bluuebunny/crossref_metadata_2025 huggingface dataset:
Sodium–Glucose Cotransporter-2 Inhibitors and the Risk of Amputation: What Is Currently Known?
Authors: Misher Anne , Ampuero Andrea , Phan Rebecca , Aziz Soma , Ebong Eti , Braich Judy , Dyches Kristin , Southwood Robin
Published: May 2020

Background:

Diabetes mellitus is a major cause of morbidity and mortality in the United States. Twelve medication classes on the market reduce serum glucose including sodium–glucose cotransporter-2 (SGLT2) inhibitors. Potential benefits of these agents include improved glycemic control, weight loss, reduction in blood pressure, and possible reduction in cardiovascular events in patients with elevated cardiovascular risk.

Areas of Uncertainty:

Recently, several adverse events have been identified including increased possible risk of amputation associated with SGLT2 inhibitor therapy.

Data Source:

We conducted a review of published literature and identified 32 trials reviewing incidence of SGLT2 inhibitor-related amputation.

Results:

The potential increased risk for amputation is mostly of the lower extremities. Of the SGLT2 inhibitors currently available, canagliflozin has the highest association with an increased risk of lower extremity amputation and is the only agent with a Food and drug Administration Black Box Warning. Most canagliflozin amputation occurred in a single study. Risk factors for amputation with SGLT2 inhibitors may include those who have a history of amputations, susceptible to foot ulcers and those with baseline cardiovascular disease.

Conclusions:

For at-risk patients who desire an agent from this drug class, empagliflozin or dapagliflozin should be considered, as studies have not found a significant increase in amputations when compared with placebo or in retrospective reviews. Despite the increased risk of amputation found with canagliflozin, providers can use SGLT2 inhibitors with frequent monitoring to safely manage diabetes in low-risk patients. Patient education on associated risks is warranted. Diabetes educators can inform patients of risk factors to assist with monitoring.
Improved Outcome of Intestinal Failure in Preterm Infants
Authors: Fredriksson Fanny , Nyström Niklas , Waldenvik Kajsa , Ördén Helene , Lindblom Maja , Paulsson Mattias , Finkel Yigael , Lilja Helene Engstrand
Published: May 2020

Objective:

The aim of the study was to evaluate the outcome and to identify predictors for survival and enteral autonomy in neonatal intestinal failure (IF).

Methods:

A retrospective observational study in a Swedish tertiary centre of children born between 1995 and 2016 with neonatal IF, defined as dependency on parenteral nutrition (PN) ≥60 days, starting with PN before the age of 44 gestational weeks. Data were extracted from medical records and predictors for survival and enteral autonomy were identified by the Cox regression model. Time to death and weaning off PN analysis were performed with Kaplan‐Meier curves including log rank test.

Results:

In total, 105 children were included. Median gestational age was 28 weeks (22–42), 50% were born extremely preterm (<28 gestational weeks). PN started at a median age of 2 days (0–147) with a median duration of 196 days (60–3091). Necrotizing enterocolitis was the dominating cause of IF (61%). Overall survival was 88%, 5 children died of sepsis and 4 of intestinal failure‐associated liver disease. Survival increased from 75% during 1995 to 2008 to 96% during 2009 to 2016 (P = 0.0040). Age‐adjusted small bowel length of >50% and birth 2009 to 2016 were predictors for survival. Enteral autonomy was achieved in 87%, with positive prediction by small bowel length of >25% of expected for gestational age and remaining ileocecal valve.

Conclusions:

Preterm neonates with IF, at high risk of IF‐associated morbidity, showed a high overall survival rate. Small‐bowel length and being born 2009 to 2016 were predictors for survival and remaining ICV and small‐bowel length were predictors for enteral autonomy.
Sudden Death Due to a Cerebellopontine Angle Epidermoid Cyst
Authors: Bel Hadj Mariem , Ben Jomâa Sami , Njima Manel , Ben Abdeljelil Nouha , Chadly Ali
Published: May 2020

Epidermoid cyst of the brain is a rare benign embryonal tumor. It has an excellent prognosis because of its slow-growing nature. Clinically, symptoms are variable and depend on the location of the cyst. Sudden death may occur as a result of lethal complications because of the tumor growth, but it is still rare. In this article, we present a rare case of sudden unexpected death of a 58-year-old man, with no neurologic history, due to an epidermoid cyst of the brain diagnosed at autopsy.
The Utility of a Travel Screen at Triage in Pediatric Emergency Medicine
Authors: Greenky David , Gillespie Scott , Levine Aly , Murray Brittany
Published: May 2020

Background

The travel screen was implemented by emergency departments (EDs) across the country in 2014 to detect patients exposed to Ebola early and prevent local outbreaks. It remains part of the triage protocol in many EDs to detect communicable disease from abroad and has become a defacto screen for other travel-related illness. Its utility has not been studied in the pediatric ED.

Methods

This was a retrospective review of electronic medical records across 3 EDs from January 1, 2016, to December 31, 2016. The screening question reads, “Has the child or a close contact of the child traveled outside the United States in the past 21 days?” A follow-up question requesting travel details is included for positive screens. We compared length of stay, return-visit rates, and differences in disposition between patients with positive and negative travel screens using generalized linear regression. Matched regression estimates, 95% confidence intervals, and P values were reported.

Results

The study population included 152,945 patients with a total of 322,229 encounters in 2016, of which 232,787 encounters had a travel screen documented during triage. There were 2258 patient encounters that had positive travel screens. Only 201 (8.9%) of these encounters had further description of the travel in the comments box. The odds of hospital admission for patients with positive travel screens were 1.76 (95% confidence interval, 1.54–2.01; P < 0.001) times the odds of hospital admission for patients screened negative. The significance of this finding was largely driven by general hospital admission. Other metrics did not differ significantly between the groups.

Conclusions

Although a positive travel screen was mildly predictive of inpatient admission, information is not available to providers about travel-related risk. Recent literature suggests integrating a travel history with presenting symptoms and region of travel and could produce a more specific travel screen. A revised travel screen should be implemented and studied in the pediatric ED.
Trends in Time From HIV Diagnosis to First Viral Suppression Following Revised US HIV Treatment Guidelines, 2012–2017
Authors: Crepaz Nicole , Song Ruiguang , Lyss Sheryl , Hall H. Irene
Published: May 2020

Background:

Since 2012, treatment guidelines have recommended initiating antiretroviral therapy for all persons as soon as possible after HIV diagnosis, irrespective of CD4 counts. If clinicians adopted the treatment guidelines, a shortened interval between diagnosis and first viral suppression (Dx-to-VS) would be expected, with greater declines among those with CD4 counts ≥500 cells/µL at diagnosis.

Methods:

Using the National HIV Surveillance System data, we examined Dx-to-VS intervals among persons aged ≥13 years with HIV infection diagnosed during 2012–2017. Analyses were stratified by the first CD4 count: CD4 ≥500 cells/µL, 200–499 cells/µL, <200 cells/µL, and no CD4 value reported within 3 months after diagnosis.

Results:

During 2012–2017 in the 27 US jurisdictions with complete laboratory reporting, 138,759 HIV diagnoses occurred. The median Dx-to-VS interval shortened overall for persons with HIV diagnosed in 2012 vs. 2017 from 9 to 5 months, a 12.3% annual decrease (P < 0.001) and in all CD4 groups. In 2012, the Dx-to-VS interval was longer for persons with CD4 ≥500 cells/µL than 200–499 cells/µL and <200 cells/µL (median, 9, 7, and 6 months, respectively). By 2017, the median interval was 4 months for these groups, compared with 25 months for those without a CD4 value within 3 months after diagnosis.

Conclusion:

Decreases in Dx-to-VS intervals across all CD4 groups with a greater decrease among those with CD4 ≥500 cells/µL are consistent with the implementation of treatment recommendations. The Dx-to-VS interval was longest among persons not linked to care within 3 months after diagnosis, underscoring the importance of addressing barriers to linkage to care for ending the HIV epidemic.
Radiologic Review With Pathology Correlation of E-Cigarette or Vaping Product Use-associated Lung Injury
Authors: Bin Saeedan Mnahi , MacMurdo Maeve G. , Mukhopadhyay Sanjay , Choi Humberto , Parkar Nadeem , Ghosh Subha
Published: May 2020

More than 2000 cases of vaping-associated lung injury have been reported in a recent outbreak, including >40 deaths. Although chest imaging is integral in the evaluation of these patients and is often abnormal, the spectrum of findings and the role of imaging in the diagnosis are not widely appreciated. The aim of this review is to highlight the imaging findings of vaping-associated lung injury. Basilar-predominant ground-glass opacities and/or consolidations, often with areas of subpleural or lobular sparing, are the most common pattern, and many other patterns are known to occur. Radiologists are encouraged to become familiar with the different imaging patterns of vaping-associated lung injury. The diagnosis should be considered in patients who have vaped within 90 days of onset of symptoms and present with bilateral lung opacities.
Associations Between Physician Prescribing Behavior and Persistent Postoperative Opioid Use Among Cancer Patients Undergoing Curative-intent Surgery
Authors: Xu Yuan , Cuthbert Colleen A. , Karim Safiya , Kong Shiying , Dort Joseph C. , Quan May Lynn , Hinther Ashley V. , Quan Hude , Hemmelgarn Brenda R. , Cheung Winson Y.
Published: May 2020

Objective:

This study aimed to evaluate the association between prescribers’ opioid prescribing history and persistent postoperative opioid use in cancer patients undergoing curative-intent surgery.

Background:

Study has shown that patients may be over-prescribed analgesics after surgery. However, whether and how the prescriber's opioid prescribing behavior impacts persistent opioid use is unclear.

Methods:

All adults with a diagnosis of solid cancers who underwent surgery during the study period (2009–2015) in Alberta, Canada and were opioid-naïve were included. The key exposure was the historical opioid-prescribing pattern of a patient's most responsible prescriber. The primary outcome was “new persistent postoperative opioid user,” was defined as a patient who was opioid-naïve before surgery and subsequently filled at least 1 opioid prescription between 60 and 180 days after surgery.

Results:

We identified 24,500 patients. Of these, 2106 (8.6%) patients became a new persistent opioid user after surgery. Multivariate analysis demonstrated that patients with most responsible prescribers that historically prescribed higher daily doses of opioids (≥50 vs <50 mg oral morphine equivalent) had an increased risk of new persistent opioid use after surgery (odds ratio = 2.41, P < 0.0001). In addition to the provider's prescribing pattern, other factors including younger age, comorbidities, presurgical opioid use, chemotherapy, type of tumor/surgical procedure were also found to be independently associated with new persistent postoperative opioid use.

Conclusions:

Our results suggest that prescriber with a history of prescribing a higher opioid dose is an important predictor of persistent postoperative opioid use among cancer patients undergoing curative-intent surgery.
Identification of Serum miRNA Signature and Establishment of a Nomogram for Risk Stratification in Patients With Pancreatic Ductal Adenocarcinoma
Authors: Kandimalla Raju , Shimura Tadanobu , Mallik Saurav , Sonohara Fuminori , Tsai Susan , Evans Douglas B. , Kim Song Cheol , Baba Hideo , Kodera Yasuhiro , Von Hoff Daniel , Chen Xi , Goel Ajay
Published: May 2020

Objective:

The aim of the study was to perform mRNA-miRNA regulatory network analyses to identify a miRNA panel for molecular subtype identification and stratification of high-risk patients with pancreatic ductal adenocarcinoma (PDAC).

Background:

Recent transcriptional profiling effort in PDAC has led to the identification of molecular subtypes that associate with poor survival; however, their clinical significance for risk stratification in patients with PDAC has been challenging.

Methods:

By performing a systematic analysis in The Cancer Genome Atlas and International Cancer Genome Consortium cohorts, we discovered a panel of miRNAs that associated with squamous and other poor molecular subtypes in PDAC. Subsequently, we used logistic regression analysis to develop models for risk stratification and Cox proportional hazard analysis to determine survival prediction probability of this signature in multiple cohorts of 433 patients with PDAC, including a tissue cohort (n = 199) and a preoperative serum cohort (n = 51).

Results:

We identified a panel of 9 miRNAs that were significantly upregulated (miR-205-5p and -934) or downregulated (miR-192-5p, 194-5p, 194-3p, 215-5p, 375-3p, 552-3p, and 1251-5p) in PDAC molecular subtypes with poor survival [squamous, area under the receiver operating characteristic curve (AUC) = 0.90; basal, AUC = 0.89; and quasimesenchymal, AUC = 0.83]. The validation of this miRNA panel in a tissue clinical cohort was a significant predictor of overall survival (hazard ratio = 2.48, P < 0.0001), and this predictive accuracy improved further in a risk nomogram which included key clinicopathological factors. Finally, we were able to successfully translate this miRNA predictive signature into a liquid biopsy–based assay in preoperative serum specimens from PDAC patients (hazard ratio: 2.85, P = 0.02).

Conclusion:

We report a novel miRNA risk-stratification signature that can be used as a noninvasive assay for the identification of high-risk patients and potential disease monitoring in patients with PDAC.
Epidemiological trends of surgical admissions to the intensive care unit in the United States
Authors: Vakayil Victor , Ingraham Nicholas E. , Robbins Alexandria J. , Freese Rebecca , Northrop Elise F. , Brunsvold Melissa E. , Pendleton Kathryn M. , Charles Anthony , Chipman Jeffrey G. , Tignanelli Christopher J.
Published: May 2020

BACKGROUND

Epidemiologic assessment of surgical admissions into intensive care units (ICUs) provides a framework to evaluate health care system efficiency and project future health care needs.

METHODS

We performed a 9-year (2008–2016), retrospective, cohort analysis of all adult admissions to 88 surgical ICUs using the prospectively and manually abstracted Cerner Acute Physiology and Chronic Health Evaluation Outcomes database. We stratified patients into 13 surgical cohorts and modeled temporal trends in admission, mortality, surgical ICU length of stay (LOS), and change in functional status (FS) using generalized mixed-effects and Quasi-Poisson models to obtain risk-adjusted outcomes.

RESULTS

We evaluated 78,053 ICU admissions and observed a significant decrease in admissions after transplant and thoracic surgery, with a concomitant increase in admissions after otolaryngological and facial reconstructive procedures (all p < 0.05). While overall risk-adjusted mortality remained stable over the study period; mortality significantly declined in orthopedic, cardiac, urologic, and neurosurgical patients (all p < 0.05). Cardiac, urologic, gastrointestinal, neurosurgical, and orthopedic admissions showed significant reductions in LOS (all p < 0.05). The overall rate of FS deterioration increased per year, suggesting ICU-related disability increased over the study period.

CONCLUSION

Temporal analysis demonstrates a significant change in the type of surgical patients admitted to the ICU over the last decade, with decreasing mortality and LOS in selected cohorts, but an increasing rate of FS deterioration. Improvement in ICU outcomes may highlight the success of health care advancements within certain surgical cohorts, while simultaneously identifying cohorts that may benefit from future intervention. Our findings have significant implications in health care systems planning, including resource and personnel allocation, education, and surgical training.

LEVEL OF EVIDENCE

Economic/decision, level IV.Epidemiologic, level IV.
Dose-Dependent Effects of Lithium Treatment on the Aggravation of Antipsychotic-Induced Pisa Syndrome
Authors: Hsieh Huai-Te , Yeh Yi-Wei
Published: May 2020

Pisa syndrome (PS) is a rare lateral truncal dystonia that is related to dopamine-acetylcholine imbalances, and most cases develop during antipsychotic treatment. Here, we report a case of PS that developed during switching to new antipsychotics and titrating lithium, and PS was aggravated when the lithium dose was increased. Truncal deviation was not relieved with switching back to prior antipsychotics or by discontinuation of all antipsychotics. Pisa syndrome resolved only after discontinuing the lithium treatment. This is the first report of dose-dependent effects of lithium treatment on the aggravation of PS, which may be related to dose-related effects on dopaminergic and cholinergic transmission.
A Case of Abulia From Left Middle Cerebral Artery Stroke in an Adolescent Treated Successfully With Short Duration Olanzapine
Authors: Connor Andrew T. , Crawford Alex , Levy Rebecca J. , Schneider Lauren M. , Hollander Seth A. , Shaw Richard J.
Published: May 2020

Introduction

Abulia is defined as a pathological state of amotivation, apathy, and global absence of willpower. It presents with a challenging array of overlapping symptoms, making effective identification and treatment difficult.

Case Presentation

We describe the first known report of an adolescent with a ventricular assist device who developed abulia following a left middle cerebral artery (MCA) stroke who responded successfully to treatment with olanzapine.

Discussion

The neurobiological etiology of abulia is still unclear but is postulated to be related to deficits in the dopaminergic reward circuitry in the frontal-subcortical-mesolimbic regions. There have been reports of poststroke patients with abulia being treated by modulating this dopamine circuitry and in some cases with short-term low-dose olanzapine.

Conclusion

Further research is needed to develop a better understanding of the pathophysiology of abulia leading to more effective treatment algorithms including more specific diagnostic tools and effective pharmacological interventions.
Evaluation of a Modified Version of the Norton Scale for Use as a Pressure Injury Risk Assessment Instrument in Critical Care
Authors: Sullivan Rhonda , Barnby Elizabeth , Graham Shannon
Published: May 2020

PURPOSE:

No risk assessment scale exists in the United States specifically designed for use among patients with critical illness. The aim of this project was to modify the Norton Scale for Pressure Sore Risk to improve its predictive power when used in the critical care setting.

PARTICIPANTS AND SETTING:

The setting for this quality improvement project was a 1157-bed academic medical center in the Southeast United States. Data were collected from 114 clinicians; 111 were critical care nurses and 3 were certified wound care nurses.

METHODS:

Participants assessed the pressure injury risks of a video-simulated critical care patient using the optimized Norton Scale (oNS); this instrument was modified from the Norton Scale. Data were collected on reliability, validity, usability, and preference.

OUTCOMES:

All 114 participants accurately predicted a patient's severe high risk for pressure injury using the oNS. Predictive validity and reliability of the oNS were excellent based on a correlation coefficient of more than 0.6 and a Cronbach α = 0.944, respectively. The intraclass correlation coefficient (ICC) was 0.933 (95% confidence interval, 0.911-0.950). From 71.2% to 84.9% of the participants agreed that the oNS represented the desired characteristics for optimal usability in the critical-care setting. Preference for the oNS was associated with perceptions that it was easier, quicker, and more critical-care-specific than the Braden Scale for Pressure Sore Risk currently used in critical care units in the project facility.

IMPLICATIONS FOR PRACTICE:

The oNS offered critical care nurses in our facility a quick, easy-to-use, critical care- specific risk assessment tool that focused on the unique vulnerabilities of patients with critical illness.
Standardized Hospital Discharge Communication for Patients With Pressure Injury
Authors: Novy Teresa K. , Woith Wendy M.
Published: May 2020

PURPOSE:

To determine if improved communication between certified wound care nurses and home health nurses, through use of standardized electronic wound care order sets and discharge instructions, decreased delay in treatment and 30-day readmission rates and improved wound healing for patients discharged to home with pressure injuries.

DESIGN:

Quasi-experimental, nonequivalent group trial.

SUBJECTS AND SETTING:

Cognitively intact adult patients hospitalized in the Midwestern United States with a stage 2 or higher pressure injury discharged to home care services.

METHODS:

We revised the electronic medical record to include an adapted, standardized version of the Project Re-Engineered Discharge wound care order set that included specific wound care instructions for use following discharge to home care. Medical records of 12 patients were reviewed prior to the change and 9 records were reviewed postchange for information about initiation of care, wound healing, and 30-day readmission. The Pressure Ulcer Scale of Healing tool was used to evaluate wound healing.

RESULTS:

Time to initiation of treatment was 2.4 days for the control group and 1.6 days for the intervention group. Missing documentation made it difficult to evaluate the control group, as 73% of all wound measurements were missing from the electronic medical record. Use of the standardized wound care order set resulted in 100% of wound care orders and 92% of discharge instructions being present in the intervention group's electronic medical record at the time of hospital discharge. There was no statistically significant difference between control and intervention group's Pressure Ulcer Scale of Healing scores for any postdischarge measurement or in 30-day readmission rates.

CONCLUSIONS:

The new standardized wound care order sets at the time of discharge did increase adherence to time to implementation and documentation of executing wound care orders by home care nurses. Further research of standardized order sets is needed to determine the impact on improving patient outcomes.
Cardiometabolic disease in the older person: prediction and prevention for the generalist physician
Authors: Sinclair Alan J. , Abdelhafiz Ahmed H.
Published: May 2020

Ageing is associated with chronic inflammation and oxidative stress that increase the risk of cardiovascular disease. Frailty and sarcopenia, which are associated with increased visceral obesity and muscle mass loss, are now emerging as new potential risk factors for cardiovascular disease. Increased muscle visceral fat leads to increased secretion of harmful proinflammatory adipokines and reduced muscle mass leads to reduced secretion of the protective myokines creating an abnormal cardiometabolic state increasing the risk of cardiovascular disease. This review: (1) explore traditional and newly emerging cardiometabolic risk factors in older people; (2) investigate methods of prediction and prevention of cardiovascular disease in those with diabetes; and (3) concludes that the development of a subspeciality of Cardiometabolic Medicine should be considered.
Sociodemographic and metabolic risk characteristics associated with metabolic weight categories in the Women’s Health Initiative
Authors: Cordola Hsu Amber R. , Ames Susan L. , Xie Bin , Peterson Darleen V. , Garcia Lorena , Going Scott B. , Wong Nathan D. , Anton-Culver Hoda
Published: May 2020

Objective

To identify sociodemographic and metabolic correlates of weight categories in postmenopausal women.

Methods

The Women’s Health Initiative enrolled 161 808 postmenopausal women ages 50–79. We included those free of cardiovascular disease (CVD) and with CVD risk factors and biomarkers (n = 19 412). Normal weight was defined as a BMI ≥18.5 and <25 kg/m2 and waist circumference <88 cm and overweight/obesity as a BMI ≥25 kg/m2 or waist circumference ≥88 cm. Metabolically healthy was based on <2 and metabolically unhealthy ≥2 traits: triglycerides ≥150 mg/dl, systolic blood pressure (BP) ≥130 mmHg or diastolic BP ≥85 mmHg or antihypertensives or diuretics, fasting glucose ≥100 mg/dl or diabetes medication, and high-density lipoprotein cholesterol <50 mg/dl. Polytomous multinomial logistic regression with generalized link logit function provided the odds of metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUHNW), metabolically healthy overweight/obese (MHO), and metabolically unhealthy overweight/obese (MUHO) according to demographic and risk factor measures.

Results

Among the 19 412 postmenopausal women, 2369 (12.2%) participants had prevalent diabetes. Advanced age was associated with an increased odds of MUHNW as compared with the MHNW after adjusting for covariates [odds ratio (OR) 1.04, P < 0.0001]. Black/African American ethnicity was associated with a decreased odds of MUHNW (OR 0.64, P < 0.0001) and MUHO (OR 0.77, P = 0.0004), while an increased odds for MHO (OR 1.50, P < 0.0001) as compared with White MHNW.

Conclusions

Advanced age and ethnicity are important indicators of metabolic weight categories among postmenopausal women.
The systemic implication of novel non-statin therapies in cardiovascular diabetology: PCSK9 as a case model
Authors: Nashawi Mouhamed , Sheikh Omar , Mir Mahnoor , Te Tri , Chilton Robert
Published: May 2020

PCSK9, like other novel non-statin drugs were primarily developed to help patients achieve low-density lipoprotein cholesterol targets, especially in patients with dyslipidemia not achieving lipid goals with statins due to poor tolerance or inadequate response. PCSK9 inhibitors, in addition to modulating lipid metabolism, improve mortality outcomes in cardiovascular disease. These benefits are markedly pronounced in patients with type 2 diabetes mellitus. However, these benefits do not come without associated risk. Multiple trials, studies, and case reports have attempted to explain observed outcomes with PCSK9 expression and administration of PCSK9 inhibitors from multiple perspectives, such as their effects on insulin sensitivity and glucose tolerance, changes in renal physiology, thyroid physiology, vascular tone, intestinal regulation of lipids, and improved cardiovascular function. These agents represent an opportunity for physicians to exercise prudence by using appropriate clinical judgement when managing comorbidities in the hyperglycemic patient, a concept that extends to other novel non-statin drugs.
Possible molecular and paracrine involvement underlying the pathogenesis of COVID-19 cardiovascular complications
Authors: AbdelMassih Antoine Fakhry , Ramzy David , Nathan Lauren , Aziz Silvia , Ashraf Mirette , Youssef Nourhan Hatem , Hafez Nouran , Saeed Rana , Agha Hala
Published: May 2020

Coronavirus disease 2019 (COVID-19) has been declared a pandemic on 11 March 2020 by the WHO. Despite being mainly a respiratory virus, cardiac complications have been described. These range from sudden cardiac death to subtle diastolic dysfunction after recovery from COVID-19. The commonest cardiac presentation to date is acute heart failure resulting from biventricular or left ventricular hypokinesis and elevation of cardiac troponins. It has been shown that COVID-19 downregulates angiotensin-converting enzyme-2, which has protective effects on the endothelium and cardiomyocytes. It has also been proven that COVID-19 induces a state of hypercytokinaemia, some cytokines such as interleukin-1 and interleukin-6 have an injurious effect on the myocardium and endothelium, respectively. Such pathogenic mechanisms might play a crucial role in induction of cardiomyocyte injury and impaired myocardial perfusion probably through coronary endothelial dysfunction. The understanding and linking of such mechanisms might help in tailoring drug repurposing for treatment or prophylaxis of COVID-19 cardiovascular complications.
Deep neural frameworks improve the accuracy of general practitioners in the classification of pigmented skin lesions
Authors: Lucius Maximiliano , De All Jorge , De All José Antonio , Belvisi Martín , Radizza Luciana , Lanfranconi Marisa , Lorenzatti Victoria , Galmarini Carlos M.
Published: May 2020

Artificial intelligence can be a key tool in the context of assisting in the diagnosis of dermatological conditions, particularly when performed by general practitioners with limited or no access to high resolution optical equipment. This study evaluates the performance of deep convolutional neural networks (DNNs) in the classification of seven pigmented skin lesions. Additionally, it assesses the improvement ratio in the classification performance when utilized by general practitioners. Open-source skin images were downloaded from the ISIC archive. Different DNNs (n=8) were trained based on a random dataset constituted by 8,015 images. A test set of 2,003 images has been used to assess the classifiers performance at low (300 × 224 RGB) and high (600 × 450 RGB) image resolution and aggregated clinical data (age, sex and lesion localization). We have also organized two different contests to compare the DNNs performance to that of general practitioners by means of unassisted image observation. Both at low and high image resolution, the DNNs framework being trained differentiated dermatological images with appreciable performance. In all cases, accuracy has been improved when adding clinical data to the framework. Finally, the lowest accurate DNN outperformed general practitioners. Physician’s accuracy was statistically improved when allowed to use the output of this algorithmic framework as guidance. DNNS are proven to be high performers as skin lesion classifiers. The aim is to include these AI tools in the context of general practitioners whilst improving their diagnosis accuracy in a routine clinical scenario when or where the use of high-resolution equipment is not accessible.
Meta-analysis of diagnostic performance of serological tests for SARS-CoV-2 antibodies and public health implications
Authors: Caini Saverio , Bellerba Federica , Corso Federica , Diaz-Basabe Angelica , Natoli Gioacchino , Paget John , Facciotti Federica , Raimondi Sara , Palli Domenico , Mazzarella Luca , Pelicci Pier Giuseppe , Vineis Paolo , Gandini Sara
Published: May 2020

Serology-based tests have become a key public health element in the COVID-19 pandemic to assess the degree of herd immunity that has been achieved in the population. These tests differ between one another in several ways. Here, we conducted a systematic review and meta-analysis of the diagnostic accuracy of currently available SARS-CoV-2 serological tests, and assessed their real-world performance under scenarios of varying proportion of infected individuals. We included independent studies that specified the antigen used for antibody detection and used quantitative methods. We identified nine independent studies, of which six were based on commercial ELISA or CMIA/CLIA assays, and three on in-house tests. Test sensitivity ranged from 68% to 93% for IgM, from 65% to 100% for IgG, and from 83% to 98% for total antibodies. Random-effects models yielded a summary sensitivity of 82% (95%CI 75-88%) for IgM, and 85% for both IgG (95%CI 73-93%) and total antibodies (95%CI 74-94%). Specificity was very high for most tests, and its pooled estimate was 98% (95%CI 92-100%) for IgM and 99% (95%CI 98-100%) for both IgG and total antibodies. The heterogeneity of sensitivity and specificity across tests was generally high (I2≤50%). In populations with a low prevalence (≤5%) of seroconverted individuals, the positive predictive value would be ≤88% for most assays, except those reporting perfect specificity. Our data suggest that the use of serological tests for large-scale prevalence surveys (or to grant "immunity passports") are currently only justified in hard-hit regions, while they should be used with caution elsewhere.
Objective Olfactory Evaluation of Self-reported Loss of Smell in a Case Series of 86 COVID-19 Patients
Authors: Lechien Jerome R. , Cabaraux Pierre , Chiesa-Estomba Carlos M. , Khalife Mohamad , Hans Stéphane , Calvo-Henriquez Christian , Martiny Delphine , Journe Fabrice , Sowerby Leigh , Saussez Sven
Published: May 2020

Objective

To investigate olfactory dysfunction (OD) in patients with mild COVID-19 through patient-reported outcome questionnaires and objective psychophysical testing.

Methods

COVID-19 patients with self-reported sudden-onset OD were recruited. Epidemiological and clinical data were collected. Nasal complaints were evaluated with the sino-nasal outcome-22 (SNOT-22). Subjective olfactory and gustatory status was evaluated with the National Health and Nutrition Examination Survey (NHNES). Objective OD was evaluated using psychophysical tests.

Results

Eighty-six patients completed the study. The most common symptoms were fatigue (72.9%), headache (60.0%), nasal obstruction (58.6%) and postnasal drip (48.6%). Total loss of smell was self-reported by 61.4% of patients. Objective olfactory testings identified 41 anosmic (47.7%), 12 hyposmic (14.0%), and 33 normosmic (38.3%) patients. There was no correlation between the objective test results and subjective reports of nasal obstruction or postnasal drip.

Conclusion

A significant proportion of COVID-19 patients reporting OD do not have OD on objective testing.
Acute mental health responses during the COVID-19 pandemic in Australia
Authors: Newby Jill M. , O’Moore Kathleen , Tang Samantha , Christensen Helen , Faasse Kate
Published: May 2020

The acute and long-term mental health impacts of the COVID-19 pandemic are unknown. The current study examined the acute mental health responses to the COVID-19 pandemic in 5070 adult participants in Australia, using an online survey administered during the peak of the outbreak in Australia (27thMarch to 7thApril 2020). Self-report questionnaires examined COVID-19 fears and behavioural responses to COVID-19, as well as the severity of psychological distress (depression, anxiety and stress), health anxiety, contamination fears, alcohol use, and physical activity. 78% of respondents reported that their mental health had worsened since the outbreak, one quarter (25.9%) were very or extremely worried about contracting COVID-19, and half (52.7%) were worried about family and friends contracting COVID-19. Uncertainty, loneliness and financial worries (50%) were common. Rates of elevated psychological distress were higher than expected, with 62%, 50%, and 64% of respondents reporting elevated depression, anxiety and stress levels respectively, and one in four reporting elevated health anxiety in the past week. Participants with self-reported history of a mental health diagnosis had significantly higher distress, health anxiety, and COVID-19 fears than those without a prior mental health diagnosis. Demographic (e.g., non-binary or different gender identity; Aboriginal and Torres Strait Islander status), occupational (e.g., being a carer or stay at home parent), and psychological (e.g., perceived risk of contracting COVID-19) factors were associated with distress. Results revealed that precautionary behaviours (e.g., washing hands, using hand sanitiser, avoiding social events) were common, although in contrast to previous research, higher engagement in hygiene behaviours was associated with higher stress and anxiety levels. These results highlight the serious acute impact of COVID-19 on the mental health of respondents, and the need for proactive, accessible digital mental health services to address these mental health needs, particularly for those most vulnerable, including people with prior history of mental health problems. Longitudinal research is needed to explore long-term predictors of poor mental health from the COVID-19 pandemic.
Protein haploinsufficiency drivers identifyMYBPC3mutations that cause hypertrophic cardiomyopathy
Authors: Suay-Corredera Carmen , Pricolo Maria Rosaria , Herrero-Galán Elías , Velázquez-Carreras Diana , Sánchez-Ortiz David , García-Giustiniani Diego , Delgado Javier , Galano-Frutos Juan José , García-Cebollada Helena , Vilches Silvia , Domínguez Fernando , Molina María Sabater , Barriales-Villa Roberto , Frisso Giulia , Sancho Javier , Serrano Luis , García-Pavía Pablo , Monserrat Lorenzo , Alegre-Cebollada Jorge
Published: May 2020

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease. Mutations inMYBPC3, the gene encoding cardiac myosin-binding protein C (cMyBP-C), are a leading cause of HCM. However, it remains challenging to define whether specific gene variants found in patients are pathogenic or not, limiting the reach of cardiovascular genetics in the management of HCM. Here, we have examined cMyBP-C haploinsufficiency drivers in 68 clinically annotated non-truncating variants ofMYBPC3. We find that 45% of the pathogenic variants show alterations in RNA splicing or protein stability, which can be linked to pathogenicity with 100% and 94% specificity, respectively. Relevant for variant annotation, we uncover that 9% of non-truncating variants ofMYBPC3currently classified as of uncertain significance induce one of these molecular phenotypes. We propose that alteration of RNA splicing or protein stability caused byMYBPC3variants provide strong evidence of their pathogenicity, leading to improved clinical management of HCM patients and their families.
Evidence of a significant secretory-IgA-dominant SARS-CoV-2 immune response in human milk following recovery from COVID-19
Authors: Fox Alisa , Marino Jessica , Amanat Fatima , Krammer Florian , Hahn-Holbrook Jennifer , Zolla-Pazner Susan , Powell Rebecca L.
Published: May 2020

SARS-CoV-2, commonly termed COVID-19 for the illness it causes, has infected >3.2 million people, including >220,000 deaths. Human milk IgG originates mainly from blood, therefore a SARS-CoV-2-reactive antibody (Ab) response in milk would be expected (1). However, IgG comprises only ~2% of milk Ab, with most milk Abs originating from mucosa-associated lymphatic tissue (1). Therefore, the extent of the milk immune response to SARS-CoV-2 is unknown (2). This response is critical for infants and young children, who tend not to suffer greatly from COVID-19 pathology but are likely responsible for significant virus transmission (3-5). Perhaps even more significant is the fact that milk Abs could be purified and used as a COVID-19 therapeutic, given they would likely be of the secretory (s) class and highly resistant to proteolytic degradation in the respiratory tissue (2, 6). In this preliminary report, 15 milk samples obtained from donors previously-infected with SARS-CoV-2 as well as 10 negative control samples obtained prior to December 2019 were tested for reactivity to the Receptor Binding Domain (RBD) of the SARS-CoV-2 Spike protein by ELISAs measuring IgA, IgG, IgM, and secretory Ab. Eighty percent of samples obtained post-COVID-19 exhibited IgA reactivity, and all these samples were also positive for secretory Ab reactivity, suggesting the IgA is predominantly sIgA. COVID-19 group mean OD values of undiluted milk were significantly greater for IgA (p<0.0001), secretory-type Abs (p<0.0001), and IgG (p=0.017), but not for IgM, compared to pre-pandemic group mean values. Overall, these data indicate that there is strong sIgA-dominant SARS-CoV-2 immune response in human milk after infection in the majority of individuals, and that a comprehensive study of this response is highly warranted.
Assessment of a serological diagnostic kit of SARS-CoV-2 availble in Iran
Authors: Shamsollahi Hamid Reza , Amini Mostafa , Alizadeh Shaban , Nedjat Saharnaz , Akbari-Sari Ali , Rezaei Mehdi , Allameh Seyed Farshad , Fotouhi Akbar , Yunesian Masud
Published: May 2020

Background

The SARS-CoV-2 epidemic broke out in December 2019 and now is characterized as a pandemic. The effective control of this infectious disease requires access to diagnostic techniques, both for case finding and epidemic size estimation. The molecular technique is routinely being used worldwide. Although it is the “standard” case detection and management method, it has its own shortcomings. Thus, some easy-to-use rapid serological tests were developed.

Methods

One hundred and fourteen positive RT-PCR-diagnosed patients were tested by VivaDiag Kit, a brand of rapid serological kits available in hospitals affiliated to Tehran University of Medical Sciences (TUMS), Tehran, Iran. Frozen serum specimens taken from healthy people in summer and autumn 2019, were also tested as negative controls.

Results

The test sensitivity was 47.9% (95% confidence interval [CI]: 38.8-56.9) for IgM and 47.0% (95% CI: 38.0-56.0) for IgG. There was no difference between IgG and IgM seropositivity except in one case. Specificity was calculated as 99.0% (95% CI: 96.4-99.9) for IgM and of 100.0% (95% CI: 0.98.2-100.0) for IgG. Sensitivity was higher in men and older participants.

Conclusion

This test can be used for epidemiological investigations especially for the estimation of the level of infection in the community, after it is properly corrected for sensitivity and specificity. The low sensitivity could be attributed to the technical limitation of the kits or low levels of antibodies after infection. The different sensitivity in age and sex groups supports the hypothesis that different people show different immune responses to this virus.
Significance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio for predicting clinical outcomes in COVID-19
Authors: Huang Shaoping , Liu Min , Li Xiaolu , Shang Zhiyin , Zhang Ting , Lu Hongzhou
Published: May 2020

Background

The epidemic of 2019 novel coronavirus (COVID-19) struck China in late December, 2019, resulting in about 200000 deaths all over the world. Numerous observational studies have suggested that the neutrophil-to-lymphocyte ratio (NLR) and lymphocyte proportion and the platelet-to-lymphocyte ratio (PLR) are inflammatory markers. Our study aimed to detect the role of NLR, PLR in predicting the prognosis of COVID-19.

Methods

Four hundred and fifteen consecutive patients were enrolled in Shanghai Public Health Clinical Center affiliated to Fudan University, between 20 January and 11 April 2020 with confirmed COVID-19. Epidemiology, symptoms, signs, and laboratory examinations during the hospital stay were collected and compared between non-severe and severe patients. Statistical analysis was performed by SPSS 25.0 software.

Results

Four hundred and fifteen laboratory-confirmed COVID-19 patients were included in our study, among which 386 (93%) patients were not severe, and 27 (7%) were severe. The proportion of males in severe cases is higher than in non-severe cases (75.86% vs. 50.52%, P=0.008). The age between the two groups is different (p=0.022). Compared with non-severe patients, severe patients exhibited more comorbidities, including hypertension (48.28% vs. 19.43%, p<0.001), diabetes (20.69% vs. 6.99%, p=0.009), chronic obstructive pulmonary disease (51.72% vs. 6.22%, p<0.001), and fatty liver (37.93% vs. 15.8%, p=0.002), respectively. NLR and PLR showed significant difference (p<0.001). Diabetes (OR 0.28; 95% CI 15.824-187.186), fatty liver (OR 21.469; 95% CI 2.306-199.872), coronary heart disease (OR 18.157; 95% CI 2.085-158.083), NLR (OR 1.729; 95% CI 1.050-2.847) were significantly associated with severe cases with COVID-19. The NLR of patients in severe group had a 1.729-fold higher than that of no-severe group (OR 1.729; 95% CI 1.050-2.847, P=0.031).

Conclusions

NLR is an independent risk factor of severe COVID-19 patients. PLR, NLR were significantly different between severe and non-severe patients, so assessment of NLR, PLR may help identify high risk cases with COVID-19.
Segmentation and shielding of the most vulnerable members of the population as elements of an exit strategy from COVID-19 lockdown
Authors: van Bunnik Bram A.D. , Morgan Alex L.K. , Bessell Paul R. , Calder-Gerver Giles , Zhang Feifei , Haynes Samuel , Ashworth Jordan , Zhao Shengyuan , Cave Nicola Rose , Perry Meghan R. , Lepper Hannah C. , Lu Lu , Kellam Paul , Sheikh Aziz , Medley Graham F. , Woolhouse Mark E.J.
Published: May 2020

In this study we demonstrate that the adoption of a segmenting and shielding (S&S) strategy could increase scope to partially exit COVID-19 lockdown while limiting the risk of an overwhelming second wave of infection.

The S&S strategy has an antecedent in the “cocooning” of infants by immunisation of close family members (Forsyth et al., 2015), and forms a pillar of infection, prevention and control (IPC) strategies (RCN, 2017). We are unaware of it being proposed as a major public health initiative previously.

We illustrate the S&S strategy using a mathematical model that segments the vulnerable population and their closest contacts, the “shielders”. We explore the effects on the epidemic curve of a gradual ramping up of protection for the vulnerable population and a gradual ramping down of restrictions on the non-vulnerable population over a period of 12 weeks after lockdown.

The most important determinants of outcome are: i) post-lockdown transmission rates within the general population segment and between the general and vulnerable segments; ii) the fraction of the population in the vulnerable and shielder segments; iii) adherence with need to be protected; and iv) the extent to which population immunity builds up in all segments.

We explored the effects of extending the duration of lockdown and faster or slower transition to post-lockdown conditions and, most importantly, the trade-off between increased protection of the vulnerable segment and fewer restrictions on the general population.

We illustrate how the potential for the relaxation of restrictions interacts with specific policy objectives. We show that the range of options for relaxation in the general population can be increased by maintaining restrictions on the shielder segment and by intensive routine screening of shielders.

We find that the outcome of any future policy is strongly influenced by the contact matrix between segments and the relationships between physical distancing measures and transmission rates. These relationships are difficult to quantify so close monitoring of the epidemic would be essential during and after the exit from lockdown.

More generally, S&S has potential applications for any infectious disease for which there are defined proportions of the population who cannot be treated or who are at risk of severe outcomes.