A Health Technology Assessment Based on Chinese Guideline: Active Vitamin D and Its Analogs in the Treatment of Osteoporosis.

Objective: To quantitatively assess all dosage forms of three active vitamin D and its analogs, namely, calcitriol, alfacalcidol, and eldecalcitol, to provide a basis for the selection of active vitamin D and its analogs in hospitals. Methods: In this study, three active vitamin D and its analogs were evaluated by quantitative scoring in five dimensions, including pharmaceutical properties (28 points), efficacy (27 points), safety (25 points), economy (10 points), and other attributes (10 points). Results: The final scores of quantitative assessment for the selection of alfacalcidol soft capsules, calcitriol soft capsules I, calcitriol soft capsules II, alfacalcidol tablets, alfacalcidol capsules, alfacalcidol oral drops, calcitriol injection, and eldecalcitol soft capsules were 73.17, 72.06, 71.52, 71.29, 69.62, 68.86, 65.60, 64.05 points. Conclusion: Based on the scoring results, alfacalcidol soft capsules, calcitriol soft capsules I, calcitriol soft capsules II, alfacalcidol tablets can be entered into the medication list of medical institutions as strongly recommended drugs. This study offers guidance on selecting and using active vitamin D and its analogs in hospitals, with consideration for the patient's needs.

Effect of bone and analytical method on assessment of bone mineralization in response to dietary phosphorus, phytase, and vitamin D in finishing pigs.

A total of 882 pigs (PIC TR4 × [Fast LW × PIC L02]; initially 33.2 ±â€…0.31 kg) were used in a 112-d study to evaluate the effects of different bones and analytical methods on the assessment of bone mineralization response to changes in dietary P, phytase, and vitamin D in growing pigs. Pens of pigs (20 pigs per pen) were randomized to one of five dietary treatments with nine pens per treatment. Dietary treatments were designed to create differences in bone mineralization and included: 1) P at 80% of NRC (2012) standardized total tract digestible (STTD) P requirement, 2) NRC STTD P with no phytase, 3) NRC STTD P with phytase providing an assumed release of 0.14% STTD P from 2,000 FYT/kg, 4) high STTD P (128% of the NRC P) using monocalcium phosphate and phytase, and 5) diet 4 with additional vitamin D3 from 25(OH)D3. On day 112, one pig per pen was euthanized for bone, blood, and urine analysis. Additionally, 11 pigs identified as having poor body condition which indicated a history of low feed intake (unhealthy) were sampled. There were no differences between treatments for final body weight, average daily gain, average daily feed intake, gain to feed, or bone ash measurements (treatment × bone interaction) regardless of bone ash method. The response to treatment for bone density and bone mineral content was dependent upon the bone sampled (density interaction, P = 0.053; mineral interaction, P = 0.078). For 10th rib bone density, pigs fed high levels of P had increased (P < 0.05) bone density compared with pigs fed NRC levels with phytase, with pigs fed deficient P, NRC levels of P with no phytase, and high STTD P with extra 25(OH)D3 intermediate, with no differences for metacarpals, fibulas, or 2nd ribs. Pigs fed extra vitamin D from 25(OH)D3 had increased (P < 0.05) 10th rib bone mineral content compared with pigs fed deficient P and NRC levels of P with phytase, with pigs fed industry P and vitamin D, and NRC P with monocalcium intermediate. Healthy pigs had greater (P < 0.05) serum Ca, P, vitamin D concentrations, and defatted bone ash than those unhealthy, with no difference between the two health statuses for non-defatted bone ash. In summary, differences between bone ash procedures were more apparent than differences between diets. Differences in bone density and mineral content in response to dietary P and vitamin D were most apparent with 10th ribs.

Lameness is defined as impaired movement or deviation from normal gait. The evaluation of bone mineralization can be an important component of a diagnostic investigation of lameness. Lameness in growing pigs can cause an increase in morbidity and mortality, which leads to economic losses and animal welfare concerns for producers. Calcium and P are the primary minerals in skeletal tissue and their deficiency is considered to be one of the causes of lameness. To evaluate bone mineralization, it is important to know the differences between methodologies used to determine bone ash and the expected differences between the bones analyzed. Furthermore, there has been limited data comparing bone mineralization and serum Ca and P concentrations between healthy pigs and those exhibiting clinical signs of illness (unhealthy). By removing the lipid in the bone (defatting) before the bone is ashed, variation across bones is decreased compared with not removing lipid before ashing (non-defatted). The reduction in variation across bones allows for more differences to be detected among dietary treatments and health statuses of pigs. The 10th rib is more sensitive to detect dietary differences using bone density than metacarpals, fibulas, and 2nd ribs. When comparing healthy vs. unhealthy pigs exhibiting clinical signs of illness, healthy pigs have increased defatted percentage bone ash and serum Ca, P, and vitamin D.

Consensus Statement on Vitamin D Status Assessment and Supplementation: Whys, Whens, and Hows.

The 6th International Conference, "Controversies in Vitamin D," was convened to discuss controversial topics, such as vitamin D metabolism, assessment, actions, and supplementation. Novel insights into vitamin D mechanisms of action suggest links with conditions that do not depend only on reduced solar exposure or diet intake and that can be detected with distinctive noncanonical vitamin D metabolites. Optimal 25-hydroxyvitamin D (25(OH)D) levels remain debated. Varying recommendations from different societies arise from evaluating different clinical or public health approaches. The lack of assay standardization also poses challenges in interpreting data from available studies, hindering rational data pooling and meta-analyses. Beyond the well-known skeletal features, interest in vitamin D's extraskeletal effects has led to clinical trials on cancer, cardiovascular risk, respiratory effects, autoimmune diseases, diabetes, and mortality. The initial negative results are likely due to enrollment of vitamin D-replete individuals. Subsequent post hoc analyses have suggested, nevertheless, potential benefits in reducing cancer incidence, autoimmune diseases, cardiovascular events, and diabetes. Oral administration of vitamin D is the preferred route. Parenteral administration is reserved for specific clinical situations. Cholecalciferol is favored due to safety and minimal monitoring requirements. Calcifediol may be used in certain conditions, while calcitriol should be limited to specific disorders in which the active metabolite is not readily produced in vivo. Further studies are needed to investigate vitamin D effects in relation to the different recommended 25(OH)D levels and the efficacy of the different supplementary formulations in achieving biochemical and clinical outcomes within the multifaced skeletal and extraskeletal potential effects of vitamin D.

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.

Vitamin D Deficiency Is Inversely Associated with Homeostatic Model Assessment of Insulin Resistance.

The study was conducted to comprehensively assess the association of the concentration of vitamin D in the blood and insulin resistance in non-diabetic subjects. The objective was to pool the results from all observational studies from the beginning of 1980 to August 2021. PubMed, Medline and Embase were systematically searched for the observational studies. Filters were used for more focused results. A total of 2248 articles were found after raw search which were narrowed down to 32 articles by the systematic selection of related articles. Homeostatic Model Assessment of Insulin Resistance (HOMAIR) was used as the measure of insulin resistance and correlation coefficient was used as a measure of the relationship between vitamin D levels and the insulin resistance. Risk of bias tables and summary plots were built using Revman software version 5.3 while Comprehensive meta-analysis version 3 was used for the construction of forest plot. The results showed an inverse association between the status of vitamin D and insulin resistance (r = -0.217; 95% CI = -0.161 to -0.272; p = 0.000). A supplement of vitamin D can help reduce the risk of insulin resistance; however further studies, like randomized controlled trials are needed to confirm the results.

Assessment the effect of vitamin D supplementation on plasma vitamin D levels, inflammation, and oxidative stress biomarkers based on vitamin D receptor genetic variation in breast cancer survivors: a protocol for clinical trial.

BACKGROUND: Both human genes and environmental exposures, due to complex interplay, play important role in the cancer etiology. Vitamin D is associated with a reduced risk of incidence and mortality of several human cancers. This study will aim to investigate the possible effects of individual polymorphisms in vitamin D receptor (VDR) as well as effects of VDR haplotypes on response to vitamin D supplementation in breast cancer survivors. METHODS: This is an interventional study in which the effects of vitamin D supplementation on plasma vitamin D levels, inflammatory and antioxidant biomarkers and factors associated with cell proliferation, differentiation, damage, and apoptosis will be investigated stratified by variations in VDR genotype. The present study will be conducted on breast cancer survivors referred to the Shohadaye Tajrish hospital and its associated clinics. One hundred ninety-eight breast cancer survivors will receive 4000 IU of vitamin D3 daily for 12 weeks. VDR Fok1, ApaI, TaqI, BsmI, and Cdx-2 genotype will be determined at the end of the study and responses to vitamin D supplements (inflammatory, antioxidant, cell proliferation, differentiation, damage, and apoptosis biomarkers) will be compared between the three subgroups of each VDR polymorphism as well as different VDR haplotype categories. DISCUSSION: Genetic variation is a fundamental factor influencing individuals' divergent responses to diet, nutritional status, metabolic response, and diet-related health disorders. Furthermore, studies of gene and environment interactions will provide a precise and accurate assessments of individuals' dietary requirements by considering both the genetic and environmental aspects simultaneously. The results of the current study, to some extent, will highlight the discrepancies existing in the findings of different studies regarding vitamin D, VDR, and cancer by considering both the genetic and environmental aspects simultaneously. If responses to vitamin D supplementation could be modified by VDR SNPs, determining the distribution of VDR polymorphisms in both breast cancer survivors and healthy populations will provide a new insight into the vitamin D requirements of individuals to prevent cancer and its related mortality based on their genotypes. Trial registration This trial has been registered on Iranian Registry of Clinical Trials (IRCT) under the identification code: IRCT2017091736244N1, registration date: 2017-11-10, http://www.irct.ir/trial/27153.

[Pharmaceutical Intervention According to Strict Management System Can Normalize Decreased Serum Calcium Level by Denosumab and Prevent Its Aggravation].

Denosumab is a fully monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand (RANKL), and prevents skeletal-related events by bone metastasis. Hypocalcemia is the most typical adverse effect of denosumab use. We have developed a management system for the more efficient and safer management of denosumab administration, and evaluated pharmaceutical interventions for the better control of hypocalcemia. All pharmaceutical interventions in the system from April 2016 to March 2020 were retrospectively evaluated. We have also assessed the incidence of hypocalcemia in 158 patients who were administered denosumab for six months or more in the period. A total of 282 pharmaceutical interventions (7.0% of the total administration) were conducted. The most conducted intervention was regarding hypocalcemia, which involved the suspension of the injection and/or the increase of calcium and vitamin D supplement with 65% adoption and 17% temporary treatment suspensions. Other interventions were about hypercalcemia, request of laboratory examination and ordering supplements, dental consultation, and poor renal function. A total of 199 interventions (70.6%) were adopted, with 33 administrations suspended. The frequency of hypocalcemia was 27.8% with just one patient having grade 2 hypocalcemia, suggesting that there were no severe cases. Moreover, hypocalcemia was significantly normalized following pharmaceutical intervention and/or handling by physicians (p=0.02) according to the system. Conversely, the normalization rate in hypercalcemia did not differ according to the countermeasures. In conclusion, pharmaceutical interventions according to our management system benefit safe denosumab treatment, especially in severe hypocalcemia prevention.

Assessment of the Methods Used to Develop Vitamin D and Calcium Recommendations-A Systematic Review of Bone Health Guidelines.

BACKGROUND: There are numerous guidelines developed for bone health. Yet, it is unclear whether the differences in guideline development methods explain the variability in the recommendations for vitamin D and calcium intake. The objective of this systematic review was to collate and compare recommendations for vitamin D and calcium across bone health guidelines, assess the methods used to form the recommendations, and explore which methodological factors were associated with these guideline recommendations. METHODS: We searched MEDLINE, EMBASE, CINAHL, and other databases indexing guidelines to identify records in English between 2009 and 2019. Guidelines or policy statements on bone health or osteoporosis prevention for generally healthy adults aged ≥40 years were eligible for inclusion. Two reviewers independently extracted recommendations on daily vitamin D and calcium intake, supplement use, serum 25 hydroxyvitamin D [25(OH)D] level, and sunlight exposure; assessed guideline development methods against 25 recommended criteria in the World Health Organization (WHO) handbook for guideline development; and, identified types identified types of evidence underpinning the recommendations. RESULTS: we included 47 eligible guidelines from 733 records: 74% of the guidelines provided vitamin D (200~600-4000 IU/day) and 70% provided calcium (600-1200 mg/day) recommendations, 96% and 88% recommended vitamin D and calcium supplements, respectively, and 70% recommended a specific 25(OH)D concentration. On average, each guideline met 10 (95% CI: 9-12) of the total of 25 methodological criteria for guideline development recommended by the WHO Handbook. There was uncertainty in the association between the methodological criteria and the proportion of guidelines that provided recommendations on daily vitamin D or calcium. Various types of evidence, including previous bone guidelines, nutrient reference reports, systematic reviews, observational studies, and perspectives/editorials were used to underpin the recommendations. CONCLUSIONS: There is considerable variability in vitamin D and calcium recommendations and in guideline development methods in bone health guidelines. Effort is required to strengthen the methodological rigor of guideline development and utilize the best available evidence to underpin nutrition recommendations in evidence-based guidelines on bone health.

Identification of drugs associated with reduced severity of COVID-19 - a case-control study in a large population.

Background: Until coronavirus disease 2019 (COVID-19) drugs specifically developed to treat COVID-19 become more widely accessible, it is crucial to identify whether existing medications have a protective effect against severe disease. Toward this objective, we conducted a large population study in Clalit Health Services (CHS), the largest healthcare provider in Israel, insuring over 4.7 million members. Methods: Two case-control matched cohorts were assembled to assess which medications, acquired in the last month, decreased the risk of COVID-19 hospitalization. Case patients were adults aged 18 to 95 hospitalized for COVID-19. In the first cohort, five control patients, from the general population, were matched to each case (n=6202); in the second cohort, two non-hospitalized SARS-CoV-2 positive control patients were matched to each case (n=6919). The outcome measures for a medication were: odds ratio (OR) for hospitalization, 95% confidence interval (CI), and the p-value, using Fisher's exact test. False discovery rate was used to adjust for multiple testing. Results: Medications associated with most significantly reduced odds for COVID-19 hospitalization include: ubiquinone (OR=0.185, 95% CI [0.058 to 0.458], p<0.001), ezetimibe (OR=0.488, 95% CI [0.377 to 0.622], p<0.001), rosuvastatin (OR=0.673, 95% CI [0.596 to 0.758], p<0.001), flecainide (OR=0.301, 95% CI [0.118 to 0.641], p<0.001), and vitamin D (OR=0.869, 95% CI [0.792 to 0.954], p<0.003). Remarkably, acquisition of artificial tears, eye care wipes, and several ophthalmological products were also associated with decreased risk for hospitalization. Conclusions: Ubiquinone, ezetimibe, and rosuvastatin, all related to the cholesterol synthesis pathway were associated with reduced hospitalization risk. These findings point to a promising protective effect which should be further investigated in controlled, prospective studies. Funding: This research was supported in part by the Intramural Research Program of the National Institutes of Health, NCI.

COVID-19 et Supplémentation en vitamine D / COVID-19 and Supplementation vitamin D

CONTEXTE: Le présent document ainsi que les constats qu'il énonce ont été rédigés dans le contexte de la crise sanitaire liée à la maladie à coronavirus (COVID-19) au Québec. L'objectif est de réaliser une recension des données publiées et de mobiliser les savoirs clés afin d'informer les décideurs publics et les professionnels de la santé et des services sociaux. Bien que les constats reposent sur un repérage exhaustif des données scientifiques publiées, l'évaluation de la qualité méthodologique des études et une appréciation du niveau de preuve scientifique par paramètre clinique d'intérêt, le processus ne repose pas sur une méthode systématique ni une validation externe selon les normes habituelles à l'INESSS. Par ailleurs, les positions ne découlent pas d'un processus de consultation élaboré. Dans les circonstances d'une telle crise de santé publique, l'INESSS reste à l'affût de toutes nouvelles données, qu'elles soient de nature scientifique ou contextuelle, susceptibles de lui faire modifier cette réponse. MÉTHODOLOGIE: Questions d'évaluation Comparativement aux standards de soins, est-ce qu'un supplément de vitamine D, chez les personnes ayant ou non une déficience ou une insuffisance, est efficace et sécuritaire pour, prévenir l'infection et les manifestations cliniques de la COVID-19? Traiter les patients (adulte, enfant, femme enceinte) COVID-19 confirmés dont l'état à l'amorce n'exige pas une hospitalisation? Traiter les patients (adulte, enfant, femme enceinte) COVID-19 confirmés dont l'état à l'amorce exige o une hospitalisation sans le recours à une oxygénothérapie; o une hospitalisation avec le recours à une oxygénothérapie non invasive (oxygène à faible débit, à haut débit, ventilation mécanique non invasive); o une hospitalisation avec le recours à une oxygénothérapie invasive (ventilation mécanique invasive, ECMO)? Quelle est la position des sociétés savantes, des agences règlementaires, des agences de santé publique et des agences d'évaluation des technologies en santé sur l'usage d'un supplément de vitamine D dans la prévention et le traitement de la COVID-19? Type de revue de littérature: Revue rapide. RÉSULTATS: ÉTAT ACTUEL DES CONNAISSANCES SCIENTIFIQUES. Données cliniques sur l'efficacité de la supplémentation en vitamine D dans le contexte de la COVID-19. Depuis l'instauration en mars 2020 de la recherche systématique en continu de la littérature scientifique sur les médicaments à visée thérapeutique, 42 027 notices ont été recensées dont 113 études cliniques où l'intervention étudiée portait sur la vitamine D. De ce nombre, 3 ECRA [Murai et al., 2021; Castillo et al., 2020; Rastogi et al., 2020] ont été retenus. Ces études sont décrites ci-dessous en fonction du type de prise en charge, soit la prophylaxie pré/post-exposition, ou le traitement de patient dont l'état de santé requiert ou non une hospitalisation. Seuls les paramètres d'intérêts sur l'évolution de la charge virale, l'amélioration ou la résolution des symptômes ou d'évolution clinique, le pronostic, l'innocuité ou la mortalité sont présentés. Supplémentation en vitamine D en prophylaxie: En date du 24 février 2021, aucun ECRA ni aucune étude observationnelle publiés n'ont été retracés par la recherche de la littérature scientifique sur les bénéfices cliniques associés à l'usage de vitamine D en prophylaxie pré- ou post- exposition au SARS-CoV-2. Par contre, il y a quelques essais cliniques actuellement enregistrés sur le site de ClinicalTrials, dont un essai comparatif à répartition aléatoire multicentrique à triple insu (PROTECT6 ) en cours de réalisation au sein de deux hôpitaux du Québec. Le principal objectif de cet essai est d'étudier les effets prophylactiques d'une supplémentation à hautes doses de vitamine D3 per os (bolus 100 000 UI suivi de 10 000 UI par semaine pendant 16 semaines) chez les travailleurs de la santé exposés à la COVID-19. Il est prévu que l'essai se termine en juin 2021. DISCUSSION: Au terme des travaux, il ressort qu'aucun ECRA ni aucune étude observationnelle publiés dans la littérature ne permettent d'évaluer l'effet d'une supplémentation en vitamine D utilisée en prophylaxie pré- ou post- exposition au SRAS-CoV-2 ni dans le traitement des sujets COVID-19 confirmés dont l'état n'exige pas une hospitalisation. Toutefois, en ce qui concerne les personnes atteintes de la COVID-19 dont l'état de santé requiert une hospitalisation, l'état actuel des connaissances scientifiques suggère qu'une supplémentation en vitamine D3 ne permet pas de réduire la durée d'hospitalisation et le nombre de nouveaux sujets ayant besoin de ventilation mécanique invasive et ne permet pas d'établir un lien en une supplémentation en vitamine D et les admissions aux soins intensifs ou la mortalité. Un supplément en vitamine D3 à raison de 60 000 UI par jour pendant 8 ou 14 jours, chez des personnes ayant une déficience en vitamine D, pourrait cependant permettre d'augmenter la proportion de sujets avec une négativation de la RTPCR sans toutefois avoir d'impact sur la durée moyenne avant la négativation de celle-ci. Il est toutefois important de souligner que les trois ECRA ont été réalisés sur des populations distinctes, hospitalisées pour une COVID-19 de sévérité variable, et avec différentes posologies et formes de vitamine D3 (calcifédiol ou cholécalciférol). Les profils d'innocuité et d'interactions médicamenteuses de la vitamine D sont aujourd'hui bien connus dans plusieurs contextes extérieurs à la COVID-19 [Euro-Pharm International Canada, 2018; Vifor Pharma, 2018]. Fondé sur 2 ECRA à double insu conduits au Brésil et en Inde dans le contexte de la COVID-19, la supplémentation de vitamine D3 à haute dose semble sécuritaire lorsque cette dernière est administrée en prise unique ou de manière quotidienne pendant une durée maximale de 14 jours chez des sujets adultes atteints de la COVID-19 et hospitalisés. Dans tous les documents consultés présentant des positions ou des recommandations cliniques, aucune organisation ne se prononce en faveur de l'usage de la vitamine D en prévention d'une infection par le SARS-CoV-2 ou comme traitement d'une telle infection en dehors d'un essai clinique, en raison d'une insuffisance de preuves. Compte tenu des risques potentiels d'effets indésirables, un suivi régulier des personnes recevant des doses de vitamine D supérieures à 4 000 UI par jour est également recommandé. Cette réponse rapide de l'INESSS comporte certaines limites qui méritent d'être soulignées. D'abord, l'analyse du niveau de preuve scientifique est basée sur 3 études primaires de type ECRA, elles aussi, empreintes de biais et de limites méthodologiques (y compris des déséquilibres dans les caractéristiques des sujets, dans la puissance statistique et dans les posologies et formes de vitamine D3 utilisées) affectant la confiance envers les résultats actuellement disponibles. Par ailleurs, le manque de résultats ne permet pas de conclure quant à d'éventuelles différences d'efficacité entre des sujets à différents stades de la maladie ou avec des niveaux de vitamine D différents au début des études (taux normal, insuffisance, déficience). Enfin, les constats ne découlent pas d'un processus de consultation élaboré. À la suite de l'analyse effectuée, la tendance pointe vers une absence de bénéfice de la supplémentation en vitamine D ayant 2021-03-08 15:16 22 un réel impact sur l'évolution clinique ou la mortalité liée à la COVID-19. Il faudra toutefois attendre les résultats d'ECRA supplémentaires dont la qualité méthodologique sera jugée acceptable avant d'infirmer ou confirmer une absence de bénéfices. L'efficacité et l'innocuité d'une supplémentation en vitamine D sont présentement évaluées dans plusieurs études cliniques en cours, soit en prophylaxie, chez des patients non hospitalisés ou chez des patients hospitalisés9 . En demeurant à l'affût de nouvelles données scientifiques, cette réponse rapide permet d'informer les professionnels de la santé et de les soutenir dans leur prise de décision clinique dans le contexte de la pandémie actuelle.

Vitamin D supplementation to the older adult population in Germany has the cost-saving potential of preventing almost 30 000 cancer deaths per year.

Recent meta-analyses of randomized controlled trials (RCTs) have demonstrated significant reduction in cancer mortality by vitamin D supplementation. We estimated costs and savings for preventing cancer deaths by vitamin D supplementation of the population aged 50+ years in Germany. Our analysis is based on national data on cancer mortality in 2016. The number of preventable cancer deaths was estimated by multiplying cancer deaths above age 50 with the estimated proportionate reduction in cancer mortality derived by vitamin D supplementation according to meta-analyses of RCTs (13%). Saved costs were estimated by multiplying this number by estimated end-of-life cancer care costs (€40 000). Annual costs of vitamin D supplementation were estimated at 25€ per person above age 50. Comprehensive sensitivity analyses were conducted. In the main analysis, vitamin D supplementation was estimated to prevent almost 30 000 cancer deaths per year at approximate costs of €900 million and savings of €1.154 billion, suggesting net savings of €254 million. Our results support promotion of supplementation of vitamin D among older adults as a cost-saving approach to substantially reduce cancer mortality.

Vitamin D supplementation and severity of atopic dermatitis: pre-post assessment.

BACKGROUND/OBJECTIVES: There is evidence that vitamin D (VD) supplementation may help in the management of atopic dermatitis (AD). The aim of this study was to assess the influence of VD supplementation on the severity of AD. METHODS: Pre-post interventional study with prospective data collection in patients younger than 14 years. The severity of AD was determined through SCORAD (SCORing Atopic Dermatitis) and classified as mild (SCORAD < 25), moderate (≥25 and <50), and severe (≥50). Skin prick test was performed in all patients. Serum VD levels were classified as sufficient (≥30 ng/mL), insufficient (29 to 21 ng/mL), and deficient (≤20 ng/mL); and those with inadequate levels received oral supplementation of VD for 3 months, and were reassessed after treatment. RESULTS: A total of 152 patients were included. Patients with sufficient vitamin levels had lower SCORAD values (p = 0.04). Further, 116 patients (76.3%) received VD supplementation and after 3 months, VD levels were significantly higher (35.9 ng/mL) compared to baseline levels (23.7 ng/mL, p < 0.001). At the same time, a reduction in the SCORAD index was observed (19.4 before vs 12.3 after supplementation, p < 0.001). Considering other factors that could influence the decrease in AD severity after VD supplementation, female gender was associated with a worse treatment response (p = 0.02). CONCLUSION: Vitamin D supplementation could be an adjuvant in reducing the severity of atopic dermatitis.

Geomapping Vitamin D Status in a Large City and Surrounding Population-Exploring the Impact of Location and Demographics.

Vitamin D status was assessed in a large urban area to compare differences in deficiency and to geomap the results. In total, 36,466 participants from 28 geographical areas were identified in this cross-sectional, retrospective analysis of general practitioner (GP)-requested 25(OH)D tests at St James's Hospital, Dublin between 2014 and 2018. The population were community-dwelling adults, median age 50.7 (18-109 years) with 15% of participants deficient (<30 nmol/L), rising to 23% in the winter. Deficiency was greatest in younger (18-39 years) and oldest (80+ years) adults, and in males versus females (18% vs. 11%, p < 0.001). Season was the biggest predictor of deficiency (OR 4.44, winter versus summer, p < 0.001), followed by location (west Dublin OR 2.17, north Dublin 1.54, south Dublin 1.42 versus rest of Ireland, p < 0.001) where several urban areas with an increased prevalence of deficiency were identified. There was no improvement in 25(OH)D over the 5-year period despite increased levels of testing. One in four adults were vitamin D deficient in the winter, with significant variations across locations and demographics. Overall this study identifies key groups at risk of 25(OH)D deficiency and insufficiency, thus providing important public health information for the targeting of interventions to optimise 25(OH)D. Mandatory fortification may be necessary to address this widespread inadequacy.

Assessment of Cardiovascular Safety of Anti-Osteoporosis Drugs.

The incidence of osteoporosis and cardiovascular disease increases with age, and there are potentially shared mechanistic associations between the two conditions. It is therefore highly relevant to understand the cardiovascular implications of osteoporosis medications. These are presented in this narrative review. Calcium supplementation could theoretically cause atheroma formation via calcium deposition, and in one study was found to be associated with myocardial infarction, but this has not been replicated. Vitamin D supplementation has been extensively investigated for cardiac benefit, but no consistent effect has been found. Despite findings in the early 21st century that menopausal hormone therapy was associated with coronary artery disease and venous thromboembolism (VTE), this therapy is now thought to be potentially safe (from a cardiac perspective) if started within the first 10 years of the menopause. Selective estrogen receptor modulators (SERMs) are associated with increased risk of VTE and may be related to fatal strokes (a subset of total strokes). Bisphosphonates could theoretically provide protection against atheroma. However, data from randomised trials and observational studies have neither robustly supported this nor consistently demonstrated the potential association with atrial fibrillation. Denosumab does not appear to be associated with cardiovascular disease and, although parathyroid hormone analogues are associated with palpitations and dizziness, no association with a defined cardiovascular pathology has been demonstrated. Finally, romosozumab has been shown to have a possible cardiovascular signal, and therefore post-market surveillance of this therapy will be vital.

Suplementos vitamínicos (Vit. C, D) y Zinc en infección por COVID-19 / Vitamin supplements (Vit. C, D) and Zinc in COVID-19 infection

CONTEXTO CLÍNICO: La enfermedad por el Coronavirus 2019 (COVID-19), por su sigla en inglés Coronavirus Disease 2019) es una enfermedad respiratoria de humanos por un nuevo Coronovirus identificado con la sigla SARS-CoV-2. TECNOLOGÍA: La vitamina C o ácido ascórbico es una vitamina soluble en agua con una función conocida sobre la síntesis de colágeno en tejidos conectivos y actúa como antioxidante. La vitamina D no solo es un nutriente sino también una hormona, que puede sintetizarse en nuestro cuerpo con la ayuda de la luz solar. El zinc es un oligoelemento dietético y es importante para el mantenimiento y el desarrollo de las células inmunes del sistema inmunitario innato y adaptativo. La deficiencia de Zinc resulta en la disfunción de la inmunidad humoral y mediada por células y aumenta la susceptibilidad a enfermedades infecciosas. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de suplementos vitamínicos (Vit. C, D) y Zinc en la infección por COVID-19. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y recomendaciones de diferentes organizaciones de salud. RESULTADOS: Se incluyeron una RS con MA, un protocolo de RS, un estudio observacional retrospectivo y ocho recomendaciones de sociedades científicas. No se hallaron estudios que evalúen la suplementación con vitaminas C y D para la prevención o tratamiento de la infección por COVID-19. Para Zinc, se halló un solo estudio que lo utiliza combinado con tratamientos discontinuados para esta patología por alertas en su seguridad. CONCLUSIONES: No hallaron estudios que evalúen la suplementación con las vitaminas C y D, solas o combinadas con otros tratamientos, en la prevención o tratamiento de la infección por COVID-19. Tampoco se encontraron estudios preventivos que evaluén el uso de Zinc. En el caso de su uso terapéutico, evidencia de muy baja calidad no permite determinar los efectos de la suplementación con Zinc en pacientes hospitalizados por COVID-19. Aunque se desconoce el efecto preventivo en relación al COVID-19, se halló evidencia de alta calidad de estudios realizados durante la era pre- COVID-19 que muestra que, en población general, la suplementación con vitamina D reduce el riesgo de infecciones respiratorias agudas. La incertidumbre actual podría reducirse a corto o mediano plazo debido a que se encuentran en curso aproximadamente 90 estudios que evaluarán el efecto de la administración C y D, y Zinc, solas o en combinación con otros tratamientos, para la prevención o tratamiento de la infección por COVID-19.

Assessment of knowledge, attitudes and practice towards Vitamin D among university students in Pakistan.

BACKGROUND: Pakistan has one of the highest reported incidence of vitamin D deficiency in studies conducted worldwide. However, there has been very limited exploration of vitamin D related knowledge, attitudes and practices among healthy youth in Pakistan. METHODS: A cross-sectional survey was conducted among youth (aged > 16 years) from two engineering universities in Pakistan. Participants were asked questions on their concern about vitamin D levels, testing, and supplementation practices. Knowledge was examined using questions about food sources, health benefits and factors affecting vitamin D production within the human body. Of the 900 eligible students invited to participate, 505 (56%) completed the questionnaire and were included in the analysis. RESULTS: Only 9% participants were able to identify the correct food sources of vitamin D, 33% were aware of the bone health benefits (bone health and calcium absorption) of vitamin D and 36% identified sunlight exposure as a factor influencing vitamin D production. Knowledge about food sources and health benefits of vitamin D was not associated with gender and individuals concern about their levels. Those tested and taking supplements were more likely to identify bone related health benefits and factors affecting vitamin D production. Forty percent male and 52% female students expressed concern that their vitamin D levels were too low. However, 72% participants reported that they had never been tested for vitamin D levels. Use of supplements was significantly higher among female students (F = 52% vs M = 37%; P = 0.003). Those who had been tested for vitamin D deficiency were more likely to take supplements. CONCLUSION: Despite being identified as a high-risk population, knowledge about vitamin D was limited among university students. Interventions are needed to increase awareness about the importance of vitamin D for health, including the need for exposure to sunlight and adequate dietary intake of vitamin D. Our study provides much needed baseline evidence for making health-policy recommendations for this vulnerable population group.

High-dose oral vitamin D supplementation and mortality in people aged 65-84 years: the VIDAL cluster feasibility RCT of open versus double-blind individual randomisation.

BACKGROUND: Randomised controlled trials demonstrating improved longevity are needed to justify high-dose vitamin D supplementation for older populations. OBJECTIVES: To demonstrate the feasibility of a large trial (n ≈ 20,000) of high-dose vitamin D in people aged 65-84 years through general practitioner (GP) practices, and to cluster randomise participating practices between open-label and double-blind randomisation to compare effects on recruitment, compliance and contamination. DESIGN: Twenty GP practices were randomised in matched pairs between open-label and double-blind allocation. Within each practice, patients were individually randomised to vitamin D or control (i.e. no treatment or placebo). Participants were invited to attend their GP practice to provide a blood sample and complete a lifestyle questionnaire at recruitment and again at 2 years. Randomisation by telephone followed receipt of a serum corrected calcium assay confirming eligibility (< 2.65 nmol/l). Treatment compliance was reported by quarterly follow-up forms sent and returned by e-mail or post (participant choice). GP visits and infections were abstracted from GP records. Hospital attendances, cancer diagnoses and deaths were ascertained by linkage to Hospital Episode Statistics and national registration through NHS Digital. SETTING: GP practices in England. PARTICIPANTS: Recruitment opened in October 2013 and closed in January 2015. A total of 1615 registered patients aged 65-84 years were randomised: 407 to vitamin D and 421 to no treatment in open practices; 395 to vitamin D and 392 to placebo in blind practices. INTERVENTIONS: There was a 24-month treatment period: 12 monthly doses (100,000 IU of vitamin D3 or placebo as 5 ml oily solution) were posted after randomisation and at 1 year (100,000 IU per month corresponds to 3300 IU per day). Reminders were sent monthly by e-mail, text message or post. MAIN OUTCOME MEASURES: Recruitment, compliance, contamination and change in circulating 25-hydroxyvitamin D [25(OH)D] from baseline to 2 years. RESULTS: Participation rates (randomised/invited) were 15.0% in open practices and 13.4% in double-blind practices (p = 0.7). The proportion still taking study medication at 2 years was 91.2% in open practices and 89.2% in double-blind practices (p = 0.4). The proportion of control participants taking > 400 IU vitamin D per day at 2 years was 5.0% in open practices and 4.8% in double-blind practices. Mean serum 25(OH)D concentration was 51.5 nmol/l [95% confidence interval (CI) 50.2 to 52.8 nmol/l] with 82.6% of participants < 75 nmol/l at baseline. At 2 years, this increased to 109.6 nmol/l (95% CI 107.1 to 112.1 nmol/l) with 12.0% < 75 nmol/l in those allocated to vitamin D and was unaltered at 51.8 nmol/l (95% CI 49.8 to 53.8 nmol/l) in those allocated to no vitamin D (no treatment or placebo). CONCLUSIONS: A trial could recruit 20,000 participants aged 65-84 years through 200 GP practices over 2 years. Approximately 80% would be expected to adhere to allocated treatment (vitamin D or placebo) for 5 years. The trial could be conducted entirely by e-mail in participants aged < 80 years, but some participants aged 80-84 years would require postal follow-up. Recruitment and treatment compliance would be similar and contamination (self-administration of vitamin D) would be minimal, whether control participants are randomised openly to no treatment with no contact during the trial or randomised double-blind to placebo with monthly reminders. TRIAL REGISTRATION: Current Controlled Trials ISRCTN46328341 and EudraCT database 2011-003699-34. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 10. See the NIHR Journals Library website for further project information.

High-dose vitamin D may reduce the risk of many diseases, but without large randomised controlled trials the evidence will remain inconclusive. We therefore proposed the Vitamin D and Longevity (VIDAL) trial, with 20,000 older people randomised to either no vitamin D medication or vitamin D medication for 5 years. The VIDAL feasibility study was conducted to establish the procedures required for the main trial, including assessment of recruitment, compliance (taking study treatment as directed) and contamination (how many control participants started taking vitamin D). This was done in two sets of general practitioner (GP) practices: (1) 'open' practices, in which participants knew their treatment allocation (2 years of 100,000 IU vitamin D monthly or no treatment), and (2) 'double-blind' practices, in which participants and their GPs did not know whether they were taking vitamin D or placebo oil. We invited 11,376 men and women aged 65­84 years from 20 GP practices in England and 1615 (14%) took part. Ninety per cent of participants allocated to monthly oil took it for 2 years and few participants used vitamin supplements outside the trial, with no marked differences between open-label and double-blind arms. The best way to conduct the main trial will therefore depend on other considerations. A double-blind trial provides reliable evidence on effects where reporting could be influenced by you or your doctor knowing your treatment, which is important for many illnesses and any side effects of treatment. However, any long-term effects are likely to be considerably greater if treatment continues instead of stopping after 5 years when the main trial ends. An open trial is easier to conduct and, when it ends, those taking vitamin D can be offered a continuing supply so that the effect of lifelong treatment can be studied for major diseases and life expectancy, which are unlikely to be affected by individuals knowing whether or not they are taking vitamin D.

Cost-effectiveness of denosumab for high-risk postmenopausal women with osteoporosis in Thailand.

Aims: This study assessed the cost-effectiveness of denosumab for treating postmenopausal women with osteoporosis (PMO) at high risk of fracture in Thailand.Materials and methods: A published Markov cohort cost-effectiveness model was populated with country-specific data as available and other published data as needed. The model used a societal perspective, lifetime horizon, efficacy data from network meta-analysis of trials, and included costs for direct medical and non-medical care, informal care, and osteoporosis treatments to compare denosumab to no pharmacologic treatment (calcium and vitamin D supplements only) and to oral weekly alendronate. The base case (high-risk population) included postmenopausal women with femoral neck T-score ≤-2.5, mean age 65 years at entry, and history of vertebral fracture.Results: High-risk women with osteoporosis using denosumab had the greatest number of life years and quality-adjusted life-years (QALYs) with higher reductions in hip and vertebral fracture incidence compared with patients with no pharmacologic treatment. The incremental cost-effectiveness ratio (ICER) was 119,575 Thai Baht (THB) per QALY for denosumab versus no pharmacologic treatment and 199,186 THB per QALY for denosumab versus alendronate. Among Thai postmenopausal women with high-risk of fractures, denosumab was cost-effective compared with no pharmacologic treatment at a willingness-to-pay threshold of 160,000 THB per QALY. One-way sensitivity analysis showed models were most sensitive to changes in denosumab pricing.Limitations: Data from other countries used when country-specific data were unavailable may not accurately reflect the true experience in Thailand. The model focused explicitly on hip, vertebral, and wrist fractures, and therefore provides a conservative estimate of the overall potential impact of osteoporosis-related fracture. The fracture risk was not adjusted to reflect potential changes in risk after denosumab treatment discontinuation.Conclusions: In Thailand, denosumab offers a cost-effective osteoporosis treatment option versus no pharmacologic treatment in postmenopausal women at high risk of fracture.

Vitamin D: can the sun stop the atopic epidemic?

PURPOSE OF REVIEW: To review recent evidence on the capacity of vitamin D to prevent atopic disease, focussing on food allergy and asthma, and potential underlying mechanisms. RECENT FINDINGS: The incidence of allergic disease continues to increase worldwide. Vitamin D status is influenced by sun exposure and dietary intake. Vitamin D deficiency is linked to an increased incidence of allergic disease and asthma. These associations are generally strongest in early life. The capacity of vitamin D to enhance antimicrobial pathways, promote peripheral immunological tolerance and maintain mucosal barrier integrity may underlie these associations. Interventional studies have addressed the capacity of vitamin D supplementation in utero and early life to reduce the incidence of disease. Ancillary studies have provided insights into potential biological mechanisms linked to these effects. SUMMARY: Observational studies show an inverse association between vitamin D levels and development of food allergy and asthma. Secondary analyses of two recent interventional studies suggest that achieving vitamin D sufficiency throughout pregnancy reduces the incidence of asthma/recurrent wheeze at 3 years. Longitudinal studies of vitamin D requirements in utero and postnatally, better understanding of factors that influence bioavailability of vitamin D and mechanistic insights into vitamin D effects on neonatal-specific immune pathways are awaited.

The value of routine laboratory screening in the neonatal intensive care unit.

BACKGROUND: Healthcare spending is expected to grow faster than the economy over the next decade, and the cost of prematurity increases annually. The aim of this study was to investigate the frequency of intervention after routine laboratory testing in preterm infants. METHODS: This was a retrospective study of preterm infants (≤34 weeks) admitted to the NYU Langone Health NICU from June 2013 to December 2014. Data collected included demographics, results of laboratory tests, and resulting interventions. Intervention after a hemogram was defined as a blood transfusion. Intervention after a hepatic panel was defined as initiation or termination of ursodiol or change in dose of vitamin D. Subjects were stratified into 3 groups based on gestation (<28 weeks, 28-31 6/7 weeks, 32-34 weeks). Chi-square analysis was used to compare the frequency of intervention between the groups. RESULTS: A total of 135 subjects were included in the study. The frequency of intervention after a hemogram was 8.4% in infants <28 weeks, 4.6% in infants 28-31 6/7 weeks, and 0% in infants 32-34 weeks; this difference was found to be statistically significant (p = 0.02). The frequency of intervention after a hepatic panel was 4.2% in infants <28 weeks, 5.7% in infants 28-31 6/7 weeks, and 0% in infants 32-34 weeks, which was not found to be a statistically significant different. CONCLUSION: No interventions were undertaken post-routine laboratory testing in any infant 32-34 weeks and routine testing in this population may be unnecessary. Further studies are needed to elucidate if routine testing affects neonatal outcomes.