Research ArticleResearchMedication SafetyPatient Education

Ralinepag reduced clinical worsening in pulmonary arterial hypertension but increased treatment stops

Lancet (London, England) (PubMed)Jul 28, 2026

AI-summarized from the linked source. Educational brief, not medical advice.

Brief summary

In the phase 3 ADVANCE OUTCOMES trial, 18% of patients receiving ralinepag and 36% receiving placebo had a first clinical-worsening event, while adverse events led to treatment discontinuation more often with ralinepag.

What NurseJet pulled from the source

The double-blind trial analyzed 687 adults with pulmonary arterial hypertension, 80% of whom were already receiving dual background therapy. Ralinepag lowered the hazard of the composite clinical-worsening outcome by 55% versus placebo, but 19% discontinued because of adverse events compared with 3% on placebo; adverse-event-related deaths were similar between groups.

Why this matters for nurses

Cardiology nurses help patients manage complex pulmonary-hypertension regimens and monitor symptoms, function, tolerance, and escalation needs. The benefit signal is clinically important, but the discontinuation difference reinforces the need for structured assessment during individualized dose titration.

Bedside takeaway

Pair ralinepag titration with structured monitoring for clinical worsening, tolerability, adherence, and treatment-limiting adverse effects.

How This Applies in Practice

Use this when: Caring for an adult with pulmonary arterial hypertension who is starting or titrating prescribed ralinepag.

On your shift

Reconcile background pulmonary-hypertension therapy, the current ralinepag dose, titration schedule, adherence, and any recent interruptions.
Trend cardiopulmonary symptoms, function, blood pressure, heart rate, and treatment effects required by the specialist pathway.
Escalate worsening dyspnea, syncope, edema, chest symptoms, hemodynamic change, or adverse effects that threaten continued treatment.

Keep in mind: Dose selection and changes belong to the pulmonary-hypertension prescribing plan. Follow the cardiology protocol, facility policy, and provider orders.

Key takeaways

The event-driven phase 3 trial analyzed 350 patients assigned to ralinepag and 337 assigned to placebo.
A first clinical-worsening event occurred in 18% with ralinepag and 36% with placebo, with a hazard ratio of 0.45.
Adverse events prompted treatment discontinuation in 19% of the ralinepag group and 3% of the placebo group.
The trial excluded data from 41 treated patients at sites in China because of regulatory and data-integrity concerns.

Practice implications

For a patient prescribed ralinepag, reconcile the full pulmonary-hypertension regimen and trend symptoms, function, blood pressure, heart rate, and ordered safety measures during titration. Escalate worsening cardiopulmonary status or treatment-limiting effects through the pulmonary-hypertension pathway.

Limitations & cautions

The trial used a composite outcome, and the largest numerical differences were in disease progression, addition of prostacyclin-pathway therapy, and unsatisfactory long-term response rather than death alone. Forty-one treated patients from sites in China were excluded, and the findings apply to specialist-managed adults meeting the trial's pulmonary arterial hypertension criteria.
AI-summarized from the linked source. Review the original article before applying to practice.

Citations

Exact source links

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Lancet (London, England) (PubMed)

Lancet (London, England) (PubMed). Ralinepag for the treatment of pulmonary arterial hypertension (ADVANCE OUTCOMES): a randomised, double-blind, placebo-controlled phase 3 study.

Open original source

https://pubmed.ncbi.nlm.nih.gov/42520828/

Professional education only

This summary does not replace clinical judgment, facility policy, provider orders, or official guidelines. Verify practice changes against the original source and local protocol.

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Neurosurgical review (PubMed)Oct 17, 2026Systematic Review

A systematic review and meta-analysis of 14 studies comprising 7,981 patients found extending single-agent antibiotic prophylaxis beyond one day did not reduce postoperative meningitis after endoscopic endonasal skull base surgery, whereas intraoperative CSF leak significantly increased infection risk.

Med-SurgAI summaryReview source

Systematic ReviewResearchInfection ControlMedication SafetyAI summary · original source linked below

Postoperative meningitis is an uncommon but severe complication following endoscopic endonasal skull base surgery (EESBS). While perioperative antimicrobial prophylaxis is universally administered, the required duration remains controversial, frequently leading to prolonged, non-evidence-based antibiotic courses. Following PRISMA guidelines, researchers meta-analyzed 14 studies covering 7,981 patients receiving single-agent antibiotic prophylaxis categorized as ultra-short (≤1 day), short (1–3 days), or long (>3 days). The pooled incidence of postoperative meningitis across all cohorts was 1.38% (95% CI: 0.92%–2.08%; I² = 65.8%). Subgroup analysis showed comparable meningitis rates across duration cohorts: 1.24% for ultra-short prophylaxis (95% CI: 0.66%–2.32%), 1.20% for short prophylaxis (95% CI: 0.38%–3.70%), and 2.12% for long prophylaxis (95% CI: 0.82%–5.36%), with no statistically significant difference (p = 0.764). Meta-regression confirmed prophylaxis duration was not associated with meningitis (p = 0.487). Instead, higher study-level prevalence of intraoperative cerebrospinal fluid (CSF) leakage was significantly associated with increased meningitis rates (β = 0.0389 per percentage point; p = 0.010).

Key takeaways

Meta-analysis evaluated 14 studies including 7,981 patients undergoing endoscopic endonasal skull base surgery.
Overall postoperative meningitis incidence was 1.38% (95% CI: 0.92%–2.08%).
Meningitis rates did not differ between ultra-short ≤1 day (1.24%), short 1–3 days (1.20%), or long >3 days (2.12%) antibiotic regimens (p = 0.764).
Intraoperative CSF leakage was a significant driver of postoperative meningitis (p = 0.010), while prolonged antibiotic coverage conferred no protective benefit.

Why this matters on shift

Infection preventionists and perioperative surgical nurses champion antimicrobial stewardship by stopping surgical prophylaxis within 24 hours post-procedure. This large-scale evidence confirms that extending prophylactic antibiotics beyond 24 hours does not prevent central nervous system infections in skull base surgery and reinforces focusing post-op surveillance on intraoperative CSF leak status rather than extended antibiotic exposure.

Bedside takeaway

In 7,981 skull base surgeries, postoperative meningitis incidence was 1.38% and did not differ between ≤1 day (1.24%) and >3 days (2.12%) of antibiotics, while CSF leak was the primary infection risk.

Nursing implications

Support timely discontinuation of perioperative antibiotics within 24 hours post-op in accordance with national surgical infection prevention guidelines, maintain high clinical vigilance for signs of CSF rhinorrhea, headache, nuchal rigidity, and fever, and ensure rapid diagnostic escalation if CSF drainage is suspected.

Limitations & cautions

Included cohorts were retrospective observational studies with moderate heterogeneity (I² = 65.8%); specific antibiotic choices and dosing regimens varied across surgical centers.
AI-summarized from the linked source. Review the original article before applying to practice.

Citations · exact source links

Neurosurgical review (PubMed). Duration of single-agent perioperative antibiotic prophylaxis and postoperative meningitis after endoscopic endonasal skull base surgery: a systematic review and meta-analysis of 7,981 patients.

Open original sourceFull brief

AI-summarized from the linked source. Review the original article before applying to practice.

Anesthesia and analgesia (PubMed)Oct 16, 2026Systematic Review

A meta-analysis of 25 randomized controlled trials with 3,344 surgical patients found perioperative ketamine and esketamine were associated with reduced postoperative delirium between days 2 and 7, but significantly increased postoperative dizziness.

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Postoperative delirium (POD) is a common, distressing complication in older surgical patients, yet effective pharmacologic prevention options remain limited. This systematic review and meta-analysis of 25 randomized controlled trials (RCTs) involving 3,344 patients evaluated perioperative administration of ketamine (9 trials) and esketamine (16 trials) compared to placebo or standard care. Both agents were associated with reduced POD incidence (ketamine: risk ratio [RR] 0.69; 95% CI, 0.49–0.98; P = .04; esketamine: RR 0.58; 95% CI, 0.36–0.95; P = .03). Risk reductions were most evident with higher-dose regimens (single bolus: ketamine >0.5 mg/kg or esketamine >0.25 mg/kg; cumulative dose: ketamine >1.0 mg/kg or esketamine >0.5 mg/kg), bolus-plus-infusion administration, and in major surgical procedures. However, the preventative association was present only when delirium was assessed between postoperative days 2 and 7, not within the first 24 hours. Furthermore, ketamine/esketamine significantly increased the risk of postoperative dizziness (RR 1.45; 95% CI, 1.14–1.84; P = .002). Trial sequential analysis indicated that total evidence remains inconclusive due to insufficient overall sample size.

Key takeaways

Meta-analysis analyzed 25 RCTs with 3,344 patients receiving perioperative ketamine (9 trials) or esketamine (16 trials).
Both agents were associated with lower POD incidence versus control: ketamine RR 0.69 (P = .04) and esketamine RR 0.58 (P = .03).
Delirium reduction was apparent at postoperative days 2 to 7, but not during the initial 24 hours.
Dizziness risk was significantly elevated in treated patients (RR 1.45; 95% CI, 1.14–1.84; P = .002), and trial sequential analysis found cumulative sample size insufficient to draw definitive conclusions.

Why this matters on shift

Surgical and post-anesthesia nurses monitor older adults recovering from general anesthesia for confusion, agitation, and fall risk. While ketamine and esketamine show potential neurocognitive protective signals beyond day 1, their heightened dizziness profile increases post-op balance instability, requiring cautious bedside mobility precautions rather than unreserved clinical adoption.

Bedside takeaway

In a meta-analysis of 25 RCTs (3,344 patients), perioperative ketamine (RR 0.69) and esketamine (RR 0.58) reduced delirium at days 2–7 but significantly increased dizziness (RR 1.45).

Nursing implications

Screen surgical patients systematically for emergence and delayed delirium using validated tools (such as CAM or CAM-ICU) through postoperative day 7, implement strict fall and dizziness precautions when ketamine derivatives are administered, and avoid assuming early alertness guarantees absence of delayed delirium.

Limitations & cautions

Trial sequential analysis confirmed current evidence remains inconclusive due to inadequate total information size; dizziness was increased (RR 1.45); high heterogeneity in surgical populations and anesthesia protocols.
AI-summarized from the linked source. Review the original article before applying to practice.

Citations · exact source links

Anesthesia and analgesia (PubMed). Effects of Ketamine and Esketamine on Postoperative Delirium After General Anesthesia: A Meta-Analysis and Meta-Regression Analysis.

Open original sourceFull brief

AI-summarized from the linked source. Review the original article before applying to practice.

Western journal of nursing research (PubMed)Oct 15, 2026Systematic Review

A systematic review and meta-analysis of 38 studies including 19,033 patients identified clinical severity scales—specifically Modified Fisher grade and Fisher grade—and hemodynamic status as the strongest predictors of cerebral vasospasm following subarachnoid hemorrhage.

Emergency ICUAI summaryReview source

Systematic ReviewResearchQuality ImprovementAI summary · original source linked below

Cerebral vasospasm is a severe complication of aneurysmal subarachnoid hemorrhage (SAH) that frequently precipitates delayed cerebral ischemia and increases patient mortality. To clarify clinical predictors and inform intensive care nursing assessments, investigators conducted a systematic review and meta-analysis across eight databases through August 2024, evaluating study quality with the Joanna Briggs Institute checklist and Risk of Bias 2.0 tool. Across 38 included studies (27 in the meta-analysis) encompassing 19,033 patients, clinical severity metrics showed the strongest association with cerebral vasospasm: Modified Fisher grade (odds ratio [OR] 2.88; 95% CI, 2.04–4.07), Fisher grade (OR 2.27; 95% CI, 1.91–2.69), and hemodynamic status (OR 2.56; 95% CI, 1.17–5.59). Aneurysm-related characteristics and comorbid conditions were also linked to increased vasospasm risk, whereas clinical biomarkers and inflammatory markers demonstrated comparatively smaller effect sizes.

Key takeaways

Systematic review and meta-analysis synthesized 38 studies (27 in meta-analysis) encompassing 19,033 patients after subarachnoid hemorrhage.
Radiographic and clinical severity scales showed the strongest association with cerebral vasospasm: Modified Fisher grade (OR 2.88; 95% CI, 2.04–4.07) and Fisher grade (OR 2.27; 95% CI, 1.91–2.69).
Hemodynamic instability was strongly associated with vasospasm risk (OR 2.56; 95% CI, 1.17–5.59).
Aneurysm features and comorbidities also increased risk, while clinical biomarkers and inflammatory markers demonstrated smaller effect sizes.

Why this matters on shift

Neurocritical care nurses are the first line of defense in detecting subtle neurological deterioration and hemodynamic shifts in patients hospitalized for subarachnoid hemorrhage. Understanding that initial Fisher grade and hemodynamic status carry the highest statistical odds for vasospasm reinforces rigorous serial neurological scoring and strict blood pressure monitoring during the peak vasospasm window.

Bedside takeaway

In a meta-analysis of 19,033 SAH patients, Modified Fisher grade (OR 2.88), Fisher grade (OR 2.27), and hemodynamic status (OR 2.56) were the strongest predictors of cerebral vasospasm.

Nursing implications

Identify admission Fisher or Modified Fisher scores during shift handoff, maintain strict hemodynamic parameters per provider orders, and immediately escalate focal neurological deficits, altered sensorium, or transcranial Doppler velocity increases.

Limitations & cautions

Synthesized observational studies with heterogeneous definitions and reporting standards; meta-analysis reflects statistical associations rather than prospective causal prediction models; abstract does not detail specific individual biomarker cutoff values.
AI-summarized from the linked source. Review the original article before applying to practice.

Citations · exact source links

Western journal of nursing research (PubMed). Key Predictors of Cerebral Vasospasm Following Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis.

Open original sourceFull brief

AI-summarized from the linked source. Review the original article before applying to practice.

How This Applies in Practice

Key takeaways

Practice implications

Limitations & cautions

Exact source links

More updates for this clinical area

Meta-analysis of 7,981 skull base surgeries finds extending antibiotic prophylaxis beyond 1 day does not reduce postoperative meningitis

Meta-analysis of 25 RCTs finds perioperative ketamine and esketamine reduce postoperative delirium risk but increase dizziness

Meta-analysis of 19,033 SAH patients identifies clinical severity and hemodynamics as top predictors of cerebral vasospasm