bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibodies specific to SARS-CoV-2 proteins N, S and E in COVID-19 patients in the normal population and in historical samples
Authors: Szymczak Aleksander , Jędruchniewicz Natalia , Torelli Alessandro , Kaczmarzyk-Radka Agata , Coluccio Rosa , Kłak Marlena , Konieczny Andrzej , Ferenc Stanisław , Witkiewicz Wojciech , Montomoli Emanuele , Miernikiewicz Paulina , Bąchor Remigiusz , Dąbrowska Krystyna
Published: November 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally; recognition of immune responses to this virus will be crucial for coronavirus disease 2019 (COVID-19) control, prevention and treatment. We comprehensively analysed IgG and IgA antibody responses to the SARS-CoV-2 nucleocapsid protein (N), spike protein domain 1 (S1) and envelope protein (E) in: SARS-CoV-2-infected patient, healthy, historical and pre-epidemic samples, including patients’ medical, epidemiological and diagnostic data, virus-neutralizing capability and kinetics. N-specific IgG and IgA are the most reliable diagnostic targets for infection. Serum IgG levels correlate to IgA levels. Half a year after infection, anti-N and anti-S1 IgG decreased, but sera preserved virus-inhibitory potency; thus, testing for IgG may underestimate the protective potential of antibodies. Historical and pre-epidemic sera did not inhibit SARS-CoV-2, thus its circulation before the pandemic and a protective role from antibodies pre-induced by other coronaviruses cannot be confirmed by this study
Electroconvulsive therapy effects on anhedonia and reward circuitry anatomy: a dimensional structural neuroimaging approach
Authors: Cano Marta , Lee Erik , Worthley Alexis , Ellard Kristen , Barbour Tracy , Soriano-Mas Carles , Camprodon Joan A.
Published: November 2021

Anhedonia is a core symptom of major depressive disorder (MDD) resulting from maladaptive reward processing. Electroconvulsive therapy (ECT) appears to be an effective treatment for patients with treatment-resistant depression (TRD). However, no previous neuroimaging studies have taken a dimensional approach to assess whether ECT-induced gray matter (GM) volume changes are specifically related to improvements in anhedonia and positive valence emotional constructs. Here we aimed to assess the relationship between right unilateral (RUL) ECT-induced brain volumetric changes and improvement in anhedonia and reward processing in patients with TRD. We evaluated 15 patients at two time points (before the first ECT session and after acute ECT completion) using magnetic resonance imaging (MRI), clinical scales (i.e., Quick Inventory of Depressive Symptomatology [QIDS] for syndromal depression severity and Snaith-Hamilton Pleasure Scale [SHAPS] for anhedonia) and the Temporal Experience of Pleasure Scale (TEPS) for anticipatory and consummatory experiences of pleasure. Patients with TRD showed a significant improvement in anhedonia symptoms and both anticipatory and consummatory pleasure after RUL ECT completion. Moreover, GM volume increases within the right reward system were related to anhedonia responders and, specifically, improvement in anticipatory (but not consummatory) reward. We highlight the importance of a dimensional and circuit-based approach to understanding target engagement and the mechanism of action of ECT, with the goal to define symptom- and circuit-specific response biomarkers for device neuromodulation therapies.
The Middle-Out Perspective – an approach to formalise ‘normal practice’ in public health advocacy
Authors: Mindell Jennifer S , Parag Yael , Bartington Suzanne E. , Stoll Laura , Barlow James , Janda Kathryn B.
Published: November 2021

Background

The Middle-Out Perspective (MOP) provides a lens to examine how actors positioned between government (top) and individuals (bottom) act to promote broader societal changes from the middle-out (rather than the top-down or bottom-up). The MOP has been used in recent years in the fields of energy, climate change, and development studies. Public health practitioners involved with advocacy activities and creating alliances to amplify health promotion actions will be familiar with the general MOP concept if not the formal name.

Methods

This paper introduces the MOP conceptual framework and customises it for a public health audience by positioning it among existing concepts and theories for actions within public health. Using two UK case studies (increasing signalised crossing times for pedestrians and the campaign for smoke-free legislation), we illustrate who middle actors are and what they can do to result in better public health outcomes.

Results

These cases studies show that involving a wider range of middle actors, including those not traditionally involved in improving the public’s health, can broaden the range and reach of organisations and individuals involving in advocating for public health measures. They also demonstrate that middle actors are not neutral. They can be recruited to improve public health outcomes, but they may also be exploited by commercial interests to block healthy policies or even promote a health-diminishing agenda.

Conclusions

Using the MOP as a formal approach can help public health organisations and practitioners consider potential ‘allies’ from outside traditional health-related bodies or professions. Formal mapping can expand the range of who are considered potential middle actors for a particular public health issue. By applying the MOP, public health organisations and staff can enlist the additional leverage that is brought to bear by involving additional middle actors in improving the public’s health.

Graphical abstract
First-generation clinical dual-source photon-counting CT: ultra-low dose quantitative spectral imaging
Authors: Liu Leening P. , Shapira Nadav , Sahbaee Pooyan , Schnall Mitchell , Litt Harold I. , Noël Peter B.
Published: November 2021

Objective

Evaluation of quantification capabilities at ultra-low radiation dose levels of a first-generation dual-source Photon-Counting Computed Tomography (PCCT) compared to a dual-source dual-energy CT (DECT) scanner.

Methods

A multi-energy CT phantom was imaged with and without extension ring on both scanners over a range of radiation dose levels (CTDIvol 0.4 - 15.0 mGy). Scans were performed in different modes of acquisition for PCCT with 120 kVp and DECT with 70/Sn150 kVp and 100/Sn150 kVp. Various tissue inserts were used to characterize the precision and repeatability of Hounsfield Units (HUs) on virtual mono-energetic images between 40 and 190 keV. Image noise was additionally investigated at ultra-low radiation dose to illustrate PCCT’s ability to remove electronic background noise.

Results

Our results demonstrate high precision of HU measurements for a wide range of inserts and radiation exposure levels with PCCT. We report high performance for both scanners across a wide range of radiation exposure levels with PCCT outperforming at low exposures compared to DECT. PCCT scans at lowest radiation exposures illustrate significant reduction in electronic background noise, with a mean percent reduction of 74% (p-value ∼10−8) compared to the 70/Sn150 kVp and 60% (p-value ∼10−6) compared to the 100/Sn150 kVp.

Conclusions

This paper reports first experiences with a clinical dual-source PCCT scanner with Quantum technology. PCCT provides reliable HUs without disruption from electronic background noise for a wide range of dose values. Diagnostic benefits are not only for quantification at ultra-low-dose but also for imaging of obese patients.

Key Points

PCCT scanners with Quantum technology provide precise and reliable quantitative Hounsfield Units at ultra-low-dose levels.

Influence of electronic background noise can be removed at ultra-low dose acquisitions with PCCT.

Both spectral platforms have high performance along a wide range of radiation exposure levels with PCCT outperforming at low radiation exposures.
COVID-19 Health Care Behaviour in The Gambia: a cross-sectional survey of 205 adults who went through mandatory institutional quarantine
Authors: Johm Penda , Nkereuwem Oluwatosin , Manjang Aji-Matty , Ceesay Omar , Leigh Lamin , Ceesay Amie , Bittaye Mustapha , Roberts Adeyemi , Manjang Buba , Sambou Sana , Sanneh Sainey , Saidy Lamin , Saidy Binta , Kampmann Beate
Published: November 2021

Background

To control the spread of the novel Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome novel Coronavirus-2 (SARS-CoV-2), countries around the world subsequently implemented several public health measures, including the adoption of mandatory institutional quarantine for close contacts. This study explored the experiences of individuals who underwent institutional quarantine in The Gambia to inform government measures to increase its effectiveness and reduce its associated negative impacts.

Methods

Questionnaires were administered via mobile phone call with data collectors calling and directly recording participant responses on a tablet in an electronic online form developed in REDCap (Research Electronic Data Capture). The questionnaire contained questions on COVID-19 related knowledge, health care behaviour, attitudes, perceptions and stigma. Data were analysed using STATA v.13 (Stata Corp, College Station, TX, USA).

Results

In total, 205 adults who observed the mandatory institutional quarantine were interviewed. There was varied knowledge of COVID-19 causes, spread, symptoms, diagnosis, treatment, and severity. Participants believed the purpose of quarantine was monitoring for signs and symptoms of coronavirus disease, testing for SARS-CoV-2, separation from the community, and protection from coronavirus disease. While a majority reported positive experiences while in quarantine, some expressed prominent dissatisfaction related to the essential services and quality of care provided. Different forms of stigma were also experienced before, during and after the quarantine experience.

Conclusion

This study provides important information on quarantine experiences in The Gambia during the global COVID-19 pandemic. The Ministry of Health in The Gambia and other countries could improve the experience of quarantined individuals by consistently providing psychosocial support, compensation for loss of earnings, and timely provision of SARS-CoV-2 test results. Furthermore, stigma experiences and practices should be addressed during and after individuals stay in quarantine via the provision of psychosocial support.
Persistent Autoimmune Activation and Proinflammatory State in Post-COVID Syndrome
Authors: Acosta-Ampudia Yeny , Monsalve Diana M , Rojas Manuel , Rodríguez Yhojan , Zapata Elizabeth , Ramírez-Santana Carolina , Anaya Juan-Manuel
Published: November 2021

Background

The immunopathological pathways enabling post-COVID syndrome (PCS) development are not entirely known. We underwent a longitudinal analysis of patients with COVID-19 who developed PCS aiming to evaluate the autoimmune and immunological status associated with this condition.

Methods

Thirty-three patients were included for longitudinal clinical and autoantibody analyses of whom 12 patients were assessed for cytokines and lymphocyte populations. Patients were followed during 7-11 months after acute COVID-19. Autoimmune profile and immunological status were evaluated mainly by enzyme-linked-immunosorbent assays and flow cytometry.

Results

Latent autoimmunity and overt autoimmunity persisted over time. A proinflammatory state was observed in patients with PCS characterized by upregulated IFN-α, TNF-α, G-CSF, IL-17A, IL-6, IL-1β, and IL-13, whereas IP-10 was decreased. In addition, PCS was characterized by increased levels of Th9, CD8+ effector T cells, naive B cells, and CD4+ effector memory T cells. Total levels of IgG S1-SARS-CoV-2 antibodies remained elevated over time.

Discussion

The clinical manifestations of PCS are associated with the persistence of a proinflammatory, and effector phenotype induced by SARS-CoV-2 infection. This long-term persistent immune activation may contribute to the development of latent and overt autoimmunity. Results suggest the need to evaluate the role of immunomodulation in the treatment of PCS.
Prescribing of antibiotics and other drugs to children from birth to age 5 in the United States: an observational study
Authors: Kissler Stephen M. , Wang Bill , Mehrotra Ateev , Barnett Michael , Grad Yonatan H.
Published: November 2021

Objectives

To inform efforts to reduce pediatric antibiotic use, we measured cumulative pediatric prescriptions for antibiotics and non-antibiotics and how this varies across geography and patient subgroups.

Design

Observational study.

Setting

United States, 2008-2018.

Participants

207,814 children under age 5 born in the United States between 2008 and 2013 with private medical insurance coverage.

Interventions

None.

Main outcome measures

Study outcomes included (1) the cumulative number of prescriptions received per child by age 5, (2) the proportion of these prescriptions that were attributable to respiratory infections, (3) the proportion of children who received at least one prescription by age 5, and (4) the fraction of total prescriptions received by the top 20% of prescription recipients.

Results

Children received a mean of 8.21 (95% confidence interval [CI] (8.19, 8.22)) prescriptions for antibiotics and 9.81 (95% CI 9.80, 9.82) prescriptions for non-antibiotics by age five. Most antibiotic prescriptions (64%, 95% CI 63, 65) and many non-antibiotic prescriptions (25%, 95% CI 24, 26) were associated with outpatient visits for respiratory infections. By age 5, 93.8% (95% CI 93.4, 94.2) of children had received at least one antibiotic prescription while 88.3% (95% CI 87.9, 88.7) had received at least one prescription for a non-antibiotic. The top 20% of antibiotic prescription recipients accounted for 50.6% of all antibiotic prescriptions, and the top 20% of non antibiotic prescription recipients accounted for 64.2% of all non-antibiotic prescriptions. Relative to other regions, the South featured higher prescribing rates and earlier time to first prescription.

Conclusions

Children in the US receive a substantial number of antibiotics and other prescription drugs early in their lives, largely related to respiratory infections.
Healthcare workers’ SARS-CoV-2 infection rates during the second wave of the pandemic: prospective follow-up study
Authors: Würtz Anne Mette , Kinnerup Martin B. , Pugdahl Kirsten , Schlünssen Vivi , Vestergaard Jesper Medom , Nielsen Kent , Cramer Christine , Bonde Jens Peter , Biering Karin , Carstensen Ole , Kærgaard Hansen Karoline , Dalbøge Annett , Flachs Esben Meulengracht , Hansen Mette Lausten , Thulstrup Ane Marie , Würtz Else Toft , Kjærsgaard Mona , Christensen Mette Wulf , Kolstad Henrik Albert
Published: November 2021

Objectives

To assess if healthcare workers during the second wave of the coronavirus disease 2019 (COVID-19) pandemic had increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates following close contact with patients, co-workers and persons outside work with COVID-19.

Methods

A prospective cohort study of 5985 healthcare workers from Denmark were followed November 2020 to April 2021 and provided day-by-day information on COVID-19 contacts. SARS-CoV-2 infection was defined by the first positive polymerase chain reaction (PCR) test ever.

Results

159 positive and 35 996 negative PCR tests were recorded during 514 165 person-days. The SARS-CoV-2 infection rate following close contact with COVID-19 patients 3-7 days earlier was 153.7 per 100,000 person-days corresponding with an incidence rate ratio (IRR) of 3.17 (40 cases, 95% CI 2.15 - 4.66) compared with no close contact. IRRs following close contact with co-workers and persons outside work with COVID-19 were 2.54 (10 cases, 95% CI 1.30 - 4.96) and 17.79 (35 cases, 95% CI 12.05 - 26.28). The estimates for close contact with COVID-19 patients, co-workers or persons outside work were mutually adjusted.

Conclusions

Despite strong focus on preventive measures during the second wave of the pandemic, healthcare workers were still at increased risk of SARS-CoV-2 infection when in close contact with patients with COVID-19. Among all health care workers, the numbers affected due to close patient contact were comparable to the numbers affected following COVID-19 contact outside work.
How many relevant SARS-CoV-2 variants might we expect in the future?
Authors: Littera Roberto , Melis Maurizio
Published: November 2021

Abstract

Objectives

The emergence of new SARS-CoV-2 variants is a major challenge in the management of Covid-19 pandemic. A crucial issue is to quantify the number of variants which may represent a potential risk for public health in the future.

Methods

We fitted the data on the most relevant SARS-CoV-2 variants recorded by the World Health Organization (WHO). The function exploited for the fit is related to the total number of infected subjects in the world since the start of the epidemic.

Results

We found that the number of new relevant variants per ten million cases diminished by 30.4% between March 2020 and March 2022 (from 1.25 to 0.87). However, the decrease is now very slow and a further reduction by 10% would happen only for 5.6 billion infections in the world, i.e. ten times the cases from the beginning of the epidemic up to June 2022.

Conclusion

Our simple mathematical model can provide an estimate of the number of relevant SARS-CoV-2 variants as the cumulative number of cases increases worldwide and may represent a useful tool in planning strategies to effectively contrast the pandemic.
Healthcare workers benefit from second dose of COVID-19 mRNA vaccine: Effects of partial and full vaccination on sick leave duration and symptoms
Authors: Strum Earl , Casagrande Yolee , Newton Kim , Unger Jennifer B.
Published: November 2021

Importance

In addition to morbidity and mortality of individuals, COVID-19 can affect staffing among organizations. It is important to determine whether vaccination can mitigate this burden. Objective: This study examined the association between COVID-19 vaccination status and time until return to work among 952 healthcare workers (HCW) who tested positive for COVID-19.

Design

Data were collected prospectively between December 2020 and July 2021. HCW who tested positive for COVID-19 completed an initial interview and were followed until they returned to work.

Setting

An academic campus in Southern California consisting of two large hospitals and multiple outpatient clinics and other facilities.

Participants

Clinical and nonclinical HCW who tested positive for COVID-19 during the study period (N=952, mean age=39.2 years, 69% female, 45% Hispanic, 14% white, 14% Asian/Pacific Islander, 5% African American, and 21% other race/ethnicity).

Exposure

COVID-19 vaccination status (unvaccinated, partially vaccinated, or fully vaccinated)

Main Outcome Measures

Days until return to work, presenting symptom

Results

Return-to-work time for fully vaccinated HCWs (mean=10.9 days) was significantly shorter than that of partially vaccinated HCWs (15.5 days), which in turn was significantly shorter than that of unvaccinated HCWs (18.0 days). Fully vaccinated HCWs also showed milder symptom profiles compared to partially vaccinated and unvaccinated HCWs.

Conclusions and Relevance

COVID-19 vaccination has the potential to prevent long absences from work and the adverse financial, staffing, and managerial consequences of these long absences.

KEY POINTS

Question

Do healthcare workers (HCW) who are vaccinated against COVID-19 return to work sooner and experience milder symptoms compared with unvaccinated HCW?

Findings

Among 952 healthcare workers who tested positive for COVID-19 between December 2020 and July 2021, return-to-work time for fully vaccinated HCWs (mean=10.9 days) was significantly shorter than that of partially vaccinated HCWs (15.5 days), which in turn was significantly shorter than that of unvaccinated HCWs (18.0 days). Fully vaccinated HCWs also showed milder symptom profiles compared to partially vaccinated and unvaccinated HCWs.

Meaning

COVID-19 vaccination has the potential to prevent long absences from work and the adverse financial, staffing, and managerial consequences of these long absences.
Quantitative Digitography Solves the Remote Measurement Problem in Parkinson’s disease
Authors: Wilkins K.B. , Petrucci M.N. , Kehnemouyi Y. , Velisar A. , Han K. , Orthlieb G. , Trager M.H. , O’Day J.J. , Aditham S. , Bronte-Stewart H.M.
Published: November 2021

Background

Assessment of motor signs in Parkinson’s disease (PD) has required an in-person examination. However, 50% of people with PD do not have access to a neurologist. Wearable sensors can provide remote measures of some motor signs but require continuous data acquisition for several days. A major unmet need is reliable metrics of all cardinal motor signs, including rigidity, from a simple short active task that can be performed remotely or in the clinic.

Objective

Investigate whether thirty seconds of repetitive alternating finger tapping (RAFT) on a portable quantitative digitography (QDG) device, which measures amplitude and timing, produces reliable metrics of all cardinal motor signs in PD

Methods

Ninety-six individuals with PD and forty-two healthy controls performed a thirty-second QDG-RAFT task and clinical motor assessment. Eighteen individuals were followed longitudinally with repeated assessments for an average of three years and up to six years.

Results

QDG-RAFT metrics differentiated individuals with PD from controls and provided validated metrics for total motor disability (MDS-UPDRS III) and for rigidity, bradykinesia, tremor, gait impairment and freezing of gait (FOG). Additionally, QDG-RAFT tracked disease progression over several years off therapy, and differentiated akinetic rigid from tremor dominant phenotypes, as well as people with from those without FOG.

Conclusions

QDG is a reliable technology, which will improve access to care, allows complex remote disease management, and accurate monitoring of disease progression over time in PD. QDG-RAFT also provides the comprehensive PD motor metrics needed for therapeutic trials.
Enoxaparin for thromboprophylaxis in hospitalized COVID-19 patients: comparison of 40 mg o.d.vs40 mg b.i.d. The X-COVID19 Randomized Clinical Trial
Authors: Morici Nuccia , Podda GianMarco , Birocchi Simone , Bonacchini Luca , Merli Marco , Trezzi Michele , Massaini Gianluca , Agostinis Marco , Carioti Giulia , Serino Francesco Saverio , Gazzaniga Gianluca , Barberis Daniela , Antolini Laura , Valsecchi Maria Grazia , Cattaneo Marco
Published: November 2021

It is uncertain whether higher doses of anticoagulants than recommended for thromboprophylaxis are necessary in COVID-19 patients hospitalized in general wards. This is a multicentre, open-label, randomized trial performed in 9 Italian centres, comparing 40 mg b.i.d. vs 40 mg o.d. enoxaparin in COVID-19 patients, between April 30, 2020 and April 25, 2021. Primary efficacy outcome was in-hospital incidence of venous thromboembolism (VTE): asymptomatic or symptomatic proximal deep vein thrombosis (DVT) diagnosed by serial compression ultrasonography (CUS), and/or symptomatic pulmonary embolism (PE) diagnosed by computed tomography angiography (CTA). Secondary endpoints included each individual component of the primary efficacy outcome and a composite of death, VTE, mechanical ventilation, stroke, myocardial infarction, admission to ICU. Safety outcomes included major bleeding. The study was interrupted prematurely due to slow recruitment. We included 183 (96%) of the 189 enrolled patients in the primary analysis (91 in b.i.d., 92 in o.d.). Primary efficacy outcome occurred in 6 patients (6·5%, 0 DVT, 6 PE) in the o.d. group and 0 in the b.id. group (ARR 6·5, 95% CI, 1·5-11·6). Absence of concomitant DVT and imaging characteristics suggest that most pulmonary artery occlusions were actually caused by local thrombi rather than PE. Statistically non-significant differences in secondary and safety endpoints were observed, with two major bleeding events in each arm. In conclusion, no DVT developed in COVID-19 patients hospitalized in general wards, independently of enoxaparin dosing used for thromboprophylaxis. Pulmonary artery occlusions developed only in the o.d. group. Our trial is underpowered and with few events.

REGISTRATION

ClinicalTrials.govIdentifier:NCT04366960

Ethics Commettee approvation number

75/2020
Managing electromyogram contamination in scalp recordings: an approach identifying reliable beta and gamma EEG features of psychoses or other disorders
Authors: Pope Kenneth J. , Lewis Trent W. , Fitzgibbon Sean P. , Janani Azin S. , Grummett Tyler S. , Williams Patricia A.H. , Battersby Malcolm , Bastiampillai Tarun , Whitham Emma M. , Willoughby John O.
Published: November 2021

Objective

In publications on the electroencephalographic (EEG) features of psychoses and other disorders, various methods are utilised to diminish electromyogram (EMG) contamination. The extent of residual EMG contamination using these methods has not been recognised. Here, we seek to emphasise the extent of residual EMG contamination of EEG.

Methods

We compared scalp electrical recordings after applying different EMG-pruning methods with recordings of EMG-free data from 6 fully-paralysed healthy subjects. We calculated the ratio of the power of pruned, normal scalp electrical recordings in the 6 subjects, to the power of unpruned recordings in the same subjects when paralysed. We produced “contamination graphs” for different pruning methods.

Results

EMG contamination exceeds EEG signals progressively more as frequencies exceed 25 Hz and with distance from the vertex. In contrast, Laplacian signals are spared in central scalp areas, even to 100 Hz.

Conclusion

Given probable EMG contamination of EEG in psychiatric and other studies, few findings on beta- or gamma-frequency power can be relied upon. Based on the effectiveness of current methods of EEG de-contamination, investigators should be able to re-analyse recorded data, re-evaluate conclusions from high frequency EEG data and be aware of limitations of the methods.
Prescription Practices of Medical Cannabinoids in Children with Cerebral Palsy - A Survey of the Swiss Cerebral Palsy Registry
Authors: Morosoli Federico , Hunziker Sandra , Zuercher Kathrin , Tscherter Anne , Grunt Sebastian
Published: November 2021

Aim

Medical cannabinoids are prescribed to children with cerebral palsy despite limited evidence. We aimed to assess the prescription practices of cannabinoids in children with cerebral palsy with a particular focus on indications and preparations used and how well cannabinoids are tolerated. Furthermore, we investigated how physicians acquire knowledge on cannabinoid medication.

Methods

We asked physicians with expertise in the care of children with CP on their prescription practices of medical cannabinoids. Data was collected through an online survey, which was distributed by email. In addition to the demographic information of participants, we also inquired about the indications for the prescription of cannabinoids, about experiences regarding efficacy and the observed side effects of the therapy.

Results

Seventy physicians from Europe, North America and Australia completed the survey. Forty-seven participants were experienced in the treatment of children with cerebral palsy by cannabinoids. The most common indication was epilepsy (69%), followed by spasticity (64%) and pain (63%). The prescribed preparations and doses varied considerably. Half of the participants evaluated the effect of the medical cannabinoids as moderate. Twenty-nine physicians reported side effects, most frequently in the form of drowsiness (26%), somnolence (19%), fatigue (13%), and diarrhoea (13%).

Conclusions

Despite the lack of evidence to date, medical cannabinoids are used to treat children with cerebral palsy in a wide variety of indications. Randomized controlled trials in this vulnerable patient group are therefore of utmost importance.

Highlights

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Cannabinoids are frequently used in children with CP, despite weak evidence.

-

Cannabinoids are prescribed in children with CP for different indications.

-

The most common indications are epilepsy, spasticity, and pain.

-

Common acute side effects are drowsiness, somnolence, fatigue, diarrhoea, and nausea.

-

Long-term side effects of cannabinoids in children with CP were not observed.
Hemodynamic profiles by non-invasive monitoring of cardiac index and vascular tone in acute heart failure patients in the emergency department: external validation and clinical outcomes
Authors: Harrison Nicholas E , Meram Sarah , Li Xiangrui , Medado Patrick , White Morgan B , Henry Sarah , Gupta Sushane , Zhu Dongxiao , Pang Peter S , Levy Phillip
Published: November 2021

Background

Non-invasive finger-cuff monitors measuring cardiac index and vascular tone (SVRI) classify emergency department (ED) patients with acute heart failure (AHF) into three otherwise-indistinguishable subgroups. Our goals were to validate these “hemodynamic profiles” in an external cohort and assess their association with clinical outcomes.

Methods

AHF patients (n=257) from five EDs were prospectively enrolled in the validation cohort (VC). Cardiac index and SVRI were measured with a ClearSight finger-cuff monitor (formerly NexFin, Edwards Lifesciences) as in a previous study (derivation cohort, DC, n=127). A control cohort (CC, n=127) of ED patients with sepsis was drawn from the same study as the DC. K-means cluster analysis previously derived two-dimensional (cardiac index and SVRI) hemodynamic profiles in the DC and CC (k=3 profiles each). The VC was subgroupedde novointo three analogous profiles by unsupervised K-means consensus clustering. PERMANOVA tested whether VC profiles 1-3 differed from profiles 1-3 in the DC and CC, by multivariate group composition of cardiac index and vascular tone.

Profiles in the VC were compared by a primary outcome of 90-day mortality and a 30-day ranked composite secondary outcome (death, mechanical cardiac support, intubation, new/emergent dialysis, coronary intervention/surgery) as time-to-event (survival analysis) and binary events (odds ratio, OR). Descriptive statistics were used to compare profiles by two validated risk scores for the primary outcome, and one validated score for the secondary outcome.

Results

The VC had median age 60 years (interquartile range {49-67}), and was 45% (n=116) female. Multivariate profile composition by cardiac index and vascular tone differed significantly between VC profiles 1-3 and CC profiles 1-3 (p=0.001, R2=0.159). A difference was not detected between profiles in the VC vs. the DC (p=0.59, R2=0.016).

VC profile 3 had worse 90-day survival than profiles 1 or 2 (HR = 4.8, 95%CI 1.4-17.1). The ranked secondary outcome was more likely in profile 1 (OR = 10.0, 1.2-81.2) and profile 3 (12.8, 1.7-97.9) compared to profile 2. Diabetes prevalence and blood urea nitrogen were lower in the high-risk profile 3 (p<0.05). No significant differences between profiles were observed for other clinical variables or the 3 clinical risk scores.

Conclusions

Hemodynamic profiles in ED patients with AHF, by non-invasive finger-cuff monitoring of cardiac index and vascular tone, were replicatedde novoin an external cohort. Profiles showed significantly different risks of clinically-important adverse patient outcomes.
Serum SARS-CoV-2 Antigens for the Determination of COVID-19 Severity
Authors: Favresse Julien , Bayart Jean-Louis , David Clara , Gillot Constant , Wieërs Grégoire , Roussel Gatien , Sondag Guillaume , Elsen Marc , Eucher Christine , Dogné Jean-Michel , Douxfils Jonathan
Published: November 2021

The diagnostic of SARS-CoV-2 infection relies on reverse transcriptase polymerase chain reactions (RT-PCR) performed on nasopharyngeal (NP) swabs. Nevertheless, false negative results can be obtained with inadequate sampling procedures making the use of other matrices of interest. This study aims at evaluating the kinetic of serum N antigen in severe and non-severe patients and compare the clinical performance of serum antigenic assays with NP RT-PCR. Ninety patients were included and monitored for several days. Disease severity was determined according to the WHO clinical progression scale. The serum N antigen was measured with a chemiluminescent assay (CLIA) and the Single Molecular Array (Simoa). Thresholds for severity were determined. In severe patients, the peak antigen response was observed 7 days after the onset of symptoms followed by a decline. No peak response was observed in non-severe patients. Severity threshold for the Simoa and the CLIA provided positive likelihood ratio of 30.0 and 10.9 for the timeframe between day 2 and day 14, respectively. Compared to NP RT-PCR, antigenic assays were able to discriminate the severity of the disease (p = 0.0174, 0.0310 and p = 0.1551 with the Simoa, the CLIA and the NP RT-PCR, respectively). Sensitive N antigen detection in serum thus provides a valuable new marker for COVID-19 diagnosis and evaluation of disease severity. When assessed during the first 2 weeks since the onset of symptoms, it may help in identifying patients at risk of developing severe COVID-19 to optimize better intensive care utilization.
Impact of inspiratory vs expiratory incentive spirometry on obstructive, restrictive, and mixed ventilatory impairments: Study protocol Effect of incentive spirometry on respiratory impairments
Authors: Oladejo Eniola Awolola , Sooknunan Sonill Maharaj
Published: November 2021

Background

Respiratory impairments are adjusted reduction in pulmonary function that manifests with adverse effects on an individual’s state of health. The basis for identifying these impairments requires differentiation between normal and abnormal ventilatory capacity to avoid inaccurate and potentially harmful drug prescriptions and a mismatch of diagnoses. Incentive Spirometry (IS) is a technique designed to help patients achieve a pre-set volume of airflow; the volume is determined from predicted values or baseline measurements.

Methods

Fifty-four (54) patients with Obstructive, Restrictive, or Mixed type of respiratory impairments attending the respiratory clinic of Lagos State University Teaching Hospital, Ikeja (LASUTH) will be assessed for eligibility for the study. The study design will be a double-blind, randomized control trial with six intervention groups and three placebo control groups.

The study’s independent variable will be an Inspiratory Incentive Spirometry (IIS) and Expiratory Incentive Spirometry (EIS), while Obstructive, Restrictive, and Mixed respiratory impairments will serve as the dependent variable for the study. Baseline Pulmonary Function Test (PFT) will be assessed on entry into the study, and after every procedure, six minutes’ walk (6MWT) test and CAT assessment test will be assessed at every two (2) weeks interval of the study. Data will be analyzed using descriptive and inferential statistics of repeated ANOVA; P<0.05.

Discussion

The study outcome will determine the relationship between inspiratory and expiratory incentive spirometry on respiratory impairments and deduce the best fit device for the respective impairment.

Trial Registration

www.pactr.org: PACTR202005904039357
Limited immune responses after three months of BNT162b2 vaccine in SARS-CoV-2 uninfected elders living in long-term care facilities
Authors: Trigueros Macedonia , Pradenas Edwards , Palacín Dolors , Ávila-Nieto Carlos , Trinité Benjamin , Bonet-Simó Josep Maria , Isnard Mar , Moreno Nemesio , Marfil Silvia , Rovirosa Carla , Puig Teresa , Grau Eulàlia , Chamorro Anna , Martinez Ana , Toledo Ruth , Font Marta , Ara Jordi , Carrillo Jorge , Mateu Lourdes , Blanco Julià , Clotet Bonaventura , Prat Nuria , Massanella Marta
Published: November 2021

Background

SARS-CoV-2 vaccination is the most effective strategy to protect elders living in long-term care facilities (LTCF) against severe COVID-19, but primary vaccine responses are less effective in older adults. Here, we characterized the humoral responses following 3 months after mRNA/BNT162b2 vaccine in institutionalized elders.

Methods

Plasma levels of specific SARS-CoV-2 total IgG, IgM and IgA antibodies were measured before and 3 months after vaccination in elders living in LTCF. Neutralization capacity was assessed in a pseudovirus neutralization assay against WH1 (original) and B.1.617.2/Delta variants. A group of younger adults was used as reference group.

Results

Three months after vaccination, uninfected-elders presented reduced specific SARS-CoV-2 IgG levels and significantly lower neutralization capacity against the WH1 and Delta virus compared to vaccinated uninfected younger individuals. In contrast, COVID-19 recovered elders showed significantly higher specific SARS-CoV-2 IgG levels after vaccination than younger counterparts, while showing similar neutralization activity against WH1 virus and increased neutralization capacity against Delta variant. Despite previously infected elders elicit potent cross-reactive immune responses similarly to younger individuals, higher quantities of specific SARS-CoV-2 IgG antibodies are required to reach the same neutralization levels.

Conclusions

While hybrid immunity seems to be active in previously infected elders after three months from mRNA/BNT162b2 vaccination, humoral immune responses are diminished in COVID-19 uninfected vaccinated residents living in LTCF. These results suggests that a vaccine booster dose should be prioritized for this particularly vulnerable population.

Word summary

While previously infected and vaccinated elders living in LTCF had comparable neutralizing antibody levels to younger individuals, vaccinated uninfected-residents showed limited neutralization capacity against both original and delta variants. Hybrid immunity seems to be active in elders and can be relevant to design vaccine boosting campaigns.
Artificial intelligence in the respiratory sounds analysis and computer diagnostics of bronchial asthma
Authors: Gelman A. , Sokolovsky V. , Furman E. , Kalinina N. , Furman G.
Published: November 2021

Using a database containing audio files of respiratory sound records of asthmatic patients and healthy patients, a method of computer-aided diagnostics based on the machine learning technique – creation of neural networks, has been developed. The database contains 952 records of respiratory sounds of asthma patients at different stages of the disease, aged from several months to 47 years, and 167 records of volunteers. Records were carried out with a quiet breathing at four points: in the oral cavity, above the trachea, on the chest, the second intercostal space on the right side, and at a point on the back.

The developed method of computer-aided diagnostics allows diagnosing bronchial asthma with high reliability: sensitivity of 89.3%, specificity of 86%, accuracy of about 88% and Youden’s index of 0.753.

The program learned once makes it possible to diagnose bronchial asthma with high reliability regardless of patient’s gender and age, a stage of disease, as well as the point of sound recording.

The developed method can be used as an additional screening method for the diagnostics of bronchial asthma and serve as the basis for development of computer control methods, including remote control (telemedicine) of patient’s condition and the effectiveness of the applied drugs in real time.
COVID-19 testing systems and their effectiveness in small, semi-isolated groups for sports events
Authors: Kamo Masashi , Murakami Michio , Naito Wataru , Takeshita Jun-ichi , Yasutaka Tetsuo , Imoto Seiya
Published: November 2021

In this study, we quantitatively assessed the effectiveness of systems for COVID-19 testing in small groups of sport teams that are semi-isolated from the general population by countermeasures against infection. Two types of group were assumed, and the dynamics of infection within each group was modeled by using a compartment model of infectious disease. One group (Group A) comprised domestic professional sports teams that play many games over a season while remaining within a relatively small region. Polymerase chain reaction (PCR) tests were routinely conducted once every 2 weeks, and the number of infected individuals that could not be removed after identification by testing or checking for symptoms was defined as the risk. The other group (Group B) comprised teams that travel across borders for mass-gathering events like the Olympic and Paralympic Games. The teams were isolated for 2 weeks at their destination; frequent testing and checking for symptoms was conducted, and any infected individuals were removed. The number of infected individuals participating in games after the isolation period was defined as the risk. In Group A, the number of infected individuals detected by routinely conducted PCR testing was lower than the number of infected individuals detected by checking for symptoms, indicating that routine testing every 2 weeks was not very effective. In Group B, daily PCR testing was the most effective, followed by daily antigen testing. Dual testing, in which individuals with a positive antigen test were given an additional PCR test, was the least effective with an effect equal to PCR testing every other day. These results indicate that repeated testing does not necessarily increase the detection of infected individuals.
Parsing Clinical Trial Eligibility Criteria for Cohort Query by a Multi-Input Multi-Output Sequence Labeling Model
Authors: Tian Shubo , Yin Pengfei , Zhang Hansi , Erdengasileng Arslan , Bian Jiang , He Zhe
Published: November 2021

To enable electronic screening of eligible patients for clinical trials, free-text clinical trial eligibility criteria should be translated to a computable format. Natural language processing (NLP) techniques have the potential to automate this process. In this study, we explored a supervised multi-input multi-output (MIMO) sequence labelling model to parse eligibility criteria into combinations of fact and condition tuples. Our experiments on a small manually annotated training dataset showed that that the performance of the MIMO framework with a BERT-based encoder using all the input sequences achieved an overall lenient-level AUROC of 0.61. Although the per-formance is suboptimal, representing eligibility criteria into logical and semantically clear tuples can potentially make subsequent translation of these tuples into database queries more reliable.
Identifying Dietary Consumption Patterns from Survey Data: A Bayesian Nonparametric Latent Class Model
Authors: Stephenson Briana J.K. , Wu Stephanie M. , Dominici Francesca
Published: November 2021

Dietary intake is one of the largest contributing factors to cardiovascular health in the United States. Amongst low-income adults, the impact is even more devastating. Dietary assessments, such as 24-hour recalls, provide snapshots of dietary habits in a study population. Questions remain on how generalizable those snapshots are in nationally representative survey data, where certain subgroups are sampled disproportionately to comprehensively examine the population. Many of the models that derive dietary patterns account for study design by incorporating the sampling weights to the derived model parameter estimates post hoc. We propose a Bayesian overfitted latent class model that accounts for survey design and sampling variability. Compared to other standard approaches used for survey data, our model showed improved identifiablity of the true population prevalence and pattern distribution in simulation. Using dietary intake data from the 2011-2018 National Health and Nutrition Examination Survey, we demonstrated the utility of our model to derive dietary patterns in adults considered low-income (at or below the 130% poverty income threshold), to understand if and how these patterns generalize in a smaller sub-population. A total of five dietary patterns were identified and characterized. Reproducible code/data are provided on GitHub to encourage further research and application in this area.
Trends and predictors of Readmissions after Left ventricular assist device
Authors: Mobil Steve
Published: November 2021

This manuscript has been withdrawn by medRxiv as it was submitted with false information.
Distinct neurocognitive bases for social trait judgments of faces in autism spectrum disorder
Authors: Yu Hongbo , Cao Runnan , Lin Chujun , Wang Shuo
Published: November 2021

Autism spectrum disorder (ASD) is characterized by difficulties in social processes, interactions, and communication. Yet, the neurocognitive bases underlying these difficulties are unclear. Here, we triangulated the ‘trans-diagnostic’ approach to personality, social trait judgments of faces, and neurophysiology to investigate (1) the relative position of autistic traits in a comprehensive social-affective personality space and (2) the distinct associations between the social-affective personality dimensions and social trait judgment from faces in individuals with ASD and neurotypical individuals. We collected personality and facial judgment data from a large sample of online participants (N = 89 self-identified ASD; N = 308 neurotypical controls). Factor analysis with 33 sub-scales of 10 social-affective personality questionnaires identified a 4-dimensional personality space. This analysis revealed that ASD and control participants did not differ significantly along the personality dimensions of empathy and prosociality, antisociality, or social agreeableness. However, the associations between these dimensions and judgments of facial trustworthiness and warmth differed across groups. Neurophysiological data also indicated that ASD and control participants might rely on distinct neuronal representations for judging trustworthiness and warmth from faces. These results suggest that the atypical association between social-affective personality and social trait judgment from faces may contribute to the social and affective difficulties associated with ASD.
Theta activity during encoding interacts with NREM sleep oscillations to predict memory generalization
Authors: Gibson Tamara , Cross Zachariah R. , Chatburn Alex
Published: November 2021

Relatively little is known regarding the interaction between encoding-related neural activity and sleep-based memory consolidation. One suggestion is that a function of encoding-related theta power may be to ‘tag’ memories for subsequent processing during sleep. This study aimed to extend previous work on the relationships between sleep spindles, slow oscillation-spindle coupling and task-related theta activity with a combined Deese-Roediger-McDermott (DRM) and nap paradigm. This allowed us to examine the influence of task- and sleep-related oscillatory activity on the recognition of both encoded list words and associative theme words. Thirty-three participants (29 females, mean age = 23.2 years) learned and recognised DRM lists separated by either a 2hr wake or sleep period. Mixed-effects modelling revealed the sleep condition endorsed more associative theme words and fewer list words in comparison to the wake group. Encoding-related theta power was also found to influence sleep spindle density, and this interaction was predictive of memory outcomes. The influence of encoding-related theta was specific to sleep spindle density, and did not appear to influence the strength of slow oscillation-spindle coupling as it relates to memory outcomes. The finding of interactions between wakeful and sleep oscillatory-related activity in promoting memory and learning has important implications for theoretical models of sleep-based memory consolidation.