One Health Program - Short Note

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pres.layout = 'LAYOUT_WIDE'; // 13.3 x 7.5 inches
pres.title = 'MDR-TB & BPaLM Regimen';
pres.author = 'KD Tripathi Reference';

// ─── COLOR PALETTE ───────────────────────────────────────────────────
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  accent1:   "E63946",  // vibrant red-orange (TB red)
  accent2:   "F4A261",  // warm amber
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  green:     "2D6A4F",
  yellow:    "FFB703",
  orange:    "FB8500",
  purple:    "6A0572",
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// ─── HELPERS ─────────────────────────────────────────────────────────
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// ══════════════════════════════════════════════════════════════
// SLIDE 1 — TITLE SLIDE
// ══════════════════════════════════════════════════════════════
{
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  // Main title
  slide.addText("MDR-TB &", {
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  slide.addText("BPaLM REGIMEN", {
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  // Tagline
  slide.addText("Bedaquiline · Pretomanid · Linezolid · Moxifloxacin", {
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  // Description
  slide.addText("A comprehensive review of the new all-oral shorter treatment regimen\nfor Multidrug-Resistant Tuberculosis based on KD Tripathi's\nEssentials of Medical Pharmacology", {
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    { text: "Gaurav Gupta (31)  ·  Nikhil Anand (32)  ·  Khairul Ahmed (33)", options: { color: C.white } }
  ], { x: 0.6, y: 6.55, w: 12, h: 0.35, fontSize: 11, fontFace: "Calibri" });
  slide.addText([
    { text: "Seajal Thottarath (34)  ·  Shreya Saha Mandal (35)  ·  Mostafizur Rahman (36)", options: { color: C.white } }
  ], { x: 0.6, y: 6.88, w: 12, h: 0.3, fontSize: 11, fontFace: "Calibri" });
}

// ══════════════════════════════════════════════════════════════
// SLIDE 2 — DEFINITION OF MDR-TB (KD Tripathi)
// ══════════════════════════════════════════════════════════════
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    { text: "MDR-TB ", options: { bold: true, color: C.accent2, fontSize: 16 } },
    { text: "(Multidrug-Resistant Tuberculosis)", options: { color: C.white, fontSize: 15, italic: true } },
    { text: " is resistance to at least ", options: { color: C.white, fontSize: 15 } },
    { text: "Isoniazid (H) AND Rifampicin (R)", options: { bold: true, color: C.accent1, fontSize: 15 } },
    { text: " — the two most potent first-line anti-TB drugs.", options: { color: C.white, fontSize: 15 } }
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      "Mycobacterium tuberculosis",
      "Acid-fast, aerobic bacillus",
      "Slow growth — 16–20 hr doubling",
      "Resistance via chromosomal mutations",
      "NO plasmid-mediated resistance"
    ]},
    { x: 4.65, title: "Resistance Criteria", bg: C.cardBg2, tc: C.orange, bullets: [
      "Isoniazid (INH) — katG/inhA mutations",
      "Rifampicin (RIF) — rpoB gene mutation",
      "RR-TB: Rifampicin-resistant alone",
      "Pre-XDR-TB: + fluoroquinolone resistance",
      "XDR-TB: + Group A drug resistance"
    ]},
    { x: 8.9, title: "KD Tripathi Reference", bg: C.cardBg3, tc: C.green, bullets: [
      "Ch. 46 — Antitubercular Drugs",
      "Resistance by spontaneous mutations",
      "1 in 10⁶–10⁸ bacilli naturally resistant",
      "Large bacterial load = higher resistance risk",
      "Monotherapy must NEVER be used"
    ]}
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// ══════════════════════════════════════════════════════════════
// SLIDE 3 — EPIDEMIOLOGY
// ══════════════════════════════════════════════════════════════
{
  let slide = addContentSlide(pres, "🌍  Global Epidemiology of MDR-TB");
  // Global stat boxes (top row)
  const stats = [
    { label: "~410,000", sub: "New MDR/RR-TB cases/year (WHO 2023)", bg: C.accent1, tc: C.white },
    { label: "~40%", sub: "MDR-TB treatment success rate (vs 85% DS-TB)", bg: C.midBg, tc: C.white },
    { label: "Top 3", sub: "India · China · Russia (highest burden)", bg: C.accent3, tc: C.textDark },
    { label: ">50%", sub: "MDR-TB cases in SEAR & EUR WHO regions", bg: C.orange, tc: C.white },
  ];
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  // Two columns below
  card(slide, pres, 0.3, 2.9, 6.1, 4.3, "Risk Factors (KD Tripathi)", C.midBg, C.cardBg, [
    "Inadequate/incomplete anti-TB treatment",
    "Monotherapy or inappropriate regimens",
    "Poor drug quality or supply interruptions",
    "HIV co-infection (immune suppression)",
    "Close contact with MDR-TB patient",
    "Previous TB treatment failure",
    "Diabetes mellitus, malnutrition, overcrowding",
    "Alcoholism, drug abuse"
  ]);
  card(slide, pres, 6.7, 2.9, 6.3, 4.3, "India Burden & NTEP Context", C.accent1, C.cardBg4, [
    "~27% of global MDR-TB cases in India",
    "Annual TB incidence: ~2.8 million (2023)",
    "Nikshay portal: case-based surveillance",
    "NTEP (formerly RNTCP) — Govt. of India program",
    "Universal Drug Susceptibility Testing (UDST)",
    "Bedaquiline access under conditional use",
    "BPaLM being scaled under NTEP from 2023",
    "Target: TB elimination by 2025 (India)"
  ]);
}

// ══════════════════════════════════════════════════════════════
// SLIDE 4 — BPaLM REGIMEN OVERVIEW
// ══════════════════════════════════════════════════════════════
{
  let slide = addContentSlide(pres, "💊  BPaLM Regimen — Overview");
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    { text: "BPaLM", options: { bold: true, color: C.accent2, fontSize: 20 } },
    { text: " = ", options: { color: C.white, fontSize: 18 } },
    { text: "B", options: { bold: true, color: C.accent1, fontSize: 20 } },
    { text: "edaquiline + ", options: { color: C.white, fontSize: 17 } },
    { text: "Pa", options: { bold: true, color: C.accent1, fontSize: 20 } },
    { text: "pretomanid + ", options: { color: C.white, fontSize: 17 } },
    { text: "L", options: { bold: true, color: C.accent1, fontSize: 20 } },
    { text: "inezolid + ", options: { color: C.white, fontSize: 17 } },
    { text: "M", options: { bold: true, color: C.accent1, fontSize: 20 } },
    { text: "oxifloxacin  |  WHO-recommended all-oral shorter regimen (2022)", options: { color: C.accent4, fontSize: 14, italic: true } }
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  // 4 Drug cards
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    { name: "Bedaquiline (B)", abbr: "B", bg: "FFF3E0", tc: C.orange, details: [
      "Class: Diarylquinoline", "Dose: 400 mg OD × 2 wks, then 200 mg TIW × 22 wks",
      "Target: Mycobacterial ATP synthase (atpE subunit)", "Bactericidal — active on dormant bacilli",
      "Long t½: ~5.5 months", "Hepatic metabolism (CYP3A4)", "ADR: QT prolongation, hepatotoxicity"
    ]},
    { name: "Pretomanid (Pa)", abbr: "Pa", bg: "E8F5E9", tc: C.green, details: [
      "Class: Nitroimidazole (bicyclic)", "Dose: 200 mg OD",
      "MOA: Inhibits mycolic acid synthesis + NO-mediated killing of anaerobic bacilli",
      "Active against both replicating AND non-replicating TB", "Bioactivated by Ddn enzyme in mycobacteria",
      "ADR: Peripheral neuropathy, hepatotoxicity, acne, thrombocytopenia"
    ]},
    { name: "Linezolid (L)", abbr: "L", bg: "EAF4FB", tc: C.midBg, details: [
      "Class: Oxazolidinone", "Dose: 600 mg OD (can reduce to 300 mg for ADR)",
      "MOA: Binds 23S rRNA of 50S ribosomal subunit", "Inhibits initiation complex formation",
      "Bacteriostatic (bactericidal at higher doses)", "No cross-resistance with other classes",
      "ADR: Myelosuppression, peripheral/optic neuropathy, serotonin syndrome, lactic acidosis"
    ]},
    { name: "Moxifloxacin (M)", abbr: "M", bg: "FCE4EC", tc: C.accent1, details: [
      "Class: 4th generation fluoroquinolone", "Dose: 400 mg OD",
      "MOA: Inhibits DNA gyrase (topoisomerase II) & topoisomerase IV",
      "Bactericidal — concentration-dependent killing", "Good CNS and tissue penetration",
      "Sterilizing action (shortens regimen duration)",
      "ADR: QT prolongation, GI upset, photosensitivity, tendinopathy"
    ]}
  ];
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    card(slide, pres, sx, 2.35, 3.1, 4.85, d.name, d.tc, d.bg, d.details);
  });
}

// ══════════════════════════════════════════════════════════════
// SLIDE 5 — MECHANISM OF ACTION (Detailed)
// ══════════════════════════════════════════════════════════════
{
  let slide = addContentSlide(pres, "⚙️  Mechanisms of Action — KD Tripathi");
  // Left: diagram-style visual column
  const moa = [
    { drug: "Bedaquiline", target: "ATP Synthase (atpE)", class: "Diarylquinoline", color: C.orange, detail: "Selectively inhibits mycobacterial F₁F₀-ATP synthase → energy depletion → cell death. Unique: active against dormant and drug-resistant strains. KD Tripathi: 'First new class in 40+ years'." },
    { drug: "Pretomanid", target: "Mycolic Acid + Nitric Oxide", class: "Bicyclic Nitroimidazole", color: C.green, detail: "Under aerobic conditions: inhibits mycolic acid biosynthesis. Under anaerobic/hypoxic conditions: generates reactive nitrogen species (RNS) → lethal to non-replicating persistent bacilli." },
    { drug: "Linezolid", target: "50S Ribosome (23S rRNA)", class: "Oxazolidinone", color: C.midBg, detail: "Binds to 23S rRNA at P-site of 50S subunit → prevents formation of initiation complex (30S+50S+mRNA). Blocks translation from the start. KD Tripathi: 'Reserve drug for MDR/XDR-TB'." },
    { drug: "Moxifloxacin", target: "DNA Gyrase & Topo IV", class: "Fluoroquinolone (4th gen)", color: C.accent1, detail: "Dual inhibition of DNA gyrase (gyrA/B) and topoisomerase IV → DNA strand breaks → bactericidal. Concentration-dependent killing with sterilizing activity shortens total regimen duration." }
  ];
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      fill: { color: "FFFFFF" }, line: { color: m.color, width: 2 }, rectRadius: 0.12
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    // Target
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    slide.addText(m.detail, { x: 2.25, y: sy + 0.45, w: 10.55, h: 0.9, fontSize: 11, color: C.textDark, fontFace: "Calibri" });
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}

// ══════════════════════════════════════════════════════════════
// SLIDE 6 — BEDAQUILINE IN DETAIL (KD Tripathi)
// ══════════════════════════════════════════════════════════════
{
  let slide = addContentSlide(pres, "🔬  Bedaquiline — KD Tripathi Deep Dive");
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  slide.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 13.3, h: 1.0, fill: { color: C.midBg } });
  slide.addShape(pres.ShapeType.rect, { x: 0, y: 1.0, w: 13.3, h: 0.05, fill: { color: C.orange } });
  slide.addText("🔬  Bedaquiline — KD Tripathi Deep Dive", { x: 0.4, y: 0.08, w: 12.5, h: 0.84, fontSize: 28, bold: true, color: C.white, fontFace: "Calibri", valign: "middle" });

  const bCards = [
    { x:0.3, y:1.15, w:4.0, h:2.9, title:"Pharmacokinetics", tc: C.orange, bg:"FFF3E0", bullets:[
      "Oral bioavailability: ↑ with food (high-fat meal)",
      "Protein binding: >99.9% (albumin)",
      "Vd: large (~164 L/kg) — extensive tissue distribution",
      "Metabolism: CYP3A4 → M2 metabolite (3–6× less active)",
      "t½ terminal: ~5.5 months (redistribution from tissues)",
      "Fecal excretion: ~>95%",
      "NOT removed by dialysis"
    ]},
    { x:0.3, y:4.15, w:4.0, h:3.1, title:"Clinical Dosing", tc: C.green, bg:"E8F5E9", bullets:[
      "Intensive phase: 400 mg OD × 2 weeks",
      "Continuation: 200 mg TIW × 22 weeks",
      "Total course: 24 weeks",
      "Always taken WITH food",
      "Drug interactions: avoid strong CYP3A4 inducers",
      "Avoid with QT-prolonging drugs (azithromycin, clofazimine)",
      "ECG monitoring mandatory"
    ]},
    { x:4.5, y:1.15, w:4.4, h:3.1, title:"Adverse Drug Reactions", tc: C.accent1, bg:"FCE4EC", bullets:[
      "QT prolongation — BLACK BOX WARNING",
      "Nausea, vomiting (most common)",
      "Arthralgia, headache, dizziness",
      "Hepatotoxicity — monitor LFTs monthly",
      "↑ Serum amylase (pancreatitis risk)",
      "Thrombocytopenia (rare)",
      "KD Tripathi: 'Reserve for MDR/XDR-TB only'"
    ]},
    { x:4.5, y:4.35, w:4.4, h:2.9, title:"Drug Interactions", tc: C.purple, bg:"F3E5F5", bullets:[
      "Rifampicin: ↓ bedaquiline AUC by ~50%",
      "Efavirenz: ↓ bedaquiline exposure",
      "Ketoconazole: ↑ bedaquiline AUC",
      "Clofazimine: additive QT prolongation",
      "Lopinavir/ritonavir: ↑ bedaquiline levels",
      "Alcohol: avoid (↑ hepatotoxicity)"
    ]},
    { x:9.1, y:1.15, w:3.9, h:6.1, title:"Mechanism (KD Tripathi)", tc: C.midBg, bg:C.cardBg, bullets:[
      "Diarylquinoline class",
      "Inhibits mycobacterial F₁F₀-ATP synthase",
      "Specifically the ε-subunit (atpE) of c-ring",
      "Disrupts proton motive force → ↓ ATP synthesis",
      "Energy depletion → cell death",
      "Active against BOTH replicating and dormant bacilli",
      "Active against drug-susceptible AND MDR/XDR strains",
      "NO cross-resistance with existing TB drugs",
      "First new anti-TB drug class in >40 years",
      "Resistance: mutations in atpE or Rv0678 (efflux pump regulator)",
      "KD Tripathi: 'A landmark in TB pharmacotherapy'"
    ]}
  ];
  bCards.forEach(c => card(slide, pres, c.x, c.y, c.w, c.h, c.title, c.tc, c.bg, c.bullets));
  slide.addText("Source: KD Tripathi — Essentials of Medical Pharmacology", { x: 0, y: 7.15, w: 13.3, h: 0.35, fontSize: 9, color: "888888", align: "right", fontFace: "Calibri", italic: true });
}

// ══════════════════════════════════════════════════════════════
// SLIDE 7 — LINEZOLID & PRETOMANID DETAIL
// ══════════════════════════════════════════════════════════════
{
  let slide = addContentSlide(pres, "🔬  Linezolid & Pretomanid — KD Tripathi");
  // Linezolid half
  slide.addShape(pres.ShapeType.roundRect, { x: 0.3, y: 1.1, w: 6.15, h: 0.55, fill: { color: C.midBg }, line: { color: C.midBg }, rectRadius: 0.08 });
  slide.addText("LINEZOLID (L) — Oxazolidinone", { x: 0.4, y: 1.12, w: 6.0, h: 0.5, fontSize: 15, bold: true, color: C.white, fontFace: "Calibri" });

  card(slide, pres, 0.3, 1.75, 2.9, 2.5, "Pharmacology", C.midBg, C.cardBg, [
    "Bacteriostatic (TB: may be cidal at higher dose)",
    "Spectrum: Gram-positive + M. tuberculosis",
    "No cross-resistance with aminoglycosides, rifampicin",
    "Oral bioavailability ~100%",
    "t½: ~5 hours; renal + non-renal excretion"
  ]);
  card(slide, pres, 3.4, 1.75, 3.0, 2.5, "ADR & Monitoring", C.accent1, C.cardBg4, [
    "Myelosuppression (thrombocytopenia, anemia)",
    "Peripheral neuropathy (dose/duration dependent)",
    "Optic neuropathy — visual monitoring monthly",
    "Lactic acidosis (mitochondrial toxicity)",
    "Serotonin syndrome (avoid SSRIs/MAOIs)",
    "Monitor: CBC, LFTs, visual acuity"
  ]);
  card(slide, pres, 0.3, 4.35, 6.1, 2.9, "KD Tripathi Notes on Linezolid", C.green, "E8F5E9", [
    "Dose reduction to 300 mg if ADR develops (maintain efficacy)",
    "Pyridoxine (Vitamin B6) supplementation may reduce neuropathy",
    "KD Tripathi: 'Linezolid is the backbone of BPaL/BPaLM regimen'",
    "MAO inhibitor properties: avoid tyramine-rich food",
    "Duration beyond 28 weeks increases toxicity significantly",
    "WHO grade: Group A drug for MDR-TB treatment (2022)"
  ]);

  // Pretomanid half
  slide.addShape(pres.ShapeType.roundRect, { x: 6.85, y: 1.1, w: 6.15, h: 0.55, fill: { color: C.green }, line: { color: C.green }, rectRadius: 0.08 });
  slide.addText("PRETOMANID (Pa) — Nitroimidazole", { x: 6.95, y: 1.12, w: 6.0, h: 0.5, fontSize: 15, bold: true, color: C.white, fontFace: "Calibri" });

  card(slide, pres, 6.85, 1.75, 2.9, 2.5, "Pharmacology", C.green, C.cardBg3, [
    "Bicyclic nitroimidazo-oxazine compound",
    "Prodrug: activated by Ddn (deazaflavin-dependent nitroreductase)",
    "Dual MOA: aerobic AND anaerobic activity",
    "t½: ~17 hours; CYP3A4 metabolism",
    "Primarily fecal excretion"
  ]);
  card(slide, pres, 9.95, 1.75, 3.05, 2.5, "ADR & Monitoring", C.orange, C.cardBg2, [
    "Peripheral neuropathy",
    "Hepatotoxicity (monitor ALT/AST monthly)",
    "Acne vulgaris (common, manageable)",
    "Thrombocytopenia, anemia",
    "Vomiting, headache",
    "Hypoglycemia (rare)"
  ]);
  card(slide, pres, 6.85, 4.35, 6.15, 2.9, "KD Tripathi Notes on Pretomanid", C.midBg, C.cardBg, [
    "Approved by FDA in 2019 for XDR-TB (BPaL regimen)",
    "Active vs. both drug-susceptible and resistant M. tuberculosis",
    "Companion drug to bedaquiline in BPaL/BPaLM",
    "Resistance: mutations in Ddn, FGD1, or nitroimidazole activation pathway",
    "KD Tripathi: 'Pretomanid expands treatment options for XDR-TB'",
    "NOT used as monotherapy (always part of BPaL/BPaLM)"
  ]);
}

// ══════════════════════════════════════════════════════════════
// SLIDE 8 — MOXIFLOXACIN DETAIL (KD Tripathi)
// ══════════════════════════════════════════════════════════════
{
  let slide = addContentSlide(pres, "🔬  Moxifloxacin — KD Tripathi");
  slide.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 13.3, h: 7.5, fill: { color: "FFF5F5" } });
  slide.addShape(pres.ShapeType.rect, { x: 0, y: 0, w: 13.3, h: 1.0, fill: { color: C.midBg } });
  slide.addShape(pres.ShapeType.rect, { x: 0, y: 1.0, w: 13.3, h: 0.05, fill: { color: C.accent1 } });
  slide.addText("🔬  Moxifloxacin — KD Tripathi", { x: 0.4, y: 0.08, w: 12.5, h: 0.84, fontSize: 28, bold: true, color: C.white, fontFace: "Calibri", valign: "middle" });

  card(slide, pres, 0.3, 1.15, 3.9, 3.0, "Mechanism of Action", C.accent1, C.cardBg4, [
    "4th generation fluoroquinolone",
    "MOA 1: Inhibits DNA gyrase (gyrA/B) → ↓ DNA supercoiling",
    "MOA 2: Inhibits Topoisomerase IV → ↓ DNA decatenation",
    "Concentration-dependent (Cmax/MIC ratio)",
    "Post-antibiotic effect present",
    "Bactericidal with sterilizing activity",
    "KD Tripathi: 'Sterilizing effect shortens regimen'"
  ]);
  card(slide, pres, 0.3, 4.25, 3.9, 3.0, "Pharmacokinetics", C.midBg, C.cardBg, [
    "Oral bioavailability: ~90% (not affected by food)",
    "Protein binding: ~30–50%",
    "Vd: ~2 L/kg — good tissue penetration",
    "Lung concentration > serum (ideal for TB)",
    "t½: ~12 hours — once daily dosing",
    "Hepatic glucuronidation + sulfation",
    "Renal + fecal excretion (dual)"
  ]);
  card(slide, pres, 4.4, 1.15, 4.3, 3.0, "ADR Profile (KD Tripathi)", C.orange, C.cardBg2, [
    "QT prolongation (major concern in BPaLM)",
    "GI: nausea, vomiting, diarrhea (most common)",
    "Headache, dizziness, insomnia",
    "Photosensitivity — avoid sun exposure",
    "Tendinopathy / Achilles tendon rupture",
    "Peripheral neuropathy",
    "Cartilage toxicity (avoid in <18 yrs)"
  ]);
  card(slide, pres, 4.4, 4.25, 4.3, 3.0, "Drug Interactions", C.purple, "F3E5F5", [
    "Antacids (Al³⁺, Mg²⁺): ↓ absorption — give 2 hr apart",
    "Sucralfate, iron, zinc: chelation → ↓ absorption",
    "Warfarin: ↑ anticoagulant effect",
    "Bedaquiline: additive QT prolongation (monitor ECG)",
    "NSAIDs: ↑ risk of CNS stimulation/seizures",
    "Class IA/III antiarrhythmics: avoid combination"
  ]);
  card(slide, pres, 8.95, 1.15, 4.05, 6.1, "KD Tripathi Clinical Notes", C.midBg, C.cardBg, [
    "Classified as Group A fluoroquinolone in MDR-TB",
    "Dose: 400 mg OD (standard for TB)",
    "Included in BPaLM to improve sterilizing activity",
    "Fluoroquinolone resistance in TB: gyrA codon 90/94 mutations",
    "Levofloxacin is alternative in FQ-sensitive MDR-TB",
    "Monitor: ECG (QTc), LFTs, CBC",
    "Not recommended in pregnancy (animal cartilage toxicity)",
    "KD Tripathi: 'Fluoroquinolones are Group A drugs for MDR-TB'",
    "Replace with levofloxacin if pre-XDR-TB suspected",
    "Drug resistance testing mandatory before use",
    "Avoid prolonged sun exposure — photoprotection advised"
  ]);
  slide.addText("Source: KD Tripathi — Essentials of Medical Pharmacology", { x: 0, y: 7.15, w: 13.3, h: 0.35, fontSize: 9, color: "888888", align: "right", fontFace: "Calibri", italic: true });
}

// ══════════════════════════════════════════════════════════════
// SLIDE 9 — REGIMEN DURATION & WHO GUIDELINES
// ══════════════════════════════════════════════════════════════
{
  let slide = addContentSlide(pres, "📅  BPaLM Regimen Duration & WHO Guidelines");

  // Timeline visual
  const phases = [
    { label: "Weeks 1–2", sub: "BED 400mg OD\n+ Pa 200mg OD\n+ LZD 600mg OD\n+ MFX 400mg OD", color: C.accent1, x: 0.3 },
    { label: "Weeks 3–24", sub: "BED 200mg TIW\n+ Pa 200mg OD\n+ LZD 600mg OD\n+ MFX 400mg OD", color: C.midBg, x: 3.7 },
    { label: "Total: 6 months", sub: "All-oral, no injections\nOutpatient feasible\nHigh adherence expected", color: C.green, x: 7.1 },
    { label: "Extension", sub: "Up to 9 months if\ninadequate response\nPer clinician judgement", color: C.orange, x: 10.4 }
  ];
  phases.forEach(p => {
    slide.addShape(pres.ShapeType.roundRect, { x: p.x, y: 1.1, w: 3.1, h: 2.3, fill: { color: p.color }, line: { color: p.color }, rectRadius: 0.15 });
    slide.addText(p.label, { x: p.x+0.1, y: 1.15, w: 2.9, h: 0.55, fontSize: 16, bold: true, color: C.white, align: "center", fontFace: "Calibri" });
    slide.addText(p.sub, { x: p.x+0.1, y: 1.72, w: 2.9, h: 1.55, fontSize: 11, color: C.white, align: "center", fontFace: "Calibri" });
  });
  // Connecting arrows
  [3.4, 6.8, 10.1].forEach(ax => {
    slide.addShape(pres.ShapeType.line, { x: ax, y: 2.25, w: 0.3, h: 0, line: { color: C.accent2, width: 2 } });
  });

  card(slide, pres, 0.3, 3.55, 6.1, 3.75, "WHO 2022 Recommendations", C.midBg, C.cardBg, [
    "BPaLM: preferred regimen for pre-XDR-TB & XDR-TB",
    "BPaL (without moxifloxacin) for FQ-resistant cases",
    "Shorter (6-month) vs. longer regimens (18–24 months)",
    "DST must confirm fluoroquinolone sensitivity for BPaLM",
    "Monthly sputum culture monitoring for treatment response",
    "Culture conversion by month 2 is key treatment milestone",
    "Adverse event monitoring: ECG, LFTs, CBC, visual acuity"
  ]);
  card(slide, pres, 6.7, 3.55, 6.3, 3.75, "KD Tripathi — Treatment Principles", C.accent3, "E0F7FA", [
    "Rational use of anti-TB drugs: avoid monotherapy",
    "Minimum 3 effective drugs in any regimen",
    "Drug susceptibility testing (DST) must guide therapy",
    "Adherence is the most critical factor for success",
    "DOT (Directly Observed Therapy) — standard of care",
    "Fixed-dose combinations (FDC) improve compliance",
    "Never add single drug to failing regimen (resistance)"
  ]);
}

// ══════════════════════════════════════════════════════════════
// SLIDE 10 — TARGET POPULATION & INCLUSION CRITERIA
// ══════════════════════════════════════════════════════════════
{
  let slide = addContentSlide(pres, "👥  Target Population & Selection Criteria");

  // Inclusion/Exclusion boxes side by side
  slide.addShape(pres.ShapeType.roundRect, { x: 0.3, y: 1.1, w: 6.1, h: 0.5, fill: { color: C.green }, line: { color: C.green }, rectRadius: 0.08 });
  slide.addText("✅  INCLUSION CRITERIA", { x: 0.4, y: 1.13, w: 5.9, h: 0.44, fontSize: 14, bold: true, color: C.white, fontFace: "Calibri" });
  card(slide, pres, 0.3, 1.7, 6.1, 5.5, "", C.green, C.cardBg3, [
    "Confirmed MDR-TB or RR-TB (by rapid molecular test or DST)",
    "Fluoroquinolone-sensitive (for BPaLM)",
    "FQ-resistant: use BPaL (without moxifloxacin)",
    "Age: ≥18 years (adult patients)",
    "No prior exposure to bedaquiline or pretomanid for >2 weeks",
    "HIV co-infected patients (ART compatible regimens)",
    "Previously treated MDR-TB treatment failures",
    "Pre-XDR-TB and XDR-TB patients",
    "Patients unable to tolerate injectable-based regimens",
    "High-burden countries (India, Russia, South Africa)"
  ]);

  slide.addShape(pres.ShapeType.roundRect, { x: 6.8, y: 1.1, w: 6.2, h: 0.5, fill: { color: C.accent1 }, line: { color: C.accent1 }, rectRadius: 0.08 });
  slide.addText("❌  EXCLUSION / CAUTION CRITERIA", { x: 6.9, y: 1.13, w: 6.0, h: 0.44, fontSize: 14, bold: true, color: C.white, fontFace: "Calibri" });
  card(slide, pres, 6.8, 1.7, 6.2, 3.0, "", C.accent1, C.cardBg4, [
    "QTc > 500 ms at baseline (bedaquiline, moxifloxacin risk)",
    "Severe hepatic impairment (Child-Pugh C)",
    "Severe renal impairment (linezolid accumulation)",
    "Pregnancy (fluoroquinolone contraindicated)",
    "Children <18 years (limited data)",
    "Prior use of bedaquiline or pretomanid",
    "Uncontrolled seizure disorders (FQ risk)"
  ]);

  card(slide, pres, 6.8, 4.8, 6.2, 2.45, "KD Tripathi — Special Populations", C.purple, "F3E5F5", [
    "HIV-TB: bedaquiline + ART is safe (avoid EFV or use adjusted dose)",
    "Diabetes: ↑ risk of neuropathy with linezolid",
    "Elderly: ↑ QT risk, neuropathy — lower linezolid dose consider",
    "Paediatrics: BPaLM data limited; weight-based dosing trials ongoing",
    "Renal impairment: no dose adjustment for BED/Pa; monitor LZD"
  ]);
}

// ══════════════════════════════════════════════════════════════
// SLIDE 11 — ADVERSE DRUG REACTIONS (Full KD Tripathi)
// ══════════════════════════════════════════════════════════════
{
  let slide = addContentSlide(pres, "⚠️  Adverse Drug Reactions — KD Tripathi");
  const adrs = [
    { drug: "Bedaquiline", color: C.orange, bg: "FFF3E0", adrs: [
      "QT prolongation ⚠ (BLACK BOX)",
      "Nausea, vomiting (most common)",
      "Arthralgia, myalgia",
      "Headache, dizziness",
      "Hepatotoxicity (↑ transaminases)",
      "↑ Serum amylase",
      "Thrombocytopenia (rare)"
    ]},
    { drug: "Pretomanid", color: C.green, bg: "E8F5E9", adrs: [
      "Peripheral neuropathy",
      "Hepatotoxicity (ALT/AST ↑)",
      "Acne vulgaris (common)",
      "Thrombocytopenia",
      "Anemia",
      "Vomiting, headache",
      "Hypoglycemia (rare)"
    ]},
    { drug: "Linezolid", color: C.midBg, bg: C.cardBg, adrs: [
      "Myelosuppression ⚠ (thrombocytopenia, anemia)",
      "Peripheral neuropathy (dose/duration dependent)",
      "Optic neuropathy (visual loss — serious)",
      "Lactic acidosis (mitochondrial inhibition)",
      "Serotonin syndrome (with SSRIs/MAOIs)",
      "Tongue discolouration",
      "Hypertensive crisis (with tyramine-rich food)"
    ]},
    { drug: "Moxifloxacin", color: C.accent1, bg: C.cardBg4, adrs: [
      "QT prolongation ⚠ (additive with bedaquiline)",
      "GI: nausea, vomiting, diarrhea",
      "Photosensitivity",
      "Tendinopathy / tendon rupture",
      "Peripheral neuropathy",
      "Seizures (rare — CNS stimulation)",
      "Cartilage toxicity (avoid in children)"
    ]}
  ];
  adrs.forEach((a, i) => {
    let sx = 0.3 + i * 3.25;
    card(slide, pres, sx, 1.1, 3.1, 5.3, a.drug, a.color, a.bg, a.adrs);
  });

  // Monitoring row
  slide.addShape(pres.ShapeType.roundRect, { x: 0.3, y: 6.5, w: 12.7, h: 0.78, fill: { color: C.midBg }, line: { color: C.accent3, width: 1.5 }, rectRadius: 0.1 });
  slide.addText([
    { text: "📋 MONITORING: ", options: { bold: true, color: C.accent2, fontSize: 13 } },
    { text: "ECG (QTc monthly) · LFTs (monthly) · CBC (monthly) · Visual acuity · Clinical response · Sputum culture conversion", options: { color: C.white, fontSize: 12 } }
  ], { x: 0.5, y: 6.55, w: 12.3, h: 0.65, valign: "middle" });
}

// ══════════════════════════════════════════════════════════════
// SLIDE 12 — ADVANTAGES vs LIMITATIONS
// ══════════════════════════════════════════════════════════════
{
  let slide = addContentSlide(pres, "⚖️  Advantages vs. Limitations of BPaLM");

  // Left — Advantages
  slide.addShape(pres.ShapeType.roundRect, { x: 0.3, y: 1.1, w: 6.1, h: 0.5, fill: { color: C.green }, line: { color: C.green }, rectRadius: 0.08 });
  slide.addText("✅  ADVANTAGES", { x: 0.4, y: 1.12, w: 5.9, h: 0.46, fontSize: 16, bold: true, color: C.white, fontFace: "Calibri" });
  const advs = [
    ["Shorter Duration", "6 months vs 18–24 months for older regimens → better adherence"],
    ["All-Oral Regimen", "No injectable drugs (avoids aminoglycoside-related ototoxicity/nephrotoxicity)"],
    ["Higher Success Rate", "ZeNix trial: 89% success at 26 weeks (BPaL with low-dose linezolid)"],
    ["Novel MOA Drugs", "Bedaquiline and pretomanid: no pre-existing resistance mechanisms"],
    ["Outpatient Feasible", "Improved quality of life; lower burden on healthcare systems"],
    ["Active on Dormant TB", "Bedaquiline + pretomanid kill non-replicating persistent bacilli"],
  ];
  advs.forEach((a, i) => {
    let ay = 1.72 + i * 0.88;
    slide.addShape(pres.ShapeType.roundRect, { x: 0.3, y: ay, w: 6.1, h: 0.78, fill: { color: "E8F5E9" }, line: { color: C.green, width: 1 }, rectRadius: 0.08 });
    slide.addText(a[0], { x: 0.5, y: ay + 0.04, w: 5.8, h: 0.3, fontSize: 12, bold: true, color: C.green, fontFace: "Calibri" });
    slide.addText(a[1], { x: 0.5, y: ay + 0.34, w: 5.8, h: 0.36, fontSize: 10, color: C.textDark, fontFace: "Calibri" });
  });

  // Right — Limitations
  slide.addShape(pres.ShapeType.roundRect, { x: 6.8, y: 1.1, w: 6.2, h: 0.5, fill: { color: C.accent1 }, line: { color: C.accent1 }, rectRadius: 0.08 });
  slide.addText("⚠️  LIMITATIONS", { x: 6.9, y: 1.12, w: 6.0, h: 0.46, fontSize: 16, bold: true, color: C.white, fontFace: "Calibri" });
  const lims = [
    ["Drug Toxicity Monitoring", "QT prolongation (BED+MFX), neuropathy (LZD), hepatotoxicity — intensive monitoring needed"],
    ["High Cost", "Bedaquiline and pretomanid are expensive; access limited in LMICs without donor funding"],
    ["Limited Pediatric Data", "Dosing for <18 years not established; trials ongoing"],
    ["Potential Drug Interactions", "CYP3A4 interactions (bedaquiline), additive QT effects, antiretroviral interactions"],
    ["Resistance Risk", "Misuse/incomplete courses can generate new resistance to novel drugs"],
    ["Restricted Availability", "Conditional access in many countries; regulatory approval pending in some nations"],
  ];
  lims.forEach((l, i) => {
    let ly = 1.72 + i * 0.88;
    slide.addShape(pres.ShapeType.roundRect, { x: 6.8, y: ly, w: 6.2, h: 0.78, fill: { color: "FCE4EC" }, line: { color: C.accent1, width: 1 }, rectRadius: 0.08 });
    slide.addText(l[0], { x: 7.0, y: ly + 0.04, w: 5.9, h: 0.3, fontSize: 12, bold: true, color: C.accent1, fontFace: "Calibri" });
    slide.addText(l[1], { x: 7.0, y: ly + 0.34, w: 5.9, h: 0.36, fontSize: 10, color: C.textDark, fontFace: "Calibri" });
  });
  slide.addText("Source: KD Tripathi — Essentials of Medical Pharmacology", { x: 0, y: 7.15, w: 13.3, h: 0.35, fontSize: 9, color: "888888", align: "right", fontFace: "Calibri", italic: true });
}

// ══════════════════════════════════════════════════════════════
// SLIDE 13 — MONITORING PARAMETERS
// ══════════════════════════════════════════════════════════════
{
  let slide = addContentSlide(pres, "🩺  Monitoring Parameters During BPaLM");

  const monitors = [
    { icon: "❤️", title: "ECG / QTc Monitoring", color: C.accent1, bg: C.cardBg4, items: [
      "Baseline ECG before starting treatment",
      "Repeat at week 2, then monthly",
      "STOP if QTc > 500 ms",
      "Avoid concurrent QT-prolonging drugs",
      "Correct electrolytes (K⁺, Mg²⁺, Ca²⁺)"
    ]},
    { icon: "🧪", title: "Liver Function Tests", color: C.orange, bg: "FFF3E0", items: [
      "Baseline LFTs (ALT, AST, bilirubin)",
      "Monthly monitoring throughout treatment",
      "Stop if ALT/AST > 8× ULN",
      "Risk drugs: bedaquiline, pretomanid",
      "Avoid alcohol during treatment"
    ]},
    { icon: "🩸", title: "Complete Blood Count", color: C.midBg, bg: C.cardBg, items: [
      "Baseline CBC (linezolid myelosuppression)",
      "Monthly CBC monitoring",
      "Watch: thrombocytopenia (<75,000/µL = dose reduce/stop)",
      "Anemia: consider iron/B12 supplementation",
      "Leukopenia: infection risk ↑"
    ]},
    { icon: "👁️", title: "Visual Acuity & Neurological", color: C.green, bg: C.cardBg3, items: [
      "Baseline visual acuity (Snellen chart)",
      "Monthly optic nerve assessment (linezolid)",
      "Peripheral neuropathy: 10-g monofilament test",
      "Stop linezolid if optic neuropathy develops",
      "Pyridoxine supplementation (B6) for neuropathy"
    ]},
    { icon: "🦠", title: "Sputum Culture & DST", color: C.accent3, bg: "E0F7FA", items: [
      "Baseline sputum smear + culture + DST",
      "Monthly sputum culture (treatment response)",
      "Culture conversion = negative at ≥2 consecutive months",
      "Non-conversion at month 2: treatment review",
      "DST: re-check if treatment failure suspected"
    ]},
    { icon: "🧠", title: "Clinical & Adherence", color: C.purple, bg: "F3E5F5", items: [
      "Weight monitoring monthly (marker of response)",
      "Symptom review: cough, fever, night sweats",
      "DOT (Directly Observed Therapy) — standard of care",
      "Nutritional support — high-calorie diet",
      "Psychosocial support — TB stigma counselling"
    ]}
  ];
  monitors.forEach((m, i) => {
    let col = i % 3;
    let row = Math.floor(i / 3);
    let sx = 0.3 + col * 4.3;
    let sy = 1.15 + row * 3.05;
    card(slide, pres, sx, sy, 4.0, 2.85, m.icon + " " + m.title, m.color, m.bg, m.items);
  });
}

// ══════════════════════════════════════════════════════════════
// SLIDE 14 — STATUS IN INDIA (NTEP)
// ══════════════════════════════════════════════════════════════
{
  let slide = addContentSlide(pres, "🇮🇳  BPaLM Status in India — NTEP");

  slide.addShape(pres.ShapeType.roundRect, {
    x: 0.3, y: 1.1, w: 12.7, h: 1.05,
    fill: { color: "FF9933" }, line: { color: "FF9933" }, rectRadius: 0.12
  });
  slide.addText("India — Highest TB Burden Country with ~27% of Global MDR-TB Cases", {
    x: 0.5, y: 1.15, w: 12.3, h: 0.95,
    fontSize: 18, bold: true, color: C.white, align: "center", fontFace: "Calibri", valign: "middle"
  });

  card(slide, pres, 0.3, 2.3, 4.0, 4.95, "NTEP Implementation", C.midBg, C.cardBg, [
    "NTEP (National TB Elimination Programme) = formerly RNTCP",
    "Bedaquiline introduced in 2016 (conditional access)",
    "BPaL scaled up in 2023 under NTEP",
    "BPaLM roll-out from 2024 in phased manner",
    "Free-of-cost to all eligible patients",
    "Nikshay portal: digital case-based surveillance",
    "Target: END TB by 2025 (India), SDG 2030 globally",
    "PMDT (Programmatic Management of DR-TB) — national SOP",
    "Culture & DST labs: networked under NTEP"
  ]);
  card(slide, pres, 4.5, 2.3, 4.3, 4.95, "KD Tripathi — Antitubercular Policy", C.orange, C.cardBg2, [
    "KD Tripathi Ch. 46: Antitubercular drugs classification",
    "Group A drugs: levofloxacin/moxifloxacin, BED, linezolid",
    "Group B: clofazimine, cycloserine/terizidone",
    "Group C: ethambutol, delamanid, pyrazinamide, imipenem",
    "Shorter MDR-TB regimen (sMDR): 9–11 months",
    "Longer MDR-TB regimen: 18–20 months",
    "BPaLM: 6-month preferred for pre-XDR/XDR-TB",
    "Pyridoxine: mandatory with cycloserine to prevent seizures",
    "Vitamin B6: co-administer with linezolid (neuropathy prevention)"
  ]);
  card(slide, pres, 9.0, 2.3, 4.0, 4.95, "Clinical Trials Evidence", C.green, C.cardBg3, [
    "TB-PRACTECAL trial (2022): BPaLM 86% success at 72 weeks",
    "ZeNix trial (2021): BPaL 89% (low-dose linezolid arm)",
    "Nix-TB (2019): BPaL first major XDR-TB trial (90% success)",
    "STREAM trial: shorter oral regimens comparable",
    "WHO endorsed BPaLM in 2022 consolidated guidelines",
    "India NTEP aligning with WHO 2022 guidance",
    "Ongoing: endTB trial (BPaLM vs. comparators)",
    "Global Fund + USAID support BPaLM access in LMICs"
  ]);
}

// ══════════════════════════════════════════════════════════════
// SLIDE 15 — KD TRIPATHI DRUG CLASSIFICATION SUMMARY
// ══════════════════════════════════════════════════════════════
{
  let slide = addContentSlide(pres, "📚  KD Tripathi — Anti-TB Drug Classification");

  // WHO Group Table
  slide.addShape(pres.ShapeType.roundRect, { x: 0.3, y: 1.12, w: 12.7, h: 0.5, fill: { color: C.midBg }, line: { color: C.midBg }, rectRadius: 0.08 });
  slide.addText("WHO Drug Groups for MDR-TB (KD Tripathi, Chapter 46 — Antitubercular Drugs)", {
    x: 0.4, y: 1.14, w: 12.5, h: 0.46, fontSize: 14, bold: true, color: C.white, fontFace: "Calibri", valign: "middle"
  });

  const groups = [
    { group: "Group A", color: C.accent1, bg: "FCE4EC", drugs: "Levofloxacin / Moxifloxacin\nBedaquiline\nLinezolid", note: "All 3 must be included if possible (CORE)" },
    { group: "Group B", color: C.orange, bg: "FFF3E0", drugs: "Clofazimine\nCycloserine / Terizidone", note: "Add one or both if Group A insufficient" },
    { group: "Group C", color: C.green, bg: "E8F5E9", drugs: "Ethambutol · Delamanid · Pyrazinamide\nImipenem-Cilastatin / Meropenem\nAmikacin / Streptomycin\nEthionamide / Prothionamide\np-aminosalicylic acid (PAS)", note: "Use to complete regimen when Groups A & B insufficient" },
    { group: "BPaLM", color: C.midBg, bg: C.cardBg, drugs: "Bedaquiline + Pretomanid\n+ Linezolid + Moxifloxacin", note: "Pre-XDR/XDR-TB (6 months, all-oral, WHO 2022)" }
  ];
  groups.forEach((g, i) => {
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    slide.addShape(pres.ShapeType.roundRect, { x: sx, y: 1.72, w: 3.05, h: 4.1, fill: { color: g.bg }, line: { color: g.color, width: 2 }, rectRadius: 0.12 });
    slide.addShape(pres.ShapeType.roundRect, { x: sx, y: 1.72, w: 3.05, h: 0.55, fill: { color: g.color }, line: { color: g.color }, rectRadius: 0.12 });
    slide.addText(g.group, { x: sx+0.1, y: 1.75, w: 2.85, h: 0.48, fontSize: 17, bold: true, color: C.white, align: "center", fontFace: "Calibri" });
    slide.addText(g.drugs, { x: sx+0.1, y: 2.34, w: 2.85, h: 2.0, fontSize: 12, color: C.textDark, fontFace: "Calibri" });
    slide.addShape(pres.ShapeType.line, { x: sx+0.1, y: 4.35, w: 2.85, h: 0, line: { color: g.color, width: 1 } });
    slide.addText(g.note, { x: sx+0.1, y: 4.4, w: 2.85, h: 1.3, fontSize: 10, color: g.color, fontFace: "Calibri", italic: true });
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  // First-line drugs reminder
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  slide.addText([
    { text: "First-Line Anti-TB Drugs (KD Tripathi): ", options: { bold: true, color: C.midBg, fontSize: 13 } },
    { text: "HRZE — Isoniazid (H) · Rifampicin (R) · Pyrazinamide (Z) · Ethambutol (E)  |  ", options: { color: C.textDark, fontSize: 12 } },
    { text: "Rifampicin resistance → defines MDR-TB → escalate to BPaLM", options: { bold: true, color: C.accent1, fontSize: 12 } }
  ], { x: 0.5, y: 6.0, w: 12.3, h: 1.2, valign: "middle" });
  slide.addText("Source: KD Tripathi — Essentials of Medical Pharmacology", { x: 0, y: 7.15, w: 13.3, h: 0.35, fontSize: 9, color: "888888", align: "right", fontFace: "Calibri", italic: true });
}

// ══════════════════════════════════════════════════════════════
// SLIDE 16 — CONCLUSION
// ══════════════════════════════════════════════════════════════
{
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  slide.addText("MDR-TB & BPaLM Regimen", {
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  const concs = [
    "BPaLM is the WHO 2022 preferred regimen for pre-XDR and XDR-TB — all-oral, 6-month duration",
    "Bedaquiline (ATP synthase inhibitor) & Pretomanid (nitroimidazole) represent landmark new anti-TB drug classes",
    "Linezolid (oxazolidinone) provides bacteriostatic/cidal activity with severe ADRs requiring dose reduction",
    "Moxifloxacin's sterilizing activity is the key pharmacological reason it shortens treatment duration",
    "QT prolongation (bedaquiline + moxifloxacin) is the most critical safety concern — mandatory ECG monitoring",
    "KD Tripathi: Group A drugs (FQ + BED + LZD) are the backbone — use all three if possible",
    "India (NTEP) is scaling up BPaLM free-of-cost under the TB Elimination Programme (target: 2025/2030)"
  ];
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}

// ─── WRITE FILE ──────────────────────────────────────────────
pres.writeFile({ fileName: "/home/daytona/workspace/mdr-tb-ppt/MDR-TB_BPaLM_KDTripathi.pptx" })
  .then(() => console.log("✅ Done: /home/daytona/workspace/mdr-tb-ppt/MDR-TB_BPaLM_KDTripathi.pptx"))
  .catch(err => { console.error("ERROR:", err); process.exit(1); });