bluuebunny/crossref_metadata_2025 huggingface dataset:
What Drives Patients’ Complaints About Adverse Events in Their Hospital Care? A Data Linkage Study of Australian Adults 45 Years and Older
Authors: Case Jennifer , Walton Merrilyn , Harrison Reema , Manias Elizabeth , Iedema Rick , Smith-Merry Jennifer
Published: January 2021

Objective

The aim of the study was to determine from patient-reported data the relationships between patients’ experiences of adverse events (AEs), the disclosure of the events, and patients propensity for complaints or legal action.

Methods

A cross-sectional survey was administered to 20,000 participants randomly chosen from the 45 and Up Study. The surveyed participants were older than 45 years and hospitalized in New South Wales, Australia, between January and June 2014. They were identified using data linkage to capture experiences of AEs.

Results

Of the 7661 respondents, 474 participants (7%) reported experiencing an AE. Those who did not receive an apology or expression of regret in the incident disclosure process were significantly more likely to make a complaint (P < 0.05). Those who found out about the event from hospital staff but did not receive a formal open disclosure process were found to be significantly more likely to seek legal advice (P < 0.05). Patients who made a complaint generally perceived that they experienced more problems in their hospital care, with significant differences identified between those who did and did not make a complaint on 13 of the 15-item Picker Patient Experience Questionnaire.

Conclusions

Although incident disclosure was not associated with whether a complaint was made or legal action pursued, significant associations between key aspects of the disclosure process and these outcomes were noted. Significant differences between those who did and did not make a complaint were noted in relation to the timing and apology components of open disclosure. The critical role of overall patient experience in the context of optimal AE management was evident from these data.
Central Venous Catheter Guidewire Retention: Lessons From England’s Never Event Database
Authors: Mariyaselvam Maryanne Z. A. , Patel Vikesh , Young Holly E. , Blunt Mark C. , Young Peter J.
Published: January 2021

Objectives

Guidewire retention during central venous catheter (CVC) insertion is considered a “never event.” We analyzed the National Health Service England Never Event database (2004–2015) to explore the process of guidewire retention and identify potential preventative measures.

Methods

We performed a systematic analysis of reported retained guidewire incidents by 3 independent reviewers.

Results

There was a rising frequency of reported retained CVC guidewires, with an average of 2 never events per month. Only 11% of retained guidewires are identified during the procedure itself, with the remainder identified during equipment clear-up (6%), after the procedure (4%), at the first check radiograph (23%), or after the first radiograph (55%). In 59 cases, the grade of the operator was reported, and among these, 88% were inserted by trainee doctors. Analysis of causative factors was only possible for 38 cases, and of these, operator’s mistake (32%), operator/human error (16%), and distraction (16%) were the most common. Of 163 reported cases, preventative measures instigated were actions taken against the individual clinician (36%), departmental actions such as investigations, additional teaching or reminders (37%), and additional checklists (27%).

Conclusions

Most retained guidewires are discovered after the procedure. Despite the introduction of safety measures, guidewire retention still occurs because the checks, alerts, reminders, and additional checklists all solely rely on the operator remembering not to make the mistake. System changes or design modifications to the CVC equipment are needed to prevent guidewire retention, this being at the top of the hierarchy of intervention effectiveness.
Acute HIV at the Time of Initiation of Pre-exposure or Post-exposure Prophylaxis: Impact on Drug Resistance and Clinical Outcomes
Authors: Johnson Kelly A. , Chen Miao-Jung , Kohn Robert , Sachdev Darpun , Bacon Oliver , Lee Sulggi , Cohen Stephanie E.
Published: January 2021

Background:

Initiating pre-exposure or post-exposure prophylaxis (PrEP/PEP) in the setting of undiagnosed acute HIV (AHI) could cause antiretroviral resistance. We sought to characterize clinical outcomes and drug resistance mutations among individuals prescribed PrEP/PEP with undiagnosed AHI at a San Francisco sexually transmitted disease clinic.

Setting:

In our PrEP/PEP program, patients are tested for HIV using a point-of-care antibody test. If negative, patients are started on prophylaxis and screened for AHI using pooled HIV RNA (5–10 days turn-around). We used 2-drug PEP until 05/2016.

Methods:

We identified patients who had as-yet-undiagnosed AHI on the day of PrEP/PEP start between 2011 and 2018, then used our clinical record and surveillance data to describe HIV resistance and clinical outcomes.

Results:

Of 1758 PrEP and 2242 PEP starts, there were 7 AHI cases among PrEP users (0.40%) and 6 among PEP users (0.30%). Median times for linkage to HIV care, initiation of HIV treatment, and viral suppression were 7, 12, and 43 days. On initiation of HIV care, 3 patients (23%) were found to have an M184 mutation 7–12 days after starting PrEP/PEP. All 3 had genotyping performed on stored serum available from the date of PrEP/PEP start, each of which demonstrated wild-type virus. All 3 patients achieved durable viral suppression.

Conclusions:

Although rare (occurring <0.5% of the time), AHI in the setting of PrEP/2-drug PEP can result in an M184 within days. Even with M184, persons with AHI achieve viral suppression when rapidly linked to care and initiated on antiretroviral therapy. Providers should consider AHI screening when starting PrEP/PEP.
Predicting Lymph Node Metastasis Using Computed Tomography Radiomics Analysis in Patients With Resectable Esophageal Squamous Cell Carcinoma
Authors: Zhao Bo , Zhu Hai-Tao , Li Xiao-Ting , Shi Yan-Jie , Cao Kun , Sun Ying-Shi
Published: January 2021

Objectives

We investigated the value of radiomics data, extracted from pretreatment computed tomography images of the primary tumor (PT) and lymph node (LN) for predicting LN metastasis in esophageal squamous cell carcinoma (ESCC) patients.

Materials and Methods

A total 338 ESCC patients were retrospectively assessed. Primary tumor, the largest short-axis diameter LN (LSLN), and PT and LSLN interaction term (IT) radiomic features were calculated. Subsequently, the radiomic signature was combined with clinical risk factors in multivariable logistic regression analysis to build various clinical-radiomic models. Model performance was evaluated with respect to the fit, overall performance, differentiation, and calibration.

Results

A clinical-radiomic model, which combined clinical and PT-LSLN-IT radiomic signature, showed favorable discrimination and calibration. The area under curve value was 0.865 and 0.841 in training and test set.

Conclusions

A venous computed tomography radiomic model based on the PT, LSLN, and IT radiomic features represents a novel noninvasive tool for prediction LN metastasis in ESCC.
Emergency Computed Tomography: How Misinterpretations Vary According to the Periods of the Nightshift?
Authors: Platon Alexandra , Etienne Leonard , Herpe Guillaume , Yan David , Massoutier Maximilien , Perneger Thomas , Becker Minerva , Poletti Pierre-Alexandre
Published: January 2021

Objective

To evaluate the accuracy of initial computed tomography (CT) interpretations made by radiology residents during nightshifts in the emergency department.

Methods

Preliminary CT reports performed by radiology residents during 120 consecutive nightshifts (08:30 pm to 08:30 am) were reviewed, attendings' final interpretation being the reference standard. Nightshifts were divided into four consecutive periods of 3 hours. Major misinterpretations were related to potentially life-threatening conditions if not treated immediately after CT. The rate of misinterpretations was calculated for all CT examinations, separately for nightshift's periods and for residents' training years.

Results

Misinterpretations were recorded in 155 (7.4%) of 2102 CT examinations, 0.6% (13/2102) were major. There were 2.2% (4/186) major misinterpretations that occurred during the last period of the nightshift versus 0.4% (9/1916) during the first periods of the night (P < 0.05). Of all misinterpretations, 8.5% (130/1526) were made by third- and fourth-year residents and 4.3% (25/576) by fifth-year residents (P < 0.005).

Conclusions

Major misinterpretations occur at the end of the nightshift, which may be explained by the fatigue effect. The rate of misinterpretations is lower among fifth-year residents, which may be related to their prior experience in reading emergency cases.
Magnetic Resonance Imaging, the Virtual Biopsy of Mesenteric Masses
Authors: Saleh Mohammed , Virarkar Mayur , Gulati Anjalie , Bhosale Priya , Sharma Smita , Faria Silvana , Gopireddy Dheeraj Reddy
Published: January 2021

The mesentery may be affected by multiple disease processes. Magnetic resonance imaging aids as a virtual pathological biopsy tool in the assessment of mesenteric masses because of superior soft tissue contrast and characterization. In this comprehensive review, we describe in detail the magnetic resonance imaging features of some solid and cystic mesenteric masses, with an emphasis on lesion-specific signal characteristics on T1- and T2-weighted images, diffusion-weighted imaging, and enhancement features on the dynamic postcontrast phase that aid in narrowing the differential diagnosis.
Magnetic Resonance Features of Lower-grade Gliomas in Prediction of the Reverse Phase Protein A
Authors: Wang Jinjun , Guo Xinghua
Published: January 2021

Objectives

The Cancer Genome Atlas Research Network identified 4 novel protein expression–defined subgroups in patients with lower-grade gliomas (LGGs). The RPPA3 subtype had high levels of Epidermal Growth Factor Receptor and Human epidermal growth factor receptor-2, further increasing the chances for targeted therapy. In this study, we aimed to explore the relationships between magnetic resonance features and reverse phase protein array (RPPA) subtypes (R1–R4).

Methods

Survival estimates for the Cancer Genome Atlas cohort were generated using the Kaplan-Meier method and time-dependent receiver operating characteristic curves. A total of 153 patients with LGG with brain magnetic resonance imaging from The Cancer Imaging Archive were retrospectively analyzed. Least absolute shrinkage and selection operator algorithm was used to reduce the feature dimensions of the RPPA3 subtype.

Results

A total of 51 (33.3%) RPPA1 subtype, 42 (27.4) RPPA2 subtype, 19 (12.4%) RPPA3 subtype, and 38 (24.8%) RPPA4 subtype were identified. On multivariate logistic regression analysis, subventricular zone involvement [odds ratio (OR), 0.370; P = 0.006; 95% confidence interval (CI), 0.181–0.757) was associated with RPPA1 subtype [area under the curve (AUC), 0.598]. Volume of 60 cm3 or greater (OR, 5.174; P < 0.001; 95% CI, 2.182–12.267) was associated with RPPA2 subtype (AUC, 0.684). Proportion contrast-enhanced tumor greater than 5% (OR, 4.722; P = 0.010; 95% CI, 1.456–15.317), extranodular growth (OR, 5.524; P = 0.010; 95% CI, 1.509–20.215), and L/CS ratio equal to or greater than median (OR, 0.132; P = 0.003; 95% CI, 0.035–0.500) were associated with RPPA3 subtype (AUC, 0.825). Proportion contrast-enhanced tumor greater than 5% (OR, 0.206; P = 0.005; 95% CI, 0.068–0.625) was associated with RPPA4 subtype (AUC, 0.638). For the prediction of RPPA3 subtype, the nomogram showed good discrimination, with an AUC of 0.825 (95% CI, 0.711–0.939) and was well calibrated. The RPPA3 subtype was associated with shortest mean overall survival (RPPA3 subtype vs other: 613 vs 873 days; P < 0.05). The time-dependent receiver operating characteristic curves for the RPPA3 subtype was 0.72 (95% CI, 0.60–0.84) for survival at 1 year. Decision curve analysis indicated that prediction for the RPPA3 model was clinically useful.

Conclusions

The RPPA3 subtype is an unfavorable prognostic biomarker for overall survival in patients with LGG. Radiogenomics analysis of magnetic resonance features can predict the RPPA subtype preoperatively and may be of clinical value in tailoring the management strategies in patients with LGG.
Meningeal Relapse of Neuroblastoma—Utility of 68Ga-DOTATOC PET/CT for Detection
Authors: Kashyap Raghava , Reddy Rakesh , Prasanna Veni
Published: January 2021

In treatment of metastatic neuroblastoma, the central nervous system seems to act as a sanctuary leading to often unexpected relapse of disease. We present a case of neuroblastoma treated with chemotherapy and autologous stem cell transplantation only to relapse in central nervous system with meningeal metastases visualized on 68Ga-DOTATOC imaging.
Role of 18F-FDG PET/CT in the Assessment of Response to Antitubercular Chemotherapy and Identification of Treatment Endpoint in Patients With Tuberculosis of the Joints
Authors: Goyal Devansh , Shriwastav Ravi , Mittal Ravi , Sharma Anshul , Sharma Vijay , Kumar Vijay D. , Sharma M.C. , Kumar Rakesh
Published: January 2021

Aims

The aim of this study was to explore the utility of 18F-FDG PET/CT in the assessment of response to antitubercular treatment (ATT) and identification of treatment endpoint.

Patients and Methods

Forty patients (mean age, 35.3 years; 27 men) with clinically, radiologically, and histopathologically proven joint tuberculosis prospectively underwent clinical, biochemical, and PET/CT evaluation at baseline and after ~6, 12, and 18 months of ATT. Two patients were lost to follow-up, and 1 defaulted treatment. The remaining 37 were followed up until complete response (CR) was achieved. Images were visually and quantitatively (SUVmax ratio and metabolically active disease volume [MV]) evaluated by 2 experienced nuclear medicine physicians.

Results

Knee (n = 18) and ankle (n = 7) were the most frequently involved sites. The median MV and SUVmax ratio at baseline were 85.10 mL and 7.21, respectively. Five patients had noncontiguous vertebral involvement, 12 had pulmonary lesions, 2 had abscesses, 6 had mediastinal, and 30 had local lymph nodal involvement. Complete response was seen in 1/39, 11/37, and 30/37 patients after 6, 12, and 18 months of ATT. Significant reductions in visual analog scale score, tenderness, joint swelling, SUVmax ratios, and MVs (Friedman test, P < 0.001) were seen after each follow-up. The median time-to-CR in skeletal lesions was significantly longer than extraskeletal lesions (591 vs 409 days; Wilcoxon signed-rank test, P < 0.001). Time-to-CR in joint lesions positively correlated with MV at first follow-up (Pearson = 0.452, P = 0.005) and negatively correlated with percentage change in MV (first follow-up from baseline) (Pearson = −0.620, P < 0.001). ROC analysis yielded a cutoff of ≤71% reduction in MV at first follow-up (80.8% sensitivity, 81.8% specificity) to predict extension of ATT beyond 12 months. Using ROC analysis at second follow-up, a cutoff of ≤12.67 mL (for CR) was derived and was validated in patients at the third follow-up, with an accuracy of 84.4%. Patients with CR in PET/CT maintained disease-free state during a mean follow-up of 271 days.

Conclusions

18F-FDG PET/CT is an excellent tool in estimating total disease burden, assessing response to ATT and identification of treatment endpoint in joint tuberculosis.
Follicular Thyroid Carcinoma Metastases on Round Ligament of Liver
Authors: García-Burillo Amparo , Monturiol-Duran Jaime Alejando , Iglesias-Felip Carmela , Villasboas-Rosciolesi Diego , Castell-Conesa Joan
Published: January 2021

We describe a case of a 69-year-old woman with follicular thyroid cancer of long evolution, with thyroidectomy 20 years before, who had remained clinically stable until now, when she started to present abnormal levels of serum thyroglobulin. An 123I whole-body scan showed a high uptake in the upper right half of her abdomen, and an 18F-FDG PET/CT located this focus at the liver’s round ligament. Pathology findings after surgery showed the focus to be a differentiated thyroid cancer metastasis. This is an unusual presentation of differentiated thyroid cancer metastasis.
Parotid Oncocytoma on 99mTc-Sestamibi Scintigraphy and SPECT/CT
Authors: Kirkland John W. , Zhao Jason M. , McWhorter Nathan E. , Banks Kevin P.
Published: January 2021

Oncocytomas in the parotid gland are a rare benign neoplasm composed of mitochondrial-rich oncocytes. Here we present the case of an 85-year-old man with a history of biopsy-proven right parotid gland oncocytoma who underwent99mTc-sestamibi scintigraphy and SPECT/CT in the context of primary hyperparathyroidism. Focal intense uptake of radiotracer is detected within the right parotid gland on sestamibi scintigraphy. SPECT/CT confirms the localization of sestamibi uptake to the hyperattenuating parotid gland oncocytoma.
The Experience of Two Independent Schools with In-Person Learning During the COVID-19 Pandemic
Authors: Gillespie Darria Long , Meyers Lauren Ancel , Lachmann Michael , Redd Stephen C , Zenilman Jonathan M
Published: January 2021

BACKGROUND

In 2020, U.S schools closed due to SARS-CoV-2 but their role in transmission was unknown. In fall 2020, national guidance for reopening omitted testing or screening recommendations. We report the experience of 2 large independent K-12 schools (School-A and School-B) that implemented an array of SARS-CoV-2 mitigation strategies that included periodic universal testing.

METHODS

SARS-CoV-2 was identified through periodic universal PCR testing, self-reporting of tests conducted outside school, and contact tracing. Schools implemented behavioral and structural mitigation measures, including mandatory masks, classroom disinfecting, and social distancing.

RESULTS

Over the fall semester, School-A identified 112 cases in 2320 students and staff; School-B identified 25 cases (2.0%) in 1200 students and staff. Most cases were asymptomatic and none required hospitalization. Of 69 traceable introductions, 63(91%) were not associated with school-based transmission, 59 cases (54%) occurred in the 2 weeks post-Thanksgiving. In 6/7 clusters, clear noncompliance with mitigation protocols was found. The largest outbreak had 28 identified cases and was traced to an off-campus party. There was no transmission from students to staff.

CONCLUSIONS

Although school-age children can contract and transmit SARS-CoV-2, rates of COVID-19 infection related to in-person education were significantly lower than those in the surrounding community. However, social activities among students outside of school undermined those measures and should be discouraged, perhaps with behavioral contracts, to ensure the safety of school communities. In addition, introduction risks were highest following extended school breaks. These risks may be mitigated with voluntary quarantines and surveillance testing prior to re-opening.
HLA-A*11:01:01:01, HLA*C*12:02:02:01-HLA-B*52:01:02:02, age and sex are associated with severity of Japanese COVID-19 with respiratory failure
Authors: Khor Seik-Soon , Omae Yosuke , Nishida Nao , Sugiyama Masaya , Kinoshita Noriko , Suzuki Tetsuya , Suzuki Michiyo , Suzuki Satoshi , Izumi Shinyu , Hojo Masayuki , Ohmagari Norio , Mizokami Masashi , Tokunaga Katsushi
Published: January 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19) was announced as an outbreak by the World Health Organization (WHO) in January 2020 and as a pandemic in March 2020. The majority of infected individuals have experienced no or only mild symptoms, ranging from fully asymptomatic cases to mild pneumonic disease. However, a minority of infected individuals develop severe respiratory symptoms. The objective of this study was to identify susceptible HLA alleles and clinical markers for the early identification of severe COVID-19 among hospitalized COVID-19 patients. A total of 137 patients with mild COVID-19 (mCOVID-19) and 53 patients with severe COVID-19 (sCOVID-19) were recruited from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan for the period of February–August 2020. High-resolution sequencing-based typing for eight HLA genes was performed using next-generation sequencing. In the HLA association studies, HLA-A*11:01:01:01 [Pc = 0.013, OR = 2.26 (1.27–3.91)] and HLA-C*12:02:02:01-HLA-B*52:01:01:02 [Pc = 0.020, OR = 2.25 (1.24–3.92)] were found to be significantly associated with the severity of COVID-19. After multivariate analysis controlling for other confounding factors and comorbidities, HLA-A*11:01:01:01 [P = 3.34E-03, OR = 3.41 (1.50–7.73)], age at diagnosis [P = 1.29E-02, OR = 1.04 (1.01–1.07)] and sex at birth [P = 8.88E-03, OR = 2.92 (1.31–6.54)] remained significant. Early identification of potential sCOVID-19 could help clinicians prioritize medical utility and significantly decrease mortality from COVID-19.
Expression of deubiquitinases in human gingiva and cultured human gingival fibroblasts
Authors: Fu Yong-Wei , Xu Hong-Zhi
Published: January 2021

Background

Although deubiquitinating enzymes (DUBs) such as CYLD, A20 and OTULIN are expressed in multiple tissues and thought to be linked with inflammatory diseases, their expression in periodontal tissues remains to be determined. This research was designed to assess the expression of CYLD, A20 and OTULIN in human gingiva, and to evaluate the regulation of these DUBs in human gingival fibroblasts (HGFs) upon different stimuli.

Methods

Immunohistochemistry assay was conducted to determine the expression of CYLD, A20 and OTULIN in human gingiva. Immunofluorescence assay was employed to observe the protein expression of CYLD, A20 and OTULIN in HGFs. RT-PCR and western blots were carried out to assess gene and protein expression changes of these DUBs in HGFs upon LPS or TNF-α.

Results

CYLD, A20 and OTULIN were found to be expressed in human gingiva and HGFs. Further, the expression of CYLD, A20 and OTULIN in HGFs exhibited distinct regulation by different stimuli.

Conclusions

Our findings suggest that CYLD, A20 and OTULIN might play a role in the progression of periodontitis.
Loneliness and the onset of new mental health problems in the general population: a systematic review
Authors: Mann Farhana , Wang Jingyi , Pearce Ellie , Ma Ruimin , Schleif Merle , Lloyd-Evans Brynmor , Johnson Sonia
Published: January 2021

Background

Loneliness is associated with poor health including premature mortality. There are cross-sectional associations with depression, anxiety, psychosis and other mental health outcomes. However, the direction of causation is unclear and clarifying the evidence from longitudinal studies is a key step in understanding this relationship.

Aims

We synthesized evidence from longitudinal studies investigating the relationship between loneliness and new onset of mental health problems, in the general population.

Method

We systematically searched six electronic databases, unpublished sources and hand-searching of references, up to March 2020. We conducted a meta-analysis of eight independent cohorts, and narrative synthesis of the remaining studies.

Results

We included 20 studies, of which the majority focused on depression. Our narrative synthesis concluded that loneliness at baseline is associated with subsequent new onset of depression. The few studies on anxiety also showed an association. Our meta-analysis found a pooled adjusted odds ratio of 2.33 (95% C.I. 1.62 – 3.34) for risk of new onset depression in adults who were often lonely compared with people who were not often lonely. This should be interpreted with caution given evidence of heterogeneity. Most of the studies were in older adults.

Conclusion

Loneliness is a public mental health issue. There is growing evidence it is associated with the onset of depression and other common mental health problems. Future studies should explore its impact across the age range, look beyond depression, and explore the mechanisms involved.
Environmental drivers of disease depend on host community context
Authors: Halliday Fletcher W. , Jalo Mikko , Laine Anna-Liisa
Published: January 2021

Predicting disease risk in an era of unprecedented biodiversity and climate change is more challenging than ever, largely because when and where hosts are at greatest risk of becoming infected depends on complex relationships between hosts, parasites, and the environment. Theory predicts that host species characterized by fast-paced life-history strategies are more susceptible to infection and contribute more to transmission than their slow-paced counterparts. Hence, disease risk should increase as host community structure becomes increasingly dominated by fast-paced hosts. Theory also suggests that environmental gradients can alter disease risk, both directly, due to abiotic constraints on parasite replication and growth, and indirectly, by changing host community structure. What is more poorly understood, however, is whether environmental gradients can also alter the effect of host community structure on disease risk. We addressed these questions using a detailed survey of host communities and infection severity along a 1100m elevational gradient in southeastern Switzerland. Consistent with prior studies, increasing elevation directly reduced infection severity, which we attribute to abiotic constraints, and indirectly reduced infection severity via changes in host richness, which we attribute to encounter reduction. Communities dominated by fast pace-of-life hosts also experienced more disease. Finally, although elevation did not directly influence host community pace-of-life, the relationship between pace-of-life and disease was sensitive to elevation: increasing elevation weakened the relationship between host community pace-of-life and infection severity. This result provides the first field evidence, to our knowledge, that an environmental gradient can alter the effect of host community structure on infection severity.
Beyond the new normal: assessing the feasibility of vaccine-based elimination of SARS-CoV-2
Authors: Stoddard Madison , Sarkar Sharanya , Nolan Ryan P. , White Douglas E. , White Laura F. , Hochberg Natasha S. , Chakravarty Arijit
Published: January 2021

As the COVID-19 pandemic drags into its second year, there is hope on the horizon, in the form of SARS-CoV-2 vaccines which promise disease elimination and a return to pre-pandemic normalcy. In this study we critically examine the basis for that hope, using an epidemiological modeling framework to establish the link between vaccine characteristics and effectiveness in bringing an end to this unprecedented public health crisis. Our findings suggest that vaccines that do not prevent infection will allow extensive endemic SARS-CoV-2 spread upon a return to pre-pandemic social and economic conditions. Vaccines that only reduce symptomatic COVID-19 or mortality will fail to mitigate serious COVID-19 mortality risks, particularly in the over-65 population, likely resulting in hundreds of thousands of US deaths on a yearly basis. Our modeling points to the possibility of complete SARS-CoV-2 elimination with high population-level compliance and a vaccine that is highly effective at reducing SARS-CoV-2 infection. Notably, vaccine-mediated reduction of transmission is critical for elimination, and in order for partially-effective vaccines to play a positive role in SARS-CoV-2 elimination, other stackable (complementary) interventions must be deployed simultaneously.
Multinational Prevalence of Neurological Phenotypes in Patients Hospitalized with COVID-19
Authors: Le Trang T. , Gutiérrez-Sacristán Alba , Son Jiyeon , Hong Chuan , South Andrew M. , Beaulieu-Jones Brett K. , Loh Ne Hooi Will , Luo Yuan , Morris Michele , Ngiam Kee Yuan , Patel Lav P. , Samayamuthu Malarkodi J. , Schriver Emily , Tan Amelia LM , Moore Jason , Cai Tianxi , Omenn Gilbert S. , Avillach Paul , Kohane Isaac S. ,   4CE Consortium, Visweswaran Shyam , Mowery Danielle L. , Xia Zongqi
Published: January 2021

OBJECTIVE

Neurological complications can worsen outcomes in COVID-19. We defined the prevalence of a wide range of neurological conditions among patients hospitalized with COVID-19 in geographically diverse multinational populations.

METHODS

Using electronic health record (EHR) data from 348 participating hospitals across 6 countries and 3 continents between January and September 2020, we performed a cross-sectional study of hospitalized adult and pediatric patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test, both with and without severe COVID-19. We assessed the frequency of each disease category and 3-character International Classification of Disease (ICD) code of neurological diseases by countries, sites, time before and after admission for COVID-19, and COVID-19 severity.

RESULTS

Among the 35,177 hospitalized patients with SARS-CoV-2 infection, there was increased prevalence of disorders of consciousness (5.8%, 95% confidence interval [CI]: 3.7%-7.8%,pFDR<.001) and unspecified disorders of the brain (8.1%, 95%CI: 5.7%-10.5%,pFDR<.001), compared to pre-admission prevalence. During hospitalization, patients who experienced severe COVID-19 status had 22% (95%CI: 19%-25%) increase in the relative risk (RR) of disorders of consciousness, 24% (95%CI: 13%-35%) increase in other cerebrovascular diseases, 34% (95%CI: 20%-50%) increase in nontraumatic intracranial hemorrhage, 37% (95%CI: 17%-60%) increase in encephalitis and/or myelitis, and 72% (95%CI: 67%-77%) increase in myopathy compared to those who never experienced severe disease.

INTERPRETATION

Using an international network and common EHR data elements, we highlight an increase in the prevalence of central and peripheral neurological phenotypes in patients hospitalized with SARS-CoV-2 infection, particularly among those with severe disease.
Unusual trend of respiratory syncytial virus burden of disease observed in primary care diagnosis of children under 5 years old in Catalonia during the COVID-19 pandemic
Authors: Coma Ermengol , Vila Jorgina , Méndez-Boo Leonardo , Antón Andrés , Mora Núria , Fina Francesc , Fàbregas Mireia , Medina Manuel
Published: January 2021

We observed an unusual pattern of respiratory syncytial virus (RSV) in children under 5 years in Catalonia (Spain). We observed a nearly absence during winter months and a subsequent surge late spring. Primary care electronic health records combined with hospital RSV laboratory confirmations could be a useful surveillance system to monitorize trends of respiratory pathogens.
Structuring clinical text with AI: old vs. new natural language processing techniques evaluated on eight common cardiovascular diseases
Authors: Zhan Xianghao , Humbert-Droz Marie , Mukherjee Pritam , Gevaert Olivier
Published: January 2021

Mining the structured data in electronic health records(EHRs) enables many clinical applications while the information in free-text clinical notes often remains untapped. Free-text notes are unstructured data harder to use in machine learning while structured diagnostic codes can be missing or even erroneous. To improve the quality of diagnostic codes, this work extracts structured diagnostic codes from the unstructured notes concerning cardiovascular diseases. Five old and new word embeddings were used to vectorize over 5 million progress notes from Stanford EHR and logistic regression was used to predict eight ICD-10 codes of common cardiovascular diseases. The models were interpreted by the important words in predictions and analyses of false positive cases. Trained on Stanford notes, the model transferability was tested in the prediction of corresponding ICD-9 codes of the MIMIC-III discharge summaries. The word embeddings and logistic regression showed good performance in the diagnostic code extraction with TF-IDF as the best word embedding model showing AU-ROC ranging from 0.9499 to 0.9915 and AUPRC ranging from 0.2956 to 0.8072. The models also showed transferability when tested on MIMIC-III data set with AUROC ranging from 0.7952 to 0.9790 and AUPRC ranging from 0.2353 to 0.8084. Model interpretability was showed by the important words with clinical meanings matching each disease. This study shows the feasibility to accurately extract structured diagnostic codes, impute missing codes and correct erroneous codes from free-text clinical notes with interpretable models for clinicians, which helps improve the data quality of diagnostic codes for information retrieval and downstream machine-learning applications.
A prediction model for COVID-19 prevalence based on demographic and healthcare parameters in Iran
Authors: Safavi Parimah Emadi , Rahimian Karim , Doustmohammadi Alireza , dastjerdei Mahla Safari , Rasouli Ahmadreza , Zahiri Javad
Published: January 2021

Coronavirus Disease 2019 (COVID-19) pandemic has become the greatest threat to global health in only a matter of months. Iran struggling with COVID-19 coincidence with Nowruz vacations has led to horrendous consequences for both people and the public health workforce. Modeling approaches have been proved to be highly advantageous in taking appropriate actions in the early stages of the pandemic. To this date, no study has been conducted to model the disease to investigate the disease, especially after travel restrictions in Iran. In this study, we exploited the opportunities that Artificial neural networks offer to investigate contributing factors of early-stage coronavirus spread via generating a model to predict daily confirmed cases in Iran. We collected publicly available data of confirmed cases in 24 provinces from April 4, 2020, to May 2, 2020, with a list of explanatory factors. The factors were checked separately for any linear associations and to train and validate a multilayer perceptron network. The accuracy of the models was evaluated, the R2 scores were 0.842 for population distribution, 0.822 for health index, and 0.864 for the population in the provinces. Our results suggest the significant impact of the mentioned factors on disease spread in the time of travel restrictions when the vacation ended. Accordingly, this information can be implicated in assessing the risk of epidemics and future policy makings in this area.
The therapeutic effect of intra-articular facet joint injection with normal saline as a comparator for chronic low back pain: a systematic review and meta-analysis
Authors: Nopsopon Tanawin , Pongpirul Krit , Rittiphairoj Thanitsara , Lertparinyaphorn Irin , Suputtitada Areerat
Published: January 2021

Background

Intra-articular facet joint injection (FJI) has been increasingly used as a treatment for chronic low back pain (LBP). Choice of the substance has been based on clinical experience with unclear evidence on marginal effectiveness of active substance over normal saline as a placebo control. This systematic review investigates the comparative effectiveness between normal saline and active substances on patient-reported outcomes (PROs).

Methods

Systematic search was conducted in five databases: PubMed, Embase, Scopus, Web of Science, and CENTRAL for randomized controlled trials and observational studies of evaluating the PROs of FJI comparing active injected substances with normal saline as placebo in chronic LBP patients in the English language without publication date restriction. Quality assessment was performed using ROB2 and ROBINS-I. The meta-analysis was done using a random-effects model. Mean difference with 95% CIs of efficacy outcomes including pain, numbness, disability, quality of life were measured.

Results

Of 2,467 potential studies, three were included in the systematic review and meta-analysis (247 patients). Compared to other active substances, normal saline provided similar therapeutic effects on pain outcome within one hour (MD 2.43, 95% CI –11.61 to 16.50), at 1–1.5 months follow up (MD –0.63, 95% CI –7.97 to 6.72), and at 3 to 6 months (MD 1.90, 95% CI –16.03 to 19.83) as well as the quality of life at one and six months follow-up.

Conclusions

The short-term and long-term clinical improvements of intra-articular FJI using normal saline are comparable to the other active substances in LBP patients.

PROSPERO

registration number CRD42020216426
More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis
Authors: Lopez-Leon Sandra , Wegman-Ostrosky Talia , Perelman Carol , Sepulveda Rosalinda , Rebolledo Paulina A , Cuapio Angelica , Villapol Sonia
Published: January 2021

COVID-19, caused by SARS-CoV-2, can involve sequelae and other medical complications that last weeks to months after initial recovery, which has come to be called Long-COVID or COVID long-haulers. This systematic review and meta-analysis aims to identify studies assessing long-term effects of COVID-19 and estimates the prevalence of each symptom, sign, or laboratory parameter of patients at a post-COVID-19 stage. LitCOVID (PubMed and Medline) and Embase were searched by two independent researchers. All articles with original data for detecting long-term COVID-19 published before 1st of January 2021 and with a minimum of 100 patients were included. For effects reported in two or more studies, meta-analyses using a random-effects model were performed using the MetaXL software to estimate the pooled prevalence with 95% CI. Heterogeneity was assessed using I2 statistics. This systematic review followed Preferred Reporting Items for Systematic Reviewers and Meta-analysis (PRISMA) guidelines, although the study protocol was not registered. A total of 18,251 publications were identified, of which 15 met the inclusion criteria. The prevalence of 55 long-term effects was estimated, 21 meta-analyses were performed, and 47,910 patients were included. The follow-up time ranged from 14 to 110 days post-viral infection. The age of the study participants ranged between 17 and 87 years. It was estimated that 80% (95% CI 65-92) of the patients that were infected with SARS-CoV-2 developed one or more long-term symptoms. The five most common symptoms were fatigue (58%), headache (44%), attention disorder (27%), hair loss (25%), and dyspnea (24%). All meta-analyses showed medium (n=2) to high heterogeneity (n=13). In order to have a better understanding, future studies need to stratify by sex, age, previous comorbidities, severity of COVID-19 (ranging from asymptomatic to severe), and duration of each symptom. From the clinical perspective, multi-disciplinary teams are crucial to developing preventive measures, rehabilitation techniques, and clinical management strategies with whole-patient perspectives designed to address long COVID-19 care.
Evaluation of COVID-19 vaccination strategies with a delayed second dose
Authors: Moghadas Seyed M. , Vilches Thomas N. , Zhang Kevin , Nourbakhsh Shokoofeh , Sah Pratha , Fitzpatrick Meagan C. , Galvani Alison P.
Published: January 2021

Two of the COVID-19 vaccines currently approved in the United States require two doses, administered three to four weeks apart. Constraints in vaccine supply and distribution capacity, together with a deadly wave of COVID-19 from November 2020 to January 2021 and the emergence of highly contagious SARS-CoV-2 variants, sparked a policy debate on whether to vaccinate more individuals with the first dose of available vaccines and delay the second dose, or to continue with the recommended two-dose series as tested in clinical trials. We developed an agent-based model of COVID-19 transmission to compare the impact of these two vaccination strategies, while varying the temporal waning of vaccine efficacy following the first dose and the level of pre-existing immunity in the population. Our results show that for Moderna vaccines, a delay of at least 9 weeks could maximize vaccination program effectiveness and avert at least an additional 17.3 (95% CrI: 7.8 − 29.7) infections, 0.71 (95% CrI: 0.52 - 0.97) hospitalizations, and 0.34 (95% CrI: 0.25 - 0.44) deaths per 10,000 population compared to the recommended 4-week interval between the two doses. Pfizer-BioNTech vaccines also averted an additional 0.61 (95% CrI: 0.37 - 0.89) hospitalizations and 0.31 (95% CrI: 0.23 - 0.45) deaths per 10,000 population in a 9-week delayed second dose strategy compared to the 3-week recommended schedule between doses. However, there was no clear advantage of delaying the second dose with Pfizer-BioNTech vaccines in reducing infections, unless the efficacy of the first dose did not wane over time. Our findings underscore the importance of quantifying the characteristics and durability of vaccine-induced protection after the first dose in order to determine the optimal time interval between the two doses.
COVID-19 mortality: positive correlation with cloudiness but no correlation with sunlight and latitude in Europe
Authors: Omer S. , Iftime A. , Burcea V.
Published: January 2021

We systematically investigated an ongoing debate about the possible correlation between SARS-CoV-2 (COVID-19) epidemiological outcomes and solar exposure in European countries, in the period of March – December 2020. For each country, we correlated its mortality data with: i) objective sky cloudiness (as cloud fraction) derived from satellite weather data, ii) solar insolation (watt/square metre at ground level), iii) latitude. We found a positive correlation between the monthly mortality rate and the overall cloudiness in that month (Pearson’s r(35)=.68, P<.001; averaged linear model fitting the data, adjusted R2 =0.45). In an additional month-by-month analysis, 17% to 59% of the variance in COVID-19 mortality/million appears to be predicted by the cloudiness fraction of the sky, except in the last two months of 2020. We did not find any statistical significant correlation with insolation, nor with latitude of the countries, when the “latitude of a country” was precisely defined as the average landmass location (country centroid). The unexpected correlation found between cloudiness and mortality could perhaps be explained by the following: 1) heavy cloudiness is linked with colder outdoor surfaces, which might aid virus survival; 2) reduced evaporation rate; 3) moderate pollution may be linked to both cloudiness and mortality; and 4) large-scale behavioural changes due to cloudiness (which perhaps drives people to spend more time indoors and thus facilitates indoor contamination).
Is vitamin D deficiency associated with the COVID-19 epidemic in Europe?
Authors: Bakaloudi Dimitra Rafailia , Chourdakis Michail
Published: January 2021

The authors have withdrawn this manuscript because, following comments received during the review process, they have updated the number of countries included in their study (and also changed from 5 to 10 years the limit for Vit-D information studies that they included), which led to non-significant correlations between mortality and infections and Vit D deficiency prevalence. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
VeloViz: RNA-velocity informed embeddings for visualizing cellular trajectories
Authors: Atta Lyla , Sahoo Arpan , Fan Jean
Published: January 2021

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Single cell transcriptomic technologies enable genome-wide gene expression measurements in individual cells but can only provide a static snapshot of cell states. RNA velocity analysis can infer cell state changes from single cell transcriptomics data. To interpret these cell state changes as part of underlying cellular trajectories, current approaches rely on visualization with principal components, t-distributed stochastic neighbor embedding, and other 2D embeddings derived from the observed single cell transcriptional states. However, these 2D embeddings can yield different representations of the underlying cellular trajectories, hindering the interpretation of cell state changes. We developed VeloViz to create RNA-velocity-informed 2D and 3D embeddings from single cell transcriptomics data. Using both real and simulated data, we demonstrate that VeloViz embeddings are able to consistently capture underlying cellular trajectories across diverse trajectory topologies, even when intermediate cell states may be missing. By taking into consideration the predicted future transcriptional states from RNA velocity analysis, VeloViz can help visualize a more reliable representation of underlying cellular trajectories. VeloViz is available as an R package on GitHub (https://github.com/JEFworks-Lab/veloviz) with additional tutorials athttps://JEF.works/veloviz/.
Comparative metabolomics of fruits and leaves in a hyperdiverse lineage suggests fruits are a key incubator of phytochemical diversification
Authors: Schneider Gerald F. , Salazar Diego , Hildreth Sherry B. , Helm Richard F. , Whitehead Susan R.
Published: January 2021

Interactions between plants and leaf herbivores have long been implicated as the major driver of plant secondary metabolite diversity. However, other plant-animal interactions, such as those between fruits and frugivores, may also be involved in phytochemical diversification. Using 12 species ofPiper, we conducted untargeted metabolomics and molecular networking with extracts of fruits and leaves. We evaluated organ-specific secondary metabolite composition and compared multiple dimensions of phytochemical diversity across organs, including richness, structural complexity, and variability across samples at multiple scales within and across species. Plant organ identity significantly influenced secondary metabolite composition, both independent of and in interaction with species identity. Leaves and fruit shared a majority of compounds, but fruits contained more unique compounds and had higher total estimated chemical richness. While organ-level chemical richness and structural complexity varied substantially across species, fruit diversity exceeded leaf diversity in more species than the reverse. Furthermore, the variance in chemical composition across samples was higher for fruits than leaves. By documenting a broad pattern of high phytochemical diversity in fruits relative to leaves, this study lays groundwork for incorporating fruit into a comprehensive and integrative understanding of the ecological and evolutionary factors shaping secondary metabolite composition at the whole-plant level.
Altered cleavage of Caspase-1 in hepatocytes limits control of malaria in the liver
Authors: Marques-da-Silva Camila , Poudel Barun , Baptista Rodrigo P. , Peissig Kristen , Hancox Lisa S. , Shiau Justine C. , Pewe Lecia L. , Shears Melanie J. , Kanneganti Thirumala-Devi , Sinnis Photini , Kyle Dennis E. , Gurung Prajwal , Harty John T. , Kurup Samarchith P.
Published: January 2021

Malaria, caused byPlasmodiumparasites, is a devastating disease that kills over half a million people each year1.Plasmodiumsporozoites inoculated by mosquitoes into mammalian hosts undergo a clinically silent phase of obligatory development and replication in hepatocytes before initiating the life-threatening blood-stage of malaria2. Thus, understanding the immune responses elicited byPlasmodiuminfection in the liver is key to controlling clinical malaria and transmission3,4. Here, we show thatPlasmodiumDNA can be detected by AIM2 (absent in melanoma 2) sensors in the infected hepatocytes, resulting in Caspase-1 activation and pyroptotic cell-death. However, Caspase-1 was observed to undergo only partial cleavage in hepatocytes, limiting pyroptosis, and the maturation of pro-inflammatory cytokines classically associated with Caspase-1 activation. We discovered that the extent of Caspase-1 cleavage in cells is determined by the expression of ASC (apoptosis-associated speck-like protein containing a CARD). ASC expression is inherently low in hepatocytes, and transgenically enhancing it in the hepatocytes induced complete processing of Caspase-1, efficient secretion of pro-inflammatory cytokines, enhanced pyroptotic cell-death, and markedly improved control of malaria infection in the liver. In addition to describing a novel pathway of natural immunity to malaria, our findings uncover a key aspect of liver biology that may have been exploited during evolution by successful hepatotropic pathogens.