bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogenetic analysis of kinetoplast DNA: kDNA ofLeishmania tropicain Thi-Qar province, Iraq
Authors: Flaih Mohammed Hassan , Al-Abady Fadhil Abbas , Hussein Khwam Reissan
Published: November 2020

Introduction

Cutaneous leishmaniasis (CL) is one of wobbling endemic disease in Iraq, that cause intracellular obligate protistan parasite returned to the genusLeishmania. This study is aimed to identify epidemiology of CL, detect the prevalence ofLeishmania tropicaand find the phylogenetic relationship.

Methodology

The current study was conducted in the main hospitals of Thi-Qar province-south of Iraq for period from November 2018 to October 2019. Nested-PCR was used to amplify kinetoplast minicircle fragments DNA.

Results

It was recorded 247 clinical cases with CL, the infections of males were higher than females, while infection rate appeared gradual reduction with age progress. Furthermore, the most CL infections were as single lesions and occurred in December. The infections of upper limbs were high when compared with other body regions. The molecular diagnosis showedL. tropicawas more frequently. DNA sequences ofkDNAgene ofL. tropicashowed confirmative genetic detection of local isolates using NCBI-Blast data and phylogenetic tree analysis after comparison with global recorded isolates. The localL. tropicaisolates showed genetically closed related to NCBI-BlastL. tropicawith accession numberAB678350.1. Generally, the analysis of kDNA nitrogen bases sequences showed that all of samples were consistent with those recorded at the NCBI.

Conclusion

The kDNA minicircle sequences analysis results showed mismatching of the local isolates decrease whenever approached from the Iranian border. In addition, genetic heterogeneity diagnosis is important for detection of therapy, control and epidemiological studies.
High performance of a novel antigen detection test on nasopharyngeal specimens for SARS-CoV-2 infection diagnosis: a prospective study
Authors: Courtellemont L. , Guinard J. , Guillaume C. , Giaché S. , Rzepecki V. , Seve A. , Gubavu C. , Baud K. , Helloco C. Le , Cassuto G.N. , Pialoux G. , Hocqueloux L. , Prazuck T.
Published: November 2020

Introduction

The SARS-CoV-2 pandemic has become a major public health issue worldwide. Developing and evaluating rapid and easy-to-perform diagnostic tests is an absolute priority. The current study was designed to assess diagnostic performances of an antigen-based rapid detection test (COVID-VIRO®) in a real-life setting.

Methods

Two nasopharyngeal specimens of symptomatic or asymptomatic adult patients hospitalized in the Infectious Diseases Department or voluntarily accessing the COVID-19 Screening Department of the Regional Hospital of Orléans, France, were concurrently collected. COVID VIRO® diagnostic specificity and sensitivity were assessed in comparison to real-time reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) results. A subset of patients underwent an additional oropharyngeal and/or a saliva swab for rapid testing.

Results

121 patients already having a confirmed infection and 127 patients having no evidence of recent or ongoing infection were enrolled, for a total of 248 couple of nasopharyngeal swab specimens. Overall COVID-VIRO® sensitivity was 96.7% (IC: 93.5%-99.9%). In asymptomatic patients, symptomatic patients having symptoms for more than 4 days and those having a RT-qPCR Cycle threshold value ≥32, sensitivity was of 100%, 95.8% and 91.9% respectively. The concordance between RT-qPCR and COVID VIRO® rapid test was 100% for the 127 patients with no SARS-CoV-2 infection.

Conclusion

COVID-VIRO® test had 100% specificity and above 95% sensitivity, better than WHO recommendations (specificity ≥97-100%, sensitivity ≥80%). These rapid tests are particularly interesting for large-scale screening in Emergency Department, low resource settings and airports.
COVID-Anosmia Checker: A rapid and low-cost alternative tool for mass screening of COVID-19
Authors: Basu Budhaditya , Riya Paul Ann , Issac Joby , Parvathy Surendran , Nair Biju Surendran , Tokdar Pradipta , Kumar Devika Sanal , Kulkarni Pranav Ravi , Hanumanram Gowtham , Jagadeesan Mohanan , Suthakaran Prasanna Karthik , Nair Lal Devayani Vasudevan , Vennila Rosy , Kannan Rajendran , Kaimal Balarama , Anoop Gopa Kumar , Joseph Iype , Nair Radhakrishnan , George Saji , James Jackson , Pillai Madhavan Radhakrishna
Published: November 2020

Background

COVID-19 curve can be flattened by adopting mass screening protocols with aggressive testing and isolating infected populations. The current approach largely depends on RT-PCR/rapid antigen tests that require expert personnel resulting in higher costs and reduced testing frequency. Loss of smell is reported as a major symptom of COVID-19, however, a precise olfactory testing tool to identify COVID-19 patient is still lacking.

Methods

To quantitatively check for the loss of smell, we developed an odor strip, “COVID-Anosmia checker”, spotted with gradients of coffee and lemon grass oil. We validated its efficiency in healthy and COVID-19 positive subjects. A trial screening to identify SARS-CoV-2 infected persons was also carried out to check the sensitivity and specificity of our screening tool.

Findings

It was observed that COVID positive participants were hyposmic instead of being anosmic when they were subjected to smelling higher odor concentration. Our tool identified 97% of symptomatic and 94% of asymptomatic COVID-19 positive subjects after excluding most confounding factors like concurrent chronic sinusitis. Further, it was possible to reliably predict COVID-19 infection by calculating a loss of smell score with 100% specificity. We coupled this tool with a mobile application, which takes the input response from the user, and can readily categorize the user in the appropriate risk groups.

Conclusion

Loss of smell can be used as a reliable marker for screening for COVID-19. Our tool can be used for first-line screening to trace out COVID-19 infection effectively. It can be used in difficult to reach geographical locations.
CD64 and CD169 could help differentiate bacterial from viral infections in Emergency Department
Authors: Bourgoin Pénélope , Soliveres Thomas , Barbaresi Alexandra , Loundou Anderson , Arnoux Isabelle , Bernot Denis , Morange Pierre-Emmanuel , Michelet Pierre , Malergue Fabrice , Markarian Thibaut
Published: November 2020

Background

The identification of a bacterial, viral or even non-infectious cause is essential in the management of febrile syndrome in the emergency department (ED) setting, especially in epidemic contexts such as flu or CoVID-19.

Objectives

The aim of this study was to assess discriminative performances of two biomarkers, CD64 on neutrophils (nCD64) and CD169 on monocytes (mCD169), using a new flow cytometry procedure, in patients presenting with fever to the ED. Human leucocyte antigen-DR on monocytes (mHLA-DR), HLA-ABC ratio (rHLA-ABC), and CD64 on monocytes (mCD64) were also assessed.

Methods

85 adult patients presenting with potential infection were included during the 2019 flu season in the ED of La Timone Hospital. They were divided into four diagnostic outcomes according to their clinical records: no-infection, bacterial infection, viral infection and co-infection.

Results

mCD169 was elevated in patients suffering from Flu A virus or Respiratory Syncytial Virus, while nCD64 was mainly found elevated in subjects with Streptococcus pneumoniae. In total, 38 (45%) patients were diagnosed with bacterial infections, 11 (13%) with viral infections and 29 (34%) with co-infections. nCD64 and mCD169 showed 90% and 80% sensitivity, and 78% and 91% specificity, respectively, for identifying patients with bacterial or viral infections. Other biomarkers had lower discriminative performances.

Conclusions

nCD64 and mCD169 have potential for accurately distinguishing bacterial and acute viral infections. Combined in an easy and rapid flow cytometry procedure, they constitute a potential improvement for infection management in the ED setting, and could even help for the triage of patients during emerging epidemics.
They’re Dying in the Suburbs: COVID-19 Cases and Deaths by Geography in Louisiana (USA)
Authors: Schnake-Mahl Alina , Bilal Usama
Published: November 2020

The national COVID-19 conversation in the US has mostly focused on urban areas, without sufficient examination of another geography with large vulnerable populations: the suburbs. While suburbs are often thought of as areas of uniform affluence and racial homogeneity, over the past 20 years, poverty and diversity have increased substantially in the suburbs. In this study, we compare geographic and temporal trends in COVID-19 cases and deaths in Louisiana, one of the few states with high rates of COVID-19 during both the spring and summer. We find that incidence and mortality rates were initially highest in New Orleans. By the second peak, trends reversed: suburban areas experienced higher rates than New Orleans and similar rates to other urban and rural areas. We also find that increased social vulnerability was associated with increased positivity and incidence during the first peak. During the second peak, these associations reversed in New Orleans while persisting in other urban, suburban, and rural areas. The work draws attention to the high rates of COVID-19 cases and deaths in suburban areas and the importance of metropolitan-wide actions to address COVID-19.

Registration

N/A

Funding source

NIH (DP5OD26429) and RWJF (77644)

Code and data availability

Code for replication along with data is available here: https://github.com/alinasmahl1/COVID_Louisiana_Suburban/.
U-shaped-aggressiveness of SARS-CoV-2: Period between initial symptoms and clinical progression to COVID-19 suspicion. A population-based cohort study
Authors: Morgenstern-Kaplan Dan , Buitano-Tang Bruno , Martínez-Gil Mercedes , Zaldívar-Pérez Pavón Andrea , Talavera Juan O.
Published: November 2020

Background

Early identification of different COVID-19 clinical presentations may depict distinct pathophysiological mechanisms and guide management strategies.

Objective

To determine the aggressiveness of SARS-CoV-2 using symptom progression in COVID-19 patients.

Design

Historic cohort study of Mexican patients. Data from January-April 2020 were provided by the Health Ministry.

Setting

Population-based. Patients registered in the Epidemiologic Surveillance System in Mexico.

Participants

Subjects who sought medical attention for clinical suspicion of COVID-19. All patients were subjected to RT-PCR testing for SARS-CoV-2.

Measurements

We measured the Period between initial symptoms and clinical progression to COVID-19 suspicion (PISYCS) and compared it to the primary outcomes (mortality and pneumonia).

Results

65,500 patients were included. Reported fatalities and pneumonia were 2176 (3.32%), and 11568 (17.66%), respectively. According to the PISYCS, patients were distributed as follows: 14.89% in <24 hours, 43.25% between 1-3 days, 31.87% between 4-7 days and 9.97% >7 days. The distribution for mortality and pneumonia was 5.2% and 22.5% in <24 hours, 2.5% and 14% between 1-3 days, 3.6% and 19.5% between 4-7 days, 4.1% and 20.6% >7 days, respectively (p<0.001). Adjusted-risk of mortality was (OR [95% CI], p-value): <24 hours= 1.75 [1.55-1.98], p<0.001; 1-3 days= 1 (reference value); 4-7 days= 1.53 [1.37-1.70], p<0.001; >7 days= 1.67 [1.44-1.94], p<0.001. For pneumonia: <24 hours= 1.49 [1.39-1.58], p<0.001; 1-3 days= 1; 4-7 days= 1.48 [1.41-1.56], p<0.001; >7 days= 1.57 [1.46-1.69], p<0.001.

Limitations

Using a database fed by large numbers of people carries the risk of data inaccuracy. However, this imprecision is expected to be random and data are consistent with previous studies.

Conclusion

The PISYCS shows a U-shaped SARS-CoV-2 aggressiveness pattern. Further studies are needed to corroborate the time-related pathophysiology behind these findings.
Use of a systems engineering framework to assess perceptions and practices about antimicrobial resistance of workers on large dairy farms in Wisconsin
Authors: Kates Ashley E. , Knobloch Mary Jo , Konkel Ali , Young Amanda , Steinberger Andrew , Shutske John , Ruegg Pamela L. , Sethi Ajay K. , Goldberg Tony , de Campos Juliana Leite , Suen Garret , Safdar Nasia
Published: November 2020

We studied farmworker practices potentially contributing to transmission of bacteria and antimicrobial resistant genes (ARGs) among animals and farm workers to identify human behavioral interventions to reduce exposure risk. Ten focus groups were conducted on eight farms to explore potentially high-risk practices and farmworker knowledge and experiences with antimicrobial use and resistance using the Systems Engineering in Patient Safety (SEIPS) framework. Farmworkers were asked to describe common tasks and the policies guiding these practices. We found workers demonstrated knowledge of the role of antibiotic stewardship in preventing the spread of ARGs. Knowledge of various forms of personal protective equipment was higher for workers who commonly reported glove-use. Knowledge regarding the importance of reducing ARG transmission varied but was greater than previously reported. Programs to reduce ARG spread on dairy farms should focus on proper hand hygiene and personal protective equipment use but at the level of knowledge, beliefs, and practices.
The association between socioeconomic status and mobility reductions in the early stage of England’s COVID-19 epidemic
Authors: Lee Won Do , Qian Matthias , Schwanen Tim
Published: November 2020

This study uses mobile phone data to examine how socioeconomic status was associated with the extent of mobility reduction during the spring 2020 lockdown in England in a manner that considers both potentially confounding effects and spatial dependency and heterogeneity. It shows that socioeconomic status as approximated through income and occupation was strongly correlated with the extent of mobility reduction. It also demonstrates that the specific nature of the association of socioeconomic status with mobility reduction varied markedly across England. Finally, the analysis suggests that the ability to restrict everyday mobility in response to a national lockdown is distributed in a spatially uneven manner, and may need to be considered a luxury or, failing that, a tactic of survival for specific social groups.
Simulating Pandemic Disease Spread and the Impact of Interventions in Complex Societal Networks
Authors: Mytelka Daniel S.
Published: November 2020

Introduction

Projecting disease spread is challenging because of the heterogeneous nature of human interactions, including both natural societal interactions and how they change in response to pandemics. Simulations can provide important guidance regarding the likely impact of interventions on an assumed base case.

Methods

This paper uses assumptions based on the COVID-19 pandemic to construct a Susceptible-Infectious-Recovered model representative of US society, focusing on the interrelationships of groups with differing contact networks (essential/non-essential workers and urban/non-urban populations). The model is used to explore the impact of interventions (reduced interactions, vaccinations and selective isolation) on overall and group-specific disease spread.

Results

In the absence of herd immunity, temporary interventions will only reduce the overall number of disease cases moderately and spread them over a greater period of time unless they virtually eliminate disease and no new infections occur from exogenous sources. Vaccinations can provide stronger benefit, but can be limited by efficacy and utilization rates.

Conclusions

While a highly effective and broadly utilized vaccine might halt disease spread, some combination of increased long-term surveillance and selective isolation of the most vulnerable populations might be necessary to minimize morbidity and mortality if only moderately effective vaccines are available.
The power and limitations of genomics to track COVID-19 outbreaks: a case study from New Zealand
Authors: Geoghegan Jemma L , Douglas Jordan , Ren Xiaoyun , Storey Matthew , Hadfield James , Silander Olin K , Freed Nikki E , Jelley Lauren , Jefferies Sarah , Sherwood Jillian , Paine Shevaun , Huang Sue , Sporle Andrew , Baker Michael G , Murdoch David R , Drummond Alexei J , Welch David , Simpson Colin R , French Nigel , Holmes Edward C , de Ligt Joep
Published: November 2020

Background

Real-time genomic sequencing has played a major role in tracking the global spread and local transmission of SARS-CoV-2, contributing greatly to disease mitigation strategies. After effectively eliminating the virus, New Zealand experienced a second outbreak of SARS-CoV-2 in August 2020. During this August outbreak, New Zealand utilised genomic sequencing in a primary role to support its track and trace efforts for the first time, leading to a second successful elimination of the virus.

Methods

We generated the genomes of 80% of the laboratory-confirmed samples of SARS-CoV-2 from New Zealand’s August 2020 outbreak and compared these genomes to the available global genomic data.

Findings

Genomic sequencing was able to rapidly identify that the new COVID-19 cases in New Zealand belonged to a single cluster and hence resulted from a single introduction. However, successful identification of the origin of this outbreak was impeded by substantial biases and gaps in global sequencing data.

Interpretation

Access to a broader and more heterogenous sample of global genomic data would strengthen efforts to locate the source of any new outbreaks.

Funding

This work was funded by the Ministry of Health of New Zealand, New Zealand Ministry of Business, Innovation and Employment COVID-19 Innovation Acceleration Fund (CIAF-0470), ESR Strategic Innovation Fund and the New Zealand Health Research Council (20/1018 and 20/1041).
Surveillance study of acute neurological manifestations among 439 Egyptian patients with COVID-19 in Assiut and Aswan university hospitals
Authors: Khedr Eman M , Abo-Elfetoh Noha , Daef Enas , Hassan Hebatallah M. , Amin Mariam T , Soliman Radwa K , Attia Alaa A , Zarzour Amro A , Zain Mohamed , Mohamed-Hussein Aliae , Hashem Maiada K , Hassany Sahar M , Aly Ahmed , Shoap Ahmed , Saber Mostafa
Published: November 2020

Background

COVID-19 can be accompanied by acute neurological complications of both central and peripheral nervous systems (CNS and PNS). In this study we estimate the frequency of such complications among hospital in-patients with COVID-19 in Assiut and Aswan University Hospitals.

Material and Methods

We screened all patients with suspected COVID-19 admitted from 1 June to 10 August 2020 to the university hospitals of Assiut and Aswan in Upper Egypt. Clinical and laboratory data, CT/MRI of chest and brain, and neurophysiology were performed for each patient if indicated.

Results

439 patients had confirmed/probable COVID-19; neurological manifestations occurred in 222. Of these 117 had acute neurological disease; the remainder had non-specific neuropsychiatric symptoms such as headache, vertigo, and depression. The CNS was affected in 75 patients: 55 had stroke; the others had convulsions (5), encephalitis (6), hypoxic encephalopathy (4), cord myelopathy (2), relapse of RR-MS (2), and meningoencephalitis (1). The PNS was affected in 42 patients: the majority had anosmia and ageusia (31); the others had GBS (4), peripheral neuropathy (3), myasthenia gravis (2), or myositis (2). Fever, respiratory symptoms and headache, were the most common general symptoms. Hypertensions, Diabetes Mellitus, ischemic heart disease were the most common comorbidities in patients with CNS affection.

Conclusion

In COVID⍰19, both the CNS and PNS are affected. Stroke was the most common complication for CNS and anosmia and/or ageusia were common for PNS diseases. However there were 6 cases encephalitis, 2 cases of spinal cord myelopathy, 2 cases of MG and 2 cases of myositis.
Face Mask Fit Hacks: Improving the Fit of KN95 Masks and Surgical Masks with Fit Alteration Techniques
Authors: O’Kelly Eugenia , Arora Anmol , Pirog Sophia , Pearson Charlotte , Ward James , Clarkson P John
Published: November 2020

The COVID-19 pandemic has drawn unprecedented attention to the use of masks and fabric face coverings to prevent the spread of respiratory viruses, such as SARS-CoV-2. The fit of a mask has been identified as one the primary factors in determining the effectiveness of masks. If substantial gaps exist between the mask and the wearers face, air may take the path of least resistance through gaps and avoid filtration, both during inhalation and exhalation. A number of techniques, referred to as fit hacks have emerged to improve the fit of face masks. In this paper we test a variety of fit hacks on surgical masks and KN95 masks to compare their effectiveness. We identify fit hacks which greatly improved the fit of masks, and thus their effectiveness.
Neurite orientation dispersion and density imaging in cocaine use disorder
Authors: Rasgado-Toledo Jalil , Shah Apurva , Ingalhalikar Madhura , Garza-Villarreal Eduardo A.
Published: November 2020

Cocaine use disorder (CUD) is characterized by compulsive searching for cocaine that produces cognitive deficits, including lack of inhibition and decision-making. Several studies have shown that cocaine users exhibit brain volume and diffusion-based white-matter alterations in a wide variety of brain regions. However, the non-specificity of standard volumetric and diffusion-tensor methods to detect structural micropathology may lead to wrong conclusions. To better understand microstructural pathology in CUD, we analyzed 60 CUD participants (3 female) and 43 non-CUD controls (HC; 2 female) retrospectively from our cross-sectional Mexican SUD neuroimaging dataset (SUDMEX-CONN), using multi-shell diffusion-weighted imaging and the neurite orientation dispersion and density imaging (NODDI) analysis whose aims to more accurately model micro-structural pathology. We used Viso values of NODDI that employ a three-compartment model in white (WM) and gray-matter (GM). These values were correlated with clinical measures, including psychiatric severity status, impulsive behavior and pattern of cocaine and tobacco use in the CUD group. As hypothesized, we found higher whole-brain microstructural pathology in WM and GM in CUD patients than controls. ROI analysis revealed higher Viso-NODDI values in superior longitudinal fasciculus, cingulum, hippocampus cingulum, forceps minor and Uncinate fasciculus, as well as in frontal and parieto-temporal GM structures. Correlations between significant ROIs showed a dependency of impulsivity and years of cocaine consumption over Viso-NODDI. However, we did not find correlations with psychopathology measures. Overall, microstructural pathology seems to be present in CUD both in gray and white-matter, however their clinical relevance remains questionable.
Cerebrospinal fluid total tau levels indicate aberrant neuronal plasticity in Alzheimer’s disease
Authors: Visser Pieter Jelle , Reus Lianne M. , Gobom Johan , Jansen Iris , Dicks Ellen , Tsolaki Magda , Verhey Frans R.J. , Popp Julius , Martinez-Lage Pablo , Vandenberghe Rik , Lleó Alberto , Molinuevo José Luís , Engelborghs Sebastiaan , Freund-Levi Yvonne , Froelich Lutz , Sleegers Kristel , Dobricic Valerija , Hong Shengjun , Lovestone Simon , Streffer Johannes , Vos Stephanie J.B. , Bos Isabelle ,   ADNI, Smit August B. , Blennow Kaj , Scheltens Philip , Teunissen Charlotte E. , Bertram Lars , Zetterberg Henrik , Tijms Betty M.
Published: November 2020

Alzheimer’s disease (AD) is characterised by abnormal amyloid beta and tau processing. Previous studies reported that cerebrospinal fluid (CSF) total tau (t-tau) levels vary between patients. Here we show that CSF t-tau variability is associated with distinct impairments in neuronal plasticity mediated by gene repression factors SUZ12 and REST. AD individuals with abnormal t-tau levels have increased CSF concentrations of plasticity proteins regulated by SUZ12 and REST. AD individuals with normal t-tau, on the contrary, have decreased concentrations of these plasticity proteins and increased concentrations in proteins associated with blood-brain and blood CSF-barrier dysfunction. Genomic analyses suggested that t-tau levels in part depend on genes involved in gene expression. The distinct plasticity abnormalities in AD as signaled by t-tau urge the need for personalised treatment.
‘Necessity is the mother of invention’: Specialist palliative care service innovation and practice change in response to COVID-19. Results from a multi-national survey (CovPall)
Authors: Dunleavy Lesley , Preston Nancy , Bajwah Sabrina , Bradshaw Andy , Cripps Rachel , Fraser Lorna K , Maddocks Matthew , Hocaoglu Mevhibe , Murtagh Fliss EM , Oluyase Adejoke , Sleeman Katherine E , Higginson Irene , Walshe Catherine
Published: November 2020

Background

Specialist palliative care services have a key role in a whole system response to COVID-19. There is a need to understand service response to share good practice and prepare for future care.

Aim

To map and understand specialist palliative care services innovations and practice changes in response to COVID-19 (CovPall).

Design

Online survey of specialist palliative care providers, disseminated via key stakeholders. Data collected on service characteristics, innovations and changes in response to COVID-19. Statistical analysis included frequencies, proportions and means, and free-text comments were analysed using a qualitative framework approach.

Setting/participants

Inpatient palliative care units, home nursing services, hospital and home palliative care teams from any country.

Results

458 respondents: 277 UK, 85 Europe (except UK), 95 World (except UK and Europe), 1 missing country. 54.8% provided care across 2+ settings; 47.4% hospital palliative care teams, 57% in-patient palliative care units, and 57% home palliative care teams. The crisis context meant services implemented rapid changes. Changes involved streamlining, extending and increasing outreach of services, using technology to facilitate communication, and implementing staff wellbeing innovations. Barriers included; fear and anxiety, duplication of effort, information overload, funding, and IT infrastructure issues. Enablers included; collaborative teamwork, pooling of staffing resources, staff flexibility, a pre-existing IT infrastructure and strong leadership.

Conclusions

Specialist palliative care services have been flexible, highly adaptive and have adopted a ‘frugal innovation’ model in response to COVID-19. In addition to financial support, greater collaboration is essential to minimise duplication of effort and optimise resource use.

ISRCTN16561225

https://doi.org/10.1186/ISRCTN16561225

Key Statements

What is already known about the topic?

Specialist palliative care is part of a whole healthcare system response to COVID-19.

Services need to make practice changes in response to the global pandemic.

What this paper adds

Specialist palliative care services responded rapidly to COVID-19 in both planning for change and then adapting to needs and requirements.

Services often relied on ‘improvisation’, ‘quick fixes’ and ‘making do’ when responding to the COVID-19 crisis.

Implications for practice, theory or policy

In addition to financial support, greater collaboration is essential to build organisational resilience and drive forward innovation, by minimising duplication of effort and optimising resource use.

The effectiveness and sustainability of any changes made during the crisis needs further evaluation.
Fine mapping of the HLA locus in Parkinson’s disease in Europeans
Authors: Yu Eric , Ambati Aditya , Andersen Maren Stolp , Krohn Lynne , Estiar Mehrdad A. , Saini Prabhjyot , Senkevich Konstantin , Sosero Yuri L. , Kumar Sreelatha Ashwin Ashok , Ruskey Jennifer A. , Asayesh Farnaz , Spiegelman Dan , Toft Mathias , Viken Marte K. , Sharma Manu , Blauwendraat Cornelis , Pihlstrøm Lasse , Mignot Emmanuel , Gan-Or Ziv
Published: November 2020

Objective

To fine map the association between human leukocyte antigen (HLA) genes and Parkinson’s disease (PD) that was discovered using genome-wide association studies (GWASs).

Methods

We performed a thorough analysis of the HLA locus in 13,770 PD patients, 20,214 proxy-cases and 490,861 controls of European origin. We used GWAS data to impute HLA types and performed multiple regression models to examine the association of specific HLA types, different haplotypes and specific amino acid changes. We further performed conditional analyzes to identify specific alleles or genetic variants that drive the association with PD.

Results

Four HLA types were associated with PD after correction for multiple comparisons, HLA-DQA1*03:01, HLA-DQB1*03:02, HLA-DRB1*04:01 and HLA-DRB1*04:04. Haplotype analyzes followed by amino-acid analysis and conditional analyzes suggested that the association is protective and primarily driven by three specific amino acid polymorphisms present in most HLA-DRB1*04 subtypes - 11V, 13H and 33H (OR=0.87 95%CI=0.83-0.90, p<8.23×10−9 for all three variants). No other effects were present after adjustment for these amino acids.

Conclusions

Our results suggest that specific variants in the HLA-DRB1 gene are associated with reduced risk of PD, providing additional evidence for the role of the immune system in PD. Although effect size is small and has no diagnostic significance, understanding the mechanism underlying this association may lead to identification of new targets for therapeutics development.
Effect of specific non-pharmaceutical intervention policies on SARS-CoV-2 transmission in the counties of the United States
Authors: Yang Bingyi , Huang Angkana T. , Garcia-Carreras Bernardo , Hart William E. , Staid Andrea , Hitchings Matt D.T. , Lee Elizabeth C. , Howe Chanelle J. , Grantz Kyra H. , Wesolowksi Amy , Lemaitre Joseph Chadi , Rattigan Susan , Moreno Carlos , Borgert Brooke , Dale Celeste , Quigley Nicole , Cummings Andrew , McLorg Alizée , LoMonaco Kaelene , Schlossberg Sarah , Barron-Kraus Drew , Shrock Harrison ,   UFCOVID Interventions Team, Lessler Justin , Laird Carl D. , Cummings Derek A.T.
Published: November 2020

Non-pharmaceutical interventions (NPIs) remain the only widely available tool for controlling the ongoing SARS-CoV-2 pandemic. We estimated weekly values of the effective basic reproductive number (Reff) using a mechanistic metapopulation model and associated these with county-level characteristics and NPIs in the United States (US). Interventions that included school and leisure activities closure and nursing home visiting bans were all associated with an Reff below 1 when combined with either stay at home orders (median Reff 0.97, 95% confidence interval (CI) 0.58-1.39)* or face masks (median Reff 0.97, 95% CI 0.58-1.39)*. While direct causal effects of interventions remain unclear, our results suggest that relaxation of some NPIs will need to be counterbalanced by continuation and/or implementation of others.
Genome-wide association study meta-analysis identifies three novel loci for circulating anti-Müllerian hormone levels in women
Authors: Verdiesen Renée MG , van der Schouw Yvonne T , van Gils Carla H , Verschuren WM Monique , Broekmans Frank JM , Borges Maria C , Soares Ana LG , Lawlor Deborah A , Eliassen A Heather , Kraft Peter , Sandler Dale P , Harlow Sioban D , Smith Jennifer A , Santoro Nanette , Schoemaker Minouk J , Swerdlow Anthony J , Murray Anna , Ruth Katherine S , Onland-Moret N Charlotte
Published: November 2020

Anti-Müllerian hormone (AMH) is expressed by antral stage ovarian follicles in women. Consequently, circulating AMH levels are detectable until menopause. Variation in age-specific AMH levels has been associated with breast cancer and polycystic ovary syndrome (PCOS), amongst other diseases. Identification of genetic variants underlying variation in AMH levels could provide clues about the physiological mechanisms that explain these AMH-disease associations. To date, only one variant in MCM8 has been identified to be associated with circulating AMH levels in women. We aimed to identify additional variants for AMH through a GWAS meta-analysis including data from 7049 premenopausal women of European ancestry, which more than doubles the sample size of the largest previous GWAS. We identified four loci associated with AMH levels at p < 5×10−8: the previously reported MCM8 locus and three novel signals in or near AMH, TEX41, and CDCA7. The strongest signal was a missense variant in the AMH gene (rs10417628). Most prioritized genes at the other three identified loci were involved in cell cycle regulation. Genetic correlation analyses indicated a strong positive correlation among SNPs for AMH levels and for age at menopause (rg= 0.82, FDR=0.003). Exploratory Mendelian randomization analyses did not support a causal effect of AMH on breast cancer or PCOS risk, but should be interpreted with caution as they may be underpowered and the validity of genetic instruments could not be extensively explored. In conclusion, we identified a variant in the AMH gene and three other loci that may affect circulating AMH levels in women.
The Association Between Tobacco Exposure During Pregnancy and Newborns’ Birth Weight in DKI Jakarta Community Members
Authors: Phowira Jason , Elvina Felicitas Tania , Wiguna Igor Ian , Bari Wahyudi Fathurohman Ramadhan Hanif , Medise Bernie Endyarni
Published: November 2020

Low birth weight (LBW), a major determinant of neonate morbidity and mortality, remains a global public health concern. Intrauterine exposure to tobacco has been discerned as an important risk factor for LBW. This study aims to investigate the association between parental smoking during pregnancy and LBW. An analytical cross-sectional study was conducted from December 2019 - July 2020 on a random sample of parents with child aged 0-5 years old from 5 health centers in DKI Jakarta, Indonesia. A total of 145 subjects met the criteria and were analysed. Data analysis was carried out using IBM SPSS Statistics software. In the study, 11% of infants were born with LBW. The prevalence of smoking in fathers and mothers were 55.2% and 3.4%, respectively. Paternal smoking status was significantly associated with LBW (p < 0.05). Although not statistically significant, there was a dose-response relationship between paternal number of cigarettes/day and duration of smoking with LBW. Maternal smoking status (p = 0.448) was not closely associated with LBW, which might be due limited number of actively smoking mothers. From multivariate logistic regression, paternal smoking status, premature delivery, birth order and inadequate food intake during pregnancy were significant predictors of LBW (p < 0.05).
Feasibility of collecting and processing of COVID-19 convalescent plasma for treatment of COVID-19 in Uganda
Authors: Muttamba Winters , Lusiba John , Namakula Loryndah Olive , Byakika-Kibwika Pauline , Ssali Francis , Ddungu Henry , Mugenyi Levicatus , Kiwanuka Noah , Sekibira Rogers , Kityo Cissy , Keyune Dorothy , Acana Susan , Musinguzi Ambrose , Masasi Ayub , Byamugisha Joseph , Mpanju David , Musoki Walter Jack , Tukamuhebwa Hellen Aanyu , Nakwagala Fred , Bagaya Bernard Sentalo , Kayongo Alex , Kimuli Ivan , Nantanda Rebecca , Katagira Winceslaus , Buregyeya Esther , Byanyima Rosemary , Byarugaba Baterana , Siddharthan Trishul , Mwebesa Henry , Charles Olaro , Joloba Moses Lutaakome , Bazeyo William , Kirenga Bruce
Published: November 2020

Introduction

Evidence that supports the use of COVID-19 convalescent plasma (CCP) for treatment of COVID-19 is increasingly emerging. However, very few African countries have undertaken the collection and processing of CCP. The aim of this study was to assess the feasibility of collecting and processing of CCP, in preparation for a randomized clinical trial of CCP for treatment of COVID-19 in Uganda.

Methods

In a cross-sectional study, persons with documented evidence of recovery from COVID-19 in Uganda were contacted and screened for blood donation via telephone calls. Those found eligible were asked to come to the blood donation centre for further screening and consent. Whole blood collection was undertaken from which plasma was processed. Plasma was tested for transfusion transmissible infections (TTIs) and anti-SARS CoV-2 antibody titers. SARS-CoV-2 testing was also done on nasopharyngeal swabs from the donors.

Results

192 participants were contacted of whom 179 (93.2%) were eligible to donate. Of the 179 eligible, 23 (12.8%) were not willing to donate and reasons given included: having no time 7(30.4%), fear of being retained at the COVID-19 treatment center 10 (43.5%), fear of stigma in the community 1 (4.3%), phobia for donating blood 1 (4.3%), religious issues 1 (4.4%), lack of interest 2 (8.7%) and transport challenges 1 (4.3%). The median age was 30 years and females accounted for 3.7% of the donors. A total of 30 (18.5%) donors tested positive for different TTIs. Antibody titer testing demonstrated titers of more than 1:320 for all the 72 samples tested. Age greater than 46 years and female gender were associated with higher titers though not statistically significant.

Conclusion

CCP collection and processing is possible in Uganda. However, concerns about stigma and lack of time, interest or transport need to be addressed in order to maximize donations.
Efficacy and safety of levetiracetam versus phenytoin as second line antiepileptic agent in Pediatric convulsive status epilepticus: A systematic review and meta-analysis of randomized controlled trials
Authors: Angurana Suresh Kumar , Suthar Renu
Published: November 2020

Objective

To evaluate the efficacy and safety of Levetiracetam (LEV) in comparison to phenytoin (PHT) as second line antiseizure medication (ASM) for Pediatric convulsive status epilepticus (SE).

Data source

PubMed, Embase, Google scholar, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials.

Study selection

Randomized controlled trials (RCTs) assessing LEV and PHT as second line agent for convulsive SE in children <18 years published between 1st January 2000 to 30th September 2020.

Data extraction

The data was pooled regarding the proportion of children achieving seizure cessation within 5-60 minutes of completion of study drug infusion (primary outcome); and seizure cessation within 5 minutes, time to achieve seizure cessation, seizure recurrence between 1-24 hours, intubation, and cardiovascular instability (secondary outcomes). Data was analysed using RevMan version 5.4 and quality analysis was done using Cochrane risk-of-bias tool. The study protocol was submitted to PROSPERO for registration.

Data synthesis

Eleven RCTs with 2177 children (1024 received LEV and 988 received PHT) were enrolled. Seizure cessation within 5-60 minutes was similar with both the drugs [81% in LEV vs. 76% in PHT, risk ratio (RR)=1.04, 95% CI 0.9-1.13, p=0.29]. Seizure recurrences within 1-24 hours was higher with PHT as comparison to LEV (15% vs 9%, RR=0.64, 95% CI 0.42-0.99, p=0.04). Seizure cessation within 5 minutes, time to achieve seizure cessation, requirement of intubation/mechanical ventilation, and cardiovascular instability were similar with both the drugs. Three studies had low risk of bias and eight studies had high risk of bias.

Conclusion

The efficacy and safety of LEV is not superior to PHT as second line ASM medication for Pediatric convulsive SE. However, the seizure recurrences between 1-24 hours were significantly higher with PHT in comparison to LEV.
A rapid systematic review of measures to protect older people in long term care facilities from COVID-19
Authors: Frazer Kate , Mitchell Lachlan , Stokes Diarmuid , Lacey Ella , Crowley Eibhlin , Kelleher Cecily
Published: November 2020

The global COVID-19 pandemic produced large-scale health and economic complications. Older people and those with comorbidities are particularly vulnerable to this virus, with nursing homes and long term care facilities experiencing significant morbidity and mortality associated with COVID-19 outbreaks. The aim of this rapid systematic review was to investigate measures implemented in long term care facilities to reduce transmission of COVID-19 and their effect on morbidity and mortality of residents, staff, and visitors. Databases (including MedRXiv pre-published repository) were systematically searched to identify studies reporting assessment of interventions to reduce transmission of COVID-19 in nursing homes among residents, staff, or visitors. Outcome measures include facility characteristics, morbidity data, case fatalities, and transmission rates. Due to study quality and heterogeneity, no meta-analysis was conducted. The search yielded 1414 articles, with 38 studies included. Reported interventions include mass testing, use of personal protective equipment, symptom screening, visitor restrictions, hand hygiene and droplet/contact precautions, and resident cohorting. Prevalence rates ranged from 1.2-85.4% in residents and 0.6-62.6% in staff. Mortality rates ranged from 5.3-55.3% in residents. Novel evidence in this review details the impact of facility size, availability of staff and practices of operating between multiple facilities, and for-profit status of facilities as factors contributing to the size and number of COVID-19 outbreaks. No causative relationships can be determined; however, this review provides evidence of interventions that reduce transmission of COVID-19 in long term care facilities.
The prevalence of common mental disorders among health care professionals during the COVID-19 pandemic at a tertiary Hospital in East Africa
Authors: Mulatu Hailu Abera , Tesfaye Muluken , Woldeyes Esubalew , Bayisa Tola , Fesseha Henok , Asrat Rodas
Published: November 2020

Background

Coronavirus disease 2019 (COVID-19) has resulted in unprecedented morbidity, mortality, and health system crisis leading to a significant psychological distress on healthcare workers (HCWs). The study aimed to determine the prevalence of symptoms of common mental disorders among HCWs during the COVID-19 pandemic at St. Paul’s Hospital, Ethiopia.

Methods

A self-administered cross-sectional study was conducted to collect socio-demographic information and symptoms of mental disorders using validated measurement tools. Accordingly, PHQ-9, GAD-7, ISI, and IES-R were used to assess the presence of symptoms of depression, anxiety, insomnia, and distress, respectively. Chi-square test, non-parametric, and logistic regression analysis were used to detect risk factors for common mental disorders.

Results

A total of 420 healthcare workers participated in the survey. The prevalence of depression, anxiety, insomnia, and psychological distress was 20.2%, 21.9%, 12.4%, and 15.5% respectively. Frontline HCWs had higher scores of mental health symptoms than other health care workers. Logistic regression analysis showed that being married was associated with a high level of depression. Working in a frontline position was an independent factor associated with a high-level depression, anxiety, and psychological distress.

Limitations

It is a single-centre cross-sectional study and the findings may not be generalizable or reveal causality.
A tipping point in cancer-immune dynamics leads to divergent immunotherapy responses and hampers biomarker discovery
Authors: Creemers Jeroen H.A. , Lesterhuis W. Joost , Mehra Niven , Gerritsen Winald R. , Figdor Carl G. , de Vries I. Jolanda M. , Textor Johannes
Published: November 2020

Background

Predicting treatment response or survival of cancer patients remains challenging in immuno-oncology. Efforts to overcome these challenges focus, among others, on the discovery of new biomarkers. Despite advances in cellular and molecular approaches, only a limited number of candidate biomarkers eventually enter clinical practice.

Methods

A computational modeling approach based on ordinary differential equations was used to simulate the fundamental mechanisms that dictate tumor-immune dynamics and to investigate its implications on responses to immune checkpoint inhibition (ICI) and patient survival. Using in silico biomarker discovery trials, we revealed fundamental principles that explain the diverging success rates of biomarker discovery programs.

Results

Our model shows that a tipping point – a sharp state transition between immune control and immune evasion – induces a strongly non-linear relationship between patient survival and both immunological and tumor-related parameters. In patients close to the tipping point, ICI therapy may lead to long-lasting survival benefits, whereas patients far from the tipping point may fail to benefit from these potent treatments.

Conclusion

These findings have two important implications for clinical oncology. First, the apparent conundrum that ICI induces substantial benefits in some patients yet completely fails in others could be, to a large extent, explained by the presence of a tipping point. Second, predictive biomarkers for immunotherapy should ideally combine both immunological and tumor-related markers, as a patient’s distance from the tipping point can typically not be reliably determined from solely one of these. The notion of a tipping point in cancer-immune dynamics helps to devise more accurate strategies to select appropriate treatments for cancer patients.
The use of compassionate Ivermectin in the management of symptomatic outpatients and hospitalized patients with clinical diagnosis of COVID-19 at the Medical Center Bournigal and the Medical Center Punta Cana, Rescue Group, Dominican Republic, from may 1 to august 10, 2020
Authors: Morgenstern José , Redondo José N. , De León Albida , Canela Juan Manuel , Torres Nelson , Tavares Johnny , Minaya Miguelina , López Óscar , María Plácido Ana , Castillo Ana , Peña Cruz Rafael , Merette Yudelka , Toribio Marlenin , Francisco Juan Asmir , Roca Santiago
Published: November 2020

No antiviral has been shown to reduce mortality in SARS-COV-2 patients to date. In the present observational and retrospective report, 3,099 patients with a definitive or highly probable diagnosis of infection due to COVID-19 were evaluated between May 1st to August 10th, 2020, at Centro Medico Bournigal (CMBO) and Centro Medico Punta Cana (CMPC), and all received compassionate treatment with Ivermectin. A total of 2,706 (87.3%) were discharged for outpatient treatment, all with mild severity of the infection. In 2,688 (99.33%) with outpatient treatment, the disease did not progress to warrant further hospitalization and there were no deaths. In 16 (0.59%) with outpatient treatment, it was necessary their subsequent hospitalization to a room without any death. In 2 (0.08%) with outpatient treatment, it was necessary their admission to the Intensive Care Unit (ICU) and 1 (0.04%) patient died. There were 411 (13.3%) patients hospitalized, being admitted at a COVID-19 room with a moderate disease 300 (9.7%) patients of which 3 (1%) died; and with a severe to critical disease were hospitalized in the ICU 111 (3.6%), 34 (30.6%) of whom died. The mortality percentage of patients admitted to the ICU of 30.6%, is similar with the percentage found in the literature of 30.9%. Total mortality was 37 (1.2%) patients, which is much lower than that reported in world statistics, which are around 3%.