scholarly journals Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study)

2020 ◽  
pp. postgradmedj-2020-139065 ◽  
Author(s):  
Ashu Rastogi ◽  
Anil Bhansali ◽  
Niranjan Khare ◽  
Vikas Suri ◽  
Narayana Yaddanapudi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Inflammatory Markers ◽  
Intervention Group ◽  
Vitamin D Supplementation ◽  
Controlled Study ◽  
Control Group ◽  
High Dose ◽  
Baseline Serum ◽  
Cholecalciferol Supplementation ◽  
And Control

BackgroundVitamin D has an immunomodulatory role but the effect of therapeutic vitamin D supplementation in SARS-CoV-2 infection is not known.AimEffect of high dose, oral cholecalciferol supplementation on SARS-CoV-2 viral clearance.DesignRandomised, placebo-controlled.ParticipantsAsymptomatic or mildly symptomatic SARS-CoV-2 RNA positive vitamin D deficient (25(OH)D<20 ng/ml) individuals.InterventionParticipants were randomised to receive daily 60 000 IU of cholecalciferol (oral nano-liquid droplets) for 7 days with therapeutic target 25(OH)D>50 ng/ml (intervention group) or placebo (control group). Patients requiring invasive ventilation or with significant comorbidities were excluded. 25(OH)D levels were assessed at day 7, and cholecalciferol supplementation was continued for those with 25(OH)D <50 ng/ml in the intervention arm. SARS-CoV-2 RNA and inflammatory markers fibrinogen, D-dimer, procalcitonin and (CRP), ferritin were measured periodically.Outcome measureProportion of patients with SARS-CoV-2 RNA negative before day-21 and change in inflammatory markers.ResultsForty SARS-CoV-2 RNA positive individuals were randomised to intervention (n=16) or control (n=24) group. Baseline serum 25(OH)D was 8.6 (7.1 to 13.1) and 9.54 (8.1 to 12.5) ng/ml (p=0.730), in the intervention and control group, respectively. 10 out of 16 patients could achieve 25(OH)D>50 ng/ml by day-7 and another two by day-14 [day-14 25(OH)D levels 51.7 (48.9 to 59.5) ng/ml and 15.2 (12.7 to 19.5) ng/ml (p<0.001) in intervention and control group, respectively]. 10 (62.5%) participants in the intervention group and 5 (20.8%) participants in the control arm (p<0.018) became SARS-CoV-2 RNA negative. Fibrinogen levels significantly decreased with cholecalciferol supplementation (intergroup difference 0.70 ng/ml; P=0.007) unlike other inflammatory biomarkers.ConclusionGreater proportion of vitamin D-deficient individuals with SARS-CoV-2 infection turned SARS-CoV-2 RNA negative with a significant decrease in fibrinogen on high-dose cholecalciferol supplementation.Trial register numberNCT04459247.

scholarly journals High-Dose Vitamin D Supplementation Improves Microcirculation and Reduces Inflammation in Diabetic Neuropathy Patients

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2518 ◽  
Author(s):  
Tatiana Karonova ◽  
Anna Stepanova ◽  
Anna Bystrova ◽  
Edward B. Jude
Keyword(s):  
Vitamin D ◽  
Peripheral Neuropathy ◽  
Inflammatory Markers ◽  
Signs And Symptoms ◽  
Vitamin D Supplementation ◽  
High Dose ◽  
Treatment Groups ◽  
Cutaneous Microcirculation ◽  
Before And After ◽  
Cholecalciferol Supplementation

We assessed the effect of different doses of vitamin D supplementation on microcirculation, signs and symptoms of peripheral neuropathy and inflammatory markers in patients with type 2 diabetes (T2DM). Sixty-seven patients with T2DM and peripheral neuropathy (34 females) were randomized into two treatment groups: Cholecalciferol 5000 IU and 40,000 IU once/week orally for 24 weeks. Severity of neuropathy (NSS, NDS scores, visual analogue scale), cutaneous microcirculation (MC) parameters and inflammatory markers (ILs, CRP, TNFα) were assessed before and after treatment. Vitamin D deficiency/insufficiency was detected in 78% of the 62 completed subjects. Following treatment with cholecalciferol 40,000 IU/week, a significant decrease in neuropathy severity (NSS, p = 0.001; NDS, p = 0.001; VAS, p = 0.001) and improvement of cutaneous MC were observed (p < 0.05). Also, we found a decrease in IL-6 level (2.5 pg/mL vs. 0.6 pg/mL, p < 0.001) and an increase in IL-10 level (2.5 pg/mL vs. 4.5 pg/mL, p < 0.001) after 24 weeks of vitamin D supplementation in this group. No changes were detected in the cholecalciferol 5000 IU/week group. High-dose cholecalciferol supplementation of 40,000 IU/week for 24 weeks was associated with improvement in clinical manifestation, cutaneous microcirculation and inflammatory markers in patients with T2DM and peripheral neuropathy.

High-dose Cholecalciferol Supplementation Reducing Morning Blood Pressure in Normotensive DM1 Patients

2020 ◽  
Vol 16 ◽  
Author(s):  
Natércia Neves Marques de Queiroz ◽  
Franciane Trindade Cunha de Melo ◽  
Fabrício de Souza Resende ◽  
Luísa Corrêa Janaú ◽  
Norberto Jorge Kzan de Souza Neto ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Vitamin D ◽  
Blood Pressure Monitoring ◽  
Vitamin D Supplementation ◽  
High Dose ◽  
Before And After ◽  
Patients With Diabetes ◽  
Morning Blood Pressure ◽  
Cholecalciferol Supplementation ◽  
Lipids Profile

Background: Vitamin D (VD) deficiency has been related to several endocrine metabolic and cardiovascular diseases. Effect of VD supplementation on blood pressure (BP) in patients with diabetes is controversial. Objective: The aim of this study was to evaluate high-dose vitamin D supplementation effects on blood pressure of normotensive type 1 diabetes mellitus (T1DM) patients by 24-hour ambulatory blood pressure monitoring (ABPM). Methods: We performed a clinical trial including 35 T1DM normotensive patients, who received doses of 4,000 or 10,000 IU/day of cholecalciferol for 12 weeks according to previous VD levels. They underwent 24-hour ABPM, along with glycated hemoglobin, creatine, lipids profile and PCRus dosage before and after VD supplementation. Results and discussion: We found an expressive reduction of systolic and diastolic morning blood pressures (117±14 vs 112±14, p<0,05; 74±9 vs 70±10 mmHg, p<0,05, respectively) with no changes in other pressoric markers. Besides, we noticed a relation between levels of VD after supplementation and diastolic morning blood pressure (r= -0,4; p<0.05). Conclusion: Our study suggests an association between supplementation of high doses of vitamin D and the reduction of morning blood pressure in normotensive T1DM patients.

scholarly journals Single High-Dose Vitamin D Supplementation as an Approach for Reducing Ultramarathon-Induced Inflammation: A Double-Blind Randomized Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1280
Author(s):  
Jan Mieszkowski ◽  
Andżelika Borkowska ◽  
Błażej Stankiewicz ◽  
Andrzej Kochanowicz ◽  
Bartłomiej Niespodziński ◽  
...  
Keyword(s):  
Vitamin D ◽  
Inflammatory Marker ◽  
Controlled Trial ◽  
Vitamin D Supplementation ◽  
Oncostatin M ◽  
Control Group ◽  
High Dose ◽  
Double Blind ◽  
Single High Dose ◽  
High Dose Vitamin

Purpose: A growing number of studies indicate the importance of vitamin D supplementation for sports performance. However, the effects of a single high-dose vitamin D supplementation on ultramarathon-induced inflammation have not been investigated. We here analyzed the effect of a single high-dose vitamin D supplementation on the inflammatory marker levels in ultramarathon runners after an ultramarathon run (maximal run 240 km). Methods: In the study, 35 runners (amateurs) were assigned into two groups: single high-dose vitamin D supplementation group, administered vitamin D (150,000 IU) in vegetable oil 24 h before the start of the run (n = 16); and placebo group (n = 19). Blood was collected for analysis 24 h before, immediately after, and 24 h after the run. Results: Serum 25(OH)D levels were significantly increased after the ultramarathon in both groups. The increase was greater in the vitamin D group than in the control group. Based on post-hoc and other analyses, the increase in interleukin 6 and 10, and resistin levels immediately after the run was significantly higher in runners in the control group than that in those in the supplementation group. Leptin, oncostatin M, and metalloproteinase tissue inhibitor levels were significantly decreased in both groups after the run, regardless of the supplementation. Conclusions: Ultramarathon significantly increases the serum 25(OH)D levels. Attenuation of changes in interleukin levels upon vitamin D supplementation confirmed that vitamin D has anti-inflammatory effect on exercise-induced inflammation.

scholarly journals Design and Main Results of STURDY: A Randomized Clinical Trial of Four Vitamin D3 Doses to Prevent Falls in Older Adults

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 759-759
Author(s):  
Lawrence Appel ◽  
Jennifer Schrack ◽  
Erin Michos ◽  
Christine Mitchell ◽  
Stephen Juraschek ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Primary Outcome ◽  
Vitamin D Supplementation ◽  
Dose Finding ◽  
High Dose ◽  
Hazard Ratios ◽  
Risk Of Falls ◽  
Event Rates ◽  
And Control

Abstract STURDY was a Bayesian, response-adaptive trial with dose-finding and confirmatory stages. Participants (n=688; ≥70years with serum 25(OH)D of 10-29ng/mL) were randomized to 200 (control), 1000, 2000, or 4000 IU/day of vitamin D3. The primary outcome was time to first fall or death over 2 years. During dose-finding, the best non-control dose was determined to be 1000IU/day based on higher primary outcome event rates in the 2000 and 4000IU/day doses than the 1000IU/day dose (posterior probability of being best dose=0.90; hazard ratios[HR] were 1.86 [95%CI: 1.16-2.97] and 1.68 [95%CI: 1.05-2.69], respectively). Participants were then switched from other non-control doses to 1000IU/day, and event rates did not differ between the pooled higher doses and control groups (HR=1.02, P=0.84). There was no heterogeneity by baseline 25(OHD). In conclusion, high-dose vitamin D supplementation ≥1000IU/day did not prevent falls. Whether vitamin D doses &gt;2000IU/day increase the risk of falls is uncertain.

Effects of Stratified Vitamin D Supplementation in Middle-Aged and Elderly Individuals with Vitamin D Insufficiency

2018 ◽  
Vol 50 (10) ◽  
pp. 747-753
Author(s):  
Yanhui Lu ◽  
Xiaomin Fu ◽  
Lili Zhang ◽  
Minyan Liu ◽  
Xiaoling Cheng ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Vitamin D3 ◽  
Intervention Group ◽  
Vitamin D Insufficiency ◽  
Vitamin D Supplementation ◽  
Control Group ◽  
Middle Aged ◽  
Oral Vitamin ◽  
Severe Vitamin

AbstractThe incidence of vitamin D deficiency is high globally, and vitamin D supplementation draws particular attention. The objective of this study was to investigate the effects of stratified vitamin D supplementation in middle-aged and elderly individuals with vitamin D insufficiency in Beijing. A total of 448 subjects aged over 40 years old were selected from a community in Beijing. Among them, 100 middle-aged and elderly people with vitamin D insufficiency were randomly selected on a voluntary basis. They were further divided into control group and intervention group. The control group received health education and lifestyle guidance, and the intervention group received lifestyle guidance and vitamin D supplementation for nine months. The doses were stratified as follows: for vitamin D insufficiency, oral vitamin D3 supplement was given at 5000 IU/w; for mild vitamin D deficiency, oral vitamin D3 supplement was given at 10 000 IU/w; for severe vitamin D deficiency, oral vitamin D3 supplement was given at 15 000 IU/w. Safety evaluation was conducted after three-month treatment. The intervention group consisted of 8%, 62%, and 30% of cases who had vitamin D insufficiency, mild vitamin D deficiency, and severe vitamin D deficiency, respectively, which were similar with the control group. It showed that the blood 25(OH)D level increased significantly in the intervention group, from 14.30±4.30 ng/ml to 33.62±6.99 ng/ml (p<0.001), in contrast to insignificant change in the control group. Stratified vitamin D supplementation effectively increased the blood 25(OH)D level, as well as the number of cases with corrected vitamin D insufficiency or deficiency.

scholarly journals Pengaruh pemberian obat anti tuberkulosis dengan vitamin D terhadap perubahan BTA pada penderita tuberkulosis paru di Kabupaten Pidie

2021 ◽  
Vol 2 (1) ◽  
pp. 25
Author(s):  
Rina Maulidar ◽  
Nurjannah Nurjannah ◽  
Aulina Adamy ◽  
Iskandar Iskandar
Keyword(s):  
Vitamin D ◽  
Drug Therapy ◽  
Intervention Group ◽  
Control Group ◽  
Significance Level ◽  
The World ◽  
Post Test ◽  
And Control ◽  
Global Health Problem ◽  
Test Control

Background: Tuberculosis (TB) is a global health problem, Indonesia had the second rank of the case in the world after India which is the fourth cause of death. Giving vitamin D together with anti-tuberculosis drugs can increase healing proses because vitamin D (anti-microbial immunomodulators) kills Mycobacterium tuberculosis.Objectives: This study aims to measure the effect of giving anti-tuberculosis drugs with vitamin D on changes in AFB in patients with pulmonary tuberculosis.Methods: This study was used a quasi-experiment design, pre-test and post-test control group was doing at 25th March – 25th July 2019. This research has been conducted in Pidie Regency. The intervention group (17 samples with tuberculosis drugs) was given Softgels vitamin D 5000 IU for 4 months, while the control group was only anti-tuberculosis drug therapy. The data were analyzed statistically using the Wilcoxon and Mann Whitney tests at a significance level of 95%.Results: Before the intervention, the BTA status of both the intervention and control group was similar (p= 0.061). After the intervention, there was a decrease in AFB interactions (p= 0.000). There was a decrease in the contribution of AFB in the control group before with after intervention (p= 0.000). There are those who support (p= 0.033) giving vitamin D the acceleration of pulmonary tuberculosis treatment. Conclusion: It is better to administer vitamin D to the successful treatment of pulmonary TB in patients undergoing anti-tuberculosis drug therapy.

scholarly journals High-dose vitamin D supplementation in multiple sclerosis – results from the randomized EVIDIMS (efficacy of vitamin D supplementation in multiple sclerosis) trial

2020 ◽  
Vol 6 (1) ◽  
pp. 205521732090347 ◽  
Author(s):  
Jan Dörr ◽  
Priscilla Bäcker-Koduah ◽  
Klaus-Dieter Wernecke ◽  
Elke Becker ◽  
Frank Hoffmann ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Disease Activity ◽  
Sample Size ◽  
Pilot Trial ◽  
Vitamin D Supplementation ◽  
High Dose ◽  
Clinical Relapse ◽  
Lesion Development ◽  
Cholecalciferol Supplementation

Background Epidemiological, preclinical, and non-interventional studies link vitamin D (VD) serum levels and disease activity in multiple sclerosis (MS). It is unclear whether high-dose VD supplementation can be used as an intervention to reduce disease activity. Objectives The study aimed to compare the effects of every other day high- (20,400 IU) versus low-dose (400 IU) cholecalciferol supplementation on clinical and imaging markers of disease activity in patients with relapsing–remitting MS or clinically isolated syndrome. Methods The EVIDIMS (efficacy of vitamin D supplementation in multiple sclerosis) trial was a multicentre randomized/stratified actively controlled explorative phase 2a pilot trial with a double-blind intervention period of 18 months, add on to interferon-β1b. Results Fifty-three patients were randomized, and 41 patients completed the study. Cholecalciferol supplementation was well tolerated and safe in both arms. After 18 months, clinical (relapse rates, disability progression) and radiographical (T2-weighted lesion development, contrast-enhancing lesion development, brain atrophy) did not differ between both treatment arms. Post-study power calculations suggested that the sample size was too low to prove the hypothesis. Conclusions The results neither support nor disprove a therapeutic benefit of high-dose VD supplementation but provide a basis for sound sample size estimations in future confirmatory studies. www.clinicaltrials.gov/NCT01440062

189 THE EFFECT OF VITAMIN D SUPPLEMENTATION ON ANTI-MULLERIAN HORMONE LEVELS IN REPRODUCTIVE-AGE WOMEN

2015 ◽  
Vol 27 (1) ◽  
pp. 185 ◽  
Author(s):  
M. Taheri ◽  
M. Modarres ◽  
A. Abdollahi
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Intervention Group ◽  
Serum Levels ◽  
Vitamin D Supplementation ◽  
T Test ◽  
Reproductive Age ◽  
Control Group ◽  
Post Intervention ◽  
Reproductive Age Women

Vitamin D deficiency has been correlated with the infertility and lower clinical pregnancy following IVF. Anti-Mullerian hormone (AMH) plays a key role during follicle development; it has been recognised as a predictor of regular ovulation and probably IVF success. Considering the critical need for experimental human study to investigate the impact of vitamin D supplementation on ovulatory function, the aim of this study was to demonstrate the effectiveness of the vitamin D supplementation on AMH serum levels among reproductive-age women with vitamin D deficiency. 195 reproductive women (18–35 year-old) with confirmed vitamin D deficiency [serum 25(OH)D <75 nmol L–1] and without diagnosed polycystic ovary syndrome (PCOS) were enrolled to this controlled clinical trial. Participants were randomly assigned to a control group (n = 96) or an intervention group (n = 99). Women in the intervention group used 2000 IU day–1 vitamin D drops for 15 weeks. 19 participants were missed during the follow-up; finally the numbers of women in the intervention and control groups were 91 and 85, respectively. At the beginning of the study and after the intervention, 25-hydroxyvitamin D and AMH serum levels were quantified using enzyme immunoassay (EIA; Immunodiagnostic Systems, Boldon, UK) and ELISA (Beckman-Coulter Inc., Fullerton, CA, USA) methods respectively. The post-intervention AMH measurement was performed after 2–5 weeks in the same day-of-cycle on which basal AMH measurement was done. Paired t-test, independent t-test, and Pearson correlation were used as appropriate and a P-value of less than 0.05 was considered significant. Significantly low AMH levels were seen in the vitamin D deficient women of this study (14.46 ± 11.92 pmol L–1 in control group and 14.09 ± 11.52 pmol L–1 in intervention group). After the intake of vitamin D supplementation in intervention group, AMH levels were increased to 24.89 ± 12.47 pmol L–1, which were significantly different from the 15.43 ± 13.03 pmol L–1 in control group (P < 0.001). Correlation coefficients for AMH with pre-intervention and post-intervention vitamin D were r = 0.489 and r = 0.599 respectively (P < 0.001). Treatment of vitamin D deficiency increases AMH to the optimum levels. Vitamin D deficient women had low levels of AMH. These findings support other studies which found a correlation of poor IVF outcomes with low vitamin D levels. Vitamin D supplementation could be useful in the improvement of controlled ovarian hyper-stimulation/IVF outcomes in case of vitamin D deficiency.

Effect of vitamin D supplementation on asthma control in patients with vitamin D deficiency: the ACVID randomised clinical trial

Thorax ◽  
2020 ◽  
pp. thoraxjnl-2019-213936
Author(s):  
Rubén Andújar-Espinosa ◽  
Lourdes Salinero-González ◽  
Fátima Illán-Gómez ◽  
Manuel Castilla-Martínez ◽  
Chunshao Hu-Yang ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Asthma Control ◽  
Intervention Group ◽  
Vitamin D Supplementation ◽  
Control Group ◽  
Asthmatic Patients ◽  
Secondary Endpoints

BackgroundThe relationship between asthma and vitamin D deficiency has been known for some time. However, interventional studies conducted in this regard have shown conflicting results.ObjectiveTo evaluate the efficacy of vitamin D supplementation in asthmatic patients in improving the degree of control of asthma.MethodsRandomised, triple-blind, placebo-controlled, parallel-group study in adult asthmatic patients with serum 25-hydroxyvitamin-D3 <30 ng/mL. The intervention group received oral supplementation with 16 000 IU of calcifediol per week, and the control group had placebo added to their usual asthma treatment. The study period was 6 months. The primary endpoint was the degree of asthma control as determined by the asthma control test (ACT). Secondary endpoints included quality of life measured using the mini Asthma Quality of Life Questionnaire, the number of asthma attacks, oral corticosteroid cycles, the dose of inhaled corticosteroids, number of emergency visits, unscheduled consultations with the primary care physician and hospitalisations for asthma.ResultsOne hundred and twelve patients were randomised (mean age 55 years, with 87 (78%) being women). Of the 112 patients, 106 (95%) completed the trial. Half the patients (56) were assigned to the intervention group and the other half to the control group. A statistically significant clinical improvement was observed in the intervention group (+3.09) compared with the control group (−0.57) (difference 3.66 (95% CI 0.89 to 5.43); p<0.001) as measured using ACT scores. Among the secondary endpoints, a significant improvement in the quality of life was found in the intervention group (5.34), compared with the control group (4.64) (difference 0.7 (95% CI 0.15 to 1.25); p=0.01).ConclusionAmong adults with asthma and vitamin D deficiency, supplementation with weekly oral calcifediol compared with placebo improved asthma control over 6 months. Further research is needed to assess long-term efficacy and safety.Trial registration numberNCT02805907.

scholarly journals Vitamin D status in full-term exclusively breastfed infants versus full-term breastfed infants receiving vitamin D supplementation in Thailand: a randomized controlled trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chayatat Ruangkit ◽  
Sukrit Suwannachat ◽  
Pornchanok Wantanakorn ◽  
Napapailin Sethaphanich ◽  
Surapat Assawawiroonhakarn ◽  
...  
Keyword(s):  
Vitamin D ◽  
Growth Parameters ◽  
Intervention Group ◽  
Serum Vitamin ◽  
Vitamin D Supplementation ◽  
Full Term ◽  
Control Group ◽  
Vitamin D Status ◽  
Serum Vitamin D ◽  
Breastfed Infants

Abstract Background Many international medical organizations recommend vitamin D supplementation for infants, especially exclusively breastfed infants. In Thailand, however, data regarding the vitamin D status in Thai infants are lacking. Such data would help to support physician decisions and guide medical practice. Methods Full-term, exclusively breastfed infants were randomized into two groups at 2 months of age to continue exclusive breastfeeding either without vitamin D supplementation (control group, n = 44) or with vitamin D3 supplementation at 400 IU/day (intervention group, n = 43) until 6 months of age. At 6 months, the serum vitamin D (25OHD) of the infants and their mothers, serum bone marker, and infants’ growth parameters were compared between the two groups. Results The infants’ serum 25OHD concentration was lower in the control group than intervention group (20.57 ± 12.66 vs. 46.01 ± 16.42 ng/mL, p < 0.01). More infants had vitamin D sufficiency (25OHD of > 20 ng/mL) in the intervention group than control group (93.0% vs. 43.2%, p < 0.01). There were no significant differences in the maternal 25OHD concentrations between the control and intervention groups (25.08 ± 7.75 vs. 23.75 ± 7.64 ng/mL, p = 0.42). Serum calcium, phosphorus, intact parathyroid hormone, alkaline phosphatase, and infants’ growth parameters were comparable between the two groups. After adjustment for the confounding factors, 25OHD concentration in the intervention group was 25.66 ng/mL higher than the control group (95% confidence interval, 19.07–32.25; p < 0.001). Vitamin D supplement contributed to an 88.7% decrease in the prevalence of vitamin D insufficiency/deficiency (relative risk, 0.11; 95% confidence interval, 0.04–0.35; p < 0.01). Conclusions Most full-term, exclusively breastfed Thai infants have serum vitamin D concentration below sufficiency level at 6 months of age. However, vitamin D supplementation (400 IU/day) improves their vitamin D status and prevents vitamin D deficiency. Trial registration The study was pre-registered in the Thai Clinical Trials Registry (TCTR20190622001) on 22/06/2019.

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