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(1)VU Research Portal. To adhere or not to adhere van der Laan, D.M.. 2019. document version Publisher's PDF, also known as Version of record. Link to publication in VU Research Portal. citation for published version (APA) van der Laan, D. M. (2019). To adhere or not to adhere: A patient-tailored, pharmacist-led intervention programme to enhance adherence to antihypertensive medication.. General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal ? Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. E-mail address: vuresearchportal.ub@vu.nl. Download date: 13. Oct. 2021.

(2) TO ADHERE OR NOT TO ADHERE A patient-tailored, pharmacist-led intervention programme to enhance adherence to antihypertensive medication. DANIELLE M. VAN DER LAAN.

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(4)  . Toadhere ornottoadhere  ’ƒ–‹‡–Ǧ–ƒ‹Ž‘”‡†ǡ’Šƒ”ƒ ‹•–ǦŽ‡†‹–‡”˜‡–‹‘’”‘‰”ƒ‡ –‘‡Šƒ ‡ƒ†Š‡”‡ ‡–‘ƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘.               DanielleM.vanderLaan.

(5) Š‹•–Š‡•‹•™ƒ•’”‡’ƒ”‡†™‹–Š‹–Š‡•–‡”†ƒ—„Ž‹  ‡ƒŽ–Š”‡•‡ƒ” Š ‹•–‹–—–‡ǡƒ––Š‡‡’ƒ”–‡–‘ˆŽ‹‹ ƒŽŠƒ”ƒ ‘Ž‘‰›ƒ†Šƒ”ƒ ›‘ˆ –Š‡•–‡”†ƒǡ•–‡”†ƒǡ–Š‡‡–Š‡”Žƒ†•Ǥ  Š‡•–—†›’”‘Œ‡ –†‡• ”‹„‡†‹–Š‹•–Š‡•‹•™ƒ•ˆ‹ƒ ‹ƒŽŽ›•—’’‘”–‡†„› –Š‡‘›ƒŽ—– ŠŠƒ”ƒ ‹•–•••‘ ‹ƒ–‹‘ȋȌǤ                   

(6) ǣ   ͻ͹ͺǦͻͶǦ͸͵͹ͷǦʹͶʹǦͺ ‘˜‡”ǣ  ƒ‡• ƒ”†‹‡ǡ™™™Ǥ†‡•‹‰›‘—”–Š‡•‹•Ǥ ‘ ”‹–‹‰ǣ  ‹††‡”’”‹–ǡ™™™Ǥ”‹††‡”’”‹–ǤŽ    ‘’›”‹‰Š–̹ʹͲͳͻƒ‹‡ŽŽ‡˜ƒ†‡”ƒƒ ŽŽ ”‹‰Š–• ”‡•‡”˜‡†Ǥ ‘ ’ƒ”– ‘ˆ –Š‹• –Š‡•‹• ƒ› „‡ ”‡’”‘†— ‡† ‘” –”ƒ•‹––‡†‹ƒ›ˆ‘”„›ƒ›‡ƒ•™‹–Š‘—–’”‹‘”’‡”‹••‹‘‘ˆ–Š‡ ƒ—–Š‘”Ǥ.

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(11) .   . Toadhereornottoadhere  ’ƒ–‹‡–Ǧ–ƒ‹Ž‘”‡†ǡ’Šƒ”ƒ ‹•–ǦŽ‡†‹–‡”˜‡–‹‘’”‘‰”ƒ‡–‘ ‡Šƒ ‡ƒ†Š‡”‡ ‡–‘ƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘   . 

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(13)   –‡”˜‡””‹Œ‰‹‰˜ƒ†‡‰”ƒƒ†‘ –‘” ƒƒ†‡”‹Œ‡‹˜‡”•‹–‡‹–•–‡”†ƒǡ ‘’‰‡œƒ‰˜ƒ†‡”‡ –‘”ƒ‰‹ˆ‹ —• ’”‘ˆǤ†”ǤǤ—„”ƒƒ‹ƒǡ ‹Š‡–‘’‡„ƒƒ”–‡˜‡”†‡†‹‰‡ –‡‘˜‡”•–ƒƒ˜ƒ†‡’”‘‘–‹‡ ‘‹••‹‡ ˜ƒ†‡ ƒ —Ž–‡‹–†‡” ‡‡‡•—†‡ ‘’˜”‹Œ†ƒ‰ͷŒ—Ž‹ʹͲͳͻ‘ͳ͵ǤͶͷ——” ‹†‡ƒ—Žƒ˜ƒ†‡—‹˜‡”•‹–‡‹–ǡ ‡‘‡Ž‡ŽƒƒͳͳͲͷ         †‘‘” DanielleMarlousvanderLaan ‰‡„‘”‡–‡ƒƒ”†‡.

(14) ’”‘‘–‘”‡ǣ  ‘’”‘‘–‘”ǣ   . †”Ǥ Ǥ Ǥ —‰–‡„—”‰ ’”‘ˆǤ†”ǤǤ ǤǤǤǤ‹Œ’‡Ž• †”ǤǤ ǤǤŽ†‡”•. .

(15)               . HAKUNAMATATA.

(16)  CONTENTS .         Chapter1. ‡‡”ƒŽ‹–”‘†— –‹‘ . . . . . ͻ. . ʹͳ. . Ͷͳ.  . Chapter2   Chapter3. ƒ –‘”•ƒ••‘ ‹ƒ–‡†™‹–Šƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘  ‘Ǧƒ†Š‡”‡ ‡ǣƒ•›•–‡ƒ–‹ ”‡˜‹‡™ .  ƒ –‘”•ƒ••‘ ‹ƒ–‡†™‹–Š ƒ”†‹‘˜ƒ• —Žƒ”‡†‹ ƒ–‹‘  ‘Ǧƒ†Š‡”‡ ‡ǣƒ ”‘••Ǧ•‡ –‹‘ƒŽ•–—†›.  . Chapter4. Š‡‹’ƒ –‘ˆ ƒ”†‹‘˜ƒ• —Žƒ”‡†‹ ƒ–‹‘—•‡‘’ƒ–‹‡–•ǯ †ƒ‹Ž›Ž‹˜‡•ǣƒ ”‘••Ǧ•‡ –‹‘ƒŽ•–—†›. ͸ͳ. Š‡ȋ ‘•–ǦȌ‡ˆˆ‡ –‹˜‡‡••‘ˆƒ’ƒ–‹‡–Ǧ–ƒ‹Ž‘”‡†‹–‡”˜‡–‹‘ ’”‘‰”ƒ‡–‘‡Šƒ ‡ƒ†Š‡”‡ ‡–‘ƒ–‹Š›’‡”–‡•‹˜‡ ‡†‹ ƒ–‹‘‹ ‘—‹–›’Šƒ”ƒ ‹‡•ǣ•–—†›’”‘–‘ ‘Ž ‘ˆƒ”ƒ†‘‹•‡† ‘–”‘ŽŽ‡†–”‹ƒŽ. ͹͹.  . Chapter5. . . .

(17)            Chapter6. ˆˆ‡ –‹˜‡‡••‘ˆƒ’ƒ–‹‡–Ǧ–ƒ‹Ž‘”‡†ǡ’Šƒ”ƒ ‹•–ǦŽ‡† ‹–‡”˜‡–‹‘’”‘‰”ƒ‡–‘‡Šƒ ‡ƒ†Š‡”‡ ‡–‘ ƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘ǣ–Š‡

(18) •–—†›. . ͻͷ.  . Chapter7. Š‡ ‘•–Ǧ‡ˆˆ‡ –‹˜‡‡••‘ˆƒ‹–‡”˜‡–‹‘’”‘‰”ƒ‡ ͳʹ͵ –‘‡Šƒ ‡ƒ†Š‡”‡ ‡–‘ƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘ ‹ ‘’ƒ”‹•‘™‹–Š—•—ƒŽ ƒ”‡‹ ‘—‹–›’Šƒ”ƒ ‹‡•. .  Chapter8.

(19) ’Ž‡‡–ƒ–‹‘ˆ‹†‡Ž‹–›‘ˆƒ‹–‡”˜‡–‹‘’”‘‰”ƒ‡ ͳͶ͵ –‘‡Šƒ ‡ƒ†Š‡”‡ ‡–‘ƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘‹ —– Š ‘—‹–›’Šƒ”ƒ ‹‡•. .  Chapter9. ‡‡”ƒŽ†‹• —••‹‘. . . . . ͳ͸ͷ.     .     .     .     . ͳͺͷ ͳͻͳ ͳͻ͹ ʹͲͳ ʹͲ͵.    Summaryȋ‰Ž‹•ŠȌ  Samenvattingȋ‡†‡”Žƒ†•Ȍ Dankwoord   Listofpublications  Abouttheauthor           . .      .

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(21) CHAPTER 1 General introduction. D.M. van der Laan.

(22) 10. Chapter 1. . Medicationadherence  †Š‡”‡ ‡‹•†‡ˆ‹‡†ƒ•Ǯ–Š‡’”‘ ‡••„›™Š‹ Š’ƒ–‹‡–•–ƒ‡–Š‡‹”‡†‹ ƒ–‹‘ƒ•ƒ‰”‡‡† —’‘™‹–Š–Š‡‹”Š‡ƒŽ–Š ƒ”‡’”‘˜‹†‡”ǯȏͳȐǤ

(23) – ‘’”‹•‡•–Š”‡‡ ‘’‘‡–•ǡ”‡ˆ‡””‹‰–‘ †‹ˆˆ‡”‡–’Šƒ•‡•‹‡†‹ ƒ–‹‘‹–ƒ‡„‡Šƒ˜‹‘—”ȋFigure1ȌǤ–‹‹–‹ƒ–‹‘’ƒ–‹‡–•–ƒ‡ –Š‡ˆ‹”•–†‘•‡‘ˆ–Š‡‹”’”‡• ”‹„‡†‡†‹ ƒ–‹‘ǤŠ‡‹’Ž‡‡–ƒ–‹‘’Šƒ•‡‹•–Š‡‡š–‡––‘ ™Š‹ Š –Š‡ ’ƒ–‹‡–•ǯ ƒ –—ƒŽ †‘•‹‰ ‘””‡•’‘†• –‘ –Š‡ ’”‡• ”‹„‡† †‘•‹‰ ”‡‰‹‡Ǥ

(24)  –Š‡•‡ ’Šƒ•‡• †‹ˆˆ‡”‡– –›’‡• ‘ˆ ‘Ǧƒ†Š‡”‡– „‡Šƒ˜‹‘—” ƒ ‘ —”Ǥ ‘” ‡šƒ’Ž‡ǡ ’ƒ–‹‡–•ƒ›†‡ ‹†‡‘––‘•–ƒ”–™‹–Š–Š‡‹”‡†‹ ƒ–‹‘ǡ—•‡Ž‡••‘ˆ–Š‡‹”‡†‹ ƒ–‹‘ǡ–ƒ‡ –Š‡‹” ‡†‹ ƒ–‹‘ ƒ– –Š‡ ™”‘‰ –‹‡ǡ –‡’‘”ƒ”‹Ž› •–‘’ —•‹‰ –Š‡‹” ‡†‹ ƒ–‹‘ ‘” –ƒ‡ ‘”‡‡†‹ ƒ–‹‘–Šƒ’”‡• ”‹„‡†ǤŠ‡ˆ‹ƒŽ’Šƒ•‡‹•–Š‡†‹• ‘–‹—ƒ–‹‘’Šƒ•‡™Š‹ Š ‘ —”•™Š‡’ƒ–‹‡–• ‘’Ž‡–‡Ž›•–‘’—•‹‰–Š‡‹”’”‡• ”‹„‡†‡†‹ ƒ–‹‘‘–Š‡‹”‘™ ‹‹–‹ƒ–‹˜‡Ǥ‘–Š‡”–‡”‘ˆ–‡—•‡†‹”‡Žƒ–‹‘–‘‡†‹ ƒ–‹‘ƒ†Š‡”‡ ‡‹•’‡”•‹•–‡ ‡ ™Š‹ Š ‹• –Š‡ Ž‡‰–Š ‘ˆ –‹‡ „‡–™‡‡ ‹‹–‹ƒ–‹‘ ƒ† –Š‡ Žƒ•– †‘•‡ǡ ™Š‹ Š ‹‡†‹ƒ–‡Ž› ’”‡ ‡†‡•†‹• ‘–‹—ƒ–‹‘ǤŠ‡•–—†‹‡•‹–Š‹•–Š‡•‹•ƒ”‡ˆ‘ —••‡†‘–Š‡‹’Ž‡‡–ƒ–‹‘ ’Šƒ•‡‘ˆ‡†‹ ƒ–‹‘‹–ƒ‡„‡Šƒ˜‹‘—”Ǥ .  Figure1Š‡’”‘ ‡••‘ˆƒ†Š‡”‡ ‡–‘‡†‹ ƒ–‹‘„›”‹Œ‡•etal.ȋʹͲͳʹȌ.  ‘Ǧƒ†Š‡”‡–„‡Šƒ˜‹‘—”‹•‘ˆ–‡ ƒ–‡‰‘”‹•‡†‹–‘‹–‡–‹‘ƒŽƒ†—‹–‡–‹‘ƒŽȏʹǦͶȐǤ

(25) –‡–‹‘ƒŽ‘Ǧƒ†Š‡”‡ ‡”‡ˆŽ‡ –•ƒƒ –‹˜‡ƒ†”‡ƒ•‘‡†’”‘ ‡••‹™Š‹ Š’ƒ–‹‡–• †‡ ‹†‡ –‘ †‡˜‹ƒ–‡ ˆ”‘ –Š‡ –”‡ƒ–‡– ’Žƒǡ ™Š‡”‡ƒ• —‹–‡–‹‘ƒŽ ‘Ǧƒ†Š‡”‡ ‡ ”‡ˆŽ‡ –• ƒ ’ƒ••‹˜‡ ’”‘ ‡•• ‹ ™Š‹ Š ’ƒ–‹‡–• ƒ”‡ ƒ”‡Ž‡•• ‘” ˆ‘”‰‡–ˆ—Ž ƒ„‘—– ’”‘’‡”Ž› ƒ†Š‡”‹‰–‘–Š‡–”‡ƒ–‡–’ŽƒǤ ‘™‡˜‡”ǡ‹–Šƒ•„‡‡ƒ”‰—‡†–Šƒ––Š‡•‡–›’‡•‘ˆ‘Ǧ ƒ†Š‡”‡ ‡ƒ›‘˜‡”Žƒ’ƒ†–Šƒ–ƒ›ˆƒ –‘”•—†‡”Ž›‹‰‹–‡–‹‘ƒŽ‘Ǧƒ†Š‡”‡ ‡ ƒ›ƒŽ•‘’Žƒ›ƒ”‘Ž‡‹—‹–‡–‹‘ƒŽ‘Ǧƒ†Š‡”‡ ‡ȏͷǡ͸ȐǤ.

(26) General introduction.  FactorsassociatedwithnonǦadherence ‡†‹ ƒ–‹‘ƒ†Š‡”‡ ‡‹•ƒ ‘’Ž‡šŠ‡ƒŽ–Š ƒ”‡’”‘„Ž‡ƒ†‹•‹ˆŽ—‡ ‡†„›—Ž–‹’Ž‡ ƒ†‹–‡””‡Žƒ–‹‰ˆƒ –‘”•ǤŠ‡‘”Ž† ‡ƒŽ–Š”‰ƒ‹•ƒ–‹‘ȋ Ȍ–Š‡”‡ˆ‘”‡‹–”‘†— ‡† –Š‡—Ž–‹†‹‡•‹‘ƒŽ†Š‡”‡ ‡‘†‡Ž™Š‹ Š Žƒ••‹ˆ‹‡•–Š‡•‡ˆƒ –‘”•ƒ ‘”†‹‰–‘ˆ‹˜‡ †‹‡•‹‘• ȏ͹Ȑǣ •‘ ‹ƒŽȀ‡ ‘‘‹  ˆƒ –‘”• ȋ‡Ǥ‰Ǥ ’‘‘” Š‡ƒŽ–Š Ž‹–‡”ƒ ›ǡ Ž‘™ Ž‡˜‡Ž ‘ˆ ‡†— ƒ–‹‘ǡ —‡’Ž‘›‡– ‘” Ž‹‹–‡† •‘ ‹ƒŽ •—’’‘”–Ȍǡ ’ƒ–‹‡–Ǧ”‡Žƒ–‡† ˆƒ –‘”• ȋ‡Ǥ‰Ǥ ‘™Ž‡†‰‡ǡƒ––‹–—†‡•‘”„‡Ž‹‡ˆ•Ȍǡ ‘†‹–‹‘Ǧ”‡Žƒ–‡†ˆƒ –‘”•ȋ‡Ǥ‰Ǥ•‡˜‡”‹–›‘ˆ•›’–‘•ǡ ‘Ǧ‘”„‹†‹–‹‡• ‘” ”ƒ–‡• ‘ˆ ’”‘‰”‡••‹‘Ȍǡ –Š‡”ƒ’›Ǧ”‡Žƒ–‡† ˆƒ –‘”• ȋ‡Ǥ‰Ǥ ‘’Ž‡š‹–› ‘ˆ ‡†‹ ƒ–‹‘ ”‡‰‹‡ǡ †—”ƒ–‹‘ ‘ˆ –”‡ƒ–‡– ‘” •‹†‡ ‡ˆˆ‡ –•Ȍ ƒ† Š‡ƒŽ–Š ƒ”‡ –‡ƒ ƒ† •›•–‡Ǧ”‡Žƒ–‡†ˆƒ –‘”•ȋ‡Ǥ‰Ǥ ‘—‹ ƒ–‹‘„‡–™‡‡Š‡ƒŽ–Š ƒ”‡’”‘˜‹†‡”ƒ†’ƒ–‹‡–Ȍ ȋFigure 2ȌǤ ‹ ‡ –Š‡•‡ ˆƒ –‘”• ƒ”‡ ‘ˆ–‡ ‹–‡””‡Žƒ–‡†ǡ ‹– Šƒ• „‡‡ •—‰‰‡•–‡† –Šƒ– ‹–‡”˜‡–‹‘• •Š‘—Ž† Šƒ˜‡ ƒ ‘†—Žƒ” ƒ’’”‘ƒ Š –ƒ”‰‡–‹‰ ‘”‡ –Šƒ ‘‡ ˆƒ –‘” ™‹–Š —Ž–‹’Ž‡‹–‡”˜‡–‹‘•ȏ͹ȐǤ .   Figure2—Ž–‹†‹‡•‹‘ƒŽ†Š‡”‡ ‡‘†‡Ž†‡˜‡Ž‘’‡†„›–Š‡ .  Measurementofadherence ‡˜‡”ƒŽ ‡–Š‘†• ƒ”‡ ƒ˜ƒ‹Žƒ„Ž‡ ˆ‘” ‡ƒ•—”‹‰ ƒ†Š‡”‡ ‡ –‘ ‡†‹ ƒ–‹‘ ȏ͸ǡ ͺȐǤ ƒ Š ‡–Š‘†Šƒ•‹–•ƒ†˜ƒ–ƒ‰‡•ƒ††‹•ƒ†˜ƒ–ƒ‰‡•Ǥˆ‘”–—ƒ–‡Ž›ǡ‘‡–Š‘†‹• ‘•‹†‡”‡† –Š‡ Ǯ‰‘Ž†‡ •–ƒ†ƒ”†ǯ ȏ͹ȐǤ „Œ‡ –‹˜‡ ‡–Š‘†• –‘ ‡ƒ•—”‡ ƒ†Š‡”‡ ‡ ‹ Ž—†‡ „‹‘Ž‘‰‹  ƒ”‡”•ǡ ’‹ŽŽ ‘—–•ǡ ’Šƒ”ƒ › ”‡ˆ‹ŽŽ ”‡ ‘”†•ƒ† ‡Ž‡ –”‘‹  ‘‹–‘”‹‰Ǥ šƒ’Ž‡• ‘ˆ •—„Œ‡ –‹˜‡‡–Š‘†•‹ Ž—†‡“—‡•–‹‘ƒ‹”‡•ǡ‹–‡”˜‹‡™•ƒ††‹ƒ”‹‡•ǤŠ‘‘•‹‰–Š‡‘•– ƒ’’”‘’”‹ƒ–‡ ‹•–”—‡– –‘ ‡ƒ•—”‡ ƒ†Š‡”‡ ‡ ‹ ‹–‡”˜‡–‹‘ •–—†‹‡• ƒ „‡ ŠƒŽŽ‡‰‹‰Ǥ ”ƒ –‹ ƒŽ ‘” ˆ‹ƒ ‹ƒŽ „ƒ””‹‡”• ‘ˆ–‡ ’Žƒ› ƒ ”‘Ž‡ ‹ •‡Ž‡ –‹‰ ƒ ‡–Š‘†Ǥ ‘”‡‘˜‡”ǡ–Š‡†‹•ƒ†˜ƒ–ƒ‰‡•‘ˆ‡ƒ Š‡–Š‘†—•–„‡ ‘•‹†‡”‡†ƒ†”‡•‡ƒ” Š‡”•—•– „‡ƒ™ƒ”‡‘ˆ™Š‹ Š–›’‡‘ˆ‘Ǧƒ†Š‡”‡–„‡Šƒ˜‹‘—” ƒ„‡‡ƒ•—”‡†™‹–Š–Š‡†‹ˆˆ‡”‡– ‡–Š‘†•Ǥ ‘”‡šƒ’Ž‡ǡ‡Ž‡ –”‘‹ ‘‹–‘”‹‰”‡ ‘”†•’ƒ ƒ‰‡‘’‡‹‰”ƒ–Š‡”–Šƒ–Š‡ ƒ –—ƒŽ ‹–ƒ‡ ‘ˆ ‡†‹ ƒ–‹‘ ƒ† ‹• ‘•‹†‡”‡† –Š‡ „‡•– ‘„Œ‡ –‹˜‡ ‡ƒ•—”‡ ȏ͸ǡ ͺǡ ͻȐǤ. 11.

(27) 12. Chapter 1.  ‘™‡˜‡”ǡ ‹– ‹• –‹‡Ǧ ‘•—‹‰ ƒ† “—‹–‡ ‡š’‡•‹˜‡Ǥ •‹‰ †ƒ–ƒ ˆ”‘ ’Šƒ”ƒ › ”‡ˆ‹ŽŽ ”‡ ‘”†• –‘ ƒŽ —Žƒ–‡ –Š‡ ‡†‹ ƒ–‹‘ ‘••‡••‹‘ ƒ–‹‘ ȋȌ ‘” ”‘’‘”–‹‘ ‘ˆ ƒ›• ‘˜‡”‡† ȋȌ ‹• ‘Ǧ‹˜ƒ•‹˜‡ ƒ† ƒ —”ƒ–‡Ž› •Š‘™• –Š‡ ˆ”‡“—‡ › ‘ˆ ’”‡• ”‹’–‹‘ ”‡ˆ‹ŽŽ•‘˜‡”ƒ•’‡ ‹ˆ‹ ’‡”‹‘†Ǥ ‘™‡˜‡”ǡ‹–†‘‡•‘–’”‘˜‹†‡‹ˆ‘”ƒ–‹‘ƒ„‘—––Š‡ƒ –—ƒŽ ‹–ƒ‡‘ˆ‡†‹ ƒ–‹‘ȏ͸ǡͺȐǤ‹ŽŽ ‘—–•ƒ”‡•‹’Ž‡ƒ†‹‡š’‡•‹˜‡ǡ„—–ƒ —”ƒ ›‡””‘”• ƒ”‡‡ƒ•›–‘„‡ƒ†‡Ǥ‡ŽˆǦ”‡’‘”–‡†“—‡•–‹‘ƒ‹”‡•ƒ”‡„”‹‡ˆƒ†•‹’Ž‡ǡƒ†ƒ••‡••‡• ‡†‹ ƒ–‹‘‹–ƒ‡„‡Šƒ˜‹‘—”ǡ”‡•’‘•‡•Š‘™‡˜‡” ƒ„‡„‹ƒ•‡†„›’ƒ–‹‡–•‰‹˜‹‰ˆƒŽ•‡ ‹ˆ‘”ƒ–‹‘ ȏ͸ǡ ͺȐǤ –—†‹‡• ‘’ƒ”‹‰ †‹ˆˆ‡”‡– ‡–Š‘†• ‡ƒ•—”‹‰ ‡†‹ ƒ–‹‘ ƒ†Š‡”‡ ‡”‡’‘”–‡†–Šƒ––Š‡–›’‡‘ˆ‡–Š‘†ƒ†–Š‡—•‡† —–Ǧ‘ˆˆ˜ƒŽ—‡‹ˆŽ—‡ ‡•–Š‡ ”‡•—Ž–• ‘„–ƒ‹‡† ȏͺǦͳͲȐǤ Š‡”‡ˆ‘”‡ǡ ‘ˆ–‡ ƒ ‘„‹ƒ–‹‘ ‘ˆ •‡˜‡”ƒŽ ‹•–”—‡–•ǡ ‘„‹‹‰ „‘–Š ‘„Œ‡ –‹˜‡ ƒ† •—„Œ‡ –‹˜‡ ‡–Š‘†•ǡ ‹• ‘•– ’”‡ˆ‡”ƒ„Ž‡ –‘ ƒ••‡•• ‡†‹ ƒ–‹‘ƒ†Š‡”‡ ‡‹‹–‡”˜‡–‹‘•–—†‹‡•ȏ͹ǡͺȐǤ  ‡†‹ ƒ–‹‘ ‘Ǧƒ†Š‡”‡ ‡ ”ƒ–‡• •–”‘‰Ž› †‡’‡† ‘ –Š‡ Šƒ”ƒ –‡”‹•–‹ • ‘ˆ –Š‡ ‘†‹–‹‘ǡ ‹–• –”‡ƒ–‡–ǡ –Š‡ ’ƒ–‹‡– ’‘’—Žƒ–‹‘ǡ –Š‡ •‡––‹‰ ƒ† –Š‡ ‡–Š‘† —•‡† –‘ ƒ••‡••ƒ†Š‡”‡ ‡ȏ͹ȐǤŠ‡ ‡•–‹ƒ–‡•–Š‡ƒ†Š‡”‡ ‡”ƒ–‡–‘Ž‘‰Ǧ–‡”–Š‡”ƒ’‹‡•ˆ‘” Š”‘‹  ‘†‹–‹‘•‹†‡˜‡Ž‘’‡† ‘—–”‹‡•‘ͷͲΨƒ†‡’Šƒ•‹œ‡•–Šƒ––Š‡‹’ƒ –‘ˆ ’‘‘”ƒ†Š‡”‡ ‡‰”‘™•ƒ•–Š‡„—”†‡‘ˆ Š”‘‹ †‹•‡ƒ•‡•‰”‘™•ȏ͹ȐǤ‡šƒ’Ž‡‘ˆƒ ‰”‘™‹‰ Š”‘‹  ‘†‹–‹‘‹•Š›’‡”–‡•‹‘Ǥ . Hypertension  •—ƒŽŽ›Š›’‡”–‡•‹‘‹•†‡ˆ‹‡†ƒ•ƒ”‡’‡ƒ–‡†Ž›‡Ž‡˜ƒ–‡†„Ž‘‘†’”‡••—”‡‡š ‡‡†‹‰ͳͶͲ  ‰‹•›•–‘Ž‹ ’Šƒ•‡ƒ†‘”ͻͲ ‰‹†‹ƒ•–‘Ž‹ ’Šƒ•‡ȏͳͳȐǤ ›’‡”–‡•‹‘ƒˆˆ‡ –• ‘”‡ –Šƒ ‘‡ „‹ŽŽ‹‘ ’‡‘’Ž‡ ™‘”Ž†™‹†‡ ƒ† ‘–”‹„—–‡• –‘ –Š‡ „—”†‡ ‘ˆ ƒ”†‹‘˜ƒ• —Žƒ” †‹•‡ƒ•‡•ǡ •— Š ƒ• •–”‘‡ ƒ† ›‘ ƒ”†‹ƒŽ ‹ˆƒ” –‹‘ ȏͳʹȐǤ ‹ ‡ Š›’‡”–‡•‹‘ ‹• ƒ ƒŒ‘” ƒ—•‡ ‘ˆ †‹•ƒ„‹Ž‹–› ƒ† ’”‡ƒ–—”‡ †‡ƒ–Šǡ ‹–• ’”‡˜‡–‹‘ ƒ† ƒƒ‰‡‡– Šƒ• „‡ ‘‡ ƒ ˆ‘ —• ‘ˆ Š‡ƒŽ–Š ƒ”‡ ’”‘˜‹†‡”• ™‘”Ž†™‹†‡Ǥ

(28)  –Š‡ ‡–Š‡”Žƒ†•ǡ–Š‡’”‡˜ƒŽ‡ ‡‘ˆŠ›’‡”–‡•‹‘‹•ƒ’’”‘š‹ƒ–‡Ž›͵ͳǤͶΨȏͳ͵ȐǤƒ˜‡”ƒ‰‡ǡ –Š‡’‡” ‡–ƒ‰‡‘ˆƒŽ‡••—ˆˆ‡”‹‰ˆ”‘Š›’‡”–‡•‹‘‹•Š‹‰Š‡”ƒ• ‘’ƒ”‡†–‘ˆ‡ƒŽ‡•Ǥ • –Š‡ ƒ‰‡ ’”‘‰”‡••‡• –Š‡ ’”‡˜ƒŽ‡ ‡ ‘ˆ Š›’‡”–‡•‹‘ ‹ ”‡ƒ•‡•ǡ „—– †‡ ”‡ƒ•‡• ƒ– ƒ Š‹‰Š‡”ƒ‰‡ȋηͺͲ›‡ƒ”•ȌǤ  Treatmentofhypertension Š‡ –”‡ƒ–‡– ‘ˆ Š›’‡”–‡•‹‘ ‹• „ƒ•‡† ‘ „‘–Š ’Šƒ”ƒ ‘Ž‘‰‹ ƒŽ ƒ† ‘Ǧ ’Šƒ”ƒ ‘Ž‘‰‹ ƒŽ –”‡ƒ–‡– •–”ƒ–‡‰‹‡•Ǥ ‘Ǧ’Šƒ”ƒ ‘Ž‘‰‹ ƒŽ –”‡ƒ–‡– ‹ Ž—†‡• ”‡ ‘‡†ƒ–‹‘•ƒ„‘—–Ž‹ˆ‡•–›Ž‡‘†‹ˆ‹ ƒ–‹‘•ȏͳʹǡͳͶȐǤŠ‡•‡‘†‹ˆ‹ ƒ–‹‘•‹ Ž—†‡ƒ Š‡ƒŽ–Š› †‹‡– ȋˆ”—‹– ƒ† ˜‡‰‡–ƒ„Ž‡• ƒ† •‘†‹— ”‡•–”‹ –‹‘Ȍǡ ‘†‡”ƒ–‹‘ ‘ˆ ƒŽ ‘Š‘Ž ‘•—’–‹‘ǡ™‡‹‰Š–”‡†— –‹‘ǡ‹ ”‡ƒ•‡†’Š›•‹ ƒŽƒ –‹˜‹–›ǡ•‘‹‰ ‡••ƒ–‹‘ƒ†•‡ŽˆǦ ‡ƒ•—”‡†„Ž‘‘†’”‡••—”‡‘‹–‘”‹‰Ǥ

(29) ˆŠ‹‰Š„Ž‘‘†’”‡••—”‡ ƒ‘–„‡ ‘–”‘ŽŽ‡†„› Ž‹ˆ‡•–›Ž‡ ‘†‹ˆ‹ ƒ–‹‘•ǡ ‹– —•– „‡ ƒ††”‡••‡† „› ’Šƒ”ƒ ‘Ž‘‰‹ ƒŽ –”‡ƒ–‡–Ǥ.

(30) General introduction.  –‹Š›’‡”–‡•‹˜‡ ‡†‹ ƒ–‹‘ ’”‡†‘‹ƒ–‡Ž› ‹ Ž—†‡• „‡–ƒǦ„Ž‘ ‡”•ǡ ƒŽ ‹— ƒ–ƒ‰‘‹•–•ǡ †‹—”‡–‹ •ǡ ƒ‰‹‘–‡•‹Ǧ ‘˜‡”–‹‰ ‡œ›‡ ȋȌ ‹Š‹„‹–‘”• ƒ† ƒ‰‹‘–‡•‹Ǧ

(31)

(32)  ”‡ ‡’–‘” ƒ–ƒ‰‘‹•–•Ǥ Š‡ ƒ„‹Ž‹–› ‘ˆ ƒ–‹Š›’‡”–‡•‹˜‡ ‡†‹ ƒ–‹‘ –‘ ‘–”‘Ž Š‹‰Š „Ž‘‘† ’”‡••—”‡ǡ –Š‡”‡„› ”‡†— ‹‰ –Š‡ ”‹• ‘ˆ ƒ”†‹‘˜ƒ• —Žƒ” ‡˜‡–• ƒ† †‡ ”‡ƒ•‹‰‘”„‹†‹–›ƒ†‘”–ƒŽ‹–›‹•™‡ŽŽ‡•–ƒ„Ž‹•Š‡†ȏ͹ǡͳͷȐǤ

(33) –Šƒ•„‡‡”‡’‘”–‡†–Šƒ– –”‡ƒ–‡–™‹–Šƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘”‡†— ‡•–Š‡”‹•‘ˆ•–”‘‡„›͵Ͳ–‘Ͷ͵Ψ ƒ†›‘ ƒ”†‹ƒŽ‹ˆƒ” –‹‘„›ͳͷΨǤ

(34) ƒ††‹–‹‘ǡ‹ƒ‡–ƒǦƒƒŽ›•‹•‘ˆͳͶ͹”ƒ†‘‹œ‡† –”‹ƒŽ•ǡ –”‡ƒ–‡– ™‹–Š ƒ–‹Š›’‡”–‡•‹˜‡ ‡†‹ ƒ–‹‘ Ž‡† –‘ ƒ ”‡Žƒ–‹˜‡ ”‹• ”‡†— –‹‘ ‘ˆ ͶͳΨƒ†ʹʹΨ‹•–”‘‡ƒ† ‘”‘ƒ”›Š‡ƒ”–†‹•‡ƒ•‡ǡ”‡•’‡ –‹˜‡Ž›ȏͳͷȐǤ  NonǦadherencetoantihypertensivemedication ˆ‘”–—ƒ–‡Ž›ǡ ƒ†Š‡”‡ ‡ –‘ ƒ–‹Š›’‡”–‡•‹˜‡ ‡†‹ ƒ–‹‘ ‹• •—„‘’–‹ƒŽǤ

(35)  ƒ ‡–ƒǦ ƒƒŽ›•‹•‘ˆ†ƒ–ƒˆ”‘͵͹͸ǡͳ͸ʹ’ƒ–‹‡–•‹™Š‹ Šƒ†Š‡”‡ ‡–‘•‡˜‡ ƒ”†‹‘˜ƒ• —Žƒ”†”—‰ Žƒ••‡•™ƒ•ƒ••‡••‡†—•‹‰–Š‡ˆ”‘’Šƒ”ƒ ›†‹•’‡•‹‰†ƒ–ƒǡ–Š‡‘Ǧƒ†Š‡”‡ ‡ ”ƒ–‡™ƒ•Ͷ͵Ψȏͳ͸ȐǤ‡’‡†‹‰‘–Š‡†”—‰ Žƒ••–Š‡‘Ǧƒ†Š‡”‡ ‡”ƒ–‡•˜ƒ”‹‡†ˆ”‘ ͵ͷΨˆ‘”ƒ‰‹‘–‡•‹

(36)

(37) Ǧ”‡ ‡’–‘”ƒ–ƒ‰‘‹•–•–‘͹ʹΨˆ‘”„‡–ƒǦ„Ž‘ ‡”•Ǥ

(38) –ƒŽ•‘ƒ––‡”• ™Š‡–Š‡” ‡†‹ ƒ–‹‘ ‹• ’”‡• ”‹„‡† ˆ‘” ’”‹ƒ”› ‘” •‡ ‘†ƒ”› ’”‡˜‡–‹‘ǡ ™‹–Š Ž‘™‡” ƒ†Š‡”‡ ‡ ”ƒ–‡• „‡‹‰ ˆ‘—† ˆ‘” ’”‹ƒ”› ’”‡˜‡–‹‘Ǥ  ‡–ƒǦƒƒŽ›•‹• ‘ˆ ʹͷ •–—†‹‡• ”‡’‘”–‹‰‘–Š‡ƒ••‡••‡–‘ˆƒ†Š‡”‡ ‡„›‡ƒ•‘ˆƒ•‡ŽˆǦ”‡’‘”–“—‡•–‹‘ƒ‹”‡‹ ͳʹǡ͸Ͳ͵Š›’‡”–‡•‹˜‡’ƒ–‹‡–•ǡ”‡’‘”–‡†ƒ‘Ǧƒ†Š‡”‡ ‡”ƒ–‡‘ˆͶͷΨȏͳ͹ȐǤ  ConsequencesofnonǦadherence —‡–‘–Š‡ƒ•›’–‘ƒ–‹ ƒ–—”‡‘ˆŠ›’‡”–‡•‹‘ƒ†–Š‡‡‡†ˆ‘”—Ž–‹’Ž‡ǡŽ‘‰Ǧ–‡” —•‡‘ˆ‡†‹ ƒ–‹‘ǡ‹’ƒ–‹‡–•™‹–ŠŠ›’‡”–‡•‹‘–Š‡”‹•‘ˆ‘Ǧƒ†Š‡”‡ ‡‹•‹ ”‡ƒ•‡† ȏͳͺȐǤŠ‡”‡ˆ‘”‡ǡ•—„•–ƒ–‹ƒŽ—„‡”•‘ˆ’ƒ–‹‡–•„‡‡ˆ‹–ˆ”‘–Š‡‹”‡†‹ ƒ–‹‘‘Ž›–‘ ƒ Ž‹‹–‡† ‡š–‡–Ǥ ‘” ‹•–ƒ ‡ǡ ‘Ǧƒ†Š‡”‡ ‡ –‘ ’”‡• ”‹„‡† ƒ–‹Š›’‡”–‡•‹˜‡ ‡†‹ ƒ–‹‘ ‹• –Š‡ ‘•– ‹’‘”–ƒ– ƒ—•‡ ‘ˆ — ‘–”‘ŽŽ‡† „Ž‘‘† ’”‡••—”‡ ȏ͹ǡ ͳͻȐǤ

(39)  ƒ††‹–‹‘ǡ‡†‹ ƒ–‹‘ ‘Ǧƒ†Š‡”‡ ‡ ”‡•—Ž–• ‹ ƒ Š‹‰Š‡” ”‹• ‘ˆ ƒ”†‹‘˜ƒ• —Žƒ” ‡˜‡–• ȏʹͲǦʹ͵ȐǡŠ‘•’‹–ƒŽƒ†‹••‹‘•ȏʹʹǡʹͶǦʹ͸Ȑƒ†‘”–ƒŽ‹–›ȏʹʹǡʹͷȐǤ ‘”‹•–ƒ ‡ǡƒ ‘Š‘”– •–—†› †‡‘•–”ƒ–‡† –Šƒ– ’ƒ–‹‡–• ™‹–Š Ž‘™ ƒ†Š‡”‡ ‡ ™‡”‡ ‘”‡ Ž‹‡Ž› –‘ Šƒ˜‡ ‘”‘ƒ”›Š‡ƒ”–†‹•‡ƒ•‡ȋͳǤͲ͹ǢͻͷΨ

(40) ͳǤͲͲȂͳǤͳ͵Ȍǡ ‡”‡„”‘˜ƒ• —Žƒ”†‹•‡ƒ•‡ȋͳǤͳ͵Ǣ ͻͷΨ

(41)  ͳǤͲ͵ǦͳǤʹͷȌ ƒ† Š”‘‹  Š‡ƒ”– ˆƒ‹Ž—”‡ ȋ ͳǤͶʹǢ ͻͷΨ

(42)  ͳǤʹ͹ǦͳǤͷͺȌ ȏʹͳȐǤ

(43)  ƒ ”‡–”‘•’‡ –‹˜‡•–—†›‰‘‘†‡†‹ ƒ–‹‘ƒ†Š‡”‡ ‡™ƒ•ƒ••‘ ‹ƒ–‡†™‹–Šƒ͵͵Ψ†‡ ”‡ƒ•‡† ”‹• ˆ‘” ƒ”†‹‘˜ƒ• —Žƒ”Ǧ”‡Žƒ–‡† Š‘•’‹–ƒŽ‹•ƒ–‹‘ ƒ† ͶͷΨ ”‹• ”‡†— –‹‘ ‘ˆ ‡‡”‰‡ › †‡’ƒ”–‡–˜‹•‹–•ȏʹ͹ȐǤ

(44) ƒ††‹–‹‘–‘•‡˜‡”ƒŽ‡‰ƒ–‹˜‡Š‡ƒŽ–Š‘—– ‘‡•ǡ‘Ǧƒ†Š‡”‡ ‡ ƒŽ•‘‹’‘•‡•ƒ•—„•–ƒ–‹ƒŽ‡ ‘‘‹ „—”†‡‘•‘ ‹‡–›ƒ•–Š‡”‡•—Ž–‘ˆ‹ ”‡ƒ•‡†Š‡ƒŽ–Š ƒ”‡ ‘•–•ȏʹͳǡʹͶǡʹͺȐƒ†Ž‘•–’”‘†— –‹˜‹–› ‘•–•†—‡–‘ƒ„•‡–‡‡‹•ƒ†’”‡•‡–‡‡‹• ȏʹͻǡ͵ͲȐǤ  . . 13.

(45) 14. Chapter 1. . Interventionstoenhanceadherence 

(46)  –Š‡ ’ƒ•– †‡ ƒ†‡•ǡ —‡”‘—• ‹–‡”˜‡–‹‘• ˆ‘” —•‡ ‹ ‘—‹–› ’Šƒ”ƒ ‹‡• Šƒ˜‡ „‡‡ †‡˜‡Ž‘’‡† ‹ ‘”†‡” –‘ ‹ ”‡ƒ•‡ ‡†‹ ƒ–‹‘ ƒ†Š‡”‡ ‡ ƒ† ‹’”‘˜‡ –”‡ƒ–‡– ”‡•—Ž–•Ǥ ‘—‹–› ’Šƒ”ƒ ‹•–• ƒ”‡ ‹ ƒ ‹†‡ƒŽ ’‘•‹–‹‘–‘ ƒ††”‡••ƒ†Š‡”‡ ‡ǡ •‹ ‡ –Š‡›ƒ”‡‡†‹ ‹‡•‡š’‡”–•‹’”‹ƒ”› ƒ”‡ƒ†–Š‡ƒŒ‘”‹–›‘ˆ ’ƒ–‹‡–•‘„–ƒ‹–Š‡‹” ‡†‹ ƒ–‹‘ ˆ”‘ ƒ ‘—‹–› ’Šƒ”ƒ ›Ǥ ˆ‘”–—ƒ–‡Ž›ǡ ”‡˜‹‡™• •—ƒ”‹œ‹‰ –Š‡ ”‡•—Ž–•‘ˆ–Š‡‡ˆˆ‡ –‹˜‡‡••‘ˆ–Š‡•‡ȋ’Šƒ”ƒ ‹•–ǦŽ‡†Ȍ‹–‡”˜‡–‹‘•”‡˜‡ƒŽ‡†–Šƒ–‘Ž› ‹ͷͲΨ‘ˆ–Š‡•–—†‹‡•–Š‡‹–‡”˜‡–‹‘”‡•—Ž–‡†‹ƒ•‹‰‹ˆ‹ ƒ–‹ ”‡ƒ•‡‘ˆƒ†Š‡”‡ ‡ ƒ†–Šƒ–‹‘Ž›ƒˆ‡™•–—†‹‡•–”‡ƒ–‡–‘—– ‘‡”‡•—Ž–•‹’”‘˜‡†ȏ͵ͳǦ͵͸ȐǤŠ—•ǡ‹ •’‹–‡‘ˆ•—„•–ƒ–‹ƒŽ‡ˆˆ‘”–•ǡ—’–‹ŽŽ‘™Ž‹––Ž‡’”‘‰”‡••Šƒ•„‡‡ƒ†‡–‘‡ˆˆ‡ –‹˜‡Ž›–ƒ Ž‡ –Š‡’‡”•‹•–‡–’”‘„Ž‡‘ˆ‘Ǧƒ†Š‡”‡ ‡Ǥ  ƒ•‡†‘–Š‡”‡•—Ž–•‘ˆ•‡˜‡”ƒŽ”‡˜‹‡™•‘ƒ†Š‡”‡ ‡Ǧ‡Šƒ ‹‰‹–‡”˜‡–‹‘•†‹ˆˆ‡”‡– ‹’Ž‹ ƒ–‹‘•ˆ‘”ˆ—–—”‡”‡•‡ƒ” ŠŠƒ˜‡„‡‡’”‘˜‹†‡†Ǥ‹‡—™Žƒƒ– etalǤ ‘ Ž—†‡†–Šƒ– ƒŽ‘•– ƒŽŽ ‹–‡”˜‡–‹‘• –Šƒ– ™‡”‡ ‡ˆˆ‡ –‹˜‡ ™‡”‡ ‘’Ž‡š ™‹–Š –ƒ‹Ž‘”‡† ƒ† ‹–‡•‡ ‘—•‡ŽŽ‹‰ȏ͵ͳȐǤ‘etalǤ ‘ Ž—†‡†–Šƒ––Š‡‘•–’”‘‹•‹‰‹–‡”˜‡–‹‘•‡’Ž‘›‡† —Ž–‹’Ž‡ ‘’‘‡–• ȏ͵͹ȐǤ Š‹• ‘ Ž—•‹‘ ‹• •‹‹Žƒ” –‘ –Š‡ ”‡ ‘‡†ƒ–‹‘ ‘ˆ –Š‡  –‘†‡˜‡Ž‘’‹–‡”˜‡–‹‘•–ƒ‹Ž‘”‡†–‘’ƒ–‹‡–•ǯ‡‡†•ƒ†’”‡ˆ‡”‡ ‡•ȏ͹ȐǤ”‹’ƒŽƒ‹ et alǤ ”‡’‘”–‡† –Šƒ– ‹–‡”˜‡–‹‘• ‹˜‘Ž˜‹‰ ‘‹–‘”‹‰ ƒ† ˆ‡‡†„ƒ ǡ ƒ• ™‡ŽŽ ƒ• ‹ˆ‘”ƒ–‹‘ƒŽ ‹–‡”˜‡–‹‘• †‡Ž‹˜‡”‡† ‘˜‡” —Ž–‹’Ž‡ •‡••‹‘•ǡ ƒ”‡ ‘•– ’”‘„ƒ„Ž› ‡ˆˆ‡ –‹˜‡ȏ͵ʹȐǤƒ—Ž‡etalǤ•—‰‰‡•–‡†–Šƒ––Š‡‹‡ˆˆ‡ –‹˜‡‡••‘ˆ‹–‡”˜‡–‹‘• ƒ „‡ ‡š’Žƒ‹‡† „› –Š‡ Žƒ  ‘ˆ ƒ ‡š’Ž‹ ‹– –Š‡‘”‡–‹ ƒŽ ‘†‡Ž ™Š‹ Š ‘’‡”ƒ–‹‘ƒŽ‹•‡• –Š‡ ‡ Šƒ‹•‘ˆƒ†Š‡”‡ ‡„‡Šƒ˜‹‘—”ȏ͵͵ȐǤ  ’ƒ–‹‡–•ǯƒ„‹Ž‹–›–‘ƒ†Š‡”‡–‘–”‡ƒ–‡–‹•‘ˆ–‡ ‘’”‘‹•‡†„›‘”‡–Šƒƒ•‹‰Ž‡ „ƒ””‹‡”ȏ͵ͺȐǤ

(47) –‡”˜‡–‹‘••Š‘—Ž†–Š‡”‡ˆ‘”‡„‡–ƒ”‰‡–‡†ƒ–†‹ˆˆ‡”‡–„ƒ””‹‡”•ƒ† •Š‘—Ž†„‡–ƒ‹Ž‘”‡†–‘–Š‡•’‡ ‹ˆ‹ ‡‡†•ƒ†’”‡ˆ‡”‡ ‡•‘ˆ’ƒ–‹‡–•Ǥ

(48) –Š‹•”‡•’‡ –ǡ‹– Šƒ•‘™‰‡‡”ƒŽŽ›„‡‡ƒ ‡’–‡†–Šƒ–‹†‹˜‹†—ƒŽ‹•‡† ‘—•‡ŽŽ‹‰‹•‘”‡‡ˆˆ‡ –‹˜‡–Šƒ– –Š‡‹†‹• ”‹‹ƒ–‡—•‡‘ˆ‘‡Ǧ•‹œ‡ˆ‹–•ǦƒŽŽ‡ƒ•—”‡•ȏ͵ͳǡ͵ͻȐǤ‡ ƒ—•‡‡†‹ ƒ–‹‘ ƒ†Š‡”‡ ‡‹•ƒ ‘–‹—‘—•ƒ††›ƒ‹ ’”‘ ‡••ǡ–Š‡ ƒŽ•‘”‡ ‘‡†‡†–Šƒ– ‹–‡”˜‡–‹‘•–”ƒ–‡‰‹‡••Š‘—Ž†‹ Ž—†‡ƒˆ‘ŽŽ‘™Ǧ—’’‡”‹‘††—”‹‰™Š‹ Šƒ†Š‡”‡ ‡‹• ‘‹–‘”‡†‘˜‡”–‹‡ȏ͹ȐǤ.  TheCATIstudy 

(49)  ‘”†‡” –‘ ‡ˆˆ‡ –‹˜‡Ž› –ƒ”‰‡– –Š‡ ’”‘„Ž‡ ‘ˆ ‘Ǧƒ†Š‡”‡ ‡ –‘ ƒ–‹Š›’‡”–‡•‹˜‡ ‡†‹ ƒ–‹‘ǡ –Š‡ Cƒ”†‹‘˜ƒ• —Žƒ” ‡†‹ ƒ–‹‘ ‘ǦA†Š‡”‡ ‡ Tƒ‹Ž‘”‡† I–‡”˜‡–‹‘ ȋ

(50) Ȍ •–—†› ™ƒ• ‘†— –‡† ȏͶͲȐǤ Š‹• •–—†› ƒ‹‡† –‘ †‡˜‡Ž‘’ ƒ ’ƒ–‹‡–Ǧ–ƒ‹Ž‘”‡†ǡ ’Šƒ”ƒ ‹•–ǦŽ‡†ƒ†–Š‡‘”›†”‹˜‡‹–‡”˜‡–‹‘ȋ

(51) ‹–‡”˜‡–‹‘’”‘‰”ƒ‡Ȍƒ†–‘ ‡˜ƒŽ—ƒ–‡ –Š‡ ȋ ‘•–ǦȌ‡ˆˆ‡ –‹˜‡‡•• ‘ˆ –Š‡ ‹–‡”˜‡–‹‘ ƒ• ‘’ƒ”‡† –‘ —•—ƒŽ ƒ”‡Ǥ Š‡.

(52) General introduction.  ‹–‡”˜‡–‹‘’”‘‰”ƒ‡Šƒ•„‡‡†‡˜‡Ž‘’‡†‘–Š‡„ƒ•‹•‘ˆ–Š‡‘‘‡•‡‘†‡Ž ‘ˆ‡ŽˆǦ”‡‰—Žƒ–‹‘ȏͶͳǦͶ͵ȐǤŠ‹•–Š‡‘”›‹•ƒ’”‘˜‡‡ˆˆ‡ –‹˜‡ˆ”ƒ‡™‘”ˆ‘”„‡Šƒ˜‹‘—”ƒŽ Šƒ‰‡ •–ƒ–‹‰ –Šƒ– ’ƒ–‹‡–• •‡‡ –‘ —†‡”•–ƒ† –Š‡‹” ‹ŽŽ‡•• „› †‡˜‡Ž‘’‹‰ ƒ ”‡’”‡•‡–ƒ–‹‘‘ˆ–Š‡‹ŽŽ‡••ǡ‹–• ƒ—•‡ǡ‡ˆˆ‡ –•ƒ††—”ƒ–‹‘ǡƒ†™Š‡–Š‡”‹– ƒ„‡ —”‡† ‘” ‘–”‘ŽŽ‡†ȏͶʹǦͶͶȐǤŠ‡•‡‹ŽŽ‡••ƒ†–”‡ƒ–‡–”‡’”‡•‡–ƒ–‹‘•—†‡”Ž‹‡ƒ’ƒ–‹‡–•ǯ Š‡ƒŽ–Š„‡Šƒ˜‹‘—”Ǥ ‘”‹•–ƒ ‡ǡ‹ˆƒ’ƒ–‹‡–”‡‰ƒ”†•Š‹•‘”Š‡”‹ŽŽ‡••‘””‹•ˆƒ –‘”ˆ‘”ƒ ‹ŽŽ‡•• ƒ• ƒ ’”‘„Ž‡ǡ –Š‡ ’ƒ–‹‡– ™‹ŽŽ ’‡”ˆ‘” ƒ •’‡ ‹ˆ‹  Š‡ƒŽ–ŠǦ”‡Žƒ–‡† „‡Šƒ˜‹‘—” ‹ ‘”†‡” –‘ ‘’‡ ™‹–Š –Š‡ ’”‘„Ž‡ǡ ‡Ǥ‰Ǥ –ƒ‹‰ ‡†‹ ƒ–‹‘ ȏͶͷǦͶͺȐǤ Š—•ǡ ƒ†Š‡”‡ ‡ „‡Šƒ˜‹‘—” ™‹ŽŽ „‡ ‹ˆŽ—‡ ‡† „› –Š‡ ’‘–‡–‹ƒŽ „‡‡ˆ‹– –Šƒ– ƒ ’ƒ–‹‡– ƒ› ‡š’‡”‹‡ ‡ ‰‹˜‡ Š‹• ‘” Š‡” ‹ŽŽ‡•• ƒ† –”‡ƒ–‡– ”‡’”‡•‡–ƒ–‹‘•Ǥ ‘”‡‘˜‡”ǡ ‰‹˜‡ –Š‡ ƒ•›’–‘ƒ–‹ ƒ–—”‡‘ˆŠ›’‡”–‡•‹‘ƒ†–Š‡‡‡†ˆ‘”Ž‘‰Ǧ–‡”—•‡‘ˆ‡†‹ ƒ–‹‘ǡƒ ’ƒ–‹‡–•ǯ—†‡”•–ƒ†‹‰‘ˆ–Š‡‹ŽŽ‡••ƒ›„‡ƒ‹’‘”–ƒ–ˆƒ –‘”‹ƒ Š‹‡˜‹‰Ž‘‰Ǧ–‡” ‡†‹ ƒ–‹‘ƒ†Š‡”‡ ‡ȏͶͻȐǤ  Š‡ 

(53)  ‹–‡”˜‡–‹‘ ’”‘‰”ƒ‡ ƒ‹‡† –‘ ‡Šƒ ‡ •‡ŽˆǦ”‡’‘”–‡† ƒ†Š‡”‡ ‡ –‘ ƒ–‹Š›’‡”–‡•‹˜‡ ‡†‹ ƒ–‹‘Ǥ Š‡ ’”‘‰”ƒ‡ ™ƒ• ‡š‡ —–‡† „› –Š‡ ‘—‹–› ’Šƒ”ƒ ‹•– ƒ† ‹ Ž—†‡• –™‘ ‘•—Ž–ƒ–‹‘• ‹ –Š‡ ’Šƒ”ƒ ›Ǥ Š‡ ˆ‹”•– ‘•—Ž–ƒ–‹‘ ‹ Ž—†‡† ‹ˆ‘”‹‰ ’ƒ–‹‡–• ƒ„‘—– Š›’‡”–‡•‹‘ ƒ† ‹–• ‘•‡“—‡ ‡• ‹ ‘”†‡” –‘ ‹’”‘˜‡‘” Šƒ‰‡‹ŽŽ‡••ƒ†–”‡ƒ–‡–”‡’”‡•‡–ƒ–‹‘•ǡ‹†‡–‹ˆ›‹‰’ƒ–‹‡–•ǯ„ƒ””‹‡”• –‘ ƒ†Š‡”‡ –‘ ‡†‹ ƒ–‹‘ǡ ’”‘˜‹†‹‰ ”‡ ‘‡†ƒ–‹‘• ƒ† •‡Ž‡ –‹‰ •’‡ ‹ˆ‹  ‹–‡”˜‡–‹‘• –‘ ‘˜‡” ‘‡ –Š‡ „ƒ””‹‡”• ‹†‡–‹ˆ‹‡†Ǥ

(54)  ƒ ˆ‘ŽŽ‘™Ǧ—’ ‘•—Ž–ƒ–‹‘ –Š‡ ’ƒ–‹‡–•ǯ‹’Ž‡‡–ƒ–‹‘‘ˆƒ†Š‹•‘”Š‡”‡š’‡”‹‡ ‡•™‹–Š–Š‡’”‘˜‹†‡†‹ˆ‘”ƒ–‹‘ ƒ†‹–‡”˜‡–‹‘”‡ ‘‡†ƒ–‹‘•™‡”‡†‹• —••‡†Ǥ—”‹‰‹‡‘–Š•‘ˆˆ‘ŽŽ‘™Ǧ—’ †ƒ–ƒ ™‡”‡ ‘ŽŽ‡ –‡† ‹ Ž—†‹‰ ’ƒ–‹‡–•ǯ †‡‘‰”ƒ’Š‹ •ǡ –”‡ƒ–‡– ƒ† ‘†‹–‹‘ Šƒ”ƒ –‡”‹•–‹ •‹ Ž—†‹‰•›•–‘Ž‹ ƒ††‹ƒ•–‘Ž‹ „Ž‘‘†’”‡••—”‡ǡ•‡ŽˆǦ”‡’‘”–‡†‡†‹ ƒ–‹‘ ƒ†Š‡”‡ ‡ǡ“—ƒŽ‹–›‘ˆŽ‹ˆ‡ǡ‹ŽŽ‡••”‡’”‡•‡–ƒ–‹‘•ƒ†„‡Ž‹‡ˆ•ƒ„‘—–‡†‹ ‹‡•Ǥ .        . . 15.

(55) 16. Chapter 1. . Aimsandresearchquestions  Š‡•–—†‹‡•†‡• ”‹„‡†‹–Š‹•–Š‡•‹• ‘ ‡”–Š‡†‡˜‡Ž‘’‡–‘ˆ–Š‡

(56) ‹–‡”˜‡–‹‘ ’”‘‰”ƒ‡ ƒ‹‡† –‘ ‡Šƒ ‡ ƒ†Š‡”‡ ‡ –‘ ƒ–‹Š›’‡”–‡•‹˜‡ ‡†‹ ƒ–‹‘ ƒ† ƒ ‡˜ƒŽ—ƒ–‹‘ ‘ˆ –Š‡ ȋ ‘•–ǦȌ‡ˆˆ‡ –‹˜‡‡•• ‘ˆ –Š‹• ’”‘‰”ƒ‡Ǥ Š‡”‡ˆ‘”‡ǡ ™‡ ƒ‹‡† –‘ ƒ•™‡”–Š‡ˆ‘ŽŽ‘™‹‰”‡•‡ƒ” Š“—‡•–‹‘•ǣ  ƒ Š‹ Š ˆƒ –‘”• ƒ”‡ ƒ••‘ ‹ƒ–‡† ™‹–Š ‘Ǧƒ†Š‡”‡ ‡ –‘ ƒ–‹Š›’‡”–‡•‹˜‡ ‡†‹ ƒ–‹‘ ƒ ‘”†‹‰–‘–Š‡Ž‹–‡”ƒ–—”‡ǫ ƒ Š‹ Šˆƒ –‘”•ƒ”‡ƒ••‘ ‹ƒ–‡†™‹–Š‘Ǧƒ†Š‡”‡ ‡–‘ ƒ”†‹‘˜ƒ• —Žƒ”‡†‹ ƒ–‹‘‹ƒ •ƒ’Ž‡‘ˆ’ƒ–‹‡–•ˆ”‘—– Š ‘—‹–›’Šƒ”ƒ ‹‡•ǫ ƒ Šƒ– ‹• –Š‡ ‹’ƒ – ‘ˆ –Š‡ —•‡ ‘ˆ Š”‘‹  ƒ”†‹‘˜ƒ• —Žƒ” ‡†‹ ƒ–‹‘ ‘ †‹ˆˆ‡”‡– ƒ•’‡ –•‘ˆ’ƒ–‹‡–•ǯ†ƒ‹Ž›Ž‹˜‡•ǫ ƒ Šƒ–‹•–Š‡‡ˆˆ‡ –‹˜‡‡••‘ˆ–Š‡

(57) ‹–‡”˜‡–‹‘’”‘‰”ƒ‡–‘‡Šƒ ‡ƒ†Š‡”‡ ‡ –‘ƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘ƒ• ‘’ƒ”‡†–‘—•—ƒŽ ƒ”‡ǫ ƒ Šƒ–‹•–Š‡ ‘•–Ǧ‡ˆˆ‡ –‹˜‡‡••‘ˆ–Š‡

(58) ‹–‡”˜‡–‹‘’”‘‰”ƒ‡ƒ• ‘’ƒ”‡†–‘ —•—ƒŽ ƒ”‡ǫ ƒ

(59) •–Š‡

(60) ‹–‡”˜‡–‹‘’”‘‰”ƒ‡‹’Ž‡‡–‡†ƒ•‹–‡†‡†ǫ . Thesisoutline  Chapter 2 ’”‡•‡–• ƒ •›•–‡ƒ–‹  Ž‹–‡”ƒ–—”‡ ”‡˜‹‡™ ‹ ‘”†‡” –‘ ‰‡– ƒ ‘’”‡Š‡•‹˜‡ —†‡”•–ƒ†‹‰‘ˆ–Š‡ ‘’Ž‡š Šƒ”ƒ –‡”‘ˆƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘‘Ǧƒ†Š‡”‡ ‡ ƒ† ‹–• ƒ••‘ ‹ƒ–‡† ˆƒ –‘”•Ǥ Chapter 3 †‡• ”‹„‡• ƒ ”‘••Ǧ•‡ –‹‘ƒŽ •–—†› ƒ‹‡† –‘ ‰‡– ‹•‹‰Š– ‹–‘ –Š‡ ˆƒ –‘”• –Šƒ– ƒ”‡ ƒ••‘ ‹ƒ–‡† ™‹–Š ƒ”†‹‘˜ƒ• —Žƒ” ‡†‹ ƒ–‹‘ ‘Ǧ ƒ†Š‡”‡ ‡‹–Š‡•–—†›’‘’—Žƒ–‹‘Ǥ

(61) Chapter4–Š‡‹’ƒ –‘ˆ Š”‘‹  ƒ”†‹‘˜ƒ• —Žƒ” ‡†‹ ƒ–‹‘—•‡‘†‹ˆˆ‡”‡–ƒ•’‡ –•‘ˆ’ƒ–‹‡–•ǯ†ƒ‹Ž›Ž‹˜‡•ƒ†–Š‡’‘••‹„Ž‡†‹ˆˆ‡”‡ ‡• ‹–Š‡•‡ƒ•’‡ –•„‡–™‡‡ƒ†Š‡”‡–ƒ†‘Ǧƒ†Š‡”‡–’ƒ–‹‡–•‹•’”‡•‡–‡†Ǥ‘ƒ••‡•• –Š‡‹’ƒ –™‡—•‡†–Š‡‹˜‹‰™‹–Š‡†‹ ‹‡•—‡•–‹‘ƒ‹”‡ǡ™Š‹ Š™‡ˆ‹”•––”ƒ•Žƒ–‡† ‹ —– ŠǤ Chapter 5 †‡• ”‹„‡• –Š‡ •–—†› ’”‘–‘ ‘Ž ‘ˆ –Š‡ 

(62)  •–—†›Ǥ Š‡ ’”‘–‘ ‘Ž ‹ Ž—†‡• ƒ †‡• ”‹’–‹‘ ‘ˆ 

(63)  ‹–‡”˜‡–‹‘ ’”‘‰”ƒ‡ ƒ† –Š‡ ’”‘ ‡†—”‡ ‘ˆ –Š‡ ”ƒ†‘‹•‡† ‘–”‘ŽŽ‡† –”‹ƒŽǤ Chapter 6 ‡˜ƒŽ—ƒ–‡• –Š‡ ‡ˆˆ‡ –‹˜‡‡•• ‘ˆ –Š‡ 

(64)  ‹–‡”˜‡–‹‘ ’”‘‰”ƒ‡ ƒ• ‘’ƒ”‡† –‘ —•—ƒŽ ƒ”‡Ǥ Chapter 7 ‡˜ƒŽ—ƒ–‡• –Š‡ ‘•–Ǧ ‡ˆˆ‡ –‹˜‡‡••‘ˆ–Š‡

(65) ‹–‡”˜‡–‹‘’”‘‰”ƒ‡ ‘’ƒ”‡†–‘—•—ƒŽ ƒ”‡Ǥ

(66) Chapter 8 –Š‡ ’”‘ ‡• ‡˜ƒŽ—ƒ–‹‘ ‘ˆ –Š‡ 

(67)  ‹–‡”˜‡–‹‘ ’”‘‰”ƒ‡ ‹• ’”‡•‡–‡†Ǥ Š‡ ‹’Ž‡‡–ƒ–‹‘ ˆ‹†‡Ž‹–› ‡˜ƒŽ—ƒ–‡• ™Š‡–Š‡” –Š‡ ‹–‡”˜‡–‹‘ ’”‘‰”ƒ‡ Šƒ• „‡‡ ‹’Ž‡‡–‡†ƒ•‹–‡†‡†Ǥ

(68) Chapter9ǡ™‡•—ƒ”‹•‡–Š‡ƒ‹ˆ‹†‹‰•‘ˆ–Š‡˜ƒ”‹‘—• Šƒ’–‡”•ǡ ‘‡–‘•‡˜‡”ƒŽ‡–Š‘†‘Ž‘‰‹ ƒŽ ‘•‹†‡”ƒ–‹‘•ǡ’”‘˜‹†‡ƒ‘˜‡”˜‹‡™‘ˆ Ž‹‹ ƒŽ‹’Ž‹ ƒ–‹‘•ƒ† ‘ Ž—†‡™‹–Š”‡ ‘‡†ƒ–‹‘•ˆ‘”ˆ—–—”‡”‡•‡ƒ” ŠǤ.

(69) General introduction. . References  ȏͳȐ”‹Œ‡•ǡ‡ ‡‡•–ǡ —‰Š‡•ǡ”œ‡›•Žƒ™ǡ ‡‘ ‡ƒ— ǡ—’’ƒ”ǡ‡–ƒŽǤ‡™–ƒš‘‘›ˆ‘” †‡• ”‹„‹‰ƒ††‡ˆ‹‹‰ƒ†Š‡”‡ ‡–‘‡†‹ ƒ–‹‘•Ǥ”  Ž‹Šƒ”ƒ ‘ŽǤʹͲͳʹǢ͹͵ȋͷȌǣ͸ͻͳǦ͹ͲͷǤ  ȏʹȐ‘™”›ǡ—†Ž‡›ǡ††‘‡ǡ‘•™‘”–Š Ǥ

(70) –‡–‹‘ƒŽƒ†—‹–‡–‹‘ƒŽ‘Ǧƒ†Š‡”‡ ‡–‘ ƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘ǤŠƒ”ƒ ‘–Š‡”Ǥ ʹͲͲͷǢ͵ͻȋ͹ǦͺȌǣͳͳͻͺǦͳʹͲ͵Ǥ  ȏ͵Ȑ‡Šƒ‡ǡ ƒ”–Š› Ǥ

(71) –‡–‹‘ƒŽƒ†—‹–‡–‹‘ƒŽ ‡†‹ ƒ–‹‘‘Ǧƒ†Š‡”‡ ‡ǣƒ ‘’”‡Š‡•‹˜‡ ˆ”ƒ‡™‘”ˆ‘” Ž‹‹ ƒŽ”‡•‡ƒ” Šƒ†’”ƒ –‹ ‡ǫ †‹• —••‹‘’ƒ’‡”Ǥ

(72) – —”•–—†ǤʹͲͲ͹ǢͶͶȋͺȌǣͳͶ͸ͺǦ ͳͶ͹͹Ǥ  ȏͶȐ”‘‡Ǥ

(73) –‡–‹‘ƒŽƒ†‹–‡–‹‘ƒŽ ‘ƒ†Š‡”‡ ‡ǣ–—†›‘ˆ‡ ‹•‹‘ƒ‹‰Ǥ ‘—”ƒŽ‘ˆ ‡Šƒ˜‹‘”ƒŽ‡†‹ ‹‡ǤʹͲͲͳǢʹͷȋͶȌǣ͵ͷͷǦ͵͹ʹǤ  ȏͷȐ ƒ†ƒ”‹ǡ ‘”‡›Ǥ‹–‡–‹‘ƒŽ‘Ǧ ƒ†Š‡”‡ ‡–‘ Š”‘‹ ’”‡• ”‹’–‹‘‡†‹ ƒ–‹‘•ǣ ‘™ —‹–‡–‹‘ƒŽ‹•‹–”‡ƒŽŽ›ǫ ‡ƒŽ–Š‡”˜‹ ‡• ‡•‡ƒ” ŠǤʹͲͳʹǢͳʹǣͻͺǤ  ȏ͸Ȑ”‘‹•Š

(74) ǡ‡Ǥ†Š‡”‡ ‡–‘ ƒ”†‹‘˜ƒ• —Žƒ” ‡†‹ ƒ–‹‘•ǣŽ‡••‘•Ž‡ƒ”‡†ƒ†ˆ—–—”‡†‹”‡ –‹‘•Ǥ ”‘‰ƒ”†‹‘˜ƒ• ‹•ǤʹͲͳ͵Ǣͷͷȋ͸ȌǣͷͻͲǦ͸ͲͲǤ  ȏ͹Ȑƒ„ƒ–‡Ǥ‘”Ž† ‡ƒŽ–Š”‰ƒ‹œƒ–‹‘Ǥ†Š‡”‡ ‡–‘ Ž‘‰–‡”–Š‡”ƒ’‹‡•Ǥ˜‹†‡ ‡ˆ‘”ƒ –‹‘Ǥ ‡‡˜ƒǣʹͲͲ͵Ǥ  ȏͺȐƒǡ ”‡• ‘Ǥ‡†‹ ƒ–‹‘†Š‡”‡ ‡‡ƒ•—”‡•ǣ ˜‡”˜‹‡™Ǥ‹‘‡†‡•

(75) –ǤʹͲͳͷǢʹͲͳͷǣʹͳ͹ͲͶ͹Ǥ  ȏͻȐ‡ŽŽ‡”ǡƒ•‡‹‡”ǡ‡ƒ‰–‡›‡”ǡƒ––‡‰ƒ›Ǥ ƒ–‹‡–•̵‡ŽˆǦ‡’‘”–‡††Š‡”‡ ‡–‘ƒ”†‹‘˜ƒ• —Žƒ” ‡†‹ ƒ–‹‘•‹‰Ž‡ –”‘‹ ‘‹–‘”•ƒ•‘’ƒ”ƒ–‘”•Ǥ ›’‡”–‡•‡•ǤʹͲͲͺǢ͵ͳǣʹͲ͵͹ǦʹͲͶ͵Ǥ  ȏͳͲȐŽŽ‹Ž‹ǡ”‹Œ‡•ǡ‡‘ ‡ƒ— ǡ˜‡”•ǡ ‹Ž‹‰•ƒǤ• ‘’‹‰”‡˜‹‡™‘ˆ•–—†‹‡• ‘’ƒ”‹‰ –Š‡‡†‹ ƒ–‹‘‡˜‡–‘‹–‘”‹‰•›•–‡ȋȌ™‹–Š ƒŽ–‡”ƒ–‹˜‡‡–Š‘†•ˆ‘”‡ƒ•—”‹‰‡†‹ ƒ–‹‘ ƒ†Š‡”‡ ‡Ǥ” Ž‹Šƒ”ƒ ‘ŽǤʹͲͳ͸ǢͺʹȋͳȌǣʹ͸ͺǦʹ͹ͻǤ  ȏͳͳȐƒ‰ƒ ǡƒ‹Œ ǡƒ‹•

(76) Ǥ Ǧ–ƒ†ƒƒ”† ƒ”†‹‘˜ƒ• —Žƒ‹””‹•‹ ‘ƒƒ‰‡‡–ȋ‡‡”•–‡Š‡”œ‹‡‹‰Ȍ ȏ‹—– ŠȐǤ —‹•ƒ”–•‡–ǤʹͲͳʹǢͷͷȋͳȌǣͳͶǦʹͺǤ  ȏͳʹȐ‘”Ž† ‡ƒŽ–Š”‰ƒ‹œƒ–‹‘Ǥ‰Ž‘„ƒŽ„”‹‡ˆ‘ Š›’‡”–‡•‹‘Ǥ‹Ž‡–‹ŽŽ‡”ǡ‰Ž‘„ƒŽ’—„Ž‹ Š‡ƒŽ–Š ”‹•‹•. ‡‡˜ƒǣʹͲͳ͵Ǥ  ȏͳ͵ȐŽ‘•–”ƒǡ‹••‹ǡ‡ƒ• ǡ ‘ŽŽ‡ƒ†ǡ ƒ†‡” Š‘—™ǡ‹– Ǥ‡†‡”Žƒ††‡ƒƒ–. ‡‘‡ǡʹͲͲͻǦʹͲͳͲǤ‘‹–‘”‹‰˜ƒ”‹•‹ ‘ˆƒ –‘”‡‹. †‡ƒŽ‰‡‡‡„‡˜‘Ž‹‰ȏ‹—– ŠȐǤ‹Ž–Š‘˜‡ǣ ‹Œ•‹•–‹–——–˜‘‘”‘Ž•‰‡œ‘†Š‡‹†‡‹Ž‹‡—ȋ

(77) Ȍǣ ʹͲͳͳǤ  ȏͳͶȐ‡œǡ‘ƒ‰ŠƒǤ‹ˆ‡•–›Ž‡‘†‹ˆ‹ ƒ–‹‘•ˆ‘” ’ƒ–‹‡–•™‹–ŠŠ›’‡”–‡•‹‘Ǥ ‘—”ƒŽ‘ˆ–Š‡‡”‹ ƒ Šƒ”ƒ ‹•–•••‘ ‹ƒ–‹‘ǤʹͲͲͺǢͶͺȋͶȌǣͻʹǦͳͲʹǤ  ȏͳͷȐƒ™ǡ‘””‹• ǡƒŽ† Ǥ•‡‘ˆ„Ž‘‘†’”‡••—”‡ Ž‘™‡”‹‰†”—‰•‹–Š‡’”‡˜‡–‹‘‘ˆ ƒ”†‹‘˜ƒ• —Žƒ” †‹•‡ƒ•‡ǣ‡–ƒǦƒƒŽ›•‹•‘ˆͳͶ͹”ƒ†‘‹•‡†–”‹ƒŽ•‹–Š‡ ‘–‡š–‘ˆ‡š’‡ –ƒ–‹‘•ˆ”‘’”‘•’‡ –‹˜‡ ‡’‹†‡‹‘Ž‘‰‹ ƒŽ•–—†‹‡•Ǥ ǤʹͲͲͻǢ͵͵ͺǣ„ͳ͸͸ͷǤ  ȏͳ͸Ȑƒ†‡”‹ ǡ‡•–™‹  ǡƒŽ†Ǥ†Š‡”‡ ‡–‘ †”—‰•–Šƒ–’”‡˜‡– ƒ”†‹‘˜ƒ• —Žƒ”†‹•‡ƒ•‡ǣ‡–ƒǦ ƒƒŽ›•‹•‘͵͹͸ǡͳ͸ʹ’ƒ–‹‡–•Ǥ ‡†Ǥ ʹͲͳʹǢͳʹͷȋͻȌǣͺͺʹǦ͹‡ͳǤ  ȏͳ͹Ȑ„‡‰ƒœǡŠ‡Šƒ„ǡ ‡„”‡›‘Šƒ‡•ǡ Šƒ‰ƒ˜ƒ–Š—ŽƒǡŽ‘—”Ǥ‘ƒ†Š‡”‡ ‡–‘ ƒ–‹Š›’‡”–‡•‹˜‡†”—‰•ǣ•›•–‡ƒ–‹ ”‡˜‹‡™ƒ†‡–ƒǦ ƒƒŽ›•‹•Ǥ‡†‹ ‹‡ȋƒŽ–‹‘”‡ȌǤʹͲͳ͹Ǣͻ͸ȋͶȌǣ‡ͷ͸ͶͳǤ  ȏͳͺȐ•–‡”„‡”‰ǡŽƒ• Š‡Ǥ†Š‡”‡ ‡–‘‡†‹ ƒ–‹‘Ǥ ‰Ž ‡†ǤʹͲͲͷǢ͵ͷ͵ǣͶͺ͹ǦͶͻ͹Ǥ  ȏͳͻȐ‘”‰ƒ†‘ǡ‘Ž‘ǡƒ ‡†‘ ǡ‡”‡‹”ƒǡƒ•–‡Ž‘Ǧ ”ƒ ‘Ǥ”‡†‹ –‘”•‘ˆ— ‘–”‘ŽŽ‡†Š›’‡”–‡•‹‘ƒ† ƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘‘ƒ†Š‡”‡ ‡Ǥ  ƒ”†‹‘˜ƒ• ‹•‡•ǤʹͲͳͲǢͳȋͶȌǣͳͻ͸ǦʹͲʹǤ  ȏʹͲȐŠ‘™†Š—”›ǡŠƒ ǡ ‡›†‘ǡŠ”‘—ˆ‹ǡ ƒŠ‹‹ ǡ‘‘”‡ǡ‡–ƒŽǤ†Š‡”‡ ‡–‘ ƒ”†‹‘˜ƒ• —Žƒ”–Š‡”ƒ’›ǣ ƒ‡–ƒǦƒƒŽ›•‹•‘ˆ’”‡˜ƒŽ‡ ‡ƒ† Ž‹‹ ƒŽ ‘•‡“—‡ ‡•Ǥ—” ‡ƒ”– ǤʹͲͳ͵Ǣ͵Ͷȋ͵ͺȌǣʹͻͶͲǦʹͻͶͺǤ  ȏʹͳȐ”ƒ‰‘‹”ǡ‘–‡ǡ‘›ǡŽƒ‹•ǡƒŽ‘†‡ǡ ‡”ƒ”†ǡ‡–ƒŽǤ

(78) ’ƒ –‘ˆƒ†Š‡”‡ ‡–‘ƒ–‹Š›’‡”–‡•‹˜‡ ƒ‰‡–•‘ Ž‹‹ ƒŽ‘—– ‘‡•ƒ†Š‘•’‹–ƒŽ‹œƒ–‹‘ ‘•–•Ǥ ‡†ƒ”‡ǤʹͲͳͲǢͶͺȋͷȌǣͶͳͺǦͶʹͷǤ  ȏʹʹȐ‹ǡŠ‹ǡ— ǡ ™ƒ‰ǡƒ”ǡ‘ ǡ ‡–ƒŽǤ‡†‹ ƒ–‹‘†Š‡”‡ ‡ƒ†–Š‡‹•‘ˆ ƒ”†‹‘˜ƒ• —Žƒ”‘”–ƒŽ‹–›ƒ† ‘•’‹–ƒŽ‹œƒ–‹‘‘‰ ƒ–‹‡–•‹–Š‡™Ž›”‡• ”‹„‡†–‹Š›’‡”–‡•‹˜‡ ‡†‹ ƒ–‹‘•Ǥ ›’‡”–‡•‹‘ǤʹͲͳ͸Ǣ͸͹ȋ͵ȌǣͷͲ͸ǦͷͳʹǤ  ȏʹ͵Ȑƒœœƒ‰Ž‹ƒ ǡ„”‘•‹‘‹ǡŽƒ “—ƒǡ ‹Ž‹’’‹ǡ ‡••ƒǡ

(79) ‘”†‹‘ǡ‡–ƒŽǤ†Š‡”‡ ‡–‘ ƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘•ƒ† ƒ”†‹‘˜ƒ• —Žƒ” ‘”„‹†‹–›ƒ‘‰‡™Ž›†‹ƒ‰‘•‡†Š›’‡”–‡•‹˜‡ ’ƒ–‹‡–•Ǥ‹” —Žƒ–‹‘ǤʹͲͲͻǢͳʹͲȋͳ͸ȌǣͳͷͻͺǦͳ͸ͲͷǤ  ȏʹͶȐ‘‘Žǡ —‹‰ƒǡ‡”„”—‰‰‡ǡ’•–‡‹Ǥ

(80) ’ƒ –‘ˆ‡†‹ ƒ–‹‘†Š‡”‡ ‡‘ ‘•’‹–ƒŽ‹œƒ–‹‘. 17.

(81) 18. Chapter 1.  ‹•ƒ† ‡ƒŽ–Š ƒ”‡‘•–Ǥ‡†‹ ƒŽƒ”‡Ǥ ʹͲͲͷǢͶ͵ȋ͸ȌǣͷʹͳǦ͵ͲǤ  ȏʹͷȐŠ‹ǡ‘‰ ǡŠǡŠ‘‹ǡ‹ ǡ ƒ‰Ǥˆˆ‡ – ‘ˆƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘ƒ†Š‡”‡ ‡‘ Š‘•’‹–ƒŽ‹œƒ–‹‘ˆ‘” ƒ”†‹‘˜ƒ• —Žƒ”†‹•‡ƒ•‡ƒ†‘”–ƒŽ‹–› ‹Š›’‡”–‡•‹˜‡’ƒ–‹‡–•Ǥ ›’‡”–‡•‡•Ǥ ʹͲͳ͵Ǣ͵͸ȋͳͳȌǣͳͲͲͲǦͳͲͲͷǤ  ȏʹ͸Ȑ— ǡƒ‰ǡƒ‘ǡ‹ǡ—ǡŠƒ‰ Ǥ‡Žƒ–‹‘•Š‹’‘ˆ„Ž‘‘†’”‡••—”‡ ‘–”‘Žƒ† Š‘•’‹–ƒŽ‹œƒ–‹‘”‹•–‘‡†‹ ƒ–‹‘ƒ†Š‡”‡ ‡ƒ‘‰ ’ƒ–‹‡–•™‹–ŠŠ›’‡”–‡•‹‘‹ƒ‹™ƒǤ  ›’‡”–‡•Ǥ ʹͲͳͲǢʹ͵ȋʹȌǣͳͷͷǦͳ͸ͲǤ  ȏʹ͹Ȑ‹––ƒ ǡƒ‘ǡŠ‡ǡ–‡––‹ Ǥ –‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘†Š‡”‡ ‡ƒ† —„•‡“—‡– ‡ƒŽ–Š ƒ”‡–‹Ž‹œƒ–‹‘ƒ†‘•–•Ǥ  ƒƒ‰ƒ”‡ǤʹͲͳͲǢͳ͸ȋͺȌǣͷ͸ͺǦͷ͹͸Ǥ  ȏʹͺȐ‘‡„— ǡ‹„‡”ƒ ǡ ‡‹ŽŽǦ‘›ƒƒǡ ”‡ƒǤ‡†‹ ƒ–‹‘ƒ†Š‡”‡ ‡Ž‡ƒ†•–‘Ž‘™‡” Š‡ƒŽ–Š ƒ”‡—•‡ƒ† ‘•–•†‡•’‹–‡‹ ”‡ƒ•‡††”—‰ •’‡†‹‰Ǥ ‡ƒŽ–Šˆˆȋ‹ŽŽ™‘‘†ȌǤʹͲͳͳǢ͵ͲȋͳȌǣͻͳǦͻͻǤ  ȏʹͻȐ—‡••‹‰ǡ ‹•Šƒǡ”‹ŒŠ‘‡ˆ ǡŽ‹••‡  ǡ ”‘••ƒǤ••‘ ‹ƒ–‹‘‘ˆ‘–”‘ŽŽ‡†ƒ†  ‘–”‘ŽŽ‡† ›’‡”–‡•‹‘‹–Š‘”’Žƒ ‡ ”‘†— –‹˜‹–›Ǥ Ž‹ ›’‡”–‡•ȋ ”‡‡™‹ ŠȌǤ ʹͲͳ͸Ǣͳͺǣʹͳ͹ǦʹʹʹǤ  ȏ͵ͲȐƒ‰‡”ǡƒ— ǡ ”‡ ŠǦƒƒ• ǡ —’–ƒǤ

(82) ’ƒ – ‘ˆ‡†‹ ƒ–‹‘†Š‡”‡ ‡‘‘””‘†— –‹˜‹–›‹ ›’‡”–‡•‹‘Ǥ Šƒ”‡‡ˆ‹–•ǤʹͲͳʹǢͶȋͶȌǣ‡ͺͺǦ‡ͻ͸Ǥ  ȏ͵ͳȐ‹‡—™Žƒƒ–ǡ‹Ž œ›•‹ǡƒ˜ƒ””‘ǡ ‘„•‘ǡ ‡ˆˆ‡”›ǡ‡‡’ƒƒ••‡”‹Žǡ‡–ƒŽǤ

(83) –‡”˜‡–‹‘•ˆ‘” ‡Šƒ ‹‰‡†‹ ƒ–‹‘ƒ†Š‡”‡ ‡ȋ”‡˜‹‡™ȌǤ‘ Š”ƒ‡ ƒ–ƒ„ƒ•‡›•–‡˜ǤʹͲͳͶȋͳͳȌǣͲͲͲͲͳͳǤ  ȏ͵ʹȐ”‹’ƒŽƒ‹ǡƒ‘ǡ ƒ›‡•Ǥ

(84) –‡”˜‡–‹‘•–‘ ‡Šƒ ‡‡†‹ ƒ–‹‘ƒ†Š‡”‡ ‡‹ Š”‘‹ ‡†‹ ƒŽ ‘†‹–‹‘•ǣƒ•›•–‡ƒ–‹ ”‡˜‹‡™Ǥ” Š

(85) –‡”‡†Ǥ ʹͲͲ͹Ǣͳ͸͹ȋ͸ȌǣͷͶͲǦͷͷͲǤ  ȏ͵͵Ȑ˜ƒ—Ž‡ǡŽ—‹Œ•ǡ˜ƒ‹Œǡ†‡‹††‡”ǡ ‡‡”†‹ǡ‡•‹‰ Ǥƒ–‹‡–ƒ†Š‡”‡ ‡–‘‡†‹ ƒŽ –”‡ƒ–‡–ǣƒ”‡˜‹‡™‘ˆ”‡˜‹‡™•Ǥ ‡ƒŽ–Š‡”˜‡•Ǥ ʹͲͲ͹Ǣ͹ǣͷͷǤ  ȏ͵ͶȐ ‘ƒŽ† ǡ ƒ”‰ǡ ƒ›‡•Ǥ

(86) –‡”˜‡–‹‘• –‘‡Šƒ ‡’ƒ–‹‡–ƒ†Š‡”‡ ‡–‘‡†‹ ƒ–‹‘ ’”‡• ”‹’–‹‘•ǣ• ‹‡–‹ˆ‹ ”‡˜‹‡™Ǥ Ǥ ʹͲͲʹǢʹͺͺȋʹʹȌǣʹͺ͸ͺǦʹͺ͹ͻǤ  ȏ͵ͷȐ‹ ǡ‡”˜Ž‘‡–ǡ˜ƒ‹Œǡ‹– ǡƒ‡‡”– Ǥˆˆ‡ –•‘ˆ‡ ‡ƒŽ–Š‹–‡”˜‡–‹‘•‘‡†‹ ƒ–‹‘ ƒ†Š‡”‡ ‡ǣƒ•›•–‡ƒ–‹ ”‡˜‹‡™‘ˆ–Š‡Ž‹–‡”ƒ–—”‡Ǥ ‡†

(87) –‡”‡–‡•ǤʹͲͳͳǢͳ͵ȋͶȌǣ‡ͳͲ͵Ǥ . ȏ͵͸Ȑ‡”˜Ž‘‡–ǡ‹ ǡ˜ƒ‡‡”– ǡ†‡ƒ‡” ǡ ‘—˜›ǡ˜ƒ‹ŒǤŠ‡‡ˆˆ‡ –‹˜‡‡••‘ˆ ‹–‡”˜‡–‹‘•—•‹‰‡Ž‡ –”‘‹ ”‡‹†‡”•–‘‹’”‘˜‡ ƒ†Š‡”‡ ‡–‘ Š”‘‹ ‡†‹ ƒ–‹‘ǣƒ•›•–‡ƒ–‹ ”‡˜‹‡™ ‘ˆ–Š‡Ž‹–‡”ƒ–—”‡Ǥ ‡†

(88) ˆ‘”••‘ Ǥ ʹͲͳʹǢͳͻȋͷȌǣ͸ͻ͸Ǧ͹ͲͶǤ  ȏ͵͹Ȑ‘ǡ—’’ƒ”ǡŠƒ•‡ ǡ”‹“—‡œǡ‘‘’‡” Ǥ

(89) –‡”˜‡–‹‘•–‘

(90) ’”‘˜‡‡†‹ ƒ–‹‘†Š‡”‡ ‡‹ ›’‡”–‡•‹˜‡ƒ–‹‡–•ǣ›•–‡ƒ–‹ ‡˜‹‡™ƒ†‡–ƒǦ ƒƒŽ›•‹•Ǥ—”” ›’‡”–‡•‡’ǤʹͲͳͷǢͳ͹ȋͳʹȌǣͻͶǤ  ȏ͵ͺȐ‡˜‹‡ ǡ†™ƒ”†•ǡ ‡Ž†ƒǤƒ””‹‡”•–‘ –”‡ƒ–‡–ǣ†‡• ”‹„‹‰–Š‡ˆ”‘ƒ†‹ˆˆ‡”‡– ’‡”•’‡ –‹˜‡Ǥƒ–‹‡–”‡ˆ‡”†Š‡”‡ ‡ǤʹͲͳͺǢͳʹǣͳʹͻǦ͵͵Ǥ  ȏ͵ͻȐ‘•™‘”–Š ǡ ”ƒ‰‡”ǡ‡†›•ǡ”‹†‹•ǡ —”Š‘Ž†‡”ǡœƒŒ‘™•‹ǡ‡–ƒŽǤ‡†‹ ƒ–‹‘ ƒ†Š‡”‡ ‡ǣƒ ƒŽŽˆ‘”ƒ –‹‘Ǥ ‡ƒ”– Ǥ ʹͲͳͳǢͳ͸ʹȋ͵ȌǣͶͳʹǦͶʹͶǤ  ȏͶͲȐ˜ƒ†‡”ƒƒǡŽ†‡”• ǡ‘‘•ǡ‘•ƒ• ǡ ‹Œ’‡Ž• ǡ —‰–‡„—”‰ ǤŠ‡ȋ ‘•–ǦȌ‡ˆˆ‡ –‹˜‡‡••‘ˆƒ ’ƒ–‹‡–Ǧ–ƒ‹Ž‘”‡†‹–‡”˜‡–‹‘’”‘‰”ƒ‡–‘‡Šƒ ‡ ƒ†Š‡”‡ ‡–‘ƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘‹ ‘—‹–›’Šƒ”ƒ ‹‡•ǣ•–—†›’”‘–‘ ‘Ž‘ˆƒ ”ƒ†‘‹•‡† ‘–”‘ŽŽ‡†–”‹ƒŽǤ”‹ƒŽ•ǤʹͲͳ͹ǢͳͺȋͳȌǣʹͻǤ  ȏͶͳȐ‡˜‡–ŠƒŽ ǡ‹‡”ƒǡ —–ƒǤ ‘’Ž‹ƒ ‡ǣ•‡ŽˆǦ”‡‰—Žƒ–‹‘’‡”•’‡ –‹˜‡Ǥ

(91) ǣ ‡–”›ǡ ‡†‹–‘”Ǥ ƒ†„‘‘‘ˆ‡Šƒ˜‹‘”ƒŽ‡†‹ ‹‡‡™‘”ǣ ‡”‰ƒ‘”‡••ǢͳͻͺͶǤ  ȏͶʹȐ‡˜‡–ŠƒŽ ǡ‡›ƒ‹‹ǡ”‘™Ž‡‡ǡ‹‡ˆ‡„ƒ Š ǡ‡˜‡–ŠƒŽǡƒ–”‹ Ǧ‹ŽŽ‡”ǡ‡–ƒŽǤ

(92) ŽŽ‡•• ‡’”‡•‡–ƒ–‹‘•Š‡‘”‡–‹ ƒŽ ‘—†ƒ–‹‘•Ǥ

(93) ǣ‡–”‹‡ ǡ ‡‹ƒ ǡ‡†‹–‘”•Ǥ‡” ‡’–‹‘•‘ˆ ‡ƒŽ–Šƒ†

(94) ŽŽ‡•• —””‡–‡•‡ƒ” Šƒ†’’Ž‹ ƒ–‹‘•Ǥ•–‡”†ƒǣ ƒ”™‘‘† ƒ†‡‹ —„Ž‹•Š‡”•Ǣͳͻͻ͹Ǥ  ȏͶ͵Ȑ‹‡ˆ‡„ƒ Šǡ‡˜‡–ŠƒŽ ǤŠ‡‘‘Ǧ‡•‡ ‘†‡Ž‘ˆ

(95) ŽŽ‡••‡’”‡•‡–ƒ–‹‘ǣŠ‡‘”‡–‹ ƒŽƒ† ”ƒ –‹ ƒŽ ‘•‹†‡”ƒ–‹‘•Ǥ ‘—”ƒŽ‘ˆ‘ ‹ƒŽ‹•–”‡••ƒ† –Š‡ ‘‡Ž‡••Ǥͳͻͻ͸ǢͷǣͳͳǦ͵ͺǤ  ȏͶͶȐ‡˜‡–ŠƒŽ ǡ‹‡ˆ‡„ƒ Šǡ‡˜‡–ŠƒŽǤ

(96) ŽŽ‡•• ‘‰‹–‹‘ǣ•‹‰ ‘‘•‡•‡–‘—†‡”•–ƒ† –”‡ƒ–‡–ƒ†Š‡”‡ ‡ƒ†ƒˆˆ‡ – ‘‰‹–‹‘‹–‡”ƒ –‹‘•Ǥ ‘‰‹–‹˜‡Š‡”ƒ’›ƒ†‡•‡ƒ” ŠǤͳͻͻʹǢͳ͸ȋʹȌǣͳͶ͵Ǧ͸͵Ǥ  ȏͶͷȐ‡›‘Ž†•ǤŠ‡’”‘„Ž‡‘ˆƒ–‹”‡–”‘˜‹”ƒŽ ƒ†Š‡”‡ ‡ǣƒ•‡ŽˆǦ”‡‰—Žƒ–‘”›‘†‡Žˆ‘”‹–‡”˜‡–‹‘Ǥ 

(97) ƒ”‡ǤʹͲͲ͵ǢͳͷȋͳȌǣͳͳ͹ǦʹͶǤ  ȏͶ͸ȐƒŒ’—”ƒ ǡƒ›ƒǤ‡†‹ ƒ–‹‘ƒ†Š‡”‡ ‡‹ƒ •ƒ’Ž‡‘ˆ‡Ž†‡”Ž›•—ˆˆ‡”‹‰ˆ”‘Š›’‡”–‡•‹‘ ‡˜ƒŽ—ƒ–‹‰–Š‡‹ˆŽ—‡ ‡‘ˆ‹ŽŽ‡••’‡” ‡’–‹‘•ǡ –”‡ƒ–‡–„‡Ž‹‡ˆ•ƒ†‹ŽŽ‡••„—”†‡Ǥ ƒƒ‰ƒ”‡ Šƒ”ǤʹͲͳͶǢʹͲȋͳȌǣͷͺǦ͸ͷǤ .

(98) General introduction.  ȏͶ͹Ȑ ‘”‡ǡ‡‹ƒ Ǥ”‡†‹ –‹‰–”‡ƒ–‡– ƒ†Š‡”‡ ‡ǣ‘˜‡”˜‹‡™‘ˆ–Š‡‘”‡–‹ ƒŽ‘†‡Ž•Ǥ

(99) ǣ ›‡”•ǡ‹†‡ ‡ǡ‡†‹–‘”•Ǥ†Š‡”‡ ‡–‘–”‡ƒ–‡– ‹‡†‹ ƒŽ ‘†‹–‹‘•Ǥ•–‡”†ƒǣ ƒ”™‘‘† ƒ†‡‹  —„Ž‹•Š‡”•ǢͳͻͻͺǤ  ȏͶͺȐ ‘”‡ǡ‡‹ƒ Ǥ‡ŽˆǦ”‡‰—Žƒ–‹‘ƒ†‡ŽˆǦ ƒƒ‰‡‡–‹•–Šƒǣš’Ž‘”‹‰Š‡‘Ž‡‘ˆ

(100) ŽŽ‡•• ‡” ‡’–‹‘•ƒ†”‡ƒ–‡–‡Ž‹‡ˆ•‹š’Žƒ‹‹‰‘Ǧ ƒ†Š‡”‡ ‡–‘”‡˜‡–‡”‡†‹ ƒ–‹‘Ǥ•› Š‘Ž‘‰›Ƭ ‡ƒŽ–ŠǤʹͲͲʹǢͳ͹ȋͳȌǣͳ͹Ǧ͵ʹǤ                                               . ȏͶͻȐ‡›‡”ǡ‡˜‡–ŠƒŽ ǡ —–ƒǤ‘‘Ǧ•‡•‡ ‘†‡Ž•‘ˆ‹ŽŽ‡••ǣŠ‡‡šƒ’Ž‡‘ˆŠ›’‡”–‡•‹‘Ǥ ‡ƒŽ–Š •› Š‘Ž‘‰›ǤͳͻͺͷǢͶȋʹȌǣͳͳͷǦ͵ͷǤ  . 19.

(101)     .                 .

(102) CHAPTER 2 Factors associated with antihypertensive medication non-adherence: a systematic review. D.M. van der Laan P.J.M. Elders C.C.L.M. Boons J.J. Beckeringh M.G.A.A.M. Nijpels J.G. Hugtenburg. Published in Journal of Human Hypertension (2017).

(103) 22. Chapter 2. . Abstract  Introduction ‘Ǧƒ†Š‡”‡ ‡ –‘ ƒ–‹Š›’‡”–‡•‹˜‡ ‡†‹ ƒ–‹‘ ‹• –Š‡ ‘•– ‹’‘”–ƒ– ƒ—•‡‘ˆ— ‘–”‘ŽŽ‡†„Ž‘‘†’”‡••—”‡ƒ†‹•‹ˆŽ—‡ ‡†„›—Ž–‹’Ž‡‹–‡””‡Žƒ–‹‰ˆƒ –‘”•Ǥ †‡”•–ƒ†‹‰–Š‡ ‘’Ž‡š‹–›‘ˆ‡†‹ ƒ–‹‘‘Ǧƒ†Š‡”‡ ‡ƒ†‹–•ƒ••‘ ‹ƒ–‡†ˆƒ –‘”• ‹•‹’‘”–ƒ––‘†‡–‡”‹‡‹–‡”˜‡–‹‘•–”ƒ–‡‰‹‡•ǤŠ‡”‡ˆ‘”‡ǡƒ•›•–‡ƒ–‹ ”‡˜‹‡™™ƒ• ’‡”ˆ‘”‡†ƒ‹‡†–‘‹†‡–‹ˆ›ˆƒ –‘”•ƒ••‘ ‹ƒ–‡†™‹–Šƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘‘Ǧ ƒ†Š‡”‡ ‡Ǥ   Methods ‹ˆˆ‡”‡– †ƒ–ƒ„ƒ•‡• ™‡”‡ •‡ƒ” Š‡† ˆ‘” ‘„•‡”˜ƒ–‹‘ƒŽ •–—†‹‡• ”‡’‘”–‹‰ ‘ ˆƒ –‘”•ƒ••‘ ‹ƒ–‡†™‹–Š‘Ǧƒ†Š‡”‡ ‡–‘ƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘Ǥ‹–Ž‡•ǡƒ„•–”ƒ –• ƒ†ˆ—ŽŽ–‡š–•™‡”‡”‡˜‹‡™‡†„›–Š”‡‡”‡•‡ƒ” Š‡”•Ǥ—„•‡“—‡–Ž›ǡ–Š‡‡–Š‘†‘Ž‘‰‹ ƒŽ “—ƒŽ‹–› ‘ˆ ‡ƒ Š •–—†› ™ƒ• ƒ••‡••‡†Ǥ ƒ –‘”• –Šƒ– ™‡”‡ ‡š–”ƒ –‡† ˆ”‘ –Š‡ ‹ Ž—†‡† •–—†‹‡•™‡”‡ ƒ–‡‰‘”‹•‡†ƒ•ˆƒ –‘”•™‹–Š ‘•‹•–‡–‘”‹ ‘•‹•–‡–‡˜‹†‡ ‡–‘’—––Š‡‹” ’‘–‡–‹ƒŽ‹’‘”–ƒ ‡‹–‘’‡”•’‡ –‹˜‡Ǥ  Results ‘”–›Ǧˆ‘—”•–—†‹‡•™‡”‡‹ Ž—†‡†Ǥ ‹‰Š‡” ‘Ǧ’ƒ›‡–ǡ•‹†‡‡ˆˆ‡ –•ƒ†ƒ’‘‘” ’ƒ–‹‡–Ǧ’”‘˜‹†‡””‡Žƒ–‹‘•Š‹’™‡”‡‹†‡–‹ˆ‹‡†ƒ•ˆƒ –‘”•™‹–Š ‘•‹•–‡–‡˜‹†‡ ‡•‹ ‡ ‘•‹•–‡–•‹‰‹ˆ‹ ƒ–”‡Žƒ–‹‘•Š‹’•™‡”‡ˆ‘—†ˆ‘”–Š‡•‡ˆƒ –‘”•™Š‡‡˜‡”•–—†‹‡†ǤŠ‡ ”‡Žƒ–‹‘•Š‹’• „‡–™‡‡ ‘Ǧƒ†Š‡”‡ ‡ ƒ† —Ž–‹’Ž‡ ‘–Š‡” ˆƒ –‘”• ™‡”‡ ‹ ‘•‹•–‡– ƒ‘‰ –Š‡ ”‡˜‹‡™‡† •–—†‹‡•Ǥ ‘™‡˜‡”ǡ •‘‡ ‘ˆ –Š‡•‡ ˆƒ –‘”• †‡•‡”˜‡ •‘‡ ‘•‹†‡”ƒ–‹‘Ǥ  Conclusion‹ ‡ǡ—Ž–‹’Ž‡’‘–‡–‹ƒŽŽ›”‡Ž‡˜ƒ–ˆƒ –‘”•™‡”‡‹†‡–‹ˆ‹‡†’ƒ–‹‡–Ǧ–ƒ‹Ž‘”‡† ‹–‡”˜‡–‹‘• ˆ‘ —••‹‰ ‘ ‹†‡–‹ˆ›‹‰ ƒ† ƒ††”‡••‹‰ ’ƒ–‹‡–•ǯ •’‡ ‹ˆ‹  „ƒ””‹‡”• –‘ ƒ†Š‡”‡ ‡ ƒ”‡ ‡‡†‡†Ǥ —”–Š‡” ”‡•‡ƒ” Š •Š‘—Ž†  Žƒ”‹ˆ› –Š‡ ‹ˆŽ—‡ ‡ ‘ˆ ‹ ‘•‹•–‡– ˆƒ –‘”•‘ƒ†Š‡”‡ ‡ƒ†–Š‡‹”’‘–‡–‹ƒŽ–‘„‡ƒ††”‡••‡†‹‹–‡”˜‡–‹‘•Ǥ.

(104) A systematic literature review. . Introduction  ›’‡”–‡•‹‘ ‘–”‹„—–‡• –‘ –Š‡ „—”†‡ ‘ˆ ƒ”†‹‘˜ƒ• —Žƒ” †‹•‡ƒ•‡ ƒ† ’”‡ƒ–—”‡ ‘”„‹†‹–›ƒ†‘”–ƒŽ‹–›ȏͳȐǤŠ‡ƒ„‹Ž‹–›‘ˆ’Šƒ”ƒ ‘Ž‘‰‹ ƒŽ–”‡ƒ–‡–‘ˆŠ›’‡”–‡•‹‘ –‘”‡†— ‡–Š‡”‹•‘ˆ ƒ”†‹‘˜ƒ• —Žƒ”‡˜‡–•ƒ††‡ ”‡ƒ•‡‘”„‹†‹–›ƒ†‘”–ƒŽ‹–›‹•™‡ŽŽ ‡•–ƒ„Ž‹•Š‡† ȏʹǡ ͵ȐǤ ‘™‡˜‡”ǡ †—‡ –‘ ’‘‘” ƒ†Š‡”‡ ‡ –‘ ƒ–‹Š›’‡”–‡•‹˜‡ ‡†‹ ƒ–‹‘ ‘’–‹ƒŽ Ž‹‹ ƒŽ‘—– ‘‡•ƒ”‡‘–ƒ Š‹‡˜‡†ȏͶǡͷȐǤ  ‡†‹ ƒ–‹‘ƒ†Š‡”‡ ‡‹•†‡ˆ‹‡†ƒ•–Š‡’”‘ ‡••„›™Š‹ Š’ƒ–‹‡–•–ƒ‡–Š‡‹”‡†‹ ƒ–‹‘ ƒ• ƒ‰”‡‡† —’‘ ™‹–Š –Š‡‹” ’”‡• ”‹„‡” ȏ͸ȐǤ Š‡ ‘”Ž† ‡ƒŽ–Š ”‰ƒ‹•ƒ–‹‘ ȋ Ȍ ‡•–‹ƒ–‡•–Š‡’”‡˜ƒŽ‡ ‡‘ˆ‘Ǧƒ†Š‡”‡ ‡–‘ƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘„‡–™‡‡͵Ͳ ƒ†ͷͲΨǤŠ‹•˜ƒ”‹ƒ–‹‘”‡Žƒ–‡•–‘–Š‡†‹ˆˆ‡”‡ ‡•‹†”—‰ Žƒ••ǡ–›’‡‘ˆ’”‡˜‡–‹‘ƒ† ‡–Š‘†•—•‡†–‘‡ƒ•—”‡ƒ†Š‡”‡ ‡ȏʹǡ͹ȐǤ†Š‡”‡ ‡–‘‡†‹ ƒ–‹‘‹•‹ˆŽ—‡ ‡†„› —Ž–‹’Ž‡‹–‡””‡Žƒ–‹‰ˆƒ –‘”•ǤŠ‡ ‹–”‘†— ‡†ƒˆ”ƒ‡™‘”–‘ Žƒ••‹ˆ›ˆƒ –‘”•–Šƒ– ‹ˆŽ—‡ ‡ ƒ†Š‡”‡ ‡ ‹–‘ ˆ‹˜‡ †‹‡•‹‘•ǣ ’ƒ–‹‡–Ǧ”‡Žƒ–‡† ˆƒ –‘”• ˆ‘” ‡šƒ’Ž‡ǡ ‹ƒ†‡“—ƒ–‡„‡Ž‹‡ˆ•‘”•‹ŽŽ•ǡ•‘ ‹ƒŽȀ‡ ‘‘‹ Ǧ”‡Žƒ–‡†ˆƒ –‘”•ǡˆ‘”‡šƒ’Ž‡ǡ’‘‘”Š‡ƒŽ–Š Ž‹–‡”ƒ › ‘” Ž‘™ •‘ ‹ƒŽ •—’’‘”–ǡ ‘†‹–‹‘Ǧ”‡Žƒ–‡† ˆƒ –‘”•ǡ ˆ‘” ‡šƒ’Ž‡ǡ ’”‡•‡ ‡ ‘ˆ ‘‘”„‹†‹–‹‡•ǡ–Š‡”ƒ’›Ǧ”‡Žƒ–‡†ˆƒ –‘”•ǡˆ‘”‡šƒ’Ž‡ǡ ‘’Ž‡š†”—‰”‡‰‹‡ƒ†Š‡ƒŽ–Š •›•–‡ȀŠ‡ƒŽ–Š ƒ”‡–‡ƒǦ”‡Žƒ–‡†ˆƒ –‘”•ǡˆ‘”‡šƒ’Ž‡ǡ‹•—ˆˆ‹ ‹‡– ‘—‹ ƒ–‹‘™‹–Š Š‡ƒŽ–Š ƒ”‡’”‘˜‹†‡”ȏʹȐǤ   —„‡” ‘ˆ ”‡˜‹‡™• Šƒ˜‡ „‡‡ ’—„Ž‹•Š‡† ‘ ‡”‹‰ –Š‡ ˜ƒ”‹ƒ„Ž‡• ƒ••‘ ‹ƒ–‡† ™‹–Š ƒ”†‹‘˜ƒ• —Žƒ” ‡†‹ ƒ–‹‘ ‘Ǧƒ†Š‡”‡ ‡ ”‡Žƒ–‡† –‘’‹ •Ǥ ‘™”› et alǤ ‡˜ƒŽ—ƒ–‡† –Š‡ ’”‡†‹ –‘”• ‘ˆ ‘Ǧƒ†Š‡”‡ ‡ –‘ ƒ”†‹‘˜ƒ• —Žƒ” ‡†‹ ƒ–‹‘ ƒ† ‘ ‡–”ƒ–‡† ‘ ”‡•‘—” ‡ǦŽ‹‹–‡†•‡––‹‰•ȏͺȐǤ‡•–”ƒƒ†Ž•ƒ„„ƒ‰ŠȏͻȐ’‡”ˆ‘”‡†ƒ‡–ƒǦƒƒŽ›•‹•‘ˆ †ƒ–ƒ„ƒ•‡ƒ† ‘Š‘”–•–—†‹‡•’”‘˜‹†‹‰‡•–‹ƒ–‡•‘ˆ”‹•‹†‹ ƒ–‘”•ƒ••‘ ‹ƒ–‡†™‹–Š‘Ǧ ƒ†Š‡”‡ ‡ –‘ ƒ–‹Š›’‡”–‡•‹˜‡ ‡†‹ ƒ–‹‘ ƒ••‡••‡† ™‹–Š ‘„Œ‡ –‹˜‡ ‡ƒ•—”‡•Ǥ  •›•–‡ƒ–‹  ”‡˜‹‡™ „› Ž Š—”ƒ‹” et alǤ ȏͳͲȐ ‡šƒ‹‡† ’ƒ–‹‡–•ǯ ƒ†Š‡”‡ ‡ „ƒ””‹‡”• –‘ ƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘ǡƒ†ƒ‹‡†–‘†‡–‡”‹‡™Š‹ Šƒ†Š‡”‡ ‡„ƒ””‹‡”•™‡”‡ ƒ••‡••‡†‹•‡ŽˆǦ”‡’‘”–‡ƒ•—”‡•Ǥ

(105) •—ǡ–Š‡•–—†›’‘’—Žƒ–‹‘•ǡ•‡––‹‰•ƒ†‡–Š‘†• ‘ˆ –Š‡•‡ ”‡˜‹‡™• †‹ˆˆ‡”‡† ™‹–Š ”‡•’‡ – –‘ –Š‹• ”‡˜‹‡™Ǥ •’‡ ‹ƒŽŽ›ǡ „› ‡ƒ• ‘ˆ ƒ–‡‰‘”‹•‹‰ ˆƒ –‘”• ƒ ‘”†‹‰ –‘ ‘•‹•–‡– ƒ† ‹ ‘•‹•–‡– ‡˜‹†‡ ‡ǡ ƒ –Š‘”‘—‰Š ‘˜‡”˜‹‡™™ƒ•’”‘˜‹†‡†‹–Š‹•”‡˜‹‡™Ǥ‘‘—”‘™Ž‡†‰‡ǡ–Š‹•—‹“—‡‡–Š‘†Šƒ•‘– „‡‡’‡”ˆ‘”‡†‹ƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘”‡•‡ƒ” Šƒ•›‡–Ǥ   ‘’”‡Š‡•‹˜‡ —†‡”•–ƒ†‹‰ ‘ˆ –Š‡ ‘’Ž‡š Šƒ”ƒ –‡” ‘ˆ ƒ–‹Š›’‡”–‡•‹˜‡ ‡†‹ ƒ–‹‘ ‘Ǧƒ†Š‡”‡ ‡ ƒ† ‹–• ƒ••‘ ‹ƒ–‡† ˆƒ –‘”• ‹• ‡ ‡••ƒ”› –‘ †‡˜‡Ž‘’ ‹–‡”˜‡–‹‘•–”ƒ–‡‰‹‡•ƒ‹‡†ƒ––Š‡‹’”‘˜‡‡–‘ˆ‡†‹ ƒ–‹‘ƒ†Š‡”‡ ‡ǤŠ‡”‡ˆ‘”‡ǡ –Š‡’”‡•‡–•›•–‡ƒ–‹ ”‡˜‹‡™ƒ‹•–‘‹†‡–‹ˆ›ˆƒ –‘”•ƒ••‘ ‹ƒ–‡†™‹–Šƒ–‹Š›’‡”–‡•‹˜‡ ‡†‹ ƒ–‹‘‘Ǧƒ†Š‡”‡ ‡Ǥ  . 23.

(106) 24. Chapter 2. . Methods  Datasourceandsearchstrategy

(107)  –Š‡ ’”‡•‡– •›•–‡ƒ–‹  ”‡˜‹‡™ –Š‡ 

(108)  •–ƒ–‡‡– ˆ‘” ”‡’‘”–‹‰ •›•–‡ƒ–‹  ”‡˜‹‡™• Šƒ• „‡‡ ˆ‘ŽŽ‘™‡† ȏͳͳȐǤ 

(109) ǡ ǡ •›

(110)   ƒ† Š‡ ‘ Š”ƒ‡ ‹„”ƒ”›™‡”‡•‡ƒ” Š‡†—’ˆ”‘ ƒ—ƒ”›ͳͻͻͲ–‘ —Ž›ʹͲͳ͸–‘‹†‡–‹ˆ›‰Ž‹•ŠǦŽƒ‰—ƒ‰‡ ”‡•‡ƒ” Š ƒ”–‹ Ž‡• ‘ˆ ‘„•‡”˜ƒ–‹‘ƒŽ •–—†‹‡• ”‡’‘”–‹‰ ‘ ˆƒ –‘”• ƒ••‘ ‹ƒ–‡† ™‹–Š ‡†‹ ƒ–‹‘ ‘Ǧƒ†Š‡”‡ ‡Ǥ Š‡ •‡ƒ” Š –‡”• ”‡Žƒ–‡† –‘ ‡†‹ ƒ–‹‘ ƒ†Š‡”‡ ‡ ™‡”‡ ƒ‰”‡‡†—’‘ƒ†–‡•–‡†„›–™‘ƒ—–Š‘”•ȋǡ ȌȋAppendix1ȌǤ

(111) –™ƒ•†‡ ‹†‡†–‘—•‡ „”‘ƒ†‡”•‡ƒ” Š–‡”•–‘’”‡˜‡–‹••‹‰‡Ž‹‰‹„Ž‡ƒ”–‹ Ž‡•ǤŠ‡•‡ƒ” Šˆ‘”ƒ”–‹ Ž‡•™ƒ• ’‡”ˆ‘”‡†„›‘‡‘ˆ–Š‡ƒ—–Š‘”•ȋȌ•—’’‘”–‡†„›ƒ‡š’‡”‹‡ ‡†Ž‹„”ƒ”‹ƒǤ  Studyselection  •ƒŽŽ —„‡” ‘ˆ –‹–Ž‡• ƒ† ƒ„•–”ƒ –• ™‡”‡ • ”‡‡‡† ƒ† ’”‡Ž‹‹ƒ”› †‹• —••‡† –‘ ”‡ƒ Š ƒ‰”‡‡‡– ‘ ‹–‡”’”‡–ƒ–‹‘•ǡ †‡ˆ‹‹–‹‘•ǡ ƒ† ‹ Ž—•‹‘ ”‹–‡”‹ƒǤ –—†‹‡• ™‡”‡ •‡Ž‡ –‡†‹–Š”‡‡•–‡’•Ǥ

(112) •–‡’‘‡ǡ–™‘ƒ—–Š‘”•ȋǡ Ȍ‹†‡’‡†‡–Ž›• ƒ‡†–‹–Ž‡• ƒ†ƒ„•–”ƒ –•–‘‹†‡–‹ˆ›ƒ”–‹ Ž‡• ‘””‡•’‘†‹‰™‹–Š–Š‡’”‡Ǧ†‡ˆ‹‡†‹ Ž—•‹‘ ”‹–‡”‹ƒ ȋTable1ȌǤ

(113) •–‡’–™‘ǡˆ—ŽŽǦ–‡š–’ƒ’‡”•‘ˆ”‡Ž‡˜ƒ–ƒ”–‹ Ž‡•™‡”‡”‡–”‹‡˜‡†ƒ†”‡˜‹‡™‡† ˆ‘” ‹ Ž—•‹‘ ‹ –Š‡ ”‡˜‹‡™ „› –Š”‡‡ ƒ—–Š‘”• ȋǡ  ‘” ǡ ȌǤ

(114)  •–‡’ –Š”‡‡ǡ –Š‡ ‡–Š‘†‘Ž‘‰‹ ƒŽ“—ƒŽ‹–›‘ˆ‡Ž‹‰‹„Ž‡ˆ—ŽŽǦ–‡š–ƒ”–‹ Ž‡•™ƒ•‹†‡’‡†‡–Ž›‡˜ƒŽ—ƒ–‡†„›–Š‡ •ƒ‡ –Š”‡‡ ƒ—–Š‘”•Ǥ ”‹‘” –‘ “—ƒŽ‹–› ƒ••‡••‡– ƒ •ƒŽŽ —„‡” ‘ˆ ƒ”–‹ Ž‡• ™ƒ• ”‡˜‹‡™‡†‹‘”†‡”–‘”‡ƒ ŠŠ‘‘‰‡‘—•“—ƒŽ‹–›ƒ••‡••‡–Ǥ‹•ƒ‰”‡‡‡–”‡‰ƒ”†‹‰ ‡Ž‹‰‹„‹Ž‹–›‘ˆƒ”–‹ Ž‡•™ƒ•†‹• —••‡†—–‹Ž ‘•‡•—•™ƒ•”‡ƒ Š‡†Ǥ  Table1

(115)  Ž—•‹‘ ”‹–‡”‹ƒˆ‘”•–—†›•‡Ž‡ –‹‘    Inclusioncriteria  —ƒ–‹–ƒ–‹˜‡ǡ‘„•‡”˜ƒ–‹‘ƒŽȋ”‡–”‘•’‡ –‹˜‡ǡ ”‘••Ǧ•‡ –‹‘ƒŽǡ’”‘•’‡ –‹˜‡Ȍ•–—†‹‡•ƒ‹‹‰–‘‹˜‡•–‹‰ƒ–‡  –Š‡ƒ••‘ ‹ƒ–‹‘‘ˆˆƒ –‘”•™‹–Š‡†‹ ƒ–‹‘‘Ǧƒ†Š‡”‡ ‡  –—†›’ƒ”–‹ ‹’ƒ–•‘ˆηͳͺ›‡ƒ”•‘Ž†ǢŽ‹˜‹‰‹ƒ‡•–‡” ‘—–”›ͳǢŠƒ˜‹‰Š›’‡”–‡•‹‘ƒ†—•‹‰  ƒ–‹Š›’‡”–‡•‹˜‡‡†‹ ƒ–‹‘ ‡†‹ ƒ–‹‘‘Ǧƒ†Š‡”‡ ‡‹•–Š‡’”‹ƒ”›‘—– ‘‡‘ˆ–Š‡•–—†›Ǣƒ†‹•ƒ••‡••‡†„›‡ƒ•‘ˆ”‡ˆ‹ŽŽ†ƒ–ƒ  ‘ˆ’Šƒ”ƒ ›†ƒ–ƒ„ƒ•‡•ƒ†Ȁ‘”˜ƒŽ‹†ƒ–‡†•‡ŽˆǦ”‡’‘”–‡†“—‡•–‹‘ƒ‹”‡•  –—†‹‡•’‡”ˆ‘”‹‰—Ž–‹˜ƒ”‹ƒ„Ž‡•–ƒ–‹•–‹ ƒŽƒƒŽ›•‹•‡–Š‘†•–‘†‡–‡”‹‡–Š‡ƒ••‘ ‹ƒ–‹‘‘ˆˆƒ –‘”•  ™‹–Š‘Ǧƒ†Š‡”‡ ‡ 1StatisticsNetherlandsdefinesaWesterncountryasacountryinEurope(excludingTurkey),NorthAmerica,Oceania,  IndonesiaorJapan  Methodologicalqualityassessment Š‡‡–Š‘†‘Ž‘‰‹ ƒŽ“—ƒŽ‹–›ƒ••‡••‡–™ƒ•„ƒ•‡†‘–Š‡—ƒŽ‹–›••‡••‡–‘‘Žˆ‘” “—ƒ–‹–ƒ–‹˜‡ •–—†‹‡• †‡˜‡Ž‘’‡† „› –Š‡ ˆˆ‡ –‹˜‡ —„Ž‹  ‡ƒŽ–Š ”ƒ –‹ ‡ ”‘Œ‡ – ȏͳʹȐǤ ‹ ‡ ‡”–ƒ‹ †‘ƒ‹• ™‡”‡ ‘– ƒ’’Ž‹ ƒ„Ž‡ –‘ –Š‹• ”‡˜‹‡™ǡ ‹ Ž—†‹‰ „Ž‹†‹‰ ƒ† ‹–‡”˜‡–‹‘ ‹–‡‰”‹–›Ǧ”‡Žƒ–‡† “—‡•–‹‘•ǡ –Š‡ –‘‘Ž ™ƒ• ƒ†ƒ’–‡† –‘ –Š‡ ‡‡†• ‘ˆ –Š‡ ’”‡•‡–•–—†›ǤŠ‡ˆ‘ŽŽ‘™‹‰ˆ‹˜‡†‘ƒ‹•™‡”‡‡˜ƒŽ—ƒ–‡†ǣ•‡Ž‡ –‹‘„‹ƒ•ǡ ‘ˆ‘—†‡”•ǡ.

(116) A systematic literature review.  †ƒ–ƒ ‘ŽŽ‡ –‹‘‡–Š‘†•ǡ™‹–Š†”ƒ™ƒŽ•ƒ††”‘’Ǧ‘—–•ǡƒ†ƒƒŽ›•‹•Ǥ•—„• ‘”‡‘ˆ™‡ƒǡ ‘†‡”ƒ–‡‘”•–”‘‰™ƒ•‰‹˜‡ˆ‘”‡ƒ Š†‘ƒ‹Ǥ–—†‹‡•™‹–Š–™‘‘”‘”‡™‡ƒ• ‘”‡• ™‡”‡‡š Ž—†‡†ˆ”‘–Š‹•”‡˜‹‡™Ǥ  Dataextraction ƒ–ƒ™‡”‡‡š–”ƒ –‡†„›‘‡‹˜‡•–‹‰ƒ–‘”ȋȌ‹–‘ƒ†ƒ–ƒ‡š–”ƒ –‹‘ˆ‘”Ǥ

(117) ˆ‘”ƒ–‹‘ ”‡‰ƒ”†‹‰ˆ‹”•–ƒ—–Š‘”ǡ ‘—–”›ǡ”‡•‡ƒ” Šƒ‹ǡ•–—†›†‡•‹‰ǡ’ƒ”–‹ ‹’ƒ–•ǡ‡ƒ•—”‡‡– ƒ††‡ˆ‹‹–‹‘‘ˆ–Š‡‘—– ‘‡™ƒ•‡š–”ƒ –‡†Ǥ—„•‡“—‡–Ž›ǡˆƒ –‘”•–Šƒ–™‡”‡‡šƒ‹‡† ‘–Š‡ƒ••‘ ‹ƒ–‹‘™‹–Šȋ‘ǦȌƒ†Š‡”‡ ‡™‡”‡‡š–”ƒ –‡†ˆ”‘‡ƒ Š•–—†›Ǥ ƒ –‘”•™‡”‡ ƒ–‡‰‘”‹•‡†ƒ•ˆƒ –‘”•™‹–Š ‘•‹•–‡–‘”‹ ‘•‹•–‡–‡˜‹†‡ ‡Ǥ ƒ –‘”•™‹–Š ‘•‹•–‡– ‡˜‹†‡ ‡ Šƒ˜‡ ‘•‹•–‡– •‹‰‹ˆ‹ ƒ– ”‡Žƒ–‹‘•Š‹’• ™‹–Š ‡†‹ ƒ–‹‘ ‘Ǧƒ†Š‡”‡ ‡ ™Š‡‡˜‡”•–—†‹‡†Ǥ ƒ –‘”•™‹–Š‹ ‘•‹•–‡–‡˜‹†‡ ‡Šƒ˜‡„‘–Š•‹‰‹ˆ‹ ƒ–ƒ†‘Ǧ •‹‰‹ˆ‹ ƒ– ”‡Žƒ–‹‘•Š‹’• ™‹–Š ‡†‹ ƒ–‹‘ ‘Ǧƒ†Š‡”‡ ‡ ƒ†Ȁ‘” Šƒ˜‡ ‘ ‘ Ž—•‹˜‡ ”‡Žƒ–‹‘•Š‹’•ǡ•‹ ‡„‘–Š’‘•‹–‹˜‡ƒ†‡‰ƒ–‹˜‡ƒ••‘ ‹ƒ–‹‘•™‡”‡ˆ‘—†Ǥ ƒ –‘”•™‡”‡ ‡š Ž—†‡† ™Š‡ •–—†‹‡† „› Ž‡•• –Šƒ –Š”‡‡ •–—†‹‡• ‘” ™Š‡ ˆƒ –‘”• ™‡”‡ ‡†‹ ƒ–‹‘ Žƒ••Ǧǡ ‘—–”›Ǧǡ’‘Ž‹ ›Ǧ‘”Š‡ƒŽ–Š•›•–‡Ǧ•’‡ ‹ˆ‹ Ǥ  . Results  Selectionofthestudies Š‡ †ƒ–ƒ„ƒ•‡ •‡ƒ” Š ”‡•—Ž–‡† ‹ ͹ͻ͵͸ ƒ”–‹ Ž‡• ‘ˆ ™Š‹ Š ͳͺͻ͸ †—’Ž‹ ƒ–‡ ƒ”–‹ Ž‡• ™‡”‡ ‡š Ž—†‡†ȋFigure1ȌǤŠ‡–‹–Ž‡•ƒ†ƒ„•–”ƒ –•‘ˆ͸ͲͶͲƒ”–‹ Ž‡•™‡”‡”‡˜‹‡™‡†ƒ ‘”†‹‰ –‘–Š‡‹ Ž—•‹‘ ”‹–‡”‹ƒŽ‡ƒ˜‹‰Ͷͳ͵ƒ”–‹ Ž‡•ǤŠ‡ˆ—ŽŽǦ–‡š–’ƒ’‡”•‘ˆ–Š‡•‡ƒ”–‹ Ž‡•™‡”‡ ”‡–”‹‡˜‡†ƒ†”‡˜‹‡™‡†ˆ‘”‹ Ž—•‹‘™Š‹ Š”‡•—Ž–‡†‹ƒ–‘–ƒŽ‘ˆͷ͵•–—†‹‡•‡Ž‹‰‹„Ž‡ˆ‘” –Š‡‡–Š‘†‘Ž‘‰‹ ƒŽ“—ƒŽ‹–›ƒ••‡••‡–Ǥˆ–‡”‡š Ž—†‹‰‹‡•–—†‹‡•™‹–Šƒ™‡ƒ“—ƒŽ‹–› • ‘”‡ǡͶͶ•–—†‹‡•™‡”‡‹ Ž—†‡†‹–Š‡ˆ‹ƒŽ•ƒ’Ž‡Ǥ .  Figure1 Ž‘™†‹ƒ‰”ƒ‘ˆ–Š‡‹ Ž—•‹‘’”‘ ‡†—”‡. . 25.

(118) 26. Chapter 2.  Characteristicsoftheincludedstudies  ‘˜‡”˜‹‡™‘ˆ–Š‡•–—†› Šƒ”ƒ –‡”‹•–‹ •‹•’”‡•‡–‡†‹Table2Ǥ‘•–•–—†‹‡•ȋnα͵ͷȌ ™‡”‡ ‘†— –‡†‹–Š‡ȏͳ͵ǦͶ͹ȐǤ

(119) ʹʹ•–—†‹‡•”‡ˆ‹ŽŽ†ƒ–ƒˆ”‘’Šƒ”ƒ ›†ƒ–ƒ„ƒ•‡• ™‡”‡—•‡†–‘ ƒŽ —Žƒ–‡‘Ǧƒ†Š‡”‡ ‡ȏͳ͵Ǧͳ͸ǡʹͳǡʹͷǡ͵ʹǡ͵͵ǡ͵ͷǡ͵͹ǡ͵ͻǦͶͷǡͶͺǦͷʹȐǤŠ‡ ‡†‹ ƒ–‹‘‘••‡••‹‘ƒ–‹‘ȋnαͳͲȌ™ƒ•–Š‡‡ƒ•—”‡‘•–—•‡†ȏͳͶǡʹͳǡʹͷǡ͵͵ǡ͵ͻǡͶͲǡ Ͷʹǡ Ͷ͵ǡ Ͷͺǡ ͶͻȐǤ

(120)  ‰‡‡”ƒŽǡ –Š‹• ‡–Š‘† ‹• —•‡† –‘ ƒŽ —Žƒ–‡ –Š‡ –‹‡ ƒ ’ƒ–‹‡– Šƒ• ‡†‹ ƒ–‹‘ƒ˜ƒ‹Žƒ„Ž‡ƒ†‹•”‡’‘”–‡†ƒ•ƒ’‡” ‡–ƒ‰‡ǤŽŽ•–—†‹‡•†‡ˆ‹‡†ƒ• ‘”‡„‡Ž‘™ ͺͲΨ ƒ• ‘Ǧƒ†Š‡”‡ ‡Ǥ

(121) ʹͳ •–—†‹‡• •‡ŽˆǦ”‡’‘”– “—‡•–‹‘ƒ‹”‡• ™‡”‡ —•‡†–‘ƒ••‡•• ‘Ǧƒ†Š‡”‡ ‡ǡȏͳ͹ǦʹͲǡʹʹǡʹͶǡʹ͸Ǧ͵ͳǡ͵Ͷǡ͵͸ǡ͵ͺǡͶ͸ǡͶ͹ǡͷ͵Ǧͷ͸Ȑ‘ˆ™Š‹ Š–™‘—•‡†–™‘ †‹ˆˆ‡”‡–“—‡•–‹‘ƒ‹”‡•ȏ͵ͶǡͷͷȐǤŠ‡ˆ‘—”Ǧ‹–‡‘”‹•›‡†‹ ƒ–‹‘†Š‡”‡ ‡ ƒŽ‡ ™ƒ•–Š‡“—‡•–‹‘ƒ‹”‡‘•–—•‡†ȋnαͳʹȌȏͳͺǡͳͻǡʹʹǡʹͶǡʹ͹Ǧ͵Ͳǡ͵Ͷǡ͵͸ǡͷͷǡͷ͸ȐǤ‡•–—†› —•‡† „‘–Š ”‡ˆ‹ŽŽ †ƒ–ƒ ƒ† •‡ŽˆǦ”‡’‘”– †ƒ–ƒ ȏʹ͵ȐǤ

(122)  •–—†‹‡• —•‹‰ •‡ŽˆǦ”‡’‘”– “—‡•–‹‘ƒ‹”‡•–Š‡•ƒ’Ž‡•‹œ‡™ƒ•”‡Žƒ–‹˜‡Ž›•ƒŽŽȋ”ƒ‰‡͹ͳǦʹͷͻͷȌǤ

(123)  ‘–”ƒ•–ǡ–Š‡ •ƒ’Ž‡•‹œ‡‘ˆ•–—†‹‡•—•‹‰’Šƒ”ƒ ›”‡ˆ‹ŽŽ†ƒ–ƒ„ƒ•‡•™ƒ•— ŠŽƒ”‰‡”ȋ”ƒ‰‡Ͷ͸ͻǦͳ͸ͺ ͷʹʹȌǤŠ‡‡ƒƒ‰‡‘ˆ’ƒ”–‹ ‹’ƒ–•‹ƒŽ‘•–ƒŽŽ•–—†‹‡•™ƒ•εͷͲ›‡ƒ”•Ǥ                          .

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