@precisa-saude/fhir-calculators 0.1.0

package/dist/index.cjs

@@ -0,0 +1,981 @@
+"use strict";Object.defineProperty(exports, "__esModule", {value: true}); function _nullishCoalesce(lhs, rhsFn) { if (lhs != null) { return lhs; } else { return rhsFn(); } } function _optionalChain(ops) { let lastAccessLHS = undefined; let value = ops[0]; let i = 1; while (i < ops.length) { const op = ops[i]; const fn = ops[i + 1]; i += 2; if ((op === 'optionalAccess' || op === 'optionalCall') && value == null) { return undefined; } if (op === 'access' || op === 'optionalAccess') { lastAccessLHS = value; value = fn(value); } else if (op === 'call' || op === 'optionalCall') { value = fn((...args) => value.call(lastAccessLHS, ...args)); lastAccessLHS = undefined; } } return value; }var __defProp = Object.defineProperty;
+var __export = (target, all) => {
+  for (var name in all)
+    __defProp(target, name, { get: all[name], enumerable: true });
+};
+
+// src/phenoage/index.ts
+var phenoage_exports = {};
+__export(phenoage_exports, {
+  BIOMARKER_DESCRIPTIONS_PT: () => BIOMARKER_DESCRIPTIONS_PT,
+  BIOMARKER_LAB_INFO: () => BIOMARKER_LAB_INFO,
+  BIOMARKER_NAMES_PT: () => BIOMARKER_NAMES_PT,
+  BIOMARKER_RANGES: () => BIOMARKER_RANGES,
+  CONVERSION_FACTORS: () => CONVERSION_FACTORS,
+  FHIR_CODE_TO_PHENOAGE: () => FHIR_CODE_TO_PHENOAGE,
+  GOMPERTZ_PARAMS: () => GOMPERTZ_PARAMS,
+  PHENOAGE_COEFFICIENTS: () => PHENOAGE_COEFFICIENTS,
+  REQUIRED_BIOMARKERS: () => REQUIRED_BIOMARKERS,
+  TARGET_UNITS: () => TARGET_UNITS,
+  autoConvertToSI: () => autoConvertToSI,
+  calculatePhenoAge: () => calculatePhenoAge,
+  convertToSI: () => convertToSI,
+  needsConversion: () => needsConversion,
+  validateBiomarkers: () => validateBiomarkers
+});
+
+// src/phenoage/constants.ts
+var PHENOAGE_COEFFICIENTS = {
+  age: 0.0804,
+  albumin: -0.0336,
+  alkalinePhosphatase: 19e-4,
+  creatinine: 95e-4,
+  glucose: 0.1953,
+  intercept: -19.9067,
+  logCrp: 0.0954,
+  lymphocytePercent: -0.012,
+  mcv: 0.0268,
+  rdw: 0.3306,
+  wbc: 0.0554
+};
+var GOMPERTZ_PARAMS = {
+  ageCoefficient: 0.090165,
+  baseAge: 141.50225,
+  gamma: 76927e-7,
+  mortalityConstant: 553e-5
+};
+var BIOMARKER_RANGES = {
+  albumin: { max: 60, min: 10, typical: { max: 50, min: 35 }, unit: "g/L" },
+  alkalinePhosphatase: { max: 500, min: 10, typical: { max: 130, min: 40 }, unit: "U/L" },
+  chronologicalAge: { max: 120, min: 18, typical: { max: 100, min: 18 }, unit: "anos" },
+  creatinine: { max: 500, min: 20, typical: { max: 110, min: 60 }, unit: "\u03BCmol/L" },
+  crp: { max: 200, min: 0.01, typical: { max: 3, min: 0 }, unit: "mg/L" },
+  glucose: { max: 30, min: 2, typical: { max: 6, min: 4 }, unit: "mmol/L" },
+  lymphocytePercent: { max: 80, min: 1, typical: { max: 40, min: 20 }, unit: "%" },
+  mcv: { max: 150, min: 50, typical: { max: 100, min: 80 }, unit: "fL" },
+  rdw: { max: 25, min: 8, typical: { max: 15, min: 11 }, unit: "%" },
+  wbc: { max: 30, min: 1, typical: { max: 11, min: 4 }, unit: "10^9/L" }
+};
+var FHIR_CODE_TO_PHENOAGE = {
+  Albumin: "albumin",
+  AlkalinePhosphatase: "alkalinePhosphatase",
+  Creatinine: "creatinine",
+  CRP: "crp",
+  Glucose: "glucose",
+  Lymphocytes: "lymphocytePercent",
+  MCV: "mcv",
+  RDW: "rdw",
+  WBC: "wbc"
+};
+var REQUIRED_BIOMARKERS = [
+  "Albumin",
+  "Creatinine",
+  "Glucose",
+  "CRP",
+  "Lymphocytes",
+  "MCV",
+  "RDW",
+  "AlkalinePhosphatase",
+  "WBC"
+];
+var BIOMARKER_NAMES_PT = {
+  age: "Idade",
+  albumin: "Albumina",
+  alkalinePhosphatase: "Fosfatase Alcalina",
+  creatinine: "Creatinina",
+  crp: "PCR",
+  glucose: "Glicose",
+  intercept: "Intercepto",
+  lymphocytePercent: "Linf\xF3citos",
+  mcv: "VCM",
+  rdw: "RDW",
+  wbc: "Leuc\xF3citos"
+};
+var BIOMARKER_DESCRIPTIONS_PT = {
+  age: "Sua idade cronol\xF3gica em anos",
+  albumin: "Prote\xEDna do f\xEDgado que indica estado nutricional e fun\xE7\xE3o hep\xE1tica",
+  alkalinePhosphatase: "Enzima que reflete sa\xFAde do f\xEDgado e dos ossos",
+  creatinine: "Marcador de fun\xE7\xE3o renal produzido pelos m\xFAsculos",
+  crp: "Prote\xEDna C-reativa, indica inflama\xE7\xE3o no corpo",
+  glucose: "N\xEDvel de a\xE7\xFAcar no sangue, relacionado ao metabolismo",
+  intercept: "Constante da f\xF3rmula de regress\xE3o",
+  lymphocytePercent: "C\xE9lulas de defesa do sistema imunol\xF3gico",
+  mcv: "Volume m\xE9dio das hem\xE1cias, indica sa\xFAde das c\xE9lulas vermelhas",
+  rdw: "Varia\xE7\xE3o no tamanho das hem\xE1cias, marcador de inflama\xE7\xE3o",
+  wbc: "Total de c\xE9lulas brancas, indica estado imunol\xF3gico"
+};
+var BIOMARKER_LAB_INFO = {
+  Albumin: {
+    loincCode: "1751-7",
+    nameEn: "Albumin [Mass/volume] in Serum or Plasma",
+    namePt: "Albumina"
+  },
+  AlkalinePhosphatase: {
+    loincCode: "6768-6",
+    nameEn: "Alkaline phosphatase [Enzymatic activity/volume] in Serum or Plasma",
+    namePt: "Fosfatase Alcalina"
+  },
+  Creatinine: {
+    loincCode: "2160-0",
+    nameEn: "Creatinine [Mass/volume] in Serum or Plasma",
+    namePt: "Creatinina"
+  },
+  CRP: {
+    loincCode: "1988-5",
+    nameEn: "C reactive protein [Mass/volume] in Serum or Plasma",
+    namePt: "Prote\xEDna C-Reativa (PCR)"
+  },
+  Glucose: {
+    loincCode: "2345-7",
+    nameEn: "Glucose [Mass/volume] in Serum or Plasma",
+    namePt: "Glicose"
+  },
+  Lymphocytes: {
+    loincCode: "736-9",
+    nameEn: "Lymphocytes/100 leukocytes in Blood by Automated count",
+    namePt: "Linf\xF3citos (%)"
+  },
+  MCV: {
+    loincCode: "787-2",
+    nameEn: "MCV [Entitic volume] by Automated count",
+    namePt: "Volume Corpuscular M\xE9dio (VCM)"
+  },
+  RDW: {
+    loincCode: "788-0",
+    nameEn: "Erythrocyte distribution width [Ratio] by Automated count",
+    namePt: "Amplitude de Distribui\xE7\xE3o dos Eritr\xF3citos (RDW)"
+  },
+  WBC: {
+    loincCode: "6690-2",
+    nameEn: "Leukocytes [#/volume] in Blood by Automated count",
+    namePt: "Contagem de Leuc\xF3citos"
+  }
+};
+
+// src/phenoage/calculator.ts
+var calculateLinearPredictor = (input) => {
+  const logCrp = Math.log(Math.max(input.crp, 0.1));
+  const components = [
+    {
+      coefficient: PHENOAGE_COEFFICIENTS.albumin,
+      key: "albumin",
+      unit: BIOMARKER_RANGES.albumin.unit,
+      value: input.albumin
+    },
+    {
+      coefficient: PHENOAGE_COEFFICIENTS.creatinine,
+      key: "creatinine",
+      unit: BIOMARKER_RANGES.creatinine.unit,
+      value: input.creatinine
+    },
+    {
+      coefficient: PHENOAGE_COEFFICIENTS.glucose,
+      key: "glucose",
+      unit: BIOMARKER_RANGES.glucose.unit,
+      value: input.glucose
+    },
+    {
+      coefficient: PHENOAGE_COEFFICIENTS.logCrp,
+      displayValue: `ln(${input.crp.toFixed(2)})`,
+      key: "crp",
+      unit: "ln(mg/L)",
+      value: logCrp
+    },
+    {
+      coefficient: PHENOAGE_COEFFICIENTS.lymphocytePercent,
+      key: "lymphocytePercent",
+      unit: BIOMARKER_RANGES.lymphocytePercent.unit,
+      value: input.lymphocytePercent
+    },
+    {
+      coefficient: PHENOAGE_COEFFICIENTS.mcv,
+      key: "mcv",
+      unit: BIOMARKER_RANGES.mcv.unit,
+      value: input.mcv
+    },
+    {
+      coefficient: PHENOAGE_COEFFICIENTS.rdw,
+      key: "rdw",
+      unit: BIOMARKER_RANGES.rdw.unit,
+      value: input.rdw
+    },
+    {
+      coefficient: PHENOAGE_COEFFICIENTS.alkalinePhosphatase,
+      key: "alkalinePhosphatase",
+      unit: BIOMARKER_RANGES.alkalinePhosphatase.unit,
+      value: input.alkalinePhosphatase
+    },
+    {
+      coefficient: PHENOAGE_COEFFICIENTS.wbc,
+      key: "wbc",
+      unit: BIOMARKER_RANGES.wbc.unit,
+      value: input.wbc
+    },
+    {
+      coefficient: PHENOAGE_COEFFICIENTS.age,
+      displayValue: `${Math.round(input.chronologicalAge)} anos`,
+      key: "age",
+      unit: "anos",
+      value: input.chronologicalAge
+    }
+  ];
+  const breakdown = components.map((c) => ({
+    coefficient: c.coefficient,
+    contribution: Math.round(c.coefficient * c.value * 1e4) / 1e4,
+    key: c.key,
+    name: _nullishCoalesce(BIOMARKER_NAMES_PT[c.key], () => ( c.key)),
+    valueWithUnit: c.displayValue ? `${c.displayValue}` : `${c.value.toFixed(2)} ${c.unit}`
+  }));
+  breakdown.push({
+    coefficient: PHENOAGE_COEFFICIENTS.intercept,
+    contribution: PHENOAGE_COEFFICIENTS.intercept,
+    key: "intercept",
+    name: _nullishCoalesce(BIOMARKER_NAMES_PT["intercept"], () => ( "Intercepto")),
+    valueWithUnit: "-"
+  });
+  const xb = PHENOAGE_COEFFICIENTS.intercept + components.reduce((sum, c) => sum + c.coefficient * c.value, 0);
+  return { breakdown, xb };
+};
+var calculateMortalityScore = (xb) => {
+  const { gamma } = GOMPERTZ_PARAMS;
+  const hazardRatio = Math.exp(xb);
+  const cumulativeHazard = hazardRatio * (Math.exp(120 * gamma) - 1) / gamma;
+  return 1 - Math.exp(-cumulativeHazard);
+};
+var mortalityScoreToPhenoAge = (mortalityScore) => {
+  const { ageCoefficient, baseAge, mortalityConstant } = GOMPERTZ_PARAMS;
+  const innerLog = Math.log(1 - mortalityScore);
+  const outerLog = Math.log(-mortalityConstant * innerLog);
+  return baseAge + outerLog / ageCoefficient;
+};
+var calculatePhenoAge = (input) => {
+  const inputValues = {
+    albumin: input.albumin,
+    alkalinePhosphatase: input.alkalinePhosphatase,
+    chronologicalAge: input.chronologicalAge,
+    creatinine: input.creatinine,
+    crp: input.crp,
+    glucose: input.glucose,
+    lymphocytePercent: input.lymphocytePercent,
+    mcv: input.mcv,
+    rdw: input.rdw,
+    wbc: input.wbc
+  };
+  for (const [key, value] of Object.entries(inputValues)) {
+    if (typeof value !== "number" || Number.isNaN(value)) {
+      throw new Error(`Invalid input value for ${key}: ${value}`);
+    }
+  }
+  const { breakdown, xb } = calculateLinearPredictor(input);
+  const mortalityScore = calculateMortalityScore(xb);
+  const phenoAge = mortalityScoreToPhenoAge(mortalityScore);
+  const ageDifference = phenoAge - input.chronologicalAge;
+  return {
+    ageDifference: Math.round(ageDifference * 10) / 10,
+    breakdown,
+    calculatedAt: (/* @__PURE__ */ new Date()).toISOString(),
+    chronologicalAge: input.chronologicalAge,
+    linearPredictor: Math.round(xb * 1e4) / 1e4,
+    mortalityScore: Math.round(mortalityScore * 1e4) / 1e4,
+    phenoAge: Math.round(phenoAge * 10) / 10
+  };
+};
+var validateBiomarkers = (input) => {
+  const errors = [];
+  const checkRange = (value, key, name) => {
+    const range = BIOMARKER_RANGES[key];
+    if (value < range.min || value > range.max) {
+      errors.push(`${name} (${value}) fora do intervalo esperado [${range.min}-${range.max}]`);
+    }
+  };
+  checkRange(input.albumin, "albumin", "Albumina");
+  checkRange(input.creatinine, "creatinine", "Creatinina");
+  checkRange(input.glucose, "glucose", "Glicose");
+  checkRange(input.crp, "crp", "PCR");
+  checkRange(input.lymphocytePercent, "lymphocytePercent", "Linf\xF3citos");
+  checkRange(input.mcv, "mcv", "VCM");
+  checkRange(input.rdw, "rdw", "RDW");
+  checkRange(input.alkalinePhosphatase, "alkalinePhosphatase", "Fosfatase Alcalina");
+  checkRange(input.wbc, "wbc", "Leuc\xF3citos");
+  checkRange(input.chronologicalAge, "chronologicalAge", "Idade");
+  if (input.crp <= 0) {
+    errors.push("PCR deve ser maior que 0");
+  }
+  return {
+    errors,
+    isValid: errors.length === 0
+  };
+};
+
+// src/phenoage/unit-converters.ts
+var CONVERSION_FACTORS = {
+  albumin: {
+    "g/dL": 10,
+    // g/dL → g/L
+    "g/L": 1
+  },
+  alkalinePhosphatase: {
+    "U/L": 1
+  },
+  creatinine: {
+    "mg/dL": 88.4,
+    // mg/dL → μmol/L
+    "umol/L": 1,
+    "\u03BCmol/L": 1
+  },
+  crp: {
+    "mg/dL": 10,
+    // mg/dL → mg/L
+    "mg/L": 1
+  },
+  glucose: {
+    "mg/dL": 1 / 18.0182,
+    // mg/dL → mmol/L
+    "mmol/L": 1
+  },
+  lymphocytePercent: {
+    "%": 1
+  },
+  mcv: {
+    fL: 1
+  },
+  rdw: {
+    "%": 1
+  },
+  wbc: {
+    "/uL": 1e-3,
+    "/\xB5L": 1e-3,
+    // cells/μL → 10^9/L
+    "10^9/L": 1,
+    "1000/\u03BCL": 1,
+    "10\xB3/\xB5L": 1,
+    // Same as 10^9/L
+    "K/uL": 1,
+    "K/\xB5L": 1,
+    "Thousand/uL": 1,
+    // Brazilian labs often use this format
+    "thousand/uL": 1,
+    "Thousand/\xB5L": 1,
+    "thousand/\xB5L": 1
+  }
+};
+var TARGET_UNITS = {
+  albumin: "g/L",
+  alkalinePhosphatase: "U/L",
+  creatinine: "\u03BCmol/L",
+  crp: "mg/L",
+  glucose: "mmol/L",
+  lymphocytePercent: "%",
+  mcv: "fL",
+  rdw: "%",
+  wbc: "10^9/L"
+};
+var convertToSI = (biomarker, value, sourceUnit) => {
+  const factors = CONVERSION_FACTORS[biomarker];
+  if (!factors) {
+    throw new Error(`Unknown biomarker: ${biomarker}`);
+  }
+  const normalizedUnit = sourceUnit.trim();
+  const factor = factors[normalizedUnit];
+  if (factor === void 0) {
+    const normalizedLower = normalizedUnit.toLowerCase();
+    const exactMatch = Object.keys(factors).find((key) => key.toLowerCase() === normalizedLower);
+    if (exactMatch) {
+      return value * factors[exactMatch];
+    }
+    const sortedKeys = Object.keys(factors).sort((a, b) => b.length - a.length);
+    const partialMatch = sortedKeys.find((key) => normalizedLower.includes(key.toLowerCase()));
+    if (partialMatch) {
+      return value * factors[partialMatch];
+    }
+    throw new Error(`Unknown unit "${sourceUnit}" for ${biomarker}`);
+  }
+  return value * factor;
+};
+var needsConversion = (biomarker, sourceUnit) => {
+  const targetUnit = TARGET_UNITS[biomarker];
+  if (!targetUnit) return false;
+  const normalizedSource = sourceUnit.trim().toLowerCase();
+  const normalizedTarget = targetUnit.toLowerCase();
+  return normalizedSource !== normalizedTarget;
+};
+var autoConvertToSI = (biomarker, value, unit) => {
+  if (unit) {
+    try {
+      const converted = convertToSI(biomarker, value, unit);
+      const wasConverted = needsConversion(biomarker, unit);
+      return {
+        unit: TARGET_UNITS[biomarker] || unit,
+        value: converted,
+        wasConverted
+      };
+    } catch (e) {
+    }
+  }
+  switch (biomarker) {
+    case "albumin":
+      if (value < 10) {
+        return { unit: "g/L", value: value * 10, wasConverted: true };
+      }
+      return { unit: "g/L", value, wasConverted: false };
+    case "creatinine":
+      if (value < 15) {
+        return { unit: "\u03BCmol/L", value: value * 88.4, wasConverted: true };
+      }
+      return { unit: "\u03BCmol/L", value, wasConverted: false };
+    case "glucose":
+      if (value > 20) {
+        return { unit: "mmol/L", value: value / 18.0182, wasConverted: true };
+      }
+      return { unit: "mmol/L", value, wasConverted: false };
+    case "wbc":
+      if (value > 100) {
+        return { unit: "10^9/L", value: value / 1e3, wasConverted: true };
+      }
+      return { unit: "10^9/L", value, wasConverted: false };
+    default:
+      return { unit: TARGET_UNITS[biomarker] || "", value, wasConverted: false };
+  }
+};
+
+// src/brdmrisc/index.ts
+var brdmrisc_exports = {};
+__export(brdmrisc_exports, {
+  BIOMARKER_NAMES_PT: () => BIOMARKER_NAMES_PT2,
+  BIOMARKER_RANGES: () => BIOMARKER_RANGES2,
+  BIOMARKER_UNITS: () => BIOMARKER_UNITS,
+  BRDMRISC_BIOMARKER_CODES: () => BRDMRISC_BIOMARKER_CODES,
+  BRDMRISC_MODELS: () => BRDMRISC_MODELS,
+  CONVERSION_FACTORS: () => CONVERSION_FACTORS2,
+  FHIR_CODE_TO_BRDMRISC: () => FHIR_CODE_TO_BRDMRISC,
+  FOLLOW_UP_YEARS: () => FOLLOW_UP_YEARS,
+  LAB_MODEL_PRIORITY: () => LAB_MODEL_PRIORITY,
+  LAB_ONLY_MODELS: () => LAB_ONLY_MODELS,
+  RISK_THRESHOLDS: () => RISK_THRESHOLDS,
+  TARGET_UNITS: () => TARGET_UNITS2,
+  autoConvertToTarget: () => autoConvertToTarget,
+  calculateBrDMrisc: () => calculateBrDMrisc,
+  classifyRisk: () => classifyRisk,
+  convertToTargetUnit: () => convertToTargetUnit,
+  selectModel: () => selectModel,
+  validateBiomarkers: () => validateBiomarkers2
+});
+
+// src/brdmrisc/constants.ts
+var FOLLOW_UP_YEARS = 7.4;
+var BRDMRISC_MODELS = [
+  // === Lab-only models (MVP) ===
+  {
+    auc: 0.776,
+    coefficients: {
+      fpg: 0.0352
+    },
+    id: 1,
+    intercept: -5.8282,
+    isLabOnly: true,
+    name: "FPG only",
+    namePt: "Apenas Glicemia de Jejum",
+    requiredBiomarkers: ["fpg"]
+  },
+  {
+    auc: 0.668,
+    coefficients: {
+      hba1c: 0.731
+    },
+    id: 2,
+    intercept: -6.3199,
+    isLabOnly: true,
+    name: "HbA1c only",
+    namePt: "Apenas HbA1c",
+    requiredBiomarkers: ["hba1c"]
+  },
+  {
+    auc: 0.793,
+    coefficients: {
+      fpg: 0.029,
+      hba1c: 0.4427
+    },
+    id: 3,
+    intercept: -7.37,
+    isLabOnly: true,
+    name: "FPG + HbA1c",
+    namePt: "Glicemia + HbA1c",
+    requiredBiomarkers: ["fpg", "hba1c"]
+  },
+  {
+    auc: 0.79,
+    coefficients: {
+      fpg: 0.0345,
+      triglycerides: 17e-4
+    },
+    id: 4,
+    intercept: -5.9706,
+    isLabOnly: true,
+    name: "FPG + Triglycerides",
+    namePt: "Glicemia + Triglicer\xEDdeos",
+    requiredBiomarkers: ["fpg", "triglycerides"]
+  },
+  {
+    auc: 0.796,
+    coefficients: {
+      fpg: 0.0338,
+      hdlc: -0.0161,
+      triglycerides: 11e-4
+    },
+    id: 5,
+    intercept: -5.3879,
+    isLabOnly: true,
+    name: "FPG + Lipids",
+    namePt: "Glicemia + Lip\xEDdios",
+    requiredBiomarkers: ["fpg", "triglycerides", "hdlc"]
+  },
+  {
+    auc: 0.813,
+    coefficients: {
+      fpg: 0.0267,
+      hba1c: 0.3943,
+      hdlc: -0.0149,
+      triglycerides: 9e-4
+    },
+    id: 6,
+    intercept: -6.9195,
+    isLabOnly: true,
+    name: "FPG + HbA1c + Lipids",
+    namePt: "Glicemia + HbA1c + Lip\xEDdios",
+    requiredBiomarkers: ["fpg", "hba1c", "triglycerides", "hdlc"]
+  },
+  // === Clinical models (Phase 2 — require user input) ===
+  {
+    auc: 0.744,
+    coefficients: {
+      bmi: 0.0642,
+      familyHistory: 0.5915,
+      waist: 0.0111
+    },
+    id: 7,
+    intercept: -6.5023,
+    isLabOnly: false,
+    name: "Clinical only",
+    namePt: "Apenas Cl\xEDnico",
+    requiredBiomarkers: ["bmi", "waist", "familyHistory"]
+  },
+  {
+    auc: 0.8,
+    coefficients: {
+      bmi: 0.0454,
+      familyHistory: 0.475,
+      fpg: 0.0305,
+      waist: 47e-4
+    },
+    id: 8,
+    intercept: -7.3297,
+    isLabOnly: false,
+    name: "Clinical + FPG",
+    namePt: "Cl\xEDnico + Glicemia",
+    requiredBiomarkers: ["bmi", "waist", "familyHistory", "fpg"]
+  },
+  {
+    auc: 0.725,
+    coefficients: {
+      bmi: 0.0471,
+      familyHistory: 0.5284,
+      hba1c: 0.6001,
+      waist: 63e-4
+    },
+    id: 9,
+    intercept: -8.0917,
+    isLabOnly: false,
+    name: "Clinical + HbA1c",
+    namePt: "Cl\xEDnico + HbA1c",
+    requiredBiomarkers: ["bmi", "waist", "familyHistory", "hba1c"]
+  },
+  {
+    auc: 0.814,
+    coefficients: {
+      bmi: 0.0373,
+      familyHistory: 0.4393,
+      fpg: 0.0253,
+      hba1c: 0.3688,
+      waist: 29e-4
+    },
+    id: 10,
+    intercept: -8.5817,
+    isLabOnly: false,
+    name: "Clinical + FPG + HbA1c",
+    namePt: "Cl\xEDnico + Glicemia + HbA1c",
+    requiredBiomarkers: ["bmi", "waist", "familyHistory", "fpg", "hba1c"]
+  },
+  {
+    auc: 0.808,
+    coefficients: {
+      bmi: 0.0427,
+      familyHistory: 0.4532,
+      fpg: 0.0299,
+      triglycerides: 15e-4,
+      waist: 31e-4
+    },
+    id: 11,
+    intercept: -7.5028,
+    isLabOnly: false,
+    name: "Clinical + FPG + Triglycerides",
+    namePt: "Cl\xEDnico + Glicemia + Triglicer\xEDdeos",
+    requiredBiomarkers: ["bmi", "waist", "familyHistory", "fpg", "triglycerides"]
+  },
+  {
+    auc: 0.813,
+    coefficients: {
+      bmi: 0.0408,
+      familyHistory: 0.4396,
+      fpg: 0.0293,
+      hdlc: -0.0128,
+      triglycerides: 9e-4,
+      waist: 19e-4
+    },
+    id: 12,
+    intercept: -6.9757,
+    isLabOnly: false,
+    name: "Clinical + FPG + Lipids",
+    namePt: "Cl\xEDnico + Glicemia + Lip\xEDdios",
+    requiredBiomarkers: ["bmi", "waist", "familyHistory", "fpg", "triglycerides", "hdlc"]
+  },
+  {
+    auc: 0.822,
+    coefficients: {
+      bmi: 0.0334,
+      familyHistory: 0.4107,
+      fpg: 0.0238,
+      hba1c: 0.3266,
+      hdlc: -0.0117,
+      triglycerides: 6e-4,
+      waist: 15e-4
+    },
+    id: 13,
+    intercept: -8.2,
+    isLabOnly: false,
+    name: "Clinical + FPG + HbA1c + Lipids",
+    namePt: "Cl\xEDnico + Glicemia + HbA1c + Lip\xEDdios",
+    requiredBiomarkers: ["bmi", "waist", "familyHistory", "fpg", "hba1c", "triglycerides", "hdlc"]
+  },
+  {
+    auc: 0.699,
+    coefficients: {
+      bmi: 0.0494,
+      ethnicity: 0.2901,
+      familyHistory: 0.557,
+      hypertension: 0.3653,
+      waist: 71e-4
+    },
+    id: 14,
+    intercept: -7.244,
+    isLabOnly: false,
+    name: "Clinical extended",
+    namePt: "Cl\xEDnico Estendido",
+    requiredBiomarkers: ["bmi", "waist", "familyHistory", "ethnicity", "hypertension"]
+  }
+];
+var LAB_ONLY_MODELS = BRDMRISC_MODELS.filter((m) => m.isLabOnly);
+var LAB_MODEL_PRIORITY = [6, 5, 3, 4, 1, 2];
+var FHIR_CODE_TO_BRDMRISC = {
+  Glucose: "fpg",
+  HbA1c: "hba1c",
+  HDL: "hdlc",
+  Triglycerides: "triglycerides"
+};
+var BRDMRISC_BIOMARKER_CODES = ["Glucose", "HbA1c", "Triglycerides", "HDL"];
+var BIOMARKER_NAMES_PT2 = {
+  fpg: "Glicemia de Jejum",
+  hba1c: "Hemoglobina Glicada",
+  hdlc: "HDL-colesterol",
+  intercept: "Intercepto",
+  triglycerides: "Triglicer\xEDdeos"
+};
+var BIOMARKER_UNITS = {
+  fpg: "mg/dL",
+  hba1c: "%",
+  hdlc: "mg/dL",
+  triglycerides: "mg/dL"
+};
+var BIOMARKER_RANGES2 = {
+  fpg: { max: 500, min: 40, unit: "mg/dL" },
+  hba1c: { max: 20, min: 3, unit: "%" },
+  hdlc: { max: 150, min: 10, unit: "mg/dL" },
+  triglycerides: { max: 2e3, min: 20, unit: "mg/dL" }
+};
+var RISK_THRESHOLDS = {
+  high: 0.2,
+  // 20-35% — high risk
+  moderate: 0.1,
+  // 10-20% — moderate risk
+  veryHigh: 0.35
+  // >= 35% — very high risk
+};
+
+// src/brdmrisc/calculator.ts
+var selectModel = (input, labOnly = true) => {
+  const available = /* @__PURE__ */ new Set();
+  if (input.fpg !== void 0 && !Number.isNaN(input.fpg)) available.add("fpg");
+  if (input.hba1c !== void 0 && !Number.isNaN(input.hba1c)) available.add("hba1c");
+  if (input.triglycerides !== void 0 && !Number.isNaN(input.triglycerides))
+    available.add("triglycerides");
+  if (input.hdlc !== void 0 && !Number.isNaN(input.hdlc)) available.add("hdlc");
+  if (available.size === 0) return null;
+  const priority = labOnly ? LAB_MODEL_PRIORITY : BRDMRISC_MODELS.map((m) => m.id);
+  for (const modelId of priority) {
+    const model = BRDMRISC_MODELS.find((m) => m.id === modelId);
+    if (!model) continue;
+    if (labOnly && !model.isLabOnly) continue;
+    const hasAll = model.requiredBiomarkers.every((b) => available.has(b));
+    if (hasAll) return model;
+  }
+  return null;
+};
+var classifyRisk = (riskPercent) => {
+  const risk = riskPercent / 100;
+  if (risk >= RISK_THRESHOLDS.veryHigh) return "very-high";
+  if (risk >= RISK_THRESHOLDS.high) return "high";
+  if (risk >= RISK_THRESHOLDS.moderate) return "moderate";
+  return "low";
+};
+var calculateBrDMrisc = (input, model) => {
+  const selectedModel = _nullishCoalesce(model, () => ( selectModel(input)));
+  if (!selectedModel) {
+    throw new Error("No suitable model found for the available biomarkers");
+  }
+  const breakdown = [];
+  let x = selectedModel.intercept;
+  for (const [key, coeff] of Object.entries(selectedModel.coefficients)) {
+    const value = input[key];
+    if (value === void 0) {
+      throw new Error(`Missing required biomarker: ${key}`);
+    }
+    const contribution = coeff * value;
+    x += contribution;
+    breakdown.push({
+      coefficient: coeff,
+      contribution: Math.round(contribution * 1e4) / 1e4,
+      key,
+      name: _nullishCoalesce(BIOMARKER_NAMES_PT2[key], () => ( key)),
+      value,
+      valueWithUnit: `${value.toFixed(1)} ${_nullishCoalesce(BIOMARKER_UNITS[key], () => ( ""))}`.trim()
+    });
+  }
+  breakdown.push({
+    coefficient: selectedModel.intercept,
+    contribution: selectedModel.intercept,
+    key: "intercept",
+    name: _nullishCoalesce(BIOMARKER_NAMES_PT2["intercept"], () => ( "Intercepto")),
+    value: 1,
+    valueWithUnit: "-"
+  });
+  const p = 1 / (1 + Math.exp(-x));
+  const risk10y = 1 - Math.pow(1 - p, 10 / FOLLOW_UP_YEARS);
+  const riskPercent = Math.round(risk10y * 1e3) / 10;
+  return {
+    breakdown,
+    calculatedAt: (/* @__PURE__ */ new Date()).toISOString(),
+    modelUsed: selectedModel,
+    risk10y: Math.round(risk10y * 1e4) / 1e4,
+    riskCategory: classifyRisk(riskPercent),
+    riskPercent
+  };
+};
+var validateBiomarkers2 = (input) => {
+  const errors = [];
+  const checkRange = (value, key, name) => {
+    if (value === void 0) return;
+    const range = BIOMARKER_RANGES2[key];
+    if (!range) return;
+    if (value < range.min || value > range.max) {
+      errors.push(
+        `${name} (${value}) fora do intervalo esperado [${range.min}-${range.max} ${range.unit}]`
+      );
+    }
+  };
+  checkRange(input.fpg, "fpg", "Glicemia de Jejum");
+  checkRange(input.hba1c, "hba1c", "HbA1c");
+  checkRange(input.triglycerides, "triglycerides", "Triglicer\xEDdeos");
+  checkRange(input.hdlc, "hdlc", "HDL-colesterol");
+  return {
+    errors,
+    isValid: errors.length === 0
+  };
+};
+
+// src/brdmrisc/unit-converters.ts
+var CONVERSION_FACTORS2 = {
+  fpg: {
+    "mg/dL": 1,
+    "mmol/L": 18.0182
+    // mmol/L → mg/dL
+  },
+  hba1c: {
+    "%": 1
+    // IFCC mmol/mol → NGSP %: HbA1c(%) = 0.0915 × HbA1c(mmol/mol) + 2.15
+    // Handled as special case in convertToTargetUnit
+  },
+  hdlc: {
+    "mg/dL": 1,
+    "mmol/L": 38.67
+    // mmol/L → mg/dL
+  },
+  triglycerides: {
+    "mg/dL": 1,
+    "mmol/L": 88.57
+    // mmol/L → mg/dL
+  }
+};
+var TARGET_UNITS2 = {
+  fpg: "mg/dL",
+  hba1c: "%",
+  hdlc: "mg/dL",
+  triglycerides: "mg/dL"
+};
+var convertToTargetUnit = (biomarker, value, sourceUnit) => {
+  const normalizedUnit = sourceUnit.trim();
+  if (biomarker === "hba1c" && normalizedUnit.includes("mmol/mol")) {
+    return 0.0915 * value + 2.15;
+  }
+  const factors = CONVERSION_FACTORS2[biomarker];
+  if (!factors) return value;
+  const factor = factors[normalizedUnit];
+  if (factor !== void 0) return value * factor;
+  const match = Object.keys(factors).find((k) => k.toLowerCase() === normalizedUnit.toLowerCase());
+  if (match) return value * factors[match];
+  return value;
+};
+var autoConvertToTarget = (biomarker, value, unit) => {
+  const targetUnit = TARGET_UNITS2[biomarker] || "";
+  if (unit) {
+    const normalizedUnit = unit.trim().toLowerCase();
+    const normalizedTarget = targetUnit.toLowerCase();
+    if (normalizedUnit === normalizedTarget) {
+      return { unit: targetUnit, value, wasConverted: false };
+    }
+    const converted = convertToTargetUnit(biomarker, value, unit);
+    return {
+      unit: targetUnit,
+      value: converted,
+      wasConverted: normalizedUnit !== normalizedTarget
+    };
+  }
+  switch (biomarker) {
+    case "fpg":
+      if (value < 30) {
+        return { unit: "mg/dL", value: value * 18.0182, wasConverted: true };
+      }
+      return { unit: "mg/dL", value, wasConverted: false };
+    case "hba1c":
+      if (value > 20) {
+        return { unit: "%", value: 0.0915 * value + 2.15, wasConverted: true };
+      }
+      return { unit: "%", value, wasConverted: false };
+    case "triglycerides":
+      if (value < 15) {
+        return { unit: "mg/dL", value: value * 88.57, wasConverted: true };
+      }
+      return { unit: "mg/dL", value, wasConverted: false };
+    case "hdlc":
+      if (value < 5) {
+        return { unit: "mg/dL", value: value * 38.67, wasConverted: true };
+      }
+      return { unit: "mg/dL", value, wasConverted: false };
+    default:
+      return { unit: targetUnit, value, wasConverted: false };
+  }
+};
+
+// src/derived/calculator.ts
+var _fhir = require('@precisa-saude/fhir');
+var CALCULATIONS = [
+  {
+    calculate: (v) => v.get("Glucose") * v.get("Insulin") / 405,
+    code: "HOMA_IR",
+    inputs: ["Glucose", "Insulin"],
+    unit: "index"
+  },
+  {
+    calculate: (v) => v.get("Triglycerides") / 5,
+    code: "VLDL",
+    inputs: ["Triglycerides"],
+    unit: "mg/dL"
+  }
+];
+var CONTEXT_CALCULATIONS = [
+  {
+    calculate: (v, ctx) => {
+      const weightKg = v.get("TotalMass");
+      const heightM = ctx.heightCm / 100;
+      return weightKg / (heightM * heightM);
+    },
+    canCalculate: (ctx) => typeof ctx.heightCm === "number" && ctx.heightCm >= 50 && ctx.heightCm <= 250,
+    code: "BMI",
+    inputs: ["TotalMass"],
+    unit: "kg/m2"
+  }
+];
+function computeDerivedBiomarkers(biomarkers, options) {
+  const lookupLoinc = _nullishCoalesce(_optionalChain([options, 'optionalAccess', _ => _.codeToLoinc]), () => ( _fhir.codeToLoinc));
+  const byCode = /* @__PURE__ */ new Map();
+  for (const b of biomarkers) {
+    byCode.set(b.code, b);
+  }
+  const added = [];
+  for (const calc of CALCULATIONS) {
+    if (byCode.has(calc.code)) continue;
+    const values = /* @__PURE__ */ new Map();
+    let allPresent = true;
+    for (const input of calc.inputs) {
+      const b = byCode.get(input);
+      if (!b || typeof b.value !== "number") {
+        allPresent = false;
+        break;
+      }
+      values.set(input, b.value);
+    }
+    if (!allPresent) continue;
+    const rawValue = calc.calculate(values);
+    const value = parseFloat(rawValue.toPrecision(10));
+    const loinc = lookupLoinc(calc.code);
+    added.push({
+      code: calc.code,
+      loincCode: _nullishCoalesce(loinc, () => ( void 0)),
+      name: calc.code,
+      unit: calc.unit,
+      value
+    });
+  }
+  if (_optionalChain([options, 'optionalAccess', _2 => _2.userContext])) {
+    for (const calc of CONTEXT_CALCULATIONS) {
+      if (byCode.has(calc.code)) continue;
+      if (!calc.canCalculate(options.userContext)) continue;
+      const values = /* @__PURE__ */ new Map();
+      let allPresent = true;
+      for (const input of calc.inputs) {
+        const b = byCode.get(input);
+        if (!b || typeof b.value !== "number") {
+          allPresent = false;
+          break;
+        }
+        values.set(input, b.value);
+      }
+      if (!allPresent) continue;
+      const rawValue = calc.calculate(values, options.userContext);
+      const value = parseFloat(rawValue.toPrecision(10));
+      const loinc = lookupLoinc(calc.code);
+      added.push({
+        code: calc.code,
+        loincCode: _nullishCoalesce(loinc, () => ( void 0)),
+        name: calc.code,
+        unit: calc.unit,
+        value
+      });
+    }
+  }
+  return added;
+}
+
+
+
+
+exports.brdmrisc = brdmrisc_exports; exports.computeDerivedBiomarkers = computeDerivedBiomarkers; exports.phenoage = phenoage_exports;
+//# sourceMappingURL=index.cjs.map