bluuebunny/crossref_metadata_2025 huggingface dataset:
Stress-Induced (Takotsubo) Cardiomyopathy After Liver Transplant Rescued with Venoarterial Extracorporeal Membrane Oxygenation
Authors: Caturegli Giorgio , Crane Matthew A. , Etchill Eric , Giuliano Kate , Nguyen Michelle , Philosophe Benjamin , Cho Sung-Min , Wittstein Ilan S. , Whitman Glenn J.R.
Published: May 2021

Here, we report the case of a 55 year old male patient without significant preexisting cardiovascular disease who received a deceased donor liver transplant. Intraoperatively, the patient developed cardiogenic shock secondary to stress-induced cardiomyopathy or Takotsubo syndrome (TTS), which was refractory to high-dose vasoactive, inotropic medical therapy. The patient was successfully managed with venoarterial extracorporeal membrane oxygenation (VA-ECMO) for 7 days, with complete recovery of cardiac function and maintenance of the hepatic graft. Given the anticipated need for only a short period of support and the expectation of full myocardial recovery, such patients may represent excellent candidates for the use of VA-ECMO.
Extracorporeal Membrane Oxygenation for Septic Shock in Children
Authors: Melnikov Georgy , Grabowski Simon , Broman Lars Mikael
Published: May 2021

Extracorporeal membrane oxygenation (ECMO) is a rescue treatment used in children and adults with reversible cardiorespiratory failure. The role of ECMO is not fully established in pediatric sepsis. In this retrospective single-center study, we aimed to investigate risk factors and survival in pediatric septic shock supported with peripheral cannulation ECMO. All patients aged 30 days to 18 years treated between 2007 and 2016 with ECMO for septic shock were included. Of 158 screened patients, 31 were enrolled in the study. The P/F ratio was 48 ± 22 mm Hg, b-lactate 8.5 ± 6.6 mmol/L, p-procalcitonin 214 (IQR 19–294) μg/L, and 2 (1–2) vasoactive drugs were infused. The number of organ failures were 3 (3–4). Ten patients were commenced on venovenous and 21 on venoarterial ECMO. Survival from ECMO was 71%, and 68% survived to hospital discharge. Hospital survival was 80% for venovenous ECMO and 62% in venoarterial support (p = 0.43). Factors associated with in-hospital mortality were high b-lactate (p = 0.015) and high creatinine (p = 0.019) at admission. Conversion between modalities was not a risk factor. Sixty percent were alive at long-term follow-up (median 6.5 years). Peripheral cannulation ECMO is feasible in pediatric septic shock. Treatment should be performed at high-volume ECMO centers experienced in sepsis, and central or peripheral type and ECMO modality according to center preference and patient’s need.
Recent Era Outcomes of Mechanical Circulatory Support in Children With Congenital Heart Disease as a Bridge to Heart Transplantation
Authors: Das Bibhuti B. , Trivedi Jaimin , Deshpande Shriprasad R. , Alsoufi Bahaaldin , Slaughter Mark S.
Published: May 2021

The objective of the study is to compare the clinical characteristics, risk factors, and overall survival (waitlist and posttransplant) outcomes in children with congenital heart disease (CHD) bridged to transplantation with either a ventricular assist device (VAD) versus extracorporeal membrane oxygenation (ECMO) versus no mechanical circulatory support (MCS) in the recent era. The study included 2,899 primary heart transplantations in patients <18 years with CHD between 2010 and 2019 from the United Network Organ Sharing database. Patients who had ECMO or VAD at listing or while listed were included, and their waitlist and posttransplant outcomes were compared with CHD patients who did not require MCS. Of all, 464 (16%) had ECMO and 200 (7%) VAD at the time of or during the listing. The VAD utilization increased over the last decade (4% in 2010 to 10% in 2019, p < 0.01). The 90 days post-MCS survival was better with VAD than ECMO (67 vs. 49%, p < 0.01). The transplantability rate at 90 days was decreased with younger age (odds ratio [OR], 0.91; 95% CI, 0.86–0.95), lower body mass index (BMI) (OR, 0.93; 95% CI, 0.89–0.98) and lower albumin <3g/dl (OR, 0.6; 95% CI, 0.53–0.7). The multivariate model predicted that lower BMI (OR, 1.12; 95% CI, 1.06–1.18), pretransplant ECMO (OR, 2.19; 95% CI, 1.39–3.45), and higher bilirubin (OR, 1.15; 95% CI, 0.97–1.36) decreased 1-year posttransplant survival. Patients transplanted with VAD had better 1-year survival than ECMO (88 vs. 70%, p = 0.01). Waiting list survival of children with CHD supported by VAD is better compared to ECMO. The 1-year posttransplantation outcome of CHD patients supported by VAD is similar to the no MCS patients and better than ECMO-supported patients. There is no significant difference in post-HT survival between patients transitioned from ECMO to VAD while listed and those with VAD-first.
Parent and Physician Report of Discussions About Prognosis for Critically Ill Children*
Authors: Rissman Lauren , Derrington Sabrina , Rychlik Karen , Michelson Kelly N.
Published: May 2021

Objectives:

Parents value clear communication with PICU clinicians about possible patient and family outcomes (prognostic conversations). We describe PICU parent and attending physician reports and agreement regarding the occurrence of prognostic conversations. We queried parents and physicians about prognostic conversation content, which healthcare providers had prognostic conversations, and whether parents wanted more prognostic information.

Design:

Prospective cross-sectional survey study.

Setting:

University-based 40-bed PICU.

Participants:

Parents and attending physicians of PICU patients with multiple organ dysfunction within 24 hours of PICU admission.

Interventions:

Surveys administered to parents and attending PICU physicians 5–10 days after PICU admission.

Measurements and Main results:

Surveys asked parents and physicians to report the occurrence of prognostic conversations related to PICU length of stay, risk of PICU mortality, and anticipated post-PICU physical, neurologic, and psychologic morbidities for patients and post-PICU psychologic morbidities for parents. Of 101 participants, 87 parents and 83 physicians reported having prognostic conversations. Overall concordance between parents and physicians was fair (Kappa = 0.22). Parents and physicians most commonly reported prognostic conversations about PICU length of stay (67.3% and 63.3%, respectively) and patient post-PICU physical morbidity (n = 48; 48.5% and n = 45; 44.5% respectively). Conversations reported less often by parents and physicians were about patient post-PICU psychologic morbidity (n = 13; 12.9% and n = 20; 19.8%, respectively). Per parent report, bedside nurses and physicians provided most prognostic information. Chaplains (n = 14; 50%) and social workers (n = 17; 60%) were more involved in conversations regarding parent psychologic morbidities. Most commonly, parents requested more information about length of stay and their child’s physical morbidities. Parents less frequently wanted information about their own psychologic morbidities.

Conclusions:

Most parents and physicians report having prognostic conversations, primarily about length of stay and post-ICU physical morbidities. Concordance between parents and physicians is suboptimal. Future studies should evaluate prognostic conversations at other timepoints, how information is delivered, and how these conversations impact the PICU experience.
Comparison of the Demographics and Visit Characteristics of Patients Who Left the Pediatric Emergency Department Without Being Seen With Those Who Were Evaluated in the Emergency Department
Authors: Suastegui Charles , Lozano Juan M. , Maniaci Vincenzo M. , Linares Marc Yves-Rene
Published: May 2021

Background

We compared those patients who left without being seen (LWBS) with those who stay for evaluation and determined which subsets were more likely to depart prematurely in the largest pediatric population studied to date.

Methods

We retrospectively extracted data from the electronic medical records of all pediatric patients who visited the emergency department between January 1, 2013, and December 31, 2015. The demographics and visit characteristics were compared between patients who LWBS and those seen by a provider. Bivariate and multivariate analyses were used to determine the odds for premature departure of specific groups within the population.

Results

Of the 271,364 pediatric patients visiting the emergency department during the 3-year study period, 3835 (1.4%) LWBS by a provider. The mean age of those LWBS was younger, and the odds of leaving slightly decreased as the patient's age increased (odds ratio [OR], 0.98). Those triaged as having “nonurgent” medical conditions had a statistically significant increase in odds of premature departure when compared with those with “urgent” medical conditions (OR, 1.16). Patients arriving during the evening and overnight hours had a much greater odds of LWBS (OR, 6.7 and 7.3, respectively).

Conclusions

Our findings demonstrated and confirmed that age, time of arrival, and acuity level upon presentation were predictors of patients leaving before evaluation. This can guide institutions with staffing and flow processes as they attempt to reduce LWBS rates but also raises further questions as to whether these subsets go forward to have worse clinical outcomes after leaving prematurely.
Evaluating Adolescent Substance Use and Suicide in the Pediatric Emergency Department
Authors: Quimby Ernika G. , Brogan Leah , Atte Tita , Diamond Guy , Fein Joel A.
Published: May 2021

Objectives

This study evaluates the relationship between substance use and impairment and current suicidal thoughts or behaviors in adolescent patients screened in a pediatric emergency department (ED).

Methods

Data were collected between June 2013 and February 2018 from adolescent patients who presented to a single, urban, pediatric ED. Adolescents completed a computerized, self-administered assessment that evaluates depression, suicide, posttraumatic stress, violence, traumatic exposure, bullying, and substance use. Assessments are administered as standard care to all ED patients aged 14 to 18 years. We used binary logistic regression to estimate the odds of reporting current suicidal thoughts or behaviors associated with patient demographics (ie, age, sex, and race), substance use in the past month, and substance-related impairment.

Results

A total of 11,623 adolescent patients (65.4% female and 52.9% African American) completed the assessment. Participants were, on average, 15.7 years old (SD = 1.27). Younger age (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.74–0.84) and substance use impairment (OR, 0.44; 95% CI, 0.33–0.58) decreased the odds of reporting current suicidal thoughts or behaviors, whereas male sex (OR, 1.51; 95% CI, 1.28–1.79) and those with past-month substance use (OR, 1.85; 95% CI, 1.51–2.26) increased the odds.

Conclusions

Recent substance use and male sex are associated with a higher likelihood of adolescents reporting current suicidal thoughts or behaviors during an ED visit. Standardized screening during pediatric ED visits may allow for more efficient evaluation of patients in higher-risk groups.
A Regional Intervention to Appoint Pediatric Emergency Care Coordinators in New England Emergency Departments
Authors: Li Joyce , Petrack Emory M. , Boggs Krislyn M. , Auerbach Marc , Foster Ashley A. , Sullivan Ashley F. , Camargo Carlos A.
Published: May 2021

Objective

The aim of this study was to describe our expansion of a Massachusetts grassroots initiative—to increase the appointment of pediatric emergency care coordinators (PECCs) in emergency departments (EDs)—to all 6 New England states.

Methods

We conducted annual surveys of all EDs in New England from 2015 to 2020 regarding 2014 to 2019, respectively. Data collection included ED characteristics. The intervention from 2018 to 2019 relied on principles of self-organization and collaboration with local stakeholders including state Emergency Medical Services for Children agencies, American College of Emergency Physician state chapters, and Emergency Nursing Association state chapters to help encourage appointment of at least 1 PECC to every ED. Most ED leadership were contacted in person at regional meetings, by e-mail and/or telephone. We reached out to each individual ED to both educate and encourage action.

Results

Survey response rates were greater than 85% in all years. From 2014 to 2016, less than 30% of New England EDs reported a PECC. In 2017, 51% of EDs in New England reported a PECC, whereas in 2019, 91% of New England EDs reported a PECC. All other ED characteristics remained relatively consistent from 2014 to 2019.

Conclusions

We successfully expanded a Massachusetts grassroots initiative to appoint PECCs to all of New England. Through individual outreach, and using principles of self-organization and creating collaborations with local stakeholders, we were able to increase the prevalence of PECCs in New England EDs from less than 30% to greater than 90%. This framework also led to the creation of a New England–wide PECC network and has fostered ongoing collaboration and communication throughout the region.
Trampoline Injuries in Children and Adolescents
Authors: Hussein Mohammad H. , Toreih Ahmad A. , Attia Abdallah S. , Alrowaili Majed , Fawzy Manal S. , Tatum Danielle , Toraih Eman A. , Kandil Emad , Duchesne Juan , Taghavi Sharven
Published: May 2021

Objective

As trampoline use grows more popular in the United States, the frequency of injuries continues to climb. We hypothesized that toddlers would be at the highest risk for trampoline injuries requiring hospitalization.

Methods

The National Electronic Injury Surveillance System database was examined for trampoline injuries from 2009 to 2018. Patients were categorized into 3 main age groups: toddlers (<2 years), children (2–12 years), and adolescents (13–18 years). Regression models were used to identify patients at high risk for injury or hospitalization.

Results

There was a total of 800,969 meeting inclusion criteria, with 433,827 (54.2%) occurring at their own homes and 86,372 (18.1%) at the sporting venue. Of the total, 36,789 (4.6%) were admitted to a hospital. Fractures (N = 270,884, 34%), strain/sprain injuries (N = 264,990, 33%), followed by skin contusions/abrasions (N = 115,708, 14%) were the most common diagnoses. The most frequent injury sites were lower and upper extremities accounting for 329,219 (41.1%) and 244,032 (30.5%), whereas 175,645 (21.9%) had head and neck injuries. Musculoskeletal injuries (74%) and concussions (2.6%) were more frequent in adolescents than children (67.6% and 1.6%) and toddlers (56.3% and 1.3%). Internal organ and soft tissue injuries were frequent in toddlers. There were no fatalities reported in the injured patients. Multivariate analysis showed adolescents, female sex, extremity injuries, and musculoskeletal injuries were associated with hospitalization. Injury at a sporting venue was not associated with hospitalization.

Conclusions

Adolescents and girls are at increased risk of trampoline injury, warranting hospitalization. Safety standards may help prevent extremity and musculoskeletal injuries in the pediatric population. Finally, use of trampolines at sporting venues does not appear to be particularly dangerous.
Stopping disease-modifying therapy in relapsing and progressive multiple sclerosis
Authors: Hartung Hans-Peter , Meuth Sven G. , Miller Deborah M. , Comi Giancarlo
Published: May 2021

Purpose of review

To assess the reasons for considering discontinuation of disease-modifying therapies (DMTs)in patients with multiple sclerosis (MS). Relevant aspects of the natural history, pathology, and immunology are analyzed.

Recent findings

A number of retrospective observational studies in aggregate indicate that stopping DMTs may be attempted in older individuals with stable disease. Prognostic factors have been identified informing about the risk of recurrence of disease activity after DMT discontinuation.

Several clinical scenarios provide a rationale to stop DMTs in people with MS. Cumulative evidence has been gathered recently allowing us to more precisely weigh the risks against the benefits. This information aids in the decision process.
Histopathological Image Analysis for Oral Squamous Cell Carcinoma classification using concatenated deep learning models
Authors: Amin Ibrar , Zamir Hina , Khan Faisal F.
Published: May 2021

Oral squamous cell carcinoma (OSCC) is a subset of head and neck squamous cell carcinoma (HNSCC), the 7th most common cancer worldwide, and accounts for more than 90% of oral malignancies. Early detection of OSCC is essential for effective treatment and reducing the mortality rate. However, the gold standard method of microscopy-based histopathological investigation is often challenging, time-consuming and relies on human expertise. Automated analysis of oral biopsy images can aid the histopathologists in performing a rapid and arguably more accurate diagnosis of OSCC. In this study, we present deep learning (DL) based automated classification of 290 normal and 934 cancerous oral histopathological images published by Tabassum et al (Data in Brief, 2020). We utilized transfer learning approach by adapting three pre-trained DL models to OSCC detection. VGG16, InceptionV3, and Resnet50 were fine-tuned individually and then used in concatenation as feature extractors. The concatenated model outperformed the individual models and achieved 96.66% accuracy (95.16% precision, 98.33% recall, and 95.00% specificity) compared to 89.16% (VGG16), 94.16% (InceptionV3) and 90.83% (ResNet50). These results demonstrate that the concatenated model can effectively replace the use of a single DL architecture.
Longer incubation periods of SARS-CoV-2 infection in infants than children
Authors: Leung Char
Published: May 2021

Objective

A large body of research has described the incubation period of SARS-CoV-2 infection, an important metric for assessing the risk of developing a disease as well as surveillance. While longer incubation periods for elderly have been found, it remains elusive whether this also holds true for infants and children, partly due to the lack of data. The present work clarified the incubation periods of COVID-19 for infants and children.

Methods

Using the data released by the Chinese health authorities and municipal offices, statistical comparisons of clinical features were made between infants (aged below 1 year) and children (aged between 1 and 17 years). An age-varying incubation period distribution period was modeled using maximum likelihood estimation modified for interval censored exposure time and age.

Discussion

Reported in 56 web pages, a total of 65 cases from 20 provinces dated between January and June 2020, including 18 infants and 47 children, were eligible for inclusion. Infants appeared to bear more severe clinical courses, as demonstrated by the higher prevalence of breathing difficulty as well as nasal congestion. In contrast, fever was less prominent in infants than in children. The incubation period was found to decrease with age, with infants appearing to have longer incubation periods.

Conclusion

Fever remained to be one of the most commonly seen symptoms in infants and children with SARS-CoV-2 infection and have continued to determine the time of symptom onset. While shorter incubation periods should be seen in patients with weaker immune system due to weaker antiviral response that is beneficial for viral growth, the longer incubation period in infants may be due to their weaker febrile response to the virus, leading to prolonged symptom onset.
Anti-SARS-CoV-2 Antibodies Persist for up to 13 Months and Reduce Risk of Reinfection
Authors: Gallais Floriane , Gantner Pierre , Bruel Timothée , Velay Aurelie , Planas Delphine , Wendling Marie-Josée , Bayer Sophie , Solis Morgane , Laugel Elodie , Reix Nathalie , Schneider Anne , Glady Ludovic , Panaget Baptiste , Collongues Nicolas , Partisani Marialuisa , Lessinger Jean-Marc , Fontanet Arnaud , Rey David , Hansmann Yves , Kling-Pillitteri Laurence , Schwartz Olivier , De Sèze Jérome , Meyer Nicolas , Gonzalez Maria , Schmidt-Mutter Catherine , Fafi-Kremer Samira
Published: May 2021

Assessment of the kinetics of SARS-CoV-2 antibodies is essential in predicting protection against reinfection and durability of vaccine protection. Here, we longitudinally measured Spike (S) and Nucleocapsid (N)-specific antibodies in 1,309 healthcare workers (HCWs), including 916 COVID-19 negative HCWs and 393 convalescent COVID-19 for up to 422 days post-symptom. From month (M)1 to M7-9 post-infection, SARS-CoV-2 antibodies decreased moderately in convalescent HCWs in a biphasic model, with men showing a slower decay of anti-N (p=0.02), and a faster decay of anti-S (p=0.0008) than women. At M11-13, anti-N dramatically decreased (half-life: 283 days) while anti-S stabilized (half-life: 725 days) at a median of 2.39 log Arbitrary Units (AU)/mL (Interquartile Range (IQR): 2.10 -2.75). Overall, 69 SARS-CoV-2 infections developed in the COVID-19 negative group (incidence of 12.22 per 100 person-years) versus one in the COVID-19 positive group (incidence of 0.40 per 100 person-years), indicating a relative reduction in the incidence of SARS-CoV-2 reinfection of 96.7% (p<0.0001). Correlation with live-virus neutralization assay revealed that variants D614G and B.1.1.7, but not B.1.351, were sensitive to anti-S antibodies at 2.3 log AU/mL, while IgG ≥ 3 log AU/mL neutralized all three variants. After SARS-CoV-2 vaccination, anti-S levels reached at least 3 logs regardless of pre-vaccination IgG levels, type of vaccine, and number of doses. Our study demonstrates a long-term persistence of anti-S IgG antibodies that may protect against reinfection. By significantly increasing cross-neutralizing antibody titers, a single-dose vaccination strengthens protection against escape mutants.
Seroconversion rates following COVID-19 vaccination amongst patients with malignant disease- the impact of diagnosis and cancer-directed therapies
Authors: Thakkar Astha , Lugo Jesus Gonzalez , Goradia Niyati , Gali Radhika , Shapiro Lauren C. , Pradhan Kith , Rahman Shafia , Kim So Yeon , Ko Brian , Sica R. Alejandro , Kornblum Noah , Bachier-Rodriguez Lizamarie , McCort Margaret , Goel Sanjay , Perez-Soler Roman , Packer Stuart , Sparano Joseph , Gartrell Benjamin , Makower Della , Goldstein Yitz D , Wolgast Lucia , Verma Amit , Halmos Balazs
Published: May 2021

As COVID-19 has been shown to adversely affect patients with cancer, prophylactic strategies are critically needed. We determined the immunogenicity of COVID-19 vaccination in a cohort of cancer patients that had received full dosing with one of the FDA-approved COVID-19 vaccines. 201 oncology patients underwent anti-spike protein SARS-CoV-2 IgG testing post vaccination and demonstrated a high rate of seroconversion (94%) overall. When compared to solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematological malignancies (85%), particularly recipients of anti-CD20 therapies (70%) and stem cell transplantation (74%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post-vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post-vaccination. Relatively lower IgG titers were noted following vaccination with the adenoviral when compared to the mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify vulnerable cohorts that need novel vaccination or passive immunization strategies.
Restricting carbohydrates and calories in the treatment of type 2 diabetes: a systematic review of the effectiveness of ‘low carbohydrate’ interventions with differing energy levels
Authors: Nicholas Anna P , Mota Adrian Soto , Lambert Helen , Collins Adam L
Published: May 2021

There are two proven dietary approaches to shift type 2 diabetes (T2D) into remission: low energy diets (LED) and low carbohydrate diets (LCD). These approaches differ in their rationale and application yet both involve carbohydrate restriction, either as an explicit goal or as a consequence of reducing overall energy intake. The aims of this systematic review were to identify, characterise and compare existing clinical trials that utilised ‘low carbohydrate’ interventions with differing energy intakes. Electronic databases CENTRAL, CINAHL, Embase, MEDLINE and Scopus were searched to identify controlled clinical trials in adults with T2D involving low carbohydrate intake (defined as <130g carbohydrate/day) and reporting weight and glycemic outcomes. The initial database search yielded 809 results, of which 18 studies met the inclusion criteria. 12/18 studies utilised low carbohydrate diets with moderate or unrestricted energy intake. Six trials utilised low energy diets (<1200kcal/day), with all except one incorporating meal-replacements as part of a commercial weight loss programme. Interventions using both restricted and unrestricted (ad libitum) energy intakes produced clinically significant weight loss and reduction in HbA1c at study end-points. Trials that restricted energy intake were not superior to those that allowed ad libitum low carbohydrate feeding at 12 and 24 months. An association was observed across studies between average weight loss and reduction in HbA1c, which strengthened with trial length, indicating that sustained weight loss is key to T2D remission. Further research is needed to specifically ascertain the weight-independent effects of carbohydrate restriction on glycemic control in T2D.

Graphical abstract
SARS-CoV-2 lineage dynamics in England from January to March 2021 inferred from representative community samples
Authors: Eales Oliver , Page Andrew J. , Tang Sonja N. , Walters Caroline E. , Wang Haowei , Haw David , Trotter Alexander J. , Viet Thanh Le , Foster-Nyarko Ebenezer , Prosolek Sophie , Atchison Christina , Ashby Deborah , Cooke Graham , Barclay Wendy , Donnelly Christl A. , O’Grady Justin , Volz Erik ,   The COVID-19 Genomics UK (COG-UK) Consortium, Darzi Ara , Ward Helen , Elliott Paul , Riley Steven
Published: May 2021

Genomic surveillance for SARS-CoV-2 lineages informs our understanding of possible future changes in transmissibility and vaccine efficacy. However, small changes in the frequency of one lineage over another are often difficult to interpret because surveillance samples are obtained from a variety of sources. Here, we describe lineage dynamics and phylogenetic relationships using sequences obtained from a random community sample who provided a throat and nose swab for rt-PCR during the first three months of 2021 as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Overall, diversity decreased during the first quarter of 2021, with the B.1.1.7 lineage (first identified in Kent) predominant, driven by a 0.3 unit higher reproduction number over the prior wild type. During January, positive samples were more likely B.1.1.7 in younger and middle-aged adults (aged 18 to 54) than in other age groups. Although individuals infected with the B.1.1.7 lineage were no more likely to report one or more classic COVID-19 symptoms compared to those infected with wild type, they were more likely to be antibody positive 6 weeks after infection. Viral load was higher in B.1.1.7 infection as measured by cycle threshold (Ct) values, but did not account for the increased rate of testing positive for antibodies. The presence of infections with non-imported B.1.351 lineage (first identified in South Africa) during January, but not during February or March, suggests initial establishment in the community followed by fade-out. However, this occurred during a period of stringent social distancing and targeted public health interventions and does not immediately imply similar lineages could not become established in the future. Sequence data from representative community surveys such as REACT-1 can augment routine genomic surveillance.
Monitors to Improve Indoor Carbon Dioxide Concentrations in the Hospital: Background, Rationale and Protocol for a Randomized, Sham-controlled, Cross-Over, Open Label Trial
Authors: Laurent Michaël R. , Frans Johan
Published: May 2021

Coronavirus disease 2019 (COVID-19) has caused considerably morbidity and mortality worldwide, mainly among older adults. Hospital outbreaks contribute to the burden of this disease, despite optimal hand hygiene and personal protective equipment such as masks and face shields. Ventilation with fresh outdoor air has emerged as an important strategy to reduce indoor aerosol transmission of COVID-19. Carbon dioxide (CO2) monitors are increasingly advocated to facilitate ventilation in schools, long-term care facilities, offices and public buildings. Moreover, several health authorities have issued guidelines for target CO2 values in work as well as clinical environments. Given that modern hospitals have superior indoor air quality control systems, it remains however unknown whether feedback from CO2 monitors is needed and/or effective to improve ventilation further. Here, we describe the rationale and protocol for a randomized, sham-controlled, crossover, open label trial of CO2 monitors in double-bed hospital rooms in two acute geriatric wards. Based on pilot data, Aranet4 Home® monitors will be used to alert nurses and other staff to raised indoor CO2 concentrations. Practical limitations in implementing CO2 monitors are discussed, and will be surveyed among staff as additional study outcomes. The Monitors to Improve Indoor Carbon Dioxide (CO2) Concentrations in the Hospital (MICH) trial is registered at ClinicalTrials.gov, identifier: NCT04770597.
Evaluation of Statistical Illiteracy in Latin American Clinicians and of the Efficacy of a 10-Hour Course
Authors: Soto-Mota Adrian , Maravilla Eduardo Carrillo , Cárdenas Fragoso Jose Luis , Lozano Cruz Óscar Arturo , Herrero Alfonso Gulías , De Leon Rosales Sergio Ponce
Published: May 2021

Introduction

All medics require statistical interpretation skills to keep up to date with the scientific advances and evidence-based recommendations of their specific field. However, statistical illiteracy among clinicians is a highly prevalent problem with far-reaching consequences. The few available studies that report statistical literacy improvements after educational interventions do not report for how long these benefits last. We measured for the first-time statistical proficiency among Latin-American clinicians with different levels of training and evaluated the efficacy of a 10-hour course at multiple timepoints.

Methods

Using an online questionnaire, we evaluated self-perceived statistical proficiency, scientific literature reading habits and statistical literacy (using an adaptation of the Quick Risk Test) across multiple levels of medical training. Separately, we evaluated statistical proficiency among Internal Medicine residents at a tertiary centre in Mexico City immediately before, immediately after and one and two months after a 10-hour statistics course using the same adaptation (allowing for “I don’t know” answers) of the Quick Risk Test. Scores across multiple time points were compared using Friedman’s Test.

Results

Data from 392 clinicians from 9 Latin American countries were analyzed. Most clinicians (85%) failed our adaptation of the Quick Risk Test (mean score = 2.6/10, IQR:1.4). The 10-hour course significantly improved the scores of the Internal Medicine Residents (n=16) from 3.8/10, IQR:1.8 to 8.3/10, IQR:1.4 (p<0.01). However, scores dropped after one and two months to 7.7/10, IQR:1.6 and 6.1 / 10, IQR:2.2, respectively.

Conclusions

Statistical Illiteracy is highly prevalent among Latin American clinicians. Short-term educational interventions are effective but, their benefits quickly fade away if they are not periodically reinforced. Medical boards and Medical schools need to periodically teach and evaluate statistical proficiency to ameliorate these issues.
In-hospital cardiac arrest in Intensive Care Unit versus non-Intensive Care Unit patients with COVID-19. A systematic review and meta-analysis
Authors: Mavrovounis Georgios , Mermiri Maria , Chalkias Athanasios , Sheth Vishad , Tsolaki Vasiliki , Gourgoulianis Konstantinos , Pantazoulos Ioannis
Published: May 2021

Aim

To estimate the incidence of in-hospital cardiac arrest (IHCA) and return of spontaneous circulation (ROSC) in COVID-19 patients, as well as to compare the incidence and outcomes of IHCA in Intensive Care Unit (ICU) versus non-ICU patients with COVID-19.

Methods

We systematically reviewed the PubMed, Scopus and clinicaltrials.gov databases to identify relevant studies.

Results

Eleven studies were included in our study. The pooled prevalence/incidence, pooled odds ratios (OR) and 95% Confidence Intervals (95% CI) were calculated, as appropriate. The quality of the included studies was assessed using appropriate tools. The pooled incidence of IHCA in COVID-19 patients was 7% [95% CI: 4 – 11%; P < 0.0001] and 44% [95% CI: 30 – 58%; P < 0.0001] achieved ROSC. Of those that survived, 58% [95% CI: 42 – 74%; P < 0.0001] had a good neurological outcome (Cerebral Performance Category 1 or 2) and the mortality at the last follow-up was 59% [95% CI: 37 – 81%; P < 0.0001]. A statistically significant higher percentage of ROSC [OR (95% CI): 5.088 (2.852, 9.079); P < 0.0001] was found among ICU patients versus those in the general wards.

Conclusion

The incidence of IHCA amongst hospitalized COVID-19 patients is 7%, with 44% of them achieving ROSC. Patients in the ICU were more likely to achieve ROSC than those in the general wards, however the mortality did not differ.

What this paper adds

Section 1: What is already known on this subject

Mortality in COVID-19 patients ranges between 20% and 40%.

it has been reported that patients with COVID-19 have a high incidence of IHCA and higher mortality.

This paper aimed to calculate the proportion of COVID-19 patients who experience IHCA and their outcome, as well as compare the outcome of IHCA between ICU and non-ICU patients.

Section 2: What this study adds

Approximately 7% of hospitalized COVID-19 patients suffer from IHCA and 44% of those achieve ROSC.

The rate of ROSC was higher in ICU patients, but the rate of mortality did not differe between ICU and non-ICU patients.
Electrical Stimulation and Time to Radiographic Healing of Acute Fractures: A Systematic Review and Meta-Analysis
Authors: Nicksic Peter J. , Rymut Kevin , Dingle Aaron , Verma Nishant , Doro Christopher , Shoffstall Andrew , Ludwig Kip , Poore Samuel O.
Published: May 2021

Objective

To determine if electrical stimulation (ES) reduces days to radiographic union of acute fractures

Data Sources

MEDLINE database search using the terms combinations of “electric stimulation AND bone healing”, “electric stimulation AND fracture,” “electric stimulation AND fracture healing,” full articles, English language, without publication date restriction

Study Selection

Inclusion criteria were (1) randomized-controlled trials concerning electrical stimulation for the purpose of healing acute fractures with (2) outcomes on radiographic union at regular time intervals. Exclusion criteria were (1) studies involving skeletally immature patients or (2) ES for non-unions, spinal fusions, and osteotomies.

Data Extraction

Study quality was assessed with the Cochrane Collaboration tool for risk of bias assessment by 2 independent reviewers. Heterogeneity between studies was assessed with the χ2and I2tests.

Data Synthesis

The mean days to radiographic union was calculated as a continuous variable with standard deviations. The meta-analysis was performed to compare the ES and non-ES groups across studies using Metafor ® software (Bell Labs, Murray Hill, NJ, United States).

Conclusion

Electrical stimulation does not reduce time to radiographic union in acute fractures. However, an improvement in the healing time was noted in the semi-invasive method of ES in which the current was delivered directly within the fracture site. This finding provides evidence that innovative methods of ES delivery may demonstrate the promising results found in smaller animal studies.

Level of Evidence

Level I
Cost-effectiveness of a whole-area testing pilot of asymptomatic SARS-CoV-2 infections with lateral flow devices: A modelling and economic analysis study
Authors: Drakesmith Mark , Collins Brendan , Jones Angela , Nnoaham Kelechi , Thomas Daniel
Published: May 2021

Background

Mass community testing for SARS-CoV-2 by lateral flow devices (LFDs) aims to reduce prevalence in the community. However its effectiveness as a public heath intervention is disputed.

Method

Data from a mass testing pilot in the Borough of Merthyr Tydfil in late 2020 was used to model cases, hospitalisations, ICU admissions and deaths prevented. Further economic analysis with a healthcare perspective assessed cost-effectiveness in terms of healthcare costs avoided and QALYs gained.

Results

An initial conservative estimate of 360 (95% CI: 311-418) cases were prevented by the mass testing, representing a would-be reduction of 11% of all cases diagnosed in Merthyr Tydfil residents during the same period. Modelling healthcare burden estimates that 24 (16 - 36) hospitalizations, 5 (3-6) ICU admissions and 15 (11-20) deaths were prevented, representing 6.37%, 11.1% and 8.2%, respectively of the actual counts during the same period. A less conservative, best-case scenario predicts 2333 (1764-3115) cases prevented, representing 80% reduction in would-be cases. Cost effectiveness analysis indicates 108 (80-143) QALYs gained, an incremental cost ratio of £2,143 (£860-£4,175) per QALY gained and net monetary benefit of £6.2m (£4.5m-£8.4m). In the best-case scenario, this increases to £15.9m (£12.3m-£20.5m).

Conclusions

A non-negligible number of cases, hospitalisations and deaths were prevented by the mass testing pilot. Considering QALYs gained and healthcare costs avoided, the pilot was cost-effective. These findings suggest mass testing with LFDs in areas of high prevalence (>2%) is likely to provide significant public health benefit. It is not yet clear whether similar benefits will be obtained in low prevalence settings or with vaccination rollout.
Exploring the extracellular transcriptome in seminal plasma for non-invasive prostate cancer diagnosis
Authors: Hulstaert Eva , Morlion Annelien , Nuytens Justine , Ponti Giovanni , Maccaferri Monia , Lau Susan , Diamandis Eleftherios , Keith Jarvi , Prassas Ioannis , Lumen Nicolaas , Mestdagh Pieter , Vandesompele Jo
Published: May 2021

A diagnostic non-invasive biomarker test for prostate cancer at an early stage, with high sensitivity and specificity, would improve diagnostic decision making. Extracellular RNAs present in seminal plasma might contain biomarker potential for the accurate detection of clinically significant prostate cancer. So far, the extracellular messenger RNA (mRNA) profile of seminal plasma has not been interrogated for its biomarker potential in the context of prostate cancer. Here, we investigate the mRNA transcriptome in seminal plasma samples obtained from prostate cancer patients (n=25), patients with benign prostate hyperplasia (n=26) and individuals without prostatic disease (n=6). Seminal plasma harbors a complex mRNA repertoire that reflects prostate as its tissue of origin. The endogenous RNA content is higher in the prostate cancer samples compared to the control samples. Prostate cancer antigen 3 (PCA3), a long non-coding RNA with prostate cancer-specific overexpression, and ATP-binding cassette transporter 1 (ABCA1), known to be involved in the prostate cancer pathogenesis, were more abundant in the prostate cancer group. In addition, twelve high confidence fusion transcripts could be detected in prostate cancer samples, including the bona-fide prostate cancer fusion transcript TMPRSS2-ERG. Our findings provide proof-of-principle that the extracellular transcriptome of seminal plasma can reveal information of an underlying prostate cancer.
Methods for identifying culprit drugs in cutaneous drug eruptions: A scoping review
Authors: Bose Reetesh , Ogbalidet Selam , Boshra Mina , Finstad Alexandra , Marzario Barbara , Huang Christina , Fahim Simone
Published: May 2021

Background

Cutaneous drug eruptions are a significant source of morbidity, mortality, and cost to the healthcare system. Identifying the culprit drug is essential; however, despite numerous methods being published, there are no consensus guidelines.

Objectives

Conduct a scoping review to identify all published methods of culprit drug identification for cutaneous drug eruptions, compare the methods, and generate hypotheses for future causality assessment studies.

Eligibility criteria

Peer-reviewed publications involving culprit drug identification methods.

Sources of evidence

Medline, Embase, and Cochrane Central Register of Controlled Trials.

Charting methods

Registered PRISMA-ScR format protocol on Open Science Forum.

Results

In total, 135 publications were included comprising 656,635 adverse drug events, most of which were cutaneous. There were 54 methods of culprit drug identification published, categorized as algorithms, probabilistic approaches, and expert judgment.

Algorithms had higher sensitivity and positive predictive value, but lower specificity and negative predictive value. Probabilistic approaches had lower sensitivity and positive predictive value, but higher specificity and negative predictive value. Expert judgment was subjective, less reproducible, but the most frequently used to validate other methods. Studies suggest that greater accuracy may be achieved by specifically assessing cutaneous drug eruptions and using combinations of causality assessment categories.

Conclusions

Culprit drug identification for adverse drug reactions remains a challenge. Many methods have been published, but there are no consensus guidelines. Using causality assessment methods specifically for cutaneous drug eruptions and combining aspects of the different causality assessment categories may improve efficacy. Further studies are needed to validate this hypothesis.
Analysis of 472,688 severe cases of COVID-19 in Brazil showed lower mortality in those vaccinated against influenza
Authors: Sardinha Daniele Melo , da Costa Lobato Diana , da Silva Ferreira Ana Lúcia , Batista Lima Karla Valéria , de Paula Souza e Guimarães Ricardo José , Costa Lima Luana Nepomuceno Gondim
Published: May 2021

Objective

To analyze the severe cases of COVID-19 in Brazil in 2020 and compare those vaccinated and unvaccinated against influenza in invasive ventilation, admission in Intensive Care Unit (ICU) and deaths.

Method

Cross-sectional study with public data from the OpenDataSUS platform, regarding confirmed severe cases for COVID-19 in Brazil in the year 2020. Data were analyzed by SPSS, from the chi-square test of independence and binary logistic regression.

Results

The population was 472,688 cases and 177,640 deaths, with a lethality of 37.58% in severe cases. The test of independence was highly significant in vaccinated survivors (<0.0001), and regression showed an almost twofold odds ratio for invasive ventilation, ICU admission, and death in unvaccinated cases.

Conclusion

We recommend mass influenza vaccination as an adjuvant in combating the COVID-19 pandemic in Brazil.
Systematic Testing for SARS-CoV-2 Infection Among Essential Workers in Montréal, Canada: A Prospective Observational and Cost Assessment Study
Authors: Campbell Jonathon R. , Dion Cynthia , Uppal Aashna , Yansouni Cedric P. , Menzies Dick
Published: May 2021

BACKGROUND

Essential workers are at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We did a prospective study to estimate the yield, acceptability, and costs of workplace-based systematic SARS-CoV-2 testing of asymptomatic essential workers.

METHODS

We recruited non-healthcare essential businesses, in Montréal, Canada. Mobile teams, composed of two non-healthcare professionals each, visited businesses. Consenting, asymptomatic employees provided saline gargle specimens under supervision. Mobile team members self-sampled weekly. Specimens were analyzed using reverse-transcription polymerase chain reaction (RT-PCR). If an outbreak was detected (≥2 positives), we retested all initially negative participants. We did logistic regression for factors associated with a positive test. We estimated costs ($CAD) of this strategy.

RESULTS

From 27 January to 12 March 2021, 69 essential businesses were visited. Of an estimated 2348 employees onsite, 2128 (90.6%) participated. Across 2626 tests, 53 (2.0%) were positive. Self-reported non-Caucasian ethnicity (aOR 3.7, 95% CI: 1.4-9.9) and a negative SARS-CoV-2 test before the study (0.4, 0.2-0.8) were positively and negatively associated with a positive test, respectively. Five businesses—3 manufacturing/supplier and 2 meat processing— were experiencing an outbreak. At these businesses, 40 (4.4%) of 917 participants were positive on the initial test. We repeated testing at three of these businesses over 2-3 weeks: 8/350 (2.3%) were positive on the second test, and zero were positive on the third and fourth test (148 tests); no employer reported new positives to 26 March 2021. In all other businesses, 1211 participants were tested once—5 (0.4%) were positive at three childcare enterprises, one grocery store, and one manufacturing/supplier. Per person, RT-PCR costs were $34.00 and all other costs $8.67. No mobile team member tested positive.

INTERPRETATION

Onsite sampling of essential workers with saline gargle is safe, acceptable, and inexpensive. Repeat testing appeared to eliminate outbreaks. Systematic testing should be considered part of SARS-CoV-2 preventive efforts.
Structural heterogeneity of cellular K5/K14 filaments as revealed by cryo-electron microscopy
Authors: Weber Miriam S. , Eibauer Matthias , Sivagurunathan Suganya , Magin Thomas M. , Goldman Robert D. , Medalia Ohad
Published: May 2021

Keratin intermediate filaments are an essential and major component of the cytoskeleton in epithelial cells. They form a stable yet dynamic filamentous network extending from the nucleus to the cell periphery. Keratin filaments provide cellular resistance to mechanical stresses, ensure cell and tissue integrity in addition to regulatory functions. Mutations in keratin genes are related to a variety of epithelial tissue diseases that mostly affect skin and hair. Despite their importance, the molecular structure of keratin filaments remains largely unknown. In this study, we analyzed the structure of keratin 5/keratin 14 filaments within ghost keratinocytes by cryo-electron microscopy and cryo-electron tomography. By averaging a large number of keratin segments, we have gained insights into the helical architecture of the filaments. Interestingly, two-dimensional classification revealed profound variations in the diameter of keratin filaments and their subunit organization. Reconstitution of filaments of substantial length from keratin segments uncovered a high degree of internal heterogeneity along single filaments, which can contain regions of helical symmetry, regions with less symmetry and regions with significant diameter fluctuations. Cross section views of filaments revealed that keratins form hollow cylinders consisting of multiple protofilaments, with an electron dense core located in the center of the filament. These findings shed light on the complex architecture of keratin filaments, which demonstrate a remarkable degree of heterogeneity, suggesting that they are highly flexible, dynamic cytoskeletal structures.