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pulm.hospital-acquired-pneumonia-non-covid.v1

Hospital-Acquired & Ventilator-Associated Pneumonia (HAP / VAP, non-COVID)

pulmonologyacuteadult
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12/12 authored

Canonical 12-phase frame with authored status for this dossier.

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Frame

Detailed

Classify: HAP = pneumonia ≥48 h after admission AND not incubating at admission; VAP = pneumonia ≥48 h after endotracheal intubation. Distinguish from ventilator-associated tracheobronchitis (VAT — purulent secretions + clinical signs but NO new infiltrate). Exclude COVID and other viral etiologies (out of scope — non-COVID engine). HCAP is a retired category (Kalil PMID 27418577)

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HAP vs VAP vs VAT classification made + non-COVID confirmed

Patient inputs (23)

Elderly risk profile (aspiration-prone, atypical presentation) + renal dose adjustment

Septic shock screening — shock is an IDSA criterion for DUAL anti-pseudomonal coverage (Kalil PMID 27418577)

Respiratory failure / qSOFA sepsis screen (Sepsis-3 Singer JAMA 2016)

Hypoxemia threshold for ICU + escalation; disproportionate hypoxia vs infiltrate raises PE on the differential

Fever / hypothermia for sepsis bundle + the clinical leg of the new-infiltrate + clinical + micro triad

Strongest IDSA MDR + MRSA + Pseudomonas risk factor — drives empiric breadth (Kalil PMID 27418577)

Prior MRSA isolation/colonisation → empiric vancomycin or linezolid (Kalil PMID 27418577)

Prior Pseudomonas / structural lung disease → broaden + consider double anti-pseudomonal (Kalil PMID 27418577)

Septic shock / high mortality risk → DUAL anti-pseudomonal (two classes) per IDSA — Melsen attributable mortality ~13%, higher in surgical/mid-severity (PMID 23622939)

LOCAL ANTIBIOGRAM is the primary empiric driver — unit MRSA prevalence ≥10–20% or GNR resistance >10% to monotherapy → broaden (Kalil PMID 27418577)

β-lactam allergy (cross-reactivity review), SSRI–linezolid serotonin-syndrome, QT, nephrotoxin stacking with vanc/AG

eGFR/CrCl for vancomycin (AUC24/MIC 400-600 — Rybak 2020 PMID 32191793), β-lactam, aminoglycoside renal dosing

Respiratory culture (BAL quantitative OR endotracheal aspirate semi-quant — NO mortality difference, Canadian Critical Care 2006) — the micro leg of the triad + de-escalation substrate; obtain BEFORE antibiotics

Bacteremia identification + SSC sepsis bundle — obtain BEFORE antibiotics

New OR progressive infiltrate is NECESSARY for HAP/VAP — no new infiltrate → VAT or non-infectious mimic (atelectasis, edema, PE)

P/F ratio — distinguishes pneumonia-with-ARDS overlap from VAT (no infiltrate); ventilator-associated event tracking

Neutropenia / SOT / HSCT / high-dose steroid → broaden to fungal (Aspergillus), PJP, viral (CMV) — changes diagnostics + empirics

Witnessed aspiration / post-stroke / dysphagia / depressed consciousness → aspiration-pneumonia overlap; route pulm.aspiration-pneumonia.core.v1

Post-operative HAP (esp. thoracic/upper-abdominal) — atelectasis is the dominant early mimic; surgical patients have higher VAP attributable mortality (Melsen PMID 23622939)

Hepatic impairment — linezolid/FQ caution; avoids over-dosing hepatically-cleared agents

Leukocytosis (≥12) / leukopenia (≤4) — the clinical leg of HAP/VAP definition + CPIS component

Sepsis severity / SSC 2021 bundle (Evans PMID 34599691) — lactate ≥4 = septic shock surrogate → DUAL anti-pseudomonal

PCT trend assists short-course duration de-escalation — de Jong SAPS RCT duration 5 vs 7 d (PMID 26947523); IDSA/ATS 2016 Kalil

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (10)

10 need judgement
  • informationallife_threateningseptic_shock_with_hap_vap
    Hypotension despite 30 mL/kg crystalloid OR lactate ≥4 with HAP/VAP — SSC 2021; IDSA/ATS 2016 Kalil
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveremrsa_risk_factors_present
    IV abx ≤90 d, unit MRSA ≥10–20%, prior MRSA, mech vent + ICU — IDSA/ATS 2016 Kalil
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveremdr_pseudomonas_risk_or_shock
    Septic shock, prior MDR Pseudomonas, structural lung disease, or recent IV abx ≤90 d — IDSA/ATS 2016 Kalil
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverevap_diagnosis_with_high_p_f_drop
    New infiltrate + P/F drop ≥50 from baseline + purulent secretions in ventilated patient — IDSA/ATS 2016 Kalil
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereno_improvement_at_72h
    No defervescence / oxygenation improvement / culture-driven narrowing not feasible at 72 h — IDSA/ATS 2016 Kalil
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepseudomonas_or_acinetobacter_confirmed
    Sputum / BAL culture confirmed Pseudomonas aeruginosa or Acinetobacter baumannii (non-fermenting GNR) — IDSA/ATS 2016 Kalil; Chastre JAMA 2003 PMID 14625336
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereimmunocompromised_broaden_non_bacterial
    Neutropenia / SOT / HSCT / high-dose steroid with new infiltrate — IDSA/ATS 2016 Kalil
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateaki_on_vancomycin_or_aminoglycoside
    Creatinine rise ≥0.3 mg/dL or 50% from baseline on vancomycin / aminoglycoside — IDSA/ATS 2016 Kalil; Vancomycin AUC Consensus 2020
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateno_new_infiltrate_consider_VAT_or_mimic
    Purulent secretions + fever/leukocytosis in a ventilated patient but NO new/progressive radiographic infiltrate — IDSA/ATS 2016 Kalil
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmildday_7_responding_stop_short_course
    Day 7 of therapy + clinically improved (afebrile, leukocyte trend down, oxygenation/secretions improving), pathogen NOT non-fermenting GNR, no empyema/abscess/immunocompromise — IDSA/ATS 2016 Kalil; Chastre JAMA 2003 PMID 14625336
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

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Recommended regimen

IDSA/ATS 2016 HAP/VAP empirical antibiotics — risk-stratified
axis: hap_vap_empiricsstep low_mdr_risk_hap - Low-MDR-risk HAP (no IV abx in 90 d, not in high-MRSA/Pseudo unit, not septic shock, not high mortality risk)
Selected step "Low-MDR-risk HAP (no IV abx in 90 d, not in high-MRSA/Pseudo unit, not septic shock, not high mortality risk)" — HAP without MDR risk factors; unit MRSA prevalence <10–20%; GNR monotherapy resistance <10%; no septic shock — single agent covering MSSA + Pseudomonas — IDSA/ATS 2016 Kalil (PMID 27418577)
  • piperacillin-tazobactam
    first line
    antipseudomonal_BLI
    4.5 g IV q6h (extended 4 h infusion preferred); renal: CrCl 20-40 → 3.375 g q6h, CrCl <20 → 2.25 g q6h; HD supplement post-dialysis • IV • q6h
    triggers: no_severe_pip_tazo_allergy
    Single anti-pseudomonal β-lactam covers GNR + MSSA — IDSA/ATS 2016 Kalil. RxCUI 74169 RxNav-confirmed 2026-05-16 = "piperacillin / tazobactam" (corrected from prior erroneous 18631 = azithromycin).
    rxcui 74169
  • cefepime
    first line
    cephalosporin_4th
    2 g IV q8h; renal: CrCl 30-60 → 2 g q12h, CrCl 11-29 → 2 g q24h, CrCl <11 → 1 g q24h (neurotoxicity risk if under-adjusted in renal failure) • IV • q8h
    Anti-pseudomonal cephalosporin alternative — IDSA/ATS 2016 Kalil. RxCUI 20481 RxNav-confirmed 2026-05-16 = cefepime.
    rxcui 20481
  • levofloxacin
    second line
    respiratory_fluoroquinolone
    750 mg IV daily; renal: CrCl 20-49 → 750 mg q48h, CrCl <20 → 750 mg ×1 then 500 mg q48h • IV • daily
    triggers: beta_lactam_allergy
    Reserve when β-lactam contraindicated (FDA 2018 tendon/aortic/neuropathy boxed warning) — IDSA/ATS 2016 Kalil. RxCUI 82122 RxNav-confirmed 2026-05-16 = levofloxacin.
    rxcui 82122

inpatient playbook — drug actions (8)

  1. 1. oxygen
    NC 1–6 L/min; HFNC if SpO2 <90% or rising RR • inhaled • continuous
    trigger: SpO2 <92% — IDSA/ATS 2016 Kalil
    Supportive — IDSA/ATS 2016 Kalil
  2. 2. piperacillin-tazobactam
    4.5 g IV q6h (extended 4 h infusion) • IV • q6h
    trigger: Empirical antipseudomonal β-lactam (default) — IDSA/ATS 2016 Kalil
    IDSA/ATS 2016 Kalil ward HAP backbone
  3. 3. cefepime (alt)
    2 g IV q8h • IV • q8h
    trigger: pip-tazo intolerance / unit-driven preference — IDSA/ATS 2016 Kalil
    Alternative antipseudomonal β-lactam — IDSA/ATS 2016 Kalil
  4. 4. meropenem
    1 g IV q8h • IV • q8h
    trigger: ESBL risk OR severe β-lactam allergy OR septic shock with high MDR prevalence — IDSA/ATS 2016 Kalil
    Carbapenem reserve — IDSA/ATS 2016 Kalil
  5. 5. vancomycin
    15–20 mg/kg IV q8–12h, target AUC24 400–600 (trough 15–20) • IV • q8–12h with PK monitoring
    trigger: MRSA risk factors OR unit MRSA prevalence ≥10–20% — IDSA/ATS 2016 Kalil
    IDSA/ATS 2016 Kalil MRSA empiric
  6. 6. linezolid (alt)
    600 mg IV/PO BID • IV/PO • q12h
    trigger: AKI, vancomycin intolerance, necrotising MRSA — IDSA/ATS 2016 Kalil
    Toxin suppression in necrotising MRSA — IDSA/ATS 2016 Kalil
  7. 7. add aminoglycoside or ciprofloxacin
    Tobramycin 7 mg/kg IV daily OR amikacin 15–20 mg/kg IV daily OR cipro 400 mg IV q8h • IV • daily / q8h × ≤72 h
    trigger: Septic shock OR MDR Gram-negative risk
    IDSA dual antipseudomonal in shock / MDR
  8. 8. de-escalate per culture
    Narrow per pathogen + susceptibility • IV/PO • per pathogen
    trigger: Culture / susceptibility result at 48–72 h — IDSA/ATS 2016 Kalil
    Stewardship — narrowest effective agent — IDSA/ATS 2016 Kalil

Auto-drafted A&P note

inpatient

Subjective

- Possible entry pathways: New fever + purulent endotracheal / sputum secretions in hospitalised patient — IDSA/ATS 2016 Kalil (PMID 27418577); New OR progressive radiographic infiltrate ≥48 h after admission / intubation (the necessary pivot — no new infiltrate → not HAP/VAP, consider VAT) — IDSA/ATS 2016 Kalil; Rising FiO2 / PEEP / new hypoxemia in ventilated patient (ventilator-associated event) — IDSA/ATS 2016 Kalil.

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Hospital-Acquired & Ventilator-Associated Pneumonia (HAP / VAP, non-COVID)** (pulm.hospital-acquired-pneumonia-non-covid.v1).
Phenotype framing: Pathogen axis: MDR Gram-negative (Pseudomonas, Acinetobacter, ESBL Klebsiella/E. coli, CRE) vs MRSA vs MSSA vs Enterobacterales vs anaerobes (aspiration overlap) vs Legionella vs respiratory virus — per Kalil Table 3. Disease axis: HAP/VAP vs VAT (no infiltrate) vs ARDS vs aspiration pneumonia vs atelectasis vs cardiogenic pulmonary edema vs PE — pivot is new infiltrate + clinical + micro positivity
Scope: Classify: HAP = pneumonia ≥48 h after admission AND not incubating at admission; VAP = pneumonia ≥48 h after endotracheal intubation. Distinguish from ventilator-associated tracheobronchitis (VAT — purulent secretions + clinical signs but NO new infiltrate). Exclude COVID and other viral etiologies (out of scope — non-COVID engine). HCAP is a retired category (Kalil PMID 27418577)

No severity triggers fired against current inputs.

Plan

Regimen axis: **IDSA/ATS 2016 HAP/VAP empirical antibiotics — risk-stratified** — step "Low-MDR-risk HAP (no IV abx in 90 d, not in high-MRSA/Pseudo unit, not septic shock, not high mortality risk)".
1. piperacillin-tazobactam 4.5 g IV q6h (extended 4 h infusion preferred); renal: CrCl 20-40 → 3.375 g q6h, CrCl <20 → 2.25 g q6h; HD supplement post-dialysis IV q6h (antipseudomonal_BLI, first line) — Single anti-pseudomonal β-lactam covers GNR + MSSA — IDSA/ATS 2016 Kalil. RxCUI 74169 RxNav-confirmed 2026-05-16 = "piperacillin / tazobactam" (corrected from prior erroneous 18631 = azithromycin).
2. cefepime 2 g IV q8h; renal: CrCl 30-60 → 2 g q12h, CrCl 11-29 → 2 g q24h, CrCl <11 → 1 g q24h (neurotoxicity risk if under-adjusted in renal failure) IV q8h (cephalosporin_4th, first line) — Anti-pseudomonal cephalosporin alternative — IDSA/ATS 2016 Kalil. RxCUI 20481 RxNav-confirmed 2026-05-16 = cefepime.
3. levofloxacin 750 mg IV daily; renal: CrCl 20-49 → 750 mg q48h, CrCl <20 → 750 mg ×1 then 500 mg q48h IV daily (respiratory_fluoroquinolone, second line) — Reserve when β-lactam contraindicated (FDA 2018 tendon/aortic/neuropathy boxed warning) — IDSA/ATS 2016 Kalil. RxCUI 82122 RxNav-confirmed 2026-05-16 = levofloxacin.

Setting playbook (inpatient) — Recognise HAP/VAP early, start empirical antipseudomonal ± MRSA coverage within 1 h of recognition (especially if septic), de-escalate at 48–72 h, complete 7-day course unless complicated
4. oxygen NC 1–6 L/min; HFNC if SpO2 <90% or rising RR inhaled continuous — SpO2 <92% — IDSA/ATS 2016 Kalil (Supportive — IDSA/ATS 2016 Kalil)
5. piperacillin-tazobactam 4.5 g IV q6h (extended 4 h infusion) IV q6h — Empirical antipseudomonal β-lactam (default) — IDSA/ATS 2016 Kalil (IDSA/ATS 2016 Kalil ward HAP backbone)
6. cefepime (alt) 2 g IV q8h IV q8h — pip-tazo intolerance / unit-driven preference — IDSA/ATS 2016 Kalil (Alternative antipseudomonal β-lactam — IDSA/ATS 2016 Kalil)
7. meropenem 1 g IV q8h IV q8h — ESBL risk OR severe β-lactam allergy OR septic shock with high MDR prevalence — IDSA/ATS 2016 Kalil (Carbapenem reserve — IDSA/ATS 2016 Kalil)
8. vancomycin 15–20 mg/kg IV q8–12h, target AUC24 400–600 (trough 15–20) IV q8–12h with PK monitoring — MRSA risk factors OR unit MRSA prevalence ≥10–20% — IDSA/ATS 2016 Kalil (IDSA/ATS 2016 Kalil MRSA empiric)
9. linezolid (alt) 600 mg IV/PO BID IV/PO q12h — AKI, vancomycin intolerance, necrotising MRSA — IDSA/ATS 2016 Kalil (Toxin suppression in necrotising MRSA — IDSA/ATS 2016 Kalil)
10. add aminoglycoside or ciprofloxacin Tobramycin 7 mg/kg IV daily OR amikacin 15–20 mg/kg IV daily OR cipro 400 mg IV q8h IV daily / q8h × ≤72 h — Septic shock OR MDR Gram-negative risk (IDSA dual antipseudomonal in shock / MDR)
11. de-escalate per culture Narrow per pathogen + susceptibility IV/PO per pathogen — Culture / susceptibility result at 48–72 h — IDSA/ATS 2016 Kalil (Stewardship — narrowest effective agent — IDSA/ATS 2016 Kalil)

Non-pharmacologic actions:
- Sepsis bundle within 1 h if shock (lactate, cultures before abx, IV fluids 30 mL/kg, antibiotics) — SSC 2021
- Head-of-bed elevation 30–45° in ventilated patients (VAP prevention bundle) — IDSA/ATS 2016 Kalil
- Daily sedation interruption + spontaneous breathing trial when appropriate — IDSA/ATS 2016 Kalil
- Subglottic suctioning ETT in expected ventilation ≥48 h — IDSA/ATS 2016 Kalil
- Oral chlorhexidine controversy noted — not routinely recommended in 2026 guidance — NICE 2019
- VTE + GI prophylaxis — SSC 2021
- Source control if loculated effusion / empyema — IDSA/ATS 2016 Kalil; SSC 2021

AVOID / contraindication checks:
- Vancomycin_AUC24_MIC_target_400_600_Bayesian_or_2level_avoid_AKI — Rybak 2020 PMID 32191793; IDSA/ATS 2016 Kalil PMID 27418577
- Linezolid_serotonin_syndrome_with_SSRI_SNRI_MAOI — IDSA/ATS 2016 Kalil
- Linezolid_thrombocytopenia_and_lactic_acidosis_if_>=14d — IDSA/ATS 2016 Kalil
- Fluoroquinolone_tendon_aortic_aneurysm_QT_neuropathy — FDA 2018 boxed warning
- Aminoglycoside_nephro_ototoxicity_keep_<=72h_PK_guided — IDSA/ATS 2016 Kalil
- Beta_lactam_allergy_cross_reactivity_review_before_carbapenem — IDSA/ATS 2016 Kalil
- Cefepime_neurotoxicity_if_renal_dose_not_adjusted — IDSA/ATS 2016 Kalil
- Hepatic_impairment_caution_linezolid_fluoroquinolone — drug labels
- Avoid_prolonged_empiric_double_coverage_de_escalate_when_mono_susceptible — Pugh PMID 26301604; Kalil PMID 27418577

Monitoring

Regimen monitoring:
- clinical response at 48 72h temp WBC secretions oxygenation — IDSA/ATS 2016 Kalil
- culture review and de escalation at 48 72h — IDSA/ATS 2016 Kalil PMID 27418577
- procalcitonin trend to support short course stop — de Jong SAPS PMID 26947523; IDSA/ATS 2016 Kalil
- vancomycin AUC24 Bayesian or 2level — Rybak 2020 PMID 32191793
- creatinine baseline and q48h with vancomycin or aminoglycoside — IDSA/ATS 2016 Kalil
- CBC q3 5d with linezolid for thrombocytopenia — IDSA/ATS 2016 Kalil
- aminoglycoside levels and stop by 72h — IDSA/ATS 2016 Kalil
- duration 7 days unless complicated — IDSA/ATS 2016 Kalil; Chastre JAMA 2003 PMID 14625336; Pugh Cochrane PMID 26301604
- duration 10 14 days for NFGNB pseudomonas acinetobacter immunocompromise or slow response — Chastre PMID 14625336; Pugh PMID 26301604
- VAP attributable mortality ~13pct higher surgical midseverity — Melsen IPD PMID 23622939

Setting (inpatient) monitoring:
- Daily T / WBC / RR / SpO2 / FiO2 trend — IDSA/ATS 2016 Kalil
- Re-image if no improvement at 48–72 h — IDSA/ATS 2016 Kalil
- Culture review at 48–72 h — IDSA/ATS 2016 Kalil
- Procalcitonin trend if used — IDSA/ATS 2016 Kalil
- Vancomycin trough or AUC; creatinine q48h — Vancomycin AUC Consensus 2020; IDSA/ATS 2016 Kalil
- CBC weekly if linezolid; SS screen if SSRI — IDSA/ATS 2016 Kalil

Follow-up plan: Total 7-day duration if responding (Chastre non-inferior mortality 18.8% vs 17.2%, more antibiotic-free days, less MDR among recurrences — PMID 14625336; Pugh +4.02 antibiotic-free days, MDR recurrence OR 0.44 — PMID 26301604). Extend to 10-14 d ONLY for non-fermenting GNR (Pseudomonas/Acinetobacter — Chastre NF-GNB recurrence 40.6% vs 25.4%; Pugh OR 2.18), structural lung disease, immunocompromise, empyema/abscess, or slow response. Reinforce VAP prevention bundle; post-ICU follow-up
- Close-out criterion: Duration set + prevention plan documented

Monitoring phase: Clinical response reassessed at 48-72 h (defervescence, oxygenation, secretion volume/purulence, leukocyte trend); culture-driven de-escalation; PCT trend assists short-course stop (de Jong SAPS PMID 26947523); daily IV→PO suitability; vancomycin AUC24 (creatinine q48h); AKI + linezolid-thrombocytopenia surveillance

Disposition

Current setting: inpatient — Recognise HAP/VAP early, start empirical antipseudomonal ± MRSA coverage within 1 h of recognition (especially if septic), de-escalate at 48–72 h, complete 7-day course unless complicated

Disposition criteria:
- Step-down to ward when off vasopressors, FiO2 ≤0.4, hemodynamically stable — IDSA/ATS 2016 Kalil
- Discharge: completed (or tolerating PO completion of) 7-day course, afebrile ≥48 h, returning to baseline oxygenation, follow-up arranged — IDSA/ATS 2016 Kalil; Chastre JAMA 2003 PMID 12409821

Escalation triggers (move to higher acuity):
- Septic shock → ICU + DUAL antipseudomonal + vasopressors — IDSA/ATS 2016 Kalil; SSC 2021
- P/F ≤200 / new ARDS → ICU + lung-protective ventilation — IDSA/ATS 2016 Kalil
- Fail to improve at 72 h → CT chest, bronchoscopy, ID consult — IDSA/ATS 2016 Kalil

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Hypotension despite 30 mL/kg crystalloid OR lactate ≥4 with HAP/VAP — SSC 2021; IDSA/ATS 2016 Kalil
- [SEVERE] IV abx ≤90 d, unit MRSA ≥10–20%, prior MRSA, mech vent + ICU — IDSA/ATS 2016 Kalil
- [SEVERE] Septic shock, prior MDR Pseudomonas, structural lung disease, or recent IV abx ≤90 d — IDSA/ATS 2016 Kalil

Citations

- IDSA/ATS 2016 HAP/VAP CPG (Kalil; PMID 27418577; current US standard 2026) + ERS/ESICM/ESCMID/ALAT 2017 (PMID 28890434) + Surviving Sepsis Campaign 2021 (Evans; PMID 34599691) [PMID:27418577](https://pubmed.ncbi.nlm.nih.gov/27418577/)
- Cited evidence (PMID 28890434) [PMID:28890434](https://pubmed.ncbi.nlm.nih.gov/28890434/)
- Cited evidence (PMID 14625336) [PMID:14625336](https://pubmed.ncbi.nlm.nih.gov/14625336/)
- Cited evidence (PMID 26301604) [PMID:26301604](https://pubmed.ncbi.nlm.nih.gov/26301604/)
- Cited evidence (PMID 21975771) [PMID:21975771](https://pubmed.ncbi.nlm.nih.gov/21975771/)

Last reconciled with current guidelines: 2026-05-16.
References
  • IDSA/ATS 2016 HAP/VAP CPG (Kalil; PMID 27418577; current US standard 2026) + ERS/ESICM/ESCMID/ALAT 2017 (PMID 28890434) + Surviving Sepsis Campaign 2021 (Evans; PMID 34599691) — PMID:27418577
  • Cited evidence (PMID 28890434) — PMID:28890434
  • Cited evidence (PMID 14625336) — PMID:14625336
  • Cited evidence (PMID 26301604) — PMID:26301604
  • Cited evidence (PMID 21975771) — PMID:21975771