bluuebunny/crossref_metadata_2025 huggingface dataset:
Cohort study protocol to characterize the incidence and severity of neuropathic pain in patients with severe acute respiratory syndrome coronavirus 2 infection
Authors: Odozor Chioma U. , Roles Kristen , Burk Carrie , Kannampallil Thomas , Clifford David B. , Piccirillo Jay F. , Haroutounian Simon
Published: April 2021

Introduction and Objectives:

The coronavirus disease 2019 (COVID-19) pandemic has resulted in patients experiencing symptoms that include neurological dysfunction. As many viral infections are associated with neuropathy, the aim of the study is to characterize the incidence and severity of neuropathic pain in patients with COVID-19.

Methods:

A cohort study will be conducted in adult (≥18 years) patients who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Washington University/Barnes-Jewish Hospital. Participants who are deceased, with incomplete test results, or who cannot be contacted will be excluded. Approximately 1320 participants will be recruited in a 1:2 ratio of those with a positive-to-negative SARS-CoV-2 test result. Each participant will be invited to complete a survey to assess their symptoms related to neuropathy, 30 to 90 days after their initial SARS-CoV-2 test. Survey responses, demographics, and clinical data from the electronic health record will be used for analysis. The primary outcome is the incidence of new symptoms of neuropathic pain. The self-reported DN4 and Neuropathic Pain Symptom Inventory questionnaires (Appendix 1, http://links.lww.com/PR9/A103) will be used for neuropathic pain screening and severity assessment, respectively. Exploratory analyses will be performed to investigate other potential clinical endpoints and trends.

Results/Conclusion:

Similar to previous coronavirus infections, an increased incidence of new-onset neuropathic pain after COVID-19 disease is expected, along with an increase in the severity experienced by patients with COVID-19 with pre-existing chronic pain. Comprehensive understanding of how COVID-19 affects the nervous system can provide a better framework for managing pain in this disease.
Bacteria-induced mineral precipitation: a mechanistic review
Authors: Hoffmann Timothy D. , Reeksting Bianca J. , Gebhard Susanne
Published: April 2021

Micro-organisms contribute to Earth’s mineral deposits through a process known as bacteria-induced mineral precipitation (BIMP). It is a complex phenomenon that can occur as a result of a variety of physiological activities that influence the supersaturation state and nucleation catalysis of mineral precipitation in the environment. There is a good understanding of BIMP induced by bacterial metabolism through the control of metal redox states and enzyme-mediated reactions such as ureolysis. However, other forms of BIMP often cannot be attributed to a single pathway but rather appear to be a passive result of bacterial activity, where minerals form as a result of metabolic by-products and surface interactions within the surrounding environment. BIMP from such processes has formed the basis of many new innovative biotechnologies, such as soil consolidation, heavy metal remediation, restoration of historic buildings and even self-healing concrete. However, these applications to date have primarily incorporated BIMP-capable bacteria sampled from the environment, while detailed investigations of the underpinning mechanisms have been lagging behind. This review covers our current mechanistic understanding of bacterial activities that indirectly influence BIMP and highlights the complexity and connectivity between the different cellular and metabolic processes involved. Ultimately, detailed insights will facilitate the rational design of application-specific BIMP technologies and deepen our understanding of how bacteria are shaping our world.
Self-collected oral, nasal and saliva samples yield sensitivity comparable to professional-collected oro-nasopharyngeal swabs in SARS-CoV-2 diagnosis
Authors: Gertler Maximilian , Krause Eva , van Loon Welmoed , Krug Niklas , Kausch Franka , Rohardt Chiara , Rössig Heike , Michel Janine , Nitsche Andreas , Mall Marcus A. , Nikolai Olga , Hommes Franziska , Burock Susen , Lindner Andreas K. , Mockenhaupt Frank P. , Pison Ulrich , Seybold Joachim
Published: April 2021

Summary/Abstract

Introduction

Containment of the COVID-19 pandemic requires broad-scale testing. Laboratory capacities for real-time-PCR were increased, and are complemented by Ag-tests. However, sample-collection still requires qualified personnel and protective equipement, may produce transmission to others during conduct and travel, and is perceived uncomfortable. We tested sensitivity of three simplified self-sampling techniques compared to professional-collected combined oro-nasopharyngeal samples (cOP/NP).

Methods

From 62 symptomatic COVID-19 outpatients, we obtained simultaneously three self- and one professional-collected sample after initial confirmation in a testing centre: (i) combination swab (tongue, cheek, both nasal vestibula, MS, (ii) saliva sponge combined with both nasal vestibula, SN, and (iii) gargled tap water, GW, (iv) professionally-collected cOP/NP (standard). We compared the results of SARS-CoV-2 PCR-assays detecting E-gene and ORF1ab for the different sample types and performed bivariate statistical analysis to determine the variables reducing sensitivity of the self-collecting procedures.

Results

SARS-CoV-2 RNA was detected in all 62 professionally-collected cOP/NP. MS and SN samples showed a sensitivity of 95.2% (95%CI 86.5-99.0) and GW samples of 88.7% (78.1-95.3). Compared to the medianct-values of cOP/NP samples forE-gene(20.7) andORF1ab(20.2) these were higher for MS (22.6 and 21.8), SN (23.3 and 22.3), and for GW (30.3 and 29.8).

For MS and SN samples but not for GW specimens, false negativity in bivariate analysis was associated with non-German mother-tongue, number of sampling errors, and with symptom duration. For symptom duration of ≤8 days, test sensitivity for SN samples was 98.2% (95%CI 90.4-100.0) and for MS 96.4% (95%CI 87.7-99.6) and drops after day 8 below 90%.

Discussion

The study is limited to sensitivity of self-collection in symptomatic patients. Still, in this group, self-collected oral/nasal/saliva samples are reliable alternatives to professional-collected cOP/NP samples, if symptom duration does not exceed eight days and operational errors are minimized. Self-sampling could contribute to up-scaling of safe and efficient testing.
Substantia nigra ferric overload and neuromelanin loss in Parkinson’s disease measured with 7T MRI
Authors: Rua Catarina , O’Callaghan Claire , Ye Rong , Hezemans Frank H. , Passamonti Luca , Jones P Simon , Williams Guy B , Rodgers Christopher T , Rowe James B
Published: April 2021

Background

Vulnerability of the substantia nigra dopaminergic neurons in Parkinson’s disease is associated with ferric overload, leading to neurodegeneration with cognitive and motor decline. Here, we quantify iron and neuromelanin-related markers in vivo using ultra-high field 7-Tesla MRI, and examine the clinical correlates of these imaging assessments.

Methods

Twenty-five people with mild-to-moderate Parkinson’s disease and twenty-six healthy controls underwent high-resolution imaging at 7-Tesla with a T2*-weighted sequence (measuring susceptibility-χ and R2*, sensitive to iron) and a magnetization transfer-weighted sequence (MT-w, sensitive to neuromelanin). From an independent control group (N=29), we created study-specific regions-of-interest for five neuromelanin- and/or iron-rich subregions within the substantia nigra. Mean R2*, susceptibility-χ and their ratio, as well as the MT-w contrast-to-noise ratio (MT-CNR) were extracted from these regions and compared between groups. We then tested the relationships between these imaging metrics and clinical severity.

Results

People with Parkinson’s disease showed a significant ~50% reduction in MT-CNR compared to healthy controls. They also showed a 1.2-fold increase in ferric iron loading (elevation of the ratio from 0.19±0.058ms/ppm to 0.22±0.059ms/ppm) in an area of the substantia nigra identified as having both high neuromelanin and susceptibility MRI signal in healthy controls. In this region, the ferric-to-ferrous iron loading was associated with disease duration (β=0.0072, pFDR=0.048) and cognitive impairment (β=−0.0115, pFDR=0.048).

Conclusions

T2*-weighted and MT-weighted high-resolution 7T imaging markers identified neurochemical consequences of Parkinson’s disease, in overlapping but not-identical regions. These changes correlated with non-motor symptoms.
Introducing the EMPIRE Index: A novel, value-based metric framework to measure the impact of medical publications
Authors: Pal Avishek , Rees Tomas James
Published: April 2021

Article-level measures of publication impact (alternative metrics or altmetrics) can help authors and other stakeholders assess engagement with their research and the success of their communication efforts. The wide variety of altmetrics can make interpretation and comparative assessment difficult; available summary tools are either narrowly focused or do not reflect the differing values of metrics from a stakeholder perspective. We created the EMPIRE (EMpirical Publication Impact and Reach Evaluation) Index, a value-based, multi-component metric framework for medical publications. Metric weighting and grouping were informed by a statistical analysis of 2891 Phase III clinical trial publications and by a panel of stakeholders who provided value assessments. The EMPIRE Index comprises three component scores (social, scholarly, and societal impact), each incorporating related altmetrics indicating a different aspect of engagement with the publication. These are averaged to provide a total impact score and benchmarked so that a score of 100 equals the mean scores of Phase III clinical trial publications in the New England Journal of Medicine (NEJM) in 2016. Predictor metrics are defined to estimate likely long-term impact. The social impact component correlated strongly with the Altmetric Attention Score and the scholarly impact component correlated modestly with CiteScore, with the societal impact component providing unique insights. Analysis of fresh metrics collected 1 year after the initial dataset, including an independent sample, showed that scholarly and societal impact scores continued to increase, whereas social impact scores did not. Analysis of NEJM ‘notable articles’ showed that observational studies had the highest total impact and component scores, except for societal impact, for which surgical studies had the highest score. The EMPIRE Index provides a richer assessment of publication value than standalone traditional and alternative metrics and may enable medical researchers to assess the impact of publications easily and to understand what characterizes impactful research.
Comparative Effectiveness of Standard and Contingency-based Cleaning in Acute and Long-Term Care Facilities amidst Staff Shortages and a COVID-19 Surge
Authors: Lesho Emil , Newhart Donna , Reno Lisa , Sleeper Scott , Nary Julia , Gutowski Jennifer , Yu Stephanie , Walsh Edward , Vargas Roberto , Riedy Dawn , Mayo Robert
Published: April 2021

Background

Cleanliness of hospital surfaces helps prevent healthcare-associated infections, but larger evaluations of the effectiveness of various cleaning strategies during SARS-CoV-2 surges and worker shortages are scarce.

Methods

In an acute care hospital (ACH) and a long-term care facility (LTCF), 417 surfaces were tested for SARS-CoV-2 and adenosine triphosphate before and after various cleaning strategies, including ultraviolet light (UV-C), electrostatic spraying, and room fogging.

Results

ACH surface contamination differed among outbreak and non-outbreak wards (p = 0.001). RNA was detected on 66% of surfaces before cleaning and on 23% of those surfaces immediately after terminal cleaning, for a 65% post-cleaning reduction (p = 0.001). UV-C resulted in an 87% reduction (p = 0.023), while spraying with electrostatic bleach resulted in a 47% reduction (p = 0.010). LTCF contamination rates differed between the dementia, rehabilitation, and the residential units (p = 0.005). 67% of surfaces had RNA after room fogging without terminal-style wiping. Fogging with wiping led to an 11% reduction in the proportion of positive surfaces.

Discussion

Baseline contamination varied by type of unit and outbreak conditions, but not facility type. Removal of viral RNA varied according to strategy. Unlike previous reports, time spent cleaning was associated with cleaning thoroughness.
Point-of-Care Ultrasound (POCUS) Predicts Clinical Outcomes in Patients with COVID-19
Authors: Kumar Andre , Weng Isabel , Graglia Sally , Lew Thomas , Gandhi Kavita , Lalani Farhan , Chia David , Duanmu Youyou , Jenson Trevor , Lobo Viveta , Nahn Jeffrey , Iverson Nicholas , Rosenthal Molly , Gordon June , Kugler John , Tran Minh Chi , Jia Xiaolin , Liao Charles , Cha Alice , Baum Evan , Halket Douglas , Madhok Jai , Fazal Muhhamad
Published: April 2021

Introduction

Point-of-care ultrasound (POCUS) may detect the cardiopulmonary manifestations of COVID-19 and expediently predict patient outcomes.

Methods

We conducted a prospective cohort study at four medical centers from 3/2020-1/2021 to evaluate POCUS findings and clinical outcomes with COVID-19. Our inclusion criteria included adult patients hospitalized for COVID-19 who received cardiac or lung POCUS with a 12-zone protocol. Images were interpreted by two reviewers blinded to clinical outcomes. Our primary outcome was ICU admission incidence. Secondary outcomes included intubation and supplemental oxygen usage.

Results

N=160 patients (N=201 scans) were included. Scans were collected a median 23 hours (IQR:7-80) from emergency department triage. Triage POCUS findings associated with ICU admission included B-lines (OR 4.41 [95% CI:1.71-14.30]; p<0.01) or consolidation (OR 2.49 [95% CI:1.35-4.86]; p<0.01). B-lines were associated with intubation (OR 3.10 [95% CI:1.15-10.27]; p=0.02) and supplemental oxygen usage (OR 3.74 [95% CI:1.63-8.63; p<0.01).

Consolidations present on triage were associated with the need for oxygen at discharge (OR 2.16 [95% CI: 1.01-4.70]; p=0.047). A normal lung triage scan was protective for ICU admission (OR 0.28 [95% CI:0.09-0.75; p<0.01) or need for supplemental oxygen during the hospitalization (OR 0.26 [95% CI:0.11-0.61]; p<0.01). Triage cardiac POCUS scans were not associated with any outcomes.

Discussion

Lung POCUS findings detected early in the hospitalization may provide expedient risk stratification for important COVID-19 clinical outcomes, including ICU admission, intubation, or need for oxygen on discharge. A normal admission scan appears protective against adverse outcomes, which may aid in triage decisions of patients.
Gender Differences in Health Protective Behaviors During the COVID-19 Pandemic in Taiwan: An Empirical Study
Authors: Tan Jasmine , Yoshida Yilin , Ma Kevin Sheng-Kai , Mauvais-Jarvis Franck
Published: April 2021

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces more severe symptoms and a higher mortality in men than in women. The role of biological sex in the immune response to SARS-CoV-2 is believed to explain this sex disparity. However, the contribution of gender factors that influence health protective behaviors and therefore health outcomes, remains poorly explored.

Methods

We assessed the contributions of gender in attitudes towards the COVID-19 pandemic, using a hypothetical influenza pandemic data from the 2014 Taiwan Social Change Survey. Participants were selected through a stratified, three-stage probability proportional-to-size sampling from across the nation, to fill in questionnaires that asked about their perception of the hypothetical pandemic, and intention to adopt health protective behaviors.

Results

A total of 1,990 participants (median age 45.92 years, 49% women) were included. Significant gender disparities (p<0.001) were observed. The risk perception of pandemic (OR=1.28, 95% CI=1.21-1.35, p<0.001), older age (1.06, 95%=1.05-1.07, p<0.001), female gender (OR = 1.18, 95% CI = 1.09□1.27, p<0.001), higher education (OR=1.10, 95% CI=1.06-1.13, p<0.001), and larger family size (OR=1.09, 95% CI=1.06-1.15, p<0.001) were positively associated with health protective behaviors. The risk perception of pandemic (OR=1.25, 95% CI=1.15-1.36), higher education (OR=1.07, 95% CI=1.02-1.13, p<0.05), being married (OR=1.17, 95% CI=1.01-1.36, p<0.05), and larger family size (OR=1.33, 95% CI=1.25-1.42, p<0.001), were positively associated with intention to receive a vaccine. However, female gender was negatively associated with intention to receive a vaccine (OR=0.85, 95% CI=0.75-0.90, p<0.01) and to comply with contact-tracing (OR=0.95, 95% CI=0.90-1.00, p<0.05) compared to men. Living with children was also negatively associated with intention to receive vaccines (OR=0.77, 95% CI=0.66-0.90, p<0.001).

Conclusion

This study unveils gender differences in risk perception, health protective behaviors, vaccine hesitancy, and compliance with contact-tracing using a hypothetical viral pandemic. Gender-specific health education raising awareness of health protective behaviors may be beneficial to prevent future pandemics.
A Bibliometric Analysis of Global Pediatric Emergency Medicine Research Networks
Authors: Barrett Michael J , Dalziel Stuart , Lyttle Mark , O’Sullivan Ronan ,   for the Pediatric Emergency Research Networks (PERN)
Published: April 2021

Objective

During the last three decades newly formed pediatric emergency medicine (PEM) research networks have been publishing research. A desire of these networks is to produce and disseminate research to improve patient health and outcomes. To quantitatively analyze and compare the literature by PEM research networks globally through numeric and visual bibliometrics.

Methods

A bibliometric analysis of articles published from 1994 to 2019 (26 years) by authors from PEM research networks globally were retrieved using PubMed®, Web of Science™ (Thompson Reuters) and accessing individual research network databases. Bibliometric analysis was performed utilizing Web of Science™, VOSviewer and Dimensions. Research was quantified to ascertain the number of articles, related articles, citations and Altmetric attention score.

Results

A total of 493 articles were published across nine research networks in three decades. Pediatric Emergency Care Applied Research Network (PECARN) produced the most articles, citations, and h-index of all networks. We identified three main groupings of productive authors across the networks who collaborate globally. The gender of the first author was female in 46% of publications and the corresponding author(s) was female in 45%. A non-significant moderate positive correlation between the number of years publishing and the number of publications was identified. There was non-significant moderate negative association between the number of countries in a network and total publications per annum.

Conclusions

This study is the first bibliometric analysis of publications from PEM research networks that collaborate globally. The gender gap in first authorship compared to high impact medical journals and high impact emergency medicine journals is narrower. Exploring the relationships of numerical bibliometric indicators and visualizations of productivity will benefit the understanding of the generation, reach and dissemination of PEM research within the global research community.
Modelling COVID-19 evolution in Italy with an augmented SIRD model using open data
Authors: Nardelli Vincenzo , Arbia Giuseppe , Palladino Andrea , Atzeni Luigi Giuseppe
Published: April 2021

We propose an augmented version of the traditional SIRD epidemic model and we estimate its parameters using the SaRs-Cov-2 Italian open-data. The model’s parameters are estimated partly using numerical optimization and partly with ABC. Our estimation procedure provides a good fit to real data.
FOCUSED REVIEW ON NUTRITIONAL STATUS OF PATIENTS WITH IMMUNOGLOBULIN LIGHT CHAIN AMYLOIDOSIS
Authors: Grigoletti Shana Souza , Zuchinali Priccila , Lemieux-Blanchard Émilie , Béchard Stéphanie , Lemieux Bernard , Bretanha Ribeiro Paula Aver , Tournoux François
Published: April 2021

Background

Immunoglobulin light chain (AL) amyloidosis is a complex disease marked by a poor clinical portrait and prognosis generally leading to organ dysfunction and shortened survival. We aimed to review the available evidence on whether AL amyloidosis can lead to malnutrition, thus having a negative impact on quality of life (QoL) and survival.

Materials

We searched Pubmed with no restrictions to the year of publication or language. Retrospective or prospective, observational, and interventional studies that reported data regarding AL amyloidosis and nutritional status were included.

Results

From 62 articles retrieved, 23 were included. Malnutrition was prevalent in up to 65% of patients with AL Amyloidosis. Prevalence of weight loss of 10% or more ranged from 6 to 22% of patients, while a body mass index of < 22 kg/m2 was found in 22 to 42%. Weight loss, lower BMI and other indicators of poor nutritional status were negatively associated with quality of life and survival. Only one RCT focused on nutritional counseling was found and reported positive results on patients QoL and survival.

Conclusion

Despite inconsistencies across assessment criteria, the available data reveal that weight loss and malnutrition are common features in patients with AL amyloidosis. This review reinforces the premise that an impaired nutritional status can be negatively associated with QoL and survival in patients with AL amyloidosis, and therefore should be further investigated.
Ascorbic acid attenuates activation and cytokine production in sepsis-like monocytes
Authors: Schmidt Tobias , Kahn Robin , Kahn Fredrik
Published: April 2021

Sepsis manifests due to the host’s dysregulated immune response to an infection. High dose ascorbic acid (AA) has emerged as a potential treatment of sepsis, yet little is known regarding how ascorbic acid influences the immune system in sepsis, such as monocytes. The objective of this study is to investigate the effects of high dose AA on monocyte polarization and cytokine production in vitro.

Monocytes were isolated from healthy donors (n=6) and polarized in vitro for 48hrs using lipopolysaccharide (LPS) and lipoteichoic acid (LTA). Polarization was confirmed by surface marker expression using flow cytometry. In parallel, monocytes from septic patients (n=3) were analyzed for polarization markers as a comparison to the in vitro polarization. The effect of AA on monocyte polarization was evaluated. Finally, monocytes were analyzed for cytokine production of TNF and IL-8 by intracellular staining.

Both LPS and LTA induced polarization in healthy monocytes in vitro, with increased expression of both pro- (CD40 and PDL1, p<0.05) and anti-inflammatory (CD16 and CD163, p<0.05) polarization markers. This pattern resembled that of monocytes from septic patients. Treatment with AA significantly inhibited surface expression of CD16 and CD163 (p<0.05) in a dose dependent manner. Finally, AA attenuated LPS or LTA-induced cytokine production of IL-8 and TNF (both p<0.05) in a dose-dependent manner.

Thus, AA attenuates cytokine production and upregulation of anti-, but not pro-inflammatory related markers in LPS or LTA polarized monocytes. This study provides important insight into the effects of high dose AA on monocytes, and potential implications in sepsis.

Summary sentence

Ascorbic acid inhibits production of IL-8, TNF, and upregulation of the polarization markers CD16 and CD163 in LPS or LTA polarized monocytes in vitro.
Knowledge and attitude of Iranian university students toward genital warts
Authors: Aryanian Zeinab , Mohammadi Maedeh , Babazadeh Arefeh , Etesami Ifa , Hatami Parvaneh , Barary Mohammad , Ebrahimpour Soheil , Sabbagh Parisa , Goodarzi Azadeh
Published: April 2021

Human papillomavirus (HPV) is one of the well-known causes of cervical cancer and one of the most prevalent sexually transmitted diseases (STDs). Since cervical cancer is one of the most common causes of morbidity and mortality in women, this study was performed to investigate students’ knowledge and attitudes in Babol University of Medical Sciences, Northern Iran, towards genital warts. This cross-sectional study assessed the perception and attitudes of 385 students at Babol University of Medical Sciences using a preconceived questionnaire. The data collection tool used in this study was a questionnaire that was confirmed to be valid and reliable. The participants’ mean age was 23.70 ± 3.27 years, with a range of 20-50 years. Evaluation of these students’ level of general information about HPV showed that 7 (1.8%) students had inadequate general information, 34 (8.8%) had moderate knowledge, and 344 (89.4%) had good general knowledge in this setting. There was also a significant association between students’ general knowledge of HPV and their field of study. Based on the present study results, the knowledge of the majority of Babol University of Medical Sciences students about genital warts was in a good range, and their knowledge about HPV routes of transmission was of moderate level. Moreover, the majority had an appropriate attitude to interact with people infected with HPV.
Incidences of poor-quality pharmaceutical products in Nepal
Authors: Neupane Astha , Bastakoti Maheshwor , Tamang Sabita , Giri Basant
Published: April 2021

Pharmaceutical products are used to treat, prevent, and save lives of millions of people globally. However, pharmaceutical products known as substandard and falsified that do not meet regulatory standards and quality threaten the health of the population of today and future leading to socio-economic hardship, drug resistances and put life of patients in danger. We analyzed the recall notice from 2010 to 2020 issued by the department of drug administration (DDA), government of Nepal to understand the overview of substandard and falsified pharmaceutical products in Nepal. The number of recalled pharmaceutical products has significantly increased over the past decade in Nepal (p-value< 0.05). The most recalled drugs were antimicrobials followed by gastrointestinal medicines, vitamins and supplements, pain and palliative medicines among others. Number of recalled drugs manufactured by domestic pharmaceutical producers and imported ones were not significantly different. Majority of imported recalled drugs originated from India. Sixty-two percentage of recalled drugs were substandard, 11% were falsified and remaining 27% were not registered at the DDA. Similarly, sixty percentage of recalled drugs were modern and 35% were traditional ones. The hand sanitizers used to minimize the COVID-19 transmission contributed significantly to the list of recalled pharmaceutical products in 2020. Most of these sanitizers contained significant amount of methanol instead of ethyl alcohol or isopropyl alcohol. We also reviewed peer-reviewed research papers that reported data of substandard and falsified drugs. Only four such papers were found in literature. These papers reported issues with labeling, unregistered drugs and drugs failed in a number of laboratory testing. Since the recall data did not include number of samples tested and location of sample collected, a systematic study to understand the prevalence of substandard and falsified drugs in Nepal is recommended.

Key questions

What is already known?

Prevalence of substandard and falsified pharmaceutical products is a global threat to public health and socio-economy.

What are the new findings?

We analyzed drug recall data from department of drug administration in Nepal and report that the substandard and falsified pharmaceutical products are increasing significantly.

Antimicrobial drugs were the most frequently recalled drugs. Drugs manufactured by domestic producers and imported ones were equally recalled. Allopathic drugs were recalled more than ayurvedic products.

What do the new findings imply?

This study suggested the problem of substandard and falsified pharmaceutical products is serious in Nepal. Integrated efforts from regulating agencies, manufacturers and pharmacies are recommended to minimize the circulation of such products in the country.
Aerosol and droplet generation in upper and lower gastrointestinal endoscopy: whole procedure and event-based analysis
Authors: Phillips Frank , Crowley Jane , Warburton Samantha , Gordon George S.D. , Parra-Blanco Adolfo
Published: April 2021

Background and Aims

Aerosol generating procedures have become an important healthcare issue due to the COVID-19 pandemic, as the SARS-CoV-2 virus can be transmitted via aerosols. We aimed to characterise aerosol and droplet generation in gastrointestinal endoscopy, where there is little evidence.

Methods

This prospective observational study included patients undergoing routine per-oral gastroscopy (POG, n=36), trans-nasal endoscopy (TNE, n=11) and lower gastrointestinal (LGI) endoscopy (n=48). Particle counters took measurements near the appropriate orifice (two models used, diameter ranges 0.3μm-25μm and 20μm-3000μm). Quantitative analysis was performed by recording specific events and subtracting the background particles.

Results

POG produced 1.96x the level of background particles (p<0.001) and TNE produced 2.00x (p<0.001) but a direct comparison shows POG produces 2.00x more particles than TNE. LGI procedures produce significant particle counts (p<0.001) with 2.4x greater production per procedure than POG but only 0.63x production per minute. Events significant relative to the room background particle count were: POG-throat spray (150.0x, p<0.001), oesophageal extubation (37.5x, p<0.001), coughing/gagging (25.8x, p<0.01); TNE-nasal spray (40.1x, p<0.001), nasal extubation (32.0x, p<0.01), coughing/gagging (20.0, p<0.01); LGI-rectal intubation (9.9x, p<0.05), rectal extubation (27.2x, p <0.01), application of abdominal pressure (9.6x, p <0.05), rectal insufflation/retroflexion (7.7x, p <0.01). These all produced particle counts larger than or comparable to volitional cough.

Conclusion

Gastrointestinal endoscopy performed via the mouth, nose or rectum all generates significant quantities of aerosols and droplets. As the infectivity of procedures is not established, we therefore suggest adequate PPE is used for all GI endoscopy where there is a high population prevalence of COVID-19. Avoiding throat and nasal spray would significantly reduce particles generated from UGI procedures.
Coupling machine learning and high throughput multiplex digital PCR enables accurate detection of carbapenem-resistant genes in clinical isolates
Authors: Miglietta Luca , Moniri Ahmad , Pennisi Ivana , Malpartida-Cardenas Kenny , Abbas Hala , Hill-Cawthorne Kerri , Bolt Frances , Jauneikaite Elita , Davies Frances , Holmes Alison , Georgiou Pantelis , Rodriguez-Manzano Jesus
Published: April 2021

Rapid and accurate identification of patients colonised with carbapenemase-producing organisms (CPOs) is essential to adopt prompt prevention measures to reduce the risk of transmission. Recent studies have demonstrated the ability to combine machine learning (ML) algorithms with real-time digital PCR (dPCR) instruments to increase classification accuracy of multiplex PCR assays when using synthetic DNA templates. We sought to determine if this novel methodology could be applied to improve identification of the five major carbapenem-resistant genes in clinical CPO-isolates, which would represent a leap forward in the use of PCR-based data-driven diagnostics for clinical applications.

We collected 253 clinical isolates (including 221 CPO-positive samples) and developed a novel 5-plex PCR assay for detection of blaIMP, blaKPC, blaNDM, blaOXA-48 and blaVIM. Combining the recently reported ML method ‘Amplification and Melting Curve Analysis’ (AMCA) with the abovementioned multiplex assay, we assessed the performance of the AMCA methodology in detecting these genes. The improved classification accuracy of AMCA relies on the usage of real-time data from a single-fluorescent channel and benefits from the kinetic/thermodynamic information encoded in the thousands of amplification events produced by high throughput real-time dPCR.

The 5-plex showed a lower limit of detection of 10 DNA copies per reaction for each primer set and no cross-reactivity with other carbapenemase genes. The AMCA classifier demonstrated excellent predictive performance with 99.6% (CI 97.8-99.9%) accuracy (only one misclassified sample out of the 253, with a total of 160,041 positive amplification events), which represents a 7.9% increase (p-value < 0.05) compared to conventional melting curve analysis.

This work demonstrates the use of the AMCA method to increase the throughput and performance of state-of-the-art molecular diagnostic platforms, without hardware modifications and additional costs, thus potentially providing substantial clinical utility on screening patients for CPO carriage.
A Tool for Translating Polygenic Scores onto the Absolute Scale Using Summary Statistics
Authors: Pain Oliver , Gillett Alexandra C. , Austin Jehannine C. , Folkersen Lasse , Lewis Cathryn M.
Published: April 2021

Background

There is growing interest in the clinical application of polygenic scores as their predictive utility increases for a range of health-related phenotypes. However, providing polygenic score predictions on the absolute scale is an important step for their safe interpretation. Currently, polygenic scores can only be converted to the absolute scale when a validation sample is available, presenting a major limitation in the interpretability and clinical utility of polygenic scores.

Methods

We have developed a method to convert polygenic scores to the absolute scale for binary and normally distributed phenotypes. This method uses summary statistics, requiring only the area-under-the-ROC curve (AUC) or variance explained (R2) by the polygenic score, and the prevalence of binary phenotypes, or mean and standard deviation of normally distributed phenotypes. Polygenic scores are converted using normal distribution theory. Given the AUC/R2of polygenic scores may be unknown, we also evaluate two methods (AVENGEME, lassosum) for estimating these values from genome-wide association study (GWAS) summary statistics alone. We validate the absolute risk conversion and AUC/R2estimation using data for eight binary and three continuous phenotypes in the UK Biobank sample.

Results

When the AUC/R2of the polygenic score is known, the observed and estimated absolute values were highly concordant. Across binary phenotypes, the mean absolute difference between the observed and estimated proportion of cases was 5%. For continuous phenotypes, the mean absolute difference between observed and estimated means was <0.3%. Estimates of AUC/R2from the lassosum pseudovalidation method were most similar to the observed AUC/R2values, though estimated values deviated substantially from the observed for autoimmune disorders.

Conclusion

This study enables accurate interpretation of polygenic scores using only summary statistics, providing a useful tool for educational and clinical purposes. Furthermore, we have created interactive webtools implementing the conversion to the absolute scale for binary and normally distributed phenotypes (https://opain.github.io/GenoPred/PRS_to_Abs_tool.html). Several further barriers must be addressed before clinical implementation of polygenic scores, such as ensuring target individuals are well represented by the GWAS sample.
Exaggerated Right Ventricular Dysfunction in Females with Group 3 Pulmonary Hypertension
Authors: Prisco Sasha Z. , Kazmirczak Felipe , Prins Kurt W. , Thenappan Thenappan
Published: April 2021

Group 3 pulmonary hypertension (PH) patients have disproportionate right ventricular dysfunction (RVD) as compared to pulmonary arterial hypertension (PAH) patients, but the cause of the divergent RV phenotypes is unknown. One potential mechanism may be biological sex as females have better RV function than males. However, the combined effects of PH type and sex on RV function are unexplored. Therefore, we evaluated how sex and PH etiology modulated RVD in a single-center cohort study. Male sex was not associated with significant differences in RV function when comparing PH etiologies. However, female Group 3 patients had more pronounced RVD than female PAH patients. In particular, Group 3 females had marked reduction in RV function when pulmonary vascular resistance was matched. Group 3 females were older than PAH females, but the exaggerated RVD was still observed in postmenopausal (age≥55) Group 3 females. This suggests lung disease exacerbates RVD in Group 3 females.
CovidEnvelope: A Fast Automated Approach to Diagnose COVID-19 from Cough Signals
Authors: Hossain Md Zakir , Uddin Md. Bashir , Ahmed Khandaker Asif
Published: April 2021

The COVID-19 pandemic has a devastating impact on the health and well-being of global population. Cough audio signals classification showed potential as a screening approach for diagnosing people, infected with COVID-19. Recent approaches need costly deep learning algorithms or sophisticated methods to extract informative features from cough audio signals. In this paper, we propose a low-cost envelope approach, called CovidEnvelope, which can classify COVID-19 positive and negative cases from raw data by avoiding above disadvantages. This automated approach can pre-process cough audio signals by filter-out back-ground noises, generate an envelope around the audio signal, and finally provide outcomes by computing area enclosed by the envelope. It has been seen that reliable datasets are also important for achieving high performance. Our approach proves that human verbal confirmation is not a reliable source of information. Finally, the approach reaches highest sensitivity, specificity, accuracy, and AUC of 0.92, 0.87, 0.89, and 0.89 respectively. The automatic approach only takes 1.8 to 3.9 minutes to compute these performances. Overall, this approach is fast and sensitive to diagnose the people living with COVID-19, regardless of having COVID-19 related symptoms or not, and thus have vast applicability in human well-being by designing HCI devices incorporating this approach.
Estimating the effect of mobility on SARS-CoV-2 transmission during the first and second wave of the COVID-19 epidemic in Switzerland: a population-based study
Authors: Lison Adrian , Persson Joel , Banholzer Nicolas , Feuerriegel Stefan
Published: April 2021

The effect of mobility and its value for surveillance in different waves of the COVID-19 epidemic is still unclear. In this study, we compared the role of mobility during the first and second epidemic wave in Switzerland by analysing the link between daily travel distances and the effective reproduction number Rt of SARS-CoV-2. Here we used aggregated mobile phone data from a representative panel survey of the Swiss population to measure human mobility. We estimated the effects of reductions in daily travel distance on Rt via a regression model. We compared mobility effects between the first wave (March 2-April 7, 2020) and the second wave (October 1-December 10, 2020) across mode of transport, travel purpose, sociodemographic subgroup and movement radius. We found that human mobility was associated with the effective reproduction number of SARS-CoV-2 during both the first and second epidemic wave in Switzerland. The estimated relative effects of mobility were similar in both waves for all modes of transport, travel purposes, and sociodemographic subgroups but differed by movement radius. Moreover, smaller mobility reductions in the second wave translated into smaller overall reductions of Rt. Mobility data from mobile phones have a continued potential to support real-time surveillance of COVID-19 during epidemic waves.
COVID-19 Vaccine Prioritisation in Japan and South Korea
Authors: Chun June Young , Jeong Hwichang , Beutels Philippe , Ohmagari Norio , Kim Yongdai , Tsuzuki Shinya
Published: April 2021

Background

Due to a limited initial supply of COVID-19 vaccines, the prioritisation of individuals for vaccination is of utmost importance for public health. Here, we provide the optimal allocation strategy for COVID-19 vaccines according to age in Japan and South Korea.

Methods

Combining national case reports, age-specific contact matrices, and observed periods between each stages of infection (Susceptible-Exposed-Infectious-Quarantined), we constructed a compartmental model. We estimated the age-stratified probability of transmission given contact (qi) using Bayesian inference method and simulated different vaccination scenarios to reduce either case numbers or death toll. We also performed sensitivity analyses on the proportion of asymptomatic cases and vaccine efficacy.

Findings

The model inferred age-stratified probability of transmission given contact (qi) showed similar age-dependent increase in Japan and South Korea. Assuming the reported COVID-19 vaccine efficacy, our results indicate that Japan and South Korea need to prioritise individuals aged 20–35 years and individuals aged over 60 years, respectively, to minimise case numbers. To minimise the death toll, both countries need to prioritise individuals aged over 75 years. These trends were not changed by proportions of asymptomatic cases and varying vaccine efficacy on individuals under 20 years.

Interpretation

We presented the optimal vaccination strategy for Japan and South Korea. Comparing the results of these countries demonstrates that not only the effective contact rates containing qi but also the age-demographics of current epidemic in Japan (dominance in 20s) and South Korea (dominant cases over 50s) affect vaccine allocation strategy.
Thromboembolism risk among patients with diabetes/stress hyperglycemia and COVID-19
Authors: Calvisi Stefania L , Ramirez Giuseppe A , Scavini Marina , Da Prat Valentina , Di Lucca Giuseppe , Laurenzi Andrea , Gallina Gabriele , Cavallo Ludovica , Borio Giorgia , Farolfi Federica , Pascali Maria , Castellani Jacopo , Lampasona Vito , D’Angelo Armando , Landoni Giovanni , Ciceri Fabio , Querini Patrizia Rovere , Tresoldi Moreno , Piemonti Lorenzo
Published: April 2021

Abstract

Purpose

Individuals with diabetes/stress hyperglycemia carry an increased risk for adverse clinical outcome in case of SARS-CoV-2 infection. The purpose of this study was to evaluate whether this risk is, at least in part, modulated by an increase of thromboembolic complications.

Methods

We prospectively followed 180 hospitalized patients with confirmed COVID-19 pneumonia admitted to the Internal Medicine Units of San Raffaele Hospital. Data from 11 out of 180 patients were considered incomplete and excluded from the analysis. We analysed inflammation, tissue damage biomarkers, hemostatic parameters, thrombotic events (TEs) and clinical outcome according to the presence of diabetes/stress hyperglycemia.

Results

Among 169 patients, 51 (30.2%) had diabetes/stress hyperglycemia. Diabetes/stress hyperglycemia and fasting blood glucose (FBG) were associated with increased inflammation and tissue damage circulating markers, higher D-dimer levels, increased prothrombin time and lower antithrombin III activity. Forty-eight venous and 10 arterial TEs were identified in 49 (29%) patients. Diabetes/stress hyperglycemia (HR 2.71, p=0.001), fasting blood glucose (HR 4.32, p<0.001) and glucose variability (HR 1.6, p < 0.009) were all associated with an increased risk of thromboembolic complication. TEs significantly increased the risk for an adverse clinical outcome only in the presence of diabetes/stress hyperglycemia (HR 3.05, p=0.01) or fasting blood glucose ≥ 7 mmol/l (HR 3.07, p=0.015).

Conclusions

Thromboembolism risk is higher among patients with diabetes/stress hyperglycemia and COVID-19 pneumonia and is associated to poor clinical outcome. In case of SARS-Cov-2 infection patients with diabetes/stress hyperglycemia could be considered for a more intensive prophylactic anticoagulation regimen.
Health effects of European colonization: An investigation of skeletal remains from 19th to early 20th century migrant settlers in South Australia
Authors: Gurr Angela , Kumaratilake Jaliya , Brook Alan Henry , Ioannou Stella , Pate F. Donald , Henneberg Maciej
Published: April 2021

Nineteenth century medical understanding of human metabolism was limited, therefore, the incidence of metabolic deficiencies was not fully recorded. In addition, the transition from agricultural based mode of life to the industrial one significantly changed the pattern of these metabolic deficiencies. They were further altered by colonisation of distant continents. Palaeopathological study of skeletal remains from the early industrialised colonial era allowed light to be shed on the metabolic stresses produced by this new mode of life. Aims of this study were to investigate manifestations of disease in skeletal remains from 65 (20 adults, 45 sub-adults) migrant settlers buried in the “free ground” of St Mary’s Anglican Church Cemetery (1847 to 1927). An area allocated for burials paid for by the South Australian Government. Skeletal manifestations were determined and interpreted in terms of their multiple aetiologies. Findings were compared with those published for two 19thcentury British samples. Skeletal manifestations, commonly related to metabolic deficiencies, were observed. Areas of abnormal porosity of bone cortices were seen in 9 adults and 12 sub-adults, flaring of metaphyses was seen in one sub-adult, flaring of costochondral junctions of the ribs was seen in one sub-adult. Porous lesions of orbital roof bones (Types 3 to 5) were seen on three sub-adults. Micro-CT scans of tooth samples located interglobular dentine in three individuals. Comparison of St Mary’s findings with St Martins, Birmingham, and St Peter’s, Wolverhampton, UK, showed more individuals from St Mary’s had areas of abnormal porosity of bone cortices possibly related to vitamin C deficiency. However, St Mary’s sample displayed fewer changes attributable to vitamin D deficiency as expected in a country with greater UV irradiation. This indicates that, although the early industrialisation produced metabolic stresses, change of the environment through colonisation of new continents altered the distribution of metabolic deficiencies.
Differences in estimates for ten-year risk of cardiovascular disease in Black versus white persons with identical risk factor profiles using pooled cohort equations
Authors: Vasan Ramachandran S. , van den Heuvel Edwin
Published: April 2021

Background

Sex- and race-specific pooled cohort equations (PCE) are recommended for estimating the 10-year risk of cardiovascular disease (CVD), with an absolute risk >7.5% indicating a clinical decision threshold.

Methods

We generated in silico 30,565 risk profiles in men and 29,515 in women by combining numerical (age, total and high-density lipoprotein cholesterol, systolic blood pressure) and binary risk factors (smoking, diabetes, antihypertensive treatment). We compared PCE-estimated 10-year CVD risk in Black versus white individuals with identical risk profiles. We performed similar comparisons in participants in the Framingham Third Generation cohort and the National Health and Nutrition Examination Survey 2017-2018.

Results

There were 6357 risk profiles associated with 10-year CVD risk >7.5% for Black but not for white men (median risk difference [RD] 6.25%, range 0.15-22.8%; median relative risk [RR] 2.40, range 1.02-12.6). There were 391 profiles with 10-year CVD risk >7.5% for white but not for Black men (median RD 2.68%, range 0.07-16.9%; median RR 1.42, range 1.01-3.57). There were 6543 risk profiles associated with 10-year estimated CVD risk >7.5% for Black but not for white women (median RD 6.14%, range 0.35-26.8%; median RR 2.29, range 1.05-12.6). There were 318 profiles with 10-year CVD risk >7.5% for white but not for Black women (median RD 3.71%, range 0.22-20.1%; median RR 1.66, range 1.03-5.46). The population-based samples demonstrated similar risk differences.

Conclusions

The PCE may generate substantially divergent CVD risk estimates for Black versus white individuals with identical risk profiles, which could introduce race-related variations in clinical recommendations for CVD prevention.