f9e70e394d7c12360f2309fde129e966  311092.pdf
bbdcb19300d050d0bcea79bf0821b1175b89cc3f  311092.pdf
64a3323292f6ffb8b000270834906e0d0e034a6dd5079f3c9ec1f04708d11cb4  311092.pdf

Title:           Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia: A Randomized Clinical Trial
Subject:         DOI: 10.1093/cid/ciae333; Clinical Infectious Diseases, 79, 5, 2024-06-24.; Abstract:  Background: Few antiviral therapies have been studied in patients with coronavirus disease 2019 (COVID-19) and kidney impairment. Herein, the efficacy, safety, and pharmacokinetics of remdesivir, its metabolites, and sulfobutylether-β-cyclodextrin excipient were evaluated in hospitalized patients with COVID-19 and severe kidney impairment. Methods: In REDPINE, a phase 3, randomized, double-blind, placebo-controlled study, participants aged ≥12 years hospitalized for COVID-19 pneumonia with acute kidney injury, chronic kidney disease, or kidney failure were randomized 2:1 to receive intravenous remdesivir (200 mg on day 1; 100 mg daily up to day 5) or placebo (enrollment from March 2021 to March 2022). The primary efficacy end point was the composite of the all-cause mortality rate or invasive mechanical ventilation rate through day 29. Safety was evaluated through day 60. Results: Although enrollme
Keywords:        SARS-CoV-2; COVID-19; remdesivir; kidney impairment
Author:          Meghan E. Sise
Creator:         Servigistics Arbortext Advanced Print Publisher 11.1.4546/W-x64
Producer:        PDFlib+PDI 9.0.7p3 (C++/Win64)
CreationDate:    Tue Nov 19 09:39:29 2024 CET
ModDate:         Thu Nov 21 05:44:51 2024 CET
Custom Metadata: yes
Metadata Stream: yes
Tagged:          yes
UserProperties:  no
Suspects:        no
Form:            AcroForm
JavaScript:      no
Pages:           10
Encrypted:       no
Page size:       593.972 x 782.986 pts
Page rot:        0
File size:       400413 bytes
Optimized:       yes
PDF version:     1.6


name                                 type              encoding         emb sub uni object ID
------------------------------------ ----------------- ---------------- --- --- --- ---------
VQNHOG+TimesNewRomanPSMT             CID TrueType      Identity-H       yes yes yes   1117  0
ZOHQGM+MinionPro-Regular             Type 1C           Custom           yes yes yes   1120  0
TZPGVB+UniversLTStd-BoldCn           Type 1C           Custom           yes yes yes   1123  0
GXHRUU+UniversLTStd-LightCn          Type 1C           Custom           yes yes yes   1126  0
ESPTUS+MinionPro-BoldIt              Type 1C           Custom           yes yes yes   1129  0
IGECQW+STIXGeneral-Regular           Type 1C           Custom           yes yes yes   1132  0
ZILKIN+MinionPro-It                  Type 1C           Custom           yes yes yes   1135  0
GPXJSK+MinionPro-Bold                Type 1C           Custom           yes yes yes   1138  0
CJFXDK+UniversLTStd-LightCnObl       Type 1C           Custom           yes yes yes   1141  0
XFKHEK+UniversLTStd-Cn               Type 1C           Custom           yes yes yes   1144  0
GWUHHE+UniversLTStd-Black            Type 1C           Custom           yes yes yes     99  0
WNMWCY+HelveticaNeueLTStd-BdCn       Type 1            Custom           yes yes no      65  0
CKYJXC+HelveticaNeueLTStd-Cn         Type 1            Custom           yes yes no      68  0
EDQXES+UniversLTStd-Light            Type 1C           Custom           yes yes yes    121  0
KZMHGN+UniversLTStd-LightObl         Type 1C           Custom           yes yes yes    125  0
Helvetica-Bold                       Type 1            Custom           no  no  no      74  0
OCPPTA+HelveticaNeueLTStd-BdCn       Type 1            Custom           yes yes no      77  0
IHHWUW+HelveticaNeueLTStd-Cn         Type 1            Custom           yes yes no      79  0
OHMNIL+HelveticaNeueLTStd-CnO        Type 1            Custom           yes yes no      81  0
Helvetica-Bold                       Type 1            Custom           no  no  no      86  0
NXCVLZ+HelveticaNeueLTStd-Cn         Type 1            Custom           yes yes no      89  0
Helvetica-Bold                       Type 1            Custom           no  no  no      91  0
WXGQCH+HelveticaNeueLTStd-BdCn       Type 1            Custom           yes yes no      93  0


Jhove (Rel. 1.28.0, 2023-05-18)
 Date: 2025-05-08 02:46:03 CEST
 RepresentationInformation: 311092.pdf
  ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16)
  LastModified: 2025-05-07 14:09:35 CEST
  Size: 400413
  Format: PDF
  Version: 1.6
  Status: Well-Formed, but not valid
  SignatureMatches:
   PDF-hul
  ErrorMessage: Invalid indirect destination - referenced object 'figciae333-B19' cannot be found
   ID: PDF-HUL-149
  ErrorMessage: Invalid indirect destination - referenced object 'figciae333-B21' cannot be found
   ID: PDF-HUL-149
  ErrorMessage: Invalid indirect destination - referenced object 'corFM1' cannot be found
   ID: PDF-HUL-149
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'corFM1' cannot be found
   ID: PDF-HUL-122
   Offset: 388893
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'figciae333-B21' cannot be found
   ID: PDF-HUL-122
   Offset: 388893
  ErrorMessage: edu.harvard.hul.ois.jhove.module.pdf.PdfInvalidException: Invalid indirect destination - referenced object 'figciae333-B19' cannot be found
   ID: PDF-HUL-122
   Offset: 388893
  MIMEtype: application/pdf
  Profile: Linearized PDF, Tagged PDF
  PDFMetadata: 
   Objects: 0
   FreeObjects: 1
   IncrementalUpdates: 0
   DocumentCatalog: 
    ViewerPreferences: 
     HideToolbar: false
     HideMenubar: false
     HideWindowUI: false
     FitWindow: false
     CenterWindow: false
     DisplayDocTitle: true
     NonFullScreenPageMode: UseNone
     Direction: L2R
     ViewArea: CropBox
     ViewClip: CropBox
     PrintArea: CropBox
     PageClip: CropBox
    PageLayout: OneColumn
    PageMode: UseOutlines
    Language: en
    Outlines: 
     Item: 
      Title: Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia: A Randomized Clinical Trial
      Destination: head1
      Children: 
       Item: 
        Title: METHODS
        Destination: secciae333-s0
        Children: 
         Item: 
          Title: Trial Design and Oversight
          Destination: secciae333-s0.1
         Item: 
          Title: Trial Participants and Procedures
          Destination: secciae333-s0.2
         Item: 
          Title: Efficacy Assessments
          Destination: secciae333-s0.3
         Item: 
          Title: Safety Assessments
          Destination: secciae333-s0.4
         Item: 
          Title: Pharmacokinetic Assessments
          Destination: secciae333-s0.5
         Item: 
          Title: Statistical Analysis
          Destination: secciae333-s0.6
       Item: 
        Title: RESULTS
        Destination: secciae333-s1
        Children: 
         Item: 
          Title: Participants
          Destination: secciae333-s1.1
         Item: 
          Title: Efficacy
          Destination: secciae333-s1.2
         Item: 
          Title: Safety
          Destination: secciae333-s1.3
         Item: 
          Title: Pharmacokinetics
          Destination: secciae333-s1.4
       Item: 
        Title: DISCUSSION
        Destination: secciae333-s2
       Item: 
        Title: Supplementary Data
        Destination: secciae333-s3
       Item: 
        Title: Notes
        Destination: secciae333-s4
       Item: 
        Title: References
        Destination: reflist
   Filters: 
    FilterPipeline: FlateDecode
   Fonts: 
    Type0: 
     Font: 
      BaseFont: VQNHOG+TimesNewRomanPSMT
      Encoding: Identity-H
      ToUnicode: true
    Type1: 
     Font: 
      BaseFont: ZOHQGM+MinionPro-Regular
      FontSubset: true
      FirstChar: 1
      LastChar: 80
      FontDescriptor: 
       FontName: ZOHQGM+MinionPro-Regular
       Flags: Nonsymbolic
       FontBBox: -290, -360, 1684, 989
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: GPXJSK+MinionPro-Bold
      FontSubset: true
      FirstChar: 1
      LastChar: 36
      FontDescriptor: 
       FontName: GPXJSK+MinionPro-Bold
       Flags: Nonsymbolic, ForceBold
       FontBBox: -318, -360, 1684, 1024
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: TZPGVB+UniversLTStd-BoldCn
      FontSubset: true
      FirstChar: 1
      LastChar: 63
      FontDescriptor: 
       FontName: TZPGVB+UniversLTStd-BoldCn
       Flags: Nonsymbolic, ForceBold
       FontBBox: -83, -250, 1000, 969
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: GWUHHE+UniversLTStd-Black
      FontSubset: true
      FirstChar: 1
      LastChar: 28
      FontDescriptor: 
       FontName: GWUHHE+UniversLTStd-Black
       Flags: Nonsymbolic, ForceBold
       FontBBox: -153, -250, 992, 986
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: CJFXDK+UniversLTStd-LightCnObl
      FontSubset: true
      FirstChar: 1
      LastChar: 17
      FontDescriptor: 
       FontName: CJFXDK+UniversLTStd-LightCnObl
       Flags: Nonsymbolic, Italic
       FontBBox: -169, -271, 1065, 953
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: GXHRUU+UniversLTStd-LightCn
      FontSubset: true
      FirstChar: 1
      LastChar: 74
      FontDescriptor: 
       FontName: GXHRUU+UniversLTStd-LightCn
       Flags: Nonsymbolic
       FontBBox: -163, -250, 1000, 953
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: XFKHEK+UniversLTStd-Cn
      FontSubset: true
      FirstChar: 1
      LastChar: 10
      FontDescriptor: 
       FontName: XFKHEK+UniversLTStd-Cn
       Flags: Nonsymbolic
       FontBBox: -166, -250, 1000, 989
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: ESPTUS+MinionPro-BoldIt
      FontSubset: true
      FirstChar: 1
      LastChar: 34
      FontDescriptor: 
       FontName: ESPTUS+MinionPro-BoldIt
       Flags: Nonsymbolic, Italic, ForceBold
       FontBBox: -230, -360, 1684, 1032
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: EDQXES+UniversLTStd-Light
      FontSubset: true
      FirstChar: 1
      LastChar: 74
      FontDescriptor: 
       FontName: EDQXES+UniversLTStd-Light
       Flags: Nonsymbolic
       FontBBox: -151, -250, 1000, 957
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: IGECQW+STIXGeneral-Regular
      FontSubset: true
      FirstChar: 1
      LastChar: 6
      FontDescriptor: 
       FontName: IGECQW+STIXGeneral-Regular
       Flags: Nonsymbolic
       FontBBox: -995, -455, 2000, 1055
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: KZMHGN+UniversLTStd-LightObl
      FontSubset: true
      FirstChar: 1
      LastChar: 22
      FontDescriptor: 
       FontName: KZMHGN+UniversLTStd-LightObl
       Flags: Nonsymbolic, Italic
       FontBBox: -151, -274, 1144, 957
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
     Font: 
      BaseFont: ZILKIN+MinionPro-It
      FontSubset: true
      FirstChar: 1
      LastChar: 18
      FontDescriptor: 
       FontName: ZILKIN+MinionPro-It
       Flags: Nonsymbolic, Italic
       FontBBox: -201, -360, 1684, 1002
       FontFile3: true
      EncodingDictionary: 
       BaseEncoding: WinAnsiEncoding
       Differences: true
      ToUnicode: true
    CIDFontType2: 
     Font: 
      BaseFont: VQNHOG+TimesNewRomanPSMT
      CIDSystemInfo: 
       Registry: Adobe
       Registry: Identity
       Supplement: 0
      FontDescriptor: 
       FontName: VQNHOG+TimesNewRomanPSMT
       Flags: Nonsymbolic
       FontBBox: -568, -307, 2046, 1040
       FontFile2: true
   XMP: <x:xmpmeta xmlns:x="adobe:ns:meta/" x:xmptk="Adobe XMP Core 5.4-c006 80.159825, 2016/09/16-03:31:08        ">
   <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about=""
            xmlns:xmpMM="http://ns.adobe.com/xap/1.0/mm/"
            xmlns:xmpRights="http://ns.adobe.com/xap/1.0/rights/"
            xmlns:pdf="http://ns.adobe.com/pdf/1.3/"
            xmlns:dc="http://purl.org/dc/elements/1.1/"
            xmlns:prism="http://prismstandard.org/namespaces/basic/2.0/"
            xmlns:xmp="http://ns.adobe.com/xap/1.0/"
            xmlns:pdfx="http://ns.adobe.com/pdfx/1.3/"
            xmlns:pdfuaid="http://www.aiim.org/pdfua/ns/id/"
            xmlns:pdfaExtension="http://www.aiim.org/pdfa/ns/extension/"
            xmlns:pdfaSchema="http://www.aiim.org/pdfa/ns/schema#"
            xmlns:pdfaProperty="http://www.aiim.org/pdfa/ns/property#">
         <xmpMM:InstanceID>uuid:e84d4019-f2ca-4318-a69b-8c35459b3aa0</xmpMM:InstanceID>
         <xmpMM:DocumentID>uuid:EE78428A-CA0D-AA42-3348-EB818B138824</xmpMM:DocumentID>
         <xmpRights:Marked>True</xmpRights:Marked>
         <pdf:Keywords>SARS-CoV-2; COVID-19; remdesivir; kidney impairment</pdf:Keywords>
         <pdf:Producer>PDFlib+PDI 9.0.7p3 (C++/Win64)</pdf:Producer>
         <dc:format>application/pdf</dc:format>
         <dc:identifier>10.1093/cid/ciae333</dc:identifier>
         <dc:lang>en</dc:lang>
         <dc:publisher>
            <rdf:Bag>
               <rdf:li>Oxford University Press</rdf:li>
            </rdf:Bag>
         </dc:publisher>
         <dc:title>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">Efficacy and Safety of Remdesivir in People With Impaired Kidney Function Hospitalized for COVID-19 Pneumonia: A Randomized Clinical Trial</rdf:li>
            </rdf:Alt>
         </dc:title>
         <dc:creator>
            <rdf:Seq>
               <rdf:li>Meghan E. Sise</rdf:li>
               <rdf:li>Jose Ramon Santos</rdf:li>
               <rdf:li>Jason D. Goldman</rdf:li>
               <rdf:li>Katherine R. Tuttle</rdf:li>
               <rdf:li>J. Pedro Teixeira</rdf:li>
               <rdf:li>Allan F. Seibert</rdf:li>
               <rdf:li>Yiannis Koullias</rdf:li>
               <rdf:li>Joe Llewellyn</rdf:li>
               <rdf:li>Sean Regan</rdf:li>
               <rdf:li>Yang Zhao</rdf:li>
               <rdf:li>Hailin Huang</rdf:li>
               <rdf:li>Robert H. Hyland</rdf:li>
               <rdf:li>Anu Osinusi</rdf:li>
               <rdf:li>Helen Winter</rdf:li>
               <rdf:li>Rita Humeniuk</rdf:li>
               <rdf:li>Henry N. Hulter</rdf:li>
               <rdf:li>Robert L. Gottlieb</rdf:li>
               <rdf:li>Dahlene N. Fusco</rdf:li>
               <rdf:li>Rita Birne</rdf:li>
               <rdf:li>Fernando F. Stancampiano</rdf:li>
               <rdf:li>Claudia R. Libertin</rdf:li>
               <rdf:li>Catherine B. Small</rdf:li>
               <rdf:li>Markus Plate</rdf:li>
               <rdf:li>Mark J. McPhail</rdf:li>
               <rdf:li>for the REDPINE Investigators</rdf:li>
            </rdf:Seq>
         </dc:creator>
         <dc:description>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">DOI: 10.1093/cid/ciae333; Clinical Infectious Diseases, 79, 5, 2024-06-24.; Abstract:  Background: Few antiviral therapies have been studied in patients with coronavirus disease 2019 (COVID-19) and kidney impairment. Herein, the efficacy, safety, and pharmacokinetics of remdesivir, its metabolites, and sulfobutylether-β-cyclodextrin excipient were evaluated in hospitalized patients with COVID-19 and severe kidney impairment. Methods: In REDPINE, a phase 3, randomized, double-blind, placebo-controlled study, participants aged ≥12 years hospitalized for COVID-19 pneumonia with acute kidney injury, chronic kidney disease, or kidney failure were randomized 2:1 to receive intravenous remdesivir (200 mg on day 1; 100 mg daily up to day 5) or placebo (enrollment from March 2021 to March 2022). The primary efficacy end point was the composite of the all-cause mortality rate or invasive mechanical ventilation rate through day 29. Safety was evaluated through day 60. Results: Although enrollme</rdf:li>
            </rdf:Alt>
         </dc:description>
         <dc:rights>
            <rdf:Alt>
               <rdf:li xml:lang="x-default">© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.</rdf:li>
            </rdf:Alt>
         </dc:rights>
         <dc:subject>
            <rdf:Bag>
               <rdf:li>SARS-CoV-2</rdf:li>
               <rdf:li>COVID-19</rdf:li>
               <rdf:li>remdesivir</rdf:li>
               <rdf:li>kidney impairment</rdf:li>
            </rdf:Bag>
         </dc:subject>
         <prism:aggregationType>Journal</prism:aggregationType>
         <prism:publicationName>Clinical Infectious Diseases</prism:publicationName>
         <prism:copyright>© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.</prism:copyright>
         <prism:issn>1058-4838</prism:issn>
         <prism:elssn>1537-6591</prism:elssn>
         <prism:volume>79</prism:volume>
         <prism:number>5</prism:number>
         <prism:issueName/>
         <prism:startingPage>1172</prism:startingPage>
         <prism:endingPage>1181</prism:endingPage>
         <prism:doi>10.1093/cid/ciae333</prism:doi>
         <prism:url>https://doi.org/10.1093/cid/ciae333</prism:url>
         <xmp:CreateDate>2024-11-19T14:09:29+05:30</xmp:CreateDate>
         <xmp:ModifyDate>2024-11-21T10:14:51+05:30</xmp:ModifyDate>
         <xmp:CreatorTool>Servigistics Arbortext Advanced Print Publisher 11.1.4546/W-x64</xmp:CreatorTool>
         <xmp:MetadataDate>2024-11-21T10:14:51+05:30</xmp:MetadataDate>
         <pdfx:EPSprocessor>PStill version 1.84.42</pdfx:EPSprocessor>
         <pdfuaid:part>1</pdfuaid:part>
         <pdfaExtension:schemas>
            <rdf:Bag>
               <rdf:li rdf:parseType="Resource">
                  <pdfaSchema:schema>PDF/UA Universal Accessibility Schema</pdfaSchema:schema>
                  <pdfaSchema:namespaceURI>http://www.aiim.org/pdfua/ns/id/</pdfaSchema:namespaceURI>
                  <pdfaSchema:prefix>pdfuaid</pdfaSchema:prefix>
                  <pdfaSchema:property>
                     <rdf:Seq>
                        <rdf:li rdf:parseType="Resource">
                           <pdfaProperty:name>part</pdfaProperty:name>
                           <pdfaProperty:valueType>Integer</pdfaProperty:valueType>
                           <pdfaProperty:category>internal</pdfaProperty:category>
                           <pdfaProperty:description>Indicates, which part of ISO 14289 standard is followed</pdfaProperty:description>
                        </rdf:li>
                     </rdf:Seq>
                  </pdfaSchema:property>
               </rdf:li>
            </rdf:Bag>
         </pdfaExtension:schemas>
      </rdf:Description>
   </rdf:RDF>
</x:xmpmeta>
   Pages: 
    Page: 
     Sequence: 1
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 101, 618, 104, 626
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 172, 618, 175, 626
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 238, 618, 241, 626
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 242, 618, 245, 626
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 309, 618, 312, 626
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 372, 618, 375, 626
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 429, 618, 432, 626
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 489, 618, 492, 626
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 542, 618, 544, 626
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 89, 608, 92, 616
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 131, 608, 133, 616
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 180, 608, 183, 616
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 242, 608, 245, 616
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 288, 608, 291, 616
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 338, 608, 341, 616
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 393, 608, 396, 616
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 451, 608, 453, 616
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 514, 608, 519, 616
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 521, 608, 526, 616
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 108, 598, 113, 606
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 150, 598, 156, 606
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 157, 598, 162, 606
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 253, 598, 258, 606
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 323, 598, 328, 606
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 394, 598, 399, 606
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 447, 598, 452, 606
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 524, 598, 529, 606
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 146, 588, 149, 596
       Flags: Print
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 449, 201, 453, 210
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 457, 201, 462, 210
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 327, 175, 332, 184
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 48, 201, 110, 208
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 161, 181, 202, 188
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 138, 134, 267, 141
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 48, 71, 137, 78
       Flags: Print
    Page: 
     Sequence: 2
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 133, 721, 138, 730
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 231, 669, 287, 678
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 48, 656, 80, 665
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 88, 656, 93, 665
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 98, 656, 102, 665
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 71, 226, 76, 236
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 167, 175, 171, 184
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 306, 721, 402, 730
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 471, 669, 476, 678
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 309, 439, 318, 448
       Flags: Print
       Destination: 32
    Page: 
     Sequence: 3
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 507, 642, 539, 651
       Flags: Print
       Destination: 4
    Page: 
     Sequence: 4
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 236, 643, 267, 652
       Flags: Print
       Destination: 10
      Annotation: 
       Subtype: Link
       Rect: 402, 656, 489, 665
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 309, 486, 346, 496
       Flags: Print
       Destination: 16
    Page: 
     Sequence: 5
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 52, 97, 91, 106
       Flags: Print
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 96, 97, 107, 106
       Flags: Print
       Destination: null
      Annotation: 
       Subtype: Link
       Rect: 130, 97, 222, 106
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 358, 136, 447, 145
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 422, 123, 513, 132
       Flags: Print
    Page: 
     Sequence: 6
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 190, 253, 223, 262
       Flags: Print
       Destination: 23
      Annotation: 
       Subtype: Link
       Rect: 487, 123, 544, 132
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 306, 110, 333, 119
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 421, 71, 453, 80
       Flags: Print
       Destination: 26
    Page: 
     Sequence: 7
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 233, 71, 237, 80
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 309, 708, 396, 717
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 415, 708, 506, 717
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 422, 383, 431, 392
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 436, 383, 445, 392
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 449, 318, 458, 327
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 491, 214, 501, 223
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 439, 201, 448, 210
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 360, 136, 369, 145
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 333, 97, 342, 106
       Flags: Print
       Destination: 32
    Page: 
     Sequence: 8
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 114, 123, 123, 132
       Flags: Print
       Destination: 32
    Page: 
     Sequence: 9
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 220, 734, 225, 743
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 230, 734, 239, 743
       Flags: Print
       Destination: 35
      Annotation: 
       Subtype: Link
       Rect: 52, 695, 56, 704
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 62, 695, 71, 704
       Flags: Print
       Destination: 35
      Annotation: 
       Subtype: Link
       Rect: 76, 695, 85, 704
       Flags: Print
       Destination: 35
      Annotation: 
       Subtype: Link
       Rect: 260, 682, 269, 691
       Flags: Print
       Destination: 35
      Annotation: 
       Subtype: Link
       Rect: 48, 477, 128, 485
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 306, 468, 312, 474
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 306, 440, 312, 447
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 306, 413, 312, 420
       Flags: Print
       Destination: 1043
      Annotation: 
       Subtype: Link
       Rect: 306, 386, 312, 393
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 306, 368, 312, 375
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 306, 341, 312, 348
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 306, 305, 312, 312
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 306, 287, 312, 294
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 306, 269, 312, 276
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 306, 251, 312, 258
       Flags: Print
       Destination: 1
      Annotation: 
       Subtype: Link
       Rect: 306, 233, 312, 240
       Flags: Print
       Destination: 23
      Annotation: 
       Subtype: Link
       Rect: 306, 206, 312, 213
       Flags: Print
       Destination: 23
      Annotation: 
       Subtype: Link
       Rect: 306, 170, 312, 177
       Flags: Print
       Destination: 23
      Annotation: 
       Subtype: Link
       Rect: 460, 161, 544, 168
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 317, 152, 513, 159
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 306, 134, 312, 141
       Flags: Print
       Destination: 23
      Annotation: 
       Subtype: Link
       Rect: 306, 116, 312, 123
       Flags: Print
       Destination: 23
      Annotation: 
       Subtype: Link
       Rect: 306, 98, 312, 105
       Flags: Print
       Destination: 23
      Annotation: 
       Subtype: Link
       Rect: 306, 80, 312, 87
       Flags: Print
       Destination: 26
    Page: 
     Sequence: 10
     Annotations: 
      Annotation: 
       Subtype: Link
       Rect: 48, 718, 55, 725
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 60, 709, 287, 716
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 60, 700, 248, 707
       Flags: Print
      Annotation: 
       Subtype: Link
       Rect: 48, 682, 55, 689
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 306, 736, 312, 743
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 306, 709, 312, 716
       Flags: Print
       Destination: 32
      Annotation: 
       Subtype: Link
       Rect: 306, 682, 312, 689
       Flags: Print
       Destination: 32
  Checksum: 3f8129b9
   Type: CRC32
  Checksum: f9e70e394d7c12360f2309fde129e966
   Type: MD5
  Checksum: bbdcb19300d050d0bcea79bf0821b1175b89cc3f
   Type: SHA-1
  Checksum: 64a3323292f6ffb8b000270834906e0d0e034a6dd5079f3c9ec1f04708d11cb4
   Type: SHA-256