ABSTRACT
Daily vitamin D supplementation using higher than normal dosing (up to the upper limit value) and intermittent (once or twice per week) dosing were studied in patients with increased risk of vitamin D deficiency. Using a PubMed database, a thorough search for published randomized controlled trials and other studies was conducted, and the results were analyzed. This review provides an overview of the use of 7000 IU daily, 30,000 IU per week or twice weekly, and 50,000 IU weekly of vitamin D for obtaining and maintaining 25(OH)D concentrations of at least 30 ng/mL in patients at high risk of vitamin D deficiency. The abovementioned dosages should be considered in adults with obesity, liver disease or malabsorption syndromes, or multi-diseased patients, mainly seniors requiring multi-drug treatment, including drugs affecting vitamin D metabolism. The simple schedules of 7000 IU/day, 30,000 IU/week or twice weekly, and 50,000 IU/week for use by patients with an increased risk of vitamin D deficiency were provided for consideration. Without monitoring of 25(OH)D, daily doses of 7000 IU or intermittent doses of 30,000 IU/week should be considered for a prolonged time as prophylactic or maintenance doses, mainly in obese patients, patients with liver disease and patients with malabsorption syndromes. For the treatment of possible vitamin D deficiency without assessment of 25(OH)D in these groups, intermittent doses of 30,000 IU twice weekly or 50,000 IU per week should be considered for a 6-8-week period only. The higher daily doses or the intermittent doses suggested above are effective, safe and responsive based on patient's preferences.
Subject(s)
Cholecalciferol , Dietary Supplements , Obesity , Vitamin D Deficiency , Humans , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/blood , Obesity/drug therapy , Cholecalciferol/administration & dosage , Cholecalciferol/therapeutic use , Vitamin D/administration & dosage , Vitamin D/blood , Vitamin D/analogs & derivatives , Drug Administration Schedule , Female , Male , Polypharmacy , Adult , AgedABSTRACT
Background: Apart from the well-established skeletal effects, vitamin D has been explored as a secretagogue influencing various adipokines, including adiponectin and irisin. Recent evidence suggests that specific forms of 25-Hydroxyvitamin D (25(OHD), such as free and bioavailable 25(OH)D, may provide more accurate measurements of vitamin D status. The relationship between vitamin D status and serum irisin and adiponectin concentrations remains largely unexplored, particularly during pregnancy. Methods: We analyzed data from 67 healthy maternal-neonatal pairs from Northern Greece at birth. Biochemical and hormonal tests were conducted on each maternal-neonatal pair. The vitamin D forms were estimated using validated mathematical models. Subsequently, regression analyses were conducted to determine the association between the vitamin D forms and adipokine levels. Results: Bioavailable maternal 25(OH)D was inversely associated with neonatal irisin concentrations [ß=-73.46 (-140.573 to -6.341), p=0.034]. No other associations were observed between maternal vitamin D status and neonatal adipokine concentrations. Conclusion: In conclusion, maternal bioavailable vitamin D concentrations are inversely associated with neonatal serum irisin concentrations, warranting further studies to evaluate the underlying mechanisms for this finding.
Subject(s)
Adiponectin , Fibronectins , Vitamin D , Humans , Fibronectins/blood , Female , Vitamin D/blood , Vitamin D/analogs & derivatives , Adiponectin/blood , Greece , Pregnancy , Infant, Newborn , Adult , MaleABSTRACT
OBJECTIVES: The role of vitamin D deficiency in cardiovascular disease (CVD) is controversial. Inherent biological and analytical limitations compromise the specificity of widely used 25-hydroxyvitamin D [25(OH)D] cut-offs. Simultaneous determination of 25(OH)D and 24,25-dihydroxyvitamin D [24,25(OH)2D] permits a functional assessment of vitamin D metabolism. The present study compared the associations of functional vitamin D deficiency and low vitamin D reservoirs with CVD mortality and CVD burden. METHODS: 25(OH)D, 24,25(OH)2D, the degree of coronary obstruction on angiography, high-sensitive cardiac troponin T (hs-cTnT), N-terminal brain natriuretic peptide (NT-proBNP), and 10-year CVD mortality were obtained from 2,456 participants of the LURIC (Ludwigshafen Risk and Cardiovascular Health) study. RESULTS: Neither low 25(OH)D concentrations nor functional vitamin D deficiency were associated with the number of atherosclerotic coronary arteries or the degree of coronary obstruction. Over a median follow-up of 9.9 years, 454 participants died (23.6â¯%) due to CVD. CVD mortality was doubled in individuals with 25(OH)D concentrations below the widely used cut-off for deficiency of <50â¯nmol/L [20â¯ng/mL] (21.6 vs. 11.5â¯%). In individuals with and without functional vitamin D deficiency, CVD mortality was 25.0 and 16.7â¯%, respectively. NT-proBNP and heart failure prevalence were also higher in vitamin D deficient individuals. CONCLUSIONS: Vitamin D deficient individuals have markedly higher CVD mortality, but only marginally higher hs-cTnT concentrations. A higher prevalence of heart failure and higher NT-proBNP concentrations suggest a link between vitamin D deficiency and cardiac function. The traditional and metabolic assessment of vitamin D status showed comparable associations for the different parameters of cardiac health.
ABSTRACT
Consensus statements can be very influential in medicine and public health. Some of these statements use systematic evidence synthesis but others fail on this front. Many consensus statements use panels of experts to deduce perceived consensus through Delphi processes. We argue that stacking of panel members toward one particular position or narrative is a major threat, especially in absence of systematic evidence review. Stacking may involve financial conflicts of interest, but nonfinancial conflicts of strong advocacy can also cause major bias. Given their emerging importance, we describe here how such consensus statements may be misleading, by analyzing in depth a recent high-impact Delphi consensus statement on COVID-19 recommendations as a case example. We demonstrate that many of the selected panel members and at least 35% of the core panel members had advocated toward COVID-19 elimination (Zero-COVID) during the pandemic and were leading members of aggressive advocacy groups. These advocacy conflicts were not declared in the Delphi consensus publication, with rare exceptions. Therefore, we propose that consensus statements should always require rigorous evidence synthesis and maximal transparency on potential biases toward advocacy or lobbyist groups to be valid. While advocacy can have many important functions, its biased impact on consensus panels should be carefully avoided.
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PURPOSE: Surgical therapy represents the first-line treatment for endogenous Cushing's syndrome (CS). While postoperative glucocorticoid replacement is mandatory after surgical remission, the role of perioperative glucocorticoid therapy is unclear. METHODS: We recruited patients with central or adrenal CS in whom curative surgery was planned and patients who underwent pituitary surgery for other reasons than CS as a control group. Patients did not receive any perioperative glucocorticoids until the morning of the first postoperative day. We performed blood samplings in the morning of surgery, immediately after surgery, in the evening of the day of surgery, and in the morning of the first and third postoperative day before any morning glucocorticoid intake. We continued clinical and biochemical monitoring during the following outpatient care. RESULTS: We recruited 12 patients with CS (seven with central CS, five with adrenal CS) and six patients without CS. In patients with CS, serum cortisol concentrations <5.0 µg/dL (<138 nmol/L) were detected in the morning of the first and third postoperative day in four (33%) and six (50%) patients, respectively. Morning serum cortisol concentrations on the third postoperative day were significantly lower when compared to preoperative measurements (8.5 ± 7.6 µg/dL vs. 19.9 ± 8.9 µg/dL [235 ± 210 nmol/L vs. 549 ± 246 nmol/L], p = 0.023). No patient developed clinical or biochemical signs associated with hypocortisolism. During follow-up, we first observed serum cortisol concentrations >5.0 µg/dL (>138 nmol/L) after 129 ± 97 days and glucocorticoids were discontinued after 402 ± 243 days. Patients without CS did not require glucocorticoid replacement at any time. CONCLUSION: Perioperative glucocorticoid replacement may be unnecessary in patients with central or adrenal CS undergoing curative surgery as first-line treatment.
Subject(s)
Cushing Syndrome , Glucocorticoids , Hydrocortisone , Humans , Cushing Syndrome/surgery , Cushing Syndrome/blood , Cushing Syndrome/drug therapy , Pilot Projects , Female , Male , Middle Aged , Adult , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Hydrocortisone/blood , Hormone Replacement Therapy/methods , Perioperative Care/methods , AgedABSTRACT
Background: In patients with stable chronic heart failure with a reduced ejection fraction (HFrEF), left ventricular ejection fraction (LVEF) provides limited prognostic value, especially in patients with moderately to severely reduced LVEF. Echocardiographic parameters of right ventricular function may be associated with adverse clinical events in these patients. Therefore, we analyzed 164 patients with HFrEF in a prospective single-center cohort study to evaluate whether the parameters of right ventricular function are associated with worsening heart failure (WHF) hospitalizations, cardiovascular and all-cause deaths and combined endpoints. Methods: Echocardiographic cine loops were analyzed using vendor-independent post-processing software. Multivariate Cox regression analyses were performed, which were then adjusted for clinical characteristics and left ventricular functional parameters. Results: In these models, higher tricuspid annular plane systolic excursion (TAPSE) was significantly associated with lower rates of WHF hospitalizations (HR 0.880, 95%CI 0.800-0.968, p = 0.008), a composite endpoint of WHF hospitalizations and cardiovascular death (HR 0.878, 95%CI 0.800-0.964, p = 0.006), and a composite endpoint of WHF hospitalization and all-cause death (HR 0.918, 95%CI 0.853-0.988, p = 0.023). These associations were more pronounced in patients with LVEF ≤ 35%. Conclusions: In conclusion, in patients with HFrEF, TAPSE is an independent prognosticator for adverse clinical outcomes, warranting further studies to elucidate whether incorporating TAPSE into established risk scores improves their diagnostic accuracy.
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AIMS: Chronic heart failure is associated with a bone-catabolic state and increases the risk of osteoporosis and fractures. Prospective studies investigating the clinical relevance of bone disease in heart failure are lacking. We aimed to assess the prevalence and prognostic impact of osteoporosis and vertebral fractures (VFs) in chronic heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: Symptomatic outpatients with chronic heart failure and a previous diagnosis of overtly reduced left ventricular ejection fraction < 40% on stable, optimal HFrEF therapy and left ventricular ejection fraction < 50% at enrolment were included into a prospective single-centre study. Osteoporosis was determined with dual-energy X-ray absorptiometry and defined as a T-score ≤ 2.5 at any site. VFs were assessed using X-ray of both thoracic and lumbar spine applying the semiquantitative Genant score. We enrolled 205 patients (22% women), with a median age of 66 (IQR 58-74) years. Median left ventricular ejection fraction was 37 (IQR 30-43) % and median N-terminal pro B-type natriuretic peptide was 964 (IQR 363-2173) pg/mL. Osteoporosis, as defined by bone mineral density, and at least one VF were prevalent in 31 (15%) and 29 patients (14%). Osteoporosis or VF were present in 55 patients (27%) and 5 patients (2%) had both osteoporosis and a VF. During a median follow-up of 4.7 (IQR 4.0-5.3) years, 18 patients (9%) died due to cardiovascular (CV) cause, and 46 patients (22%) had a worsening heart failure (WHF) hospitalization. In multivariate Cox regression analyses, presence of VF independently predicted CV death (HR 2.82, 95% CI 1.04-7.65, P = 0.042), WHF hospitalizations (HR 2.39, 95% CI 1.18-4.82, P = 0.015), and a composite endpoint of CV death and WHF hospitalizations (HR 2.44, 95% CI 1.23-4.82, P = 0.011). Osteoporosis was not significantly associated with CV events. CONCLUSIONS: In a prospective study, bone disease affected every fourth patient with HFrEF, and patients with VF at baseline had a two-fold risk of subsequent CV death or WHF hospitalization. Prevalent bone disease, particularly VF, should be considered as a clinically relevant comorbidity in HFrEF.
Subject(s)
Heart Failure , Stroke Volume , Humans , Female , Male , Heart Failure/physiopathology , Heart Failure/epidemiology , Heart Failure/complications , Stroke Volume/physiology , Prospective Studies , Prevalence , Aged , Prognosis , Middle Aged , Osteoporosis/epidemiology , Osteoporosis/physiopathology , Bone Density/physiology , Ventricular Function, Left/physiology , Follow-Up Studies , Absorptiometry, Photon , Risk Factors , Chronic DiseaseABSTRACT
Circulating 25-hydroxyvitamin D (25(OH)D) is the generally accepted indicator of vitamin D status. Since hydroxylation of 25(OH)D to 24-25-dihydroxyvitamin D (24,25(OH)2D) is the first step of its catabolism, it has been suggested that a low 24,25(OH)D level and a low vitamin D metabolite ratio (VMR), i.e., 24,25(OH)2D divided by 25(OH)D, may indicate high vitamin D requirements and provide additional diagnostic information beyond serum 25(OH)D. We, therefore, evaluated whether the classification of "functional vitamin D deficiency", i.e., 25(OH)D below 50 nmol/L, 24,25(OH)2D below 3 nmol/L and a VMR of less than 4%, identifies individuals who benefit from vitamin D supplementation. In participants of the Styrian Vitamin D Hypertension trial, a randomized controlled trial (RCT) in 200 hypertensive patients with serum 25(OH)D below 75 nmol/L, who received either 2.800 international units of vitamin D per day or placebo over 8 weeks, 51 participants had functional vitamin D deficiency. In these individuals, there was no treatment effect of vitamin D supplementation on various parameters of bone metabolism and cardiovascular risk except for a significant effect on parathyroid hormone (PTH) and expected changes in vitamin D metabolites. In conclusion, a low vitamin D metabolite profile did not identify individuals who significantly benefit from vitamin D supplementation with regard to bone markers and cardiovascular risk factors. The clinical significance of functional vitamin D deficiency requires further evaluation in large vitamin D RCTs.
Subject(s)
Hypertension , Vitamin D Deficiency , Humans , Vitamin D , Calcifediol , Vitamins/therapeutic use , Parathyroid Hormone , Hypertension/drug therapy , Dietary SupplementsABSTRACT
Vitamin D deficiency is considered a public health problem due to its worldwide high prevalence and adverse clinical consequences regarding musculoskeletal health. In addition, vitamin D may also be crucial for the prevention of certain extraskeletal diseases. Despite decades of intensive scientific research, several knowledge gaps remain regarding the precise definition of vitamin D deficiency and sufficiency, the health benefits of improving vitamin D status, and the required vitamin D intakes. Consequently, various societies and expert groups have released heterogeneous recommendations on the dosages for vitamin D supplementation. In this brief narrative review, we outline and discuss recent advances regarding the scientific evidence arguing for a daily vitamin D supplementation with 2000 international units (IU) (50 µg) of vitamin D3 to prevent and treat vitamin D deficiency. According to data from randomized controlled trials (RCTs), such a dose may improve some health outcomes and is sufficient to raise and maintain serum 25(OH)D concentrations above 50 nmol/L (20 ng/mL) and above 75 nmol/L (30 ng/mL) in >99% and >90% of the general adult population, respectively. According to large vitamin D RCTs, there are no significant safety concerns in supplementing such a dose for several years, even in individuals with an already sufficient vitamin D status at baseline. A daily vitamin D supplementation with 2000 IU (50 µg) may be considered a simple, effective, and safe dosage to prevent and treat vitamin D deficiency in the adult general population.
Subject(s)
Vitamin D Deficiency , Vitamin D , Adult , Humans , Dietary Supplements , Vitamins/therapeutic use , Cholecalciferol , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/prevention & controlABSTRACT
Sufficient vitamin D status is crucial for successful pregnancy and fetal development. The assessment of 25-hydroxyvitamin D (25(OH)D) concentrations is commonly used to evaluate vitamin D status. Our objective was to examine the interrelated biodynamics of maternal and neonatal total, free and bioavailable 25(OH)D in maternal-neonatal dyads at birth and their associations with homeostasis and neonatal birth anthropometry. We analysed a cohort of seventy full-term mother-child pairs. We found positive associations between all neonatal measures of vitamin D status. Maternal forms exhibited a similar pattern of association, except for the bioavailable maternal form. In multivariate analysis, both total and free maternal 25(OH)D concentrations were correlated with all neonatal forms (neonatal total 25(OH)D: 1·29 (95 % CI, 1·12, 1·46) for maternal total 25(OH)D, 10·89 (8·16, 13·63) for maternal free 25(OH)D), (neonatal free 25(OH)D: 0·15 for maternal total 25(OH)D, 1·28 (95 % CI, 0·89, 1·68) for maternal free 25(OH)D) and (0·13 (95 % CI, 0·10, 0·16), 1·06 (95 % CI, 0·68, 1·43) for maternal free 25(OH)D), respectively, with the exclusion of the bioavailable maternal form. We observed no significant interactions within or between groups regarding maternal and neonatal vitamin D parameters and maternal calcium and parathyroid hormone concentrations, and neonatal birth anthropometry. Our study indicates that bioavailable maternal and neonatal 25(OH)D have no significant effects on vitamin D equilibrium, Ca homeostasis and neonatal anthropometry at birth. However, we observed an interaction between maternal and neonatal total and free 25(OH)D concentrations at the maternal-neonatal interface, with no associations observed with other calciotropic or anthropometric outcomes.
Subject(s)
Calcium , Vitamin D Deficiency , Vitamin D/analogs & derivatives , Pregnancy , Infant, Newborn , Female , Humans , Calcifediol , Vitamins , Calcium, Dietary , Anthropometry , Mother-Child RelationsABSTRACT
INTRODUCTION: Evidence is limited on the effectiveness of a fourth vaccine dose against coronavirus disease 2019 (COVID-19) in populations with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We estimated the risk of COVID-19 deaths and SARS-CoV-2 infections according to vaccination status in previously infected individuals in Austria. METHODS: This is a nationwide retrospective observational study. We calculated age and gender adjusted Cox proportional hazard ratios (HRs) of COVID-19 deaths (primary outcome) and SARS-CoV-2 infections (secondary outcome) from 1 November to 31 December 2022, primarily comparing individuals with four versus three vaccine doses. Relative vaccine effectiveness (rVE) was calculated as (1-HR) X 100. RESULTS: Among 3,986,312 previously infected individuals, 281,291 (7,1%) had four and 1,545,242 (38.8%) had three vaccinations at baseline. We recorded 69 COVID-19 deaths and 89,056 SARS-CoV-2 infections. rVE for four versus three vaccine doses was -24% (95% CI: -120 to 30) against COVID-19 deaths, and 17% (95% CI: 14-19) against SARS-CoV-2 infections. This latter effect rapidly diminished over time and infection risk with four vaccinations was higher compared to less vaccinated individuals during extended follow-up until June 2023. Adjusted HR (95% CI) for all-cause mortality for four versus three vaccinations was 0.79 (0.74-0.85). DISCUSSION: In previously infected individuals, a fourth vaccination was not associated with COVID-19 death risk, but with transiently reduced risk of SARS-CoV-2 infections and reversal of this effect in longer follow-up. All-cause mortality data suggest healthy vaccinee bias.
Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Austria/epidemiology , SARS-CoV-2 , VaccinationABSTRACT
BACKGROUND: Determining serum 25-hydroxyvitamin D [25(OH)D], 24,25-dihydroxyvitamin D [24,25(OH)2D] and the vitamin D metabolite ratio (VMR) allows the identification of individuals with a low vitamin D metabolite profile. Here, we evaluated if such a functional approach provides superior diagnostic information to serum 25(OH)D alone. METHODS: 25(OH)D, 24,25(OH)2D, and the VMR were determined in participants of the DESIRE (Desirable Vitamin D Concentrations, n = 2010) and the LURIC (Ludwigshafen Risk and Cardiovascular Health, n = 2456) studies. A low vitamin D metabolite profile (vitamin D insufficiency) was defined by a 24,25(OH)2D concentration <1.2â ng/mL (<3â nmol/L) and a VMR <4%. Parathyroid hormone (PTH) and bone turnover markers were measured in both cohorts, whereas 10-year mortality data was recorded in LURIC only. RESULTS: The median age in DESIRE and LURIC was 43.3 and 63.8 years, respectively. Median 25(OH)D concentrations were 27.2â ng/mL (68.0â nmol/L) and 15.5â ng/mL (38.8â nmol/L), respectively. Serum 25(OH)D deficiency, defined as <20.2â ng/mL (<50â nmol/L), was present in 483 (24.0%) and 1701 (69.3%) participants of DESIRE and LURIC, respectively. In contrast, only 77 (3.8%) and 521 (21.2%) participants had a low vitamin D metabolite profile. Regardless of the serum 25(OH)D concentration, a low vitamin D metabolite profile was associated with a significantly higher PTH, accelerated bone metabolism, and higher all-cause mortality than an unremarkable vitamin D metabolite profile. CONCLUSIONS: The personalized assessment of vitamin D status using a functional approach better identifies patients with accelerated bone metabolism and increased mortality than the use of a fixed 25(OH)D cutoff of 20â ng/mL (50â nmol/L).
Subject(s)
Vitamin D Deficiency , Humans , Adult , Middle Aged , Vitamin D , Parathyroid HormoneABSTRACT
Primary aldosteronism (PA), characterized by inappropriately high concentrations of the adrenal-derived hormone aldosterone, is the most common endocrine cause of arterial hypertension. As compared with individuals with essential hypertension, patients with PA have a significantly increased cardiovascular risk that cannot be fully reversed by common antihypertensive treatment because of blood pressure-independent deleterious effects of aldosterone. Measurement of the aldosterone to renin ratio (ARR), reflecting the degree of aldosterone excess, is the classic screening test for PA, but thresholds for an elevated ARR vary substantially and are arbitrary, as there exists a wide disease continuum that spans from preclinical stages to overt PA. Treatment approaches for PA with either mineralocorticoid receptor antagonists for bilateral disease or unilateral adrenalectomy for aldosterone-producing adenomas (APA) are highly effective to mitigate the excess cardiovascular risk associated with PA. Subtype classification according to the dichotomous concept of unilateral PA, mainly due to APAs, vs bilateral PA, mainly due to bilateral adrenal hyperplasia, has been recently challenged by advances in the pathophysiologic understanding and therapeutic spectrum of PA. The implementation of current PA guidelines into clinical routine is extremely poor, as reflected by the fact that most patients suffering from PA remain undiagnosed and probably untreated. Pragmatic approaches are required to address this public health problem. In this review, we present an uptodate overview on the clinical significance, diagnosis, and treatment of PA, with the aim to provide guidance for clinicians regarding the management of this disease, paying particular attention to its feasible implementation into daily clinical routine.
Subject(s)
Hyperaldosteronism , Humans , Adrenalectomy , Adrenocortical Adenoma/complications , Aldosterone/adverse effects , Hyperaldosteronism/diagnosis , Hyperaldosteronism/therapy , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/etiologyABSTRACT
Hypothyroidism is a condition where the patient's thyroid gland cannot produce sufficient thyroid hormones (mainly triiodothyronine and thyroxine). The primary cause of hypothyroidism is autoimmune-mediated destruction of the thyroid gland, referred to as Hashimoto's thyroiditis. A patient's desired thyroid hormone concentration is achieved by oral administration of thyroid hormone, usually levothyroxine. Establishing individual levothyroxine doses to achieve desired thyroid hormone concentrations requires several patient visits. Additionally, clear guidance for the dosing regimen is lacking, and significant inter-individual differences exist. This study aims to design a digital automatic dosing algorithm for patients suffering from Hashimoto's thyroiditis. The dynamic behaviour of the relevant thyroid function is mathematically modelled. Methods of automatic control are exploited for the design of the proposed robust model-based levothyroxine dosing algorithm. Numerical simulations are performed to evaluate the mathematical model and the dosing algorithm. With the help of the developed controller thyroid hormone concentrations of patients, emulated using Thyrosim, have been regulated under the euthyroid state. The proposed concept demonstrates reliable responses amidst varying patient parameters. Our developed model provides a useful basis for the design of automatic levothyroxine dosing algorithms. The proposed robust feedback loop contributes to the first results for computer-assisted thyroid dosing algorithms.
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Accumulating evidence supports the potential protective effects of vitamin D against chronic diseases such as Alzheimer's disease, autoimmune diseases, cancers, cardiovascular disease (ischaemic heart disease and stroke), type 2 diabetes, hypertension, chronic kidney disease, stroke, and infectious diseases such as acute respiratory tract diseases, COVID-19, influenza, and pneumonia, as well as adverse pregnancy outcomes. The respective evidence is based on ecological and observational studies, randomized controlled trials, mechanistic studies, and Mendelian randomization studies. However, randomized controlled trials on vitamin D supplementation have largely failed to show benefits, probably due to poor design and analysis. In this work, we aim to use the best available evidence on the potential beneficial effects of vitamin D to estimate the expected reduction in incidence and mortality rates of vitamin D-related diseases in the Kingdom of Saudi Arabia and the United Arab Emirates if minimum serum 25(OH)D concentrations were to be raised to 30 ng/mL. Estimated reductions by 25% for myocardial infarction incidence, 35% for stroke incidence, 20 to 35% for cardiovascular disease mortality, and 35% for cancer mortality rates depicted a promising potential for raising serum 25(OH)D. Methods to increase serum 25(OH)D concentrations at the population level could include food fortification with vitamin D3, vitamin D supplementation, improved dietary vitamin D intake, and sensible sun exposure.
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Branched-chain amino acids (BCAAs) are effectors of metabolic diseases, but their impact on mortality is largely unknown. We investigated the association of BCAA with risk factors and mortality in 2,236 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study using linear and Cox regression. Adiponectin, hemoglobin, C-peptide, hemoglobin A1c, and homoarginine showed the strongest association with BCAA concentration (all p < 0.001). During a median follow-up of 10.5 years, 715 participants died, including 450 cardiovascular-related deaths. BCAA concentrations were inversely associated with the risk of all-cause and cardiovascular mortality (HR [95% CI] per 1-SD increase in log-BCAA: 0.75 [0.69-0.82] and 0.72 [0.65-0.80], respectively) after adjustment for potential confounders. BCAAs are directly associated with metabolic risk but inversely with mortality in persons with intermediate-to-high cardiovascular risk. Further studies are warranted to evaluate the diagnostic and therapeutic utility of BCAA in the context of cardiovascular diseases.
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Driveline infection is a frequent complication in recipients of durable left ventricular assist devices (LVAD), but its cause is largely unclear. Since vitamin D supplementation can reduce the risk of infections, we aimed at investigating the association of vitamin D deficiency with driveline infection. In 154 patients with continuous flow LVAD implants, we assessed 2-year risk of driveline infection according to vitamin D status (circulating 25-hydroxyvitamin D < 25 nmol/L or ⩾25 nmol/L). Of the study cohort, 34% (n = 53) had 25-hydroxyvitamin D concentrations <25 nmol/L. Kaplan-Meir estimates of 2-year freedom from driveline infection were in the vitamin D deficient and vitamin D non-deficient groups 49.7% and 74.2%, respectively (p = 0.017). Covariate-adjusted hazard ratio of driveline infection for the vitamin D deficient versus non-deficient group was 2.51 [95% CI: 1.11-5.69; p = 0.028). Circulating concentrations of endocrine regulators of calcium and phosphorus metabolism such as parathyroid hormone, 1,25-dihydroxyvitamin D, and fibroblast growth factor-23 were not significantly associated with the risk of driveline infection (p-values > 0.15). In total, our data indicate that in LVAD recipients deficient vitamin D status is a predictor of driveline infection, but future studies are needed to investigate whether these associations are causal.
Subject(s)
Heart Failure , Heart-Assist Devices , Prosthesis-Related Infections , Vitamin D Deficiency , Humans , Heart-Assist Devices/adverse effects , Vitamin D Deficiency/diagnosis , Vitamin D Deficiency/complications , Vitamin D , Heart Failure/complications , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/epidemiology , Prosthesis-Related Infections/etiologyABSTRACT
This work aims to investigate the structural, mechanical and electronic properties of four novel ß-type (100-x)(Ti-45Nb)-xGa alloys (x = 2, 4, 6, 8 wt%) for implant applications by means of experimental and theoretical (ab initio) methods. All alloys retain the bcc ß phase in the solution-treated and quenched state while the lattice parameter decreases with increase in Ga content. This is due to its smaller atomic radius compared to Ti and Nb, in line with the present density functional theory (DFT) calculations. Tensile and microhardness tests indicate a clear strengthening effect with increasing Ga content, with yield strengths in the range 551 ÷ 681 MPa and microhardness in the range 174 ÷ 232 HV0.1, mainly attributed to grain refinement and solid solution strengthening. Ga also positively affects ductility, with a maximum value of tensile strain at fracture of 32%. Non-destructive ultrasonic measurements and DFT calculations reveal that the bulk modulus is unaffected by the Ga presence. This phenomenon might be due to the fact that Ga introduced bonding and anti-bonding electron low energy states which balance the average bond strength among the atoms in the metallic matrix. Nevertheless, the introduction of new Ga-Ti super sp-like bonding orbitals along the [110] and [-110] directions in the Ga neighborhood could explain the increase of the Young's modulus upon Ga addition (73 ÷ 82.5 GPa) that was found experimentally in the present work. Hence, Ga addition to Ti-45Nb leads to a suitable balance between increased strength and low Young's modulus.
Subject(s)
Alloys , Titanium , Alloys/chemistry , Titanium/chemistry , Elastic Modulus , Prostheses and Implants , Tensile StrengthABSTRACT
Introduction: All epidemiological studies suggest that vitamin D deficiency is prevalent among the Polish general population. Since vitamin D deficiency was shown to be among the risk factors for many diseases and for all-cause mortality, concern about this problem led us to update the previous Polish recommendations. Methods: After reviewing the epidemiological evidence, case-control studies and randomized control trials (RCTs), a Polish multidisciplinary group formulated questions on the recommendations for prophylaxis and treatment of vitamin D deficiency both for the general population and for the risk groups of patients. The scientific evidence of pleiotropic effects of vitamin D as well as the results of panelists' voting were reviewed and discussed. Thirty-four authors representing different areas of expertise prepared position statements. The consensus group, representing eight Polish/international medical societies and eight national specialist consultants, prepared the final Polish recommendations. Results: Based on networking discussions, the ranges of total serum 25-hydroxyvitamin D concentration indicating vitamin D deficiency [<20 ng/mL (<50 nmol/L)], suboptimal status [20-30 ng/mL (50-75 nmol/L)], and optimal concentration [30-50 ng/mL (75-125 nmol/L)] were confirmed. Practical guidelines for cholecalciferol (vitamin D3) as the first choice for prophylaxis and treatment of vitamin D deficiency were developed. Calcifediol dosing as the second choice for preventing and treating vitamin D deficiency was introduced. Conclusions: Improving the vitamin D status of the general population and treatment of risk groups of patients must be again announced as healthcare policy to reduce a risk of spectrum of diseases. This paper offers consensus statements on prophylaxis and treatment strategies for vitamin D deficiency in Poland.
Subject(s)
Dietary Supplements , Vitamin D Deficiency , Humans , Poland/epidemiology , Vitamin D , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/prevention & control , Vitamins , Cholecalciferol , CalcifediolABSTRACT
PURPOSE: The upper tolerable intake level for vitamin D in the general population has been set at 4000 international units (IU) daily, but considerable uncertainty remains. We summarized reported harmful effects of a daily vitamin D supplement of 3200-4000 IU in trials lasting ≥ 6 months. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials in several databases and identified 22 trials reporting safety data. Parameters of calcium metabolism, falls, hospitalization, and mortality were assessed. RESULTS: The selected trials comprised a total number of 12,952 participants. All trials used supplemental vitamin D3. The relative risk (RR) of hypercalcemia in the vitamin D vs. control arm was 2.21 (95%CI: 1.26-3.87; 10 studies), with a vitamin D-induced frequency of hypercalcemia of 4 cases per 1000 individuals. Subgroup analysis in trials with > 100 and ≤ 100 study participants revealed an RR of 2.63 (95%CI: 1.30-5.30; 7 studies) and 0.80 (95%CI: 0.24-2.62; 3 studies), respectively (Pinteraction = 0.06). Risks of falls and hospitalization were also significantly increased in the vitamin D arm with an RR of 1.25 (95%CI: 1.01-1.55; 4 studies) and 1.16 (95%CI: 1.01-1.33; 7 studies), respectively. Risks of hypercalciuria, kidney stones, and mortality did not differ significantly between study arms. Quality assessment revealed high risk of incomplete reporting of safety-related outcome data. CONCLUSION: Supplemental vitamin D doses of 3200-4000 IU/d appear to increase the risk of hypercalcemia and some other adverse events in a small proportion of individuals, indicating that this dose is not completely safe. In future studies, rigorous reporting of safety-related outcomes is needed when using moderately high doses of vitamin D.