bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical therapy, intra-articular dextrose prolotherapy, botulinum neurotoxin, and hyaluronic acid for knee osteoarthritis: randomized clinical trial
Authors: Rezasoltani Zahra , Azizi Sirous , Najafi Sharif , Sanati Ehsan , Dadarkhah Afsaneh , Abdorrazaghi Fateme
Published: April 2020

This study aimed to compare the efficacy of four treatments in the management of knee osteoarthritis. We carried out a randomized clinical trial with four study arms in an outpatient Department of Physical Medicine and Rehabilitation at a University Hospital. In total, 120 patients with knee osteoarthritis ≥50 years of age were randomly allocated to four groups. The primary outcome was knee pain in visual analog scale and the secondary outcome was the Knee Injury and Osteoarthritis Outcome Score. The exercise was prescribed daily for all participants throughout the study. For physical therapy (group 1), participants received superficial heat, transcutaneous electrical nerve stimulation and pulsed ultrasound. We administered a single intra-articular injection of botulinum neurotoxin type A (group 2) and three injections of hyaluronic acid (group 3) or 20% dextrose (group 4) to patients in the corresponding groups. Mixed analysis of variance showed that there was statistically significant difference between the groups in pain (P < 0.001), and Knee Injury and Osteoarthritis Outcome Score (P < 0.001). Pairwise between- and within-group comparisons showed that botulinum neurotoxin and dextrose prolotherapy were the most, and hyaluronic acid was the least efficient treatments for controlling pain and recovering function in patients. An intra-articular injection of botulinum toxin type A or dextrose prolotherapy is effective first-line treatments. In the next place stands physical therapy particularly if the patient is not willing to continue regular exercise programs. Our study was not very supportive of intra-articular injection of hyaluronic acid as an effective treatment of knee osteoarthritis.
Magnet® and Pathway to Excellence®
Authors: Nelson-Brantley Heather V. , Beckman Dee , Parchment Joy , Smith-Miller Cheryl A. , Weaver Susan H.
Published: April 2020

Healthcare organizations seeking to achieve or maintain Magnet® or Pathway to Excellence® designation are increasingly challenged to demonstrate how nurses are leading or are engaged in research and evidence-based practice. This article describes common barriers to and effective strategies for developing a culture of research and evidence-based practice, with recommendations for Magnet- and Pathway-seeking organizations.
Transforming Healthcare to Evidence-Based Healthcare
Authors: Gallagher-Ford Lynn , Connor Linda
Published: April 2020

The adoption of evidence-based decision-making and practice in healthcare has been slow. This article discusses the critical role of leaders in steering this transformative work.
Staff Nurses' Perceptions of Nurse Manager Caring Behaviors
Authors: Kostich Kelley , Lasiter Sue , Gorrell Renee
Published: April 2020

OBJECTIVE

The purpose of this scoping study is to review the published evidence regarding staff nurses' perceptions of nurse manager caring behaviors.

BACKGROUND

As healthcare administration becomes more complex and financial challenges continue, the ability of nurse managers to lead patient care environments that produce desirable outcomes becomes critical. Demonstrating caring behaviors that build relationships with individuals and groups is a necessary competency of nursing administrators to advance healthcare.

METHODS

This scoping study was guided by Arksey and O′Malley's methodology to review existing literature.

RESULTS

Published literature provided knowledge of staff nurses' perceptions of nurse manager caring behaviors. The final sample was 13 publications. The results were summarized in both numeric and thematic analysis.

CONCLUSIONS

Further research is needed to explore the relationship between nurse manager caring behaviors and patient outcomes.
Apocrine Variant of Pleomorphic Lobular Carcinoma In Situ
Authors: Zhong Elaine , Solomon James P. , Cheng Esther , Baum Jordan , Song Wei , Hoda Syed A.
Published: April 2020

To date, the apocrine variant of lobular carcinoma in situ (AP-LCIS) has been cursorily described as a subtype of lobular carcinoma in situ (LCIS). We retrospectively reviewed 34 cases of AP-LCIS (including 23 associated with invasive lobular carcinoma) to fully characterize it. AP-LCIS typically presented with screen-detected calcifications in older women (mean age: 65 y) and was characterized by distended terminal duct lobular units with relatively large “pleomorphic” cells, central necrosis, and calcifications. AP-LCIS cells exhibited abundant eosinophilic occasionally granular cytoplasm, hyperchromatic nuclei, and prominent nucleoli. Synchronous classic and/or florid LCIS was identified in 24/34 (70%) AP-LCIS, and in 9/11 (82%) pure AP-LCIS. Most (68%) cases of AP-LCIS were estrogen receptor–positive (50% strongly), 35% were progesterone receptor–positive, 26% were human epidermal growth factor 2–positive, 18% demonstrated high-proliferation rate (Ki67: >15%), and 90% were androgen receptor–positive. Aurora kinase A, immunoreactive in 38% of AP-LCIS cases, was not significantly associated with recurrence, development of invasion, or nodal positivity (P>0.05). Compared with conventional (nonapocrine) pleomorphic lobular carcinoma in situ (P-LCIS), aurora kinase A was expressed in a significantly greater proportion of P-LCIS (100%). AP-LCIS and P-LCIS did not otherwise differ in clinicopathologic features. Next-generation sequencing utilizing the Oncomine Comprehensive Panel v2, performed on 27 AP-LCIS cases, showed no specific molecular findings. In a mean follow-up of 57 months, 2 (of 11, 18%) pure AP-LCIS cases recurred (2 both in situ and invasive) and none metastasized or proved fatal. AP-LCIS should be regarded as another high-grade LCIS similar to P-LCIS in many respects, and pending additional studies should be managed similarly.
Targeting Calcium Release–activated Calcium Channel Is Not Sufficient to Prevent Rejection in Nonhuman Primate Kidney Transplantation
Authors: Kwun Jean , Ezekian Brian , Manook Miriam , Park Jaeberm , Yoon Janghoon , Freischlag Kyle , Song Mingqing , Farris Alton B. , Sloan-Lancaster Joanne , Fortier Caroline , Rao Patricia E. , Knechtle Stuart J.
Published: April 2020

Background.

Calcineurin inhibitors successfully control rejection of transplanted organs but also cause nephrotoxicity. This study, using a rhesus monkey renal transplantation model, sought to determine the applicability of a new immunomodulatory drug inhibiting the store-operated calcium release–activated calcium channel of lymphocytes to control transplant rejection without nephrotoxicity.

Methods.

Animals underwent kidney transplantation and were treated with tacrolimus alone (n = 3), a CRACM1 inhibitor (PRCL-02) (n = 6) alone, or with initial tacrolimus monotherapy followed by gradual conversion at 3 weeks to PRCL-02 alone (n = 3). PRCL-02 was administered via a surgically inserted gastrostomy tube BID.

Results.

Dose-related drug exposure in monkeys was established and renal transplants were then performed using PRCL-02 monotherapy. Oral dosing of PRCL-02 was well tolerated and resulted in suppressed T-cell proliferation in in vitro MLR comparable to animals in the tacrolimus control arm. Animals receiving tacrolimus monotherapy were e on day 100 without rejection. PRCL-02 monotherapy only marginally prolonged graft survival (MST = 13.16 d; group 2) compared with untreated controls. Animals treated initially with tacrolimus and converted to PRCL-02 monotherapy had a mean graft survival of 35.3 days which was prolonged compared with PRCL-02 monotherapy but not compared with the tacrolimus-treated group. Pharmacokinetic studies showed inconsistent drug exposures despite attempts to adjust dose and exposure which may have contributed to the rejections.

Conclusions.

We conclude that, in this nonhuman primate model of kidney transplantation, PRCL-02 demonstrated evidence of in vivo immunosuppressive activity but was inferior to tacrolimus treatment with respect to suppressing immune transplant rejection.
Sphingorhabdus lacus sp. nov. and Sphingorhabdus profundilacus sp. nov., isolated from freshwater environments
Authors: Park Miri , Jung Ilsuk , Song Jaeho , Cho Jang-Cheon
Published: April 2020

Two Gram-stain-negative, aerobic, non-motile bacteria, designated IMCC1753T and IMCC26285T, were isolated from a shallow eutrophic pond and a deep oligotrophic lake, respectively. Results of 16S rRNA gene sequence analysis indicated that the two strains shared 99.8 % sequence similarity and were most closely related to

Sphingorhabdus contaminans

JC216T(98.7–98.8 %). The whole genome sequences of strains IMCC1753T and IMCC26285T were 3.5 and 2.9 Mbp in size with 56.6 and 55.5 mol% DNA G+C content, respectively. Average nucleotide identity (ANI) and digital DNA–DNA hybridization (dDDH) values between the two strains were 82.2 and 25.8 %, respectively, indicating that they are separate species. The two strains showed ≤98.8 % 16S rRNA gene sequence similarities and ≤82.2 % ANI and ≤28.7 % dDDH values to closely related species of the genus

Sphingorhabdus

, indicating that the two strains each represent novel species. Major fatty acid constituents of strain IMCC1753T were C17 : 1
 ω6c, C17 : 1
 ω8c and summed features 3 (C16 : 1
 ω6c and/or C16 : 1
 ω7c) and 8 (C18 : 1
 ω6c and/or C18 : 1
 ω7c); those of strain IMCC26285T were summed features 3 and 8. The predominant isoprenoid quinone detected in both strains was ubiquinone-10 and the most abundant polyamine was spermidine. Both strains contained phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol and sphingoglycolipid as major polar lipids. On the basis of the phylogenetic and phenotypic characteristics, strains IMCC1753T and IMCC26285T were considered to represent two distinct novel species in the genus

Sphingorhabdus

, for which the names Sphingorhabdus lacus (IMCC1753T=KCTC 52480T=KACC 18985T=NBRC 112442T) and Sphingorhabdus profundilacus (IMCC26285T=KCTC 52479T=KACC 18986T=NBRC 112454T) are proposed, respectively.
Nocardiopsis deserti sp. nov., isolated from a high altitude Atacama Desert soil
Authors: Asem Mipeshwaree Devi , Salam Nimaichand , Idris Hamidah , Zhang Xiao-Tong , Bull Alan T. , Li Wen-Jun , Goodfellow Michael
Published: April 2020

The taxonomic status of a

Nocardiopsis

strain, designated H13T, isolated from a high altitude Atacama Desert soil, was established by using a polyphasic approach. The strain was found to have chemotaxonomic, cultural and morphological characteristics consistent with its classification within the genus

Nocardiopsis

and formed a well-supported clade in the

Nocardiopsis

phylogenomic tree together with the type strains of

Nocardiopsis alborubida

,

Nocardiopsis dassonvillei

and Nocardiopsis synnematoformans. Strain H13T was distinguished from its closest relatives by low average nucleotide identity (93.2–94.9 %) and in silico DNA–DNA hybridization (52.5–62.4 %) values calculated from draft genome assemblies and by a range of phenotypic properties. On the basis of these results, it is proposed that the isolate be assigned to the genus

Nocardiopsis

as Nocardiopsis deserti sp. nov. with isolate H13T (=CGMCC 4.7585T=KCTC 49249T) as the type strain.
Sodium salicylate interferes with quorum-sensing-regulated virulence in chronic wound isolates of Pseudomonas aeruginosa in simulated wound fluid
Authors: Gerner Erik , Almqvist Sofia , Werthén Maria , Trobos Margarita
Published: April 2020

Introduction. An important factor for delayed healing of chronic wounds is the presence of bacteria. Quorum sensing (QS), a cell density-dependent signalling system, controls the production of many virulence factors and biofilm formation in

Pseudomonas aeruginosa

.

Aim. Inhibition by sodium salicylate (NaSa) of QS-regulated virulence expression was evaluated in QS-characterized clinical wound isolates of P. aeruginosa, cultured in serum-containing medium.

Methodology. Fourteen clinical

P. aeruginosa

strains from chronic wounds were evaluated for the production of QS signals and virulence factors. Inhibition of QS by NaSa in

P. aeruginosa

clinical strains, wild-type PAO1 and QS reporter strains was evaluated using in vitro assays for the production of biofilm, pyocyanin, siderophores, alkaline protease, elastase and stapholytic protease.

Results. Six clinical strains secreted several QS-associated virulence factors and signal molecules and two were negative for all factors. Sub-inhibitory concentrations of NaSa downregulated the expression of the QS-related genes lasB, rhlA and pqsA and reduced the secretion of several virulence factors in PAO1 and clinical strains cultured in serum. Compared to serum-free media, the presence of serum increased the expression of QS genes and production of siderophores and pyocyanin but decreased biofilm formation.

Conclusions.

Pseudomonas aeruginosa

from chronic wound infections showed different virulence properties. While very few strains showed no QS activity, approximately half were highly virulent and produced QS signals, suggesting that the targeting of QS is a viable and relevant strategy for infection control. NaSa showed activity as a QS-inhibitor by lowering the virulence phenotypes and QS signals at both transcriptional and extracellular levels.
Does TB Vaccination Reduce COVID-19 Infection? No Evidence from a Regression Discontinuity Analysis
Authors: Fukui Masao , Kawaguchi Kohei , Matsuura Hiroaki
Published: April 2020

In the middle of the global COVID-19 pandemic, the BCG hypothesis, the prevalence and severity of the COVID-19 outbreak seems to be correlated with whether a country has a universal coverage of Bacillus-Calmette-Guérin (BCG), a vaccine for tuberculosis disease (TB), has emerged and attracted the attention of scientific community and media outlets. However, all existing claims are based on cross-country correlations that do not exclude the possibility of spurious correlation. We merged country-age-level case statistics with the start/termination years of BCG vaccination policy and conducted a regression discontinuity and difference-indifference analysis. The results do not support the BCG hypothesis.
The impact of Attachment Styles and Defense Mechanisms on psychological distress in a non-clinical young adult sample: a path analysis
Authors: Ciocca Giacomo , Rossi Rodolfo , Collazzoni Alberto , Gorea Fiorela , Vallaj Blerina , Stratta Paolo , Longo Lucia , Limoncin Erika , Mollaioli Daniele , Gibertoni Dino , Santarnecchi Emiliano , Pacitti Francesca , Niolu Cinzia , Siracusano Alberto , Jannini Emmanuele A. , Di Lorenzo Giorgio
Published: April 2020

Introduction

Insecure attachment styles and immature or neurotic defense mechanisms are related to psychological distress. However, their mutual interaction in influencing psychological distress deserves further investigation.

Methods

One-thousand-one-hundred-twenty-nine University students were evaluated using the Global Severity Index of Symptoms Check List 90-Revised for psychological distress, Relationship Questionnaire for attachment styles and Defense Style Questionnaire for defense mechanisms. Following exploratory analyses, a Path Analysis was performed with psychological distress as outcome.

Results

Fearful and preoccupied attachment styles had a substantial impact on psychological distress. About 30% of their effect was mediated by Immature and Neurotic defenses, with the former having the major effect. Dismissing attachment showed no substantial effect on psychological distress. Secure Attachment and Mature Defenses had a small protective effect on psychological distress, but their inclusion in the path model did not improve overall goodness-of-fit. Attachment style and defense mechanisms accounted for nearly 25% of the variance in psychological distress.

Conclusions

The results showed that attachment styles and defense mechanisms have a substantial impact on psychological distress. The effect of attachment style is mediated by defense mechanisms. Individual differences in attachment style and defense mechanisms represent risk factors for psychological distress in young adults.
A transcriptomics-based meta-analysis combined with machine learning approach identifies a secretory biomarker panel for diagnosis of pancreatic adenocarcinoma
Authors: Khatri Indu , Bhasin Manoj K.
Published: April 2020

Pancreatic ductal adenocarcinoma (PDAC) is largely incurable due to late diagnosis and absence of markers that are concordant with expression in several sample sources (i.e. tissue, blood, plasma) and platform (i.e. Microarray, sequencing). We optimized meta-analysis of 19 PDAC (tissue and blood) transcriptome studies from multiple platforms. The key biomarkers for PDAC diagnosis with secretory potential were identified and validated in different cohorts. Machine learning approach i.e. support vector machine supported by leave-one-out cross-validation was used to build and test the classifier. We identified a 9-gene panel (IFI27, ITGB5, CTSD, EFNA4, GGH, PLBD1, HTATIP2, IL1R2, CTSA) that achieved ∼0.92 average sensitivity and ∼0.90 specificity in discriminating PDAC from non-tumor samples in five training-sets on cross-validation. This classifier accurately discriminated PDAC from chronic-pancreatitis (AUC=0.95), early stages of progression (Stage I and II (AUC=0.82), IPMA and IPMN (AUC=1), IPMC (AUC=0.81)). The 9-gene marker outperformed the previously known markers in blood studies particularly (AUC=0.84). The discrimination of PDAC from early precursor lesions in non-malignant tissue (AUC>0.81) and peripheral blood (AUC>0.80) may facilitate early blood-diagnosis and risk stratification upon validation in prospective clinical-trials. Furthermore, the validation of these markers in proteomics and single-cell transcriptomics studies suggest their prognostic role in the diagnosis of PDAC.
Lessons from mainland China’s epidemic experience about the growth rules of infected and recovered cases of COVID-19 worldwide
Authors: Han Chuanliang , Liu Yimeng , Tang Jiting , Zhu Yuyao , Jaeger Carlo , Yang Saini
Published: April 2020

The novel coronavirus disease (COVID-19) that emerged at the end of 2019 has been controlled in mainland China so far, while it is still spreading globally. When the pandemic will end is a question of great concern. A logistic model depicting the growth rules of infected and recovered cases in mainland China may shed some light on this question. We extended this model to 31 countries outside China experiencing serious COVID-2019 outbreaks. The model well explained the data in our study (R2≥ 0.95). For infected cases, the semi-saturation period (SSP) ranges from 63 to 170 days (March 3 to June 18). The logistic growth rate of infected cases is positively correlated with that of recovered cases, and the same holds for the SSP. According to the linear connection between the growth rules for infected and recovered cases identified from the Chinese data, we predicted that the SSP of the recovered cases outside China ranges from 82 to 196 days (March 22 to July 8). More importantly, we found a strong positive correlation between the SSP of infected cases and the timing of government’s response, providing strong evidence for the effectiveness of rapid epidemic control measures in various countries.
Estimates of COVID-19 case-fatality risk from individual-level data
Authors: Assche Simona Bignami-Van , Ghio Daniela , Van Assche Ari
Published: April 2020

When calculated from aggregate data on confirmed cases and deaths, the case-fatality risk (CFR) is a simple ratio between the former and the latter, which is prone to numerous biases. With individual-level data, the CFR can be estimated as a true measure of risk as the proportion of incidence for the disease. We present the first estimates of the CFR for COVID-19 by age and sex based on event history modelling of the risk of dying among confirmed positive individuals in the Canadian province of Ontario, which maintains one of the few individual-level datasets on COVID-19 in the world.
Mental health outcomes among front and second line health workers associated with the COVID-19 pandemic in Italy
Authors: Rossi Rodolfo , Socci Valentina , Pacitti Francesca , Di Lorenzo Giorgio , Di Marco Antinisca , Siracusano Alberto , Rossi Alessandro
Published: April 2020

In this study, we report on mental health outcomes among health workers (HWs) involved with the COVID-19 pandemic in Italy.

Data on mental health on 1379 HWs were collected between March 27th and March 31th 2020 using an on-line questionnaire spread throughout social networks, using a snowball technique along with sponsored social network advertisement. Key mental health outcomes were Post-Traumatic Stress Disorder symptoms (PTSD), severe depression, anxiety, insomnia and perceived stress.

PTSD symptoms, severe depression, anxiety and insomnia, and high perceived stress were endorsed respectively by 681 (49.38%), 341 (24.73%), 273 (19.80%), 114 (8.27%) and 302 (21.90%) respondents. Regression analysis show that younger age, female gender, being a front-line HWs, having a colleague deceased, hospitalised or in quarantine were associated with poor mental health outcomes.

This is the first report on mental health outcomes and associated risk factors among HWs associated with the COVID-19 pandemic in Italy, confirming a substantial proportion of health workers involved with the COVID-19 pandemic having mental health issues, in particular young women, first-line HWs.
LONG-TERM CLINICAL OUTCOMES IN SURVIVORS OF CORONAVIRUS OUTBREAKS AFTER HOSPITALISATION OR ICU ADMISSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF FOLLOW-UP STUDIES
Authors: Ahmed Hassaan , Patel Kajal , Greenwood Darren , Halpin Stephen , Lewthwaite Penny , Salawu Abayomi , Eyre Lorna , Breen Andrew , O’Connor Rory , Jones Anthony , Sivan Manoj
Published: April 2020

Objective

To determine the long-term clinical problems in adult survivors of coronavirus (CoV) infection [Coronavirus disease 2019 (COVID-19), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)] after hospitalisation or Intensive Care Unit (ICU) admission.

Design

Systematic review and meta-analysis of the literature.

Data sources

Ovid MEDLINE, EMBASE, CINAHL Plus and PsycINFO were searched using the strategy: (Coronavirus OR Coronavirus Infections OR COVID OR SARS virus OR Severe acute respiratory syndrome OR MERS OR Middle east respiratory syndrome) AND (Follow-up OR Follow-up studies OR Prevalence). Original studies reporting the clinical outcomes of adult survivors of coronavirus outbreaks two months after discharge or three months after admission were included. The quality of the studies was assessed using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2009 Level of Evidence Tool. Meta-analysis was conducted to derive pooled estimates of prevalence and severity for different outcomes at time points up to 6 months follow-up and beyond 6 months follow-up.

Results

The search yielded 1169 studies of which 28 were included in this review. There were 15 Level 1b, 8 Level 2b, 2 Level 3b and 3 Level 4 studies by OCEBM grading. Pooled analysis of studies revealed that complications commonly observed were impaired diffusing capacity for carbon monoxide (DLCO) [prevalence of 27.26%, 95% CI 14.87 to 44.57] and reduced exercise capacity [(6-minute walking distance (6MWD) mean 461m, 95% CI 449.66 to 472.71] at 6 months with limited improvement beyond 6 months. Coronavirus survivors had considerable prevalence of psychological disorders such as post-traumatic stress disorder (PTSD) [38.80%, CI 30.93 to 47.31], depression [33.20%, CI 19.80 to 50.02] and anxiety [30.04%, CI 10.44 to 61.26) beyond 6 months. These complications were accompanied by low Short Form 36 (SF-36) scores at 6 months and beyond indicating reduced quality of life which is present long-term.

Conclusions

The long term clinical problems in survivors of CoV infections (SARS and MERS) after hospitalisation or Intensive Care Unit (ICU) admission include respiratory dysfunction, reduced exercise capacity, psychological problems such as PTSD, depression and anxiety, and reduced quality of life. Critical care, rehabilitation and mental health services should anticipate a high prevalence of these problems following COVID-19 and ensure their adequate and timely management with the aim of restoring premorbid quality of life.
Projections for first-wave COVID-19 deaths across the US using social-distancing measures derived from mobile phones
Authors: Woody Spencer , Tec Mauricio , Dahan Maytal , Gaither Kelly , Lachmann Michael , Fox Spencer J. , Meyers Lauren Ancel , Scott James ,   The University of Texas at Austin COVID-19 Modeling Consortium
Published: April 2020

We propose a Bayesian model for projecting first-wave COVID-19 deaths in all 50 U.S. states. Our model’s projections are based on data derived from mobile-phone GPS traces, which allows us to estimate how social-distancing behavior is “flattening the curve” in each state. In a two-week look-ahead test of out-of-sample forecasting accuracy, our model significantly outperforms the widely used model from the Institute for Health Metrics and Evaluation (IHME), achieving 42% lower prediction error: 13.2 deaths per day average error across all U.S. states, versus 22.8 deaths per day average error for the IHME model. Our model also provides an accurate, if slightly conservative, assessment of forecasting accuracy: in the same look-ahead test, 98% of data points fell within the model’s 95% credible intervals. Our model’s projections are updated daily at https://covid-19.tacc.utexas.edu/projections/.
Review of Current Evidence of Hydroxychloroquine in Pharmacotherapy of COVID-19
Authors: Suranagi Umesh Devappa , Rehan Harmeet Singh , Goyal Nitesh
Published: April 2020

Importance

The COVID-19 Pandemic has literally left the world breathless in the chase for pharmacotherapy. With vaccine and novel drug development in early clinical trials, repurposing of existing drugs takes the center stage.

Objective

A potential drug discussed in global scientific community is hydroxychloroquine. We intend to systematically explore, analyze, rate the existing evidence of hydroxychloroquine in the light of published, unpublished and clinical trial data.

Evidence review

PubMed Ovid MEDLINE, EMBASE, Google scholar databases, pre-proof article repositories, clinical trial registries were comprehensively searched with focused question of use of hydroxychloroquine in COVID-19 patients. The literature was systematically explored as per PRISMA guidelines.

Findings

Total 156 articles were available as of 7th May 2020; of which 11 articles of relevance were analyzed. Three in-vitro studies were reviewed. Two open label non-randomized trials, two open label randomized control trials, one large observational study, one follow-up study and two retrospective cohort studies were systematically analyzed and rated by oxford CEBM and GRADE framework for quality and strength of evidence. Also 27 clinical trials registered in three clinical trial registries were analyzed and summarized. Hydroxychloroquine seems to be efficient in inhibiting SARS-CoV-2 in in-vitro cell lines. However, there is lack of strong evidence from human studies. It was found that overall quality of available evidence ranges from ‘very low’ to ‘low’.

Conclusions and relevance

The in-vitro cell culture based data of viral inhibition does not suffice for the use of hydroxychloroquine in the patients with COVID-19. Current literature shows inadequate, low level evidence in human studies. Scarcity of safety and efficacy data warrants medical communities, health care agencies and governments across the world against the widespread use of hydroxychloroquine in COVID-19 prophylaxis and treatment, until robust evidence becomes available.

KEY POINTS

Question

What is the current evidence for use of Hydroxychloroquine in pharmacotherapy of COVID-19?

Findings

We electronically explored various databases and clinical trial registries and identified 11 publications and 27 clinical trials with active recruitment. The in-vitro study data demonstrates the viral inhibition by hydroxychloroquine. The clinical studies are weakly designed and conducted with insufficient reporting and significant limitations. Well designed robust clinical trials are being conducted all over the world and results of few such robust studies are expected shortly.

Meaning

Current evidence stands inadequate to support the use of hydroxychloroquine in pharmacotherapy of COVID-19.
COVID-19 Outbreak Situations in Bangladesh: An Empirical Analysis
Authors: Rahaman Khan Md Hasinur , Hossain Ahmed
Published: April 2020

COVID-19 disease, as popularly known as Coronavirus 2019 disease, has been emerged from Wuhan, China in December 2019 and now is a pandemic for almost every nation in the earth. It affects every country without considering country’s race, nationality and economic status. This paper aims at analysing primarily the current situations of Bangladesh and predicting infections and deaths for moderated term intervals by a proposed projection technique called Infection Trajectory-Pathway Strategy (ITPS) and for short term intervals prediction for total infections, deaths along with total number of severe patients and Intensive Care Unit (ICU) patients by polynomial regression modeling approach. Since April 7, Bangladesh has started to face critical situations as the number of infections has accelerated very fast in the following days. However, the fatality rate decreases considerably from 15.7 on April 1 to 4.9 on April 14, which is still high among the south asian countries. Of the 1012 cases reported on April 14, almost 70% are the male, 42% are from the capital Dhaka. We have found that the potential pathway of infections for Bangldesh would be the similar pathways that are experienced by Austria, Netherlands, Israel, France and United Kingdom. These countries are ahead a number of weeks and days in terms of infection cases since their 100-th confirmed cases. Our proposed projection method ITPS suggests that by May 10, Bangladesh will cross 12000 incidences and 720 deaths which, by May 16 will be 27000 and 1644 respectively. On the other hand, the regression model suggests that by the end of April, total number of infections, deaths, severe patients and ICU patients will be 5780, 347, 775, and 694 respectively. This study will be favorable for the administrative units of Bangladesh to plan for the next few weeks and to consider various aspects related to the control of COVID-19 outspread in Bangladesh.
Power calculations for detecting differences in efficacy of fecal microbiota donors
Authors: Olesen Scott W.
Published: April 2020

Fecal microbiota transplantation (FMT) is a recommended therapy for recurrent Clostridioides difficile infection and is being investigated as a potential therapy for dozens of other indications, notably inflammatory bowel disease. The immense variability in human stool, combined with anecdotal reports from FMT studies, have suggested the existence of “donor effects”, in which stool from some FMT donors is more efficacious than stool from other donors. In this study, simulated clinical trials were used to estimate the number of patients that would be required to detect donor effects under a variety of study designs. In most cases, reliable detection of donor effects required more than 100 patients treated with FMT. These results suggest that previous reports of donor effects need to be verified with results from large clinical trials and that patient biomarkers may be the most promising route to robustly identifying donor effects.
Prediction of Coronavirus Disease (covid-19) Evolution in USA with the Model Based on the Eyring’s Rate Process Theory and Free Volume Concept
Authors: Hao Tian
Published: April 2020

A modification arguing that the human movement energy may change with time is made on our previous infectious disease model, in which infectious disease transmission is considered as a sequential chemical reaction and reaction rate constants obey the Eyring’s rate process theory and free volume concept. The modified model is employed to fit current covid-19 outbreak data in USA and to make predictions on the numbers of the infected, the removed and the death in the foreseeable future. Excellent fitting curves and regression quality are obtained, indicating that the model is working and the predictions may be close to reality. Our work could provide some ideas on what we may expect in the future and how we can prepare accordingly for this difficult period.
Automatic Identification of Upper Extremity Rehabilitation Exercise Type and Dose Using Body-Worn Sensors and Machine Learning: A Pilot Study
Authors: Balestra Noah , Sharma Gaurav , Riek Linda M. , Busza Ania
Published: April 2020

Stroke is a major cause of adult-onset disability worldwide, and approximately 40% of stroke survivors have residual impairment in upper-extremity function. Prior studies suggest that increased participation in rehabilitation exercises improves motor function post-stroke,1however further clarification of optimal exercise dose and timing has been limited by the technical challenge of quantifying exercise activities over multiple days. In this exploratory study, we assessed the feasibility of using body-worn sensors to track rehabilitation exercises in the inpatient setting, and investigated which recording parameters and data analysis strategies are sufficient for accurately identifying and counting exercise repetitions. MC10 BioStampRC® sensors were used to measure accelerometry and gyroscopy from arms of healthy controls (n=11) and patients with arm weakness due to recent stroke (n=13) while the subjects performed three pre-selected upper extremity exercises. Sensor data was then labeled by exercise type, and this labeled data set was used to train a machine learning classification algorithm for identifying exercise type. The machine-learning algorithm and a peak-finding algorithm was used to count exercise repetitions in non-labeled data sets. We achieved a repetition counting accuracy of 95.6 ± 2.4 % overall, and 95.0 ± 2.3 % in patients with arm weakness due to stroke. Accuracy was decreased when using fewer sensors or using accelerometry alone. Our exploratory study suggests that body-worn sensor systems are technically feasible, well-tolerated in subjects with recent stroke, and may ultimately be useful for developing a system to measure total exercise “dose” in post-stroke patients during clinical rehabilitation or clinical trials.
Effectiveness and Safety of Glucocorticoids to Treat COVID-19: A Rapid Review and Meta-Analysis
Authors: Lu Shuya , Zhou Qi , Huang Liping , Shi Qianling , Zhao Siya , Wang Zijun , Li Weiguo , Tang Yuyi , Ma Yanfang , Luo Xufei , Fukuoka Toshio , Ahn Hyeong Sik , Lee Myeong Soo , Luo Zhengxiu , Liu Enmei , Chen Yaolong , Zhou Chenyan , Peng Donghong
Published: April 2020

Background

Glucocorticoids are widely used in the treatment of various pulmonary inflammatory diseases, but they are also often accompanied by significant adverse reactions. Published guidelines point out that low dose and short duration systemic glucocorticoid therapy may be considered for patients with rapidly progressing COVID-19 while the evidence is still limited.

Methods

We comprehensively searched electronic databases and supplemented the screening by conducting a manual search. We included RCTs and cohort studies evaluating the effectiveness and safety of glucocorticoids in children and adults with COVID-19, SARS and MERS, and conducted meta-analyses of the main indicators that were identified in the studies.

Results

Our search retrieved 23 studies, including one RCT and 22 cohort studies, with a total of 13,815 patients. In adults with COVID-19, the use of systemic glucocorticoid did not reduce mortality (RR=2.00, 95% CI: 0.69 to 5.75,I2=90.9%) or the duration of lung inflammation (WMD=-1 days, 95% CI: -2.91 to 0.91), while a significant reduction was found in the duration of fever (WMD=-3.23 days, 95% CI: -3.56 to -2.90). In patients with SARS, glucocorticoids also did not reduce the mortality (RR=1.52, 95% CI: 0.89 to 2.60,I2=84.6%), duration of fever (WMD=0.82 days, 95% CI: -2.88 to 4.52,I2=97.9%) or duration of lung inflammation absorption (WMD=0.95 days, 95% CI: -7.57 to 9.48,I2=94.6%). The use of systemic glucocorticoid therapy prolonged the duration of hospital stay in all patients (COVID-19, SARS and MERS).

Conclusions

Glucocorticoid therapy was found to reduce the duration of fever, but not mortality, duration of hospitalization or lung inflammation absorption. Long-term use of high-dose glucocorticoids increased the risk of adverse reactions such as coinfections, so routine use of systemic glucocorticoids for patients with COVID-19 cannot be recommend.
CAN-NPI: A Curated Open Dataset of Canadian Non-Pharmaceutical Interventions in Response to the Global COVID-19 Pandemic
Authors: McCoy Liam G. , Smith Jonathan , Anchuri Kavya , Berry Isha , Pineda Joanna , Harish Vinyas , Lam Andrew T. , Yi Seung Eun , Hu Sophie ,   COVID-19 Canada Open Data Working Group: Non-Pharmaceutical Interventions, Fine Benjamin
Published: April 2020

Non-pharmaceutical interventions (NPIs) have been the primary tool used by governments and organizations to mitigate the spread of the ongoing pandemic of COVID-19. Natural experiments are currently being conducted on the impact of these interventions, but most of these occur at the subnational level - data not available in early global datasets. We describe the rapid development of the first comprehensive, labelled dataset of 1640 NPIs implemented at federal, provincial/territorial and municipal levels in Canada to guide COVID-19 research. For each intervention, we provide: a) information on timing to aid in longitudinal evaluation, b) location to allow for robust spatial analyses, and c) classification based on intervention type and target population, including classification aligned with a previously developed measure of government response stringency. This initial dataset release (v1.0) spans January 1st, and March 31st, 2020; bi-weekly data updates to continue for the duration of the pandemic. This novel dataset enables robust, inter-jurisdictional comparisons of pandemic response, can serve as a model for other jurisdictions and can be linked with other information about case counts, transmission dynamics, health care utilization, mobility data and economic indicators to derive important insights regarding NPI impact.
The effect of BCG vaccination on COVID-19 examined by a statistical approach: no positive results from the Diamond Princess and cross-national differences previously reported by world-wide comparisons are flawed in several ways
Authors: Asahara Masakazu
Published: April 2020

Recently, the controversial hypothesis that past BCG (Bacillus Calmette–Guérin) vaccination reduces infection or severity of COVID-19 has been proposed. The present study examined this hypothesis using statistical approaches based on the public data. Three approaches were utilized: 1) comparing the infection and mortality ratio of people on the cruise ship Diamond Princess, 2) comparing the number of mortalities among nations, and 3) comparing the maximum daily increase rate of total mortalities among nations. The result of 1) showed that there is no significant difference in infection per person onboard or mortality-infection between Japanese citizens vs. US citizens and BCG obligatory nations vs. non-BCG obligatory nations on the Diamond Princess. The result of 2) showed that the number of mortalities among nations is similar to the previous studies, but this analysis also considered the timing of COVID-19 arrival in each nation. After correcting for arrival time, previously reported effect of BCG vaccination on decreasing total mortality disappeared. This is because nations that lack BCG vaccination are concentrated in Western Europe, which is near an epicenter of COVID-19. Therefore some previous reports are now considered to be affected by this artifact; the result may have been flawed by dispersal from an epicenter. However, some results showed weakly significant differences in the number of deaths at a particular time among BCG obligatory and non-BCG nations (especially the use of Japanese BCG strain Tokyo 172). However, these results are affected by the results of three countries and the effect of BCG vaccination remains inconclusive. The result of 3) showed that the maximum daily increasing rate in death among nations showed no significant difference among BCG vaccination policies. In the present study, although some results showed statistically significant differences among BCG vaccination policies, they may be affected by the impact of various other factors, such as national infection-control policies, social distancing, behavioral changes of people, possible previous local epidemics of closely related viruses, or inter-population differences in ACE2 or other genetic polymorphism. Further research is needed to better understand the underlying cause of the observed differences in infection and mortality of the disease among nations. Nevertheless, our results show that the effect of past BCG vaccination, if any, can be masked by many other factors. Therefore, the possible effect might be relatively small. In fact, in Japan, where almost all citizens have been vaccinated, COVID-19 cases are constantly increasing. Given the importance of people’s behavior in preventing viral propagation, the spread of optimism triggered by this hypothesis would be harmful to BCG vaccination nations.
Estimation of salt intake, potassium intake and sodium-to-potassium ratio by 24-hour urinary excretion: an urban rural study in Sri Lanka
Authors: Jayatissa R , Yamori Y , De Silva AH , Mori M , De Silva PC , De Silva KH
Published: April 2020

Background

Sodium intakes of different populations around the world became of interest after a positive correlation was drawn between dietary sodium intake and prevalence of hypertension. Sri Lanka has adopted a salt reduction strategy to combat high blood pressure in the population with escalation of non-communicable diseases.

Objective

To measure intake of salt, potassium and sodium/potassium ratio of adults in urban and rural settings.

Design

A community based study of 328 adults between 30-59 years, including equal numbers from urban and rural sectors. Weight, height and waist circumference were measured. Blood pressure was measured by a standardized automated measurement system and the mean of two readings was used for analysis. 24-hour urine was collected and measured for creatinine, sodium, potassium levels.

Results

Mean daily salt consumption was 8.3g (95%CI:7.9,8.8), which is 1.6 times higher than WHO recommendation. Mean daily potassium intake was 1,265g (95%CI:1191.0,1339.3), which is 2.8 times lower and sodium/potassium ratio was 4.3 (95%CI:4.2,4.5), which is 7 times higher than WHO recommendation. Daily salt consumption was significantly higher in males (9.0g;95%CI:8.3,9.8) than females (7.7g;95%CI:7.2,8.2); rural (8.9g;95%CI:8.2-9.6,) than urban (7.7g;95%CI:7.2,8.3) with increasing body mass index (8.2g;95%CI:6.1,10.2 to 10.0g;95%CI:8.5,11.6). Systolic blood pressure was significantly positively correlated with high BMI and waist circumference.

Conclusions

High salt consumption, low potassium intake and high sodium/potassium ratio was found in this population. This information can be used to set targets to reduce salt intake in the population. Need to create awareness to enhance the consumption of potassium rich food while reducing salt intake to minimize future NCD burden.
Triad entanglement of estrogen-sulfotransferase (SULT1E1), NFκβ and Nrf-2 confers matrix-metalloprotease (MMP 2/9) action in breast carcinogenesis
Authors: Nazmeen Aarifa , Maiti Sayantani , Maiti Smarajit
Published: April 2020

Estrogen (E2) is one of the most important signaling molecules that control cell-differentiation/early-embryogenesis/organogenesis in gender-independent manner. Nevertheless, during adolescence/adulthood it influences female reproductive-functions by delicate cellular proliferative-events via nongenomic (cellular-signaling)/genomic (transcriptional-signaling) pathways to recruit a number of genes/proteins. In case of post-menopausal-women high E2 may initiates tumors in breast/gynaecological-tissues. Impired estrogenic signaling may be the results from abnormal redox-regulations of estrogen-metabolizing-enzyme estrogen-sulfotransferase(SULT1E1), transcriptional-factors NFκβ, Nrf-2 and Matrixmetalloproteases (specially MMP 2/9) in the breast-tumor. Here, tumor and its surrounding tissues were obtained from the district-hospital. Intracellular redox-environment of tumors was screened with some in vitro-studies. RT-PCR for SULT1E1 expression and MMP 2/9-zymogram were conducted in lasoprazole (Nrf-2 inducer) or dexamethasone (SULT1E1 inducer) treted rat liver tissues. Immunohistochemistry was performed to analyze SULT1E1/NFκβ localization and MMP 2/9-zymogram in human breast-cancer versus its surrounding tissues. It can be hypothesized that transcription-factors (NFκβ/Nrf-2) imposes effect on MMPs expressions resulting in significant impacts on metastatic transition of breast-cancer. Breast tumor reveals higher (vs surrounding-tissue) expression/immunolocalization of NFκB/SULT1E1 paralleling to our previous finding of Nrf-2 induction. The relation between Nrf2/NFκB is determined by oxidative-stress and by CBP recruitment of HDAC3. Further, this relation is a determinant of MMP-regulations and SULT1E1-mediated E2 levels. Adaptively, augmented Nrf-2 may induce SULT1E1 resulting in lower active-estrogen. The triad regulations of NFκβ, SULT1E1 and Nrf2 are proposed here to execute MMPs function in the severity of human breast-carcinogenesis. Therapeutically this triad system may be effectively targeted for breast cancer treatment. Further studies are necessary in this regard.
An e-Leadership Training Academy for Practicing Clinicians in Primary Care and Public Health Settings
Authors: Sullivan Erin , Moftah Dena , Mbye PaMalick , Weilnau Taylor , Tobin Jonathan N.
Published: April 2020

Problem

There is a lack of leadership training in health care despite it being an essential competency for providers to deliver accessible, high quality healthcare and navigate a continually changing system. The barriers to adding leadership development to the various stages of medical training are numerous. A specific barrier is the lack of access to resources for this training. This group aimed to tackle this barrier within post-graduate medical education and training through their e- Leadership Academy.

Approach

The e-Leadership Academy was developed as a partnership between the Harvard Medical School Center for Primary Care and Clinical Directors Network, Inc. (CDN). The result of the collaboration was a virtual leadership academy, offered over a 10-month period that covered the fundamental concepts and skills for leading within a clinical practice. The audience for this program were clinicians and staff of community health centers and health departments in the United States.

Outcomes

For the results of this article, primary outcome analysis was of participant responses to both formative and summative evaluations that took place throughout and at the end of the course. Results were used to assess course quality, participant satisfaction, participant engagement, and provide data about future offerings that would be useful to the target audience.

Next Steps

The group proposes future training programs could measure the changes in the behavior of teams and clinical outcomes utilizing expanded evaluations. Proposed plans for expansion of the e- Leadership Academy include developing additional modules and the potential integration of an in- person component.