyngeal specimens positive for SARS-CoV-2 and other coronaviruses collected in universal viral transport (UVT) medium were pre-processed by several commercial and laboratory-developed methods and tested by RT-qPCR assays without RNA extraction using different RT-qPCR master mixes. The results were compared to that of standard approach that involves RNA extraction. Incubation of specimens at 65°C for 10 minutes along with the use of TaqPath™ 1-Step RT-qPCR Master Mix provides higher analytical sensitivity for detection of SARS-CoV-2 RNA than many other conditions tested. The optimized direct RT-qPCR approach demonstrated a limit of detection of 6.6×103 copy/ml and high reproducibility (co-efficient of variation = 1.2%). In 132 nasopharyngeal specimens submitted for SARS-CoV-2 testing, the sensitivity, specificity and accuracy of our optimized approach were 95%, 99% and 98.5%, respectively, with reference to the standard approach. Also, the RT-qPCR CT values obtained by the two methods were positively correlated (Pearson correlation coefficient r=0.6971, p=0.0013). The rate of PCR inhibition by the direct approach was 8% compared to 9% by the standard approach. Our simple approach to detect SARS-CoV-2 RNA by direct RT-qPCR may help laboratories continue testing for the virus despite reagent shortages or expand their testing capacity in resource limited settings.
Analysis of the impact of lockdown on the reproduction number of the SARS-Cov-2 in Spain
Authors: Hyafil Alexandre , Moriña David
Published: April 2020

Objective

The late 2019 Covid-19 disease outbreak has put the health systems of many countries to the limit of their capacity. The most affected European countries are, so far, Italy and Spain. In both countries (and others), the authorities decreed a lockdown, with local specificities. The objective of this work is to evaluate the impact of the measures undertaken in Spain to deal with the pandemic.

Method

We estimated the number of cases and the impact of lockdown on the reproducibility number based on the hospitalization reports up to April 15th 2020.

Results

The estimated number of cases shows a sharp increase until the lockdown, followed by a slowing down and then a decrease after full quarantine was implemented. Differences in the basic reproduction ratio are also very significant, dropping from de 5.89 (95% CI: 5.46-7.09) before the lockdown to 0.48 (95% CI: 0.15-1.17) afterwards.

Conclusions

Handling a pandemic like Covid-19 is very complex and requires quick decision making. The large differences found in the speed of propagation of the disease show us that being able to implement interventions at the earliest stage is crucial to minimise the impact of a potential infectious threat. Our work also stresses the importance of reliable up to date epidemiological data in order to accurately assess the impact of Public Health policies on viral outbreak.
Early Evidence and Predictors of Mental Distress of Adults One Month in the COVID-19 Epidemic in Brazil
Authors: Zhang Stephen Xu , Wang Yifei , Jahanshahi Asghar Afshar , Li Jizhen , Schmitt Valentina Gomes Haensel
Published: April 2020

Objective

We aim to provide early evidence of mental distress and its associated predictors among adults one month into the COVID-19 crisis in Brazil.

Methods

We conducted an online survey of 638 adults in Brazil on March 25–28, 2020, about one month (32 days) cross-sectionally after the first COVID-19 case in South America was confirmed in São Paulo. The 638 adults were in 25 states out of the 26 Brazilian states, with the only exception being Roraima, the least populated state in the Amazon. Of all the participating adults, 24%, 20%, and 18% of them were located in Rio de Janeiro state, Santa Catarina state, and São Paulo state respectively.

Results

In Brazil, 52% (332) of the sampled adults experienced mild or moderate distress, and 18.8% (120) suffered severe distress. Adults who were female, younger, more educated, and exercised less reported higher levels of distress. Each individual’s distance from the Brazilian epicenter of São Paulo interacted with age and workplace attendance to predict the level of distress. The “typhoon eye effect” was stronger for people who were older or attended their workplace less. The most vulnerable adults were those who were far from the epicenter and did not go to their workplace in the week before the survey.

Conclusion

Identifying the predictors of distress enables mental health services to better target finding and helping the more mentally vulnerable adults during the ongoing COVID-19 crisis.
Ongoing outbreak of COVID-19 in Iran: challenges and signs of concern with under-reporting of prevalence and deaths
Authors: Ghafari Mahan , Hejazi Bardia , Karshenas Arman , Dascalu Stefan , Kadvidar Alireza , Khosravi Mohammad A. , Abbasalipour Maryam , Heydari Majid , Zeinali Sirous , Ferretti Luca , Ledda Alice , Katzourakis Aris
Published: April 2020

Many countries with an early outbreak of SARS-CoV-2 struggled to gauge the size and start date of the epidemic mainly due to limited testing capacities and a large proportion of undetected asymptomatic and mild infections. Iran was among the first countries with a major outbreak outside China. Using all genomic sequences collected from patients with a travel link to Iran, we estimate that the epidemic started on 21/01/2020 (95% HPD: 05/12/2019 – 14/02/2020) with a doubling time of 3 days (95% HPD: 1.68 – 16.27). We also show, using air travel data from confirmed exported cases, that from late February to early March the number of active cases across the country were more than a hundred times higher than the reported cases at the time. A detailed province-level analysis of all-cause mortality shows 20,718 (CI 95%: 18,859 – 22,576) excess deaths during winter and spring 2020 compared to previous years, almost twice the number of reported COVID-19-related deaths at the time. Correcting for under-reporting of prevalence and deaths, we use an SEIR model to reconstruct the outbreak dynamics in Iran. Our model forecasted the second epidemic peak and suggests that by 14/07/2020 a total of 9M (CI 95%: 118K – 44M) have recovered from the disease across the country. These findings have profound implications for assessing the stage of the epidemic in Iran and shed light on the dynamics of SARS-CoV-2 transmissions in Iran and central Asia despite significant levels of under-reporting.

One Sentence Summary

We use epidemiological and genetic data to investigate the origins of the SARS-CoV-2 outbreak in Iran and assess the degree of under-reporting in prevalence and deaths.
Towards harmonizing subtyping methods for neuroimaging studies in Alzheimer’s disease
Authors: Mohanty Rosaleena , Mårtensson Gustav , Poulakis Konstantinos , Muehlboeck J-Sebastian , Rodriguez-Vieitez Elena , Chiotis Konstantinos , Grothe Michel J. , Nordberg Agneta , Ferreira Daniel , Westman Eric
Published: April 2020

Background

Biological subtypes in Alzheimer’s disease (AD), originally identified on neuropathological data, have been translated toin vivobiomarkers such as structural magnetic resonance imaging (sMRI) and positron emission tomography (PET), to disentangle the heterogeneity within AD. Although there is methodological variability across studies, comparable characteristics of subtypes are reported at the group level. In this study, we investigated whether group-level similarities translate to individual-level agreement across subtyping methods, in a head-to-head context.

Methods

We compared five previously published subtyping methods. Firstly, we validated the subtyping methods in 89 amyloid-beta positive (Aβ+) AD dementia patients (reference group: 70 Aβ-healthy individuals; HC) using sMRI. Secondly, we extended and applied the subtyping methods to 53 Aβ+ prodromal AD and 30 Aβ+ AD dementia patients (reference group: 200 Aβ-HC) using both sMRI and tau PET. Subtyping methods were implemented as outlined in each original study. Group-level and individual-level comparisons across methods were performed.

Results

Each individual method was replicated and the proof-of-concept was established. All methods captured subtypes with similar patterns of demographic and clinical characteristics, and with similar maps of cortical thinning and tau PET uptake, at the group level. However, large disagreements were found at the individual level.

Conclusions

Although characteristics of subtypes may be comparable at the group level, there is a large disagreement at the individual level across subtyping methods. Therefore, there is an urgent need for consensus and harmonization across subtyping methods. We call for establishment of an open benchmarking framework to overcome this problem.
Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients
Authors: Hadjadj Jérôme , Yatim Nader , Barnabei Laura , Corneau Aurélien , Boussier Jeremy , Péré Hélène , Charbit Bruno , Bondet Vincent , Chenevier-Gobeaux Camille , Breillat Paul , Carlier Nicolas , Gauzit Rémy , Morbieu Caroline , Pène Frédéric , Marin Nathalie , Roche Nicolas , Szwebel Tali-Anne , Smith Nikaïa , Merkling Sarah H , Treluyer Jean-Marc , Verer David , Mouthon Luc , Blanc Catherine , Tharaux Pierre-Louis , Rozenberg Flore , Fischer Alain , Duffy Darragh , Rieux-Laucat Frédéric , Kernéis Solen , Terrier Benjamin
Published: April 2020

Background

Coronavirus disease 2019 (Covid-19) is a major global threat that has already caused more than 100,000 deaths worldwide. It is characterized by distinct patterns of disease progression implying a diverse host immune response. However, the immunological features and molecular mechanisms involved in Covid-19 severity remain so far poorly known.

Methods

We performed an integrated immune analysis that included in-depth phenotypical profiling of immune cells, whole-blood transcriptomic and cytokine quantification on a cohort of fifty Covid19 patients with a spectrum of disease severity. All patient were tested 8 to 12 days following first symptoms and in absence of anti-inflammatory therapy.

Results

A unique phenotype in severe and critically ill patients was identified. It consists in a profoundly impaired interferon (IFN) type I response characterized by a low interferon production and activity, with consequent downregulation of interferon-stimulated genes. This was associated with a persistent blood virus load and an exacerbated inflammatory response that was partially driven by the transcriptional factor NFĸB. It was also characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling as well as increased innate immune chemokines.

Conclusion

We propose that type-I IFN deficiency in the blood is a hallmark of severe Covid-19 and could identify and define a high-risk population. Our study provides a rationale for testing IFN administration combined with adapted anti-inflammatory therapy targeting IL-6 or TNF-α in most severe patients. These data also raise concern for utilization of drugs that interfere with the IFN pathway.
COVID-19 Asymptomatic Infection Estimation
Authors: Yu Yang , Liu Yu-Ren , Luo Fan-Ming , Tu Wei-Wei , Zhan De-Chuan , Yu Guo , Zhou Zhi-Hua
Published: April 2020

Background

Mounting evidence suggests that there is an undetected pool of COVID-19 asymptomatic but infectious cases. Estimating the number of asymptomatic infections has been crucial to understand the virus and contain its spread, which is, however, hard to be accurately counted.

Methods

We propose an approach of machine learning based fine-grained simulator (ML-Sim), which integrates multiple practical factors including disease progress in the incubation period, cross-region population movement, undetected asymptomatic patients, and prevention and containment strength. The interactions among these factors are modeled by virtual transmission dynamics with several undetermined parameters, which are determined from epidemic data by machine learning techniques. When MLSim learns to match the real data closely, it also models the number of asymptomatic patients. MLSim is learned from the open Chinese global epidemic data.

Findings

MLSim showed better forecast accuracy than the SEIR and LSTM-based prediction models. The MLSim learned from the data of China’s mainland reveals that there could have been 150,408 (142,178-157,417) asymptomatic and had self-healed patients, which is 65% (64% – 65%) of the inferred total infections including undetected ones. The numbers of asymptomatic but infectious patients on April 15, 2020, were inferred as, Italy: 41,387 (29,037 – 57,151), Germany: 21,118 (11,484 – 41,646), USA: 354,657 (277,641 – 495,128), France: 40,379 (10,807 – 186,878), and UK: 144,424 (127,215 – 171,930). To control the virus transmission, the containment measures taken by the government were crucial. The learned MLSim also reveals that if the date of containment measures in China’s mainland was postponed for 1, 3, 5, and 7 days later than Jan. 23, there would be 109,039 (129%), 183,930 (218%), 313,342 (371%), 537,555 (637%) confirmed cases on June 12.

Conclusions

Machine learning based fine-grained simulators can better model the complex real-world disease transmission process, and thus can help decision-making of balanced containment measures. The simulator also revealed the potential great number of undetected asymptomatic infections, which poses a great risk to the virus containment.

Funding

National Natural Science Foundation of China.
Reduced expression of COVID-19 host receptor,ACE2is associated with small bowel inflammation, more severe disease, and response to anti-TNF therapy in Crohn’s disease
Authors: Potdar Alka A. , Dube Shishir , Naito Takeo , Botwin Gregory , Haritunians Talin , Li Dalin , Yang Shaohong , Bilsborough Janine , Denson Lee A. , Daly Mark , Targan Stephan R. , Fleshner Phillip , Braun Jonathan , Kugathasan Subra , Stappenbeck Thaddeus S. , McGovern Dermot P.B.
Published: April 2020

Angiotensin-Converting Enzyme 2 (ACE2) has been identified as the host receptor for SARS-coronavirus 2 (SARS-CoV-2) which has infected millions world-wide and likely caused hundreds of thousands of deaths. Utilizing transcriptomic data from four cohorts taken from Crohn’s disease (CD) and non-inflammatory bowel disease (IBD) subjects, we observed evidence of increasedACE2mRNA in ileum with demographic features that have been associated with poor outcomes in COVID-19 including age and raised BMI.ACE2was downregulated in CD compared to controls in independent cohorts. Within CD,ACE2expression was reduced in inflamed ileal tissue and also remarkably, from un-involved tissue in patients with a worse prognosis in both adult and pediatric cohorts. In active CD, small bowelACE2expression was restored by anti-TNF therapy particularly in anti-TNF responders. Collectively our data suggest thatACE2downregulation is associated with inflammation and worse outcomes in CD.
The Novel Coronavirus Disease (COVID-19): A PRISMA Systematic Review and Meta-analysis of Clinical and Paraclinical characteristics
Authors: Hasani Hamidreza , Mardi Shayan , Shakerian Sareh , Taherzadeh-Ghahfarokhi Nooshin , Mardi Parham
Published: April 2020

An outbreak of pneumonia, caused by a novel coronavirus (COVID-19) was Identified in China in Dec 2019. This virus expanded worldwide, causing global concern. Clinical, laboratory and imaging features of this infection are characterized in some observational studies. We undertook a systematic review and meta-analysis to assess the frequency of clinical, laboratory, and CT features in COVID-19 patients.

We did a systematic review and meta-analysis using three databases to identify clinical, laboratory, and CT features of rRT-PCR confirmed cases of COVID-19. Data for 3420 patients from 30 observational studies were included.

Overall, the results showed that fever (84.2%, 95%CI 82.6-85.7), cough (62%, 95%CI 60-64), and fatigue (39.4%, 95%CI 37.2-41.6%) were the most prevalent symptoms in COVID-19 patients. Increased CRP level, decreased lymphocyte count, and increased D-dimer level were the most common laboratory findings. Among COVID-19 patients, 92% had a positive CT finding, most prevalently GGO (60%, 95%CI 58-62) and peripheral distribution (64%, 95%CI 60-69).

These results demonstrate the clinical, paraclinical, and imaging features of COIVD-19.