Economic evaluation of a national vitamin D supplementation program among Iranian adolescents for the prevention of adulthood type 2 diabetes mellitus

Background This study aimed to evaluate the cost-effectiveness of vitamin D supplementation in preventing type 2 diabetes mellitus (T2DM) among Iranian adolescents. Methods This analytical observational study was conducted, using the decision tree model constructed in TreeAge Pro to assess the cost per quality-adjusted life-year (QALY) of monthly intake vitamin D supplements to prevent T2DM compared to no intervention from the viewpoint of Iran’s Ministry of Health and through an one-year horizon. In the national program of vitamin D supplementation, 1,185,211 Iranian high-school students received 50,000 IU vitamin D supplements monthly for nine months. The costs-related data were modified to 2018. The average cost and effectiveness were compared based on the Incremental Cost-Effectiveness Ratio (ICER). Results Our analytical analysis estimated the 4071.25 (USD / QALY) cost per AQALY gained of the monthly intake of 50,000 IU vitamin D for nine months among adolescents over a one-year horizon. Based on the ICER threshold of 1032–2666, vitamin D supplementation was cost-effective for adolescents to prevent adulthood T2DM. It means that vitamin D supplementation costs were substantially less than the costs of T2DM treatments than the no intervention. Conclusions Based on the findings, the national vitamin D supplementation program for Iranian adolescents could be a cost-effective strategy to reduce the risk of diabetes in adulthood. From an economic perspective, vitamin D supplementation, especially in adolescents with vitamin D deficiency, would be administrated.

Delay in assessing vitamin D supplements and live vaccines for tuberculosis, polio, and measles to protect people from Covid-19

Introduction: In March 2020, less than three months after China reported a cluster of pneumonia cases in Wuhan, the United States (US) government budgeted money to support development of Covid-19 vaccines. By mid-December 2020, two had been developed, tested, and received the US government’s experimental use authorization. Given evidence that vitamin D supplements and live vaccines for tuberculosis, polio, and measles reduce risks for acute respiratory infection, many experts hypothesized they might reduce risks for Covid-19 infection. Expedited randomized controlled trials, as done for Covid-19 vaccines, could have assessed their protection against C19 no later than end-July 2020. Methods: On 21 April 2021, I searched trial registries maintained by the US National Institutes of Medicine and the World Health Organization for trials with ≥400 participants to assess vitamin D or live vaccines to prevent Covid-19 infections (all or symptomatic). On 10-13 November 2021, I searched PubMed and medRxiv for results reported from these trials.Results: In April 2021, I found 32 trials (9 for vitamin D and 23 for live vaccines) proposing to assess the impact of these interventions on rates of new Covid-19 infections (all or symptomatic). Only 10 trials proposed to begin by June 2020, and only one to end in 2020. My search on 10-13 November 2021, almost 11 months after the US approved the first two Covid-19 vaccines, found results reported from only one of the 32 trials (live measles vaccine significantly reduced new symptomatic infections). Conclusions: If health experts had demonstrated similar urgency in assessing vitamin D supplements and live vaccines for tuberculosis, polio, and measles as in developing Covid-19 vaccines, trials could have reported by end-July 2020. Depending on what trials reported, these interventions could have prevented a large percentage of more than 600,000 Covid-19 deaths reported in the US from August 2020 through November 2021. Delay in assessing vitamin D has racial implications as well, since vitamin D deficiency and Covid-19 deaths in the US have been far more common among Blacks and Hispanics compared to Whites. Going forward, depending on what trials report, these interventions could help people live with Covid-19 as an endemic virus.

Should Vitamin D Supplements be Used as Adjunct Treatment for COVID-19: A Rapid Review

Background. Pooled data from observational studies suggest that patients with serum vitamin D levels below 30 ng/mL had an increased risk of infection and mortality from COVID-19. This rapid review aimed to determine the efficacy and safety of vitamin D as an adjunct treatment for COVID-19. Methods. We searched MEDLINE (PubMed) and CENTRAL up to July 18, 2021. We also searched trial registries, gray literature, and reference lists of included and excluded studies in the search as well as COVID-19 guidelines. Two reviewers independently screened titles and abstracts, collected data, and assessed for risk of bias. Meta-analysis was conducted, and an evidence profile table using GRADEpro was generated. Outcomes included were mortality, need for mechanical ventilator or progression of oxygen support, duration of mechanical ventilation, ICU admission, hospital length of stay, SARS-CoV-2 positivity at day 21, and adverse events. Results. We found four RCTs (3 low risk of bias and 1 high risk of bias). The sources of bias among the RCTs were unclear allocation, lack of blinding of patients, caregivers, and outcome assessors, and high drop-out rate. This rapid review found that the effects of vitamin D are inconclusive for the following outcomes: mortality (pooled RR 0.62, 95% CI [0.16 to 2.41], I2=49%; n=443, 3 RCTs, very low certainty of evidence), need for mechanical ventilator or progression of oxygen support (RR 0.52, 95% CI [0.24 to 1.13], n=237, 1 RCT, low certainty of evidence), and ICU admission (pooled RR 0.37, 95% CI [0.09 to 1.61], I2=78%; n=443, 3 RCTs, very low certainty of evidence. No significant reduction in hospital length of stay was found among those treated with vitamin D (MD 0 days, 95% CI [-1.19 to 1.09], low certainty of evidence). The duration of mechanical ventilation was also was also not significantly shortened in the treatment group (15 days) compared with placebo (12.8 days), MD 2.2 days, 95% CI [-8.4 to 12.8], low certainty of evidence. Interestingly, a higher proportion of those supplemented with vitamin D showed virologic clearance for COVID-19 on day 21 (RR 3.0, 95% CI [1.26 to 7.14], n=40, 1 RCT). At dosages between 60,000 to 200,000 IU of cholecalciferol, only one episode of vomiting (0.8%) was reported. Conclusion. Based on the evidence found, we are uncertain whether vitamin D is beneficial or harmful for patients with COVID-19. There is very low certainty of evidence to recommend the use of vitamin D supplements as an adjunct treatment for patients with COVID-19. Vitamin D supplementation for patients with COVID-19 should be limited to clinical trials or among those with proven vitamin D deficiency. More published studies are awaited to explore the benefit or harm of vitamin D for COVID-19.

Unzureichende Vitamin-D-Versorgung im Alter: Konsequenzen und Lösungsansätze für die Praxis

ZusammenfassungVitamin D ist eine für den Menschen essenzielle Substanz, die eine zentrale Rolle bei der Regulation des Kalzium- und Phosphathaushalts spielt, aber auch für eine normale Immunfunktion und Zellteilung wichtig ist. Als essenzielle Substanz muss Vitamin D dem Körper lebenslang in ausreichender Menge zur Verfügung gestellt werden. In Deutschland liegt bei Senioren ähnlich wie in der jüngeren Allgemeinbevölkerung der Blutspiegel an 25-Hydroxyvitamin D (Indikator des Vitamin-D-Status) zu über 50 % im defizitären/insuffizienten Bereich (< 50 nmol/L), wobei die unzureichende Versorgungslage deutliche saisonale Schwankungen aufweist (41 % am Ende des Sommers und 75 % am Ende des Winters). Im klinischen Bereich können Vitamin-D-Supplemente bei Personen mit defizitärer Vitamin-D-Versorgung zu einer Reduktion des Risikos von osteoporotischen Frakturen und akuten Atemwegsinfekte beitragen sowie möglicherweise bei einigen Erkrankungen wie Asthma und chronisch obstruktiver Lungenerkrankung die Krankheitsschübe reduzieren. Ein Vitamin-D-Mangel kann in der Regel durch die tägliche Einnahme eines Vitamin-D-Supplements in Höhe von 800–1000 IE (20–25 µg) effektiv verhindert werden. Von hochdosierten, intermittierenden Vitamin-D-Gaben, die zu 25OHD-Spiegeln > 125 nmol/L führen, ist abzuraten. Vitamin-D-Tests werden im klinischen Bereich häufig zur Beurteilung der Versorgungslage von Einzelpersonen durchgeführt. Hier sind sie zur Bestätigung eines Verdachts auf eine Vitamin-D-Intoxikation hilfreich. Ansonsten sind sie aber als Screening auf einen Vitamin-D-Mangel meist unnötig und manchmal verunsichernd.

Effect of Two Different Doses of Vitamin D Supplementation on Uterine Myoma on South East Iranian Population; A Clinical Trial

Objective: Uterine myoma is the most common benign tumor however with significant distress and reduced quality of life in affected women. Besides, vitamin D deficiency may be a risk factor for uterine myoma. This study aimed to evaluate the effect of vitamin D supplements on the size of myoma in women with vitamin D insufficiency or deficiency. Materials and methods: This clinical trial was conducted in a teaching hospital from 2019 to 2020. According to baseline vitamin D level, participants were assigned into two interventional equal groups (vitamin D deficiency or insufficiency) to receive either 1000 IU daily or 50000 IU weekly vitamin D for 12 weeks. The size and location of the uterine myoma were compared before and after the intervention. Results: Totally, 137 women with uterine myoma were enrolled. Based on baseline vitamin D level, 52 cases had vitamin D insufficiency and 85 cases had vitamin D deficiency. No significant difference was observed in age and BMI in both groups. The location of the subserosal and intramural myoma did not differ, otherwise, the percent of the submucosal myomas were increased significantly (p=0.020) after the intervention. In both groups decreased myoma size otherwise not significant was seen after the intervention (p=0.148 and p=0.664 respectively). Conclusion: Vitamin D supplementation may not be effective in women with vitamin D insufficiency or deficiency in the short term to reduce myoma size.

Bulbar-Predominant Weakness

A 61-year-old man sought care for recurrent episodes of dysarthria for about 1 year. This symptom was more common after prolonged speaking. Six months before his evaluation he had significant slurring of his speech after talking for 3½ hours at work about a new project. This led to emergency evaluation and his symptoms were thought to represent a transient ischemic attack; he started aspirin and a statin. The episodes continued to recur. He also experienced intermittent binocular double vision, which did not improve with new eyeglasses, and a sensation that chewing and swallowing was more effortful. He noted that his arms and legs felt “heavy” at times. All these symptoms tended to occur later in the day or after exertion. Neurologic examination was remarkable for binocular double vision with prolonged gaze upward or to the far right. He could squat and rise 5 times but with difficulty by the 5th attempt. The patient’s symptoms suggested myasthenia gravis. The differential diagnosis for autoimmune myasthenia gravis, particularly with prominent ocular and facial muscle involvement, can include central nervous system disorders, motor neuron disease, and myopathy. Serologic evaluation showed positivity for acetylcholine receptor-binding antibody and acetylcholine receptor-modulating antibody. Striated muscle antibody was also positive. Thiopurine S-methyltransferase activity was low. Repetitive stimulation studies showed a decrement in the right facial nerve, which partially improved after exercise. Routine needle examination showed motor unit variation in the right orbicularis oculi. Single-fiber electromyography showed increased jitter in the right orbicularis oculi. Chest computed tomography showed scattered tiny pulmonary nodules but no evidence of thymoma or other neoplasm. The clinical diagnosis was autoimmune generalized myasthenia gravis, seropositive for acetylcholine receptor antibody, without evident thymoma or other neoplasm. The patient was initially treated with oral pyridostigmine with some symptomatic benefit. Oral prednisone was then initiated; symptoms resolved when the dose was titrated. Calcium and vitamin D supplements, as well as Pneumocystis prophylactic therapy, were initiated concurrently. Mycophenolate mofetil was added as a steroid-sparing agent. On thoracic surgery consultation, thymectomy was recommended. Autoimmune myasthenia gravis is a disorder of impaired neuromuscular transmission caused by immunoglobulin G-mediated attack on a critical component of the acetylcholine receptor signaling complex in the muscle’s postsynaptic membrane. The most commonly identified antibodies, target the nicotinic acetylcholine receptor.

382. Vitamin D Supplementation and Covid 19: Results from the U.S. N3C Data Enclave

Background It is estimated that 18% of adults in the U.S. take Vitamin D supplements. Some observational studies suggest that vitamin D supplementation activates the innate immune system and reduces the incidence and severity of viral infections. During the SARS-CoV-2 pandemic, vitamin D supplements were touted as a potential therapy to prevent the disease and/or complications. However, supportive evidence is lacking. Methods The National COVID Cohort Collaborative (N3C) enclave is the largest COVID-19 data base with nearly 1.4 million positive patients at 56 sites in the U.S. We performed a retrospective analysis of vitamin D supplementation, either prescribed before or during hospitalization for SARS-CoV-2. Results 137,399 people took vitamin D supplements out of 1.4 million. Females prescribed vitamin D outnumbered males by almost 2:1, whereas in non-users there were no sex differences. Most supplement users were older than 50. African Americans constituted 13% of the non-users, but 23% of those prescribed vitamin D. Infected individuals with any vitamin D supplementation, pre-Covid, post-Covid or both, had a 6.66% mortality rate vs 2% mortality in non-users. Similarly, nearly a third of the supplement users were hospitalized compared to 11% in the non-users. The Charlson Co-Morbidity Index was 3.0±3 (SD) in users vs 1.0±2 (SD) in non-users. Conclusion 10% of SARS-CoV-2 infected patients were taking vitamin D. They tended to be older, more likely to be African American and have significant co-morbidities. Hospitalization and mortality were higher among those taking Vitamin D in this cohort. Vitamin D is widely used to prevent and treat SARS-CoV-2 but without evidence of efficacy. Disclosures Sally L. Hodder, M.D., Gilead (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Viiv Healthcare (Grant/Research Support, Advisor or Review Panel member)

Low vitamin D levels do not aggravate COVID-19 risk or death, and vitamin D supplementation does not improve outcomes in hospitalized patients with COVID-19: a meta-analysis and GRADE assessment of cohort studies and RCTs

Background The associations between vitamin D and coronavirus disease 2019 (COVID-19) infection and clinical outcomes are controversial. The efficacy of vitamin D supplementation in COVID-19 is also not clear. Methods We identified relevant cohort studies that assessed the relationship between vitamin D, COVID-19 infection and associated death and randomized controlled trials (RCTs) that reported vitamin D supplementation on the outcomes in patients with COVID-19 by searching the PubMed, EMBASE, and medRxiv databases up to June 5th, 2021. Evidence quality levels and recommendations were assessed using the GRADE system. Results Eleven cohort studies with 536,105 patients and two RCTs were identified. Vitamin D deficiency (< 20 ng/ml) or insufficiency (< 30 ng/ml) was not associated with an significant increased risk of COVID-19 infection (OR for < 20 ng/ml: 1.61, 95% CI: 0.92–2.80, I2 = 92%) or in-hospital death (OR for < 20 ng/ml: 2.18, 95% CI: 0.91–5.26, I2 = 72%; OR for < 30 ng/ml: 3.07, 95% CI: 0.64–14.78, I2 = 66%). Each 10 ng/ml increase in serum vitamin D was not associated with a significant decreased risk of COVID-19 infection (OR: 0.92, 95% CI: 0.79–1.08, I2 = 98%) or death (OR: 0.65, 95% CI: 0.40–1.06, I2 = 79%). The overall quality of evidence (GRADE) for COVID-19 infection and associated death was very low. Vitamin D supplements did not significantly decrease death (OR: 0.57, I2 = 64%) or ICU admission (OR: 0.14, I2 = 90%) in patients with COVID-19. The level of evidence as qualified using GRADE was low. Conclusions Current evidence suggested that vitamin D deficiency or insufficiency was not significantly linked to susceptibility to COVID-19 infection or its associated death. Vitamin D supplements did not significantly improve clinical outcomes in patients with COVID-19. The overall GRADE evidence quality was low, we suggest that vitamin D supplementation was not recommended for patients with COVID-19.

Concentration of 25(OH)D in blood serum and certain aspects of the clinical course of juvenile scleroderma

Purpose — to assess the vitamin D supply in children and adolescents with systemic juvenile scleroderma (JS), taking into account its onset and clinical course at different periods of the child's development. Materials and methods. 14 children of 1 year 3 months —17 years old with systemic JS and 10 healthy children of the control group were examined. The concentration of 25(OH)D was determined in blood serum using commercial kits Vitamin D3 — Screeningkit, Switzerland, according to the manufacturer's instructions. Results. All patients with systemic JS showed a decrease in serum 25(OH)D levels — (24.55±9.32) ng/ml, compared to healthy children — (39.98±3.11) ng/ml. The lowest concentrations of the circulating form of vitamin D in the blood serum were in patients with limited form of systemic JS with Parry–Romberg hemiatrophy and «saber strike» — (14.07±3.38) ng/ml, as well as with the onset of generalized rapidly progressive JS in children at puberty — (16.31±4.6) ng/ml. Conclusions. Children with JS are shown to assess their vitamin D status by monitoring the serum concentration of 25(OH)D in order to decide whether to prescribe vitamin D supplements. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: children, juvenile scleroderma, vitamin D.