Cookbook 378: Offline Clinical Allergy, Immunology & Resuscitation Acute Anaphylaxis WAO / EAACI / AAAAI Diagnostic Staging, Brighton Collaboration Level Engine, Weight-Tiered Epinephrine Autoinjector Titrator & Refractory Shock Vasopressor Infusion Protocol

#!/usr/bin/env python3
"""
OpenPHR Cookbook 378: Offline Clinical Allergy & Emergency Resuscitation Engine
WAO/EAACI 2020 Anaphylaxis Diagnostic Criteria, Brighton Collaboration Certainty,
Weight-Tiered Epinephrine Autoinjector Titrator & Refractory Shock Vasopressor Engine.

Dependencies: Python 3.8+ (Standard Library Only).
"""

import math
from dataclasses import dataclass, field
from enum import Enum
from typing import Dict, List, Optional, Tuple, Union


class BrightonCertaintyLevel(Enum):
    LEVEL_1 = "Level 1 (Highest Diagnostic Certainty: Multi-system Major Organ Involvement)"
    LEVEL_2 = "Level 2 (Intermediate Diagnostic Certainty)"
    LEVEL_3 = "Level 3 (Lower Diagnostic Certainty / Probable Anaphylaxis)"
    INSUFFICIENT = "Insufficient Evidence for Anaphylaxis Case Definition"


class WAOSeverityGrade(Enum):
    GRADE_1_MILD = "Grade 1 (Mild: Cutaneous and Subcutaneous Only)"
    GRADE_2_MODERATE = "Grade 2 (Moderate: Mild Respiratory, GI, or Cardiovascular)"
    GRADE_3_SEVERE = "Grade 3 (Severe: Bronchospasm, Stridor, Severe GI)"
    GRADE_4_LIFE_THREATENING = "Grade 4 (Life-Threatening: Hypotension, Shock, Hypoxemia, Syncope)"
    GRADE_5_FATAL = "Grade 5 (Fatal: Cardiopulmonary Arrest)"


class EpinephrineDeliveryDevice(Enum):
    MANUAL_SYRINGE = "Manual 1:1000 (1 mg/mL) Ampule with 1 mL Tuberculin Syringe (IM)"
    AUTOINJECTOR_INFANT_01 = "0.10 mg Epinephrine Autoinjector (Auvi-Q 0.1 mg)"
    AUTOINJECTOR_JUNIOR_015 = "0.15 mg Epinephrine Autoinjector (EpiPen Jr / Auvi-Q 0.15 mg)"
    AUTOINJECTOR_ADULT_03 = "0.30 mg Epinephrine Autoinjector (EpiPen / Auvi-Q 0.3 mg)"
    AUTOINJECTOR_ADULT_05 = "0.50 mg Epinephrine Autoinjector (Emerade 0.5 mg / High-Dose Adult IM)"


@dataclass
class AnaphylaxisPatientPresentation:
    age_years: float
    weight_kg: float
    is_adult: bool
    # Vital signs
    heart_rate_bpm: int
    systolic_bp_mmhg: int
    diastolic_bp_mmhg: int
    spo2_percent: float
    respiratory_rate_bpm: int
    # Allergen exposure history
    known_allergen_exposure: bool
    probable_allergen_exposure: bool
    trigger_type: str  # "Food", "Venom", "Medication", "Contrast", "Idiopathic", "Unknown"
    minutes_since_exposure: int
    # Cutaneous / Mucosal signs
    generalized_urticaria: bool
    generalized_erythema_flushing: bool
    angioedema_lips_tongue_uvula_face: bool
    generalized_pruritus: bool
    # Respiratory signs
    audible_stridor_laryngeal_edema: bool
    wheezing_bronchospasm: bool
    severe_dyspnea_hypoxemia: bool
    rhinorrhea_sneezing_cough: bool
    pef_percent_baseline: Optional[float] = None
    # Cardiovascular signs
    measured_hypotension: bool = False
    shock_capillary_refill_delayed: bool = False
    syncope_loss_of_consciousness: bool = False
    incontinence: bool = False
    # Gastrointestinal signs
    severe_crampy_abdominal_pain: bool = False
    recurrent_vomiting: bool = False
    diarrhea: bool = False
    # Medication and Medical History
    on_chronic_beta_blocker: bool = False
    on_ace_inhibitor: bool = False
    history_of_asthma: bool = False
    history_of_prior_anaphylaxis: bool = False
    history_of_biphasic_reaction: bool = False
    # Diagnostic tests
    acute_serum_tryptase_ug_l: Optional[float] = None
    baseline_serum_tryptase_ug_l: Optional[float] = None


@dataclass
class EpinephrineDosingRecommendation:
    recommended_dose_mg: float
    delivery_device: EpinephrineDeliveryDevice
    route: str
    anatomical_site: str
    needle_gauge_and_length: str
    repeat_frequency_minutes: str
    max_single_dose_mg: float
    clinical_instructions: str


@dataclass
class AnaphylaxisClinicalDecisionReport:
    meets_wao_criteria: bool
    wao_diagnostic_rationale: str
    brighton_level: BrightonCertaintyLevel
    wao_severity_grade: WAOSeverityGrade
    epinephrine_recommendation: EpinephrineDosingRecommendation
    beta_blocker_resistant_protocol: Optional[Dict[str, str]]
    crystalloid_resuscitation_guidelines: Dict[str, Union[float, str]]
    refractory_vasopressor_guidelines: Optional[Dict[str, Union[float, str]]]
    secondary_pharmacotherapy: List[Dict[str, str]]
    tryptase_kinetics_interpretation: Optional[Dict[str, Union[float, str, bool]]]
    biphasic_risk_stratification: Dict[str, Union[str, int]]


class AcuteAnaphylaxisDecisionEngine:
    """
    Clinical Decision Support Engine for Acute Anaphylaxis Staging,
    Diagnostic Certainty, Weight-Tiered Epinephrine Dosing, and Resuscitation.
    """

    @staticmethod
    def evaluate_pediatric_hypotension(age_years: float, sbp: int) -> bool:
        """
        Evaluates pediatric hypotension based on age-specific thresholds (PALS/AHA):
        - Term neonates (0-28 days): SBP < 60 mmHg
        - Infants (1-12 months): SBP < 70 mmHg
        - Children (1-10 years): SBP < 70 + (2 * age) mmHg
        - Children > 10 years and Adults: SBP < 90 mmHg
        """
        if age_years < (1.0 / 12.0):
            return sbp < 60
        elif age_years < 1.0:
            return sbp < 70
        elif age_years <= 10.0:
            return sbp < (70 + int(2 * age_years))
        else:
            return sbp < 90

    @classmethod
    def evaluate_wao_eaaci_criteria(
        cls, p: AnaphylaxisPatientPresentation
    ) -> Tuple[bool, str]:
        """
        Evaluates WAO/EAACI 2020 Diagnostic Criteria for Anaphylaxis:
        Criterion 1: Acute onset (minutes to several hours) of skin/mucosal symptoms
                     AND at least ONE of:
                     - Respiratory compromise
                     - Reduced BP / symptoms of end-organ dysfunction
                     - Severe gastrointestinal symptoms (crampy pain, vomiting)
        Criterion 2: Acute onset of hypotension, bronchospasm, or laryngeal involvement
                     AFTER exposure to a KNOWN or HIGHLY PROBABLE allergen, even WITHOUT skin signs.
        """
        has_skin = (
            p.generalized_urticaria
            or p.generalized_erythema_flushing
            or p.angioedema_lips_tongue_uvula_face
            or p.generalized_pruritus
        )

        has_resp = (
            p.audible_stridor_laryngeal_edema
            or p.wheezing_bronchospasm
            or p.severe_dyspnea_hypoxemia
            or p.spo2_percent < 92.0
            or (p.pef_percent_baseline is not None and p.pef_percent_baseline < 70.0)
        )

        is_hypotensive = p.measured_hypotension or cls.evaluate_pediatric_hypotension(
            p.age_years, p.systolic_bp_mmhg
        )

        has_circ = (
            is_hypotensive
            or p.shock_capillary_refill_delayed
            or p.syncope_loss_of_consciousness
            or p.incontinence
        )

        has_severe_gi = p.severe_crampy_abdominal_pain or p.recurrent_vomiting

        # Criterion 1: Skin + (Resp OR Circ OR Severe GI)
        if has_skin and (has_resp or has_circ or has_severe_gi):
            rationale = (
                "Meets WAO/EAACI 2020 Criterion 1: Acute onset of mucocutaneous symptoms "
                "with associated multi-system compromise ("
            )
            components = []
            if has_resp:
                components.append("Respiratory")
            if has_circ:
                components.append("Circulatory")
            if has_severe_gi:
                components.append("Severe Gastrointestinal")
            rationale += ", ".join(components) + ")."
            return True, rationale

        # Criterion 2: Known/Probable allergen + (Hypotension OR Bronchospasm OR Stridor)
        has_known_or_probable = p.known_allergen_exposure or p.probable_allergen_exposure
        has_isolated_severe_target = (
            is_hypotensive
            or p.wheezing_bronchospasm
            or p.audible_stridor_laryngeal_edema
            or p.syncope_loss_of_consciousness
        )

        if has_known_or_probable and has_isolated_severe_target:
            rationale = (
                "Meets WAO/EAACI 2020 Criterion 2: Acute onset of severe airway, respiratory, "
                "or circulatory collapse following exposure to a known/probable allergen, "
                "without requiring cutaneous manifestations."
            )
            return True, rationale

        return False, "Does not meet WAO/EAACI 2020 clinical criteria for acute anaphylaxis."

    @classmethod
    def evaluate_brighton_certainty(
        cls, p: AnaphylaxisPatientPresentation
    ) -> BrightonCertaintyLevel:
        """
        Stratifies presentation into Brighton Collaboration Diagnostic Certainty Levels.
        """
        # Major dermatological
        major_derm = (
            p.generalized_urticaria
            or p.generalized_erythema_flushing
            or p.angioedema_lips_tongue_uvula_face
        )

        # Major cardiovascular
        is_hypotensive = p.measured_hypotension or cls.evaluate_pediatric_hypotension(
            p.age_years, p.systolic_bp_mmhg
        )
        major_cardio = is_hypotensive or p.shock_capillary_refill_delayed or p.syncope_loss_of_consciousness

        # Major respiratory
        major_resp = (
            p.audible_stridor_laryngeal_edema
            or p.wheezing_bronchospasm
            or p.severe_dyspnea_hypoxemia
            or p.spo2_percent < 92.0
        )

        # Minor signs
        minor_cardio = p.heart_rate_bpm > 100 and not major_cardio
        minor_resp = p.rhinorrhea_sneezing_cough or (p.respiratory_rate_bpm > 24 and not major_resp)
        minor_gi = p.severe_crampy_abdominal_pain or p.recurrent_vomiting or p.diarrhea
        minor_derm = p.generalized_pruritus and not major_derm

        # Level 1: >=1 Major Derm AND (>=1 Major Cardio OR >=1 Major Resp)
        if major_derm and (major_cardio or major_resp):
            return BrightonCertaintyLevel.LEVEL_1

        # Level 2:
        # (a) >=1 Major Cardio AND >=1 Major Resp
        # (b) >=1 Major Derm AND (>=1 Minor Cardio OR Minor Resp) AND >=1 Other System
        if major_cardio and major_resp:
            return BrightonCertaintyLevel.LEVEL_2
        if major_derm and (minor_cardio or minor_resp) and minor_gi:
            return BrightonCertaintyLevel.LEVEL_2

        # Level 3:
        # >=1 Major Cardio OR >=1 Major Resp with minor supporting features
        if (major_cardio or major_resp) and (minor_gi or minor_derm or p.known_allergen_exposure):
            return BrightonCertaintyLevel.LEVEL_3

        return BrightonCertaintyLevel.INSUFFICIENT

    @classmethod
    def evaluate_wao_severity_grade(
        cls, p: AnaphylaxisPatientPresentation
    ) -> WAOSeverityGrade:
        """
        Grades severity based on World Allergy Organization (WAO) clinical scoring.
        """
        is_hypotensive = p.measured_hypotension or cls.evaluate_pediatric_hypotension(
            p.age_years, p.systolic_bp_mmhg
        )

        if p.heart_rate_bpm == 0 or p.systolic_bp_mmhg == 0:
            return WAOSeverityGrade.GRADE_5_FATAL

        if is_hypotensive or p.syncope_loss_of_consciousness or p.spo2_percent < 88.0:
            return WAOSeverityGrade.GRADE_4_LIFE_THREATENING

        if (
            p.wheezing_bronchospasm
            or p.audible_stridor_laryngeal_edema
            or p.recurrent_vomiting
            or p.severe_crampy_abdominal_pain
        ):
            return WAOSeverityGrade.GRADE_3_SEVERE

        if (
            p.rhinorrhea_sneezing_cough
            or p.heart_rate_bpm > 100
            or p.respiratory_rate_bpm > 20
        ):
            return WAOSeverityGrade.GRADE_2_MODERATE

        return WAOSeverityGrade.GRADE_1_MILD

    @staticmethod
    def calculate_epinephrine_dosing(
        weight_kg: float, is_adult: bool, severity: WAOSeverityGrade
    ) -> EpinephrineDosingRecommendation:
        """
        Calculates exact weight-tiered epinephrine autoinjector and manual dosing
        respecting pediatric and adult weight cutoffs.
        Standard IM dose: 0.01 mg/kg of 1:1000 (1 mg/mL); max single dose 0.5 mg.
        """
        calculated_exact_dose = min(0.5, round(weight_kg * 0.01, 2))

        # Device and recommended dose selection
        if weight_kg < 7.5:
            dose = max(0.05, round(weight_kg * 0.01, 2))
            device = EpinephrineDeliveryDevice.MANUAL_SYRINGE
            needle = "25G, 5/8-inch (16 mm) needle"
            instructions = (
                f"Draw {dose:.2f} mL (1 mg/mL = 1:1000) using a 1 mL tuberculin syringe. "
                "Inject into anterolateral mid-thigh. Never delay for autoinjector unavailability."
            )
        elif 7.5 <= weight_kg < 15.0:
            dose = 0.10
            device = EpinephrineDeliveryDevice.AUTOINJECTOR_INFANT_01
            needle = "22-25G, 0.5-inch needle"
            instructions = (
                "Administer 0.10 mg autoinjector (Auvi-Q 0.1 mg) or manual 0.10 mL (1:1000) "
                "into anterolateral mid-thigh."
            )
        elif 15.0 <= weight_kg < 30.0:
            dose = 0.15
            device = EpinephrineDeliveryDevice.AUTOINJECTOR_JUNIOR_015
            needle = "22G, 0.5-inch needle"
            instructions = (
                "Administer 0.15 mg autoinjector (EpiPen Jr / Auvi-Q 0.15 mg) into anterolateral mid-thigh. "
                "Hold firmly against thigh for 3 seconds."
            )
        elif 30.0 <= weight_kg < 50.0:
            dose = 0.30
            device = EpinephrineDeliveryDevice.AUTOINJECTOR_ADULT_03
            needle = "22G, 5/8-inch needle"
            instructions = (
                "Administer 0.30 mg autoinjector (EpiPen / Auvi-Q 0.3 mg) into anterolateral mid-thigh. "
                "Hold firmly against thigh for 3 seconds."
            )
        else:
            # Weight >= 50 kg
            if severity in [WAOSeverityGrade.GRADE_4_LIFE_THREATENING, WAOSeverityGrade.GRADE_5_FATAL]:
                dose = 0.50
                device = EpinephrineDeliveryDevice.AUTOINJECTOR_ADULT_05
                instructions = (
                    "Administer 0.50 mg IM (Emerade 0.5 mg autoinjector or 0.50 mL of 1:1000 solution "
                    "via 21-23G 1-inch needle) into anterolateral mid-thigh for severe circulatory collapse."
                )
            else:
                dose = 0.30
                device = EpinephrineDeliveryDevice.AUTOINJECTOR_ADULT_03
                instructions = (
                    "Administer 0.30 mg autoinjector (EpiPen / Auvi-Q 0.3 mg) into anterolateral mid-thigh. "
                    "If severe symptoms persist at 5 minutes, escalate to 0.50 mg IM."
                )
            needle = "21-23G, 1.0 to 1.5-inch needle (ensure adequate muscle penetration in obesity)"

        return EpinephrineDosingRecommendation(
            recommended_dose_mg=dose,
            delivery_device=device,
            route="Intramuscular (IM) strictly - subcutaneous and IV push bolus PROHIBITED in first-line",
            anatomical_site="Anterolateral Mid-Thigh (Vastus Lateralis)",
            needle_gauge_and_length=needle,
            repeat_frequency_minutes="Every 5 to 15 minutes as needed for persistent or refractory symptoms",
            max_single_dose_mg=0.50,
            clinical_instructions=instructions,
        )

    @staticmethod
    def evaluate_beta_blocker_refractoriness(
        p: AnaphylaxisPatientPresentation
    ) -> Optional[Dict[str, str]]:
        """
        Provides Glucagon rescue protocol for patients taking chronic beta-blockers
        who experience bradycardia, refractory hypotension, or poor response to IM epinephrine.
        """
        if not p.on_chronic_beta_blocker:
            return None

        return {
            "protocol_name": "Glucagon Secondary-Messenger Rescue for Beta-Blocker Anaphylaxis",
            "mechanism": (
                "Glucagon activates adenylate cyclase directly via non-adrenergic cell-surface receptors, "
                "bypassing blocked beta-1 and beta-2 receptors to increase intracellular cAMP, "
                "restoring cardiac inotropy and chronotropy without adrenergic receptor binding."
            ),
            "iv_bolus_dose": "Adult: 1.0 - 5.0 mg IV over 5 minutes (Pediatric: 20 - 30 mcg/kg, max 1.0 mg)",
            "continuous_iv_infusion": "2.0 to 10.0 mg/hour titrated to target MAP >= 65 mmHg",
            "side_effects_sentinel": (
                "Glucagon frequently triggers acute vomiting and nausea. Position patient in left lateral "
                "decubitus or protect airway immediately to prevent aspiration pneumonitis."
            ),
            "adjunct_agents": "Isoproterenol infusion or temporary transcutaneous/transvenous pacing if refractory bradycardia persists.",
        }

    @staticmethod
    def calculate_crystalloid_resuscitation(
        weight_kg: float, is_adult: bool, severity: WAOSeverityGrade
    ) -> Dict[str, Union[float, str]]:
        """
        Calculates rapid crystalloid fluid resuscitation volume for post-capillary venodilation
        and plasma extravasation. Up to 35% of circulating volume can extravasate in 10 minutes.
        """
        if is_adult:
            initial_bolus_ml = 1000.0 if severity != WAOSeverityGrade.GRADE_4_LIFE_THREATENING else 2000.0
            max_first_hour_ml = 4000.0
            rate_desc = "Pressure bag infusion of 1000-2000 mL Normosol-R, Plasmalyte, or Normal Saline over 15-30 min."
        else:
            initial_bolus_ml = round(weight_kg * 20.0, 1)
            max_first_hour_ml = round(weight_kg * 60.0, 1)
            rate_desc = f"Rapid push of 20 mL/kg ({initial_bolus_ml:.0f} mL) isotonic crystalloid over 10-20 min; repeat up to 3x."

        return {
            "fluid_type": "Isotonic Balanced Crystalloid (Plasmalyte-A, Lactated Ringer's, or 0.9% Normal Saline)",
            "initial_bolus_ml": initial_bolus_ml,
            "max_first_hour_ml": max_first_hour_ml,
            "administration_rate": rate_desc,
            "positioning_sentinel": (
                "PLACE PATIENT IN SUPINE POSITION WITH LEGS ELEVATED (Trendelenburg/Passive Leg Raise). "
                "NEVER ALLOW PATIENT TO SUDDENLY SIT UP OR STAND: Abrupt standing causes 'empty ventricle syndrome' "
                "and instantaneous pulseless electrical activity (PEA) arrest due to acute venous return cessation."
            ),
        }

    @staticmethod
    def calculate_refractory_vasopressors(
        weight_kg: float, is_adult: bool
    ) -> Dict[str, Union[float, str]]:
        """
        Provides continuous IV vasopressor infusion parameters for refractory anaphylactic shock
        unresponsive to 2 or more IM epinephrine doses and aggressive fluid resuscitation.
        """
        # IV Epinephrine infusion: 0.05 to 0.5 mcg/kg/min (or 2-10 mcg/min in adults)
        min_epi_rate_mcg_min = 2.0 if is_adult else round(weight_kg * 0.05, 2)
        max_epi_rate_mcg_min = 10.0 if is_adult else round(weight_kg * 0.50, 2)

        return {
            "indication": "Refractory Anaphylaxis failing >= 2 doses of IM Epinephrine + 20 mL/kg IV Crystalloids",
            "first_line_infusion": "Continuous IV Epinephrine Infusion via dedicated IV cannula with continuous cardiac monitoring",
            "adult_infusion_range": "2.0 to 10.0 mcg/min (titrate up by 1 mcg/min every 2-3 minutes to MAP >= 65 mmHg)",
            "pediatric_infusion_range": f"{min_epi_rate_mcg_min:.2f} to {max_epi_rate_mcg_min:.2f} mcg/kg/min",
            "push_dose_epinephrine_bridge": (
                "While preparing infusion: Push-Dose Epinephrine (10 mcg/mL). "
                "Dilute 1 mL of 1:10,000 (0.1 mg) in 9 mL Normal Saline. "
                "Administer 0.5 - 2.0 mL (5 - 20 mcg) IV every 2 to 5 minutes as temporizing bridge."
            ),
            "second_line_vasopressor": "Norepinephrine infusion (0.05 - 0.5 mcg/kg/min) for persistent profound vasodilation.",
            "vasopressin_refractory_rescue": "Vasopressin 0.03 units/min IV infusion for catecholamine-resistant vasodilatory collapse.",
        }

    @staticmethod
    def evaluate_tryptase_kinetics(
        acute_tryptase: Optional[float], baseline_tryptase: Optional[float]
    ) -> Optional[Dict[str, Union[float, str, bool]]]:
        """
        Interprets serum mast cell tryptase kinetics based on the international consensus formula:
        Acute Tryptase >= (1.2 * Baseline Tryptase) + 2.0 ug/L.
        """
        if acute_tryptase is None:
            return None

        if baseline_tryptase is None:
            return {
                "acute_tryptase_ug_l": acute_tryptase,
                "baseline_tryptase_ug_l": "Pending (Draw convalescent sample >= 24h post-resolution)",
                "diagnostic_threshold_calculated": "Requires baseline sample",
                "confirms_mast_cell_activation": acute_tryptase > 11.4,
                "interpretation": (
                    f"Acute serum tryptase is {acute_tryptase} ug/L (normal reference < 11.4 ug/L). "
                    "A convalescent sample must be drawn 24 hours later to evaluate the (1.2 * Baseline + 2) formula."
                ),
            }

        threshold = round((1.2 * baseline_tryptase) + 2.0, 2)
        is_positive = acute_tryptase >= threshold

        return {
            "acute_tryptase_ug_l": acute_tryptase,
            "baseline_tryptase_ug_l": baseline_tryptase,
            "diagnostic_threshold_calculated": threshold,
            "confirms_mast_cell_activation": is_positive,
            "interpretation": (
                f"Acute tryptase ({acute_tryptase} ug/L) vs threshold ({threshold} ug/L) based on "
                f"baseline ({baseline_tryptase} ug/L). "
                + (
                    "CONFIRMS MAST CELL ACTIVATION with high clinical specificity."
                    if is_positive
                    else "Does NOT meet threshold for systemic mast cell degranulation. Note: Clinical diagnosis takes precedence."
                )
            ),
        }

    @staticmethod
    def stratify_biphasic_risk(
        p: AnaphylaxisPatientPresentation, severity: WAOSeverityGrade
    ) -> Dict[str, Union[str, int]]:
        """
        Stratifies risk for biphasic anaphylactic recurrence to determine mandatory observation window.
        Biphasic risk factors: severe initial presentation (Grade 3-4), wide pulse pressure,
        delay in epinephrine > 30 min, multiple epinephrine doses required, history of biphasic reaction.
        """
        risk_score = 0
        reasons = []

        if severity in [WAOSeverityGrade.GRADE_3_SEVERE, WAOSeverityGrade.GRADE_4_LIFE_THREATENING]:
            risk_score += 2
            reasons.append("Severe initial clinical presentation (Grade 3 or 4)")

        if p.minutes_since_exposure > 30:
            risk_score += 1
            reasons.append("Delayed presentation/epinephrine > 30 minutes from exposure")

        if p.history_of_biphasic_reaction:
            risk_score += 2
            reasons.append("Prior history of biphasic anaphylaxis")

        if p.history_of_asthma:
            risk_score += 1
            reasons.append("Underlying active asthma / reactive airway disease")

        if p.trigger_type.lower() == "medication":
            risk_score += 1
            reasons.append("Drug-induced anaphylaxis (higher incidence of protracted/biphasic course)")

        if risk_score >= 3:
            category = "HIGH BIPHASIC RISK"
            observation_hours = 12
            rec = (
                "Mandatory 12 to 24 hour inpatient/ICU observation. High probability of secondary "
                "inflammatory recrudescence. Discharge with two unexpired epinephrine autoinjectors."
            )
        elif risk_score >= 1:
            category = "MODERATE BIPHASIC RISK"
            observation_hours = 6
            rec = (
                "Minimum 6 to 8 hour emergency department observation window following complete "
                "resolution of all symptoms. Prescribe autoinjector pair upon discharge."
            )
        else:
            category = "LOW BIPHASIC RISK"
            observation_hours = 4
            rec = "Minimum 4 to 6 hour observation following symptom resolution and epinephrine response."

        return {
            "risk_category": category,
            "risk_score": risk_score,
            "mandatory_observation_hours": observation_hours,
            "clinical_recommendation": rec,
            "risk_factors_present": "; ".join(reasons) if reasons else "No high-risk features identified",
        }

    @classmethod
    def run_clinical_evaluation(
        cls, p: AnaphylaxisPatientPresentation
    ) -> AnaphylaxisClinicalDecisionReport:
        """
        Runs the full end-to-end clinical anaphylaxis decision-support engine.
        """
        meets_wao, wao_rationale = cls.evaluate_wao_eaaci_criteria(p)
        brighton_level = cls.evaluate_brighton_certainty(p)
        severity_grade = cls.evaluate_wao_severity_grade(p)
        epi_rec = cls.calculate_epinephrine_dosing(p.weight_kg, p.is_adult, severity_grade)
        bb_protocol = cls.evaluate_beta_blocker_refractoriness(p)
        crystalloids = cls.calculate_crystalloid_resuscitation(p.weight_kg, p.is_adult, severity_grade)

        vasopressors = None
        if severity_grade in [WAOSeverityGrade.GRADE_4_LIFE_THREATENING, WAOSeverityGrade.GRADE_5_FATAL]:
            vasopressors = cls.calculate_refractory_vasopressors(p.weight_kg, p.is_adult)

        secondary_tx = [
            {
                "drug": "Albuterol (Salbutamol) Inhalation",
                "dose": "2.5 to 5.0 mg nebulized in 3 mL Normal Saline every 20 min as needed",
                "role": "Adjunctive bronchodilator for wheezing/bronchospasm. DOES NOT treat mucosal edema or hypotension.",
            },
            {
                "drug": "Cetirizine / Diphenhydramine (H1 Antihistamine)",
                "dose": "Cetirizine 10 mg IV/oral OR Diphenhydramine 25-50 mg IV/IM (Pediatric: 1 mg/kg, max 50 mg)",
                "role": "Symptomatic relief of pruritus, urticaria, and angioedema. Second-line; never replaces epinephrine.",
            },
            {
                "drug": "Famotidine (H2 Antihistamine)",
                "dose": "Famotidine 20 mg IV over 2 min (Pediatric: 0.5 mg/kg, max 20 mg)",
                "role": "Synergistic H1+H2 blockade for refractory cutaneous flushing and vasodilation.",
            },
            {
                "drug": "Methylprednisolone / Dexamethasone (Corticosteroids)",
                "dose": "Methylprednisolone 1-2 mg/kg IV (max 125 mg) OR Dexamethasone 10 mg IV",
                "role": "Theoretical reduction in biphasic reaction severity. Delayed onset (4-6 hours); zero acute shock reversal.",
            },
        ]

        tryptase_report = cls.evaluate_tryptase_kinetics(
            p.acute_serum_tryptase_ug_l, p.baseline_serum_tryptase_ug_l
        )

        biphasic_report = cls.stratify_biphasic_risk(p, severity_grade)

        return AnaphylaxisClinicalDecisionReport(
            meets_wao_criteria=meets_wao,
            wao_diagnostic_rationale=wao_rationale,
            brighton_level=brighton_level,
            wao_severity_grade=severity_grade,
            epinephrine_recommendation=epi_rec,
            beta_blocker_resistant_protocol=bb_protocol,
            crystalloid_resuscitation_guidelines=crystalloids,
            refractory_vasopressor_guidelines=vasopressors,
            secondary_pharmacotherapy=secondary_tx,
            tryptase_kinetics_interpretation=tryptase_report,
            biphasic_risk_stratification=biphasic_report,
        )


# =====================================================================
# SELF-CONTAINED VERIFICATION & CLINICAL VALIDATION SUITE
# =====================================================================

def verify_clinical_scenarios():
    print("=" * 80)
    print("OpenPHR Cookbook 378: Acute Anaphylaxis WAO/EAACI & Resuscitation Suite")
    print("=" * 80)

    # Test Case 1: Pediatric Peanut Anaphylaxis (22 kg, Grade 3, Wheezing + Hives)
    pt_peds = AnaphylaxisPatientPresentation(
        age_years=6.0,
        weight_kg=22.0,
        is_adult=False,
        heart_rate_bpm=135,
        systolic_bp_mmhg=88,  # Normal for 6yo is > 70 + (2*6) = 82
        diastolic_bp_mmhg=55,
        spo2_percent=91.0,
        respiratory_rate_bpm=32,
        known_allergen_exposure=True,
        probable_allergen_exposure=True,
        trigger_type="Food",
        minutes_since_exposure=15,
        generalized_urticaria=True,
        generalized_erythema_flushing=True,
        angioedema_lips_tongue_uvula_face=True,
        generalized_pruritus=True,
        audible_stridor_laryngeal_edema=False,
        wheezing_bronchospasm=True,
        severe_dyspnea_hypoxemia=True,
        rhinorrhea_sneezing_cough=True,
        pef_percent_baseline=60.0,
        history_of_asthma=True,
        acute_serum_tryptase_ug_l=18.5,
        baseline_serum_tryptase_ug_l=4.2,
    )

    report_peds = AcuteAnaphylaxisDecisionEngine.run_clinical_evaluation(pt_peds)

    assert report_peds.meets_wao_criteria is True, "Peds must meet WAO criteria"
    assert report_peds.brighton_level == BrightonCertaintyLevel.LEVEL_1, "Must be Brighton Level 1"
    assert report_peds.wao_severity_grade == WAOSeverityGrade.GRADE_3_SEVERE, "Must be Grade 3 Severe"
    assert report_peds.epinephrine_recommendation.recommended_dose_mg == 0.15, "22 kg child receives 0.15 mg autoinjector"
    assert report_peds.tryptase_kinetics_interpretation["confirms_mast_cell_activation"] is True

    print("[*] Test Case 1 (Pediatric Food Anaphylaxis - 22 kg) PASSED")
    print(f"    - WAO Criteria: {report_peds.meets_wao_criteria} | Severity: {report_peds.wao_severity_grade.value}")
    print(f"    - Recommended Epinephrine: {report_peds.epinephrine_recommendation.recommended_dose_mg} mg IM ({report_peds.epinephrine_recommendation.delivery_device.value})")
    print(f"    - Tryptase Result: {report_peds.tryptase_kinetics_interpretation['interpretation']}")

    # Test Case 2: Adult Beta-Blocker Hymenoptera Venom Anaphylactic Shock (75 kg, Grade 4)
    pt_adult_bb = AnaphylaxisPatientPresentation(
        age_years=58.0,
        weight_kg=75.0,
        is_adult=True,
        heart_rate_bpm=52,  # Relative bradycardia from beta-blocker
        systolic_bp_mmhg=72,  # Profound hypotension
        diastolic_bp_mmhg=40,
        spo2_percent=87.0,
        respiratory_rate_bpm=28,
        known_allergen_exposure=True,
        probable_allergen_exposure=True,
        trigger_type="Venom",
        minutes_since_exposure=20,
        generalized_urticaria=False,  # Anaphylactic shock without hives
        generalized_erythema_flushing=False,
        angioedema_lips_tongue_uvula_face=False,
        generalized_pruritus=False,
        audible_stridor_laryngeal_edema=True,
        wheezing_bronchospasm=True,
        severe_dyspnea_hypoxemia=True,
        rhinorrhea_sneezing_cough=False,
        measured_hypotension=True,
        shock_capillary_refill_delayed=True,
        syncope_loss_of_consciousness=True,
        on_chronic_beta_blocker=True,
        history_of_prior_anaphylaxis=True,
    )

    report_adult = AcuteAnaphylaxisDecisionEngine.run_clinical_evaluation(pt_adult_bb)

    assert report_adult.meets_wao_criteria is True, "Adult without skin signs meets WAO Criterion 2"
    assert report_adult.wao_severity_grade == WAOSeverityGrade.GRADE_4_LIFE_THREATENING, "Must be Grade 4 Life-Threatening"
    assert report_adult.epinephrine_recommendation.recommended_dose_mg == 0.50, "Life-threatening adult collapse gets 0.50 mg"
    assert report_adult.beta_blocker_resistant_protocol is not None, "Must trigger Glucagon rescue protocol"
    assert report_adult.refractory_vasopressor_guidelines is not None, "Must trigger vasopressor protocol"

    print("[*] Test Case 2 (Adult Venom Shock on Beta-Blocker - 75 kg) PASSED")
    print(f"    - WAO Criteria: {report_adult.meets_wao_criteria} (Without Cutaneous Signs - Criterion 2)")
    print(f"    - Recommended Epinephrine: {report_adult.epinephrine_recommendation.recommended_dose_mg} mg IM ({report_adult.epinephrine_recommendation.anatomical_site})")
    print(f"    - Glucagon Rescue: {report_adult.beta_blocker_resistant_protocol['iv_bolus_dose']}")
    print(f"    - Vasopressor Rescue: {report_adult.refractory_vasopressor_guidelines['first_line_infusion']}")
    print(f"    - Positioning Sentinel: {report_adult.crystalloid_resuscitation_guidelines['positioning_sentinel'][:75]}...")

    print("\n>>> ALL CLINICAL VERIFICATION TESTS PASSED (100% CONCORDANCE) <<<")


if __name__ == "__main__":
    verify_clinical_scenarios()