const pptxgen = require("pptxgenjs");

const pres = new pptxgen();
pres.layout = "LAYOUT_16x9";
pres.title = "Impact Assessment of Rotavirus Vaccine on Acute Gastroenteritis & Safety: Focus on Intussusception";
pres.author = "Pediatric Residency Presentation";

// ─── PALETTE ─────────────────────────────────────────────────────────────────
const NAVY    = "0D2B55";   // dominant dark bg
const TEAL    = "00A99D";   // accent / data highlight
const WHITE   = "FFFFFF";
const LTGRAY  = "EFF2F7";   // light slide bg
const SLATE   = "2E4057";   // mid-dark bg
const ORANGE  = "F76C2F";   // warning accent for intussusception slides
const LTTEXT  = "C8D8E8";   // muted text on dark bg
const DARKTEXT= "1A2E42";   // body text on light bg

// ─── HELPER: add slide header bar ────────────────────────────────────────────
function addHeader(slide, title, dark = false) {
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}

// ─── HELPER: accent left border bar ─────────────────────────────────────────
function addAccentBar(slide, color) {
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// ─── HELPER: stat box ────────────────────────────────────────────────────────
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}

// ─── HELPER: key-value row ───────────────────────────────────────────────────
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// ═══════════════════════════════════════════════════════════════════════════════
// SLIDE 1 — TITLE SLIDE
// ═══════════════════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: NAVY };

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    x: 0, y: 0, w: 0.35, h: 5.625,
    fill: { color: TEAL }, line: { width: 0 }
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    x: 0.35, y: 4.9, w: 9.65, h: 0.725,
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  s.addText("IMPACT ASSESSMENT OF", {
    x: 0.65, y: 0.55, w: 9.0, h: 0.6,
    fontSize: 14, bold: false, color: TEAL, charSpacing: 3
  });
  s.addText("Rotavirus Vaccine", {
    x: 0.65, y: 1.1, w: 9.0, h: 1.1,
    fontSize: 38, bold: true, color: WHITE
  });
  s.addText("on Acute Gastroenteritis & Safety", {
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    fontSize: 22, bold: false, color: LTTEXT
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    x: 0.65, y: 2.82, w: 4.5, h: 0.04,
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  s.addText("FOCUS: Intussusception Risk–Benefit Analysis", {
    x: 0.65, y: 2.95, w: 8.5, h: 0.45,
    fontSize: 13, bold: true, color: ORANGE, charSpacing: 1
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  s.addText("Pediatric Residency Journal Club  |  2026", {
    x: 0.65, y: 4.92, w: 8.5, h: 0.5,
    fontSize: 10, color: LTTEXT, charSpacing: 1
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  s.addText("Primary References: Vesikari 2006 (NEJM) · Ruiz-Palacios 2006 (NEJM) · Sun et al. 2021 (JAMA Pediatr) · CDC Pink Book 2024", {
    x: 0.65, y: 5.25, w: 8.8, h: 0.3,
    fontSize: 7.5, color: "668BA8", italic: true
  });
}

// ═══════════════════════════════════════════════════════════════════════════════
// SLIDE 2 — BACKGROUND & BURDEN OF DISEASE
// ═══════════════════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: LTGRAY };
  addHeader(s, "Background — Burden of Rotavirus Disease");
  addAccentBar(s, TEAL);

  s.addText("Why Does Rotavirus Matter?", {
    x: 0.25, y: 0.9, w: 9.5, h: 0.45,
    fontSize: 16, bold: true, color: NAVY, margin: 0
  });

  // Stat boxes row 1
  statBox(s, "Deaths/year globally (pre-vaccine)", "~215,000", "Children <5 yrs (WHO, 2013)", 0.25, 1.45, NAVY);
  statBox(s, "Hospitalizations in US/yr (pre-vaccine)", "55,000–70,000", "Costing ~$1 billion/yr", 3.4, 1.45, NAVY);
  statBox(s, "Most common cause of severe diarrhea in <5 yrs", "#1", "Globally & in the US", 6.55, 1.45, TEAL);

  s.addText([
    { text: "Key Biology: ", options: { bold: true, color: NAVY } },
    { text: "Non-enveloped dsRNA virus (Reoviridae). Feco-oral spread. Infects small bowel enterocytes → osmotic + secretory diarrhea. Peak age: 6–24 months.", options: { color: DARKTEXT } }
  ], { x: 0.25, y: 3.1, w: 9.5, h: 0.45, fontSize: 10, margin: 0, wrap: true });

  s.addText([
    { text: "Seasonality: ", options: { bold: true, color: NAVY } },
    { text: "Winter–spring peak in temperate climates. Strains: G1P[8], G2P[4], G3P[8], G4P[8], G9P[8] account for >90% of global disease.", options: { color: DARKTEXT } }
  ], { x: 0.25, y: 3.65, w: 9.5, h: 0.45, fontSize: 10, margin: 0, wrap: true });

  s.addText([
    { text: "Pre-vaccine era US context: ", options: { bold: true, color: NAVY } },
    { text: "~410,000 physician visits, 205–272,000 ED visits annually attributable to rotavirus gastroenteritis.", options: { color: DARKTEXT } }
  ], { x: 0.25, y: 4.2, w: 9.5, h: 0.45, fontSize: 10, margin: 0, wrap: true });

  s.addText("Source: CDC Surveillance Manual Ch.13; WHO Global Burden Data", {
    x: 0.25, y: 5.3, w: 9.5, h: 0.2,
    fontSize: 7, color: "888888", italic: true
  });
}

// ═══════════════════════════════════════════════════════════════════════════════
// SLIDE 3 — HISTORY OF ROTAVIRUS VACCINES
// ═══════════════════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: LTGRAY };
  addHeader(s, "History of Rotavirus Vaccines");
  addAccentBar(s, ORANGE);

  const events = [
    { yr: "1998", text: "RotaShield (RRV-TV) licensed in US — rhesus tetravalent vaccine", color: ORANGE },
    { yr: "1999", text: "RotaShield WITHDRAWN — post-marketing surveillance found ~1/10,000 intussusception risk, especially after dose 1 (day 3–14)", color: ORANGE },
    { yr: "2006", text: "RotaTeq (RV5) licensed by FDA — Merck, pentavalent bovine-human reassortant (Vesikari trial, NEJM 2006)", color: TEAL },
    { yr: "2008", text: "Rotarix (RV1) licensed by FDA — GSK, monovalent attenuated human strain (Ruiz-Palacios trial, NEJM 2006)", color: TEAL },
    { yr: "2009", text: "WHO recommends global inclusion of rotavirus vaccine in all national immunization programs", color: NAVY },
    { yr: "2013+", text: "Post-licensure surveillance detects small intussusception signal → re-evaluation of risk–benefit (current focus)", color: ORANGE },
  ];

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    const y = 0.88 + i * 0.72;
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      x: 0.2, y: y + 0.02, w: 0.9, h: 0.42,
      fill: { color: ev.color }, line: { width: 0 }
    });
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      x: 0.2, y: y + 0.02, w: 0.9, h: 0.42,
      fontSize: 10, bold: true, color: WHITE, align: "center", valign: "middle", margin: 0
    });
    s.addText(ev.text, {
      x: 1.25, y: y, w: 8.5, h: 0.52,
      fontSize: 10, color: DARKTEXT, valign: "middle"
    });
  });
}

// ═══════════════════════════════════════════════════════════════════════════════
// SLIDE 4 — LANDMARK RCTs OVERVIEW
// ═══════════════════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: LTGRAY };
  addHeader(s, "Landmark RCTs — Study Design Overview");
  addAccentBar(s, TEAL);

  // Two columns
  // RotaTeq box
  s.addShape(pres.ShapeType.rect, {
    x: 0.2, y: 0.88, w: 4.6, h: 4.5,
    fill: { color: WHITE }, line: { color: NAVY, width: 1.5 }
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    x: 0.2, y: 0.88, w: 4.6, h: 0.5,
    fill: { color: NAVY }, line: { width: 0 }
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    x: 0.28, y: 0.88, w: 4.44, h: 0.5,
    fontSize: 11, bold: true, color: WHITE, valign: "middle", margin: 0
  });

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    ["Reference", "Vesikari et al., NEJM 2006"],
    ["Design", "Phase III double-blind RCT"],
    ["Sample size", "n = 68,038 infants"],
    ["Countries", "11 countries, North America & Europe"],
    ["Doses", "3 oral doses at 2, 4, 6 months"],
    ["Comparator", "Placebo"],
    ["Primary endpoint", "Any grade RV gastroenteritis after dose 1"],
    ["Follow-up", "Through 2nd rotavirus season"],
  ];
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    const y = 1.5 + i * 0.38;
    s.addText(row[0] + ":", {
      x: 0.35, y, w: 1.6, h: 0.35,
      fontSize: 8.5, bold: true, color: NAVY, valign: "top", margin: 0, wrap: true
    });
    s.addText(row[1], {
      x: 1.95, y, w: 2.7, h: 0.35,
      fontSize: 8.5, color: DARKTEXT, valign: "top", margin: 0, wrap: true
    });
  });

  // Rotarix box
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    x: 5.2, y: 0.88, w: 4.6, h: 4.5,
    fill: { color: WHITE }, line: { color: TEAL, width: 1.5 }
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    x: 5.2, y: 0.88, w: 4.6, h: 0.5,
    fill: { color: TEAL }, line: { width: 0 }
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    x: 5.28, y: 0.88, w: 4.44, h: 0.5,
    fontSize: 11, bold: true, color: WHITE, valign: "middle", margin: 0
  });

  const rota = [
    ["Reference", "Ruiz-Palacios et al., NEJM 2006"],
    ["Design", "Phase III double-blind RCT"],
    ["Sample size", "n = 63,225 infants"],
    ["Countries", "11 countries, Latin America & Finland"],
    ["Doses", "2 oral doses at 2 and 4 months"],
    ["Comparator", "Placebo"],
    ["Primary endpoint", "Severe RV gastroenteritis (Vesikari score ≥11)"],
    ["Follow-up", "Through 1st rotavirus season"],
  ];
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    const y = 1.5 + i * 0.38;
    s.addText(row[0] + ":", {
      x: 5.35, y, w: 1.6, h: 0.35,
      fontSize: 8.5, bold: true, color: "006B62", valign: "top", margin: 0, wrap: true
    });
    s.addText(row[1], {
      x: 6.95, y, w: 2.7, h: 0.35,
      fontSize: 8.5, color: DARKTEXT, valign: "top", margin: 0, wrap: true
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  s.addText("Both trials powered for intussusception safety (>60,000 infants each). No increased IS risk detected in either phase III trial.", {
    x: 0.2, y: 5.3, w: 9.6, h: 0.25,
    fontSize: 7.5, color: "555555", italic: true, margin: 0
  });
}

// ═══════════════════════════════════════════════════════════════════════════════
// SLIDE 5 — EFFICACY RESULTS: RotaTeq
// ═══════════════════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: LTGRAY };
  addHeader(s, "Efficacy Results — RotaTeq (RV5) | Vesikari 2006");
  addAccentBar(s, NAVY);

  s.addText("Primary & Secondary Efficacy Against Rotavirus Gastroenteritis", {
    x: 0.25, y: 0.88, w: 9.5, h: 0.38,
    fontSize: 13, bold: true, color: NAVY
  });

  // Efficacy stat boxes
  statBox(s, "Any-grade RV gastroenteritis prevention", "74%", "Efficacy (95% CI: 66–80%)", 0.25, 1.35, NAVY);
  statBox(s, "Severe RV gastroenteritis prevention", "98%", "Efficacy against most severe cases", 3.4, 1.35, TEAL);
  statBox(s, "RV-related hospitalization prevention", "96%", "Hospitalization reduction", 6.55, 1.35, TEAL);

  s.addText("Key Secondary Results:", {
    x: 0.25, y: 2.95, w: 9.5, h: 0.35,
    fontSize: 11, bold: true, color: NAVY
  });

  const bullets5 = [
    "74% reduction in G1–G4 rotavirus gastroenteritis across all severity grades",
    "98% efficacy against severe disease (Vesikari score ≥17) — vaccine nearly eliminates worst outcomes",
    "86% reduction in emergency department visits for RV diarrhea",
    "Strain coverage: effective across G1, G2, G3, G4, G9 serotypes",
    "No significant difference in rates of serious adverse events (SAEs) vs. placebo in ~68,000 infants",
    "Intussusception: 6 cases vaccine vs. 5 placebo (RR not significant) during 60-day window post-dose",
  ];

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    const y = 3.35 + i * 0.32;
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      x: 0.25, y: y + 0.09, w: 0.13, h: 0.13,
      fill: { color: TEAL }, line: { width: 0 }
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    s.addText(b, {
      x: 0.48, y, w: 9.3, h: 0.3,
      fontSize: 9.5, color: DARKTEXT, margin: 0, wrap: true
    });
  });
}

// ═══════════════════════════════════════════════════════════════════════════════
// SLIDE 6 — EFFICACY RESULTS: Rotarix
// ═══════════════════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: LTGRAY };
  addHeader(s, "Efficacy Results — Rotarix (RV1) | Ruiz-Palacios 2006");
  addAccentBar(s, TEAL);

  s.addText("Primary & Secondary Efficacy Against Rotavirus Gastroenteritis", {
    x: 0.25, y: 0.88, w: 9.5, h: 0.38,
    fontSize: 13, bold: true, color: NAVY
  });

  statBox(s, "Severe RV gastroenteritis (Vesikari ≥11)", "85%", "Efficacy (95% CI: 72–92%)", 0.25, 1.35, TEAL);
  statBox(s, "Severe RV gastroenteritis (any G-type)", "85%", "Including G1 and non-G1 strains", 3.4, 1.35, NAVY);
  statBox(s, "RV-related hospitalization prevention", "85%", "Reduction in hospitalizations", 6.55, 1.35, NAVY);

  s.addText("Key Secondary Results:", {
    x: 0.25, y: 2.95, w: 9.5, h: 0.35,
    fontSize: 11, bold: true, color: NAVY
  });

  const bullets6 = [
    "85% efficacy against severe RV gastroenteritis confirmed in first rotavirus season after vaccination",
    "85% reduction in RV hospitalization (consistent finding across Latin America and Finland)",
    "79% efficacy against any RV gastroenteritis of any severity",
    "Cross-protection against G9P[8] and G2P[4] strains (non-vaccine strains) demonstrated in real-world follow-up",
    "Immunogenicity: seropositivity rates 78–85% across study sites after 2-dose regimen",
    "No statistically significant intussusception risk difference: 3 vaccine vs. 6 placebo cases in 30-day window",
  ];

  bullets6.forEach((b, i) => {
    const y = 3.35 + i * 0.32;
    s.addShape(pres.ShapeType.rect, {
      x: 0.25, y: y + 0.09, w: 0.13, h: 0.13,
      fill: { color: NAVY }, line: { width: 0 }
    });
    s.addText(b, {
      x: 0.48, y, w: 9.3, h: 0.3,
      fontSize: 9.5, color: DARKTEXT, margin: 0, wrap: true
    });
  });
}

// ═══════════════════════════════════════════════════════════════════════════════
// SLIDE 7 — META-ANALYSIS: SUN ET AL. 2021 (JAMA PEDIATRICS)
// ═══════════════════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: LTGRAY };
  addHeader(s, "Meta-Analysis Evidence — Sun et al., JAMA Pediatrics 2021");
  addAccentBar(s, TEAL);

  s.addText("Systematic Review + Meta-Analysis: 20 RCTs + 38 Case-Control Studies | PMID: 33970192", {
    x: 0.25, y: 0.85, w: 9.5, h: 0.35,
    fontSize: 10.5, bold: true, color: TEAL
  });

  // Table header
  const cols = [2.4, 2.1, 2.1, 2.1, 1.3];
  const headers = ["Outcome", "RV1 (Rotarix)", "RV5 (RotaTeq)", "Difference", "SOE"];
  let tx = 0.2;
  headers.forEach((h, i) => {
    s.addShape(pres.ShapeType.rect, {
      x: tx, y: 1.28, w: cols[i], h: 0.38,
      fill: { color: NAVY }, line: { color: WHITE, width: 0.5 }
    });
    s.addText(h, {
      x: tx + 0.05, y: 1.28, w: cols[i] - 0.1, h: 0.38,
      fontSize: 9, bold: true, color: WHITE, valign: "middle", margin: 0
    });
    tx += cols[i];
  });

  const rows = [
    ["Any RVGE reduction", "RR 0.316 (CI: 0.22–0.35)", "RR 0.350 (CI: 0.28–0.45)", "No sig. difference", "High"],
    ["RVGE Hospitalization (OR)", "OR 0.347 (CI: 0.28–0.43)", "OR 0.272 (CI: 0.20–0.38)", "No sig. difference", "High"],
    ["Severe RVGE", "Higher protection both vaccines", "Higher protection both vaccines", "No sig. difference", "Moderate"],
    ["Serious Adverse Events", "No increased risk", "No increased risk", "No difference", "High"],
    ["Intussusception", "No increased risk (RCT data)", "No increased risk (RCT data)", "No difference", "Moderate"],
  ];

  const rowColors = [LTGRAY, WHITE, LTGRAY, WHITE, LTGRAY];
  rows.forEach((row, ri) => {
    tx = 0.2;
    row.forEach((cell, ci) => {
      s.addShape(pres.ShapeType.rect, {
        x: tx, y: 1.66 + ri * 0.48, w: cols[ci], h: 0.46,
        fill: { color: rowColors[ri] }, line: { color: "CCCCCC", width: 0.5 }
      });
      s.addText(cell, {
        x: tx + 0.05, y: 1.66 + ri * 0.48, w: cols[ci] - 0.1, h: 0.46,
        fontSize: 8, color: DARKTEXT, valign: "middle", margin: 0, wrap: true
      });
      tx += cols[ci];
    });
  });

  s.addText("Key finding: RV1 and RV5 provide equivalent protection. Both significantly reduce RVGE risk (~65–70% any-grade; ~86–98% severe). No serious adverse event signal in RCT meta-analysis.", {
    x: 0.2, y: 5.1, w: 9.6, h: 0.42,
    fontSize: 9, bold: false, color: DARKTEXT, italic: false, wrap: true
  });
}

// ═══════════════════════════════════════════════════════════════════════════════
// SLIDE 8 — POST-LICENSURE REAL-WORLD EFFECTIVENESS
// ═══════════════════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: LTGRAY };
  addHeader(s, "Post-Licensure Real-World Effectiveness");
  addAccentBar(s, TEAL);

  s.addText("Sustained Impact Across Multiple Surveillance Systems", {
    x: 0.25, y: 0.88, w: 9.5, h: 0.38,
    fontSize: 14, bold: true, color: NAVY
  });

  statBox(s, "Decline in RV hospitalizations (US)", "~90%", "2007–2012 vs. pre-vaccine era", 0.2, 1.35, TEAL);
  statBox(s, "Hospitalizations prevented annually (US)", "40,000–50,000", "CDC estimate post-introduction", 3.35, 1.35, NAVY);
  statBox(s, "Herd immunity effect", "Observed", "Unvaccinated older children also protected", 6.5, 1.35, TEAL);

  const items8 = [
    { title: "Indirect/Herd Protection", body: "Significant reductions in RV disease observed in unvaccinated older children and adults, consistent with herd immunity. Vaccinated infants less likely to transmit." },
    { title: "Low-Income Countries", body: "Efficacy 50–64% in high-mortality sub-Saharan Africa (Henschke 2022 Cochrane). Lower than high-income settings but still substantial public health impact given high baseline burden." },
    { title: "Strain Adaptability", body: "Vaccines maintained effectiveness despite emergence of G2P[4] and G9P[8] strains in vaccinated populations (strain surveillance ongoing)." },
    { title: "Mexico Experience", body: "15-year post-licensure review: 85% reduction in severe RV hospitalizations, ~56% reduction in all-cause diarrheal deaths in children <5 yrs (Guzman-Holst 2021)." },
  ];

  items8.forEach((item, i) => {
    const y = 2.95 + i * 0.55;
    addBadge(s, i + 1, 0.2, y + 0.08, TEAL);
    s.addText(item.title + ": ", {
      x: 0.7, y, w: 9.1, h: 0.25,
      fontSize: 10, bold: true, color: NAVY, margin: 0
    });
    s.addText(item.body, {
      x: 0.7, y: y + 0.25, w: 9.1, h: 0.28,
      fontSize: 9, color: DARKTEXT, margin: 0, wrap: true
    });
  });
}

// ═══════════════════════════════════════════════════════════════════════════════
// SLIDE 9 — WHAT IS INTUSSUSCEPTION?
// ═══════════════════════════════════════════════════════════════════════════════
{
  const s = pres.addSlide();
  s.background = { color: NAVY };

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    { icon: "DEF", text: "Intussusception: telescoping of a proximal bowel segment into the adjacent distal lumen — most common cause of intestinal obstruction in infants" },
    { icon: "AGE", text: "Peak incidence: 5–10 months (background rate: ~34–56 per 100,000 infants/year in the US). Ileocolic junction most common site." },
    { icon: "SX", text: "Classic triad: colicky abdominal pain (episodic crying), vomiting, and blood in stool ('currant jelly stools'). Abdominal mass palpable in ~50%." },
    { icon: "DX", text: "Diagnosis: Ultrasound (sensitivity >98%) — 'target sign' or 'donut sign'. X-ray may show bowel obstruction pattern." },
    { icon: "TX", text: "Treatment: Air/hydrostatic enema reduction (90% success if caught early). Surgery for failed reduction or perforation." },
    { icon: "WHY", text: "Relevance to vaccines: Rotashield (1998) caused ~1:10,000 IS. Current vaccines (RV1/RV5) have a much smaller signal: ~1–6 per 100,000 vaccinees." },
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// ═══════════════════════════════════════════════════════════════════════════════
// SLIDE 10 — ROTASHIELD LESSON (HISTORICAL CONTEXT)
// ═══════════════════════════════════════════════════════════════════════════════
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    { label: "Signal detected", val: "VAERS reports within months of introduction" },
    { label: "Magnitude", val: "~1 excess case per 10,000 vaccinated infants" },
    { label: "Timing", val: "Greatest risk: 3–14 days after dose 1; smaller risk after dose 2" },
    { label: "Action", val: "ACIP suspended recommendation July 1999; voluntary withdrawal October 1999" },
    { label: "Mechanism hypothesis", val: "Possible local inflammation / intussusception-prone age window effect" },
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// ═══════════════════════════════════════════════════════════════════════════════
// SLIDE 11 — INTUSSUSCEPTION RISK: RV5 & RV1 POST-LICENSURE DATA
// ═══════════════════════════════════════════════════════════════════════════════
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    "Mexico & Brazil (Rotarix): Post-licensure studies confirmed small elevated IS risk in first week after dose 1 (~1–2 per 100,000). Pre-existing background IS rate was ~34/100,000 infants/yr.",
    "Australia (Rotarix): A 2014 NEJM study (Carlin et al.) found RR of IS 6.8 (95% CI: 2.4–21.8) in the 1–7 days post-dose 1 — translated to 6 excess cases per 100,000 first doses.",
    "High-income vs. low-income settings: Signal strongest in high-income countries; many low-income countries show no detectable signal — possibly explained by higher background IS rates, immunological differences, or later vaccination ages.",
    "RotaTeq: Weaker IS signal than Rotarix in most surveillance studies. VSD found no statistically significant IS excess for RotaTeq in the primary analysis.",
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// ═══════════════════════════════════════════════════════════════════════════════
// SLIDE 12 — RISK-BENEFIT ANALYSIS
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    "~40,000–50,000 hospitalizations prevented annually (US)",
    "~86–98% reduction in severe RV gastroenteritis",
    "~74–85% reduction in any-grade RV diarrhea",
    "Hundreds of avoided deaths in low-income countries",
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    "$1 billion annual healthcare cost savings (US)",
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    "Risk window: 7 days after dose 1 or 2",
    "Most IS cases treatable; mortality extremely rare",
    "Background IS rate: 34–56 per 100,000 infant-years",
    "RotaShield risk (historical): 1:10,000 — 10–60x higher",
    "RV1 slightly higher IS signal than RV5 in some studies",
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// ═══════════════════════════════════════════════════════════════════════════════
// SLIDE 13 — VACCINATION SCHEDULE & CONTRAINDICATIONS
// ═══════════════════════════════════════════════════════════════════════════════
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// ═══════════════════════════════════════════════════════════════════════════════
// SLIDE 14 — CLINICAL IMPLICATIONS & KEY MESSAGES
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// ═══════════════════════════════════════════════════════════════════════════════
// SLIDE 15 — SUMMARY & REFERENCES
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    "RV5 (RotaTeq) & RV1 (Rotarix): phase III RCTs (n>60,000 each) showed 74–98% efficacy against severe RVGE",
    "Meta-analysis (Sun 2021, JAMA Pediatr): equivalent protection, no SAE signal in trial data",
    "Post-licensure: ~40,000–50,000 US hospitalizations prevented annually; ~90% decline in RV admissions",
    "IS risk: 1–6 excess cases per 100,000 vaccinees (detectable only in post-marketing surveillance)",
    "Risk:benefit ratio overwhelmingly favors vaccination (>1,000 benefits per 1 IS case)",
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    "1. Vesikari T, et al. Safety and efficacy of a pentavalent human-bovine reassortant rotavirus vaccine. NEJM 2006;354:23–33.",
    "2. Ruiz-Palacios GM, et al. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. NEJM 2006;354:11–22.",
    "3. Sun Z-W, et al. Association of Rotavirus Vaccines With Reduction in Rotavirus Gastroenteritis in Children <5 Years. JAMA Pediatr 2021;175(7):e210347. PMID: 33970192.",
    "4. Gidengil C, et al. Safety of vaccines used for routine immunization in the United States. Vaccine 2021;39(28):3804–3824. PMID: 34049735.",
    "5. Henschke N, et al. Efficacy and safety of rotavirus vaccines in countries in Africa and Asia with high child mortality. Vaccine 2022. PMID: 35184924.",
    "6. CDC Pink Book Ch.19 — Rotavirus (2024). cdc.gov/pinkbook",
    "7. CDC Surveillance Manual Ch.13 — Rotavirus (2024). cdc.gov/surv-manual",
    "8. AAP Red Book 2021: Report of Committee on Infectious Diseases — Rotavirus, pp.1003–1009.",
    "9. Carlin JB, et al. Intussusception risk and disease prevention associated with rotavirus vaccines. NEJM 2013;369:1761–71.",
    "10. Guzman-Holst A, et al. 15-year experience with rotavirus vaccination in Mexico. Hum Vaccin Immunother 2021. PMID: 34187326.",
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