Internal Medicine
Dose-Response Meta-Analysis: At Least 150 Weekly Minutes of Aerobic Exercise Needed for Significant Waist and Fat Reduction
2 Jan, 2025 | 09:30h | UTCBackground: 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
Systematic Review and Bayesian Meta-Analysis: Higher Protein Delivery May Increase Mortality in Critically Ill Patients
2 Jan, 2025 | 08:30h | UTCBackground: Nutritional guidelines often recommend higher protein doses (approximately 1.2–2.0 g/kg/d) to mitigate muscle loss in critically ill patients. However, recent multicenter trials have raised concerns that elevated protein targets might increase mortality and adversely affect patient-centered outcomes. This study applied a Bayesian approach to synthesize current evidence regarding the effect of higher versus lower protein delivery on mortality, infections, mechanical ventilation duration, and health-related quality of life in critically ill adults.
Objective: To estimate the probability of beneficial or harmful effects of increased protein delivery on clinically important outcomes, with emphasis on quantifying the likelihood of mortality benefit versus risk.
Methods: A systematic review and Bayesian meta-analysis were conducted according to a preregistered protocol (PROSPERO CRD42024546387) and PRISMA 2020 guidelines. Twenty-two randomized controlled trials comparing higher (mean 1.5 g/kg/d) versus lower (mean 0.9 g/kg/d) protein delivery in adult ICU patients were included, ensuring similar energy intake in both groups. A hierarchical random-effects Bayesian model was applied, using vague priors to estimate relative risks for mortality and infections, mean differences for ventilator days, and standardized mean differences for quality of life.
Results: A total of 4,164 patients were analyzed. The posterior probability that higher protein intake increases mortality was 56.4%, compared with a 43.6% probability of any mortality benefit. Probabilities for a clinically relevant (≥5%) mortality decrease were low (22.9%), while the probability of at least a 5% increase reached 32.4%. Infections were slightly more likely with higher protein, although the likelihood of a major detrimental effect remained modest. The probability of a clinically meaningful difference in ventilator days was negligible, suggesting near equivalence for that endpoint. Conversely, quality of life might be negatively impacted by higher protein dosing, although few trials measured this outcome.
Conclusions: Under a Bayesian framework, current evidence suggests that high protein delivery in critically ill patients might pose a meaningful risk of increased mortality. Although a beneficial effect cannot be fully excluded, its probability appears comparatively small. These findings challenge the longstanding assumption that more protein universally translates to better outcomes.
Implications for Practice: Clinicians should exercise caution when aiming for higher protein targets. Individual patient characteristics, such as severity of illness, renal function, and underlying comorbidities, may modulate outcomes. The data support considering a personalized protein prescription rather than routinely pushing intake beyond conventional targets.
Study Strengths and Limitations: Strengths include a robust Bayesian analysis that evaluates probabilities of both benefit and harm across multiple thresholds, as well as the inclusion of recently published large trials. Limitations involve heterogeneity in protein dosing strategies, potential publication bias (indicated by Egger’s test), and limited data on quality of life.
Future Research: Ongoing trials, such as TARGET Protein and REPLENISH, will provide valuable insights into optimal protein dosing, particularly in specific subgroups. Further investigation should explore mechanistic underpinnings of how high protein intake could adversely affect recovery in critically ill patients.
Reference: Heuts S, Lee ZY, Lew CCH, et al. Higher Versus Lower Protein Delivery in Critically Ill Patients: A Systematic Review and Bayesian Meta-Analysis. Critical Care Medicine. December 27, 2024. DOI: http://doi.org/10.1097/CCM.0000000000006562
Cohort Study: Higher Telehealth Intensity May Reduce Certain Office-Based Low-Value Services in Medicare Primary Care
2 Jan, 2025 | 08:00h | UTCBackground: The rapid expansion of telehealth has raised concerns about its potential to foster wasteful services, especially in primary care. While telehealth can eliminate certain in-person interventions, it might also increase unnecessary laboratory or imaging requests, given the more limited physical exam. Evaluating how telehealth intensity affects the provision of low-value care is crucial for guiding future policy and clinical practice.
Objective: To determine whether higher telehealth utilization at the practice level is associated with changes in the rates of common low-value services among Medicare fee-for-service beneficiaries in Michigan.
Methods: Using Medicare claims data from January 1, 2019, to December 31, 2022, this retrospective cohort employed a difference-in-differences design. A total of 577,928 beneficiaries attributed to 2,552 primary care practices were included. Practices were stratified into low, medium, or high telehealth tertiles based on the volume of virtual visits per 1,000 beneficiaries in 2022. Eight low-value services relevant to primary care were grouped into four main categories: office-based (e.g., cervical cancer screening in women older than 65), laboratory-based, imaging-based, and mixed-modality services.
Results: Among the 577,928 beneficiaries (332,100 women; mean age, 76 years), practices with high telehealth utilization had a greater reduction in office-based cervical cancer screening (−2.9 [95% CI, −5.3 to −0.4] services per 1,000 beneficiaries) and low-value thyroid testing (−40 [95% CI, −70 to −9] tests per 1,000 beneficiaries), compared with low-utilization practices. No significant association emerged for other laboratory- or imaging-based low-value services, including PSA testing for men over 75 or imaging for uncomplicated low back pain. These findings suggest that while telehealth can lower certain office-based low-value services, it does not appear to substantially increase other types of wasteful care.
Conclusions: High telehealth intensity was linked to reductions in specific low-value procedures delivered in-office, without raising the overall rates of other potentially unnecessary interventions. These data may alleviate some policy concerns that telehealth drives excessive or wasteful care due to its convenience. Instead, substituting certain in-person visits with virtual encounters might curtail opportunities for procedures with minimal clinical benefit.
Implications for Practice: For clinicians and policymakers, these results underscore the possibility that carefully implemented telehealth may reduce some low-value services. Nonetheless, sustained monitoring is needed to confirm whether telehealth encourages or discourages appropriate clinical decision-making across a broader range of interventions.
Study Strengths and Limitations: Strengths include a sizable cohort, a pre- versus post-pandemic time frame, and comprehensive analysis of multiple low-value outcomes. Limitations involve the exclusive focus on beneficiaries in Michigan, the inability to capture prescription-related low-value practices (e.g., antibiotic overuse), and the reliance on claims-based measures, which lack clinical details.
Future Research: Subsequent studies should expand to different geographic areas, assess additional low-value endpoints such as overtreatment with medications, and explore whether demographic or socioeconomic factors modify telehealth’s impact on care quality.
Reference: Liu T, Zhu Z, Thompson MP, et al. Primary Care Practice Telehealth Use and Low-Value Care Services. JAMA Netw Open. 2024;7(11):e2445436. DOI: http://doi.org/10.1001/jamanetworkopen.2024.45436
Meta-analysis: One-day Low-residue Diet Achieves Comparable Bowel Cleansing Compared to Multi-day Regimens
26 Dec, 2024 | 18:21h | UTCBackground: Colorectal cancer remains a leading cause of cancer-related morbidity worldwide, making early detection through colonoscopy essential. Adequate bowel preparation is crucial to maximize mucosal visibility and detect lesions effectively. Although low-residue diets (LRDs) are commonly recommended before colonoscopy, guidelines vary regarding the optimal duration (one day versus multiple days). This systematic review and meta-analysis evaluated whether a one-day LRD regimen is non-inferior to multi-day protocols in achieving satisfactory bowel cleansing and lesion detection.
Objective: To compare the efficacy of 1-day versus >1-day LRD regimens for bowel preparation in adult patients undergoing elective colonoscopy, focusing on bowel cleanliness, polyp detection, and adenoma detection rates.
Methods: A comprehensive search of PubMed, Cochrane Central Register of Controlled Trials, ScienceDirect, Scopus, and ClinicalTrials.gov was conducted for randomized controlled trials (RCTs) comparing 1-day with >1-day LRD regimens. Six RCTs involving 2,469 participants met inclusion criteria. Patients were randomized to either a 1-day LRD (n=1,237) or a multi-day LRD (n=1,232). Adequate bowel preparation was primarily defined by a Boston Bowel Preparation Scale (BBPS) score ≥2 in each segment or total BBPS ≥6. Secondary outcomes included polyp detection rate (PDR), adenoma detection rate (ADR), withdrawal time, cecal intubation rate, and cecal intubation time.
Results: Both groups demonstrated similar rates of adequate bowel preparation (87.2% in the 1-day LRD vs. 87.1% in the multi-day group), with no significant difference (OR=1.03, 95% CI, 0.76–1.41; p=0.84; I2=0%). PDR was likewise comparable (OR=0.91, 95% CI, 0.76–1.09; p=0.29; I2=16%), as was ADR (OR=0.87, 95% CI, 0.71–1.08; p=0.21; I2=0%). Withdrawal time did not differ (MD=–0.01 minutes, 95% CI, –0.25 to 0.24; p=0.97; I2=63%), and cecal intubation parameters were also statistically similar. Across studies, the pooled mean global BBPS revealed minimal difference (MD=0.16, 95% CI, –0.02 to 0.34; p=0.08; I2=15%), confirming the non-inferiority of a shorter LRD protocol.
Conclusions: A one-day LRD achieves bowel cleansing outcomes comparable to those of multi-day LRDs, without compromising polyp or adenoma detection. This shorter regimen may help optimize patient adherence, reduce dietary restriction burden, and simplify procedural logistics, especially for busy endoscopy practices.
Implications for Practice: Adopting a 1-day LRD can streamline preparation, improve patient satisfaction, and maintain high-quality visualization. Clinicians should weigh individual patient factors such as chronic constipation or comorbidities but may generally favor a shorter dietary restriction period to enhance compliance and comfort.
Study Strengths and Limitations: This meta-analysis included only RCTs, strengthening its internal validity. Heterogeneity for primary outcomes was minimal. However, the included trials employed varied dietary protocols and bowel preparation solutions. Additionally, some studies lacked uniform reporting of cecal intubation endpoints, limiting direct comparisons. Future investigations with standardized outcome measures could offer more definitive guidance.
Future Research: Further large-scale RCTs should assess cost-effectiveness, patient-reported outcomes, and LRD composition in specific populations. Identifying optimal dietary instructions for individuals with slower colonic transit or specific nutritional needs would refine colonoscopy preparation guidelines and potentially increase detection of precancerous lesions.
Reference: Putri RD, et al. One-day low-residue diet is equally effective as the multiple-day low-residue diet in achieving adequate bowel cleansing: a meta-analysis of randomized controlled trials. Clinical Endoscopy. 2024. DOI: https://doi.org/10.5946/ce.2024.061
Three Phase 3, Placebo-Controlled Trials Show Rapid Benefits of Oral Atogepant for Migraine Prevention
26 Dec, 2024 | 12:17h | UTCBackground: Preventive therapies for migraine often require long titration and may take weeks to achieve their full effect. This analysis integrates data from three randomized, placebo-controlled Phase 3 trials (ADVANCE, ELEVATE, PROGRESS) assessing atogepant 60 mg once daily (QD) over 12 weeks, focusing on the first four weeks. A key point is that atogepant was compared only to placebo, not to other well-established migraine preventives.
Objective: To determine whether atogepant provides early efficacy in reducing migraine frequency and improving functional outcomes within the initial weeks of therapy, for both episodic and chronic migraine.
Methods: All three studies enrolled participants aged 18–80 years with a ≥1-year history of migraine. ADVANCE and ELEVATE focused on episodic migraine (EM; 4–14 monthly migraine days), while PROGRESS studied chronic migraine (CM; ≥15 monthly headache days, ≥8 of which met migraine criteria). In ELEVATE, participants had previously failed 2–4 classes of oral migraine preventives. Throughout each trial, patients recorded daily migraine-related data and completed validated functional assessments (AIM-D and EQ-5D-5L). For this pooled analysis, only the atogepant 60 mg QD and placebo arms were examined.
Results: Atogepant recipients had a significantly lower proportion of patients with a migraine day on day 1 in all three trials, suggesting a rapid onset of benefit. Reductions in weekly migraine days (WMDs) emerged as early as week 1 and remained consistently greater than placebo over the first four weeks. Functional measures improved within this same timeframe, with patients on atogepant reporting reductions in activity impairment and enhanced self-rated health. These positive findings were observed in EM (with or without prior prophylaxis failures) and in CM populations.
Conclusions: Atogepant 60 mg QD was linked to early and significant reductions in migraine days, as well as enhancements in physical functioning and daily activities, across three placebo-controlled studies. The data suggest that atogepant may offer clinically meaningful, rapid-onset prophylactic benefits.
Implications for Practice: Clinicians may consider atogepant for patients seeking a preventive migraine therapy that demonstrates a potentially faster impact on symptom frequency and daily functioning. However, direct comparisons with established active treatments are lacking, and appropriate caution in interpreting the early onset of benefit is recommended.
Study Strengths and Limitations: Major strengths include robust, double-blind methodologies and consistent findings across diverse migraine populations. A key limitation is the exclusive use of placebo as the comparator, so the relative advantage over standard preventives remains unknown. The predominantly female and White study cohorts also restrict generalizability.
Future Research: Further investigations should evaluate atogepant in direct comparisons with existing active migraine preventives, examine long-term outcomes, and recruit more diverse populations. Such efforts could better define the therapy’s place in routine migraine care.
Reference: Lipton RB, et al. Early Improvements With Atogepant for the Preventive Treatment of Migraine: Results From 3 Randomized Phase 3 Trials. Neurology. 2025;104(2). DOI: https://doi.org/10.1212/WNL.0000000000210212
Management of Adult Sepsis in Resource-Limited Settings: A Global Delphi-Based Consensus
26 Dec, 2024 | 02:06h | UTCIntroduction: This summary presents key points from a recent expert consensus on managing adult sepsis under limited-resource conditions, where patients may lack access to an ICU bed, advanced monitoring technologies, or sufficient staffing. The statements were developed through a Delphi process involving an international panel of clinicians, aiming to complement existing sepsis guidelines by focusing on pragmatic approaches and context-specific adaptations. These consensus statements address unique challenges such as limited diagnostic tests, alternative strategies for hemodynamic monitoring, and management of sepsis in areas with tropical infections.
Key Recommendations:
- Location of Care and Transfer
- When an ICU bed is unavailable, care can be provided in a non-ICU setting if minimum monitoring (neurological status, blood pressure, peripheral perfusion) is ensured.
- Before transferring a patient, ensure airway patency, initiate intravenous fluids and antimicrobials, and maintain safe transport conditions.
- Incorporate telemedicine or phone consultation with critical care specialists whenever feasible.
- Diagnostic Considerations
- Employ screening tools (e.g., qSOFA) in areas with limited resources, acknowledging its diagnostic constraints.
- Use clinical parameters like altered mental state, capillary refill time (CRT), and urine output to gauge tissue perfusion when lactate measurement is unavailable.
- Insert an indwelling urinary catheter in septic shock to monitor urine output accurately, balancing infection risks against close monitoring needs.
- Hemodynamic Management
- Rely on clinical indicators (CRT, urine output) to guide fluid resuscitation when serum lactate is not accessible.
- Use fluid responsiveness tests (e.g., passive leg raising, pulse pressure variation) if advanced hemodynamic monitoring is impractical.
- Consider balanced solutions such as Ringer’s lactate or Hartmann’s solution for fluid resuscitation.
- Recognize that patients with tropical infections (e.g., malaria, dengue) may require cautious fluid volumes to avoid overload.
- Initiate epinephrine if norepinephrine or vasopressin is unavailable, and use vasopressors through peripheral lines if central access cannot be established.
- Antimicrobial Therapy
- Administer antibiotics without delay (ideally within one hour) in suspected sepsis or septic shock.
- In severe infections of parasitic origin (e.g., malaria), start antiparasitic agents promptly.
- In settings where laboratory investigations are limited, begin broad-spectrum antimicrobial coverage when infection cannot be ruled out.
- De-escalate or discontinue therapy based on clinical improvement, declining white blood cell counts, and adequate source control.
- Respiratory Support
- For acute hypoxemic respiratory failure in septic patients, noninvasive ventilation (NIV) can be used if high-flow nasal oxygen is not available, provided close monitoring for potential failure is ensured.
Conclusion: These consensus-based statements offer practical guidance for clinicians treating sepsis in resource-limited environments. By adapting globally accepted recommendations and incorporating alternative strategies—such as clinical markers of perfusion, use of peripheral vasopressors, and prioritizing immediate antimicrobial therapy—these principles aim to improve patient outcomes where healthcare resources are scarce. Further research and context-specific adaptations will be essential to address remaining uncertainties and refine these expert recommendations.
Reference:
Thwaites, L., Nasa, P., Abbenbroek, B. et al. Management of adult sepsis in resource-limited settings: global expert consensus statements using a Delphi method. Intensive Care Medicine (2024). https://doi.org/10.1007/s00134-024-07735-7
VisionFM: A Generalist AI Surpasses Single-Modality Models in Ophthalmic Diagnostics
25 Dec, 2024 | 13:41h | UTCBackground: Ophthalmic AI models typically address single diseases or modalities. Their limited generalizability restricts broad clinical application. This study introduces VisionFM, a novel foundation model trained on 3.4 million images from over 500,000 individuals. It covers eight distinct ophthalmic imaging modalities (e.g., fundus photography, OCT, slit-lamp, ultrasound, MRI) and encompasses multiple diseases. Compared with prior single-task or single-modality approaches, VisionFM’s architecture and large-scale pretraining enable diverse tasks such as disease screening, lesion segmentation, prognosis, and prediction of systemic markers.
Objective: To develop and validate a generalist ophthalmic AI framework that can handle multiple imaging modalities, recognize multiple diseases, and adapt to new clinical tasks through efficient fine-tuning, potentially easing the global burden of vision impairment.
Methods: VisionFM employs individual Vision Transformer–based encoders for each of the eight imaging modalities, pretrained with self-supervised learning (iBOT) focused on masked image modeling. After pretraining, various task-specific decoders were fine-tuned for classification, segmentation, and prediction tasks. The model was evaluated on 53 public and 12 private datasets, covering eight disease categories (e.g., diabetic retinopathy, glaucoma, cataract), five imaging modalities (fundus photographs, OCT, etc.), plus additional tasks (e.g., MRI-based orbital tumor segmentation). Performance metrics included AUROCs, Dice similarity coefficients, F1 scores, and comparisons with ophthalmologists of varying clinical experience.
Results: VisionFM achieved an average AUROC of 0.950 (95% CI, 0.941–0.959) across eight disease categories in internal validation. External validation showed AUROCs of 0.945 (95% CI, 0.934–0.956) for diabetic retinopathy and 0.974 (95% CI, 0.966–0.983) for AMD, surpassing baseline deep learning approaches. In a 12-disease classification test involving 38 ophthalmologists, VisionFM’s accuracy matched intermediate-level specialists. It successfully handled modality shifts (e.g., grading diabetic retinopathy on previously unseen OCTA), with an AUROC of 0.935 (95% CI, 0.902–0.964). VisionFM also predicted glaucoma progression (F1, 72.3%; 95% CI, 55.0–86.3) and flagged possible intracranial tumors (AUROC, 0.986; 95% CI, 0.960–1.00) from fundus images.
Conclusions: VisionFM offers a versatile, scalable platform for comprehensive ophthalmic tasks. Through self-supervised learning and efficient fine-tuning, it extends specialist-level performance to multiple clinical scenarios and imaging modalities. The study demonstrates that large-scale, multimodal pretraining can enable robust generalization to unseen data, potentially reducing data annotation burdens and accelerating AI adoption worldwide.
Implications for Practice: VisionFM may help address global shortages of qualified ophthalmologists and expand care in low-resource settings, though clinical decision-making still requires appropriate human oversight. Further multicenter studies are needed before widespread implementation, especially for higher-risk use cases such as tumor detection.
Study Strengths and Limitations: Strengths include its unique multimodal design, large-scale pretraining, and extensive external validation. Limitations involve demographic bias toward Chinese datasets, the need for larger cohorts in certain applications (e.g., intracranial tumor detection), and the challenges of matching real-world clinical complexity when only image-based data are used.
Future Research: Further validation in diverse populations, integration of new imaging modalities (e.g., widefield imaging, ultrasound variants), and expansion to additional diseases are planned. Hybridization with large language models could facilitate automatic generation of clinical reports.
Reference: Qiu J, Wu J, Wei H, et al. Development and Validation of a Multimodal Multitask Vision Foundation Model for Generalist Ophthalmic Artificial Intelligence. NEJM AI 2024;1(12). DOI: http://doi.org/10.1056/AIoa2300221
Meta-analysis: Incidence Rate Difference of Adverse Events from Canabinoids in Middle-Aged and Older Adults
25 Dec, 2024 | 12:19h | UTCBackground: Growing evidence suggests that cannabinoid-based medicines (CBMs) are increasingly prescribed to individuals aged 50 years and above for various clinical conditions. While these agents may offer therapeutic benefits, questions remain about the incidence of adverse events (AEs), particularly in older adults with multiple comorbidities. This systematic review and meta-analysis aims to quantify the incidence rate difference (IRD) of AEs and determine whether weekly doses of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are associated with any dose-dependent increase in risk.
Objective: To evaluate whether adults aged ≥50 years exposed to CBMs, including THC-alone formulations and THC combined with CBD, experience a higher incidence of AEs than controls, and to assess how variations in weekly THC and CBD doses might affect AE rates.
Methods: Researchers searched MEDLINE, PubMed, EMBASE, CINAHL, PsychInfo, Cochrane Library, and ClinicalTrials.gov from January 1, 1990, to June 12, 2023. Randomized clinical trials involving middle-aged and older adults (mean age ≥50 years) using medicinal CBMs for all indications were included. Data on common and serious AEs, withdrawals, and deaths were extracted and pooled using a random-effects model. Further meta-regression analyses examined THC and CBD weekly doses as predictors of AEs in THC-only and THC:CBD trials.
Results: Fifty-eight randomized clinical trials (n=6611) met inclusion criteria, with 3450 participants receiving CBMs. Compared to controls, individuals on THC-alone experienced significantly higher incidence of dizziness, somnolence, impaired coordination, dissociative symptoms, and dry mouth, often in a dose-dependent manner. Similarly, THC:CBD combinations increased nausea, vomiting, fatigue, dizziness, and disorientation. The incidence of serious AEs, withdrawals, or mortality did not differ significantly between CBM and control groups, although neurological or psychiatric side effects were more pronounced with higher THC doses.
Conclusions: THC-containing CBMs can provoke dose-related gastrointestinal, neurological, and psychiatric adverse events, posing additional risks in older adults susceptible to falls and cognitive disturbances. However, the meta-analysis found no significant increases in serious AEs or deaths. Clinicians should weigh potential benefits against the likelihood of common side effects, especially when prescribing higher THC doses or combining cannabinoids with other medications frequently used by older patients.
Implications for Practice:
- Physicians should exercise caution when initiating or escalating THC-based therapies in middle-aged and older adults, monitoring for neurological or psychiatric AEs.
- Using lower THC doses, titrating gradually, and adding CBD may mitigate some side effects.
- Though severe AEs are uncommon, vigilance is warranted in individuals with complex medication regimens.
Study Strengths and Limitations:
- Strength: This review merges diverse clinical conditions and provides a comprehensive assessment of THC vs. THC:CBD. Its large pooled population allows for more precise IRD estimates.
- Limitation: Short treatment durations in many trials limit understanding of long-term toxicity, and some studies lacked rigorous reporting of randomization and outcome measures, potentially introducing bias.
Future Research:
- Longer-duration trials focused on older populations are needed to clarify chronic safety profiles.
- Studies exploring drug-drug interactions between CBMs and medications commonly prescribed to older adults will further elucidate real-world tolerability.
Reference: Velayudhan L, Pisani S, Dugonjic M, McGoohan K, Bhattacharyya S. Adverse events caused by cannabinoids in middle aged and older adults for all indications: a meta-analysis of incidence rate difference. Age and Ageing. 2024;53(11):afae261. DOI: https://doi.org/10.1093/ageing/afae261
Bayesian Network Meta-Analysis: Chlorpromazine IV/IM Emerges as a Top Choice for Acute Migraine Relief in the ED
25 Dec, 2024 | 11:18h | UTCBackground: Acute migraine is a prevalent cause of emergency department (ED) visits, necessitating prompt pain control. Although numerous drugs are available, there is debate about the most effective and safest options. Traditional pairwise meta-analyses fail to capture all treatment comparisons in a single framework, making network meta-analyses, particularly Bayesian, an appealing approach to inform clinical decision-making.
Objective: This systematic review and Bayesian network meta-analysis aimed to compare multiple pharmacologic therapies—single agents or combinations—for acute migraine relief in adults presenting to the ED. The goal was to identify those most likely to achieve adequate pain relief, reduce rescue medication use, and minimize significant adverse reactions.
Methods: The authors searched MEDLINE, Embase, and Web of Science from inception to February 9, 2024, for randomized controlled trials comparing any pharmacologic therapy to another or to placebo in ED patients with migraine. Four primary outcomes were analyzed: (1) adequate pain relief at two hours, (2) change in pain intensity at one hour, (3) need for rescue drug at two hours, and (4) significant adverse reaction (eg, sedation, akathisia, hypotension).
Results: Twenty-four to twenty-seven trials contributed to each outcome network. Chlorpromazine IV/IM was ranked highest for adequate pain relief (SUCRA=87.3%) and also significantly reduced the need for rescue medication (SUCRA=93.2%). Ibuprofen IV and valproate IV emerged among the least effective for pain relief, while dexamethasone IV was the most probable to cause fewer serious adverse reactions (SUCRA=79.5%). However, most comparisons were of low or very low certainty, limiting the strength of the findings.
Conclusions: Chlorpromazine IV/IM appears among the most effective single agents for acute migraine in the ED, although it may carry higher risks of sedation or hypotension. Certain analgesics (eg, ibuprofen IV, valproate IV, and possibly ketorolac IV/IM) demonstrated lower efficacy. Due to variability in trial size, dosing, and participant characteristics, the overall certainty of evidence remains limited.
Implications for Practice: Clinicians may consider parenteral chlorpromazine for rapid migraine relief, balancing its adverse event profile with potential efficacy. Dexamethasone’s lower probability of serious side effects could make it a complementary option. The findings highlight the need for individualized treatment, taking into account patient comorbidities and preferences.
Study Strengths and Limitations: This network meta-analysis offers a broad comparative perspective on diverse pharmacologic interventions for ED-based migraine management. Nonetheless, there is notable heterogeneity in study methodologies, small sample sizes, and sparse direct comparisons for many interventions, all of which reduce certainty in the estimates.
Future Research: Larger, more standardized trials are needed to confirm these results and directly compare drugs like chlorpromazine, prochlorperazine, and metoclopramide-NSAID combinations. Rigorous safety reporting is crucial to clarify adverse reaction risks for various agents, especially those with less available evidence.
Reference: deSouza IS, Anthony N, Thode H Jr, et al. Effectiveness and Safety of Pharmacologic Therapies for Migraine in the Emergency Department: A Systematic Review and Bayesian Network Meta-analysis. Annals of Emergency Medicine. DOI: http://doi.org/10.1016/j.annemergmed.2024.11.004
AGA Clinical Practice Update on Screening and Surveillance in High-Risk US Populations for Gastric Cancer: Expert Review
25 Dec, 2024 | 11:02h | UTCIntroduction:
This American Gastroenterological Association (AGA) Clinical Practice Update provides guidance on primary and secondary prevention strategies for gastric cancer (GC) among high-risk groups in the United States. GC disproportionately affects racial and ethnic minorities, certain first-generation immigrants from countries with elevated GC incidence, and individuals with specific hereditary syndromes or family histories of GC. Given ongoing disparities in diagnosis and outcomes, this document outlines best practices for recognizing at-risk individuals, performing high-quality endoscopic screening, and establishing surveillance protocols for gastric precancerous conditions.
Key Recommendations:
- Identify High-Risk Groups: Consider screening among first-generation immigrants from high-incidence regions, people with a family history of GC in a first-degree relative, individuals with hereditary gastrointestinal syndromes, and patients with multiple risk factors (eg, chronic Helicobacter pylori infection, smoking, diets high in salt and processed meats).
- Preferred Screening Modality: Upper endoscopy is considered the best method for detecting precancerous lesions (atrophic gastritis and intestinal metaplasia) and early malignancies. It allows direct visualization of the gastric mucosa, systematic biopsy, and accurate histologic staging.
- High-Quality Endoscopic Examination: Essential elements include high-definition endoscopes, optimal mucosal cleansing and insufflation, adequate inspection time, systematic photodocumentation, and biopsy protocols (such as the updated Sydney System) to detect and characterize precancerous changes or early cancer.
- H. pylori Eradication: Opportunistic screening for H. pylori and its eradication are key adjunctive measures in preventing GC development. Family-based testing—screening adult household members of H. pylori–positive individuals—may further reduce reinfection rates and disease progression.
- Systematic Biopsy Protocols: When atrophic gastritis or intestinal metaplasia is suspected, obtain at least five biopsies (antrum/incisura and corpus in separate containers). Any suspicious lesion should be sampled independently.
- Recognition of Metaplasia and Dysplasia: Endoscopists should be trained to accurately identify visual patterns associated with gastric intestinal metaplasia (GIM) and dysplasia. Artificial intelligence may hold promise, but current data are insufficient to recommend routine use.
- Risk Stratification and Surveillance Intervals: Patients with confirmed GIM or dysplasia, especially those with severe or extensive metaplasia, may require follow-up endoscopy every three years. Individuals with multiple risk factors or severe metaplastic changes could benefit from shorter intervals.
- Management of Dysplasia and Early GC: All dysplasia should be reviewed by an expert gastrointestinal pathologist. Visible high-grade dysplasia or early GC lesions generally warrant endoscopic submucosal dissection (ESD) at specialized centers to achieve en bloc, R0 resection and enable accurate pathology.
- Post-Resection Surveillance: Individuals with successfully resected dysplasia or early cancer need ongoing endoscopic surveillance to detect metachronous lesions. Surveillance intervals vary depending on pathology results and patient-level factors.
- De-Escalation of Screening: Discontinue screening or surveillance when the patient is no longer fit for potential endoscopic or surgical treatment.
- Equity and Sustainability: To reduce GC mortality, it is crucial to address modifiable risk factors, enhance patient access to endoscopy and skilled practitioners, and integrate research advances, especially in noninvasive biomarker development and improved endoscopic technologies.
Conclusion:
An effective US-based GC screening and surveillance program requires robust preprocedural identification of high-risk individuals, intraprocedural adherence to quality endoscopy standards, and consistent postprocedural follow-up to ensure equitable access to treatment. By refining these clinical practices and prioritizing research, meaningful reductions in GC incidence and mortality can be achieved, ultimately improving patient outcomes and addressing healthcare disparities.
Reference:
Shah SC, Wang AY, Wallace MB, Hwang JH. AGA Clinical Practice Update on Screening and Surveillance in Individuals at Increased Risk for Gastric Cancer in the United States: Expert Review. Gastroenterology. Published online December 23, 2024.
https://doi.org/10.1053/j.gastro.2024.11.001
RCT: Levofloxacin for the Prevention of Multidrug-Resistant Tuberculosis in Vietnam
24 Dec, 2024 | 12:53h | UTCBackground:
Multidrug-resistant (MDR) and rifampin-resistant tuberculosis pose significant global health challenges. Preventing active disease among contacts exposed to resistant strains is critical, yet limited evidence exists on targeted chemopreventive interventions. This study investigated whether a six-month course of daily levofloxacin could reduce the incidence of bacteriologically confirmed tuberculosis among household contacts of individuals with confirmed MDR or rifampin-resistant tuberculosis in Vietnam.
Objective:
To assess if levofloxacin prophylaxis decreases the 30-month incidence of active tuberculosis among high-risk contacts. Primary endpoints included bacteriologically confirmed disease, and secondary outcomes encompassed adverse events, mortality, and development of fluoroquinolone-resistant Mycobacterium tuberculosis.
Methods:
Researchers conducted a double-blind, placebo-controlled, randomized trial. Eligible participants were household contacts of persons who had started MDR tuberculosis treatment within the previous three months, had a positive tuberculin skin test or immunosuppressive condition, and showed no clinical or radiographic signs of active disease. Enrolled individuals received weight-based oral levofloxacin (up to 750 mg/day) or an identical placebo for 180 days. Monthly visits supported adherence and monitored adverse events. Participants underwent follow-up visits every six months until 30 months for tuberculosis screening, chest radiography, and sputum testing where indicated.
Results:
Of 2041 randomized contacts, 1995 (97.7%) completed 30 months of follow-up or reached a primary endpoint. Confirmed tuberculosis was diagnosed in 6 participants (0.6%) in the levofloxacin group and 11 (1.1%) in the placebo group (incidence rate ratio, 0.55; 95% CI, 0.19–1.62), a difference that did not achieve statistical significance. Severe (grade 3 or 4) adverse events were infrequent in both groups, while mild adverse events were more common with levofloxacin (31.9% vs. 13.0%). Acquired fluoroquinolone resistance was not detected.
Conclusions:
Daily levofloxacin for six months showed a numerically lower incidence of tuberculosis than placebo, but the difference was not statistically significant due to lower-than-expected case counts. Treatment was generally well tolerated; however, higher discontinuation rates occurred among levofloxacin recipients, often due to mild musculoskeletal complaints. Further studies may clarify the role of fluoroquinolone-based regimens in preventing MDR tuberculosis across diverse epidemiologic contexts.
Implications for Practice:
These findings suggest that levofloxacin prophylaxis could benefit contacts at high risk of MDR tuberculosis, albeit with caution regarding adherence challenges and low-grade side effects. Broader implementation would require diligent screening, consideration of background fluoroquinolone resistance, and strategies to manage mild adverse events that could undermine treatment completion.
Study Strengths and Limitations:
Strengths include a rigorous double-blind, placebo-controlled design, nearly complete follow-up, and thorough exclusion of prevalent tuberculosis at baseline. Limitations involve an unexpectedly low incidence of confirmed disease, limiting statistical power, and a study population with low HIV prevalence, which may reduce generalizability.
Future Research:
Further research is necessary to confirm these findings in diverse settings, explore alternative or shorter regimens (including newer agents like delamanid), and investigate optimal approaches for patients with fluoroquinolone-resistant strains. The long-term impact on transmission dynamics and microbiome shifts also warrants additional investigation.
Guideline: Metformin to Prevent Antipsychotic-Induced Weight Gain
23 Dec, 2024 | 20:55h | UTCIntroduction:
This guideline was developed to address a pressing need for strategies to prevent antipsychotic-induced weight gain (AIWG), a frequent and troubling adverse effect of treatment in individuals with severe mental illness (SMI). Although metformin has shown consistent benefits in mitigating weight gain when initiated alongside antipsychotics, clinical uptake remains limited. The guideline follows the AGREE II framework and synthesizes both randomized and observational research, including Cochrane and meta-analytic data. The primary objective is to outline explicit indications, dosing approaches, and duration for using metformin to avert AIWG.
Key Recommendations:
- Co-initiation With High-Risk Agents: In patients requiring higher-risk antipsychotics (olanzapine, clozapine), start metformin simultaneously. Evidence suggests that concurrent treatment may lessen weight gain by 3 to 5 kg in the early months, potentially yielding greater benefits over time.
- Co-initiation With Medium-Risk Agents: For individuals prescribed quetiapine, paliperidone, or risperidone who have at least one cardiometabolic risk factor (such as diabetes, prediabetes, hypertension, or BMI above 25) or who are 10 to 25 years old, begin metformin at antipsychotic initiation to curb rapid weight changes.
- Initiation During the First Year: If, at any point in the first year of antipsychotic treatment, weight gain exceeds 3% over baseline, consider adding metformin regardless of the antipsychotic being used.
- Titration Schedule and Safety: The guideline advises starting at 500 mg once daily, then moving to 500 mg twice daily after about two weeks, with subsequent increases every two weeks up to 1 g twice daily (2 g/day) as tolerated. Metformin must be discontinued if lactic acidosis is suspected, if BMI falls below 20, or if the antipsychotic is stopped. Avoid its use in harmful alcohol consumption.
- Additional Treatment Options: In cases of obesity (BMI ≥30) or comorbid metabolic disorders, clinicians should consider adding glucagon-like peptide-1 receptor agonists (GLP-1) where available. If cost, supply, or access is limited, metformin remains a practical alternative.
Conclusion:
This is the first evidence-based guideline focused on preventing AIWG by starting metformin at the time of antipsychotic initiation or upon early weight gain signs. By reducing the magnitude of weight increase, metformin may alleviate health risks tied to obesity, as well as psychological distress and nonadherence to treatment. Implementing the guideline involves continuous weight monitoring, structured dose adjustments, and shared decision-making. Ensuring clear communication about benefits and potential side effects will be crucial for sustaining adherence and improving patient outcomes.
Reference:
Carolan A, Hynes-Ryan C, Agarwal SM, Bourke R, Cullen W, Gaughran F, Hahn MK, Krivoy A, Lally J, Leucht S, et al. Metformin for the Prevention of Antipsychotic-Induced Weight Gain: Guideline Development and Consensus Validation. Schizophrenia Bulletin. 2024; sbae205.
DOI: https://doi.org/10.1093/schbul/sbae205
Additional Commentaries:
- Psychiatric News Alert: https://alert.psychnews.org/2024/12/new-guideline-advises-metformin-to.html
- Zagorski N. Metformin May Reduce Weight Gain in Youth Taking Antipsychotics. Psychiatric News. 2024; 59(01). https://psychiatryonline.org/doi/full/10.1176/appi.pn.2024.01.1.22
2025 ASA Practice Advisory for the Perioperative Care of Older Adults Undergoing Inpatient Surgery
23 Dec, 2024 | 20:27h | UTCIntroduction: This summary outlines the American Society of Anesthesiologists (ASA) 2025 advisory on optimizing perioperative care for older adults (age 65 years or older) undergoing inpatient surgery. It focuses on preoperative, intraoperative, and postoperative measures to mitigate cognitive complications, especially delirium and longer-term cognitive decline, in a population that is highly vulnerable to functional deterioration and loss of independence. The recommendations are based on systematic reviews and meta-analyses, supplemented by expert consensus where evidence is limited. Although not intended as strict standards of care, these advisory statements provide practical guidance that can be adapted to local contexts and patient-specific needs.
Key Recommendations:
- Expanded Preoperative Evaluation:
- Incorporate frailty assessment, cognitive screening, and psychosocial or nutritional evaluations into routine preoperative workups for older patients.
- Patients identified with frailty or cognitive deficits should receive targeted interventions, such as geriatric co-management, deprescribing when indicated, and early family education about delirium risks.
- Evidence suggests a modest decrease in postoperative delirium when such evaluations are included.
- Choice of Primary Anesthetic (Neuraxial vs. General):
- Current studies do not demonstrate a clear advantage of neuraxial over general anesthesia in reducing postoperative delirium risk.
- Both approaches are acceptable; individualize decisions based on patient factors, surgical requirements, and preference-sensitive discussions.
- Maintenance of General Anesthesia (Total Intravenous vs. Inhaled Agents):
- Data are inconclusive regarding delirium prevention, with no significant difference between total intravenous anesthesia (TIVA) and inhaled volatile agents.
- Some low-level evidence indicates TIVA might reduce short-term cognitive decline, but this effect is inconsistent over longer follow-up.
- Dexmedetomidine for Delirium Prophylaxis:
- Moderate-level evidence supports dexmedetomidine for reducing delirium incidence in older patients, yet its use may increase bradycardia and hypotension.
- Optimal dosing and timing remain uncertain, and baseline patient vulnerability should inform decisions.
- Medications with Potential Central Nervous System Effects:
- Drugs such as benzodiazepines, antipsychotics, anticholinergics, ketamine, and gabapentinoids warrant careful risk-benefit analysis.
- Current findings are inconclusive, suggesting neither a firm endorsement nor outright disapproval; preexisting conditions and polypharmacy should guide individualized treatment plans.
Conclusion: Preserving cognitive function and independence in older adults undergoing inpatient surgery is a growing priority. These recommendations highlight the importance of comprehensive preoperative screenings (frailty, cognition, and psychosocial domains), shared decision-making when choosing anesthetic techniques, and thoughtful use of pharmacologic agents. While dexmedetomidine shows promise in mitigating delirium, vigilance regarding hypotension and bradycardia is essential. Ultimately, these strategies aim to reduce anesthesia-related complications in older patients by addressing the multifaceted determinants of postoperative cognitive outcomes.
RCT: Early Restrictive vs Liberal Oxygen Strategy in Severe Trauma – No Significant Outcome Difference
22 Dec, 2024 | 17:21h | UTCBackground: The Advanced Trauma Life Support (ATLS) guidelines recommend providing supplemental oxygen to severely injured patients in the early phase after trauma, although the evidence base is limited. Observational research suggests that liberal oxygen administration may raise the risk of death and respiratory complications. Therefore, the TRAUMOX2 trial examined whether an 8-hour restrictive oxygen strategy (targeting an SpO₂ of 94%) could improve outcomes compared with a liberal strategy (12–15 L/min or FiO₂ 0.6–1.0) initiated prehospital or upon trauma center admission.
Objective: To determine whether an early restrictive oxygen approach, as compared with a liberal approach, reduces the composite outcome of death and/or major respiratory complications (pneumonia or ARDS) within 30 days in severely injured adults.
Methods: This investigator-initiated, international, multicenter, open-label, randomized controlled trial enrolled patients aged 18 years or older with blunt or penetrating trauma requiring full trauma team activation and anticipated hospital stay of at least 24 hours. Randomization occurred either prehospital or upon trauma center arrival in a 1:1 ratio to restrictive (lowest dose of oxygen to maintain SpO₂ at 94%) versus liberal therapy (12–15 L/min via nonrebreather mask or FiO₂ 0.6–1.0). The intervention lasted 8 hours, with all other management per standard care. The primary outcome—death or major respiratory complications (pneumonia per CDC criteria or ARDS per the Berlin definition)—was evaluated by blinded assessors within 30 days. Statistical analyses employed logistic regression, adjusted for stratification variables.
Results: Among 1979 randomized patients, 1508 completed the study (median age, 50 years; Injury Severity Score [ISS], 14). The composite primary outcome occurred in 16.1% (118/733) of restrictive-group patients and 16.7% (121/724) of liberal-group patients (odds ratio, 1.01; 95% CI, 0.75–1.37; p=0.94). Mortality alone (8.6% vs 7.3%) and major respiratory complications alone (8.9% vs 10.8%) showed no significant differences between groups. Adverse and serious adverse events were similar, except atelectasis was less frequent in the restrictive group (27.6% vs 34.7%).
Conclusions: In severely injured trauma patients, an 8-hour restrictive oxygen strategy did not significantly reduce death or major respiratory complications compared with a liberal strategy. Both approaches produced similar 30-day outcomes. Nevertheless, restricting oxygen may limit atelectasis and could be a reasonable alternative to giving high-flow oxygen to all trauma patients.
Implications for Practice: Clinicians may choose to target approximately 94% SpO₂ in the early trauma phase without compromising major outcomes. This approach potentially avoids the risks of hyperoxia, though no definitive survival benefit was identified. Pragmatic implementation of a conservative oxygen strategy seems feasible in diverse prehospital and hospital settings.
Study Strengths and Limitations: Notable strengths include multicenter design, randomized enrollment in prehospital and in-hospital settings, and blinded outcome assessment. Limitations include postrandomization exclusions of patients with minor injuries, a relatively short intervention period (8 hours), and an overall open-label design. These factors, along with lower-than-expected event rates, may have limited the power to detect differences in mortality. Commentary from https://bit.ly/bottomline_traumox2 also highlights that the median ISS of 14 indicates moderate rather than extremely severe trauma, possibly contributing to the modest event rates.
Future Research: Large-scale studies with extended intervention durations and targeted subgroups (e.g., severe traumatic brain injury) could clarify optimal oxygen thresholds in trauma care. Ongoing trials with larger sample sizes may better capture smaller but clinically meaningful differences in mortality or complications.
Meta-Analysis: Endovascular Therapy for Vertebrobasilar Occlusion Improves Functional Outcomes
19 Dec, 2024 | 22:56h | UTCBackground: Acute vertebrobasilar artery occlusion (VBAO) is associated with high mortality and severe neurological deficits. Previous randomized trials of endovascular therapy (EVT) for VBAO have shown inconsistent results, leaving uncertainty about its efficacy across different patient subgroups.
Objective: To determine whether EVT confers improved 90-day functional outcomes compared with standard medical therapy alone in patients with acute VBAO and to explore treatment effect heterogeneity in prespecified subgroups.
Methods: This individual patient data meta-analysis included all four major randomized controlled trials (ATTENTION, BAOCHE, BASICS, BEST) that enrolled patients with VBAO treated within 24 hours of estimated onset. Participants received either EVT or best medical therapy. The primary outcome was a favorable functional status at 90 days (modified Rankin Scale [mRS] score 0–3). Secondary outcomes included functional independence (mRS 0–2), distribution of mRS scores (shift analysis), symptomatic intracranial hemorrhage (sICH), and all-cause mortality at 90 days.
Results: Among 988 patients (556 EVT; 432 control), median age 67 years, EVT significantly increased the proportion achieving mRS 0–3 (45% vs 30%; adjusted odds ratio [aOR] 2.41, 95% CI 1.78–3.26) and mRS 0–2 (35% vs 21%; aOR 2.52, 95% CI 1.82–3.48). EVT improved the overall distribution of functional outcomes (aOR for mRS shift 2.09, 95% CI 1.61–2.71) and reduced 90-day mortality (36% vs 45%; aOR 0.60, 95% CI 0.45–0.80). Although sICH was more common with EVT (5% vs <1%; aOR 11.98, 95% CI 2.82–50.81), the net clinical benefit remained strongly in favor of EVT. Subgroup analyses showed broadly consistent benefit, though the advantage was uncertain for patients with mild baseline severity (NIHSS <10).
Conclusions: EVT for acute VBAO significantly improves functional outcomes and reduces mortality despite a higher sICH risk. These results support EVT as a standard consideration in appropriately selected patients with moderate-to-severe VBAO. The benefit’s magnitude is comparable to that seen in anterior circulation large vessel occlusions, although caution is advised in mild cases and those with extensive baseline infarction.
Implications for Practice: Clinicians should consider EVT for most patients presenting with acute VBAO. While sICH risk is increased, the substantial improvements in function and survival justify its use in suitable candidates. Careful imaging and clinical assessment remain critical for optimal patient selection.
Study Strengths and Limitations: Strengths include a pooled individual patient dataset from all major VBAO EVT trials, allowing detailed subgroup analyses. Limitations involve early trial termination, underrepresentation of women, predominance of Asian populations, and exclusion of patients with very mild symptoms or large baseline infarcts, potentially limiting generalizability.
Future Research: Further trials are needed to define EVT’s role in patients with mild symptoms, isolated vertebral occlusion, large infarcts, or those presenting beyond 24 hours. Additional studies should assess real-world applicability and diverse patient populations.
Guideline: Doxycycline Postexposure Prophylaxis to Reduce Bacterial STI Incidence in High-Risk Populations
19 Dec, 2024 | 22:32h | UTCIntroduction: This summary presents key recommendations from the 2024 Centers for Disease Control and Prevention (CDC) guidelines on using doxycycline postexposure prophylaxis (doxyPEP) to prevent bacterial sexually transmitted infections (STIs), including syphilis, gonorrhea, and chlamydia. Targeting men who have sex with men (MSM) and transgender women with at least one bacterial STI in the past 12 months, these guidelines aim to reduce recurrence rates and improve sexual health outcomes through timely prophylactic intervention.
Key Recommendations:
- Offer doxyPEP counseling to MSM and transgender women with a recent bacterial STI history, addressing the benefits, harms, and uncertainties of prophylactic doxycycline use.
- Advise eligible patients to take a single 200 mg dose of doxycycline as soon as possible (ideally within 72 hours) following condomless oral, anal, or vaginal sexual exposure to reduce their subsequent STI risk.
- Reinforce periodic screening (every 3–6 months) for STI markers, including syphilis and HIV serologies, as well as nucleic acid amplification tests for gonorrhea and chlamydia at relevant anatomical sites.
- Integrate doxyPEP into comprehensive sexual health services that include risk-reduction counseling, condom use, recommended immunizations, and linkage to HIV preexposure prophylaxis (PrEP) or HIV care, thereby enhancing overall prevention strategies.
- Consider extending doxyPEP to other high-risk groups, including heterosexual individuals with recurrent STIs, guided by clinical judgment and shared decision-making.
- Monitor and address adverse events, particularly gastrointestinal symptoms, and acknowledge the potential for antimicrobial resistance. Continued vigilance is warranted given the risk of resistance in commensal flora and key STI pathogens, such as Neisseria gonorrhoeae.
- Assess social and ethical dimensions of doxyPEP implementation, ensuring equitable access and minimizing potential harms, including stigma or intimate partner violence related to prophylaxis disclosure.
Conclusion: Implementing doxyPEP for MSM and transgender women who have experienced a recent bacterial STI can substantially lower the incidence of recurrent infections. By combining prophylactic doxycycline with routine surveillance, comprehensive preventive services, and careful consideration of resistance patterns, clinicians may enhance patient care and strengthen STI control efforts. Further investigation is needed to establish efficacy in cisgender women, transgender men, nonbinary persons, and other populations at risk. Longer-term, population-based studies focused on antimicrobial resistance and community-level effects will help guide sustainable and equitable use of this prevention strategy.
Review: New and Emerging Treatments for Major Depressive Disorder
19 Dec, 2024 | 22:21h | UTCIntroduction: This is a summary of a review on new and emerging treatments for major depressive disorder (MDD), a globally prevalent condition with substantial morbidity and socioeconomic burden. While conventional monoaminergic antidepressants often provide benefit, many patients do not achieve remission, leading to treatment-resistant depression. Novel approaches, including psychedelics (psilocybin, ketamine/esketamine), anti-inflammatory agents, opioid modulators, neuropeptides, botulinum toxin injections, and various neuromodulatory techniques (newer forms of transcranial magnetic stimulation and light-based therapies), are under investigation. This summary highlights their potential efficacy, tolerability, and current limitations.
Key Recommendations:
- Ketamine and Esketamine: Consider these as adjunctive treatments for patients with refractory MDD, given their rapid antidepressant and anti-suicidal effects. Carefully monitor for blood pressure elevations and potential habituation. Long-term cost-effectiveness and sustained benefits remain uncertain.
- Psychedelics (Psilocybin, Ayahuasca): Psilocybin-assisted therapy may produce rapid symptom improvement, but scalability, required therapeutic support, and possible increases in suicidality raise concern. Ayahuasca shows early promise, yet lacks robust long-term data and standardized administration protocols.
- Neuromodulation (rTMS, TBS, Accelerated TMS, Light Therapy): Repetitive transcranial magnetic stimulation (rTMS) and its variants (theta burst stimulation, accelerated protocols) demonstrate modest efficacy with good tolerability. Bright light therapy may enhance neuromodulation outcomes. Optimal protocols and positioning in treatment pathways are not well established.
- Anti-inflammatory and Other Agents: Preliminary findings suggest potential adjunctive roles for minocycline, NSAIDs, statins, omega-3 fatty acids, and a buprenorphine-samidorphan combination. However, larger, high-quality trials are needed to confirm their efficacy and safety profiles.
- Onabotulinumtoxin A: A single glabellar injection may confer antidepressant effects, but the underlying mechanism and durability are unclear. Methodological issues, including difficulties with blinding, limit strong recommendations.
- More Invasive Interventions (DBS, MST): Deep brain stimulation (DBS) and magnetic seizure therapy (MST) are invasive approaches supported by limited evidence, restricting their use to highly refractory cases. The balance of benefit, risk, and resource intensity remains uncertain.
Conclusion: Although these emerging treatments offer potential avenues beyond traditional antidepressants, most remain investigational. Key challenges include limited comparative data, uncertain long-term outcomes, and scaling difficulties. Further rigorous research, including head-to-head trials, long-term follow-ups, and clarity regarding optimal psychotherapeutic support, is required. As evidence matures, these novel interventions may become more integrated into standard care, potentially improving outcomes for patients with difficult-to-treat MDD.
Review: Nonsurgical Management of Chronic Venous Insufficiency
19 Dec, 2024 | 16:45h | UTCIntroduction: 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:
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Review: Management of Atrial Fibrillation
18 Dec, 2024 | 14:22h | UTCIntroduction: This summary of a comprehensive review on atrial fibrillation (AF) focuses on an increasingly prevalent arrhythmia affecting more than 10 million adults in the United States. AF significantly elevates the risks of stroke, heart failure (HF), cognitive decline, and mortality. This guideline-based overview examines the pathophysiology, detection, prevention, and treatment strategies for AF, emphasizing risk factor modification, appropriate anticoagulation, and early rhythm control interventions to improve clinical outcomes and quality of life.
Key Recommendations:
- Risk Factor and Lifestyle Modification: Implement weight reduction, regular exercise, optimal blood pressure control, smoking cessation, and reduced alcohol intake at all AF stages to prevent new-onset AF, reduce recurrences, and mitigate complications.
- Screening and Diagnosis: Consider AF screening in high-risk patients using wearable devices or implantable loop recorders. Confirm suspected AF with electrocardiography and extended rhythm monitoring in those with cryptogenic stroke.
- Stroke Prevention: Assess stroke risk using CHA2DS2-VASc. For patients with annual stroke risk ≥2%, initiate oral anticoagulation (preferably direct oral anticoagulants over warfarin) to lower stroke risk by up to 80%. Avoid aspirin monotherapy for AF-related stroke prevention due to inferior efficacy.
- Early Rhythm Control: Begin rhythm control within one year of AF diagnosis, particularly in symptomatic patients or those with HF and reduced ejection fraction (HFrEF). Early use of antiarrhythmic drugs or catheter ablation can improve symptoms, cardiac function, and reduce hospitalizations.
- Catheter Ablation: Utilize ablation as a first-line therapy in symptomatic paroxysmal AF to maintain sinus rhythm and prevent progression. In patients with AF and HFrEF, ablation enhances quality of life, improves left ventricular function, and lowers mortality and HF hospitalization rates.
- Rate Control Strategies: For patients who are not candidates for rhythm control, use beta-blockers or nondihydropyridine calcium channel blockers to achieve satisfactory ventricular rate control. Consider atrioventricular nodal ablation plus pacemaker implantation if pharmacologic therapy is inadequate.
- Staging and Long-Term Management: Recognize four AF stages (at risk, pre-AF, clinically apparent AF, and permanent AF) to tailor management. After ablation, continue anticoagulation for at least three months, then reassess stroke risk before considering discontinuation.
- Addressing Inequities: Improve access to guideline-directed AF therapies, including ablation and specialized care, and address social determinants of health that influence disparities in diagnosis, treatment, and outcomes.
Conclusion: Guideline-directed AF management, encompassing comprehensive risk factor modification, appropriate anticoagulation, and timely rhythm control strategies, can reduce stroke incidence, improve HF outcomes, and prolong life. Catheter ablation is a key intervention for appropriate patients, especially those with symptomatic paroxysmal AF or HFrEF, while striving for equitable and evidence-based care across diverse populations remains a critical priority.
Review: Diagnosis and Management of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
18 Dec, 2024 | 11:08h | UTCIntroduction: DRESS is a severe T-cell–mediated hypersensitivity reaction triggered by prolonged exposure to certain medications, characterized by extensive rash, fever, hematologic abnormalities (notably eosinophilia or atypical lymphocytosis), lymphadenopathy, and involvement of internal organs such as the liver, kidneys, and lungs. Common culprits include aromatic anticonvulsants, allopurinol, and specific antibiotics. Although relatively rare, DRESS accounts for a substantial proportion of severe cutaneous adverse drug reactions (SCARs) in hospitalized patients and can be life-threatening, with mortality rates around 5%. Its pathogenesis involves complex immune dysregulation, including Th2 predominance, possible viral reactivation (e.g., HHV-6), and genetic predispositions related to certain HLA alleles. Diagnosis typically relies on clinical criteria, such as the validated RegiSCAR scoring system, and on excluding other SCARs like Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP).
Key Recommendations:
- Identify and Discontinue the Culprit Drug: Prompt removal of the offending medication is the cornerstone of therapy.
- Supportive Care and Monitoring: Hospitalization, often in an intensive care setting, may be required for organ function support and close monitoring of disease progression. Regular assessment of liver enzymes, renal function, blood counts, and cardiac and pulmonary status is critical.
- Systemic Glucocorticoids: High-dose corticosteroids (e.g., prednisone 0.5–1 mg/kg/day) are first-line therapy. A gradual taper over 6–12 weeks is recommended to minimize relapse.
- Steroid-Sparing and Targeted Therapies: In refractory cases or when steroids are contraindicated, consider other immunosuppressants (e.g., cyclosporine, mycophenolate mofetil) or targeted biologic agents (e.g., anti–IL-5 therapies) to control persistent eosinophilia and organ involvement.
- Diagnostic Testing and Specialist Involvement: Although no single test confirms DRESS, dermatology or allergy/immunology consultation may help identify culprit drugs and safer therapeutic alternatives. Patch testing, delayed intradermal testing, and HLA genotyping can sometimes clarify drug causality.
- Long-Term Follow-Up: Patients require prolonged observation due to risks of relapse, potential autoimmune sequelae (e.g., thyroiditis, type 1 diabetes), and psychological distress. Ongoing multidisciplinary care and support are essential.
Conclusion: Early recognition of DRESS, prompt discontinuation of the offending drug, and initiation of systemic corticosteroids are key steps in management. Emerging therapies offer additional treatment options for severe or refractory cases. Long-term follow-up is vital to address relapses, organ damage, and autoimmune complications. A coordinated, multidisciplinary approach improves clinical outcomes and quality of life for affected patients.
RCT: A Single Dose of Ceftriaxone Reduces Early Ventilator-Associated Pneumonia in Acute Brain Injury Patients
17 Dec, 2024 | 12:26h | UTCBackground: Patients with acute brain injury are at increased risk for early ventilator-associated pneumonia (VAP), which can worsen their clinical course. Although short-term antibiotic prophylaxis has been considered, its utility remains uncertain. This study evaluated whether a single early dose of ceftriaxone could reduce the incidence of early VAP in these patients.
Objective: To determine if a single 2-g intravenous dose of ceftriaxone administered within 12 hours of intubation reduces the incidence of early VAP (day 2 to day 7 of mechanical ventilation) in comatose adults (Glasgow Coma Scale ≤12) requiring prolonged mechanical ventilation after acute brain injury.
Methods: This multicenter, randomized, double-blind, placebo-controlled, assessor-masked superiority trial was conducted in nine ICUs across eight French university hospitals. Patients with acute brain injury from trauma, stroke, or subarachnoid hemorrhage who required at least 48 hours of mechanical ventilation were enrolled. Participants received either ceftriaxone 2 g or placebo once, early after endotracheal intubation. All patients received standard VAP prevention measures, but no selective oropharyngeal or digestive decontamination. The primary endpoint was the incidence of early VAP confirmed by blinded assessors using standard clinical, radiological, and microbiological criteria.
Results: Among 319 patients included in the analysis (162 ceftriaxone, 157 placebo), early VAP incidence was significantly lower with ceftriaxone (14%) compared to placebo (32%) (HR 0.60 [95% CI 0.38–0.95]; p=0.030). Patients receiving ceftriaxone had fewer overall VAP episodes, fewer ventilator and antibiotic exposure days, shorter ICU and hospital stays, and reduced 28-day mortality (15% vs 25%). No significant increase in resistant organisms or adverse events attributable to ceftriaxone was observed.
Conclusions: A single early dose of ceftriaxone significantly reduced early VAP risk in acute brain injury patients undergoing mechanical ventilation. This prophylactic approach may improve clinical outcomes without evident safety concerns.
Implications for Practice: Incorporating a single early ceftriaxone dose into VAP prevention protocols for brain-injured patients could mitigate early respiratory infections and potentially enhance clinical outcomes. Nonetheless, clinicians should remain cautious, considering overall antibiotic stewardship and the need for further evidence on long-term microbial resistance patterns.
Study Strengths and Limitations: Strengths include a robust, multicenter, double-blind, placebo-controlled design and blinded adjudication of VAP cases. Limitations include the lack of long-term assessment of the intestinal microbiota and antimicrobial resistance. Further investigation is required to confirm the safety profile regarding microbial ecology and to explore neurological outcomes in greater depth.
Future Research: Future studies should examine the long-term effects of this single-dose approach on resistance patterns, microbial flora, and functional neurological recovery.
RCT: Liberal vs Restrictive Transfusion Yields No Neurologic Outcome Benefit in Aneurysmal Subarachnoid Hemorrhage
16 Dec, 2024 | 11:26h | UTCBackground: Aneurysmal subarachnoid hemorrhage (SAH) is a critical neurologic condition associated with high morbidity and mortality. Anemia is common in this setting and may worsen cerebral oxygenation and outcomes. However, the impact of a liberal transfusion threshold compared with a restrictive approach on long-term neurologic outcomes has been uncertain.
Objective: To determine whether a liberal red blood cell transfusion strategy (transfusion at hemoglobin ≤10 g/dL) improves 12-month neurologic outcomes compared with a restrictive strategy (transfusion at hemoglobin ≤8 g/dL) in patients with aneurysmal SAH and anemia.
Methods: This was a multicenter, pragmatic, open-label, randomized controlled trial conducted at 23 specialized neurocritical care centers. Critically ill adults with a first-ever aneurysmal SAH and hemoglobin ≤10 g/dL within 10 days of admission were randomized to a liberal or restrictive transfusion strategy. The primary outcome was unfavorable neurologic outcome at 12 months, defined as a modified Rankin scale score ≥4. Secondary outcomes included the Functional Independence Measure (FIM), quality of life assessments, and imaging-based outcomes such as vasospasm and cerebral infarction. Outcome assessors were blinded to group allocation.
Results: Among 742 randomized patients, 725 were analyzed for the primary outcome. At 12 months, unfavorable neurologic outcome occurred in 33.5% of patients in the liberal group and 37.7% in the restrictive group (risk ratio 0.88; 95% CI, 0.72–1.09; p=0.22). There were no clinically meaningful differences in secondary outcomes. Mortality at 12 months was similar (approximately 27% in both arms). Radiographic vasospasm was more frequently detected in the restrictive group, though this did not translate into improved functional outcomes in the liberal arm. Adverse events and transfusion reactions were comparable between groups.
Conclusions: In patients with aneurysmal SAH and anemia, a liberal transfusion strategy did not lead to a significantly lower risk of unfavorable neurologic outcome at 12 months compared with a restrictive approach.
Implications for Practice: These findings suggest that routinely maintaining higher hemoglobin levels does not confer substantial long-term functional benefit. Clinicians may consider a more restrictive threshold (≤8 g/dL) to minimize unnecessary transfusions without compromising outcomes. Some skepticism toward adopting a more liberal transfusion policy is warranted given the lack of demonstrable benefit.
Study Strengths and Limitations: Strengths include the randomized, multicenter design, blinded outcome assessment, and a 12-month follow-up. Limitations include potential unmeasured subtle benefits, the inability to blind clinical teams, and the challenge of capturing all aspects of functional recovery with current measurement tools. Further research may clarify if more tailored transfusion strategies can yield modest but meaningful improvements.
Future Research: Future studies should evaluate intermediate hemoglobin thresholds, develop more sensitive measures of functional and cognitive recovery, and consider individualized transfusion strategies based on specific patient factors and biomarkers of cerebral ischemia.
Guidelines for the Management of Hyperglycemic Crises in Adult Patients with Diabetes
15 Dec, 2024 | 13:18h | UTCIntroduction: Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are critical, acute complications of type 1 and type 2 diabetes. Recent data show a global rise in DKA and HHS admissions, driven by factors such as psychosocial challenges, suboptimal insulin use, infection, and certain medications (e.g., SGLT2 inhibitors). This consensus report, developed by leading diabetes organizations (ADA, EASD, JBDS, AACE, DTS), provides updated recommendations on epidemiology, pathophysiology, diagnosis, treatment, and prevention of DKA and HHS in adults, aiming to guide clinical practice and improve outcomes.
Key Recommendations:
- Diagnosis and Classification:
- DKA is defined by hyperglycemia (>11.1 mmol/l [200 mg/dl] or known diabetes), elevated ketone levels (β-hydroxybutyrate ≥3.0 mmol/l), and metabolic acidosis (pH <7.3 or bicarbonate <18 mmol/l).
- HHS is characterized by marked hyperglycemia, severe hyperosmolality (>320 mOsm/kg), significant dehydration, and minimal ketonaemia or acidosis.
- Consider euglycemic DKA, especially with SGLT2 inhibitor use.
- Classify DKA severity (mild, moderate, severe) to guide the setting of care.
- Fluid and Electrolyte Management:
- Initiate isotonic or balanced crystalloid solutions to restore intravascular volume, enhance renal perfusion, and reduce hyperglycemia.
- Adjust fluids based on hydration, sodium levels, and glucose trends.
- Add dextrose when glucose falls below ~13.9 mmol/l (250 mg/dl) to allow ongoing insulin therapy until ketoacidosis resolves.
- Carefully monitor potassium and provide adequate replacement to prevent severe hypokalemia.
- Insulin Therapy:
- Start a continuous intravenous infusion of short-acting insulin as soon as feasible after confirming adequate potassium.
- For mild or moderate DKA, subcutaneous rapid-acting insulin analogs may be used under close supervision.
- Continue insulin until DKA resolves (pH ≥7.3, bicarbonate ≥18 mmol/l, β-hydroxybutyrate <0.6 mmol/l) or HHS improves (osmolality <300 mOsm/kg, improved mental status).
- Overlap subcutaneous basal insulin by 1–2 hours before discontinuing intravenous insulin to prevent rebound hyperglycemia.
- Additional Considerations:
- Avoid routine bicarbonate; use only if pH <7.0.
- Phosphate supplementation is not routinely recommended unless levels are severely low.
- Identify and treat underlying precipitating causes (infection, psychological factors, medication-related triggers).
- Address social determinants of health and mental health conditions to reduce recurrence.
Conclusion: By implementing these evidence-based recommendations—early diagnosis, structured fluid and insulin therapy, careful electrolyte management, and addressing precipitating factors—clinicians can improve patient care, reduce morbidity and mortality, and enhance the quality of life for adults experiencing DKA and HHS.
Retrospective Cohort Study: As-Needed Blood Pressure Medications Associated With Increased AKI and Other Adverse Outcomes in Hospitalized Veterans
8 Dec, 2024 | 21:34h | UTCBackground: Inpatient asymptomatic blood pressure (BP) elevations are common, and clinicians frequently use as-needed BP medications to rapidly lower BP values. However, there is limited evidence supporting this practice, and abrupt BP reductions may increase the risk of ischemic events, including acute kidney injury (AKI).
Objective: To examine whether as-needed BP medication use during hospitalization is associated with increased risk of AKI and other adverse outcomes compared to no as-needed use.
Methods: This retrospective cohort study used a target trial emulation and propensity score matching. Adults hospitalized for ≥3 days in non-ICU VA hospital wards from 2015-2020, who received at least one scheduled BP medication within the first 24 hours and had at least one systolic BP reading >140 mm Hg, were included. Patients were categorized into two groups: those receiving at least one as-needed BP medication (oral or IV) and those receiving only scheduled BP medications. The primary outcome was time-to-first AKI event. Secondary outcomes included a >25% drop in systolic BP within 3 hours and a composite of myocardial infarction (MI), stroke, or death.
Results: Among 133,760 veterans (mean age 71.2 years; 96% male), 21% received as-needed BP medications. As-needed BP medication use was associated with a 23% higher risk of AKI (HR=1.23; 95% CI, 1.18-1.29). The IV route showed a particularly pronounced AKI risk (HR=1.64). Secondary analyses indicated a 1.5-fold increased risk of rapid BP reduction and a 1.69-fold higher rate of the composite outcome (MI, stroke, death) among as-needed users.
Conclusions: In a large, national cohort of hospitalized veterans, as-needed BP medication use was associated with increased AKI risk and other adverse outcomes. These findings suggest that routine as-needed BP medication use for asymptomatic BP elevations may be harmful.
Implications for Practice: Clinicians should carefully reconsider the use of as-needed BP medications in the inpatient setting, especially in older individuals or those with significant cardiovascular risk. Given the lack of clear benefit and potential for harm, greater caution and potentially more conservative approaches are warranted.
Study Strengths and Limitations: Strengths include a large, nationally representative sample and robust analytic methods. Limitations include the retrospective design, potential residual confounding, and limited generalizability to non-veteran or surgical populations. While causal inferences cannot be made, the findings strongly support the need to question current practice.
Future Research: Prospective, randomized trials are needed to determine the optimal management of asymptomatic inpatient hypertension and to assess whether avoiding or reducing as-needed BP medication use improves clinical outcomes.
RCT: FFR-Guided PCI Plus TAVI is Non-inferior and Superior to SAVR Plus CABG in Patients With Severe Aortic Stenosis and Complex Coronary Disease
8 Dec, 2024 | 21:22h | UTCBackground: Patients with severe aortic stenosis frequently present with concomitant complex coronary artery disease. Current guidelines recommend combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) as first-line therapy. However, transcatheter aortic valve implantation (TAVI) and fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) have emerged as alternative treatments. Assessing their efficacy compared to SAVR plus CABG has been an unmet need.
Objective: To determine whether FFR-guided PCI plus TAVI is non-inferior and, if demonstrated, superior to SAVR plus CABG in patients with severe aortic stenosis and complex or multivessel coronary disease.
Methods: This international, multicenter, prospective, open-label, non-inferiority randomized controlled trial included patients aged ≥70 years with severe aortic stenosis and complex coronary disease who were deemed suitable for either percutaneous or surgical treatment by a Heart Team. Participants were randomized (1:1) to FFR-guided PCI plus TAVI or SAVR plus CABG. The primary endpoint was a composite of all-cause mortality, myocardial infarction, disabling stroke, clinically driven target-vessel revascularization, valve reintervention, and life-threatening or disabling bleeding at 1 year.
Results: Among 172 enrolled patients, 91 were assigned to FFR-guided PCI plus TAVI and 81 to SAVR plus CABG. At 1 year, the primary endpoint occurred in 4% of patients in the PCI/TAVI group versus 23% in the SAVR/CABG group (risk difference –18.5%; 90% CI –27.8 to –9.7; p<0.001 for non-inferiority; p<0.001 for superiority). The difference was driven mainly by lower all-cause mortality (0% vs 10%, p=0.0025) and reduced life-threatening bleeding (2% vs 12%, p=0.010).
Conclusions: In patients with severe aortic stenosis and complex coronary artery disease, FFR-guided PCI plus TAVI was non-inferior and in fact superior to SAVR plus CABG at 1 year, predominantly due to lower mortality and serious bleeding events.
Implications for Practice: These findings suggest that a percutaneous strategy may be a viable and potentially preferable alternative to surgery in selected patients. Nevertheless, given this is the first trial of its kind, cautious interpretation is advised, and routine adoption should await further corroboration.
Study Strengths and Limitations: Strengths include a randomized, multicenter design and standardized endpoint assessment. Limitations involve early trial termination resulting in a smaller sample size and the use of a single TAVI device type, limiting generalizability.
Future Research: Larger trials with longer follow-up, evaluation of other TAVI prostheses, and broader patient populations are needed to validate these findings and determine the optimal patient selection criteria.