Physical Medicine & Rehabilitation (all articles)

2024 VA/DOD Clinical Practice Guideline for Stroke Rehabilitation

26 Jan, 2025 | 17:07h | UTC

Introduction:
This document summarizes the updated 2024 clinical practice guideline (CPG) jointly developed by the U.S. Department of Veterans Affairs (VA) and the U.S. Department of Defense (DOD). It addresses stroke rehabilitation across inpatient, outpatient, and community settings, emphasizing an interdisciplinary approach. The main objective is to provide evidence-based recommendations to guide clinical decision-making and improve functional outcomes and quality of life for adult stroke survivors.

Key Recommendations:

1. Transition to Community
   • Case Management: Suggest using case management services at discharge to enhance activities of daily living (ADLs) and functional independence (“weak for”).
   • Behavioral/Psychosocial Interventions: Recommend psychosocial supports, such as stress management and motivational interviewing, to improve patient and caregiver depression, family function, and overall quality of life (“weak for”).
   • Psychoeducation: Encourage structured education on stroke care and self-management for patients and their caregivers to boost functional independence and social support.
2. Motor Therapy
   • Task-Specific Practice: Strongly recommend repetitive or task-oriented practice to improve motor function, gait, posture, and ADLs (“strong for”).
   • Mirror Therapy: Suggest mirror therapy to improve motor outcomes, ADLs, and unilateral spatial neglect (“weak for”).
   • Rhythmic Auditory Stimulation: Suggest adding external auditory cues (e.g., music or metronome) to assist in gait training (“weak for”).
   • Neuromuscular Electrical Stimulation: Suggest neuromuscular electrical stimulation for enhancing upper- or lower-extremity motor recovery (“weak for”).
   • Botulinum Toxin for Spasticity: Suggest botulinum toxin for focal spasticity, considering patient-specific characteristics and preferences, though evidence shows comparable efficacy to oral baclofen except in ankle spasticity (“weak for”).
3. Dysphagia, Aphasia, and Cognition
   • Dysphagia Rehabilitation:
     • Chin tuck against resistance for swallowing impairment (“weak for”).
     • Respiratory muscle strength training (for those without tracheostomy) to reduce aspiration risk (“weak for”).
   • Aphasia Rehabilitation:
     • No specific intensity level of language therapy is proven superior; tailor therapy duration and frequency to individual needs (“neither for nor against”).
   • Cognitive Outcomes:
     • Current evidence does not support or refute SSRIs for cognitive recovery; consider other individualized cognitive rehabilitation strategies (“neither for nor against”).
   • Unilateral Spatial Neglect:
     • Mirror therapy may help address neglect and improve ADLs (“weak for”).
4. Mental Health
   • Depression Treatment:
     • Suggest SSRIs or SNRIs for patients with established poststroke depression (“weak for”).
     • Recommend psychotherapy (e.g., cognitive behavioral therapy) and consider mindfulness-based therapies for depression following stroke (“weak for”).
   • Prevention of Depression:
     • Suggest against prophylactic antidepressants for preventing poststroke depression due to risk of adverse effects, such as fractures (“weak against”).
5. Telehealth
   • Consider telerehabilitation as an alternative or adjunct to in-person therapy if it aligns with patient preferences and clinical feasibility (“weak for”).
   • Evidence is inconclusive regarding telerehabilitation for dysphagia, aphasia, or caregiver support; use individualized judgment (“neither for nor against”).
6. Noninvasive Brain Stimulation
   • Insufficient evidence to recommend for or against repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), or continuous theta burst stimulation to enhance motor recovery (“neither for nor against”).

Conclusion:
These updated 2024 VA/DOD stroke rehabilitation guidelines underscore the importance of an interdisciplinary and patient-centered approach that integrates medical, psychological, and rehabilitative strategies. Adopting these recommendations—particularly around early case management, targeted motor therapies (task-specific practice, mirror therapy, neuromuscular electrical stimulation), dysphagia interventions, and tailored mental health treatments—can improve functional outcomes, optimize quality of life, and reduce poststroke morbidity.

Reference:

• Eapen BC, Tran J, Ballard-Hernandez J, et al. Stroke Rehabilitation: Synopsis of the 2024 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guidelines. Annals of Internal Medicine. 2025. DOI: https://doi.org/10.7326/ANNALS-24-02205
• Cramer SC. Moving Stroke Rehabilitation Forward and Into the Future. Annals of Internal Medicine. 2025. DOI: https://doi.org/10.7326/ANNALS-24-03568

 

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RCT: Infrequent Zoledronate Infusions Reduce Vertebral Fractures in Early Postmenopausal Women Without Osteoporosis

18 Jan, 2025 | 16:48h | UTC

Background: Osteoporosis prevention typically targets older, higher-risk populations with significantly reduced bone mineral density (BMD). However, many fragility fractures occur in women who do not meet the traditional diagnostic threshold for osteoporosis (T score ≤ –2.5). This study investigated whether infrequent administration of zoledronate could prevent vertebral fractures in early postmenopausal women (50 to 60 years of age) who have BMD values between normal and osteoporotic ranges.

Objective: To determine if administering intravenous zoledronate once at baseline—and again 5 years later—could reduce the incidence of morphometric vertebral fractures and other fracture types over a 10-year period in early postmenopausal women without osteoporosis.

Methods:

• Design: A 10-year, prospective, double-blind, randomized, placebo-controlled trial.
• Population: 1054 women (mean age 56.0) within 10 years post-menopause, with lumbar spine or hip T scores <0 but >–2.5, recruited from the electoral roll in Auckland, New Zealand.
• Interventions: Participants were randomly assigned (1:1:1) to receive:
  1. Zoledronate 5 mg at baseline and again at Year 5 (zoledronate–zoledronate)
  2. Zoledronate 5 mg at baseline and placebo at Year 5 (zoledronate–placebo)
  3. Placebo infusions at baseline and Year 5 (placebo–placebo)
• Follow-up: 10 years, with repeated BMD and spine X-ray assessments at baseline, Year 5, and Year 10.
• Primary Endpoint: Incidence of new morphometric vertebral fractures, defined by semiquantitative radiographic methods.
• Secondary Endpoints: Fragility fracture, any fracture, major osteoporotic fracture, changes in BMD, and bone-turnover markers.

Results:

• Vertebral Fractures: Over 10 years, 6.3% of participants in the zoledronate–zoledronate group and 6.6% in the zoledronate–placebo group experienced a new morphometric vertebral fracture, versus 11.1% in placebo–placebo. After imputation, the relative risks versus placebo–placebo were 0.56 (95% CI, 0.34–0.92; p=0.04) and 0.59 (95% CI, 0.36–0.97; p=0.08), respectively.
• Other Fractures: The zoledronate–zoledronate group had a 30% reduced risk of any fracture (RR, 0.70; 95% CI, 0.56–0.88), and zoledronate–placebo showed a 23% reduction (RR, 0.77; 95% CI, 0.62–0.97), both compared with placebo–placebo.
• Bone Mineral Density: At Year 10, the zoledronate–zoledronate group had sustained BMD gains (~7–9 percentage points above placebo), whereas the zoledronate–placebo group retained a moderate advantage (~5–6 percentage points above placebo).
• Bone-Turnover Markers: Markers remained suppressed in the zoledronate–zoledronate group through Year 10, while in the zoledronate–placebo group, they gradually rose after Year 5 but stayed below baseline levels.
• Safety: Few adverse events were reported. Uveitis or episcleritis after the first infusion occurred in 1.1% of zoledronate recipients. No cases of osteonecrosis of the jaw or atypical femoral fractures were observed.

Conclusions: A single 5-mg dose of zoledronate, with an optional additional dose at five years, reduced the incidence of morphometric vertebral fractures and helped preserve BMD in younger postmenopausal women without osteoporosis. Both zoledronate regimens showed notable fracture-risk reductions and sustained effects on bone turnover.

Implications for Practice: These findings extend the potential role of zoledronate in fracture prevention to younger, early postmenopausal women without osteoporosis. Infrequent infusions are attractive because of their prolonged pharmacologic action and generally favorable safety profile. However, caution is warranted before broadly implementing this strategy for all postmenopausal women, as the data come from a relatively homogenous population and do not address other risk factors or comorbidities. Real-world adherence, healthcare resource allocation, and patient preferences must all be considered. Moreover, further evaluation of cost-effectiveness is essential, especially if expanding use to large populations. Longer follow-up in broader and more diverse groups may reveal less common adverse events that were not detected in this trial. Clinicians should therefore weigh individual risk–benefit profiles and await additional data before making universal recommendations.

Study Strengths and Limitations:

• Strengths: The trial’s 10-year duration, double-blind design, and high retention rate enhance its internal validity. Using radiographic assessments for vertebral fractures adds objectivity and robustness.
• Limitations: The trial predominantly involved healthy, early postmenopausal women of European descent, limiting the applicability of the findings to other ethnicities, older populations, or those with complex comorbidities. Only two zoledronate infusions at a five-year interval were evaluated, leaving the optimal dosing frequency unresolved. Further, while adverse events appeared uncommon here, the sample size and population profile may not adequately capture rare or long-latency adverse outcomes.

Future Research: Larger trials in more diverse demographic and clinical settings are necessary to determine whether infrequent zoledronate can safely and effectively reduce fracture risk across broader patient groups. Studies comparing different dosing schedules, as well as investigations into cost-effectiveness and logistics of administration, would be highly valuable. Longer-term surveillance in real-world cohorts should help clarify the incidence of uncommon adverse events. Ultimately, such additional evidence will guide whether infrequent zoledronate infusions might be integrated into routine practice for fracture prevention in postmenopausal women without osteoporosis.

Reference:

1. Bolland MJ, Nisa Z, Mellar A, et al. Fracture Prevention with Infrequent Zoledronate in Women 50 to 60 Years of Age. New England Journal of Medicine. 2025;392:239-248. DOI: http://doi.org/10.1056/NEJMoa2407031
2. Chapurlat R. Infrequent Zoledronate — Small Individual Gain, Larger Population Gain. New England Journal of Medicine. 2025;392:281-283. DOI: http://doi.org/10.1056/NEJMe2415376

 

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Screening for Osteoporosis to Prevent Fractures: Updated USPSTF Guidelines

18 Jan, 2025 | 15:19h | UTC

Introduction: This document summarizes the 2025 US Preventive Services Task Force (USPSTF) guideline on screening for osteoporosis to prevent fragility fractures. Osteoporosis, characterized by low bone mass and decreased bone quality, can lead to fractures that impair independence, increase morbidity, and raise mortality. The revised guidance builds on evidence that screening in select populations reduces fracture risk. Although the Task Force finds moderate net benefit for screening certain groups, it concludes that evidence remains insufficient to assess benefits and harms in other segments.

Key Recommendations:

1. Population and Rationale:
   • Women 65 years or older: The USPSTF concludes with moderate certainty that screening for osteoporosis in this age group leads to moderate net benefit for preventing osteoporotic fractures.
   • Postmenopausal women younger than 65 years at increased risk: Screening is recommended if a formal risk assessment or clinical risk factors indicate elevated risk, as moderate certainty suggests moderate benefit.
   • Men: The current evidence is insufficient to establish the balance of benefits and harms of screening men without known osteoporosis or prior fragility fractures.
2. Screening Methods:
   • The USPSTF identifies central dual-energy x-ray absorptiometry (DXA) of the hip or lumbar spine as the key screening test.
   • In younger postmenopausal women, a two-step approach is suggested: (1) assess risk factors (e.g., low body weight, smoking, parental history of hip fracture); (2) apply a validated tool (e.g., Osteoporosis Risk Assessment Instrument [ORAI] or Osteoporosis Self-assessment Tool [OST]) to determine who should proceed to DXA.
   • Tools such as FRAX may be used with or without BMD input to estimate 10-year fracture probability, but clinicians should be aware that tool accuracy and calibration vary by age, race/ethnicity, and underlying data sources.
3. Screening Intervals:
   • Current data do not clearly define an optimal interval for repeated screening.
   • Some evidence suggests little added value in repeating BMD tests within four to eight years if initial results are normal or only mildly low.
4. Management Following a Positive Screening Result:
   • After osteoporosis is confirmed, patients should be counseled on modifiable risk factors (e.g., smoking cessation, fall prevention) and assessed for pharmacotherapy.
   • Approved treatments (e.g., bisphosphonates, denosumab) have demonstrated benefit in reducing vertebral, hip, and other major fractures.
5. Harms of Screening and Treatment:
   • Screening anxiety and overdiagnosis are minimal concerns, though data are limited.
   • Bisphosphonate use has not been associated with significant excess serious adverse events in short- to medium-term trials, but rare events (e.g., atypical femur fractures, osteonecrosis of the jaw) remain possible with long-term use.
   • Denosumab reduces multiple fracture outcomes, though discontinuation can lead to rebound bone loss and increased risk of vertebral fractures without follow-up management.
   • The USPSTF underscores that treatment decisions should be individualized, especially in diverse populations and those with complex comorbidities.

Conclusion: These updated recommendations highlight the importance of osteoporosis screening in women 65 years or older and in younger postmenopausal women at higher fracture risk. Early detection with central DXA, informed by clinical risk tools, can reduce fracture incidence and related burdens. Further research is needed to clarify optimal screening intervals, the role of screening in men, and long-term treatment strategies. In the meantime, clinicians should collaborate with patients to personalize screening and treatment plans, considering both clinical risks and patient preferences.

Reference:

• US Preventive Services Task Force. Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement. JAMA. Published online January 14, 2025. DOI: http://doi.org/10.1001/jama.2024.27154
• Editorials:
  • Ensrud KE, Crandall CJ. Fracture Risk Assessment as a Component of Osteoporosis Screening—Easier Said Than Done. JAMA. Published online January 14, 2025. DOI: http://doi.org/10.1001/jama.2024.27416
  • Ott SM. Research That Could Broaden the Scope of Bone Density Screening. JAMA Netw Open. 2025;8(1):e2460746. DOI: http://doi.org/10.1001/jamanetworkopen.2024.60746
• Evidence Report:
  • Kahwati LC, Kistler CE, Booth G, et al. Screening for Osteoporosis to Prevent Fractures: A Systematic Evidence Review for the US Preventive Services Task Force. JAMA. Published online January 14, 2025. DOI: http://doi.org/10.1001/jama.2024.21653

 

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RCT: High-Flow Nasal Oxygen Noninferior to Noninvasive Ventilation for Most Acute Respiratory Failure Causes

13 Jan, 2025 | 13:11h | UTC

Background: Acute respiratory failure (ARF) arises from diverse etiologies and can manifest as hypoxemic or hypercapnic events. High-flow nasal oxygen (HFNO) and noninvasive ventilation (NIV) are common noninvasive respiratory support modalities, but robust comparative data in various ARF subgroups have been limited. Prior research suggests NIV may benefit chronic obstructive pulmonary disease (COPD) exacerbations and acute cardiogenic pulmonary edema (ACPE), yet for hypoxemic failure (including COVID-19 and immunocompromised populations), HFNO is often favored for its comfort and physiological advantages. The RENOVATE trial was designed to assess whether HFNO is noninferior to NIV for preventing intubation or death among five distinct groups of patients with ARF.

Objective: To determine if HFNO is noninferior to NIV in terms of the composite outcome of endotracheal intubation or death within seven days in patients with ARF, categorized into five subgroups: (1) nonimmunocompromised with hypoxemic ARF, (2) immunocompromised with hypoxemic ARF, (3) COPD exacerbation with respiratory acidosis, (4) ACPE, and (5) hypoxemic COVID-19.

Methods: This multicenter, adaptive, noninferiority randomized clinical trial enrolled 1800 hospitalized adults across 33 Brazilian centers. Patients were stratified by ARF etiology and randomized 1:1 to receive either HFNO or NIV. Treatment protocols allowed HFNO escalation to NIV (particularly for COPD or ACPE) if needed. The primary outcome was defined using a Bayesian hierarchical model with dynamic borrowing across subgroups; noninferiority was met if the posterior probability for an odds ratio (OR) below 1.55 reached ≥0.992. Predefined futility and superiority thresholds guided interim analyses, with a maximum sample size of 2000.

Results: Of 1800 randomized patients, 1766 completed the study (mean age 64 years; 40% women). The primary outcome (intubation or death by day 7) occurred in 39.0% (HFNO) vs 38.1% (NIV). HFNO was noninferior in four subgroups:

• Nonimmunocompromised with hypoxemia: 32.5% vs 33.1% (OR 1.02; posterior probability of noninferiority 0.999).
• COPD exacerbation with respiratory acidosis: 28.6% vs 26.2% (OR 1.05; probability 0.992).
• ACPE: 10.3% vs 21.3% (OR 0.97; probability 0.997).
• Hypoxemic COVID-19: 51.3% vs 47.0% (OR 1.13; probability 0.997).

The immunocompromised subgroup stopped enrollment early for futility; final results there did not confirm noninferiority (57.1% vs 36.4%; OR 1.07; probability 0.989). No significant differences in 28- or 90-day mortality emerged, although mortality rates were generally higher than in some previous trials. Comfort scores favored HFNO, and rates of serious adverse events were similar between groups.

Conclusions: In four of five ARF subgroups, HFNO met predefined noninferiority criteria compared with NIV regarding endotracheal intubation or death at seven days. However, immunocompromised patients with hypoxemic ARF remain an area of uncertainty, as do smaller subgroups (e.g., COPD) under non-borrowing analyses. Clinicians may consider HFNO as an alternative initial approach, recognizing that rescue NIV may still be necessary, particularly in COPD exacerbations.

Implications for Practice: These findings support using HFNO for a broad range of ARF etiologies as a first-line therapy. HFNO’s ease of use, patient comfort, and comparable safety profile may make it especially appealing. Nevertheless, clinicians should remain vigilant in immunocompromised patients and in COPD exacerbations when hypercapnia is pronounced. Potential cost variations between HFNO and NIV may influence real-world adoption, and local resources, staff expertise, and patient tolerance should guide final decisions.

Study Strengths and Limitations: Strengths include a large, diverse sample and a robust Bayesian adaptive design that allowed dynamic borrowing across subgroups. This approach increased precision but also introduced heterogeneity concerns. Some patient groups (particularly immunocompromised and COPD) were relatively small, limiting definitive conclusions in those strata. Additionally, early stopping for futility in immunocompromised patients curtailed full enrollment, and the trial compared HFNO only with face-mask NIV (rather than alternatives such as helmet CPAP).

Future Research: Further large-scale studies should refine whether HFNO can supplant NIV in COPD exacerbations and immunocompromised populations. Investigations on cost-effectiveness, patient-centered outcomes (comfort, quality of life), and comparative models (e.g., helmet NIV) are also warranted.

Reference:
• RENOVATE Investigators and the BRICNet Authors. High-Flow Nasal Oxygen vs Noninvasive Ventilation in Patients With Acute Respiratory Failure: The RENOVATE Randomized Clinical Trial. JAMA. Published online December 10, 2024. DOI: http://doi.org/10.1001/jama.2024.26244
• Frat JP, Le Pape S, Thille AW. Editorial: Is High-Flow Oxygen the Standard for All Patients With Acute Respiratory Failure? JAMA. Published online December 10, 2024. DOI: http://doi.org/10.1001/jama.2024.25906
• Freund Y, Vromant A. Editorial: Reevaluating Respiratory Support in Acute Respiratory Failure—Insights From the RENOVATE Trial and Implications for Practice. JAMA. Published online December 10, 2024. DOI: http://doi.org/10.1001/jama.2024.25869

 

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SR: Efficacy and Safety of Non-Pharmacological, Pharmacological, and Surgical Treatments for Hand Osteoarthritis

16 Jan, 2025 | 10:54h | UTC

Background: Hand osteoarthritis (OA) affects a substantial proportion of older adults, contributing to pain, reduced grip strength, and functional limitations. While several clinical guidelines recommend patient education, exercise, and topical or oral non-steroidal anti-inflammatory drugs (NSAIDs), the level of evidence remains varied. In 2018, a systematic review identified efficacy data from 126 studies. This updated review includes 65 new randomized controlled trials (RCTs) published through December 2023, aiming to provide the most current evidence on hand OA treatments.

Objective: To summarize and evaluate the efficacy and safety of non-pharmacological, pharmacological, and surgical interventions for hand OA, highlighting both short-term (<3 months) and long-term (≥3 months) outcomes for pain, function, and grip strength.

Methods: The authors searched PubMed/MEDLINE, Embase, and Cochrane CENTRAL for RCTs published from June 2017 to December 2023. Risk of bias was assessed using the RoB2 tool, and certainty of evidence was evaluated with GRADE criteria. Interventions included hand exercises, orthoses, assistive devices, thermal modalities, pharmacologic therapies (e.g., oral/topical NSAIDs, glucocorticoids, disease-modifying anti-rheumatic drugs), and various surgical techniques. Meta-analyses were conducted when appropriate, and outcomes were expressed as standardized mean differences or relative risks with 95% confidence intervals.

Results:

• Non-Pharmacological Interventions: Low- to moderate-certainty evidence supports hand exercises, thumb orthoses, and assistive devices for improving pain and function. Hand exercises showed a small long-term effect on pain, while thumb orthoses offered a moderate long-term effect on pain. Assistive devices demonstrated a moderate long-term benefit for function. Few mild adverse events were reported in these categories.
• Pharmacological Interventions: There is high-certainty evidence for a very small short-term functional improvement with topical NSAIDs and low-certainty evidence of moderate short-term pain relief with oral NSAIDs. Oral glucocorticoids likely yield a small, short-term functional benefit. Methotrexate showed a possible small long-term effect on pain but no clear impact on function. No new data support intra-articular steroid injections, hydroxychloroquine, or biologic DMARDs for meaningful improvements; in these trials, sponsor bias and cost considerations underscore the need for critical appraisal, given the typically higher expense of advanced agents like biologics.
• Surgical Interventions: Ten new studies compared various surgical techniques but did not include robust controls versus nonsurgical management or sham surgery. Heterogeneity precluded pooling of results, and no definitive superiority emerged for any particular procedure.

Conclusions: This systematic review reaffirms the central role of non-pharmacological interventions, especially exercise, orthoses, and assistive devices, for improving pain and function in hand OA with minimal adverse events. Pharmacological treatments offer modest short-term benefits, particularly oral NSAIDs, although cost, side-effect profiles, and real-world adherence should be considered. Surgical approaches lack high-quality comparative data, highlighting the need for well-designed trials.

Implications for Practice: Clinicians should prioritize patient education, exercises, and readily accessible interventions (e.g., orthoses, assistive devices) given their demonstrated safety and moderate efficacy. Oral or topical NSAIDs remain suitable options for acute pain management, with the understanding that longer-term use warrants caution due to possible adverse effects. In contexts where advanced pharmacologic agents (such as biologics) are evaluated, practitioners must scrutinize costs, potential sponsor influence, and marginal benefits relative to standard care.

Study Strengths and Limitations: Strengths of this review include a comprehensive literature search, systematic appraisal of risk of bias, and application of GRADE to gauge certainty. However, most RCTs were small in size or had high or unclear risk of bias, and considerable heterogeneity in study designs reduced comparability. Additional limitations include the scarcity of direct comparisons for surgical versus non-surgical approaches and inconsistent reporting of adverse events.

Future Research: High-quality, larger-scale RCTs are needed to clarify subtypes of hand OA and tailor treatments accordingly. Trials should evaluate long-term outcomes, systematically measure adverse events, and compare surgery directly with non-surgical options. Studies employing mobile health (mHealth) tools and addressing ways to enhance grip strength may further advance evidence-based hand OA management.

Reference:
Kjeken I, Bordvik DH, Osteras N, Haugen IK, Fjeldstad KAA, Skaalvik I, Kloppenburg M, Kroon FPB, Tveter AT, Smedslund G. Efficacy and safety of non-pharmacological, pharmacological and surgical treatments for hand osteoarthritis in 2024: a systematic review. RMD Open. 2024; e004963. DOI: https://doi.org/10.1136/rmdopen-2024-004963

 

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Review: Nutritional Support in Critically Ill Patients

6 Jan, 2025 | 11:00h | UTC

Introduction: This summary is derived from a state-of-the-art review on nutritional support in the intensive care unit (ICU) published in The BMJ. Critically ill patients experience metabolic disturbances, inflammation, and profound muscle wasting. Nutritional therapy aims to mitigate these effects, though recent randomized controlled trials (RCTs) challenge the dogma of early, aggressive provision of high-calorie and high-protein diets for all ICU patients. Instead, emerging evidence indicates that moderate energy and protein restriction, particularly during the first week, may enhance recovery and reduce complications such as hospital-acquired infections, muscle weakness, and ICU-acquired morbidity. Nonetheless, identifying ideal feeding strategies remains complex, given the dynamic nature of critical illness and the interplay with other interventions such as sedation and physical rehabilitation.

Key Recommendations:

1. Individualized Timing and Dose: Limit caloric and protein loads during the acute phase (roughly the first seven days), especially in patients with hemodynamic instability or shock. Later, as patients transition to recovery, gradually increase macronutrient delivery to meet evolving metabolic needs.
2. Preferred Feeding Route: Enteral nutrition is generally recommended when the gastrointestinal tract is functional, particularly after shock resolution. Parenteral nutrition can be reserved for prolonged gut dysfunction or inability to meet needs enterally. Studies comparing enteral versus parenteral feeding have shown no clear outcome differences, but early enteral feeding is often favored for physiological and cost reasons.
3. Avoid Overfeeding and Overzealous Protein Provision: Several large RCTs (including EFFORT-Protein, EDEN, and NUTRIREA-3) observed no mortality benefit—and in some instances, worse outcomes—when patients received full or high doses of energy and protein in the first week. Metabolic “resistance” and inhibition of protective processes such as autophagy might explain why restricted early feeding sometimes confers advantages.
4. Monitoring and Assessment: Traditional tools (NUTRIC, NRS-2002) and biomarkers (albumin, prealbumin) do not reliably predict who benefits from higher or lower feeding levels. Ultrasound or computed tomography to assess muscle mass may hold promise, but no validated approach exists to guide individualized macronutrient targets.
5. Micronutrients and Specialized Formulations: Broad-spectrum pharmaconutrients (glutamine, antioxidants, etc.) have not improved outcomes in well-powered trials. Instead, standard vitamin and trace element supplementation consistent with recommended daily allowances appears sufficient in most cases.
6. Long-term Rehabilitation: Combined nutritional support and physical exercise are critical for mitigating long-term impacts of ICU-acquired weakness and functional decline. Evidence increasingly highlights the need for prolonged, structured rehabilitation to optimize muscle recovery and quality of life.

Conclusion: Although nutritional support remains central to critical care, it is most effective when carefully adapted to disease phase, patient comorbidities, and evolving organ dysfunction. Key evidence suggests a more conservative approach to energy and protein during the acute phase, followed by gradual escalation and integration with rehabilitation. Ongoing research seeks to identify physiological markers that distinguish when to intensify nutritional therapy and how best to align macronutrient delivery with other therapies to promote muscle function and reduce complications.

Reference: Reignier J, Rice TW, Arabi YM, Casaer M. Nutritional Support in the ICU. BMJ. 2025;388:e077979. DOI: https://doi.org/10.1136/bmj-2023-077979

 

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Dose-Response Meta-Analysis: At Least 150 Weekly Minutes of Aerobic Exercise Needed for Significant Waist and Fat Reduction

2 Jan, 2025 | 09:30h | UTC

Background: Elevated body weight and adiposity remain major public health concerns worldwide, with overweight and obesity affecting nearly half of the adult population. Although various guidelines advocate for aerobic exercise as a core strategy in weight management, robust meta-analyses exploring dose-response relationships are scarce.

Objective: To clarify how different doses and intensities of supervised aerobic exercise affect body weight, waist circumference, and body fat in adults with overweight or obesity.

Methods: This systematic review and meta-analysis encompassed 116 randomized clinical trials (RCTs) including a total of 6880 participants (mean [SD] age, 46 [13] years). All studies involved supervised continuous aerobic interventions (e.g., walking or running) for at least 8 weeks. Comparisons were made against sedentary or usual-activity controls. Frequency, duration (minutes per week), and intensity (moderate, vigorous, or combined) of aerobic sessions were extracted.

Results: Across all trials, each additional 30 minutes per week of aerobic exercise was linked to a mean reduction of 0.52 kg in body weight (95% CI, −0.61 to −0.44), 0.56 cm in waist circumference, and 0.37 percentage points in body fat. Body weight and waist circumference showed largely linear decreases with increasing weekly exercise, whereas body fat percentage displayed a pattern suggesting that at least 150 minutes per week may be required to achieve clinically meaningful reductions (>2% reduction in body fat). Aerobic training was generally well tolerated, although a modest increase in mild musculoskeletal complaints was noted (risk difference, 2 more events per 100 participants).

Conclusions: Engaging in up to 300 minutes per week of aerobic exercise was associated with progressively greater benefits for weight control, waist circumference, and body fat. While even small doses yielded modest improvements, these findings suggest that an intensity of at least moderate level and a duration of at least 150 minutes per week may be necessary to achieve clinically important reductions in central obesity and fat percentage.

Implications for Practice: Clinicians managing patients with overweight or obesity can recommend a minimum of 150 minutes per week of moderate-to-vigorous aerobic training to achieve significant anthropometric changes. Gradual progression is essential to balance effectiveness and safety, especially in individuals with musculoskeletal constraints.

Study Strengths and Limitations: Strengths include the large number of RCTs, robust dose-response analyses, and consistent directions of effects. However, high heterogeneity, publication bias for certain fat measures, and limited data on medication use and health-related quality of life in longer trials were noted.

Future Research: Further trials should explore additional subgroup analyses (e.g., older adults, individuals with chronic comorbidities), longer durations of follow-up, and the integration of resistance training to optimize cardiometabolic outcomes.

Reference: Jayedi A, Soltani S, Emadi A, et al. Aerobic Exercise and Weight Loss in Adults: A Systematic Review and Dose-Response Meta-Analysis. JAMA Network Open. 2024;7(12):e2452185. DOI: http://doi.org/10.1001/jamanetworkopen.2024.52185

 

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Review: Nonsurgical Management of Chronic Venous Insufficiency

19 Dec, 2024 | 16:45h | UTC

Introduction: This summary highlights key points from a recent review on the nonsurgical management of chronic venous insufficiency, a condition characterized by persistent venous hypertension leading to edema, skin changes, and venous ulcers. Chronic venous insufficiency is influenced by both structural factors (e.g., venous reflux, obstruction) and functional elements (e.g., obesity, impaired calf-muscle pump). While interventional procedures may improve symptoms in patients with significant structural abnormalities, most cases require comprehensive nonsurgical strategies targeting venous hypertension and improving quality of life.

Key Recommendations:

1. Comprehensive Assessment: Distinguish between structural and functional components of venous disease. Structural issues may warrant endovenous procedures, whereas functional insufficiency (e.g., due to obesity, weak calf muscles) requires behavioral and medical interventions.
2. Compression Therapy (Class 1A for Venous Ulcers): Use tailored compression stockings or wraps to reduce venous pressure, alleviate swelling, and aid ulcer healing. Compression levels above 30 mm Hg can facilitate healing, but lower levels (20–30 mm Hg) may improve adherence.
3. Lifestyle Modifications: Implement weight reduction measures in obese patients to lower central venous pressure and improve venous return. Consider evaluating and managing obstructive sleep apnea or cardiac dysfunction that may elevate venous pressure.
4. Exercise and Leg Elevation: Encourage exercises that strengthen calf and foot muscles, thereby enhancing the venous pump function and reducing stasis. Advise regular leg elevation to alleviate edema and discomfort.
5. Medication Review: Assess current medications (e.g., calcium-channel blockers, gabapentinoids) that may cause edema and consider alternatives. Avoid unnecessary diuretics unless true volume overload is confirmed.
6. Venous Interventions for Structural Lesions (Class IB for Varicose Veins): In patients with symptomatic varicose veins and axial reflux, procedural interventions (e.g., endovenous ablation, sclerotherapy, or surgical stripping) can be more effective than long-term compression alone. Early intervention may expedite ulcer healing in selected cases.
7. Cautious Use of Venoactive Agents: Although certain supplements (e.g., flavonoids, horse chestnut) are widely available, current guidelines provide only weak recommendations, with limited evidence for clinically meaningful outcomes.

Conclusion: Nonsurgical management of chronic venous insufficiency emphasizes reducing venous hypertension, improving calf muscle pump function, and addressing central factors such as obesity and cardiac conditions. By combining compression therapy, exercise, weight reduction, and appropriate medication adjustments, clinicians can alleviate symptoms, enhance patient comfort, and potentially improve wound healing. Procedural interventions remain essential adjuncts for selected structural abnormalities, but long-term functional management is key to sustained clinical benefit.

Reference: Fukaya E, Kolluri R. Nonsurgical Management of Chronic Venous Insufficiency. The New England Journal of Medicine. 2024;391:2350–2359. DOI: https://doi.org/10.1056/NEJMcp2310224

 

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Review: Acute Respiratory Distress Syndrome

28 Nov, 2024 | 13:06h | UTC

Introduction: Acute respiratory distress syndrome (ARDS) is a severe inflammatory lung condition characterized by diffuse alveolar damage, leading to hypoxemia and respiratory failure. Since its initial description in 1967, the understanding and definition of ARDS have significantly evolved, integrating advances in basic science and clinical practice. A newly recommended global definition expands diagnostic criteria to enhance early recognition and management, especially in resource-limited settings. This review summarizes current insights into the epidemiology, pathophysiology, and evidence-based management of ARDS, highlighting key updates and future research priorities.

Key Recommendations:

1. New Global Definition of ARDS: Adoption of an expanded definition that includes patients receiving high-flow nasal oxygen (HFNO) support and allows diagnosis using pulse oximetry and thoracic ultrasonography. This makes ARDS identification feasible in diverse clinical environments, including those with limited resources.
2. Established Critical Care Interventions: Emphasis on early implementation of proven strategies such as low tidal volume ventilation (6 mL/kg predicted body weight) with plateau pressures ≤30 cm H₂O, prone positioning for patients with PaO₂/FiO₂ <150 mm Hg, and conservative fluid management after initial resuscitation. These interventions have consistently reduced mortality and are recommended as standard care.
3. Personalized Approaches and Phenotyping: Recognition of the heterogeneity in ARDS pathophysiology underscores the need for personalized treatment strategies. Identification of hyper-inflammatory and hypo-inflammatory phenotypes may guide targeted therapies and improve outcomes, although prospective validation is required.
4. Impact of COVID-19 on ARDS: Acknowledgment of the significant increase in ARDS incidence due to the COVID-19 pandemic. While COVID-19 ARDS shares similarities with traditional ARDS, notable differences in endothelial dysfunction and immune response highlight the necessity for tailored management approaches in these patients.
5. Pharmacologic Interventions: Updated guidelines provide conditional recommendations for the use of corticosteroids in ARDS, particularly in early moderate to severe cases. Ongoing research into pharmacologic agents such as statins, mesenchymal stromal cells, and other cell-based therapies shows potential but requires further clinical trials to establish efficacy.
6. Future Research Priorities: Identification of key areas for investigation, including the long-term sequelae of ARDS, optimization of non-invasive and invasive ventilation strategies, exploration of genetic and environmental risk factors, and development of rapid biomarker assays for real-time phenotyping and targeted therapy.

Conclusion: The evolving definition and understanding of ARDS aim to improve early detection and standardization of care across various clinical settings. Reinforcing established critical care interventions while advancing personalized and novel therapeutic approaches holds promise for reducing mortality and enhancing long-term patient outcomes. Continuous research into the pathophysiology and management of ARDS, enriched by insights from the COVID-19 pandemic, is essential to address ongoing challenges and improve patient care.

Reference: Wick KD, Ware LB, Matthay MA. Acute respiratory distress syndrome. BMJ. 2024;387:e076612. DOI: http://doi.org/10.1136/bmj-2023-076612

 

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Review: Management of Degenerative Rotator-Cuff Disorders

28 Nov, 2024 | 12:48h | UTC

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RCT: Once-Weekly Semaglutide Reduces Weight and Knee Osteoarthritis Pain in Obese Patients

16 Nov, 2024 | 13:41h | UTC

Background: Obesity is a major risk factor for the development and progression of knee osteoarthritis, leading to chronic pain and reduced mobility. Weight reduction has been shown to alleviate symptoms, but sustained, non-surgical interventions are limited. Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, have demonstrated efficacy in weight management; however, their impact on knee osteoarthritis pain is not well established.

Objective: To assess the efficacy of once-weekly subcutaneous semaglutide (2.4 mg) versus placebo, alongside lifestyle interventions, on body weight reduction and pain related to knee osteoarthritis in adults with obesity.

Methods: In this 68-week, double-blind, randomized, placebo-controlled trial conducted at 61 sites across 11 countries, 407 adults with obesity (BMI ≥30) and moderate knee osteoarthritis with at least moderate pain were enrolled. Participants were randomized in a 2:1 ratio to receive semaglutide or placebo, in addition to counseling on a reduced-calorie diet and increased physical activity. The primary endpoints were the percentage change in body weight and the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from baseline to week 68.

Results: Semaglutide treatment resulted in a mean weight reduction of −13.7% compared to −3.2% with placebo (P<0.001). The mean change in WOMAC pain score was −41.7 points with semaglutide versus −27.5 points with placebo (P<0.001), indicating a significant reduction in pain. Additionally, semaglutide led to greater improvements in physical function scores and a decrease in the use of nonsteroidal anti-inflammatory drugs. Serious adverse events were similar between groups; however, gastrointestinal disorders led to more discontinuations in the semaglutide group (6.7% vs. 3.0%).

Conclusions: Once-weekly subcutaneous semaglutide significantly reduces body weight and alleviates pain related to knee osteoarthritis in obese adults, compared to placebo, when combined with lifestyle modifications. These findings support semaglutide as an effective non-surgical intervention for weight management and symptom relief in this population.

Implications for Practice: Semaglutide may be considered as part of a comprehensive treatment strategy for obese patients with knee osteoarthritis, potentially improving pain, physical function, and reducing reliance on analgesics. Clinicians should weigh the benefits against potential gastrointestinal side effects.

Study Strengths and Limitations: Strengths include the randomized, double-blind design and a sizable, diverse cohort. Limitations involve the absence of imaging follow-up, lack of metabolic and inflammatory marker assessments, and no post-treatment outcome data to evaluate the sustainability of benefits after discontinuation.

Future Research: Further studies are warranted to explore the long-term effects of semaglutide on knee osteoarthritis progression, its mechanisms of action on joint pathology, and its effectiveness in broader patient populations.

Reference: Bliddal H, Bays H, Czernichow S, et al. Once-Weekly Semaglutide in Persons with Obesity and Knee Osteoarthritis. New England Journal of Medicine. 2024;391(17):1573-1583. DOI: http://doi.org/10.1056/NEJMoa2403664

 

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Meta-Analysis: Spinal Cord Stimulation May Be Effective for Chronic Back and Leg Pain

15 Nov, 2024 | 13:43h | UTC

Background: Chronic back and leg pain causes significant disability worldwide. Spinal cord stimulation (SCS) offers treatment for patients unresponsive to conventional medical management (CMM). The comparative efficacy of conventional and novel SCS forms versus CMM is debated, requiring thorough evaluation.

Objective: To evaluate the efficacy of conventional and novel SCS therapies compared with CMM in adults with chronic back or leg pain who had not previously used SCS.

Methods: A systematic review and Bayesian network meta-analysis per PRISMA guidelines were performed. MEDLINE, Embase, and Cochrane Library were searched up to September 2, 2022. Thirteen RCTs with 1,561 patients were included. Interventions were conventional SCS, novel SCS modalities (e.g., high-frequency, burst stimulation), and CMM. Primary outcomes were pain intensity (visual analog scale) and responder rates (≥50% pain relief) in back or leg. Secondary outcomes were quality of life (EQ-5D index) and functional disability (Oswestry Disability Index).

Results: At 6 months, both conventional and novel SCS were superior to CMM in five of six outcomes. For back pain responder rates, conventional SCS had an OR of 3.00 (95% CrI, 1.49–6.72) and novel SCS had an OR of 8.76 (95% CrI, 3.84–22.31) versus CMM. Pain intensity in the back decreased significantly with conventional SCS (MD, –1.17; 95% CrI, –1.64 to –0.70) and novel SCS (MD, –2.34; 95% CrI, –2.96 to –1.73). Leg pain intensity also decreased significantly with conventional SCS (MD, –2.89; 95% CrI, –4.03 to –1.81) and novel SCS (MD, –4.01; 95% CrI, –5.31 to –2.75) compared to CMM. Quality of life improved with both SCS therapies (conventional SCS MD, 0.15; 95% CrI, 0.09–0.21; novel SCS MD, 0.17; 95% CrI, 0.13–0.21). Functional disability improved significantly with conventional SCS (MD, –7.10; 95% CrI, –10.91 to –3.36).

Conclusions: Both conventional and novel SCS therapies are associated with significant improvements in pain relief, quality of life, and functional ability compared with CMM in patients with chronic back and leg pain at 6 months.

Implications for Practice: The results support integrating SCS therapies into clinical practice for patients with chronic back and leg pain unresponsive to CMM.

Study Strengths and Limitations: Strengths include inclusion of recent RCTs and use of Bayesian network meta-analysis, allowing comprehensive evidence synthesis with both direct and indirect comparisons, enhancing reliability. Limitations involve potential biases due to challenges in blinding participants and assessors, as patients can perceive whether a device is active. Heterogeneity among studies in patient populations and interventions may affect generalizability. Inability to include long-term efficacy data due to crossover in many trials limits understanding of sustained outcomes.

Future Research: Long-term RCTs are needed to assess sustained efficacy and safety of SCS therapies. Future studies should compare different SCS modalities directly and identify patient subgroups most likely to benefit.

Reference: Huygen FJPM, et al. Spinal Cord Stimulation vs Medical Management for Chronic Back and Leg Pain: A Systematic Review and Network Meta-Analysis. JAMA Network Open. 2024; doi: http://doi.org/10.1001/jamanetworkopen.2024.44608

 

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Review: Frailty in Older Adults

10 Nov, 2024 | 18:03h | UTC

Introduction: Frailty is a state of decreased physiological reserve and increased vulnerability to adverse health outcomes, becoming more prevalent with age. This review by Kim and Rockwood outlines definitions, biological mechanisms, measurement, and management of frailty in older adults, aiming to guide clinical practice.

Key Recommendations:

1. Definitions of Frailty: Clinicians should recognize two predominant concepts: the Fried frailty phenotype, defining frailty as a clinical syndrome with features like exhaustion, weakness, slowness, inactivity, and weight loss; and the deficit-accumulation model, quantifying frailty based on accumulated health deficits.
2. Biology of Frailty: Understanding biological mechanisms—such as chronic inflammation, cellular senescence, mitochondrial dysfunction, deregulated nutrient sensing, and hormonal changes—is essential for identifying modifiable risk factors and developing targeted interventions.
3. Measurement of Frailty: Utilize validated assessment tools appropriate to the clinical context. The Fried frailty phenotype and the deficit-accumulation frailty index are widely used; brief screening tools and performance measures like gait speed can be practical, especially in acute care settings.
4. Management and Interventions for Frailty: Management should focus on increasing physiological reserve through multicomponent interventions. Exercise (aerobic and resistance training), combined with nutritional support, comprehensive geriatric assessment, and medication optimization, has been shown to ameliorate frailty and improve mobility, strength, and daily functioning.
5. Frailty Screening Before Stressful Treatments: In high-risk clinical contexts such as oncology and surgery, pre-treatment frailty assessment can guide decision-making, personalize care plans, and improve outcomes by reducing treatment-related adverse effects.
6. Evidence Gaps and Future Directions: More research is needed on effective strategies for frailty identification, interventions to prevent or reverse frailty, and the cost-effectiveness of frailty-guided care models, particularly in primary care settings.

Conclusion: Incorporating frailty assessment into clinical practice enables personalized, holistic care that aligns with older patients’ health goals and needs. Interventions targeting frailty can enhance physiological reserve, reduce vulnerability to stressors, and improve clinical outcomes. Further research is essential to optimize frailty management strategies and fully realize the benefits of frailty-guided care in our aging society.

Reference: Kim DH, Rockwood K. Frailty in Older Adults. New England Journal of Medicine. 2024;391(6):538-548. DOI:http://doi.org/10.1056/NEJMra2301292

 

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RCT: Total Hip Replacement Superior to Resistance Training for Severe Hip Osteoarthritis

3 Nov, 2024 | 01:23h | UTC

Background: Severe hip osteoarthritis (OA) is often treated with total hip replacement (THR), yet randomized trials comparing THR with nonsurgical interventions like resistance training (RT) are lacking. While exercise is recommended for hip OA, its efficacy relative to surgery remains unclear.

Objective: To compare the effectiveness of THR with RT in patients aged 50 years or older with severe hip OA and an indication for surgery.

Methods: In a multicenter, randomized controlled trial, 109 patients were assigned to undergo THR (n=53) or participate in a 12-week supervised RT program (n=56). The primary outcome was the change in patient-reported hip pain and function from baseline to 6 months, measured by the Oxford Hip Score (OHS; range 0–48, higher scores indicate less pain and better function). Secondary outcomes included measures of pain, function, quality of life, physical activity, and functional performance. Safety was also assessed.

Results: At 6 months, the mean improvement in OHS was 15.9 points in the THR group and 4.5 points in the RT group (between-group difference: 11.4 points; 95% CI, 8.9 to 14.0; P<0.001). Significant improvements favoring THR were also observed in all secondary patient-reported outcomes. Serious adverse events occurred in 12% of patients in the THR group and 9% in the RT group; most were known complications of THR. At 6 months, 9% of patients assigned to THR had not undergone surgery, and 21% of those assigned to RT had undergone THR.

Conclusions: In patients aged 50 years or older with severe hip OA and an indication for surgery, THR resulted in clinically important, superior reductions in hip pain and improvements in function compared to RT at 6 months.

Implications for Practice: These findings support the use of THR over RT for patients with severe hip OA who are surgical candidates, affirming current clinical recommendations. However, RT may still be considered as an initial treatment option for some patients, especially those preferring to delay surgery.

Study Strengths and Limitations: Strengths include the randomized controlled design and multicenter approach. Limitations involve lack of blinding, potential selection bias due to low enrollment (14% of eligible patients), and crossovers between treatment groups, which may underestimate the true treatment effects.

Future Research: Further studies should investigate long-term outcomes, optimal timing of THR, and factors influencing patient choice and response to RT versus surgery.

Reference: Frydendal T, Christensen R, Mechlenburg I, et al. Total Hip Replacement or Resistance Training for Severe Hip Osteoarthritis. New England Journal of Medicine. 2024;391(17):1610-1620. DOI: http://doi.org/10.1056/NEJMoa2400141

 

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RCT: More Frequent Screening with Pressure-Supported SBTs Delayed Extubation in Mechanically Ventilated Adults

13 Oct, 2024 | 13:15h | UTC

Background: Prompt liberation from mechanical ventilation is crucial to reduce complications associated with prolonged ventilator use. The optimal frequency of weaning readiness screening and the most effective spontaneous breathing trial (SBT) technique are not well established.

Objective: To evaluate whether the frequency of screening for weaning readiness (once-daily vs more frequent) and the SBT technique used (pressure-supported vs T-piece) affect the time to successful extubation in adults receiving invasive mechanical ventilation.

Methods: In a multicenter randomized clinical trial with a 2×2 factorial design, 797 critically ill adults who had been mechanically ventilated for at least 24 hours were enrolled. Participants were randomized to either once-daily or more frequent screening for weaning readiness and to undergo either pressure-supported SBTs (pressure support >0 to ≤8 cm H₂O with PEEP >0 to ≤5 cm H₂O) or T-piece SBTs, each lasting 30–120 minutes. The primary outcome was the time to successful extubation, defined as the time from starting unsupported spontaneous breathing that was sustained for at least 48 hours post-extubation.

Results: Among the 797 patients (mean age 62.4 years; 59.2% male), there was no significant difference in time to successful extubation when comparing screening frequencies (hazard ratio [HR] 0.88; 95% CI, 0.76–1.03; P = .12) or SBT techniques (HR 1.06; 95% CI, 0.91–1.23; P = .45) individually. However, a significant interaction between screening frequency and SBT technique was identified (P = .009). Specifically, in patients undergoing pressure-supported SBTs, more frequent screening *delayed* time to successful extubation compared to once-daily screening (HR 0.70; 95% CI, 0.50–0.96; P = .02). Conversely, when T-piece SBTs were used, the frequency of screening did not significantly affect extubation time. The median time to successful extubation was shortest in the once-daily screening with pressure-supported SBT group (2.0 days) and longest in the more frequent screening with pressure-supported SBT group (3.9 days).

Conclusions: More frequent screening combined with pressure-supported SBTs resulted in a *longer* time to successful extubation, suggesting this combination may delay weaning from mechanical ventilation. Once-daily screening with pressure-supported SBTs showed a trend toward faster extubation compared to other strategies, although this was not statistically significant.

Implications for Practice: Clinicians should be cautious about combining more frequent screening with pressure-supported SBTs, as this may unintentionally prolong mechanical ventilation. Adopting once-daily screening with pressure-supported SBTs might facilitate earlier extubation.

Study Strengths and Limitations: Strengths of the study include its large sample size, multicenter design, and high adherence to the intervention protocols. Limitations involve the unexpected significant interaction between interventions, which may limit the generalizability of the results.

Future Research: Additional studies are warranted to confirm the interaction between screening frequency and SBT technique and to explore the mechanisms underlying the delayed extubation with more frequent screening and pressure-supported SBTs.

Reference: Burns KEA, et al (2024). Frequency of Screening and Spontaneous Breathing Trial Techniques: A Randomized Clinical Trial. JAMA. DOI: http://doi.org/10.1001/jama.2024.20631

 

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ATS Guideline: Evaluation and Management of Obesity Hypoventilation Syndrome

12 Oct, 2024 | 23:04h | UTC

Introduction: Obesity Hypoventilation Syndrome (OHS) is a serious condition characterized by obesity (BMI ≥30 kg/m²), sleep-disordered breathing, and daytime hypercapnia (PaCO₂ ≥45 mm Hg), after excluding other causes of hypoventilation. Recognizing the need for standardized evaluation and management, the American Thoracic Society (ATS) has developed comprehensive guidelines. These aim to improve early recognition, optimize treatment strategies, and reduce variability in clinical practice to enhance patient outcomes.

Key Recommendations:

1. Screening for OHS:
   • Serum Bicarbonate Measurement: For patients with low to moderate probability of OHS (<20%), a serum bicarbonate level can guide the need for arterial blood gas (ABG) analysis. A bicarbonate level <27 mmol/L suggests that measuring PaCO₂ may be unnecessary, while levels ≥27 mmol/L indicate that ABG measurement is warranted. (Quality of evidence: very low; Recommendation: conditional)
   • PaCO₂ Measurement: In patients with a high pretest probability of OHS, direct measurement of PaCO₂ is recommended over relying on serum bicarbonate or oxygen saturation levels. (Quality of evidence: very low; Recommendation: conditional)
2. Positive Airway Pressure (PAP) Therapy:
   • Use of PAP: Stable ambulatory patients diagnosed with OHS should be treated with PAP during sleep to improve gas exchange and alleviate symptoms. (Quality of evidence: very low; Recommendation: conditional)
   • Choice of Modality: For patients with OHS and coexisting severe obstructive sleep apnea (OSA) (apnea–hypopnea index ≥30 events/hour), continuous positive airway pressure (CPAP) is suggested as the first-line treatment over noninvasive ventilation (NIV). (Quality of evidence: very low; Recommendation: conditional)
3. Hospitalized Patients:
   • Discharge Planning: Patients hospitalized with respiratory failure suspected of having OHS should be discharged with NIV therapy until outpatient diagnostic evaluations and PAP titration can be completed, ideally within 2–3 months. (Quality of evidence: very low; Recommendation: conditional)
4. Weight Loss Interventions:
   • Significant Weight Reduction: Patients with OHS are advised to engage in weight-loss interventions aiming for a sustained loss of 25–30% of actual body weight to resolve hypoventilation. Bariatric surgery may be considered to achieve this goal when appropriate. (Quality of evidence: very low; Recommendation: conditional)

Conclusion: Implementing these guidelines is expected to enhance the early detection and standardized management of OHS. By following these recommendations, healthcare providers can improve patient care, reduce morbidity and mortality associated with OHS, and promote better clinical outcomes.

Reference: Mokhlesi B, et al. (2019) Evaluation and Management of Obesity Hypoventilation Syndrome: An Official American Thoracic Society Clinical Practice Guideline. American Journal of Respiratory and Critical Care Medicine. DOI: http://doi.org/10.1164/rccm.201905-1071ST

 

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RCT: Preoxygenation with Noninvasive Ventilation Reduced Hypoxemia during Emergency Intubation

19 Sep, 2024 | 12:53h | UTC

Background: Hypoxemia during tracheal intubation in critically ill adults increases the risk of cardiac arrest and death. Preoxygenation aims to mitigate this risk, but the optimal method remains uncertain. Noninvasive ventilation (NIV) may offer advantages over oxygen masks by providing positive pressure and higher inspired oxygen fractions, but evidence is limited.

Objective: To determine whether preoxygenation with noninvasive ventilation reduces the incidence of hypoxemia during tracheal intubation compared to preoxygenation with an oxygen mask among critically ill adults.

Methods: In a multicenter, pragmatic, unblinded, randomized trial conducted at 24 emergency departments and intensive care units in the United States, 1301 critically ill adults (age ≥18 years) undergoing tracheal intubation were randomized 1:1 to receive preoxygenation with either noninvasive ventilation (n=645) or an oxygen mask (n=656). Patients already receiving positive-pressure ventilation or at high risk of aspiration were excluded. In the NIV group, preoxygenation was administered using a tight-fitting mask connected to a ventilator, with an FiO₂ of 100%, expiratory pressure ≥5 cm H₂O, and inspiratory pressure ≥10 cm H₂O. In the oxygen-mask group, preoxygenation was provided using a nonrebreather mask or bag-mask device without manual ventilation, with oxygen flow ≥15 liters per minute. The primary outcome was hypoxemia during intubation, defined as oxygen saturation <85% between induction of anesthesia and 2 minutes after tracheal intubation.

Results: Hypoxemia occurred in 9.1% of patients in the NIV group versus 18.5% in the oxygen-mask group (difference –9.4 percentage points; 95% CI, –13.2 to –5.6; P<0.001). Cardiac arrest during intubation occurred in 0.2% of patients in the NIV group and 1.1% in the oxygen-mask group (difference –0.9 percentage points; 95% CI, –1.8 to –0.1). Aspiration occurred in 0.9% of patients in the NIV group and 1.4% in the oxygen-mask group (difference –0.4 percentage points; 95% CI, –1.6 to 0.7). No significant differences were observed in other adverse events.

Conclusions: Preoxygenation with noninvasive ventilation significantly reduced the incidence of hypoxemia during tracheal intubation among critically ill adults compared to preoxygenation with an oxygen mask, without increasing the risk of aspiration.

Implications for Practice: Preoxygenation with noninvasive ventilation should be considered for critically ill adults undergoing emergency tracheal intubation to reduce the risk of hypoxemia and potential cardiac arrest. Clinicians should ensure appropriate equipment and training are available for the use of NIV during preoxygenation.

Study Strengths and Limitations: Strengths include a large sample size, multicenter design across diverse emergency departments and ICUs, and pragmatic approach enhancing generalizability. Limitations include exclusion of patients already receiving positive-pressure ventilation or at high risk of aspiration, potentially limiting applicability to these populations. The unblinded design may introduce bias, although outcome data were collected by independent observers.

Future Research: Further studies are needed to evaluate the effectiveness of noninvasive ventilation for preoxygenation in patients at high risk of aspiration and to compare its efficacy with high-flow nasal cannula. Research should also assess long-term clinical outcomes and cost-effectiveness of implementing NIV for preoxygenation.

Reference: Gibbs K.W., et al. (2024) Noninvasive Ventilation for Preoxygenation during Emergency Intubation. New England Journal of Medicine. DOI: http://doi.org/10.1056/NEJMoa2313680

 

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RCT: High-Intensity NPPV Reduced Criteria for Intubation in Acute COPD Exacerbations

16 Sep, 2024 | 16:50h | UTC

Background: Acute exacerbations of chronic obstructive pulmonary disease (COPD) often lead to hypercapnic respiratory failure requiring ventilatory support. Noninvasive positive pressure ventilation (NPPV) is standard care, commonly delivered at low intensity with lower inspiratory pressures. However, approximately 15% of patients still require endotracheal intubation despite low-intensity NPPV. High-intensity NPPV, using higher inspiratory pressures to achieve greater reductions in PaCO₂, has shown benefits in stable hypercapnic COPD patients, but its effect during acute exacerbations is unclear.

Objective: To determine whether high-intensity NPPV reduces the need for endotracheal intubation in patients with acute COPD exacerbations and persistent hypercapnia compared to low-intensity NPPV.

Methods: In a multicenter, randomized clinical trial conducted at 30 respiratory wards in China from January 2019 to January 2022, 300 patients with acute COPD exacerbations and PaCO₂ greater than 45 mm Hg after 6 hours of low-intensity NPPV were enrolled. Participants were randomized 1:1 to receive either high-intensity NPPV (inspiratory positive airway pressure [IPAP] adjusted to achieve tidal volumes of 10–15 mL/kg predicted body weight, typically IPAP 20–30 cm H₂O) or to continue low-intensity NPPV (IPAP adjusted for tidal volumes of 6–10 mL/kg, maximum IPAP 20 cm H₂O). Patients in the low-intensity group meeting prespecified criteria for intubation were allowed to crossover to high-intensity NPPV. The primary outcome was the need for endotracheal intubation during hospitalization, defined by prespecified clinical and gas exchange criteria. Secondary outcomes included actual endotracheal intubation rates, mortality, length of hospital stay, and adverse events.

Results: Of the 300 patients (mean age 73 years; 68% male), the primary outcome occurred in 4.8% of the high-intensity group versus 13.7% of the low-intensity group (absolute difference –9.0%; 95% CI, –15.4% to –2.5%; one-sided P = .004; adjusted risk ratio [RR], 0.35; 95% CI, 0.14–0.76). However, actual endotracheal intubation rates did not differ significantly between groups (3.4% vs 3.9%; absolute difference –0.5%; 95% CI, –4.8% to 3.7%; P = .81). The high-intensity group had greater reductions in PaCO₂ levels over 72 hours (mean PaCO₂ at 72 hours: 53 mm Hg vs 64 mm Hg; P < .001) and higher rates of achieving normocapnia (21.8% vs 4.6%; P < .001). Abdominal distension occurred more frequently in the high-intensity group (37.4% vs 25.5%; absolute difference 11.9%; 95% CI, 1.5%–22.4%; P = .03), but other adverse events and serious adverse events were similar between groups.

Conclusions: High-intensity NPPV reduced the proportion of patients meeting criteria for endotracheal intubation compared to low-intensity NPPV in patients with acute COPD exacerbations and persistent hypercapnia. However, actual intubation rates did not differ, possibly due to crossover from low- to high-intensity NPPV in patients meeting intubation criteria.

Implications for Practice: High-intensity NPPV may be considered for patients with acute COPD exacerbations who remain hypercapnic after initial low-intensity NPPV, as it may reduce progression to severe respiratory failure requiring intubation criteria. Clinicians should monitor for abdominal distension and potential alkalosis, although these did not significantly affect overall tolerance or safety.

Study Strengths and Limitations: Strengths include the multicenter randomized design, clear enrollment criteria, and standardized protocols. Limitations include early trial termination, unblinded interventions, potential bias due to allowed crossover, and lack of power to detect differences in mortality or actual intubation rates.

Future Research: Further large-scale trials are needed to confirm these findings, assess the impact on actual intubation rates and mortality, and explore the efficacy of high-intensity NPPV in different clinical settings and patient populations, including those without prior NPPV exposure or with more severe respiratory distress.

Reference: Luo Z, Li Y, Li W, et al. Effect of High-Intensity vs Low-Intensity Noninvasive Positive Pressure Ventilation on the Need for Endotracheal Intubation in Patients With an Acute Exacerbation of Chronic Obstructive Pulmonary Disease: The HAPPEN Randomized Clinical Trial. JAMA. Published online September 16, 2024. http://doi.org/10.1001/jama.2024.15815

 

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RCT: 24-Hour Oxygen Therapy Does Not Reduce Hospitalization or Mortality Compared to 15-Hour Therapy in Severe Hypoxemia

12 Sep, 2024 | 13:21h | UTC

Study Design and Population: This multicenter, registry-based randomized controlled trial compared the effects of 24-hour versus 15-hour daily oxygen therapy in 241 patients with chronic, severe hypoxemia. Patients, recruited between 2018 and 2022, were assigned to either 24 hours (117 patients) or 15 hours (124 patients) of oxygen therapy daily. The study’s primary outcome was the composite of hospitalization or death from any cause within 1 year.

Main Findings: After 12 months, the results showed no significant difference between the two groups in the primary outcome. The event rates for hospitalization or death were similar in the 24-hour and 15-hour groups (124.7 vs. 124.5 events per 100 person-years, hazard ratio 0.99, 95% CI, 0.72-1.36). Secondary outcomes, including individual rates of hospitalization and mortality, also showed no meaningful differences, and adverse event rates were comparable between groups.

Implications for Practice: These findings suggest that increasing oxygen therapy from 15 to 24 hours per day does not reduce hospitalization or mortality in patients with severe hypoxemia. Therefore, the less burdensome 15-hour regimen may be preferable in clinical practice, as it is equally effective while reducing patient burden.

Reference: Ekström M. et al. (2024). Long-term oxygen therapy for 24 or 15 hours per day in severe hypoxemia. New England Journal of Medicine. DOI: http://doi.org/10.1056/NEJMoa2402638

 

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Meta-Analysis: ERAS Protocols Improve Recovery and Reduce Complications After Emergency Laparotomy – Am J Surg

18 Aug, 2024 | 19:32h | UTC

Study Design and Population: This systematic review and meta-analysis assessed the effects of Enhanced Recovery After Surgery (ERAS) protocols compared to standard care (SC) in patients undergoing emergency laparotomy. The analysis included six randomized clinical trials (RCTs) with a total of 509 patients.

Main Findings: The ERAS group showed a reduction in length of hospital stay (mean difference: -2.92 days) and quicker recovery milestones, such as time to ambulation (mean difference: -1.67 days) and first bowel opening (mean difference: -1.26 days). The ERAS protocols were also associated with lower rates of pulmonary complications (odds ratio [OR]: 0.43) and surgical site infections (OR: 0.33). Mortality rates were similar between the ERAS and SC groups.

Implications for Practice: These findings suggest that ERAS protocols may enhance recovery and reduce complications in patients undergoing emergency laparotomy. Implementation of these protocols could be beneficial in emergency surgical settings, where feasible.

Reference: Amir AH, Davey MG, Donlon NE. (2024). Evaluating the Impact of Enhanced Recovery After Surgery Protocols following Emergency Laparotomy – A Systematic Review and Meta-Analysis of Randomised Clinical Trials. The American Journal of Surgery. DOI: https://doi.org/10.1016/j.amjsurg.2024.115857.

 

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Meta-Analysis: Daily Sedation Interruption Shortens PICU Stay Without Impacting Mortality or Ventilation Duration in Pediatric MV Patients – JAMA Netw Open

11 Aug, 2024 | 13:19h | UTC

Study Design and Population: This systematic review and meta-analysis included six randomized clinical trials (RCTs) involving 2,810 pediatric patients receiving mechanical ventilation (MV) in the pediatric intensive care unit (PICU). The trials compared the effects of daily sedation interruption (DSI) with continuous intravenous (IV) sedation on clinical outcomes such as MV duration and PICU length of stay.

Main Findings: The analysis found that DSI was associated with a significant reduction in the length of PICU stay (mean difference of -1.45 days, p = 0.03). However, there was no significant difference in the duration of MV between DSI and continuous sedation (mean difference of -0.93 days, p = 0.06). Additionally, there were no significant differences in total sedative doses, adverse events, or mortality between the two groups.

Implications for Practice: The findings suggest that DSI may reduce the length of PICU stay without increasing the risk of adverse events, making it a potentially valuable strategy in managing sedation for pediatric patients on MV. However, further research is needed to explore the long-term neurodevelopmental outcomes associated with DSI.

Reference: Shu Wen Toh, T. et al. (2024). Daily Sedation Interruption vs Continuous Sedation in Pediatric Patients Receiving Mechanical Ventilation: A Systematic Review and Meta-analysis. JAMA Network Open, 7(8), e2426225. DOI: 10.1001/jamanetworkopen.2024.26225.

 

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Cohort Study: Thick liquids not linked to better outcomes in hospitalized patients with dementia—further studies required – JAMA Intern Med

25 May, 2024 | 19:41h | UTC

– This matched cohort study evaluated the impact of thick vs. thin liquids on clinical outcomes in 8916 hospitalized patients aged 65 and older with Alzheimer Disease and Related Dementias (ADRD) and oropharyngeal dysphagia. Conducted across 11 diverse hospitals in New York from January 2017 to September 2022, the study utilized propensity score matching to ensure comparability between the two diet groups based on demographic and clinical characteristics.

– The study found no significant difference in mortality rates between the thick and thin liquid groups (hazard ratio, 0.92; 95% CI, 0.75-1.14; P = .46). Patients on a thick liquid diet were less likely to require intubation (odds ratio [OR], 0.66; 95% CI, 0.54-0.80) but exhibited a higher incidence of respiratory complications such as pneumonia (OR, 1.73; 95% CI, 1.56-1.91).

– The findings suggest that while thick liquids may reduce the need for intubation, they may increase the risk of respiratory complications. These results underscore the necessity for future prospective studies to more definitively ascertain the effectiveness of thick liquids in improving clinical outcomes for this patient population.

 

Reference (link to abstract – $ for full-text):
Makhnevich, A. et al. (2024). Thick Liquids and Clinical Outcomes in Hospitalized Patients With Alzheimer Disease and Related Dementias and Dysphagia. JAMA Intern Med. Published online May 6, 2024. doi:10.1001/jamainternmed.2024.0736

 

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RCT: Lower oxygenation target improves days alive without life support in severe COVID-19 hypoxemia

21 Mar, 2024 | 13:46h | UTC

Study Design and Population: This multicenter randomized clinical trial investigated the impact of different oxygenation targets on the survival of adult patients with COVID-19 and severe hypoxemia in the ICU. Conducted across 11 European ICUs from August 2020 to March 2023, the study involved 726 patients requiring at least 10 L/min of oxygen or mechanical ventilation. Participants were randomly assigned to receive an oxygenation target of either 60 mm Hg (lower oxygenation group, n=365) or 90 mm Hg (higher oxygenation group, n=361) for up to 90 days.

Main Findings: The primary outcome was the number of days alive without life support at 90 days post-intervention. Patients in the lower oxygenation group achieved a median of 80.0 days alive without life support compared to 72.0 days in the higher oxygenation group, a difference that was statistically significant (P=0.009). Although there was a slight reduction in mortality at 90 days in the lower oxygenation group (30.2% vs 34.7% in the higher group), this was not statistically significant. No significant differences were observed in the proportion of patients with serious adverse events or the number of days alive and out of hospital.

Implications for Practice: Targeting a lower Pao2 of 60 mm Hg in ICU patients with COVID-19 and severe hypoxemia appears to increase the days alive without life support compared to a higher target of 90 mm Hg, without increasing serious adverse events. This finding suggests that a lower oxygenation target could be more beneficial for this patient population, potentially guiding clinical practice in managing oxygen therapy for severe COVID-19 cases.

Reference

Reference: Nielsen FM et al. (2024). Randomized Clinical Trial: Effect of Oxygenation Targets on Survival Without Life Support in COVID-19 Patients with Severe Hypoxemia. JAMA, Published online March 19, 2024. DOI: 10.1001/jama.2024.2934. Access the study here: [Link]

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Meta-Analysis: Efficacy of exercise modalities in major depressive disorder treatment

20 Mar, 2024 | 17:54h | UTC

Study Design and Population: This article presents a systematic review and network meta-analysis of randomized controlled trials to assess the optimal dose and modality of exercise for treating major depressive disorder, comparing its effects to psychotherapy, antidepressants, and control conditions such as usual care or placebo. The review included 218 unique studies encompassing 495 arms with a total of 14,170 participants who met the clinical cutoffs for major depression.

Main Findings: The findings revealed moderate reductions in depression symptoms for several exercise modalities when compared to active controls. Notably, walking or jogging, yoga, and strength training demonstrated the most significant effects. The effectiveness of exercise was found to be proportional to the intensity of the activity prescribed. Among these, yoga and strength training were identified as the most acceptable modalities for participants. However, the overall confidence in these results is low due to the high risk of bias in the included studies, with only one study meeting the criteria for a low risk of bias.

Implications for Practice: The study concludes that exercise, particularly walking or jogging, yoga, and strength training at sufficient intensities, can be an effective treatment for major depressive disorder. These modalities could be recommended alongside traditional treatments such as psychotherapy and antidepressants. Future research should focus on blinding participants and staff to mitigate expectancy effects and improve the reliability of findings. The inclusivity of exercise as a core treatment for depression could significantly impact treatment strategies and patient outcomes.

Reference: Noetel, M., et al. (2024). Effect of exercise for depression: systematic review and network meta-analysis of randomised controlled trials. BMJ, 384, e075847. DOI: https://doi.org/10.1136/bmj-2023-075847. Access the study here: [Link]

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RCT – 2ry analysis | Aerobic exercise intervention shows potential to reduce chemotherapy-induced peripheral neuropathy

11 Aug, 2023 | 15:17h | UTC

Effect of Exercise on Chemotherapy-Induced Peripheral Neuropathy Among Patients Treated for Ovarian Cancer: A Secondary Analysis of a Randomized Clinical Trial – JAMA Network Open

See also: Visual Abstract

Commentary: Aerobic Exercise Cuts Chemotherapy-Induced Peripheral Neuropathy Symptoms – HealthDay

 

Commentary on Twitter

Aerobic exercise improves chemotherapy-induced peripheral neuropathy (CIPN) in women who were treated for ovarian cancer. Incorporating referral to exercise programs as a part of standard of oncology care is recommended. https://t.co/lp9C9seyM6 @anlan_cao

— JAMA Network Open (@JAMANetworkOpen) August 1, 2023

 

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