Nutrition (all articles)

Review: Enteral Nutrition in Hospitalized Adults

21 Apr, 2025 | 13:23h | UTC

Introduction:
This is a summary of a new review published in the New England Journal of Medicine discussing the rationale, evidence, and practical considerations for administering enteral nutrition to hospitalized adults. The main objective is to provide guidance on identifying patients with disease-related malnutrition, initiating enteral feeding, and differentiating strategies for critically ill versus non–critically ill patients who require nutritional support.

Key Recommendations:

1. Identify Malnutrition Early:

   • Screen all hospitalized patients for malnutrition (e.g., using the Malnutrition Screening Tool) on admission.

   • Confirm high-risk cases with a comprehensive nutrition assessment (e.g., GLIM or AAIM criteria).

2. Optimize Oral Intake First:

   • Whenever possible, use strategies such as dietary modifications and oral nutritional supplements before initiating enteral nutrition.

   • Implement medical nutrition therapy with the goal of meeting at least 75% of estimated energy and protein requirements orally; consider EN/PN if this goal is not reached within approximately 5 days.

3. Initiate Enteral Nutrition if Oral Intake Is Inadequate:

   • Consider enteral feeding for patients who fail to meet energy and protein goals and do not have contraindications (e.g., intestinal obstruction, severe shock, intestinal ischemia, or active gastrointestinal hemorrhage).

   • Dosing considerations differ significantly by patient population and clinical phase:

     • In critical illness (acute phase, first week), evidence suggests potential harm from early full caloric feeding or high protein doses (e.g., ≥2.2 g/kg/day), particularly in patients with shock or organ failure. A more “trophic” or hypocaloric approach (<70% of estimated energy needs) is often appropriate, especially if there is acute kidney injury or multiorgan dysfunction.

     • In contrast, for non–critically ill medical or surgical patients at risk of malnutrition, studies show that underfeeding is associated with worse outcomes, making it important to achieve closer to full nutritional requirements sooner.

4. Select the Appropriate Route and Timing:

   • For short-term use (up to 6 weeks), place a nasoenteric tube.

   • For anticipated long-term support, consider a gastrostomy or jejunostomy tube.

   • Postpyloric feeding (duodenal or jejunal) may reduce aspiration risk in certain patients.

5. Adjust Dose According to Clinical Phase:

   • In the ICU acute phase, avoid early full feeding; consider “trophic” or hypocaloric regimens.

   • As the patient recovers from critical illness, gradually increase caloric and protein delivery to meet estimated needs if tolerated, though exact targets remain under investigation.

   • In non–critically ill patients, aim to meet estimated requirements unless specific clinical issues necessitate lower delivery.

6. Mitigate Complications:

   • Use continuous pump-assisted infusion, though volume-based feeding can improve goal attainment.

   • Monitor regularly for refeeding syndrome (e.g., hypophosphatemia, hypokalemia, hypomagnesemia) and correct electrolyte abnormalities.

   • Employ glucose management strategies to avoid hyperglycemia.

7. Coordinate Interdisciplinary Care:

   • Engage dietitians, nursing staff, pharmacists, and other professionals to tailor therapy and optimize patient acceptance.

   • Involve patients in shared decision-making, particularly regarding personal values and treatment goals.

Conclusion:
These recommendations underscore enteral nutrition’s essential role in preventing and treating disease-related malnutrition. However, the direct impact on major outcomes (e.g., mortality, complications) varies by patient population, feeding strategy, and timing. In critically ill patients, especially during the first week of ICU care, lower-dose or “trophic” enteral feeding may be safer, whereas non–critically ill patients generally benefit from achieving nutritional targets more fully. Our understanding of optimal feeding approaches continues to evolve, particularly with regard to feeding dose during different phases of illness and recovery.

Reference:
Gramlich L, Guenter P. Enteral Nutrition in Hospitalized Adults. New England Journal of Medicine. 2025;392:1518-1530. DOI: https://doi.org/10.1056/NEJMra2406030

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Diagnosis and Management of Eosinophilic Esophagitis: Updated ACG Clinical Guideline Summary

14 Jan, 2025 | 13:46h | UTC

Introduction: This summary highlights the updated American College of Gastroenterology (ACG) Clinical Guideline on eosinophilic esophagitis (EoE), a chronic, immune-mediated disease of the esophagus characterized by esophageal eosinophilia and clinical symptoms of esophageal dysfunction. Over the last decade, the incidence and prevalence of EoE have increased significantly. This guideline incorporates new diagnostic strategies, therapeutic advances, and monitoring practices, aiming to improve patient outcomes and minimize disease complications such as strictures, food impactions, and impaired quality of life. The document underscores the importance of assessing both the inflammatory and fibrostenotic components of EoE through endoscopy, histopathology, and symptom evaluation.

Key Recommendations:

• Diagnosis:
  • Diagnose EoE when patients present with symptoms of esophageal dysfunction and at least 15 eosinophils per high-power field (eos/hpf) on esophageal biopsies, after exclusion of other causes of esophageal eosinophilia.
  • Use a systematic scoring tool such as the EoE Endoscopic Reference Score (EREFS) to assess edema, rings, exudates, furrows, and strictures at every endoscopy.
  • Obtain at least six esophageal biopsies from two or more levels (e.g., distal and proximal) to minimize diagnostic miss rates; quantify peak eosinophil counts in each specimen.
• Pharmacologic Therapy:
  1. Proton Pump Inhibitors (PPIs):
     • Consider high-dose PPIs (e.g., twice daily) as a first-line treatment option. Although originally used for acid suppression, PPIs also reduce eotaxin-3 expression and improve esophageal barrier function in EoE.
     • Maintain therapy long term in patients who respond, as discontinuation frequently leads to disease recurrence.
  2. Topical Corticosteroids (Swallowed Steroids):
     • Budesonide or fluticasone can be delivered via specially formulated suspensions/tablets or by swallowing inhaler medication.
     • Expect histologic remission rates of around 60%–70%.
     • Oral/esophageal candidiasis is the most common adverse event. Routine adrenal suppression testing is generally not necessary for short-term use.
  3. Dietary Elimination:
     • Empiric elimination diets (e.g., 2-food or 6-food elimination) help identify specific food triggers. Histologic remission rates can exceed 70%, particularly with the 6-food approach.
     • Less-restrictive diets (e.g., milk-only elimination) may be tried first (the “step-up” approach).
     • Do not rely on currently available skin prick or Ig-based tests to guide elimination diets, as these have poor predictive value for EoE triggers.
  4. Biologic Therapy:
     • Dupilumab (anti–IL-4 receptor alpha) is recommended in adolescents and adults (≥12 years, ≥40 kg) and is now approved for children as young as 1 year (≥15 kg) with moderate to severe, PPI-refractory EoE. Expect significant histologic, endoscopic, and symptom improvements in most patients, along with an overall favorable safety profile.
     • Other biologics (e.g., cendakimab, benralizumab, mepolizumab) remain under investigation; current data are insufficient for routine clinical use.
  5. Esophageal Dilation:
     • Perform endoscopic dilation to treat symptomatic strictures or narrow-caliber esophagi. Dilation reduces dysphagia promptly but does not alter the underlying inflammation.
     • Combine dilation with anti-inflammatory therapy to address the disease’s inflammatory component and help prevent recurrent stricture formation.
• Maintenance and Monitoring:
  • Because EoE is chronic, continue effective therapy over the long term. Abrupt cessation of treatment often leads to relapses in symptoms and inflammation.
  • Evaluate treatment response by assessing symptoms, endoscopic findings (e.g., EREFS), and histopathology (peak eosinophil counts).
  • A target of <15 eos/hpf and near-normal endoscopic appearance (EREFS ≤2) is commonly used to define remission, although some patients aim for histologic normalization.
  • In children, ensure regular assessment of growth, development, and feeding behaviors. Referral to a nutritionist or feeding therapist is recommended if feeding difficulties or failure to thrive are present.

Conclusion: These updated ACG guidelines underscore the importance of a comprehensive, individualized approach to EoE that encompasses diagnosis, treatment of the inflammatory state, dilation of fibrotic strictures, and ongoing monitoring to maintain long-term remission. The introduction of biologics (particularly dupilumab) expands treatment options for patients nonresponsive to PPIs or topical steroids. Clinicians should adopt a structured assessment strategy—integrating clinical history, endoscopic scoring, and histological evaluation—to guide therapy selection, document treatment response, and prevent complications. With improved understanding of disease pathogenesis and evolving therapeutic tools, outcomes for patients with EoE are expected to continue to improve.

Reference: Dellon ES, Muir AB, Katzka DA, Shah SC, Sauer BG, Aceves SS, Furuta GT, Gonsalves N, Hirano I. ACG Clinical Guideline: Diagnosis and Management of Eosinophilic Esophagitis. The American Journal of Gastroenterology. 2025;120(1):31–59. DOI: https://doi.org/10.14309/ajg.0000000000003194

 

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Comprehensive Glycemic Goals and Hypoglycemia Management in Diabetes: 2025 ADA Standards

13 Jan, 2025 | 12:39h | UTC

Introduction: This summary provides key points from the American Diabetes Association’s (ADA) 2025 guidance on glycemic targets, monitoring, and hypoglycemia management in type 1 and type 2 diabetes. It emphasizes individualized A1C goals, the clinical use of continuous glucose monitoring (CGM)—a system that measures interstitial glucose levels throughout the day—and the prevention and treatment of hypoglycemia. The main objective is to help clinicians optimize glucose control, reduce acute and chronic complications, and improve patient outcomes.

Key Recommendations:

1. Individualized Glycemic Targets
   • An A1C goal of <7% (<53 mmol/mol) is generally appropriate for many nonpregnant adults without frequent or severe hypoglycemia.
   • Lower or higher A1C goals may be appropriate in specific situations. For example:
     • Comorbidities: Individuals with significant cardiovascular disease, kidney dysfunction, or other conditions may benefit from a more conservative A1C target (e.g., <8%), balancing the risks of intensive treatment (such as hypoglycemia) against the benefits of tighter control.
     • Hypoglycemia Risk: Those with a history of severe or frequent hypoglycemia might need to relax A1C targets to avoid life-threatening low glucose episodes. In contrast, highly motivated patients with robust hypoglycemia awareness and access to advanced monitoring tools could safely aim for A1C closer to 6%.
     • Life Expectancy: Younger, healthier individuals with fewer complications can pursue tighter A1C targets because they have time to benefit from reduced microvascular and macrovascular risks. Older adults or those with serious illnesses and limited life expectancy may adopt higher A1C goals to reduce treatment burden and prevent hypoglycemic events.
2. Monitoring Glycemic Status
   • A1C Testing: Measure at least twice a year when glucose levels are stable and quarterly (or more often) when adjusting therapy or when targets are not met. If A1C is unreliable (e.g., hemoglobin variants), fructosamine or glycated albumin may be used.
   • Continuous Glucose Monitoring (CGM): CGM devices automatically measure glucose day and night, providing valuable data for clinical decision-making. Key CGM metrics include:
     • Time in Range (TIR): The percentage of readings between 70 and 180 mg/dL, with >70% as a common target in most nonpregnant adults.
     • Time Below Range: Ideal is <4% of readings under 70 mg/dL and <1% for older adults.
     • Time Above Range: Common goals are <25% for mild hyperglycemia and <5% for severe hyperglycemia, though this may vary with age and comorbidities.
   • When refining diabetes therapies, review CGM reports (e.g., ambulatory glucose profiles) to identify patterns of high or low glucose. This helps personalize adjustments to medications, diet, and exercise. For instance, consistent nocturnal hypoglycemia might prompt a reduction or timing change of basal insulin, while excessive morning hyperglycemia may require earlier medication dosing or lifestyle interventions.
3. Hypoglycemia Prevention and Management
   • Classification: Level 1 (<70 mg/dL), Level 2 (<54 mg/dL), and Level 3 (severe, requiring assistance).
   • Assessment: At each visit, review hypoglycemia history, symptom awareness, and potential triggers (e.g., exercise, medication errors, missed meals).
   • Treatment: In conscious patients, use 15 g of fast-acting carbohydrates (glucose tablets or similar). Recheck glucose in 15 minutes and repeat if still low.
   • Glucagon Prescription: Recommended for anyone on insulin or otherwise high-risk. Ready-to-inject or nasal glucagon formulations are preferred for ease of use.
   • Therapeutic Adjustment: Deintensify or modify medications (insulin, sulfonylureas) if patients experience recurrent moderate or any severe hypoglycemia.
4. Hyperglycemic Crises
   • DKA and HHS: Promptly recognize and treat diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS), especially in patients presenting with nausea, vomiting, dehydration, or altered mental status.
   • Prevention: Provide “sick day” advice on ketone checks, hydration, and insulin adjustments during illness. Recurrent crises often reflect limited access to medications or inadequate education; address these barriers to reduce re-hospitalizations.
5. Long-Term Impact on Complications
   • Early intensive glycemic control significantly lowers the risk of microvascular complications (retinopathy, nephropathy, neuropathy) in both type 1 and type 2 diabetes.
   • Long-term studies in type 1 diabetes show that sustained glucose management can reduce cardiovascular events. In type 2 diabetes, the addition of newer agents (e.g., GLP-1 receptor agonists or SGLT2 inhibitors) can further decrease cardiovascular and kidney risks, independent of current A1C levels.

Conclusion: The 2025 ADA Standards reinforce the need for customized glycemic targets, informed by comorbidities, hypoglycemia risk, life expectancy, and patient preferences. Using a combination of A1C and CGM data provides a more complete picture of glucose patterns and helps clinicians fine-tune therapies. Preventing hypoglycemia through medication adjustments, structured self-management education, and tailored CGM strategies is paramount. Overall, consistent and individualized glucose control offers better long-term outcomes, fewer complications, and improved quality of life for individuals with diabetes.

Reference: American Diabetes Association Professional Practice Committee. 6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes—2025. Diabetes Care 2025;48(Supplement_1):S128–S145.
https://doi.org/10.2337/dc25-S006

 

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Systematic Review: GLP-1 Receptor Agonists and Co-Agonists Facilitate Significant Weight Loss in Adults Without Diabetes

8 Jan, 2025 | 11:04h | UTC

Background: Obesity is increasingly treated as a chronic disease requiring long-term management. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were originally developed for type 2 diabetes but subsequently demonstrated substantial weight loss benefits in individuals with overweight or obesity. Although several GLP-1 RAs and related dual or triple co-agonists have been assessed in diverse populations, their overall efficacy and safety profile among adults without diabetes had not been thoroughly evaluated.

Objective: To systematically appraise the efficacy and safety of GLP-1 RAs (including single, dual, and triple agonists) for weight loss in otherwise healthy adults with overweight or obesity and without diabetes.

Methods: Investigators searched MEDLINE, Embase, and Cochrane CENTRAL through 4 October 2023 for placebo-controlled randomized controlled trials (RCTs). Eligible studies enrolled adults with body mass index (BMI) ≥27 kg/m^2 (plus one weight-related comorbidity) or ≥30 kg/m^2, in the absence of diabetes or other major diseases. Trials had to last at least 16 weeks and report changes in body weight and safety outcomes. The primary endpoint was percent or absolute change in body weight from baseline. Safety assessments included adverse events (AEs), serious AEs (SAEs), and gastrointestinal (GI) events.

Results: Twenty-six RCTs encompassing 15,491 participants (72% female; mean BMI range, 30–41 kg/m^2; mean age range, 34–57 years) evaluated 12 agents. Three drugs (liraglutide, semaglutide, tirzepatide) are commercially available for weight management; nine are premarket (e.g., retatrutide, orforglipron, mazdutide). Treatment periods ranged from 16 to 104 weeks (median, 43 weeks). Across studies, GLP-1 RAs and co-agonists consistently demonstrated significant weight reductions compared with placebo. Tirzepatide (15 mg weekly) reached up to a 17.8% (95% CI, 16.3% to 19.3%) weight reduction after 72 weeks, whereas semaglutide (2.4 mg weekly) achieved up to 13.9% (95% CI, 11.0% to 16.7%) after 68 weeks. Liraglutide produced more modest losses of up to 5.8% (95% CI, 3.6% to 8.0%) after 26 weeks. Novel agents, particularly the triple agonist retatrutide (12 mg weekly), reported greater average weight losses of up to 22.1% (95% CI, 19.3% to 24.9%) after 48 weeks. Although AEs were often very common (GLP-1 RA vs. placebo: 80%–97% vs. 63%–100%), most were GI-related (47%–84% vs. 13%–63%) and mild or moderate. Importantly, only a smaller proportion of participants (0%–26% vs. 0%–9%) discontinued treatment due to AEs, and SAEs (0%–10% vs. 0%–12%) occurred at relatively lower rates overall. While select SAEs of interest, including severe GI events, biliary disorders, pancreatitis, and psychiatric disorders, were inconsistently reported, they were generally rare (severe GI and biliary disorders, ≤3.5%; pancreatitis, <2%; psychiatric disorders, ≤15% [including less severe events, such as insomnia and mood alterations]).

Conclusions: GLP-1 RAs and co-agonists appear highly efficacious for weight reduction in adults without diabetes, with GI events as the principal safety concern. Among emerging agents, retatrutide in particular has shown even greater efficacy, though further research is needed to clarify comparative effectiveness, costs, and real-world feasibility.

Implications for Practice: Clinicians considering GLP-1 RAs or dual and triple co-agonists for obesity treatment should monitor for GI side effects and counsel patients about long-term use to sustain weight loss. As these newer treatments often come with higher price points and uncertain insurance coverage, cost-effectiveness and sponsor bias should be weighed. Careful patient selection, ongoing monitoring, and discussion of adherence requirements are critical to optimize outcomes in real-world practice.

Study Strengths and Limitations: This review incorporated RCTs with substantial sample sizes and used predefined inclusion criteria focused on healthy adults without diabetes, ensuring a clearer understanding of weight-loss outcomes in this group. However, head-to-head comparisons among agents were lacking, and heterogeneity in trial designs (varying lifestyle interventions, follow-up durations, and dose-escalation approaches) precluded meta-analysis of pooled data. Reporting of specific adverse outcomes was also inconsistent.

Future Research: Larger, longer-term head-to-head RCTs are warranted to evaluate comparative effectiveness, durability of weight loss, and cost implications. Investigations should also explore safety beyond GI events, including rare but serious outcomes such as thyroid disease, gallbladder disorders, or pancreatitis, and determine whether combination therapies (e.g., cagrilintide–semaglutide) confer added benefits.

Reference: Moiz A, Filion KB, Toutounchi H, Tsoukas MA, Yu OHY, Peters TM, Eisenberg MJ. Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss Among Adults Without Diabetes: A Systematic Review of Randomized Controlled Trials. Annals of Internal Medicine. DOI: https://doi.org/10.7326/ANNALS-24-01590

 

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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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Systematic Review and Bayesian Meta-Analysis: Higher Protein Delivery May Increase Mortality in Critically Ill Patients

2 Jan, 2025 | 08:30h | UTC

Background: 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

 

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Meta-analysis: One-day Low-residue Diet Achieves Comparable Bowel Cleansing Compared to Multi-day Regimens

26 Dec, 2024 | 18:21h | UTC

Background: 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

 

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Phase 3 RCT: Resmetirom Significantly Improves NASH Resolution and Liver Fibrosis

16 Nov, 2024 | 13:56h | UTC

Background: Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatments. It significantly increases the risk of liver-related complications, especially in patients with type 2 diabetes. Resmetirom, a thyroid hormone receptor beta-selective agonist, is being investigated for its potential to treat NASH and liver fibrosis.

Objective: To evaluate the efficacy and safety of resmetirom in resolving NASH and improving fibrosis in adults with biopsy-confirmed NASH and fibrosis stages F1B to F3.

Methods: This double-blind, placebo-controlled phase 3 trial randomized 966 adults with NASH to receive once-daily resmetirom (80 mg or 100 mg) or placebo for 52 weeks. Primary endpoints included (1) NASH resolution with no fibrosis worsening and (2) fibrosis improvement by at least one stage without NAFLD activity score worsening. Secondary outcomes included changes in lipid profiles and liver biomarkers.

Results: At 52 weeks, NASH resolution occurred in 25.9% of patients receiving 80 mg and 29.9% receiving 100 mg of resmetirom, compared with 9.7% in the placebo group (P<0.001 for both doses vs. placebo). Fibrosis improved by at least one stage in 24.2% (80 mg) and 25.9% (100 mg) of resmetirom-treated patients versus 14.2% for placebo (P<0.001). LDL cholesterol reductions were −13.6% (80 mg) and −16.3% (100 mg) at 24 weeks versus 0.1% for placebo (P<0.001). Improvements were also noted in triglycerides, liver enzymes, and imaging biomarkers. Adverse events, primarily mild gastrointestinal symptoms, were more frequent with resmetirom. Serious adverse events were similar across groups (10.9%–12.7%).

Conclusions: Resmetirom significantly improved NASH resolution and fibrosis compared to placebo, demonstrating its potential as a treatment for NASH with liver fibrosis.

Implications for Practice: Resmetirom offers a promising treatment option for NASH, potentially altering the disease course and improving outcomes. Clinicians should monitor for regulatory approval and long-term safety data.

Study Strengths and Limitations: Strengths include robust biopsy-confirmed endpoints and a large sample size. Limitations include short follow-up and lack of clinical-outcome data.

Future Research: Long-term studies are needed to assess durability, safety, and effects on clinical outcomes like cirrhosis and liver-related mortality.

Reference: Harrison SA, Bedossa P, Guy CD, et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. New England Journal of Medicine. 2024;390(6):497-509. DOI: http://doi.org/10.1056/NEJMoa2309000

 

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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: Vitamin K2 Reduces Nocturnal Leg Cramps in Older Adults

28 Oct, 2024 | 18:59h | UTC

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RCT: Low-Dose Amitriptyline Effective as Second-Line Treatment for Irritable Bowel Syndrome

20 Oct, 2024 | 15:56h | UTC

Background: Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies—such as dietary changes and antispasmodic drugs—are ineffective, the UK National Institute for Health and Care Excellence (NICE) recommends considering low-dose tricyclic antidepressants as second-line treatment. However, their effectiveness in primary care is uncertain, and they are infrequently prescribed in this setting.

Objective: To determine whether titrated low-dose amitriptyline is effective as a second-line treatment for IBS in primary care.

Methods: In a randomized, double-blind, placebo-controlled, phase 3 trial (ATLANTIS) conducted at 55 general practices in England, 463 adults aged 18 years or older with Rome IV IBS and ongoing symptoms despite first-line therapies were randomized 1:1 to receive low-dose oral amitriptyline (10 mg once daily) or placebo for 6 months. Dose titration over 3 weeks up to 30 mg once daily was allowed according to symptoms and tolerability. The primary outcome was the IBS Severity Scoring System (IBS-SSS) score at 6 months. Secondary outcomes included subjective global assessment (SGA) of relief of IBS symptoms, adequate relief for at least 50% of weeks, and adverse events.

Results: Among 463 participants (mean age 48.5 years; 68% female), low-dose amitriptyline was superior to placebo at 6 months, with a significant mean difference in IBS-SSS score between groups (–27.0; 95% CI, –46.9 to –7.1; P = .0079). More participants reported relief of IBS symptoms with amitriptyline compared to placebo (61% vs 45%; odds ratio [OR] 1.78; 95% CI, 1.19–2.66; P = .0050). Adequate relief of IBS symptoms for at least 50% of weeks was higher with amitriptyline (41% vs 30%; OR 1.56; 95% CI, 1.20–2.03; P = .0008). Adverse events were more frequent with amitriptyline, mainly related to anticholinergic effects such as dry mouth (54%) and drowsiness (53%), but most were mild. Withdrawals due to adverse events were slightly higher with amitriptyline (13% vs 9%).

Conclusions: Low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care and was safe and well tolerated.

Implications for Practice: General practitioners should consider prescribing low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, providing appropriate support for patient-led dose titration.

Study Strengths and Limitations: Strengths include the large sample size, primary care setting, and extended treatment duration. Limitations involve underrepresentation of patients with IBS with constipation, potential unblinding due to side effects, and a predominantly White participant population.

Future Research: Further trials assessing amitriptyline as a first-line therapy for IBS in primary care and studies on long-term outcomes are recommended.

Reference: Ford AC, Wright-Hughes A, Alderson SL, et al. Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in Primary Care (ATLANTIS): a Randomised, Double-Blind, Placebo-Controlled, Phase 3 Trial. Lancet. 2023; DOI: http://doi.org/10.1016/S0140-6736(23)01523-4

 

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RCT: Milk Elimination Diet Comparable to Four-Food Elimination in Pediatric EoE

20 Oct, 2024 | 15:04h | UTC

Background: Eosinophilic esophagitis (EoE) is a chronic immune-mediated condition characterized by eosinophil infiltration of the esophageal mucosa, leading to symptoms such as nausea, vomiting, abdominal pain, and dysphagia in children. While elimination of six common food allergens is effective, this approach is highly restrictive and may adversely affect quality of life (QoL). Less restrictive diets could potentially balance efficacy with improved QoL.

Objective: To compare the efficacy of a one-food elimination diet excluding milk (1FED) versus a four-food elimination diet excluding milk, egg, wheat, and soy (4FED) in treating pediatric EoE.

Methods: In this multicenter, randomized, nonblinded trial conducted at ten sites in the United States, 63 children aged 6 to 17 years with histologically active and symptomatic EoE were randomized 1:1 to either 1FED (n = 38) or 4FED (n = 25) for 12 weeks. The primary endpoint was symptom improvement measured by the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS). Secondary endpoints included the proportion achieving histologic remission (<15 eosinophils per high-power field), changes in histologic features (histology scoring system), endoscopic severity (endoscopic reference score), transcriptome profiling (EoE diagnostic panel), QoL scores, and predictors of remission.

Results: Out of 63 participants, 51 completed the study (1FED, n = 34; 4FED, n = 17). The 4FED group showed a greater improvement in mean PEESS scores compared to the 1FED group (−25.0 vs. −14.5; P = .04). However, histologic remission rates were similar between 4FED and 1FED (41% vs. 44%; P = 1.00). Changes in the histology scoring system (−0.25 vs. −0.29; P = .77), endoscopic reference score (−1.10 vs. −0.58; P = .47), and QoL scores were comparable between groups. The withdrawal rate was higher in the 4FED group compared to the 1FED group (32% vs. 11%; P = .0496).

Conclusions: While the 4FED moderately improved symptoms more than the 1FED, both diets resulted in similar histologic, endoscopic, QoL, and transcriptomic outcomes. Given its comparable effectiveness, better tolerability, and simplicity, the 1FED is a reasonable first-choice therapy for pediatric EoE.

Implications for Practice: Eliminating cow’s milk alone may be preferable as initial dietary therapy for children with EoE due to its simplicity and similar efficacy compared to more restrictive diets. Clinicians should consider starting with a milk elimination diet before progressing to more restrictive elimination diets if necessary.

Study Strengths and Limitations: Strengths of the study include its randomized, multicenter design; standardized treatment instructions; and use of validated symptom and QoL instruments. Limitations include early termination due to low enrollment, a higher withdrawal rate in the 4FED group, nonblinded interventions, and potential bias from participant expectations.

Future Research: Further large-scale, randomized studies are needed to confirm these findings and to identify biomarkers that predict response to dietary therapy in pediatric EoE.

Reference: Kliewer KL, Abonia JP, Aceves SS, et al. (2024) One-food versus 4-food elimination diet for pediatric eosinophilic esophagitis: A multisite randomized trial. Journal of Allergy and Clinical Immunology. DOI: http://doi.org/10.1016/j.jaci.2024.08.023

 

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Phase 2 RCT: Ponsegromab Shows Promise for the Treatment of Cancer Cachexia

23 Sep, 2024 | 21:48h | UTC

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RCT: Liraglutide for Children Aged 6 to <12 Years with Obesity

14 Sep, 2024 | 19:40h | UTC

Summary:

A recent phase 3a randomized, double-blind, placebo-controlled trial published in the New England Journal of Medicine examined the efficacy and safety of liraglutide in children aged 6 to less than 12 years with obesity. Currently, no medications are approved for treating nonmonogenic, nonsyndromic obesity in this age group, making this study particularly noteworthy.

Methods:

• Participants: 82 children with obesity (BMI ≥95th percentile for age and sex).
• Design: Participants were randomized in a 2:1 ratio to receive once-daily subcutaneous liraglutide (up to 3.0 mg) or placebo, alongside lifestyle interventions, over a 56-week treatment period, followed by a 26-week follow-up.
• Primary Endpoint: Percentage change in BMI from baseline to week 56.
• Secondary Endpoints: Percentage change in body weight and the proportion achieving a ≥5% reduction in BMI.

Results:

• BMI Reduction: At week 56, the liraglutide group experienced a mean BMI reduction of –5.8%, compared to a +1.6% increase in the placebo group. The estimated difference was –7.4 percentage points (95% CI, –11.6 to –3.2; P<0.001).
• Body Weight: Mean body weight increased by 1.6% in the liraglutide group versus 10.0% in the placebo group, a difference of –8.4 percentage points (95% CI, –13.4 to –3.3; P=0.001).
• BMI Reduction ≥5%: Achieved by 46% of participants in the liraglutide group versus 9% in the placebo group (adjusted odds ratio, 6.3; 95% CI, 1.4 to 28.8; P=0.02).
• Adverse Events: Reported in 89% of the liraglutide group and 88% of the placebo group. Gastrointestinal events were more common with liraglutide (80% vs. 54%).

Discussion:

While the study suggests that liraglutide can lead to a statistically significant reduction in BMI among children aged 6 to less than 12 years with obesity, several considerations should temper our enthusiasm:

1. Sample Size and Diversity: The trial included only 82 participants, with a predominantly White population (72%), which may limit the generalizability of the findings to broader, more diverse populations.
2. Duration and Long-Term Effects: The study spanned 56 weeks, with a 26-week follow-up. The long-term efficacy and safety of liraglutide in this age group remain uncertain, particularly concerning growth, development, and potential rebound weight gain after discontinuation.
3. Clinical Significance: Although the reduction in BMI was statistically significant, the clinical significance—especially regarding long-term health outcomes and obesity-related comorbidities—is less clear. Obesity is a chronic and relapsing condition, and a modest reduction in BMI may not translate into substantial health benefits without sustained intervention.
4. Adverse Events: The high incidence of gastrointestinal adverse events raises questions about the tolerability of liraglutide in young children. Managing these side effects in a pediatric population can be challenging and may affect adherence.
5. Lack of Consensus on BMI Reduction: There’s no international consensus on what constitutes a clinically meaningful BMI reduction in children, complicating the interpretation of the results.

Conclusion:

This trial provides preliminary evidence that liraglutide, combined with lifestyle interventions, may help reduce BMI in children under 12 with obesity. However, given the limitations—including small sample size, short duration, and safety concerns—it’s prudent to approach these findings with cautious optimism. More extensive studies with longer follow-up periods and more diverse populations are necessary to fully assess the long-term efficacy and safety of liraglutide in this vulnerable age group.

Takeaway:

While liraglutide shows promise as an adjunct therapy for pediatric obesity, it’s essential to weigh the benefits against the potential risks and uncertainties. Clinicians should continue to prioritize established lifestyle interventions and consider pharmacotherapy on a case-by-case basis, pending further evidence.

Reference: Fox CK., et al (2024). Liraglutide for Children 6 to <12 Years of Age with Obesity – A Randomized Trial. N Engl J Med. DOI: http://doi.org/10.1056/NEJMoa2407379

 

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News Release: SCOFF Trial Confirms Fasting Not Necessary Before Cardiac Catheterisation Procedures

7 Sep, 2024 | 10:10h | UTC

1 September 2024 – London, United Kingdom – New findings from the SCOFF trial, presented at ESC Congress 2024, suggest that fasting prior to minimally invasive cardiac catheterisation procedures under conscious sedation does not increase the risk of complications. The trial supports reconsidering current guidelines on pre-procedural fasting.

Key Points for Physicians:

– No increased complications: The SCOFF trial found no significant difference in adverse outcomes, such as aspiration pneumonia or hypoglycemia, between patients who fasted and those who ate normally before cardiac catheterisation.

– Improved patient satisfaction: Patients who did not fast reported higher satisfaction, with fewer complaints of discomfort and hunger.

– Potential guideline change: These findings, in line with previous studies like CHOW-NOW and TONIC, challenge the necessity of fasting before such procedures.

The trial’s lead investigator, Dr. David Ferreira (John Hunter Hospital, Australia), emphasized that avoiding fasting may improve patient experience without increasing risks, making it time to reconsider fasting guidelines for these procedures.

Study Overview:

– Trial design: Prospective, randomized, open-label, with blinded endpoint assessment.

– Participants: 716 patients undergoing coronary angiography, coronary intervention, or cardiac implantable electronic device procedures.

– Primary endpoint: Composite of hypotension, aspiration pneumonia, hyperglycemia, and hypoglycemia, showing a lower event rate in the non-fasting group (12.0%) compared to the fasting group (19.1%).

These results are likely to influence future clinical practice, providing greater flexibility for both patients and healthcare systems.

Source: https://www.escardio.org/The-ESC/Press-Office/Press-releases/SCOFF-trial-confirms-that-fasting-is-not-needed-before-cath-lab-procedures

 

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Systematic Review: Nasogastric Feeding Increases Diarrhea and Pain Compared to Nasojejunal Feeding in Acute Pancreatitis – BMC Gastroenterol

18 Aug, 2024 | 19:23h | UTC

Study Design and Population: This systematic review and meta-analysis compared the safety and efficacy of nasogastric (NG) versus nasojejunal (NJ) feeding initiated within 48 hours of hospital admission in patients with moderate to severe acute pancreatitis. The analysis included four randomized controlled trials (RCTs) involving a total of 217 patients.

Main Findings: The review found no significant difference in mortality between NG and NJ feeding groups. However, NG feeding was associated with a higher incidence of diarrhea (RR 2.75, P = 0.02) and pain (RR 2.91, P = 0.002). The risk of infection was also higher in the NG group (6.67% vs. 3.33%, P = 0.027). No significant differences were observed in the need for surgical intervention, the requirement for parenteral nutrition, or the success rates of feeding procedures.

Implications for Practice: The findings suggest that while NG feeding does not increase mortality in acute pancreatitis, it is associated with higher rates of certain complications, particularly diarrhea and pain. Clinicians should consider these risks when choosing a feeding strategy for patients with acute pancreatitis, especially within the critical early 48-hour period post-admission.

Reference: Wang M, Shi H, Chen Q, Su B, Dong X, Shi H, Xu S. (2024). Comparative safety assessment of nasogastric versus nasojejunal feeding initiated within 48 hours post-admission versus unrestricted timing in moderate or severe acute pancreatitis: a systematic review and meta-analysis. BMC Gastroenterology, 24(207), 1-11. DOI: 10.1186/s12876-024-03290-z.

 

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Meta-Analysis: Long-Term Low-Carbohydrate Diets Improve Dyslipidemia but Not Glycemic Control in Type 2 Diabetes – J Diabetes Investig

17 Aug, 2024 | 19:14h | UTC

Study Design and Population: This systematic review and meta-analysis examined the impact of long-term low-carbohydrate diets (LCD) on glycemic control and other metabolic parameters in adults with type 2 diabetes. Six randomized controlled trials (RCTs) involving 524 participants were included, with intervention durations ranging from 12 to 24 months.

Main Findings: The meta-analysis found no significant difference in glycated hemoglobin (HbA1c) levels between participants on long-term LCD and those on control diets (SMD -0.11, 95% CI -0.33 to 0.11, P = 0.32). Similarly, there were no significant differences in weight loss, blood pressure, or low-density lipoprotein (LDL) cholesterol levels. However, LCDs were associated with a significant increase in high-density lipoprotein (HDL) cholesterol (SMD 0.22, 95% CI 0.04 to 0.41, P = 0.02) and a decrease in triglyceride levels (SMD -0.19; 95% CI -0.37 to -0.02; P = 0.03).

Implications for Practice: While long-term LCDs do not appear to improve glycemic control in individuals with type 2 diabetes, they may be beneficial for managing dyslipidemia, specifically by increasing HDL cholesterol and reducing triglycerides. These findings suggest that LCDs could be considered as part of a strategy for addressing cardiovascular risk factors in this population, but they should not be relied upon for glycemic management.

Reference: Ichikawa, T., Okada, H., Hironaka, J., Nakajima, H., Okamura, T., Majima, S., … & Fukui, M. (2024). Efficacy of long‐term low carbohydrate diets for patients with type 2 diabetes: A systematic review and meta‐analysis. Journal of Diabetes Investigation. https://doi.org/10.1111/jdi.14271.

 

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RCT: Dietary Acid Reduction with Fruits and Vegetables Slows CKD Progression and Lowers CVD Risk in Hypertensive Patients – Am J Med

17 Aug, 2024 | 15:49h | UTC

Study Design and Population: This five-year randomized control trial included 153 hypertensive patients with macroalbuminuria and normal kidney function. Participants were randomly assigned to one of three groups: a diet rich in base-producing fruits and vegetables, oral sodium bicarbonate (NaHCO3), or Usual Care. The primary objective was to assess the effects of dietary acid reduction on chronic kidney disease (CKD) progression and cardiovascular disease (CVD) risk.

Main Findings: The study found that both fruits and vegetables and NaHCO3 slowed CKD progression compared to Usual Care, with significantly higher estimated glomerular filtration rates in the intervention groups. However, only the fruits and vegetables group showed significant reductions in systolic blood pressure, LDL cholesterol, and body mass index, leading to greater improvements in CVD risk indices.

Implications for Practice: The results support using fruits and vegetables as a foundational treatment for hypertension to reduce CKD progression and lower CVD risk, potentially with reduced reliance on pharmacological interventions.

Reference: Goraya, N., Madias, N. E., Simoni, J., Kahlon, M., Aksan, N., & Wesson, D. E. (2024). Kidney and Cardiovascular Protection Using Dietary Acid Reduction in Primary Hypertension: A Five-Year, Interventional, Randomized, Control Trial. The American Journal of Medicine, 000(000), 1-14. DOI: https://doi.org/10.1016/j.amjmed.2024.06.006.

 

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RCT: Eliminating Fasting Before Contrast-Enhanced CT in Outpatients Reduces Nausea and Vomiting Without Increasing Acute Adverse Reactions – Insights Imaging

11 Aug, 2024 | 13:41h | UTC

Study Design and Population: This single-center, randomized clinical trial was conducted in Spain with 1,103 adult outpatients undergoing non-emergency contrast-enhanced CT scans. Patients were randomized into two groups: one group fasted for at least 6 hours (control), while the other group had no food restrictions (intervention). The primary aim was to assess whether eliminating fasting affects the incidence of acute adverse reactions (AARs), such as nausea and vomiting.

Main Findings: The study found no significant difference in the overall incidence of acute adverse reactions between the fasting and non-fasting groups (3.21% vs. 2.30%; p = 0.36). However, the non-fasting group had a significantly lower incidence of nausea and vomiting (0.92% vs. 2.86%; p = 0.02). Multivariate logistic regression identified fasting, age, allergies, neurological diseases, and contrast media concentration as independent risk factors for nausea and vomiting.

Implications for Practice: The findings suggest that the traditional practice of fasting before contrast-enhanced CT scans is unnecessary and may increase the risk of nausea and vomiting. Therefore, unrestricted food intake should be allowed for most contrast-enhanced CT exams, reserving fasting only for specific imaging procedures.

Reference: Zitan Saidi et al. (2024). Fasting before contrast-enhanced CT and the incidence of acute adverse reactions: a single-center randomized clinical trial. Insights into Imaging, 15(195). DOI: 10.1186/s13244-024-01767-9.

 

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Systematic Review: Uncertain Impact of Vitamin D Supplementation During Pregnancy on Key Maternal and Neonatal Outcomes – Cochrane Database Syst Rev

11 Aug, 2024 | 12:42h | UTC

Study Design and Population: This Cochrane systematic review evaluates the effects of vitamin D supplementation alone or in combination with calcium and other vitamins/minerals during pregnancy. The analysis included 10 randomized controlled trials (RCTs) with a total of 2,313 pregnant women. The review excluded 20 studies from previous versions due to trustworthiness concerns and incorporated one new study.

Main Findings: The evidence regarding vitamin D supplementation alone was very uncertain for its impact on pre-eclampsia, gestational diabetes, preterm birth, and nephritic syndrome. There is low-certainty evidence suggesting that vitamin D may reduce the risk of severe postpartum hemorrhage and low birthweight, though the possibility of increased risk cannot be excluded. Supplementation with vitamin D plus calcium showed very uncertain effects on preterm birth and low birthweight, with no conclusive data on pre-eclampsia, gestational diabetes, or maternal adverse events. The combination of vitamin D, calcium, and other vitamins/minerals also yielded very uncertain evidence for all outcomes examined.

Implications for Practice: The current evidence does not provide strong support for routine vitamin D supplementation during pregnancy due to the low and very uncertain evidence on key outcomes. Further high-quality RCTs are needed to better understand the effects, particularly concerning maternal adverse events and neonatal health.

Reference: Palacios, C., Kostiuk, L. L., Cuthbert, A., & Weeks, J. (2024). Vitamin D supplementation for women during pregnancy. Cochrane Database of Systematic Reviews, 7(7), CD008873. DOI: 10.1002/14651858.CD008873.pub5.

 

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Consensus Recommendations: Cardiovascular Risks in People With Narcolepsy – J Am Hear Assoc

10 Aug, 2024 | 21:48h | UTC

Introduction: The Journal of the American Heart Association recently published a consensus guideline by a panel of sleep and cardiology experts to address the heightened cardiovascular risks in individuals with narcolepsy. Given the increased prevalence of hypertension and cardiometabolic comorbidities in this population, the panel developed recommendations aimed at mitigating these risks.

Key Points:

1 – Increased Cardiovascular Risk in Narcolepsy:

– Individuals with narcolepsy, both Type 1 (NT1) and Type 2 (NT2), exhibit higher rates of cardiovascular and cardiometabolic diseases, such as hypertension, obesity, and diabetes, compared to the general population.

– The association of narcolepsy with conditions like obstructive sleep apnea (OSA) and restless legs syndrome further elevates cardiovascular risk.

2 – Monitoring and Early Detection:

– Clinicians should annually monitor blood pressure, weight, and waist circumference in patients with narcolepsy, even in the absence of existing cardiovascular disease.

– Screening for lipid levels and hemoglobin A1c is recommended, especially in patients with risk factors like hypertension, obesity, and diabetes.

3 – Lifestyle and Therapeutic Interventions:

– Patients should be educated about the link between narcolepsy and cardiovascular disease. Emphasis should be placed on maintaining optimal sleep duration, regular exercise, healthy eating, and reducing sodium intake.

– The American Heart Association’s “Life’s Essential 8” guidelines should be followed to enhance overall cardiovascular health.

4 – Medication Management:

– Narcolepsy medications, particularly stimulants and sodium oxybate, can increase cardiovascular risk. Clinicians should consider the patient’s cardiovascular profile when prescribing these treatments and explore alternatives with lower cardiovascular impact if necessary.

5 – Sodium Reduction:

– High sodium intake, from both diet and certain narcolepsy medications, is associated with increased blood pressure and cardiovascular disease. Patients should be advised to reduce sodium intake, and clinicians should consider prescribing lower-sodium alternatives when possible.

Conclusion: These expert consensus recommendations underscore the importance of proactive cardiovascular risk management in patients with narcolepsy. By implementing these guidelines, clinicians can help mitigate the long-term cardiovascular risks associated with this chronic sleep disorder.

Guideline Reference: Kwon Y, Gami AS, Javaheri S, et al. Cardiovascular Risks in People With Narcolepsy: Expert Panel Consensus Recommendations. Journal of the American Heart Association. 2024;13. DOI: 10.1161/JAHA.124.035168. Available at: https://doi.org/10.1161/JAHA.124.035168.

 

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Erythritol Ingestion Increases Platelet Reactivity and Thrombosis Potential in Healthy Adults – Arterioscler Thromb Vasc Biol

10 Aug, 2024 | 21:11h | UTC

Study Design and Population: This interventional study evaluated the effects of erythritol versus glucose on platelet reactivity and thrombosis potential in 20 healthy volunteers, with 10 participants in each group. Researchers measured erythritol plasma levels and assessed platelet function through aggregometry and granule marker analysis both before and after ingestion of 30 g of erythritol or glucose.

Main Findings: Erythritol ingestion resulted in a more than 1000-fold increase in plasma erythritol concentration and significantly enhanced stimulus-dependent platelet aggregation and release of serotonin and CXCL4, markers of platelet activation. In contrast, glucose ingestion did not significantly alter platelet reactivity or granule marker release, highlighting erythritol’s unique pro-thrombotic effects.

Implications for Practice: These findings raise concerns regarding the safety of erythritol as a non-nutritive sweetener, particularly its potential to enhance thrombosis risk. The results suggest a need to reevaluate erythritol’s safety status and consider its impact on cardiovascular health in regulatory guidelines.

Reference: Witkowski, M., Wilcox, J., Province, V., Wang, Z., Nemet, I., Tang, W. H. W., & Hazen, S. L. (2024). Ingestion of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity and thrombosis potential in healthy volunteers. Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/ATVBAHA.124.321019

 

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New Guidelines Recommend Against Routine Vitamin D Testing and Treatment for Healthy Adults – J Clin Endocrinol Metab

4 Aug, 2024 | 19:19h | UTC

Introduction: The Endocrine Society has developed new clinical practice guidelines focused on the use of vitamin D for the prevention of various diseases. These guidelines were created by a multidisciplinary panel, including experts in adult and pediatric endocrinology, internal medicine, obstetrics and gynecology, nutrition, and epidemiology.

Key Points:

1 – Empiric Vitamin D Supplementation in Children and Adolescents:

– Recommended to prevent nutritional rickets.

– May lower the risk of respiratory tract infections.

– Dosage in trials ranged from 300 to 2000 IU daily, with an average of about 1200 IU per day.

2 – Empiric Vitamin D Supplementation or Testing in Adults Under 75:

– Not recommended for generally healthy adults without specific indications.

3 – Empiric Vitamin D Supplementation in Adults Over 75:

– Suggested due to its potential to lower the risk of mortality.

– Treatment should be empirical, no testing recommended if there are no established indications for testing (e.g., hypocalcemia).

– Recommended daily rather than intermittent high doses. Dosage in clinical trials ranged from 400 to 3333 IU daily equivalent.

4 – Vitamin D Supplementation During Pregnancy:

– Suggested to lower the risk of preeclampsia, intrauterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality.

– Empiric supplementation recommended without routine 25(OH)D testing unless there are established indications for testing.

– Dosages in trials ranged from 600 to 5000 IU daily equivalent, with an average of about 2500 IU per day.

5 – Vitamin D and High-Risk Prediabetes:

– Suggested to reduce the progression to diabetes.

– In clinical trials, vitamin D dosages ranged from 842 to 7543 IU daily. The estimated weighted average was approximately 3500 IU per day.

6 – Routine 25(OH)D Testing:

– Not recommended for the general population, including those with obesity or dark complexion.

– No clear evidence defining optimal target levels for disease prevention.

Conclusion: These guidelines emphasize the importance of targeted vitamin D supplementation for specific age groups and conditions, while advising against routine testing for vitamin D levels in the general population. Empiric supplementation is considered beneficial, particularly in children, pregnant women, and older adults, and is feasible, cost-effective, and generally acceptable.

Guideline Reference: Demay, M. B., et al. (2024). Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism, 109, 1907-1947. Available at: https://doi.org/10.1210/clinem/dgae290

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RCT: Effects of combined time-restricted eating and high-intensity functional training on body composition and cardiometabolic health in women with obesity – PLOS One

7 May, 2024 | 15:28h | UTC

This randomized clinical trial investigated the effects of time-restricted eating (TRE) and high-intensity functional training (HIFT), both separately and in combination, on body composition and cardiometabolic health in inactive women with obesity. Sixty-four participants were assigned to three groups: TRE alone, HIFT alone, and both TRE and HIFT (TRE-HIFT). Over 12 weeks, the TRE-HIFT group showed the most significant improvements in waist and hip circumference, fat mass, total cholesterol, triglyceride levels, insulin sensitivity, and blood glucose levels compared to the other groups. Weight and BMI reductions were also more substantial in the TRE-HIFT group than in the HIFT-only group. Furthermore, while all groups exhibited improvements, those combining both interventions experienced more pronounced changes in cardiometabolic parameters, suggesting the potential of integrated lifestyle interventions for enhancing health outcomes in this population.

 

Reference (link to free full-text):

Ranya Ameur et al. (2024). Unlocking the power of synergy: High-intensity functional training and early time-restricted eating for transformative changes in body composition and cardiometabolic health in inactive women with obesity. PLOS ONE. DOI: https://doi.org/10.1371/journal.pone.0301369

 

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