Individual participant data (IPD)-level meta-analysis of randomised controlled trials with vitamin D-fortified foods to estimate Dietary Reference Values for vitamin D.

CONTEXT AND PURPOSE: Individual participant data-level meta-regression (IPD) analysis is superior to meta-regression based on aggregate data in determining Dietary Reference Values (DRV) for vitamin D. Using data from randomized controlled trials (RCTs) with vitamin D3-fortified foods, we undertook an IPD analysis of the response of winter serum 25-hydroxyvitamin (25(OH)D) to total vitamin D intake among children and adults and derived DRV for vitamin D. METHODS: IPD analysis using data from 1429 participants (ages 2-89 years) in 11 RCTs with vitamin D-fortified foods identified via a systematic review and predefined eligibility criteria. Outcome measures were vitamin D DRV estimates across a range of serum 25(OH)D thresholds using unadjusted and adjusted models. RESULTS: Our IPD-derived estimates of vitamin D intakes required to maintain 97.5% of winter 25(OH)D concentrations ≥ 25 and ≥ 30 nmol/L are 6 and 12 µg/day, respectively (unadjusted model). The intake estimates to maintain 90%, 95% and 97.5% of concentrations ≥ 50 nmol/L are 33.4, 57.5 and 92.3 µg/day, respectively (unadjusted) and 17.0, 28.1 and 43.6 µg/day, respectively (adjusted for mean values for baseline serum 25(OH)D, age and BMI). CONCLUSIONS: IPD-derived vitamin D intakes required to maintain 90%, 95% and 97.5% of winter 25(OH)D concentrations ≥ 50 nmol/L are much higher than those derived from standard meta-regression based on aggregate data, due to the inability of the latter to capture between person-variability. Our IPD provides further evidence that using food-based approaches to achieve an intake of 12 µg/day could prevent vitamin D deficiency (i.e., serum 25(OH)D < 30 nmol/L) in the general population.

Large-Scale Telemedicine Implementation for Outpatient Clinicians: Results From a Pandemic-Adapted Learning Collaborative.

Learning collaboratives are seldom used outside of health care quality improvement. We describe a condensed, 10-week learning collaborative ("Telemedicine Hack") that facilitated telemedicine implementation for outpatient clinicians early in the COVID-19 pandemic. Live attendance averaged 1688 participants per session. Of 1005 baseline survey respondents, 57% were clinicians with one-third identifying as from a racial/ethnic minoritized group. Practice characteristics included primary care (71%), rural settings (51%), and community health centers (28%). Of three surveys, a high of 438 (81%) of 540 clinicians had billed ≥1 video-based telemedicine visit. Our learning collaborative "sprint" is a promising model for scaling knowledge during emergencies and addressing health inequities.

Mushroom data creation, curation, and simulation to support classification tasks.

Predicting if a set of mushrooms is edible or not corresponds to the task of classifying them into two groups-edible or poisonous-on the basis of a classification rule. To support this binary task, we have collected the largest and most comprehensive attribute based data available. In this work, we detail the creation, curation and simulation of a data set for binary classification. Thanks to natural language processing, the primary data are based on a text book for mushroom identification and contain 173 species from 23 families. While the secondary data comprise simulated or hypothetical entries that are structurally comparable to the 1987 data, it serves as pilot data for classification tasks. We evaluated different machine learning algorithms, namely, naive Bayes, logistic regression, and linear discriminant analysis (LDA), and random forests (RF). We found that the RF provided the best results with a five-fold Cross-Validation accuracy and F2-score of 1.0 ([Formula: see text], [Formula: see text]), respectively. The results of our pilot are conclusive and indicate that our data were not linearly separable. Unlike the 1987 data which showed good results using a linear decision boundary with the LDA. Our data set contains 23 families and is the largest available. We further provide a fully reproducible workflow and provide the data under the FAIR principles.

Examining Treatment Patterns and Real-World Outcomes in Chronic Lymphocytic Leukemia Using Administrative Data in Ontario.

Information on the real-world experience of Canadians diagnosed with chronic lymphocytic leukemia (CLL) is limited. This study was conducted to report treatment patterns and outcomes of CLL using Ontario administrative data. A retrospective cohort study was conducted in patients diagnosed with CLL between 1 January 2010 and 31 December 2017 identified in the Ontario Cancer Registry (OCR). Data were accessed using the Institute of Clinical Evaluative Sciences (ICES), which collects various population-level health information. In the Ontario Cancer Registry, 2887 CLL patients receiving treatment and diagnosed between 2010-2017 were identified. Fludarabine, cyclophosphamide and rituximab (FCR) chemoimmunotherapy was most frequently used as a first line, but use declined since ibrutinib and obinutuzumab combinations were funded in 2015. In patients treated with frontline FCR, survival at year one was 89% pre-2015 and 96% post-2015; at year four, survival was 73% and 87%, respectively. Survival in patients treated with frontline chlorambucil was 76% pre-2015 and 75% post-2015 in year 1, and 45% and 56% in year 3. Our analysis shows that, as the treatment landscape for CLL has shifted, use of newer and novel agents as a first line or earlier in the relapsed/refractory setting has resulted in improved survival outcomes.

Intrathecal narcotic infusion pumps for intractable pain of chronic pancreatitis: a pilot series.

OBJECTIVES: The aim of this study was to evaluate the efficacy of intrathecal narcotics pump (ITNP) as an alternative treatment for patients with pain from chronic pancreatitis (CP). ITNP offers the advantages of reversibility, lower total narcotic dose, and the pancreas remaining intact. METHODS: Thirteen patients (8 female, 5 male), with mean age 40.6 years (s.d. 9.6 years), who had experienced intractable upper abdominal pain from CP were reviewed. Each patient had multiple other failed treatment modalities, including partial pancreatic resection (n = 6). They were offered ITNP after a successful intraspinal opioid trial. Etiologies of CP included idiopathy (n = 3), cystic fibrosis (n = 2), alcohol (n = 2), and pancreas divisum (n = 6). RESULTS: The median duration of severe, intractable pain prior to ITNP was 6 years (2-22 years). The median follow-up time after ITNP was 29 months (range, 7-94 months). The ITNP was in situ for a mean duration of 29 months (range, 0.5-94 months). Seven patients had pump exchange or removal for various reasons; improvement of pain at month 53 (n = 1), meningitis (n = 1), meningitis with subsequent replacement (n = 1), pump failure at month 31, 68, 79, and 84 (n = 4). There were no deaths. The mean pain score prior to implantation (score = 8.3, s.d. = 0.9) was significantly higher than 1 year after (score = 2.7, s.d. = 1.9) (P < 0.01) and last follow-up (score = 0.75, s.d. = 2.1) (P < 0.01). The median oral narcotic dose before and 1 year after ITNP were morphine sulfate equivalents 337.5 mg per day (range, 67.5-1,320) and 40 mg per day (range, 0-1,680), respectively (P < 0.01). Two patients were considered failures, as they still require a high dosage of both oral and intrathecal medications to control their pain, despite significant pain-score improvement. One patient who was excluded due to meningitis was also considered a failure. Therefore, the overall success rate of ITNP based on an intention-to-treat analysis was 76.9% (10/13). The major complications of ITNP were central nervous system infection requiring pump removal (n = 1), cerebrospinal fluid leak requiring laminectomy (n = 1), and perispinal abscess with bacterial meningitis requiring pump removal (n = 1). CONCLUSIONS: This study shows the many risks and benefits of ITNP. A longer follow-up is awaited; such pumps appear to be one alternative to aggressive surgical intervention. Failed ITNP trials leave other options open. Therapeutic trials directly comparing pancreatectomy, ITNP, and implanted nerve stimulators are of interest.

The bioavailability of vitamin D from fortified cheeses and supplements is equivalent in adults.

There is a need to increase the options for vitamin D fortification. We have developed a method to fortify hard cheese with vitamin D. Our aim was to characterize the bioavailability of vitamin D from fortified cheeses. Eighty adults were randomized to weekly servings of fortified cheddar cheese (DC) (34 g; n = 20); fortified low-fat cheese (DLF) (41 g; n = 10); liquid vitamin D supplement (1 mL), taken with food (DS+) (n = 20) or without food (DS-) (n = 10); placebo cheddar cheese (n = 10); or placebo supplement (n = 10). The treatments contained 28,000 IU cholecalciferol (vitamin D3), equivalent to 4000 IU (100 microg/d). The primary outcome was the comparison of vitamin D bioavailability, as measured by the serum 25-hydroxyvitamin D [25(OH)D] response, between fortified cheeses and supplement. In the placebo groups, initial 25(OH)D, 55.0 +/- 25.3 nmol/L, declined over the 8-wk winter protocol, to 50.7 +/- 24.2 nmol/L (P = 0.046). In the vitamin D-treated groups, the mean increases in 25(OH)D over 8 wk were: 65.3 +/- 24.1 (DC), 69.4 +/- 21.7 (DLF), 59.3 +/- 23.3 (DS+), and 59.3 +/- 19.6 nmol/L (DS-); these changes differed from the placebo groups (P < 0.0001) but not from one another (P = 0.62). Compared with baseline, serum parathyroid hormone decreased with both fortification (P = 0.003) and supplementation (P = 0.012). These data demonstrate that vitamin D is equally bioavailable from fortified hard cheeses and supplements, making cheese suitable for vitamin D fortification.

Low wintertime vitamin D levels in a sample of healthy young adults of diverse ancestry living in the Toronto area: associations with vitamin D intake and skin pigmentation.

BACKGROUND: Vitamin D plays a critical role in bone metabolism and many cellular and immunological processes. Recent research indicates that concentrations of serum 25-hydroxyvitamin D [25(OH)D], the main indicator of vitamin D status, should be in excess of 75 nmol/L. Low levels of 25(OH)D have been associated with several chronic and infectious diseases. Previous studies have reported that many otherwise healthy adults of European ancestry living in Canada have low vitamin D concentrations during the wintertime. However, those of non-European ancestry are at a higher risk of having low vitamin D levels. The main goal of this study was to examine the vitamin D status and vitamin D intake of young Canadian adults of diverse ancestry during the winter months. METHODS: One hundred and seven (107) healthy young adults self-reporting their ancestry were recruited for this study. Each participant was tested for serum 25(OH)D concentrations and related biochemistry, skin pigmentation indices and basic anthropometric measures. A seven-day food diary was used to assess their vitamin D intake. An ANOVA was used to test for significant differences in the variables among groups of different ancestry. Linear regression was employed to assess the impact of relevant variables on serum 25(OH)D concentrations. RESULTS: More than 93% of the total sample had concentrations below 75 nmol/L. Almost three-quarters of the subjects had concentrations below 50 nmol/L. There were significant differences in serum 25(OH)D levels (p < 0.001) and vitamin D intake (p = 0.034) between population groups. Only the European group had a mean vitamin D intake exceeding the current Recommended Adequate Intake (RAI = 200 IU/day). Total vitamin D intake (from diet and supplements) was significantly associated with 25(OH)D levels (p < 0.001). Skin pigmentation, assessed by measuring skin melanin content, showed an inverse relationship with serum 25(OH)D (p = 0.033). CONCLUSION: We observe that low vitamin D levels are more prevalent in our sample of young healthy adults than previously reported, particularly amongst those of non-European ancestry. Major factors influencing 25(OH)D levels were vitamin D intake and skin pigmentation. These data suggest a need to increase vitamin D intake either through improved fortification and/or supplementation.

US organ donation breakthrough collaborative increases organ donation.

More than 92000 Americans are on waiting lists for organ transplants, and an average of 17 of them die each day while waiting. The US Organ Donation Breakthrough Collaborative (ODBC), which began in 2003 at the request of the Secretary of the US Department of Health and Human Services, was a formal, concerted effort of the donation and transplantation community to bring about a major change to improve the organ donation system. The nationwide Collaborative was housed within a Health and Human Services agency, the Health Resources and Services Administration (HRSA) Division of Transplantation, and included participation of the organ procurement organizations (OPOs) throughout the United States and the American hospitals with the largest organ-donor potential. HRSA leaders used the Breakthrough Series Collaborative method, originally developed by the Institute for Healthcare Improvement, as the model for the intervention. Expert practitioners drawn from hospitals and OPOs that had already demonstrated their ability to achieve and sustain high organ donation rates were chosen as faculty for the collaborative and best practices were gleaned from their institutions. The number of organ donors in Collaborative hospitals increased 14.1% in the first year, a 70% greater increase than the 8.3% increase experienced by non-Collaborative hospitals. Moreover, the increased organ recovery continued into the post-Collaborative periods. Between October 2003 and September 2006, the number of total US organ donors increased 22.5%, an increase 4-fold greater than the 5.5% increase measured over the same number of years in the immediate pre-Collaborative period. The study did not involve a randomized design, but time-series analysis using statistical process control charts shows a highly significant discontinuity in the rate of increase in participating hospitals concurrent with the Collaborative program, and strongly suggests that the activities of the Collaborative were a major contributor to this increase. Given the stable nature of the historical increases over many years, the HRSA estimates that more than 4000 annual additional transplants have occurred in association and apparently as a result of these increases in organ donation.

microRNAs and DICER1 are regulated by 1,25-dihydroxyvitamin D in prostate stroma.

Vitamin D deficiency increases the risk of lethal prostate adenocarcinomas (PCa) and the majority of older men are deficient. Although PCa arises from the epithelium, the surrounding stroma has hormonal regulatory control over the epithelium and contributes to carcinogenesis. Herein, we describe regulation of microRNAs (miRs) by the active hormone dihydroxyvitamin D (1,25(OH)2D) in human prostate stroma. 1,25(OH)2D binds the vitamin D receptor (VDR) transcription factor to regulate gene expression, including miRs, which have emerged as potent regulators of protein expression. 1,25(OH)2D-regulated miRs were identified by profiling in primary human prostatic stromal cells (PrS) and three miRs, miR-126-3p, miR 154-5p and miR-21-5p were subsequently validated in laser-capture micro-dissected prostate stromal tissue from a vitamin D3 clinical trial (N=45). Regulation of these miRs by 1,25(OH)2D was VDR-dependent. Network analysis of known and putative mRNA targets of these miRs was enriched with cancer and inflammation pathways, consistent with known roles of stroma and of vitamin D in carcinogenesis. Expression of the miR processing ribonuclease, DICER1, positively correlated with vitamin D metabolite levels in the clinical trial specimens. High epithelial/stromal ratios of DICER1 were significantly associated biochemical recurrence (OR 3.1, p=0.03) in a tissue microarray of 170 matched PCa patients. In summary, these results underscore the role of the prostate stroma in regulating responses to the hormone 1,25(OH)2D and identified miRs and DICER1 as being regulated in human prostate stroma. Regulation of stromal DICER1 by 1,25(OH)2D may also have clinical relevance in protection against aggressive PCa.

Differential expression and regulation of vitamin D hydroxylases and inflammatory genes in prostate stroma and epithelium by 1,25-dihydroxyvitamin D in men with prostate cancer and an in vitro model.

Previous work on vitamin D in the prostate has focused on the prostatic epithelium, from which prostate cancer arises. Prostatic epithelial cells are surrounded by stroma, which has well-established regulatory control over epithelial proliferation, differentiation, and the inflammatory response. Here we examined the regulation of vitamin D-related genes and inflammatory genes by 1α,25-dihydroxyvitamin D3 (1,25(OH)2D) in laser-capture microdissected prostate tissue from a vitamin D3 clinical trial and in an in vitro model that facilitates stromal-epithelial crosstalk. Analysis of the trial tissues showed that VDR was present in both cell types, whereas expression of the hydroxylases was the highest in the epithelium. Examination of gene expression by prostatic (1,25(OH)2D) concentrations showed that VDR was significantly lower in prostate tissues with the highest concentration of 1,25(OH)2D, and down-regulation of VDR by 1,25(OH) 2D was confirmed in the primary cell cultures. Analysis of inflammatory genes in the patient tissues revealed that IL-6 expression was the highest in the prostate stroma while PTGS2 (COX2) levels were lowest in the prostate cancer tissues from men in the highest tertile of prostatic 1,25(OH)2D. In vitro, TNF-α, IL-6 and IL-8 were suppressed by 1,25 (OH)2D in the primary epithelial cells, whereas TNF-α and PTGS2 were suppressed by 1,25(OH) 2D in the stromal cells. Importantly, the ability of 1,25(OH)2D to alter pro-inflammatory-induced changes in epithelial cell growth were dependent on the presence of the stromal cells. In summary, whereas both stromal and epithelial cells of the prostate express VDR and can presumably respond to 1,25(OH)2D, the prostatic epithelium appears to be the main producer of 1,25(OH)2D. Further, while the prostate epithelium was more responsive to the anti-inflammatory activity of 1,25 (OH)2D than stromal cells, stroma-epithelial crosstalk enhanced the phenotypic effects of 1,25(OH)2D and the inflammatory process in the prostate gland.

Quality of life after bilateral thoracoscopic splanchnicectomy: long-term evaluation in patients with chronic pancreatitis.

We prospectively evaluated quality of life and visual analogue scale pain scores after bilateral thoracoscopic splanchnicectomy in 55 patients with small-duct chronic pancreatitis and abdominal pain. The perioperative morbidity rate was 11% and there were no perioperative deaths. Four late deaths occurred (7%), and three patients were lost to follow-up. Patients were divided into those who had prior operative or endoscopic interventions (N = 38) and those who did not (N = 17). Preoperatively there were no significant differences between the two groups with regard to age, sex, etiology, pain score, or narcotic use. Pain score, narcotic use, and symptoms scales improved significantly in both groups at 3 and 6 months postoperatively (P < 0.0001). The group with no prior surgical or endoscopic intervention did significantly better initially (P < 0.007), and the improvements in their quality-of-life and pain scores continued for the remainder of the study. In contrast, quality-of-life and pain scores in patients who had undergone prior surgical or endoscopic intervention returned to baseline by 12 months postoperatively and remained poor throughout the remainder of the study. Bilateral thoracoscopic splanchnicectomy appears to work best in patients who have had no prior operative or endoscopic interventions.

An overview of measurement activities in the partnership for patients.

The Partnership for Patients, launched in April 2011, is a national quality improvement initiative from the Department of Health and Human Services that has set ambitious goals for U.S. providers to improve patient safety and care transitions. This paper outlines the initiative's measurement strategy, describing four measurement-related objectives: (1) to track national progress toward the program goals that U.S. hospitals reduce preventable adverse events by 40% and readmissions by 20%; (2) to support local quality improvement measurement in participating hospitals by providing the appropriate tools, training, and programmatic structure; (3) to obtain feedback on hospital and contractor progress, in close to real time, so the project can be effectively managed; and (4) to evaluate the program's impact on adverse event and readmission rates.

Tumor suppressor microRNAs, miR-100 and -125b, are regulated by 1,25-dihydroxyvitamin D in primary prostate cells and in patient tissue.

MiR-100 and miR-125b are lost in many cancers and have potential function as tumor suppressors. Using both primary prostatic epithelial cultures and laser capture-microdissected prostate epithelium from 45 patients enrolled in a vitamin D3 randomized trial, we identified miR-100 and -125b as targets of 1,25-dihydroxyvitamin D3 (1,25D). In patients, miR-100 and -125b levels were significantly lower in tumor tissue than in benign prostate. Similarly, miR-100 and -125b were lower in primary prostate cancer cells than in cells derived from benign prostate. Prostatic concentrations of 1,25D positively correlated with these miRNA levels in both prostate cancer and benign epithelium, showing that patients with prostate cancer may still benefit from vitamin D3. In cell assays, upregulation of these miRNAs by 1,25D was vitamin D receptor dependent. Transfection of pre-miR-100 and pre-miR-125b in the presence or absence of 1,25D decreased invasiveness of cancer cell, RWPE-2. Pre-miR-100 and pre-miR-125b decreased proliferation in primary cells and cancer cells respectively. Pre-miR-125b transfection suppressed migration and clonal growth of prostate cancer cells, whereas knockdown of miR-125b in normal cells increased migration indicates a tumor suppressor function. 1,25D suppressed expression of previously bona fide mRNA targets of these miRNAs, E2F3 and Plk1, in a miRNA-dependent manner. Together, these findings show that vitamin D3 supplementation augments tumor suppressive miRNAs in patient prostate tissue, providing evidence that miRNAs could be key physiologic mediators of vitamin D3 activity in prevention and early treatment of prostate cancer.

Randomized clinical trial of vitamin D3 doses on prostatic vitamin D metabolite levels and ki67 labeling in prostate cancer patients.

CONTEXT: Vitamin D3 might benefit prostate cancer (PCa) patients because prostate cells can locally synthesize the active hormone calcitriol. OBJECTIVE: Our objective was to determine the effects of oral vitamin D3 on vitamin D metabolites and PCa proliferative activity in prostate tissue. DESIGN AND SETTING: We conducted a double-blind randomized clinical trial at surgical oncology clinics in Toronto, Canada. PATIENTS: PCa patients (Gleason 6 or 7) participated in the study. Of 66 subjects who were enrolled, 63 completed the dosing protocol. INTERVENTION: Vitamin D3 (400, 10 000, or 40 000 IU/d) was orally administered before radical prostatectomy. MAIN OUTCOME MEASURES: We evaluated vitamin D metabolite levels and Ki67 labeling in surgical prostate tissue. Safety measures, PTH, and prostate-specific antigen (PSA) were also assessed. RESULTS: Prostate tissue and serum levels of vitamin D metabolites, including calcitriol, increased dose dependently (P < .03) and were significantly higher in the 40 000-IU/d group than in every other dose group (P < .03). Prostate vitamin D metabolites correlated positively with serum levels (P < .0001). Ki67 measures did not differ significantly among vitamin D dose groups. However, cross-sectional analysis indicated that the calcitriol level attained in prostate was inversely associated with Ki67 intensity and Ki67 (3+) percent positive nuclei in PCa and benign tissue (P < .05). Safety measures did not change adversely with dosing. Compared with the 400-IU/d group, serum PTH and PSA were lower in the combined higher-dose groups at the end of the study (P < .02). CONCLUSIONS: Oral vitamin D3 raised prostate calcitriol levels (level 1 evidence) and modestly lowered both PSA and PTH. Although Ki67 expression did not differ among dose groups, its levels correlated inversely with prostate calcitriol. These suggestions of clinical benefit justify continued clinical research.

Determination of 1,25-dihydroxyvitamin D concentrations in human colon tissues and matched serum samples.

BACKGROUND: A novel method to measure 1,25-dihydroxyvitamin D (1,25(OH)(2)D) in human tissue was developed and validated. The objectives of this study were to determine whether 1,25(OH)(2)D is present in human colon tissue and to characterize the relationship between human colon tissue and serum 1,25(OH)(2)D concentrations. MATERIALS AND METHODS: Normal colon tissue specimens and matched serum samples were obtained from 30 patients who had undergone colectomy. Colon 1,25(OH)(2)D was measured by lipid extraction followed by enzyme immunoassay (EIA). Serum 1,25(OH)(2)D and 25-hydroxyvitamin D (25(OH)D) were measured by EIA. Vitamin D binding protein (DBP) was measured in a subset of serum and tissue samples. RESULTS: Regression analysis indicated a significant positive correlation between serum and colon 1,25(OH)(2)D concentrations (r=0.58, p=0.0008). The corresponding intercept at zero serum 1,25(OH)(2)D was 21.5 pmol/kg (95% CI=16.95-25.98; p<0.001). Colon 1,25(OH)(2)D did not correlate significantly with serum 25(OH)D. DBP levels in tissue samples were negligible. CONCLUSION: The hormone 1,25(OH)(2)D can be successfully detected in human colon at physiologically relevant concentrations, partly determined by serum 1,25(OH)(2)D. The results support the notion of in vivo synthesis of 1,25(OH)(2)D within colon tissues.

The ratio of serum 24,25-dihydroxyvitamin D(3) to 25-hydroxyvitamin D(3) is predictive of 25-hydroxyvitamin D(3) response to vitamin D(3) supplementation.

24,25-Dihydroxyvitamin D (24,25VD) is a major catabolite of 25-hydroxyvitamin D (25VD) metabolism, and may be physiologically active. Our objectives were to: (1) characterize the response of serum 24,25VD(3) to vitamin D(3) (VD(3)) supplementation; (2) test the hypothesis that a higher 24,25VD(3) to 25VD(3) ratio (24,25:25VD(3)) predicts 25VD(3) response. Serum samples (n=160) from wk 2 and wk 6 of a placebo-controlled, randomized clinical trial of VD(3) (28,000IU/wk) were analyzed for serum 24,25VD(3) and 25VD(3) by mass spectrometry. Serum 24,25VD(3) was highly correlated with 25VD(3) in placebo- and VD(3)-treated subjects at each time point (p<0.0001). At wk 2, the 24,25:25VD(3) ratio was lower with VD(3) than with placebo (p=0.035). From wk 2 to wk 6, the 24,25:25VD(3) ratio increased with the VD(3) supplement (p<0.001) but not with placebo, such that at wk 6 this ratio did not significantly differ between groups. After correcting for potential confounders, we found that 24,25:25VD(3) at wk 2 was inversely correlated to the 25VD(3) increment by wk 6 in the supplemented group (r=-0.32, p=0.02) but not the controls. There is a strong correlation between 24,25VD(3) and 25VD(3) that is only modestly affected by VD(3) supplementation. This indicates that the catabolism of 25VD(3) to 24,25VD(3) rises with increasing 25VD(3). Furthermore, the initial ratio of serum 24,25VD(3) to 25VD(3) predicted the increase in 25VD(3). The 24,25:25VD(3) ratio may therefore have clinical utility as a marker for VD(3) catabolism and a predictor of serum 25VD(3) response to VD(3) supplementation.

An evaluation of automated methods for measurement of serum 25-hydroxyvitamin D.

OBJECTIVES: To compare two new automated assays with the well-established reference method, DiaSorin radioimmunoassay (RIA), for quantitation of serum total 25-hydroxyvitamin D [25(OH)D]. METHODS: 25(OH)D from human sera (n=158) was measured using DiaSorin RIA and two automated platforms, DiaSorin "LIAISON 25 OH Vitamin D TOTAL", and Roche Modular "Vitamin D3 (25-OH)". Methods were compared by regression and Bland-Altman analyses. RESULTS: DiaSorin LIAISON demonstrated a stronger correlation (r=0.918) and better agreement (bias=-0.88 nmol/L) with DiaSorin RIA than the Roche Modular assay (r=0.871, bias=-2.55 nmol/L). Precision ranges (CV%) for the RIA, LIAISON, and Roche Modular assays, respectively, were: within run (6.8-12.9%, 2.8-8.1%, and 1.9-5.5%), and total precision (7.4-14.5%, 7.3-17.5%, and 7.6-14.5%). CONCLUSION: DiaSorin LIAISON displayed the best correlation and agreement with DiaSorin RIA. The DiaSorin LIAISON 25 OH Vitamin D TOTAL assay is an accurate and precise automated tool for serum total 25(OH)D determination.