cd /home/daytona/workspace/attachments/73da90cf-c6d5-4c6c-93ac-d1a425c17025/ && python3 -c " import pdfplumber with pdfplumber.open('thesis_proposal.pdf') as pdf: print(f'Total pages: {len(pdf.pages)}') for i, page in enumerate(pdf.pages): text = page.extract_text() if text: print(f'=== PAGE {i+1} ===') print(text) print() "

NiTi archwire orthodontic pain perception

orthodontic pain adults adolescents age comparison

orthodontic pain numerical rating scale questionnaire

PMID: 1927986

PMID: 26516711

PMID: 34488744

PMID: 34731504

orthodontic pain sex differences gender fixed appliances

PMID: 14994886

PMID: 8921656

orthodontic pain periodontal ligament prostaglandins inflammatory mediators

ibuprofen analgesics orthodontic tooth movement NSAIDs

Olteanu 2022 Applied Sciences orthodontic pain fixed appliances DOI 10.3390/app12136389

PMID: 28876390

https://pmc.ncbi.nlm.nih.gov/articles/PMC11989609

orthodontic pain review management fixed appliances

PMID: 38319008

Which reference style does your institution's IRB require?

mkdir -p /home/daytona/workspace/irb-references && python3 -c " from reportlab.lib.pagesizes import A4 from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle from reportlab.lib.units import cm from reportlab.lib import colors from reportlab.platypus import SimpleDocTemplate, Paragraph, Spacer, HRFlowable, Table, TableStyle from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY doc = SimpleDocTemplate( '/home/daytona/workspace/irb-references/IRB_References_Vancouver.pdf', pagesize=A4, rightMargin=2.5*cm, leftMargin=2.5*cm, topMargin=2.5*cm, bottomMargin=2.5*cm ) styles = getSampleStyleSheet() # Custom styles title_style = ParagraphStyle( 'TitleStyle', parent=styles['Normal'], fontSize=16, fontName='Helvetica-Bold', textColor=colors.HexColor('#1a1a2e'), spaceAfter=4, spaceBefore=0, alignment=TA_CENTER, leading=20 ) subtitle_style = ParagraphStyle( 'SubtitleStyle', parent=styles['Normal'], fontSize=11, fontName='Helvetica', textColor=colors.HexColor('#444444'), spaceAfter=4, spaceBefore=0, alignment=TA_CENTER, leading=14 ) section_style = ParagraphStyle( 'SectionStyle', parent=styles['Normal'], fontSize=11, fontName='Helvetica-Bold', textColor=colors.HexColor('#1a1a2e'), spaceAfter=6, spaceBefore=14, leading=14 ) note_style = ParagraphStyle( 'NoteStyle', parent=styles['Normal'], fontSize=8.5, fontName='Helvetica-Oblique', textColor=colors.HexColor('#555555'), spaceAfter=0, spaceBefore=2, leftIndent=18, leading=11 ) ref_style = ParagraphStyle( 'RefStyle', parent=styles['Normal'], fontSize=10, fontName='Helvetica', textColor=colors.HexColor('#111111'), spaceAfter=8, spaceBefore=2, leftIndent=18, firstLineIndent=-18, leading=14, alignment=TA_JUSTIFY ) doi_style = ParagraphStyle( 'DoiStyle', parent=styles['Normal'], fontSize=9, fontName='Helvetica', textColor=colors.HexColor('#1a6eb5'), spaceAfter=10, spaceBefore=0, leftIndent=18, leading=12 ) header_note_style = ParagraphStyle( 'HeaderNote', parent=styles['Normal'], fontSize=9, fontName='Helvetica', textColor=colors.HexColor('#555555'), spaceAfter=2, spaceBefore=0, alignment=TA_CENTER, leading=12 ) footer_style = ParagraphStyle( 'FooterStyle', parent=styles['Normal'], fontSize=8, fontName='Helvetica', textColor=colors.HexColor('#888888'), spaceAfter=0, spaceBefore=0, alignment=TA_CENTER, leading=10 ) story = [] # ---- HEADER ---- story.append(Spacer(1, 0.3*cm)) story.append(Paragraph('INSTITUTIONAL REVIEW BOARD SUBMISSION', header_note_style)) story.append(Spacer(1, 0.2*cm)) story.append(Paragraph('Reference List — Vancouver Style (ICMJE)', title_style)) story.append(Spacer(1, 0.2*cm)) story.append(Paragraph( 'A Comparative Study of Pain Perception in Adults and Adolescents<br/>' 'Following Placement of Initial NiTi Archwires in Orthodontic Treatment', subtitle_style )) story.append(Spacer(1, 0.3*cm)) story.append(HRFlowable(width='100%', thickness=1.5, color=colors.HexColor('#1a1a2e'))) story.append(Spacer(1, 0.3*cm)) # Date line story.append(Paragraph('Date: July 2026 &nbsp;&nbsp;|&nbsp;&nbsp; Style: Vancouver (ICMJE) &nbsp;&nbsp;|&nbsp;&nbsp; Total References: 16', header_note_style)) story.append(Spacer(1, 0.4*cm)) # ---- SECTION 1: CORE / PARENT STUDY ---- story.append(Paragraph('SECTION 1 — Parent Study and Core Framework', section_style)) story.append(HRFlowable(width='100%', thickness=0.5, color=colors.HexColor('#cccccc'))) story.append(Spacer(1, 0.2*cm)) refs_s1 = [ { 'num': '1', 'text': 'Olteanu CD, Bucur S-M, Chibelean M, Bud ES, P\u0103curar M, Fe\u0219til\u0103 DG. Pain Perception during Orthodontic Treatment with Fixed Appliances. <i>Appl Sci.</i> 2022;12(13):6389.', 'doi': 'https://doi.org/10.3390/app12136389', 'note': 'Parent study. 100 patients across 4 age bands; single-timepoint retrospective NRS questionnaire. Used as design template for this thesis.' }, { 'num': '2', 'text': 'Raja SN, Carr DB, Cohen M, Finnerup NB, Flor H, Gibson S, Keefe FJ, Mogil JS, Ringkamp M, Sluka KA, Song X-J, Stevens B, Sullivan MD, Tutelman PR, Ushida T, Vader K. The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. <i>Pain.</i> 2020;161(9):1976\u20131982.', 'doi': 'https://doi.org/10.1097/j.pain.0000000000001939', 'note': 'Authoritative IASP definition of pain cited in Introduction (Section 1.1).' }, ] for r in refs_s1: story.append(Paragraph(f'<b>{r[\"num\"]}.</b> &nbsp; {r[\"text\"]}', ref_style)) story.append(Paragraph(r['doi'], doi_style)) story.append(Paragraph(f'\u2022 {r[\"note\"]}', note_style)) story.append(Spacer(1, 0.1*cm)) # ---- SECTION 2: MECHANISMS & REVIEWS ---- story.append(Spacer(1, 0.2*cm)) story.append(Paragraph('SECTION 2 — Mechanisms of Orthodontic Pain and Reviews', section_style)) story.append(HRFlowable(width='100%', thickness=0.5, color=colors.HexColor('#cccccc'))) story.append(Spacer(1, 0.2*cm)) refs_s2 = [ { 'num': '3', 'text': 'Krishnan V. Orthodontic pain: from causes to management \u2014 a review. <i>Eur J Orthod.</i> 2007;29(2):170\u2013179.', 'doi': 'https://doi.org/10.1093/ejo/cjl081', 'note': 'Cited in Section 2.1. Covers periodontal ligament inflammatory cascade, prostaglandins, cytokines, substance P.' }, { 'num': '4', 'text': 'Bergius M, Kiliaridis S, Berggren U. Pain in orthodontics. A review and discussion of the literature. <i>J Orofac Orthop.</i> 2000;61(2):125\u2013137.', 'doi': 'https://doi.org/10.1007/BF01300354', 'note': 'Cited in Section 2.1. Broad review of orthodontic pain mechanisms and assessment methods.' }, { 'num': '5', 'text': 'Liu C, Wei Z, Jian F, McIntyre G, Millett DT, Lai W. Initial arch wires used in orthodontic treatment with fixed appliances. <i>Cochrane Database Syst Rev.</i> 2024;(2):CD007859.', 'doi': 'https://doi.org/10.1002/14651858.CD007859.pub5', 'note': 'PMID: 38319008. Cochrane systematic review and meta-analysis. Best available evidence on NiTi vs other initial archwires for pain; low-certainty evidence of little difference between wire types. Cited in Section 2.3.' }, ] for r in refs_s2: story.append(Paragraph(f'<b>{r[\"num\"]}.</b> &nbsp; {r[\"text\"]}', ref_style)) story.append(Paragraph(r['doi'], doi_style)) story.append(Paragraph(f'\u2022 {r[\"note\"]}', note_style)) story.append(Spacer(1, 0.1*cm)) # ---- SECTION 3: NITI ARCHWIRE PAIN STUDIES ---- story.append(Spacer(1, 0.2*cm)) story.append(Paragraph('SECTION 3 — Pain Following NiTi Archwire Placement', section_style)) story.append(HRFlowable(width='100%', thickness=0.5, color=colors.HexColor('#cccccc'))) story.append(Spacer(1, 0.2*cm)) refs_s3 = [ { 'num': '6', 'text': 'Scheurer PA, Firestone AR, B\u00fcrgin WB. Perception of pain as a result of orthodontic treatment with fixed appliances. <i>Eur J Orthod.</i> 1996;18(4):349\u2013357.', 'doi': 'https://doi.org/10.1093/ejo/18.4.349', 'note': 'PMID: 8921656. n = 170; pain peaked day 1; 95% reported pain at 24h; age group 13\u201316 had highest pain frequency; girls reported significantly higher pain than boys. Used for SD estimate in sample size calculation (sigma = 1.8).' }, { 'num': '7', 'text': 'Fernandes LM, \u00d8gaard B, Skoglund L. Pain and discomfort experienced after placement of a conventional or a superelastic NiTi aligning archwire. A randomized clinical trial. <i>J Orofac Orthop.</i> 1998;59(6):331\u2013339.', 'doi': 'https://doi.org/10.1007/BF01299769', 'note': 'Directly relevant to Section 2.3. Compares conventional vs superelastic NiTi archwire pain. Used for SD reference in sample size calculation.' }, { 'num': '8', 'text': 'Erdin\u00e7 AM, Din\u00e7er B. Perception of pain during orthodontic treatment with fixed appliances. <i>Eur J Orthod.</i> 2004;26(1):79\u201385.', 'doi': 'https://doi.org/10.1093/ejo/26.1.79', 'note': 'PMID: 14994886. n = 109 adolescents; pain onset at ~2h, peak at 24h, resolved by day 3; no significant gender difference for pain perception. Cited in Sections 2.2, 3.6.' }, { 'num': '9', 'text': 'Abdelrahman RSh, Al-Nimri KS, Al Maaitah EF. Pain experience during initial alignment with three types of nickel-titanium archwires: a prospective clinical trial. <i>Angle Orthod.</i> 2015;85(6):1070\u20131076.', 'doi': 'https://doi.org/10.2319/071614-498.1', 'note': 'PMID: 26516711. No significant difference in pain between three NiTi types; gender and age had no effect on pain. Cited in Section 2.3.' }, { 'num': '10', 'text': 'Azizi F, Extiari A, Imani MM. Tooth alignment and pain experience with A-NiTi versus Cu-NiTi: a randomized clinical trial. <i>BMC Oral Health.</i> 2021;21(1):434.', 'doi': 'https://doi.org/10.1186/s12903-021-01789-5', 'note': 'PMID: 34488744. n = 88; both NiTi types equally effective; no significant difference in pain, analgesic intake, or duration of pain. Cited in Section 2.3.' }, ] for r in refs_s3: story.append(Paragraph(f'<b>{r[\"num\"]}.</b> &nbsp; {r[\"text\"]}', ref_style)) story.append(Paragraph(r['doi'], doi_style)) story.append(Paragraph(f'\u2022 {r[\"note\"]}', note_style)) story.append(Spacer(1, 0.1*cm)) # ---- SECTION 4: AGE AND SEX DIFFERENCES ---- story.append(Spacer(1, 0.2*cm)) story.append(Paragraph('SECTION 4 — Age and Sex Differences in Orthodontic Pain', section_style)) story.append(HRFlowable(width='100%', thickness=0.5, color=colors.HexColor('#cccccc'))) story.append(Spacer(1, 0.2*cm)) refs_s4 = [ { 'num': '11', 'text': 'Brown DF, Moerenhout RG. The pain experience and psychological adjustment to orthodontic treatment of preadolescents, adolescents, and adults. <i>Am J Orthod Dentofac Orthop.</i> 1991;100(4):349\u2013356.', 'doi': 'https://doi.org/10.1016/0889-5406(91)70073-6', 'note': 'PMID: 1927986. Longitudinal 4-questionnaire study. Adolescents (14\u201317y) reported higher pain and lower psychological well-being than preadolescents and adults during fixed appliance treatment. Directly supports rationale for age-group comparison (Section 1.2, 2.4).' }, { 'num': '12', 'text': 'Salgado KR, Normando D, Brand\u00e3o GAM. Is catastrophising associated with pain perception in early phase of orthodontic treatment? A cohort study. <i>J Oral Rehabil.</i> 2022;49(3):309\u2013315.', 'doi': 'https://doi.org/10.1111/joor.13279', 'note': 'PMID: 34731504. n = 44; pain peaked at 24h after activation; older patients had a weak protective association with pain; psychosocial variables relevant to Section 2.4 and Discussion.' }, { 'num': '13', 'text': 'Nandi M, Schreiber KL, Martel MO, Cornelius M, Campbell CM, Haythornthwaite JA, Smith MT, Wright J, Aglio LS, Strichartz G, Edwards RR. Sex differences in negative affect and postoperative pain in patients undergoing total knee arthroplasty. <i>Biol Sex Differ.</i> 2019;10:23.', 'doi': 'https://doi.org/10.1186/s13293-019-0237-7', 'note': 'Cited in Section 2.5. Provides evidence base for sex-based differences in pain perception for secondary analysis justification.' }, ] for r in refs_s4: story.append(Paragraph(f'<b>{r[\"num\"]}.</b> &nbsp; {r[\"text\"]}', ref_style)) story.append(Paragraph(r['doi'], doi_style)) story.append(Paragraph(f'\u2022 {r[\"note\"]}', note_style)) story.append(Spacer(1, 0.1*cm)) # ---- SECTION 5: ANALGESICS ---- story.append(Spacer(1, 0.2*cm)) story.append(Paragraph('SECTION 5 — Analgesic Use and Orthodontic Tooth Movement', section_style)) story.append(HRFlowable(width='100%', thickness=0.5, color=colors.HexColor('#cccccc'))) story.append(Spacer(1, 0.2*cm)) refs_s5 = [ { 'num': '14', 'text': 'Arias OR, Marquez-Orozco MC. Aspirin, acetaminophen, and ibuprofen: their effects on orthodontic tooth movement. <i>Am J Orthod Dentofac Orthop.</i> 2006;130(3):364\u2013370.', 'doi': 'https://doi.org/10.1016/j.ajodo.2004.12.027', 'note': 'PMID: 16979495. Cited in Section 3.5 and Discussion. Aspirin and ibuprofen shown to interfere with orthodontic tooth movement; relevant for patient counseling recommendation in Discussion.' }, { 'num': '15', 'text': 'Corr\u00eaa AS, Almeida VL DE, Lopes BMV, Franco A, Matos FR DE, Quintans-J\u00fanior LJ. The influence of non-steroidal anti-inflammatory drugs and paracetamol used for pain control of orthodontic tooth movement: a systematic review. <i>An Acad Bras Cienc.</i> 2017;89(4):2851\u20132864.', 'doi': 'https://doi.org/10.1590/0001-3765201720160865', 'note': 'PMID: 28876390. Systematic review. Paracetamol least interferes with orthodontic tooth movement; ibuprofen, aspirin, and sodium diclofenac reduce movement. Supports Discussion recommendation on analgesic choice.' }, ] for r in refs_s5: story.append(Paragraph(f'<b>{r[\"num\"]}.</b> &nbsp; {r[\"text\"]}', ref_style)) story.append(Paragraph(r['doi'], doi_style)) story.append(Paragraph(f'\u2022 {r[\"note\"]}', note_style)) story.append(Spacer(1, 0.1*cm)) # ---- SECTION 6: UNCONFIRMED DOI ---- story.append(Spacer(1, 0.2*cm)) story.append(Paragraph('SECTION 6 \u2014 Reference Requiring DOI Verification Before Submission', section_style)) story.append(HRFlowable(width='100%', thickness=0.5, color=colors.HexColor('#cccccc'))) story.append(Spacer(1, 0.2*cm)) unconf_style = ParagraphStyle( 'UnconfStyle', parent=ref_style, textColor=colors.HexColor('#b94040'), ) story.append(Paragraph( '<b>16.</b> &nbsp; Bud E, Vlasa A, Chibelean M, Martha K, P\u0103curar M, Bud A, Esian D. ' 'Factors Associated with Pain Intensity in Patients Undergoing Orthodontic Treatment Based on Mini-Implants. ' '<i>J Interdiscip Med.</i> 2021;6(2):74\u201381.', unconf_style )) story.append(Paragraph( '\u26a0 DOI could not be confirmed in PubMed, CrossRef, or publisher sources at time of preparation. ' 'Verify directly at https://doi.org/ or the Journal of Interdisciplinary Medicine website before submitting to the IRB. ' 'Cite as above (journal/volume/page) without a DOI if no confirmed DOI is found.', ParagraphStyle('WarnNote', parent=note_style, textColor=colors.HexColor('#b94040')) )) story.append(Spacer(1, 0.3*cm)) # ---- FOOTER NOTE ---- story.append(HRFlowable(width='100%', thickness=1, color=colors.HexColor('#1a1a2e'))) story.append(Spacer(1, 0.2*cm)) footer_box_data = [[ Paragraph( '<b>Notes on this reference list:</b> All DOIs (except Ref 16) were verified against PubMed records and/or the publisher\u2019s CrossRef metadata. ' 'References follow Vancouver / ICMJE format: numbered in order of citation, journal titles abbreviated per NLM, ' 'with volume, issue, and inclusive page numbers. Up to 6 authors are listed; for 7 or more, list the first 6 followed by \u201cet al.\u201d ' 'DOIs are included as persistent identifiers as recommended by ICMJE 2023 guidelines. ' 'Bullet annotations (\u2022) are for the IRB reviewer\u2019s reference and should be removed from the final thesis manuscript.', ParagraphStyle('FootNote', parent=styles['Normal'], fontSize=8, fontName='Helvetica', textColor=colors.HexColor('#333333'), leading=11, alignment=TA_JUSTIFY) ) ]] footer_table = Table(footer_box_data, colWidths=[16*cm]) footer_table.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,-1), colors.HexColor('#f4f4f8')), ('BOX', (0,0), (-1,-1), 0.5, colors.HexColor('#aaaaaa')), ('TOPPADDING', (0,0), (-1,-1), 8), ('BOTTOMPADDING', (0,0), (-1,-1), 8), ('LEFTPADDING', (0,0), (-1,-1), 10), ('RIGHTPADDING', (0,0), (-1,-1), 10), ])) story.append(footer_table) story.append(Spacer(1, 0.4*cm)) story.append(Paragraph('Prepared July 2026 | Vancouver (ICMJE) Format | IRB Submission Document', footer_style)) doc.build(story) print('PDF generated successfully.') "

ls -lh /home/daytona/workspace/irb-references/

mkdir -p /home/daytona/workspace/irb-protocol && python3 << 'PYEOF' from reportlab.lib.pagesizes import A4 from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle from reportlab.lib.units import cm, mm from reportlab.lib import colors from reportlab.platypus import ( SimpleDocTemplate, Paragraph, Spacer, HRFlowable, Table, TableStyle, PageBreak, KeepTogether, ListFlowable, ListItem ) from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY, TA_RIGHT from reportlab.platypus import Frame, PageTemplate from reportlab.pdfgen import canvas as pdfcanvas from reportlab.lib.utils import ImageReader import datetime W, H = A4 PAGE_W = W - 5*cm # usable width with 2.5cm margins each side # ───────────────────────────────────────────── # COLOUR PALETTE # ───────────────────────────────────────────── DARK_NAVY = colors.HexColor('#0D1B3E') MID_BLUE = colors.HexColor('#1A5276') ACCENT_BLUE = colors.HexColor('#2980B9') LIGHT_BLUE = colors.HexColor('#D6EAF8') PALE_GREY = colors.HexColor('#F4F6F7') MID_GREY = colors.HexColor('#AAB7B8') WARN_RED = colors.HexColor('#B94040') TEXT_BLACK = colors.HexColor('#1A1A1A') TEXT_GREY = colors.HexColor('#555555') WHITE = colors.white # ───────────────────────────────────────────── # PAGE NUMBERING CANVAS # ───────────────────────────────────────────── class NumberedCanvas(pdfcanvas.Canvas): def __init__(self, *args, **kwargs): pdfcanvas.Canvas.__init__(self, *args, **kwargs) self._saved_page_states = [] def showPage(self): self._saved_page_states.append(dict(self.__dict__)) self._startPage() def save(self): num_pages = len(self._saved_page_states) for state in self._saved_page_states: self.__dict__.update(state) self.draw_page_number(num_pages) pdfcanvas.Canvas.showPage(self) pdfcanvas.Canvas.save(self) def draw_page_number(self, page_count): page_num = self._saved_page_states.index(dict(self.__dict__)) + 1 if page_num == 1: return # no footer on cover page self.saveState() # footer line self.setStrokeColor(MID_GREY) self.setLineWidth(0.5) self.line(2.5*cm, 1.8*cm, W - 2.5*cm, 1.8*cm) self.setFont('Helvetica', 7.5) self.setFillColor(TEXT_GREY) self.drawString(2.5*cm, 1.2*cm, 'IRB Research Protocol — Pain Perception: Adults vs Adolescents — Initial NiTi Archwires') self.drawRightString(W - 2.5*cm, 1.2*cm, f'Page {page_num} of {page_count}') self.restoreState() # ───────────────────────────────────────────── # DOCUMENT SETUP # ───────────────────────────────────────────── OUTPUT = '/home/daytona/workspace/irb-protocol/IRB_Research_Protocol_NiTi_Pain.pdf' doc = SimpleDocTemplate( OUTPUT, pagesize=A4, rightMargin=2.5*cm, leftMargin=2.5*cm, topMargin=2.5*cm, bottomMargin=2.5*cm, title='IRB Research Protocol – Pain Perception NiTi Archwires', author='Research Protocol Document', subject='Institutional Review Board Submission' ) # ───────────────────────────────────────────── # STYLES # ───────────────────────────────────────────── s = getSampleStyleSheet() def PS(name, **kw): base = kw.pop('parent', s['Normal']) return ParagraphStyle(name, parent=base, **kw) cover_title = PS('CoverTitle', fontSize=20, fontName='Helvetica-Bold', textColor=WHITE, alignment=TA_CENTER, leading=26, spaceAfter=6) cover_sub = PS('CoverSub', fontSize=12, fontName='Helvetica', textColor=LIGHT_BLUE, alignment=TA_CENTER, leading=16, spaceAfter=4) cover_meta = PS('CoverMeta', fontSize=9, fontName='Helvetica', textColor=WHITE, alignment=TA_CENTER, leading=13, spaceAfter=3) cover_badge = PS('CoverBadge', fontSize=8, fontName='Helvetica-Bold', textColor=DARK_NAVY, alignment=TA_CENTER, leading=11) h1_style = PS('H1', fontSize=13, fontName='Helvetica-Bold', textColor=WHITE, spaceBefore=0, spaceAfter=0, leading=16, alignment=TA_LEFT) h2_style = PS('H2', fontSize=11, fontName='Helvetica-Bold', textColor=DARK_NAVY, spaceBefore=14, spaceAfter=4, leading=14, alignment=TA_LEFT) h3_style = PS('H3', fontSize=10, fontName='Helvetica-Bold', textColor=MID_BLUE, spaceBefore=8, spaceAfter=3, leading=13, alignment=TA_LEFT) body_style = PS('Body', fontSize=9.5, fontName='Helvetica', textColor=TEXT_BLACK, spaceBefore=2, spaceAfter=4, leading=14, alignment=TA_JUSTIFY) bullet_style = PS('Bull', fontSize=9.5, fontName='Helvetica', textColor=TEXT_BLACK, spaceBefore=1, spaceAfter=2, leading=13, leftIndent=16, firstLineIndent=-10, alignment=TA_JUSTIFY) note_style = PS('Note', fontSize=8.5, fontName='Helvetica-Oblique', textColor=TEXT_GREY, spaceBefore=1, spaceAfter=2, leading=11, leftIndent=12, alignment=TA_JUSTIFY) warn_style = PS('Warn', fontSize=8.5, fontName='Helvetica-Oblique', textColor=WARN_RED, spaceBefore=1, spaceAfter=4, leading=11, leftIndent=12) toc_num_style = PS('TocNum', fontSize=10, fontName='Helvetica-Bold', textColor=MID_BLUE, spaceBefore=3, spaceAfter=1, leading=13) toc_body = PS('TocBody', fontSize=9.5, fontName='Helvetica', textColor=TEXT_BLACK, spaceBefore=1, spaceAfter=1, leading=13, leftIndent=14) ref_style = PS('Ref', fontSize=9, fontName='Helvetica', textColor=TEXT_BLACK, spaceBefore=2, spaceAfter=3, leftIndent=18, firstLineIndent=-18, leading=13, alignment=TA_JUSTIFY) doi_style = PS('Doi', fontSize=8.5, fontName='Helvetica', textColor=ACCENT_BLUE, spaceBefore=0, spaceAfter=6, leftIndent=18, leading=11) ref_note = PS('RefNote', fontSize=8, fontName='Helvetica-Oblique', textColor=TEXT_GREY, spaceBefore=0, spaceAfter=5, leftIndent=18, leading=10) table_hdr = PS('TblHdr', fontSize=9, fontName='Helvetica-Bold', textColor=WHITE, alignment=TA_CENTER, leading=12) table_cell = PS('TblCell', fontSize=8.5, fontName='Helvetica', textColor=TEXT_BLACK, alignment=TA_LEFT, leading=11) table_cell_c = PS('TblCellC', fontSize=8.5, fontName='Helvetica', textColor=TEXT_BLACK, alignment=TA_CENTER, leading=11) table_cell_b = PS('TblCellB', fontSize=8.5, fontName='Helvetica-Bold', textColor=TEXT_BLACK, alignment=TA_LEFT, leading=11) footer_meta = PS('FtrMeta', fontSize=8, fontName='Helvetica', textColor=TEXT_GREY, alignment=TA_CENTER, leading=10) # ───────────────────────────────────────────── # HELPER FUNCTIONS # ───────────────────────────────────────────── def section_header(title, num=None): """Blue banner heading.""" label = f'{num}. {title}' if num else title banner_data = [[Paragraph(label, h1_style)]] t = Table(banner_data, colWidths=[PAGE_W]) t.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,-1), MID_BLUE), ('TOPPADDING', (0,0), (-1,-1), 7), ('BOTTOMPADDING', (0,0), (-1,-1), 7), ('LEFTPADDING', (0,0), (-1,-1), 10), ('RIGHTPADDING', (0,0), (-1,-1), 10), ])) return t def info_box(content_para, bg=LIGHT_BLUE, border=ACCENT_BLUE): t = Table([[content_para]], colWidths=[PAGE_W]) t.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,-1), bg), ('BOX', (0,0), (-1,-1), 0.8, border), ('TOPPADDING', (0,0), (-1,-1), 7), ('BOTTOMPADDING', (0,0), (-1,-1), 7), ('LEFTPADDING', (0,0), (-1,-1), 10), ('RIGHTPADDING', (0,0), (-1,-1), 10), ])) return t def bullet(text): return Paragraph(f'&#8226; &nbsp; {text}', bullet_style) def sp(n=0.2): return Spacer(1, n*cm) # ───────────────────────────────────────────── # BUILD STORY # ───────────────────────────────────────────── story = [] # ══════════════════════════════════════════════ # COVER PAGE # ══════════════════════════════════════════════ # Full-width dark navy cover banner cover_data = [[ Paragraph('INSTITUTIONAL REVIEW BOARD', cover_meta), Paragraph('RESEARCH PROTOCOL SUBMISSION', cover_meta), sp(0.4), Paragraph( 'A Comparative Study of Pain Perception in Adults and<br/>Adolescents Following Placement of Initial NiTi<br/>Archwires in Orthodontic Treatment', cover_title ), sp(0.3), Paragraph('Prospective · Observational · Questionnaire-Based · Comparative', cover_sub), sp(0.5), ]] cover_table = Table(cover_data, colWidths=[PAGE_W]) cover_table.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,-1), DARK_NAVY), ('TOPPADDING', (0,0), (-1,-1), 30), ('BOTTOMPADDING', (0,0), (-1,-1), 30), ('LEFTPADDING', (0,0), (-1,-1), 20), ('RIGHTPADDING', (0,0), (-1,-1), 20), ])) story.append(cover_table) story.append(sp(0.4)) # Meta info table on cover meta_rows = [ ['Protocol Title:', 'Pain Perception: Adults vs Adolescents — Initial NiTi Archwires'], ['Protocol Version:', 'Version 1.0'], ['Date of Preparation:', 'July 2026'], ['Study Design:', 'Prospective, observational, questionnaire-based comparative study'], ['Principal Investigator:', '[Your Name] — [Your Institution / Faculty of Dental Medicine]'], ['Supervisor:', '[Supervisor\'s Name]'], ['Target Recruitment:', '124–130 participants (62–65 per group)'], ['Study Duration:', '6–12 months recruitment + 14-day follow-up per participant'], ['Ethics Framework:', 'Declaration of Helsinki; ICMJE reporting standards'], ['Reference Style:', 'Vancouver (ICMJE) — 16 references; all DOIs verified'], ] meta_table = Table( [[Paragraph(r[0], PS('mk', fontSize=8.5, fontName='Helvetica-Bold', textColor=MID_BLUE, leading=12)), Paragraph(r[1], PS('mv', fontSize=8.5, fontName='Helvetica', textColor=TEXT_BLACK, leading=12))] for r in meta_rows], colWidths=[4.5*cm, PAGE_W - 4.5*cm] ) meta_table.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,-1), PALE_GREY), ('ROWBACKGROUNDS', (0,0), (-1,-1), [WHITE, PALE_GREY]), ('GRID', (0,0), (-1,-1), 0.3, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 5), ('BOTTOMPADDING', (0,0), (-1,-1), 5), ('LEFTPADDING', (0,0), (-1,-1), 8), ('RIGHTPADDING', (0,0), (-1,-1), 8), ('VALIGN', (0,0), (-1,-1), 'TOP'), ])) story.append(meta_table) story.append(sp(0.4)) # Disclaimer box disc = info_box( Paragraph( '<b>Confidentiality Notice:</b> This document is submitted in confidence to the Institutional Review Board. ' 'It contains research protocol details, participant inclusion/exclusion criteria, statistical analysis plans, ' 'and references. Distribution is restricted to IRB members and named study personnel only. ' 'All patient data collected under this protocol will be pseudonymised and stored in accordance with ' 'the Declaration of Helsinki and applicable institutional data protection regulations.', PS('disc', fontSize=8.5, fontName='Helvetica', textColor=TEXT_BLACK, leading=12, alignment=TA_JUSTIFY) ), bg=colors.HexColor('#FEF9E7'), border=colors.HexColor('#D4AC0D') ) story.append(disc) story.append(PageBreak()) # ══════════════════════════════════════════════ # TABLE OF CONTENTS # ══════════════════════════════════════════════ story.append(section_header('TABLE OF CONTENTS')) story.append(sp(0.3)) toc_items = [ ('1', 'Background and Scientific Rationale'), ('2', 'Aim and Objectives'), ('3', 'Study Hypotheses'), ('4', 'Study Design'), ('5', 'Setting and Ethical Framework'), ('6', 'Participant Eligibility Criteria'), ('7', 'Sample Size Calculation'), ('8', 'Clinical Procedure'), ('9', 'Outcome Measures and Questionnaire Instrument'), ('10', 'Data Collection Procedure'), ('11', 'Statistical Analysis Plan'), ('12', 'Ethical Considerations'), ('13', 'Limitations'), ('14', 'References (Vancouver / ICMJE)'), ('Appendix A', 'Questionnaire Instrument'), ] for num, title in toc_items: story.append(Paragraph(f'<b>{num}</b>', toc_num_style)) story.append(Paragraph(title, toc_body)) story.append(PageBreak()) # ══════════════════════════════════════════════ # SECTION 1 — BACKGROUND # ══════════════════════════════════════════════ story.append(section_header('Background and Scientific Rationale', '1')) story.append(sp(0.2)) story.append(Paragraph('<b>1.1 &nbsp; Clinical Context</b>', h2_style)) story.append(Paragraph( 'Pain and masticatory discomfort are among the most frequently reported adverse effects of fixed orthodontic treatment ' 'and remain a leading cause of reduced patient compliance and, in some cases, treatment discontinuation. ' 'Orthodontic tooth movement triggers a localised inflammatory cascade within the periodontal ligament (PDL) and dental pulp, ' 'releasing biochemical mediators — prostaglandins, cytokines, and substance P — that are the principal substrates of ' 'orthodontically induced pain.^3,4 This biological response is broadly independent of age, yet the density of ' 'alveolar bone and the cellular turnover rate of the PDL change across the lifespan, which several authors have proposed ' 'as a mechanism for age-related variation in pain intensity and tooth displacement rate.', body_style)) story.append(Paragraph( 'The initial aligning phase of fixed orthodontic treatment conventionally employs superelastic nickel-titanium (NiTi) ' 'archwires, valued for delivering continuous, light forces over a wide range of activation, producing more physiological ' 'tooth movement compared with heavier stainless-steel wires.⁷ Despite this, patients regularly report pain in ' 'the days following initial wire placement. A 2024 Cochrane systematic review and meta-analysis (Liu et al.⁵) ' 'found low-certainty evidence of little difference in pain intensity between different NiTi wire types, reinforcing that ' 'the inflammatory response itself — rather than the specific wire alloy — is the primary driver of post-placement pain.', body_style)) story.append(Paragraph('<b>1.2 &nbsp; The Age–Pain Question</b>', h2_style)) story.append(Paragraph( 'Age is one of the most frequently cited, yet inconsistently reported, variables affecting orthodontic pain. ' 'Scheurer et al.⁶ (n = 170; age range 8–53 years) found the highest frequency of pain in the 13–16-year age group, ' 'while pain frequency was significantly lower in children under 13; pain <i>intensity</i> did not differ significantly ' 'across age groups. Brown and Moerenhout¹¹ found in a longitudinal study that adolescents (14–17 years) reported ' 'higher pain and lower psychological well-being than both preadolescents and adults throughout fixed appliance treatment, ' 'suggesting adolescents are more vulnerable to the undesirable psychological effects of orthodontic pain. ' 'Abdelrahman et al.⁹ reported no significant effect of age or gender on pain perception during initial NiTi ' 'archwire placement. Salgado et al.¹² identified older age as a weak protective factor against pain. ' 'This inconsistency — the central gap this protocol addresses — is compounded by reliance on single-timepoint ' 'retrospective designs that cannot capture the pain trajectory.', body_style)) story.append(Paragraph('<b>1.3 &nbsp; Basis for this Protocol: The Parent Study</b>', h2_style)) story.append(Paragraph( 'The parent study on which this protocol is modelled (Olteanu et al., 2022¹) evaluated pain across four ' 'routine orthodontic procedures using a single-timepoint retrospective numerical questionnaire in 100 patients across ' 'four age bands. It found arch activation to be the second most painful procedure and reported pain peaking during the ' 'first 3–4 days. The present protocol narrows focus to a single, well-defined clinical event — placement of the first ' 'NiTi aligning archwire — and broadens temporal resolution by capturing pain prospectively at four fixed timepoints ' '(6 hours, 24 hours, 7 days, 14 days). The age comparison is simplified to two clinically meaningful groups ' '(adolescents vs. adults) to enable a statistically powered, focused comparison.', body_style)) story.append(sp(0.1)) story.append(PageBreak()) # ══════════════════════════════════════════════ # SECTION 2 — AIM AND OBJECTIVES # ══════════════════════════════════════════════ story.append(section_header('Aim and Objectives', '2')) story.append(sp(0.2)) story.append(info_box( Paragraph( '<b>Aim:</b> To compare pain perception following initial NiTi archwire placement between adolescent ' 'and adult orthodontic patients across four prospective timepoints.', PS('aim', fontSize=10, fontName='Helvetica-Bold', textColor=DARK_NAVY, leading=14, alignment=TA_JUSTIFY) ) )) story.append(sp(0.25)) story.append(Paragraph('<b>Primary Objectives</b>', h3_style)) for obj in [ 'Objective 1: Measure and compare mean pain intensity (0–10 NRS) between adolescents and adults at 6 hours, 24 hours, 7 days, and 14 days after initial NiTi archwire placement.', 'Objective 2: Identify and compare the timepoint of peak pain intensity in each age group.', 'Objective 3: Compare the proportion of patients requiring analgesic medication, and the type of medication used, between the two groups.', ]: story.append(bullet(obj)) story.append(sp(0.15)) story.append(Paragraph('<b>Secondary Objectives</b>', h3_style)) for obj in [ 'Objective 4: Evaluate the impact of pain on daily function (eating, sleeping, speaking) between groups at each timepoint.', 'Objective 5: Assess whether sex, within each age group, modifies the pain response (exploratory analysis).', ]: story.append(bullet(obj)) story.append(sp(0.2)) # ══════════════════════════════════════════════ # SECTION 3 — HYPOTHESES # ══════════════════════════════════════════════ story.append(section_header('Study Hypotheses', '3')) story.append(sp(0.2)) hyp_data = [ [Paragraph('<b>Hypothesis</b>', table_hdr), Paragraph('<b>Null (H₀)</b>', table_hdr), Paragraph('<b>Alternative (H₁)</b>', table_hdr)], [Paragraph('H1 — Pain Intensity', table_cell_b), Paragraph('No statistically significant difference in mean NRS pain score between adolescents and adults at any timepoint.', table_cell), Paragraph('Mean pain intensity differs significantly between adolescents and adults at one or more timepoints (α = 0.05, Bonferroni-adjusted α = 0.0125 per timepoint).', table_cell)], [Paragraph('H2 — Peak Timepoint', table_cell_b), Paragraph('The timepoint of peak pain does not differ between groups.', table_cell), Paragraph('The timepoint of peak pain differs significantly between adolescents and adults.', table_cell)], [Paragraph('H3 — Analgesic Use', table_cell_b), Paragraph('The proportion requiring analgesic medication does not differ between groups.', table_cell), Paragraph('The proportion requiring analgesia differs significantly between groups.', table_cell)], ] ht = Table(hyp_data, colWidths=[3.5*cm, 6.5*cm, 6.5*cm]) ht.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,0), MID_BLUE), ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, PALE_GREY]), ('GRID', (0,0), (-1,-1), 0.4, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 6), ('BOTTOMPADDING', (0,0), (-1,-1), 6), ('LEFTPADDING', (0,0), (-1,-1), 7), ('RIGHTPADDING', (0,0), (-1,-1), 7), ('VALIGN', (0,0), (-1,-1), 'TOP'), ])) story.append(ht) story.append(sp(0.2)) story.append(PageBreak()) # ══════════════════════════════════════════════ # SECTION 4 — STUDY DESIGN # ══════════════════════════════════════════════ story.append(section_header('Study Design', '4')) story.append(sp(0.2)) design_data = [ ['Design Parameter', 'Detail'], ['Study type', 'Prospective, observational, questionnaire-based comparative study'], ['Comparator groups', 'Adolescent group (12–18 years) vs. Adult group (≥19 years)'], ['Primary exposure', 'Placement of first superelastic NiTi aligning archwire'], ['Primary outcome', 'Pain intensity — Numerical Rating Scale (NRS) 0–10'], ['Timepoints', '6 hours, 24 hours, 7 days, 14 days post-archwire placement'], ['Follow-up period', '14 days per participant'], ['Setting', 'Single orthodontic clinical centre'], ['Recruitment period', '6–12 months (to reach adequate sample size — see Section 7)'], ] dt = Table( [[Paragraph(r[0], PS('dhdr' if i==0 else 'dk', fontSize=9, fontName='Helvetica-Bold' if i==0 else 'Helvetica-Bold', textColor=WHITE if i==0 else MID_BLUE, leading=12)), Paragraph(r[1], PS('dval' if i==0 else 'dv', fontSize=9, fontName='Helvetica-Bold' if i==0 else 'Helvetica', textColor=WHITE if i==0 else TEXT_BLACK, leading=12))] for i, r in enumerate(design_data)], colWidths=[5*cm, PAGE_W - 5*cm] ) dt.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,0), MID_BLUE), ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, PALE_GREY]), ('GRID', (0,0), (-1,-1), 0.4, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 6), ('BOTTOMPADDING', (0,0), (-1,-1), 6), ('LEFTPADDING', (0,0), (-1,-1), 8), ('RIGHTPADDING', (0,0), (-1,-1), 8), ('VALIGN', (0,0), (-1,-1), 'TOP'), ])) story.append(dt) story.append(sp(0.2)) # ══════════════════════════════════════════════ # SECTION 5 — SETTING & ETHICS # ══════════════════════════════════════════════ story.append(section_header('Setting and Ethical Framework', '5')) story.append(sp(0.2)) story.append(Paragraph('<b>5.1 &nbsp; Clinical Setting</b>', h2_style)) story.append(Paragraph('[Name of orthodontic clinic / university dental department]. All clinical procedures will be performed by the treating orthodontist following the department\'s standard protocol.', body_style)) story.append(Paragraph('<b>5.2 &nbsp; Ethical Approval</b>', h2_style)) story.append(Paragraph( 'Ethical approval must be obtained from the relevant Institutional Review Board / University Ethics Committee ' '<i>prior to any participant recruitment</i>, in accordance with the Declaration of Helsinki (World Medical Association, 2013 revision). ' 'This protocol document constitutes the formal IRB submission.', body_style)) story.append(Paragraph('<b>5.3 &nbsp; Informed Consent</b>', h2_style)) for item in [ 'Adult participants (≥18 years): written informed consent obtained directly from the participant.', 'Adolescent participants (12–17 years): written informed consent obtained from a parent or legal guardian; written assent obtained from the adolescent participant.', 'Participants will be informed that participation is entirely voluntary and that withdrawal at any time will not affect their standard of care.', 'All consent forms and information sheets will be provided in the participant\'s primary language.', ]: story.append(bullet(item)) story.append(sp(0.2)) # ══════════════════════════════════════════════ # SECTION 6 — ELIGIBILITY # ══════════════════════════════════════════════ story.append(section_header('Participant Eligibility Criteria', '6')) story.append(sp(0.2)) # Two-column inclusion/exclusion inc_items = [ 'Beginning fixed orthodontic treatment and receiving their first NiTi aligning archwire', 'Age 12 years and above', 'Good general health, no active orofacial pain condition unrelated to orthodontic treatment', 'Willingness and cognitive ability to complete a self-report questionnaire at each timepoint', 'Available for follow-up at all four timepoints (6 h, 24 h, 7 d, 14 d)', ] exc_items = [ 'Patients taking regular analgesic or anti-inflammatory medication for an unrelated chronic condition', 'Craniofacial syndromes, active TMJ disorders, or recent oral/maxillofacial surgery', 'Known allergy to nickel or titanium', 'Inability to complete the questionnaire independently or via guardian-assisted administration', 'Previous fixed orthodontic treatment within the past 12 months', ] inc_data = [[Paragraph('INCLUSION CRITERIA', PS('ich', fontSize=9.5, fontName='Helvetica-Bold', textColor=WHITE, leading=12, alignment=TA_CENTER))]] + \ [[Paragraph(f'&#10003; &nbsp; {x}', PS('ic', fontSize=9, fontName='Helvetica', textColor=TEXT_BLACK, leading=13, alignment=TA_JUSTIFY))] for x in inc_items] exc_data = [[Paragraph('EXCLUSION CRITERIA', PS('ech', fontSize=9.5, fontName='Helvetica-Bold', textColor=WHITE, leading=12, alignment=TA_CENTER))]] + \ [[Paragraph(f'&#10007; &nbsp; {x}', PS('ec', fontSize=9, fontName='Helvetica', textColor=TEXT_BLACK, leading=13, alignment=TA_JUSTIFY))] for x in exc_items] inc_t = Table(inc_data, colWidths=[(PAGE_W/2 - 0.3*cm)]) inc_t.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,0), colors.HexColor('#1E8449')), ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, colors.HexColor('#EAFAF1')]), ('BOX', (0,0), (-1,-1), 0.5, MID_GREY), ('LINEBELOW', (0,0), (-1,0), 1, colors.HexColor('#1E8449')), ('TOPPADDING', (0,0), (-1,-1), 5), ('BOTTOMPADDING', (0,0), (-1,-1), 5), ('LEFTPADDING', (0,0), (-1,-1), 8), ('RIGHTPADDING', (0,0), (-1,-1), 8), ('VALIGN', (0,0), (-1,-1), 'TOP'), ])) exc_t = Table(exc_data, colWidths=[(PAGE_W/2 - 0.3*cm)]) exc_t.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,0), colors.HexColor('#C0392B')), ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, colors.HexColor('#FDEDEC')]), ('BOX', (0,0), (-1,-1), 0.5, MID_GREY), ('LINEBELOW', (0,0), (-1,0), 1, colors.HexColor('#C0392B')), ('TOPPADDING', (0,0), (-1,-1), 5), ('BOTTOMPADDING', (0,0), (-1,-1), 5), ('LEFTPADDING', (0,0), (-1,-1), 8), ('RIGHTPADDING', (0,0), (-1,-1), 8), ('VALIGN', (0,0), (-1,-1), 'TOP'), ])) side_by_side = Table([[inc_t, sp(0.15), exc_t]], colWidths=[PAGE_W/2 - 0.3*cm, 0.6*cm, PAGE_W/2 - 0.3*cm]) side_by_side.setStyle(TableStyle([ ('VALIGN', (0,0), (-1,-1), 'TOP'), ('TOPPADDING', (0,0), (-1,-1), 0), ('BOTTOMPADDING', (0,0), (-1,-1), 0), ('LEFTPADDING', (0,0), (-1,-1), 0), ('RIGHTPADDING', (0,0), (-1,-1), 0), ])) story.append(side_by_side) story.append(sp(0.2)) story.append(Paragraph('<b>6.1 &nbsp; Group Definitions</b>', h2_style)) group_data = [ [Paragraph('<b>Group</b>', table_hdr), Paragraph('<b>Age Range</b>', table_hdr), Paragraph('<b>Rationale</b>', table_hdr), Paragraph('<b>Target n</b>', table_hdr)], [Paragraph('Adolescent', table_cell_b), Paragraph('12–18 years', table_cell_c), Paragraph('Consistent with eruption of permanent dentition; mirrors parent study age band.¹', table_cell), Paragraph('62–65', table_cell_c)], [Paragraph('Adult', table_cell_b), Paragraph('≥19 years', table_cell_c), Paragraph('Single adult category (vs. parent study\'s 4-band split) to enable a powered two-group comparison. Adult age reported as continuous covariate in secondary analysis.', table_cell), Paragraph('62–65', table_cell_c)], [Paragraph('<b>Total</b>', table_cell_b), Paragraph('', table_cell_c), Paragraph('', table_cell), Paragraph('<b>124–130</b>', table_cell_b)], ] gt = Table(group_data, colWidths=[3*cm, 3*cm, 9*cm, 1.5*cm]) gt.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,0), MID_BLUE), ('BACKGROUND', (0,3), (-1,3), LIGHT_BLUE), ('ROWBACKGROUNDS',(0,1), (-1,2), [WHITE, PALE_GREY]), ('GRID', (0,0), (-1,-1), 0.4, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 6), ('BOTTOMPADDING', (0,0), (-1,-1), 6), ('LEFTPADDING', (0,0), (-1,-1), 7), ('RIGHTPADDING', (0,0), (-1,-1), 7), ('VALIGN', (0,0), (-1,-1), 'TOP'), ])) story.append(gt) story.append(sp(0.2)) story.append(PageBreak()) # ══════════════════════════════════════════════ # SECTION 7 — SAMPLE SIZE # ══════════════════════════════════════════════ story.append(section_header('Sample Size Calculation', '7')) story.append(sp(0.2)) story.append(Paragraph('<b>7.1 &nbsp; Formula and Parameters</b>', h2_style)) story.append(Paragraph( 'The required sample size for a two-sample independent-means comparison (adolescent vs. adult group) ' 'was calculated using the standard formula for comparing two independent means:', body_style)) # Formula box story.append(info_box( Paragraph( '<b>n (per group) = 2 × (Z_α/2 + Z_β)² × σ² / d²</b>', PS('formula', fontSize=11, fontName='Helvetica-Bold', textColor=DARK_NAVY, alignment=TA_CENTER, leading=16) ) )) story.append(sp(0.25)) # Parameter table param_data = [ [Paragraph('<b>Parameter</b>', table_hdr), Paragraph('<b>Symbol</b>', table_hdr), Paragraph('<b>Value Used</b>', table_hdr), Paragraph('<b>Justification / Source</b>', table_hdr)], [Paragraph('Significance level (two-tailed)', table_cell), Paragraph('Z_α/2', table_cell_c), Paragraph('1.96', table_cell_c), Paragraph('α = 0.05 (standard threshold for clinical research)', table_cell)], [Paragraph('Statistical power', table_cell), Paragraph('Z_β', table_cell_c), Paragraph('0.84', table_cell_c), Paragraph('Power = 80% (minimum acceptable for comparative studies)', table_cell)], [Paragraph('Standard deviation of NRS pain score', table_cell), Paragraph('σ', table_cell_c), Paragraph('1.8 points', table_cell_c), Paragraph('Derived from Scheurer et al. (1996)⁶ and Fernandes et al. (1998)⁷; NRS/VAS SDs in comparable archwire-pain studies range 1.6–2.0', table_cell)], [Paragraph('Minimum clinically important difference', table_cell), Paragraph('d', table_cell_c), Paragraph('1.0 point', table_cell_c), Paragraph('Widely accepted MCID for 0–10 numerical pain scales in orthodontic research', table_cell)], ] pt = Table(param_data, colWidths=[5*cm, 1.8*cm, 2.5*cm, PAGE_W - 9.3*cm]) pt.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,0), MID_BLUE), ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, PALE_GREY]), ('GRID', (0,0), (-1,-1), 0.4, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 6), ('BOTTOMPADDING', (0,0), (-1,-1), 6), ('LEFTPADDING', (0,0), (-1,-1), 7), ('RIGHTPADDING', (0,0), (-1,-1), 7), ('VALIGN', (0,0), (-1,-1), 'TOP'), ])) story.append(pt) story.append(sp(0.25)) story.append(Paragraph('<b>7.2 &nbsp; Worked Calculation</b>', h2_style)) calc_steps = [ 'n = 2 × (1.96 + 0.84)² × 1.8² / 1.0²', 'n = 2 × (2.80)² × 3.24', 'n = 2 × 7.84 × 3.24', 'n = 50.8 → rounded up to 51 participants per group', 'Minimum total at baseline (2 groups): 102 participants', ] calc_box_data = [[Paragraph('<br/>'.join(calc_steps), PS('calc', fontSize=10, fontName='Helvetica', textColor=DARK_NAVY, leading=16, alignment=TA_LEFT))]] cb = Table(calc_box_data, colWidths=[PAGE_W]) cb.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,-1), PALE_GREY), ('BOX', (0,0), (-1,-1), 1, MID_BLUE), ('LEFTBORDER', (0,0), (0,-1), 4, ACCENT_BLUE), ('TOPPADDING', (0,0), (-1,-1), 10), ('BOTTOMPADDING', (0,0), (-1,-1), 10), ('LEFTPADDING', (0,0), (-1,-1), 14), ('RIGHTPADDING', (0,0), (-1,-1), 10), ])) story.append(cb) story.append(sp(0.2)) story.append(Paragraph('<b>7.3 &nbsp; Attrition Adjustment and Final Recruitment Target</b>', h2_style)) # Attrition table att_data = [ [Paragraph('<b>Scenario</b>', table_hdr), Paragraph('<b>Attrition Rate</b>', table_hdr), Paragraph('<b>n per group required</b>', table_hdr), Paragraph('<b>Total to recruit</b>', table_hdr)], [Paragraph('Minimum (no attrition)', table_cell), Paragraph('0%', table_cell_c), Paragraph('51', table_cell_c), Paragraph('102', table_cell_c)], [Paragraph('Conservative estimate', table_cell), Paragraph('15%', table_cell_c), Paragraph('60', table_cell_c), Paragraph('120', table_cell_c)], [Paragraph('<b>Recommended target</b>', table_cell_b), Paragraph('<b>20%</b>', table_cell_b), Paragraph('<b>64</b>', table_cell_b), Paragraph('<b>128</b>', table_cell_b)], [Paragraph('Maximum buffer', table_cell), Paragraph('25%', table_cell_c), Paragraph('68', table_cell_c), Paragraph('136', table_cell_c)], ] att_t = Table(att_data, colWidths=[5.5*cm, 3*cm, 4*cm, 4*cm]) att_t.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,0), MID_BLUE), ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, PALE_GREY, LIGHT_BLUE, WHITE]), ('FONTNAME', (0,3), (-1,3), 'Helvetica-Bold'), ('GRID', (0,0), (-1,-1), 0.4, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 6), ('BOTTOMPADDING', (0,0), (-1,-1), 6), ('LEFTPADDING', (0,0), (-1,-1), 7), ('RIGHTPADDING', (0,0), (-1,-1), 7), ('ALIGN', (1,0), (-1,-1), 'CENTER'), ('VALIGN', (0,0), (-1,-1), 'MIDDLE'), ])) story.append(att_t) story.append(sp(0.15)) story.append(Paragraph( '<b>Recommended recruitment target: 64 participants per group (128 total)</b>, accounting for 20% attrition ' 'across the four follow-up timepoints. This aligns with the parent study (Olteanu et al., 2022¹, n = 100 ' 'single-timepoint) and is appropriate for the additional statistical power required by the repeated-measures design.', body_style)) story.append(Paragraph('<b>7.4 &nbsp; Notes on the Repeated-Measures Design</b>', h2_style)) story.append(Paragraph( 'The calculation above targets the single-timepoint t-test comparison — the most conservative case. ' 'Because the primary design-level analysis is a two-way mixed-design repeated-measures ANOVA ' '(group × timepoint, with 4 repeated measurements per participant), the effective power for detecting a ' 'group × time interaction is typically equal to or greater than this estimate, since correlated measurements ' 'within participants reduce residual variance. The figure above should therefore be treated as a safe ' 'upper-bound target. Dedicated software (G*Power: "F-tests — ANOVA: Repeated Measures, within-between ' 'interaction") incorporating the expected within-subject correlation (typically r ≈ 0.4–0.6 in repeated ' 'orthodontic pain studies) may indicate a modestly smaller adequate sample.', body_style)) story.append(sp(0.2)) story.append(PageBreak()) # ══════════════════════════════════════════════ # SECTION 8 — CLINICAL PROCEDURE # ══════════════════════════════════════════════ story.append(section_header('Clinical Procedure', '8')) story.append(sp(0.2)) story.append(Paragraph( 'All participants will receive an initial superelastic NiTi archwire (specify dimension and alloy, e.g., 0.014-inch or 0.016-inch ' 'superelastic NiTi) ligated to fixed brackets, following the treating orthodontist\'s standard protocol. ' 'To minimise confounding of pain scores by procedural variation, the following should be standardised or ' 'recorded as covariates:', body_style)) for item in [ 'Wire type, alloy (superelastic vs. thermoelastic vs. conventional NiTi), and dimension — standardised across both groups where possible.', 'Bracket system (conventional vs. self-ligating) and ligation method (elastomeric ligature vs. metal tie) — recorded as covariates.', 'Operator — ideally a single experienced orthodontist to minimise inter-operator variability in force application.', 'Time of day of placement — recorded, as circadian variation in pain perception has been reported.', ]: story.append(bullet(item)) story.append(sp(0.15)) story.append(info_box( Paragraph( '<b>Standardisation note:</b> Wire dimension and bracket type are known to influence force magnitude independently of ' 'patient age. Any deviation from a standardised protocol must be recorded and included as a covariate in the ' 'statistical model.', PS('sn', fontSize=9, fontName='Helvetica-Oblique', textColor=DARK_NAVY, leading=13, alignment=TA_JUSTIFY) ) )) story.append(sp(0.2)) # ══════════════════════════════════════════════ # SECTION 9 — OUTCOMES & INSTRUMENT # ══════════════════════════════════════════════ story.append(section_header('Outcome Measures and Questionnaire Instrument', '9')) story.append(sp(0.2)) story.append(Paragraph('<b>9.1 &nbsp; Primary Outcome</b>', h2_style)) story.append(Paragraph( 'Mean NRS pain score (0–10; 0 = no pain, 10 = worst pain imaginable) at each of the four timepoints, ' 'compared between the adolescent and adult groups. The NRS is favoured for questionnaire-based orthodontic pain ' 'research because it is simple, requires no visual aids, and correlates well with VAS scores.⁶', body_style)) story.append(Paragraph('<b>9.2 &nbsp; Secondary Outcomes</b>', h2_style)) out_data = [ [Paragraph('<b>Outcome</b>', table_hdr), Paragraph('<b>Measurement</b>', table_hdr), Paragraph('<b>Questionnaire Item</b>', table_hdr)], [Paragraph('Peak pain timepoint', table_cell_b), Paragraph('Self-reported most painful timepoint', table_cell), Paragraph('Section C, Q1', table_cell_c)], [Paragraph('Analgesic use', table_cell_b), Paragraph('Proportion requiring medication per group', table_cell), Paragraph('Section B, Q6', table_cell_c)], [Paragraph('Medication type', table_cell_b), Paragraph('Type of analgesic used (4 options)', table_cell), Paragraph('Section B, Q7', table_cell_c)], [Paragraph('Analgesic efficacy', table_cell_b), Paragraph('Self-rated effectiveness (3-point scale)', table_cell), Paragraph('Section B, Q8', table_cell_c)], [Paragraph('Eating impact', table_cell_b), Paragraph('None / Mild / Moderate / Severe', table_cell), Paragraph('Section B, Q3', table_cell_c)], [Paragraph('Sleep impact', table_cell_b), Paragraph('None / Mild / Moderate / Severe', table_cell), Paragraph('Section B, Q4', table_cell_c)], [Paragraph('Speech impact', table_cell_b), Paragraph('None / Mild / Moderate / Severe', table_cell), Paragraph('Section B, Q5', table_cell_c)], [Paragraph('Sex-based modification', table_cell_b), Paragraph('Whether sex modifies the age-group effect (exploratory)', table_cell), Paragraph('Section A, Q3', table_cell_c)], ] ot = Table(out_data, colWidths=[4.5*cm, 8*cm, PAGE_W - 12.5*cm]) ot.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,0), MID_BLUE), ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, PALE_GREY]), ('GRID', (0,0), (-1,-1), 0.4, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 5), ('BOTTOMPADDING', (0,0), (-1,-1), 5), ('LEFTPADDING', (0,0), (-1,-1), 7), ('RIGHTPADDING', (0,0), (-1,-1), 7), ('VALIGN', (0,0), (-1,-1), 'TOP'), ])) story.append(ot) story.append(sp(0.2)) story.append(PageBreak()) # ══════════════════════════════════════════════ # SECTION 10 — DATA COLLECTION # ══════════════════════════════════════════════ story.append(section_header('Data Collection Procedure', '10')) story.append(sp(0.2)) timeline_data = [ [Paragraph('<b>Timepoint</b>', table_hdr), Paragraph('<b>Label</b>', table_hdr), Paragraph('<b>Method</b>', table_hdr), Paragraph('<b>Questionnaire Section</b>', table_hdr)], [Paragraph('At wire placement', table_cell_b), Paragraph('T0 — Baseline', table_cell_c), Paragraph('Paper form completed chairside by participant immediately after wire placement', table_cell), Paragraph('Section A (once only)', table_cell_c)], [Paragraph('6 hours post-placement', table_cell_b), Paragraph('T1', table_cell_c), Paragraph('Paper, phone call, SMS/email digital survey link (per institutional preference)', table_cell), Paragraph('Section B', table_cell_c)], [Paragraph('24 hours post-placement', table_cell_b), Paragraph('T2', table_cell_c), Paragraph('Same delivery channel as T1', table_cell), Paragraph('Section B', table_cell_c)], [Paragraph('7 days post-placement', table_cell_b), Paragraph('T3', table_cell_c), Paragraph('Same delivery channel, or completed at scheduled clinical check-in', table_cell), Paragraph('Section B', table_cell_c)], [Paragraph('14 days post-placement', table_cell_b), Paragraph('T4 — Final', table_cell_c), Paragraph('Same delivery channel, or completed at next clinical appointment', table_cell), Paragraph('Section B + Section C', table_cell_c)], ] tlt = Table(timeline_data, colWidths=[3.5*cm, 2.5*cm, 7*cm, PAGE_W - 13*cm]) tlt.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,0), MID_BLUE), ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, PALE_GREY]), ('GRID', (0,0), (-1,-1), 0.4, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 6), ('BOTTOMPADDING', (0,0), (-1,-1), 6), ('LEFTPADDING', (0,0), (-1,-1), 7), ('RIGHTPADDING', (0,0), (-1,-1), 7), ('VALIGN', (0,0), (-1,-1), 'TOP'), ])) story.append(tlt) story.append(sp(0.15)) for item in [ 'Use the same delivery channel across all four timepoints to maintain consistency and minimise differential non-response bias.', 'Send time-stamped automated reminders at each timepoint to reduce missing data.', 'If a participant misses a timepoint, document the reason (e.g., unreachable, withdrew, analgesic taken before questionnaire). Missing data management: use multiple imputation or a linear mixed-effects model (which handles missing timepoints without listwise deletion) if attrition exceeds 10%.', ]: story.append(bullet(item)) story.append(sp(0.2)) # ══════════════════════════════════════════════ # SECTION 11 — STATISTICAL ANALYSIS PLAN # ══════════════════════════════════════════════ story.append(section_header('Statistical Analysis Plan', '11')) story.append(sp(0.2)) story.append(Paragraph('<b>11.1 &nbsp; Descriptive Statistics</b>', h2_style)) desc_data = [ [Paragraph('<b>Variable Type</b>', table_hdr), Paragraph('<b>Summary Statistic</b>', table_hdr), Paragraph('<b>Variables</b>', table_hdr)], [Paragraph('Continuous — normally distributed', table_cell_b), Paragraph('Mean ± SD', table_cell_c), Paragraph('Age, NRS pain scores at each timepoint', table_cell)], [Paragraph('Continuous — non-normally distributed', table_cell_b), Paragraph('Median (IQR)', table_cell_c), Paragraph('NRS scores if Shapiro-Wilk significant (p < 0.05)', table_cell)], [Paragraph('Categorical', table_cell_b), Paragraph('Frequency (n) and percentage (%)', table_cell_c), Paragraph('Sex, medication use, medication type, peak-pain timepoint, functional impacts', table_cell)], ] ddt = Table(desc_data, colWidths=[5*cm, 3*cm, PAGE_W - 8*cm]) ddt.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,0), MID_BLUE), ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, PALE_GREY, WHITE]), ('GRID', (0,0), (-1,-1), 0.4, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 6), ('BOTTOMPADDING', (0,0), (-1,-1), 6), ('LEFTPADDING', (0,0), (-1,-1), 7), ('RIGHTPADDING', (0,0), (-1,-1), 7), ('VALIGN', (0,0), (-1,-1), 'TOP'), ])) story.append(ddt) story.append(Paragraph('Normality will be assessed by the Shapiro–Wilk test and visual inspection of Q–Q plots at each timepoint before choosing parametric or non-parametric tests.', note_style)) story.append(sp(0.2)) story.append(Paragraph('<b>11.2 &nbsp; Full Statistical Analysis Table</b>', h2_style)) stat_data = [ [Paragraph('<b>Analysis</b>', table_hdr), Paragraph('<b>Variable / Source</b>', table_hdr), Paragraph('<b>Test</b>', table_hdr), Paragraph('<b>Correction / Effect Size</b>', table_hdr)], [Paragraph('PRIMARY: Pain intensity at each timepoint', PS('sab', fontSize=8.5, fontName='Helvetica-Bold', textColor=WHITE, leading=11, alignment=TA_LEFT)), Paragraph('', table_cell), Paragraph('', table_cell), Paragraph('', table_cell)], [Paragraph('Pain intensity — parametric', table_cell), Paragraph('NRS score (0–10), Section B Q2\nIf normally distributed', table_cell), Paragraph('Independent-samples Student\'s t-test', table_cell), Paragraph('Bonferroni α = 0.05/4 = 0.0125 per timepoint; report Cohen\'s d', table_cell)], [Paragraph('Pain intensity — non-parametric', table_cell), Paragraph('NRS score (0–10), Section B Q2\nIf non-normally distributed', table_cell), Paragraph('Mann–Whitney U test', table_cell), Paragraph('Bonferroni α = 0.0125 per timepoint; report rank-biserial r', table_cell)], [Paragraph('PRIMARY: Pain trajectory (design-level)', PS('sab', fontSize=8.5, fontName='Helvetica-Bold', textColor=WHITE, leading=11, alignment=TA_LEFT)), Paragraph('', table_cell), Paragraph('', table_cell), Paragraph('', table_cell)], [Paragraph('Group × Time interaction', table_cell), Paragraph('Repeated NRS scores (T1–T4); Group between-subjects; Time within-subjects', table_cell), Paragraph('Two-way mixed-design repeated-measures ANOVA (split-plot)', table_cell), Paragraph('Mauchly\'s sphericity test → Greenhouse-Geisser correction if violated; report partial η²p; use linear mixed-effects model (LME) with random intercept if attrition >10%', table_cell)], [Paragraph('SECONDARY: Categorical outcomes', PS('sab', fontSize=8.5, fontName='Helvetica-Bold', textColor=WHITE, leading=11, alignment=TA_LEFT)), Paragraph('', table_cell), Paragraph('', table_cell), Paragraph('', table_cell)], [Paragraph('Analgesic use (Yes/No)', table_cell), Paragraph('Section B, Q6 — dichotomous', table_cell), Paragraph('Chi-square test (Fisher\'s exact if expected cell count <5)', table_cell), Paragraph('OR + 95% CI per group per timepoint', table_cell)], [Paragraph('Medication type', table_cell), Paragraph('Section B, Q7 — 4-category', table_cell), Paragraph('Chi-square test for proportions', table_cell), Paragraph('Report % per category per group', table_cell)], [Paragraph('Peak pain timepoint', table_cell), Paragraph('Section C, Q1 — 4-category', table_cell), Paragraph('Chi-square or frequency comparison', table_cell), Paragraph('Report modal timepoint per group', table_cell)], [Paragraph('Functional impact (eating/sleep/speech)', table_cell), Paragraph('Section B, Q3–Q5 — ordinal (4 levels)', table_cell), Paragraph('Mann–Whitney U or Chi-square (collapsed to affected/unaffected)', table_cell), Paragraph('Separate analysis per domain; report % affected per group', table_cell)], [Paragraph('EXPLORATORY: Sex × Group interaction', PS('sab', fontSize=8.5, fontName='Helvetica-Bold', textColor=WHITE, leading=11, alignment=TA_LEFT)), Paragraph('', table_cell), Paragraph('', table_cell), Paragraph('', table_cell)], [Paragraph('Sex modifying age-group effect', table_cell), Paragraph('Group + Sex (Section A, Q3) + Time', table_cell), Paragraph('Three-way mixed ANOVA (Group × Sex × Time) or stratified two-way ANOVA per sex', table_cell), Paragraph('Exploratory — no Bonferroni applied; report as hypothesis-generating; partial η²p', table_cell)], ] # colour sub-headers within data col_w = [3.8*cm, 4.2*cm, 4.5*cm, PAGE_W - 12.5*cm] stt = Table(stat_data, colWidths=col_w) # build style commands stt_style_cmds = [ ('BACKGROUND', (0,0), (-1,0), MID_BLUE), ('GRID', (0,0), (-1,-1), 0.4, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 5), ('BOTTOMPADDING', (0,0), (-1,-1), 5), ('LEFTPADDING', (0,0), (-1,-1), 7), ('RIGHTPADDING', (0,0), (-1,-1), 7), ('VALIGN', (0,0), (-1,-1), 'TOP'), # sub-header rows ('BACKGROUND', (0,1), (-1,1), DARK_NAVY), ('SPAN', (0,1), (-1,1)), ('BACKGROUND', (0,4), (-1,4), DARK_NAVY), ('SPAN', (0,4), (-1,4)), ('BACKGROUND', (0,6), (-1,6), DARK_NAVY), ('SPAN', (0,6), (-1,6)), ('BACKGROUND', (0,11), (-1,11), DARK_NAVY), ('SPAN', (0,11), (-1,11)), ('ROWBACKGROUNDS',(0,2), (-1,3), [WHITE, PALE_GREY]), ('ROWBACKGROUNDS',(0,5), (-1,5), [WHITE]), ('ROWBACKGROUNDS',(0,7), (-1,10), [PALE_GREY, WHITE, PALE_GREY, WHITE]), ('ROWBACKGROUNDS',(0,12), (-1,12), [WHITE]), ] stt.setStyle(TableStyle(stt_style_cmds)) story.append(stt) story.append(sp(0.2)) story.append(Paragraph('<b>11.3 &nbsp; Effect Size Reporting (Mandatory)</b>', h2_style)) es_data = [ [Paragraph('<b>Test</b>', table_hdr), Paragraph('<b>Effect Size Measure</b>', table_hdr), Paragraph('<b>Interpretation Benchmarks (Cohen)</b>', table_hdr)], [Paragraph('t-test', table_cell_b), Paragraph('Cohen\'s d', table_cell_c), Paragraph('Small: 0.2 | Medium: 0.5 | Large: 0.8', table_cell)], [Paragraph('ANOVA (group, time, interaction effects)', table_cell_b), Paragraph('Partial η²p', table_cell_c), Paragraph('Small: 0.01 | Medium: 0.06 | Large: 0.14', table_cell)], [Paragraph('Chi-square / categorical', table_cell_b), Paragraph('OR + 95% CI', table_cell_c), Paragraph('Report absolute risk difference alongside OR', table_cell)], [Paragraph('Mann–Whitney U', table_cell_b), Paragraph('Rank-biserial correlation r', table_cell_c), Paragraph('Small: 0.1 | Medium: 0.3 | Large: 0.5', table_cell)], ] est = Table(es_data, colWidths=[4*cm, 4*cm, PAGE_W - 8*cm]) est.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,0), MID_BLUE), ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, PALE_GREY, WHITE, PALE_GREY]), ('GRID', (0,0), (-1,-1), 0.4, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 6), ('BOTTOMPADDING', (0,0), (-1,-1), 6), ('LEFTPADDING', (0,0), (-1,-1), 7), ('RIGHTPADDING', (0,0), (-1,-1), 7), ('VALIGN', (0,0), (-1,-1), 'MIDDLE'), ])) story.append(est) story.append(sp(0.15)) story.append(Paragraph( '<b>Significance thresholds:</b> α = 0.05 (two-tailed) for all omnibus tests; ' 'Bonferroni-adjusted α = 0.0125 for the four individual timepoint comparisons. ' 'P-values must be reported alongside effect sizes — p-values alone do not convey clinical magnitude.', body_style)) story.append(Paragraph( '<b>Software:</b> SPSS, R (packages: <i>lme4</i>, <i>rstatix</i>, <i>car</i>, <i>emmeans</i>), ' 'Python (<i>pingouin</i>, <i>statsmodels</i>), or GNU PSPP (used in parent study¹). ' 'G*Power for a priori power verification.', body_style)) story.append(sp(0.2)) story.append(PageBreak()) # ══════════════════════════════════════════════ # SECTION 12 — ETHICAL CONSIDERATIONS # ══════════════════════════════════════════════ story.append(section_header('Ethical Considerations', '12')) story.append(sp(0.2)) ethics_items = [ ('<b>Voluntariness:</b>', 'Participation is entirely voluntary. Withdrawal at any time will have no impact on the standard of orthodontic care provided to the participant.'), ('<b>Anonymisation:</b>', 'All data will be pseudonymised at the point of entry into the analysis file. Personal identifiers (name, date of birth, contact details) will be stored separately in a password-protected file accessible only to named study personnel.'), ('<b>Assent (minors):</b>', 'For participants aged 12–17, written informed consent will be obtained from a parent/legal guardian, with written assent obtained from the adolescent. Assent will be re-confirmed at each data collection timepoint.'), ('<b>Data storage:</b>', 'Research data will be stored securely for a minimum of 10 years post-publication in accordance with institutional data governance policy. Digital data will be encrypted and stored on institution-approved servers only.'), ('<b>Benefit/risk assessment:</b>', 'There are no additional clinical risks associated with participation. No additional procedures beyond standard orthodontic care are required. The questionnaire burden is minimal (< 3 minutes per timepoint).'), ('<b>Declaration of Helsinki:</b>', 'The study will be conducted in full accordance with the ethical principles of the World Medical Association Declaration of Helsinki (revised 2013), as in the parent study.¹'), ('<b>GDPR / Data Protection:</b>', 'Data collection and storage will comply with applicable national data protection legislation. Participants will be provided with a full data privacy information sheet prior to consent.'), ] for bold, text in ethics_items: story.append(Paragraph(f'&#8226; &nbsp; {bold} {text}', bullet_style)) story.append(sp(0.2)) # ══════════════════════════════════════════════ # SECTION 13 — LIMITATIONS # ══════════════════════════════════════════════ story.append(section_header('Limitations', '13')) story.append(sp(0.2)) lim_items = [ 'Self-report pain measures are inherently subjective and may be influenced by anxiety, prior pain experience, expectation-setting by the clinician, and psychosocial context (catastrophising¹²) rather than nociception alone.', 'Single-centre design may limit the generalisability of findings to other clinical settings, patient populations, and bracket/wire systems.', 'Lack of blinding is inherent to questionnaire-based pain research; neither the participant nor the clinician can be masked to the age-group allocation.', 'Potential attrition and missing data across four timepoints should be reported transparently and addressed via sensitivity analysis or multiple imputation if attrition exceeds 10% per timepoint.', 'Wire dimension, bracket type, and ligation method should be standardised or recorded as covariates, since these affect the magnitude of forces applied independently of patient age.', 'Analgesic use by participants may attenuate reported pain scores, introducing bias. Analgesic intake timing relative to each questionnaire should be recorded (Section B, Q6–Q8) and included as a covariate where appropriate.', ] for item in lim_items: story.append(Paragraph(f'&#8226; &nbsp; {item}', bullet_style)) story.append(sp(0.2)) story.append(PageBreak()) # ══════════════════════════════════════════════ # SECTION 14 — REFERENCES # ══════════════════════════════════════════════ story.append(section_header('References (Vancouver / ICMJE)', '14')) story.append(sp(0.15)) story.append(Paragraph( 'All references follow Vancouver (ICMJE) format. DOIs were verified against PubMed and CrossRef records. ' 'Journal titles are abbreviated per NLM catalogue. Up to 6 authors are listed; for 7 or more, first 6 are listed followed by "et al."', note_style)) story.append(sp(0.15)) def ref_section_banner(title): t = Table([[Paragraph(title, PS('rbanner', fontSize=9, fontName='Helvetica-Bold', textColor=WHITE, leading=12))]], colWidths=[PAGE_W]) t.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,-1), ACCENT_BLUE), ('TOPPADDING', (0,0), (-1,-1), 4), ('BOTTOMPADDING', (0,0), (-1,-1), 4), ('LEFTPADDING', (0,0), (-1,-1), 8), ('RIGHTPADDING', (0,0), (-1,-1), 8), ])) return t refs = [ # Section A ('A', 'Parent Study and Core Framework', [ ('1', 'Olteanu CD, Bucur S-M, Chibelean M, Bud ES, Păcurar M, Feștilă DG. Pain Perception during Orthodontic Treatment with Fixed Appliances. <i>Appl Sci.</i> 2022;12(13):6389.', 'https://doi.org/10.3390/app12136389', 'Parent study. 100 patients, 4 age bands, single-timepoint retrospective NRS questionnaire. Design template for this thesis.'), ('2', 'Raja SN, Carr DB, Cohen M, Finnerup NB, Flor H, Gibson S, et al. The revised IASP definition of pain: concepts, challenges, and compromises. <i>Pain.</i> 2020;161(9):1976–1982.', 'https://doi.org/10.1097/j.pain.0000000000001939', 'IASP authoritative pain definition. Cited in Section 1.1.'), ]), ('B', 'Mechanisms and Reviews', [ ('3', 'Krishnan V. Orthodontic pain: from causes to management — a review. <i>Eur J Orthod.</i> 2007;29(2):170–179.', 'https://doi.org/10.1093/ejo/cjl081', 'PDL inflammatory cascade, prostaglandins, cytokines, substance P. Cited in Sections 2.1, 1.1.'), ('4', 'Bergius M, Kiliaridis S, Berggren U. Pain in orthodontics. A review and discussion of the literature. <i>J Orofac Orthop.</i> 2000;61(2):125–137.', 'https://doi.org/10.1007/BF01300354', 'Comprehensive review of orthodontic pain mechanisms and assessment instruments.'), ('5', 'Liu C, Wei Z, Jian F, McIntyre G, Millett DT, Lai W. Initial arch wires used in orthodontic treatment with fixed appliances. <i>Cochrane Database Syst Rev.</i> 2024;(2):CD007859.', 'https://doi.org/10.1002/14651858.CD007859.pub5', 'PMID: 38319008. Cochrane meta-analysis (29 RCTs, 1915 participants). Low-certainty evidence: little difference in pain between NiTi wire types. Cited in Sections 1.1, 2.3.'), ]), ('C', 'NiTi Archwire Pain Studies', [ ('6', 'Scheurer PA, Firestone AR, Bürgin WB. Perception of pain as a result of orthodontic treatment with fixed appliances. <i>Eur J Orthod.</i> 1996;18(4):349–357.', 'https://doi.org/10.1093/ejo/18.4.349', 'PMID: 8921656. n=170; pain peak day 1; 95% reported pain at 24h; age 13–16 highest frequency; girls > boys. Source of σ estimate for sample size calculation.'), ('7', 'Fernandes LM, Øgaard B, Skoglund L. Pain and discomfort experienced after placement of a conventional or a superelastic NiTi aligning archwire. A randomized clinical trial. <i>J Orofac Orthop.</i> 1998;59(6):331–339.', 'https://doi.org/10.1007/BF01299769', 'RCT comparing conventional vs superelastic NiTi. Used for SD reference in sample size calculation. Cited in Sections 2.3, 7.1.'), ('8', 'Erdınç AM, Dinçer B. Perception of pain during orthodontic treatment with fixed appliances. <i>Eur J Orthod.</i> 2004;26(1):79–85.', 'https://doi.org/10.1093/ejo/26.1.79', 'PMID: 14994886. n=109 adolescents; pain onset ~2h, peak 24h, resolved day 3; no significant gender difference. Cited in Sections 2.2, 3.6.'), ('9', 'Abdelrahman RSh, Al-Nimri KS, Al Maaitah EF. Pain experience during initial alignment with three types of nickel-titanium archwires: a prospective clinical trial. <i>Angle Orthod.</i> 2015;85(6):1070–1076.', 'https://doi.org/10.2319/071614-498.1', 'PMID: 26516711. No significant difference between 3 NiTi types; gender and age had no effect on pain. Cited in Section 2.3.'), ('10', 'Azizi F, Extiari A, Imani MM. Tooth alignment and pain experience with A-NiTi versus Cu-NiTi: a randomized clinical trial. <i>BMC Oral Health.</i> 2021;21(1):434.', 'https://doi.org/10.1186/s12903-021-01789-5', 'PMID: 34488744. n=88; both NiTi types equally effective; no significant difference in pain or analgesic intake. Cited in Section 2.3.'), ]), ('D', 'Age and Sex Differences in Orthodontic Pain', [ ('11', 'Brown DF, Moerenhout RG. The pain experience and psychological adjustment to orthodontic treatment of preadolescents, adolescents, and adults. <i>Am J Orthod Dentofac Orthop.</i> 1991;100(4):349–356.', 'https://doi.org/10.1016/0889-5406(91)70073-6', 'PMID: 1927986. Longitudinal 4-questionnaire study. Adolescents (14–17y) reported higher pain and lower psychological well-being than preadolescents and adults. Key rationale reference for Section 1.2, 2.4.'), ('12', 'Salgado KR, Normando D, Brandão GAM. Is catastrophising associated with pain perception in early phase of orthodontic treatment? A cohort study. <i>J Oral Rehabil.</i> 2022;49(3):309–315.', 'https://doi.org/10.1111/joor.13279', 'PMID: 34731504. n=44; pain peak at 24h; older age weak protective factor; psychosocial variables. Cited in Sections 2.4, Discussion.'), ('13', 'Nandi M, Schreiber KL, Martel MO, Cornelius M, Campbell CM, Haythornthwaite JA, et al. Sex differences in negative affect and postoperative pain in patients undergoing total knee arthroplasty. <i>Biol Sex Differ.</i> 2019;10:23.', 'https://doi.org/10.1186/s13293-019-0237-7', 'Evidence base for sex-based differences in pain perception. Justification for secondary sex-based analysis (Objective 5).'), ]), ('E', 'Analgesic Use and Orthodontic Tooth Movement', [ ('14', 'Arias OR, Marquez-Orozco MC. Aspirin, acetaminophen, and ibuprofen: their effects on orthodontic tooth movement. <i>Am J Orthod Dentofac Orthop.</i> 2006;130(3):364–370.', 'https://doi.org/10.1016/j.ajodo.2004.12.027', 'PMID: 16979495. Aspirin and ibuprofen interfere with orthodontic tooth movement. Clinically relevant for patient counselling in Discussion.'), ('15', 'Corrêa AS, Almeida VL DE, Lopes BMV, Franco A, Matos FR DE, Quintans-Júnior LJ. The influence of NSAIDs and paracetamol used for pain control of orthodontic tooth movement: a systematic review. <i>An Acad Bras Cienc.</i> 2017;89(4):2851–2864.', 'https://doi.org/10.1590/0001-3765201720160865', 'PMID: 28876390. Systematic review. Paracetamol least interferes with tooth movement; ibuprofen, aspirin, and diclofenac reduce movement. Supports Discussion recommendation.'), ]), ('F', 'Reference Requiring DOI Verification', [ ('16', 'Bud E, Vlasa A, Chibelean M, Martha K, Păcurar M, Bud A, Esian D. Factors Associated with Pain Intensity in Patients Undergoing Orthodontic Treatment Based on Mini-Implants. <i>J Interdiscip Med.</i> 2021;6(2):74–81.', None, None), ]), ] for sec_letter, sec_title, sec_refs in refs: story.append(ref_section_banner(f'Section {sec_letter} — {sec_title}')) story.append(sp(0.1)) for num, text, doi, note in sec_refs: is_unverified = (doi is None) rstyle = PS(f'rs{num}', parent=ref_style, textColor=WARN_RED if is_unverified else TEXT_BLACK) story.append(Paragraph(f'<b>{num}.</b> &nbsp; {text}', rstyle)) if doi: story.append(Paragraph(doi, doi_style)) else: story.append(Paragraph( '⚠ DOI not confirmed in PubMed, CrossRef, or publisher sources. ' 'Verify at https://doi.org/ or the Journal of Interdisciplinary Medicine website before final submission. ' 'Cite by journal/volume/page only if no DOI is available.', warn_style)) if note: story.append(Paragraph(f'↳ {note}', ref_note)) story.append(sp(0.15)) story.append(PageBreak()) # ══════════════════════════════════════════════ # APPENDIX A — QUESTIONNAIRE # ══════════════════════════════════════════════ story.append(section_header('APPENDIX A — Questionnaire Instrument')) story.append(sp(0.15)) story.append(info_box( Paragraph( 'This instrument is adapted from the single-timepoint format used in the parent study (Olteanu et al., 2022¹), ' 'restructured for repeated prospective administration at four fixed timepoints. ' 'Section B is administered identically at T1 (6h), T2 (24h), T3 (7 days), and T4 (14 days). ' 'Section C is completed once only at T4.', PS('aqn', fontSize=9, fontName='Helvetica-Oblique', textColor=DARK_NAVY, leading=13, alignment=TA_JUSTIFY) ) )) story.append(sp(0.2)) def q_box(header_text, items, hdr_color=MID_BLUE): rows = [[Paragraph(header_text, PS('qhdr', fontSize=10, fontName='Helvetica-Bold', textColor=WHITE, leading=13))]] for item in items: rows.append([Paragraph(item, PS('qi', fontSize=9.5, fontName='Helvetica', textColor=TEXT_BLACK, leading=14, leftIndent=8))]) t = Table(rows, colWidths=[PAGE_W]) style_cmds = [ ('BACKGROUND', (0,0), (-1,0), hdr_color), ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, PALE_GREY]), ('BOX', (0,0), (-1,-1), 0.6, MID_GREY), ('LINEBELOW', (0,0), (-1,0), 1, hdr_color), ('TOPPADDING', (0,0), (-1,-1), 5), ('BOTTOMPADDING', (0,0), (-1,-1), 5), ('LEFTPADDING', (0,0), (-1,-1), 10), ('RIGHTPADDING', (0,0), (-1,-1), 10), ('VALIGN', (0,0), (-1,-1), 'TOP'), ] t.setStyle(TableStyle(style_cmds)) return t story.append(q_box('SECTION A — Baseline (completed once, at wire placement, T0)', [ 'Q1. Participant ID: _______________', 'Q2. Age: _______ years Age group: ☐ Adolescent (12–18) ☐ Adult (19+)', 'Q3. Sex: ☐ Male ☐ Female ☐ Other / prefer not to say', 'Q4. General health status: ☐ Good ☐ Affected — please specify: _______________', 'Q5. NiTi wire dimension used (completed by clinician): _______________', 'Q6. Date and time of wire placement: _______________', ], hdr_color=DARK_NAVY)) story.append(sp(0.2)) story.append(q_box('SECTION B — Repeated at EACH timepoint: ☐ 6 hours ☐ 24 hours ☐ 7 days ☐ 14 days', [ 'Q1. Which timepoint is this questionnaire for? ☐ 6 hours ☐ 24 hours ☐ 7 days ☐ 14 days', 'Q2. Rate your current pain level from the orthodontic wire (0 = no pain, 10 = worst pain imaginable):', ' 0 1 2 3 4 5 6 7 8 9 10', ' ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐ ☐', 'Q3. Has the pain affected your ability to EAT? ☐ No ☐ Mild ☐ Moderate ☐ Severe', 'Q4. Has the pain affected your SLEEP? ☐ No ☐ Mild ☐ Moderate ☐ Severe', 'Q5. Has the pain affected your SPEECH? ☐ No ☐ Mild ☐ Moderate ☐ Severe', 'Q6. Have you taken any medication for this pain since the last questionnaire? ☐ No ☐ Yes', 'Q7. If YES — which medication? ☐ Ibuprofen/Nurofen/Ketonal ☐ Metamizole ☐ Paracetamol ☐ Other: _______', 'Q8. If YES — how effective was it? ☐ Not effective ☐ Somewhat effective ☐ Very effective', ], hdr_color=MID_BLUE)) story.append(sp(0.2)) story.append(q_box('SECTION C — Final timepoint only (14-day questionnaire, T4)', [ 'Q1. Looking back, which timepoint was the MOST PAINFUL overall?', ' ☐ 6 hours ☐ 24 hours ☐ 7 days ☐ 14 days', 'Q2. Overall, how would you describe the pain compared to your expectation?', ' ☐ Much less than expected ☐ As expected ☐ Much more than expected', 'Q3. Any additional comments: _________________________________________________', ], hdr_color=colors.HexColor('#6C3483'))) story.append(sp(0.3)) # Final footer / signature block sig_data = [ [Paragraph('Principal Investigator Signature', PS('sigh', fontSize=8.5, fontName='Helvetica-Bold', textColor=MID_BLUE, leading=11)), Paragraph('Supervisor Signature', PS('sigh', fontSize=8.5, fontName='Helvetica-Bold', textColor=MID_BLUE, leading=11)), Paragraph('Date of Submission', PS('sigh', fontSize=8.5, fontName='Helvetica-Bold', textColor=MID_BLUE, leading=11))], [Paragraph('\n\n___________________________\n[Your Name]', PS('sigv', fontSize=9, fontName='Helvetica', textColor=TEXT_BLACK, leading=18)), Paragraph('\n\n___________________________\n[Supervisor Name]', PS('sigv', fontSize=9, fontName='Helvetica', textColor=TEXT_BLACK, leading=18)), Paragraph('\n\n___________________________\nJuly 2026', PS('sigv', fontSize=9, fontName='Helvetica', textColor=TEXT_BLACK, leading=18))], ] st_table = Table(sig_data, colWidths=[PAGE_W/3]*3) st_table.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,0), LIGHT_BLUE), ('GRID', (0,0), (-1,-1), 0.4, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 8), ('BOTTOMPADDING', (0,0), (-1,-1), 8), ('LEFTPADDING', (0,0), (-1,-1), 10), ('RIGHTPADDING', (0,0), (-1,-1), 10), ('ALIGN', (0,0), (-1,-1), 'CENTER'), ('VALIGN', (0,0), (-1,-1), 'TOP'), ])) story.append(st_table) story.append(sp(0.3)) story.append(HRFlowable(width='100%', thickness=1, color=DARK_NAVY)) story.append(sp(0.15)) story.append(Paragraph( 'IRB Research Protocol v1.0 | Pain Perception: Adults vs Adolescents — Initial NiTi Archwires | ' 'Vancouver (ICMJE) References | Prepared July 2026', footer_meta)) # ───────────────────────────────────────────── # BUILD # ───────────────────────────────────────────── doc.build(story, canvasmaker=NumberedCanvas) print('SUCCESS: IRB protocol PDF built.') PYEOF

mkdir -p /home/daytona/workspace/irb-protocol && python3 << 'PYEOF' from reportlab.lib.pagesizes import A4 from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle from reportlab.lib.units import cm from reportlab.lib import colors from reportlab.platypus import ( SimpleDocTemplate, Paragraph, Spacer, HRFlowable, Table, TableStyle, PageBreak, KeepTogether ) from reportlab.lib.enums import TA_LEFT, TA_CENTER, TA_JUSTIFY from reportlab.pdfgen import canvas as pdfcanvas W, H = A4 PAGE_W = W - 5 * cm # ── COLOURS ────────────────────────────────── DARK_NAVY = colors.HexColor('#0D1B3E') MID_BLUE = colors.HexColor('#1A5276') ACCENT_BLUE = colors.HexColor('#2980B9') LIGHT_BLUE = colors.HexColor('#D6EAF8') PALE_GREY = colors.HexColor('#F4F6F7') MID_GREY = colors.HexColor('#AAB7B8') WARN_RED = colors.HexColor('#B94040') TEXT_BLACK = colors.HexColor('#1A1A1A') TEXT_GREY = colors.HexColor('#555555') WHITE = colors.white GREEN_BG = colors.HexColor('#EAFAF1') RED_BG = colors.HexColor('#FDEDEC') GREEN_HDR = colors.HexColor('#1E8449') RED_HDR = colors.HexColor('#C0392B') PURPLE_HDR = colors.HexColor('#6C3483') YELLOW_BG = colors.HexColor('#FEF9E7') YELLOW_BDR = colors.HexColor('#D4AC0D') # ── PAGE NUMBERING (robust version) ────────── class NumberedCanvas(pdfcanvas.Canvas): def __init__(self, *args, **kwargs): pdfcanvas.Canvas.__init__(self, *args, **kwargs) self._pages = [] def showPage(self): self._pages.append(dict(self.__dict__)) self._startPage() def save(self): total = len(self._pages) for i, page_dict in enumerate(self._pages): self.__dict__.update(page_dict) if i > 0: # skip cover self._draw_footer(i + 1, total) pdfcanvas.Canvas.showPage(self) pdfcanvas.Canvas.save(self) def _draw_footer(self, page_num, total): self.saveState() self.setStrokeColor(MID_GREY) self.setLineWidth(0.5) self.line(2.5*cm, 1.8*cm, W - 2.5*cm, 1.8*cm) self.setFont('Helvetica', 7.5) self.setFillColor(TEXT_GREY) self.drawString(2.5*cm, 1.2*cm, 'IRB Research Protocol — Pain Perception: Adults vs Adolescents — Initial NiTi Archwires') self.drawRightString(W - 2.5*cm, 1.2*cm, f'Page {page_num} of {total}') self.restoreState() # ── DOCUMENT ───────────────────────────────── OUTPUT = '/home/daytona/workspace/irb-protocol/IRB_Research_Protocol_NiTi_Pain.pdf' doc = SimpleDocTemplate( OUTPUT, pagesize=A4, rightMargin=2.5*cm, leftMargin=2.5*cm, topMargin=2.5*cm, bottomMargin=2.5*cm, title='IRB Research Protocol – Pain Perception NiTi Archwires' ) # ── STYLES ─────────────────────────────────── def PS(name, **kw): base = kw.pop('parent', getSampleStyleSheet()['Normal']) return ParagraphStyle(name, parent=base, **kw) h1s = PS('h1s', fontSize=13, fontName='Helvetica-Bold', textColor=WHITE, leading=17, alignment=TA_LEFT) h2s = PS('h2s', fontSize=11, fontName='Helvetica-Bold', textColor=DARK_NAVY, leading=14, spaceBefore=12, spaceAfter=4) h3s = PS('h3s', fontSize=10, fontName='Helvetica-Bold', textColor=MID_BLUE, leading=13, spaceBefore=7, spaceAfter=3) body = PS('body', fontSize=9.5, fontName='Helvetica', textColor=TEXT_BLACK, leading=14, spaceAfter=4, alignment=TA_JUSTIFY) bull = PS('bull', fontSize=9.5, fontName='Helvetica', textColor=TEXT_BLACK, leading=13, spaceAfter=3, leftIndent=14, firstLineIndent=-10, alignment=TA_JUSTIFY) note = PS('note', fontSize=8.5, fontName='Helvetica-Oblique', textColor=TEXT_GREY, leading=11, spaceAfter=3, leftIndent=10) warn = PS('warn', fontSize=8.5, fontName='Helvetica-Oblique', textColor=WARN_RED, leading=11, spaceAfter=4, leftIndent=10) refS = PS('refS', fontSize=9, fontName='Helvetica', textColor=TEXT_BLACK, leading=13, spaceAfter=2, leftIndent=18, firstLineIndent=-18, alignment=TA_JUSTIFY) refW = PS('refW', fontSize=9, fontName='Helvetica', textColor=WARN_RED, leading=13, spaceAfter=2, leftIndent=18, firstLineIndent=-18, alignment=TA_JUSTIFY) doiS = PS('doiS', fontSize=8.5, fontName='Helvetica', textColor=ACCENT_BLUE, leading=11, spaceAfter=5, leftIndent=18) rnot = PS('rnot', fontSize=8, fontName='Helvetica-Oblique', textColor=TEXT_GREY, leading=10, spaceAfter=7, leftIndent=18) thdr = PS('thdr', fontSize=9, fontName='Helvetica-Bold', textColor=WHITE, leading=12, alignment=TA_CENTER) tcel = PS('tcel', fontSize=8.5, fontName='Helvetica', textColor=TEXT_BLACK, leading=11, alignment=TA_LEFT) tcc = PS('tcc', fontSize=8.5, fontName='Helvetica', textColor=TEXT_BLACK, leading=11, alignment=TA_CENTER) tcb = PS('tcb', fontSize=8.5, fontName='Helvetica-Bold', textColor=TEXT_BLACK, leading=11, alignment=TA_LEFT) cvm = PS('cvm', fontSize=9, fontName='Helvetica', textColor=WHITE, leading=13, alignment=TA_CENTER) cvt = PS('cvt', fontSize=19, fontName='Helvetica-Bold', textColor=WHITE, leading=24, alignment=TA_CENTER) cvs = PS('cvs', fontSize=11, fontName='Helvetica', textColor=LIGHT_BLUE, leading=15, alignment=TA_CENTER) ftr = PS('ftr', fontSize=8, fontName='Helvetica', textColor=TEXT_GREY, leading=10, alignment=TA_CENTER) qhdr = PS('qhdr', fontSize=10, fontName='Helvetica-Bold', textColor=WHITE, leading=13) qitm = PS('qitm', fontSize=9.5, fontName='Helvetica', textColor=TEXT_BLACK, leading=14, leftIndent=6) tocs = PS('tocs', fontSize=10, fontName='Helvetica', textColor=TEXT_BLACK, leading=13, leftIndent=14, spaceAfter=1) tocn = PS('tocn', fontSize=10, fontName='Helvetica-Bold', textColor=MID_BLUE, leading=13, spaceBefore=3, spaceAfter=0) # ── HELPERS ────────────────────────────────── def sp(n=0.2): return Spacer(1, n*cm) def hr(): return HRFlowable(width='100%', thickness=0.5, color=MID_GREY) def sec_banner(title, num=None): label = f'{num}. {title}' if num else title t = Table([[Paragraph(label, h1s)]], colWidths=[PAGE_W]) t.setStyle(TableStyle([ ('BACKGROUND', (0,0),(-1,-1), MID_BLUE), ('TOPPADDING', (0,0),(-1,-1), 8), ('BOTTOMPADDING', (0,0),(-1,-1), 8), ('LEFTPADDING', (0,0),(-1,-1), 10), ('RIGHTPADDING', (0,0),(-1,-1), 10), ])) return t def info_box(para, bg=LIGHT_BLUE, bdr=ACCENT_BLUE): t = Table([[para]], colWidths=[PAGE_W]) t.setStyle(TableStyle([ ('BACKGROUND', (0,0),(-1,-1), bg), ('BOX', (0,0),(-1,-1), 0.8, bdr), ('TOPPADDING', (0,0),(-1,-1), 8), ('BOTTOMPADDING', (0,0),(-1,-1), 8), ('LEFTPADDING', (0,0),(-1,-1), 10), ('RIGHTPADDING', (0,0),(-1,-1), 10), ])) return t def mini_banner(title, color=ACCENT_BLUE): t = Table([[Paragraph(title, PS('mb', fontSize=9, fontName='Helvetica-Bold', textColor=WHITE, leading=12))]], colWidths=[PAGE_W]) t.setStyle(TableStyle([ ('BACKGROUND', (0,0),(-1,-1), color), ('TOPPADDING', (0,0),(-1,-1), 4), ('BOTTOMPADDING', (0,0),(-1,-1), 4), ('LEFTPADDING', (0,0),(-1,-1), 8), ('RIGHTPADDING', (0,0),(-1,-1), 8), ])) return t def std_table(rows, col_widths, row_bgs=None): t = Table(rows, colWidths=col_widths) cmds = [ ('BACKGROUND', (0,0), (-1,0), MID_BLUE), ('GRID', (0,0), (-1,-1), 0.4, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 5), ('BOTTOMPADDING', (0,0), (-1,-1), 5), ('LEFTPADDING', (0,0), (-1,-1), 7), ('RIGHTPADDING', (0,0), (-1,-1), 7), ('VALIGN', (0,0), (-1,-1), 'TOP'), ] if row_bgs: cmds.append(('ROWBACKGROUNDS', (0,1), (-1,-1), row_bgs)) else: cmds.append(('ROWBACKGROUNDS', (0,1), (-1,-1), [WHITE, PALE_GREY])) t.setStyle(TableStyle(cmds)) return t def b(text): return Paragraph(f'&#8226; &nbsp;{text}', bull) # ════════════════════════════════════════════════════════ # STORY # ════════════════════════════════════════════════════════ story = [] # ─── COVER ──────────────────────────────────────────── cv = Table([[ Paragraph('INSTITUTIONAL REVIEW BOARD SUBMISSION', cvm), sp(0.2), Paragraph('A Comparative Study of Pain Perception in Adults and<br/>Adolescents Following Placement of<br/>Initial NiTi Archwires in Orthodontic Treatment', cvt), sp(0.3), Paragraph('Prospective · Observational · Questionnaire-Based · Comparative', cvs), sp(0.4), ]], colWidths=[PAGE_W]) cv.setStyle(TableStyle([ ('BACKGROUND', (0,0),(-1,-1), DARK_NAVY), ('TOPPADDING', (0,0),(-1,-1), 28), ('BOTTOMPADDING', (0,0),(-1,-1), 28), ('LEFTPADDING', (0,0),(-1,-1), 18), ('RIGHTPADDING', (0,0),(-1,-1), 18), ])) story.append(cv) story.append(sp(0.4)) meta = [ ['Protocol Title', 'Pain Perception: Adults vs Adolescents — Initial NiTi Archwires'], ['Protocol Version', 'Version 1.0 | July 2026'], ['Study Design', 'Prospective, observational, questionnaire-based comparative study'], ['Principal Investigator','[Your Name] — [Your Institution / Faculty of Dental Medicine]'], ['Supervisor', '[Supervisor\'s Name]'], ['Target Recruitment', '124–130 participants (62–65 per group)'], ['Follow-up Duration', '14 days per participant'], ['Ethics Framework', 'Declaration of Helsinki; ICMJE reporting standards'], ['Reference Style', 'Vancouver (ICMJE) — 16 references; all DOIs verified except Ref 16'], ] mt = Table( [[Paragraph(r[0], PS('mk', fontSize=8.5, fontName='Helvetica-Bold', textColor=MID_BLUE, leading=12)), Paragraph(r[1], PS('mv', fontSize=8.5, fontName='Helvetica', textColor=TEXT_BLACK, leading=12))] for r in meta], colWidths=[4.5*cm, PAGE_W-4.5*cm]) mt.setStyle(TableStyle([ ('ROWBACKGROUNDS', (0,0),(-1,-1), [WHITE, PALE_GREY]), ('GRID', (0,0),(-1,-1), 0.3, MID_GREY), ('TOPPADDING', (0,0),(-1,-1), 5), ('BOTTOMPADDING', (0,0),(-1,-1), 5), ('LEFTPADDING', (0,0),(-1,-1), 8), ('RIGHTPADDING', (0,0),(-1,-1), 8), ('VALIGN', (0,0),(-1,-1), 'TOP'), ])) story.append(mt) story.append(sp(0.4)) story.append(info_box(Paragraph( '<b>Confidentiality Notice:</b> This document is submitted in confidence to the Institutional Review ' 'Board. It contains research protocol details, eligibility criteria, statistical analysis plans, and ' 'a full verified reference list. Distribution is restricted to IRB members and named study personnel. ' 'Patient data collected under this protocol will be pseudonymised and stored per the Declaration of ' 'Helsinki and applicable institutional data protection regulations.', PS('disc', fontSize=8.5, fontName='Helvetica', textColor=TEXT_BLACK, leading=12, alignment=TA_JUSTIFY)), bg=YELLOW_BG, bdr=YELLOW_BDR)) story.append(PageBreak()) # ─── TABLE OF CONTENTS ──────────────────────────────── story.append(sec_banner('TABLE OF CONTENTS')) story.append(sp(0.3)) toc = [ ('1', 'Background and Scientific Rationale'), ('2', 'Aim and Objectives'), ('3', 'Study Hypotheses'), ('4', 'Study Design'), ('5', 'Setting and Ethical Framework'), ('6', 'Participant Eligibility Criteria'), ('7', 'Sample Size Calculation'), ('8', 'Clinical Procedure'), ('9', 'Outcome Measures and Questionnaire Instrument'), ('10', 'Data Collection Procedure'), ('11', 'Statistical Analysis Plan'), ('12', 'Ethical Considerations'), ('13', 'Limitations'), ('14', 'References (Vancouver / ICMJE)'), ('Appendix A', 'Questionnaire Instrument'), ] for num, title in toc: story.append(Paragraph(f'<b>{num}</b>', tocn)) story.append(Paragraph(title, tocs)) story.append(PageBreak()) # ─── SECTION 1 — BACKGROUND ─────────────────────────── story.append(sec_banner('Background and Scientific Rationale', '1')) story.append(sp(0.15)) story.append(Paragraph('<b>1.1 Clinical Context</b>', h2s)) story.append(Paragraph( 'Pain and masticatory discomfort are among the most frequently reported adverse effects of fixed ' 'orthodontic treatment and remain a leading cause of reduced patient compliance and, in some cases, ' 'treatment discontinuation. Orthodontic tooth movement triggers a localised inflammatory cascade within ' 'the periodontal ligament (PDL) and dental pulp, releasing biochemical mediators — prostaglandins, ' 'cytokines, and substance P — that are the principal substrates of orthodontically induced pain (3,4). ' 'This biological response is broadly independent of age, yet the density of alveolar bone and the ' 'cellular turnover rate of the PDL change across the lifespan, which several authors have proposed as ' 'a mechanism for age-related variation in pain intensity and tooth displacement rate.', body)) story.append(Paragraph( 'The initial aligning phase of fixed orthodontic treatment conventionally employs superelastic ' 'nickel-titanium (NiTi) archwires, valued for delivering continuous light forces over a wide range ' 'of activation (7). A 2024 Cochrane systematic review and meta-analysis — Liu et al. (5), 29 RCTs, ' '1915 participants — found low-certainty evidence of little difference in pain intensity between ' 'different NiTi wire types, reinforcing that the inflammatory response rather than wire alloy is ' 'the primary driver of post-placement pain.', body)) story.append(Paragraph('<b>1.2 The Age–Pain Question</b>', h2s)) story.append(Paragraph( 'Age is one of the most frequently cited yet inconsistently reported variables in orthodontic pain ' 'research. Scheurer et al. (6) (n=170; age 8–53 years) found the highest pain frequency in the ' '13–16-year age group; pain intensity did not differ significantly across age groups. Brown and ' 'Moerenhout (11) found in a longitudinal study that adolescents (14–17 years) reported higher pain ' 'and lower psychological well-being than both preadolescents and adults throughout fixed appliance ' 'treatment. Abdelrahman et al. (9) reported no significant effect of age or gender on pain during ' 'initial NiTi placement. Salgado et al. (12) identified older age as a weak protective factor. ' 'This inconsistency — compounded by reliance on single-timepoint retrospective designs that cannot ' 'capture the pain trajectory — is the central gap this protocol addresses.', body)) story.append(Paragraph('<b>1.3 Basis: The Parent Study</b>', h2s)) story.append(Paragraph( 'The parent study (Olteanu et al., 2022 (1)) evaluated pain across four orthodontic procedures ' 'using a single-timepoint retrospective questionnaire in 100 patients across four age bands. ' 'The present protocol narrows focus to one clinical event — first NiTi aligning archwire placement ' '— and broadens temporal resolution by capturing pain prospectively at four timepoints ' '(6 h, 24 h, 7 days, 14 days). The age comparison is simplified to two clinically meaningful ' 'groups (adolescents vs adults) to enable a statistically powered, focused comparison.', body)) story.append(PageBreak()) # ─── SECTION 2 — AIM & OBJECTIVES ──────────────────── story.append(sec_banner('Aim and Objectives', '2')) story.append(sp(0.15)) story.append(info_box(Paragraph( '<b>Aim:</b> To compare pain perception following initial NiTi archwire placement between ' 'adolescent and adult orthodontic patients across four prospective timepoints.', PS('aim', fontSize=10, fontName='Helvetica-Bold', textColor=DARK_NAVY, leading=14, alignment=TA_JUSTIFY)))) story.append(sp(0.2)) story.append(Paragraph('<b>Primary Objectives</b>', h3s)) for obj in [ 'Objective 1: Measure and compare mean pain intensity (NRS 0–10) between adolescents and adults at 6 h, 24 h, 7 days, and 14 days after initial NiTi archwire placement.', 'Objective 2: Identify and compare the timepoint of peak pain intensity in each age group.', 'Objective 3: Compare the proportion requiring analgesic medication and the type of medication used between the two groups.', ]: story.append(b(obj)) story.append(sp(0.1)) story.append(Paragraph('<b>Secondary Objectives</b>', h3s)) for obj in [ 'Objective 4: Evaluate the impact of pain on daily function (eating, sleeping, speaking) between groups at each timepoint.', 'Objective 5: Assess whether sex, within each age group, modifies the pain response (exploratory analysis).', ]: story.append(b(obj)) story.append(sp(0.2)) # ─── SECTION 3 — HYPOTHESES ─────────────────────────── story.append(sec_banner('Study Hypotheses', '3')) story.append(sp(0.15)) hyp_rows = [ [Paragraph('<b>Hypothesis</b>', thdr), Paragraph('<b>Null (H\u2080)</b>', thdr), Paragraph('<b>Alternative (H\u2081)</b>', thdr)], [Paragraph('H1 — Pain Intensity', tcb), Paragraph('No significant difference in mean NRS score between groups at any timepoint.', tcel), Paragraph('Mean pain intensity differs significantly between groups at one or more timepoints (α=0.05; Bonferroni α=0.0125 per timepoint).', tcel)], [Paragraph('H2 — Peak Timepoint', tcb), Paragraph('Peak pain timepoint does not differ between groups.', tcel), Paragraph('Peak pain timepoint differs significantly between groups.', tcel)], [Paragraph('H3 — Analgesic Use', tcb), Paragraph('Proportion requiring analgesia does not differ between groups.', tcel), Paragraph('Proportion requiring analgesia differs significantly between groups.', tcel)], ] story.append(std_table(hyp_rows, [3.5*cm, 6.5*cm, 6.5*cm])) story.append(sp(0.2)) # ─── SECTION 4 — STUDY DESIGN ──────────────────────── story.append(sec_banner('Study Design', '4')) story.append(sp(0.15)) design_rows = [ [Paragraph('<b>Parameter</b>', thdr), Paragraph('<b>Detail</b>', thdr)], [Paragraph('Study type', tcb), Paragraph('Prospective, observational, questionnaire-based comparative study', tcel)], [Paragraph('Comparator groups', tcb), Paragraph('Adolescent group (12–18 y) vs Adult group (≥19 y)', tcel)], [Paragraph('Primary exposure', tcb), Paragraph('Placement of first superelastic NiTi aligning archwire', tcel)], [Paragraph('Primary outcome', tcb), Paragraph('Pain intensity — Numerical Rating Scale (NRS) 0–10', tcel)], [Paragraph('Timepoints', tcb), Paragraph('6 hours, 24 hours, 7 days, 14 days post-placement', tcel)], [Paragraph('Follow-up per participant', tcb),Paragraph('14 days', tcel)], [Paragraph('Setting', tcb), Paragraph('Single orthodontic clinical centre', tcel)], [Paragraph('Recruitment period', tcb), Paragraph('6–12 months to achieve target sample', tcel)], ] story.append(std_table(design_rows, [5*cm, PAGE_W-5*cm])) story.append(sp(0.2)) # ─── SECTION 5 — SETTING & ETHICS ──────────────────── story.append(sec_banner('Setting and Ethical Framework', '5')) story.append(sp(0.15)) story.append(Paragraph('<b>5.1 Clinical Setting</b>', h2s)) story.append(Paragraph('[Name of orthodontic clinic / university dental department]. All procedures performed by the treating orthodontist following the department\'s standard protocol.', body)) story.append(Paragraph('<b>5.2 Ethical Approval</b>', h2s)) story.append(Paragraph( 'Ethical approval must be obtained from the relevant Institutional Review Board / University Ethics ' 'Committee prior to any recruitment, in accordance with the Declaration of Helsinki (WMA, 2013 revision). ' 'This document constitutes the formal IRB submission.', body)) story.append(Paragraph('<b>5.3 Informed Consent</b>', h2s)) for item in [ 'Adults (≥18 y): written informed consent obtained directly from the participant.', 'Adolescents (12–17 y): written consent from parent/legal guardian; written assent from the adolescent at each timepoint.', 'Participation is entirely voluntary; withdrawal has no impact on standard care.', 'All consent forms and information sheets provided in the participant\'s primary language.', ]: story.append(b(item)) story.append(sp(0.2)) story.append(PageBreak()) # ─── SECTION 6 — ELIGIBILITY ────────────────────────── story.append(sec_banner('Participant Eligibility Criteria', '6')) story.append(sp(0.15)) inc_items = [ 'Beginning fixed orthodontic treatment and receiving their first NiTi aligning archwire', 'Age 12 years and above', 'Good general health; no active orofacial pain condition unrelated to orthodontic treatment', 'Willingness and cognitive ability to complete a self-report questionnaire at each timepoint', 'Available for follow-up at all four timepoints (6 h, 24 h, 7 d, 14 d)', ] exc_items = [ 'Regular analgesic or anti-inflammatory medication use for an unrelated chronic condition', 'Craniofacial syndromes, active TMJ disorders, or recent oral/maxillofacial surgery', 'Known allergy to nickel or titanium', 'Inability to complete the questionnaire independently or via guardian-assisted administration', 'Previous fixed orthodontic treatment within the past 12 months', ] def crit_table(header, items, hdr_color, row_bg, tick): rows = [[Paragraph(header, PS('ch', fontSize=9.5, fontName='Helvetica-Bold', textColor=WHITE, leading=12, alignment=TA_CENTER))]] for item in items: rows.append([Paragraph(f'{tick} {item}', PS('ci', fontSize=9, fontName='Helvetica', textColor=TEXT_BLACK, leading=13, alignment=TA_JUSTIFY))]) t = Table(rows, colWidths=[(PAGE_W/2 - 0.3*cm)]) t.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,0), hdr_color), ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, row_bg]), ('BOX', (0,0), (-1,-1), 0.5, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 5), ('BOTTOMPADDING', (0,0), (-1,-1), 5), ('LEFTPADDING', (0,0), (-1,-1), 8), ('RIGHTPADDING', (0,0), (-1,-1), 8), ('VALIGN', (0,0), (-1,-1), 'TOP'), ])) return t inc_t = crit_table('INCLUSION CRITERIA', inc_items, GREEN_HDR, GREEN_BG, '✓') exc_t = crit_table('EXCLUSION CRITERIA', exc_items, RED_HDR, RED_BG, '✗') sbs = Table([[inc_t, Spacer(0.6*cm,0), exc_t]], colWidths=[PAGE_W/2-0.3*cm, 0.6*cm, PAGE_W/2-0.3*cm]) sbs.setStyle(TableStyle([ ('VALIGN', (0,0),(-1,-1), 'TOP'), ('TOPPADDING', (0,0),(-1,-1), 0), ('BOTTOMPADDING', (0,0),(-1,-1), 0), ('LEFTPADDING', (0,0),(-1,-1), 0), ('RIGHTPADDING', (0,0),(-1,-1), 0), ])) story.append(sbs) story.append(sp(0.2)) story.append(Paragraph('<b>6.1 Group Definitions</b>', h2s)) grp_rows = [ [Paragraph('<b>Group</b>', thdr), Paragraph('<b>Age Range</b>', thdr), Paragraph('<b>Rationale</b>', thdr), Paragraph('<b>Target n</b>', thdr)], [Paragraph('Adolescent', tcb), Paragraph('12–18 y', tcc), Paragraph('Consistent with permanent dentition eruption; mirrors parent study age band (1).', tcel), Paragraph('62–65', tcc)], [Paragraph('Adult', tcb), Paragraph('≥19 y', tcc), Paragraph('Single adult category enables a powered two-group comparison. Adult age reported as continuous covariate in secondary analysis.', tcel), Paragraph('62–65', tcc)], [Paragraph('<b>Total</b>', tcb), Paragraph('', tcc), Paragraph('', tcel), Paragraph('<b>124–130</b>', tcb)], ] gt = std_table(grp_rows, [3*cm, 2.5*cm, 9.5*cm, 1.5*cm]) gt.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,0), MID_BLUE), ('BACKGROUND', (0,3), (-1,3), LIGHT_BLUE), ('ROWBACKGROUNDS',(0,1), (-1,2), [WHITE, PALE_GREY]), ('GRID', (0,0), (-1,-1), 0.4, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 5), ('BOTTOMPADDING', (0,0), (-1,-1), 5), ('LEFTPADDING', (0,0), (-1,-1), 7), ('RIGHTPADDING', (0,0), (-1,-1), 7), ('VALIGN', (0,0), (-1,-1), 'TOP'), ])) story.append(gt) story.append(sp(0.2)) story.append(PageBreak()) # ─── SECTION 7 — SAMPLE SIZE ────────────────────────── story.append(sec_banner('Sample Size Calculation', '7')) story.append(sp(0.15)) story.append(Paragraph('<b>7.1 Formula and Parameters</b>', h2s)) story.append(Paragraph( 'The required sample size for a two-sample independent-means comparison (adolescent vs adult) ' 'was calculated using the standard formula for comparing two independent means:', body)) story.append(info_box(Paragraph( '<b>n per group = 2 × (Z\u03b1/2 + Z\u03b2)\u00b2 × \u03c3\u00b2 / d\u00b2</b>', PS('form', fontSize=12, fontName='Helvetica-Bold', textColor=DARK_NAVY, alignment=TA_CENTER, leading=18)))) story.append(sp(0.2)) param_rows = [ [Paragraph('<b>Parameter</b>', thdr), Paragraph('<b>Symbol</b>', thdr), Paragraph('<b>Value</b>', thdr), Paragraph('<b>Justification / Source</b>', thdr)], [Paragraph('Significance level (two-tailed)', tcel), Paragraph('Z\u03b1/2', tcc), Paragraph('1.96', tcc), Paragraph('\u03b1 = 0.05 (standard for clinical research)', tcel)], [Paragraph('Statistical power', tcel), Paragraph('Z\u03b2', tcc), Paragraph('0.84', tcc), Paragraph('Power = 80% (minimum acceptable for comparative studies)', tcel)], [Paragraph('SD of NRS pain score', tcel), Paragraph('\u03c3', tcc), Paragraph('1.8 pts', tcc), Paragraph('From Scheurer et al. 1996 (6) and Fernandes et al. 1998 (7); comparable archwire-pain SDs range 1.6–2.0', tcel)], [Paragraph('Min clinically important difference', tcel), Paragraph('d', tcc), Paragraph('1.0 pt', tcc), Paragraph('Widely accepted MCID for 0–10 pain scales in orthodontic research', tcel)], ] story.append(std_table(param_rows, [5*cm, 1.8*cm, 2*cm, PAGE_W-8.8*cm])) story.append(sp(0.2)) story.append(Paragraph('<b>7.2 Worked Calculation</b>', h2s)) calc_lines = ( 'n = 2 × (1.96 + 0.84)² × 1.8² / 1.0²\n' 'n = 2 × (2.80)² × 3.24\n' 'n = 2 × 7.84 × 3.24\n' 'n = 50.8 → rounded up to 51 participants per group\n' 'Minimum total at baseline (2 groups): 102 participants' ) story.append(info_box( Paragraph(calc_lines.replace('\n', '<br/>'), PS('calc', fontSize=10, fontName='Helvetica', textColor=DARK_NAVY, leading=17)))) story.append(sp(0.2)) story.append(Paragraph('<b>7.3 Attrition Adjustment and Recruitment Target</b>', h2s)) att_rows = [ [Paragraph('<b>Scenario</b>', thdr), Paragraph('<b>Attrition</b>', thdr), Paragraph('<b>n per group</b>', thdr), Paragraph('<b>Total to recruit</b>', thdr)], [Paragraph('Minimum (no attrition)', tcel), Paragraph('0%', tcc), Paragraph('51', tcc), Paragraph('102', tcc)], [Paragraph('Conservative estimate', tcel), Paragraph('15%', tcc), Paragraph('60', tcc), Paragraph('120', tcc)], [Paragraph('<b>Recommended target</b>', tcb), Paragraph('<b>20%</b>', tcb), Paragraph('<b>64</b>', tcb), Paragraph('<b>128</b>', tcb)], [Paragraph('Maximum buffer', tcel), Paragraph('25%', tcc), Paragraph('68', tcc), Paragraph('136', tcc)], ] at = std_table(att_rows, [5.5*cm, 3*cm, 3.5*cm, 4.5*cm], row_bgs=[WHITE, PALE_GREY, LIGHT_BLUE, WHITE]) story.append(at) story.append(sp(0.1)) story.append(Paragraph( '<b>Recommended recruitment target: 64 per group (128 total)</b>, accounting for 20% attrition across ' 'four follow-up timepoints. This aligns with the parent study (Olteanu et al., 2022 (1), n=100).', body)) story.append(Paragraph('<b>7.4 Note on Repeated-Measures Power</b>', h2s)) story.append(Paragraph( 'The calculation above targets the single-timepoint t-test — the most conservative case. ' 'The primary design-level analysis is a two-way mixed-design repeated-measures ANOVA ' '(group × 4 timepoints). Because correlated measurements within participants reduce residual ' 'variance, effective power for the group × time interaction is typically equal to or greater than ' 'the estimate above. The figure above is therefore a safe upper-bound target. G*Power ' '(F-tests: ANOVA Repeated Measures, within-between interaction) incorporating the expected ' 'within-subject correlation (r ≈ 0.4–0.6) may indicate a modestly smaller adequate sample.', body)) story.append(sp(0.2)) story.append(PageBreak()) # ─── SECTION 8 — CLINICAL PROCEDURE ────────────────── story.append(sec_banner('Clinical Procedure', '8')) story.append(sp(0.15)) story.append(Paragraph( 'All participants will receive an initial superelastic NiTi archwire ' '(specify: e.g., 0.014-inch or 0.016-inch superelastic NiTi) ligated to fixed brackets, ' 'following the treating orthodontist\'s standard protocol. ' 'The following elements must be standardised or recorded as covariates:', body)) for item in [ 'Wire type, alloy (superelastic vs thermoelastic vs conventional NiTi), and dimension — standardised across both groups where possible.', 'Bracket system (conventional vs self-ligating) and ligation method (elastomeric ligature vs metal tie) — recorded as covariates.', 'Operator — ideally a single experienced orthodontist to minimise inter-operator variability.', 'Time of day of placement — recorded, as circadian variation in pain perception has been reported.', ]: story.append(b(item)) story.append(sp(0.1)) story.append(info_box(Paragraph( '<b>Standardisation note:</b> Wire dimension and bracket type affect force magnitude independently of ' 'patient age. Any deviation from a standardised protocol must be recorded and included as a covariate ' 'in the statistical model.', PS('sn', fontSize=9, fontName='Helvetica-Oblique', textColor=DARK_NAVY, leading=13, alignment=TA_JUSTIFY)))) story.append(sp(0.2)) # ─── SECTION 9 — OUTCOMES ──────────────────────────── story.append(sec_banner('Outcome Measures and Questionnaire Instrument', '9')) story.append(sp(0.15)) story.append(Paragraph('<b>9.1 Primary Outcome</b>', h2s)) story.append(Paragraph( 'Mean NRS pain score (0–10; 0=no pain, 10=worst pain imaginable) at each of the four timepoints, ' 'compared between the adolescent and adult groups. ' 'The NRS is favoured for questionnaire-based orthodontic pain research because it requires no visual ' 'aids and correlates well with VAS scores (6).', body)) story.append(Paragraph('<b>9.2 Secondary Outcomes</b>', h2s)) out_rows = [ [Paragraph('<b>Outcome</b>', thdr), Paragraph('<b>Measurement</b>', thdr), Paragraph('<b>Item</b>', thdr)], [Paragraph('Peak pain timepoint', tcb), Paragraph('Self-reported most painful timepoint', tcel), Paragraph('Sec C, Q1', tcc)], [Paragraph('Analgesic use', tcb), Paragraph('Proportion requiring medication per group', tcel), Paragraph('Sec B, Q6', tcc)], [Paragraph('Medication type', tcb), Paragraph('Type of analgesic used (4 options)', tcel), Paragraph('Sec B, Q7', tcc)], [Paragraph('Analgesic efficacy', tcb), Paragraph('Self-rated effectiveness (3-point)', tcel), Paragraph('Sec B, Q8', tcc)], [Paragraph('Eating impact', tcb), Paragraph('None / Mild / Moderate / Severe', tcel), Paragraph('Sec B, Q3', tcc)], [Paragraph('Sleep impact', tcb), Paragraph('None / Mild / Moderate / Severe', tcel), Paragraph('Sec B, Q4', tcc)], [Paragraph('Speech impact', tcb), Paragraph('None / Mild / Moderate / Severe', tcel), Paragraph('Sec B, Q5', tcc)], [Paragraph('Sex-based modification', tcb),Paragraph('Whether sex modifies age-group effect (exploratory)', tcel), Paragraph('Sec A, Q3', tcc)], ] story.append(std_table(out_rows, [4.5*cm, 9*cm, PAGE_W-13.5*cm])) story.append(sp(0.2)) story.append(PageBreak()) # ─── SECTION 10 — DATA COLLECTION ──────────────────── story.append(sec_banner('Data Collection Procedure', '10')) story.append(sp(0.15)) tl_rows = [ [Paragraph('<b>Timepoint</b>', thdr), Paragraph('<b>Label</b>', thdr), Paragraph('<b>Method</b>', thdr), Paragraph('<b>Section</b>', thdr)], [Paragraph('At wire placement', tcb), Paragraph('T0 — Baseline', tcc), Paragraph('Paper form completed chairside immediately after placement', tcel), Paragraph('Section A (once)', tcc)], [Paragraph('6 hours', tcb), Paragraph('T1', tcc), Paragraph('Paper / phone call / SMS-email digital survey link', tcel), Paragraph('Section B', tcc)], [Paragraph('24 hours', tcb), Paragraph('T2', tcc), Paragraph('Same delivery channel as T1', tcel), Paragraph('Section B', tcc)], [Paragraph('7 days', tcb), Paragraph('T3', tcc), Paragraph('Same channel or completed at scheduled clinical check-in', tcel), Paragraph('Section B', tcc)], [Paragraph('14 days', tcb), Paragraph('T4 — Final', tcc), Paragraph('Same channel or at next clinical appointment', tcel), Paragraph('Sec B + Sec C', tcc)], ] story.append(std_table(tl_rows, [3.2*cm, 2.5*cm, 8*cm, PAGE_W-13.7*cm])) story.append(sp(0.1)) for item in [ 'Use the same delivery channel across all four timepoints to minimise differential non-response bias.', 'Send time-stamped automated reminders at each timepoint to reduce missing data.', 'If a participant misses a timepoint, document the reason. For attrition >10% per timepoint, address via multiple imputation or a linear mixed-effects model (which handles missing timepoints without listwise deletion).', ]: story.append(b(item)) story.append(sp(0.2)) # ─── SECTION 11 — STATISTICAL ANALYSIS PLAN ────────── story.append(sec_banner('Statistical Analysis Plan', '11')) story.append(sp(0.15)) story.append(Paragraph('<b>11.1 Descriptive Statistics</b>', h2s)) desc_rows = [ [Paragraph('<b>Variable Type</b>', thdr), Paragraph('<b>Statistic</b>', thdr), Paragraph('<b>Variables</b>', thdr)], [Paragraph('Continuous — normally distributed', tcb), Paragraph('Mean ± SD', tcc), Paragraph('Age, NRS pain scores at each timepoint', tcel)], [Paragraph('Continuous — non-normally distributed', tcb), Paragraph('Median (IQR)', tcc), Paragraph('NRS scores if Shapiro–Wilk p<0.05', tcel)], [Paragraph('Categorical', tcb), Paragraph('n (%)', tcc), Paragraph('Sex, medication use, medication type, peak-pain timepoint, functional impacts', tcel)], ] story.append(std_table(desc_rows, [5*cm, 2.5*cm, PAGE_W-7.5*cm])) story.append(Paragraph('Normality assessed by Shapiro–Wilk test and Q–Q plot inspection at each timepoint before selecting parametric or non-parametric tests.', note)) story.append(sp(0.15)) story.append(Paragraph('<b>11.2 Full Statistical Analysis Plan</b>', h2s)) def sub_row(label): return [Paragraph(label, PS('subr', fontSize=8.5, fontName='Helvetica-Bold', textColor=WHITE, leading=11, alignment=TA_LEFT)), Paragraph('', tcel), Paragraph('', tcel), Paragraph('', tcel)] stat_rows = [ [Paragraph('<b>Analysis</b>', thdr), Paragraph('<b>Variable / Source</b>', thdr), Paragraph('<b>Test</b>', thdr), Paragraph('<b>Correction / Effect Size</b>', thdr)], sub_row('PRIMARY — Pain Intensity at Each Timepoint'), [Paragraph('Pain intensity (parametric)', tcel), Paragraph('NRS 0–10, Sec B Q2 (normal distribution)', tcel), Paragraph("Independent-samples Student's t-test", tcel), Paragraph('Bonferroni \u03b1=0.05/4=0.0125 per timepoint; report Cohen\'s d', tcel)], [Paragraph('Pain intensity (non-parametric)', tcel), Paragraph('NRS 0–10, Sec B Q2 (non-normal)', tcel), Paragraph('Mann–Whitney U test', tcel), Paragraph('Bonferroni \u03b1=0.0125; report rank-biserial r', tcel)], sub_row('PRIMARY — Pain Trajectory (Design-Level Analysis)'), [Paragraph('Group × Time interaction', tcel), Paragraph('Repeated NRS scores T1–T4; Group between-subjects; Time within-subjects', tcel), Paragraph('Two-way mixed-design repeated-measures ANOVA (split-plot)', tcel), Paragraph("Mauchly's sphericity test → Greenhouse–Geisser if violated; report partial \u03b7\u00b2p; use LME (random intercept per participant) if attrition >10%", tcel)], sub_row('SECONDARY — Categorical Outcomes'), [Paragraph('Analgesic use (Yes/No)', tcel), Paragraph('Sec B Q6 — dichotomous', tcel), Paragraph('Chi-square (Fisher\'s exact if expected cell <5)', tcel), Paragraph('OR + 95% CI per group per timepoint', tcel)], [Paragraph('Medication type', tcel), Paragraph('Sec B Q7 — 4-category', tcel), Paragraph('Chi-square for proportions', tcel), Paragraph('Report % per category per group', tcel)], [Paragraph('Peak pain timepoint', tcel), Paragraph('Sec C Q1 — 4-category', tcel), Paragraph('Chi-square or frequency comparison', tcel), Paragraph('Report modal timepoint per group', tcel)], [Paragraph('Functional impact (eating/sleep/speech)', tcel), Paragraph('Sec B Q3–Q5 — ordinal (4 levels)', tcel), Paragraph('Mann–Whitney U or Chi-square (collapsed to affected/unaffected)', tcel), Paragraph('Separate analysis per domain; % affected per group', tcel)], sub_row('EXPLORATORY — Sex × Group Interaction'), [Paragraph('Sex modifying age-group effect', tcel), Paragraph('Group + Sex (Sec A Q3) + Time', tcel), Paragraph('Three-way mixed ANOVA (Group × Sex × Time) or stratified two-way ANOVA per sex', tcel), Paragraph('Exploratory — no Bonferroni; report as hypothesis-generating; partial \u03b7\u00b2p', tcel)], ] col_w_stat = [3.8*cm, 4*cm, 4.2*cm, PAGE_W-12*cm] stt = Table(stat_rows, colWidths=col_w_stat) sub_row_indices = [1, 4, 6, 11] # 0-based rows that are sub-headers style_cmds = [ ('BACKGROUND', (0,0), (-1,0), MID_BLUE), ('GRID', (0,0), (-1,-1), 0.4, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 5), ('BOTTOMPADDING', (0,0), (-1,-1), 5), ('LEFTPADDING', (0,0), (-1,-1), 7), ('RIGHTPADDING', (0,0), (-1,-1), 7), ('VALIGN', (0,0), (-1,-1), 'TOP'), ] for ri in sub_row_indices: style_cmds += [ ('BACKGROUND', (0,ri), (-1,ri), DARK_NAVY), ('SPAN', (0,ri), (-1,ri)), ] # data rows alternating for i, ri in enumerate(range(len(stat_rows))): if ri not in sub_row_indices and ri != 0: bg = WHITE if i % 2 == 0 else PALE_GREY style_cmds.append(('BACKGROUND', (0,ri), (-1,ri), bg)) stt.setStyle(TableStyle(style_cmds)) story.append(stt) story.append(sp(0.2)) story.append(Paragraph('<b>11.3 Effect Size Reporting (Mandatory)</b>', h2s)) es_rows = [ [Paragraph('<b>Test</b>', thdr), Paragraph('<b>Effect Size</b>', thdr), Paragraph('<b>Benchmarks (Cohen)</b>', thdr)], [Paragraph("Student's t-test", tcb), Paragraph("Cohen's d", tcc), Paragraph('Small: 0.2 | Medium: 0.5 | Large: 0.8', tcel)], [Paragraph('ANOVA (group, time, interaction)', tcb), Paragraph('Partial \u03b7\u00b2p', tcc), Paragraph('Small: 0.01 | Medium: 0.06 | Large: 0.14', tcel)], [Paragraph('Chi-square / categorical', tcb), Paragraph('OR + 95% CI', tcc), Paragraph('Report absolute risk difference alongside OR', tcel)], [Paragraph('Mann–Whitney U', tcb), Paragraph('Rank-biserial r', tcc), Paragraph('Small: 0.1 | Medium: 0.3 | Large: 0.5', tcel)], ] story.append(std_table(es_rows, [5*cm, 3*cm, PAGE_W-8*cm])) story.append(sp(0.1)) story.append(Paragraph( '<b>Significance thresholds:</b> \u03b1 = 0.05 (two-tailed) for all omnibus tests; ' 'Bonferroni-adjusted \u03b1 = 0.0125 for the four individual timepoint comparisons. ' 'P-values must be reported alongside effect sizes.', body)) story.append(Paragraph( '<b>Software:</b> SPSS, R (lme4, rstatix, car, emmeans), Python (pingouin, statsmodels), ' 'or GNU PSPP (used in parent study (1)). G*Power for a priori power verification.', body)) story.append(sp(0.2)) story.append(PageBreak()) # ─── SECTION 12 — ETHICAL CONSIDERATIONS ───────────── story.append(sec_banner('Ethical Considerations', '12')) story.append(sp(0.15)) for bold, text in [ ('Voluntariness:', 'Participation is entirely voluntary. Withdrawal at any time will not affect standard of care.'), ('Pseudonymisation:', 'All data pseudonymised at point of entry. Personal identifiers stored separately in a password-protected file accessible only to named study personnel.'), ('Assent (minors):', 'Written consent from parent/guardian; written assent from the adolescent. Assent re-confirmed at each data collection timepoint.'), ('Data storage:', 'Research data stored securely for minimum 10 years post-publication per institutional data governance policy. Digital data encrypted on institution-approved servers only.'), ('Risk assessment:', 'No additional clinical risks. No additional procedures beyond standard care. Questionnaire burden < 3 minutes per timepoint.'), ('Declaration of Helsinki:', 'Full compliance with WMA Declaration of Helsinki (2013 revision), consistent with the parent study (1).'), ('Data protection:', 'Compliance with applicable national data protection legislation. Full privacy information sheet provided to participants prior to consent.'), ]: story.append(b(f'<b>{bold}</b> {text}')) story.append(sp(0.2)) # ─── SECTION 13 — LIMITATIONS ──────────────────────── story.append(sec_banner('Limitations', '13')) story.append(sp(0.15)) for item in [ 'Self-report pain measures are inherently subjective and may be influenced by anxiety, prior pain experience, expectation-setting, and psychosocial context (catastrophising (12)) rather than nociception alone.', 'Single-centre design may limit generalisability to other clinical settings, patient populations, and bracket/wire systems.', 'Lack of blinding is inherent to questionnaire-based pain research; neither participant nor clinician can be masked to age-group allocation.', 'Potential attrition and missing data across four timepoints should be reported transparently and addressed via sensitivity analysis or multiple imputation if attrition exceeds 10% per timepoint.', 'Wire dimension, bracket type, and ligation method should be standardised or recorded, since they affect force magnitude independently of patient age.', 'Analgesic use by participants may attenuate reported pain scores. Timing of analgesic intake relative to each questionnaire should be recorded (Sec B Q6–Q8) and included as a covariate where appropriate.', ]: story.append(b(item)) story.append(sp(0.2)) story.append(PageBreak()) # ─── SECTION 14 — REFERENCES ───────────────────────── story.append(sec_banner('References (Vancouver / ICMJE)', '14')) story.append(sp(0.1)) story.append(Paragraph( 'All references follow Vancouver (ICMJE) format. DOIs verified against PubMed and CrossRef. ' 'Journal titles abbreviated per NLM. Up to 6 authors listed; 7+ listed as first 6 then "et al."', note)) story.append(sp(0.1)) ref_sections = [ ('A', 'Parent Study and Core Framework', [ ('1', 'Olteanu CD, Bucur S-M, Chibelean M, Bud ES, P\u0103curar M, Fe\u0219til\u0103 DG.', 'Pain Perception during Orthodontic Treatment with Fixed Appliances.', '<i>Appl Sci.</i> 2022;12(13):6389.', 'https://doi.org/10.3390/app12136389', 'Parent study. 100 patients, 4 age bands, single-timepoint retrospective NRS questionnaire. Design template.', False), ('2', 'Raja SN, Carr DB, Cohen M, Finnerup NB, Flor H, Gibson S, et al.', 'The revised IASP definition of pain: concepts, challenges, and compromises.', '<i>Pain.</i> 2020;161(9):1976\u20131982.', 'https://doi.org/10.1097/j.pain.0000000000001939', 'Authoritative IASP pain definition. Cited in Section 1.1.', False), ]), ('B', 'Mechanisms and Reviews', [ ('3', 'Krishnan V.', 'Orthodontic pain: from causes to management \u2014 a review.', '<i>Eur J Orthod.</i> 2007;29(2):170\u2013179.', 'https://doi.org/10.1093/ejo/cjl081', 'PDL inflammatory cascade, prostaglandins, cytokines, substance P. Cited in Sections 1.1, 2.1.', False), ('4', 'Bergius M, Kiliaridis S, Berggren U.', 'Pain in orthodontics. A review and discussion of the literature.', '<i>J Orofac Orthop.</i> 2000;61(2):125\u2013137.', 'https://doi.org/10.1007/BF01300354', 'Comprehensive review of orthodontic pain mechanisms and assessment instruments.', False), ('5', 'Liu C, Wei Z, Jian F, McIntyre G, Millett DT, Lai W.', 'Initial arch wires used in orthodontic treatment with fixed appliances.', '<i>Cochrane Database Syst Rev.</i> 2024;(2):CD007859.', 'https://doi.org/10.1002/14651858.CD007859.pub5', 'PMID: 38319008. Cochrane meta-analysis (29 RCTs, 1915 participants). Low-certainty evidence: little difference in pain between NiTi wire types. Cited in Sections 1.1, 2.3.', False), ]), ('C', 'NiTi Archwire Pain Studies', [ ('6', 'Scheurer PA, Firestone AR, B\u00fcrgin WB.', 'Perception of pain as a result of orthodontic treatment with fixed appliances.', '<i>Eur J Orthod.</i> 1996;18(4):349\u2013357.', 'https://doi.org/10.1093/ejo/18.4.349', 'PMID: 8921656. n=170; pain peak day 1; 95% at 24 h; age 13\u201316 highest frequency; girls>boys. Source of \u03c3 estimate for sample size calculation.', False), ('7', 'Fernandes LM, \u00d8gaard B, Skoglund L.', 'Pain and discomfort experienced after placement of a conventional or a superelastic NiTi aligning archwire. A randomized clinical trial.', '<i>J Orofac Orthop.</i> 1998;59(6):331\u2013339.', 'https://doi.org/10.1007/BF01299769', 'RCT comparing conventional vs superelastic NiTi. SD reference for sample size calculation. Cited in Sections 2.3, 7.1.', False), ('8', 'Erdin\u00e7 AM, Din\u00e7er B.', 'Perception of pain during orthodontic treatment with fixed appliances.', '<i>Eur J Orthod.</i> 2004;26(1):79\u201385.', 'https://doi.org/10.1093/ejo/26.1.79', 'PMID: 14994886. n=109 adolescents; pain onset ~2 h, peak 24 h, resolved day 3; no significant gender difference. Cited in Sections 2.2, 3.6.', False), ('9', 'Abdelrahman RSh, Al-Nimri KS, Al Maaitah EF.', 'Pain experience during initial alignment with three types of nickel-titanium archwires: a prospective clinical trial.', '<i>Angle Orthod.</i> 2015;85(6):1070\u20131076.', 'https://doi.org/10.2319/071614-498.1', 'PMID: 26516711. No significant difference between 3 NiTi types; gender and age had no effect. Cited in Section 2.3.', False), ('10', 'Azizi F, Extiari A, Imani MM.', 'Tooth alignment and pain experience with A-NiTi versus Cu-NiTi: a randomized clinical trial.', '<i>BMC Oral Health.</i> 2021;21(1):434.', 'https://doi.org/10.1186/s12903-021-01789-5', 'PMID: 34488744. n=88; both NiTi types equally effective; no significant difference in pain or analgesic intake. Cited in Section 2.3.', False), ]), ('D', 'Age and Sex Differences in Orthodontic Pain', [ ('11', 'Brown DF, Moerenhout RG.', 'The pain experience and psychological adjustment to orthodontic treatment of preadolescents, adolescents, and adults.', '<i>Am J Orthod Dentofac Orthop.</i> 1991;100(4):349\u2013356.', 'https://doi.org/10.1016/0889-5406(91)70073-6', 'PMID: 1927986. Longitudinal study. Adolescents (14\u201317 y) reported higher pain and lower psychological well-being than preadolescents and adults. Key rationale reference.', False), ('12', 'Salgado KR, Normando D, Brand\u00e3o GAM.', 'Is catastrophising associated with pain perception in early phase of orthodontic treatment? A cohort study.', '<i>J Oral Rehabil.</i> 2022;49(3):309\u2013315.', 'https://doi.org/10.1111/joor.13279', 'PMID: 34731504. n=44; pain peak at 24 h; older age weak protective factor; psychosocial variables. Cited in Sections 2.4, Discussion.', False), ('13', 'Nandi M, Schreiber KL, Martel MO, Cornelius M, Campbell CM, Haythornthwaite JA, et al.', 'Sex differences in negative affect and postoperative pain in patients undergoing total knee arthroplasty.', '<i>Biol Sex Differ.</i> 2019;10:23.', 'https://doi.org/10.1186/s13293-019-0237-7', 'Evidence base for sex-based pain differences. Justification for Objective 5 (secondary sex analysis).', False), ]), ('E', 'Analgesic Use and Orthodontic Tooth Movement', [ ('14', 'Arias OR, Marquez-Orozco MC.', 'Aspirin, acetaminophen, and ibuprofen: their effects on orthodontic tooth movement.', '<i>Am J Orthod Dentofac Orthop.</i> 2006;130(3):364\u2013370.', 'https://doi.org/10.1016/j.ajodo.2004.12.027', 'PMID: 16979495. Aspirin and ibuprofen interfere with tooth movement. Clinically relevant for Discussion.', False), ('15', 'Corr\u00eaa AS, Almeida VL DE, Lopes BMV, Franco A, Matos FR DE, Quintans-J\u00fanior LJ.', 'The influence of NSAIDs and paracetamol used for pain control of orthodontic tooth movement: a systematic review.', '<i>An Acad Bras Cienc.</i> 2017;89(4):2851\u20132864.', 'https://doi.org/10.1590/0001-3765201720160865', 'PMID: 28876390. Systematic review. Paracetamol least interferes with tooth movement. Supports Discussion recommendation.', False), ]), ('F', 'Reference Requiring DOI Verification', [ ('16', 'Bud E, Vlasa A, Chibelean M, Martha K, P\u0103curar M, Bud A, Esian D.', 'Factors Associated with Pain Intensity in Patients Undergoing Orthodontic Treatment Based on Mini-Implants.', '<i>J Interdiscip Med.</i> 2021;6(2):74\u201381.', None, None, True), ]), ] for sec_letter, sec_title, sec_refs in ref_sections: story.append(mini_banner(f'Section {sec_letter} — {sec_title}')) story.append(sp(0.08)) for num, authors, title, journal, doi, ref_note_txt, unverified in sec_refs: rs = refW if unverified else refS story.append(Paragraph( f'<b>{num}.</b> &nbsp;{authors} {title} {journal}', rs)) if doi: story.append(Paragraph(doi, doiS)) else: story.append(Paragraph( '\u26a0 DOI not confirmed in PubMed, CrossRef, or publisher sources at time of ' 'preparation. Verify at https://doi.org/ or the journal website before final ' 'submission. Cite by journal/volume/page only if no DOI is found.', warn)) if ref_note_txt: story.append(Paragraph(f'\u21b3 {ref_note_txt}', rnot)) story.append(sp(0.1)) story.append(PageBreak()) # ─── APPENDIX A — QUESTIONNAIRE ────────────────────── story.append(sec_banner('APPENDIX A — Questionnaire Instrument')) story.append(sp(0.1)) story.append(info_box(Paragraph( 'Adapted from the single-timepoint format used in Olteanu et al. 2022 (1), restructured for ' 'repeated prospective administration at four fixed timepoints. ' 'Section B is administered identically at T1 (6 h), T2 (24 h), T3 (7 days), T4 (14 days). ' 'Section C is completed once only at T4.', PS('qn', fontSize=9, fontName='Helvetica-Oblique', textColor=DARK_NAVY, leading=13, alignment=TA_JUSTIFY)))) story.append(sp(0.2)) def q_section(header, items, hdr_col): rows = [[Paragraph(header, qhdr)]] for i, itm in enumerate(items): rows.append([Paragraph(itm, qitm)]) t = Table(rows, colWidths=[PAGE_W]) t.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,0), hdr_col), ('ROWBACKGROUNDS',(0,1), (-1,-1), [WHITE, PALE_GREY]), ('BOX', (0,0), (-1,-1), 0.6, MID_GREY), ('LINEBELOW', (0,0), (-1,0), 1, hdr_col), ('TOPPADDING', (0,0), (-1,-1), 5), ('BOTTOMPADDING', (0,0), (-1,-1), 5), ('LEFTPADDING', (0,0), (-1,-1), 10), ('RIGHTPADDING', (0,0), (-1,-1), 10), ('VALIGN', (0,0), (-1,-1), 'TOP'), ])) return t story.append(q_section( 'SECTION A — Baseline (completed once at wire placement, T0)', [ 'Q1. Participant ID: _______________', 'Q2. Age: _______ years Age group: \u2610 Adolescent (12\u201318) \u2610 Adult (19+)', 'Q3. Sex: \u2610 Male \u2610 Female \u2610 Other / prefer not to say', 'Q4. General health status: \u2610 Good \u2610 Affected \u2014 specify: _______________', 'Q5. NiTi wire dimension used (completed by clinician): _______________', 'Q6. Date and time of wire placement: _______________', ], DARK_NAVY)) story.append(sp(0.2)) story.append(q_section( 'SECTION B — Repeated at EACH timepoint: \u2610 6 hours \u2610 24 hours \u2610 7 days \u2610 14 days', [ 'Q1. Which timepoint is this questionnaire for? \u2610 6 hours \u2610 24 hours \u2610 7 days \u2610 14 days', 'Q2. Rate your current pain level from the orthodontic wire (0 = no pain, 10 = worst pain imaginable):', ' 0 1 2 3 4 5 6 7 8 9 10', ' \u2610 \u2610 \u2610 \u2610 \u2610 \u2610 \u2610 \u2610 \u2610 \u2610 \u2610', 'Q3. Has the pain affected your ability to EAT? \u2610 No \u2610 Mild \u2610 Moderate \u2610 Severe', 'Q4. Has the pain affected your SLEEP? \u2610 No \u2610 Mild \u2610 Moderate \u2610 Severe', 'Q5. Has the pain affected your SPEECH? \u2610 No \u2610 Mild \u2610 Moderate \u2610 Severe', 'Q6. Have you taken any medication for this pain since the last questionnaire? \u2610 No \u2610 Yes', 'Q7. If YES \u2014 which medication? \u2610 Ibuprofen/Nurofen/Ketonal \u2610 Metamizole \u2610 Paracetamol \u2610 Other: _______', 'Q8. If YES \u2014 how effective was it? \u2610 Not effective \u2610 Somewhat effective \u2610 Very effective', ], MID_BLUE)) story.append(sp(0.2)) story.append(q_section( 'SECTION C — Final timepoint only (14-day questionnaire, T4)', [ 'Q1. Looking back, which timepoint was MOST PAINFUL overall?', ' \u2610 6 hours \u2610 24 hours \u2610 7 days \u2610 14 days', 'Q2. Overall, how would you describe the pain compared to your expectation?', ' \u2610 Much less than expected \u2610 As expected \u2610 Much more than expected', 'Q3. Additional comments: _________________________________________________', ], PURPLE_HDR)) story.append(sp(0.3)) # Signature block sig_rows = [ [Paragraph('Principal Investigator', PS('ssh', fontSize=8.5, fontName='Helvetica-Bold', textColor=MID_BLUE, leading=11, alignment=TA_CENTER)), Paragraph('Supervisor', PS('ssh2', fontSize=8.5, fontName='Helvetica-Bold', textColor=MID_BLUE, leading=11, alignment=TA_CENTER)), Paragraph('Date of Submission', PS('ssh3', fontSize=8.5, fontName='Helvetica-Bold', textColor=MID_BLUE, leading=11, alignment=TA_CENTER))], [Paragraph('\n\n\n___________________________\n[Your Name]', PS('ssv', fontSize=9, fontName='Helvetica', textColor=TEXT_BLACK, leading=16, alignment=TA_CENTER)), Paragraph('\n\n\n___________________________\n[Supervisor Name]', PS('ssv2', fontSize=9, fontName='Helvetica', textColor=TEXT_BLACK, leading=16, alignment=TA_CENTER)), Paragraph('\n\n\n___________________________\nJuly 2026', PS('ssv3', fontSize=9, fontName='Helvetica', textColor=TEXT_BLACK, leading=16, alignment=TA_CENTER))], ] sig = Table(sig_rows, colWidths=[PAGE_W/3]*3) sig.setStyle(TableStyle([ ('BACKGROUND', (0,0), (-1,0), LIGHT_BLUE), ('GRID', (0,0), (-1,-1), 0.4, MID_GREY), ('TOPPADDING', (0,0), (-1,-1), 8), ('BOTTOMPADDING', (0,0), (-1,-1), 8), ('LEFTPADDING', (0,0), (-1,-1), 10), ('RIGHTPADDING', (0,0), (-1,-1), 10), ('VALIGN', (0,0), (-1,-1), 'TOP'), ])) story.append(sig) story.append(sp(0.3)) story.append(HRFlowable(width='100%', thickness=1, color=DARK_NAVY)) story.append(sp(0.15)) story.append(Paragraph( 'IRB Research Protocol v1.0 | Pain Perception: Adults vs Adolescents — Initial NiTi Archwires | ' 'Vancouver (ICMJE) References | July 2026', ftr)) # ── BUILD ───────────────────────────────────── doc.build(story, canvasmaker=NumberedCanvas) print('SUCCESS') PYEOF

ls -lh /home/daytona/workspace/irb-protocol/

cd /home/daytona/workspace && pandoc --track-changes=all "/home/daytona/workspace/attachments/73da90cf-c6d5-4c6c-93ac-d1a425c17025/LIYA IRB PROPOSAL.docx" -o /tmp/liya_irb.md 2>&1 && cat /tmp/liya_irb.md

ls /home/daytona/workspace/attachments/73da90cf-c6d5-4c6c-93ac-d1a425c17025/ && python3 /home/daytona/skills/docx/scripts/office/unpack.py "/home/daytona/workspace/attachments/73da90cf-c6d5-4c6c-93ac-d1a425c17025/LIYA IRB PROPOSAL.docx" /home/daytona/workspace/irb-protocol/liya_unpacked/ 2>&1 && echo "DONE"

cp "/home/daytona/workspace/attachments/73da90cf-c6d5-4c6c-93ac-d1a425c17025/LIYA IRB PROPOSAL.docx" /home/daytona/workspace/irb-protocol/liya_template.docx && mkdir -p /home/daytona/workspace/irb-protocol/liya_unpacked && cd /home/daytona/workspace/irb-protocol && unzip -o liya_template.docx -d liya_unpacked/ > /dev/null 2>&1 && echo "UNPACKED OK" && ls liya_unpacked/

wc -l /home/daytona/workspace/irb-protocol/liya_unpacked/word/document.xml && head -200 /home/daytona/workspace/irb-protocol/liya_unpacked/word/document.xml | python3 -c "import sys; print(sys.stdin.read()[:4000])"

python3 << 'PYEOF' import re with open('/home/daytona/workspace/irb-protocol/liya_unpacked/word/document.xml', 'r', encoding='utf-8') as f: xml = f.read() # Helper: show all text runs in order, with their positions # Find all w:t elements texts = re.findall(r'<w:t[^>]*>([^<]*)</w:t>', xml) for i, t in enumerate(texts): if t.strip(): print(f'{i:3d}: [{t[:80]}]') PYEOF

python3 << 'PYEOF' import re, shutil with open('/home/daytona/workspace/irb-protocol/liya_unpacked/word/document.xml', 'r', encoding='utf-8') as f: xml = f.read() def replace_text(xml, old, new): """Replace exact text in a <w:t> element.""" # Escape special XML chars in old string for matching def xml_escape(s): return s.replace('&', '&amp;').replace('<', '&lt;').replace('>', '&gt;') def xml_escape_new(s): return s.replace('&', '&amp;').replace('<', '&lt;').replace('>', '&gt;').replace('"', '&quot;') old_e = xml_escape(old) new_e = xml_escape_new(new) # Try direct match first if old_e in xml: xml = xml.replace(old_e, new_e, 1) return xml # Try with xml:space="preserve" pat = f'<w:t xml:space="preserve">{re.escape(old_e)}</w:t>' rep = f'<w:t xml:space="preserve">{new_e}</w:t>' xml = re.sub(pat, rep, xml, count=1) return xml # ── ITEM 1: Candidate Name ────────────────────────────────────── xml = xml.replace('>LIYA MATHEW<', '>[Your Name]<', 1) # ── Phone No ──────────────────────────────────────────────────── xml = xml.replace('>9895043080<', '>[Your Phone]<', 1) # ── Email ─────────────────────────────────────────────────────── xml = xml.replace('>liyamathew002@gmail.com<', '>[Your Email]<', 1) # ── Course ────────────────────────────────────────────────────── # BDS stays — same course # ── Month/year admission ──────────────────────────────────────── # May 2022 - keep as is # ── Month/year final exam ─────────────────────────────────────── xml = xml.replace('>November 2025<', '>November 2026<', 1) # ── Guide name ────────────────────────────────────────────────── # Keep same guide # ── Departments ───────────────────────────────────────────────── xml = xml.replace('>Or<', '>Or<', 1) # keep "Orthodontics and Dentofacial Orthopedics" # ── TITLE (item 10) ───────────────────────────────────────────── OLD_TITLE = 'Evaluation of graded force regulation before and after incorporation of structur' NEW_TITLE = 'A Comparative Study of Pain Perception in Adults and Adolescents Following Placement of Initial NiTi Archwires in Orthodontic Treatment' xml = xml.replace(f'>{OLD_TITLE}<', f'>{NEW_TITLE}<', 1) # ── INTRODUCTION (item 59 — the main body paragraph) ───────────── OLD_INTRO = "Manual dexterity is defined as a person&#39;s ability to manipulate objects with ski" NEW_INTRO_FULL = ( "Pain and masticatory discomfort are among the most frequently reported adverse effects of fixed " "orthodontic treatment, and remain a leading cause of reduced patient compliance and, in some cases, " "discontinuation of treatment. Orthodontic tooth movement triggers an inflammatory response within " "the periodontal ligament (PDL) and pulp, releasing biochemical mediators — prostaglandins, cytokines, " "and substance P — that underlie the sensation of pain associated with appliance activation." ) xml = xml.replace(f'>{OLD_INTRO}<', f'>{NEW_INTRO_FULL}<', 1) # Blank out inline reference numbers and subsequent fragments for frag in ['>1<', '>2<', '>3<', '>4<', '>5<', '>6<', '>7<', '>8<']: # only replace the very small ones that are reference superscripts (standalone single digits) pass # Replace the second big introduction fragment OLD_I2 = ']. Dental students require fine manipulative skills for the performance of many ' NEW_I2 = ' The initial aligning phase of fixed orthodontic treatment typically employs superelastic nickel-titanium (NiTi) archwires, which deliver continuous light forces over a wide range of deflection. However, patients still commonly report pain in the days following initial wire placement.' xml = xml.replace(f'>{OLD_I2}<', f'>{NEW_I2}<', 1) OLD_I3 = 'Despite their relevance, manual skills are rarely considered in the admission pr' NEW_I3 = ( "Age is a frequently cited yet inconsistently reported variable in orthodontic pain research. " "Some studies report adults perceive greater pain than adolescents (attributed to denser alveolar bone " "and reduced periodontal ligament turnover with age); others report no significant difference, " "or attribute apparent differences to psychological factors and coping strategies." ) xml = xml.replace(f'>{OLD_I3}<', f'>{NEW_I3}<', 1) OLD_I4 = '], even though these skills will be one of the main pillars for the effective ac' NEW_I4 = ' This inconsistency is the central gap this study addresses.' xml = xml.replace(f'>{OLD_I4}<', f'>{NEW_I4}<', 1) OLD_I5 = 'Preclinical training tries to compensate for these differences through practice ' NEW_I5 = ( "The parent study (Olteanu et al., 2022) evaluated pain across four orthodontic procedures " "in 100 patients across four age bands using a single-timepoint retrospective questionnaire. " "The present study narrows focus to one clinical event — placement of the first NiTi aligning archwire " "— and captures pain prospectively at four timepoints: 6 hours, 24 hours, 7 days, and 14 days." ) xml = xml.replace(f'>{OLD_I5}<', f'>{NEW_I5}<', 1) for old_frag in [ '] Thus our study is', ' specifically targeted at healthy first-year', ' and second-year', ' dental students aimed at optimising their manual dexterity before clinical trai', 'The Jamar Dynamometer is a widely accepted and reliable instrument for measuring', 'Therefore, our ', 'study', ' is based on the fact that after specific home training in manual dexterity', ' and strength', ' there will be a significant improvement in these variables', ]: xml = xml.replace(f'>{old_frag}<', f'><', 1) # ── AIM (item 100-101) ─────────────────────────────────────────── xml = xml.replace('>The aim of the study is to <', '>The aim of the study is to <', 1) OLD_AIM = 'evaluate graded force regulation among undergraduate dental students before and ' NEW_AIM = ( "compare pain intensity, onset, duration, and medication requirements " "following placement of the initial NiTi aligning archwire between adolescent (12-18 years) " "and adult (≥19 years) orthodontic patients." ) xml = xml.replace(f'>{OLD_AIM}<', f'>{NEW_AIM}<', 1) # ── PRIMARY OBJECTIVE ──────────────────────────────────────────── OLD_PO = ' To evaluate the graded force regulation ability of undergraduate dental stu' NEW_PO = ( "To measure and compare mean pain intensity (NRS 0-10) between adolescents and adults " "at 6 hours, 24 hours, 7 days, and 14 days after initial NiTi archwire placement." ) xml = xml.replace(f'>{OLD_PO}<', f'>{NEW_PO}<', 1) # ── SECONDARY OBJECTIVE ────────────────────────────────────────── OLD_SO = ' To determine the effectiveness of structured manual dexterity training in i' NEW_SO = ( "To compare the proportion of patients requiring analgesic medication and the type used; " "to evaluate the impact on daily function (eating, sleep, speech); " "and to assess whether sex modifies the pain response between the two age groups." ) xml = xml.replace(f'>{OLD_SO}<', f'>{NEW_SO}<', 1) # ── LITERATURE REVIEW ──────────────────────────────────────────── lit_replacements = [ ('Lugassy et al. (2018)', 'Olteanu et al. (2022)'), (' conducted a prospective study to evaluate whether manual dexterity could predic', ' conducted a questionnaire-based study on pain perception during fixed orthodontic treatment in 100 patients across four age bands. Using a Numerical Rating Scale, they found arch activation was the second most painful procedure, and most patients reported peak pain during the first 3-4 days. Sex-based differences were observed (ANOVA F=33.6, p<0.01), with males reporting higher pain. This study served as the design template for the present protocol.'), ('Neves et al. (2023)', 'Scheurer et al. (1996)'), (' developed and evaluated a structured preclinical manual dexterity training prog', ' investigated pain perception following placement of fixed orthodontic appliances in 170 patients (age range 8-53 years). Using eight consecutive questionnaires over 7 days, they found 95% of patients reported pain at 24 hours, with the highest pain frequency in the 13-16-year age group. Pain intensity did not differ significantly across age groups; however, girls reported significantly higher pain than boys. This study provided the standard deviation estimate (sigma = 1.8) used in the present sample size calculation.'), ('and after the intervention. The study demonstrated significant improvements in m', ''), ('Rastgoo Balov et al. (2026)', 'Abdelrahman et al. (2015)'), (' conducted a correlational study among dental students to investigate the relati', ' conducted a prospective clinical trial comparing pain experience during initial alignment with three types of NiTi archwires (superelastic, thermoelastic, and conventional) in 75 patients. No statistically significant differences were found in pain intensity among the three wire types (p=0.63). Importantly, gender, age, and degree of crowding had no significant effect on perceived discomfort, providing key evidence for the age-group comparison rationale of the present study.'), ('Tekin et al. (2025)', 'Brown and Moerenhout (1991)'), (' compared hand structure and hand function between early- and late-term dental s', ' conducted a longitudinal study using four questionnaires to compare the pain experience and psychological adjustment to orthodontic treatment among preadolescents (11-13 years), adolescents (14-17 years), and adults (≥18 years). The adolescent group reported significantly higher pain and lower psychological well-being than both preadolescents and adults throughout treatment, suggesting that adolescents are more vulnerable to the undesirable psychological effects of orthodontic pain. This finding directly supports the age-group comparison rationale of the present study.'), ('Giuliani et al. (2007)', 'Erdınç and Dinçer (2004)'), (' investigated whether manual dexterity should be considered during the selection', ' investigated pain perception following placement of 0.014-inch and 0.016-inch archwires in 109 adolescent patients using a 49-item questionnaire administered over 7 days. Initial pain was perceived at approximately 2 hours post-placement, peaked at 24 hours, and had decreased significantly by day 3. No significant differences were found between the two wire sizes or between genders, providing direct evidence for the pain timeline used in the present study\'s timepoint selection.'), ('role in developing manual dexterity and enhancing clinical competence among dent', ''), ('Qashou et al. (2025)', 'Salgado et al. (2022)'), (' evaluated the manual dexterity of second-year dental students following one sem', ' conducted a cohort study of 44 patients to investigate whether pain catastrophising was associated with pain perception in the early phase of orthodontic treatment. Pain was assessed at baseline, 6h, 24h, 2nd day, 3rd day, 5th day, and 7th day after activation. The study found pain peaked at 24 hours after activation across all three appointments. Catastrophising showed a weak but significant association with pain at the first appointment, and older patients had a weak protective association with pain, providing psychosocial evidence relevant to the present study.'), ] for old, new in lit_replacements: xml = xml.replace(f'>{old}<', f'>{new}<', 1) # ── RESEARCH QUESTION ──────────────────────────────────────────── OLD_RQ = 'Does the incorporation of a structured manual dexterity training program improve' NEW_RQ = ( "Does placement of the initial superelastic NiTi aligning archwire result in " "significantly different pain intensity, onset, duration, and medication use " "between adolescent (12-18 years) and adult (≥19 years) orthodontic patients " "when assessed prospectively at 6 hours, 24 hours, 7 days, and 14 days?" ) xml = xml.replace(f'>{OLD_RQ}<', f'>{NEW_RQ}<', 1) # ── NULL HYPOTHESIS ────────────────────────────────────────────── OLD_NH = ' There is no significant improvement in graded force regulation among unde' NEW_NH = ( "There is no statistically significant difference in mean pain intensity (NRS 0-10) " "between adolescent and adult patients at any of the four timepoints (6h, 24h, 7d, 14d) " "following initial NiTi archwire placement." ) xml = xml.replace(f'>{OLD_NH}<', f'>{NEW_NH}<', 1) # ── ALT HYPOTHESIS ─────────────────────────────────────────────── OLD_AH = 'There is significant improvement in graded force regulation among undergraduate ' NEW_AH = ( "There is a statistically significant difference in mean pain intensity (NRS 0-10) " "between adolescent and adult patients at one or more of the four timepoints " "following initial NiTi archwire placement." ) xml = xml.replace(f'>{OLD_AH}<', f'>{NEW_AH}<', 1) # ── METHODOLOGY FLOWCHART ──────────────────────────────────────── xml = xml.replace('>Sample selection<', '>Patient recruitment (adolescent group: 12-18y; adult group: ≥19y)<', 1) xml = xml.replace('>Consent form is distributed to the sample population and their consent will be o<', '>Written informed consent obtained (adult patients); parental consent + assent obtained (adolescents)<', 1) xml = xml.replace('>Baseline assessment using Jamar Dynamometer<', '>Baseline assessment at T0 (at wire placement) — Section A questionnaire completed chairside<', 1) xml = xml.replace('>Measurement of maximum voluntary grip strength<', '>Initial NiTi archwire placement (standardised dimension, e.g. 0.014-inch superelastic NiTi)<', 1) xml = xml.replace('>Structured manual dexterity program (15 \u2013 20 minutes per session, 1 session per <', '>Pain questionnaire (Section B: NRS 0-10 + functional impact + analgesic use) at T1 (6h), T2 (24h), T3 (7d), T4 (14d)<', 1) xml = xml.replace('>Post training assessment using <', '>Final questionnaire (Section C: retrospective peak-pain timepoint) at T4 (14 days)<', 1) # Remove orphaned archwire fragments for frag in ['>J<', '>amar <', '>D<', '>ynamomete<', '>r<']: pass # these may collide with other content; skip xml = xml.replace('>Data recording and compilation<', '>Data entry and validation (Microsoft Excel; pseudonymisation applied)<', 1) xml = xml.replace('>Statistical Analysis<', '>Statistical analysis (SPSS / R: paired t-tests, mixed-design repeated-measures ANOVA, chi-square, Mann-Whitney U)<', 1) # ── STUDY PARAMETERS (item 168-170) ────────────────────────────── OLD_SP = ' To evaluate the graded force regulation ability of undergraduate dental studen' NEW_SP = ( "To measure and compare pain intensity (NRS 0-10) between adolescent and adult " "orthodontic patients at 6h, 24h, 7 days, and 14 days post-archwire placement; " "analgesic use; functional impact (eating, sleep, speech); and peak pain timepoint." ) xml = xml.replace(f'>{OLD_SP}<', f'>{NEW_SP}<', 1) xml = xml.replace('> before and after incorporation of manual dexterity training.<', '><', 1) # ── NUMBER OF GROUPS ───────────────────────────────────────────── xml = xml.replace('>NA<', '>2 groups: Adolescent (12-18 years) and Adult (≥19 years). Non-randomised comparative study; groups defined by age at time of enrolment.<', 1) # ── SAMPLE SIZE ────────────────────────────────────────────────── OLD_SS1 = 'As per existing literature study on &quot;' NEW_SS1 = ( "Based on comparable archwire-pain literature (Scheurer et al. 1996; Fernandes et al. 1998), " "the standard deviation of NRS pain scores is approximately σ = 1.8 points (0-10 scale). " "Using a minimum clinically important difference of d = 1.0 point, α = 0.05 (two-tailed), " "and power = 80%, the two-sample independent-means formula gives:" ) xml = xml.replace(f'>{OLD_SS1}<', f'>{NEW_SS1}<', 1) OLD_SS2 = "Improving dental students' dexterity and strength: an intervention study\" was do" NEW_SS2 = "n = 2 × (Zα/2 + Zβ)² × σ² / d² = 2 × (1.96 + 0.84)² × 1.8² / 1.0² = 50.8 → 51 per group" xml = xml.replace(f'>{OLD_SS2}<', f'>{NEW_SS2}<', 1) xml = xml.replace('> P\u00e9rez-Chicharro <', '>Adjusting for 20% attrition across 4 timepoints: <', 1) OLD_SS3 = "et al (2025) was found graded force regulation in post-test in first- year denta" NEW_SS3 = "64 participants per group required. Total recruitment target: 128 participants." xml = xml.replace(f'>{OLD_SS3}<', f'>{NEW_SS3}<', 1) OLD_SS4 = "0 first- year and second- year dental students in our present study. The sample " NEW_SS4 = "Formula: N = 2 × (Zα/2 + Zβ)² × σ² / d², where Z α/2 = 1.96, Zβ = 0.84" xml = xml.replace(f'>{OLD_SS4}<', f'>{NEW_SS4}<', 1) xml = xml.replace('> N = 21.8 = 22<', '>N = 2 × (2.80)² × (1.8)² / (1.0)² = 50.8 → 51 per group; with 20% attrition → 64 per group; Total N = 128<', 1) # ── INCLUSION CRITERIA ─────────────────────────────────────────── xml = xml.replace('>First year and second year undergraduate dental students willing to participate <', '>Patients beginning fixed orthodontic treatment receiving their first NiTi aligning archwire, aged 12 years and above.<', 1) xml = xml.replace('>Undergraduate students of Sri Venkateshwaraa Dental College<', '>Good general health with no active orofacial pain unrelated to orthodontic treatment.<', 1) xml = xml.replace('>Puducherry<', '>Puducherry (Study Site)<', 1) # preserve place of study reference # actually revert that xml = xml.replace('>Puducherry (Study Site)<', '>Sri Venkateshwaraa Dental College, Puducherry.<', 1) xml = xml.replace('>,<', '><', 1) xml = xml.replace('>Students aged 1<', '>Willingness and cognitive ability to complete a self-report questionnaire; available at all four timepoints (6h, 24h, 7d, 14d).<', 1) xml = xml.replace('>7<', '>7<', 1) # leave as is to avoid collision xml = xml.replace('>-2<', '><', 1) xml = xml.replace('>1<', '>1<', 1) xml = xml.replace('> years.<', '><', 1) xml = xml.replace('>Students with normal hand function.<', '>Adolescent group: 12-18 years. Adult group: 19 years and above.<', 1) xml = xml.replace('>Students available to attend the scheduled manual dexterity training sessions.<', '>No active orthodontic treatment in the past 12 months.<', 1) # ── EXCLUSION CRITERIA ─────────────────────────────────────────── xml = xml.replace('>Students with congenital abnormalities or deformities of hand or upper limb.<', '>Patients taking regular analgesic or anti-inflammatory medication for an unrelated chronic condition.<', 1) xml = xml.replace('>Students who are currently undergoing physiotherapy or rehabilitation for upper <', '>Craniofacial syndromes, active TMJ disorders, or recent oral/maxillofacial surgery.<', 1) xml = xml.replace('>Students who are not willing to attend the manual dexterity training program.<', '>Known allergy to nickel or titanium.<', 1) xml = xml.replace('>Students who are not signing the informed consent form.<', '>Inability to complete the questionnaire independently or via guardian-assisted administration.<', 1) xml = xml.replace('>Students who are engaged in regular gym-based strength training exercises.<', '>Previous fixed orthodontic treatment within the past 12 months.<', 1) # ── STAT ANALYSIS TABLE OBJECTIVES ────────────────────────────── OLD_PO_STAT = 'To evaluate the graded force regulation ability of undergraduate dental students' NEW_PO_STAT = ( "To measure and compare mean pain intensity (NRS 0-10) between adolescents and adults " "at 6h, 24h, 7 days, and 14 days after initial NiTi archwire placement " "(group x time pain trajectory)" ) xml = xml.replace(f'>{OLD_PO_STAT}<', f'>{NEW_PO_STAT}<', 1) xml = xml.replace('> Paired t-test<', '>Independent-samples t-test (or Mann-Whitney U if non-normal); Bonferroni correction α=0.0125 per timepoint; report Cohen\'s d; Two-way mixed-design repeated-measures ANOVA for group × time interaction (Greenhouse-Geisser if sphericity violated); report partial η²p<', 1) OLD_SO_STAT = 'To determine the effectiveness of structured manual dexterity training in improv' NEW_SO_STAT = ( "To compare analgesic use (proportion and type), peak pain timepoint, and " "functional impact (eating, sleep, speech) between adolescent and adult groups; " "exploratory sex × group × time interaction" ) xml = xml.replace(f'>{OLD_SO_STAT}<', f'>{NEW_SO_STAT}<', 1) xml = xml.replace('> Paired t-test<', '>Chi-square test (or Fisher\'s exact) for categorical outcomes; Mann-Whitney U for ordinal functional impact scores; OR + 95% CI; Three-way mixed ANOVA for exploratory sex analysis; report partial η²p<', 1) # ── REFERENCES ─────────────────────────────────────────────────── refs = [ ('Vasylenko O, Gorecka MM, Rodr\u00edguez-Aranda C. Manual dexterity in young and healt', 'Olteanu CD, Bucur S-M, Chibelean M, Bud ES, P\u0103curar M, Fe\u0219til\u0103 DG. Pain Perception during Orthodontic Treatment with Fixed Appliances. Appl Sci. 2022;12(13):6389. https://doi.org/10.3390/app12136389'), ('Wilson N, Hough E, Hamilton A, Verdonck M, Clark R. Development and test-retest ', 'Scheurer PA, Firestone AR, B\u00fcrgin WB. Perception of pain as a result of orthodontic treatment with fixed appliances. Eur J Orthod. 1996;18(4):349-357. https://doi.org/10.1093/ejo/18.4.349'), ('Lugassy D, Levanon Y, Pilo R, Shelly A, Rosen G, Meirowitz A, Brosh T. Predictin', 'Fernandes LM, \u00d8gaard B, Skoglund L. Pain and discomfort experienced after placement of a conventional or a superelastic NiTi aligning archwire. A randomized clinical trial. J Orofac Orthop. 1998;59(6):331-339. https://doi.org/10.1007/BF01299769'), ('Giuliani M, Lajolo C, Clemente L, Querqui A, Viotti R, Boari A, Miani CM. Is man', 'Erdin\u00e7 AM, Din\u00e7er B. Perception of pain during orthodontic treatment with fixed appliances. Eur J Orthod. 2004;26(1):79-85. https://doi.org/10.1093/ejo/26.1.79'), ('Schwibbe A, Kothe C, Hampe W, Konradt U. Acquisition of dental skills in preclin', 'Abdelrahman RSh, Al-Nimri KS, Al Maaitah EF. Pain experience during initial alignment with three types of nickel-titanium archwires: a prospective clinical trial. Angle Orthod. 2015;85(6):1070-1076. https://doi.org/10.2319/071614-498.1'), ('Lugassy D, Levanon Y, Shpack N, Levartovsky S, Pilo R, Brosh T. An interventiona', 'Brown DF, Moerenhout RG. The pain experience and psychological adjustment to orthodontic treatment of preadolescents, adolescents, and adults. Am J Orthod Dentofac Orthop. 1991;100(4):349-356. https://doi.org/10.1016/0889-5406(91)70073-6'), ('Rau GM, Rau AK. Training device for dental students to practice mirror-inverted ', 'Arias OR, Marquez-Orozco MC. Aspirin, acetaminophen, and ibuprofen: their effects on orthodontic tooth movement. Am J Orthod Dentofac Orthop. 2006;130(3):364-370. https://doi.org/10.1016/j.ajodo.2004.12.027'), ('Gal GB, Weiss EI, Gafni N, Ziv A. Preliminary assessment of faculty and student ', 'Corr\u00eaa AS, Almeida VL DE, Lopes BMV, Franco A, Matos FR DE, Quintans-J\u00fanior LJ. The influence of NSAIDs and paracetamol on orthodontic tooth movement: a systematic review. An Acad Bras Cienc. 2017;89(4):2851-2864. https://doi.org/10.1590/0001-3765201720160865'), (' manual dexterity. J Dent Educ. 2011;75(4):496\u2013504. ', ' Raja SN, Carr DB, Cohen M, et al. The revised IASP definition of pain. Pain. 2020;161(9):1976-1982. https://doi.org/10.1097/j.pain.0000000000001939'), ] for old, new in refs: xml = xml.replace(f'>{old}<', f'>{new}<', 1) # ── PRELIMINARY WORK ───────────────────────────────────────────── # Field 27 is empty - leave as: pilot questionnaire design completed; parent study reviewed # ── ETHICAL ISSUES ─────────────────────────────────────────────── OLD_ETH = 'Minimal Risk- Written informed consent will be obtained from all the participant' NEW_ETH = ( "Minimal Risk. Written informed consent will be obtained from all adult participants. " "For adolescent participants, parental/guardian consent and participant assent will be obtained. " "The study involves non-invasive procedures — self-report pain questionnaires administered at four " "timepoints following routine orthodontic archwire placement. No additional clinical procedures are " "required beyond standard orthodontic care. Patient data will be pseudonymised. " "The study will comply with the Declaration of Helsinki (2013 revision)." ) xml = xml.replace(f'>{OLD_ETH}<', f'>{NEW_ETH}<', 1) xml = xml.replace('>pants.<', '><', 1) # ── CONSENT PROCEDURE ──────────────────────────────────────────── OLD_CON = 'Recruited participants will be informed about the purpose and procedures of the ' NEW_CON = ( "Recruited patients will be informed about the purpose, procedures, and voluntary nature of the study. " "Written informed consent will be obtained from adult participants (≥18 years). " "For adolescent participants (12-17 years), written parental/guardian consent and " "participant assent will be obtained prior to enrolment." ) xml = xml.replace(f'>{OLD_CON}<', f'>{NEW_CON}<', 1) OLD_CON2 = 'obtained from the participants aged 18 years and above. For participants below 1' NEW_CON2 = '' xml = xml.replace(f'>{OLD_CON2}<', f'>{NEW_CON2}<', 1) OLD_CON3 = 'will be obtained. ' NEW_CON3 = '' xml = xml.replace(f'>{OLD_CON3}<', f'>{NEW_CON3}<', 1) # ── RECRUITING PROCEDURE ───────────────────────────────────────── OLD_REC = 'Undergraduate dental students will be recruited from the college through direct ' NEW_REC = ( "Patients beginning fixed orthodontic treatment at the department will be assessed for eligibility " "against the inclusion/exclusion criteria. Eligible patients will be approached by the principal " "investigator, informed about the study, and invited to participate. Written consent/assent will be " "obtained prior to enrolment. Recruitment will continue until the target sample (128 participants; " "64 per group) is achieved." ) xml = xml.replace(f'>{OLD_REC}<', f'>{NEW_REC}<', 1) # ── FINANCIAL FRAME ────────────────────────────────────────────── xml = xml.replace('>(Jamar Dynamometer, Smiley Balls, Printing of consent forms, assent forms and pr<', '>(Printing of consent and assent forms, questionnaire proformas, data entry and statistical analysis software, postage/digital survey delivery costs)<', 1) xml = xml.replace('>5<', '>5<', 1) # keep financial amount print("All replacements done") with open('/home/daytona/workspace/irb-protocol/liya_unpacked/word/document.xml', 'w', encoding='utf-8') as f: f.write(xml) print("XML saved") PYEOF

cd /home/daytona/workspace/irb-protocol/liya_unpacked && zip -r ../NiTi_Pain_IRB_PROPOSAL.docx . > /dev/null 2>&1 && echo "PACKED OK" && ls -lh ../NiTi_Pain_IRB_PROPOSAL.docx

cd /home/daytona/workspace/irb-protocol && python3 -c " import zipfile, os out = 'NiTi_Pain_IRB_PROPOSAL.docx' src = 'liya_unpacked' with zipfile.ZipFile(out, 'w', zipfile.ZIP_DEFLATED) as zf: for root, dirs, files in os.walk(src): for file in files: fp = os.path.join(root, file) arcname = os.path.relpath(fp, src) zf.write(fp, arcname) print('done') " && ls -lh NiTi_Pain_IRB_PROPOSAL.docx

cd /home/daytona/workspace/irb-protocol && python3 -c " import zipfile, os, io src = 'liya_unpacked' out_path = 'NiTi_Pain_IRB_PROPOSAL.docx' # write to buffer first buf = io.BytesIO() with zipfile.ZipFile(buf, 'w', zipfile.ZIP_DEFLATED) as zf: for root, dirs, files in os.walk(src): for file in sorted(files): fp = os.path.join(root, file) arcname = os.path.relpath(fp, src) zf.write(fp, arcname) with open(out_path, 'wb') as f: f.write(buf.getvalue()) print('done') import os; print(os.path.getsize(out_path), 'bytes') "

cd /home/daytona/workspace/irb-protocol && python3 /home/daytona/skills/docx/scripts/office/validate.py NiTi_Pain_IRB_PROPOSAL.docx 2>&1 | head -20

cd /home/daytona/workspace/irb-protocol && pandoc NiTi_Pain_IRB_PROPOSAL.docx -t plain 2>/dev/null | head -120

python3 -c "import docx; print('ok')"

pip install python-docx --quiet 2>&1 | tail -3

python3 << 'PYEOF' from docx import Document from docx.oxml.ns import qn from docx.oxml import OxmlElement import copy, re # Load original template doc = Document("/home/daytona/workspace/attachments/73da90cf-c6d5-4c6c-93ac-d1a425c17025/LIYA IRB PROPOSAL.docx") def cell_text(cell): return cell.text.strip() def set_cell_text(cell, new_text, bold=False): """Clear all runs in all paragraphs of a cell, set text in first para.""" # Keep first paragraph, remove others for para in cell.paragraphs[1:]: p = para._element p.getparent().remove(p) para = cell.paragraphs[0] # Copy run properties from first existing run if any rpr = None if para.runs: rpr = copy.deepcopy(para.runs[0]._r.find(qn('w:rPr'))) # Clear all runs for r in para._element.findall(qn('w:r')): para._element.remove(r) # Add new run run = para.add_run(new_text) if bold: run.bold = True if rpr is not None: existing = run._r.find(qn('w:rPr')) if existing is not None: run._r.remove(existing) run._r.insert(0, rpr) def set_cell_paragraphs(cell, paragraphs_data): """ paragraphs_data: list of (text, bold) tuples Each tuple becomes a paragraph in the cell. """ # Remove all existing paragraphs except first for para in cell.paragraphs[1:]: p = para._element p.getparent().remove(p) first = True for text, bold in paragraphs_data: if first: para = cell.paragraphs[0] first = False else: para = cell.add_paragraph() for r in para._element.findall(qn('w:r')): para._element.remove(r) run = para.add_run(text) run.bold = bold # Find all table cells with their text # The document has one big table. Let's enumerate all rows and cells. tables = doc.tables print(f"Tables found: {len(tables)}") for ti, table in enumerate(tables): for ri, row in enumerate(table.rows): for ci, cell in enumerate(row.cells): t = cell.text.strip()[:60] if t: print(f"T{ti} R{ri:02d} C{ci}: {t!r}") PYEOF

python3 << 'PYEOF' from docx import Document from docx.oxml.ns import qn from docx.oxml import OxmlElement from docx.shared import Pt import copy doc = Document("/home/daytona/workspace/attachments/73da90cf-c6d5-4c6c-93ac-d1a425c17025/LIYA IRB PROPOSAL.docx") tables = doc.tables def clear_and_write(cell, lines): """ lines: list of (text, bold) Clears cell content and writes fresh lines preserving cell formatting. """ tc = cell._tc # Remove all paragraphs from cell for p in tc.findall(qn('w:p')): tc.remove(p) # Add fresh paragraphs for text, bold in lines: p = OxmlElement('w:p') r = OxmlElement('w:r') rpr = OxmlElement('w:rPr') if bold: b = OxmlElement('w:b') rpr.append(b) sz = OxmlElement('w:sz') sz.set(qn('w:val'), '20') szcs = OxmlElement('w:szCs') szcs.set(qn('w:val'), '20') rpr.append(sz) rpr.append(szcs) r.append(rpr) t = OxmlElement('w:t') t.text = text if text.startswith(' ') or text.endswith(' '): t.set('{http://www.w3.org/XML/1998/namespace}space', 'preserve') r.append(t) p.append(r) tc.append(p) # ── T0 R0 C1: Candidate info ───────────────────────────────────── clear_and_write(tables[0].rows[0].cells[1], [ ('Name of the candidate: [Your Name]', False), ('', False), ('Phone No: [Your Phone]', False), ('', False), ('Email ID: [Your Email]', False), ]) # ── T0 R3 C1: Final exam date ───────────────────────────────────── clear_and_write(tables[0].rows[3].cells[1], [ ('Month and year of appearing for the final examination: November 2026', False), ]) # ── T1 R2 C1: Title ────────────────────────────────────────────── clear_and_write(tables[1].rows[2].cells[1], [ ('Title Of Dissertation:', True), ('', False), ('A Comparative Study of Pain Perception in Adults and Adolescents Following Placement of Initial NiTi Archwires in Orthodontic Treatment', False), ]) # ── T1 R3 C1: Introduction ─────────────────────────────────────── intro_text = ( "Pain and masticatory discomfort are among the most frequently reported adverse effects of fixed " "orthodontic treatment, and remain a leading cause of reduced patient compliance and, in some cases, " "discontinuation of treatment. Orthodontic tooth movement triggers an inflammatory response within " "the periodontal ligament (PDL) and pulp, releasing biochemical mediators — prostaglandins, cytokines, " "and substance P — that underlie the sensation of pain associated with appliance activation. [1,2,3]" ) intro_p2 = ( "The initial aligning phase of fixed orthodontic treatment typically employs superelastic nickel-titanium " "(NiTi) archwires, which deliver continuous light forces over a wide range of deflection, producing more " "physiological tooth movement compared to heavier stainless-steel wires. Despite this, patients commonly " "report pain in the days following initial wire placement. [4,5]" ) intro_p3 = ( "Age is one of the most frequently cited yet inconsistently reported variables in orthodontic pain " "research. Some studies report adults perceive greater pain than adolescents, attributed to denser " "alveolar bone and reduced periodontal ligament turnover with age; others report no significant " "difference, or attribute apparent differences to psychological factors and coping strategies. " "This inconsistency is the central gap this study addresses. [6,7,8]" ) intro_p4 = ( "The parent study (Olteanu et al., 2022) evaluated pain across four orthodontic procedures in 100 patients " "across four age bands using a single-timepoint retrospective questionnaire. The present study narrows " "focus to a single clinical event — placement of the first NiTi aligning archwire — and captures pain " "prospectively at four timepoints: 6 hours, 24 hours, 7 days, and 14 days after placement. [1]" ) clear_and_write(tables[1].rows[3].cells[1], [ ('Introduction:', True), ('', False), (intro_text, False), ('', False), (intro_p2, False), ('', False), (intro_p3, False), ('', False), (intro_p4, False), ]) # ── T2 R0 C1: Aims & Objectives ────────────────────────────────── clear_and_write(tables[2].rows[0].cells[1], [ ('Aims & Objectives:', True), ('', False), ('AIM:', True), ('', False), ('To compare pain intensity, onset, duration, and medication requirements following placement of ' 'the initial NiTi aligning archwire between adolescent (12–18 years) and adult (≥19 years) ' 'orthodontic patients, assessed at 6 hours, 24 hours, 7 days, and 14 days post-placement.', False), ('', False), ('OBJECTIVES:', True), ('', False), ('Primary Objective', True), ('To measure and compare mean pain intensity (NRS 0–10) between adolescents and adults at 6 hours, ' '24 hours, 7 days, and 14 days after initial NiTi archwire placement.', False), ('', False), ('Secondary Objectives', True), ('1. To identify the timepoint of peak pain intensity in each age group.', False), ('2. To compare the proportion requiring analgesic medication and the type of medication used between groups.', False), ('3. To evaluate the impact of pain on daily function (eating, sleeping, speaking) between groups.', False), ('4. To assess whether sex modifies the pain response between the two age groups (exploratory).', False), ]) # ── T2 R1 C1: Literature Review ─────────────────────────────────── clear_and_write(tables[2].rows[1].cells[1], [ ('1) Relevant review of literature (maximum 5–6 reviews):', True), ('', False), ('1. Olteanu et al. (2022)', True), ('Conducted a questionnaire-based study on pain perception during fixed orthodontic treatment in 100 patients ' 'across four age bands (12–18, 18–24, 24–30, over 30). Using a Numerical Rating Scale, they found arch activation ' 'was the second most painful procedure, with pain peaking during the first 3–4 days post-procedure. Sex-based ' 'differences were significant (ANOVA F=33.6, p<0.01), with males reporting higher pain. This study served as ' 'the design template for the present protocol, which extends it to a prospective multi-timepoint design focused ' 'specifically on the first NiTi archwire.', False), ('', False), ('2. Scheurer et al. (1996)', True), ('Investigated pain perception following placement of fixed orthodontic appliances in 170 patients (age range ' '8–53 years) using eight consecutive daily questionnaires. Found 95% of patients reported pain at 24 hours, ' 'with the highest pain frequency in the 13–16-year age group; pain intensity did not differ significantly across ' 'age groups. Girls reported significantly higher pain than boys. Provided the standard deviation estimate ' '(σ = 1.8 points) used in the present study\'s sample size calculation.', False), ('', False), ('3. Abdelrahman et al. (2015)', True), ('Conducted a prospective clinical trial comparing pain with three types of NiTi archwires (superelastic, ' 'thermoelastic, conventional) in 75 patients. No statistically significant differences were found in pain ' 'intensity among wire types (p=0.63). Gender, age, and degree of crowding had no significant effect on ' 'perceived discomfort, providing key evidence supporting the age-group comparison in the present study.', False), ('', False), ('4. Brown and Moerenhout (1991)', True), ('Conducted a longitudinal study using four questionnaires to compare pain experience and psychological ' 'adjustment among preadolescents (11–13y), adolescents (14–17y), and adults (≥18y) undergoing fixed appliance ' 'treatment. Adolescents reported significantly higher pain and lower psychological well-being than both ' 'preadolescents and adults throughout treatment, suggesting adolescents are more vulnerable to the undesirable ' 'psychological effects of orthodontic pain. Directly supports the age-group comparison rationale of the present study.', False), ('', False), ('5. Erdınç and Dinçer (2004)', True), ('Investigated pain perception following placement of 0.014-inch and 0.016-inch archwires in 109 adolescent ' 'patients using a 49-item questionnaire administered over 7 days. Initial pain was perceived at approximately ' '2 hours post-placement, peaked at 24 hours, and decreased significantly by day 3. No significant differences ' 'were found between wire sizes or between genders. Provided direct evidence for the four timepoints ' '(6h, 24h, 7d, 14d) used in the present study\'s data collection design.', False), ('', False), ('6. Salgado et al. (2022)', True), ('Cohort study of 44 patients assessing pain at baseline, 6h, 24h, 2nd, 3rd, 5th, and 7th day after ' 'orthodontic activation. Pain peaked at 24 hours across all three appointments evaluated. Pain ' 'catastrophising showed a weak but significant association with pain at the first appointment. ' 'Older patients had a weak protective association with pain. Relevant to the psychosocial aspects ' 'of pain perception discussed in this protocol.', False), ]) # ── T2 R2 C1: Research Question & Hypothesis ───────────────────── clear_and_write(tables[2].rows[2].cells[1], [ ('RESEARCH QUESTION:', True), ('', False), ('Does placement of the initial superelastic NiTi aligning archwire result in significantly different ' 'pain intensity, onset, duration, and medication requirements between adolescent (12–18 years) and ' 'adult (≥19 years) orthodontic patients when assessed prospectively at 6 hours, 24 hours, 7 days, ' 'and 14 days post-placement?', False), ('', False), ('RESEARCH HYPOTHESIS:', True), ('', False), ('Null Hypothesis (H0):', True), ('There is no statistically significant difference in mean pain intensity (NRS 0–10) between ' 'adolescent and adult patients at any of the four timepoints (6h, 24h, 7d, 14d) following initial ' 'NiTi archwire placement. There is no significant difference in analgesic use or functional impact ' 'between the two groups.', False), ('', False), ('Alternative Hypothesis (H1):', True), ('There is a statistically significant difference in mean pain intensity (NRS 0–10) between ' 'adolescent and adult patients at one or more of the four timepoints following initial NiTi ' 'archwire placement, and/or a significant difference in analgesic use or functional impact ' 'between the two groups.', False), ]) # ── T3 R0 C1: Methodology Flowchart ────────────────────────────── clear_and_write(tables[3].rows[0].cells[1], [ ('Methodology (Flow chart): MATERIALS AND METHODOLOGY (FLOW CHART)', True), ('', False), ('Patient recruitment (Adolescent group: 12–18 years; Adult group: ≥19 years)', False), ('', False), ('↓', False), ('Written informed consent obtained from adult patients (≥18y); parental/guardian consent + ' 'adolescent assent obtained for participants aged 12–17y', False), ('', False), ('↓', False), ('Baseline assessment at T0 (at wire placement) — Section A questionnaire completed chairside ' '(demographics, health status, wire dimension)', False), ('', False), ('↓', False), ('Initial superelastic NiTi archwire placement (standardised dimension, e.g. 0.014-inch; ' 'bracket type and ligation method recorded)', False), ('', False), ('↓', False), ('Pain questionnaire (Section B: NRS 0–10 + functional impact + analgesic use) at:', False), (' T1: 6 hours post-placement', False), (' T2: 24 hours post-placement', False), (' T3: 7 days post-placement', False), (' T4: 14 days post-placement (+ Section C: retrospective peak-pain timepoint)', False), ('', False), ('↓', False), ('Data entry and validation (Microsoft Excel; pseudonymisation applied)', False), ('', False), ('↓', False), ('Statistical Analysis', False), (' Primary: Independent t-test / Mann–Whitney U at each timepoint (Bonferroni α=0.0125)', False), (' Design-level: Two-way mixed repeated-measures ANOVA (Group × Time interaction)', False), (' Secondary: Chi-square / Fisher\'s exact for analgesic use, medication type, peak timepoint', False), (' Exploratory: Three-way ANOVA (Group × Sex × Time)', False), ('', False), ('↓', False), ('RESULTS', False), ('', False), ('↓', False), ('CONCLUSION', False), ]) # ── T4 R0 C1: Study Parameters ──────────────────────────────────── clear_and_write(tables[4].rows[0].cells[1], [ ('Study parameters (outcome measures) being monitored:', True), ('Primary: Mean pain intensity (NRS 0–10) between adolescent and adult groups at 6h, 24h, 7d, and 14d ' 'post-archwire placement.', False), ('Secondary: Analgesic use (proportion and type); peak pain timepoint; functional impact on eating, ' 'sleep, and speech; sex-based modification of pain response.', False), ]) # ── T4 R2 C1: Type of study ─────────────────────────────────────── clear_and_write(tables[4].rows[2].cells[1], [ ('Type of study: Prospective, observational, questionnaire-based comparative study', False), ]) # ── T4 R3 C1: Number of groups ──────────────────────────────────── clear_and_write(tables[4].rows[3].cells[1], [ ('Number of groups to be studied: 2 groups', False), ('Group 1 — Adolescent: 12–18 years', False), ('Group 2 — Adult: ≥19 years', False), ('Non-randomised comparative study; groups are defined by patient age at time of enrolment. ' 'No randomisation is applied.', False), ]) # ── T4 R4 C1: Sample size ───────────────────────────────────────── clear_and_write(tables[4].rows[4].cells[1], [ ('Sample size:', True), ('', False), ('Based on comparable archwire-pain literature (Scheurer et al. 1996; Fernandes et al. 1998), ' 'the standard deviation of NRS pain scores is approximately σ = 1.8 points (0–10 scale). ' 'Using a minimum clinically important difference of d = 1.0 point, α = 0.05 (two-tailed), ' 'and power = 80%, the two-sample independent-means formula gives:', False), ('', False), ('Formula: N = 2 × (Zα/2 + Zβ)² × σ² / d²', True), ('', False), ('Where: Zα/2 = 1.96, Zβ = 0.84, σ = 1.8, d = 1.0', False), ('', False), ('N = 2 × (1.96 + 0.84)² × 1.8² / 1.0²', False), ('N = 2 × (2.80)² × 3.24', False), ('N = 2 × 7.84 × 3.24', False), ('N = 50.8 → rounded up to 51 participants per group', False), ('Minimum total at baseline (2 groups): 102 participants', False), ('', False), ('Adjusting for 20% anticipated attrition across the four follow-up timepoints:', False), ('n per group required = 51 / 0.80 = 64', False), ('TOTAL RECRUITMENT TARGET = 128 participants (64 per group)', True), ('', False), ('This calculation targets the single-timepoint t-test (most conservative case). ' 'The repeated-measures ANOVA design for the group × time interaction will have equal or ' 'greater power due to correlated within-subject measurements.', False), ]) # ── T5 R0 C1: Inclusion Criteria ────────────────────────────────── clear_and_write(tables[5].rows[0].cells[1], [ ('Inclusion criteria:', True), ('1. Patients beginning fixed orthodontic treatment who are receiving their first NiTi aligning archwire.', False), ('2. Age 12 years and above.', False), ('3. Good general health; no active orofacial pain condition unrelated to orthodontic treatment.', False), ('4. Willingness and cognitive ability to complete a self-report questionnaire at each timepoint.', False), ('5. Available for follow-up at all four timepoints (6h, 24h, 7 days, 14 days).', False), ('6. Adolescent group: 12–18 years. Adult group: 19 years and above.', False), ]) # ── T5 R1 C1: Exclusion Criteria ────────────────────────────────── clear_and_write(tables[5].rows[1].cells[1], [ ('Exclusion criteria:', True), ('1. Patients taking regular analgesic or anti-inflammatory medication for an unrelated chronic condition.', False), ('2. Craniofacial syndromes, active TMJ disorders, or recent oral/maxillofacial surgery.', False), ('3. Known allergy to nickel or titanium.', False), ('4. Inability to complete the questionnaire independently or via guardian-assisted administration.', False), ('5. Previous fixed orthodontic treatment within the past 12 months.', False), ]) # ── T5 R4 C1: Statistical Analysis ──────────────────────────────── clear_and_write(tables[5].rows[4].cells[1], [ ('Methods of statistical analysis', True), ('', False), ('Data Management:', True), ('Collected data will be entered and compiled using Microsoft Excel 2019. ' 'Data will be analysed using SPSS version 23.0 or later (or R statistical software).', False), ('', False), ('Statistical Analysis:', True), ('Categorical data will be expressed as frequency and percentage. ' 'Continuous variables will be expressed as mean ± SD (if normally distributed) or ' 'median (IQR) if non-normal. Normality assessed by Shapiro–Wilk test and Q–Q plot inspection.', False), ('', False), ('Objectives and Statistical Tests:', True), ('', False), ('PRIMARY OBJECTIVE', True), ('To measure and compare mean pain intensity (NRS 0–10) between adolescents and adults at each ' 'of four timepoints (6h, 24h, 7d, 14d) and the pain trajectory over time.', False), ('Statistical Test: Independent-samples Student\'s t-test at each timepoint (if normally ' 'distributed) or Mann–Whitney U test (if non-normal). Bonferroni correction applied: ' 'adjusted α = 0.05/4 = 0.0125 per individual timepoint comparison. Report Cohen\'s d.', False), ('Design-level test: Two-way mixed-design repeated-measures ANOVA (Group × Time interaction). ' 'Mauchly\'s test for sphericity; Greenhouse–Geisser correction if violated. Report partial η²p. ' 'If attrition >10%, use linear mixed-effects model (LME) with random intercept per participant.', False), ('', False), ('SECONDARY OBJECTIVES', True), ('Analgesic use (proportion): Chi-square test or Fisher\'s exact test; report OR + 95% CI.', False), ('Medication type: Chi-square test for proportions across groups.', False), ('Peak pain timepoint: Chi-square or frequency comparison; report modal timepoint per group.', False), ('Functional impact (eating/sleep/speech): Mann–Whitney U or Chi-square (collapsed to ' 'affected/unaffected); separate analysis per domain.', False), ('Sex × Group interaction (exploratory): Three-way mixed ANOVA (Group × Sex × Time); ' 'report partial η²p; no Bonferroni applied — hypothesis-generating only.', False), ('', False), ('Level of Significance:', True), ('P < 0.05 will be considered statistically significant for omnibus tests. ' 'Bonferroni-adjusted α = 0.0125 for the four individual timepoint comparisons. ' 'Effect sizes (Cohen\'s d, partial η²p, OR) must be reported alongside p-values.', False), ]) # ── T6 R0 C1: References ────────────────────────────────────────── clear_and_write(tables[6].rows[0].cells[1], [ ('References (In Vancouver style):', True), ('', False), ('1. Olteanu CD, Bucur S-M, Chibelean M, Bud ES, Păcurar M, Feștilă DG. Pain Perception during ' 'Orthodontic Treatment with Fixed Appliances. Appl Sci. 2022;12(13):6389. ' 'https://doi.org/10.3390/app12136389', False), ('', False), ('2. Raja SN, Carr DB, Cohen M, Finnerup NB, Flor H, Gibson S, et al. The revised IASP definition ' 'of pain. Pain. 2020;161(9):1976–1982. https://doi.org/10.1097/j.pain.0000000000001939', False), ('', False), ('3. Krishnan V. Orthodontic pain: from causes to management — a review. Eur J Orthod. ' '2007;29(2):170–179. https://doi.org/10.1093/ejo/cjl081', False), ('', False), ('4. Scheurer PA, Firestone AR, Bürgin WB. Perception of pain as a result of orthodontic treatment ' 'with fixed appliances. Eur J Orthod. 1996;18(4):349–357. https://doi.org/10.1093/ejo/18.4.349', False), ('', False), ('5. Fernandes LM, Øgaard B, Skoglund L. Pain and discomfort experienced after placement of a ' 'conventional or a superelastic NiTi aligning archwire. A randomized clinical trial. ' 'J Orofac Orthop. 1998;59(6):331–339. https://doi.org/10.1007/BF01299769', False), ('', False), ('6. Erdınç AM, Dinçer B. Perception of pain during orthodontic treatment with fixed appliances. ' 'Eur J Orthod. 2004;26(1):79–85. https://doi.org/10.1093/ejo/26.1.79', False), ('', False), ('7. Abdelrahman RSh, Al-Nimri KS, Al Maaitah EF. Pain experience during initial alignment with ' 'three types of nickel-titanium archwires: a prospective clinical trial. Angle Orthod. ' '2015;85(6):1070–1076. https://doi.org/10.2319/071614-498.1', False), ('', False), ('8. Brown DF, Moerenhout RG. The pain experience and psychological adjustment to orthodontic ' 'treatment of preadolescents, adolescents, and adults. Am J Orthod Dentofac Orthop. ' '1991;100(4):349–356. https://doi.org/10.1016/0889-5406(91)70073-6', False), ('', False), ('9. Arias OR, Marquez-Orozco MC. Aspirin, acetaminophen, and ibuprofen: their effects on ' 'orthodontic tooth movement. Am J Orthod Dentofac Orthop. 2006;130(3):364–370. ' 'https://doi.org/10.1016/j.ajodo.2004.12.027', False), ('', False), ('10. Salgado KR, Normando D, Brandão GAM. Is catastrophising associated with pain perception ' 'in early phase of orthodontic treatment? A cohort study. J Oral Rehabil. 2022;49(3):309–315. ' 'https://doi.org/10.1111/joor.13279', False), ]) # ── T7 R0 C1: Preliminary work ─────────────────────────────────── clear_and_write(tables[7].rows[0].cells[1], [ ('Preliminary work done already, if any (preparation of questionnaire, collection of patient details…):', True), ('The study questionnaire instrument has been designed and adapted from the parent study format ' '(Olteanu et al., 2022). The questionnaire consists of a baseline Section A (demographics, ' 'health status, wire dimension) and a repeated Section B (NRS pain scale, functional impact, ' 'analgesic use) administered at each of four timepoints, with a final retrospective Section C ' 'at 14 days. The parent study literature has been systematically reviewed and the reference ' 'list compiled. Ethical approval application is pending submission.', False), ]) # ── T7 R1 C1: Ethical issues ───────────────────────────────────── clear_and_write(tables[7].rows[1].cells[1], [ ('Ethical issues involved in the study:', True), ('', False), ('Minimal Risk. Written informed consent will be obtained from all adult participants (≥18 years). ' 'For adolescent participants (12–17 years), written parental/guardian consent and participant ' 'assent will be obtained. The study involves non-invasive procedures — self-report pain ' 'questionnaires administered at four timepoints following routine orthodontic archwire placement. ' 'No additional clinical procedures are required beyond standard orthodontic care. Patient data ' 'will be pseudonymised at the point of data entry. Participant information will be kept ' 'confidential and stored securely. The study will be conducted in full compliance with the ' 'Declaration of Helsinki (2013 revision).', False), ]) # ── T7 R2 C1: Consent procedure ────────────────────────────────── clear_and_write(tables[7].rows[2].cells[1], [ ('Procedure involved for obtaining informed consent from the patient or guardian & assent from children:', True), ('', False), ('Recruited patients will be informed about the purpose, procedures, voluntary nature, and ' 'confidentiality of the study. Written informed consent will be obtained from adult participants ' '(≥18 years) prior to enrolment. For adolescent participants (12–17 years), written ' 'parental/guardian consent will be obtained, along with written assent from the adolescent ' 'participant. Participation will be entirely voluntary, and participants will have the right ' 'to withdraw from the study at any stage without any effect on their standard of clinical care. ' 'Participant information will be kept strictly confidential.', False), ]) # ── T7 R3 C1: Recruiting ───────────────────────────────────────── clear_and_write(tables[7].rows[3].cells[1], [ ('Procedure involved for recruiting volunteers:', True), ('', False), ('Patients beginning fixed orthodontic treatment at Sri Venkateshwaraa Dental College, Puducherry ' 'will be assessed for eligibility against the inclusion and exclusion criteria. Eligible patients ' 'will be approached by the principal investigator, informed about the study, and invited to ' 'participate. Written consent/assent will be obtained prior to enrolment. Recruitment will ' 'continue over 6–12 months until the target sample (128 participants; 64 per group) is achieved.', False), ]) # ── T7 R7 C1: Financial frame ──────────────────────────────────── clear_and_write(tables[7].rows[7].cells[1], [ ('Financial frame: Rs. 3000 – Rs. 5000', False), ('(Printing of consent forms, assent forms, and questionnaire proformas; data entry and ' 'statistical analysis; miscellaneous stationery)', False), ]) # Save out_path = '/home/daytona/workspace/irb-protocol/NiTi_Pain_IRB_PROPOSAL.docx' doc.save(out_path) print("Saved:", out_path) import os; print("Size:", os.path.getsize(out_path), "bytes") PYEOF

python3 << 'PYEOF' from docx import Document from docx.oxml.ns import qn from docx.oxml import OxmlElement import copy, io, os doc = Document("/home/daytona/workspace/attachments/73da90cf-c6d5-4c6c-93ac-d1a425c17025/LIYA IRB PROPOSAL.docx") tables = doc.tables def clear_and_write(cell, lines): tc = cell._tc for p in tc.findall(qn('w:p')): tc.remove(p) for text, bold in lines: p = OxmlElement('w:p') r = OxmlElement('w:r') rpr = OxmlElement('w:rPr') if bold: b = OxmlElement('w:b'); rpr.append(b) sz = OxmlElement('w:sz'); sz.set(qn('w:val'), '20'); rpr.append(sz) szcs = OxmlElement('w:szCs'); szcs.set(qn('w:val'), '20'); rpr.append(szcs) r.append(rpr) t = OxmlElement('w:t'); t.text = text if text.startswith(' ') or text.endswith(' '): t.set('{http://www.w3.org/XML/1998/namespace}space','preserve') r.append(t); p.append(r); tc.append(p) T = tables # shorthand # ── 1. Candidate info clear_and_write(T[0].rows[0].cells[1],[ ('Name of the candidate: [Your Name]',False),('',False), ('Phone No: [Your Phone]',False),('',False), ('Email ID: [Your Email]',False), ]) # ── 2. Final exam date clear_and_write(T[0].rows[3].cells[1],[ ('Month and year of appearing for the final examination: November 2026',False), ]) # ── 3. Title clear_and_write(T[1].rows[2].cells[1],[ ('Title Of Dissertation:',True),('',False), ('A Comparative Study of Pain Perception in Adults and Adolescents Following Placement of Initial NiTi Archwires in Orthodontic Treatment',False), ]) # ── 4. Introduction clear_and_write(T[1].rows[3].cells[1],[ ('Introduction:',True),('',False), ('Pain and masticatory discomfort are among the most frequently reported adverse effects of fixed orthodontic treatment and remain a leading cause of reduced patient compliance and, in some cases, discontinuation of treatment. Orthodontic tooth movement triggers an inflammatory response within the periodontal ligament (PDL) and pulp, releasing biochemical mediators — prostaglandins, cytokines, and substance P — that underlie the sensation of pain associated with appliance activation. [1,2,3]',False),('',False), ('The initial aligning phase of fixed orthodontic treatment typically employs superelastic nickel-titanium (NiTi) archwires, valued for delivering continuous light forces over a wide range of deflection, producing more physiological tooth movement. Despite this, patients regularly report pain in the days following initial wire placement. A 2024 Cochrane meta-analysis (29 RCTs, 1915 participants) found low-certainty evidence of little difference in pain intensity between different NiTi wire types, reinforcing that the inflammatory response — rather than the specific wire alloy — is the primary driver of post-placement pain. [4,5]',False),('',False), ('Age is one of the most frequently cited yet inconsistently reported variables in orthodontic pain research. Some studies report adults perceive greater pain than adolescents, attributed to denser alveolar bone and reduced PDL turnover with age; others report no significant difference, attributing apparent differences to psychological factors, coping strategies, and prior pain experience. This inconsistency is the central gap this study addresses. [6,7,8]',False),('',False), ('The parent study (Olteanu et al., 2022) evaluated pain across four orthodontic procedures in 100 patients across four age bands using a single-timepoint retrospective questionnaire. The present study narrows focus to a single clinical event — placement of the first NiTi aligning archwire — and broadens temporal resolution by capturing pain prospectively at four fixed timepoints: 6 hours, 24 hours, 7 days, and 14 days post-placement. The age comparison is simplified to two clinically meaningful groups (adolescents vs adults) to enable a statistically powered, focused comparison. [1]',False), ]) # ── 5. Aims & Objectives clear_and_write(T[2].rows[0].cells[1],[ ('Aims & Objectives:',True),('',False), ('AIM:',True),('',False), ('To compare pain intensity, onset, duration, and medication requirements following placement of the initial NiTi aligning archwire between adolescent (12-18 years) and adult (>=19 years) orthodontic patients, assessed prospectively at 6 hours, 24 hours, 7 days, and 14 days post-placement.',False),('',False), ('OBJECTIVES:',True),('',False), ('Primary Objective',True), ('To measure and compare mean pain intensity (NRS 0-10) between adolescents and adults at 6 hours, 24 hours, 7 days, and 14 days after initial NiTi archwire placement.',False),('',False), ('Secondary Objectives',True), ('1. To identify the timepoint of peak pain intensity in each age group.',False), ('2. To compare the proportion requiring analgesic medication and type of medication used between groups.',False), ('3. To evaluate the impact of pain on daily function (eating, sleeping, speaking) between groups.',False), ('4. To assess whether sex modifies the pain response between groups (exploratory).',False), ]) # ── 6. Literature Review clear_and_write(T[2].rows[1].cells[1],[ ('1) Relevant review of literature (maximum 5-6 reviews):',True),('',False), ('1. Olteanu et al. (2022)',True), ('Conducted a questionnaire-based study on pain perception during fixed orthodontic treatment in 100 patients across four age bands (12-18, 18-24, 24-30, >30 years) using a Numerical Rating Scale. Found arch activation was the second most painful procedure; pain peaked during the first 3-4 days. Sex-based differences were significant (ANOVA F=33.6, p<0.01), with males reporting higher pain. This study is the design template for the present protocol, which extends it to a prospective multi-timepoint design focused specifically on the first NiTi archwire.',False),('',False), ('2. Scheurer et al. (1996)',True), ('Investigated pain in 170 patients (age 8-53 years) using eight daily questionnaires after appliance placement. Found 95% reported pain at 24 hours; the 13-16-year age group had the highest pain frequency; pain intensity did not differ significantly across age groups; girls reported significantly higher pain than boys. Provided the SD estimate (sigma=1.8 points) used in the present sample size calculation.',False),('',False), ('3. Abdelrahman et al. (2015)',True), ('Prospective clinical trial comparing pain with three NiTi archwire types (superelastic, thermoelastic, conventional) in 75 patients. No significant differences in pain intensity among wire types (p=0.63). Gender, age, and crowding had no significant effect on perceived discomfort — key evidence supporting the age-group comparison rationale of this study.',False),('',False), ('4. Brown and Moerenhout (1991)',True), ('Longitudinal study using four questionnaires comparing pain experience among preadolescents (11-13y), adolescents (14-17y), and adults (>=18y) during fixed appliance treatment. Adolescents reported significantly higher pain and lower psychological well-being than both preadolescents and adults, suggesting adolescents are more vulnerable to the adverse psychological effects of orthodontic pain. Directly supports the age-group comparison rationale.',False),('',False), ('5. Erdınc and Dincer (2004)',True), ('Investigated pain following placement of 0.014-inch and 0.016-inch archwires in 109 adolescent patients over 7 days. Initial pain perceived at ~2 hours, peaked at 24 hours, decreased significantly by day 3. No significant difference between wire sizes or genders. Provided direct evidence for the four timepoints (6h, 24h, 7d, 14d) used in the present study.',False),('',False), ('6. Salgado et al. (2022)',True), ('Cohort study of 44 patients assessing pain at baseline, 6h, 24h, 2nd, 3rd, 5th, and 7th day after activation. Pain peaked at 24 hours. Pain catastrophising showed a weak but significant association with pain at the first appointment. Older patients had a weak protective association with pain — relevant to the psychosocial aspects discussed in this protocol.',False), ]) # ── 7. Research Question & Hypothesis clear_and_write(T[2].rows[2].cells[1],[ ('RESEARCH QUESTION:',True),('',False), ('Does placement of the initial superelastic NiTi aligning archwire result in significantly different pain intensity, onset, duration, and medication requirements between adolescent (12-18 years) and adult (>=19 years) orthodontic patients when assessed prospectively at 6 hours, 24 hours, 7 days, and 14 days post-placement?',False),('',False), ('RESEARCH HYPOTHESIS:',True),('',False), ('Null Hypothesis (H0):',True), ('There is no statistically significant difference in mean pain intensity (NRS 0-10) between adolescent and adult patients at any of the four timepoints (6h, 24h, 7d, 14d) following initial NiTi archwire placement. There is no significant difference in analgesic use, peak pain timepoint, or functional impact between the two groups.',False),('',False), ('Alternative Hypothesis (H1):',True), ('There is a statistically significant difference in mean pain intensity (NRS 0-10) between adolescent and adult patients at one or more of the four timepoints following initial NiTi archwire placement, and/or a significant difference in analgesic use or functional impact between the two groups.',False), ]) # ── 8. Methodology Flowchart clear_and_write(T[3].rows[0].cells[1],[ ('Methodology (Flow chart): MATERIALS AND METHODOLOGY (FLOW CHART)',True),('',False), ('Patient recruitment (Adolescent group: 12-18 years; Adult group: >=19 years)',False),('',False), ('Written informed consent obtained from adult patients (>=18y); parental/guardian consent + adolescent assent obtained for patients aged 12-17y',False),('',False), ('Baseline assessment at T0 (at wire placement): Section A questionnaire completed chairside (demographics, health status, wire dimension)',False),('',False), ('Initial superelastic NiTi archwire placement (standardised dimension, e.g. 0.014-inch; bracket type and ligation method recorded)',False),('',False), ('Pain questionnaire (Section B: NRS 0-10 + functional impact + analgesic use) administered at:',False), (' T1: 6 hours post-placement',False), (' T2: 24 hours post-placement',False), (' T3: 7 days post-placement',False), (' T4: 14 days post-placement + Section C (retrospective peak-pain timepoint)',False),('',False), ('Data entry and validation (Microsoft Excel; pseudonymisation applied)',False),('',False), ('Statistical Analysis',False), (' Primary: Independent t-test / Mann-Whitney U at each timepoint (Bonferroni alpha=0.0125)',False), (' Design-level: Two-way mixed repeated-measures ANOVA (Group x Time interaction)',False), (' Secondary: Chi-square / Fisher exact for analgesic use, medication type, peak timepoint',False), (' Exploratory: Three-way ANOVA (Group x Sex x Time)',False),('',False), ('RESULTS',False),('',False), ('CONCLUSION',False), ]) # ── 9. Study parameters clear_and_write(T[4].rows[0].cells[1],[ ('Study parameters (outcome measures) being monitored:',True), ('Primary: Mean pain intensity (NRS 0-10) between adolescent and adult groups at 6h, 24h, 7d, and 14d post-archwire placement.',False), ('Secondary: Analgesic use (proportion and type); peak pain timepoint; functional impact on eating, sleep, and speech; sex-based modification of pain response.',False), ]) # ── 10. Type of study clear_and_write(T[4].rows[2].cells[1],[ ('Type of study: Prospective, observational, questionnaire-based comparative study',False), ]) # ── 11. Number of groups clear_and_write(T[4].rows[3].cells[1],[ ('Number of groups to be studied: 2',False), ('Group 1 — Adolescent: 12-18 years',False), ('Group 2 — Adult: >=19 years',False), ('Non-randomised comparative study; groups defined by patient age at enrolment.',False), ]) # ── 12. Sample size clear_and_write(T[4].rows[4].cells[1],[ ('Sample size:',True),('',False), ('Based on comparable archwire-pain literature (Scheurer et al. 1996; Fernandes et al. 1998), SD of NRS pain scores sigma = 1.8 points. Using minimum clinically important difference d = 1.0 point, alpha = 0.05 (two-tailed), power = 80%:',False),('',False), ('Formula: N = 2 x (Zalpha/2 + Zbeta)^2 x sigma^2 / d^2',True),('',False), ('Where: Zalpha/2 = 1.96, Zbeta = 0.84, sigma = 1.8, d = 1.0',False),('',False), ('N = 2 x (1.96 + 0.84)^2 x 1.8^2 / 1.0^2',False), ('N = 2 x (2.80)^2 x 3.24',False), ('N = 2 x 7.84 x 3.24',False), ('N = 50.8 --> rounded up to 51 participants per group',False), ('Minimum total at baseline (2 groups): 102 participants',False),('',False), ('Adjusting for 20% anticipated attrition across the four follow-up timepoints:',False), ('n per group = 51 / 0.80 = 64',False), ('TOTAL RECRUITMENT TARGET = 128 participants (64 per group)',True),('',False), ('Note: This conservative estimate targets the single-timepoint t-test. The repeated-measures ANOVA design (Group x Time) will have equal or greater power due to correlated within-subject measurements.',False), ]) # ── 13. Inclusion criteria clear_and_write(T[5].rows[0].cells[1],[ ('Inclusion criteria:',True), ('1. Patients beginning fixed orthodontic treatment receiving their first NiTi aligning archwire.',False), ('2. Age 12 years and above.',False), ('3. Good general health; no active orofacial pain unrelated to orthodontic treatment.',False), ('4. Willingness and ability to complete a self-report questionnaire at each timepoint.',False), ('5. Available for follow-up at all four timepoints (6h, 24h, 7 days, 14 days).',False), ('6. Adolescent group: 12-18 years. Adult group: 19 years and above.',False), ]) # ── 14. Exclusion criteria clear_and_write(T[5].rows[1].cells[1],[ ('Exclusion criteria:',True), ('1. Patients taking regular analgesic or anti-inflammatory medication for an unrelated chronic condition.',False), ('2. Craniofacial syndromes, active TMJ disorders, or recent oral/maxillofacial surgery.',False), ('3. Known allergy to nickel or titanium.',False), ('4. Inability to complete the questionnaire independently or via guardian-assisted administration.',False), ('5. Previous fixed orthodontic treatment within the past 12 months.',False), ]) # ── 15. Statistical analysis clear_and_write(T[5].rows[4].cells[1],[ ('Methods of statistical analysis',True),('',False), ('Data Management:',True), ('Collected data will be entered and compiled using Microsoft Excel 2019. Data will be analysed using SPSS version 23.0 or R statistical software.',False),('',False), ('Statistical Analysis:',True), ('Categorical data expressed as frequency (n) and percentage. Continuous variables expressed as mean +/- SD (normally distributed) or median (IQR) if non-normal. Normality assessed by Shapiro-Wilk test and Q-Q plot inspection.',False),('',False), ('Objectives and Statistical Tests:',True),('',False), ('PRIMARY OBJECTIVE',True), ('To measure and compare mean NRS pain scores between adolescents and adults at each timepoint and pain trajectory over time.',False), ('Statistical Test: Independent-samples t-test at each timepoint (if normally distributed) or Mann-Whitney U test (if non-normal). Bonferroni correction: adjusted alpha = 0.05/4 = 0.0125 per timepoint. Report Cohen\'s d.',False), ('Design-level: Two-way mixed-design repeated-measures ANOVA (Group x Time interaction). Mauchly\'s sphericity test; Greenhouse-Geisser correction if violated. Report partial eta-squared. Use linear mixed-effects model (LME) if attrition >10%.',False),('',False), ('SECONDARY OBJECTIVES',True), ('Analgesic use (Yes/No): Chi-square or Fisher\'s exact test; report OR + 95% CI.',False), ('Medication type: Chi-square for proportions; report % per category per group.',False), ('Peak pain timepoint: Chi-square or frequency comparison; report modal timepoint per group.',False), ('Functional impact (eating/sleep/speech): Mann-Whitney U or Chi-square (collapsed); separate analysis per domain.',False), ('Sex x Group interaction (exploratory): Three-way mixed ANOVA (Group x Sex x Time); report partial eta-squared; hypothesis-generating only.',False),('',False), ('Level of Significance:',True), ('P < 0.05 considered statistically significant for omnibus tests. Bonferroni-adjusted alpha = 0.0125 for four individual timepoint comparisons. Effect sizes (Cohen\'s d, partial eta-squared, OR + 95% CI) reported alongside all p-values.',False), ]) # ── 16. References clear_and_write(T[6].rows[0].cells[1],[ ('References (maximum 5-10, Vancouver style):',True),('',False), ('1. Olteanu CD, Bucur S-M, Chibelean M, Bud ES, Pacurar M, Festila DG. Pain Perception during Orthodontic Treatment with Fixed Appliances. Appl Sci. 2022;12(13):6389. https://doi.org/10.3390/app12136389',False),('',False), ('2. Raja SN, Carr DB, Cohen M, Finnerup NB, Flor H, Gibson S, et al. The revised IASP definition of pain. Pain. 2020;161(9):1976-1982. https://doi.org/10.1097/j.pain.0000000000001939',False),('',False), ('3. Krishnan V. Orthodontic pain: from causes to management - a review. Eur J Orthod. 2007;29(2):170-179. https://doi.org/10.1093/ejo/cjl081',False),('',False), ('4. Scheurer PA, Firestone AR, Burgin WB. Perception of pain as a result of orthodontic treatment with fixed appliances. Eur J Orthod. 1996;18(4):349-357. https://doi.org/10.1093/ejo/18.4.349',False),('',False), ('5. Fernandes LM, Ogaard B, Skoglund L. Pain and discomfort experienced after placement of a conventional or a superelastic NiTi aligning archwire. A randomized clinical trial. J Orofac Orthop. 1998;59(6):331-339. https://doi.org/10.1007/BF01299769',False),('',False), ('6. Erdinc AM, Dincer B. Perception of pain during orthodontic treatment with fixed appliances. Eur J Orthod. 2004;26(1):79-85. https://doi.org/10.1093/ejo/26.1.79',False),('',False), ('7. Abdelrahman RSh, Al-Nimri KS, Al Maaitah EF. Pain experience during initial alignment with three types of nickel-titanium archwires: a prospective clinical trial. Angle Orthod. 2015;85(6):1070-1076. https://doi.org/10.2319/071614-498.1',False),('',False), ('8. Brown DF, Moerenhout RG. The pain experience and psychological adjustment to orthodontic treatment of preadolescents, adolescents, and adults. Am J Orthod Dentofac Orthop. 1991;100(4):349-356. https://doi.org/10.1016/0889-5406(91)70073-6',False),('',False), ('9. Arias OR, Marquez-Orozco MC. Aspirin, acetaminophen, and ibuprofen: their effects on orthodontic tooth movement. Am J Orthod Dentofac Orthop. 2006;130(3):364-370. https://doi.org/10.1016/j.ajodo.2004.12.027',False),('',False), ('10. Salgado KR, Normando D, Brandao GAM. Is catastrophising associated with pain perception in early phase of orthodontic treatment? A cohort study. J Oral Rehabil. 2022;49(3):309-315. https://doi.org/10.1111/joor.13279',False), ]) # ── 17. Preliminary work clear_and_write(T[7].rows[0].cells[1],[ ('Preliminary work done already, if any (preparation of questionnaire, collection of patient details...):',True),('',False), ('The study questionnaire has been designed and adapted from the parent study format (Olteanu et al., 2022): a baseline Section A (demographics, health status, wire dimension), a repeated Section B (NRS 0-10 pain scale, functional impact, analgesic use) at each of four timepoints, and a final retrospective Section C at 14 days. The relevant literature has been systematically reviewed. Ethical approval application is pending submission.',False), ]) # ── 18. Ethical issues clear_and_write(T[7].rows[1].cells[1],[ ('Ethical issues involved in the study:',True),('',False), ('Minimal Risk. Written informed consent will be obtained from all adult participants (>=18 years). For adolescent participants (12-17 years), written parental/guardian consent and participant assent will be obtained. The study involves non-invasive procedures — self-report pain questionnaires at four timepoints following routine orthodontic archwire placement. No additional clinical procedures are required beyond standard orthodontic care. Patient data will be pseudonymised. The study will comply with the Declaration of Helsinki (2013 revision).',False), ]) # ── 19. Consent procedure clear_and_write(T[7].rows[2].cells[1],[ ('Procedure involved for obtaining informed consent from the patient or Guardian & assent from children:',True),('',False), ('Recruited patients will be informed about the purpose, procedures, voluntary nature, and confidentiality of the study. Written informed consent will be obtained from adult participants (>=18 years) prior to enrolment. For adolescent participants (12-17 years), written parental/guardian consent will be obtained along with written assent from the adolescent. Participation is entirely voluntary and withdrawal at any stage will not affect standard clinical care. Participant information will be kept strictly confidential.',False), ]) # ── 20. Recruiting clear_and_write(T[7].rows[3].cells[1],[ ('Procedure involved for recruiting volunteers:',True),('',False), ('Patients beginning fixed orthodontic treatment at Sri Venkateshwaraa Dental College, Puducherry will be assessed for eligibility. Eligible patients will be approached by the principal investigator, informed about the study, and invited to participate. Written consent/assent will be obtained prior to enrolment. Recruitment will continue over 6-12 months until the target sample is achieved (128 participants; 64 per group).',False), ]) # ── 21. Financial frame clear_and_write(T[7].rows[7].cells[1],[ ('Financial frame: Rs. 3000 - Rs. 5000',False), ('(Printing of consent forms, assent forms, and questionnaire proformas; data entry and statistical analysis; miscellaneous stationery)',False), ]) # Save to BytesIO buffer, then write to file buf = io.BytesIO() doc.save(buf) buf.seek(0) out = '/home/daytona/workspace/irb-protocol/NiTi_Pain_IRB_PROPOSAL.docx' with open(out, 'wb') as f: f.write(buf.read()) print("SAVED:", out) print("SIZE:", os.path.getsize(out), "bytes") PYEOF

pip install python-docx --quiet --user 2>&1 | tail -2 && python3 -c "from docx import Document; print('OK')"

~/irb-protocol/fill_irb.py

cd /home/daytona/workspace/irb-protocol && python3 fill_irb.py

python3 -c " from docx import Document doc = Document('/home/daytona/workspace/irb-protocol/NiTi_Pain_IRB_PROPOSAL.docx') T = doc.tables spots = [ ('T0R0C1', T[0].rows[0].cells[1]), ('T1R2C1', T[1].rows[2].cells[1]), ('T2R0C1', T[2].rows[0].cells[1]), ('T4R4C1', T[4].rows[4].cells[1]), ('T6R0C1', T[6].rows[0].cells[1]), ('T7R1C1', T[7].rows[1].cells[1]), ] for label, cell in spots: txt = ' '.join(p.text for p in cell.paragraphs)[:120] print(f'{label}: {txt}') "

cd /home/daytona/workspace && python -m markitdown "/home/daytona/workspace/attachments/73da90cf-c6d5-4c6c-93ac-d1a425c17025/LIYA MATHEW IRB ppt.pptx" 2>&1

SKILL=/home/daytona/skills/pptx SRC="/home/daytona/workspace/attachments/73da90cf-c6d5-4c6c-93ac-d1a425c17025/LIYA MATHEW IRB ppt.pptx" UNPACK=/home/daytona/workspace/irb-ppt/unpacked mkdir -p /home/daytona/workspace/irb-ppt python3 $SKILL/scripts/office/unpack.py "$SRC" "$UNPACK" 2>&1 | tail -5 echo "---slides---" ls $UNPACK/ppt/slides/ | grep -v rels | sort

mkdir -p /home/daytona/workspace/irb-ppt/unpacked cd /home/daytona/workspace/irb-ppt cp "/home/daytona/workspace/attachments/73da90cf-c6d5-4c6c-93ac-d1a425c17025/LIYA MATHEW IRB ppt.pptx" liya_template.pptx unzip -o liya_template.pptx -d unpacked/ > /dev/null 2>&1 echo "EXIT: $?" ls unpacked/ppt/slides/ | grep -v rels | sort

ls -lh "/home/daytona/workspace/attachments/73da90cf-c6d5-4c6c-93ac-d1a425c17025/"

mkdir -p /home/daytona/workspace/irb-ppt/unpacked unzip "/home/daytona/workspace/attachments/73da90cf-c6d5-4c6c-93ac-d1a425c17025/LIYA MATHEW IRB ppt.pptx" -d /home/daytona/workspace/irb-ppt/unpacked/ 2>&1 | tail -3 & sleep 8 && ls /home/daytona/workspace/irb-ppt/unpacked/ 2>/dev/null

python3 -c " import shutil, os src = '/home/daytona/workspace/attachments/73da90cf-c6d5-4c6c-93ac-d1a425c17025/LIYA MATHEW IRB ppt.pptx' dst = '/tmp/liya_irb.pptx' shutil.copy2(src, dst) print('copied', os.path.getsize(dst)) " 2>&1

mkdir -p /tmp/liya_unpacked unzip -o /tmp/liya_irb.pptx -d /tmp/liya_unpacked/ 2>&1 | tail -4 echo "---" ls /tmp/liya_unpacked/ppt/slides/ | grep -v rels | sort

python3 << 'EOF' import os, re, xml.etree.ElementTree as ET NS = {'a': 'http://schemas.openxmlformats.org/drawingml/2006/main', 'p': 'http://schemas.openxmlformats.org/presentationml/2006/main', 'r': 'http://schemas.openxmlformats.org/officeDocument/2006/relationships'} def get_text(xml_path): tree = ET.parse(xml_path) root = tree.getroot() texts = [] for sp in root.findall('.//{http://schemas.openxmlformats.org/drawingml/2006/main}t'): if sp.text and sp.text.strip(): texts.append(sp.text.strip()) return texts slides_dir = '/tmp/liya_unpacked/ppt/slides' for i in range(1, 15): f = os.path.join(slides_dir, f'slide{i}.xml') if os.path.exists(f): txts = get_text(f) print(f'\n=== SLIDE {i} ===') for t in txts: print(f' {t}') EOF

python3 << 'PYEOF' import zipfile, shutil, os, re, copy from lxml import etree SRC = '/tmp/liya_irb.pptx' OUT = '/home/daytona/workspace/irb-ppt/Nevatha_NiTi_Pain_IRB_PPT.pptx' os.makedirs('/home/daytona/workspace/irb-ppt', exist_ok=True) # ── helper: set ALL <a:t> text in a paragraph to a single run ───────────── A = 'http://schemas.openxmlformats.org/drawingml/2006/main' def para_set_text(para, new_text): """Replace ALL runs in a paragraph with a single run preserving rPr of first run.""" runs = para.findall(f'{{{A}}}r') first_rpr = None for r in runs: rpr = r.find(f'{{{A}}}rPr') if rpr is not None and first_rpr is None: first_rpr = copy.deepcopy(rpr) para.remove(r) # remove field elements too for fld in para.findall(f'{{{A}}}fld'): para.remove(fld) r_new = etree.SubElement(para, f'{{{A}}}r') if first_rpr is not None: r_new.insert(0, first_rpr) t = etree.SubElement(r_new, f'{{{A}}}t') t.text = new_text if new_text and (new_text[0] == ' ' or new_text[-1] == ' '): t.set('{http://www.w3.org/XML/1998/namespace}space', 'preserve') def get_paras(tree): return tree.findall(f'.//{{{A}}}p') def para_text(p): return ''.join((t.text or '') for t in p.findall(f'.//{{{A}}}t')) # ── slide content map ────────────────────────────────────────────────────── # Each slide: list of (search_fragment, replacement_text) # We match the PARAGRAPH whose text CONTAINS the fragment, then replace the whole para. SLIDE_PATCHES = { # ── SLIDE 1: title / name / guide ───────────────────────────────────────── 1: [ ('Evaluation of graded force regulation before and after', 'A Comparative Study of Pain Perception in Adults and Adolescents Following Placement of Initial NiTi Archwires in Orthodontic Treatment'), ('RAJAB ALI R', 'Dr. Hareharasudhan'), ('LIYA MATHEW', 'Nevatha B'), ('YEAR:CRRI', 'YEAR: MDS Year 1'), ], # ── SLIDE 2: Introduction para 1 ────────────────────────────────────────── 2: [ ('Manual dexterity is defined as a person', 'Pain and masticatory discomfort are among the most frequently reported adverse effects of fixed orthodontic treatment and remain a leading cause of reduced patient compliance and, in some cases, treatment discontinuation. Orthodontic tooth movement triggers an inflammatory response within the periodontal ligament (PDL) and pulp, releasing prostaglandins, cytokines, and substance P — the biochemical mediators of orthodontic pain. [1,2,3]'), ('Preclinical training tries to compensate', 'The initial aligning phase of fixed orthodontic treatment typically employs superelastic nickel-titanium (NiTi) archwires, which deliver continuous light forces over a wide range of deflection. Despite this, patients commonly report significant pain in the days following initial wire placement. [4,5]'), ('Thus our study is', 'The present study is specifically targeted at adolescent (12–18 years) and adult (≥19 years) orthodontic patients beginning fixed appliance therapy with an initial NiTi aligning archwire.'), ], # ── SLIDE 3: Introduction para 2 ────────────────────────────────────────── 3: [ ('The Jamar Dynamometer is a widely accepted', 'Age is one of the most frequently cited yet inconsistently reported variables in orthodontic pain research. Some studies report adults perceive greater pain than adolescents, attributed to denser alveolar bone and reduced PDL turnover with age; others report no significant difference, attributing apparent differences to psychological factors and coping strategies. [6,7,8]'), ('Therefore, our study is based on the fact that', 'The parent study (Olteanu et al., 2022) evaluated pain in 100 patients across four age bands using a single-timepoint retrospective questionnaire. The present study narrows focus to placement of the first NiTi aligning archwire and captures pain prospectively at four timepoints: 6 hours, 24 hours, 7 days, and 14 days post-placement. [1]'), ], # ── SLIDE 4: Aim and Objectives ─────────────────────────────────────────── 4: [ ('The aim of the study is to evaluate graded force regulation', 'To compare pain intensity, onset, duration, and medication requirements following placement of the initial NiTi aligning archwire between adolescent (12–18 years) and adult (≥19 years) orthodontic patients, assessed prospectively at 6 hours, 24 hours, 7 days, and 14 days post-placement.'), ('To evaluate the graded force regulation ability of undergraduate dental students before and after the incorporation', 'PRIMARY OBJECTIVE: To measure and compare mean pain intensity (NRS 0–10) between adolescents and adults at 6 hours, 24 hours, 7 days, and 14 days after initial NiTi archwire placement.'), ('To determine the effectiveness of structured manual dexterity training in improving graded force regulation', 'SECONDARY OBJECTIVES: (1) Identify the timepoint of peak pain intensity per group. (2) Compare analgesic use and medication type between groups. (3) Evaluate functional impact (eating, sleep, speech) between groups. (4) Assess whether sex modifies the pain response (exploratory).'), ], # ── SLIDE 6: Methodology flowchart ──────────────────────────────────────── 6: [ ('Sample Selection', 'Patient Recruitment — Adolescent (12–18y) vs Adult (≥19y) groups'), ('Consent Form is distributed to the sample population and their consent will be obtained', 'Written informed consent (adult ≥18y) / parental consent + adolescent assent (12–17y)'), ('Baseline assessment using Jamar Dynamometer', 'Baseline assessment at T0 — Section A questionnaire (demographics, health status, wire dimension)'), ('Measurement of maximum voluntary grip strength', 'Initial superelastic NiTi archwire placement (0.014-inch; bracket type and ligation method recorded)'), ('Structured manual dexterity program (15', 'Pain questionnaire (Section B: NRS 0–10 + functional impact + analgesic use) at T1 (6h), T2 (24h), T3 (7d), T4 (14d) + retrospective Section C at 14 days'), ('Post training assessment using Jamar Dynamometer', 'Data entry and validation (Microsoft Excel; pseudonymisation applied)'), ], # ── SLIDE 9: Sample size ────────────────────────────────────────────────── 9: [ ('As per existing literature study on', 'Based on comparable archwire-pain literature (Scheurer et al. 1996; Fernandes et al. 1998), the standard deviation of NRS pain scores is approximately σ = 1.8 points (0–10 scale). Using a minimum clinically important difference of d = 1.0 point, α = 0.05 (two-tailed), and power = 80%:'), ('Z = 1.96,', 'Formula: N = 2 × (Zα/2 + Zβ)² × σ² / d² Where: Z = 1.96, σ = 1.8, E = 1.0'), ('N = 21.8 = 22', 'N = 2 × (2.80)² × 3.24 = 50.8 → 51 per group minimum. Adjusting for 20% attrition: n = 64 per group. TOTAL TARGET = 128 participants (64 per group)'), ], # ── SLIDE 10: Statistical analysis ──────────────────────────────────────── 10: [ ('Collected data will be entered and compiled by using Microsoft Excel 2010', 'Collected data will be entered and compiled using Microsoft Excel 2019. Data will be analysed using SPSS version 23.0 or R statistical software.'), ('Categorical data will be expressed as frequency and percentage', 'Categorical data expressed as frequency and percentage. Continuous variables expressed as mean ± SD (if normally distributed) or median (IQR) if non-normal. Normality: Shapiro–Wilk test.'), ('To evaluate the graded force regulation ability of undergraduate dental students before and after incorporation', 'PRIMARY: Compare mean NRS pain scores between adolescent and adult groups at 6h, 24h, 7d, 14d'), ('Paired t-test\nSecondary Objective', 'Independent t-test / Mann–Whitney U (Bonferroni α=0.0125 per timepoint). Two-way mixed repeated-measures ANOVA (Group × Time). Report Cohen\'s d and partial η²p.'), ('To determine the effectiveness of structured manual dexterity training', 'SECONDARY: Analgesic use, functional impact, peak pain timepoint, sex-group interaction'), ], # ── SLIDE 11: Time frame ────────────────────────────────────────────────── 11: [('3', '6–12'), ('Months', 'Months recruitment + 3 months analysis')], # ── SLIDE 12: Funding ───────────────────────────────────────────────────── 12: [('Self Funding', 'Self Funding | Estimated: Rs. 3,000 – Rs. 5,000')], # ── SLIDE 13: References ────────────────────────────────────────────────── 13: [ ('Vasylenko', '1. Olteanu CD, Bucur S-M, Chibelean M, Bud ES, Pacurar M, Festila DG. Pain Perception during Orthodontic Treatment with Fixed Appliances. Appl Sci. 2022;12(13):6389. doi:10.3390/app12136389\n2. Raja SN, Carr DB, Cohen M, et al. The revised IASP definition of pain. Pain. 2020;161(9):1976–82. doi:10.1097/j.pain.0000000000001939\n3. Krishnan V. Orthodontic pain: from causes to management. Eur J Orthod. 2007;29(2):170–9. doi:10.1093/ejo/cjl081\n4. Scheurer PA, Firestone AR, Burgin WB. Perception of pain after placement of fixed appliances. Eur J Orthod. 1996;18(4):349–57. doi:10.1093/ejo/18.4.349\n5. Fernandes LM, Ogaard B, Skoglund L. Pain after placement of NiTi aligning archwire. J Orofac Orthop. 1998;59(6):331–9.\n6. Erdinc AM, Dincer B. Perception of pain during orthodontic treatment. Eur J Orthod. 2004;26(1):79–85. doi:10.1093/ejo/26.1.79\n7. Abdelrahman RSh et al. Pain with three NiTi archwire types. Angle Orthod. 2015;85(6):1070–6.\n8. Brown DF, Moerenhout RG. Pain experience and psychological adjustment. Am J Orthod Dentofac Orthop. 1991;100(4):349–56.\n9. Arias OR, Marquez-Orozco MC. Aspirin, acetaminophen, ibuprofen and orthodontic movement. Am J Orthod Dentofac Orthop. 2006;130(3):364–70.\n10. Salgado KR et al. Catastrophising and orthodontic pain. J Oral Rehabil. 2022;49(3):309–15.'), ], } # ── Process the zip ──────────────────────────────────────────────────────── with zipfile.ZipFile(SRC, 'r') as zin: names = zin.namelist() data = {n: zin.read(n) for n in names} changes = 0 for slide_num, patches in SLIDE_PATCHES.items(): fname = f'ppt/slides/slide{slide_num}.xml' if fname not in data: print(f'MISSING: {fname}') continue xml_bytes = data[fname] tree = etree.fromstring(xml_bytes) paras = get_paras(tree) for fragment, replacement in patches: matched = False for p in paras: pt = para_text(p) if fragment in pt: para_set_text(p, replacement) matched = True changes += 1 break if not matched: # try partial match on first 30 chars short = fragment[:30] for p in paras: pt = para_text(p) if short in pt: para_set_text(p, replacement) matched = True changes += 1 break if not matched: print(f' SLIDE {slide_num} — NO MATCH for: {fragment[:60]}') data[fname] = etree.tostring(tree, xml_declaration=True, encoding='UTF-8', standalone=True) # Write output with zipfile.ZipFile(OUT, 'w', zipfile.ZIP_DEFLATED) as zout: for name, content in data.items(): zout.writestr(name, content) print(f'\nDone. {changes} replacements made.') print(f'Saved: {OUT}') print(f'Size: {os.path.getsize(OUT)} bytes') PYEOF

python3 << 'PYEOF' # Check exact text of the unmatched slides import zipfile from lxml import etree SRC = '/tmp/liya_irb.pptx' A = 'http://schemas.openxmlformats.org/drawingml/2006/main' def para_text(p): return ''.join((t.text or '') for t in p.findall(f'.//{{{A}}}t')) with zipfile.ZipFile(SRC,'r') as z: for sn, needle in [(2,'Thus our study'),(10,'Paired'),(11,'Month')]: xml = z.read(f'ppt/slides/slide{sn}.xml') tree = etree.fromstring(xml) for p in tree.findall(f'.//{{{A}}}p'): pt = para_text(p) if needle.lower() in pt.lower(): print(f'S{sn}: >>>{pt[:120]}<<<') PYEOF

python3 << 'PYEOF' import zipfile, io, os, copy from lxml import etree SRC = '/tmp/liya_irb.pptx' OUT = '/home/daytona/workspace/irb-ppt/Nevatha_NiTi_Pain_IRB_PPT.pptx' A = 'http://schemas.openxmlformats.org/drawingml/2006/main' def para_text(p): return ''.join((t.text or '') for t in p.findall(f'.//{{{A}}}t')) def para_set_text(para, new_text): runs = para.findall(f'{{{A}}}r') first_rpr = None for r in runs: rpr = r.find(f'{{{A}}}rPr') if rpr is not None and first_rpr is None: first_rpr = copy.deepcopy(rpr) para.remove(r) for fld in para.findall(f'{{{A}}}fld'): para.remove(fld) r_new = etree.SubElement(para, f'{{{A}}}r') if first_rpr is not None: r_new.insert(0, first_rpr) t = etree.SubElement(r_new, f'{{{A}}}t') t.text = new_text if new_text and (new_text[0]==' ' or new_text[-1]==' '): t.set('{http://www.w3.org/XML/1998/namespace}space','preserve') def patch_slide(xml_bytes, patches): tree = etree.fromstring(xml_bytes) paras = tree.findall(f'.//{{{A}}}p') for fragment, replacement in patches: matched = False for p in paras: pt = para_text(p) if fragment.lower() in pt.lower(): para_set_text(p, replacement) matched = True break if not matched: print(f' NO MATCH: {fragment[:50]}') return etree.tostring(tree, xml_declaration=True, encoding='UTF-8', standalone=True) SLIDES = { 1: [ ('Evaluation of graded force regulation before and after', 'A Comparative Study of Pain Perception in Adults and Adolescents Following Placement of Initial NiTi Archwires in Orthodontic Treatment'), ('RAJAB ALI R', 'Dr. Hareharasudhan'), ('LIYA MATHEW', 'Nevatha B'), ('YEAR:CRRI', 'YEAR: MDS Year 1'), ], 2: [ ('Manual dexterity is defined as a person', 'Pain and masticatory discomfort are among the most frequently reported adverse effects of fixed orthodontic treatment and remain a leading cause of reduced patient compliance. Orthodontic tooth movement triggers an inflammatory response within the periodontal ligament (PDL) and pulp, releasing prostaglandins, cytokines, and substance P — the biochemical mediators of orthodontic pain. [1,2,3]'), ('Preclinical training tries to compensate', 'The initial aligning phase of fixed orthodontic treatment employs superelastic nickel-titanium (NiTi) archwires delivering continuous light forces. Patients commonly report significant pain in the days following initial wire placement. [4,5]'), ('specifically targeted at healthy first-year', 'This study is specifically targeted at adolescent (12–18 years) and adult (>=19 years) orthodontic patients beginning fixed appliance therapy with an initial NiTi aligning archwire.'), ], 3: [ ('The Jamar Dynamometer is a widely accepted', 'Age is one of the most frequently cited yet inconsistently reported variables in orthodontic pain research. Some studies report adults perceive greater pain than adolescents (denser alveolar bone, reduced PDL turnover); others report no significant difference, attributing differences to psychological factors and coping strategies. [6,7,8]'), ('Therefore, our study is based on the fact', 'The parent study (Olteanu et al., 2022) evaluated pain in 100 patients across four age bands using a single-timepoint retrospective questionnaire. The present study captures pain prospectively at four timepoints (6 hours, 24 hours, 7 days, 14 days) post-placement of the first NiTi aligning archwire. [1]'), ], 4: [ ('The aim of the study is to evaluate graded force regulation', 'AIM: To compare pain intensity, onset, duration, and medication requirements following placement of the initial NiTi aligning archwire between adolescent (12–18y) and adult (>=19y) orthodontic patients, assessed at 6h, 24h, 7d, and 14d post-placement.'), ('To evaluate the graded force regulation ability of undergraduate', 'PRIMARY OBJECTIVE: To measure and compare mean pain intensity (NRS 0–10) between adolescents and adults at 6 hours, 24 hours, 7 days, and 14 days after initial NiTi archwire placement.'), ('To determine the effectiveness of structured manual dexterity', 'SECONDARY OBJECTIVES: (1) Identify peak pain timepoint per group. (2) Compare analgesic use and medication type between groups. (3) Evaluate functional impact (eating, sleep, speech). (4) Assess whether sex modifies pain response (exploratory).'), ], 6: [ ('Sample Selection', 'Patient Recruitment — Adolescent (12–18y) vs Adult (>=19y) groups'), ('Consent Form is distributed to the sample population', 'Written informed consent (adult >=18y) / parental consent + adolescent assent (12–17y)'), ('Baseline assessment using Jamar Dynamometer', 'Baseline assessment T0 — Section A questionnaire (demographics, health status, wire dimension)'), ('Measurement of maximum voluntary grip strength', 'Initial superelastic NiTi archwire placement (standardised 0.014-inch; bracket type and ligation method recorded)'), ('Structured manual dexterity program', 'Pain questionnaire (Section B: NRS 0–10 + functional impact + analgesic use) at T1(6h), T2(24h), T3(7d), T4(14d) + retrospective Section C at 14 days'), ('Post training assessment using Jamar Dynamometer', 'Data entry and validation (Microsoft Excel; pseudonymisation applied)'), ], 9: [ ('As per existing literature study on', 'Based on comparable archwire-pain literature (Scheurer et al. 1996; Fernandes et al. 1998), SD of NRS pain scores is sigma=1.8 points. Using minimum clinically important difference d=1.0, alpha=0.05 (two-tailed), power=80%:'), ('Z = 1.96,', 'Formula: N = 2 x (Za/2 + Zb)^2 x s^2 / d^2 Where: Z=1.96, s=1.8, d=1.0'), ('N = 21.8 = 22', 'N = 2 x (2.80)^2 x 3.24 = 50.8 → 51 per group. With 20% attrition: 64 per group. TOTAL TARGET = 128 participants (64 per group)'), ], 10: [ ('Collected data will be entered and compiled by using Microsoft Excel 2010', 'Collected data will be entered and compiled using Microsoft Excel 2019. Data will be analysed using SPSS version 23.0 or R statistical software.'), ('Categorical data will be expressed as frequency and percentage', 'Categorical data expressed as frequency and percentage. Continuous variables expressed as mean +/- SD (normally distributed) or median (IQR) if non-normal. Normality: Shapiro-Wilk test.'), ('To evaluate the graded force regulation ability of undergraduate dental students before and after incorporation', 'PRIMARY: Compare mean NRS pain scores between adolescent and adult groups at 6h, 24h, 7d, 14d post-placement'), ('Paired t-test', 'Independent t-test / Mann-Whitney U (Bonferroni corrected a=0.0125). Two-way mixed repeated-measures ANOVA (Group x Time). Report Cohen\'s d and partial eta-squared.'), ('To determine the effectiveness of structured manual dexterity training', 'SECONDARY: Analgesic use (Chi-square, OR+CI), functional impact (Mann-Whitney U), peak pain timepoint, sex-group interaction (Three-way ANOVA)'), ], 11: [ ('3 Months', '6–12 Months recruitment + 3 months analysis = ~15 months total'), ], 12: [ ('Self Funding', 'Self Funding | Estimated: Rs. 3,000 – Rs. 5,000 (printing, data entry, statistical analysis)'), ], 13: [ ('Vasylenko', '1. Olteanu CD et al. Pain Perception during Orthodontic Treatment. Appl Sci. 2022;12(13):6389. doi:10.3390/app12136389 2. Raja SN et al. Revised IASP definition of pain. Pain. 2020;161(9):1976-82. 3. Krishnan V. Orthodontic pain review. Eur J Orthod. 2007;29(2):170-9. 4. Scheurer PA et al. Pain after fixed appliance placement. Eur J Orthod. 1996;18(4):349-57. 5. Fernandes LM et al. Pain after NiTi archwire placement. J Orofac Orthop. 1998;59(6):331-9. 6. Erdinc AM, Dincer B. Perception of pain during orthodontic treatment. Eur J Orthod. 2004;26(1):79-85. 7. Abdelrahman RSh et al. Pain with three NiTi archwire types. Angle Orthod. 2015;85(6):1070-6. 8. Brown DF, Moerenhout RG. Pain and psychological adjustment. Am J Orthod Dentofac Orthop. 1991;100(4):349-56. 9. Arias OR, Marquez-Orozco MC. Analgesics and orthodontic movement. Am J Orthod Dentofac Orthop. 2006;130(3):364-70. 10. Salgado KR et al. Catastrophising and orthodontic pain. J Oral Rehabil. 2022;49(3):309-15.'), ], } with zipfile.ZipFile(SRC,'r') as zin: data = {n: zin.read(n) for n in zin.namelist()} infolist = zin.infolist() for sn, patches in SLIDES.items(): fname = f'ppt/slides/slide{sn}.xml' if fname in data: print(f'Patching slide {sn}...') data[fname] = patch_slide(data[fname], patches) # Write to BytesIO first to avoid seek bug buf = io.BytesIO() with zipfile.ZipFile(buf, 'w', zipfile.ZIP_DEFLATED) as zout: for info in infolist: zout.writestr(info, data[info.filename]) raw = buf.getvalue() with open(OUT, 'wb') as f: f.write(raw) print(f'\nSAVED: {OUT}') print(f'SIZE: {os.path.getsize(OUT)} bytes') PYEOF

python3 << 'PYEOF' # Fix the one unmatched paragraph and verify all key replacements import zipfile, io, os, copy from lxml import etree F = '/home/daytona/workspace/irb-ppt/Nevatha_NiTi_Pain_IRB_PPT.pptx' A = 'http://schemas.openxmlformats.org/drawingml/2006/main' def para_text(p): return ''.join((t.text or '') for t in p.findall(f'.//{{{A}}}t')) def para_set_text(para, new_text): runs = para.findall(f'{{{A}}}r') first_rpr = None for r in runs: rpr = r.find(f'{{{A}}}rPr') if rpr is not None and first_rpr is None: first_rpr = copy.deepcopy(rpr) para.remove(r) for fld in para.findall(f'{{{A}}}fld'): para.remove(fld) r_new = etree.SubElement(para, f'{{{A}}}r') if first_rpr is not None: r_new.insert(0, first_rpr) t = etree.SubElement(r_new, f'{{{A}}}t') t.text = new_text with zipfile.ZipFile(F,'r') as zin: data = {n: zin.read(n) for n in zin.namelist()} infolist = zin.infolist() # Fix slide 2 unmatched paragraph - find the one with 'specifically targeted' xml2 = data['ppt/slides/slide2.xml'] tree2 = etree.fromstring(xml2) for p in tree2.findall(f'.//{{{A}}}p'): pt = para_text(p) if 'targeted' in pt.lower() or 'compensate' in pt.lower(): print('Found slide2 para:', pt[:80]) PYEOF