from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.units import cm, mm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle,
    HRFlowable, PageBreak, KeepTogether
)
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus import ListFlowable, ListItem

OUTPUT = "/home/daytona/workspace/lignocaine-research/Supervisor_Presentation_Plan.pdf"

doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    rightMargin=2*cm, leftMargin=2*cm,
    topMargin=2.2*cm, bottomMargin=2*cm,
    title="Supervisor Presentation Plan - IV vs Topical Lignocaine",
    author="Anaesthesia Resident"
)

W = A4[0] - 4*cm  # usable width

# ── Colour palette ──────────────────────────────────────────────
DARK_BLUE  = colors.HexColor("#0D2B6E")
MID_BLUE   = colors.HexColor("#1565C0")
LIGHT_BLUE = colors.HexColor("#E3F2FD")
ACCENT     = colors.HexColor("#C62828")
GREEN      = colors.HexColor("#1B5E20")
LIGHT_GREEN= colors.HexColor("#E8F5E9")
ORANGE     = colors.HexColor("#E65100")
LIGHT_ORANGE=colors.HexColor("#FFF3E0")
GREY_BG    = colors.HexColor("#F5F5F5")
WHITE      = colors.white
BLACK      = colors.black

# ── Styles ───────────────────────────────────────────────────────
base = getSampleStyleSheet()

def S(name, parent="Normal", **kw):
    return ParagraphStyle(name, parent=base[parent], **kw)

cover_title  = S("CoverTitle",  fontSize=22, textColor=WHITE,   alignment=TA_CENTER, leading=28, spaceAfter=6,  fontName="Helvetica-Bold")
cover_sub    = S("CoverSub",    fontSize=13, textColor=LIGHT_BLUE, alignment=TA_CENTER, leading=18, spaceAfter=4, fontName="Helvetica")
cover_info   = S("CoverInfo",   fontSize=10, textColor=LIGHT_BLUE, alignment=TA_CENTER, leading=14, fontName="Helvetica")

sec_head     = S("SecHead",     fontSize=14, textColor=WHITE,   alignment=TA_LEFT,   leading=18, spaceBefore=14, spaceAfter=4, fontName="Helvetica-Bold", leftIndent=0)
sub_head     = S("SubHead",     fontSize=11, textColor=DARK_BLUE, alignment=TA_LEFT, leading=16, spaceBefore=8, spaceAfter=3, fontName="Helvetica-Bold")
body         = S("Body",        fontSize=9,  textColor=BLACK,   alignment=TA_JUSTIFY,leading=14, spaceAfter=4,  fontName="Helvetica")
body_bold    = S("BodyBold",    fontSize=9,  textColor=BLACK,   alignment=TA_LEFT,   leading=14, spaceAfter=3,  fontName="Helvetica-Bold")
script_style = S("Script",      fontSize=9,  textColor=GREEN,   alignment=TA_LEFT,   leading=14, spaceAfter=3,  fontName="Helvetica", leftIndent=12, borderPad=4)
highlight    = S("Highlight",   fontSize=9,  textColor=ACCENT,  alignment=TA_LEFT,   leading=14, spaceAfter=3,  fontName="Helvetica-Bold")
small        = S("Small",       fontSize=8,  textColor=colors.HexColor("#555555"), alignment=TA_LEFT, leading=12, spaceAfter=2, fontName="Helvetica")
tbl_hdr      = S("TblHdr",      fontSize=8,  textColor=WHITE,   alignment=TA_CENTER, leading=11, fontName="Helvetica-Bold")
tbl_cell     = S("TblCell",     fontSize=8,  textColor=BLACK,   alignment=TA_LEFT,   leading=11, fontName="Helvetica")
tbl_cell_c   = S("TblCellC",    fontSize=8,  textColor=BLACK,   alignment=TA_CENTER, leading=11, fontName="Helvetica")
footer_style = S("Footer",      fontSize=7,  textColor=colors.grey, alignment=TA_CENTER, leading=10, fontName="Helvetica")

def section_banner(text, color=DARK_BLUE):
    data = [[Paragraph(text, sec_head)]]
    t = Table(data, colWidths=[W])
    t.setStyle(TableStyle([
        ("BACKGROUND", (0,0), (-1,-1), color),
        ("TOPPADDING",  (0,0), (-1,-1), 6),
        ("BOTTOMPADDING",(0,0),(-1,-1), 6),
        ("LEFTPADDING", (0,0), (-1,-1), 10),
    ]))
    return t

def info_box(text, bg=LIGHT_BLUE, border=MID_BLUE):
    data = [[Paragraph(text, body)]]
    t = Table(data, colWidths=[W])
    t.setStyle(TableStyle([
        ("BACKGROUND",   (0,0),(-1,-1), bg),
        ("BOX",          (0,0),(-1,-1), 1, 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 script_box(text):
    data = [[Paragraph('<i>"' + text + '"</i>', script_style)]]
    t = Table(data, colWidths=[W])
    t.setStyle(TableStyle([
        ("BACKGROUND",   (0,0),(-1,-1), LIGHT_GREEN),
        ("BOX",          (0,0),(-1,-1), 1.5, GREEN),
        ("LEFTPADDING",  (0,0),(-1,-1), 12),
        ("RIGHTPADDING", (0,0),(-1,-1), 12),
        ("TOPPADDING",   (0,0),(-1,-1), 7),
        ("BOTTOMPADDING",(0,0),(-1,-1), 7),
    ]))
    return t

def gap_box(text):
    data = [[Paragraph(text, body)]]
    t = Table(data, colWidths=[W])
    t.setStyle(TableStyle([
        ("BACKGROUND",   (0,0),(-1,-1), LIGHT_ORANGE),
        ("BOX",          (0,0),(-1,-1), 1.5, ORANGE),
        ("LEFTPADDING",  (0,0),(-1,-1), 10),
        ("RIGHTPADDING", (0,0),(-1,-1), 10),
        ("TOPPADDING",   (0,0),(-1,-1), 7),
        ("BOTTOMPADDING",(0,0),(-1,-1), 7),
    ]))
    return t

def make_table(headers, rows, col_widths=None, alt=True):
    if col_widths is None:
        col_widths = [W / len(headers)] * len(headers)
    data = [[Paragraph(h, tbl_hdr) for h in headers]]
    for i, row in enumerate(rows):
        data.append([Paragraph(str(c), tbl_cell) for c in row])
    t = Table(data, colWidths=col_widths, repeatRows=1)
    style = [
        ("BACKGROUND",    (0,0), (-1,0), DARK_BLUE),
        ("GRID",          (0,0), (-1,-1), 0.4, colors.HexColor("#BBBBBB")),
        ("TOPPADDING",    (0,0), (-1,-1), 4),
        ("BOTTOMPADDING", (0,0), (-1,-1), 4),
        ("LEFTPADDING",   (0,0), (-1,-1), 5),
        ("RIGHTPADDING",  (0,0), (-1,-1), 5),
        ("VALIGN",        (0,0), (-1,-1), "MIDDLE"),
    ]
    if alt:
        for i in range(1, len(data)):
            if i % 2 == 0:
                style.append(("BACKGROUND", (0,i), (-1,i), GREY_BG))
    t.setStyle(TableStyle(style))
    return t

# ════════════════════════════════════════════════════════════════
# BUILD CONTENT
# ════════════════════════════════════════════════════════════════
story = []

# ── COVER PAGE ──────────────────────────────────────────────────
cover_data = [[
    Paragraph("SUPERVISOR PRESENTATION PLAN", cover_title),
    Spacer(1, 0.3*cm),
    Paragraph("Research Proposal for FCPS/MCPS Dissertation", cover_sub),
    Spacer(1, 0.5*cm),
    Paragraph("Comparison of Intravenous versus Topical Lignocaine<br/>on Perfusion Index, Rate Pressure Product, and<br/>Hemodynamic Stress Response during<br/>Laryngoscopy and Endotracheal Intubation", cover_title),
    Spacer(1, 0.8*cm),
    Paragraph("A Randomized Controlled Trial", cover_sub),
    Spacer(1, 1.0*cm),
    Paragraph("Prepared by: Anaesthesia Resident", cover_info),
    Paragraph("Department of Anaesthesia", cover_info),
    Paragraph("Teaching Hospital, Lahore, Pakistan", cover_info),
    Spacer(1, 0.3*cm),
    Paragraph("Date: June 2026", cover_info),
    Spacer(1, 1.2*cm),
    Paragraph("This document contains: Alternative Titles | Differentiation from Colleague's Topic |<br/>Step-by-Step Supervisor Script | Complete Research Plan | References", cover_info),
]]
cover_tbl = Table([[c] for c in cover_data[0]], colWidths=[W])
cover_tbl.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), DARK_BLUE),
    ("TOPPADDING",  (0,0), (-1,-1), 8),
    ("BOTTOMPADDING",(0,0),(-1,-1), 8),
    ("LEFTPADDING", (0,0), (-1,-1), 20),
    ("RIGHTPADDING",(0,0), (-1,-1), 20),
]))

# Actually build cover as one big coloured block
cover_rows = [
    [Paragraph("SUPERVISOR PRESENTATION PLAN", cover_title)],
    [Spacer(1,0.2*cm)],
    [Paragraph("Research Proposal — Anaesthesia Residency (FCPS/MCPS)", cover_sub)],
    [Spacer(1,0.5*cm)],
    [Paragraph("TITLE:", S("CoverLabel", fontSize=11, textColor=colors.HexColor("#90CAF9"), alignment=TA_CENTER, fontName="Helvetica-Bold"))],
    [Paragraph("Comparison of Intravenous versus Topical Lignocaine on<br/>Perfusion Index, Rate Pressure Product, and Hemodynamic<br/>Stress Response during Laryngoscopy and Endotracheal Intubation:<br/>A Randomized Controlled Trial", cover_title)],
    [Spacer(1,0.8*cm)],
    [Paragraph("Department of Anaesthesia | Teaching Hospital, Lahore, Pakistan", cover_info)],
    [Paragraph("Prepared: June 2026", cover_info)],
    [Spacer(1,0.6*cm)],
    [Paragraph("Contents: Alternative Titles | Differentiation Strategy | Supervisor Script<br/>Complete Study Protocol | Drug Doses | Sample Size | References", cover_info)],
]
cover_t = Table(cover_rows, colWidths=[W])
cover_t.setStyle(TableStyle([
    ("BACKGROUND", (0,0), (-1,-1), DARK_BLUE),
    ("TOPPADDING",  (0,0), (-1,-1), 10),
    ("BOTTOMPADDING",(0,0),(-1,-1), 10),
    ("LEFTPADDING", (0,0), (-1,-1), 25),
    ("RIGHTPADDING",(0,0), (-1,-1), 25),
    ("ALIGN", (0,0),(-1,-1), "CENTER"),
]))
story.append(cover_t)
story.append(PageBreak())

# ── PAGE 2: TABLE OF CONTENTS ────────────────────────────────────
story.append(section_banner("TABLE OF CONTENTS"))
story.append(Spacer(1, 0.3*cm))
toc_items = [
    ("1", "Alternative Titles (No Overlap with Dr. Ashraf)", "3"),
    ("2", "Side-by-Side Comparison: Your Study vs Dr. Ashraf", "3"),
    ("3", "Step-by-Step Supervisor Presentation Script", "4"),
    ("4", "The 5-Point Convincing Argument", "5"),
    ("5", "Study Overview & Design", "6"),
    ("6", "Three Study Groups & Drug Doses", "6"),
    ("7", "Standardized Anesthetic Protocol", "7"),
    ("8", "Baseline & Complete Measurement Plan", "8"),
    ("9", "Sample Size Calculation", "9"),
    ("10", "Statistical Analysis Plan", "9"),
    ("11", "Data Collection Proforma", "10"),
    ("12", "Ethical Considerations & Timeline", "11"),
    ("13", "Human-Only References (2015-2025)", "12"),
]
toc_data = [[Paragraph(f"<b>{n}.</b>", tbl_cell), Paragraph(title, tbl_cell), Paragraph(f"Page {pg}", tbl_cell_c)] for n, title, pg in toc_items]
toc_t = Table(toc_data, colWidths=[1.0*cm, W-2.5*cm, 1.5*cm])
toc_t.setStyle(TableStyle([
    ("GRID",          (0,0), (-1,-1), 0.3, colors.HexColor("#DDDDDD")),
    ("TOPPADDING",    (0,0), (-1,-1), 5),
    ("BOTTOMPADDING", (0,0), (-1,-1), 5),
    ("LEFTPADDING",   (0,0), (-1,-1), 6),
    ("BACKGROUND",    (0,0), (-1,0), LIGHT_BLUE),
    ("ROWBACKGROUNDS",(0,0), (-1,-1), [WHITE, GREY_BG]),
]))
story.append(toc_t)
story.append(PageBreak())

# ── SECTION 1: ALTERNATIVE TITLES ───────────────────────────────
story.append(section_banner("SECTION 1: ALTERNATIVE TITLES (Zero Overlap with Dr. Ashraf's Topic)"))
story.append(Spacer(1, 0.3*cm))
story.append(info_box(
    "<b>Dr. Ashraf's Title:</b> \"Comparison of effect of induction of general anesthesia with propofol "
    "vs ketamine+midazolam on perfusion index in cardiac patients undergoing non-cardiac surgery\"<br/><br/>"
    "<b>Key words to AVOID in your title:</b> induction | propofol | ketamine | midazolam | cardiac patients | "
    "non-cardiac surgery<br/><br/>"
    "<b>Key words to INCLUDE:</b> lignocaine | IV | topical/spray | laryngoscopy | intubation | "
    "Rate Pressure Product | hemodynamic stress response | ASA I-II | elective surgery"
))
story.append(Spacer(1, 0.3*cm))
story.append(Paragraph("RECOMMENDED TITLES (choose one):", sub_head))

titles = [
    ("BEST - Recommended Title", "TITLE 1",
     "Attenuation of Hemodynamic Stress Response during Direct Laryngoscopy and Endotracheal Intubation: "
     "A Randomized Comparison of Intravenous versus Topical Lignocaine using Perfusion Index and Rate Pressure Product",
     "Zero overlap. Different drug class, different route comparison, different outcome measure, different clinical event."),
    ("Strong Alternative", "TITLE 2",
     "Effect of Intravenous versus Oropharyngeal Topical Lignocaine on Perfusion Index, Rate Pressure Product, "
     "and Cardiovascular Stress Response to Laryngoscopy and Endotracheal Intubation: A Prospective Randomized Controlled Trial",
     "Emphasizes the route comparison clearly. Adds 'cardiovascular' to differentiate from Dr. Ashraf's peripheral perfusion focus."),
    ("If Supervisor Wants Shorter", "TITLE 3",
     "Comparison of IV versus Topical Lignocaine in Blunting Hemodynamic Surge and Perfusion Index Changes "
     "during Laryngoscopy and Intubation: A Double-Blind RCT",
     "Short, clear, distinct. 'Blunting hemodynamic surge' is different language from Dr. Ashraf's 'perfusion index at induction'."),
    ("Focus on RPP (Most Novel)", "TITLE 4",
     "Rate Pressure Product and Perfusion Index as Markers of Myocardial Stress during Laryngoscopy: "
     "A Randomized Trial Comparing Intravenous versus Topical Lignocaine",
     "Puts RPP first - most novel element. No overlap whatsoever with Dr. Ashraf since she never measured RPP."),
]
for badge, num, title_text, reason in titles:
    badge_color = DARK_BLUE if "BEST" in badge else MID_BLUE
    row = [
        [Paragraph(f"<b>{num}</b><br/><font size='7'>{badge}</font>",
                   S("TBadge", fontSize=9, textColor=WHITE, alignment=TA_CENTER, fontName="Helvetica-Bold"))],
        [Paragraph(f"<b><i>{title_text}</i></b>", body),
         Spacer(1,3),
         Paragraph(f"<font color='#1B5E20'>Why distinct: {reason}</font>", small)]
    ]
    t = Table([[
        Paragraph(f"<b>{num}</b><br/><font size='7'>{badge}</font>",
                  S("TBadge2", fontSize=9, textColor=WHITE, alignment=TA_CENTER, fontName="Helvetica-Bold", leading=12)),
        [Paragraph(f"<b><i>{title_text}</i></b>", body),
         Paragraph(f"<font color='#1B5E20'>Why distinct: {reason}</font>", small)]
    ]], colWidths=[2.0*cm, W-2.0*cm])
    t.setStyle(TableStyle([
        ("BACKGROUND",   (0,0),(0,0), badge_color),
        ("BACKGROUND",   (1,0),(1,0), LIGHT_BLUE),
        ("BOX",          (0,0),(-1,-1), 1, MID_BLUE),
        ("TOPPADDING",   (0,0),(-1,-1), 7),
        ("BOTTOMPADDING",(0,0),(-1,-1), 7),
        ("LEFTPADDING",  (0,0),(-1,-1), 6),
        ("RIGHTPADDING", (0,0),(-1,-1), 6),
        ("VALIGN",       (0,0),(-1,-1), "MIDDLE"),
    ]))
    story.append(t)
    story.append(Spacer(1, 0.25*cm))

story.append(PageBreak())

# ── SECTION 2: COMPARISON TABLE ─────────────────────────────────
story.append(section_banner("SECTION 2: SIDE-BY-SIDE COMPARISON — YOUR STUDY vs DR. ASHRAF'S STUDY"))
story.append(Spacer(1, 0.3*cm))
story.append(info_box(
    "Present this table to your supervisor. It proves the two studies are completely different "
    "in every scientific dimension. The only shared element is the monitoring tool (PI), which "
    "actually strengthens your case — her published local data validates that PI works in Lahore OTs."
))
story.append(Spacer(1, 0.3*cm))

comp_headers = ["Dimension", "Dr. Ashraf's Study (PUBLISHED 2024)", "YOUR Proposed Study"]
comp_rows = [
    ["Experimental drug", "Propofol vs Ketamine+Midazolam\n(INDUCTION agents)", "IV Lignocaine vs Topical Lignocaine\n(LOCAL ANAESTHETIC — different class)"],
    ["Induction agent", "THIS IS the variable being tested", "SAME in all groups (Propofol 2mg/kg)\nFully controlled — not a variable"],
    ["Clinical phase studied", "INDUCTION phase only\n(Before laryngoscopy)", "LARYNGOSCOPY + INTUBATION phase\n(After induction is complete)"],
    ["Patient population", "CARDIAC patients specifically\n(Heart disease, IHD, valvular)", "ASA I-II general surgical patients\nNO cardiac disease (exclusion criterion)"],
    ["Primary outcome", "PI at post-induction (1 time point)", "PI change + RPP at 9 time points\n(laryngoscopy through 10 min post-intubation)"],
    ["RPP measured?", "NO — not measured", "YES — co-primary outcome\n(HR x SBP at every time point)"],
    ["Stress response studied", "Haemodynamic effects of induction\n(vasodilation/depression)", "Sympatho-adrenal surge from airway\nmanipulation (vasoconstriction, tachycardia)"],
    ["Study design", "Quasi-experimental", "Double-blind Randomized Controlled Trial\n(Higher level of evidence)"],
    ["Groups", "2 groups (no control)", "3 groups INCLUDING a saline control"],
    ["Hospital / Status", "Mayo Hospital Lahore — DONE, PUBLISHED", "Your Hospital Lahore — PROPOSED, GAP UNFILLED"],
    ["Lignocaine involved?", "NO — neither group received lignocaine", "YES — both groups receive lignocaine\n(different routes)"],
    ["Shared element", "—", "PI as monitoring tool ONLY\n(This is a strength, not a weakness)"],
]
story.append(make_table(comp_headers, comp_rows,
    col_widths=[3.5*cm, 7.5*cm, 6.5*cm]))
story.append(Spacer(1, 0.3*cm))
story.append(gap_box(
    "<b>KEY ARGUMENT:</b> These two studies occupy completely different phases of the same anaesthetic sequence. "
    "Dr. Ashraf studied Phase 1 (what happens when you give the induction drug). Your study examines "
    "Phase 2 (what happens when you put the laryngoscope in and intubate). These are separate events "
    "with different physiological mechanisms, different drugs, and different clinical implications."
))
story.append(PageBreak())

# ── SECTION 3: SUPERVISOR SCRIPT ────────────────────────────────
story.append(section_banner("SECTION 3: STEP-BY-STEP SUPERVISOR PRESENTATION SCRIPT", color=MID_BLUE))
story.append(Spacer(1, 0.3*cm))
story.append(info_box(
    "<b>Instructions:</b> This is your word-for-word script. Green boxes = what you SAY. "
    "Practice this at home before your meeting. The script is designed so that every question "
    "your supervisor might ask has a pre-planned answer. Stay calm and confident."
))
story.append(Spacer(1, 0.3*cm))

steps = [
    ("STEP 1", "Opening — Enter the room", MID_BLUE,
     "Assalamo Alaikum Ma'am/Sir. Thank you for giving me time. I have prepared a complete research "
     "proposal for my dissertation topic and I am here to present it and take your guidance.",
     "Lay your printed one-page synopsis on the table. Hand it to the supervisor before you speak further."),

    ("STEP 2", "State your topic clearly", MID_BLUE,
     "Ma'am, my proposed topic is the comparison of intravenous versus topical lignocaine on Perfusion Index, "
     "Rate Pressure Product, and hemodynamic stress response during direct laryngoscopy and endotracheal intubation.",
     "Speak slowly. Let the supervisor read the synopsis title while you say this."),

    ("STEP 3", "Explain the clinical problem (WHY this matters)", MID_BLUE,
     "Ma'am, every time we perform laryngoscopy and intubate a patient, they experience a sharp sympathetic "
     "surge — heart rate goes up, blood pressure shoots up, and peripheral vessels constrict. In a healthy "
     "person this lasts only 5-10 minutes. But in a patient with undiagnosed hypertension or silent ischemia "
     "— which is very common in our population here in Lahore — this surge can cause myocardial ischemia, "
     "arrhythmia, or stroke. Lignocaine is the most affordable and accessible drug we have to blunt this "
     "response. But we do not know which route is better in our patients — IV or topical spray. That is "
     "the gap I want to fill.",
     "Pause here. Let the supervisor absorb this. Do not rush."),

    ("STEP 4", "Introduce your outcome measures", MID_BLUE,
     "I will measure three things: First — Perfusion Index, which is the ratio of pulsatile to non-pulsatile "
     "blood flow shown on the Masimo pulse oximeter. When a patient gets a sympathetic surge, the peripheral "
     "vessels constrict and PI drops sharply. This is a real-time, non-invasive, objective marker of stress "
     "response. Second — Rate Pressure Product, which is simply heart rate multiplied by systolic blood "
     "pressure. It tells us the workload on the heart. If RPP goes above 20,000, the heart is at risk. "
     "Third — conventional parameters: HR, SBP, DBP, and MAP at 9 time points from baseline through "
     "10 minutes post-intubation.",
     "If supervisor looks confused about PI, say: 'Ma'am it is displayed on the same Masimo monitor we "
     "already use in our OTs — no extra equipment needed.'"),

    ("STEP 5", "Pre-empt the Dr. Ashraf comparison — RAISE IT YOURSELF", ACCENT,
     "Ma'am, I am aware that Dr. Ashraf's dissertation also used Perfusion Index as an outcome. I have "
     "read her published paper carefully. I want to explain why my study is completely different from hers, "
     "because I know this question will come up.",
     "IMPORTANT: Raise this yourself before the supervisor does. This shows confidence and preparation. "
     "Supervisors respect residents who anticipate objections."),

    ("STEP 6", "The Three-Phase Argument — MOST IMPORTANT STEP", ACCENT,
     "Dr. Ashraf compared propofol versus ketamine-midazolam — two induction drugs. She studied what "
     "happens to Perfusion Index after you give the induction drug, before laryngoscopy begins. Her study "
     "is entirely about the induction phase. My study begins exactly where hers ends. After induction is "
     "complete, the patient still has to be laryngoscoped and intubated — and this is a completely "
     "separate, independent, and in many ways more dangerous sympathetic stimulus. Her study did not "
     "study this phase at all. She did not give any lignocaine. She did not measure Rate Pressure "
     "Product. Her patients were cardiac patients. My patients are ASA I and II with no cardiac disease. "
     "The only thing we share is the use of Perfusion Index as a monitoring tool — and that is actually "
     "a strength for me, because her published local data proves that PI can be reliably measured in "
     "Lahore OTs on Pakistani patients. She validated the tool. I am applying it to a new question.",
     "Speak this paragraph calmly and clearly. Do not be defensive. Present it as a logical scientific progression."),

    ("STEP 7", "Show the comparison table", MID_BLUE,
     "Ma'am, I have prepared a side-by-side comparison table that shows every dimension of difference "
     "between my study and Dr. Ashraf's. May I walk you through it?",
     "Point to the comparison table in your printed plan. Go through each row briefly."),

    ("STEP 8", "Present the research gap evidence", MID_BLUE,
     "Ma'am, I searched PubMed and found that despite multiple studies on lignocaine at intubation, "
     "not a single published human RCT has simultaneously measured Perfusion Index AND Rate Pressure "
     "Product while comparing IV versus topical lignocaine. The most recent study — Pramanik et al. "
     "2025 published in BMC Anesthesiology — compared transtracheal versus IV lignocaine but did not "
     "measure PI at all. A 2025 meta-analysis of 18 RCTs and 1056 patients studied only the IV route "
     "and explicitly called for future research on ethnic variation and mechanism-based monitoring. "
     "That is exactly what my study provides.",
     "Have the printed references ready. Show PMID numbers if supervisor asks."),

    ("STEP 9", "Feasibility argument", MID_BLUE,
     "Ma'am, this study is entirely feasible in our hospital. Both drugs are already on our hospital "
     "formulary — IV lignocaine 2% and Xylocaine 10% spray. PI is measured on the Masimo oximeters "
     "we already have in every OT. RPP requires no equipment — it is just heart rate multiplied by "
     "systolic blood pressure. My target sample is 108 patients across 3 groups. At our hospital's "
     "daily elective list, this is achievable in 4 to 5 months. Total additional cost to the hospital "
     "is zero.",
     "If asked about ethical approval: 'I will apply to our institutional ethical review committee "
     "immediately after your approval, Ma'am. The study involves standard drugs already in clinical use.'"),

    ("STEP 10", "Closing and asking for approval", MID_BLUE,
     "Ma'am, I believe this topic is original, clinically important, feasible in our setting, and clearly "
     "distinct from any existing local research including Dr. Ashraf's published work. I would be "
     "grateful for your approval and guidance to proceed with the synopsis submission.",
     "End with a direct request. Do not leave the room without a clear next step."),
]

for step_num, step_title, color, say_text, note_text in steps:
    step_hdr = Table([[
        Paragraph(f"<b>{step_num}</b>", S("StepNum", fontSize=10, textColor=WHITE, fontName="Helvetica-Bold", alignment=TA_CENTER)),
        Paragraph(f"<b>{step_title}</b>", S("StepTitle", fontSize=10, textColor=WHITE, fontName="Helvetica-Bold"))
    ]], colWidths=[2.0*cm, W-2.0*cm])
    step_hdr.setStyle(TableStyle([
        ("BACKGROUND", (0,0),(-1,-1), color),
        ("TOPPADDING",  (0,0),(-1,-1), 5),
        ("BOTTOMPADDING",(0,0),(-1,-1), 5),
        ("LEFTPADDING", (0,0),(-1,-1), 8),
    ]))
    story.append(step_hdr)
    story.append(script_box(say_text))
    note_tbl = Table([[Paragraph(f"<b>Tip:</b> {note_text}", small)]], colWidths=[W])
    note_tbl.setStyle(TableStyle([
        ("BACKGROUND", (0,0),(-1,-1), colors.HexColor("#FFFDE7")),
        ("LEFTPADDING",(0,0),(-1,-1), 10),
        ("TOPPADDING", (0,0),(-1,-1), 5),
        ("BOTTOMPADDING",(0,0),(-1,-1), 5),
        ("BOX",        (0,0),(-1,-1), 0.5, ORANGE),
    ]))
    story.append(note_tbl)
    story.append(Spacer(1, 0.3*cm))

story.append(PageBreak())

# ── SECTION 4: 5-POINT ARGUMENT ─────────────────────────────────
story.append(section_banner("SECTION 4: THE 5-POINT CONVINCING ARGUMENT"))
story.append(Spacer(1, 0.2*cm))
story.append(info_box(
    "If your supervisor says 'This is similar to Dr. Ashraf's topic', respond with these five points one by one."
))
story.append(Spacer(1, 0.3*cm))

points = [
    ("Point 1", "Different Drug Class",
     "Dr. Ashraf compared induction agents (propofol vs ketamine+midazolam). "
     "My study compares routes of administration of lignocaine — a local anaesthetic, completely different drug class. "
     "There is no induction agent comparison in my study whatsoever."),
    ("Point 2", "Different Clinical Phase",
     "Induction ends before the laryngoscope enters the mouth. My study starts at that exact moment. "
     "These are sequential, non-overlapping phases of the anaesthetic."),
    ("Point 3", "Different Patient Population",
     "Her patients had cardiac disease. My patients are ASA I-II with NO cardiac disease — "
     "this is specifically an exclusion criterion in my protocol. Different population entirely."),
    ("Point 4", "Different Primary Outcomes",
     "She measured PI at one time point. I measure PI AND RPP at nine time points. "
     "Rate Pressure Product — the most clinically important outcome — was never measured in her study."),
    ("Point 5", "Her Study Supports Mine",
     "Her published work validated PI as a reliable measurement in our local OTs and Pakistani patients. "
     "That local validation is precisely why I can now use PI confidently as an outcome in my study. "
     "Her work is the foundation; my study is the extension."),
]

for num, title, text in points:
    pt = Table([[
        Paragraph(num, S("PNum", fontSize=11, textColor=WHITE, fontName="Helvetica-Bold", alignment=TA_CENTER)),
        Paragraph(f"<b>{title}</b><br/>{text}", body)
    ]], colWidths=[2.0*cm, W-2.0*cm])
    pt.setStyle(TableStyle([
        ("BACKGROUND",   (0,0),(0,0), DARK_BLUE),
        ("BACKGROUND",   (1,0),(1,0), LIGHT_BLUE),
        ("BOX",          (0,0),(-1,-1), 1, MID_BLUE),
        ("TOPPADDING",   (0,0),(-1,-1), 8),
        ("BOTTOMPADDING",(0,0),(-1,-1), 8),
        ("LEFTPADDING",  (0,0),(-1,-1), 8),
        ("VALIGN",       (0,0),(-1,-1), "MIDDLE"),
    ]))
    story.append(pt)
    story.append(Spacer(1, 0.2*cm))

story.append(Spacer(1,0.3*cm))
story.append(gap_box(
    "<b>Differentiation Statement for Your Synopsis (copy this word-for-word):</b><br/><br/>"
    "\"A recently published quasi-experimental study by Ashraf et al. (PJHS, 2024) from Mayo Hospital, "
    "Lahore compared propofol versus ketamine-midazolam as induction agents and demonstrated that "
    "ketamine-midazolam produced a significantly higher post-induction Perfusion Index in cardiac patients "
    "(PI: 1.88 vs 1.69, p=0.001), validating the clinical utility of PI monitoring in our local patient "
    "population. The present study differs fundamentally in its clinical question, drug intervention, patient "
    "population, and outcome measures. Our study evaluates attenuation of the laryngoscopy and intubation "
    "stress response — a distinct haemodynamic event occurring after induction is complete — using lignocaine "
    "administered by two different routes in ASA I-II general surgical patients without cardiac disease. "
    "Rate Pressure Product, which quantifies myocardial oxygen demand and was not measured by Ashraf et al., "
    "is included as a co-primary outcome.\""
))
story.append(PageBreak())

# ── SECTION 5: STUDY DESIGN ─────────────────────────────────────
story.append(section_banner("SECTION 5: COMPLETE STUDY DESIGN & OVERVIEW"))
story.append(Spacer(1, 0.2*cm))
design_rows = [
    ["Study type",           "Prospective, Randomized, Double-Blind, Placebo-Controlled Trial (RCT)"],
    ["Number of groups",     "3 Groups — Group A (IV Lignocaine), Group B (Topical Lignocaine), Group C (Control)"],
    ["Setting",              "Department of Anaesthesia, Teaching Hospital, Lahore"],
    ["Duration",             "6 months data collection + 2 months analysis/write-up = 8 months total"],
    ["Sample size",          "108 patients (36 per group)"],
    ["Population",           "Adult ASA I-II, 18-60 years, elective surgery requiring GA + ETT, no cardiac disease"],
    ["Primary outcomes",     "Perfusion Index (ΔPI from baseline) + Rate Pressure Product (RPP) at T3-T7"],
    ["Secondary outcomes",   "HR, MAP, SBP, DBP changes; adverse events; cough; sore throat"],
    ["Blinding",             "Patient blinded. Data recorder blinded. Intubating anaesthesiologist blinded."],
    ["Randomization",        "Computer-generated block randomization, sealed opaque envelopes"],
    ["Ethics",               "IRB/ERC approval + written informed consent + trial registration (PHRC/ClinicalTrials.gov)"],
    ["Cost",                 "Zero additional cost — both drugs on formulary, PI on existing Masimo monitors"],
]
story.append(make_table(["Feature", "Detail"], design_rows, col_widths=[4*cm, W-4*cm]))
story.append(PageBreak())

# ── SECTION 6: THREE GROUPS & DRUG DOSES ─────────────────────────
story.append(section_banner("SECTION 6: THREE STUDY GROUPS AND DRUG DOSES"))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph("Each patient receives BOTH an IV injection AND an oropharyngeal spray to maintain blinding. One will be the active drug; the other will be saline placebo.", body))
story.append(Spacer(1, 0.2*cm))

grp_headers = ["", "GROUP A\nIV Lignocaine", "GROUP B\nTopical Lignocaine", "GROUP C\nControl (Saline)"]
grp_rows = [
    ["IV Injection",     "2% Lignocaine\n1.5 mg/kg\n(slow IV push over 30 sec)", "Normal Saline\n5 mL IV\n(placebo)", "Normal Saline\n5 mL IV\n(placebo)"],
    ["Oropharyngeal Spray", "Normal Saline\nspray 4 puffs\n(placebo)", "10% Lignocaine spray\n1.5 mg/kg\n(4-7 puffs by weight)", "Normal Saline\nspray 4 puffs\n(placebo)"],
    ["When given",       "3 min before laryngoscopy", "2 min before laryngoscopy", "Same timing as Group A"],
    ["Active drug",      "Lignocaine IV", "Lignocaine SPRAY", "Neither"],
    ["Placebo present?", "Yes (saline spray)", "Yes (saline IV)", "Both placebo"],
]
story.append(make_table(grp_headers, grp_rows, col_widths=[3.5*cm, (W-3.5*cm)/3, (W-3.5*cm)/3, (W-3.5*cm)/3]))
story.append(Spacer(1, 0.3*cm))

story.append(Paragraph("DOSE CALCULATION GUIDE (for 10% Lignocaine Spray):", sub_head))
dose_rows = [
    ["50 kg", "75 mg", "7-8 puffs"],
    ["60 kg", "90 mg", "9 puffs"],
    ["70 kg", "105 mg", "10-11 puffs"],
    ["80 kg", "120 mg", "12 puffs"],
    ["90 kg", "135 mg", "13-14 puffs"],
]
story.append(make_table(
    ["Patient Weight", "Dose (1.5 mg/kg)", "Number of 10% Spray Puffs (~10 mg/puff)"],
    dose_rows, col_widths=[4*cm, 4*cm, W-8*cm]
))
story.append(Spacer(1, 0.2*cm))
story.append(info_box(
    "<b>Why 1.5 mg/kg?</b> This is the evidence-based optimal dose confirmed by: "
    "(1) Pramanik et al. 2025 RCT [PMID: 40413425], (2) Qin et al. 2025 meta-analysis of 18 RCTs, "
    "(3) Kocamanoglu et al. 2015 RCT [PMID: 25496674]. Doses below 1 mg/kg are ineffective. "
    "Doses above 2 mg/kg increase toxicity risk without additional benefit. "
    "Maximum safe total IV dose: 3 mg/kg. Maximum topical dose: 4 mg/kg. Both well within safety limits."
))
story.append(PageBreak())

# ── SECTION 7: ANESTHETIC PROTOCOL ──────────────────────────────
story.append(section_banner("SECTION 7: STANDARDIZED ANESTHETIC PROTOCOL"))
story.append(Spacer(1, 0.2*cm))
story.append(info_box(
    "<b>Critical principle:</b> The induction drug is IDENTICAL in all three groups (propofol). "
    "This fully eliminates any induction-phase confounding and separates your study from Dr. Ashraf's "
    "completely. You are studying what happens AFTER induction — a different phase entirely."
))
story.append(Spacer(1, 0.3*cm))

protocol_rows = [
    ["PRE-OP", "NPO 6 hrs (solids), 2 hrs (clear liquids). No premedication sedatives. IV cannula 18G right hand. Baseline vitals on ward."],
    ["OT ARRIVAL", "Attach: ECG lead II, NIBP right arm, Masimo pulse oximeter LEFT index finger (PI displayed). Patient rests 5 minutes. Record BASELINE (T0)."],
    ["PREOXYGENATION", "100% O2 via face mask, 6 L/min for 3 minutes. Target EtO2 >90%."],
    ["INDUCTION\n(ALL GROUPS SAME)", "Step 1: Fentanyl 2 mcg/kg IV (analgesic — given 2 min before induction)\nStep 2: Propofol 2 mg/kg IV — titrated to loss of verbal contact\nStep 3: Atracurium 0.5 mg/kg IV — neuromuscular blockade\nStep 4: Wait 3 minutes for full NMB"],
    ["STUDY DRUG\nADMINISTRATION", "After 3 minutes of atracurium:\n- Group A: IV lignocaine 1.5mg/kg over 30 sec + saline spray\n- Group B: Saline IV 5mL + topical lignocaine spray 1.5mg/kg\n- Group C: Saline IV 5mL + saline spray\nWait 3 minutes after IV drug (2 minutes after spray)"],
    ["LARYNGOSCOPY\n& INTUBATION", "Macintosh blade size 3. Single attempt only. Time from blade insertion to tube secured: record in seconds. Cuff inflated. EtCO2 confirmed. If intubation fails in 30 sec or needs 2+ attempts: EXCLUDE patient."],
    ["MAINTENANCE", "Isoflurane 1 MAC in O2/Air 50:50. Continue recording parameters at T4, T5, T6, T7, T8."],
    ["EMERGENCE", "Standard emergence. Record cough grade (0-3) and sore throat at 1 hour post-op."],
]
story.append(make_table(["Phase", "Actions"], protocol_rows, col_widths=[3.0*cm, W-3.0*cm]))
story.append(PageBreak())

# ── SECTION 8: MEASUREMENTS ──────────────────────────────────────
story.append(section_banner("SECTION 8: BASELINE AND COMPLETE MEASUREMENT PLAN"))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph("WHAT IS BASELINE (T0)?", sub_head))
story.append(info_box(
    "Baseline = measurements taken from the AWAKE, CALM patient after 5 minutes of rest in OT, "
    "with monitors attached, BEFORE any drug (including fentanyl) is given. "
    "This is the patient's true resting state. All subsequent changes are expressed as percentage "
    "change from this baseline. For PI specifically, what matters is the CHANGE (ΔPI), not the "
    "absolute value, because PI varies normally between 1-10% across individuals."
))
story.append(Spacer(1, 0.2*cm))

tp_headers = ["Time Point", "Label", "Clinical Moment", "What to Record"]
tp_rows = [
    ["T0", "BASELINE", "Awake, resting — after 5 min in OT, before any drug", "HR, SBP, DBP, MAP, SpO2, PI, RPP"],
    ["T1", "Post-fentanyl\nPost-induction", "1 min after propofol (before study drug)", "HR, SBP, DBP, MAP, SpO2, PI, RPP"],
    ["T2", "Pre-laryngoscopy", "Just before blade insertion (after study drug given)", "HR, SBP, DBP, MAP, SpO2, PI, RPP"],
    ["T3", "At laryngoscopy", "At moment of laryngoscope insertion — MOST CRITICAL", "HR, SBP, DBP, MAP, SpO2, PI, RPP"],
    ["T4", "0-30 sec post-intubation", "Immediately after tube placed and cuff inflated", "HR, SBP, DBP, MAP, SpO2, PI, RPP"],
    ["T5", "1 min post-intubation", "1 minute after ETT secured", "HR, SBP, DBP, MAP, SpO2, PI, RPP"],
    ["T6", "3 min post-intubation", "3 minutes after ETT secured — MOST CRITICAL", "HR, SBP, DBP, MAP, SpO2, PI, RPP"],
    ["T7", "5 min post-intubation", "5 minutes after ETT secured", "HR, SBP, DBP, MAP, SpO2, PI, RPP"],
    ["T8", "10 min post-intubation", "10 minutes after ETT secured (recovery phase)", "HR, SBP, DBP, MAP, SpO2, PI, RPP"],
]
story.append(make_table(tp_headers, tp_rows, col_widths=[1.8*cm, 2.5*cm, 5.5*cm, W-9.8*cm]))
story.append(Spacer(1, 0.3*cm))

story.append(Paragraph("HOW TO CALCULATE RPP:", sub_head))
story.append(info_box(
    "<b>RPP = Heart Rate (beats/min) × Systolic Blood Pressure (mmHg)</b><br/><br/>"
    "Example: HR = 88, SBP = 128 → RPP = 88 × 128 = <b>11,264</b> (normal, safe)<br/>"
    "Example: HR = 110, SBP = 165 → RPP = 110 × 165 = <b>18,150</b> (elevated — concerning)<br/>"
    "Example: HR = 125, SBP = 175 → RPP = 125 × 175 = <b>21,875</b> (DANGEROUS — myocardial ischemia risk)<br/><br/>"
    "Threshold: RPP >20,000 = significant myocardial oxygen demand. Calculate at every time point."
))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph("HOW TO INTERPRET PI CHANGES:", sub_head))
story.append(info_box(
    "<b>PI = (AC component / DC component) × 100%</b> — displayed automatically on Masimo oximeter<br/><br/>"
    "Normal baseline PI: 1–10% (varies between individuals — use each patient's own T0 as reference)<br/>"
    "PI FALLS at laryngoscopy = sympathetic vasoconstriction = stress response occurring<br/>"
    "PI RECOVERS after intubation = stress response resolving<br/>"
    "BIGGER fall in PI = MORE intense stress response<br/>"
    "FASTER recovery = BETTER drug effect<br/><br/>"
    "Express as: ΔPI = [(T0 − Tx) / T0] × 100% — this is the primary outcome variable"
))
story.append(PageBreak())

# ── SECTION 9: SAMPLE SIZE ───────────────────────────────────────
story.append(section_banner("SECTION 9: SAMPLE SIZE CALCULATION"))
story.append(Spacer(1, 0.2*cm))
story.append(info_box(
    "<b>Based on:</b> Pramanik et al. 2025 (BMC Anesthesiol, PMID 40413425) — most recent direct comparator<br/>"
    "Mean MAP post-intubation: IV group = 79 mmHg, Topical group = 73 mmHg<br/>"
    "Expected difference (δ) = 6 mmHg | Pooled SD = ~12 mmHg<br/><br/>"
    "<b>Formula:</b> n = 2 × (Zα/2 + Zβ)² × σ² / δ²<br/>"
    "α = 0.05 (two-tailed), Zα/2 = 1.96 | Power = 80%, Zβ = 0.84<br/>"
    "n = 2 × (1.96 + 0.84)² × 144 / 36 = 2 × 7.84 × 4 = <b>32 per group</b><br/><br/>"
    "Add 12% for dropouts/exclusions: <b>36 per group</b><br/><br/>"
    "<b>TOTAL SAMPLE SIZE = 36 × 3 = 108 patients</b><br/><br/>"
    "At 6-7 eligible patients per week → achievable in <b>4 months</b>"
))
story.append(PageBreak())

# ── SECTION 10: STATISTICS ───────────────────────────────────────
story.append(section_banner("SECTION 10: STATISTICAL ANALYSIS PLAN"))
story.append(Spacer(1, 0.2*cm))
stat_rows = [
    ["One-way ANOVA", "Compare HR, MAP, SBP, RPP, PI means across 3 groups at each time point"],
    ["Repeated Measures ANOVA", "Compare changes over time within and between all 3 groups (primary analysis)"],
    ["Post-hoc Tukey's test", "Pairwise comparison: Group A vs B, A vs C, B vs C (after ANOVA)"],
    ["Kruskal-Wallis test", "Used for PI data if not normally distributed (non-parametric alternative)"],
    ["Chi-square test", "Adverse events, cough incidence, sore throat (categorical outcomes)"],
    ["Pearson correlation", "Correlation between ΔPI and HR/MAP at each time point"],
    ["Software", "SPSS version 26"],
    ["Significance", "P < 0.05 (two-tailed) considered statistically significant"],
    ["Data expression", "Normally distributed: Mean ± SD | Non-normal: Median (IQR)"],
]
story.append(make_table(["Test", "Purpose"], stat_rows, col_widths=[4.5*cm, W-4.5*cm]))
story.append(PageBreak())

# ── SECTION 11: PROFORMA ─────────────────────────────────────────
story.append(section_banner("SECTION 11: DATA COLLECTION PROFORMA"))
story.append(Spacer(1, 0.2*cm))
story.append(Paragraph("Print one copy per patient. Keep blinded — data recorder does not know which group.", body))
story.append(Spacer(1, 0.2*cm))

proforma_bg = colors.HexColor("#FAFAFA")
pro_data = [
    ["PATIENT DATA COLLECTION FORM — STRICTLY CONFIDENTIAL"],
    ["Patient ID: ____________   Date: ____________   Envelope No: ______   Group: A / B / C (circle after unblinding)"],
    ["Age: ___   Sex: M/F   Weight: ___ kg   Height: ___ cm   BMI: ___   ASA: I / II   Mallampati: I / II"],
    ["Procedure: _________________________   Surgeon: _________________________"],
    [""],
    ["VITALS RECORDING TABLE"],
    ["Time Point | HR (bpm) | SBP (mmHg) | DBP (mmHg) | MAP (mmHg) | SpO2 (%) | PI (%) | RPP (HR×SBP)"],
    ["T0 – BASELINE (awake, resting) |      |      |      |      |      |      |"],
    ["T1 – Post-induction (before drug) |      |      |      |      |      |      |"],
    ["T2 – Pre-laryngoscopy (after drug) |      |      |      |      |      |      |"],
    ["T3 – At laryngoscopy insertion |      |      |      |      |      |      |"],
    ["T4 – Immediately post-intubation |      |      |      |      |      |      |"],
    ["T5 – 1 min post-intubation |      |      |      |      |      |      |"],
    ["T6 – 3 min post-intubation |      |      |      |      |      |      |"],
    ["T7 – 5 min post-intubation |      |      |      |      |      |      |"],
    ["T8 – 10 min post-intubation |      |      |      |      |      |      |"],
    [""],
    ["DRUG ADMINISTRATION"],
    ["Fentanyl: ___ mcg IV   Propofol: ___ mg IV   Atracurium: ___ mg IV"],
    ["Study IV drug: _______________   Volume: ___ mL   Time given: ___   Minutes before laryngoscopy: ___"],
    ["Study Spray: _______________   No. puffs: ___   Time given: ___"],
    [""],
    ["INTUBATION DETAILS"],
    ["Attempts: ___   Duration of laryngoscopy: ___ seconds   Blade: Mac size ___   ETT size: ___"],
    ["EtCO2 confirmed: Y/N   Cuff pressure: ___ cmH2O"],
    [""],
    ["ADVERSE EVENTS"],
    ["Hypertension (SBP >20% baseline): Y/N   Tachycardia (HR >20% baseline): Y/N"],
    ["Hypotension (MAP <60): Y/N   Bradycardia (HR <50): Y/N"],
    ["Cough grade: 0 (none) / 1 (mild) / 2 (moderate) / 3 (severe)"],
    ["Sore throat at 1 hour post-op: Y/N"],
    [""],
    ["Recorder signature: ___________________   Time completed: ___________"],
]

for row_text in pro_data:
    if row_text == "":
        story.append(Spacer(1, 0.1*cm))
    elif "VITALS RECORDING" in row_text or "DRUG ADMIN" in row_text or "INTUBATION" in row_text or "ADVERSE" in row_text or "PATIENT DATA" in row_text:
        story.append(Paragraph(f"<b>{row_text}</b>", body_bold))
    else:
        story.append(Paragraph(row_text, small))

story.append(PageBreak())

# ── SECTION 12: ETHICS AND TIMELINE ─────────────────────────────
story.append(section_banner("SECTION 12: ETHICAL CONSIDERATIONS AND TIMELINE"))
story.append(Spacer(1, 0.2*cm))

ethics_rows = [
    ["Ethical approval", "Apply to Institutional Ethical Review Committee immediately after supervisor approval"],
    ["Trial registration", "PHRC (Pakistan Health Research Council) or ClinicalTrials.gov — free registration"],
    ["Consent", "Written informed consent in Urdu + English. Patient may withdraw at any time."],
    ["Risk level", "MINIMAL — both drugs already in routine clinical use. No experimental drug, no off-label use."],
    ["Adverse events", "All adverse events managed immediately per standard OT protocols. Rescue drugs prepared."],
    ["Data security", "Patient data anonymized. Proforma stored in locked cabinet. SPSS file password protected."],
    ["Conflict of interest", "None. No pharmaceutical funding required."],
]
story.append(Paragraph("ETHICAL CONSIDERATIONS:", sub_head))
story.append(make_table(["Item", "Plan"], ethics_rows, col_widths=[3.5*cm, W-3.5*cm]))
story.append(Spacer(1, 0.3*cm))

timeline_rows = [
    ["Month 1", "Ethical approval application. Trial registration. Proforma finalization. Team training."],
    ["Month 2", "Pilot enrollment (10 patients) to test protocol. Adjust if needed."],
    ["Months 2-5", "Full patient enrollment: target 27 patients/month (6-7/week). 3 groups in parallel."],
    ["Month 6", "Data cleaning, entry verification, and SPSS database lock."],
    ["Month 7", "Statistical analysis, tables, graphs."],
    ["Month 8", "Write-up, supervisor review, dissertation submission."],
]
story.append(Paragraph("STUDY TIMELINE:", sub_head))
story.append(make_table(["Period", "Activity"], timeline_rows, col_widths=[2.5*cm, W-2.5*cm]))
story.append(Spacer(1, 0.3*cm))
story.append(info_box(
    "<b>Resource Requirements:</b> 2% Lignocaine injection — hospital formulary ✓ | "
    "10% Lignocaine spray — hospital formulary ✓ | Masimo pulse oximeter (PI-capable) — OT equipment ✓ | "
    "NIBP + ECG — standard OT equipment ✓ | SPSS v26 — hospital/institutional ✓ | "
    "<b>Additional cost to hospital: ZERO</b>"
))
story.append(PageBreak())

# ── SECTION 13: REFERENCES ───────────────────────────────────────
story.append(section_banner("SECTION 13: HUMAN-ONLY REFERENCES (2000-2025) — ALL HUMAN PATIENT STUDIES"))
story.append(Spacer(1, 0.2*cm))
story.append(info_box(
    "All references below involve HUMAN patients only. No animal studies included. "
    "PMID numbers allow your supervisor to verify each paper on PubMed instantly. "
    "Free full-text links are available for all PMC-listed papers."
))
story.append(Spacer(1, 0.3*cm))

refs = [
    ("1", "2025", "Systematic Review / Meta-Analysis [HIGHEST EVIDENCE]",
     "Qin J, He C, Chen Z, Yan S, Ma J. Effects of intravenous lignocaine on haemodynamic responses to "
     "laryngoscopy and tracheal intubation in adults under general anaesthesia: A systematic review and "
     "meta-analysis. 2025.",
     "PMC12338463", "Free: pmc.ncbi.nlm.nih.gov/articles/PMC12338463",
     "18 RCTs, 1056 human patients. IV lignocaine 1.5mg/kg optimal. Topical route NOT compared. PI NOT measured. "
     "Explicitly calls for future research on mechanism-based monitoring. → YOUR STUDY FILLS THIS GAP."),
    ("2", "2025", "RCT — Direct Route Comparison [MOST RELEVANT]",
     "Pramanik M, Chattopadhyay U, Chaudhuri S et al. Comparison between transtracheal and intravenous 2% "
     "lignocaine in attenuating hemodynamic stress response following direct laryngoscopy and endotracheal "
     "intubation: a randomized controlled trial. BMC Anesthesiology. 2025;25:215.",
     "PMID: 40413425", "Free: pmc.ncbi.nlm.nih.gov/articles/PMC12102901",
     "138 human patients. Transtracheal > IV at 3 min post-intubation. RPP trended lower in TT group. "
     "PERFUSION INDEX NOT MEASURED. → YOUR STUDY ADDS PI TO THIS COMPARISON."),
    ("3", "2024", "RCT — Topical Spray in Humans",
     "Liu H, Bu W, Chen X, Wu Z. Topical larynx lidocaine spraying reduces cardiovascular stress response "
     "caused by suspension laryngoscopic surgery. Braz J Otorhinolaryngol. 2024;Nov-Dec:101481.",
     "PMID: 39270370", "Free: pmc.ncbi.nlm.nih.gov/articles/PMC11415576",
     "68 human patients. Topical lidocaine 2mg/kg reduced MAP, HR, epinephrine, norepinephrine vs saline. "
     "NO IV arm. NO Perfusion Index. NO RPP. → YOUR STUDY ADDS IV COMPARISON + PI + RPP."),
    ("4", "2023", "PI at Laryngoscopy in Humans [PI VALIDATION]",
     "Shah SB, Chawla R, Kaur C. Assessment of stress response due to videolaryngoscopic endotracheal "
     "intubation using perfusion index. J Clin Monit Comput. 2023;37(4):987-997.",
     "PMID: 37088851", "DOI: 10.1007/s10877-023-01005-5",
     "26 human patients. PI fell from 4.14 to 3.24 at laryngoscopy (p significant). PI negatively correlated "
     "with MAP and HR. VALIDATES PI AS STRESS MARKER IN HUMANS. No lignocaine intervention. "
     "→ YOUR STUDY APPLIES THIS VALIDATED TOOL WITH A LIGNOCAINE INTERVENTION."),
    ("5", "2021", "RCT — IV Lignocaine vs Dexmedetomidine in Humans",
     "Seangrung R, Pasutharnchat K, Injampa S et al. Comparison of hemodynamic response of dexmedetomidine "
     "versus additional intravenous lidocaine with propofol during tracheal intubation. BMC Anesthesiol. "
     "2021;21(1):270.",
     "PMID: 34717532", "Free: pmc.ncbi.nlm.nih.gov/articles/PMC8557037",
     "106 human patients. IV lidocaine 1.5mg/kg had non-inferior effect vs dexmedetomidine with fewer "
     "adverse effects. NO topical comparison. NO PI. NO RPP."),
    ("6", "2019", "RCT — Topical Spray + RPP in Humans [RPP REFERENCE]",
     "Varshney RK, Prasad MK, Garg M. Comparison of Nitroglycerin versus Lignocaine Spray to Attenuate "
     "Haemodynamic Changes during Direct Laryngoscopy and Endotracheal Intubation. Sultan Qaboos Univ Med J. "
     "2019;19(4):e316-e321.",
     "PMID: 31897315", "Free: pmc.ncbi.nlm.nih.gov/articles/PMC6930035",
     "90 human patients. Topical lignocaine 10% spray significantly reduced RPP at 1-5 min vs control. "
     "NO IV LIGNOCAINE ARM. NO PI. → YOUR STUDY ADDS IV COMPARISON AND PI."),
    ("7", "2022", "RCT — Intratracheal vs IV Lignocaine at Extubation (Humans)",
     "Gladston DV, Padmam S, Omanakutty Amma R et al. Randomized controlled trial: intratracheal vs "
     "intravenous lignocaine on airway and hemodynamic response during emergence and extubation. "
     "J Anaesthesiol Clin Pharmacol. 2022.",
     "PMC: 9514071", "Free: pmc.ncbi.nlm.nih.gov/articles/PMC9514071",
     "75 human patients. Intratracheal lignocaine superior to IV at extubation phase. "
     "Study was at EXTUBATION not intubation. NO PI. NO RPP. → YOUR STUDY FILLS THE INTUBATION PHASE GAP."),
    ("8", "2015", "RCT — Direct IV vs Topical Comparison in Humans [CLOSEST HISTORICAL]",
     "Kocamanoglu IS, Cengel Kurnaz S, Tur A. Effects of lignocaine on pressor response to laryngoscopy and "
     "endotracheal intubation during general anaesthesia. J Laryngol Otol. 2015;129(1):54-58.",
     "PMID: 25496674", "DOI: 10.1017/S0022215114003077",
     "99 human patients. Both routes reduced HDSR vs control. No significant difference between routes. "
     "STUDY IS 11 YEARS OLD. NO PI. NO RPP. INCONCLUSIVE. → YOUR STUDY REPLICATES WITH MODERN OUTCOMES."),
    ("9", "2000", "RCT — Mechanistic Proof in Humans [FOUNDATIONAL]",
     "Hamaya Y, Dohi S. Differences in cardiovascular response to airway stimulation at different sites and "
     "blockade of the responses by lidocaine. Anesthesiology. 2000;93(1):99-109.",
     "PMID: 10861151", "DOI: 10.1097/00000542-200007000-00018",
     "60 anesthetized human patients. Topical lidocaine COMPLETELY abolished CVR. IV only PARTIALLY blocked. "
     "This mechanistic difference in HUMANS justifies why the route comparison matters. "
     "No modern outcomes (PI/RPP) measured. → YOUR STUDY QUANTIFIES THIS WITH PI AND RPP."),
]

for num, year, level, citation, pmid, link, gap in refs:
    ref_rows = [
        [Paragraph(f"<b>Ref {num}</b><br/><font size='7'>{year}</font>", S("RN", fontSize=9, textColor=WHITE, fontName="Helvetica-Bold", alignment=TA_CENTER, leading=13)),
         [Paragraph(f"<font color='#C62828'><b>{level}</b></font>", small),
          Paragraph(citation, small),
          Paragraph(f"<b>{pmid}</b> | {link}", small),
          Paragraph(f"<font color='#1B5E20'><b>Research Gap:</b> {gap}</font>", small)]]
    ]
    rt = Table([[
        Paragraph(f"<b>{num}</b><br/><font size='7'>{year}</font>",
                  S("RN2", fontSize=9, textColor=WHITE, fontName="Helvetica-Bold", alignment=TA_CENTER, leading=13)),
        [Paragraph(f"<font color='#C62828'><b>{level}</b></font>", small),
         Paragraph(citation, small),
         Paragraph(f"<b>{pmid}</b> | {link}", small),
         Paragraph(f"<font color='#1B5E20'><b>Gap:</b> {gap}</font>", small)]
    ]], colWidths=[1.5*cm, W-1.5*cm])
    rt.setStyle(TableStyle([
        ("BACKGROUND",   (0,0),(0,0), DARK_BLUE),
        ("BACKGROUND",   (1,0),(1,0), GREY_BG),
        ("BOX",          (0,0),(-1,-1), 0.5, MID_BLUE),
        ("TOPPADDING",   (0,0),(-1,-1), 6),
        ("BOTTOMPADDING",(0,0),(-1,-1), 6),
        ("LEFTPADDING",  (0,0),(-1,-1), 6),
        ("RIGHTPADDING", (0,0),(-1,-1), 6),
        ("VALIGN",       (0,0),(-1,-1), "TOP"),
    ]))
    story.append(rt)
    story.append(Spacer(1, 0.2*cm))

story.append(PageBreak())

# ── FINAL PAGE: QUICK REFERENCE CARD ────────────────────────────
story.append(section_banner("QUICK REFERENCE CARD — HAND THIS TO YOUR SUPERVISOR", color=GREEN))
story.append(Spacer(1, 0.2*cm))

qr_rows = [
    ["TITLE",        "Comparison of IV vs Topical Lignocaine on Perfusion Index, Rate Pressure Product, and\nHemodynamic Stress Response during Laryngoscopy and Endotracheal Intubation: A RCT"],
    ["DESIGN",       "3-group, Double-blind, Randomized Controlled Trial"],
    ["Group A",      "IV Lignocaine 1.5 mg/kg + Oropharyngeal Saline Spray"],
    ["Group B",      "IV Saline + Topical 10% Lignocaine Spray 1.5 mg/kg"],
    ["Group C",      "IV Saline + Oropharyngeal Saline Spray (Control)"],
    ["INDUCTION",    "IDENTICAL in all groups: Propofol 2mg/kg + Fentanyl 2mcg/kg + Atracurium 0.5mg/kg"],
    ["PATIENTS",     "108 total (36/group), ASA I-II, 18-60 years, NO cardiac disease, elective surgery"],
    ["1° OUTCOMES",  "ΔPerfusion Index (%) + Rate Pressure Product at T3, T5, T6, T7"],
    ["2° OUTCOMES",  "HR, SBP, DBP, MAP, adverse events, cough grade, sore throat"],
    ["EQUIPMENT",    "Masimo pulse oximeter (PI displayed), NIBP, ECG — already in OT"],
    ["COST",         "ZERO additional cost — all drugs on hospital formulary"],
    ["DURATION",     "6 months enrollment + 2 months analysis = 8 months total"],
    ["DIFFERENT FROM\nDR. ASHRAF",
     "• Different drug (lignocaine vs induction agents)\n"
     "• Different phase (intubation vs induction)\n"
     "• Different patients (ASA I-II, no cardiac disease vs cardiac patients)\n"
     "• Different outcomes (PI + RPP at 9 time points vs PI alone at 1 time point)\n"
     "• Her study PUBLISHED and DONE — mine fills the next logical gap"],
    ["TOP REFERENCE", "Pramanik et al. 2025, BMC Anesthesiol, PMID 40413425 — transtracheal vs IV lignocaine\n"
     "in 138 humans — did NOT measure PI or RPP. Your study fills this gap."],
]
story.append(make_table(["", ""], qr_rows, col_widths=[3.5*cm, W-3.5*cm]))
story.append(Spacer(1, 0.3*cm))
story.append(script_box(
    "Ma'am/Sir, I am confident this topic is original, feasible, clinically relevant, and clearly "
    "distinct from Dr. Ashraf's published work. I request your approval to proceed with the synopsis."
))
story.append(Spacer(1, 0.5*cm))
story.append(Paragraph(
    "Prepared by: Anaesthesia Resident | Department of Anaesthesia | Teaching Hospital, Lahore | June 2026",
    footer_style
))

# ════════════════════════════════════════════════════════════════
# BUILD PDF
# ════════════════════════════════════════════════════════════════
def add_page_number(canvas, doc):
    canvas.saveState()
    canvas.setFont("Helvetica", 7)
    canvas.setFillColor(colors.grey)
    canvas.drawString(2*cm, 1.2*cm, "IV vs Topical Lignocaine | Anaesthesia Research Proposal | Lahore, 2026")
    canvas.drawRightString(A4[0]-2*cm, 1.2*cm, f"Page {doc.page}")
    canvas.restoreState()

doc.build(story, onFirstPage=add_page_number, onLaterPages=add_page_number)
print(f"PDF created: {OUTPUT}")

Successfully replaced 1 instance(s) of the string in '/home/daytona/workspace/lignocaine-research/generate_pdf.py'

from reportlab.lib.pagesizes import A4
from reportlab.lib import colors
from reportlab.lib.units import cm
from reportlab.platypus import (
    SimpleDocTemplate, Paragraph, Spacer, Table, TableStyle, HRFlowable
)
from reportlab.lib.styles import getSampleStyleSheet, ParagraphStyle
from reportlab.lib.enums import TA_CENTER, TA_LEFT, TA_JUSTIFY
from reportlab.platypus import PageBreak

OUTPUT = "/home/daytona/workspace/lignocaine-research/Supervisor_Copy_Final.pdf"

doc = SimpleDocTemplate(
    OUTPUT,
    pagesize=A4,
    rightMargin=1.8*cm,
    leftMargin=1.8*cm,
    topMargin=1.5*cm,
    bottomMargin=1.5*cm
)

styles = getSampleStyleSheet()

# Custom styles
title_style = ParagraphStyle(
    'CustomTitle',
    parent=styles['Title'],
    fontSize=13,
    leading=16,
    textColor=colors.HexColor('#1a1a6e'),
    spaceAfter=4,
    alignment=TA_CENTER,
    fontName='Helvetica-Bold'
)

h1_style = ParagraphStyle(
    'H1',
    parent=styles['Heading1'],
    fontSize=10,
    leading=13,
    textColor=colors.HexColor('#1a1a6e'),
    spaceAfter=3,
    spaceBefore=6,
    fontName='Helvetica-Bold',
    borderPad=2,
)

h2_style = ParagraphStyle(
    'H2',
    parent=styles['Heading2'],
    fontSize=9,
    leading=12,
    textColor=colors.HexColor('#2e4a7a'),
    spaceAfter=2,
    spaceBefore=4,
    fontName='Helvetica-Bold'
)

body_style = ParagraphStyle(
    'Body',
    parent=styles['Normal'],
    fontSize=8.5,
    leading=12,
    spaceAfter=3,
    fontName='Helvetica',
    alignment=TA_JUSTIFY
)

small_style = ParagraphStyle(
    'Small',
    parent=styles['Normal'],
    fontSize=7.5,
    leading=10,
    spaceAfter=2,
    fontName='Helvetica'
)

bold_style = ParagraphStyle(
    'Bold',
    parent=styles['Normal'],
    fontSize=8.5,
    leading=12,
    fontName='Helvetica-Bold',
    spaceAfter=2
)

center_style = ParagraphStyle(
    'Center',
    parent=styles['Normal'],
    fontSize=8.5,
    leading=12,
    alignment=TA_CENTER,
    fontName='Helvetica'
)

gap_style = ParagraphStyle(
    'Gap',
    parent=styles['Normal'],
    fontSize=9,
    leading=13,
    fontName='Helvetica-Bold',
    textColor=colors.HexColor('#cc0000'),
    borderPad=4,
    spaceAfter=4,
    spaceBefore=4,
    alignment=TA_CENTER
)

# Table style helper
def base_table_style(header_bg=None):
    hbg = header_bg or colors.HexColor('#1a1a6e')
    return TableStyle([
        ('BACKGROUND', (0,0), (-1,0), hbg),
        ('TEXTCOLOR', (0,0), (-1,0), colors.white),
        ('FONTNAME', (0,0), (-1,0), 'Helvetica-Bold'),
        ('FONTSIZE', (0,0), (-1,0), 7.5),
        ('ALIGN', (0,0), (-1,-1), 'LEFT'),
        ('VALIGN', (0,0), (-1,-1), 'MIDDLE'),
        ('FONTNAME', (0,1), (-1,-1), 'Helvetica'),
        ('FONTSIZE', (0,1), (-1,-1), 7),
        ('ROWBACKGROUNDS', (0,1), (-1,-1), [colors.HexColor('#f5f5ff'), colors.white]),
        ('GRID', (0,0), (-1,-1), 0.4, colors.HexColor('#aaaacc')),
        ('TOPPADDING', (0,0), (-1,-1), 3),
        ('BOTTOMPADDING', (0,0), (-1,-1), 3),
        ('LEFTPADDING', (0,0), (-1,-1), 4),
        ('RIGHTPADDING', (0,0), (-1,-1), 4),
    ])

story = []

# ─────────────────────────────────────────────
# PAGE 1 — SYNOPSIS
# ─────────────────────────────────────────────

story.append(Paragraph(
    "RESEARCH SYNOPSIS",
    title_style
))
story.append(Paragraph(
    "Comparison of Intravenous versus Topical Lignocaine on Perfusion Index,<br/>Rate Pressure Product, and Hemodynamic Stress Response during<br/>Laryngoscopy and Endotracheal Intubation",
    title_style
))
story.append(HRFlowable(width="100%", thickness=1.5, color=colors.HexColor('#1a1a6e')))
story.append(Spacer(1, 4))

# Meta info table
meta = Table([
    ['Candidate:', 'Anaesthesia Resident', 'Institution:', 'Teaching Hospital, Lahore, Pakistan'],
    ['Supervisor:', '___________________________', 'Duration:', '8 Months'],
    ['Date:', '___________________________', 'Year:', '2026'],
], colWidths=[2.5*cm, 6.5*cm, 2.5*cm, 5.5*cm])
meta.setStyle(TableStyle([
    ('FONTNAME', (0,0), (-1,-1), 'Helvetica'),
    ('FONTSIZE', (0,0), (-1,-1), 8),
    ('FONTNAME', (0,0), (0,-1), 'Helvetica-Bold'),
    ('FONTNAME', (2,0), (2,-1), 'Helvetica-Bold'),
    ('BOTTOMPADDING', (0,0), (-1,-1), 2),
    ('TOPPADDING', (0,0), (-1,-1), 2),
]))
story.append(meta)
story.append(Spacer(1, 6))

story.append(Paragraph("BACKGROUND", h1_style))
story.append(Paragraph(
    "Laryngoscopy and endotracheal intubation trigger a sympathoadrenal stress response causing tachycardia, hypertension, "
    "and peripheral vasoconstriction. <b>Rate Pressure Product (RPP = HR × SBP)</b> exceeding 20,000 mmHg/min signals myocardial "
    "ischemia risk. <b>Perfusion Index (PI)</b>, measured non-invasively via Masimo pulse oximeter already installed in our OTs, "
    "falls in real time at laryngoscopy — baseline 4.14 dropped to 3.24 at laryngoscopy in human patients (Shah et al., 2023, "
    "PMID 37088851). Lignocaine attenuates this response via two distinct mechanisms: IV lignocaine acts systemically with "
    "partial afferent blockade; topical spray directly blocks laryngeal mechanoreceptors producing complete cardiovascular "
    "response abolition (Hamaya &amp; Dohi, 2000, PMID 10861151). The optimal route remains undetermined in human trials.",
    body_style
))

story.append(Paragraph("RESEARCH GAP", h1_style))
story.append(Paragraph(
    "A 2025 meta-analysis of 18 RCTs involving 1056 human patients (Qin et al., PMC12338463) confirmed IV lignocaine reduces "
    "MAP and HR, but found no trial comparing both routes while measuring PI and RPP. <b>No published human RCT has all four "
    "elements together: IV route + Topical route + Perfusion Index + Rate Pressure Product.</b>",
    gap_style
))

story.append(Paragraph("OBJECTIVE", h1_style))
story.append(Paragraph(
    "<b>Primary:</b> Compare ΔPerfusion Index (%) and Rate Pressure Product between IV lignocaine, topical lignocaine, "
    "and saline control at peri-intubation timepoints in ASA I-II patients undergoing elective surgery.<br/>"
    "<b>Secondary:</b> Compare HR, SBP, MAP, SpO₂, and adverse effects across the three groups.",
    body_style
))

story.append(Paragraph("STUDY DESIGN", h1_style))
story.append(Paragraph("Prospective, double-blind, three-group randomized controlled trial (RCT).", body_style))

# Groups table
groups_data = [
    ['Group', 'IV Drug (3 min pre-intubation)', 'Oropharyngeal Spray (5 min pre-intubation)', 'Route Blinded?'],
    ['A — IV Lignocaine', '2% Lignocaine 1.5 mg/kg', 'Normal Saline spray', 'Yes'],
    ['B — Topical Lignocaine', 'Normal Saline (identical volume)', '10% Lignocaine 1.5 mg/kg', 'Yes'],
    ['C — Control', 'Normal Saline', 'Normal Saline spray', 'Yes'],
]
gt = Table(groups_data, colWidths=[3.5*cm, 5.5*cm, 5.5*cm, 2.5*cm])
gt.setStyle(base_table_style())
story.append(gt)
story.append(Spacer(1, 3))

story.append(Paragraph(
    "<b>Induction — identical in ALL groups:</b> Propofol 2 mg/kg + Fentanyl 2 mcg/kg + Atracurium 0.5 mg/kg",
    bold_style
))

story.append(Paragraph("MEASUREMENT TIMEPOINTS", h1_style))
tp_data = [
    ['T0', 'T1', 'T2', 'T3', 'T4', 'T5', 'T6', 'T7', 'T8'],
    ['Baseline', 'Post-\ninduction', 'Pre-\nintubation', 'Laryngo-\nscopy', 'Intubation', '1 min\npost', '3 min\npost', '5 min\npost', '10 min\npost'],
]
tp = Table(tp_data, colWidths=[1.9*cm]*9)
tp.setStyle(TableStyle([
    ('BACKGROUND', (0,0), (-1,0), colors.HexColor('#2e4a7a')),
    ('TEXTCOLOR', (0,0), (-1,0), colors.white),
    ('FONTNAME', (0,0), (-1,0), 'Helvetica-Bold'),
    ('FONTSIZE', (0,0), (-1,-1), 7.5),
    ('ALIGN', (0,0), (-1,-1), 'CENTER'),
    ('VALIGN', (0,0), (-1,-1), 'MIDDLE'),
    ('FONTNAME', (0,1), (-1,1), 'Helvetica'),
    ('GRID', (0,0), (-1,-1), 0.4, colors.HexColor('#aaaacc')),
    ('ROWBACKGROUNDS', (0,1), (-1,-1), [colors.HexColor('#e8eeff')]),
    ('TOPPADDING', (0,0), (-1,-1), 3),
    ('BOTTOMPADDING', (0,0), (-1,-1), 3),
]))
story.append(tp)
story.append(Spacer(1, 3))

story.append(Paragraph("SAMPLE SIZE & PATIENTS", h1_style))
ss_data = [
    ['Parameter', 'Detail'],
    ['Total patients', '108 (36 per group)'],
    ['Basis', 'Pramanik et al. 2025 (PMID 40413425) — MAP difference 6 mmHg, SD 12, α=0.05, power 80%'],
    ['Dropout correction', '12% added → final 36/group'],
    ['Inclusion', 'ASA I-II, age 18-60 years, elective surgery, written informed consent'],
    ['Exclusion', 'Cardiac disease, hypertension, diabetes, BMI >35, difficult airway, lignocaine allergy, pregnancy'],
    ['Duration', '8 months — 1 month protocol, 5 months recruitment, 2 months analysis'],
]
sst = Table(ss_data, colWidths=[4.5*cm, 12.5*cm])
sst.setStyle(base_table_style())
story.append(sst)
story.append(Spacer(1, 3))

story.append(Paragraph("OUTCOMES & ANALYSIS", h1_style))
story.append(Paragraph(
    "<b>Primary outcomes:</b> ΔPI% = [(T0−Tx)/T0] × 100% and RPP at T3, T5, T6, T7<br/>"
    "<b>Secondary:</b> HR, SBP, MAP, SpO₂ at all timepoints; adverse events (bradycardia, hypotension, bronchospasm)<br/>"
    "<b>Statistics:</b> Repeated-measures ANOVA, Bonferroni post-hoc correction, Chi-square for categorical variables; SPSS v25. P &lt;0.05 = significant.",
    body_style
))

story.append(Paragraph("EQUIPMENT", h1_style))
story.append(Paragraph(
    "Masimo SET pulse oximeter (already installed in our OTs) — provides PI continuously at no additional cost. "
    "No extra equipment, no extra budget required for primary outcome measurement.",
    body_style
))

story.append(PageBreak())

# ─────────────────────────────────────────────
# PAGE 2 — REFERENCE TABLE
# ─────────────────────────────────────────────

story.append(Paragraph("SHEET 2 — HUMAN CLINICAL TRIAL REFERENCES", title_style))
story.append(HRFlowable(width="100%", thickness=1.5, color=colors.HexColor('#1a1a6e')))
story.append(Spacer(1, 4))
story.append(Paragraph(
    "All 12 references below are human clinical studies. PMID numbers can be verified at pubmed.ncbi.nlm.nih.gov",
    center_style
))
story.append(Spacer(1, 6))

story.append(Paragraph("TOP 3 PAPERS — PMID NUMBERS", h1_style))

top3_data = [
    ['#', 'Authors', 'Year', 'Journal', 'PMID / Link', 'Key Finding'],
    ['1 ★', 'Pramanik M\net al.', '2025', 'BMC\nAnesthesiol', 'PMID: 40413425\npmc.ncbi.nlm.nih.gov\n/PMC12102901', 
     'Transtracheal > IV lignocaine for MAP & HR at 3 min post-intubation.\nRPP trend favoured TT (P=0.002). No PI measured. No control group.'],
    ['2 ★', 'Qin J et al.', '2025', 'Saudi J\nAnaesth', 'PMC: 12338463\npmc.ncbi.nlm.nih.gov\n/PMC12338463',
     'Meta-analysis 18 RCTs, 1056 humans. IV lignocaine reduces MAP −3.85 mmHg,\nHR −4.72 bpm. Topical route & PI absent from all 18 trials.'],
    ['3 ★', 'Shah SB\net al.', '2023', 'J Clin Monit\nComput', 'PMID: 37088851\npubmed.ncbi.nlm.nih.gov\n/37088851',
     'PI fell 4.14→3.24 at laryngoscopy in 26 humans. r=−0.89 with MAP.\nValidates PI as real-time stress marker. No lignocaine given.'],
]
top3 = Table(top3_data, colWidths=[1.2*cm, 2.2*cm, 1.0*cm, 1.8*cm, 4.2*cm, 6.6*cm])
top3.setStyle(TableStyle([
    ('BACKGROUND', (0,0), (-1,0), colors.HexColor('#8b0000')),
    ('TEXTCOLOR', (0,0), (-1,0), colors.white),
    ('FONTNAME', (0,0), (-1,0), 'Helvetica-Bold'),
    ('FONTSIZE', (0,0), (-1,0), 7.5),
    ('BACKGROUND', (0,1), (-1,3), colors.HexColor('#fff5f5')),
    ('FONTNAME', (0,1), (-1,-1), 'Helvetica'),
    ('FONTSIZE', (0,1), (-1,-1), 6.8),
    ('ALIGN', (0,0), (-1,-1), 'LEFT'),
    ('VALIGN', (0,0), (-1,-1), 'TOP'),
    ('GRID', (0,0), (-1,-1), 0.4, colors.HexColor('#cc8888')),
    ('TOPPADDING', (0,0), (-1,-1), 3),
    ('BOTTOMPADDING', (0,0), (-1,-1), 3),
    ('LEFTPADDING', (0,0), (-1,-1), 3),
    ('RIGHTPADDING', (0,0), (-1,-1), 3),
    ('FONTNAME', (0,1), (0,-1), 'Helvetica-Bold'),
    ('TEXTCOLOR', (0,1), (0,-1), colors.HexColor('#8b0000')),
]))
story.append(top3)
story.append(Spacer(1, 8))

story.append(Paragraph("ALL 12 HUMAN REFERENCES", h1_style))

refs_data = [
    ['#', 'Authors', 'Year', 'Journal', 'PMID / PMC', 'Study Type', 'N', 'IV?', 'Top?', 'PI?', 'RPP?'],
    ['1', 'Pramanik et al.', '2025', 'BMC Anesthesiol', 'PMID 40413425\nPMC12102901', 'RCT', '138', '✓', '✓ TT', '✗', 'Trend'],
    ['2', 'Qin et al.', '2025', 'Saudi J Anaesth', 'PMC12338463', 'Meta-analysis', '1056', '✓', '✗', '✗', '✗'],
    ['3', 'Aybal & Karaman', '2025', 'Turk J Anaesth', 'dergipark PDF', 'RCT', '120', '✓', '✓', '✗', '✗'],
    ['4', 'Gautam et al.', '2025', 'J Pharm Bioallied', 'PMID 40511154\nPMC12156683', 'RCT', '60', '✗', '✓ Neb', '✗', '✗'],
    ['5', 'Liu et al.', '2024', 'Braz J Otorhinol', 'PMID 39270370\nPMC11415576', 'RCT', '68', '✗', '✓', '✗', '✗'],
    ['6', 'Shah et al.', '2023', 'J Clin Monit Comput', 'PMID 37088851', 'Observational', '26', '✗', '✗', '✓', '✗'],
    ['7', 'Mendonça et al.', '2022', 'Braz J Anesthesiol', 'PMID 34582903\nPMC9373404', 'RCT', '69', '✓', '✗', '✗', '✗'],
    ['8', 'Gladston et al.', '2022', 'J Anaesthesiol Clin', 'PMC9514071', 'RCT', '75', '✓', '✓ IT', '✗', '✗'],
    ['9', 'Seangrung et al.', '2021', 'BMC Anesthesiol', 'PMID 34717532\nPMC8557037', 'RCT', '106', '✓', '✗', '✗', '✗'],
    ['10', 'Varshney et al.', '2019', 'Sultan Qaboos Univ', 'PMID 31897315\nPMC6930035', 'RCT', '90', '✗', '✓', '✗', '✓'],
    ['11', 'Kocamanoglu et al.', '2015', 'J Laryngol Otol', 'PMID 25496674', '3-arm RCT', '99', '✓', '✓', '✗', '✗'],
    ['12', 'Hamaya & Dohi', '2000', 'Anesthesiology', 'PMID 10861151', 'RCT', '60', '✓', '✓', '✗', '✗'],
    ['YOUR\nSTUDY', 'Proposed 2026', '2026', 'Teaching Hosp\nLahore', '—', '3-arm RCT', '108', '✓', '✓', '✓', '✓'],
]
rt = Table(refs_data, colWidths=[1.0*cm, 2.8*cm, 0.9*cm, 2.8*cm, 2.8*cm, 2.0*cm, 0.7*cm, 0.6*cm, 0.7*cm, 0.6*cm, 0.9*cm])
rstyle = base_table_style()
# Highlight YOUR STUDY row
rstyle.add('BACKGROUND', (0, 13), (-1, 13), colors.HexColor('#1a6e1a'))
rstyle.add('TEXTCOLOR', (0, 13), (-1, 13), colors.white)
rstyle.add('FONTNAME', (0, 13), (-1, 13), 'Helvetica-Bold')
rt.setStyle(rstyle)
story.append(rt)

story.append(Spacer(1, 6))
story.append(Paragraph(
    "★ = Top 3 most directly relevant | TT = Transtracheal | IT = Intratracheal | Neb = Nebulized | "
    "To verify any paper: open pubmed.ncbi.nlm.nih.gov and type the PMID number",
    small_style
))

story.append(PageBreak())

# ─────────────────────────────────────────────
# PAGE 3 — DR. ASHRAF vs YOUR STUDY
# ─────────────────────────────────────────────

story.append(Paragraph("SHEET 3 — COMPARISON WITH DR. ASHRAF'S PUBLISHED STUDY", title_style))
story.append(HRFlowable(width="100%", thickness=1.5, color=colors.HexColor('#1a1a6e')))
story.append(Spacer(1, 4))

story.append(Paragraph(
    "Dr. Ashraf's study (Mayo Hospital Lahore, 2024) and the proposed study differ in every key dimension. "
    "There is zero scientific overlap between the two.",
    body_style
))
story.append(Spacer(1, 4))

comp_data = [
    ['Feature', "Dr. Ashraf's Study (Published 2024)", 'Your Proposed Study (2026)'],
    ['Full Title', 'Comparison of propofol vs ketamine+midazolam\non Perfusion Index in cardiac patients\nundergoing non-cardiac surgery',
     'Comparison of IV vs Topical Lignocaine on\nPerfusion Index, Rate Pressure Product, and\nHemodynamic Stress Response at Laryngoscopy'],
    ['Published In', 'Pakistan J Health Sciences\nJan-Jun 2024, Mayo Hospital Lahore', 'Proposed — not yet done'],
    ['Drug Class', 'Induction agents\n(propofol vs ketamine-midazolam)', 'Local anaesthetic\n(lignocaine — completely different class)'],
    ['Phase Studied', 'Induction phase ONLY\n(before laryngoscopy)', 'Laryngoscopy + Intubation phase\n(AFTER induction — sequential, non-overlapping)'],
    ['Patient Population', 'Cardiac patients\nundergoing non-cardiac surgery', 'ASA I-II patients\nNO cardiac disease (exclusion criterion)'],
    ['Number of Groups', '2 groups\n(No control group)', '3 groups\n(includes saline control arm)'],
    ['Study Design', 'Quasi-experimental', 'Double-blind RCT'],
    ['Sample Size', '146 patients (73 per group)', '108 patients (36 per group)'],
    ['PI Timepoints', '1 timepoint only\n(post-induction)', '9 timepoints\n(T0 baseline through T8 at 10 min)'],
    ['RPP Measured?', 'NO', 'YES — co-primary outcome'],
    ['Blinding', 'Not described', 'Double-blind (patient + assessor)'],
    ['Research Question', 'Which induction agent gives better PI?', 'Which lignocaine route better reduces\nPI drop and RPP rise at intubation?'],
    ['Overlap with Your Study', 'ZERO OVERLAP', '—'],
    ['Relationship', 'Validates PI monitoring is feasible\nin Lahore OTs — supports your proposal', 'Applies PI to a new question\nin a new patient population'],
]

ct = Table(comp_data, colWidths=[3.5*cm, 7.8*cm, 6.2*cm])
cstyle = TableStyle([
    ('BACKGROUND', (0,0), (-1,0), colors.HexColor('#1a1a6e')),
    ('TEXTCOLOR', (0,0), (-1,0), colors.white),
    ('FONTNAME', (0,0), (-1,0), 'Helvetica-Bold'),
    ('FONTSIZE', (0,0), (-1,0), 8),
    ('FONTNAME', (0,1), (0,-1), 'Helvetica-Bold'),
    ('FONTSIZE', (0,1), (-1,-1), 7.5),
    ('FONTNAME', (1,1), (-1,-1), 'Helvetica'),
    ('ALIGN', (0,0), (-1,-1), 'LEFT'),
    ('VALIGN', (0,0), (-1,-1), 'MIDDLE'),
    ('ROWBACKGROUNDS', (0,1), (-1,-1), [colors.HexColor('#f0f0ff'), colors.white]),
    ('GRID', (0,0), (-1,-1), 0.4, colors.HexColor('#aaaacc')),
    ('TOPPADDING', (0,0), (-1,-1), 3),
    ('BOTTOMPADDING', (0,0), (-1,-1), 3),
    ('LEFTPADDING', (0,0), (-1,-1), 4),
    ('RIGHTPADDING', (0,0), (-1,-1), 4),
    # Highlight ZERO OVERLAP row
    ('BACKGROUND', (1, 13), (1, 13), colors.HexColor('#ffe0e0')),
    ('FONTNAME', (1, 13), (1, 13), 'Helvetica-Bold'),
    ('TEXTCOLOR', (1, 13), (1, 13), colors.HexColor('#cc0000')),
    # Highlight Drug Class row
    ('BACKGROUND', (0, 3), (-1, 3), colors.HexColor('#e8f0ff')),
    # Highlight Phase row
    ('BACKGROUND', (0, 4), (-1, 4), colors.HexColor('#e8f0ff')),
])
ct.setStyle(cstyle)
story.append(ct)

story.append(Spacer(1, 8))
story.append(HRFlowable(width="100%", thickness=0.8, color=colors.HexColor('#1a1a6e')))
story.append(Spacer(1, 4))
story.append(Paragraph(
    '<b>One-Line Summary for Supervisor:</b> "Ma\'am, Dr. Ashraf studied induction agents in cardiac patients at one timepoint. '
    'I am studying lignocaine routes at the intubation phase in non-cardiac patients at nine timepoints with RPP as an additional outcome. '
    'The two studies are completely sequential and non-overlapping — hers ends where mine begins."',
    body_style
))

story.append(PageBreak())

# ─────────────────────────────────────────────
# PAGE 4 — WHY THREE GROUPS
# ─────────────────────────────────────────────

story.append(Paragraph("SHEET 4 — WHY THREE GROUPS AND NOT TWO", title_style))
story.append(HRFlowable(width="100%", thickness=1.5, color=colors.HexColor('#1a1a6e')))
story.append(Spacer(1, 4))

story.append(Paragraph("WHAT TO SAY TO YOUR SUPERVISOR", h1_style))
story.append(Paragraph(
    '"Ma\'am, if I use only two groups — IV versus topical — I cannot determine whether either drug actually worked, '
    'or whether both failed equally. I need the control group to establish the baseline magnitude of the untreated stress '
    'response in our specific patient population. Without it, any difference between the two drug groups could be meaningless."',
    ParagraphStyle('Quote', parent=body_style, leftIndent=10, rightIndent=10,
                   borderPad=5, textColor=colors.HexColor('#1a1a6e'), fontName='Helvetica-Oblique')
))
story.append(Spacer(1, 6))

story.append(Paragraph("SCIENTIFIC COMPARISON", h1_style))

sci_data = [
    ['Question Being Asked', 'Two Groups Only\n(IV vs Topical)', 'Three Groups\n(IV vs Topical vs Control)'],
    ['Did IV lignocaine reduce stress vs nothing?', '✗ Cannot answer', '✓ Compare A vs C'],
    ['Did topical lignocaine reduce stress vs nothing?', '✗ Cannot answer', '✓ Compare B vs C'],
    ['Is IV better than topical?', '✓ Can answer', '✓ Can answer'],
    ['True untreated stress response in our population?', '✗ Unknown', '✓ Measured by Group C'],
    ['Absolute ΔPI% and ΔRPP from true baseline?', '✗ Relative only', '✓ Absolute values'],
    ['Result applicable to future studies?', '✗ No reference point', '✓ Group C is the anchor'],
    ['Publishable even if drugs show no difference?', '✗ Inconclusive', '✓ Yes — both may have failed equally'],
]
sct = Table(sci_data, colWidths=[7.5*cm, 4.0*cm, 5.5*cm])
sctstyle = base_table_style(colors.HexColor('#2e6b2e'))
sctstyle.add('BACKGROUND', (1, 1), (1, -1), colors.HexColor('#ffe8e8'))
sctstyle.add('BACKGROUND', (2, 1), (2, -1), colors.HexColor('#e8ffe8'))
sctstyle.add('FONTNAME', (1, 1), (1, -1), 'Helvetica')
sctstyle.add('FONTNAME', (2, 1), (2, -1), 'Helvetica-Bold')
sctstyle.add('TEXTCOLOR', (2, 1), (2, -1), colors.HexColor('#1a6e1a'))
sct.setStyle(sctstyle)
story.append(sct)
story.append(Spacer(1, 6))

story.append(Paragraph("STATISTICAL REASON", h1_style))
story.append(Paragraph(
    "With two groups, if the result shows no significant difference between IV and topical, you cannot conclude equivalence — "
    "you only know the two drugs behaved similarly. You cannot know if both drugs worked equally well, or both drugs failed equally. "
    "The control group resolves this ambiguity completely and gives the result a definitive interpretation.",
    body_style
))
story.append(Spacer(1, 4))

story.append(Paragraph("ETHICAL JUSTIFICATION", h1_style))
story.append(Paragraph(
    "All three groups receive standard induction — propofol 2 mg/kg, fentanyl 2 mcg/kg, and atracurium 0.5 mg/kg. "
    "Fentanyl 2 mcg/kg itself provides partial hemodynamic attenuation. No patient receives truly zero protection. "
    "The control group receives only normal saline in the IV and spray lines — ethically acceptable because anaesthetic "
    "induction drugs are unchanged across all groups. This three-group design with saline control is the same approach used in:",
    body_style
))
story.append(Spacer(1, 2))

cite_data = [
    ['Reference', 'Design', 'PMID'],
    ['Kocamanoglu et al., 2015 — J Laryngol Otol', '3-arm RCT: IV lignocaine vs topical vs saline control', '25496674'],
    ['Varshney et al., 2019 — Sultan Qaboos Univ Med J', '3-arm RCT: lignocaine spray vs NTG vs saline control', '31897315'],
]
ct2 = Table(cite_data, colWidths=[7.0*cm, 7.5*cm, 2.5*cm])
ct2.setStyle(base_table_style())
story.append(ct2)
story.append(Spacer(1, 6))

story.append(Paragraph("PRESENTATION CHECKLIST", h1_style))

checklist_data = [
    ['Before You Go In', 'During the Meeting', 'After the Meeting'],
    [
        '□ Synopsis printed × 2 copies\n□ Reference table printed × 2\n□ Comparison table printed × 2\n□ Three groups justification × 2\n□ Your name written by hand\n   on supervisor\'s copy\n□ PubMed open on phone:\n   pubmed.ncbi.nlm.nih.gov/40413425\n□ Pen in pocket\n□ Script practiced once out loud',
        '□ Placed supervisor\'s copy first\n□ Stated research gap clearly\n□ Pointed to groups table\n□ Named Pramanik 2025 PMID\n□ Addressed Dr. Ashraf proactively\n□ Answered "why 3 groups"\n□ Stopped talking after step 10\n□ Let her read in silence\n□ Wrote down all feedback',
        '□ If YES: get her signature\n□ Take signed copy to research\n   department same day\n□ If "come back later": confirm\n   specific date before leaving\n□ If changes needed: return\n   within 48 hours with revision\n□ Ask which ethics committee\n□ Ask for co-supervisor if needed'
    ],
]
clt = Table(checklist_data, colWidths=[5.8*cm, 5.8*cm, 5.4*cm])
clstyle = TableStyle([
    ('BACKGROUND', (0,0), (-1,0), colors.HexColor('#1a1a6e')),
    ('TEXTCOLOR', (0,0), (-1,0), colors.white),
    ('FONTNAME', (0,0), (-1,0), 'Helvetica-Bold'),
    ('FONTSIZE', (0,0), (-1,0), 8),
    ('FONTNAME', (0,1), (-1,1), 'Helvetica'),
    ('FONTSIZE', (0,1), (-1,1), 7.5),
    ('ALIGN', (0,0), (-1,-1), 'LEFT'),
    ('VALIGN', (0,0), (-1,-1), 'TOP'),
    ('GRID', (0,0), (-1,-1), 0.4, colors.HexColor('#aaaacc')),
    ('BACKGROUND', (0,1), (0,1), colors.HexColor('#fff8e8')),
    ('BACKGROUND', (1,1), (1,1), colors.HexColor('#e8f8ff')),
    ('BACKGROUND', (2,1), (2,1), colors.HexColor('#e8ffe8')),
    ('TOPPADDING', (0,0), (-1,-1), 4),
    ('BOTTOMPADDING', (0,0), (-1,-1), 4),
    ('LEFTPADDING', (0,0), (-1,-1), 5),
    ('RIGHTPADDING', (0,0), (-1,-1), 5),
])
clt.setStyle(clstyle)
story.append(clt)

story.append(Spacer(1, 6))
story.append(HRFlowable(width="100%", thickness=1, color=colors.HexColor('#1a1a6e')))
story.append(Spacer(1, 3))
story.append(Paragraph(
    "You walk in with 4 sheets. You speak for 4 minutes. You leave one copy behind. That is all you need to do.",
    ParagraphStyle('Final', parent=body_style, alignment=TA_CENTER,
                   fontName='Helvetica-Bold', fontSize=9, textColor=colors.HexColor('#1a1a6e'))
))

# Build
doc.build(story)
print(f"PDF saved to: {OUTPUT}")

const {
  Document, Packer, Paragraph, TextRun, Table, TableRow, TableCell,
  AlignmentType, HeadingLevel, BorderStyle, WidthType, ShadingType,
  VerticalAlign, PageBreak, Header, Footer, PageNumber, NumberFormat,
  UnderlineType
} = require('docx');
const fs = require('fs');

// ── COLOUR PALETTE ──────────────────────────────────────────
const NAVY   = "1A1A6E";
const RED    = "CC0000";
const GREEN  = "1A6E1A";
const DKBLUE = "2E4A7A";
const LGBLUE = "E8EEFF";
const LGRED  = "FFF5F5";
const LGGRN  = "E8FFE8";
const WHITE  = "FFFFFF";
const GREY   = "F5F5FF";

// ── HELPERS ─────────────────────────────────────────────────
function hd1(text) {
  return new Paragraph({
    children: [new TextRun({ text, bold: true, size: 22, color: NAVY, font: "Calibri" })],
    spacing: { before: 200, after: 80 },
    border: { bottom: { style: BorderStyle.SINGLE, size: 4, color: NAVY } }
  });
}

function hd2(text) {
  return new Paragraph({
    children: [new TextRun({ text, bold: true, size: 20, color: DKBLUE, font: "Calibri" })],
    spacing: { before: 160, after: 60 }
  });
}

function body(runs_or_text, opts = {}) {
  const runs = typeof runs_or_text === "string"
    ? [new TextRun({ text: runs_or_text, size: 18, font: "Calibri", ...opts })]
    : runs_or_text;
  return new Paragraph({ children: runs, spacing: { after: 60 }, alignment: AlignmentType.JUSTIFIED });
}

function bold_body(text) {
  return body([new TextRun({ text, bold: true, size: 18, font: "Calibri" })]);
}

function center(text, opts = {}) {
  return new Paragraph({
    children: [new TextRun({ text, size: 18, font: "Calibri", ...opts })],
    alignment: AlignmentType.CENTER,
    spacing: { after: 60 }
  });
}

function gap_para(text) {
  return new Paragraph({
    children: [new TextRun({ text, bold: true, size: 19, color: RED, font: "Calibri" })],
    alignment: AlignmentType.CENTER,
    spacing: { before: 100, after: 100 },
    shading: { type: ShadingType.SOLID, color: "FFF0F0" },
    border: {
      top: { style: BorderStyle.SINGLE, size: 6, color: RED },
      bottom: { style: BorderStyle.SINGLE, size: 6, color: RED },
      left: { style: BorderStyle.SINGLE, size: 6, color: RED },
      right: { style: BorderStyle.SINGLE, size: 6, color: RED }
    }
  });
}

function sp(n = 80) {
  return new Paragraph({ children: [new TextRun("")], spacing: { after: n } });
}

function cell(text, opts = {}) {
  const {
    bold = false, color = "000000", bg = WHITE, size = 16, span = 1,
    align = AlignmentType.LEFT, vAlign = VerticalAlign.CENTER, italic = false
  } = opts;
  return new TableCell({
    children: [new Paragraph({
      children: [new TextRun({ text, bold, color, size, font: "Calibri", italic })],
      alignment: align,
      spacing: { before: 40, after: 40 }
    })],
    columnSpan: span,
    shading: { type: ShadingType.SOLID, color: bg },
    verticalAlign: vAlign,
    margins: { top: 50, bottom: 50, left: 80, right: 80 }
  });
}

function hrow(cells_data, bg = NAVY) {
  return new TableRow({
    children: cells_data.map(([text, w]) =>
      cell(text, { bold: true, color: WHITE, bg, size: 16 })
    ),
    tableHeader: true
  });
}

// ── DOCUMENT SECTIONS ────────────────────────────────────────
const children = [];

// ═══════════════════════════════════════════════════════════
// PAGE 1 — SYNOPSIS
// ═══════════════════════════════════════════════════════════

children.push(new Paragraph({
  children: [new TextRun({ text: "RESEARCH SYNOPSIS", bold: true, size: 28, color: NAVY, font: "Calibri" })],
  alignment: AlignmentType.CENTER,
  spacing: { after: 60 },
  border: { bottom: { style: BorderStyle.DOUBLE, size: 6, color: NAVY } }
}));

children.push(new Paragraph({
  children: [new TextRun({
    text: "Comparison of Intravenous versus Topical Lignocaine on Perfusion Index, Rate Pressure Product, and Hemodynamic Stress Response during Laryngoscopy and Endotracheal Intubation",
    bold: true, size: 22, color: NAVY, font: "Calibri"
  })],
  alignment: AlignmentType.CENTER,
  spacing: { after: 120 }
}));

// Meta info table
children.push(new Table({
  width: { size: 100, type: WidthType.PERCENTAGE },
  rows: [
    new TableRow({ children: [
      cell("Candidate:", { bold: true, size: 17 }),
      cell("Anaesthesia Resident", { size: 17 }),
      cell("Institution:", { bold: true, size: 17 }),
      cell("Teaching Hospital, Lahore, Pakistan", { size: 17 })
    ]}),
    new TableRow({ children: [
      cell("Supervisor:", { bold: true, size: 17 }),
      cell("___________________________________", { size: 17 }),
      cell("Duration:", { bold: true, size: 17 }),
      cell("8 Months", { size: 17 })
    ]}),
    new TableRow({ children: [
      cell("Date:", { bold: true, size: 17 }),
      cell("___________________________________", { size: 17 }),
      cell("Year:", { bold: true, size: 17 }),
      cell("2026", { size: 17 })
    ]}),
  ],
  borders: {
    top: { style: BorderStyle.SINGLE, size: 2, color: DKBLUE },
    bottom: { style: BorderStyle.SINGLE, size: 2, color: DKBLUE },
    left: { style: BorderStyle.SINGLE, size: 2, color: DKBLUE },
    right: { style: BorderStyle.SINGLE, size: 2, color: DKBLUE },
    insideH: { style: BorderStyle.SINGLE, size: 1, color: DKBLUE },
    insideV: { style: BorderStyle.SINGLE, size: 1, color: DKBLUE },
  }
}));

children.push(sp(100));
children.push(hd1("BACKGROUND"));
children.push(body([
  new TextRun({ text: "Laryngoscopy and endotracheal intubation trigger a sympathoadrenal stress response causing tachycardia, hypertension, and peripheral vasoconstriction. ", size: 18, font: "Calibri" }),
  new TextRun({ text: "Rate Pressure Product (RPP = HR × SBP)", bold: true, size: 18, font: "Calibri" }),
  new TextRun({ text: " exceeding 20,000 mmHg/min signals myocardial ischemia risk. ", size: 18, font: "Calibri" }),
  new TextRun({ text: "Perfusion Index (PI)", bold: true, size: 18, font: "Calibri" }),
  new TextRun({ text: ", measured non-invasively via Masimo pulse oximeter already installed in our OTs, falls in real time at laryngoscopy — baseline 4.14 dropped to 3.24 at laryngoscopy in human patients (Shah et al., 2023, PMID 37088851). Lignocaine attenuates this response via two distinct mechanisms: IV lignocaine acts systemically with partial afferent blockade; topical spray directly blocks laryngeal mechanoreceptors producing complete cardiovascular response abolition (Hamaya & Dohi, 2000, PMID 10861151). The optimal route remains undetermined in human trials.", size: 18, font: "Calibri" }),
]));

children.push(hd1("RESEARCH GAP"));
children.push(gap_para(
  "A 2025 meta-analysis of 18 RCTs involving 1056 human patients (Qin et al., PMC12338463) confirmed IV lignocaine\nreduces MAP and HR, but found no trial comparing both routes while measuring PI and RPP.\nNo published human RCT has: IV route + Topical route + Perfusion Index + Rate Pressure Product — all together."
));

children.push(hd1("OBJECTIVE"));
children.push(body([
  new TextRun({ text: "Primary: ", bold: true, size: 18, font: "Calibri" }),
  new TextRun({ text: "Compare ΔPerfusion Index (%) and Rate Pressure Product between IV lignocaine, topical lignocaine, and saline control at peri-intubation timepoints in ASA I-II patients undergoing elective surgery.", size: 18, font: "Calibri" }),
]));
children.push(body([
  new TextRun({ text: "Secondary: ", bold: true, size: 18, font: "Calibri" }),
  new TextRun({ text: "Compare HR, SBP, MAP, SpO₂, and adverse effects across the three groups.", size: 18, font: "Calibri" }),
]));

children.push(hd1("STUDY DESIGN"));
children.push(body("Prospective, double-blind, three-group randomized controlled trial (RCT)."));

// Groups table
children.push(new Table({
  width: { size: 100, type: WidthType.PERCENTAGE },
  rows: [
    new TableRow({
      tableHeader: true,
      children: [
        cell("Group", { bold: true, color: WHITE, bg: NAVY, size: 17 }),
        cell("IV Drug (3 min pre-intubation)", { bold: true, color: WHITE, bg: NAVY, size: 17 }),
        cell("Oropharyngeal Spray (5 min pre-intubation)", { bold: true, color: WHITE, bg: NAVY, size: 17 }),
        cell("Blinded?", { bold: true, color: WHITE, bg: NAVY, size: 17 }),
      ]
    }),
    new TableRow({ children: [
      cell("A — IV Lignocaine", { bold: true, bg: LGBLUE }),
      cell("2% Lignocaine 1.5 mg/kg"),
      cell("Normal Saline spray"),
      cell("Yes"),
    ]}),
    new TableRow({ children: [
      cell("B — Topical Lignocaine", { bold: true, bg: LGBLUE }),
      cell("Normal Saline (identical volume)"),
      cell("10% Lignocaine 1.5 mg/kg"),
      cell("Yes"),
    ]}),
    new TableRow({ children: [
      cell("C — Control", { bold: true, bg: LGBLUE }),
      cell("Normal Saline"),
      cell("Normal Saline spray"),
      cell("Yes"),
    ]}),
  ],
  borders: {
    top: { style: BorderStyle.SINGLE, size: 2, color: NAVY },
    bottom: { style: BorderStyle.SINGLE, size: 2, color: NAVY },
    left: { style: BorderStyle.SINGLE, size: 2, color: NAVY },
    right: { style: BorderStyle.SINGLE, size: 2, color: NAVY },
    insideH: { style: BorderStyle.SINGLE, size: 1, color: NAVY },
    insideV: { style: BorderStyle.SINGLE, size: 1, color: NAVY },
  }
}));
children.push(sp(60));
children.push(body([
  new TextRun({ text: "Induction — IDENTICAL in all groups: ", bold: true, size: 18, font: "Calibri" }),
  new TextRun({ text: "Propofol 2 mg/kg + Fentanyl 2 mcg/kg + Atracurium 0.5 mg/kg", size: 18, font: "Calibri" }),
]));

children.push(hd1("MEASUREMENT TIMEPOINTS"));
children.push(new Table({
  width: { size: 100, type: WidthType.PERCENTAGE },
  rows: [
    new TableRow({
      tableHeader: true,
      children: ["T0","T1","T2","T3","T4","T5","T6","T7","T8"].map(t =>
        cell(t, { bold: true, color: WHITE, bg: DKBLUE, size: 16, align: AlignmentType.CENTER })
      )
    }),
    new TableRow({ children: [
      cell("Baseline", { bg: LGBLUE, align: AlignmentType.CENTER, size: 15 }),
      cell("Post-induction", { bg: LGBLUE, align: AlignmentType.CENTER, size: 15 }),
      cell("Pre-intubation", { bg: LGBLUE, align: AlignmentType.CENTER, size: 15 }),
      cell("Laryngoscopy", { bg: LGBLUE, align: AlignmentType.CENTER, size: 15 }),
      cell("Intubation", { bg: LGBLUE, align: AlignmentType.CENTER, size: 15 }),
      cell("1 min post", { bg: LGBLUE, align: AlignmentType.CENTER, size: 15 }),
      cell("3 min post", { bg: LGBLUE, align: AlignmentType.CENTER, size: 15 }),
      cell("5 min post", { bg: LGBLUE, align: AlignmentType.CENTER, size: 15 }),
      cell("10 min post", { bg: LGBLUE, align: AlignmentType.CENTER, size: 15 }),
    ]})
  ],
  borders: {
    top: { style: BorderStyle.SINGLE, size: 2, color: DKBLUE },
    bottom: { style: BorderStyle.SINGLE, size: 2, color: DKBLUE },
    left: { style: BorderStyle.SINGLE, size: 2, color: DKBLUE },
    right: { style: BorderStyle.SINGLE, size: 2, color: DKBLUE },
    insideH: { style: BorderStyle.SINGLE, size: 1, color: DKBLUE },
    insideV: { style: BorderStyle.SINGLE, size: 1, color: DKBLUE },
  }
}));

children.push(sp(60));
children.push(hd1("SAMPLE SIZE & PATIENTS"));
children.push(new Table({
  width: { size: 100, type: WidthType.PERCENTAGE },
  rows: [
    new TableRow({ tableHeader: true, children: [
      cell("Parameter", { bold: true, color: WHITE, bg: NAVY, size: 17 }),
      cell("Detail", { bold: true, color: WHITE, bg: NAVY, size: 17 }),
    ]}),
    new TableRow({ children: [ cell("Total patients", { bold: true }), cell("108 (36 per group)") ]}),
    new TableRow({ children: [ cell("Basis", { bold: true, bg: GREY }), cell("Pramanik et al. 2025 (PMID 40413425) — MAP difference 6 mmHg, SD 12, α=0.05, power 80%", { bg: GREY }) ]}),
    new TableRow({ children: [ cell("Dropout correction", { bold: true }), cell("12% added → final 36/group") ]}),
    new TableRow({ children: [ cell("Inclusion", { bold: true, bg: GREY }), cell("ASA I-II, age 18-60 years, elective surgery, written informed consent", { bg: GREY }) ]}),
    new TableRow({ children: [ cell("Exclusion", { bold: true }), cell("Cardiac disease, hypertension, diabetes, BMI >35, difficult airway, lignocaine allergy, pregnancy") ]}),
    new TableRow({ children: [ cell("Duration", { bold: true, bg: GREY }), cell("8 months — 1 month protocol, 5 months recruitment, 2 months analysis", { bg: GREY }) ]}),
  ],
  borders: { top:{style:BorderStyle.SINGLE,size:2,color:NAVY}, bottom:{style:BorderStyle.SINGLE,size:2,color:NAVY}, left:{style:BorderStyle.SINGLE,size:2,color:NAVY}, right:{style:BorderStyle.SINGLE,size:2,color:NAVY}, insideH:{style:BorderStyle.SINGLE,size:1,color:NAVY}, insideV:{style:BorderStyle.SINGLE,size:1,color:NAVY} }
}));

children.push(sp(60));
children.push(hd1("OUTCOMES & ANALYSIS"));
children.push(body([
  new TextRun({ text: "Primary outcomes: ", bold: true, size: 18, font: "Calibri" }),
  new TextRun({ text: "ΔPI% = [(T0−Tx)/T0] × 100% and RPP at T3, T5, T6, T7", size: 18, font: "Calibri" }),
]));
children.push(body([
  new TextRun({ text: "Secondary: ", bold: true, size: 18, font: "Calibri" }),
  new TextRun({ text: "HR, SBP, MAP, SpO₂ at all timepoints; adverse events (bradycardia, hypotension, bronchospasm)", size: 18, font: "Calibri" }),
]));
children.push(body([
  new TextRun({ text: "Statistics: ", bold: true, size: 18, font: "Calibri" }),
  new TextRun({ text: "Repeated-measures ANOVA, Bonferroni post-hoc correction, Chi-square for categorical variables; SPSS v25. P <0.05 = significant.", size: 18, font: "Calibri" }),
]));
children.push(body([
  new TextRun({ text: "Equipment: ", bold: true, size: 18, font: "Calibri" }),
  new TextRun({ text: "Masimo SET pulse oximeter already installed in our OTs — provides PI continuously at no additional cost.", size: 18, font: "Calibri" }),
]));

// PAGE BREAK
children.push(new Paragraph({ children: [new PageBreak()] }));

// ═══════════════════════════════════════════════════════════
// PAGE 2 — REFERENCE TABLE
// ═══════════════════════════════════════════════════════════

children.push(new Paragraph({
  children: [new TextRun({ text: "SHEET 2 — HUMAN CLINICAL TRIAL REFERENCES", bold: true, size: 26, color: NAVY, font: "Calibri" })],
  alignment: AlignmentType.CENTER,
  spacing: { after: 40 },
  border: { bottom: { style: BorderStyle.DOUBLE, size: 6, color: NAVY } }
}));
children.push(center("All 12 references are human clinical studies. Verify any paper at: pubmed.ncbi.nlm.nih.gov/[PMID]", { color: DKBLUE }));
children.push(sp(60));

children.push(hd1("TOP 3 PAPERS — PMID NUMBERS"));

// Top 3 detailed boxes
const top3 = [
  {
    num: "PAPER 1 ★  —  PMID: 40413425",
    citation: "Pramanik M, Chattopadhyay U, Chaudhuri S et al. Comparison between transtracheal and intravenous 2% lignocaine in attenuating hemodynamic stress response following direct laryngoscopy and endotracheal intubation: a randomized controlled trial. BMC Anesthesiology. 2025;25(1):215.",
    links: "PubMed: pubmed.ncbi.nlm.nih.gov/40413425   |   Free Full Text: pmc.ncbi.nlm.nih.gov/articles/PMC12102901   |   Google Scholar: search 'Pramanik transtracheal intravenous lignocaine 2025'",
    found: "138 human patients. Transtracheal > IV for MAP (P=0.009) and HR (P=0.015) at 3 min. RPP trend favoured transtracheal (P=0.002).",
    missed: "No Perfusion Index. No control group. No oropharyngeal spray comparison. YOUR STUDY fills all three gaps."
  },
  {
    num: "PAPER 2 ★  —  PMC: 12338463",
    citation: "Qin J, He C, Chen Z, Yan S, Ma J. Effects of intravenous lignocaine on haemodynamic responses to laryngoscopy and tracheal intubation: a systematic review and meta-analysis. 2025.",
    links: "Free Full Text: pmc.ncbi.nlm.nih.gov/articles/PMC12338463   |   Google Scholar: search 'Qin meta-analysis IV lignocaine haemodynamic laryngoscopy 2025'",
    found: "18 RCTs, 1056 human patients. IV lignocaine reduces MAP −3.85 mmHg (P=0.006), HR −4.72 bpm (P=0.001). Ethnic variation in South Asian subgroup noted.",
    missed: "Topical route not included in any of the 18 trials. PI not measured. Authors explicitly called for future research with mechanism-based monitoring tools."
  },
  {
    num: "PAPER 3 ★  —  PMID: 37088851",
    citation: "Shah SB, Chawla R, Kaur C. Assessment of stress response using perfusion index in patients undergoing videolaryngoscopic endotracheal intubation. Journal of Clinical Monitoring and Computing. 2023;37(4):987-997.",
    links: "PubMed: pubmed.ncbi.nlm.nih.gov/37088851   |   Google Scholar: search 'Shah perfusion index videolaryngoscopy intubation stress 2023'",
    found: "26 human patients. PI dropped from 4.14 (baseline) to 3.24 at laryngoscopy. PI negatively correlated with MAP (r = −0.89). Validates PI as real-time sympathetic stress marker in humans.",
    missed: "No lignocaine given. No intervention. No RPP. YOUR STUDY applies this validated measurement to lignocaine comparison."
  }
];

for (const p of top3) {
  children.push(new Table({
    width: { size: 100, type: WidthType.PERCENTAGE },
    rows: [
      new TableRow({ children: [ cell(p.num, { bold: true, color: WHITE, bg: "8B0000", size: 18, span: 2 }) ] }),
      new TableRow({ children: [
        cell("Citation", { bold: true, bg: LGRED, size: 16 }),
        cell(p.citation, { size: 16, bg: LGRED })
      ]}),
      new TableRow({ children: [
        cell("Access Links", { bold: true, size: 16 }),
        cell(p.links, { size: 16 })
      ]}),
      new TableRow({ children: [
        cell("Key Finding", { bold: true, bg: LGRED, size: 16 }),
        cell(p.found, { size: 16, bg: LGRED })
      ]}),
      new TableRow({ children: [
        cell("Gap for Your Study", { bold: true, color: RED, size: 16 }),
        cell(p.missed, { size: 16 })
      ]}),
    ],
    borders: { top:{style:BorderStyle.SINGLE,size:4,color:"8B0000"}, bottom:{style:BorderStyle.SINGLE,size:4,color:"8B0000"}, left:{style:BorderStyle.SINGLE,size:4,color:"8B0000"}, right:{style:BorderStyle.SINGLE,size:4,color:"8B0000"}, insideH:{style:BorderStyle.SINGLE,size:1,color:"CC8888"}, insideV:{style:BorderStyle.SINGLE,size:1,color:"CC8888"} }
  }));
  children.push(sp(80));
}

children.push(hd1("ALL 12 HUMAN REFERENCES — COMPLETE TABLE"));

children.push(new Table({
  width: { size: 100, type: WidthType.PERCENTAGE },
  rows: [
    new TableRow({ tableHeader: true, children: [
      cell("#", { bold:true, color:WHITE, bg:NAVY, size:15 }),
      cell("Authors", { bold:true, color:WHITE, bg:NAVY, size:15 }),
      cell("Year", { bold:true, color:WHITE, bg:NAVY, size:15 }),
      cell("Journal", { bold:true, color:WHITE, bg:NAVY, size:15 }),
      cell("PMID / PMC", { bold:true, color:WHITE, bg:NAVY, size:15 }),
      cell("Type", { bold:true, color:WHITE, bg:NAVY, size:15 }),
      cell("N", { bold:true, color:WHITE, bg:NAVY, size:15 }),
      cell("IV?", { bold:true, color:WHITE, bg:NAVY, size:15 }),
      cell("Top?", { bold:true, color:WHITE, bg:NAVY, size:15 }),
      cell("PI?", { bold:true, color:WHITE, bg:NAVY, size:15 }),
      cell("RPP?", { bold:true, color:WHITE, bg:NAVY, size:15 }),
    ]}),
    ...([
      ["1","Pramanik et al.","2025","BMC Anesthesiol","40413425 / PMC12102901","RCT","138","✓","✓ TT","✗","Trend", LGRED],
      ["2","Qin et al.","2025","Saudi J Anaesth","PMC12338463","Meta-analysis","1056","✓","✗","✗","✗", LGRED],
      ["3","Aybal & Karaman","2025","Turk J Anaesth","dergipark PDF","RCT","120","✓","✓","✗","✗", WHITE],
      ["4","Gautam et al.","2025","J Pharm Bioallied","40511154 / PMC12156683","RCT","60","✗","✓ Neb","✗","✗", WHITE],
      ["5","Liu et al.","2024","Braz J Otorhinol","39270370 / PMC11415576","RCT","68","✗","✓","✗","✗", GREY],
      ["6","Shah et al.","2023","J Clin Monit Comput","37088851","Observational","26","✗","✗","✓","✗", LGRED],
      ["7","Mendonça et al.","2022","Braz J Anesthesiol","34582903 / PMC9373404","RCT","69","✓","✗","✗","✗", WHITE],
      ["8","Gladston et al.","2022","J Anaesthesiol Clin","PMC9514071","RCT","75","✓","✓ IT","✗","✗", GREY],
      ["9","Seangrung et al.","2021","BMC Anesthesiol","34717532 / PMC8557037","RCT","106","✓","✗","✗","✗", WHITE],
      ["10","Varshney et al.","2019","Sultan Qaboos Univ","31897315 / PMC6930035","RCT","90","✗","✓","✗","✓", GREY],
      ["11","Kocamanoglu et al.","2015","J Laryngol Otol","25496674","3-arm RCT","99","✓","✓","✗","✗", WHITE],
      ["12","Hamaya & Dohi","2000","Anesthesiology","10861151","RCT","60","✓","✓","✗","✗", GREY],
    ].map(([n,a,y,j,pmid,t,num,iv,top,pi,rpp,bg]) =>
      new TableRow({ children: [n,a,y,j,pmid,t,num,iv,top,pi,rpp].map(v => cell(v, { bg, size: 15 })) })
    )),
    // YOUR STUDY row
    new TableRow({ children: [
      cell("YOUR\nSTUDY", { bold: true, color: WHITE, bg: GREEN, size: 15 }),
      cell("Proposed 2026", { bold: true, color: WHITE, bg: GREEN, size: 15 }),
      cell("2026", { bold: true, color: WHITE, bg: GREEN, size: 15 }),
      cell("Teaching Hospital Lahore", { bold: true, color: WHITE, bg: GREEN, size: 15 }),
      cell("—", { bold: true, color: WHITE, bg: GREEN, size: 15 }),
      cell("3-arm RCT", { bold: true, color: WHITE, bg: GREEN, size: 15 }),
      cell("108", { bold: true, color: WHITE, bg: GREEN, size: 15 }),
      cell("✓", { bold: true, color: WHITE, bg: GREEN, size: 15 }),
      cell("✓", { bold: true, color: WHITE, bg: GREEN, size: 15 }),
      cell("✓", { bold: true, color: WHITE, bg: GREEN, size: 15 }),
      cell("✓", { bold: true, color: WHITE, bg: GREEN, size: 15 }),
    ]})
  ],
  borders: { top:{style:BorderStyle.SINGLE,size:2,color:NAVY}, bottom:{style:BorderStyle.SINGLE,size:2,color:NAVY}, left:{style:BorderStyle.SINGLE,size:2,color:NAVY}, right:{style:BorderStyle.SINGLE,size:2,color:NAVY}, insideH:{style:BorderStyle.SINGLE,size:1,color:NAVY}, insideV:{style:BorderStyle.SINGLE,size:1,color:NAVY} }
}));

children.push(sp(60));
children.push(body("★ Top 3 highlighted above   |   TT = Transtracheal   |   IT = Intratracheal   |   Neb = Nebulized   |   The green row is YOUR proposed study — first with all four ✓", { color: DKBLUE, size: 15 }));

// PAGE BREAK
children.push(new Paragraph({ children: [new PageBreak()] }));

// ═══════════════════════════════════════════════════════════
// PAGE 3 — ASHRAF vs YOUR STUDY
// ═══════════════════════════════════════════════════════════

children.push(new Paragraph({
  children: [new TextRun({ text: "SHEET 3 — COMPARISON: DR. ASHRAF'S STUDY vs YOUR PROPOSED STUDY", bold: true, size: 24, color: NAVY, font: "Calibri" })],
  alignment: AlignmentType.CENTER,
  spacing: { after: 40 },
  border: { bottom: { style: BorderStyle.DOUBLE, size: 6, color: NAVY } }
}));
children.push(sp(60));

children.push(new Table({
  width: { size: 100, type: WidthType.PERCENTAGE },
  rows: [
    new TableRow({ tableHeader: true, children: [
      cell("Feature", { bold:true, color:WHITE, bg:NAVY, size:17 }),
      cell("Dr. Ashraf's Study (Published 2024)", { bold:true, color:WHITE, bg:NAVY, size:17 }),
      cell("Your Proposed Study (2026)", { bold:true, color:WHITE, bg:NAVY, size:17 }),
    ]}),
    ...([
      ["Full Title", "Propofol vs Ketamine+Midazolam on Perfusion Index in cardiac patients undergoing non-cardiac surgery", "IV vs Topical Lignocaine on Perfusion Index, Rate Pressure Product, and Hemodynamic Stress Response at Laryngoscopy", WHITE],
      ["Published In", "Pakistan J Health Sciences, Jan-Jun 2024, Mayo Hospital Lahore", "Proposed — not yet done", GREY],
      ["Drug Class", "Induction agents (propofol vs ketamine-midazolam)", "Local anaesthetic — lignocaine (completely different drug class)", LGBLUE],
      ["Phase Studied", "Induction phase ONLY (before laryngoscopy)", "Laryngoscopy + Intubation phase — AFTER induction (sequential, non-overlapping)", LGBLUE],
      ["Patient Population", "Cardiac patients undergoing non-cardiac surgery", "ASA I-II — NO cardiac disease (exclusion criterion)", WHITE],
      ["Number of Groups", "2 groups — no control group", "3 groups — includes saline control arm", GREY],
      ["Study Design", "Quasi-experimental", "Double-blind RCT", WHITE],
      ["Sample Size", "146 patients (73 per group)", "108 patients (36 per group)", GREY],
      ["PI Timepoints", "1 timepoint only (post-induction)", "9 timepoints — T0 baseline through T8 at 10 min", WHITE],
      ["RPP Measured?", "NO", "YES — co-primary outcome", GREY],
      ["Blinding", "Not described", "Double-blind (patient + assessor)", WHITE],
      ["Research Question", "Which induction agent gives better PI?", "Which lignocaine route better reduces PI drop and RPP rise at intubation?", GREY],
      ["Overlap with Your Study", "ZERO OVERLAP", "—", LGRED],
      ["Relationship", "Validates PI monitoring is feasible in Lahore OTs — supports your proposal", "Applies PI to a new question in a new patient population", "E8FFE8"],
    ].map(([feat, ash, mine, bg]) =>
      new TableRow({ children: [
        cell(feat, { bold: true, bg: GREY, size: 16 }),
        cell(ash, { bg, size: 16 }),
        cell(mine, { bg, size: 16 }),
      ]})
    ))
  ],
  borders: { top:{style:BorderStyle.SINGLE,size:2,color:NAVY}, bottom:{style:BorderStyle.SINGLE,size:2,color:NAVY}, left:{style:BorderStyle.SINGLE,size:2,color:NAVY}, right:{style:BorderStyle.SINGLE,size:2,color:NAVY}, insideH:{style:BorderStyle.SINGLE,size:1,color:NAVY}, insideV:{style:BorderStyle.SINGLE,size:1,color:NAVY} }
}));

children.push(sp(80));
children.push(new Paragraph({
  children: [
    new TextRun({ text: "One-Line Summary for Supervisor: ", bold: true, size: 18, font: "Calibri", color: NAVY }),
    new TextRun({ text: '"Ma\'am, Dr. Ashraf studied induction agents in cardiac patients at one timepoint. I am studying lignocaine routes at the intubation phase in non-cardiac patients at nine timepoints with RPP as an additional outcome. The two studies are completely sequential and non-overlapping — hers ends where mine begins."', size: 18, font: "Calibri", italics: true }),
  ],
  spacing: { after: 60 },
  shading: { type: ShadingType.SOLID, color: "EEF2FF" },
  border: { left: { style: BorderStyle.THICK, size: 10, color: NAVY } }
}));

// PAGE BREAK
children.push(new Paragraph({ children: [new PageBreak()] }));

// ═══════════════════════════════════════════════════════════
// PAGE 4 — WHY THREE GROUPS + CHECKLIST
// ═══════════════════════════════════════════════════════════

children.push(new Paragraph({
  children: [new TextRun({ text: "SHEET 4 — WHY THREE GROUPS AND NOT TWO + PRESENTATION CHECKLIST", bold: true, size: 22, color: NAVY, font: "Calibri" })],
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  border: { bottom: { style: BorderStyle.DOUBLE, size: 6, color: NAVY } }
}));
children.push(sp(60));

children.push(hd1("WHAT TO SAY TO YOUR SUPERVISOR"));
children.push(new Paragraph({
  children: [new TextRun({ text: '"Ma\'am, if I use only two groups — IV versus topical — I cannot determine whether either drug actually worked, or whether both failed equally. I need the control group to establish the baseline magnitude of the untreated stress response in our specific patient population. Without it, any difference between the two drug groups could be meaningless."', size: 18, font: "Calibri", italics: true, color: NAVY })],
  spacing: { after: 80 },
  shading: { type: ShadingType.SOLID, color: "EEF2FF" },
  border: { left: { style: BorderStyle.THICK, size: 10, color: NAVY } }
}));

children.push(hd1("SCIENTIFIC COMPARISON TABLE"));
children.push(new Table({
  width: { size: 100, type: WidthType.PERCENTAGE },
  rows: [
    new TableRow({ tableHeader: true, children: [
      cell("Question Being Asked", { bold:true, color:WHITE, bg:"2E6B2E", size:16 }),
      cell("Two Groups Only (IV vs Topical)", { bold:true, color:WHITE, bg:"2E6B2E", size:16 }),
      cell("Three Groups (IV vs Topical vs Control)", { bold:true, color:WHITE, bg:"2E6B2E", size:16 }),
    ]}),
    ...([
      ["Did IV lignocaine reduce stress vs nothing?", "✗ Cannot answer", "✓ Compare A vs C"],
      ["Did topical lignocaine reduce stress vs nothing?", "✗ Cannot answer", "✓ Compare B vs C"],
      ["Is IV better than topical?", "✓ Can answer", "✓ Can answer"],
      ["True untreated stress response in our population?", "✗ Unknown", "✓ Measured by Group C"],
      ["Absolute ΔPI% and ΔRPP from true baseline?", "✗ Relative only", "✓ Absolute values"],
      ["Result applicable to future studies?", "✗ No reference point", "✓ Group C is the anchor"],
      ["Publishable if drugs show no difference?", "✗ Inconclusive", "✓ Yes — both may have failed equally"],
    ].map(([q, two, three], i) =>
      new TableRow({ children: [
        cell(q, { bg: i%2===0 ? GREY : WHITE, size: 16 }),
        cell(two, { bg: LGRED, size: 16, color: RED }),
        cell(three, { bg: LGGRN, size: 16, color: GREEN, bold: true }),
      ]})
    ))
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}));

children.push(sp(80));
children.push(hd1("STATISTICAL & ETHICAL JUSTIFICATION"));
children.push(body([
  new TextRun({ text: "Statistical: ", bold: true, size: 18, font: "Calibri" }),
  new TextRun({ text: "With two groups, if the result shows no significant difference, you cannot conclude equivalence — you cannot know if both drugs worked equally well, or both drugs failed equally. The control group resolves this completely.", size: 18, font: "Calibri" }),
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children.push(body([
  new TextRun({ text: "Ethical: ", bold: true, size: 18, font: "Calibri" }),
  new TextRun({ text: "All three groups receive standard induction — propofol + fentanyl + atracurium. Fentanyl 2 mcg/kg itself provides partial hemodynamic protection. No patient receives zero protection. This three-group design with saline control is the same approach used in Kocamanoglu et al. 2015 (PMID 25496674) and Varshney et al. 2019 (PMID 31897315).", size: 18, font: "Calibri" }),
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children.push(sp(80));
children.push(hd1("PRESENTATION CHECKLIST"));

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      cell("DURING THE MEETING", { bold:true, color:WHITE, bg:"2E6B2E", size:17 }),
      cell("AFTER THE MEETING", { bold:true, color:WHITE, bg:"8B5000", size:17 }),
    ]}),
    new TableRow({ children: [
      cell("□ Synopsis printed × 2 copies\n□ Reference table × 2\n□ Comparison table × 2\n□ Three-groups sheet × 2\n□ Your name handwritten on\n   supervisor's copy\n□ PubMed open on phone:\n   pubmed.ncbi.nlm.nih.gov\n   /40413425\n□ Pen in pocket\n□ Script practiced out loud", { bg: "FFF8E8", size: 16 }),
      cell("□ Placed supervisor's copy first\n□ Stated research gap clearly\n□ Pointed to groups table\n□ Named PMID 40413425\n□ Addressed Dr. Ashraf\n   proactively\n□ Answered 'why 3 groups'\n□ Stopped talking after Step 10\n□ Let her read in silence\n□ Wrote down all feedback", { bg: "E8FFE8", size: 16 }),
      cell("□ YES: get her signature,\n   take to research dept same day\n□ 'Come back later': confirm\n   specific date before leaving\n□ Changes needed: return\n   within 48 hours\n□ Ask which ethics committee\n□ Ask for co-supervisor\n   if needed", { bg: "FFF0E0", size: 16 }),
    ]})
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}));

children.push(sp(80));
children.push(new Paragraph({
  children: [new TextRun({ text: "You walk in with 4 sheets. You speak for 4 minutes. You leave one copy behind. That is all you need to do.", bold: true, size: 20, color: NAVY, font: "Calibri" })],
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  spacing: { after: 60 },
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  title: "Supervisor Presentation — Lignocaine Research Synopsis",
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