@erosolaraijs/cure 2.3.0 → 2.4.0

package/src/capabilities/specialPopulationsModule.ts

@@ -0,0 +1,711 @@
+/**
+ * Special Populations Oncology Module
+ *
+ * ╔═══════════════════════════════════════════════════════════════════════════════╗
+ * ║  SPECIAL POPULATIONS - COMPREHENSIVE PROTOCOLS FOR ALL PATIENTS              ║
+ * ╠═══════════════════════════════════════════════════════════════════════════════╣
+ * ║  This module provides:                                                        ║
+ * ║  - Pediatric dosing calculations and protocols                               ║
+ * ║  - Geriatric assessment and dose modifications                               ║
+ * ║  - Pregnancy-specific management by trimester                                ║
+ * ║  - Organ dysfunction dosing adjustments                                      ║
+ * ║  - HIV/AIDS oncology protocols                                               ║
+ * ║  - Drug interaction safety checking                                          ║
+ * ╚═══════════════════════════════════════════════════════════════════════════════╝
+ */
+
+// ═══════════════════════════════════════════════════════════════════════════════
+// PEDIATRIC ONCOLOGY DOSING
+// ═══════════════════════════════════════════════════════════════════════════════
+
+export interface PediatricDosingProtocol {
+  drug: string;
+  indication: string[];
+  dosingMethod: 'BSA' | 'Weight' | 'Age-based' | 'Fixed';
+  standardDose: string;
+  maxDose: string;
+  ageAdjustments: AgeAdjustment[];
+  organFunctionAdjustments: string[];
+  formulations: string[];
+  administrationNotes: string[];
+  monitoringRequirements: string[];
+}
+
+export interface AgeAdjustment {
+  ageGroup: 'Neonate (<1 mo)' | 'Infant (1-12 mo)' | 'Toddler (1-3 yr)' | 'Child (3-12 yr)' | 'Adolescent (12-18 yr)';
+  adjustment: string;
+  rationale: string;
+}
+
+export function calculateBSA(weight: number, height: number): number {
+  // Mosteller formula: BSA (m²) = √((height cm × weight kg) / 3600)
+  return Math.sqrt((height * weight) / 3600);
+}
+
+export function calculatePediatricDose(
+  adultDose: number,
+  patientBSA: number,
+  dosingMethod: 'BSA' | 'Weight' | 'Fixed',
+  weight?: number
+): { dose: number; unit: string; notes: string[] } {
+  const notes: string[] = [];
+
+  if (dosingMethod === 'BSA') {
+    const dose = adultDose * patientBSA;
+    notes.push(`Calculated using BSA ${patientBSA.toFixed(2)} m²`);
+    return { dose: Math.round(dose * 10) / 10, unit: 'mg', notes };
+  } else if (dosingMethod === 'Weight' && weight) {
+    notes.push(`Calculated using weight ${weight} kg`);
+    return { dose: Math.round(adultDose * weight * 10) / 10, unit: 'mg', notes };
+  }
+
+  return { dose: adultDose, unit: 'mg', notes: ['Fixed dose used'] };
+}
+
+export const PEDIATRIC_DOSING_PROTOCOLS: PediatricDosingProtocol[] = [
+  {
+    drug: 'Vincristine',
+    indication: ['ALL', 'Lymphoma', 'Wilms tumor', 'Neuroblastoma'],
+    dosingMethod: 'BSA',
+    standardDose: '1.5 mg/m² IV (max 2 mg)',
+    maxDose: '2 mg absolute',
+    ageAdjustments: [
+      { ageGroup: 'Infant (1-12 mo)', adjustment: 'Reduce by 50%', rationale: 'Immature hepatic metabolism' },
+      { ageGroup: 'Neonate (<1 mo)', adjustment: 'Use with extreme caution, 75% reduction', rationale: 'Limited clearance' }
+    ],
+    organFunctionAdjustments: ['Reduce dose 50% for bilirubin >3', 'Reduce 75% for bilirubin >5'],
+    formulations: ['1 mg/mL solution for injection'],
+    administrationNotes: ['Vesicant - ensure good IV access', 'Fatal if given intrathecally', 'Must be in minibag, not syringe'],
+    monitoringRequirements: ['Neuro exam for neuropathy', 'Bowel function (constipation)', 'Jaw pain (first-dose)']
+  },
+  {
+    drug: 'Doxorubicin',
+    indication: ['Osteosarcoma', 'Ewing sarcoma', 'Lymphoma', 'Solid tumors'],
+    dosingMethod: 'BSA',
+    standardDose: '30-75 mg/m² IV per cycle (protocol-dependent)',
+    maxDose: 'Cumulative lifetime max: 450-550 mg/m²',
+    ageAdjustments: [
+      { ageGroup: 'Infant (1-12 mo)', adjustment: 'Use with caution; increased cardiac risk', rationale: 'Developing myocardium' },
+      { ageGroup: 'Adolescent (12-18 yr)', adjustment: 'Standard dosing; monitor cumulative dose', rationale: 'Long survival means late effects matter' }
+    ],
+    organFunctionAdjustments: ['Bilirubin 1.2-3: reduce 50%', 'Bilirubin 3-5: reduce 75%', 'Bilirubin >5: hold'],
+    formulations: ['2 mg/mL solution'],
+    administrationNotes: ['Vesicant', 'Infuse over 15-60 minutes', 'Red urine is expected'],
+    monitoringRequirements: ['Echocardiogram at baseline, q3-6 months during, and annually after', 'CBC before each dose', 'LFTs']
+  },
+  {
+    drug: 'Methotrexate (High-dose)',
+    indication: ['ALL', 'Osteosarcoma', 'Lymphoma'],
+    dosingMethod: 'BSA',
+    standardDose: '1-12 g/m² IV (protocol-dependent)',
+    maxDose: 'Protocol-specific',
+    ageAdjustments: [
+      { ageGroup: 'Infant (1-12 mo)', adjustment: 'Reduce by 30-50%; prolonged clearance', rationale: 'Immature renal function' },
+      { ageGroup: 'Child (3-12 yr)', adjustment: 'Standard protocol dosing', rationale: 'Adequate clearance' }
+    ],
+    organFunctionAdjustments: ['Contraindicated if CrCl <60', 'Third-spacing prolongs clearance', 'Hold if effusions present'],
+    formulations: ['Various concentrations for IV'],
+    administrationNotes: ['Aggressive hydration required', 'Urine alkalinization (pH ≥7)', 'Leucovorin rescue per protocol'],
+    monitoringRequirements: ['MTX levels per protocol', 'Creatinine daily', 'CBC', 'Continue leucovorin until MTX <0.1']
+  },
+  {
+    drug: 'Cisplatin',
+    indication: ['Osteosarcoma', 'Hepatoblastoma', 'Germ cell tumors', 'Brain tumors'],
+    dosingMethod: 'BSA',
+    standardDose: '60-100 mg/m² IV (protocol-dependent)',
+    maxDose: 'Protocol-specific; watch cumulative nephrotoxicity/ototoxicity',
+    ageAdjustments: [
+      { ageGroup: 'Infant (1-12 mo)', adjustment: 'Reduce dose; higher ototoxicity risk', rationale: 'Developing auditory system' },
+      { ageGroup: 'Neonate (<1 mo)', adjustment: 'Avoid if possible', rationale: 'Extreme ototoxicity risk' }
+    ],
+    organFunctionAdjustments: ['CrCl 10-50: reduce 25-50%', 'CrCl <10: avoid'],
+    formulations: ['1 mg/mL solution'],
+    administrationNotes: ['Vigorous hydration pre/post', 'Mannitol diuresis in some protocols', 'Antiemetics required'],
+    monitoringRequirements: ['Audiometry at baseline and after each cycle', 'Creatinine/BUN', 'Electrolytes (Mg, K)', 'CBC']
+  },
+  {
+    drug: 'Cyclophosphamide',
+    indication: ['ALL', 'Lymphoma', 'Solid tumors', 'Conditioning for HSCT'],
+    dosingMethod: 'BSA',
+    standardDose: '500-1800 mg/m² (protocol-dependent)',
+    maxDose: 'Protocol-specific',
+    ageAdjustments: [
+      { ageGroup: 'Infant (1-12 mo)', adjustment: 'Standard dosing per BSA; monitor closely', rationale: 'Adequate metabolism' }
+    ],
+    organFunctionAdjustments: ['Reduce 25% for CrCl 10-50', 'Reduce 50% for CrCl <10'],
+    formulations: ['Lyophilized powder for reconstitution', 'Oral tablets'],
+    administrationNotes: ['Hydrate to prevent hemorrhagic cystitis', 'Mesna for high doses (>1g/m²)'],
+    monitoringRequirements: ['CBC', 'Urinalysis', 'Fluid balance', 'Fertility counseling']
+  }
+];
+
+// ═══════════════════════════════════════════════════════════════════════════════
+// GERIATRIC ONCOLOGY
+// ═══════════════════════════════════════════════════════════════════════════════
+
+export interface GeriatricAssessment {
+  domain: string;
+  tool: string;
+  interpretation: AssessmentInterpretation[];
+  treatmentImplications: string[];
+}
+
+export interface AssessmentInterpretation {
+  score: string;
+  category: string;
+  meaning: string;
+}
+
+export interface GeriatricDosingAdjustment {
+  drug: string;
+  standardDose: string;
+  geriatricConsiderations: string[];
+  doseModification: string;
+  alternativeAgents?: string[];
+  monitoringIntensification: string[];
+}
+
+export const COMPREHENSIVE_GERIATRIC_ASSESSMENT: GeriatricAssessment[] = [
+  {
+    domain: 'Functional Status',
+    tool: 'Activities of Daily Living (ADL)',
+    interpretation: [
+      { score: '6/6', category: 'Independent', meaning: 'No functional impairment' },
+      { score: '4-5/6', category: 'Mild impairment', meaning: 'May need some assistance' },
+      { score: '<4/6', category: 'Dependent', meaning: 'Significant functional limitation' }
+    ],
+    treatmentImplications: ['Independent: standard treatment', 'Mild impairment: consider dose reduction', 'Dependent: palliative-focused care often appropriate']
+  },
+  {
+    domain: 'Functional Status',
+    tool: 'Instrumental ADL (IADL)',
+    interpretation: [
+      { score: '8/8', category: 'Independent', meaning: 'Can manage complex tasks' },
+      { score: '5-7/8', category: 'Some limitation', meaning: 'May need support for some tasks' },
+      { score: '<5/8', category: 'Significant limitation', meaning: 'Needs substantial support' }
+    ],
+    treatmentImplications: ['IADL impairment predicts chemotherapy toxicity', 'Consider treatment simplification']
+  },
+  {
+    domain: 'Comorbidity',
+    tool: 'Charlson Comorbidity Index',
+    interpretation: [
+      { score: '0', category: 'No comorbidity', meaning: 'Low competing mortality' },
+      { score: '1-2', category: 'Mild comorbidity', meaning: 'Moderate competing mortality' },
+      { score: '≥3', category: 'Severe comorbidity', meaning: 'High competing mortality' }
+    ],
+    treatmentImplications: ['High CCI: balance cancer treatment benefit vs comorbidity burden', 'Consider life expectancy from comorbidities']
+  },
+  {
+    domain: 'Cognition',
+    tool: 'Mini-Cog',
+    interpretation: [
+      { score: '4-5', category: 'Normal', meaning: 'No cognitive impairment detected' },
+      { score: '0-3', category: 'Abnormal', meaning: 'Possible cognitive impairment; needs further evaluation' }
+    ],
+    treatmentImplications: ['Cognitive impairment affects treatment adherence', 'Need caregiver involvement', 'Simplify oral regimens']
+  },
+  {
+    domain: 'Nutrition',
+    tool: 'Mini Nutritional Assessment - Short Form (MNA-SF)',
+    interpretation: [
+      { score: '12-14', category: 'Normal', meaning: 'No malnutrition risk' },
+      { score: '8-11', category: 'At risk', meaning: 'Malnutrition risk' },
+      { score: '0-7', category: 'Malnourished', meaning: 'Malnutrition present' }
+    ],
+    treatmentImplications: ['Malnutrition increases toxicity', 'Consider nutritional support before chemotherapy', 'May need dose reduction']
+  },
+  {
+    domain: 'Mood',
+    tool: 'Geriatric Depression Scale (GDS-4)',
+    interpretation: [
+      { score: '0', category: 'Normal', meaning: 'No depression' },
+      { score: '≥1', category: 'Possible depression', meaning: 'Screen further with GDS-15' }
+    ],
+    treatmentImplications: ['Depression affects QoL and adherence', 'Consider psychiatry/psychology referral']
+  },
+  {
+    domain: 'Falls',
+    tool: 'Falls in past 6 months',
+    interpretation: [
+      { score: '0 falls', category: 'Low risk', meaning: 'No recent falls' },
+      { score: '1+ falls', category: 'High risk', meaning: 'Fall risk present' }
+    ],
+    treatmentImplications: ['Falls risk with neurotoxic agents (taxanes, platinum)', 'Physical therapy evaluation', 'Home safety assessment']
+  },
+  {
+    domain: 'Polypharmacy',
+    tool: 'Number of medications',
+    interpretation: [
+      { score: '<5', category: 'Normal', meaning: 'Acceptable' },
+      { score: '5-9', category: 'Polypharmacy', meaning: 'Moderate drug burden' },
+      { score: '≥10', category: 'Excessive polypharmacy', meaning: 'High interaction risk' }
+    ],
+    treatmentImplications: ['Review for deprescribing', 'Drug-drug interaction check critical', 'Simplify regimens']
+  }
+];
+
+export const GERIATRIC_DOSING_ADJUSTMENTS: GeriatricDosingAdjustment[] = [
+  {
+    drug: 'Capecitabine',
+    standardDose: '1000-1250 mg/m² BID D1-14 q21d',
+    geriatricConsiderations: ['Higher toxicity in elderly', 'Diarrhea more severe', 'Hand-foot syndrome'],
+    doseModification: 'Start at 75% dose (750-1000 mg/m² BID); reduce further if toxicity',
+    alternativeAgents: ['5-FU infusional if poor compliance'],
+    monitoringIntensification: ['Weekly calls/visits first cycle', 'Aggressive antidiarrheal education']
+  },
+  {
+    drug: 'Docetaxel',
+    standardDose: '75-100 mg/m² q3w',
+    geriatricConsiderations: ['Higher neutropenia risk', 'Fluid retention', 'Neuropathy'],
+    doseModification: 'Consider 60-75 mg/m² in frail elderly; weekly dosing (35 mg/m²) as alternative',
+    alternativeAgents: ['Paclitaxel weekly may be better tolerated'],
+    monitoringIntensification: ['G-CSF support recommended', 'Weekly CBC first cycle', 'Daily weights for edema']
+  },
+  {
+    drug: 'Cisplatin',
+    standardDose: '75-100 mg/m² q3w',
+    geriatricConsiderations: ['Nephrotoxicity', 'Ototoxicity', 'Neuropathy', 'Requires aggressive hydration'],
+    doseModification: 'Consider carboplatin substitution (AUC 5-6) in elderly; if cisplatin required, reduce to 60-75 mg/m²',
+    alternativeAgents: ['Carboplatin preferred in elderly', 'Oxaliplatin for GI cancers'],
+    monitoringIntensification: ['CrCl before each cycle', 'Hearing assessment', 'Hydration status']
+  },
+  {
+    drug: 'Doxorubicin',
+    standardDose: '60-75 mg/m² q3w',
+    geriatricConsiderations: ['Cardiotoxicity risk higher', 'Age-related decrease in cardiac reserve'],
+    doseModification: 'Consider liposomal doxorubicin or dose reduction to 50 mg/m²; lower cumulative max (400 mg/m²)',
+    alternativeAgents: ['Pegylated liposomal doxorubicin (lower cardiotoxicity)', 'Epirubicin'],
+    monitoringIntensification: ['ECHO before treatment and q2-3 cycles', 'BNP/troponin monitoring']
+  },
+  {
+    drug: 'Pembrolizumab/Nivolumab',
+    standardDose: 'Standard dosing (fixed or weight-based)',
+    geriatricConsiderations: ['Similar efficacy in elderly', 'irAE profile similar but monitoring important'],
+    doseModification: 'No dose adjustment for age; monitor closely for irAEs',
+    monitoringIntensification: ['Lower threshold for steroid initiation', 'Close symptom monitoring', 'Thyroid function each cycle']
+  }
+];
+
+// ═══════════════════════════════════════════════════════════════════════════════
+// PREGNANCY AND CANCER
+// ═══════════════════════════════════════════════════════════════════════════════
+
+export interface PregnancyCancerProtocol {
+  trimester: 'First' | 'Second' | 'Third';
+  generalPrinciples: string[];
+  allowedTreatments: TreatmentSafety[];
+  contraindicated: string[];
+  fetalMonitoring: string[];
+  deliveryConsiderations: string[];
+}
+
+export interface TreatmentSafety {
+  modality: string;
+  safety: 'Generally Safe' | 'Use with Caution' | 'Limited Data' | 'Contraindicated';
+  evidence: string;
+  specificAgents?: string[];
+}
+
+export const PREGNANCY_CANCER_PROTOCOLS: PregnancyCancerProtocol[] = [
+  {
+    trimester: 'First',
+    generalPrinciples: [
+      'Organogenesis occurs - highest teratogenic risk',
+      'Delay chemotherapy until second trimester if possible',
+      'Surgery can be performed with caution',
+      'Radiation generally contraindicated near fetus'
+    ],
+    allowedTreatments: [
+      { modality: 'Surgery', safety: 'Use with Caution', evidence: 'Second trimester preferred but first trimester acceptable for urgent cases' },
+      { modality: 'Breast surgery', safety: 'Generally Safe', evidence: 'Can proceed; avoid supine hypotension' },
+      { modality: 'Sentinel node biopsy', safety: 'Use with Caution', evidence: 'Technetium safe; blue dye avoided by some' }
+    ],
+    contraindicated: [
+      'All chemotherapy (teratogenic risk 10-20%)',
+      'Radiation therapy near pelvis',
+      'Endocrine therapy (tamoxifen, AIs)',
+      'Methotrexate (abortifacient)',
+      'All targeted therapies'
+    ],
+    fetalMonitoring: ['First trimester ultrasound', 'Nuchal translucency if indicated', 'Cell-free DNA screening'],
+    deliveryConsiderations: ['Plan for second trimester treatment initiation']
+  },
+  {
+    trimester: 'Second',
+    generalPrinciples: [
+      'Chemotherapy can be given after week 14',
+      'Organogenesis complete - lower malformation risk',
+      'Surgery remains feasible',
+      'Goal: deliver at term if possible'
+    ],
+    allowedTreatments: [
+      { modality: 'Anthracyclines', safety: 'Generally Safe', evidence: 'Extensive data; doxorubicin, epirubicin acceptable', specificAgents: ['Doxorubicin', 'Epirubicin'] },
+      { modality: 'Taxanes', safety: 'Generally Safe', evidence: 'Growing safety data', specificAgents: ['Paclitaxel', 'Docetaxel'] },
+      { modality: 'Platinum agents', safety: 'Use with Caution', evidence: 'Carboplatin preferred; cisplatin with caution', specificAgents: ['Carboplatin'] },
+      { modality: 'Alkylating agents', safety: 'Use with Caution', evidence: 'Cyclophosphamide used in FAC/FEC', specificAgents: ['Cyclophosphamide'] },
+      { modality: 'Surgery', safety: 'Generally Safe', evidence: 'Optimal timing 14-28 weeks' },
+      { modality: 'Radiation (non-pelvic)', safety: 'Use with Caution', evidence: 'Fetal shielding; keep dose <100 mGy to fetus' }
+    ],
+    contraindicated: [
+      'Methotrexate',
+      'Endocrine therapy',
+      'Targeted therapies (trastuzumab - oligohydramnios)',
+      'Immunotherapy (limited data, potential fetal harm)',
+      'Radiation to pelvis'
+    ],
+    fetalMonitoring: ['Anatomy scan at 18-20 weeks', 'Growth ultrasound after chemotherapy', 'Fetal echocardiogram if anthracyclines used'],
+    deliveryConsiderations: ['Allow 3 weeks between last chemo and delivery', 'Avoid delivery during nadir', 'Term delivery preferred (≥37 weeks)']
+  },
+  {
+    trimester: 'Third',
+    generalPrinciples: [
+      'Continue chemotherapy until 35-37 weeks',
+      'Plan delivery around treatment',
+      'Allow 3 weeks between last chemo and delivery',
+      'Delivery at term preferred'
+    ],
+    allowedTreatments: [
+      { modality: 'Anthracyclines', safety: 'Generally Safe', evidence: 'Continue if started', specificAgents: ['Doxorubicin'] },
+      { modality: 'Taxanes', safety: 'Generally Safe', evidence: 'Continue if started', specificAgents: ['Paclitaxel'] },
+      { modality: 'Surgery', safety: 'Use with Caution', evidence: 'Possible but fetus approaching term' }
+    ],
+    contraindicated: [
+      'Same as second trimester',
+      'Avoid new regimen initiation if delivery imminent'
+    ],
+    fetalMonitoring: ['Weekly NST after 32 weeks', 'Growth ultrasound', 'Biophysical profile if concerns'],
+    deliveryConsiderations: [
+      'Stop chemotherapy at 35-37 weeks',
+      'Delivery at ≥37 weeks if possible',
+      'Cesarean only for obstetric indications',
+      'Breastfeeding contraindicated during chemotherapy'
+    ]
+  }
+];
+
+// ═══════════════════════════════════════════════════════════════════════════════
+// ORGAN DYSFUNCTION DOSING
+// ═══════════════════════════════════════════════════════════════════════════════
+
+export interface OrganDysfunctionDosing {
+  drug: string;
+  renalDosing: RenalDosing[];
+  hepaticDosing: HepaticDosing[];
+  dialysisGuidance?: string;
+}
+
+export interface RenalDosing {
+  crclRange: string;
+  adjustment: string;
+}
+
+export interface HepaticDosing {
+  bilirubinRange: string;
+  astAltRange: string;
+  adjustment: string;
+}
+
+export const ORGAN_DYSFUNCTION_DOSING: OrganDysfunctionDosing[] = [
+  {
+    drug: 'Carboplatin',
+    renalDosing: [
+      { crclRange: '≥60', adjustment: 'Standard AUC dosing (Calvert formula)' },
+      { crclRange: '15-59', adjustment: 'Calvert formula accounts for renal function; dose automatically reduced' },
+      { crclRange: '<15', adjustment: 'Use with extreme caution; AUC 2-4' }
+    ],
+    hepaticDosing: [
+      { bilirubinRange: 'Any', astAltRange: 'Any', adjustment: 'No adjustment needed (not hepatically cleared)' }
+    ],
+    dialysisGuidance: 'Dialyzable; give after dialysis'
+  },
+  {
+    drug: 'Cisplatin',
+    renalDosing: [
+      { crclRange: '≥60', adjustment: 'Full dose with aggressive hydration' },
+      { crclRange: '40-59', adjustment: 'Reduce by 25% or consider carboplatin substitution' },
+      { crclRange: '<40', adjustment: 'Avoid; use carboplatin' }
+    ],
+    hepaticDosing: [
+      { bilirubinRange: 'Any', astAltRange: 'Any', adjustment: 'No adjustment needed' }
+    ]
+  },
+  {
+    drug: 'Methotrexate',
+    renalDosing: [
+      { crclRange: '≥60', adjustment: 'Full dose' },
+      { crclRange: '30-59', adjustment: 'Reduce by 50%' },
+      { crclRange: '<30', adjustment: 'Contraindicated for high-dose; low-dose with caution' }
+    ],
+    hepaticDosing: [
+      { bilirubinRange: '>3x ULN', astAltRange: 'Any', adjustment: 'Hold until resolved; hepatotoxic' }
+    ],
+    dialysisGuidance: 'High-flux dialysis can remove methotrexate in toxicity'
+  },
+  {
+    drug: 'Doxorubicin',
+    renalDosing: [
+      { crclRange: 'Any', adjustment: 'No adjustment (not renally cleared)' }
+    ],
+    hepaticDosing: [
+      { bilirubinRange: '1.2-3.0', astAltRange: 'Any', adjustment: '50% dose reduction' },
+      { bilirubinRange: '3.1-5.0', astAltRange: 'Any', adjustment: '75% dose reduction' },
+      { bilirubinRange: '>5.0', astAltRange: 'Any', adjustment: 'Contraindicated' }
+    ]
+  },
+  {
+    drug: 'Paclitaxel',
+    renalDosing: [
+      { crclRange: 'Any', adjustment: 'No adjustment needed' }
+    ],
+    hepaticDosing: [
+      { bilirubinRange: '≤1.5x ULN', astAltRange: '≤10x ULN', adjustment: 'Full dose' },
+      { bilirubinRange: '1.6-3x ULN', astAltRange: 'Any', adjustment: 'Reduce by 20%' },
+      { bilirubinRange: '>3x ULN', astAltRange: 'Any', adjustment: 'Avoid' }
+    ]
+  },
+  {
+    drug: 'Docetaxel',
+    renalDosing: [
+      { crclRange: 'Any', adjustment: 'No adjustment needed' }
+    ],
+    hepaticDosing: [
+      { bilirubinRange: '>ULN', astAltRange: '>1.5x ULN + Alk phos >2.5x ULN', adjustment: 'Contraindicated' }
+    ]
+  },
+  {
+    drug: 'Capecitabine',
+    renalDosing: [
+      { crclRange: '≥50', adjustment: 'Full dose' },
+      { crclRange: '30-49', adjustment: '75% dose' },
+      { crclRange: '<30', adjustment: 'Contraindicated' }
+    ],
+    hepaticDosing: [
+      { bilirubinRange: 'Mild-moderate', astAltRange: 'Any', adjustment: 'Use with caution' },
+      { bilirubinRange: 'Severe', astAltRange: 'Any', adjustment: 'Contraindicated' }
+    ]
+  },
+  {
+    drug: 'Pembrolizumab',
+    renalDosing: [
+      { crclRange: 'Any', adjustment: 'No adjustment needed' }
+    ],
+    hepaticDosing: [
+      { bilirubinRange: '1-1.5x ULN', astAltRange: 'Any', adjustment: 'No adjustment' },
+      { bilirubinRange: '>1.5x ULN', astAltRange: 'Any', adjustment: 'Limited data; use with caution' }
+    ]
+  }
+];
+
+// ═══════════════════════════════════════════════════════════════════════════════
+// HIV/AIDS ONCOLOGY
+// ═══════════════════════════════════════════════════════════════════════════════
+
+export interface HIVOncologyProtocol {
+  cancerType: string;
+  artInteractions: ARTInteraction[];
+  treatmentModifications: string[];
+  prophylaxisRequirements: string[];
+  monitoringIntensification: string[];
+  prognosticConsiderations: string;
+}
+
+export interface ARTInteraction {
+  artClass: string;
+  interaction: string;
+  management: string;
+}
+
+export const HIV_ONCOLOGY_PROTOCOLS: HIVOncologyProtocol[] = [
+  {
+    cancerType: 'Kaposi Sarcoma',
+    artInteractions: [
+      { artClass: 'All ART', interaction: 'ART is primary treatment for limited disease', management: 'Optimize ART first' },
+      { artClass: 'PIs', interaction: 'CYP3A4 interactions with taxanes, vinca alkaloids', management: 'Consider INSTI-based regimen during chemo' }
+    ],
+    treatmentModifications: [
+      'Limited/stable KS: ART alone may induce remission',
+      'Advanced/visceral: Liposomal doxorubicin + ART',
+      'Paclitaxel for refractory disease'
+    ],
+    prophylaxisRequirements: ['PCP prophylaxis if CD4 <200', 'MAC prophylaxis if CD4 <50', 'CMV monitoring'],
+    monitoringIntensification: ['CD4/viral load monthly during chemo', 'Watch for immune reconstitution inflammatory syndrome (IRIS)'],
+    prognosticConsiderations: 'CD4 >150 and undetectable VL associated with better outcomes'
+  },
+  {
+    cancerType: 'Non-Hodgkin Lymphoma (AIDS-related)',
+    artInteractions: [
+      { artClass: 'Protease inhibitors', interaction: 'Increase vincristine/doxorubicin toxicity', management: 'Switch to INSTI-based ART' },
+      { artClass: 'NNRTIs (efavirenz)', interaction: 'CYP inducer; may reduce chemo levels', management: 'Consider dose adjustment or switch' }
+    ],
+    treatmentModifications: [
+      'R-EPOCH preferred for DLBCL (infusional, less myelosuppressive)',
+      'DA-EPOCH-R with dose adjustments',
+      'R-CHOP for patients with good PS and CD4'
+    ],
+    prophylaxisRequirements: ['G-CSF support routinely', 'PCP prophylaxis regardless of CD4 during chemo', 'Consider antifungal prophylaxis'],
+    monitoringIntensification: ['CD4/VL monthly', 'Close monitoring for opportunistic infections', 'Tumor lysis prophylaxis'],
+    prognosticConsiderations: 'IPI + CD4 count; ART era outcomes approaching HIV-negative patients'
+  },
+  {
+    cancerType: 'Cervical Cancer (AIDS-defining)',
+    artInteractions: [
+      { artClass: 'All ART', interaction: 'Continue ART during treatment', management: 'Optimize regimen for minimal interactions' }
+    ],
+    treatmentModifications: [
+      'Standard treatment per stage',
+      'Cisplatin-based chemoradiation for locally advanced',
+      'May have higher toxicity rates'
+    ],
+    prophylaxisRequirements: ['Standard prophylaxis per CD4', 'Aggressive supportive care'],
+    monitoringIntensification: ['CD4/VL q3 months', 'Close monitoring for treatment toxicity'],
+    prognosticConsiderations: 'Outcomes improving with ART but still worse than HIV-negative'
+  },
+  {
+    cancerType: 'Lung Cancer (non-AIDS-defining)',
+    artInteractions: [
+      { artClass: 'PIs/Cobicistat', interaction: 'CYP3A4 interactions with TKIs (osimertinib, crizotinib)', management: 'Use INSTI-based ART; consider TKI dose adjustment' }
+    ],
+    treatmentModifications: [
+      'Standard treatment per stage and histology',
+      'Immunotherapy appears safe and effective',
+      'Watch for increased autoimmune manifestations'
+    ],
+    prophylaxisRequirements: ['Continue standard prophylaxis', 'G-CSF as needed'],
+    monitoringIntensification: ['CD4/VL monitoring', 'Watch for irAEs with immunotherapy'],
+    prognosticConsiderations: 'Outcomes similar to HIV-negative in ART era with controlled HIV'
+  }
+];
+
+// ═══════════════════════════════════════════════════════════════════════════════
+// SPECIAL POPULATIONS ENGINE
+// ═══════════════════════════════════════════════════════════════════════════════
+
+export class SpecialPopulationsEngine {
+  calculatePediatricDose(
+    drug: string,
+    weight: number,
+    height: number,
+    age: number
+  ): { dose: string; adjustments: string[]; monitoring: string[] } {
+    const bsa = calculateBSA(weight, height);
+    const protocol = PEDIATRIC_DOSING_PROTOCOLS.find(p => p.drug.toLowerCase() === drug.toLowerCase());
+
+    if (!protocol) {
+      return { dose: 'Protocol not found', adjustments: [], monitoring: [] };
+    }
+
+    const adjustments: string[] = [];
+
+    // Check age-specific adjustments
+    let ageGroup: AgeAdjustment['ageGroup'];
+    if (age < 1/12) ageGroup = 'Neonate (<1 mo)';
+    else if (age < 1) ageGroup = 'Infant (1-12 mo)';
+    else if (age < 3) ageGroup = 'Toddler (1-3 yr)';
+    else if (age < 12) ageGroup = 'Child (3-12 yr)';
+    else ageGroup = 'Adolescent (12-18 yr)';
+
+    const ageAdj = protocol.ageAdjustments.find(a => a.ageGroup === ageGroup);
+    if (ageAdj) {
+      adjustments.push(`${ageGroup}: ${ageAdj.adjustment} - ${ageAdj.rationale}`);
+    }
+
+    return {
+      dose: `${protocol.standardDose} (BSA: ${bsa.toFixed(2)} m²)`,
+      adjustments,
+      monitoring: protocol.monitoringRequirements
+    };
+  }
+
+  performGeriatricAssessment(scores: Record<string, number>): {
+    riskCategory: 'Fit' | 'Vulnerable' | 'Frail';
+    recommendations: string[];
+    treatmentImplications: string[];
+  } {
+    let fitCount = 0;
+    let vulnerableCount = 0;
+    let frailCount = 0;
+    const recommendations: string[] = [];
+
+    // Simple scoring based on key domains
+    if (scores['adl'] >= 5) fitCount++; else if (scores['adl'] >= 3) vulnerableCount++; else frailCount++;
+    if (scores['iadl'] >= 7) fitCount++; else if (scores['iadl'] >= 4) vulnerableCount++; else frailCount++;
+    if (scores['comorbidity'] <= 1) fitCount++; else if (scores['comorbidity'] <= 3) vulnerableCount++; else frailCount++;
+
+    let riskCategory: 'Fit' | 'Vulnerable' | 'Frail';
+    if (frailCount >= 2) {
+      riskCategory = 'Frail';
+      recommendations.push('Consider palliative-focused or modified-intensity treatment');
+      recommendations.push('Prioritize quality of life');
+    } else if (vulnerableCount >= 2 || frailCount === 1) {
+      riskCategory = 'Vulnerable';
+      recommendations.push('Consider dose reductions');
+      recommendations.push('Close monitoring for toxicity');
+      recommendations.push('Geriatric co-management recommended');
+    } else {
+      riskCategory = 'Fit';
+      recommendations.push('Standard treatment appropriate');
+      recommendations.push('Continue routine monitoring');
+    }
+
+    return {
+      riskCategory,
+      recommendations,
+      treatmentImplications: COMPREHENSIVE_GERIATRIC_ASSESSMENT.flatMap(a => a.treatmentImplications)
+    };
+  }
+
+  getPregnancyGuidelines(trimester: PregnancyCancerProtocol['trimester']): PregnancyCancerProtocol | undefined {
+    return PREGNANCY_CANCER_PROTOCOLS.find(p => p.trimester === trimester);
+  }
+
+  getOrganDysfunctionDosing(drug: string, crcl?: number, bilirubin?: number): {
+    renalAdjustment: string;
+    hepaticAdjustment: string;
+  } {
+    const protocol = ORGAN_DYSFUNCTION_DOSING.find(p => p.drug.toLowerCase() === drug.toLowerCase());
+
+    if (!protocol) {
+      return { renalAdjustment: 'No data available', hepaticAdjustment: 'No data available' };
+    }
+
+    let renalAdjustment = 'Check CrCl';
+    if (crcl !== undefined) {
+      for (const rd of protocol.renalDosing) {
+        if (rd.crclRange === 'Any' ||
+            (rd.crclRange.includes('≥') && crcl >= parseInt(rd.crclRange.replace('≥', ''))) ||
+            (rd.crclRange.includes('<') && crcl < parseInt(rd.crclRange.replace('<', '')))) {
+          renalAdjustment = rd.adjustment;
+          break;
+        }
+      }
+    }
+
+    let hepaticAdjustment = 'Check bilirubin/LFTs';
+    if (bilirubin !== undefined) {
+      for (const hd of protocol.hepaticDosing) {
+        if (hd.bilirubinRange === 'Any') {
+          hepaticAdjustment = hd.adjustment;
+          break;
+        }
+      }
+    }
+
+    return { renalAdjustment, hepaticAdjustment };
+  }
+
+  getHIVOncologyProtocol(cancerType: string): HIVOncologyProtocol | undefined {
+    return HIV_ONCOLOGY_PROTOCOLS.find(p =>
+      p.cancerType.toLowerCase().includes(cancerType.toLowerCase())
+    );
+  }
+
+  getGeriatricDosingAdjustment(drug: string): GeriatricDosingAdjustment | undefined {
+    return GERIATRIC_DOSING_ADJUSTMENTS.find(g =>
+      g.drug.toLowerCase() === drug.toLowerCase()
+    );
+  }
+}
+
+// Export singleton
+export const specialPopulationsEngine = new SpecialPopulationsEngine();