bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Benign Paroxysmal Positional Vertigo After Endothelial Keratoplasty–A Unique Cause of Postoperative Nausea and Headache
Authors: Patel Sachin , Yuan Amy , Pineda Roberto
Published: November 2020

Purpose:

To describe a case of new-onset benign paroxysmal positional vertigo (BPPV) after uncomplicated Descemet stripping automated endothelial keratoplasty.

Methods:

Case report and review of literature.

Results:

A 61-year-old woman with a history of steroid-induced glaucoma and penetrating keratoplasty for Fuchs endothelial dystrophy, and no history of BPPV or other vertigo, underwent Descemet stripping automated endothelial keratoplasty for penetrating keratoplasty graft failure. On the third postoperative day, she developed acute spinning vertigo, nausea, and headache on sitting up after 3 days of strict supine positioning. Her ophthalmic examination was benign, with no evidence of a pupillary block, and she was diagnosed by an otologist with BPPV. Her symptoms resolved after 1 week without further intervention.

Conclusions:

BPPV is a benign but rare complication of nonotologic surgery and has not been previously reported with ophthalmic surgery. The overlap in symptomatology between BPPV and other serious and potentially vision-threatening causes of postoperative nausea and headache, such as pupillary block glaucoma, makes this a relevant etiology to consider in the spectrum of postendothelial keratoplasty complications.
Efficacy, safety, and predictability of transepithelial photorefractive keratectomy: meta-analysis
Authors: Sabau Alexandra , Daas Loay , Behkit Abdelshafi , Wagenpfeil Stefan , Langenbucher Achim , Ardjomand Navid , Flockerzi Elias , Seitz Berthold
Published: November 2020

Purpose:

To evaluate the efficacy, safety, and predictability of transepithelial photorefractive keratectomy (TransPRK) for correcting myopia, astigmatism, and hyperopia.

Setting:

Department of Ophthalmology, Saarland University Medical Center, Homburg/Saar, Germany.

Design:

Meta-analysis of retrospective or prospective studies.

Methods:

Relevant studies were collected from Medline and included when meeting the following predefined criteria: randomized controlled trials, at least 1 of the main outcome measures as efficacy, safety, or predictability, and 1 common TransPRK laser (Schwind Amaris). The parameters estimates and 95% CI were derived from random-effects meta-analysis to account for possible heterogeneity.

Results:

Because hyperopia studies did not meet the inclusion criteria, the results are centered on myopia and astigmatism. Sixteen studies with a total of 1924 treated eyes were included in the meta-analysis. The mean efficacy, safety, and predictability had a probability of 94% (CI, 0.86-0.97), 0% (CI, 0.00-0.03), and 89% (CI, 0.82-0.93), respectively. The mean correction index, difference vector, and index of success had a value of 1.01 (CI, 1.01-1.02), 0.20 (CI, 0.06-0.34), and 0.12 (CI, 0.07-0.18), respectively.

Conclusions:

This summary estimate showed that TransPRK was highly effective, safe, and predictable in correcting myopia and/or astigmatism.
Correlations Between Stress, Depression, Body Mass Index, and Food Addiction Among Korean Nursing Students
Authors: Hong Hyon Joo , Kim Ran , Kim Ae Sil , Kim Jung Ho , Kim Hyun Ji , Song Ji Hyeun , Shin Sung Hee
Published: November 2020

This study examined the relationships between stress, depression, body mass index, and food addiction in South Korean nursing students. Data from 323 nursing students in Seoul, Gangwon-do, Jeollanam-do, Gyeongsangnam-do, and Jeju-do were collected via self-report questionnaires and analyzed using chi-square tests, Mann–Whitney U tests, logistic regression analyses, and the receiver operating characteristic curve using SPSS 21.0. Overall, 7.1% of students were classified as having a food addiction. Stress and depression affected food addiction, and food addiction influenced obesity. Depression and stress combined were predictors of food addiction. These findings suggest that effective stress management and interventions for depression prevention may be beneficial to prevent food addiction in nursing students.
The Relationships Between Prenatal Smoking Exposure and Telomere Lengths in Fetuses, Infants, and Children
Authors: Wei Holly , Zhang Chongben , Silveyra Patricia
Published: November 2020

Objective

The aim of this study was to evaluate the relationships between prenatal smoking exposure and telomere lengths (TLs) in fetuses, infants, and children.

Methods

This is a systematic review guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Databases searched were Biomedical Reference Collection, MEDLINE via PubMed, CINAHL, PsycINFO, and Google Scholar. The latest search was on October 18, 2019.

Results

Seven studies met the inclusion criteria and thus were reviewed. Five of the studies showed significant inverse relationships between prenatal tobacco exposure and TLs in fetuses, infants, and children. One study showed a modification effect of the postconceptual age, indicating that older fetuses with prenatal smoking exposure had shorter TLs than their counterparts. This effect was more prominent after 93 days of postconception. Another study reported a finding that was contrary to the above results, showing that the telomeres of newborns with prenatal smoking exposure were longer than those of their counterparts.

Conclusion/Recommendations

This review shows that the impact of prenatal smoking on the health of unborn fetuses, infants, and children is an understudied area. Because of the inconsistent findings and cross-sectional study designs, more research is required, especially longitudinally studies. Nonetheless, the findings of the review provide partial evidence that prenatal smoking can potentially impact the genetic biomarker, TLs, and, thus, health of fetuses, infants, and children. The evidence confirms the current practice that pregnant women should be encouraged to stop smoking as soon as they become pregnant.
Depressive Symptom Trajectories in Family Caregivers of Stroke Survivors During First Year of Caregiving
Authors: Chung Misook L. , Lee Suk Jeong , Son Youn-Jung , Miller Jennifer L. , King Rosemarie B.
Published: November 2020

Background

The purpose of this study was to identify patterns of depressive symptom trajectory and examine the associations of the symptom trajectory with caregiving burden, family function, social support, and perceived health status of caregivers of stroke survivors during the first year of caregiving after discharge from rehabilitation center.

Methods

Caregivers of stroke survivors completed a survey of depressive symptoms, caregiving burden, family function, perceived availability of social support, and perceived health status at postdischarge and 1 year. Patterns of depressive symptom trajectory (ie, symptom-free, symptom relieved, symptom developed, and persistent symptom groups) were identified by grouping depressive symptoms based on 2 assessments using the Center for Epidemiologic Studies-Depression. Repeated-measures analysis of variance and multinomial logistic regression were used to examine the associations.

Results

Of the 102 caregivers, 57.8% were symptom-free, 20.6% experienced persistent depressive symptoms, 11.8% relieved depressive symptoms, and 9.8% developed depressive symptoms. There were significant changes in family function (Wilks λ = 0.914, P = .038) and perceived health status (Wilks λ = 0.914, P = .033) among the groups during the first year of caregiving. The persistent symptom group reported the highest level of burden and the lowest level of family function and perceived availability of social support at both assessment times. Compared with symptom-free caregivers, caregivers with persistent depressive symptoms were 7 times more likely to have fair/poor health rather than excellent/very good health at 1 year (odds ratio, 7.149; P = .012).

Conclusion

Caregivers with persistent depressive symptoms are the most vulnerable to negative psychosocial outcomes and poor perceived health status during the first year of caregiving from discharge for stroke survivors.
Creating a Healthier Workplace Environment in an Era of Rising Workforce Pressures
Authors: Edmonson Cole , Marshall June , Gogek Jim
Published: November 2020

Challenges in the nurse work environment, particularly those resulting from nurse shortages and the retirement wave, can affect the health and well-being of all Americans, not just nurses themselves or the health care organizations where they work. Many of the solutions to significantly expand the number of nurses in America will take many years to realize. However, there are some important changes that health care organizations can put into effect relatively quickly to enhance the work environment for nurses, which can improve care quality and safety, patient satisfaction, and the well-being of nurses. The biennial Survey of Registered Nurses by AMN Healthcare, which polled nearly 20 000 RNs, found that nurses are eager for many workplace changes that would create a healthier workplace while enhancing their professional and personal lives. These institutional changes also create opportunities for improving the health of the organizations themselves. Analysis of survey data found that improving professional development, flexibility and work-life balance, safety and team engagement, and organizational response to workplace violence can create a healthier workplace for nurses. These are known solutions that have yet to be fully engaged.
Case Report: Ocular Tilt Reaction with Internuclear Ophthalmoplegia and Multiple Cranial Nerve Palsies
Authors: Teo Shee Kiang , Mohd Khialdin Safinaz , Yong Meng Hsien , Othman Othmaliza , Ami Malisa
Published: November 2020

SIGNIFICANCE

Ocular tilt reaction (OTR) is an abnormal eye-head postural reaction that consists of skew deviation, head tilt, and bilateral ocular torsion. Understanding of the pathway of the vestibulo-ocular reflex (VOR) is essential because this will help to localize the pathology.

PURPOSE

The aim of this study was to report a case of OTR with contralateral internuclear ophthalmoplegia (INO) and fifth and seventh cranial nerve palsies.

CASE REPORT

A 51-year-old gentleman with underlying diabetes mellitus presented with sudden onset of diplopia for 3 days. On examination, his visual acuity was 20/30 bilaterally without a relative afferent pupillary defect. He had a right OTR consisting of a right head tilt, a skew deviation with a left eye hypertropia, and bilateral ocular torsion (right excyclotorsion and left incyclotorsion) with nystagmus. He also had a left adduction deficit and right abduction nystagmus consistent with a left INO. Ocular examination revealed evidence of proliferative diabetic retinopathy bilaterally. Two days after the initial presentation, the patient developed left seventh and fifth cranial nerve palsies. MRI showed left pontine infarction and multiple chronic lacunar infarctions. There was an incidental finding of a vascular loop compression on cisternal portions of the left trigeminal, facial, and vestibulocochlear nerves. Antiplatelet treatment was started on top of a better diabetic control. The diplopia was gradually resolved with improved clinical signs. In this case, the left pontine infarction had likely affected the terminal decussated part of the vestibulocochlear nerve from the right VOR pathway, medial longitudinal fasciculus, and cranial nerve nuclei in the left pons.

CONCLUSIONS

The OTR can be ipsilateral to the lesion if the lesion is before the decussation of the VOR pathway in the pons, or it can be contralateral to the lesion if the lesion is after the decussation. In case of an OTR that is associated with contralateral INO and other contralateral cranial nerves palsy, a pathology in the pons that is contralateral to the OTR should be considered. Neuroimaging study can hence be targeted to identify the possible cause.
Assessing Physical Medicine and Rehabilitation Residency Education Using the Neurological Assessment Competency Evaluation System
Authors: Yeh Peter Chia , Gilbert-Baffoe Ekua , Michael Ashley , Frontera Joel
Published: November 2020

Competent neurologic examination and clinical skills are essential components in the care for patients in acute hospital and rehabilitation settings. To enhance the evaluation and education of Physical Medicine and Rehabilitation residents, the authors developed an educational objective structured clinical examination, the Neurological Exam Assessment Competency Evaluation System, and gathered 2 yrs of baseline data. The Neurological Exam Assessment Competency Evaluation System consisted of nine 9-min examination stations, seven with written clinical scenario with instructions for junior residents to complete the appropriate examination (stations: Altered Mental Status, Mild Traumatic Brain Injury, Dementia, Stroke, Falls, and the International Standards for Neurological Classification of Spinal Cord Injury Sensory and Motor Examinations). Examinees provided written responses to posed questions for the other two stations—Modified Ashworth Scale and brachial plexus. The assessment tools for this examination were designed for residency programs to evaluate the basic competencies as outlined by the Accreditation Council for Graduate Medical Education and Physical Medicine and Rehabilitation milestones. Based on the feedback received from the examinees and examiners, the Neurological Exam Assessment Competency Evaluation System can serve as an educational objective structured clinical examination for the improvement of trainee core competencies.
Systematic scoping review of interactions between analgesic drug therapy and mindfulness-based interventions for chronic pain in adults: current evidence and future directions
Authors: Park Rex , Mohiuddin Mohammed , Poulin Patricia A. , Salomons Tim , Edwards Robert , Nathan Howard , Haley Chris , Gilron Ian
Published: November 2020

Most patients with chronic pain do not find adequate pain relief with a single treatment, and accumulating evidence points to the added benefits of rational combinations of different treatments. Given that psychological therapies, such as mindfulness-based interventions (MBIs), are often delivered in conjunction with concomitant analgesic drug therapies (CADTs), this systematic scoping review examines the evidence for any interactions between MBIs and CADTs. The protocol for this review has been published and registered. MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, and PsycINFO databases were searched until July 2019. We included randomized controlled trials that evaluated the efficacy of MBIs for the treatment of chronic pain. A total of 40 randomized controlled trials (2978 participants) were included. Thirty-nine of 40 (97.5%) included mindfulness-based clinical trials allowed the use of CADTs. However, only 6 of these 39 (15.4%) trials provided adequate details of what these CADTs were, and only 4 (10.3%) trials controlled for CADTs. Of great relevance to this review, none of the included trials analyzed the interactions between MBIs and the CADTs to determine whether they have an additive, synergistic, or antagonistic effect on chronic pain. Adverse events were inconsistently reported, and no judgment could be made about safety. Future trials assessing the interactions between MBIs and CADTs, with better harms reporting, are needed to better define the role of MBIs in the management of chronic pain.
Association of SNPs in HLA-C and ZNRD1 Genes With HIV-1 Mother-to-Child Transmission in Zambia Population
Authors: Celerino da Silva Ronaldo , Segat Ludovica , Kuhn Louise , Chies José Artur Bogo , Crovella Sergio
Published: November 2020

Background:

Human leukocyte antigen C (HLA-C) and Zinc ribbon domain containing 1 (ZNRD1) are considered HIV-1 restriction factors and are expressed in the placenta. Variations in HLA-C and ZNRD1 genes are known to influence HIV-1 infection, including viral replication and progression to AIDS. Little is known about the role of variants in these genes in HIV-1 mother-to-child transmission.

Methods:

We evaluated the distribution of HLA-C (rs10484554, rs9264942) and ZNRD1 (rs8321, rs3869068) variants in a Zambian population composed of 333 children born to HIV-1+ mothers (248 HIV-1 noninfected/85 HIV-1 infected) and 97 HIV-1+ mothers.

Results:

Genotypic distribution of HLA-C and ZNRD1 were in Hardy–Weinberg equilibrium, except for HLA-C rs10484554 in both groups. In mothers, no significant differences were observed in their allele and genotypic distributions for both genes. The T and TT variants (rs10484554—HLA-C) were significantly more frequent among HIV-1+ children, specifically those who acquired the infection in utero (IU) and intrapartum (IP). For ZNRD1, the T allele (rs3869068) was more frequent in HIV-1− children, showing significant differences in relation to those infected via IP and postpartum (PP). The CT and TT genotypes were significantly more frequent in HIV-1− children.

Conclusions:

Variations in HLA-C (T and TT—rs10484554) and ZNRD1 (T and CT/TT—rs3869068) can increase and decrease the susceptibility to HIV-1 infection via mother-to-child transmission, respectively. Further studies are encouraged focusing on a greater number of variants and sample size, with functional validation and in other populations.
Assessing Readability of Patient Education Materials on Breast Reconstruction by Major US Academic Hospitals as Compared With Nonacademic Sites
Authors: Powell Lauren E. , Andersen Emily S. , Pozez Andrea L.
Published: November 2020

Purpose

Women undergoing postmastectomy breast reconstruction face many complex choices. A myriad of online patient education materials exist to assist in decision making. Understanding of these materials, termed health literacy, affects surgical decision making and outcomes. The National Institutes of Health recommends writing patient education materials at a sixth- to seventh-grade reading level. The primary goal of this study was to assess readability of online breast reconstruction materials.

Methods and Materials

Resources were collected from every academic hospital with a plastic surgery residency program, 97 in total. These data were compared with the top nonacademic Web sites ranked by search engine results, 14 in total. Materials were analyzed using 3 validated readability assessment scales: Coleman-Liau Index, SMOG (Simplified Measure of Gobbledygook) Readability Formula, and Flesch-Kincaid Grade Level. Average readability was analyzed, and results were compared using a 1-way analysis of variance to assess for significance between the different tools and a 2-sided t test to assess for significance between academic and nonacademic readability results.

Results

The mean readability scores across the academic programs were a Coleman-Liau Index of 13.38 (standard Deviation [SD] 2.81, 13th to 14th grade), Flesch-Kincaid Grade Level of 13.04 (SD = 3.9, 13th grade), and SMOG Readability of 13.64 (SD = 2.99, 13th to 14th grade). For the 14 nonacademic sites, results showed a Coleman-Liau Index of 11.93 (SD = 1.14, 12th grade), Flesch-Kincaid of 11.82 (SD = 2.33, 11th to 12th grade), and SMOG Readability of 10.91 (SD = 1.79, 11th grade). One-way analysis of variance demonstrated no significant differences in mean readability scores across the 3 readability tools used (academic F = 2.7804, P = 0.06; nonacademic F = 1.14, P = 0.33). Two-tailed t test results demonstrated that there was statistical significance between readability of the academic in comparison with nonacademic search engine results (t = 2.04, P = 0.04).

Conclusions

Average readability across all Web sites were much higher than the recommended reading level, at a 13th to 14th grade reading level for academic institutions, and an 11th to 12th grade for nonacademic Web sites. Plastic surgeons may contribute to improving patient understanding and perioperative outcomes through revising patient education materials.
State of Microsurgery Training in 2020
Authors: Morrison Kerry A. , Verzella Alexandra , Hacquebord Jacques H.
Published: November 2020

Background

Given the current national conundrum of decreasing microsurgery case volume performed by hand surgery fellows despite interest, program directors were surveyed to evaluate opinions of exposure gaps in training and to determine the current state of microsurgery training in 2020.

Methods

Anonymous national surveys were distributed to hand surgery fellowship program directors by the American Society for Surgery of the Hand. Subgroups were compared by training location and size of the fellowship program. Accreditation Council for Graduate Medical Education public national data on graduate case log procedures by hand surgery fellows were reviewed.

Results

Eighty-eight surveys were distributed by the American Society for Surgery of the Hand to hand surgery fellowship program directors with a 44% (n = 39) response rate. Hand surgery fellowship programs from 19 US states participated. Most program's fellows had previous orthopedic surgery residency training with 41.03% of programs surveyed having 100% orthopedic surgery–trained fellows. The average number of weekly vascular microsurgical cases ranged from 25% of fellowships having no microsurgery cases per week, 46.2% having 1 per week, and only 7.7% having 5 or more cases per week. However, 60.5% of program directors prioritized a microvascular surgery case as the most valuable educational opportunity for fellows. Most program directors agreed (79.5%) that a 1-year hand surgery fellowship is sufficient to train a competent hand surgeon, who is proficient in microsurgery. In contrast, the majority disagreed (53.8%) that hand surgery microsurgery skills after a 1-year hand surgery fellowship are equivalent among graduates, regardless of a prior plastic surgery or orthopedic surgery residency training. There was a statistically significant difference in program directors’ responses by geographic location regarding prior residency background impacting microsurgical skills (Kendall τ, −0.439; P = 0.001). Graduate case log data revealed an increasing trend in the number of microsurgery procedures performed by orthopedic hand surgery fellows until 2014, with a decline in cases per year and stagnating trend at 7% thereafter.

Conclusions

In 2020, most hand surgery fellowship program directors highly value and prioritize microsurgery exposure for their hand surgery fellows' education despite the decrease in case volume for hand surgery fellows.
Modafinil Induced Spontaneous Ejaculation Without Orgasm: A Case Report
Authors: Aras Neriman
Published: November 2020

Modafinil is used for the treatment of narcolepsy and obstructive sleep apnea syndrome, and as add-on therapy for psychiatric diseases such as attention-deficit/hyperactivity disorder, schizophrenia, depression, cocaine addiction. The exact mechanism of action is unknown. Modafinil may be helpful for the treatment of erectile dysfunction and premature ejaculation. The addition of modafinil to antidepressant treatment may provide positive effects on sexual dysfunction. However, side effects such as hypersexuality and unwanted orgasm have been reported with modafinil treatment. In this article, a patient who had developed spontaneous ejaculations after the addition of modafinil for the treatment of depression with venlafaxine is discussed. Although venlafaxine treatment continued after the discontinuation of modafinil, spontaneous ejaculation did not continue. It should be kept in mind that agents with dopaminergic and noradrenergic effects, such as modafinil, can cause undesirable sexual side effects.
The past, present and future of ancient bacterial DNA
Authors: Arning Nicolas , Wilson Daniel J.
Published: November 2020

Groundbreaking studies conducted in the mid-1980s demonstrated the possibility of sequencing ancient DNA (aDNA), which has allowed us to answer fundamental questions about the human past. Microbiologists were thus given a powerful tool to glimpse directly into inscrutable bacterial history, hitherto inaccessible due to a poor fossil record. Initially plagued by concerns regarding contamination, the field has grown alongside technical progress, with the advent of high-throughput sequencing being a breakthrough in sequence output and authentication. Albeit burdened with challenges unique to the analysis of bacteria, a growing number of viable sources for aDNA has opened multiple avenues of microbial research. Ancient pathogens have been extracted from bones, dental pulp, mummies and historical medical specimens and have answered focal historical questions such as identifying the aetiological agent of the black death as

Yersinia pestis

. Furthermore, ancient human microbiomes from fossilized faeces, mummies and dental plaque have shown shifts in human commensals through the Neolithic demographic transition and industrial revolution, whereas environmental isolates stemming from permafrost samples have revealed signs of ancient antimicrobial resistance. Culminating in an ever-growing repertoire of ancient genomes, the quickly expanding body of bacterial aDNA studies has also enabled comparisons of ancient genomes to their extant counterparts, illuminating the evolutionary history of bacteria. In this review we summarize the present avenues of research and contextualize them in the past of the field whilst also pointing towards questions still to be answered.
The efficacy and safety of hydroxychloroquine in COVID19 patients : a multicenter national retrospective cohort
Authors: Abdulrahman Abdulkarim , AlSayed Islam , AlMadhi Marwa , AlArayed Jumana , Mohammed Sara Jaafar , Sharif Aesha Khalid , Alansari Khadija , AlAwadhi Abdulla I , AlQahtani Manaf
Published: November 2020

Background

Hydroxychloroquine is an antimalarial drug that received worldwide news and media attention in the treatment of COVID-19 patients. This drug was used based on its antimicrobial and antiviral properties despite lack of definite evidence of clinical efficacy. In this study, we aim to assess the efficacy and safety of using Hydroxychloroquine in treatment of COVID-19 patients who are admitted in acute care hospitals in Bahrain.

Methodology

We conducted retrospective cohort study on a random sample of admitted COVID19 patients between 24 February and 31 July 2020. The study was conducted in four acute care COVID19 hospitals in Bahrain. Data was extracted from the medical records. The primary endpoint was the requirement of non-invasive ventilation, intubation or death. Secondary endpoint was length of hospitalization for survivors. Three methods of analysis were used to control for confounding factors: logistic multivariate regression, propensity score adjusted regression and matched propensity score analysis.

Results

A random sample of 1571 patients were included, 440 of which received HCQ (treatment group) and 1131 did not receive it (control group). Our results showed that HCQ did not have a significant effect on primary outcomes due to COVID-19 infection when compared to controls after adjusting for confounders (OR 1.43 95% CI 0.85 to 2.37, P value=0.17). Co-administration of azithromycin had no effect on primary outcomes (OR 2.7 95% CI 0.82 to 8.85 P value =0.10). HCQ was found to be associated with increased risk of hypoglycemia (OR 10.9 95% CI 1.72 - 69.49, P value =0.011) and diarrhea(OR 2.8, 95% CI 1.4-5.5, P value =0.003), but not QT prolongation(OR=1.92, 95% CI 0.95-3.9, P value =0.06) or cardiac arrhythmia.(OR=1.06, 95% CI 0.55-2.05, P value =0.85).

Conclusion

Our results showed no significant beneficial effect of using hydroxychloroquine on the outcome of COVID-19 patients. Moreover, the risk of hypoglycemia due to hydroxychloroquine would possess a significant risk for out of hospital use.
T cell and antibody functional correlates of severe COVID-19
Authors: Yu Krystle K.Q. , Fischinger Stephanie , Smith Malisa T. , Atyeo Caroline , Cizmeci Deniz , Wolf Caitlin R. , Layton Erik D. , Logue Jennifer K. , Aguilar Melissa S. , Shuey Kiel , Loos Carolin , Yu Jingyou , Franko Nicholas , Choi Robert Y. , Wald Anna , Barouch Dan H. , Koelle David M. , Lauffenburger Douglas , Chu Helen Y. , Alter Galit , Seshadri Chetan
Published: November 2020

Comorbid medical illnesses, such as obesity and diabetes, are associated with more severe COVID-19, hospitalization, and death. However, the role of the immune system in mediating these clinical outcomes has not been determined. We used multi-parameter flow cytometry and systems serology to comprehensively profile the functions of T cells and antibodies targeting spike, nucleocapsid, and envelope proteins in a convalescent cohort of COVID-19 subjects who were either hospitalized (n=20) or not hospitalized (n=40). To avoid confounding, subjects were matched by age, sex, ethnicity, and date of symptom onset. Surprisingly, we found that the magnitude and functional breadth of virus-specific CD4 T cell and antibody responses were consistently higher among hospitalized subjects, particularly those with medical comorbidities. However, an integrated analysis identified more coordination between polyfunctional CD4 T-cells and antibodies targeting the S1 domain of spike among subjects that were not hospitalized. These data reveal a functionally diverse and coordinated response between T cells and antibodies targeting SARS-CoV-2 which is reduced in the presence of comorbid illnesses that are known risk factors for severe COVID-19. Our data suggest that isolated measurements of the magnitudes of spike-specific immune responses are likely insufficient to anticipate vaccine efficacy in high-risk populations.
Genetic Mutations Associated with Hormone-Positive Breast Cancer in Ethiopian Women
Authors: Schwartz Alyssa D. , Adusei Afua , Tsegaye Solomon , Moskaluk Christopher A. , Schneider Sallie S. , Platt Manu O. , Seifu Daniel , Peyton Shelly R. , Babbitt Courtney C.
Published: November 2020

In Ethiopia, a breast cancer diagnosis is associated with a prognosis significantly worse than that of Europe and the US. Further, patients presenting with breast cancer in Ethiopia are far younger, on average, and patients are typically diagnosed at very late stages, relative to breast cancer patients of European descent. Emerging data suggest that a large proportion of Ethiopian patients have hormone-positive (ER +) breast cancer. This is surprising given 1) the aggressive nature of the disease, 2) that African Americans with breast cancer frequently have triple negative breast cancer (TNBC), and 3) these patients typically receive chemotherapy, not hormone-targeting drugs. To further examine the similarity of Ethiopian breast tumors to those of African Americans or of those of European descent, we sequenced matched normal and tumor tissue from Ethiopian patients from a small pilot collection. We identified mutations in 615 genes across all three patients, unique to the tumor tissue. Across this analysis, we found far more mutations shared between Ethiopian patient tissue and White patients (103) than we did comparing to African Americans (3). Several mutations were found in extracellular matrix encoding genes with known roles in tumor cell growth and metastasis. We suggest future mechanistic studies on this disease focus on these genes first, toward finding new treatment strategies for breast cancer patients in Ethiopia.
Universities and COVID-19 Growth at the Start of the 2020 Academic Year
Authors: Penuliar Mike , Clark Candice , Curti Debbie , Hudson Cathy , Philips Billy
Published: November 2020

The global pandemic of 2020 caused by the novel coronavirus of 2019 (COVID-19) has uprooted the education system of the United States. As American colleges and universities try to resume regular instruction for the 2020-2021 academic year, outbreaks have begun to emerge and university towns across the country are now virus hotspots. The current paper provides two studies. First, the current work investigates how the growth of COVID-19 compares in areas with large universities against those without. Results showed markedly increase case growth in counties with large universities at the start of the fall 2020 semester. Secondly, this work provides a highly accessible and modifiable epidemiological tool known as a susceptible-infected-removed model for educational administrators that will allow users to see the impact of COVID-19 historically and predictively. The results of an exemplar model using a large public research university, Texas Tech University, are discussed.
Optimal shutdown strategies for COVID-19 with economic and mortality costs: BC as a case study
Authors: Barlow M.T. , Marshall N.D. , Tyson R.C.
Published: November 2020

Decision makers with the responsibility of managing policy for the COVID-19 epidemic have faced difficult choices in balancing the competing claims of saving lives and the high economic cost of shutdowns. In this paper we formulate a model with both epidemiological and economic content to assist this decision making process. We consider two ways to handle the balance between economic costs and deaths. First, we use the statistical value of life, which in Canada is about C$7 million, to optimise over a single variable, which is the sum of the economic cost and the value of lives lost. Our second method is to calculate the Pareto optimal front when we look at the two variables – deaths and economic costs.

In both cases we find that, for most parameter values, the optimal policy is to adopt an initial shutdown level which reduces the reproduction number of the epidemic to close to 1. This level is then reduced once a vaccination program is underway. Our model also indicates that an oscillating policy of strict and mild shutdowns is less effective than a policy which maintains a moderate shutdown level.
Characterisation, identification, clustering, and classification of disease
Authors: Webster A.J. , Gaitskell K. , Turnbull I. , Cairns B.J. , Clarke R.
Published: November 2020

Data-driven classifications are improving statistical power and refining prognoses for a range of respiratory, infectious, autoimmune, and neurological diseases. Studies have used molecular information, age of disease incidence, and sequences of disease onset (“disease trajectories”). Here we consider whether easily measured risk factors such as height and BMI can usefully characterise diseases in UK Biobank data, combining established statistical methods in new but rigorous ways to provide clinically relevant comparisons and clusters of disease. Over 400 common diseases were selected for study on the basis of clinical and epidemiological criteria, and a conventional proportional hazards model was used to estimate associations with 12 established risk factors. Comparing men and women, several diseases had strongly sex-dependent associations of disease risk with BMI. Despite this, a large proportion of diseases affecting both sexes could be identified by their risk factors, and equivalent diseases tended to cluster adjacently. This included 10 diseases presently classified as “Symptoms, signs, and abnormal clinical and laboratory findings, not elsewhere classified”. Many clusters are associated with a shared, known pathogenesis, others suggest likely but presently unconfirmed causes. The specificity of associations and shared pathogenesis of many clustered diseases, provide a new perspective on the interactions between biological pathways, risk factors, and patterns of disease such as multimorbidity.
Automated Western immunoblotting detection of anti-SARS-CoV-2 serum antibodies
Authors: Edouard S. , Jaafar R. , Orain N. , Parola P. , Colson P. , La Scola B. , Fournier P-E. , Raoult D. , Drancourt M.
Published: November 2020

ELISA and chemiluminescence serological assays for COVID-19 are currently incorporating only one or two SARS-CoV-2 antigens. We developed an automated Western immunoblotting as a complementary serologic assay for COVID-19. The Jess™ Simple Western system, an automated capillary-based assay was used, incorporating an inactivated SARS-CoV-2 lineage 20a strain as antigen, and IgT detection. In total, 602 sera were tested including 223 from RT-PCR-confirmed COVID-19 patients, 76 from patients diagnosed with seasonal HCoVs and 303 from coronavirus-negative control sera. We also compared this assay with the EUROIMMUN® SARS-CoV-2 IgG ELISA kit. Among 223 sera obtained from RT-PCR-confirmed COVID-19 patients, 180/223 (81%) exhibited reactivity against the nucleocapsid and 70/223 (31%) against the spike protein. Nucleocapsid reactivity was further detected in 9/76 (14%) samples collected from patients diagnosed with seasonal HCoVs and in 15/303 (5%) coronavirus-negative control samples. In the subset of sera collected more than 2 weeks after the onset of symptoms, the sensitivity was 94% and the specificity 93%, the latter value probably reflecting cross-reactivity of SARS-CoV-2 with other coronaviruses. The automated Western immunoblotting presented a substantial agreement (90%) with the compared ELISA (Cohen’s Kappa=0.64). Automated Western immunoblotting may be used as a second line test to monitor exposition of people to HCoVs including SARS-CoV-2.
Using Whole Genome Sequences to Investigate Adenovirus Outbreaks, Including Five Deaths in a Haematopoietic Stem Cell Transplant Unit
Authors: Myers Chloe E. , Houldcroft Charlotte J. , Roy Sunando , Margetts Ben K. , Best Timothy , Venturini Cristina , Guerra-Assunção José A. , Williams Charlotte A. , Williams Rachel , Dunn Helen , Hartley John C. , Rolfe Kathryn J. , Breuer Judith
Published: November 2020

Background

Human mastadenoviruses (HAdV) are associated with significant morbidity and mortality amongst the immunocompromised population. A recent surge in HAdV cases, including five deaths, amongst a haematopoietic stem cell transplant population led us to use whole genome sequencing (WGS) to investigate.

Methods

To gain a complete transmission picture, we compared outbreak and non-outbreak sequences (54 sequences from 37 patients) with GenBank sequences and our own database of previously sequenced HAdVs (132 sequences from 37 patients). An improved bait set for WGS was used. Maximum likelihood trees and pairwise differences were used to evaluate genotypic relationships paired with epidemiological data from routine Infection, Prevention and Control (IPC) activity.

Results

Nine monophyletic clusters were identified, seven of which were corroborated by epidemiological evidence and by comparison of single nucleotide polymorphisms. Two incomplete patient clusters were identified by IPC over the same time period. Of the five patients who died, one had a mixed HAdV infection and two were the source of transmission events.

Conclusions

The clinical consequences of unmitigated HAdV transmission events are high. Focusing on two high risk wards using WGS we identified six transmission events, over prolonged periods, that would have gone unnoticed using traditional polymerase chain reaction and epidemiology. Mixed infection is frequent (10% of patients), providing a sentinel source of recombination and superinfection. Immunosuppressed patients harbouring a high rate of HAdV positivity require comprehensive surveillance. As a consequence of these findings, HAdV WGS is being incorporated routinely into a clinical algorithm to prevent transmission and influence IPC policy in real-time.

Whole genome sequencing of adenovirus, direct from clinical samples, can be used to identify cryptic health care associated transmission events, and to resolve transmission suspected by traditional epidemiology. It can also identify mixed genotype infections in immunocompromised patient populations.
Changing case fatality risk for COVID-19 over time in selected European countries
Authors: Becher Heiko , Olszewski Katharina , Wiegel Sarah , Mueller Olaf
Published: November 2020

Objectives To illustrate the development of the case fatality risk (CFR) for COVID-19 over time using different assumptions for calculating the CFR.
Design Observational study.
Setting Selected European countries, 28 January to October 29 2020.
Participants Laboratory-confirmed COVID-19 cases and deaths due to COVID-19
Main outcome measure case fatality risk (CFR)
Results We show that the CFR has considerably decreased over time. This seems to be driven not only by increased testing but also by a reduced CFR among cases older than 60 years. Our data also confirm a significantly higher fatality risk for men than for women. The decline in the CFR is even more pronounced when only cases and deaths occurring in a specified time window are considered. This alternative estimation method has the advantage that early data where the bias due to the incomplete ascertainment of cases was arguably largest do not affect CFR estimates later on. We find similar results for other European countries.
Conclusion CFR estimates vary considerably depending on the underlying assumptions concerning their calculation. Reliable CFR estimates should not be based on cumulative numbers from the beginning of the pandemic but rather be based on more recent data only.
The evolving worldwide dynamic state of the COVID-19 outbreak
Authors: Vilar Jose M. G. , Saiz Leonor
Published: November 2020

The dynamic characterization of the COVID-19 outbreak is critical to implement effective actions for its control and eradication but the information available at a global scale is not sufficiently reliable to be used directly. Here, we integrate multiple data sources through dynamical constraints to quantify its temporal evolution and controllability around the world and within the United States. Overall, the numbers of actively infectious individuals have remained high beyond targeted controllability, with worldwide estimates of 10.24 million on November 24, 2020, totaling in 266.1 million cumulative infections growing at a rate of 11.12 million new infections per week. The actively infectious population reached a local maximum of 7.33 million on July 16, 2020 and remained virtually stagnant at a global scale, with growth rates for most countries around zero that compensated each other, until reverting to net growth on September 22, 2020. We validated the approach, contrasting with prevalence data and the effects of nonpharmaceutical interventions, and we identified general patterns of recession, stabilization, and resurgence. The diversity of dynamic behaviors of the outbreak across countries is paralleled by those of states and territories in the United States, converging to remarkably similar global states in both cases. Our results offer precise insights into the dynamics of the outbreak and an efficient avenue for the estimation of the prevalence rates over time.
Auricular Vagus Neuromodulation – A Systematic Review on Quality of Evidence and Clinical Effects
Authors: Verma Nishant , Mudge Jonah D , Kasole Maïsha , Chen Rex C , Blanz Stephan L , Trevathan James K , Lovett Eric , Williams Justin C , Ludwig Kip A
Published: November 2020

This review is intended to identify key gaps in the mechanistic knowledge and execution of aVNS studies, to be addressed in future works, and aid the successful translation of neuromodulation therapies.

Background

The auricular branch of the vagus nerve runs superficial to the surface of the skin, which makes it a favorable target for non-invasive stimulation techniques to modulate vagal activity. For this reason, there have been many early-stage clinical trials on a diverse range of conditions. These trials often report conflicting results for the same indication.

Methods

Using the Cochrane Risk of Bias tool we conducted a systematic review of auricular vagus nerve stimulation (aVNS) randomized controlled trials (RCTs) to identify the factors that led to these conflicting results. As is common for early-stage studies, the majority of aVNS studies were assessed as having ‘some’ or ‘high’ risk of bias, which makes it difficult to interpret their results in a broader context.

Results

There is evidence of a modest decrease in heart rate during higher stimulation dosages, sometimes at above the level of sensory discomfort. Findings on heart rate variability conflict between studies and are hindered by trial design, including inappropriate washout periods, and multiple methods used to quantify heart rate variability. There is early-stage evidence to suggest aVNS may reduce circulating levels and endotoxin-induced levels of inflammatory markers. Studies on epilepsy reached primary endpoints similar to previous RCTs testing implantable vagus nerve stimulation (VNS) therapy, albeit with concerns over quality of blinding. Preliminary evidence shows that aVNS ameliorated pathological pain but not evoked pain.

Discussion

Based on results of the Cochrane analysis we list common improvements for the reporting of results, which can be implemented immediately to improve the quality of evidence. In the long term, existing data from aVNS studies and salient lessons from drug development highlight the need for direct measures of local neural target engagement. Direct measures of neural activity around the electrode will provide data for the optimization of electrode design, placement, and stimulation waveform parameters to improve on-target engagement and minimize off-target activation. Furthermore, direct measures of target engagement, along with consistent evaluation of blinding success, must be used to improve the design of controls in the long term – a major source of concern identified in the Cochrane analysis.

Conclusion

The need for direct measures of neural target engagement and consistent evaluation of blinding success is applicable to the development of other paresthesia-inducing neuromodulation therapies and their control designs.
Timing ofM. tuberculosisexposure explains variation in BCG effectiveness: A systematic review and meta-analysis
Authors: Trauer James M , Kawai Andrew , Coussens Anna , Datta Manjula , Williams Bridget M , McBryde Emma S , Ragonnet Romain
Published: November 2020

Background

The variable efficacy observed in studies of BCG vaccination is incompletely explained by currently accepted hypotheses, such as latitudinal gradient in non-tuberculous mycobacteria exposure. We investigated heterogeneity in BCG vaccination in the context of participant demography, diagnostic approach and TB-related epidemiological context.

Methods

We updated previous systematic reviews of the effectiveness of BCG vaccination to 31stDecember 2018. We employed an identical search strategy and inclusion/exclusion criteria to past reviews, but reclassified several studies and developed an alternative classification system.

Results

Of 21 included trials, those recruiting neonates and children aged under five were consistent in demonstrating considerable protection for several years. Trials in high-burden settings with shorter follow-up also showed considerable protection, as did most trials in settings of declining burden with longer follow-up. However, the few trials performed in high-burden settings with longer follow-up showed no protection, sometimes with higher case rates in the vaccinated than the controls in the later follow-up period.

Conclusions

The most plausible explanatory hypothesis is that BCG protects against TB that results from exposure shortly after vaccination. However, risk is equivalent or increased when exposure occurs later from vaccination, a phenomenon which is predominantly observed in adults in high-burden settings with longer follow-up. In settings of declining burden, most exposure occurs shortly following vaccination and the sustained protection thereafter represents continued protection against this early exposure. By contrast, in settings of continued intense transmission, initial protection subsequently declines due to repeated exposure toM. tuberculosisor other pathogens.