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Nat Rev Endocrinol. 2011;7(6):337-345.

Steroids. 2011;76(12):1305-1309.

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PLoS One. 2014;9(1):e86755.

Am J Physiol Lung Cell Mol Physiol. 2005;289(4):L617-626.

Science. 2006;311(5768):1770-1773.

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INTRODUCTION

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INTRODUCTION

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Crit Care Med. 2015;43(9):1928-1937.

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JAMA 2014; 312: 1520-30

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INTRODUCTION��

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INTRODUCTION,��-

Primary Endpoint:

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492��Placebo��vitamin D� ��"��#�� 475�!*.(%��6��!+'-.&),��$#��

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INTRODUCTIONC�68#D

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INTRODUCTION��

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INTRODUCTION��

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INTRODUCTION��

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INTRODUCTION

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INTRODUCTION

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Vitamin D to Improve Outcomes by Leveraging Early Treatment / VIOLET 0 trial

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METHODS

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METHODS

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METHODS

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METHODS

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METHODS

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METHODS ��

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METHODS +.)'0-

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METHODS (+&$-*

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METHODS 463275

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METHODS .5+'74

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METHODS

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METHODS

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METHODS

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METHODS

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METHODS

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METHODS

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METHODS

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METHODS

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METHODS156/-

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RESULTS��

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RESULTS"$% #%!

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RESULTS ��

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RESULTS ��!�

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RESULTS ��

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RESULTS ��

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RESULTS PrimaryEndpoint

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Page 60: ICU 2020.1.28 · ICU #" vitamin D $ $ ! RCT $ Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized

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RESULTSSecondaryEndpoints&physiological'

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Page 65: ICU 2020.1.28 · ICU #" vitamin D $ $ ! RCT $ Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized

RESULTSSecondaryEndpoints%safety&

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$14��#�!�Ca�$90��#�!��$90��#�!��!��

��

Page 66: ICU 2020.1.28 · ICU #" vitamin D $ $ ! RCT $ Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized

RESULTSSecondaryEndpointsBsubgroup)

=A:>7@�.25OHD��-�63&��-�,�/�234,#('�0'��.9;8?A<��*�234'� ��vitamin D��

��*.��.��!-�%)� ��*/� 1%5vitamin D�.$��.�"��+,()"'�

Page 67: ICU 2020.1.28 · ICU #" vitamin D $ $ ! RCT $ Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized

��vitamin D��vitamin D��

Page 68: ICU 2020.1.28 · ICU #" vitamin D $ $ ! RCT $ Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized

�5vitamin D��vitamin D��5<:>@=?;"��

&��5��'$&��,874ARDS2(0/��'6Placebo��5�+��4��9��,-1)/%.5�$� #�2��!4�� 63*0/%

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DISCUSSION

•5*�.H��G54��Hvitamin DT��@QD8vitamin D��I3O;G� >R8��2NJDUEF;BA9

•!�#KAI/�&8%$&8�&EndpointsG6?C8,0�&G��IF=8L?SPlacebo-H�<�F+�@P:BA9

•"'�<) >RAAM8(�HW[YZWVXG4@Q�G817I��G��>RA9

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DISCUSSION

• subgroup5�KP:9�Ovitamin D �O�1T&�O_][��Z�I�1Z�R:vitamin D4�O��Z CJ?G\`a^PMAHG;

•&N:<�3*O�1=L<$�#�EXWNARDSZ,*FJ?G�1=O!�'Bvitamin D��/KQFY9AHGDLP��K>V:�-Ovitamin DO�)6.�N�FJ?W;

• vitamin DO��7B�87L"+7K(MHJ?W�2�S0@UXGB:�%O�2�S>W;

Page 71: ICU 2020.1.28 · ICU #" vitamin D $ $ ! RCT $ Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized

DISCUSSION

VITdAL-ICU trial=ICU��FB��3��M��>75Z��E�-B,1'��2A8�Nvitamin D��CQ?USWYVXT �NO@99Z��E)�

�+/J�6+/JN9D

VIOLET trial=ICU��%�FB14�:�M��>ARDSP#�N<WUS�2[�5(B3&B ��LK\

A8�Nvitamin D��R��HG?LS/MS/MSI2" �R��@�!L�.B$�

0�*4�7; 0�*4�7;

Page 72: ICU 2020.1.28 · ICU #" vitamin D $ $ ! RCT $ Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized

LIMITATION

+'�A��C�&�B� K(�8>1I<E.FHPLRSUAWVK�I6@3?4:.#*)�K'�?A1� B�G;<�!�30I/

,OMSUQTN?vitamin DC��3A1@��7J.��K5A2=<� C��D%$8>1A1/

-vitamin D�� K��B��9I6@K� 8>1<<E.%��D"=>1A1/

Page 73: ICU 2020.1.28 · ICU #" vitamin D $ $ ! RCT $ Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized

�$ �

•�#TWSQXV�1vitamin DF&��G*NMD7?=81ICU��FHY�9KF��B45FG1vitamin DF+�# B;@�DF7!�8�L2

•�)F."�E/<L,�8ARDSI��FURP��E/NL�0%O,�;@4L>:A3K1APACHE�ISAPS�DCF'�$D,�O;=�8-�AGD47B(6JML2

Page 74: ICU 2020.1.28 · ICU #" vitamin D $ $ ! RCT $ Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized

��

•��8$&ICU��,�'-?0��4(23$�/.:&ICU4�#�'7��486+20%��+<:!� 5.38;; 96��,(=$��8�0.3!�1207+�,�>%

•��8FIHCD4�@?0,$AEGB7ICU5FIHCD7ICU48��7"�J!� K:�623)>5�*<?>%

Page 75: ICU 2020.1.28 · ICU #" vitamin D $ $ ! RCT $ Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized

B<�[34

• 0�]M1T5�2:�?GN<a`UL_J• �<34rVITdAL-ICU trials[;9VK_Amrein^[34J• H�vitamin D'�8[(�/Z.+b6SR34J

t34jgdpu��OI�!>I-�,�I�C1&I5�2:�?Gt!>ueqhkncImofqIhdhIldiIdfnhYX[30!>t%Eu2017�8$10"v2023�2$r0�]�F�st�@uICUZ ��72#E�I 48#E�[*�N=A\`_H�vitamin D'�r25OHD≦12ng/mls[��9t )uICU ��72#E�Zloading doseWPU54��[vitamin Db��JQ[�90"E4000�/"7�DV��J

Page 76: ICU 2020.1.28 · ICU #" vitamin D $ $ ! RCT $ Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized

Primary Endpoints'�&�28�[RW�"�"�(

Secondary Endpointso*@CICURW90�G\Y1�?W"�o*@CICUW%��?o5�+W2 1A�W qSOFAro90�+[RW*@CICUZW��@o<@�o90�+[RW�34I�6U��o)$W9

bdiekW7�X�,-S�JKX `OQG]MC;:�?I>FCgnjlgchI�JFCICU��HPvitamin DB�!�0V�8a.OQF_Cvitamin DW/��IE_CUTW=FIE^CjmifplSLQX�5,-V#ON�VUOQF_D

Page 77: ICU 2020.1.28 · ICU #" vitamin D $ $ ! RCT $ Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: the VITdAL-ICU randomized

;6<6�$

•&��!81@vitamin D#��:"��8=)%��>RCT-?=��.(;34+2.)�':)��:negative study8�B32*

•��9 �-?)ICU��!80)vitamin DC��0)��04+2?#�1@6+,��: ��5: �/A7+*

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LFMF&.

• �1,�I$'O3�/�*O��U 8E�"�U%A$'J��E<R:N?SG6;3��I(�U�=3��H9=Rvitamin D-�!�I$'J��KF:7F)8QSB4

• >IP7Gnegative study;NEJMH0CB>F+�H�;5RF�@3>>536�2�,CE6Bvitamin DI$'H�#;D6BP7H�TSB4

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