Recent Guidelines for Pharmacotherapeutics II Diseases

from docx import Document
from docx.shared import Pt, Inches, RGBColor
from docx.enum.text import WD_ALIGN_PARAGRAPH
from docx.oxml.ns import qn
from docx.oxml import OxmlElement
import datetime

doc = Document()

# ── Page margins ──────────────────────────────────────────────────────────────
for section in doc.sections:
    section.top_margin    = Inches(1.0)
    section.bottom_margin = Inches(1.0)
    section.left_margin   = Inches(1.2)
    section.right_margin  = Inches(1.2)

# ── Base styles ───────────────────────────────────────────────────────────────
normal = doc.styles["Normal"]
normal.font.name = "Calibri"
normal.font.size = Pt(11)

# ── Helper: coloured heading ──────────────────────────────────────────────────
DARK_BLUE  = RGBColor(0x1F, 0x49, 0x7D)   # title / H1
MID_BLUE   = RGBColor(0x2E, 0x75, 0xB6)   # H2 unit headings
TEAL       = RGBColor(0x00, 0x70, 0x70)   # H3 disease headings
DARK_GREY  = RGBColor(0x40, 0x40, 0x40)

def add_heading(text, level, color):
    p = doc.add_heading(text, level=level)
    for run in p.runs:
        run.font.color.rgb = color
        run.font.bold = True
    return p

def add_bullet(text, bold_prefix=None):
    """Add a bullet paragraph, optionally with a bold prefix followed by normal text."""
    p = doc.add_paragraph(style="List Bullet")
    p.paragraph_format.space_after = Pt(3)
    if bold_prefix:
        run_b = p.add_run(bold_prefix)
        run_b.bold = True
        run_b.font.size = Pt(11)
        run = p.add_run(text)
        run.font.size = Pt(11)
    else:
        run = p.add_run(text)
        run.font.size = Pt(11)
    return p

def add_sub_bullet(text):
    p = doc.add_paragraph(style="List Bullet 2")
    p.paragraph_format.space_after = Pt(2)
    run = p.add_run(text)
    run.font.size = Pt(10.5)
    return p

def add_body(text, italic=False, color=None):
    p = doc.add_paragraph(text)
    p.paragraph_format.space_after = Pt(4)
    for run in p.runs:
        run.font.size = Pt(11)
        if italic:
            run.italic = True
        if color:
            run.font.color.rgb = color
    return p

def add_note(text):
    p = doc.add_paragraph()
    p.paragraph_format.left_indent = Inches(0.3)
    p.paragraph_format.space_after = Pt(4)
    run = p.add_run("NOTE: " + text)
    run.italic = True
    run.font.size = Pt(10)
    run.font.color.rgb = RGBColor(0x80, 0x40, 0x00)
    return p

def add_divider():
    p = doc.add_paragraph()
    pPr = p._p.get_or_add_pPr()
    pBdr = OxmlElement('w:pBdr')
    bottom = OxmlElement('w:bottom')
    bottom.set(qn('w:val'), 'single')
    bottom.set(qn('w:sz'), '6')
    bottom.set(qn('w:space'), '1')
    bottom.set(qn('w:color'), '2E75B6')
    pBdr.append(bottom)
    pPr.append(pBdr)
    p.paragraph_format.space_after = Pt(6)

def guideline_entry(guideline_name, year, body, pmid=None):
    """Render one guideline entry as a bullet with sub-bullets."""
    label = f"{guideline_name} ({year})"
    p = doc.add_paragraph(style="List Bullet")
    p.paragraph_format.space_after = Pt(3)
    r1 = p.add_run(label)
    r1.bold = True
    r1.font.color.rgb = MID_BLUE
    r1.font.size = Pt(11)
    if pmid:
        r2 = p.add_run(f"  [PMID: {pmid}]")
        r2.font.size = Pt(9)
        r2.font.color.rgb = RGBColor(0x80, 0x80, 0x80)
    for line in body:
        add_sub_bullet(line)

# ══════════════════════════════════════════════════════════════════════════════
# COVER PAGE
# ══════════════════════════════════════════════════════════════════════════════
doc.add_paragraph()
doc.add_paragraph()

title_p = doc.add_paragraph()
title_p.alignment = WD_ALIGN_PARAGRAPH.CENTER
tr = title_p.add_run("Recent Clinical Guidelines")
tr.bold = True
tr.font.size = Pt(26)
tr.font.color.rgb = DARK_BLUE

sub_p = doc.add_paragraph()
sub_p.alignment = WD_ALIGN_PARAGRAPH.CENTER
sr = sub_p.add_run("Pharmacotherapeutics II  |  MPP 202T")
sr.font.size = Pt(14)
sr.font.color.rgb = MID_BLUE

doc.add_paragraph()
doc.add_paragraph()

scope_p = doc.add_paragraph()
scope_p.alignment = WD_ALIGN_PARAGRAPH.CENTER
scr = scope_p.add_run(
    "A comprehensive summary of the most recent evidence-based guidelines\n"
    "across all disease categories covered in the Pharmacotherapeutics II syllabus.\n"
    "Compiled July 2026."
)
scr.font.size = Pt(12)
scr.italic = True
scr.font.color.rgb = DARK_GREY

doc.add_paragraph()
doc.add_paragraph()

issuing_p = doc.add_paragraph()
issuing_p.alignment = WD_ALIGN_PARAGRAPH.CENTER
ir = issuing_p.add_run(
    "Key sources: AAN · AHA/ASA · ILAE · KDIGO · IDSA · WHO · ASCO · EACS · ESC · NCCN · ESMO"
)
ir.font.size = Pt(10)
ir.font.color.rgb = RGBColor(0x60, 0x60, 0x60)

doc.add_page_break()

# ══════════════════════════════════════════════════════════════════════════════
# UNIT 1 – NERVOUS SYSTEM
# ══════════════════════════════════════════════════════════════════════════════
add_heading("UNIT 1: NERVOUS SYSTEM DISORDERS", level=1, color=DARK_BLUE)
add_body(
    "This unit covers epilepsy, Parkinson's disease, stroke, headache, Alzheimer's disease, "
    "neuralgias, and pain management.",
    italic=True, color=DARK_GREY
)
add_divider()

# 1. Epilepsy
add_heading("1. Epilepsy", level=2, color=TEAL)
guideline_entry(
    "ILAE Task Force on Neonatal Seizures", "2023",
    ["Consensus recommendations for treatment of seizures in the neonate.",
     "Phenobarbital remains first-line; levetiracetam as alternative.",
     "Published in Epilepsia."],
    pmid="37655702"
)
guideline_entry(
    "Clinical Practice Guidelines: Status Epilepticus in Adults", "2024",
    ["Systematic review of CPGs on status epilepticus management.",
     "Benzodiazepines (lorazepam IV, diazepam) as first-line; valproate or levetiracetam IV for second-line.",
     "Published in Epilepsia."],
    pmid="38606469"
)
guideline_entry(
    "AAN/AES/SMFM Practice Guideline: Antiseizure Medications in Pregnancy", "2024",
    ["Avoid sodium valproate in women of childbearing potential due to teratogenicity.",
     "Lamotrigine and levetiracetam are preferred in pregnancy.",
     "Monitor serum levels of antiseizure medications throughout pregnancy."],
    pmid="38748979"
)
add_bullet("First-line ASMs (general): Sodium valproate, lamotrigine, levetiracetam, carbamazepine.")
add_bullet("Drug-resistant epilepsy: Brivaracetam, cenobamate, perampanel added per ILAE 2023 updates.")

# 2. Parkinson's Disease
add_heading("2. Parkinson's Disease", level=2, color=TEAL)
guideline_entry(
    "AAN Guideline: Dopaminergic Therapy for Motor Symptoms in Early PD", "2021 (current)",
    ["Levodopa/carbidopa remains the gold standard for motor symptom control.",
     "Dopamine receptor agonists (ropinirole, pramipexole, rotigotine patch) as monotherapy or adjunct.",
     "No definitive evidence for one agent over another in early PD."]
)
guideline_entry(
    "German Society of Neurology: Autonomic Failure, Pain & Sleep Disturbances in PD", "2025",
    ["Covers insomnia, REM sleep behavior disorder (RBD), autonomic dysfunction.",
     "Insomnia: eszopiclone, doxepin, melatonin, zolpidem (low evidence); CBT-I preferred first.",
     "RBD: clonazepam or melatonin; safe sleep environment essential.",
     "Orthostatic hypotension: midodrine, droxidopa.",
     "Published in Journal of Neurology (Jan 2025)."]
)
guideline_entry(
    "IHS Formulary Brief: Treatment of Parkinson's Disease", "April 2025",
    ["Pimavanserin (FDA-approved) preferred for PD psychosis (does not worsen motor symptoms).",
     "Clozapine (low dose) and quetiapine as alternatives for psychosis.",
     "Rivastigmine (FDA-approved) for PD dementia; donepezil and galantamine also used.",
     "Avoid typical antipsychotics in PD."]
)

# 3. Stroke
add_heading("3. Stroke", level=2, color=TEAL)
guideline_entry(
    "AHA/ASA 2026 Guideline: Early Management of Acute Ischemic Stroke", "2026",
    ["Most current comprehensive stroke guideline.",
     "Tenecteplase now preferred over alteplase for IV thrombolysis (simpler dosing, non-inferior outcomes).",
     "Endovascular thrombectomy (EVT) window extended up to 24 hours in selected patients.",
     "Blood pressure: maintain <185/110 mmHg before thrombolysis.",
     "Dual antiplatelet therapy (aspirin + clopidogrel) for 21 days after minor ischemic stroke/TIA.",
     "Published in Stroke journal."],
    pmid="41582814"
)
add_bullet("Hemorrhagic stroke: BP target <140 mmHg within 1 hour; reversal of anticoagulants; neurosurgical consult for large hematomas.")
add_bullet("Secondary prevention: Statins, antihypertensives, anticoagulation for AF-related stroke (DOACs preferred over warfarin).")

# 4. Headache/Migraine
add_heading("4. Headache / Migraine", level=2, color=TEAL)
guideline_entry(
    "EHF Evidence-Based Guidelines: Pharmacological Treatment of Migraine", "2025",
    ["Triptans (sumatriptan, rizatriptan) remain first-line for acute moderate-to-severe migraine.",
     "NSAIDs (ibuprofen, naproxen) + antiemetics for mild-to-moderate attacks.",
     "Gepants (ubrogepant, rimegepant): CGRP antagonists; option for triptan non-responders.",
     "Lasmiditan: 5-HT1F agonist for cardiovascular-contraindicated patients.",
     "Preventive therapy: CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) - first-line for episodic/chronic migraine prevention.",
     "Beta-blockers (propranolol, metoprolol) and topiramate as traditional preventive options.",
     "Published in Cephalalgia, April 2025."],
    pmid="40277319"
)

# 5. Alzheimer's Disease
add_heading("5. Alzheimer's Disease", level=2, color=TEAL)
guideline_entry(
    "Alzheimer's Association Clinical Practice Guideline: Blood-Based Biomarkers", "2025",
    ["Plasma phospho-tau 217 (p-tau217) and amyloid-beta 42/40 ratio recommended for diagnostic workup.",
     "Blood-based biomarkers can guide appropriate use of anti-amyloid therapies.",
     "Published in Alzheimer's & Dementia, July 2025."],
    pmid="40729527"
)
add_bullet("Disease-modifying therapies (2024-2025):", "")
add_sub_bullet("Lecanemab (Leqembi) - FDA-approved 2023; anti-amyloid monoclonal antibody; slows decline in early AD.")
add_sub_bullet("Donanemab (Kisunla) - FDA-approved 2024; significant reduction in amyloid plaque burden.")
add_sub_bullet("Both require ARIA (amyloid-related imaging abnormalities) monitoring via MRI.")
add_bullet("Symptomatic management:", "")
add_sub_bullet("Mild-to-moderate: Donepezil, rivastigmine, galantamine (AChE inhibitors).")
add_sub_bullet("Moderate-to-severe: Add memantine (NMDA antagonist).")
add_sub_bullet("Combination donepezil + memantine for moderate-to-severe disease.")

doc.add_page_break()

# ══════════════════════════════════════════════════════════════════════════════
# UNIT 2 – PSYCHIATRIC & RENAL
# ══════════════════════════════════════════════════════════════════════════════
add_heading("UNIT 2: PSYCHIATRIC DISORDERS & RENAL SYSTEM", level=1, color=DARK_BLUE)
add_body(
    "Covers schizophrenia, depression, anxiety disorders, sleep disorders, drug-induced psychiatric disorders, "
    "acute/chronic renal failure, renal dialysis, and drug-induced renal disease.",
    italic=True, color=DARK_GREY
)
add_divider()

# 6. Schizophrenia
add_heading("6. Schizophrenia", level=2, color=TEAL)
guideline_entry(
    "WFSBP/APA Guidelines: Schizophrenia Management", "2023-2024 (updated)",
    ["Second-generation (atypical) antipsychotics as first-line: risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone.",
     "Clozapine remains gold standard for treatment-resistant schizophrenia (TRS) - requires WBC monitoring.",
     "Long-acting injectable antipsychotics (LAIs) now recommended earlier, not just for non-adherence.",
     "Recommended LAIs: paliperidone palmitate, aripiprazole lauroxil, risperidone microspheres.",
     "Monitor: metabolic syndrome (weight, glucose, lipids), EPS, tardive dyskinesia, QTc prolongation.",
     "Psychosocial interventions (CBT, family therapy, supported employment) are essential adjuncts."]
)

# 7. Depression
add_heading("7. Depression", level=2, color=TEAL)
guideline_entry(
    "APA Practice Guideline: Major Depressive Disorder", "2023 (updated)",
    ["SSRIs and SNRIs as first-line pharmacotherapy: sertraline, escitalopram, venlafaxine, duloxetine.",
     "If inadequate response at 4-8 weeks: switch within class or augment (lithium, atypical antipsychotic, T3).",
     "Treatment-resistant depression (TRD): esketamine (Spravato) intranasal - FDA-approved; ketamine IV infusions.",
     "Bupropion: useful when sexual side effects or sedation problematic; also for comorbid smoking cessation.",
     "TCAs and MAOIs: reserved for refractory cases due to side-effect profile.",
     "Maintenance therapy recommended for 6-12 months after first episode; indefinitely after 3+ episodes."]
)

# 8. Anxiety Disorders
add_heading("8. Anxiety Disorders", level=2, color=TEAL)
guideline_entry(
    "BAP/NICE Guidelines: Management of Anxiety Disorders", "2023-2024",
    ["SSRIs/SNRIs as first-line for GAD, panic disorder, social anxiety disorder (SAD), PTSD.",
     "Pregabalin: effective for GAD; second-line option.",
     "Benzodiazepines (lorazepam, alprazolam): short-term acute use only; risk of dependence.",
     "Buspirone: for GAD, non-sedating, no abuse potential; takes 2-4 weeks for effect.",
     "CBT is as effective as pharmacotherapy; combination preferred for severe cases.",
     "Beta-blockers (propranolol): for situational/performance anxiety (off-label)."]
)

# 9. Sleep Disorders
add_heading("9. Sleep Disorders", level=2, color=TEAL)
guideline_entry(
    "ACP Clinical Practice Guideline: Management of Chronic Insomnia Disorder", "2023",
    ["CBT-I (Cognitive Behavioral Therapy for Insomnia) is first-line - superior to pharmacotherapy long-term.",
     "Pharmacotherapy (short-term only if CBT-I unavailable or failed):",
     "  - Dual orexin receptor antagonists (DORAs): suvorexant (Belsomra), lemborexant - preferred.",
     "  - Low-dose doxepin (3-6 mg): for sleep maintenance insomnia.",
     "  - Melatonin receptor agonist: ramelteon - for sleep onset insomnia, low abuse potential.",
     "  - Avoid prolonged benzodiazepine use (Z-drugs: zolpidem, zopiclone - short-term only).",
     "Obstructive sleep apnea (OSA): CPAP remains gold standard."]
)

# 10. Drug-Induced Psychiatric Disorders
add_heading("10. Drug-Induced Psychiatric Disorders", level=2, color=TEAL)
add_bullet("Corticosteroid-induced psychosis: dose reduction; antipsychotics (haloperidol, quetiapine) if severe.")
add_bullet("Drug-induced depression: discontinue offending agent (beta-blockers, interferon, isotretinoin); SSRI if persists.")
add_bullet("Stimulant-induced psychosis (amphetamines, cocaine): benzodiazepines + antipsychotics; supportive care.")
add_bullet("Cannabis/cannabinoid-induced psychosis: discontinue use; antipsychotics (risperidone, olanzapine).")

# 11. Acute Renal Failure (AKI)
add_heading("11. Acute Kidney Injury (AKI)", level=2, color=TEAL)
guideline_entry(
    "KDIGO Clinical Practice Guideline for AKI", "2023 (active)",
    ["Staging: KDIGO stages 1-3 based on serum creatinine rise and urine output.",
     "Remove nephrotoxic agents; optimize hemodynamics; avoid contrast agents.",
     "Fluid management: isotonic crystalloids preferred; avoid colloids in sepsis-AKI.",
     "Renal replacement therapy (RRT) indication: refractory hyperkalemia (K+ >6.5), severe metabolic acidosis (pH <7.15), fluid overload, uremia.",
     "CRRT (continuous) preferred over intermittent hemodialysis in hemodynamically unstable patients."]
)

# 12. Chronic Kidney Disease (CKD)
add_heading("12. Chronic Kidney Disease (CKD)", level=2, color=TEAL)
guideline_entry(
    "KDIGO 2024 CKD Guidelines", "2024",
    ["SGLT2 inhibitors (dapagliflozin, empagliflozin) now recommended across all CKD stages for nephroprotection, regardless of diabetes status.",
     "ACE inhibitors or ARBs: first-line for CKD with proteinuria; target BP <130/80 mmHg.",
     "Finerenone (non-steroidal MRA): reduces CKD progression and cardiovascular events in diabetic CKD.",
     "GLP-1 receptor agonists: cardiovascular and renal benefits in overweight CKD patients.",
     "Manage complications: anemia (ESAs + IV iron), hyperphosphatemia (phosphate binders), metabolic acidosis (oral bicarbonate)."]
)
guideline_entry(
    "KDIGO 2025: Kidney Disease and Heart Failure Controversies Conference", "2026",
    ["Cardiorenal syndrome management: coordinated heart-kidney approach.",
     "SGLT2 inhibitors benefit both cardiac and renal outcomes.",
     "Published in JACC Heart Failure, April 2026."],
    pmid="41793402"
)
add_note("Drug-induced renal disease: NSAIDs, aminoglycosides, contrast agents, and calcineurin inhibitors are major causes; KDIGO advises avoidance or dose adjustment based on GFR.")

doc.add_page_break()

# ══════════════════════════════════════════════════════════════════════════════
# UNIT 3 – INFECTIOUS DISEASES (Part 1)
# ══════════════════════════════════════════════════════════════════════════════
add_heading("UNIT 3: INFECTIOUS DISEASES – PART 1", level=1, color=DARK_BLUE)
add_body(
    "Covers antibiotic use principles, surgical prophylaxis, UTI, respiratory tract infections, "
    "gastroenteritis, tuberculosis, malaria, bacterial endocarditis, and septicemia.",
    italic=True, color=DARK_GREY
)
add_divider()

# 13. General Antibiotic Principles
add_heading("13. General Guidelines for Rational Use of Antibiotics", level=2, color=TEAL)
guideline_entry(
    "WHO AWaRe Antibiotic Classification", "2023 (updated)",
    ["Access-Watch-Reserve (AWaRe) framework guides rational antibiotic prescribing.",
     "Access antibiotics (amoxicillin, doxycycline): use as first-line wherever possible.",
     "Watch antibiotics (fluoroquinolones, 3rd-gen cephalosporins): use only for specific indications.",
     "Reserve antibiotics (carbapenems, colistin, ceftazidime-avibactam): last resort for MDR organisms.",
     "Antibiotic stewardship programs (ASP): mandatory in all hospital settings."]
)
guideline_entry(
    "ASHP/IDSA Surgical Prophylaxis Guidelines", "2023",
    ["Cefazolin remains the preferred surgical prophylaxis agent for most procedures.",
     "Administer within 60 minutes before incision (120 minutes for vancomycin/fluoroquinolones).",
     "Single dose usually sufficient; do not continue beyond 24 hours post-operatively.",
     "Beta-lactam allergy: clindamycin or vancomycin alternatives."]
)

# 14. UTI
add_heading("14. Urinary Tract Infections (UTI)", level=2, color=TEAL)
guideline_entry(
    "IDSA 2025 Guideline: Complicated UTI Management", "July 2025",
    ["Most current IDSA guidance (PMID: 41419448).",
     "Uncomplicated UTI: nitrofurantoin 5 days OR fosfomycin single dose OR TMP-SMX 3 days (if local resistance <20%).",
     "Complicated UTI (mild-moderate): oral fluoroquinolone or TMP-SMX based on culture.",
     "Complicated UTI with sepsis: IV ceftriaxone, cefepime, piperacillin-tazobactam, or carbapenem.",
     "Shorter antibiotic courses recommended to reduce resistance.",
     "Step-down from IV to oral once clinically stable and culture results available.",
     "Novel beta-lactam/BLI combinations (ceftazidime-avibactam) for ESBL/CRE organisms."],
    pmid="41419448"
)

# 15. Respiratory Tract Infections
add_heading("15. Respiratory Tract Infections", level=2, color=TEAL)
guideline_entry(
    "IDSA/ATS Guidelines: Community-Acquired Pneumonia (CAP)", "2019 (reaffirmed 2023)",
    ["Outpatient (no comorbidities): amoxicillin 1g TDS OR doxycycline.",
     "Outpatient (comorbidities): amoxicillin-clavulanate + macrolide OR respiratory fluoroquinolone (levofloxacin, moxifloxacin).",
     "Inpatient (non-ICU): beta-lactam + macrolide OR respiratory fluoroquinolone.",
     "ICU: beta-lactam + azithromycin + anti-pseudomonal if risk factors.",
     "Duration: 5 days (mild-moderate CAP); 7 days for ICU-level severity."]
)
guideline_entry(
    "GOLD 2024 Guidelines: COPD Exacerbation (Respiratory Infections)", "2024",
    ["Antibiotics for acute exacerbation: amoxicillin-clavulanate, azithromycin, doxycycline.",
     "Short-course systemic corticosteroids (5 days prednisone 40 mg) for moderate-severe exacerbations.",
     "Hospitalized patients: IV corticosteroids; consider IV antibiotics for severe exacerbations."]
)

# 16. Gastroenteritis
add_heading("16. Gastroenteritis", level=2, color=TEAL)
guideline_entry(
    "WHO/IDSA Guidelines: Management of Acute Gastroenteritis", "2023",
    ["Oral rehydration solution (ORS) remains the cornerstone of treatment for all ages.",
     "Antibiotics NOT routinely recommended for viral gastroenteritis.",
     "Antibiotics indicated for: Shigella (azithromycin or ciprofloxacin), Vibrio cholerae (azithromycin/doxycycline), severe Salmonella in immunocompromised/elderly.",
     "Zinc supplementation for children under 5 with diarrhea (10-20 mg/day for 10-14 days).",
     "Ondansetron: effective antiemetic for vomiting in acute gastroenteritis, reduces IV fluid need."]
)

# 17. Tuberculosis
add_heading("17. Tuberculosis (TB)", level=2, color=TEAL)
guideline_entry(
    "WHO Consolidated Guidelines on TB - Module 3: Diagnosis", "April 2025",
    ["First comprehensive update integrating new molecular diagnostics.",
     "Xpert MTB/RIF Ultra and TrueNat recommended as initial diagnostic tests (replace smear microscopy).",
     "Urine LAM antigen testing for TB in immunocompromised/HIV patients.",
     "Drug susceptibility testing (DST) mandatory before starting MDR-TB treatment."]
)
guideline_entry(
    "WHO TB Treatment Guidelines: Drug-Sensitive TB", "2022 (active)",
    ["Standard regimen: 2HRZE/4HR (isoniazid, rifampicin, pyrazinamide, ethambutol x 2 months; then HRx4 months).",
     "NEW 4-month regimen (2HPMZ/2HPM): isoniazid + pyrazinamide + moxifloxacin + rifapentine - WHO-recommended, non-inferior to 6-month.",
     "Directly Observed Therapy (DOT) recommended.",
     "Pyridoxine (B6) supplementation with isoniazid to prevent peripheral neuropathy."]
)
guideline_entry(
    "WHO Guidelines: Drug-Resistant TB (MDR/XDR-TB)", "2022-2023",
    ["Preferred regimen: BPaL (bedaquiline + pretomanid + linezolid) for 6 months - ZeNix/TB-PRACTECAL data.",
     "BPaLM: bedaquiline + pretomanid + linezolid + moxifloxacin - 6 months for MDR-TB.",
     "QTc monitoring mandatory with bedaquiline (moxifloxacin interaction).",
     "Avoid kanamycin and capreomycin (injectable agents) - WHO 2022 removes them."]
)

# 18. Malaria
add_heading("18. Malaria", level=2, color=TEAL)
guideline_entry(
    "WHO Malaria Guidelines", "August 2025 (most current)",
    ["Artemisinin-based combination therapies (ACTs) remain first-line for uncomplicated P. falciparum malaria.",
     "Preferred ACTs: artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), artesunate-mefloquine.",
     "Severe malaria: IV artesunate is superior to IV quinine (WHO recommends artesunate).",
     "P. vivax / P. ovale: chloroquine (sensitive areas) + primaquine for radical cure (G6PD test first).",
     "Artemisinin resistance: emerging in Africa; surveillance ongoing; switch to non-artemisinin ACTs if confirmed.",
     "Drug interactions: rifampicin (for TB co-infection) significantly reduces ACT levels - adjust doses."]
)

# 19. Bacterial Endocarditis
add_heading("19. Bacterial Endocarditis", level=2, color=TEAL)
guideline_entry(
    "ESC Guidelines on Infective Endocarditis", "2023",
    ["'Endocarditis Team' multidisciplinary approach is mandatory.",
     "Native valve endocarditis (streptococci): amoxicillin (or penicillin G) + gentamicin; can use 2-week short-course for sensitive streptococci.",
     "Staphylococcal IE: flucloxacillin (MSSA) or vancomycin (MRSA) for 4-6 weeks.",
     "Enterococcal IE: ampicillin + ceftriaxone (preferred) or ampicillin + gentamicin.",
     "HACEK organisms: ceftriaxone 4 weeks.",
     "Surgical indications: heart failure, uncontrolled infection (abscess, fistula), embolism prevention with large vegetations (>10mm).",
     "Prophylaxis: amoxicillin 2g oral pre-procedure for high-risk patients undergoing dental procedures."]
)

# 20. Septicemia / Sepsis
add_heading("20. Septicemia / Sepsis", level=2, color=TEAL)
guideline_entry(
    "Surviving Sepsis Campaign (SSC) Bundle Update", "2024",
    ["Hour-1 Bundle (implement within 1 hour of recognition):",
     "  1. Measure serum lactate (re-measure if >2 mmol/L).",
     "  2. Obtain blood cultures BEFORE antibiotics.",
     "  3. Broad-spectrum antibiotics within 1 hour.",
     "  4. 30 mL/kg IV crystalloid for hypotension or lactate ≥4 mmol/L.",
     "  5. Vasopressors (norepinephrine first-line) if MAP <65 mmHg after fluids.",
     "De-escalation based on culture sensitivity results; reassess at 48-72 hours.",
     "Source control: drainage of abscess, removal of infected devices within 6-12 hours."]
)

doc.add_page_break()

# ══════════════════════════════════════════════════════════════════════════════
# UNIT 4 – INFECTIOUS DISEASES (Part 2) & GYNECOLOGY
# ══════════════════════════════════════════════════════════════════════════════
add_heading("UNIT 4: INFECTIOUS DISEASES (PART 2) & GYNECOLOGICAL DISORDERS", level=1, color=DARK_BLUE)
add_body(
    "Covers meningitis, HIV and opportunistic infections, rheumatic fever, dengue fever, H1N1, "
    "helminthiasis, fungal infections, dysmenorrhea, and hormone replacement therapy.",
    italic=True, color=DARK_GREY
)
add_divider()

# 21. Meningitis
add_heading("21. Meningitis", level=2, color=TEAL)
guideline_entry(
    "WHO Guidelines on Meningitis Diagnosis, Treatment and Care", "April 2025",
    ["Empiric therapy for bacterial meningitis (adults): ceftriaxone 2g IV BD.",
     "Add dexamethasone 0.15 mg/kg QDS x 4 days (gives before or with first antibiotic dose) - reduces neurological sequelae.",
     "Add ampicillin/amoxicillin for Listeria monocytogenes coverage in: age >50, immunocompromised, pregnant women.",
     "Neonatal meningitis: ampicillin + cefotaxime OR ampicillin + gentamicin.",
     "Meningococcal meningitis: penicillin G or ceftriaxone x 7 days.",
     "Viral (aseptic) meningitis: supportive; aciclovir if HSV suspected.",
     "Cryptococcal meningitis (HIV): liposomal amphotericin B + flucytosine x 1 week; then fluconazole consolidation."]
)

# 22. HIV
add_heading("22. HIV and Opportunistic Infections", level=2, color=TEAL)
guideline_entry(
    "IAS-USA Panel: Antiretroviral Drugs for Treatment and Prevention of HIV", "2024-2025",
    ["Preferred first-line ART: bictegravir/tenofovir alafenamide/emtricitabine (Biktarvy) - single tablet once daily.",
     "Alternative first-line: dolutegravir-based regimens (dolutegravir + lamivudine or tenofovir/FTC).",
     "Long-acting ART: cabotegravir + rilpivirine IM injection every 1-2 months - option for adherence issues.",
     "Treatment initiation: as soon as HIV diagnosis is confirmed, regardless of CD4 count.",
     "U=U (Undetectable = Untransmittable): ART achieving viral suppression prevents sexual transmission."],
    pmid="39616604"
)
guideline_entry(
    "European AIDS Clinical Society (EACS) Guidelines Version 13.0", "2026",
    ["Comprehensive update on ART, opportunistic infection management, and comorbidities.",
     "Opportunistic infection prophylaxis: TMP-SMX for PCP if CD4 <200 cells/µL; azithromycin for MAC if CD4 <50.",
     "ART and TB co-infection: start ART within 2 weeks of TB therapy (if CD4 <50); use efavirenz with rifampicin.",
     "HPV vaccination, screening, and STI management updated."],
    pmid="41088922"
)

# 23. Rheumatic Fever
add_heading("23. Rheumatic Fever", level=2, color=TEAL)
guideline_entry(
    "AHA Scientific Statement: Prevention and Treatment of Acute Rheumatic Fever", "2022-2023",
    ["Acute episode: benzathine penicillin G IM single dose (or oral amoxicillin x 10 days) for GAS pharyngitis.",
     "Anti-inflammatory: aspirin or naproxen for arthritis; corticosteroids for severe carditis.",
     "Secondary prophylaxis: benzathine penicillin G 1.2 million units IM every 4 weeks (every 3 weeks in high-risk regions).",
     "Duration of secondary prophylaxis depends on severity of carditis:",
     "  - No carditis: 5 years or until age 21 (whichever is longer).",
     "  - Carditis without residual disease: 10 years or until age 21.",
     "  - Carditis with residual valve disease: at least 10 years or until age 40; sometimes lifelong."]
)

# 24. Dengue Fever
add_heading("24. Dengue Fever", level=2, color=TEAL)
guideline_entry(
    "WHO Dengue Guidelines and Management Protocols", "2024",
    ["No specific antiviral agent; treatment is supportive.",
     "Group A (outpatient): oral rehydration, paracetamol for fever (avoid NSAIDs and aspirin - risk of bleeding).",
     "Group B (inpatient): IV crystalloids for warning signs (severe abdominal pain, vomiting, bleeding, rapid clinical deterioration); monitor hematocrit.",
     "Group C (severe dengue/shock): aggressive fluid resuscitation; blood transfusion for severe bleeding.",
     "Dengvaxia (CYD-TDV) vaccine: only for seropositive individuals aged 9-45 years.",
     "TAK-003 (Qdenga): WHO-prequalified 2024; suitable for seronegative individuals; broader use."]
)

# 25. H1N1 Influenza
add_heading("25. H1N1 Influenza", level=2, color=TEAL)
guideline_entry(
    "WHO/CDC Influenza Treatment Guidelines", "2023-2024",
    ["Oseltamivir (Tamiflu) remains first-line antiviral for influenza A (H1N1).",
     "Treatment should begin within 48 hours of symptom onset for greatest benefit.",
     "High-risk patients (pregnant, elderly, immunocompromised, severe disease): treat regardless of symptom duration.",
     "Peramivir IV and zanamivir inhaled as alternatives; baloxavir marboxil (single-dose oral) for uncomplicated influenza.",
     "Vaccination: annual trivalent/quadrivalent influenza vaccine; H1N1 component updated annually by WHO."]
)

# 26. Helminthiasis
add_heading("26. Helminthiasis", level=2, color=TEAL)
guideline_entry(
    "WHO Guidelines: Preventive Chemotherapy for Soil-Transmitted Helminths (STH)", "2023",
    ["Albendazole 400 mg single oral dose for mass drug administration (MDA) programs.",
     "Mebendazole 500 mg single dose as alternative.",
     "Repeated annually for preschool children, school-age children, and women of reproductive age in endemic areas.",
     "Specific indications:",
     "  - Ascariasis, hookworm, trichuriasis: albendazole or mebendazole.",
     "  - Strongyloidiasis: ivermectin 200 µg/kg/day x 2 days (drug of choice).",
     "  - Trichinosis: albendazole for 10-15 days.",
     "  - Filariasis: diethylcarbamazine (DEC) or ivermectin + albendazole (MDA)."]
)

# 27. Fungal Infections
add_heading("27. Fungal Infections", level=2, color=TEAL)
guideline_entry(
    "ECIL 2025 Guidelines: Primary Antifungal Prophylaxis in Hematological Malignancies", "2025",
    ["Posaconazole remains the preferred prophylactic agent in high-risk patients (AML induction, HSCT).",
     "Isavuconazole: alternative prophylaxis with a better safety profile (less hepatotoxicity, no QTc prolongation).",
     "Voriconazole: for Aspergillus prophylaxis in HSCT recipients.",
     "Published in Leukemia, July 2025."],
    pmid="40200079"
)
guideline_entry(
    "IDSA Guidelines: Management of Candidiasis (updated principles)", "2024",
    ["Invasive candidiasis: echinocandins (caspofungin, micafungin, anidulafungin) as first-line.",
     "Fluconazole: for Candida species susceptible (step-down after clinical improvement).",
     "Candida auris (multidrug-resistant): echinocandins; close infection control measures.",
     "Invasive aspergillosis: voriconazole or isavuconazole as first-line; liposomal amphotericin B for salvage.",
     "Duration: at least 14 days after last positive culture for invasive candidiasis."]
)

# 28. Dysmenorrhea
add_heading("28. Dysmenorrhea", level=2, color=TEAL)
guideline_entry(
    "ACOG/SOGC Clinical Practice Guidelines: Primary Dysmenorrhea", "2023-2024",
    ["NSAIDs are the most effective first-line treatment (ibuprofen 400-600 mg TDS, naproxen 500 mg BD starting before menses onset).",
     "Combined oral contraceptive pill (COCP): second-line; reduces endometrial prostaglandin production.",
     "Levonorgestrel-releasing IUD: effective for endometriosis-related secondary dysmenorrhea.",
     "GnRH analogues (leuprolide): for severe endometriosis; limited to 6 months (bone density loss).",
     "Heat therapy (topical): as effective as ibuprofen for mild primary dysmenorrhea.",
     "Secondary dysmenorrhea (endometriosis): ESHRE 2023 guidelines recommend hormonal therapy first; surgical laparoscopy if refractory."]
)

# 29. Hormone Replacement Therapy
add_heading("29. Hormone Replacement Therapy (HRT / MHT)", level=2, color=TEAL)
guideline_entry(
    "2025 Menopausal Hormone Therapy (MHT) Guidelines", "2025",
    ["MHT remains the most effective intervention for vasomotor symptoms (hot flushes, night sweats).",
     "Transdermal estradiol (patch/gel): preferred over oral estrogen - lower risk of VTE and stroke.",
     "Women with intact uterus: combined estrogen + progestogen (micronized progesterone preferred - best safety profile).",
     "Post-hysterectomy: estrogen alone (no progestogen needed).",
     "Tibolone: particularly effective for improving sexual function and libido.",
     "Benefits: reduces VMS, improves sleep, joint/muscle pain, mood, metabolic markers.",
     "Risks: individualize - VTE (oral route), breast cancer (combined MHT >5 years), endometrial cancer (unopposed estrogen).",
     "Non-hormonal alternatives (if contraindicated): SSRIs (escitalopram, paroxetine), SNRIs (venlafaxine), gabapentin, clonidine."]
)

doc.add_page_break()

# ══════════════════════════════════════════════════════════════════════════════
# UNIT 5 – ONCOLOGY
# ══════════════════════════════════════════════════════════════════════════════
add_heading("UNIT 5: ONCOLOGY & PALLIATIVE CARE", level=1, color=DARK_BLUE)
add_body(
    "Covers general principles of chemotherapy, breast cancer, lung cancer, head & neck cancer, "
    "hematological malignancies, chemotherapy-induced nausea and vomiting (CINV), and palliative care.",
    italic=True, color=DARK_GREY
)
add_divider()

# 30. Chemotherapy Principles
add_heading("30. General Principles of Cancer Chemotherapy", level=2, color=TEAL)
add_bullet("Chemotherapy regimens classified by mechanism: alkylating agents, antimetabolites, topoisomerase inhibitors, vinca alkaloids, taxanes, platinum compounds.")
add_bullet("Combination chemotherapy exploits cell cycle kinetics and reduces resistance development.")
add_bullet("Response assessment: RECIST 1.1 criteria used for solid tumors (complete, partial response, stable disease, progression).")
add_bullet("Dose-limiting toxicities: myelosuppression (most common), mucositis, nausea/vomiting, nephrotoxicity, cardiotoxicity.")
add_bullet("G-CSF (filgrastim, pegfilgrastim): recommended as primary prophylaxis when febrile neutropenia risk >20%.")

# 31. Breast Cancer
add_heading("31. Breast Cancer", level=2, color=TEAL)
guideline_entry(
    "ASCO/NCCN Guidelines: Breast Cancer Management", "2024-2025",
    ["HR+/HER2- (most common): CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) + aromatase inhibitor (letrozole, anastrozole) - standard first-line for metastatic.",
     "HER2+: trastuzumab + pertuzumab + docetaxel (THP) neoadjuvant; ado-trastuzumab emtansine (T-DM1) for residual disease after neoadjuvant.",
     "Triple-negative breast cancer (TNBC): pembrolizumab + chemotherapy (KEYNOTE-522); olaparib for BRCA1/2-mutated.",
     "Early-stage: surgery (BCS or mastectomy) + sentinel lymph node biopsy + radiation.",
     "Adjuvant: tamoxifen (pre-menopausal), aromatase inhibitors (post-menopausal); 5-10 years.",
     "Neratinib: for early HER2+ BC after trastuzumab-based adjuvant therapy."]
)

# 32. Lung Cancer
add_heading("32. Lung Cancer", level=2, color=TEAL)
guideline_entry(
    "IASLC/ESMO/NCCN Guidelines: Lung Cancer Management", "2024-2025",
    ["NSCLC - Molecular testing mandatory: EGFR, ALK, ROS1, KRAS G12C, MET, BRAF, PD-L1 (IHC).",
     "EGFR-mutated (exon 19/21): osimertinib (3rd-gen TKI) - FLAURA trial; first-line.",
     "ALK-rearranged: alectinib or brigatinib first-line (superior to crizotinib).",
     "KRAS G12C: sotorasib or adagrasib.",
     "PD-L1 ≥50%: pembrolizumab monotherapy (KEYNOTE-024); PD-L1 1-49%: pembrolizumab + chemotherapy.",
     "SCLC (limited stage): concurrent cisplatin-etoposide + thoracic radiation.",
     "SCLC (extensive stage): cisplatin/carboplatin-etoposide + atezolizumab (IMpower133) or durvalumab."]
)

# 33. Head & Neck Cancer
add_heading("33. Head & Neck Cancer", level=2, color=TEAL)
guideline_entry(
    "ESMO Clinical Practice Guidelines: Head and Neck Cancer", "2024",
    ["Locally advanced (resectable): surgery + adjuvant radiation OR concurrent cisplatin-based chemoradiation.",
     "Locally advanced (unresectable): platinum-based chemoradiation (cisplatin 100 mg/m² every 3 weeks).",
     "HPV-positive oropharyngeal cancer: better prognosis; de-escalation trials ongoing.",
     "Recurrent/metastatic: pembrolizumab monotherapy (CPS ≥1) or pembrolizumab + chemotherapy (CPS ≥1) - KEYNOTE-048; first-line.",
     "Cetuximab: option for platinum-ineligible patients.",
     "Reirradiation: French SFRO guidelines (2025) provide updated recommendations."]
)

# 34. Hematological Malignancies
add_heading("34. Hematological Malignancies", level=2, color=TEAL)
guideline_entry(
    "ASH/EHA Guidelines: Hematological Malignancies", "2024-2025",
    ["AML (fit patients <60): intensive induction 7+3 (cytarabine + daunorubicin/idarubicin); midostaurin if FLT3-mutated.",
     "AML (older/unfit): venetoclax + azacitidine - standard of care (VIALE-A trial).",
     "CML: imatinib, dasatinib, or nilotinib as first-line TKIs; ABL1 mutation testing guides selection.",
     "CLL: venetoclax + obinutuzumab (fixed duration) or ibrutinib/acalabrutinib for first-line.",
     "B-cell ALL: blinatumomab (BiTE antibody), inotuzumab ozogamicin for relapsed/refractory.",
     "Hodgkin Lymphoma: ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) remains standard; brentuximab vedotin + AVD for advanced-stage.",
     "Multiple Myeloma: VRd (bortezomib + lenalidomide + dexamethasone); daratumumab-based quadruplets for transplant-eligible."]
)

# 35. CINV
add_heading("35. Chemotherapy-Induced Nausea & Vomiting (CINV)", level=2, color=TEAL)
guideline_entry(
    "ASCO/MASCC/ESMO Guidelines: Prevention of CINV", "2023",
    ["Highly emetogenic chemotherapy (HEC): Triple/Quadruple antiemetic prophylaxis:",
     "  - NK1 receptor antagonist: aprepitant (oral) or fosaprepitant (IV) on Day 1.",
     "  - 5-HT3 receptor antagonist: ondansetron or palonosetron on Day 1.",
     "  - Dexamethasone: 12 mg on Day 1; 8 mg on Days 2-4.",
     "  - Add olanzapine 10 mg on Days 1-4 for carboplatin/cisplatin regimens.",
     "Moderately emetogenic (MEC): 5-HT3 antagonist + dexamethasone ± NK1 antagonist.",
     "Low emetogenic: dexamethasone or metoclopramide or prochlorperazine.",
     "Anticipatory nausea: lorazepam or alprazolam; behavioral interventions.",
     "Breakthrough CINV: olanzapine, haloperidol, or prochlorperazine."]
)

# 36. Palliative Care
add_heading("36. Palliative Care", level=2, color=TEAL)
guideline_entry(
    "ASCO 2024 Guideline Update: Palliative Care for Patients with Cancer", "2024",
    ["Early integration of palliative care alongside active oncology treatment - within 8 weeks of diagnosis of advanced cancer.",
     "Dedicated multidisciplinary palliative care team (physician, nurse, social worker, chaplain).",
     "New guidance: Early referral at cancer diagnosis for hematological malignancy patients.",
     "Phase I trial patients should also receive specialized palliative care.",
     "Health equity: palliative care services must address disparities in access.",
     "Pain management: WHO analgesic ladder still core; strong opioids (morphine, oxycodone, fentanyl) for severe cancer pain.",
     "Dyspnea: low-dose opioids; oxygen only if hypoxic.",
     "Published in J Clin Oncol 2024 (doi: 10.1200/JCO.24.00542)."]
)

doc.add_page_break()

# ══════════════════════════════════════════════════════════════════════════════
# SUMMARY TABLE
# ══════════════════════════════════════════════════════════════════════════════
add_heading("QUICK REFERENCE: GUIDELINE ISSUING BODIES", level=1, color=DARK_BLUE)
add_divider()

table = doc.add_table(rows=1, cols=3)
table.style = "Table Grid"

# Header row
hdr = table.rows[0].cells
hdr[0].text = "Abbreviation"
hdr[1].text = "Full Name"
hdr[2].text = "Domain"
for cell in hdr:
    for para in cell.paragraphs:
        for run in para.runs:
            run.bold = True
            run.font.color.rgb = RGBColor(0xFF, 0xFF, 0xFF)
        shading = OxmlElement('w:shd')
        shading.set(qn('w:fill'), '1F497D')
        shading.set(qn('w:val'), 'clear')
        cell._tc.get_or_add_tcPr().append(shading)

orgs = [
    ("ILAE",    "International League Against Epilepsy",       "Epilepsy"),
    ("AAN",     "American Academy of Neurology",               "Neurology"),
    ("AHA/ASA", "American Heart/Stroke Association",           "Stroke, Cardiology"),
    ("IDSA",    "Infectious Diseases Society of America",      "Infectious Diseases"),
    ("WHO",     "World Health Organization",                   "Global guidelines"),
    ("KDIGO",   "Kidney Disease: Improving Global Outcomes",   "Nephrology"),
    ("ASCO",    "American Society of Clinical Oncology",       "Oncology"),
    ("NCCN",    "National Comprehensive Cancer Network",       "Oncology"),
    ("ESC",     "European Society of Cardiology",              "Cardiology, Endocarditis"),
    ("EACS",    "European AIDS Clinical Society",              "HIV"),
    ("ESMO",    "European Society for Medical Oncology",       "Oncology"),
    ("MASCC",   "Multinational Association Supportive Cancer Care", "CINV, Supportive care"),
    ("APA",     "American Psychiatric Association",            "Psychiatry"),
    ("IASLC",   "Int'l Association for Study of Lung Cancer",  "Lung Cancer"),
    ("ACOG",    "American College of Obstetricians/Gynecologists","Gynecology"),
    ("ECIL",    "European Conference on Infections in Leukemia","Fungal infections"),
    ("GOLD",    "Global Initiative for Chronic Obstructive Lung Disease","COPD"),
    ("IAS-USA", "International Antiviral Society - USA",       "HIV"),
]

for abbr, full, domain in orgs:
    row = table.add_row().cells
    row[0].text = abbr
    row[1].text = full
    row[2].text = domain

# Set column widths
for row in table.rows:
    row.cells[0].width = Inches(1.3)
    row.cells[1].width = Inches(3.5)
    row.cells[2].width = Inches(1.9)
    for i, cell in enumerate(row.cells):
        for para in cell.paragraphs:
            para.paragraph_format.space_before = Pt(2)
            para.paragraph_format.space_after = Pt(2)
            for run in para.runs:
                run.font.size = Pt(10)

doc.add_paragraph()
add_note(
    "All PMIDs listed in this document can be searched at https://pubmed.ncbi.nlm.nih.gov/ "
    "for full-text access where available. Guidelines from WHO are freely available at who.int."
)

# Footer
add_body(
    f"\nDocument compiled: July 2026  |  For educational use in Pharmacotherapeutics II (MPP 202T)",
    italic=True, color=RGBColor(0x80, 0x80, 0x80)
)

# ── Save ───────────────────────────────────────────────────────────────────────
out = "/tmp/workspace/pharmacotherapeutics-guidelines/Pharmacotherapeutics_II_Recent_Guidelines.docx"
doc.save(out)
print(f"Saved: {out}")