scholarly journals Maternal 17q21 genotype influences prenatal vitamin D effects on offspring asthma/recurrent wheeze

2021 ◽  
pp. 2002012
Author(s):  
Hanna M. Knihtilä ◽  
Rachel S. Kelly ◽  
Nicklas Brustad ◽  
Mengna Huang ◽  
Priyadarshini Kachroo ◽  
...  
Keyword(s):  
Vitamin D ◽  
High Risk ◽  
Protective Effect ◽  
High Dose ◽  
Protective Effects ◽  
Maternal Genotype ◽  
Genotype Variation ◽  
Recurrent Wheeze ◽  
Randomised Controlled ◽  
Reduced Risk

BackgroundPrenatal vitamin D3 supplementation has been linked to reduced risk of early life asthma/recurrent wheeze. This protective effect appears to be influenced by variations in the 17q21 functional SNP rs12936231 of the child, which regulates the expression of ORMDL3, and for which the high-risk CC-genotype is associated with early-onset asthma. However, this does not fully explain the differential effects of supplementation. We investigated the influence of maternal rs12936231 genotype variation on the protective effect of prenatal vitamin D3 supplementation against offspring asthma/recurrent wheeze.MethodsWe determined the rs12936231 genotype of mother-child pairs from two randomised-controlled trials: the Vitamin D Antenatal Asthma Reduction Trial (VDAART, n=613) and the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010, n=563) to examine the effect of maternal genotype variation on offspring asthma/recurrent wheeze at age 0–3 years between groups who received high-dose prenatal vitamin D3 supplementation versus placebo.ResultsOffspring of mothers with low-risk GG-genotype or GC-genotype who received high-dose vitamin D3 supplementation had a significantly reduced risk of asthma/recurrent wheeze when compared to the placebo group (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.37–0.77; p<0.001 for VDAART and HR, 0.56; 95% CI, 0.35–0.92; p=0.021 for COPSAC2010), whereas no difference was observed among the offspring of mothers with high-risk CC-genotype (HR, 1.05; 95% CI, 0.61–1.84; p=0.853 for VDAART and HR, 1.11; 95% CI, 0.54–2.28; p=0.785 for COPSAC2010).ConclusionMaternal 17q21 genotype has an important influence on the protective effects of prenatal vitamin D3 supplementation against offspring asthma/recurrent wheeze.

scholarly journals High-Dose Cholecalciferol Booster Therapy is Associated with a Reduced Risk of Mortality in Patients with COVID-19: A Cross-Sectional Multi-Centre Observational Study

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3799
Author(s):  
Stephanie F. Ling ◽  
Eleanor Broad ◽  
Rebecca Murphy ◽  
Joseph M. Pappachan ◽  
Satveer Pardesi-Newton ◽  
...  
Keyword(s):  
Vitamin D ◽  
Observational Study ◽  
Large Population ◽  
Public Health Issue ◽  
High Dose ◽  
Cross Sectional ◽  
Pharmacological Management ◽  
Baseline Serum ◽  
Risk Of Mortality ◽  
Reduced Risk

The worldwide pandemic of 2019 novel coronavirus disease (COVID-19) has posed the most substantial and severe public health issue for several generations, and therapeutic options have not yet been optimised. Vitamin D (in its “parent” form, cholecalciferol) has been proposed in the pharmacological management of COVID-19 by various sources. We aimed to determine whether COVID-19 mortality was affected by serum 25-hydroxyvitamin D (25(OH)D) levels, vitamin D status, or cholecalciferol therapy, and to elucidate any other predictors of COVID-19 mortality. Patients hospitalised with COVID-19 were opportunistically recruited from three UK hospitals, and their data were collected retrospectively. Logistic regression was used to determine any relationships between COVID-19 mortality and potential predictors, including 25(OH)D levels and cholecalciferol booster therapy. A total of 986 participants with COVID-19 were studied, of whom 151 (16.0%) received cholecalciferol booster therapy. In the primary cohort of 444 patients, cholecalciferol booster therapy was associated with a reduced risk of COVID-19 mortality, following adjustment for potential confounders (ORadj 0.13, 95% CI 0.05–0.35, p < 0.001). This finding was replicated in a validation cohort of 541 patients (ORadj 0.38, 95% CI 0.17–0.84, p = 0.018). In this observational study, treatment with cholecalciferol booster therapy, regardless of baseline serum 25(OH)D levels, appears to be associated with a reduced risk of mortality in acute in-patients admitted with COVID-19. Further work with large population studies needs to be carried out to determine adequate serum 25(OH)D levels, as well as multi-dose clinical trials of cholecalciferol therapy to assess maximum efficacy.

scholarly journals Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials

2020 ◽  
Author(s):  
David A Jolliffe ◽  
Carlos A Camargo ◽  
John D Sluyter ◽  
Mary Aglipay ◽  
John F Aloia ◽  
...  
Keyword(s):  
Vitamin D ◽  
Randomised Controlled Trials ◽  
Respiratory Infections ◽  
Meta Analysis ◽  
Vitamin D Supplementation ◽  
Controlled Trials ◽  
Acute Respiratory Infections ◽  
Dosing Regimen ◽  
Randomised Controlled ◽  
Reduced Risk

AbstractBackgroundA 2017 meta-analysis of data from 25 randomised controlled trials of vitamin D supplementation for the prevention of acute respiratory infections revealed a protective effect of the intervention. Since then, 20 new RCTs have been completed.MethodsSystematic review and meta-analysis of data from randomised controlled trials (RCTs) of vitamin D for ARI prevention using a random effects model. Pre-specified sub-group analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and the ClinicalTrials.gov registry from inception to 1st May 2020. Double-blind RCTs of supplementation with vitamin D or calcidiol, of any duration, were eligible if they were approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Aggregate data, stratified by baseline 25(OH)D concentration, were obtained from study authors. The study was registered with PROSPERO (no. CRD42020190633).FindingsWe identified 45 eligible RCTs (total 73,384 participants). Data were obtained for 46,331 (98.0%) of 47,262 participants in 42 studies, aged 0 to 95 years. For the primary comparison of vitamin D supplementation vs. placebo, the intervention reduced risk of ARI overall (Odds Ratio [OR] 0.91, 95% CI 0.84 to 0.99; P for heterogeneity 0.01). No statistically significant effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D concentration. However, protective effects were seen for trials in which vitamin D was given using a daily dosing regimen (OR 0.75, 95% CI 0.61 to 0.93); at daily dose equivalents of 400-1000 IU (OR 0.70, 95% CI 0.55 to 0.89); and for a duration of ≤12 months (OR 0.82, 95% CI 0.72 to 0.93). No significant interaction was seen between allocation to vitamin D vs. placebo and dose frequency, dose size, or study duration. Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0.97, 95% CI 0.86 to 1.09). Risk of bias within individual studies was assessed as being low for all but three trials. A funnel plot showed left-sided asymmetry (P=0.008, Egger’s test).InterpretationVitamin D supplementation was safe and reduced risk of ARI, despite evidence of significant heterogeneity across trials. Protection was associated with administration of daily doses of 400-1000 IU vitamin D for up to 12 months. The relevance of these findings to COVID-19 is not known and requires investigation.FundingNone

scholarly journals Randomised controlled trial for high-dose intravenous zinc as adjunctive therapy in SARS-CoV-2 (COVID-19) positive critically ill patients: trial protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e040580
Author(s):  
Marlon Perera ◽  
John El Khoury ◽  
Vidyasagar Chinni ◽  
Damien Bolton ◽  
Liang Qu ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Respiratory Illness ◽  
Organ Injury ◽  
High Dose ◽  
Protective Effects ◽  
Double Blind ◽  
Hospitalised Patients ◽  
Randomised Controlled ◽  
Ventilated Patients

IntroductionSARS-CoV-2 (COVID-19) has caused an international pandemic of respiratory illness, resulting in significant healthcare and economic turmoil. To date, no robust vaccine or treatment has been identified. Elemental zinc has previously been demonstrated to have beneficial effects on coronaviruses and other viral respiratory infections due to its effect on RNA polymerase. Additionally, zinc has well-demonstrated protective effects against hypoxic injury—a clear mechanism of end-organ injury in respiratory distress syndrome. We aimed to assess the effect of high-dose intravenous zinc (HDIVZn) on SARS-CoV-2 infection. The end of study analyses will evaluate the reduction of impact of oxygen saturations or requirement of oxygen supplementation.Methods and analysisWe designed a double-blind randomised controlled trial of daily HDIVZn (0.5 mg/kg) versus placebo. Primary outcome measures are lowest oxygen saturation (or greatest level of supplemental oxygenation) for non-ventilated patients and worst PaO2/FiO2 for ventilated patients. Following power calculations, 60 hospitalised patients and 100 ventilated patients will be recruited to demonstrate a 20% difference. The duration of follow-up is up to the point of discharge.Ethics and disseminationEthical approval was obtained through the independent Human Research Ethics Committee. Participant recruitment will commence in May 2020. Results will be published in peer-reviewed medical journals.Trial registration numberACTRN126200000454976.

scholarly journals High-dose vitamin D supplementation to prevent prostate cancer progression in localised cases with low-to-intermediate risk of progression on active surveillance (ProsD): protocol of a phase II randomised controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. e044055
Author(s):  
Visalini Nair-Shalliker ◽  
David P Smith ◽  
Val Gebski ◽  
Manish I Patel ◽  
Mark Frydenberg ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Vitamin D ◽  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Vitamin D Supplementation ◽  
High Dose ◽  
Intermediate Risk ◽  
Risk Of Progression ◽  
Randomised Controlled ◽  
High Dose Vitamin

IntroductionActive surveillance (AS) for patients with prostate cancer (PC) with low risk of PC death is an alternative to radical treatment. A major drawback of AS is the uncertainty whether a patient truly has low risk PC based on biopsy alone. Multiparametric MRI scan together with biopsy, appears useful in separating patients who need curative therapy from those for whom AS may be safe. Two small clinical trials have shown short-term high-dose vitamin D supplementation may prevent PC progression. There is no substantial evidence for its long-term safety and efficacy, hence its use in the care of men with PC on AS needs assessment. This protocol describes the ProsD clinical trial which aims to determine if oral high-dose vitamin D supplementation taken monthly for 2 years can prevent PC progression in cases with low-to-intermediate risk of progression.Method and analysisThis is an Australian national multicentre, 2:1 double-blinded placebo-controlled phase II randomised controlled trial of monthly oral high-dose vitamin D supplementation (50 000 IU cholecalciferol), in men diagnosed with localised PC who have low-to-intermediate risk of disease progression and are being managed by AS. This trial will assess the feasibility, efficacy and safety of supplementing men with an initial oral loading dose of 500 000 IU cholecalciferol, followed by a monthly oral dose of 50 000 IU during the 24 months of AS. The primary trial outcome is the commencement of active therapy for clinical or non-clinical reason, within 2 years of AS.Ethics and disseminationThis trial is approved by Bellberry Ethics Committee (2016-06-459). All results will be reported in peer-reviewed journals.Trial registration numberACTRN12616001707459.

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