83071ec9451943e5a7bec1dadfa2b4d8 pmc_11116820.pdf 5a2f514c7fd1e7e9eeca23a974004ff0cff14832 pmc_11116820.pdf 0f457211a5f59135c6e659cc515b2b2ef6b6e904ad8944928f72d4c522d13d55 pmc_11116820.pdf Title: Trends of use and characterisation of anti-dementia drugs users: a large multinational-network population-based study Subject: AcademicSubjects/MED00280, DOI: 10.1093/ageing/afae106, Age and Ageing, 53, 00, 18 5 2024. Abstract: Background: An updated time-trend analysis of anti-dementia drugs (ADDs) is lacking. The aim of this study is to assess the incident rate (IR) of ADD in individuals with dementia using real-world data.Setting: Primary care data (country/database) from the UK/CPRD-GOLD (2007–20), Spain/SIDIAP (2010–20) and the Netherlands/IPCI (2008–20), standardised to a common data model.Methods: Cohort study. Participants: dementia patients ≥40 years old with ≥1 year of previous data. Follow-up: until the end of the study period, transfer out of the catchment area, death or incident prescription of rivastigmine, galantamine, donepezil or memantine. Other variables: age/sex, type of dementia, comorbidities. Statistics: overall and yearly age/sex IR, with 95% confidence interval, per 100,000 person-years (IR per 10 PY (95%CI)).Results: We identified a total of (incident anti-dementia users/dementia patients) 41,024/110,642 in UK/CPRD-GOLD, 51,667/134,927 in Spain/SIDIAP and 2,088/17,559 in the Netherlands/IPCI. In the UK, IR (per 10 PY (95%CI)) of ADD decreased from 2007 (30,829 (28,891–32,862)) to 2010 (17,793 (17,083–18,524)), then increased up to 2019 (31,601 (30,483 to 32,749)) and decrease in 2020 (24,067 (23,021–25,148)). In Spain, IR (per 10 PY (95%CI)) of ADD decreased by 72% from 2010 (51,003 (49,199–52,855)) to 2020 (14,571 (14,109–15,043)). In the Netherlands, IR (per 10 PY (95%CI)) of ADD decreased by 77% from 2009 (21,151 (14,967–29,031)) to 2020 (4763 (4176–5409)). Subjects aged ≥65–79 years and men (in the UK and the Netherlands) initiated more frequently an ADD.Conclusions: Treatment of dementia remains highly heterogeneous. Further consensus in the pharmacological management of patients living with dementia is urgently needed. Keywords: Author: Creator: LaTeX with hyperref package Producer: Acrobat Distiller 23.0 (Windows) CreationDate: Wed May 22 11:57:18 2024 CEST ModDate: Wed May 22 11:57:18 2024 CEST Custom Metadata: yes Metadata Stream: yes Tagged: yes UserProperties: no Suspects: no Form: none JavaScript: no Pages: 9 Encrypted: no Page size: 612.332 x 790.759 pts Page rot: 0 File size: 865447 bytes Optimized: yes PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- GIJNCL+GillSansStd-Bold Type 1C Custom yes yes yes 1630 0 GIJNDM+GillSansStd-LightItalic Type 1C Custom yes yes yes 1574 0 GIJNDN+GillSansStd-Light Type 1C Custom yes yes yes 1575 0 GIJNDO+GillSansMTStd-Light Type 1C Custom yes yes yes 1576 0 GIJNHN+AGaramondPro-Bold Type 1C Custom yes yes yes 1631 0 GIJNHO+AGaramondPro-Regular Type 1C Custom yes yes yes 1632 0 GIJNHP+MTSYN Type 1C Custom yes yes yes 1633 0 GIJNLP+GillSansStd-BoldItalic Type 1C Custom yes yes yes 33 0 GIJOKK+AGaramondPro-Italic Type 1C Custom yes yes yes 34 0 GIJPAJ+MTMI Type 1C Custom yes yes yes 35 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-02-06 02:50:57 CET RepresentationInformation: pmc_11116820.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-12-18 02:31:53 CET Size: 865447 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf Profile: Linearized PDF, Tagged PDF PDFMetadata: Objects: 1662 FreeObjects: 1 IncrementalUpdates: 1 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: true NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseOutlines Language: en Outlines: Item: Title: Trends of use and characterisation of anti-dementia drugs users: a large multinational-network population-based study Destination: toc.chapter Children: Item: Title: Introduction Destination: section.12.1.1 Item: Title: Methods Destination: section.13.1.2 Item: Title: Results Destination: section.19.1.3 Item: Title: Discussion Destination: section.25.1.4 Item: Title: Conclusions Destination: section.27.1.5 Item: Title: 6 Supplementary Data: Destination: section.28.1.6 Item: Title: 7 Acknowledgements: Destination: section.29.1.7 Item: Title: 8 Declaration of Conflicts of Interest: Destination: section.30.1.8 Item: Title: 9 Declaration of Sources of Funding: Destination: section.31.1.9 Item: Title: 10 Data availability: Destination: section.32.1.10 Info: Title: Trends of use and characterisation of anti-dementia drugs users: a large multinational-network population-based study Author: Subject: AcademicSubjects/MED00280, DOI: 10.1093/ageing/afae106, Age and Ageing, 53, 00, 18 5 2024. Abstract: Background: An updated time-trend analysis of anti-dementia drugs (ADDs) is lacking. The aim of this study is to assess the incident rate (IR) of ADD in individuals with dementia using real-world data.Setting: Primary care data (country/database) from the UK/CPRD-GOLD (2007–20), Spain/SIDIAP (2010–20) and the Netherlands/IPCI (2008–20), standardised to a common data model.Methods: Cohort study. Participants: dementia patients ≥40 years old with ≥1 year of previous data. Follow-up: until the end of the study period, transfer out of the catchment area, death or incident prescription of rivastigmine, galantamine, donepezil or memantine. Other variables: age/sex, type of dementia, comorbidities. Statistics: overall and yearly age/sex IR, with 95% confidence interval, per 100,000 person-years (IR per 10 PY (95%CI)).Results: We identified a total of (incident anti-dementia users/dementia patients) 41,024/110,642 in UK/CPRD-GOLD, 51,667/134,927 in Spain/SIDIAP and 2,088/17,559 in the Netherlands/IPCI. In the UK, IR (per 10 PY (95%CI)) of ADD decreased from 2007 (30,829 (28,891–32,862)) to 2010 (17,793 (17,083–18,524)), then increased up to 2019 (31,601 (30,483 to 32,749)) and decrease in 2020 (24,067 (23,021–25,148)). In Spain, IR (per 10 PY (95%CI)) of ADD decreased by 72% from 2010 (51,003 (49,199–52,855)) to 2020 (14,571 (14,109–15,043)). In the Netherlands, IR (per 10 PY (95%CI)) of ADD decreased by 77% from 2009 (21,151 (14,967–29,031)) to 2020 (4763 (4176–5409)). Subjects aged ≥65–79 years and men (in the UK and the Netherlands) initiated more frequently an ADD.Conclusions: Treatment of dementia remains highly heterogeneous. Further consensus in the pharmacological management of patients living with dementia is urgently needed. Keywords: Creator: LaTeX with hyperref package Producer: Acrobat Distiller 23.0 (Windows) CreationDate: Wed May 22 12:27:18 CEST 2024 ModDate: Wed May 22 12:27:18 CEST 2024 ID: 0x3ee60d5ea2eb8ccc23794e88adeb4047, 0xe03a12bf7e493125b510cc0627a66e18 Filters: FilterPipeline: FlateDecode FilterPipeline: DCTDecode Images: Image: NisoImageMetadata: FormatName: image/jpg CompressionScheme: JPEG ImageWidth: 1980 ImageHeight: 564 ColorSpace: RGB BitsPerSample: 8 BitsPerSampleUnit: integer Fonts: Type1: Font: BaseFont: GIJNHO+AGaramondPro-Regular FontSubset: true FirstChar: 2 LastChar: 243 FontDescriptor: FontName: GIJNHO+AGaramondPro-Regular Flags: Serif, Symbolic FontBBox: -183, -354, 1356, 917 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GIJNHP+MTSYN FontSubset: true FirstChar: 2 LastChar: 43 FontDescriptor: FontName: GIJNHP+MTSYN Flags: Symbolic FontBBox: 0, -954, 1043, 900 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GIJNLP+GillSansStd-BoldItalic FontSubset: true FirstChar: 97 LastChar: 116 FontDescriptor: FontName: GIJNLP+GillSansStd-BoldItalic Flags: Symbolic, Italic, ForceBold FontBBox: -190, -250, 1074, 915 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GIJOKK+AGaramondPro-Italic FontSubset: true FirstChar: 46 LastChar: 121 FontDescriptor: FontName: GIJOKK+AGaramondPro-Italic Flags: Serif, Symbolic, Italic FontBBox: -182, -338, 1668, 917 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GIJPAJ+MTMI FontSubset: true FirstChar: 60 LastChar: 62 FontDescriptor: FontName: GIJPAJ+MTMI Flags: Serif, Symbolic, Italic FontBBox: 0, -213, 987, 680 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GIJNDM+GillSansStd-LightItalic FontSubset: true FirstChar: 65 LastChar: 110 FontDescriptor: FontName: GIJNDM+GillSansStd-LightItalic Flags: Symbolic, Italic FontBBox: -205, -250, 1051, 894 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GIJNDN+GillSansStd-Light FontSubset: true FirstChar: 2 LastChar: 243 FontDescriptor: FontName: GIJNDN+GillSansStd-Light Flags: Symbolic FontBBox: -215, -250, 1036, 897 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GIJNDO+GillSansMTStd-Light FontSubset: true FirstChar: 2 LastChar: 86 FontDescriptor: FontName: GIJNDO+GillSansMTStd-Light Flags: Symbolic FontBBox: -215, -232, 1036, 937 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GIJNCL+GillSansStd-Bold FontSubset: true FirstChar: 2 LastChar: 121 FontDescriptor: FontName: GIJNCL+GillSansStd-Bold Flags: Symbolic, ForceBold FontBBox: -177, -250, 1167, 929 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true Font: BaseFont: GIJNHN+AGaramondPro-Bold FontSubset: true FirstChar: 46 LastChar: 148 FontDescriptor: FontName: GIJNHN+AGaramondPro-Bold Flags: Serif, Symbolic, ForceBold FontBBox: -158, -302, 1147, 899 FontFile3: true EncodingDictionary: Differences: true ToUnicode: true XMP: application/pdf Trends of use and characterisation of anti-dementia drugs users: a large multinational-network population-based study Reyes CarlenNewby DanielleRaventós BertaVerhamme KatiaMosseveld MeesPrieto-Alhambra DanielBurn EdwardDuarte-Salles Talita AcademicSubjects/MED00280, DOI: 10.1093/ageing/afae106, Age and Ageing, 53, 00, 18 5 2024. Abstract: Background: An updated time-trend analysis of anti-dementia drugs (ADDs) is lacking. The aim of this study is to assess the incident rate (IR) of ADD in individuals with dementia using real-world data.Setting: Primary care data (country/database) from the UK/CPRD-GOLD (2007–20), Spain/SIDIAP (2010–20) and the Netherlands/IPCI (2008–20), standardised to a common data model.Methods: Cohort study. Participants: dementia patients ≥40 years old with ≥1 year of previous data. Follow-up: until the end of the study period, transfer out of the catchment area, death or incident prescription of rivastigmine, galantamine, donepezil or memantine. Other variables: age/sex, type of dementia, comorbidities. Statistics: overall and yearly age/sex IR, with 95% confidence interval, per 100,000 person-years (IR per 10 PY (95%CI)).Results: We identified a total of (incident anti-dementia users/dementia patients) 41,024/110,642 in UK/CPRD-GOLD, 51,667/134,927 in Spain/SIDIAP and 2,088/17,559 in the Netherlands/IPCI. In the UK, IR (per 10 PY (95%CI)) of ADD decreased from 2007 (30,829 (28,891–32,862)) to 2010 (17,793 (17,083–18,524)), then increased up to 2019 (31,601 (30,483 to 32,749)) and decrease in 2020 (24,067 (23,021–25,148)). In Spain, IR (per 10 PY (95%CI)) of ADD decreased by 72% from 2010 (51,003 (49,199–52,855)) to 2020 (14,571 (14,109–15,043)). In the Netherlands, IR (per 10 PY (95%CI)) of ADD decreased by 77% from 2009 (21,151 (14,967–29,031)) to 2020 (4763 (4176–5409)). Subjects aged ≥65–79 years and men (in the UK and the Netherlands) initiated more frequently an ADD.Conclusions: Treatment of dementia remains highly heterogeneous. Further consensus in the pharmacological management of patients living with dementia is urgently needed. dementiadrug utilization studiescohort studiesolder people © The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com. True Pages: Page: Label: 1 Annotations: Annotation: Subtype: Link Rect: 343, 725, 367, 734 Annotation: Subtype: Link Rect: 367, 725, 382, 734 Annotation: Subtype: Link Rect: 382, 725, 386, 734 Annotation: Subtype: Link Rect: 386, 725, 394, 734 Annotation: Subtype: Link Rect: 394, 725, 403, 734 Annotation: Subtype: Link Rect: 403, 725, 422, 734 Annotation: Subtype: Link Rect: 422, 725, 436, 734 Annotation: Subtype: Link Rect: 436, 725, 445, 734 Annotation: Subtype: Link Rect: 445, 725, 449, 734 Annotation: Subtype: Link Rect: 449, 725, 457, 734 Annotation: Subtype: Link Rect: 457, 725, 469, 734 Annotation: Subtype: Link Rect: 469, 725, 474, 734 Annotation: Subtype: Link Rect: 474, 725, 486, 734 Annotation: Subtype: Link Rect: 486, 725, 497, 734 Annotation: Subtype: Link Rect: 497, 725, 522, 734 Annotation: Subtype: Link Rect: 115, 572, 119, 577 Destination: 1564 Annotation: Subtype: Link Rect: 120, 572, 124, 577 Destination: 1564 Annotation: Subtype: Link Rect: 211, 572, 214, 577 Destination: 1564 Annotation: Subtype: Link Rect: 299, 572, 303, 577 Destination: 1564 Annotation: Subtype: Link Rect: 304, 572, 308, 577 Destination: 1564 Annotation: Subtype: Link Rect: 394, 572, 397, 577 Destination: 1564 Annotation: Subtype: Link Rect: 483, 572, 487, 577 Destination: 1564 Annotation: Subtype: Link Rect: 171, 560, 174, 565 Destination: 1564 Annotation: Subtype: Link Rect: 176, 560, 180, 565 Destination: 1564 Annotation: Subtype: Link Rect: 255, 560, 258, 565 Destination: 1564 Annotation: Subtype: Link Rect: 386, 560, 389, 565 Destination: 1564 Annotation: Subtype: Link Rect: 391, 560, 394, 565 Destination: 1564 Annotation: Subtype: Link Rect: 47, 538, 51, 543 Destination: 1564 Annotation: Subtype: Link Rect: 47, 526, 51, 531 Destination: 1564 Annotation: Subtype: Link Rect: 47, 514, 51, 519 Destination: 1564 Annotation: Subtype: Link Rect: 47, 490, 51, 495 Destination: 1564 Annotation: Subtype: Link Rect: 47, 478, 51, 483 Destination: 1564 Annotation: Subtype: Link Rect: 72, 429, 151, 438 Annotation: Subtype: Link Rect: 72, 429, 84, 438 Annotation: Subtype: Link Rect: 84, 429, 93, 438 Annotation: Subtype: Link Rect: 93, 429, 106, 438 Annotation: Subtype: Link Rect: 106, 429, 117, 438 Annotation: Subtype: Link Rect: 117, 429, 134, 438 Annotation: Subtype: Link Rect: 134, 429, 143, 438 Annotation: Subtype: Link Rect: 143, 429, 151, 438 Page: Label: 2 Annotations: Annotation: Subtype: Link Rect: 129, 651, 135, 658 Destination: 27 Annotation: Subtype: Link Rect: 66, 627, 71, 634 Destination: 27 Annotation: Subtype: Link Rect: 76, 627, 81, 635 Destination: 27 Annotation: Subtype: Link Rect: 202, 567, 207, 574 Destination: 27 Annotation: Subtype: Link Rect: 277, 543, 282, 551 Destination: 27 Annotation: Subtype: Link Rect: 287, 543, 298, 550 Destination: 27 Annotation: Subtype: Link Rect: 153, 531, 159, 539 Destination: 27 Annotation: Subtype: Link Rect: 165, 531, 176, 538 Destination: 27 Annotation: Subtype: Link Rect: 265, 531, 270, 539 Destination: 27 Annotation: Subtype: Link Rect: 277, 531, 282, 538 Destination: 27 Annotation: Subtype: Link Rect: 287, 531, 298, 538 Destination: 27 Annotation: Subtype: Link Rect: 185, 496, 196, 502 Destination: 27 Annotation: Subtype: Link Rect: 201, 496, 211, 503 Destination: 27 Annotation: Subtype: Link Rect: 113, 484, 124, 490 Destination: 27 Annotation: Subtype: Link Rect: 188, 483, 198, 490 Destination: 27 Annotation: Subtype: Link Rect: 95, 472, 105, 479 Destination: 27 Annotation: Subtype: Link Rect: 122, 435, 132, 443 Destination: 27 Annotation: Subtype: Link Rect: 138, 436, 148, 443 Destination: 27 Annotation: Subtype: Link Rect: 291, 423, 301, 431 Destination: 27 Annotation: Subtype: Link Rect: 62, 412, 73, 419 Destination: 27 Annotation: Subtype: Link Rect: 130, 399, 141, 407 Destination: 27 Annotation: Subtype: Link Rect: 146, 400, 156, 407 Destination: 27 Annotation: Subtype: Link Rect: 66, 364, 76, 371 Destination: 27 Annotation: Subtype: Link Rect: 293, 340, 299, 348 Destination: 27 Annotation: Subtype: Link Rect: 62, 328, 73, 335 Destination: 27 Annotation: Subtype: Link Rect: 79, 328, 89, 335 Destination: 27 Annotation: Subtype: Link Rect: 94, 328, 105, 336 Destination: 27 Annotation: Subtype: Link Rect: 111, 328, 121, 336 Destination: 30 Annotation: Subtype: Link Rect: 236, 328, 241, 336 Destination: 27 Annotation: Subtype: Link Rect: 247, 328, 252, 335 Destination: 27 Annotation: Subtype: Link Rect: 258, 328, 268, 335 Destination: 27 Annotation: Subtype: Link Rect: 274, 328, 284, 335 Destination: 27 Annotation: Subtype: Link Rect: 290, 328, 301, 336 Destination: 30 Annotation: Subtype: Link Rect: 164, 91, 174, 98 Destination: 30 Annotation: Subtype: Link Rect: 192, 79, 203, 87 Destination: 30 Annotation: Subtype: Link Rect: 209, 79, 219, 86 Destination: 30 Annotation: Subtype: Link Rect: 287, 67, 298, 74 Destination: 30 Annotation: Subtype: Link Rect: 461, 719, 471, 726 Destination: 30 Annotation: Subtype: Link Rect: 481, 717, 528, 727 Annotation: Subtype: Link Rect: 322, 426, 356, 436 Annotation: Subtype: Link Rect: 356, 426, 366, 436 Annotation: Subtype: Link Rect: 366, 426, 377, 436 Annotation: Subtype: Link Rect: 377, 426, 402, 436 Annotation: Subtype: Link Rect: 402, 426, 414, 436 Annotation: Subtype: Link Rect: 340, 402, 387, 412 Annotation: Subtype: Link Rect: 472, 301, 483, 308 Destination: 30 Page: Label: 3 Annotations: Annotation: Subtype: Link Rect: 142, 396, 172, 403 Destination: 7 Annotation: Subtype: Link Rect: 109, 226, 143, 236 Destination: 10 Annotation: Subtype: Link Rect: 467, 418, 504, 427 Destination: 10 Annotation: Subtype: Link Rect: 510, 420, 515, 428 Destination: 17 Page: Label: 4 Page: Label: 5 Page: Label: 6 Annotations: Annotation: Subtype: Link Rect: 435, 174, 440, 181 Destination: 27 Annotation: Subtype: Link Rect: 447, 175, 452, 181 Destination: 27 Annotation: Subtype: Link Rect: 459, 175, 470, 181 Destination: 27 Annotation: Subtype: Link Rect: 477, 174, 488, 181 Destination: 30 Annotation: Subtype: Link Rect: 495, 174, 505, 181 Destination: 30 Annotation: Subtype: Link Rect: 547, 151, 557, 158 Destination: 27 Annotation: Subtype: Link Rect: 425, 114, 436, 122 Destination: 30 Annotation: Subtype: Link Rect: 363, 90, 373, 98 Destination: 30 Page: Label: 7 Annotations: Annotation: Subtype: Link Rect: 220, 719, 231, 726 Destination: 27 Annotation: Subtype: Link Rect: 236, 719, 246, 727 Destination: 27 Annotation: Subtype: Link Rect: 275, 683, 286, 691 Destination: 30 Annotation: Subtype: Link Rect: 245, 635, 256, 643 Destination: 30 Annotation: Subtype: Link Rect: 94, 599, 105, 607 Destination: 30 Annotation: Subtype: Link Rect: 175, 587, 186, 594 Destination: 30 Annotation: Subtype: Link Rect: 250, 527, 261, 535 Destination: 30 Annotation: Subtype: Link Rect: 259, 346, 313, 356 Annotation: Subtype: Link Rect: 82, 336, 87, 344 Annotation: Subtype: Link Rect: 186, 229, 191, 237 Destination: 27 Annotation: Subtype: Link Rect: 196, 229, 201, 236 Destination: 27 Annotation: Subtype: Link Rect: 207, 229, 217, 236 Destination: 27 Annotation: Subtype: Link Rect: 222, 229, 233, 236 Destination: 30 Annotation: Subtype: Link Rect: 165, 121, 195, 129 Destination: 7 Annotation: Subtype: Link Rect: 189, 109, 194, 117 Destination: 27 Annotation: Subtype: Link Rect: 201, 109, 206, 116 Destination: 27 Annotation: Subtype: Link Rect: 214, 109, 224, 116 Destination: 27 Annotation: Subtype: Link Rect: 413, 539, 423, 547 Destination: 30 Annotation: Subtype: Link Rect: 307, 83, 388, 93 Page: Label: 8 Annotations: Annotation: Subtype: Link Rect: 94, 340, 124, 350 Annotation: Subtype: Link Rect: 124, 340, 130, 350 Annotation: Subtype: Link Rect: 130, 340, 143, 350 Annotation: Subtype: Link Rect: 143, 340, 156, 350 Annotation: Subtype: Link Rect: 156, 340, 170, 350 Annotation: Subtype: Link Rect: 170, 340, 185, 350 Annotation: Subtype: Link Rect: 185, 340, 192, 350 Annotation: Subtype: Link Rect: 192, 340, 216, 350 Annotation: Subtype: Link Rect: 216, 340, 225, 350 Annotation: Subtype: Link Rect: 225, 340, 233, 350 Annotation: Subtype: Link Rect: 233, 340, 238, 350 Annotation: Subtype: Link Rect: 238, 340, 245, 350 Annotation: Subtype: Link Rect: 245, 340, 254, 350 Annotation: Subtype: Link Rect: 254, 340, 271, 350 Annotation: Subtype: Link Rect: 271, 340, 276, 350 Annotation: Subtype: Link Rect: 146, 328, 229, 338 Annotation: Subtype: Link Rect: 146, 328, 152, 338 Annotation: Subtype: Link Rect: 152, 328, 165, 338 Annotation: Subtype: Link Rect: 165, 328, 181, 338 Annotation: Subtype: Link Rect: 181, 328, 193, 338 Annotation: Subtype: Link Rect: 193, 328, 211, 338 Annotation: Subtype: Link Rect: 211, 328, 221, 338 Annotation: Subtype: Link Rect: 221, 328, 229, 338 Annotation: Subtype: Link Rect: 67, 270, 75, 277 Destination: 1 Annotation: Subtype: Link Rect: 67, 227, 75, 233 Destination: 1 Annotation: Subtype: Link Rect: 67, 182, 75, 189 Destination: 1 Annotation: Subtype: Link Rect: 67, 161, 75, 168 Destination: 1 Annotation: Subtype: Link Rect: 67, 128, 75, 134 Destination: 1 Annotation: Subtype: Link Rect: 67, 84, 75, 91 Destination: 1 Annotation: Subtype: Link Rect: 327, 731, 334, 737 Destination: 1 Annotation: Subtype: Link Rect: 327, 676, 334, 682 Destination: 1 Annotation: Subtype: Link Rect: 327, 643, 334, 650 Destination: 1 Annotation: Subtype: Link Rect: 322, 600, 334, 606 Destination: 1 Annotation: Subtype: Link Rect: 322, 556, 334, 562 Destination: 1 Annotation: Subtype: Link Rect: 322, 512, 334, 518 Destination: 1 Annotation: Subtype: Link Rect: 322, 468, 334, 475 Destination: 1 Annotation: Subtype: Link Rect: 322, 424, 334, 431 Destination: 1 Annotation: Subtype: Link Rect: 322, 391, 334, 398 Destination: 1 Annotation: Subtype: Link Rect: 322, 348, 334, 354 Destination: 1 Annotation: Subtype: Link Rect: 476, 312, 503, 321 Annotation: Subtype: Link Rect: 503, 312, 524, 321 Annotation: Subtype: Link Rect: 524, 312, 531, 321 Annotation: Subtype: Link Rect: 531, 312, 542, 321 Annotation: Subtype: Link Rect: 542, 312, 548, 321 Annotation: Subtype: Link Rect: 548, 312, 563, 321 Annotation: Subtype: Link Rect: 340, 301, 355, 311 Annotation: Subtype: Link Rect: 355, 301, 361, 311 Annotation: Subtype: Link Rect: 361, 301, 384, 311 Annotation: Subtype: Link Rect: 384, 301, 395, 311 Annotation: Subtype: Link Rect: 395, 301, 406, 311 Annotation: Subtype: Link Rect: 406, 301, 422, 311 Annotation: Subtype: Link Rect: 422, 301, 451, 311 Annotation: Subtype: Link Rect: 451, 301, 464, 311 Annotation: Subtype: Link Rect: 322, 292, 334, 299 Destination: 1 Annotation: Subtype: Link Rect: 322, 238, 334, 244 Destination: 1 Annotation: Subtype: Link Rect: 322, 205, 334, 212 Destination: 1 Annotation: Subtype: Link Rect: 322, 161, 334, 167 Destination: 1 Annotation: Subtype: Link Rect: 322, 117, 334, 124 Destination: 1 Annotation: Subtype: Link Rect: 322, 95, 334, 102 Destination: 1 Page: Label: 9 Annotations: Annotation: Subtype: Link Rect: 47, 731, 60, 737 Destination: 1 Annotation: Subtype: Link Rect: 47, 709, 60, 716 Destination: 1 Annotation: Subtype: Link Rect: 47, 665, 60, 672 Destination: 1 Annotation: Subtype: Link Rect: 47, 632, 60, 639 Destination: 1 Annotation: Subtype: Link Rect: 47, 588, 60, 595 Destination: 1 Annotation: Subtype: Link Rect: 47, 556, 60, 562 Destination: 1 Annotation: Subtype: Link Rect: 47, 512, 60, 518 Destination: 1 Annotation: Subtype: Link Rect: 47, 468, 60, 474 Destination: 1 Annotation: Subtype: Link Rect: 194, 455, 221, 464 Annotation: Subtype: Link Rect: 221, 455, 232, 464 Annotation: Subtype: Link Rect: 232, 455, 239, 464 Annotation: Subtype: Link Rect: 239, 455, 246, 464 Annotation: Subtype: Link Rect: 246, 455, 259, 464 Annotation: Subtype: Link Rect: 259, 455, 265, 464 Annotation: Subtype: Link Rect: 265, 455, 278, 464 Annotation: Subtype: Link Rect: 278, 455, 289, 464 Annotation: Subtype: Link Rect: 65, 444, 75, 453 Annotation: Subtype: Link Rect: 75, 444, 83, 453 Annotation: Subtype: Link Rect: 83, 444, 92, 453 Annotation: Subtype: Link Rect: 92, 444, 104, 453 Annotation: Subtype: Link Rect: 104, 444, 112, 453 Annotation: Subtype: Link Rect: 112, 444, 121, 453 Annotation: Subtype: Link Rect: 121, 444, 133, 453 Annotation: Subtype: Link Rect: 133, 444, 141, 453 Annotation: Subtype: Link Rect: 141, 444, 154, 453 Annotation: Subtype: Link Rect: 154, 444, 165, 453 Annotation: Subtype: Link Rect: 165, 444, 173, 453 Annotation: Subtype: Link Rect: 173, 444, 179, 453 Annotation: Subtype: Link Rect: 179, 444, 198, 453 Annotation: Subtype: Link Rect: 198, 444, 211, 453 Annotation: Subtype: Link Rect: 211, 444, 218, 453 Annotation: Subtype: Link Rect: 218, 444, 235, 453 Annotation: Subtype: Link Rect: 47, 424, 60, 431 Destination: 17 Annotation: Subtype: Link Rect: 47, 391, 60, 397 Destination: 17 Annotation: Subtype: Link Rect: 307, 709, 319, 715 Destination: 17 Annotation: Subtype: Link Rect: 307, 665, 319, 672 Destination: 24 Annotation: Subtype: Link Rect: 307, 621, 319, 628 Destination: 24 Annotation: Subtype: Link Rect: 307, 566, 319, 574 Destination: 24 Annotation: Subtype: Link Rect: 393, 553, 421, 563 Annotation: Subtype: Link Rect: 421, 553, 426, 563 Annotation: Subtype: Link Rect: 426, 553, 443, 563 Annotation: Subtype: Link Rect: 443, 553, 454, 563 Annotation: Subtype: Link Rect: 454, 553, 461, 563 Annotation: Subtype: Link Rect: 461, 553, 482, 563 Annotation: Subtype: Link Rect: 482, 553, 493, 563 Annotation: Subtype: Link Rect: 493, 553, 503, 563 Annotation: Subtype: Link Rect: 503, 553, 520, 563 Annotation: Subtype: Link Rect: 520, 553, 532, 563 Annotation: Subtype: Link Rect: 532, 553, 540, 563 Annotation: Subtype: Link Rect: 540, 553, 548, 563 Annotation: Subtype: Link Rect: 325, 542, 336, 552 Annotation: Subtype: Link Rect: 336, 542, 355, 552 Annotation: Subtype: Link Rect: 355, 542, 363, 552 Annotation: Subtype: Link Rect: 363, 542, 372, 552 Annotation: Subtype: Link Rect: 372, 542, 379, 552 Annotation: Subtype: Link Rect: 379, 542, 391, 552 Annotation: Subtype: Link Rect: 391, 542, 397, 552 Annotation: Subtype: Link Rect: 397, 542, 411, 552 Annotation: Subtype: Link Rect: 411, 542, 417, 552 Annotation: Subtype: Link Rect: 417, 542, 433, 552 Annotation: Subtype: Link Rect: 433, 542, 445, 552 Annotation: Subtype: Link Rect: 445, 542, 453, 552 Annotation: Subtype: Link Rect: 453, 542, 462, 552 Annotation: Subtype: Link Rect: 462, 542, 470, 552 Annotation: Subtype: Link Rect: 470, 542, 475, 552 Annotation: Subtype: Link Rect: 307, 522, 319, 529 Destination: 24 Annotation: Subtype: Link Rect: 521, 499, 548, 508 Annotation: Subtype: Link Rect: 325, 488, 345, 497 Annotation: Subtype: Link Rect: 345, 488, 352, 497 Annotation: Subtype: Link Rect: 352, 488, 359, 497 Annotation: Subtype: Link Rect: 359, 488, 368, 497 Annotation: Subtype: Link Rect: 368, 488, 375, 497 Annotation: Subtype: Link Rect: 375, 488, 384, 497 Annotation: Subtype: Link Rect: 384, 488, 395, 497 Annotation: Subtype: Link Rect: 395, 488, 401, 497 Annotation: Subtype: Link Rect: 401, 488, 414, 497 Annotation: Subtype: Link Rect: 414, 488, 420, 497 Annotation: Subtype: Link Rect: 420, 488, 430, 497 Annotation: Subtype: Link Rect: 430, 488, 439, 497 Annotation: Subtype: Link Rect: 439, 488, 445, 497 Annotation: Subtype: Link Rect: 445, 488, 452, 497 Annotation: Subtype: Link Rect: 452, 488, 459, 497 Annotation: Subtype: Link Rect: 459, 488, 466, 497 Annotation: Subtype: Link Rect: 466, 488, 480, 497 Annotation: Subtype: Link Rect: 480, 488, 490, 497 Annotation: Subtype: Link Rect: 490, 488, 501, 497 Annotation: Subtype: Link Rect: 501, 488, 510, 497 Annotation: Subtype: Link Rect: 510, 488, 520, 497 Annotation: Subtype: Link Rect: 520, 488, 531, 497 Annotation: Subtype: Link Rect: 325, 477, 338, 486 Annotation: Subtype: Link Rect: 338, 477, 349, 486 Annotation: Subtype: Link Rect: 349, 477, 361, 486 Annotation: Subtype: Link Rect: 360, 477, 374, 486 Annotation: Subtype: Link Rect: 374, 477, 391, 486 Annotation: Subtype: Link Rect: 391, 477, 402, 486 Annotation: Subtype: Link Rect: 402, 477, 417, 486 Annotation: Subtype: Link Rect: 417, 477, 429, 486 Annotation: Subtype: Link Rect: 429, 477, 467, 486 Annotation: Subtype: Link Rect: 467, 477, 480, 486 Annotation: Subtype: Link Rect: 307, 457, 319, 463 Destination: 24 Annotation: Subtype: Link Rect: 307, 424, 319, 430 Destination: 24 Checksum: 66268492 Type: CRC32 Checksum: 83071ec9451943e5a7bec1dadfa2b4d8 Type: MD5 Checksum: 5a2f514c7fd1e7e9eeca23a974004ff0cff14832 Type: SHA-1 Checksum: 0f457211a5f59135c6e659cc515b2b2ef6b6e904ad8944928f72d4c522d13d55 Type: SHA-256