Publications by authors named "Omer Or"

1,871 Publications

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Communicating With Vaccine-Hesitant Parents: A Narrative Review.

Acad Pediatr 2021 May-Jun;21(4S):S24-S29

University of Colorado Denver (A Dempsey, C Spina, and SO Leary), Denver, Colo.

Although vaccines are considered one of the most effective medical interventions to prevent vaccine preventable disease and associated morbidity and mortality, a number of recent outbreaks are threatening the gains made by vaccines. Vaccine hesitancy is a key driver of vaccine refusal and has been associated with vaccine preventable outbreaks. While parents seek information from many sources to inform their vaccine decision-making process, they continue to view their child's pediatric provider as a trusted source of vaccine information. The communication that occurs between a provider and parent with regards to vaccination is critical in reducing concerns and nudging parents toward vaccine acceptance. However, vaccine-hesitant parents raise issues in this encounter that many providers feel ill-equipped to answer, due to lack of training on evidence-based communication strategies. We focus on promising approaches related to patient-provider communication within the context of vaccination. We found empirical evidence that the use of a presumptive format to recommend vaccines, motivational interviewing, and tailoring information to increase message salience are approaches that can positively affect vaccine acceptance. As providers continue to serve as important influencers in the vaccine decision-making process, it is evident that there is a need to continue to identify evidence-based, and practically implementable approaches to mitigate parental vaccine hesitancy. Providers play a key role in improving coverage rates, and therefore it is paramount to seek ways to improve how providers communicate about vaccines.
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http://dx.doi.org/10.1016/j.acap.2021.01.018DOI Listing
July 2020

Presence of biogenic amines in food and their public health concerns.

J Food Prot 2021 May 6. Epub 2021 May 6.

University of Van Yȕzȕncȕ Yıl, Veterinary College, Department of Food Hygiene and Technology, Van, Turkey.

Essential foods of a daily meal have been reported to comprise of numerous kinds of biogenic amines (BAs) at different levels. BAs have a variety of toxicological impacts on human health, and they have been connected to multiple outbreaks of foodborne disease. They also are known to cause cancer based on their ability to react with nitrite salts resulting in the production of a carcinogenic organic compound (i.e. nitrosamines). BAs toxicity is often linked to the ingestion of large quantities of BAs in food that causes toxicological threats and health disorders and has psychoactive, vasoactive, and hypertensive effects and can cause respiratory, gastrointestinal, cardiovascular and neurological disorders. Toxicity properties of BAs are linked closely to histamine and tyramine. Other amines, such as phenylethylamine, putrescine, and cadaverine are meaningful because they could increase histamine's negative effects. The key method for reducing BA concentration and foodborne disease is bacterial load management. It helps to control the formation of histamine and other BAs, and also reduce histamine and tyramine toxicity by applying basic good handling and hygiene practices. A greater understanding of BAs is essential to enhance food safety and quality. This review paper discusses the public health concerns of BAs in foods.
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http://dx.doi.org/10.4315/JFP-21-047DOI Listing
May 2021

Delayed production of neutralizing antibodies correlates with fatal COVID-19.

Nat Med 2021 May 5. Epub 2021 May 5.

Department of Medicine, Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT, USA.

Recent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). However, the exact features of antibody responses that govern COVID-19 disease outcomes remain unclear. In this study, we analyzed humoral immune responses in 229 patients with asymptomatic, mild, moderate and severe COVID-19 over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-spike (S) immunoglobulin G (IgG) levels, length of hospitalization and clinical parameters associated with worse clinical progression. Although high anti-S IgG levels correlated with worse disease severity, such correlation was time dependent. Deceased patients did not have higher overall humoral response than discharged patients. However, they mounted a robust, yet delayed, response, measured by anti-S, anti-receptor-binding domain IgG and neutralizing antibody (NAb) levels compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, although sera from 85% of patients displayed some neutralization capacity during their disease course, NAb generation before 14 d of disease onset emerged as a key factor for recovery. These data indicate that COVID-19 mortality does not correlate with the cross-sectional antiviral antibody levels per se but, rather, with the delayed kinetics of NAb production.
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http://dx.doi.org/10.1038/s41591-021-01355-0DOI Listing
May 2021

Effects of Agronomic Practices on the Severity of Sweet Basil Downy Mildew ().

Plants (Basel) 2021 Apr 30;10(5). Epub 2021 Apr 30.

Department of Plant Pathology and Weed Research, Agricultural Research Organization, The Volcani Center, Bet Dagan 50250, Israel.

Downy mildew (caused by ) is a severe disease of sweet basil () crops around the world. We examined cultural methods for reducing the severity of sweet basil downy mildew (SBDM) under commercial conditions in greenhouses and walk-in tunnels. The effects of the orientation of walk-in tunnels, air circulation in greenhouses, plant density, and soil mulch were tested. SBDM was less severe in the tunnels that were oriented north-south than in those oriented east-west, but the yields in both types of tunnels were similar. Increased air circulation reduced SBDM severity, but did not affect yield. Gray or transparent polyethylene mulch reduced SBDM severity and, in most cases, increased yield relative to bare soil/growth medium. Yellow polyethylene mulch provided a smaller amount of control. The combination of increased air circulation and yellow polyethylene mulch provided synergistic SBDM control, whereas no synergism was observed when we combined increased air circulation with the other two types of mulch. Planting at half the usual density reduced disease severity. The reduced plant density was associated with reduced yield in the greenhouses, but not in the tunnels. All of the tested methods provided an intermediate level of SBDM control that varied among the different experiments.
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http://dx.doi.org/10.3390/plants10050907DOI Listing
April 2021

Single-Dose del Nido Cardioplegia Compared With Standard Cardioplegia During Coronary Artery Bypass Grafting at a Veterans Affairs Hospital.

Tex Heart Inst J 2021 Jan;48(1)

Division of Cardiothoracic Surgery, Baylor College of Medicine, Houston, Texas.

Del Nido cardioplegic solution (DNC), used chiefly in pediatric patients, rapidly induces prolonged cardiac arrest during cardiac surgery. To determine whether surgical outcomes after coronary artery bypass grafting in a United States military veteran population differed when DNC was used instead of our standard Plegisol cardioplegia, we retrospectively reviewed 155 consecutive operations performed from July 2016 through June 2017. Del Nido cardioplegia was used to induce cardiac arrest in 70 patients, and Plegisol in 85. Compared with the Plegisol group, the DNC group had a shorter mean cardiopulmonary bypass time (96.8 vs 117 min; P <0.01) and aortic cross-clamp time (63.9 vs 71.7 min; P=0.02). On multiple linear regression, DNC use and number of bypasses performed were predictors of cardiopulmonary bypass time. The groups were similar in median number of bypasses performed, median time to extubation, intensive care unit stay, and total postoperative stay; however, the DNC group had a shorter mean operating room time (285.8 vs 364.5 min; P <0.01). Del Nido cardioplegia, number of bypasses, cardiopulmonary bypass time, and red blood cell transfusion were predictors of operating room time. Outcomes in the groups were similar for 30- and 180-day death, stroke, renal failure, ventilation time >48 hours, atrial fibrillation, tracheostomy, reintubation, and mechanical circulatory support. We conclude that single-dose DNC is safe, effective, and cost-effective for achieving cardiac arrest in U.S. veteran populations.
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http://dx.doi.org/10.14503/THIJ-19-6981DOI Listing
January 2021

Enteric mesenchymal cells support the growth of postnatal enteric neural stem cells.

Stem Cells 2021 May 2. Epub 2021 May 2.

Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Interplay between embryonic enteric neural stem cells (ENSCs) and enteric mesenchymal cells (EMCs) in the embryonic gut is essential for normal development of the enteric nervous system. Disruption of these interactions underlies the pathogenesis of intestinal aganglionosis in Hirschsprung disease (HSCR). ENSC therapy has been proposed as a possible treatment for HSCR, but whether the survival and development of postnatal-derived ENSCs similarly rely on signals from the mesenchymal environment is unknown and has important implications for developing protocols to expand ENSCs for cell transplantation therapy. Enteric neural crest-derived cells (ENCDCs) and EMCs were cultured from the small intestine of Wnt1-Rosa26-tdTomato mice. EMCs promoted the expansion of ENCDCs 9.5-fold by inducing ENSC properties, including expression of Nes, Sox10, Sox2, and Ngfr. EMCs enhanced the neurosphere-forming ability of ENCDCs, and this persisted after withdrawal of the EMCs. These effects were mediated by paracrine factors and several ligands known to support neural stem cells were identified in EMCs. Using the optimized expansion procedures, neurospheres were generated from small intestine of the Ednrb mouse model of HSCR. These ENSCs had similar proliferative and migratory capacity to Ednrb ENSCs, albeit neurospheres contained fewer neurons. ENSCs derived from Ednrb mice generated functional neurons with similar calcium responses to Ednrb ENSCs and survived after transplantation into the aganglionic colon of Ednrb recipients. EMCs act as supporting cells to ENSCs postnatally via an array of synergistically acting paracrine signaling factors. These properties can be leveraged to expand autologous ENSCs from patients with HSCR mutations for therapeutic application.
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http://dx.doi.org/10.1002/stem.3388DOI Listing
May 2021

Multivessel Versus Culprit-Vessel Percutaneous Coronary Intervention in Patients With Non-ST-Segment Elevation Myocardial Infarction and Cardiogenic Shock.

JACC Cardiovasc Interv 2021 Apr 21. Epub 2021 Apr 21.

Saint Luke's Mid America Heart Institute and the University of Missouri-Kansas City, Kansas City, Missouri, USA.

Objectives: The aim of this study was to compare in-hospital outcomes and long-term mortality of multivessel versus culprit vessel-only percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation myocardial infarction (NSTEMI), multivessel disease (MVD) and cardiogenic shock.

Background: The clinical benefits of complete revascularization in patients with NSTEMI, MVD, and cardiogenic shock remain uncertain.

Methods: Among 25,324 patients included in the National Cardiovascular Data Registry CathPCI Registry from July 2009 to March 2018, the rates of in-hospital procedural outcomes were compared between those undergoing multivessel PCI and those undergoing culprit vessel-only PCI after 1:1 propensity score matching. Among patients ≥65 years of age matched to the Centers for Medicare and Medicaid Services database, long-term mortality was compared using proportional hazards analysis.

Results: Multivessel PCI was performed in 9,791 patients (38.7%), which increased from 32.2% in 2010 to 44.2% in 2017 (p for trend < 0.001). After 1:1 propensity matching (n = 7,864 in each group), those undergoing multivessel PCI had a 3.5% (95% confidence interval [CI]: 2.0% to 5.0%) lower absolute rate of in-hospital mortality (30.9% vs. 34.4%; p < 0.001; odds ratio [OR]: 0.85; 95% CI: 0.80 to 0.91), but a higher risk for bleeding (13.2% vs. 10.8%; p < 0.001; OR: 1.26; 95% CI: 1.15 to 1.40) and new requirement for dialysis (5.7% vs. 4.6%; p = 0.001; OR: 1.26; 95% CI: 1.10 to 1.46). Among those surviving to discharge, all-cause mortality was similar through 7 years (conditional hazard ratio: 0.95; 95% CI: 0.87 to 1.03; p = 0.20).

Conclusions: Nearly 40% of patients with NSTEMI with MVD and cardiogenic shock underwent multivessel PCI, which was associated with lower in-hospital mortality but greater periprocedural complications. Among those surviving to discharge, multivessel PCI did not confer additional long-term mortality benefit.
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http://dx.doi.org/10.1016/j.jcin.2021.02.021DOI Listing
April 2021

Coronary artery bypass grafting after acute ST-elevation myocardial infarction.

J Thorac Cardiovasc Surg 2021 Mar 31. Epub 2021 Mar 31.

Section of Cardiology, Baylor School of Medicine, Houston, Tex. Electronic address:

Objectives: The study objectives were to describe the trends and outcomes of isolated coronary artery bypass grafting after ST-elevation myocardial infarction using a nationwide database.

Methods: We queried the 2002-2016 National Inpatient Sample database for hospitalized patients with ST-elevation myocardial infarction who underwent isolated coronary artery bypass grafting. We report temporal trends, predictors, and outcomes of coronary artery bypass grafting in the early (2002-2010) and recent (2011-2016) cohorts.

Results: Of 3,347,470 patients hospitalized for ST-elevation myocardial infarction, 7.7% underwent isolated coronary artery bypass grafting. The incidence of isolated coronary artery bypass grafting after ST-elevation myocardial infarction decreased over time (9.2% in 2002 vs 5.5% in 2016, P < .001), whereas perioperative crude in-hospital mortality did not change (5.1% in 2002 vs 4.2% in 2016, P = .66), coinciding with an increase in the burden of comorbidities. There was an increase in performing isolated coronary artery bypass grafting on hospitalization day 3 or more, as well as an increase in the use of mechanical support devices and precoronary artery bypass grafting percutaneous coronary intervention. In the early cohort, isolated coronary artery bypass grafting on days 1 and 2 was associated with higher in-hospital mortality. In the recent cohort, coronary artery bypass grafting on day 2 had similar in-hospital mortality compared with day 3 or more and lower rates of acute kidney injury, ischemic stroke, ventricular arrhythmia, and length of hospital stay.

Conclusions: In this nationwide analysis, there has been a decline in the use of isolated coronary artery bypass grafting after ST-elevation myocardial infarction. Isolated coronary artery bypass grafting on day 1 was performed in sicker patients and was associated with higher in-hospital mortality than coronary artery bypass grafting performed on day 3 or more. In the recent cohort, isolated coronary artery bypass grafting on day 2 had similar in-hospital mortality compared with day 3 or more.
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http://dx.doi.org/10.1016/j.jtcvs.2021.03.081DOI Listing
March 2021

Maintaining Essential Nutrition Services to Underfive Children in Yemen: A Programmatic Adaptation Amidst the COVID-19 Pandemic.

Children (Basel) 2021 Apr 28;8(5). Epub 2021 Apr 28.

Nutrition and Food Sciences Department, Faculty of Agriculture and Food Sciences, American University of Beirut, Beirut 11-0236, Lebanon.

The World Health Organization (WHO) acknowledged that, as health services divert their attention to the COVID-19 pandemic, the delivery of essential nutrition services may be compromised. This impact may be more pronounced in the context of humanitarian crises, such as the one currently unfolding in Yemen. In line with Pillar 9 of the WHO's COVID-19 Strategic Preparedness and Response Plan, this paper reports on the nutrition program adaptations in Yemen to maintain the delivery of essential nutrition services to under-five children. The process of adaptation focused on the services provided within the nutrition surveillance system (NSS), therapeutic feeding centers (TFC), and isolation units (IU). It was conducted in five steps: (1) situation analysis; (2) development of guidance documents; (3) consultation process; (4) capacity-building programs; and (5) incorporation of programmatic adaptation within nutrition services. As of September 2020, NSS, TFC, and IUs services have shifted their standard operating procedures in line with the context-specific adaptations. The process described in this paper may serve as a case-study for other countries that intend to undertake similar adaptations in their nutrition program to contribute to the implementation of the WHO response plan and maintain the delivery of essential nutrition services to children.
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http://dx.doi.org/10.3390/children8050350DOI Listing
April 2021

Development of Epirubicin-Loaded Biocompatible Polymer PLA-PEG-PLA Nanoparticles: Synthesis, Characterization, Stability, and In Vitro Anticancerous Assessment.

Polymers (Basel) 2021 Apr 9;13(8). Epub 2021 Apr 9.

Developmental Medicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard- Health Affairs (MNG-HA), Riyadh 11481, Saudi Arabia.

Epirubicin (EPI) is an anti-cancerous chemotherapeutic drug that is an effective epimer of doxorubicin with less cardiotoxicity. Although EPI has fewer side effects than its analog, doxorubicin, this study aims to develop EPI nanoparticles as an improved formula of the conventional treatment of EPI in its free form.

Methods: In this study, EPI-loaded polymeric nanoparticles (EPI-NPs) were prepared by the double emulsion method using a biocompatible poly (lactide) poly (ethylene glycol) poly(lactide) (PLA-PEG-PLA) polymer. The physicochemical properties of the EPI-NPs were determined by dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), entrapment efficiency and stability studies. The effect of EPI-NPs on cancer cells was determined by high throughput imaging and flow cytometry.

Results: The synthesis process resulted in monodisperse EPI-NPs with a size of 166.93 ± 1.40 nm and an elevated encapsulation efficiency (EE) of 88.3%. In addition, TEM images revealed the spherical uniformness of EPI-NPs with no aggregation, while the cellular studies presented the effect of EPI-NPs on MCF-7 cells' viability; after 96 h of treatment, the MCF-7 cells presented considerable apoptotic activity. The stability study showed that the EPI-NPs remained stable at room temperature at physiological pH for over 30 days.

Conclusion: EPI-NPs were successfully encapsulated within a highly stable biocompatible polymer with minimal loss of the drug. The used polymer has low cytotoxicity and EPI-NPs induced apoptosis in estrogen-positive cell line, making them a promising, safe treatment for cancer with less adverse side effects.
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http://dx.doi.org/10.3390/polym13081212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070301PMC
April 2021

Influence of Soil-Borne Inoculum of Measured by qPCR on Disease Severity of Clubroot-Resistant Cultivars of Winter Oilseed Rape ( L.).

Pathogens 2021 Apr 6;10(4). Epub 2021 Apr 6.

RISE, Research Institutes of Sweden AB, Box 187, SE-532 32 Skara, Sweden.

Use of resistant cultivars is considered the most effective tool in managing clubroot. Three clubroot-resistant commercial winter oilseed rape (OSR) cultivars and a susceptible 'Cultivar mix' were evaluated for disease severity index (DSI) and yield performance in field soils, selected for varying abundance of natural inoculum of . Seven field trials were carried out during 2017-2019 in winter OSR crops, and comparative bioassays were performed in a growth chamber. Substantial variation in clubroot infection between years was observed in the field trials. For Cultivar mix, a negative correlation (y = -252.3ln(x) + 58,897.6) was found between inoculum density and seed yield in five trials, whereas no correlation was found for the resistant cultivars. In bioassays, Cultivar mix exhibited a significantly high correlation between DSI and number of gene copies g soil (R = 0.72). For resistant cvs., Mentor and Alister, correlation was R = 0.45 and 0.58, respectively, indicating that resistance was under pressure. In field trials, DSI of the resistant cultivars was lower (<27). The recommendation is thus to use clubroot-resistant cultivars of OSR as part of Integrated Pest Management in situations where abundance of DNA exceeds 1300 gene copies g soil.
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http://dx.doi.org/10.3390/pathogens10040433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067420PMC
April 2021

Recognition of brain tumors in MRI images using texture analysis.

Saudi J Biol Sci 2021 Apr 29;28(4):2381-2387. Epub 2021 Jan 29.

Imam Abdulrahman Bin Faisal University, College Of Science & Humanities, Computer Science department, Saudi Arabia.

Objectives: Brain neoplasms or intracranial tumors, which are more common in older adults, can affect individuals of any age including pediatric and children. Exposure to carcinogenic agents including ionizing radiation and family history is one of the main causes of the disease. Early diagnosis is crucial to avoid prolonged. patients' suffering. The aim of the study was to efficiently recognize the brain tumors from the other brain tissues which include grey and white matter as well as cerebrospinal fluid (CSF).

Materials And Methods: This study was performed using axial, sagittal and coronal views for fifty brain tumor patients randomly selected from a set of 200 patients, with a "control" set consisting of images showing no sign of disease; and the "test" brain MRI images for patients diagnosed with brain tumor. The study includes both genders with age ranging from 18 years to 83 years old, (56.5 ± 17.2). The brain images were acquired using a standard head coil Philips Intera 1.5 Tesla machine (USA). The thickness of each section in the entire sequence was 8 mm. Acquisition of T2-weighted and T1-weighted were performed. Interactive Data Language software was used to analyze the data.

Results: The results of this study showed that: the overall accuracy of classification process was 94.8%, and for the tumor; the sensitivity was 97.3%. White matter and grey matter showed a classification accuracy of 95.7% and 89.7% and for CSF the accuracy was 94.3%.

Conclusion: The results showed that brain tumor can be classified successfully and delineated using texture analysis with minimum efforts and with high accuracy for brain tumors.
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http://dx.doi.org/10.1016/j.sjbs.2021.01.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071912PMC
April 2021

Utilization of a Mixture Cure Rate Model based on the Generalized Modified Weibull Distribution for the Analysis of Leukemia Patients.

Asian Pac J Cancer Prev 2021 Apr 1;22(4):1045-1053. Epub 2021 Apr 1.

Department of Mathematics, Faculty of Science, Universiti Putra Malaysia, 43400 UPM, Serdang, Malaysia.

Objective: Cure rate models are survival models, commonly applied to model survival data with a cured fraction. In the existence of a cure rate, if the distribution of survival times for susceptible patients is specified, researchers usually prefer cure models to parametric models. Different distributions can be assumed for the survival times, for instance, generalized modified Weibull (GMW), exponentiated Weibull (EW), and log-beta Weibull. The purpose of this study is to select the best distribution for uncured patients' survival times by comparing the mixture cure models based on the GMW distribution and its particular cases.

Materials And Methods: A data set of 91 patients with high-risk acute lymphoblastic leukemia (ALL) followed for five years from 1982 to 1987 was chosen for fitting the mixture cure model. We used the maximum likelihood estimation technique via R software 3.6.2 to obtain the estimates for parameters of the proposed model in the existence of cure rate, censored data, and covariates. For the best model choice, the Akaike information criterion (AIC) was implemented.

Results: After comparing different parametric models fitted to the data, including or excluding cure fraction, without covariates, the smallest AIC values were obtained by the EW and the GMW distributions, (953.31/969.35) and (955.84/975.99), respectively. Besides, assuming a mixture cure model based on GMW with covariates, an estimated ratio between cure fractions for allogeneic and autologous bone marrow transplant groups (and its 95% confidence intervals) were 1.42972 (95% CI: 1.18614 - 1.72955).

Conclusion: The results of this study reveal that the EW and the GMW distributions are the best choices for the survival times of Leukemia patients.
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http://dx.doi.org/10.31557/APJCP.2021.22.4.1045DOI Listing
April 2021

GPU based parallel framework for receiver coil sensitivity estimation in SENSE reconstruction.

Magn Reson Imaging 2021 Apr 24;80:58-70. Epub 2021 Apr 24.

Medical Image Processing Research Group (MIPRG), Department of Electrical & Computer Engineering, COMSATS University Islamabad, Pakistan.

Magnetic Resonance Imaging (MRI) uses non-ionizing radiations and is safer as compared to CT and X-ray imaging. MRI is broadly used around the globe for medical diagnostics. One main limitation of MRI is its long data acquisition time. Parallel MRI (pMRI) was introduced in late 1990's to reduce the MRI data acquisition time. In pMRI, data is acquired by under-sampling the Phase Encoding (PE) steps which introduces aliasing artefacts in the MR images. SENSitivity Encoding (SENSE) is a pMRI based method that reconstructs fully sampled MR image from the acquired under-sampled data using the sensitivity information of receiver coils. In SENSE, precise estimation of the receiver coil sensitivity maps is vital to obtain good quality images. Eigen-value method (a recently proposed method in literature for the estimation of receiver coil sensitivity information) does not require a pre-scan image unlike other conventional methods of sensitivity estimation. However, Eigen-value method is computationally intensive and takes a significant amount of time to estimate the receiver coil sensitivity maps. This work proposes a parallel framework for Eigen-value method of receiver coil sensitivity estimation that exploits its inherent parallelism using Graphics Processing Units (GPUs). We evaluated the performance of the proposed algorithm on in-vivo and simulated MRI datasets (i.e. human head and simulated phantom datasets) with Peak Signal-to-Noise Ratio (PSNR) and Artefact Power (AP) as evaluation metrics. The results show that the proposed GPU implementation reduces the execution time of Eigen-value method of receiver coil sensitivity estimation (providing up to 30 times speed up in our experiments) without degrading the quality of the reconstructed image.
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http://dx.doi.org/10.1016/j.mri.2021.04.009DOI Listing
April 2021

Protein kinase D1 variant associated with human epilepsy and peripheral nerve hypermyelination.

Clin Genet 2021 Apr 27. Epub 2021 Apr 27.

Department of Anesthesiology, Vanderbilt University School of Medicine, Nashville.

We report the case of a patient with severe progressive epilepsy and peripheral neuropathy and a novel de novo inactivating variant (p.E79X) in Protein Kinase D1 (PKD1). Using CRISPR/Cas9, we engineered the homologous variant in mice and showed that in the homozygote mouse, it recapitulated the patient peripheral nerve hypermyelination pathology. The lethality of the homozygote mouse prevented us from performing an assessment of locomotor behavior. The mutant heterozygote mouse, however, exhibited a significant increase in kainate-induced seizure activity over wild-type mice, supporting the hypothesis that the PKD1 variant is a candidate for the cause of the patient epilepsy. Because PKD1 was previously identified in a kinomic screen as an interacting partner of the K-Cl cotransporter 3 (KCC3), and since KCC3 is involved in peripheral nerve disease and brain hyperexcitability, one possible mechanism of action of PKD1 in disease is through KCC3. We show that catalytically inactive PKD1 stimulates KCC3 activity, consistent with tonic relief of inhibitory phosphorylation. Our findings implicate a novel role for PKD1 in the human nervous system, and uncover a mechanism that could serve as a potential target to promote nervous system myelination. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/cge.13973DOI Listing
April 2021

External validity and clinical usefulness of a risk prediction model for 30 day unplanned hospitalization in patients receiving outpatient parenteral antimicrobial therapy.

J Antimicrob Chemother 2021 Apr 25. Epub 2021 Apr 25.

Laboratory of Biostatistics, School of Medicine, University of Crete, Heraklion, Greece.

Objectives: Outpatient parenteral antimicrobial therapy (OPAT) is increasingly used to treat a variety of infections. However, hospital readmissions remain relatively common. We examined the external validity and clinical usefulness of a previously derived risk prediction model for 30 day unplanned hospitalization in patients receiving OPAT.

Methods: A retrospective cohort study was conducted at two large teaching hospitals in the UK. The design comprised quasi-external temporal validation on patients from the same OPAT setting as the model development, and broader external validation on patients from a different setting. The model predictors were age, prior hospitalizations in the preceding 12 months, Charlson comorbidity score, concurrent IV antimicrobial therapy, type of infection and mode of OPAT treatment. Discriminative ability, calibration and clinical usefulness were assessed.

Results: Data from 2578 OPAT patients were analysed. The rates of 30 day unplanned hospitalization were 11.5% (123/1073), 12.9% (140/1087) and 25.4% (106/418) in the model derivation, temporal validation and broader external validation cohorts, respectively. The discriminative ability of the prediction model was adequate on temporal validation (c-statistic 0.75; 95% CI: 0.71-0.79) and acceptable on broader validation (c-statistic 0.67; 95% CI: 0.61-0.73). In both external cohorts, the model displayed excellent calibration between observed and predicted probabilities. Decision curve analysis showed increased net benefit across a range of meaningful risk thresholds.

Conclusions: A simple risk prediction model for unplanned readmission in OPAT patients demonstrated reproducible predictive performance, broad clinical transportability and clinical usefulness. This model may help improve OPAT outcomes through better identification of high-risk patients and provision of tailored care.
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http://dx.doi.org/10.1093/jac/dkab127DOI Listing
April 2021

A study of red cell distribution width and neonatal sepsis at Soba University Hospital, Khartoum, Sudan.

Sudan J Paediatr 2021 ;21(1):42-47

Soba University Hospital, Khartoum, Sudan.

Neonatal sepsis is one of the most critical illnesses in newborns with significant morbidity and mortality, particularly in developing countries. The present, cross-sectional, hospital-based, study was conducted to evaluate the association of red cell distribution width (RDW) with neonatal sepsis and its role as a predictive marker in the diagnosis of neonatal sepsis at Soba University Hospital, during the period July 2018 to April 2019. The study population was term neonates, aged 1-28 days, who were diagnosed with neonatal sepsis, with positive blood culture. A total of 111 full-term neonates had blood culture proven neonatal sepsis and the majority of them (100%, 90%) had positive C-reactive protein (CRP). The average RDW in this study was 19.3% and was elevated in 103 (92%) of the study participants with a significant association with positive blood culture. The majority (65%, 58.6%) of mothers of the studied neonates did not have an illness during pregnancy, 19 (17.1%) had diabetes mellitus, 9 (8.1%) had hypertension, in addition to other different conditions in 18 (16.2%). The common causes of admission of the studied newborns included respiratory distress (70%, 79%), jaundice (33%, 29.7%) and lethargy (28%, 25.2%). was the most common organism isolated from blood culture in 50 (45.0%) patients, and was the least one, isolated in only one (0.9%) newborn. There is a significant association between positive blood culture, CRP and elevated RDW (-value 0.01). RDW was found to be significantly elevated in the studied newborns with neonatal sepsis.
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http://dx.doi.org/10.24911/SJP.106-1597237251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026007PMC
January 2021

Outcomes of Acute Myocardial Infarction in Patients with Familial Hypercholesteremia.

Am J Med 2021 Apr 16. Epub 2021 Apr 16.

Section of Cardiology, Baylor School of Medicine, Houston, TX. Electronic address:

Background: There is a paucity of contemporary data regarding the outcomes of acute myocardial infarction among patients with familial hypercholesteremia.

Methods: We queried the Nationwide Readmissions Database (2016-2018) for hospitalizations with acute myocardial infarction. Multivariable regression analysis was used to compare in-hospital outcomes and 30-day readmissions among patients with and without familial hypercholesteremia.

Results: The analysis included 1,363,488 hospitalizations with acute myocardial infarction. The prevalence of familial hypercholesteremia was 0.07% among acute myocardial infarction admissions. Compared to those without familial hypercholesteremia, admissions with familial hypercholesteremia were younger and had less comorbidities, but were more likely to have had prior infarct and revascularization. Admissions with familial hypercholesteremia were more likely to present with ST-elevation myocardial infarction and undergo revascularization. After multivariable adjustment, there was no difference in in-hospital case fatality among patients with versus without familial hypercholesteremia (adjusted-OR 0.76; 95% CI 0.41-1.39). Admissions with acute myocardial infarction and familial hypercholesteremia had higher adjusted rates of cardiac arrest and utilization of mechanical support. There were no group differences in overall 30-day readmission (adjusted-OR 0.75; 95% CI 0.51-1.10) or 30-day readmission for AMI. However, a non-significant trend towards higher readmission for PCI was observed among patients with familial hypercholesteremia (adjusted-OR 1.89; 95% CI 0.98-3.64).

Conclusion: In this contemporary nationwide observational analysis, patients with familial hypercholesteremia represent a small proportion of the overall population with acute myocardial infarction and have a distinctive clinical profile, but do not appear to have worse in-hospital case fatality compared to those without familial hypercholesteremia.
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http://dx.doi.org/10.1016/j.amjmed.2021.03.013DOI Listing
April 2021

COVID-19 severity in relation to sociodemographics and vitamin D use.

Open Med (Wars) 2021 8;16(1):591-609. Epub 2021 Apr 8.

Department of Physiology, College of Medicine, University of Sulaimani, New-Street-27, Zone 209, P. O. Box: 334, Kurdistan Region, Sulaymaniyah, Iraq.

Most COVID-19 cases are treated as outpatients, while the majority of studies on COVID-19 focus on inpatients. Little is known about the self-reporting and self-rating of the disease's symptoms, and the associations of prophylactic use of dietary supplements with COVID-19 severity have not been addressed. The aims of this study are to evaluate COVID-19 severity and to relate them to sociodemographic characteristics and prophylactic dietary supplements. An observational patient-based study conducted through an online questionnaire on recovered COVID-19 patients. The patients were assessed for several severity parameters, sociodemographic parameters, and prophylactic dietary supplement use. A total of 428 patients were evaluated. Age and presence of comorbidities had positive associations with the severity parameters. The severe infection group had the highest proportion of patients stressed about COVID-19 ( < 0.05). Cigarette, but not hookah, smoking was significantly associated with less severe symptoms. Vitamin D negatively predicted disease severity ( < 0.05). In conclusion, stress, age, and presence of comorbidities were the most important positive predictors of COVID-19 severity, while prophylactic vitamin D use and smoking were significant negative predictors. The use of protective measures and other prophylactic dietary supplements was not significantly associated with symptom severity.
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http://dx.doi.org/10.1515/med-2021-0273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034240PMC
April 2021

Three species of Echinococcus granulosus sensu lato infect camels on the Arabian Peninsula.

Parasitol Res 2021 Apr 17. Epub 2021 Apr 17.

Parasitology Unit 190p, Institute of Biology, University of Hohenheim, Emil-Wolff-Straße 34, 70599, Stuttgart, Germany.

We report on the genetic identity of 36 Echinococcus cysts that were collected during a recent slaughterhouse survey of 810 locally bred camels (dromedaries) in the Eastern Province of the Kingdom of Saudi Arabia. Analysis of a partial nad1 gene sequence showed that the majority (n = 29) belonged to E. granulosus sensu stricto, four to E. canadensis G6/7, and three to E. ortleppi. Eight of the 29 E. granulosus s.s. cysts contained protoscoleces; all other cysts were calcified and non-viable. This is the first report of the presence E. ortleppi from the Arabian Peninsula, a parasite that is typically transmitted via cattle. The results indicate widespread infection of camels with CE in eastern Saudi Arabia and an active role of camels in the lifecycles of at least E. granulosus s.s.. Complete cox1 haplotype analysis of 21 E. granulosus s.s. isolates shows that the majority of variants circulating in eastern Saudi Arabia is distinct from but closely related to haplotypes from neighboring countries in the Middle East, which indicates the presence of this parasite in KSA for a longer period of time. All isolates of E. granulosus s.s. in this study belonged to the G1 cluster, although the G3 genotype has previously also been reported from the Middle East.
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http://dx.doi.org/10.1007/s00436-021-07156-1DOI Listing
April 2021

Fast development of high quality vaccines in a pandemic.

Chest 2021 Apr 10. Epub 2021 Apr 10.

Yale School of Medicine, Department of Medicine, Section of Infectious Diseases, New Haven, CT 06510, USA; Yale School of Public Health, New Haven, CT 06510, USA; Yale Institute of Global Health, New Haven, CT 06510, USA; Yale School of Nursing, Orange, CT 06510, USA.

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http://dx.doi.org/10.1016/j.chest.2021.03.063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102080PMC
April 2021

Decision-making process for introduction of maternal vaccines in Kenya, 2017-2018.

Implement Sci 2021 Apr 12;16(1):39. Epub 2021 Apr 12.

Department of Medicine, Division of Pediatrics, Emory University School of Medicine, 1518 Clifton Rd NE, Atlanta, GA, 30322, USA.

Background: Maternal immunization is a key strategy for reducing morbidity and mortality associated with infectious diseases in mothers and their newborns. Recent developments in the science and safety of maternal vaccinations have made possible development of new maternal vaccines ready for introduction in low- and middle-income countries. Decisions at the policy level remain the entry point for maternal immunization programs. We describe the policy and decision-making process in Kenya for the introduction of new vaccines, with particular emphasis on maternal vaccines, and identify opportunities to improve vaccine policy formulation and implementation process.

Methods: We conducted 29 formal interviews with government officials and policy makers, including high-level officials at the Kenya National Immunization Technical Advisory Group, and Ministry of Health officials at national and county levels. All interviews were recorded and transcribed. We analyzed the qualitative data using NVivo 11.0 software.

Results: All key informants understood the vaccine policy formulation and implementation processes, although national officials appeared more informed compared to county officials. County officials reported feeling left out of policy development. The recent health system decentralization had both positive and negative impacts on the policy process; however, the negative impacts outweighed the positive impacts. Other factors outside vaccine policy environment such as rumours, sociocultural practices, and anti-vaccine campaigns influenced the policy development and implementation process.

Conclusions: Public policy development process is complex and multifaceted by its nature. As Kenya prepares for introduction of other maternal vaccines, it is important that the identified policy gaps and challenges are addressed.
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http://dx.doi.org/10.1186/s13012-021-01101-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042952PMC
April 2021

Causes of short birth interval (kunika) in Bauchi State, Nigeria: systematizing local knowledge with fuzzy cognitive mapping.

Reprod Health 2021 Apr 6;18(1):74. Epub 2021 Apr 6.

CIET-PRAM, Department of Family Medicine, McGill University, 5858 Chemin de la Côte-des-Neiges, 3rd floor, Montreal, QC, H3S 1Z1, Canada.

Background: Short birth intervals, defined by the World Health Organization as less than 33 months, may damage the health and wellbeing of children, mothers, and their families. People in northern Nigeria recognise many adverse effects of short birth interval (kunika in the Hausa language) but it remains common. We used fuzzy cognitive mapping to systematize local knowledge of causes of kunika to inform the co-design of culturally safe strategies to address it.

Methods: Male and female groups in twelve communities built 48 maps of causes and protective factors for kunika, and government officers from the Local Government Area (LGA) and State made four maps. Each map showed causes of kunika or no-kunika, with arrows showing relationships with the outcome and between causes. Participants assigned weights for the perceived strength of relationships between 5 (strongest) and 1 (weakest). We combined maps for each group: men, women, and government officers. Fuzzy transitive closure calculated the maximum influence of each factor on the outcome, taking account of all relationships in the map. To condense the maps, we grouped individual factors into broader categories and calculated the cumulative net influence of each category. We made further summarised maps and presented these to the community mapping groups to review.

Results: The community maps identified frequent sex, not using modern or traditional contraception, and family dynamics (such as competition between wives) as the most influential causes of kunika. Women identified forced sex and men highlighted lack of awareness about contraception and fear of side effects as important causes of kunika. Lack of male involvement featured in women's maps of causes and in the maps from LGA and State levels. Maps of protective factors largely mirrored those of the causes. Community groups readily appreciated and approved the summary maps resulting from the analysis.

Conclusions: The maps showed how kunika results from a complex network of interacting factors, with culture-specific dynamics. Simply promoting contraception alone is unlikely to be enough to reduce kunika. Outputs from transitive closure analysis can be made accessible to ordinary stakeholders, allowing their meaningful participation in interpretation and use of the findings. For people in Bauchi State, northern Nigeria, kunika describes a short interval between successive births, understood as becoming pregnant again before the previous child is weaned. They recognise it is bad for children, mothers and households. We worked with 12 communities in Bauchi to map their knowledge of the causes and protective factors for kunika. Separate groups of men and women built 48 maps, and government officers at local and state level built four maps. Each group drew two maps showing causes of kunika or of no-kunika with arrows showing the links between causes and the outcome. Participants marked the strength of each link with a number (between 5 for the strongest and 1 for the weakest). We combined maps for women, men and government officers. We grouped similar causes together into broader categories. We calculated the overall influence of each category on kunika or no-kunika and produced summary maps to communicate findings. The maps identified the strongest causes of kunika as frequent sex, not using modern or traditional contraception, and family dynamics. Women indicated forced sex as an important cause, but men focused on lack of awareness about contraception and fear of side effects. The maps of protective factors mirrored those of the causes. The groups who created the maps approved the summary maps. The maps showed the complex causes of kunika in Bauchi. Promoting contraception is unlikely to be enough on its own to reduce kunika. The summary maps will help local stakeholders to co-design culturally safe ways of reducing kunika.
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http://dx.doi.org/10.1186/s12978-021-01066-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022364PMC
April 2021

In Search of the Best Way to Identify Those Who Would Benefit Most From COVID-19 Vaccination-Who Goes First?

JAMA Netw Open 2021 04 1;4(4):e214623. Epub 2021 Apr 1.

Yale Institute for Global Health, Division of Infectious Diseases, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.4623DOI Listing
April 2021

Measuring voluntary and policy-induced social distancing behavior during the COVID-19 pandemic.

Proc Natl Acad Sci U S A 2021 04;118(16)

Yale Institute for Global Health, New Haven, CT 06510.

Staying home and avoiding unnecessary contact is an important part of the effort to contain COVID-19 and limit deaths. Every state in the United States enacted policies to encourage distancing and some mandated staying home. Understanding how these policies interact with individuals' voluntary responses to the COVID-19 epidemic is a critical initial step in understanding the role of these nonpharmaceutical interventions in transmission dynamics and assessing policy impacts. We use variation in policy responses along with smart device data that measures the amount of time Americans stayed home to disentangle the extent that observed shifts in staying home behavior are induced by policy. We find evidence that stay-at-home orders and voluntary response to locally reported COVID-19 cases and deaths led to behavioral change. For the median county, which implemented a stay-at-home order with about two cases, we find that the response to stay-at-home orders increased time at home as if the county had experienced 29 additional local cases. However, the relative effect of stay-at-home orders was much greater in select counties. On the one hand, the mandate can be viewed as displacing a voluntary response to this rise in cases. On the other hand, policy accelerated the response, which likely helped reduce spread in the early phase of the pandemic. It is important to be able to attribute the relative role of self-interested behavior or policy mandates to understand the limits and opportunities for relying on voluntary behavior as opposed to imposing stay-at-home orders.
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http://dx.doi.org/10.1073/pnas.2008814118DOI Listing
April 2021

A hydrological perspective on drought risk-assessment in the Yellow River Basin under future anthropogenic activities.

J Environ Manage 2021 Jul 2;289:112429. Epub 2021 Apr 2.

International Center for Climate and Environment Sciences, Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing, China.

Since the late 1970s, the Yellow River Basin (YRB) has experienced accelerated land-use/land cover changes (LULCC) and consumptive water use (CWU) that have imposed low-flow regimes. Upon the continuation of these anthropogenic activities in the future, significant hydrological alteration is expected. This study takes a hydrological perspective on drought to project changes in the YRB drought risk under future LULCC and CWU business-as-usual (BAU) scenarios. A combination of seasonal trend forecasting, drought indices, land-use and hydrological modeling techniques was used. Future LULCC is assessed based on two BAU scenarios to explore the patterns of LULCC with (LULCC-BAU1) and without (LULCC-BAU2) the continuation of the Chinese Grain for Green Program. The results indicated that LULCC-BAU2 will increase the risk of mild and moderate droughts, while CWU and LULCC-BAU1 will impose higher risk of severe and extreme events. LULCC-BAU1 is projected to exacerbate the duration and intensity of the agricultural/hydrological droughts. The frequency of hydrological drought under LULCC-BAU1 and CWU scenarios is projected to increase by 43% and 53% during 2021-2050. The future agricultural droughts will likely be more intense and prolonged than meteorological droughts. Hydrological droughts, however, will be characterized by prolonged but less intense drought comparing to the metrological droughts. The meteorological to agricultural drought propagation will likely be driven by LULCC under BAU1, while the meteorological to hydrological drought propagation is controlled by CWU changes.
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http://dx.doi.org/10.1016/j.jenvman.2021.112429DOI Listing
July 2021

Diagnostic value of plasma viscosity testing for patients with COVID-19.

Int J Lab Hematol 2021 Apr 4. Epub 2021 Apr 4.

Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

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http://dx.doi.org/10.1111/ijlh.13532DOI Listing
April 2021

Derivation of a Contextually-Appropriate COVID-19 Mortality Scale for Low-Resource Settings.

Ann Glob Health 2021 03 26;87(1):31. Epub 2021 Mar 26.

Division of Emergency Medicine, University of Cape Town, Cape Town, South Africa.

Background: In many low- and middle-income countries, where vaccinations will be delayed and healthcare systems are underdeveloped, the COVID-19 pandemic will continue for the foreseeable future. Mortality scales can aid frontline providers in low-resource settings (LRS) in identifying those at greatest risk of death so that limited resources can be directed towards those in greatest need and unnecessary loss of life is prevented. While many prognostication tools have been developed for, or applied to, COVID-19 patients, no tools to date have been purpose-designed for, and validated in, LRS.

Objectives: This study aimed to develop a pragmatic tool to assist LRS frontline providers in evaluating in-hospital mortality risk using only easy-to-obtain demographic and clinical inputs.

Methods: Machine learning was used on data from a retrospective cohort of Sudanese COVID-19 patients at two government referral hospitals to derive contextually appropriate mortality indices for COVID-19, which were then assessed by C-indices.

Findings: Data from 467 patients were used to derive two versions of the AFEM COVID-19 Mortality Scale (AFEM-CMS), which evaluates in-hospital mortality risk using demographic and clinical inputs that are readily obtainable in hospital receiving areas. Both versions of the tool include age, sex, number of comorbidities, Glasgow Coma Scale, respiratory rate, and systolic blood pressure; in settings pulse oximetry, oxygen saturation is included and in settings access, heart rate is included. The AFEM-CMS showed good discrimination: the model including pulse oximetry had a C-statistic of 0.775 (95% CI: 0.737-0.813) and the model excluding it had a C-statistic of 0.719 (95% CI: 0.678-0.760).

Conclusions: In the face of an enduring pandemic in many LRS, the AFEM-CMS serves as a practical solution to aid frontline providers in effectively allocating healthcare resources. The tool's generalisability is likely narrow outside of similar extremely LRS settings, and further validation studies are essential prior to broader use.
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http://dx.doi.org/10.5334/aogh.3278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996452PMC
March 2021

Association of Vitamin D Deficiency with Cardiovascular Disease Among Saudi Patients in Saudi Arabia.

Int J Prev Med 2020 11;11:191. Epub 2020 Dec 11.

Department of Public Health, College of Public Health, Imamm Abdul Rehman Bin Faisal University, Dammam, KSA.

Background: Vitamin D deficiency has a far-reaching impact on several metabolic functions including cardiovascular health. This study aimed to test the association of serum 25 [OH]-vitamin D3 levels among cardiovascular disease (i.e., hypertension and ischemic heart disease) patients.

Methods: A cross-sectional study was conducted among 360 participants from the tertiary care hospital. The simple random technique was used to select the participants. Only Saudi nationals were included in the study. Sociodemographic information, nutritional status, biochemical parameter (lipid profile, blood glucose level), and questions relating to cardiovascular disease were collected from the hospital record through data collection sheet. Serum Vit D level was determined by serum 25 (OH) blood test. Statistical package for social science (SPSS) software version 24 was used for data analysis. Binary logistic regression model was fitted to indentify the associated factors of vitamin D deficiency among cardiovascular disease patients.

Results: Approximately 40.6% and 27.8% of study participants had vitamin D deficiency and insufficiency, respectively. After adjustment of covariates, among cardiac patients, vitamin D deficiency was associated with ischemic heart disease (OR 2.24, 95% CI 1.11-4.52), and blood triglyceride level (OR 2.27, 95% CI 1.22-4.22).

Conclusions: Vitamin D deficiency and insufficiency are associated with ischemic heart disease, hyperglycemia, and hypertriglyceridemia. There is a need for the screening of cardiovascular disease patients for vitamin D levels.
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http://dx.doi.org/10.4103/ijpvm.IJPVM_349_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000152PMC
December 2020