Longitudinal

Type 2 Diabetes Mellitus (T2DM)

Key LOINC codes

Typical HbA1c trajectory

• Diagnosis: 7.5–12.0% (median ~9.0%)
• After 3 months on Metformin 500mg: drops ~0.5–1.0%
• After 6 months on Metformin 1000mg: drops additional 0.5–1.0%
• Controlled (target reached): 6.5–7.0%, stable
• Suboptimal despite Metformin: >8.0% → trigger GLP-1 or SGLT-2 addition
• Requiring insulin: >9.0% on dual therapy → add basal insulin

Medication escalation (RxNorm codes)

Step 1: Metformin 500mg BID (RxNorm: 6809)   → at diagnosis
Step 2: Metformin 1000mg BID (RxNorm: 6809)  → 3 months if HbA1c > 7.5%
Step 3: Add Semaglutide 0.5mg (RxNorm: 2200644) OR Empagliflozin 10mg (RxNorm: 1544385)
        → 6–12 months if HbA1c > 7.5% on max Metformin
Step 4: Add Glargine insulin 10 units QHS (RxNorm: 274783)
        → if HbA1c > 9.0% on dual oral therapy

Example 18-month T2DM timeline (month_offset values)

• 0: Diagnosis encounter — HbA1c 9.2%, start Metformin 500mg
• 3: Follow-up — HbA1c 8.1%, titrate to Metformin 1000mg, renal panel
• 6: Follow-up — HbA1c 7.4%, continue, annual labs (lipids, uACR)
• 12: Annual — HbA1c 7.1%, well-controlled, foot exam, dilated eye referral
• 18: Follow-up — HbA1c 6.9%, target maintained

Hypertension (HTN)

Key LOINC codes

BP trajectory on treatment

• Uncontrolled: 155–180 / 95–110 mm[Hg]
• 4 weeks on ACEI/ARB: 10–15 mm[Hg] reduction systolic
• 6–8 weeks controlled: <130/80
• Resistant HTN (>3 drugs): add spironolactone or clonidine

Medication escalation (RxNorm codes)

Step 1: Lisinopril 10mg QD (RxNorm: 29046)   → first-line
Step 2: Amlodipine 5mg QD (RxNorm: 17767)    → add if BP > 140/90 at 4 weeks
Step 3: Hydrochlorothiazide 25mg QD (RxNorm: 5487) → add if BP > 140/90 on 2 agents
Step 4: Spironolactone 25mg QD (RxNorm: 9997) → resistant HTN

Chronic Kidney Disease (CKD)

Key LOINC codes

Progression rate (with diabetes/HTN): ~3–5 mL/min/1.73m²/year decline in eGFR

• Medications: ACE inhibitor (nephroprotective) + phosphate binders at Stage 4
• Anemia: start erythropoietin when Hb < 10 g/dL
• At eGFR < 20: nephrology referral, AV fistula planning

Heart Failure (HFrEF)

Key LOINC codes

Medication escalation (GDMT — Guideline-Directed Medical Therapy)

Pillar 1: Carvedilol 6.25mg BID → titrate to 25mg BID (RxNorm: 20352)
Pillar 2: Lisinopril 5mg QD → titrate to 40mg QD (RxNorm: 29046)
Pillar 3: Spironolactone 25mg QD (RxNorm: 9997) — MRA
Pillar 4: Dapagliflozin 10mg QD (RxNorm: 2371643) — SGLT2i

• Diuresis: Furosemide 40mg QD (RxNorm: 4603) — add for volume overload
• Decompensation encounter: weight +3kg, dyspnea → IV diuresis → discharge with uptitration

COPD

Key LOINC codes

GOLD staging by FEV1 (% predicted)

• GOLD 1: ≥80% (mild)
• GOLD 2: 50–79% (moderate) — most common at diagnosis
• GOLD 3: 30–49% (severe)
• GOLD 4: <30% (very severe)

Medication escalation

GOLD 1–2: SABA PRN → Tiotropium 18mcg QD (RxNorm: 274091)
GOLD 3: LABA + LAMA → Budesonide/Formoterol 160/4.5 BID (RxNorm: 895994)
GOLD 4: Triple therapy + pulmonology referral + O2 assessment

• Exacerbation: Prednisone 40mg x5d + Azithromycin 500mg x5d

Depression (MDD)

Key LOINC codes

Treatment timeline

• Weeks 0–2: Start SSRI (Sertraline 50mg QD, RxNorm: 36437)
• Week 4: Partial response → titrate to 100mg
• Week 8: PHQ-9 reassessment — if <50% improvement, augment or switch
• Week 12: SNRI switch (Venlafaxine 75mg, RxNorm: 39786) if SSRI failure
• Remission: PHQ-9 < 5

Hyperlipidemia

Key LOINC codes

Medication escalation

Step 1: Atorvastatin 40mg QD (RxNorm: 617310) — high-intensity statin
Step 2: Atorvastatin 80mg QD — maximum intensity
Step 3: Add Ezetimibe 10mg QD (RxNorm: 341248) — if LDL > 70 on max statin
Step 4: Add Evolocumab 140mg SQ Q2W (PCSK9i, RxNorm: 1860487) — very high risk

• LDL reduction: statin ~50%, + ezetimibe additional ~15–20%
• Check LFTs and CK at baseline; recheck lipids at 6–12 weeks after any change

Vital Signs by Age Group (LOINC codes)

Generating Temporally Consistent Lab Trends

When building a timeline, follow these rules:

1. Treatment response lag: labs improve 4–12 weeks after medication start, not immediately
2. Regression to mean: untreated values drift toward disease-typical ranges over time
3. Comorbidity interactions: CKD raises creatinine AND lowers eGFR simultaneously; HF raises BNP AND lowers sodium
4. Normal variation: add ±5–10% random variation to repeated labs — perfect reproducibility is unrealistic
5. Critical values trigger encounters: HbA1c > 10%, K+ > 6.0, Na+ < 125 → urgent/emergency encounter

Example causal chain (T2DM + HTN + CKD)

Month 0:  HbA1c 10.2%, BP 168/102, eGFR 52, uACR 85  → start Metformin + Lisinopril
Month 3:  HbA1c 8.9%,  BP 145/92,  eGFR 49, uACR 62  → titrate both, add Amlodipine
Month 6:  HbA1c 7.8%,  BP 132/82,  eGFR 48, uACR 45  → on track, continue
Month 12: HbA1c 7.1%,  BP 128/78,  eGFR 46, uACR 38  → well-controlled
Month 18: HbA1c 7.4%,  BP 130/80,  eGFR 44, uACR 42  → slight CKD progression
Month 24: HbA1c 7.2%,  BP 128/76,  eGFR 41, uACR 55  → nephrology referral

Encounter Class Selection

Stage 2 Code Generation Notes

When generating code from a longitudinal plan:

1. Compute encounter dates: care_start_date + relativedelta(months=month_offset)
2. Create Encounter first, then reference it in all observations/procedures via encounter: {"reference": f"Encounter/{enc_id}"}
3. Use effectiveDateTime on Observations (not issued)
4. Observations within the same encounter share encounter reference
5. MedicationRequest authoredOn = encounter date; status = "stopped" for MedicationAction.action == "stop"
6. Set Encounter period.start = encounter date, period.end = same day (outpatient) or +3 days (inpatient)
7. Order resources in output: Patient → Practitioner → Encounter → Observation → Condition → Procedure → MedicationRequest (within each encounter group)