This study analyzed the relationship between baseline serum 25-hydroxyvitamin D (25-(OH)D) concentration and risk of major clinical disease events in 1621 older white adults over a median 11-year follow up period. The composite primary outcome included hip fracture, myocardial infarction, incident cancer, and death. Results showed the association between low 25-(OH)D and risk of the composite outcome varied by season. A 25-(OH)D concentration lower than season-specific Z-scores of -0.54 was associated with a 24% higher risk and corresponded to concentrations of 43, 50, 61, and 55 nmol/L in winter, spring, summer and autumn respectively. The study suggests season-specific 25
- Lowering LDL-C has traditionally been the goal for preventing atherosclerotic cardiovascular disease (ASCVD), but controversy exists regarding whether LDL-C is the best lipid biomarker.
- Research shows that other biomarkers like non-HDL-C and apolipoprotein B (apoB) better predict ASCVD risk, with apoB being superior to non-HDL-C.
- For rural primary care settings without advanced laboratories, non-HDL-C is recommended for evaluating ASCVD risk since it is universally available, low cost, and does not require fasting.
Glycation plays a role as risk factor in Alzheimer’s Disease (AD) and D-ribose is one of the important contributors to protein glycation.
Here, we recruited 93 participants (49 AD patients, 44 cognitively normal participants) and measured their cognitive abilities with
Mini-Mental State Examination (MMSE), D-ribose and formaldehyde levels in the morning urine. Urine D-ribose levels of AD patients
(especially women) were signifi cantly higher than those of cognitively normal participants. Like formaldehyde, D-ribose levels were
negatively correlated with MMSE scores in all participants. Unlike formaldehyde, D-ribose levels still showed the negative correlation in
cognitively normal participants. These data may provide a novel clue to study AD.
This study investigated hypocalcemia in patients with acute gastroenteritis at Liaquat University Hospital in Hyderabad, Pakistan. The study included 66 patients with acute gastroenteritis and 66 healthy control subjects. The mean serum calcium level was significantly lower in patients with acute gastroenteritis (6.8455 ± 1.8266 mg/dL) compared to the control group (9.2167 ± 0.4534 mg/dL). Hypocalcemia was observed in 62 (94%) of gastroenteritis patients but only 13 (20%) of controls. The results demonstrated that low serum calcium or hypocalcemia is common in patients with acute gastroenteritis.
A predictive model to reduce allogenic transfusions in primary total hip arth...anemo_site
This document presents a predictive model to reduce allogenic blood transfusions in primary total hip arthroplasty patients. The authors developed a model to predict bleeding and subsequent anemia based on age, gender, and pre-operative hemoglobin levels using data from 580 patients. Statistical analysis showed that post-operative hemoglobin levels were significantly associated with gender, age, and pre-operative hemoglobin concentration. The predictive model estimates expected post-operative hemoglobin differences compared to a threshold of 10 g/dL based on patient characteristics to help guide transfusion decisions. The goal is to ensure adequate hemoglobin levels to reduce risks and speed rehabilitation while minimizing unnecessary transfusions.
Clinical Validation of a Noninvasive, Raman Spectroscopic Method to Assess Ca...MarkLongstaff
This study aimed to validate a noninvasive Raman spectroscopy method for measuring carotenoid levels in human skin by comparing it to the established serum carotenoid measurements using HPLC. 372 healthy adults provided 3 blood samples and 3 Raman spectroscopy skin measurements over an 8 day period. A strong positive correlation of 0.81 was observed between total serum carotenoids measured by HPLC and total skin carotenoids measured by Raman spectroscopy. The Raman spectroscopy method also exhibited less intra-individual variability than the HPLC serum measurements. Therefore, Raman spectroscopy is a valid and reliable noninvasive technique for assessing human carotenoid nutritional status.
1. A randomized trial compared restrictive (transfuse if Hb <7 g/dL) vs liberal (transfuse if Hb <9 g/dL) transfusion strategies in critically ill cancer patients with septic shock.
2. At 28 days, all-cause mortality was not significantly different between groups. However, at 90 days mortality was significantly higher in the restrictive group.
3. Secondary outcomes including ventilation, renal replacement therapy, inotropes, and length of stay showed no significant differences.
4. The results suggest a liberal transfusion strategy may be preferable for critically ill cancer patients with septic shock, as a restrictive strategy was associated with higher 90-day mortality.
How to Survive in Paris? - Presentation of month MOTIS project / 31.01.13Anastasya Azarova
This document outlines a student project to create a guidebook for new students on how to survive in Paris. It includes an overview of objectives, team member profiles, roles and responsibilities, activities, and a project plan. The team of 5 students from various countries and educational backgrounds aims to help future students by developing both print and digital guidebooks. They identify risks like time management and use tools like setting ground rules and regular meetings to manage the project successfully.
This document appears to be part of an English learning game or application that presents lessons on numbers, vocabulary words, images and sentences to choose the correct words. Each lesson screen shows some numbers in English, images or objects to identify, and sentences with missing or incorrect words to replace. The document provides content for at least 4 lessons to help users learn English vocabulary, numbers and grammar through interactive exercises.
- Lowering LDL-C has traditionally been the goal for preventing atherosclerotic cardiovascular disease (ASCVD), but controversy exists regarding whether LDL-C is the best lipid biomarker.
- Research shows that other biomarkers like non-HDL-C and apolipoprotein B (apoB) better predict ASCVD risk, with apoB being superior to non-HDL-C.
- For rural primary care settings without advanced laboratories, non-HDL-C is recommended for evaluating ASCVD risk since it is universally available, low cost, and does not require fasting.
Glycation plays a role as risk factor in Alzheimer’s Disease (AD) and D-ribose is one of the important contributors to protein glycation.
Here, we recruited 93 participants (49 AD patients, 44 cognitively normal participants) and measured their cognitive abilities with
Mini-Mental State Examination (MMSE), D-ribose and formaldehyde levels in the morning urine. Urine D-ribose levels of AD patients
(especially women) were signifi cantly higher than those of cognitively normal participants. Like formaldehyde, D-ribose levels were
negatively correlated with MMSE scores in all participants. Unlike formaldehyde, D-ribose levels still showed the negative correlation in
cognitively normal participants. These data may provide a novel clue to study AD.
This study investigated hypocalcemia in patients with acute gastroenteritis at Liaquat University Hospital in Hyderabad, Pakistan. The study included 66 patients with acute gastroenteritis and 66 healthy control subjects. The mean serum calcium level was significantly lower in patients with acute gastroenteritis (6.8455 ± 1.8266 mg/dL) compared to the control group (9.2167 ± 0.4534 mg/dL). Hypocalcemia was observed in 62 (94%) of gastroenteritis patients but only 13 (20%) of controls. The results demonstrated that low serum calcium or hypocalcemia is common in patients with acute gastroenteritis.
A predictive model to reduce allogenic transfusions in primary total hip arth...anemo_site
This document presents a predictive model to reduce allogenic blood transfusions in primary total hip arthroplasty patients. The authors developed a model to predict bleeding and subsequent anemia based on age, gender, and pre-operative hemoglobin levels using data from 580 patients. Statistical analysis showed that post-operative hemoglobin levels were significantly associated with gender, age, and pre-operative hemoglobin concentration. The predictive model estimates expected post-operative hemoglobin differences compared to a threshold of 10 g/dL based on patient characteristics to help guide transfusion decisions. The goal is to ensure adequate hemoglobin levels to reduce risks and speed rehabilitation while minimizing unnecessary transfusions.
Clinical Validation of a Noninvasive, Raman Spectroscopic Method to Assess Ca...MarkLongstaff
This study aimed to validate a noninvasive Raman spectroscopy method for measuring carotenoid levels in human skin by comparing it to the established serum carotenoid measurements using HPLC. 372 healthy adults provided 3 blood samples and 3 Raman spectroscopy skin measurements over an 8 day period. A strong positive correlation of 0.81 was observed between total serum carotenoids measured by HPLC and total skin carotenoids measured by Raman spectroscopy. The Raman spectroscopy method also exhibited less intra-individual variability than the HPLC serum measurements. Therefore, Raman spectroscopy is a valid and reliable noninvasive technique for assessing human carotenoid nutritional status.
1. A randomized trial compared restrictive (transfuse if Hb <7 g/dL) vs liberal (transfuse if Hb <9 g/dL) transfusion strategies in critically ill cancer patients with septic shock.
2. At 28 days, all-cause mortality was not significantly different between groups. However, at 90 days mortality was significantly higher in the restrictive group.
3. Secondary outcomes including ventilation, renal replacement therapy, inotropes, and length of stay showed no significant differences.
4. The results suggest a liberal transfusion strategy may be preferable for critically ill cancer patients with septic shock, as a restrictive strategy was associated with higher 90-day mortality.
How to Survive in Paris? - Presentation of month MOTIS project / 31.01.13Anastasya Azarova
This document outlines a student project to create a guidebook for new students on how to survive in Paris. It includes an overview of objectives, team member profiles, roles and responsibilities, activities, and a project plan. The team of 5 students from various countries and educational backgrounds aims to help future students by developing both print and digital guidebooks. They identify risks like time management and use tools like setting ground rules and regular meetings to manage the project successfully.
This document appears to be part of an English learning game or application that presents lessons on numbers, vocabulary words, images and sentences to choose the correct words. Each lesson screen shows some numbers in English, images or objects to identify, and sentences with missing or incorrect words to replace. The document provides content for at least 4 lessons to help users learn English vocabulary, numbers and grammar through interactive exercises.
This document contains instructions and questions for a final examination for an English for Early Childhood Education course. It is divided into two sections - Section A contains 6 short answer questions assessing language learning theories, teaching methods, teacher roles, and child development. Section B contains 2 essay questions asking students to list children's songs and provide input to make them comprehensible for different learning styles, and to write a detailed lesson plan teaching one of the songs. The examination is 3 hours long and candidates are not allowed to bring unauthorized items into the exam hall.
The Actor Network Theory, which is one of the indispensable tools of Project Management, was implemented by ANT's team in Android Application Technology. Over a course of one short summer month of June team members tried to attain the principle objectives.
The document provides tips for landscape photography. It recommends shooting early in the morning or late afternoon to take advantage of good light. It also suggests using the rule of thirds for composition by dividing the frame into thirds and placing subjects at the intersection points. Additionally, the document advises using a circular polarizing filter to reduce glare and increase color and saturation. It also notes that using a small aperture can increase depth of field but may require slower shutter speeds and a tripod.
This document discusses cloud computing, including its definition, evolution over time, present development among companies, related domains, advantages and disadvantages, and future predictions. It provides a timeline of cloud computing from the 1960s to present day. The key advantages listed are lower costs, unlimited storage, easy access and integration. Disadvantages include security risks, lack of standardization, and compliance issues. The future of cloud computing is predicted to include personal clouds replacing personal computers by 2014 and growth of software as a service (SaaS) and platform as a service (PaaS) offerings.
Este documento presenta una propuesta metodológica para trabajar la obra "El Principito" de Antoine de Saint-Exupéry con alumnos de 3o primaria a través de tres sesiones. La primera se centrará en presentar la historia y hacer reflexionar a los alumnos. La segunda incluirá ejercicios sobre comprensión lectora. Y la tercera repasará contenidos gramaticales utilizando fragmentos del libro. El objetivo es que los niños analicen los temas profundos del libro y mejoren su comprensión y
The document discusses vitamin D, its production, metabolism, and biological functions. It notes that vitamin D acts more like a hormone than a vitamin, as it is synthesized in one part of the body, transported through the bloodstream, and exerts effects in distant tissues by binding to receptors. The document also summarizes several studies that found associations between low vitamin D levels and increased risks of various diseases such as colorectal cancer, metabolic syndrome, and type 2 diabetes.
Effects of raising vit D levels on birth complications
"Differences by race/ethnicity were not statistically significant when 25(OH)D concentration was included as a covariate in multivariable regression analysis."
The document summarizes evidence on preventing falls in older adults through vitamin D supplementation. It finds that vitamin D supplementation reduces falls by 13-23% and that higher doses (700-1000 IU) achieving serum levels over 24 ng/mL and active forms of vitamin D are most effective. A meta-analysis of randomized controlled trials found vitamin D significantly reduced falls, especially in those getting sufficient vitamin D or using active forms. Risk factors for falls like impairments in balance, vision and strength can be addressed through vitamin D supplementation.
—Chronic patients of spinal cord injury has been detected severe reduction of bone density. Patients with SCI show mostly osteopenia or osteoporosis of the hip and spine. Vitamin D deficiency may contribute to development of osteoporosis in SCI. So a study was conducted on 100 chronic SCI patients to find out status of correlation of Vitamine D and bone mineral density (BMD). Blood samples were collected and investigated routine biochemistry with serum 25(OH)D. DXA scan of hip and spine was also done. This study observed that 55% patients had suboptimal vitamin D. Positive correlation was found between vitamin D & bone mineral density. It is concluded from this study that monitoring of Serum 25(OH)D levels and annual surveillance of bone mineral density is crucial among persons with chronic SCI to reduce progression of osteoporosis and minimize the risk for further fractures. Keywords: 25(OH)D: 25 Hydroxy Vitamin D, DXA: Dual Energy X-Ray Absorptiometry, BMD: Bone Mineral Density.
Article Type: Editorial
Title: Challenges Met by Healthcare Professionals (Nurses) at the time of Covid-19 Pandemic
Year: 2021; Volume: 1; Issue: 2; Page No: 3 – 4
Author: Sumathi Senthilvel
DOI: 10.55349/ijmsnr.20211234
Affiliation: Associate Editor, IJMSNR, Formerly Assistant Professor in Nursing, Department of Fundamental Nursing, Amrita College of Nursing. Ponekkara, Kochi, Kerala. Email ID: AssociateEditor@ijmsnr.com
Article Summary: Submitted : 26-October-2021
Revised : 10-November-2021
Accepted : 02-December-2021
Published : 31-December-2021
This document contains instructions and questions for a final examination for an English for Early Childhood Education course. It is divided into two sections - Section A contains 6 short answer questions assessing language learning theories, teaching methods, teacher roles, and child development. Section B contains 2 essay questions asking students to list children's songs and provide input to make them comprehensible for different learning styles, and to write a detailed lesson plan teaching one of the songs. The examination is 3 hours long and candidates are not allowed to bring unauthorized items into the exam hall.
The Actor Network Theory, which is one of the indispensable tools of Project Management, was implemented by ANT's team in Android Application Technology. Over a course of one short summer month of June team members tried to attain the principle objectives.
The document provides tips for landscape photography. It recommends shooting early in the morning or late afternoon to take advantage of good light. It also suggests using the rule of thirds for composition by dividing the frame into thirds and placing subjects at the intersection points. Additionally, the document advises using a circular polarizing filter to reduce glare and increase color and saturation. It also notes that using a small aperture can increase depth of field but may require slower shutter speeds and a tripod.
This document discusses cloud computing, including its definition, evolution over time, present development among companies, related domains, advantages and disadvantages, and future predictions. It provides a timeline of cloud computing from the 1960s to present day. The key advantages listed are lower costs, unlimited storage, easy access and integration. Disadvantages include security risks, lack of standardization, and compliance issues. The future of cloud computing is predicted to include personal clouds replacing personal computers by 2014 and growth of software as a service (SaaS) and platform as a service (PaaS) offerings.
Este documento presenta una propuesta metodológica para trabajar la obra "El Principito" de Antoine de Saint-Exupéry con alumnos de 3o primaria a través de tres sesiones. La primera se centrará en presentar la historia y hacer reflexionar a los alumnos. La segunda incluirá ejercicios sobre comprensión lectora. Y la tercera repasará contenidos gramaticales utilizando fragmentos del libro. El objetivo es que los niños analicen los temas profundos del libro y mejoren su comprensión y
The document discusses vitamin D, its production, metabolism, and biological functions. It notes that vitamin D acts more like a hormone than a vitamin, as it is synthesized in one part of the body, transported through the bloodstream, and exerts effects in distant tissues by binding to receptors. The document also summarizes several studies that found associations between low vitamin D levels and increased risks of various diseases such as colorectal cancer, metabolic syndrome, and type 2 diabetes.
Effects of raising vit D levels on birth complications
"Differences by race/ethnicity were not statistically significant when 25(OH)D concentration was included as a covariate in multivariable regression analysis."
The document summarizes evidence on preventing falls in older adults through vitamin D supplementation. It finds that vitamin D supplementation reduces falls by 13-23% and that higher doses (700-1000 IU) achieving serum levels over 24 ng/mL and active forms of vitamin D are most effective. A meta-analysis of randomized controlled trials found vitamin D significantly reduced falls, especially in those getting sufficient vitamin D or using active forms. Risk factors for falls like impairments in balance, vision and strength can be addressed through vitamin D supplementation.
—Chronic patients of spinal cord injury has been detected severe reduction of bone density. Patients with SCI show mostly osteopenia or osteoporosis of the hip and spine. Vitamin D deficiency may contribute to development of osteoporosis in SCI. So a study was conducted on 100 chronic SCI patients to find out status of correlation of Vitamine D and bone mineral density (BMD). Blood samples were collected and investigated routine biochemistry with serum 25(OH)D. DXA scan of hip and spine was also done. This study observed that 55% patients had suboptimal vitamin D. Positive correlation was found between vitamin D & bone mineral density. It is concluded from this study that monitoring of Serum 25(OH)D levels and annual surveillance of bone mineral density is crucial among persons with chronic SCI to reduce progression of osteoporosis and minimize the risk for further fractures. Keywords: 25(OH)D: 25 Hydroxy Vitamin D, DXA: Dual Energy X-Ray Absorptiometry, BMD: Bone Mineral Density.
Article Type: Editorial
Title: Challenges Met by Healthcare Professionals (Nurses) at the time of Covid-19 Pandemic
Year: 2021; Volume: 1; Issue: 2; Page No: 3 – 4
Author: Sumathi Senthilvel
DOI: 10.55349/ijmsnr.20211234
Affiliation: Associate Editor, IJMSNR, Formerly Assistant Professor in Nursing, Department of Fundamental Nursing, Amrita College of Nursing. Ponekkara, Kochi, Kerala. Email ID: AssociateEditor@ijmsnr.com
Article Summary: Submitted : 26-October-2021
Revised : 10-November-2021
Accepted : 02-December-2021
Published : 31-December-2021
Background: Diabetic Retinopathy is a non-communicable disease and metabolic disorder. It is a public health problem in Worldwide. In this paper, finding influencing factors and how much probability to development of DR among known T2DM patients.
Materials and Methods: This was a hospital-based cross-sectional and observational study among T2DM patients, with and without DR in the diabetes clinic with sample of 150 patients. Statistical analysis used chi-square and binary logistic regression analysis was used to identify correlates of DR after controlling of confounders.
Results: In this present study, among 150 patients, 39 (26%) patients had DR. Smoking habit was strongly associated with development of DR (AOR=15.39, p=0.002), patients had history of hypertension was associated with DR (AOR=1.10, p=0.016), medication, in that insulin users were strongly associated with DR (AOR=5.72, p=0.002), duration of diabetes mellitus with >10 years was associated with DR (AOR=1.18, p=0.001), total cholesterol with abnormal was 5-fold more increase in risk with the development of DR (AOR=5.86, p=0.065) but not significant, high hba1c with >6.5% was associated with the progression of DR (AOR=1.34, p=0.035), and fasting blood sugar with abnormal was associated with the progression of DR (AOR=1.01, p=0.027) except age but, showed positive association with DR. Probability of developing DR in a T2DM patient was 98%.
Conclusion: From this study, we revealed that influencing variables were hba1c, smoking habit, intake of tablet/insulin, duration of DM, history of hypertension and fasting blood sugar. The chance/probability of developing retinopathy was very high among known diabetes patients those who had longer duration of DM. Hence, we have recommended a periodic eye screening is mandatory in T2DM patients.
Keywords: diabetes mellitus, diabetic retinopathy, influencing factors, probability, multivariate analysis
The study evaluated 47 female SLE patients to determine if low vitamin D levels were associated with cardiovascular risk factors and subclinical atherosclerosis. 61.7% of patients were vitamin D deficient, with mean levels of 31.91 nmol/l. Patients taking calcium and vitamin D supplements had significantly higher vitamin D levels than those not taking supplements. Higher vitamin D levels were positively correlated with increased arterial stiffness measures, and patients taking supplements showed increased arterial stiffness. The findings suggest calcium and vitamin D supplementation may increase arterial stiffness in SLE patients.
Raccomandazioni della iof (international osteoporosis foundation) sull’impieg...Merqurio
This position paper from the International Osteoporosis Foundation makes recommendations for vitamin D intake in older adults. Based on randomized controlled trials, daily vitamin D intake of 20-25 μg (800-1000 IU) is estimated to achieve a target serum 25OHD level of 75 nmol/L (30 ng/ml), which is associated with reduced risk of falls and fractures. Higher daily intakes may be needed for those with risk factors like obesity, limited sun exposure, or malabsorption. Doses above 20 μg/day have not been thoroughly evaluated, so higher intakes cannot be generally recommended at this time.
This document summarizes a large systematic review and meta-analysis examining the relationship between vitamin D levels and supplementation on mortality outcomes. The review included over 900,000 participants from observational studies and 30,000 participants from randomized controlled trials. The results indicate an inverse association between circulating vitamin D levels and risk of death from all causes, particularly cardiovascular disease and cancer. Vitamin D3 supplementation was also found to reduce overall mortality among older adults compared to placebo. However, the authors note that more research is still needed to determine optimal dosing strategies before widespread supplementation recommendations can be made.
1) The study examined the impact of maternal vitamin D status on fetal skeletal development through 3D ultrasound measurements in 424 pregnant women.
2) It found that suboptimal maternal vitamin D status was associated with increased femur cross-sectional area and splaying in utero, resembling characteristics of rickets.
3) This suggests that maternal vitamin D insufficiency could influence fetal skeletal development and morphology early in gestation, though future studies are still needed to establish causality.
1) The study examined the impact of maternal vitamin D status on fetal skeletal development through 3D ultrasound measurements in 424 pregnant women.
2) It found that suboptimal maternal vitamin D status was associated with increased femur cross-sectional area and splaying in utero, resembling signs of rickets.
3) This suggests that ensuring optimal maternal vitamin D levels during pregnancy may be important for proper fetal skeletal development.
Study on achievement of target LDC-C in Dyslipidimic patientspharmaindexing
This study analyzed 80 dyslipidemic patients to assess achievement of target LDL-C levels as recommended by ATP III guidelines. The majority of patients had high LDL-C levels and were receiving statin therapy. Based on risk factors, patients were categorized as CHD, high risk non-CHD, or low risk non-CHD. Only 22.5% of patients achieved their target LDL-C levels, which was unsatisfactory. More aggressive lipid management is needed to help more patients reach targets through interventions like pharmacist counseling and medication adjustments.
The document discusses vitamin D levels and deficiencies. It notes that over a billion people worldwide have inadequate vitamin D levels. Studies in Saudi Arabia show vitamin D deficiency rates as high as 99%, with more recent studies finding rates of 62.65% in females and 40.6% in males. There is lack of agreement on what constitutes deficient vitamin D levels, and different assays can produce varying results. The document argues for a consensus on vitamin D level standards to guide patient care and alleviate concerns.
ABSTRACTBackground Obesity is associated with vitamin D ins.docxransayo
ABSTRACT
Background: Obesity is associated with vitamin D insufficiency
and secondary hyperparathyroidism.
Objective: This study assessed whether obesity alters the cuta-
neous production of vitamin D3 (cholecalciferol) or the intestinal
absorption of vitamin D2 (ergocalciferol).
Design: Healthy, white, obese [body mass index (BMI; in kg/m2)
≥ 30] and matched lean control subjects (BMI ≤ 25) received
either whole-body ultraviolet radiation or a pharmacologic dose
of vitamin D2 orally.
Results: Obese subjects had significantly lower basal 25-
hydroxyvitamin D concentrations and higher parathyroid hor-
mone concentrations than did age-matched control subjects.
Evaluation of blood vitamin D3 concentrations 24 h after
whole-body irradiation showed that the incremental increase
in vitamin D3 was 57% lower in obese than in nonobese sub-
jects. The content of the vitamin D3 precursor 7-dehydrocho-
lesterol in the skin of obese and nonobese subjects did not dif-
fer significantly between groups nor did its conversion to
previtamin D3 after irradiation in vitro. The obese and
nonobese subjects received an oral dose of 50 000 IU (1.25
mg) vitamin D2. BMI was inversely correlated with serum
vitamin D3 concentrations after irradiation (r = �0.55,
P = 0.003) and with peak serum vitamin D2 concentrations
after vitamin D2 intake (r = �0.56, P = 0.007).
Conclusions: Obesity-associated vitamin D insufficiency is
likely due to the decreased bioavailability of vitamin D3 from
cutaneous and dietary sources because of its deposition in body
fat compartments. Am J Clin Nutr 2000;72:690–3.
KEY WORDS Vitamin D, ultraviolet radiation, tanning bed,
obesity, 25-hydroxyvitamin D, parathyroid hormone, obesity,
vitamin D3, sunlight, obesity, 25-hydroxyvitamin D3, bioavailability
INTRODUCTION
Obese individuals, as a group, have low plasma concentra-
tions of 25-hydroxyvitamin D [25(OH)D] (1–5), which are asso-
ciated with increased plasma concentrations of immunoreactive
parathyroid hormone (1, 6, 7). Although the explanation for the
increased risk of vitamin D deficiency in obesity is unknown, it
has been postulated that obese individuals may avoid exposure to
solar ultraviolet (UV) radiation, which is indispensable for the
cutaneous synthesis of vitamin D3 (3). Alternatively, it has been
proposed that production of the active vitamin D metabolite
1,25-dihydroxyvitamin D [1,25(OH)2D] is enhanced and thus, its
higher concentrations exert negative feedback control on the
hepatic synthesis of 25(OH)D (1). It has also been suggested that
the metabolic clearance of vitamin D may increase in obesity,
possibly with enhanced uptake by adipose tissue (2).
Clarification of the mechanism for the subnormal concentra-
tions of 25(OH)D in obesity is nevertheless relevant for the man-
agement of this highly prevalent condition. If, for example, the
increased risk of vitamin D deficiency were the expression of a
lack of exposure to sunlight, it would perhaps be only of acade-
mic in.
This document discusses vitamin D, beginning with an overview that while vitamin D is called a vitamin, it acts more like a hormone in the body. It describes how vitamin D is synthesized in the skin and transported to tissues where its active form binds to receptors. It then summarizes several roles and physiological functions of vitamin D related to calcium homeostasis, bone and muscle health, and potential extraskeletal effects. Finally, it provides details on vitamin D production, metabolism, and biological function, showing how vitamin D is converted to its active form in the body and its role in various health processes.
This study assessed the link between season of birth, neonatal vitamin D status measured from dried blood samples, and later life cardiovascular disease risk in 284 Swedish subjects. The results showed that subjects born in winter had lower neonatal vitamin D levels than those born in summer. Higher neonatal vitamin D levels were associated with higher fasting insulin, triglycerides, and cholesterol in adult women, as well as higher risk of overweight. However, neonatal vitamin D levels did not correlate with other adult cardiovascular risk factors like blood pressure and glucose. This suggests that lower vitamin D status at birth may influence later metabolic health outcomes but not other risk factors for cardiovascular disease.
A Randomized Trial of Vitamin D Supplementation on Vascular Function in CKD, ...Moh'd sharshir
Vitamin D deficiency is common in CKD patients and linked to increased cardiovascular disease risk. This study found that cholecalciferol supplementation in nondiabetic CKD patients with vitamin D deficiency significantly improved brachial artery flow-mediated dilation and pulse wave velocity, markers of endothelial function and arterial stiffness respectively, over 16 weeks. Biomarkers of endothelial function, inflammation, and vascular calcification also improved. These results provide evidence that correcting vitamin D deficiency reduces cardiovascular risk in CKD patients.
Vitamin D is an important prohormone for optimal intestinal calcium absorption for mineralization of bone. Because the vitamin D receptor is present in multiple tissues, there has been interest in evaluating other potential functions of vitamin D, particularly, in cardiovascular diseases (CVD). Cross-sectional studies have reported that vitamin D deficiency is associated with increased risk of CVD, including hypertension, heart failure, and ischemic heart disease. Initial prospective studies have also demonstrated that vitamin D deficiency increases the risk of developing incident hypertension or sudden cardiac death in individuals with preexisting CVD. Very few prospective clinical studies have been conducted to examine the effect of vitamin D supplementation on cardiovascular outcomes. The mechanism for how vitamin D may improve CVD outcomes remains obscure; however, potential hypotheses include the downregulation of the renin-angiotensin-aldosterone system, direct effects on the heart, and vasculature or improvement of glycemic control. This review will examine the epidemiologic and clinical evidence for vitamin D deficiency as a cardiovascular risk factor and explore potential mechanisms for the cardioprotective effect of vitamin D.
Our backs are like superheroes, holding us up and helping us move around. But sometimes, even superheroes can get hurt. That’s where slip discs come in.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
2. (OH)D targets are highly controversial—the Institute of
Medicine (IOM) recently recommended a threshold of 50
nmol/L (20 ng/mL), substantially less than the 75-nmol/L
(30-ng/mL) threshold recommended by other professional
societies and expert panels (1, 12–15).
The goal of this study was to examine the relationship
of serum 25-(OH)D concentration to vitamin D in terms
of risk for major clinical disease events of global pathophys-
iologic relevance, focusing on threshold concentrations as-
sociated with disease risk.
METHODS
Study Population
The CHS (Cardiovascular Health Study) is a prospec-
tive, community-based cohort study designed to examine
risk factors for the development and progression of cardio-
vascular disease in people aged 65 years or older (21). Par-
ticipants were recruited from 4 U.S. communities: Forsyth
County, North Carolina; Sacramento County, California;
Washington County, Maryland; and Pittsburgh, Pennsyl-
vania. Eligible participants were sampled by using Medi-
care eligibility lists, were not institutionalized, and were
expected to remain in the area for at least 3 years. Persons
who were wheelchair-bound in the home or receiving hos-
pice treatment, radiation therapy, or chemotherapy were
excluded. The original CHS cohort of 5201 participants
was enrolled between 1989 and 1990, with an additional
687 predominantly black participants enrolled between
1992 and 1993.
We measured serum 25-(OH)D concentration at the
1992–1993 study visit for 2312 CHS participants who had
no clinical evidence of cardiovascular disease at that time
and who had available frozen serum (11). To expand our
focus to incident cancer and hip fracture for this study, we
additionally excluded 328 participants with a history of
cancer and 13 participants with a previous hip fracture. We
also excluded 45 participants with missing data on smok-
ing and physical activity (Supplement 1, available at www
.annals.org). Because 25-(OH)D concentrations and
possibly their associations with health outcomes vary by
race, we focused on the 1621 white persons meeting
these criteria.
25-(OH)D Concentration
Fasting serum was collected from CHS participants at
the 1992–1993 study visit and stored at Ϫ70 °C. We mea-
sured total 25-(OH)D [25-(OH)D2 and 25-(OH)D3] by
using high-performance liquid chromatography–tandem
mass spectrometry on a Waters Quattro micro mass spec-
trometer (Waters Corporation, Milford, Massachusetts) in
2008. The interassay coefficient of variation was less than
3.4%. The assay was validated by using NIST Standard
Reference Material 972 (accuracy within 5%) (20). 25-
Hydroxyvitamin D is known to be stable for long periods
at Ϫ70 °C (22).
Composite Clinical Outcome
The primary study outcome was time to first occur-
rence of incident hip fracture, incident myocardial infarc-
tion (MI), incident cancer, or death from any cause. This
composite outcome was chosen before analysis to capture
previously described associations of 25-(OH)D with dis-
ease outcomes. We defined hip fracture by the Interna-
tional Classification of Diseases, Ninth Revision, codes
820.xx without a concomitant code for motor vehicle ac-
cident (E810–E819) or pathologic fracture (733.1x) (6).
The CHS Events Committee adjudicated cases of MI by
using available hospital discharge summaries, diagnostic
test records, and consultation reports (23). Investigators for
the CHS identified incident cancer cases by linking CHS
records with population-based cancer registries serving the
4 CHS regions (24). We omitted outcomes that may be
causally related to low 25-(OH)D concentration but have a
diagnosis that is imprecisely ascertained or is made largely
on the basis of physical measurements, such as diabetes,
hypertension, and impaired muscle function. We defined
time to composite outcome as the time elapsed between
the 1992–1993 examination, when serum 25-(OH)D con-
centrations were measured (baseline), and either the earliest
event or the end of follow-up for cancer ascertainment
(31 December 2005 for the California, Pennsylvania,
and North Carolina sites, and 31 December 2006 for the
Maryland site).
Covariates
Covariates were ascertained at the 1992–1993 CHS
study visit and were selected on the basis of their suspected
confounding influence on associations of 25-(OH)D with
study outcomes. Total physical activity was estimated by
using the Minnesota Leisure Time Physical Activity Ques-
tionnaire, which assesses a range of common activities,
Context
Vitamin D deficiency is defined by its association with
markers of bone metabolism, not by its association with
clinical outcomes.
Contribution
This study followed elderly people and found that base-
line levels of 25-hydroxyvitamin D less than 50 nmol/L
(20 ng/mL) were associated with a composite outcome
that included hip fracture, myocardial infarction, incident
cancer, and death.
Caution
This was an observational study of white persons.
Implication
The threshold identified in this study is closer to the value
recently recommended by the Institute of Medicine than
to the value recommended by most other professional
societies and expert panels (75 nmol/L [30 ng/mL]).
—The Editors
Original Research Serum 25-(OH)D and Risk for Major Clinical Disease Events
628 1 May 2012 Annals of Internal Medicine Volume 156 • Number 9 www.annals.org
3. such as walking for exercise, jogging, biking, aerobics, golf,
tennis, swimming, weight training, mowing the lawn,
strenuous household chores, and use of a treadmill or aer-
obic machine (25, 26). Current smoking was ascertained
by questionnaire. Time of blood collection was categorized
in 3-month blocks to reflect the 4 seasons and the observed
pattern of seasonal variation in 25-(OH)D concentration
in our population.
Statistical Analysis
We tested associations of 25-(OH)D concentration
with study outcomes by using Cox proportional hazards
models with robust SEs, adjusted for age, sex, clinical site,
smoking (current or not current), body mass index (in
categories), and physical activity (kilocalories per week in
categories). This set of covariates was chosen before anal-
ysis to include important demographic characteristics
and potential strong confounders while also maintaining
a relatively parsimonious model. We censored partici-
pants at the time of death in analyses of nonfatal
outcomes.
We evaluated 25-(OH)D as a dichotomous variable to
address the clinical utility of a 25-(OH)D threshold for
risk assessment and because we and others have seen
threshold associations of 25-(OH)D concentration with
risks for fracture, MI, and death (6–10). Given known
seasonal variability in 25-(OH)D concentration (16–19)
and its associated effect on modeling (27), we planned
before analysis to assess the effect of season on the relation-
ship of 25-(OH)D concentration and the composite out-
come. We compared nested models with and without in-
teraction terms for 25-(OH)D concentration by season by
using a multivariate Wald test. When we saw significant
heterogeneity, we examined season-specific 25-(OH)D
concentrations as exposures. This approach has been ap-
plied previously and reduces bias (27, 28).
To describe the functional form of the association of
25-(OH)D concentration with the composite outcome, we
first calculated unadjusted incidence rates by season-
specific decile of 25-(OH)D concentration. Second, we
created an adjusted penalized spline model with season-
specific 25-(OH)D Z score as the flexibly modeled expo-
sure variable and graphically displayed the spline at the
mean values of adjustment covariates (29). The penalized
spline was computed by using the default algorithm of the
survival package in R 2.12.1 (R Foundation for Statis-
tical Computing, Vienna, Austria), which uses evenly
spaced knots, cubic polynomials, and a penalty to re-
strict the overall flexibility of the fitted curve (30).
Third, we used a simple statistical approach similar to the
Contal–O’Quigley method to estimate an “optimal” season-
specific 25-(OH)D Z score cut-point (31). For each possi-
ble threshold from the inner 90% of the season-specific
25-(OH)D Z score distribution (0.01 unit increments), we
computed the Wald statistic with robust SE to describe the
strength of the adjusted association between 25-(OH)D
deficiency (using that candidate cut-point) and rates of the
composite outcome. The Z score cut-point that produced
the largest Wald statistic was defined as “optimal” in the
sense that it best discriminated between low- and high-risk
participants with these statistical criteria. We quantified the
uncertainty in our estimated optimal threshold by comput-
ing approximate CIs based on the observed quantiles of the
distribution of estimates across 2000 nonparametric boot-
strap samples (32). Because an optimal cut-point with high
statistical precision is difficult to estimate, we present
both standard 95% CIs and the narrower 75% CIs. We
computed net reclassification improvement to assess
whether season-specific 25-(OH)D concentration im-
proved prediction of the primary composite outcome
(cumulative incidence at 10 years, through which
follow-up was 100% complete) compared with static
25-(OH)D concentration (50 nmol/L [20 ng/mL] re-
gardless of season) (33).
All P values are 2-sided. Statistical analyses were com-
pleted using R 2.12.1 and STATA 10.1 (Stata Corp, Col-
lege Station, Texas).
Role of the Funding Source
The National Institutes of Health provided funding
for this study. The funding source had no role in the de-
sign, conduct, or analysis of this study or the decision to
submit the manuscript for publication.
Figure 1. Box plot of 25-(OH)D concentration by season,
showing the 25th, 50th, and 75th percentiles of
distributions, with outliers not shown.
25-(OH)DConcentration,nmol/L
20
40
60
80
100
120
Winter Spring Summer Autumn
Mean 25-(OH)D was 56 nmol/L (SD, 24), 63 nmol/L (SD, 24), 74
nmol/L (SD, 25), and 69 nmol/L (SD, 26) (22 ng/mL [SD, 10], 25
ng/mL [SD, 10], 30 ng/mL [SD, 10], and 28 ng/mL [SD, 11]) in winter
(January–March), spring (April–June), summer (July–September),
and autumn (October–December), respectively. 25-(OH)D ϭ 25-
hydroxyvitamin D.
Original ResearchSerum 25-(OH)D and Risk for Major Clinical Disease Events
www.annals.org 1 May 2012 Annals of Internal Medicine Volume 156 • Number 9 629
4. RESULTS
Baseline Characteristics
Baseline 25-(OH)D concentration varied strongly by
season (Figure 1). It was lowest in January through March
(“winter”), highest in July through September (“summer”),
and intermediate in April through June (“spring”) and Oc-
tober through December (“autumn”). Low season-specific
25-(OH)D concentration, defined as less than the season-
specific 29th percentile, was more common among women
and participants at more northerly study sites and was as-
sociated with higher body mass index, hypertension, re-
duced physical activity, and higher circulating concentra-
tions of parathyroid hormone (Table 1).
Events
Median follow-up for the 1621 participants was 11
years (interquartile range, 6 to 13 years). The composite
clinical outcome occurred in 1018 participants (63%)
(Supplement 2, available at www.annals.org). The qualify-
ing event was hip fracture for 137 participants (8%), MI
for 186 participants (11%), cancer for 335 participants
(21%), and death for 360 participants (22%). Qualifying
events are tabulated by cause in Supplement 3 available at
www.annals.org).
Associations of 25-(OH)D With Events
We first evaluated the association of 25-(OH)D with
the composite outcome by using the previously published
25-(OH)D threshold of 50 nmol/L (20 ng/mL) (1, 3).
Using this approach, we saw borderline statistical evidence
of heterogeneity by season (P ϭ 0.057). Deviations from
strong associations occurred in winter and summer, the
extremes of seasonal variation in 25-(OH)D (Supplement
4, available at www.annals.org).
We next evaluated the associations of 25-(OH)D with
the composite outcome by season. Participants in the low-
est 2 to 3 deciles of 25-(OH)D concentration (lowest 20%
to 30%) tended to have increased risk for the composite
clinical outcome, compared with those in the highest 7 to
8 deciles (Supplement 5, available at www.annals.org).
Evaluation of a season-based 25-(OH)D Z score similarly
suggested that elevated risk for the composite outcome was
Table 1. Characteristics of Participants in 1992 to 1993*
Characteristic Overall (n ؍ 1621) Normal 25-(OH)D (n ؍ 1126) Low 25-(OH)D (n ؍ 495)†
Demographic data
Age, y 74.0 (4.6) 73.7 (4.5) 74.5 (4.7)
Men 491 (30) 406 (36) 85 (17)
Site
Forsythe County, North Carolina 450 (28) 330 (29) 120 (24)
Sacramento County, California 370 (23) 277 (25) 93 (19)
Washington County, Maryland 457 (28) 295 (26) 162 (33)
Pittsburgh, Pennsylvania 344 (21) 224 (20) 120 (24)
Medical history and lifestyle
Diabetes‡ 162 (10) 90 (8) 72 (15)
Hypertension‡ 906 (56) 609 (54) 297 (60)
Current smoking 151 (9) 93 (8) 58 (12)
Current alcohol use 740 (46) 521 (46) 219 (44)
Physical activity category
Ͻ500 kcal/wk 453 (28) 261 (23) 192 (39)
500–1000 kcal/wk 329 (20) 214 (19) 115 (23)
1000–2000 kcal/wk 393 (24) 298 (26) 95 (19)
Ͼ2000 kcal/wk 446 (28) 353 (31) 93 (19)
Physical examination
BMI category
Ͻ25 kg/m2
664 (41) 484 (43) 180 (36)
25–30 kg/m2
660 (41) 466 (41) 194 (39)
30–35 kg/m2
229 (14) 143 (13) 86 (17)
Ͼ35 kg/m2
68 (4) 33 (3) 35 (7)
Laboratory data
Estimated GFR, mL/min per 1.73 m2
‡ 75.3 (17.8) 75.9 (17.7) 74.0 (17.8)
Parathyroid hormone, ng/L 54.7 (27.3) 50.9 (25.4) 63.1 (31.1)
Bone alkaline phosphate, g/L 14.6 (6.9) 14.1 (6.7) 15.8 (7.1)
Calcium
mg/dL 9.5 (0.4) 9.5 (0.4) 9.5 (0.4)
mmol/L 2.4 (0.1) 2.4 (0.1) 2.4 (0.1)
Phosphate, mmol/L 1.2 (0.2) 1.2 (0.2) 1.2 (0.2)
Total 25-(OH)D
nmol/L 66.2 (25.8) 77.8 (21.5) 39.8 (11.1)
ng/mL 26.5 (10.3) 31.2 (8.6) 15.9 (4.5)
25-(OH)D ϭ 25-hydroxyvitamin D; BMI ϭ body mass index; GFR ϭ glomerular filtration rate.
* Values are means (SDs) for continuous variables or numbers (percentages) for categorical variables.
† Defined as less than the lowest season-specific 29th percentile (43, 50, 61, and 55 nmol/L [17, 20, 24, and 22 ng/mL] in winter, spring, summer, and fall, respectively).
‡ Diabetes was defined as use of insulin or oral hypoglycemic agents or fasting blood glucose level Ն6.99 mmol/L (Ն126 mg/dL). Hypertension was defined as systolic blood
pressure Ն140 mm Hg, diastolic blood pressure Ն90 mm Hg, or use of an antihypertensive medication. Serum cystatin C was measured by using a BNII nephelometer (N
Latex Cystatin C; Dade Behring, Deerfield, Illinois) and used to estimate GFR with the following equation: GFR ϭ 76.7 ϫ [cystatin C]Ϫ1.18
.
Original Research Serum 25-(OH)D and Risk for Major Clinical Disease Events
630 1 May 2012 Annals of Internal Medicine Volume 156 • Number 9 www.annals.org
5. greatest below a Z score of approximately Ϫ0.5 (near 30%
of the normal distribution) (Figure 2).
Based on a simple statistical approach, the season-
specific 25-(OH)D Z score that best separated low- and
high-risk 25-(OH)D groups with respect to the composite
outcome was Ϫ0.54 (29th percentile of the normal distri-
bution). This threshold corresponded to season-specific
cut-points of 43, 50, 61, and 55 nmol/L (17, 20, 24, and
22 ng/mL) under the normal approximation to the distri-
bution of 25-(OH)D concentration for winter, spring,
summer, and autumn, respectively (mean threshold of 52
nmol/L [21 ng/mL]). The observed season-specific distri-
butions of 25-(OH)D concentrations in this population,
although slightly right-skewed, suggested that the normal
approximation was reasonable. A 25-(OH)D concentration
below the season-specific 29th percentile was associated
with a 24% increased risk for the composite outcome in
the adjusted model (95% CI, 9% to 42%) and with simi-
larly increased risks for each component of the composite
outcome (Table 2).
We did several analyses to evaluate whether the iden-
tified optimal threshold was robust. Statistical significance
of the association of low season-specific 25-(OH)D con-
centration with risk for the composite outcomes decreased
markedly when a threshold Z score above Ϫ0.44 was used;
this corresponds to season-specific cut-points of 45, 52, 63,
and 57 nmol/L (18, 21, 24, and 23 ng/mL) for winter,
spring, summer, and autumn, respectively (mean threshold
of 54 nmol/L [22 ng/mL]) (Supplement 6, available at
www.annals.org). In bootstrap analyses, 95% of optimal
25-(OH)D Z score thresholds fell between Ϫ1.48 and
0.13 (mean season-specific thresholds of 29 and 69 nmol/L
[12 and 28 ng/mL], respectively), whereas 75% fell be-
tween Ϫ1.38 and Ϫ0.40 (mean thresholds of 31 and 55
nmol/L [12 and 22 ng/mL], respectively).
Reclassification
Nine percent of participants were reclassified compar-
ing low 25-(OH)D concentration defined by season-
specific thresholds (29th percentile) versus the static
threshold of 50 nmol/L (20 ng/mL) (Table 3). When low
season-specific 25-(OH)D concentration was compared
with a concentration less than 50 nmol/L (20 ng/mL), net
reclassification improvement was 2.4% (95% CI, Ϫ0.6%
to 5.3%; P ϭ 0.118).
DISCUSSION
We characterized associations of NIST-verified serum
25-(OH)D concentration with risk for adverse clinical
events that are pathophysiologically relevant to pleiotropic
vitamin D actions in a community-based population. The
association of 25-(OH)D with a composite clinical out-
come of hip fracture, MI, cancer, and death varied by sea-
son, supporting use of season-specific 25-(OH)D thresh-
olds. In our study population, threshold 25-(OH)D
concentrations optimally associated with risk for the com-
posite outcome were 43 nmol/L (17 ng/mL) in winter
months, 50 nmol/L (20 ng/mL) in spring months, 61
nmol/L (24 ng/mL) in summer months, and 55 nmol/L
(22 ng/mL) in autumn months.
Figure 2. Association of season-specific 25-(OH)D Z score
with the risk for incident myocardial infarction, cancer,
hip fracture, or death (composite outcome) among 1621
participants in the Cardiovascular Health Study, evaluated
using a penalized spline.
LogHazardRatio
–0.05
0.05
0.10
0.15
0.20
0.25
0.00
–1.5 –0.5
25 50 75
755025
50 75 100
100
1007550
–1 0.5 1.50 1
Winter
Spring
Summer
Autumn
Season-Specific 25-(OH)D Z Score
25-(OH)D Concentration, nmol/L
Proportional hazards model adjusts for age, sex, clinical site, body mass
index, physical activity, and smoking. The shaded area represents Z score
less than Ϫ0.54 (29th percentile of the normal distribution), which best
discriminated risk for the composite outcome. The x-axis is displayed as
season-specific Z score (uppermost x-axis, reflecting the primary method
of analysis) and as corresponding season-specific absolute 25-(OH)D
concentrations (lower 4 axes). 25-(OH)D ϭ 25-hydroxyvitamin D.
Table 2. Associations of Low Season-Specific 25-(OH)D
Concentration With Rates of the Composite Outcome of MI,
Cancer, Hip Fracture, or Death Among Participants
Outcome Events (Incidence Rate), n* Hazard Ratio
(95% CI)†
Normal
25-(OH)D
Low
25-(OH)D‡
Composite 681 (6.4) 337 (7.7) 1.24 (1.09–1.42)
MI 154 (1.2) 67 (1.3) 1.24 (0.91–1.70)
Cancer 259 (2.3) 111 (2.3) 1.13 (0.90–1.42)
Hip fracture 118 (0.9) 72 (1.4) 1.34 (0.97–1.84)
Death 539 (4.0) 287 (5.3) 1.32 (1.14–1.53)
25-(OH)D ϭ 25-hydroxyvitamin D; MI ϭ myocardial infarction.
* Participants may be included in more than 1 event category, but only the first
event for each participant was used in analysis of the composite outcome. Inci-
dence rates are unadjusted event rates per 100 person-years of follow-up.
† Adjusted for age, sex, clinical site, smoking, body mass index, and physical
activity.
‡ Defined as less than the lowest season-specific 29th percentile (43, 50, 61, and
55 nmol/L [17, 20, 24, and 22 ng/mL] in winter, spring, summer, and autumn,
respectively).
Original ResearchSerum 25-(OH)D and Risk for Major Clinical Disease Events
www.annals.org 1 May 2012 Annals of Internal Medicine Volume 156 • Number 9 631
6. The IOM recently evaluated the clinical application of
25-(OH)D testing in the context of vitamin D supplemen-
tation (1). In reviewing available data, it concluded that
inadequate vitamin D can contribute to bone disease, vita-
min D supplementation can decrease risk for bone disease
in at-risk populations, and 25-(OH)D concentration less
than 50 nmol/L (20 ng/mL) identifies persons at increased
risk. The proposed threshold of 50 nmol/L (20 ng/mL)
was lower than that of 75 nmol/L (30 ng/mL) recom-
mended by many professional societies and vitamin D re-
searchers (12–15). The IOM noted a lack of high-quality
data about the effects of vitamin D supplementation on
risk for nonbone health outcomes, including MI, cancer,
and death, and it did not, therefore, base its estimate of
target 25-(OH)D concentration on these outcomes. These
findings were echoed in an updated clinical practice sum-
mary on vitamin D deficiency (3).
In comparison with existing literature and recommen-
dations, we have 2 principal findings. First, 25-(OH)D
thresholds associated with risk for diverse major clinical
disease events in our work center close to the 50 nmol/L
(20 ng/mL) recommended by the IOM for bone health.
We agree with the IOM’s conclusions that high-quality
intervention studies are needed to test whether vitamin D
deficiency is causally related to nonbone outcomes in hu-
mans. Until these data are available, the finding of a similar
25-(OH)D threshold for risk for major clinical disease
events to that recommended by the IOM for bone health is
reassuring and supports generally targeting 50 nmol/L (20
ng/mL) over 75 nmol/L (30 ng/mL) when 25-(OH)D test-
ing is clinically indicated.
In our study, 30.5% of participants had a 25-(OH)D
concentration less than the season-specific threshold cen-
tered near 50 nmol/L (20 ng/mL). This proportion is con-
gruent with the prevalence of 25-(OH)D concentrations
less than 50 nmol/L (20 ng/mL) in other populations and
emphasizes the large number of people at risk for potential
complications of low 25-(OH)D concentration (34). How-
ever, the distinction between 50 and 75 nmol/L (20 and
30 ng/mL) is important because more than 40% of the
U.S. population has concentrations between 50 and 75
nmol/L (20 and 30 ng/mL) (34). Our estimate of the 25-
(OH)D threshold that best discriminates risk for clinical
disease events was generated with some statistical uncer-
tainty, but a threshold as high as 75 nmol/L (30 ng/mL)
was unlikely to be congruent with our data.
Second, our data suggest that season-specific targets
are most appropriate for 25-(OH)D concentration. Varia-
tion in 25-(OH)D concentration within persons and pop-
ulations over the calendar year is well-known to be large
relative to mean concentration (16–19). This is probably
due to seasonal variation in exposure to ultraviolet light. As
a result, clinical decisions about initiation and dose of year-
long vitamin D supplementation are likely to be heavily
influenced by time of ascertainment, which is often arbi-
trary. Combined with this background knowledge, our re-
sults that demonstrated heterogeneity of the 25-(OH)D–
composite outcome association by season and a trend
toward improved classification of risk using season-specific
25-(OH)D thresholds suggest that season-specific targets
for 25-(OH)D concentration are more appropriate than
the static targets previously recommended when the need
for year-long vitamin D supplementation is being consid-
ered (1, 12–15).
We examined a composite end point of clinical disease
events that plausibly reflect net pleiotropic vitamin D ac-
tions, are supported by existing literature, and have a quan-
tifiable time of onset, understanding that this may include
1 or more outcomes that are not causally related to 25-
(OH)D and may omit some important vitamin D–related
effects. Associations of low season-specific 25-(OH)D con-
centration with the composite outcome and each of its
components were of similar magnitude, enabling this ap-
proach. Statistical significance using the standard ␣ level of
0.05 was achieved only for the composite outcome and for
death. However, this study was not powered to detect as-
sociations with individual composite outcome compo-
nents, and statistical confidence is likely to be inflated by
testing inference in the same data set in which threshold
25-(OH)D concentrations were derived. Moreover, the
primary goal of this study was to study the pattern of the
25-(OH)D–composite outcome relationship, not its exis-
tence, which has been demonstrated in previous studies
(5–11).
Strengths of this study include the use of a
community-based population of older adults, who are of-
ten targeted for 25-(OH)D testing; the use of NIST-
verified 25-(OH)D concentration, which has not, to our
knowledge, been previously applied to large epidemiologic
studies; and the ascertainment of clinical outcomes directly
relevant to both bone and nonbone vitamin D actions over
Table 3. Classification of 10-Year Risk for Composite
Outcome of MI, Cancer, Hip Fracture, or Death Among
Participants
Static 25-(OH)D* Season-Specific 25-(OH)D
Normal,
n (%)
Low,
n (%)†
Total,
n
Participants who have an event
Ն50 nmol/L (Ն20 ng/mL) 484 (90) 55 (10) 539
Ͻ50 nmol/L (Ͻ20 ng/mL) 18 (8) 199 (92) 217
Total 502 254 756
Participants who do not have an event
Ն50 nmol/L (Ն20 ng/mL) 598 (93) 48 (7) 646
Ͻ50 nmol/L (Ͻ20 ng/mL) 26 (12) 193 (88) 219
Total 624 241 865
25-(OH)D ϭ 25-hydroxyvitamin D.
* Year-long static threshold of 50 nmol/L (20 ng/mL).
† Defined as less than the lowest season-specific 29th percentile (43, 50, 61, and
55 nmol/L [17, 20, 24, and 22 ng/mL] in winter, spring, summer, and autumn,
respectively).
Original Research Serum 25-(OH)D and Risk for Major Clinical Disease Events
632 1 May 2012 Annals of Internal Medicine Volume 156 • Number 9 www.annals.org
7. long-term follow-up. Limitations include the inclusion of
only older adults; the availability of only white participants
in sufficient numbers to rigorously evaluate relationships of
25-(OH)D with study outcomes; the availability of only
one 25-(OH)D measurement per participant, which may
bias magnitudes of association toward the null; and the
inability of available statistical methods to precisely deter-
mine optimal threshold concentrations with statistical confi-
dence. Most important, this study is observational. Ulti-
mately, optimal 25-(OH)D concentrations should be defined
as the baseline 25-(OH)D concentrations above which vita-
min D supplementation does not improve relevant clinical
outcomes in large, diverse, randomized clinical trials.
In conclusion, we found that “optimal” concentrations
of 25-(OH)D, gauged by associations with major clinical
disease events, centered near 50 nmol/L (20 ng/mL), the
level recently recommended by the IOM for bone health.
We further report that the association of 25-(OH)D with
clinical health events varies by season and suggest that
season-specific targets for 25-(OH)D concentration are
more appropriate than static targets when considering po-
tential implications for long-term health.
From the University of Washington, Seattle, Washington.
Grant Support: By the National Heart, Lung, and Blood Institute (con-
tracts N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-
HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, and N01-
HC-45133 and grant HL080295), with additional contribution from the
National Institute of Neurologic Disorders and Stroke. Additional sup-
port was provided by the National Institute on Aging (AG-023629,
AG-15928, AG-20098, and AG-027058); the National Heart, Lung,
and Blood Institute (grants R01HL084443 and R01HL096875); and
the National Institute of Diabetes and Digestive and Kidney Diseases
(grant R01DK088762). A full list of principal CHS investigators and
institutions can be found at www.chs-nhlbi.org/pi.htm.
Potential Conflicts of Interest: Disclosures can be viewed at www
.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNumϭM11
-2074.
Reproducible Research Statement: Study protocol and statistical code:
Available from Dr. de Boer (e-mail, deboer@u.washington.edu). Data
set: Not available.
Requests for Single Reprints: Ian H. de Boer, MD, MS, Box 359606,
325 9th Avenue, Seattle, WA 98104; e-mail, deboer@u.washington.edu.
Current author addresses and author contributions are available at www
.annals.org.
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Original Research Serum 25-(OH)D and Risk for Major Clinical Disease Events
634 1 May 2012 Annals of Internal Medicine Volume 156 • Number 9 www.annals.org
9. Current Author Addresses: Drs. de Boer and Kestenbaum and Ms.
Robinson-Cohen: Kidney Research Institute, Box 359606, 325 9th Av-
enue, Seattle, WA 98104.
Mr. Levin: Department of Biostatistics, Box 357232, 1959 Northeast
Pacific Street, Seattle, WA 98195.
Dr. Biggs: Collaborative Health Studies Coordinating Center, Building
29, Suite 310, 6200 Northeast 74th Street, Seattle, WA 98115.
Dr. Hoofnagle: Department of Laboratory Medicine, Box 357110, 1959
Northeast Pacific Street, Seattle, WA 98195.
Dr. Siscovick: Cardiovascular Health Research Unit, 1730 Minor Ave-
nue, Suite 1360, Seattle, WA 98101.
Author Contributions: Conception and design: I.H. de Boer, G. Levin,
B. Kestenbaum.
Analysis and interpretation of the data: I.H. de Boer, G. Levin,
C. Robinson-Cohen, A.N. Hoofnagle, D.S. Siscovick, B. Kestenbaum.
Drafting of the article: I.H. de Boer, G. Levin, C. Robinson-Cohen.
Critical revision of the article for important intellectual content:
G. Levin, C. Robinson-Cohen, M.L. Biggs, A.N. Hoofnagle,
D.S. Siscovick, B. Kestenbaum.
Final approval of the article: I.H. de Boer, C. Robinson-Cohen,
M.L. Biggs, A.N. Hoofnagle, D.S. Siscovick, B. Kestenbaum.
Statistical expertise: G. Levin, C. Robinson-Cohen, A.N. Hoofnagle.
Obtaining of funding: I.H. de Boer, B. Kestenbaum.
Collection and assembly of data: G. Levin, M.L. Biggs, A.N. Hoofnagle,
D.S. Siscovick.
Annals of Internal Medicine
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