/**
 * Comprehensive Palliative Care and Pain Management Module
 *
 * ╔═══════════════════════════════════════════════════════════════════════════════╗
 * ║  PALLIATIVE CARE - COMFORT AND QUALITY OF LIFE FOR ALL PATIENTS             ║
 * ╠═══════════════════════════════════════════════════════════════════════════════╣
 * ║  This module provides:                                                        ║
 * ║  - Comprehensive pain management (nociceptive, neuropathic, visceral)        ║
 * ║  - Symptom cluster management by cancer type                                 ║
 * ║  - Refractory symptom escalation protocols                                   ║
 * ║  - End-of-life care and hospice transition                                   ║
 * ║  - Goals of care communication frameworks                                    ║
 * ║  - Advance care planning integration                                         ║
 * ╚═══════════════════════════════════════════════════════════════════════════════╝
 */

// ═══════════════════════════════════════════════════════════════════════════════
// PAIN MANAGEMENT DEFINITIONS
// ═══════════════════════════════════════════════════════════════════════════════

export interface PainAssessment {
  location: string[];
  intensity: number; // 0-10 NRS
  quality: PainQuality[];
  temporalPattern: 'Constant' | 'Intermittent' | 'Breakthrough' | 'Incident';
  aggravatingFactors: string[];
  relievingFactors: string[];
  functionalImpact: FunctionalImpact;
  psychologicalImpact: string[];
  painType: PainType[];
}

export type PainQuality =
  | 'Sharp' | 'Dull' | 'Aching' | 'Burning' | 'Shooting' | 'Stabbing'
  | 'Throbbing' | 'Cramping' | 'Pressure' | 'Tingling' | 'Numbness';

export type PainType =
  | 'Nociceptive-Somatic' | 'Nociceptive-Visceral' | 'Neuropathic-Peripheral'
  | 'Neuropathic-Central' | 'Mixed' | 'Bone' | 'Inflammatory';

export interface FunctionalImpact {
  sleepDisturbance: 0 | 1 | 2 | 3; // None, Mild, Moderate, Severe
  mobilityImpairment: 0 | 1 | 2 | 3;
  selfCareImpairment: 0 | 1 | 2 | 3;
  socialImpairment: 0 | 1 | 2 | 3;
  overallQoL: number; // 0-10
}

export interface PainManagementProtocol {
  painType: PainType;
  severity: 'Mild' | 'Moderate' | 'Severe';
  firstLine: PainIntervention[];
  secondLine: PainIntervention[];
  thirdLine: PainIntervention[];
  adjuvants: AdjuvantTherapy[];
  interventional: InterventionalProcedure[];
  monitoring: PainMonitoring;
}

export interface PainIntervention {
  medication: string;
  class: string;
  startingDose: string;
  titrationSchedule: string;
  maxDose: string;
  routeOptions: string[];
  precautions: string[];
  contraindications: string[];
  monitoringRequired: string[];
}

export interface AdjuvantTherapy {
  medication: string;
  indication: string;
  dose: string;
  mechanism: string;
  evidence: string;
}

export interface InterventionalProcedure {
  procedure: string;
  indication: string;
  technique: string;
  expectedBenefit: string;
  duration: string;
  risks: string[];
  contraindications: string[];
}

export interface PainMonitoring {
  assessmentFrequency: string;
  tools: string[];
  escalationCriteria: string[];
  deescalationCriteria: string[];
}

// ═══════════════════════════════════════════════════════════════════════════════
// WHO PAIN LADDER - ENHANCED
// ═══════════════════════════════════════════════════════════════════════════════

export const WHO_PAIN_LADDER: PainManagementProtocol[] = [
  {
    painType: 'Nociceptive-Somatic',
    severity: 'Mild',
    firstLine: [
      {
        medication: 'Acetaminophen',
        class: 'Non-opioid analgesic',
        startingDose: '650-1000mg PO q6h',
        titrationSchedule: 'Fixed dosing',
        maxDose: '3000mg/day (2000mg if hepatic impairment)',
        routeOptions: ['PO', 'IV', 'PR'],
        precautions: ['Hepatic impairment', 'Alcohol use'],
        contraindications: ['Severe hepatic failure'],
        monitoringRequired: ['LFTs if prolonged use']
      },
      {
        medication: 'Ibuprofen',
        class: 'NSAID',
        startingDose: '400mg PO q6-8h',
        titrationSchedule: 'Fixed dosing',
        maxDose: '2400mg/day',
        routeOptions: ['PO'],
        precautions: ['GI bleeding risk', 'Renal impairment', 'Cardiovascular disease'],
        contraindications: ['Active GI bleed', 'CKD stage 4-5', 'Aspirin-sensitive asthma'],
        monitoringRequired: ['Creatinine', 'GI symptoms']
      }
    ],
    secondLine: [
      {
        medication: 'Tramadol',
        class: 'Weak opioid',
        startingDose: '50mg PO q6h',
        titrationSchedule: 'Increase by 50mg q3d as needed',
        maxDose: '400mg/day',
        routeOptions: ['PO'],
        precautions: ['Seizure risk', 'Serotonin syndrome with SSRIs'],
        contraindications: ['Seizure disorder', 'MAO inhibitor use'],
        monitoringRequired: ['Pain relief', 'Side effects']
      }
    ],
    thirdLine: [],
    adjuvants: [],
    interventional: [],
    monitoring: {
      assessmentFrequency: 'Weekly until stable',
      tools: ['NRS', 'BPI-SF'],
      escalationCriteria: ['NRS >3 despite max non-opioid', 'Functional impairment'],
      deescalationCriteria: ['NRS ≤3 sustained', 'Improved function']
    }
  },
  {
    painType: 'Nociceptive-Somatic',
    severity: 'Moderate',
    firstLine: [
      {
        medication: 'Morphine IR',
        class: 'Strong opioid',
        startingDose: '5-10mg PO q4h (opioid-naive)',
        titrationSchedule: 'Increase by 25-50% q24-48h',
        maxDose: 'No ceiling (titrate to effect)',
        routeOptions: ['PO', 'IV', 'SC', 'PR'],
        precautions: ['Respiratory depression', 'Constipation', 'Sedation'],
        contraindications: ['Severe respiratory depression', 'Paralytic ileus'],
        monitoringRequired: ['Pain relief', 'RR', 'Sedation', 'Bowel function']
      },
      {
        medication: 'Oxycodone IR',
        class: 'Strong opioid',
        startingDose: '5mg PO q4-6h (opioid-naive)',
        titrationSchedule: 'Increase by 25-50% q24-48h',
        maxDose: 'No ceiling',
        routeOptions: ['PO'],
        precautions: ['Same as morphine'],
        contraindications: ['Same as morphine'],
        monitoringRequired: ['Same as morphine']
      }
    ],
    secondLine: [
      {
        medication: 'Hydromorphone',
        class: 'Strong opioid',
        startingDose: '2mg PO q4-6h',
        titrationSchedule: 'Increase by 25-50% q24-48h',
        maxDose: 'No ceiling',
        routeOptions: ['PO', 'IV', 'SC'],
        precautions: ['More potent than morphine (5:1)'],
        contraindications: ['Same as morphine'],
        monitoringRequired: ['Same as morphine']
      }
    ],
    thirdLine: [
      {
        medication: 'Fentanyl Transdermal',
        class: 'Strong opioid',
        startingDose: '25mcg/hr patch (only if opioid-tolerant)',
        titrationSchedule: 'Increase by 25mcg/hr q72h',
        maxDose: 'No ceiling',
        routeOptions: ['Transdermal'],
        precautions: ['Only for opioid-tolerant patients', 'Takes 12-24h to reach steady state'],
        contraindications: ['Opioid-naive patients', 'Acute pain'],
        monitoringRequired: ['Pain relief', 'Patch adherence', 'Fever (increases absorption)']
      }
    ],
    adjuvants: [
      {
        medication: 'Acetaminophen',
        indication: 'Opioid-sparing',
        dose: '650mg q6h',
        mechanism: 'Central COX inhibition',
        evidence: 'Reduces opioid requirement 20-30%'
      },
      {
        medication: 'NSAID (if not contraindicated)',
        indication: 'Inflammatory component',
        dose: 'Variable',
        mechanism: 'COX-1/2 inhibition',
        evidence: 'Synergistic with opioids'
      }
    ],
    interventional: [],
    monitoring: {
      assessmentFrequency: 'Daily during titration, then weekly',
      tools: ['NRS', 'BPI-SF', 'Opioid Risk Tool'],
      escalationCriteria: ['Inadequate relief at current dose', 'Dose escalation >50% in 1 week'],
      deescalationCriteria: ['Stable pain control', 'Disease response to treatment']
    }
  },
  {
    painType: 'Nociceptive-Somatic',
    severity: 'Severe',
    firstLine: [
      {
        medication: 'Morphine IV/SC',
        class: 'Strong opioid',
        startingDose: '2-4mg IV q2-4h or PCA',
        titrationSchedule: 'Rapid titration: redose at 50% q15-30min until controlled',
        maxDose: 'No ceiling',
        routeOptions: ['IV', 'SC'],
        precautions: ['Rapid titration requires monitoring'],
        contraindications: ['Severe respiratory compromise'],
        monitoringRequired: ['Continuous pulse ox initially', 'RR q1h', 'Sedation scale']
      }
    ],
    secondLine: [
      {
        medication: 'Hydromorphone IV',
        class: 'Strong opioid',
        startingDose: '0.5-1mg IV q2-4h',
        titrationSchedule: 'Rapid titration as above',
        maxDose: 'No ceiling',
        routeOptions: ['IV', 'SC'],
        precautions: ['5x more potent than morphine'],
        contraindications: ['Same'],
        monitoringRequired: ['Same']
      },
      {
        medication: 'Fentanyl IV',
        class: 'Strong opioid',
        startingDose: '25-50mcg IV q30min-1h',
        titrationSchedule: 'Rapid onset, short duration - good for titration',
        maxDose: 'No ceiling',
        routeOptions: ['IV'],
        precautions: ['Short duration requires frequent dosing or infusion'],
        contraindications: ['Same'],
        monitoringRequired: ['Same']
      }
    ],
    thirdLine: [
      {
        medication: 'Methadone',
        class: 'Strong opioid + NMDA antagonist',
        startingDose: 'Complex conversion - specialist required',
        titrationSchedule: 'Slow titration due to long half-life (specialist only)',
        maxDose: 'Variable',
        routeOptions: ['PO', 'IV'],
        precautions: ['QTc prolongation', 'Complex pharmacokinetics', 'Drug interactions'],
        contraindications: ['QTc >500ms', 'Concurrent QTc-prolonging drugs'],
        monitoringRequired: ['ECG at baseline and during titration', 'QTc monitoring']
      }
    ],
    adjuvants: [
      {
        medication: 'Dexamethasone',
        indication: 'Inflammatory pain, nerve compression, bone pain',
        dose: '4-8mg daily',
        mechanism: 'Anti-inflammatory, reduces edema',
        evidence: 'Effective for bone mets, liver capsule pain'
      },
      {
        medication: 'Ketamine',
        indication: 'Opioid-refractory pain, central sensitization',
        dose: '0.1-0.5mg/kg/hr IV',
        mechanism: 'NMDA antagonist',
        evidence: 'Reduces opioid tolerance, effective for refractory pain'
      }
    ],
    interventional: [
      {
        procedure: 'Intrathecal Drug Delivery System (IDDS)',
        indication: 'Refractory pain despite high-dose systemic opioids',
        technique: 'Implanted pump with intrathecal catheter',
        expectedBenefit: '50-70% pain reduction',
        duration: 'Permanent (pump refills q1-3 months)',
        risks: ['Infection', 'Catheter malfunction', 'CSF leak'],
        contraindications: ['Active infection', 'Coagulopathy', 'Limited life expectancy <3 months']
      },
      {
        procedure: 'Neurolytic Celiac Plexus Block',
        indication: 'Pancreatic cancer pain, upper abdominal malignancy',
        technique: 'Alcohol or phenol injection to celiac plexus',
        expectedBenefit: '70-90% pain reduction',
        duration: '3-6 months',
        risks: ['Hypotension', 'Diarrhea', 'Paraplegia (rare)'],
        contraindications: ['Coagulopathy', 'Bowel obstruction']
      }
    ],
    monitoring: {
      assessmentFrequency: 'Q4h during titration',
      tools: ['NRS', 'RASS for sedation', 'CPOT if non-verbal'],
      escalationCriteria: ['Pain crisis', 'Respiratory compromise'],
      deescalationCriteria: ['Stable control', 'Can convert to oral']
    }
  }
];

// ═══════════════════════════════════════════════════════════════════════════════
// NEUROPATHIC PAIN PROTOCOLS
// ═══════════════════════════════════════════════════════════════════════════════

export const NEUROPATHIC_PAIN_PROTOCOLS: PainManagementProtocol[] = [
  {
    painType: 'Neuropathic-Peripheral',
    severity: 'Moderate',
    firstLine: [
      {
        medication: 'Gabapentin',
        class: 'Anticonvulsant',
        startingDose: '100-300mg PO TID',
        titrationSchedule: 'Increase by 300mg q3-7d',
        maxDose: '3600mg/day (in divided doses)',
        routeOptions: ['PO'],
        precautions: ['Sedation', 'Dizziness', 'Peripheral edema', 'Renal dosing required'],
        contraindications: ['Severe renal impairment without dose adjustment'],
        monitoringRequired: ['Sedation', 'Renal function', 'Suicidal ideation']
      },
      {
        medication: 'Pregabalin',
        class: 'Anticonvulsant',
        startingDose: '75mg PO BID',
        titrationSchedule: 'Increase to 150mg BID after 3-7d, then 300mg BID',
        maxDose: '600mg/day',
        routeOptions: ['PO'],
        precautions: ['Same as gabapentin', 'Controlled substance'],
        contraindications: ['Same'],
        monitoringRequired: ['Same']
      }
    ],
    secondLine: [
      {
        medication: 'Duloxetine',
        class: 'SNRI',
        startingDose: '30mg PO daily',
        titrationSchedule: 'Increase to 60mg after 1-2 weeks',
        maxDose: '120mg/day',
        routeOptions: ['PO'],
        precautions: ['Nausea initially', 'Hepatic metabolism', 'Hypertension', 'Bleeding risk with anticoagulants'],
        contraindications: ['MAO inhibitors', 'Uncontrolled glaucoma', 'Severe hepatic impairment'],
        monitoringRequired: ['BP', 'Mood', 'LFTs']
      },
      {
        medication: 'Amitriptyline',
        class: 'TCA',
        startingDose: '10-25mg PO qhs',
        titrationSchedule: 'Increase by 10-25mg q1-2 weeks',
        maxDose: '150mg/day',
        routeOptions: ['PO'],
        precautions: ['Anticholinergic effects', 'Sedation', 'Cardiac conduction', 'Falls risk in elderly'],
        contraindications: ['Recent MI', 'Arrhythmia', 'Glaucoma', 'Urinary retention'],
        monitoringRequired: ['ECG if cardiac risk', 'Anticholinergic burden']
      }
    ],
    thirdLine: [
      {
        medication: 'Lidocaine 5% Patch',
        class: 'Local anesthetic',
        startingDose: '1-3 patches to affected area 12h on/12h off',
        titrationSchedule: 'Fixed',
        maxDose: '3 patches simultaneously',
        routeOptions: ['Topical'],
        precautions: ['Local skin reaction'],
        contraindications: ['Severe hepatic impairment'],
        monitoringRequired: ['Skin integrity']
      },
      {
        medication: 'Capsaicin 8% Patch',
        class: 'TRPV1 agonist',
        startingDose: 'Applied for 60 min (healthcare setting)',
        titrationSchedule: 'Repeat q3 months if effective',
        maxDose: '4 patches per application',
        routeOptions: ['Topical'],
        precautions: ['Intense burning during application', 'Requires pretreatment analgesia'],
        contraindications: ['Broken skin'],
        monitoringRequired: ['BP during application']
      }
    ],
    adjuvants: [
      {
        medication: 'Opioids',
        indication: 'Add if neuropathic-specific agents insufficient',
        dose: 'Per WHO ladder',
        mechanism: 'Mu-opioid agonism',
        evidence: 'Less effective for neuropathic than nociceptive but still helpful'
      },
      {
        medication: 'Dexamethasone',
        indication: 'Nerve compression',
        dose: '4-8mg daily',
        mechanism: 'Reduces perineural edema',
        evidence: 'Effective for tumor-related nerve compression'
      }
    ],
    interventional: [
      {
        procedure: 'Spinal Cord Stimulation',
        indication: 'Refractory neuropathic pain',
        technique: 'Epidural electrode placement with implanted pulse generator',
        expectedBenefit: '50% pain reduction in 60-70% of patients',
        duration: 'Permanent',
        risks: ['Infection', 'Lead migration', 'Hardware failure'],
        contraindications: ['Active infection', 'Coagulopathy', 'Pacemaker (relative)']
      }
    ],
    monitoring: {
      assessmentFrequency: 'Weekly during titration',
      tools: ['NRS', 'DN4', 'painDETECT'],
      escalationCriteria: ['Inadequate relief', 'Intolerable side effects'],
      deescalationCriteria: ['Stable control', 'Resolved neuropathy']
    }
  }
];

// ═══════════════════════════════════════════════════════════════════════════════
// CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY (CIPN)
// ═══════════════════════════════════════════════════════════════════════════════

export interface CIPNProtocol {
  causingAgent: string;
  riskFactors: string[];
  prevention: PreventionStrategy[];
  treatment: PainIntervention[];
  doseModification: DoseModificationGuideline[];
  prognosis: string;
}

export interface PreventionStrategy {
  intervention: string;
  evidence: string;
  recommendation: 'Recommended' | 'May Consider' | 'Not Recommended';
}

export interface DoseModificationGuideline {
  grade: number;
  description: string;
  action: string;
}

export const CIPN_PROTOCOLS: CIPNProtocol[] = [
  {
    causingAgent: 'Taxanes (Paclitaxel, Docetaxel)',
    riskFactors: ['Cumulative dose', 'Pre-existing neuropathy', 'Diabetes', 'Alcohol use'],
    prevention: [
      {
        intervention: 'Cryotherapy (frozen gloves/socks during infusion)',
        evidence: 'Moderate evidence for reduction',
        recommendation: 'May Consider'
      },
      {
        intervention: 'Compression therapy',
        evidence: 'Limited evidence',
        recommendation: 'May Consider'
      },
      {
        intervention: 'Vitamin E, glutamine, acetyl-L-carnitine',
        evidence: 'Insufficient evidence',
        recommendation: 'Not Recommended'
      }
    ],
    treatment: [
      {
        medication: 'Duloxetine',
        class: 'SNRI',
        startingDose: '30mg PO daily x1 week, then 60mg',
        titrationSchedule: 'Increase after 1 week',
        maxDose: '60mg/day (studied dose)',
        routeOptions: ['PO'],
        precautions: ['Nausea', 'Hepatic metabolism'],
        contraindications: ['MAO inhibitors'],
        monitoringRequired: ['Mood', 'BP']
      }
    ],
    doseModification: [
      { grade: 1, description: 'Mild paresthesias, no functional impairment', action: 'Continue at current dose with monitoring' },
      { grade: 2, description: 'Moderate symptoms limiting instrumental ADLs', action: 'Consider dose reduction 20-25%' },
      { grade: 3, description: 'Severe symptoms limiting self-care ADLs', action: 'Hold until grade ≤1, resume at reduced dose or discontinue' }
    ],
    prognosis: 'Often improves after treatment cessation but may persist in 30-40%'
  },
  {
    causingAgent: 'Platinum agents (Oxaliplatin, Cisplatin)',
    riskFactors: ['Cumulative dose', 'Cold sensitivity', 'Pre-existing neuropathy'],
    prevention: [
      {
        intervention: 'Calcium/Magnesium infusions',
        evidence: 'Conflicting evidence',
        recommendation: 'May Consider'
      },
      {
        intervention: 'Avoid cold exposure during and 3 days after infusion',
        evidence: 'Standard practice',
        recommendation: 'Recommended'
      },
      {
        intervention: 'Stop-and-go strategy (oxaliplatin holiday)',
        evidence: 'OPTIMOX studies',
        recommendation: 'Recommended'
      }
    ],
    treatment: [
      {
        medication: 'Duloxetine',
        class: 'SNRI',
        startingDose: '30mg PO daily',
        titrationSchedule: 'Increase to 60mg after 1 week',
        maxDose: '60mg/day',
        routeOptions: ['PO'],
        precautions: ['Same as above'],
        contraindications: ['Same'],
        monitoringRequired: ['Same']
      },
      {
        medication: 'Gabapentin/Pregabalin',
        class: 'Anticonvulsant',
        startingDose: 'Per neuropathic protocol',
        titrationSchedule: 'Per protocol',
        maxDose: 'Per protocol',
        routeOptions: ['PO'],
        precautions: ['Sedation'],
        contraindications: ['Renal impairment without adjustment'],
        monitoringRequired: ['Sedation']
      }
    ],
    doseModification: [
      { grade: 1, description: 'Cold-induced dysesthesias resolving', action: 'Continue with precautions' },
      { grade: 2, description: 'Persistent paresthesias between cycles', action: 'Consider dose reduction or stop-and-go' },
      { grade: 3, description: 'Functional impairment', action: 'Discontinue oxaliplatin' }
    ],
    prognosis: 'Acute cold sensitivity resolves; chronic sensory neuropathy may persist'
  },
  {
    causingAgent: 'Vinca alkaloids (Vincristine, Vinblastine)',
    riskFactors: ['Cumulative dose', 'Hepatic impairment', 'Pre-existing neuropathy'],
    prevention: [
      {
        intervention: 'Dose capping (vincristine 2mg max)',
        evidence: 'Standard practice',
        recommendation: 'Recommended'
      }
    ],
    treatment: [
      {
        medication: 'Gabapentin/Pregabalin',
        class: 'Anticonvulsant',
        startingDose: 'Per neuropathic protocol',
        titrationSchedule: 'Per protocol',
        maxDose: 'Per protocol',
        routeOptions: ['PO'],
        precautions: ['Sedation'],
        contraindications: [],
        monitoringRequired: ['Neuropathy assessment']
      }
    ],
    doseModification: [
      { grade: 1, description: 'Mild sensory changes', action: 'Continue with monitoring' },
      { grade: 2, description: 'Motor weakness, constipation', action: 'Reduce dose 25-50%' },
      { grade: 3, description: 'Significant motor impairment', action: 'Hold or discontinue' }
    ],
    prognosis: 'Often reversible after cessation but may take months'
  },
  {
    causingAgent: 'Bortezomib',
    riskFactors: ['Pre-existing neuropathy', 'Cumulative dose', 'IV route (vs SC)'],
    prevention: [
      {
        intervention: 'Subcutaneous administration (vs IV)',
        evidence: 'Reduced neuropathy incidence',
        recommendation: 'Recommended'
      },
      {
        intervention: 'Weekly dosing (vs twice weekly)',
        evidence: 'Reduced toxicity with similar efficacy',
        recommendation: 'Recommended'
      }
    ],
    treatment: [
      {
        medication: 'Per neuropathic pain protocols',
        class: 'Various',
        startingDose: 'Per protocol',
        titrationSchedule: 'Per protocol',
        maxDose: 'Per protocol',
        routeOptions: ['PO'],
        precautions: [],
        contraindications: [],
        monitoringRequired: []
      }
    ],
    doseModification: [
      { grade: 1, description: 'Pain or paresthesias without functional loss', action: 'Continue or reduce to 1.0mg/m²' },
      { grade: 2, description: 'Functional impairment', action: 'Hold until ≤G1, resume at 0.7mg/m²' },
      { grade: 3, description: 'Severe symptoms', action: 'Discontinue' }
    ],
    prognosis: 'Often improves after dose modification or cessation'
  }
];

// ═══════════════════════════════════════════════════════════════════════════════
// BONE PAIN MANAGEMENT
// ═══════════════════════════════════════════════════════════════════════════════

export interface BonePainProtocol {
  indication: string;
  pharmacological: PainIntervention[];
  boneTargeted: BoneTargetedTherapy[];
  radiation: RadiationForPain[];
  interventional: InterventionalProcedure[];
  surgical: string[];
}

export interface BoneTargetedTherapy {
  agent: string;
  class: string;
  dose: string;
  frequency: string;
  painBenefit: string;
  skeletalEventReduction: string;
  precautions: string[];
}

export interface RadiationForPain {
  technique: string;
  dose: string;
  fractionation: string;
  responseRate: string;
  timeToResponse: string;
  retreatmentOption: boolean;
}

export const BONE_PAIN_PROTOCOL: BonePainProtocol = {
  indication: 'Painful bone metastases from solid tumors or multiple myeloma',
  pharmacological: [
    {
      medication: 'NSAIDs (if not contraindicated)',
      class: 'Anti-inflammatory',
      startingDose: 'Ibuprofen 400-600mg TID or Naproxen 500mg BID',
      titrationSchedule: 'Fixed',
      maxDose: 'Standard NSAID limits',
      routeOptions: ['PO'],
      precautions: ['GI, renal, CV risk'],
      contraindications: ['Active bleeding', 'CKD', 'High CV risk'],
      monitoringRequired: ['Creatinine', 'GI symptoms']
    },
    {
      medication: 'Dexamethasone',
      class: 'Corticosteroid',
      startingDose: '4-8mg PO daily',
      titrationSchedule: 'Taper if possible after 1-2 weeks',
      maxDose: '16mg/day',
      routeOptions: ['PO', 'IV'],
      precautions: ['Hyperglycemia', 'Insomnia', 'Immunosuppression'],
      contraindications: ['Active infection (relative)'],
      monitoringRequired: ['Blood glucose', 'Mood']
    },
    {
      medication: 'Opioids per WHO ladder',
      class: 'Strong opioid',
      startingDose: 'Per severity',
      titrationSchedule: 'Per protocol',
      maxDose: 'No ceiling',
      routeOptions: ['Various'],
      precautions: ['Standard opioid precautions'],
      contraindications: ['Standard'],
      monitoringRequired: ['Standard']
    }
  ],
  boneTargeted: [
    {
      agent: 'Zoledronic acid',
      class: 'Bisphosphonate',
      dose: '4mg IV',
      frequency: 'Every 3-4 weeks (may extend to q12 weeks after 1 year)',
      painBenefit: 'Reduces bone pain in 30-50% of patients',
      skeletalEventReduction: '40% reduction in SREs',
      precautions: ['Renal dosing required', 'ONJ risk', 'Hypocalcemia']
    },
    {
      agent: 'Denosumab',
      class: 'RANK-L inhibitor',
      dose: '120mg SC',
      frequency: 'Every 4 weeks',
      painBenefit: 'Similar to zoledronic acid',
      skeletalEventReduction: 'Superior to zoledronic acid',
      precautions: ['Hypocalcemia (severe)', 'ONJ risk', 'No renal adjustment needed']
    }
  ],
  radiation: [
    {
      technique: 'Single fraction EBRT',
      dose: '8 Gy',
      fractionation: 'Single fraction',
      responseRate: '60-70% (complete response 25-30%)',
      timeToResponse: '2-4 weeks',
      retreatmentOption: true
    },
    {
      technique: 'Multi-fraction EBRT',
      dose: '30 Gy',
      fractionation: '10 fractions',
      responseRate: '60-70% (similar to single)',
      timeToResponse: '2-4 weeks',
      retreatmentOption: true
    },
    {
      technique: 'SBRT',
      dose: '24-27 Gy',
      fractionation: '3 fractions',
      responseRate: '80-90%',
      timeToResponse: '1-3 months',
      retreatmentOption: false
    }
  ],
  interventional: [
    {
      procedure: 'Vertebroplasty/Kyphoplasty',
      indication: 'Painful vertebral compression fracture',
      technique: 'Cement injection into vertebral body',
      expectedBenefit: '70-90% pain relief',
      duration: 'Immediate and lasting',
      risks: ['Cement leak', 'Adjacent fracture'],
      contraindications: ['Posterior wall destruction', 'Active infection']
    },
    {
      procedure: 'Radiofrequency Ablation (RFA)',
      indication: 'Painful bone metastasis not amenable to RT',
      technique: 'CT-guided thermal ablation',
      expectedBenefit: '70-95% pain reduction',
      duration: 'Weeks to months',
      risks: ['Nerve injury', 'Fracture'],
      contraindications: ['Near critical structures']
    },
    {
      procedure: 'Cryoablation',
      indication: 'Same as RFA',
      technique: 'CT-guided freezing',
      expectedBenefit: 'Similar to RFA',
      duration: 'Weeks to months',
      risks: ['Similar to RFA'],
      contraindications: ['Similar']
    }
  ],
  surgical: [
    'Prophylactic fixation for impending fracture (Mirels score ≥9)',
    'Surgical stabilization for pathologic fracture',
    'Decompression for spinal cord compression'
  ]
};

// ═══════════════════════════════════════════════════════════════════════════════
// CANCER-SPECIFIC SYMPTOM CLUSTERS
// ═══════════════════════════════════════════════════════════════════════════════

export interface SymptomCluster {
  cancerType: string;
  commonSymptoms: SymptomManagement[];
  psychologicalSymptoms: string[];
  interventions: ClusterIntervention[];
}

export interface SymptomManagement {
  symptom: string;
  prevalence: string;
  firstLineManagement: string[];
  secondLineManagement: string[];
  refractory: string[];
}

export interface ClusterIntervention {
  type: string;
  intervention: string;
  evidence: string;
}

export const CANCER_SYMPTOM_CLUSTERS: SymptomCluster[] = [
  {
    cancerType: 'Pancreatic Cancer',
    commonSymptoms: [
      {
        symptom: 'Pain (epigastric/back)',
        prevalence: '80-85%',
        firstLineManagement: ['Opioids', 'NSAIDs', 'Dexamethasone'],
        secondLineManagement: ['Celiac plexus block', 'Intrathecal pump'],
        refractory: ['Ketamine infusion', 'Palliative sedation']
      },
      {
        symptom: 'Cachexia/Anorexia',
        prevalence: '80%',
        firstLineManagement: ['Nutritional counseling', 'Oral supplements', 'Megestrol acetate'],
        secondLineManagement: ['Dronabinol', 'Mirtazapine', 'Olanzapine'],
        refractory: ['Accept as disease trajectory', 'Comfort-focused care']
      },
      {
        symptom: 'Nausea/Vomiting',
        prevalence: '50-60%',
        firstLineManagement: ['Ondansetron', 'Metoclopramide (if no obstruction)'],
        secondLineManagement: ['Dexamethasone', 'Haloperidol', 'Olanzapine'],
        refractory: ['Octreotide (if obstruction)', 'Continuous antiemetic infusion']
      },
      {
        symptom: 'Jaundice/Pruritus',
        prevalence: '50%',
        firstLineManagement: ['Biliary stenting (ERCP/PTC)', 'Cholestyramine'],
        secondLineManagement: ['Rifampin', 'Naltrexone', 'Sertraline'],
        refractory: ['Biliary drainage', 'Plasmapheresis (rare)']
      }
    ],
    psychologicalSymptoms: ['Depression (50%)', 'Anxiety (40%)', 'Existential distress'],
    interventions: [
      {
        type: 'Early palliative care integration',
        intervention: 'Concurrent palliative care from diagnosis',
        evidence: 'Improves QoL and may improve survival (Temel NEJM 2010 model)'
      },
      {
        type: 'Celiac plexus neurolysis',
        intervention: 'Early consideration for pain',
        evidence: '70-90% pain relief, may reduce opioid requirement'
      }
    ]
  },
  {
    cancerType: 'Lung Cancer',
    commonSymptoms: [
      {
        symptom: 'Dyspnea',
        prevalence: '65-75%',
        firstLineManagement: ['Opioids (morphine 2.5-5mg q4h)', 'Oxygen if hypoxic', 'Fan therapy'],
        secondLineManagement: ['Benzodiazepines (for anxiety component)', 'Bronchodilators if obstruction'],
        refractory: ['Continuous opioid infusion', 'Palliative sedation']
      },
      {
        symptom: 'Cough',
        prevalence: '50-70%',
        firstLineManagement: ['Dextromethorphan', 'Codeine', 'Benzonatate'],
        secondLineManagement: ['Gabapentin', 'Nebulized lidocaine'],
        refractory: ['Opioids', 'Endobronchial intervention if obstruction']
      },
      {
        symptom: 'Hemoptysis',
        prevalence: '20-30%',
        firstLineManagement: ['Tranexamic acid', 'Radiation therapy'],
        secondLineManagement: ['Bronchial artery embolization'],
        refractory: ['Endobronchial laser/electrocautery', 'Palliative sedation if massive']
      },
      {
        symptom: 'Pain',
        prevalence: '50-70%',
        firstLineManagement: ['Per WHO ladder'],
        secondLineManagement: ['Chest wall blocks', 'Radiation'],
        refractory: ['Intrathecal pump', 'Ketamine']
      }
    ],
    psychologicalSymptoms: ['Anxiety (35-45%)', 'Depression (25-35%)', 'Panic with dyspnea'],
    interventions: [
      {
        type: 'Breathlessness clinic',
        intervention: 'Multicomponent intervention (breathing techniques, fan, positioning)',
        evidence: 'Improves dyspnea and reduces anxiety'
      },
      {
        type: 'Palliative thoracentesis/pleurodesis',
        intervention: 'For malignant pleural effusion',
        evidence: 'Relieves dyspnea in 70-90%'
      }
    ]
  },
  {
    cancerType: 'Brain Tumors',
    commonSymptoms: [
      {
        symptom: 'Headache',
        prevalence: '50-60%',
        firstLineManagement: ['Dexamethasone (4-16mg daily)', 'Acetaminophen', 'NSAIDs'],
        secondLineManagement: ['Opioids if needed'],
        refractory: ['Increase steroids', 'Consider decompressive surgery']
      },
      {
        symptom: 'Seizures',
        prevalence: '40-60%',
        firstLineManagement: ['Levetiracetam', 'Lacosamide', 'Valproate'],
        secondLineManagement: ['Add second AED', 'Clobazam'],
        refractory: ['Phenobarbital', 'Midazolam infusion']
      },
      {
        symptom: 'Cognitive Decline',
        prevalence: '40-80%',
        firstLineManagement: ['Treat reversible causes (steroids, seizures)', 'Cognitive rehabilitation'],
        secondLineManagement: ['Methylphenidate', 'Modafinil', 'Memantine (radiation-induced)'],
        refractory: ['Supportive care', 'Caregiver support']
      },
      {
        symptom: 'Fatigue',
        prevalence: '60-90%',
        firstLineManagement: ['Treat underlying causes', 'Energy conservation', 'Exercise'],
        secondLineManagement: ['Methylphenidate', 'Modafinil'],
        refractory: ['Accept and adapt']
      }
    ],
    psychologicalSymptoms: ['Depression (15-40%)', 'Anxiety', 'Personality changes', 'Caregiver burden'],
    interventions: [
      {
        type: 'Steroid management',
        intervention: 'Use lowest effective dose, taper when possible',
        evidence: 'Reduces steroid myopathy, hyperglycemia, insomnia'
      },
      {
        type: 'Seizure prophylaxis',
        intervention: 'Continue AED for life if seizure history',
        evidence: 'Prevents breakthrough seizures, ensures safety'
      }
    ]
  },
  {
    cancerType: 'Gastrointestinal Cancers (Gastric, Esophageal)',
    commonSymptoms: [
      {
        symptom: 'Dysphagia',
        prevalence: '60-80%',
        firstLineManagement: ['Esophageal stenting', 'Dietary modification'],
        secondLineManagement: ['Radiation therapy', 'Dilation'],
        refractory: ['Feeding tube (G-tube, J-tube)', 'TPN']
      },
      {
        symptom: 'Nausea/Vomiting',
        prevalence: '40-70%',
        firstLineManagement: ['Metoclopramide (if no obstruction)', 'Ondansetron'],
        secondLineManagement: ['Dexamethasone', 'Haloperidol'],
        refractory: ['Octreotide', 'Venting gastrostomy']
      },
      {
        symptom: 'Bowel Obstruction',
        prevalence: 'Variable',
        firstLineManagement: ['NPO, NG tube', 'IV fluids', 'Dexamethasone'],
        secondLineManagement: ['Octreotide', 'Hyoscine butylbromide'],
        refractory: ['Venting gastrostomy', 'Surgical bypass if appropriate']
      },
      {
        symptom: 'Ascites',
        prevalence: '30-50% in advanced disease',
        firstLineManagement: ['Diuretics (spironolactone ± furosemide)', 'Sodium restriction'],
        secondLineManagement: ['Therapeutic paracentesis'],
        refractory: ['Indwelling drain', 'Peritoneovenous shunt (rare)']
      }
    ],
    psychologicalSymptoms: ['Depression', 'Anxiety', 'Loss of eating enjoyment'],
    interventions: [
      {
        type: 'Nutritional support',
        intervention: 'Early dietitian involvement, consider enteral feeding',
        evidence: 'Maintains nutrition, improves tolerance of treatment'
      }
    ]
  }
];

// ═══════════════════════════════════════════════════════════════════════════════
// END-OF-LIFE CARE PROTOCOLS
// ═══════════════════════════════════════════════════════════════════════════════

export interface EndOfLifeProtocol {
  phase: 'Last weeks' | 'Last days' | 'Actively dying';
  clinicalIndicators: string[];
  symptomPriorities: string[];
  medicationChanges: MedicationTransition;
  familySupport: string[];
  practicalConsiderations: string[];
}

export interface MedicationTransition {
  currentRoute: string;
  alternativeRoutes: string[];
  essentialMedications: string[];
  medicationsToDiscontinue: string[];
  prnProtocols: PRNProtocol[];
}

export interface PRNProtocol {
  symptom: string;
  medication: string;
  dose: string;
  route: string;
  frequency: string;
  maxDose24h: string;
}

export const END_OF_LIFE_PROTOCOLS: EndOfLifeProtocol[] = [
  {
    phase: 'Last weeks',
    clinicalIndicators: [
      'PPS ≤50%',
      'Declining oral intake',
      'Increasing weakness',
      'Spending >50% of day in bed',
      'Progressive weight loss'
    ],
    symptomPriorities: ['Pain control', 'Nausea/vomiting', 'Dyspnea', 'Anxiety/depression'],
    medicationChanges: {
      currentRoute: 'Oral preferred if tolerated',
      alternativeRoutes: ['Sublingual', 'Transdermal', 'Subcutaneous'],
      essentialMedications: ['Pain medications', 'Anti-anxiety', 'Antiemetics'],
      medicationsToDiscontinue: [
        'Vitamins/supplements',
        'Preventive medications (statins, antihypertensives - with caution)',
        'Medications for long-term benefit'
      ],
      prnProtocols: []
    },
    familySupport: [
      'Goals of care discussion',
      'Advance directive review',
      'Hospice referral discussion',
      'Anticipatory grief support'
    ],
    practicalConsiderations: [
      'Ensure medications available at home',
      'Equipment needs (hospital bed, oxygen)',
      'Emergency contact plan',
      '24/7 support availability'
    ]
  },
  {
    phase: 'Last days',
    clinicalIndicators: [
      'PPS ≤30%',
      'Bedbound',
      'Minimal oral intake (sips only)',
      'Altered consciousness',
      'Mottled extremities',
      'Changes in breathing pattern'
    ],
    symptomPriorities: ['Comfort', 'Minimize distressing symptoms', 'Family support'],
    medicationChanges: {
      currentRoute: 'Non-oral routes',
      alternativeRoutes: ['Subcutaneous', 'Sublingual', 'Rectal'],
      essentialMedications: [
        'Morphine/hydromorphone SC (pain, dyspnea)',
        'Midazolam/lorazepam SC (anxiety, agitation)',
        'Haloperidol SC (nausea, agitation)',
        'Glycopyrrolate/hyoscine SC (secretions)'
      ],
      medicationsToDiscontinue: [
        'All non-essential medications',
        'Anticoagulants (if not for symptom control)',
        'Most oral medications'
      ],
      prnProtocols: [
        {
          symptom: 'Pain/Dyspnea',
          medication: 'Morphine',
          dose: '2.5-5mg',
          route: 'SC',
          frequency: 'Q1h PRN',
          maxDose24h: 'No ceiling'
        },
        {
          symptom: 'Anxiety/Agitation',
          medication: 'Midazolam',
          dose: '2.5-5mg',
          route: 'SC',
          frequency: 'Q1h PRN',
          maxDose24h: 'No ceiling'
        },
        {
          symptom: 'Nausea',
          medication: 'Haloperidol',
          dose: '0.5-1mg',
          route: 'SC',
          frequency: 'Q4-6h PRN',
          maxDose24h: '10mg'
        },
        {
          symptom: 'Secretions (death rattle)',
          medication: 'Glycopyrrolate',
          dose: '0.2mg',
          route: 'SC',
          frequency: 'Q4h PRN',
          maxDose24h: '1.2mg'
        }
      ]
    },
    familySupport: [
      'Prepare family for what to expect',
      'Signs of imminent death education',
      'Permission to be present or take breaks',
      'Chaplain/spiritual care'
    ],
    practicalConsiderations: [
      'Continuous care if available (hospice)',
      'Mouth care supplies',
      'Positioning aids',
      'Quiet, peaceful environment'
    ]
  },
  {
    phase: 'Actively dying',
    clinicalIndicators: [
      'Unresponsive or minimal response',
      'No oral intake',
      'Cheyne-Stokes or irregular breathing',
      'Peripheral cyanosis',
      'Mottling extending centrally',
      'Mandibular breathing'
    ],
    symptomPriorities: ['Comfort only', 'Minimize interventions', 'Family presence'],
    medicationChanges: {
      currentRoute: 'SC only',
      alternativeRoutes: ['Continuous SC infusion if needed'],
      essentialMedications: ['Comfort medications only'],
      medicationsToDiscontinue: ['All except comfort medications'],
      prnProtocols: [
        {
          symptom: 'Any distress',
          medication: 'Morphine + Midazolam',
          dose: '2.5mg each',
          route: 'SC',
          frequency: 'Q15-30min PRN',
          maxDose24h: 'As needed for comfort'
        }
      ]
    },
    familySupport: [
      'Continuous presence of support',
      'What to do when death occurs',
      'After-death care planning',
      'Bereavement resources'
    ],
    practicalConsiderations: [
      'Notify funeral home of expected death',
      'DNR confirmed and visible',
      'After-hours contact numbers',
      'Expected vs unexpected death documentation'
    ]
  }
];

// ═══════════════════════════════════════════════════════════════════════════════
// PALLIATIVE SEDATION PROTOCOL
// ═══════════════════════════════════════════════════════════════════════════════

export interface PalliativeSedationProtocol {
  indications: string[];
  prerequisites: string[];
  sedationTypes: SedationType[];
  medications: SedationMedication[];
  monitoring: string[];
  documentation: string[];
  ethicalConsiderations: string[];
}

export interface SedationType {
  type: string;
  description: string;
  indication: string;
}

export interface SedationMedication {
  medication: string;
  startingDose: string;
  titration: string;
  maxDose: string;
  notes: string;
}

export const PALLIATIVE_SEDATION_PROTOCOL: PalliativeSedationProtocol = {
  indications: [
    'Refractory symptoms unresponsive to all other interventions',
    'Intolerable suffering despite optimal palliative care',
    'Imminent death (hours to days expected)',
    'Patient/surrogate consent obtained'
  ],
  prerequisites: [
    'Palliative care specialist consultation',
    'Ethics consultation if any uncertainty',
    'Documentation of all attempted interventions',
    'Clear goals of care discussion',
    'Informed consent or surrogate decision',
    'DNR status confirmed'
  ],
  sedationTypes: [
    {
      type: 'Proportionate Palliative Sedation',
      description: 'Sedation titrated to relieve suffering, consciousness reduced only as needed',
      indication: 'Refractory symptoms with awareness causing distress'
    },
    {
      type: 'Continuous Deep Sedation',
      description: 'Continuous sedation to unconsciousness until death',
      indication: 'Refractory suffering in imminently dying patient (hours to days)'
    },
    {
      type: 'Respite Sedation',
      description: 'Temporary sedation (24-48h) with planned re-emergence',
      indication: 'Severe symptom crisis, patient/family need respite'
    }
  ],
  medications: [
    {
      medication: 'Midazolam',
      startingDose: '0.5-1mg/hr SC/IV infusion',
      titration: 'Increase by 0.5-1mg/hr q1h until comfortable',
      maxDose: 'No ceiling (typical range 1-20mg/hr)',
      notes: 'First-line agent, rapid onset, easily titratable'
    },
    {
      medication: 'Propofol',
      startingDose: '10-20mg/hr IV',
      titration: 'Increase by 10mg/hr as needed',
      maxDose: 'Variable',
      notes: 'Requires IV access, rapid onset, ICU or specialized setting'
    },
    {
      medication: 'Phenobarbital',
      startingDose: '100-200mg SC/IV load, then 50-100mg q6-8h',
      titration: 'Increase maintenance by 50mg/dose as needed',
      maxDose: 'Variable',
      notes: 'Long half-life, useful when midazolam tolerance develops'
    }
  ],
  monitoring: [
    'Comfort assessment (RASS, sedation scale)',
    'Respiratory status',
    'Facial expression for distress',
    'Family presence and coping',
    'Documentation of sedation level and comfort'
  ],
  documentation: [
    'Indication and refractory nature of symptoms',
    'All alternative treatments attempted',
    'Consent process and participants',
    'Sedation level and titration rationale',
    'Ongoing assessment of comfort'
  ],
  ethicalConsiderations: [
    'Intent is comfort, not hastening death (doctrine of double effect)',
    'Proportionality - sedation level matched to symptom severity',
    'Patient autonomy respected',
    'Distinction from euthanasia (sedation does not cause death)',
    'Availability of nutrition/hydration discussed separately'
  ]
};

// ═══════════════════════════════════════════════════════════════════════════════
// OPIOID CONVERSION AND ROTATION
// ═══════════════════════════════════════════════════════════════════════════════

export interface OpioidEquivalence {
  opioid: string;
  oralMorphineEquivalent: number; // mg morphine equivalent per mg of drug
  routes: RouteConversion[];
  specialConsiderations: string[];
}

export interface RouteConversion {
  from: string;
  to: string;
  ratio: number;
}

export const OPIOID_EQUIVALENCE_TABLE: OpioidEquivalence[] = [
  {
    opioid: 'Morphine',
    oralMorphineEquivalent: 1,
    routes: [
      { from: 'PO', to: 'IV/SC', ratio: 3 }, // 30mg PO = 10mg IV
      { from: 'PO', to: 'PR', ratio: 1 }
    ],
    specialConsiderations: ['Renally cleared (avoid in severe renal impairment)', 'Active metabolites (M6G, M3G)']
  },
  {
    opioid: 'Oxycodone',
    oralMorphineEquivalent: 1.5, // 20mg oxycodone = 30mg morphine
    routes: [
      { from: 'PO', to: 'IV', ratio: 2 }
    ],
    specialConsiderations: ['No active metabolites', 'OK in mild-moderate renal impairment']
  },
  {
    opioid: 'Hydromorphone',
    oralMorphineEquivalent: 4, // 7.5mg PO HM = 30mg PO morphine
    routes: [
      { from: 'PO', to: 'IV/SC', ratio: 5 } // 7.5mg PO = 1.5mg IV
    ],
    specialConsiderations: ['Preferred in renal impairment', 'Less histamine release', 'Available in high-potency formulations']
  },
  {
    opioid: 'Fentanyl Transdermal',
    oralMorphineEquivalent: 2.4, // 25mcg/hr patch ≈ 60-90mg oral morphine/24h
    routes: [
      { from: 'Transdermal', to: 'IV', ratio: 1 } // mcg/hr patch ≈ mcg/hr IV
    ],
    specialConsiderations: ['For stable pain only', 'Not for opioid-naive', '12-24h to steady state', 'Avoid in cachexia (absorption issues)']
  },
  {
    opioid: 'Methadone',
    oralMorphineEquivalent: -1, // Variable - see conversion table
    routes: [
      { from: 'PO', to: 'IV', ratio: 2 }
    ],
    specialConsiderations: [
      'Complex conversion - specialist required',
      'Conversion ratio changes with total daily morphine dose:',
      '≤30mg morphine: 3:1',
      '31-99mg: 5:1',
      '100-299mg: 10:1',
      '300-499mg: 12:1',
      '500-999mg: 15:1',
      '≥1000mg: 20:1',
      'Long half-life (15-60h), accumulation risk',
      'QTc monitoring required'
    ]
  }
];

// ═══════════════════════════════════════════════════════════════════════════════
// PALLIATIVE CARE ENGINE
// ═══════════════════════════════════════════════════════════════════════════════

export class PalliativeCareEngine {
  assessPain(assessment: PainAssessment): PainManagementProtocol | undefined {
    // Find matching protocol based on pain type and severity
    const severity = assessment.intensity <= 3 ? 'Mild' : assessment.intensity <= 6 ? 'Moderate' : 'Severe';

    // Check for neuropathic pain
    if (assessment.painType.some(t => t.includes('Neuropathic'))) {
      return NEUROPATHIC_PAIN_PROTOCOLS.find(p => p.severity === severity);
    }

    // Default to WHO ladder for nociceptive
    return WHO_PAIN_LADDER.find(p => p.severity === severity);
  }

  getCIPNProtocol(agent: string): CIPNProtocol | undefined {
    return CIPN_PROTOCOLS.find(p =>
      p.causingAgent.toLowerCase().includes(agent.toLowerCase())
    );
  }

  getBonePainProtocol(): BonePainProtocol {
    return BONE_PAIN_PROTOCOL;
  }

  getSymptomCluster(cancerType: string): SymptomCluster | undefined {
    return CANCER_SYMPTOM_CLUSTERS.find(c =>
      cancerType.toLowerCase().includes(c.cancerType.toLowerCase()) ||
      c.cancerType.toLowerCase().includes(cancerType.toLowerCase())
    );
  }

  getEndOfLifeProtocol(phase: EndOfLifeProtocol['phase']): EndOfLifeProtocol | undefined {
    return END_OF_LIFE_PROTOCOLS.find(p => p.phase === phase);
  }

  calculateOpioidConversion(
    fromOpioid: string,
    fromDose: number,
    fromRoute: string,
    toOpioid: string,
    toRoute: string
  ): { dose: number; notes: string[] } {
    const fromEquiv = OPIOID_EQUIVALENCE_TABLE.find(o =>
      o.opioid.toLowerCase() === fromOpioid.toLowerCase()
    );
    const toEquiv = OPIOID_EQUIVALENCE_TABLE.find(o =>
      o.opioid.toLowerCase() === toOpioid.toLowerCase()
    );

    if (!fromEquiv || !toEquiv) {
      return { dose: 0, notes: ['Opioid not found in conversion table'] };
    }

    // Convert to oral morphine equivalent
    let morphineEquiv = fromDose * fromEquiv.oralMorphineEquivalent;

    // Adjust for route if parenteral
    const fromRouteConv = fromEquiv.routes.find(r => r.to === fromRoute || r.from === fromRoute);
    if (fromRouteConv && fromRoute !== 'PO') {
      morphineEquiv *= fromRouteConv.ratio;
    }

    // Convert to new opioid
    let newDose = morphineEquiv / toEquiv.oralMorphineEquivalent;

    // Adjust for target route
    const toRouteConv = toEquiv.routes.find(r => r.to === toRoute || r.from === toRoute);
    if (toRouteConv && toRoute !== 'PO') {
      newDose /= toRouteConv.ratio;
    }

    // Apply cross-tolerance reduction (25-50%)
    const reducedDose = newDose * 0.75; // 25% reduction

    return {
      dose: Math.round(reducedDose * 10) / 10,
      notes: [
        `Calculated from ${fromDose}${fromRoute} ${fromOpioid} to ${toRoute} ${toOpioid}`,
        '25% reduction applied for cross-tolerance',
        'Titrate based on response',
        ...toEquiv.specialConsiderations
      ]
    };
  }

  getPalliativeSedationProtocol(): PalliativeSedationProtocol {
    return PALLIATIVE_SEDATION_PROTOCOL;
  }
}

// Export singleton
export const palliativeCareEngine = new PalliativeCareEngine();