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Systematic Reviews & Meta-analysis

Network Meta-Analysis: Potent Corticosteroids, JAK Inhibitors, and Tacrolimus 0.1% Among the Most Effective Topical Treatments for Eczema – Cochrane Library

25 Aug, 2024 | 12:03h | UTC

Study Design and Population: This network meta-analysis included 291 randomized controlled trials involving 45,846 participants with varying eczema severity. The trials primarily focused on adults in high-income countries and assessed various topical anti-inflammatory treatments over a median duration of 21 to 28 days. The study aimed to compare the efficacy and safety of these treatments.

Main Findings: Potent topical corticosteroids (TCS), JAK inhibitors, and tacrolimus 0.1% were consistently ranked as the most effective treatments for reducing eczema symptoms and signs. In contrast, phosphodiesterase-4 (PDE-4) inhibitors like crisaborole 2% and mild TCS were among the least effective. Notably, tacrolimus, pimecrolimus, and crisaborole were more likely to cause local adverse effects such as burning and stinging, while short-term TCS use did not show an increased risk of skin thinning, although long-term use did.

Implications for Practice: The findings suggest that potent TCS, JAK inhibitors, and tacrolimus 0.1% are effective for short-term eczema control. However, given the risk of skin thinning with long-term TCS use and potential adverse effects with certain treatments, clinicians should consider patient preferences, treatment availability, and cost when selecting therapies.

Reference: Cochrane Skin Group, et al. (2024). Topical anti-inflammatory treatments for eczema: network meta-analysis. Cochrane Database of Systematic Reviews. http://doi.org/10.1002/14651858.CD015064.pub2

 


Meta-Analysis: High-Dose Psilocybin Shows Small Advantage Over Escitalopram for Depression – The BMJ

24 Aug, 2024 | 16:41h | UTC

Study Design and Population: This systematic review and Bayesian network meta-analysis evaluated the effectiveness of oral monotherapy with psychedelics (psilocybin, LSD, MDMA, ayahuasca) compared to escitalopram in adults with depressive symptoms. The analysis included 15 trials with psychedelics and 5 trials with escitalopram, covering a total of 811 participants in psychedelic trials and 1968 in escitalopram trials.

Main Findings: The analysis revealed that only high-dose psilocybin demonstrated a significant improvement in depressive symptoms compared to placebo when considered in the context of antidepressant trials, but the effect size was small (standardized mean difference of 0.31). High-dose psilocybin also outperformed escitalopram (10 mg and 20 mg), with a mean difference exceeding the minimal important difference. However, the placebo response was generally lower in psychedelic trials compared to antidepressant trials, suggesting potential overestimation of effect sizes in psychedelic studies.

Implications for Practice: The findings suggest that while high-dose psilocybin may offer a small advantage over escitalopram for treating depression, the overall effect size is comparable to traditional antidepressants. The results highlight the importance of considering the impact of blinding and placebo response in psychedelic trials, and suggest that improved blinding and standardized psychotherapies could help better assess the true efficacy of these treatments.

Reference: Hsu, T.-W., Tsai, C.-K., Kao, Y.-C., Thompson, T., Carvalho, A. F., Yang, F.-C., Tseng, P.-T., Hsu, C.-W., Yu, C.-L., Tu, Y.-K., & Liang, C.-S. (2024). Comparative oral monotherapy of psilocybin, lysergic acid diethylamide, 3,4-methylenedioxymethamphetamine, ayahuasca, and escitalopram for depressive symptoms: systematic review and Bayesian network meta-analysis. BMJ, 386, e078607. DOI: https://doi.org/10.1136/bmj-2023-078607

 


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.

 


Systematic Review: Immune Checkpoint Inhibitors Plus Chemotherapy Improves Survival in NSCLC for Patients Aged 65-75 – Cochrane Database Syst Rev

18 Aug, 2024 | 15:24h | UTC

Study Design and Population: This Cochrane systematic review evaluated the efficacy and safety of immune checkpoint inhibitors (ICIs) combined with platinum-based chemotherapy versus platinum-based chemotherapy alone (with or without bevacizumab) in treatment-naïve older adults with advanced non-small cell lung cancer (NSCLC). The review included 17 randomized controlled trials (RCTs) with a total of 4,276 participants, focusing on three age groups: 65 years and older, 65-75 years, and 75 years and older.

Main Findings: The addition of ICIs to chemotherapy likely improves overall survival (HR 0.78, 95% CI 0.70 to 0.88) and progression-free survival (HR 0.61, 95% CI 0.54 to 0.68) in patients aged 65 years and older. For those aged 65-75, the benefits are more pronounced (HR 0.75 for overall survival; HR 0.64 for progression-free survival), although there may be an increase in treatment-related adverse events (RR 1.47). However, in patients over 75, the benefits in overall survival and progression-free survival are unclear, with a low-certainty evidence suggesting no significant improvement (HR 0.90 and HR 0.83, respectively).

Implications for Practice: The findings support the use of ICIs combined with chemotherapy in older adults aged 65-75 with advanced NSCLC, but caution is advised for those over 75 due to the lack of clear survival benefit and the potential for increased toxicity. Further research is needed to better understand the risks and benefits in the oldest patients.

Reference: Orillard E, Adhikari A, Malouf RS, Calais F, Marchal C, Westeel V. (2024). Immune checkpoint inhibitors plus platinum-based chemotherapy compared to platinum-based chemotherapy with or without bevacizumab for first-line treatment of older people with advanced non-small cell lung cancer. Cochrane Database of Systematic Reviews, Issue 8, Art. No.: CD015495. DOI: 10.1002/14651858.CD015495.

 


Meta-Analysis: Effects of Psychological, Psychosocial, Pharmacological, Physical and Combined Treatments for Adults with a New Episode of Depression – eClinicalMedicine

17 Aug, 2024 | 19:49h | UTC

Study Design and Population: This systematic review and network meta-analysis examined 676 randomized controlled trials (RCTs) involving 105,477 participants, comparing psychological, psychosocial, pharmacological, physical, and combined treatments for adults with a new episode of unipolar depression. The study stratified interventions based on depressive symptom severity (less severe and more severe).

Main Findings: For less severe depression, group cognitive behavioral therapy (CBT) was the only treatment class that significantly improved depressive symptoms compared to treatment as usual (TAU). For more severe depression, effective interventions included combined individual CBT with antidepressants, individual behavioral therapies, and combined treatments like acupuncture or exercise with antidepressants. Notably, antidepressants alone did not show significant effects in less severe depression.

Implications for Practice: These findings suggest that group CBT may be an effective first-line treatment for less severe depression, while combined therapies, particularly those involving antidepressants and individual psychological interventions, are more effective in treating more severe depression. This evidence could guide clinical decision-making and inform updates to treatment guidelines.

Reference: Mavranezouli I et al. (2024). A systematic review and network meta-analysis of psychological, psychosocial, pharmacological, physical and combined treatments for adults with a new episode of depression. eClinicalMedicine, 75: 102780. DOI: 10.1016/j.eclinm.2024.102780.

 


Meta-Analysis: 1-Month Dual Antiplatelet Therapy Reduces Major Bleeding Without Increasing Stent Thrombosis After PCI with DES – Am J Cardiol

17 Aug, 2024 | 19:29h | UTC

Main Findings: The analysis found that 1-month DAPT significantly reduced the risk of major bleeding (OR 0.66, 95% CI 0.45-0.97, p = 0.03) compared to >1-month DAPT. Additionally, there was no significant difference in stent thrombosis rates between the groups (OR 1.08, 95% CI 0.81-1.44, p = 0.60). Secondary outcomes, including all-cause mortality, cardiovascular death, myocardial infarction, stroke, and major adverse cardiovascular or cerebrovascular events were also similar between the groups.

Implications for Practice: The findings support the use of 1-month DAPT followed by aspirin or a P2Y12 receptor inhibitor as a safer alternative to longer-term DAPT in patients undergoing PCI with DES. This strategy may help reduce bleeding risks without increasing the likelihood of thrombotic events, making it a viable option for routine clinical practice, particularly in patients at high risk for bleeding.

Reference: Bajraktari G, Bytyçi I, Abdyli G, et al. (2024). One-Month Dual Antiplatelet Therapy Reduces Major Bleeding Compared With Longer-Term Treatment Without Excess Stent Thrombosis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. The American Journal of Cardiology, 227, 91-97. DOI: https://doi.org/10.1016/j.amjcard.2024.07.010.

 


Network Meta-Analysis: Preoperative Chemoradiotherapy and Chemotherapy Equally Improve Survival in Esophagogastric Adenocarcinoma – JAMA Netw Open

17 Aug, 2024 | 19:21h | UTC

Study Design and Population: This network meta-analysis included 17 randomized clinical trials (RCTs) with a total of 2,549 patients, predominantly male (86.5%), with a mean age of 61 years. The study compared the effects of preoperative chemoradiotherapy (CRT) versus preoperative and/or perioperative chemotherapy, and surgery alone on overall survival and disease-free survival in patients with adenocarcinoma of the esophagus and esophagogastric junction (AEG).

Main Findings: Both preoperative CRT plus surgery (HR, 0.75) and preoperative/perioperative chemotherapy plus surgery (HR, 0.78) significantly improved overall survival compared to surgery alone. Disease-free survival was similarly prolonged with both treatments. No significant difference was observed between CRT and chemotherapy in overall survival, though CRT was associated with higher postoperative morbidity.

Implications for Practice: The findings suggest that both preoperative CRT and preoperative/perioperative chemotherapy are effective in extending survival in AEG patients, with no clear superiority of one approach over the other. Clinicians can consider either modality based on patient-specific factors, although the increased morbidity associated with CRT warrants careful consideration.

Reference: Ronellenfitsch U, Friedrichs J, Barbier E, et al. (2024). Preoperative Chemoradiotherapy vs Chemotherapy for Adenocarcinoma of the Esophagogastric Junction: A Network Meta-Analysis. JAMA Network Open, 7(8), e2425581. DOI: 10.1001/jamanetworkopen.2024.25581.

 


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.

 


Meta-Analysis: Renal Denervation Modestly Reduces Blood Pressure in Uncontrolled Hypertension – J Am Heart Assoc

17 Aug, 2024 | 16:14h | UTC

Study Design and Population: This updated meta-analysis evaluated 15 randomized clinical trials, encompassing 2,581 patients, to assess the efficacy and safety of catheter-based renal denervation (RDN) in patients with uncontrolled hypertension. The trials included both patients on antihypertensive medications (ON-Med) and those off medications (OFF-Med), with comparisons made between RDN and sham or standard therapy.

Main Findings: RDN led to a modest but statistically significant reduction in blood pressure across both ON-Med and OFF-Med groups. In the OFF-Med group, 24-hour ambulatory systolic BP was reduced by 3.7 mm Hg (95% CI, -5.41 to -2.00). In the ON-Med group, the reduction was 2.23 mm Hg (95% CI, -3.56 to -0.90). Sham-controlled trials reinforced these findings, showing consistent BP reductions, thus validating the effect of RDN. However, the degree of BP reduction is modest and may be clinically limited.

Implications for Practice: While RDN appears to have a favorable safety profile and provides consistent BP reductions, the modest nature of these reductions suggests that its clinical utility may be more limited. Further research is needed to identify which patient populations might benefit the most from RDN and to optimize procedural techniques for greater efficacy.

Reference: Mufarrih et al. (2024). Randomized Trials of Renal Denervation for Uncontrolled Hypertension: An Updated Meta-Analysis. Journal of the American Heart Association, 13(e034910). DOI: 10.1161/JAHA.124.034910.

 


Meta-analysis: SSRIs Significantly Reduce Symptoms but Increase Adverse Events in Premenstrual Syndrome – Cochrane Database Syst Rev

17 Aug, 2024 | 16:04h | UTC

Study Design and Population: This systematic review and meta-analysis included 34 randomized controlled trials (RCTs) involving 4,563 women diagnosed with premenstrual syndrome (PMS) or premenstrual dysphoric disorder (PMDD). The studies primarily focused on evaluating the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) compared to placebo. The trials involved a diverse population, predominantly from Western countries, with participants aged between 18 and 49 years.

Main Findings: SSRIs likely reduce overall self-rated premenstrual symptoms in women with PMS and PMDD, with a standardized mean difference (SMD) of -0.57 (95% CI: -0.72 to -0.42). Continuous SSRI administration was more effective than luteal phase administration (SMD -0.69 vs. -0.39). However, SSRIs were associated with a higher risk of adverse events, including nausea (OR 3.30), insomnia (OR 1.99), sexual dysfunction (OR 2.32), and fatigue (OR 1.52).

Implications for Practice: SSRIs are an effective treatment option for reducing premenstrual symptoms in women with PMS and PMDD, particularly when administered continuously. However, the increased risk of adverse events must be carefully considered, and patients should be monitored closely. Further research is necessary to confirm these findings and explore long-term safety.

Reference: Jespersen C, Lauritsen MP, Frokjaer VG, Schroll JB. (2024). Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder. Cochrane Database of Systematic Reviews, 2024(8), CD001396. DOI: 10.1002/14651858.CD001396.pub4.

 


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

11 Aug, 2024 | 13:19h | UTC

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

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

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

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

 


Meta-Analysis: Inhaled Antibiotics Offer Modest Reductions in Exacerbations and Quality of Life Gains in Bronchiectasis – CHEST

11 Aug, 2024 | 13:12h | UTC

Study Design and Population: This study is an updated systematic review and meta-analysis of 20 randomized controlled trials involving 3,468 adults with bronchiectasis, who were treated with inhaled antibiotics. The trials included in the analysis were selected based on criteria such as a minimum treatment duration of 4 weeks and involved patients diagnosed by CT imaging. The primary endpoint was exacerbation frequency, while secondary endpoints included severe exacerbations, bacterial load, symptoms, quality of life, and FEV1.

Main Findings: The meta-analysis found that inhaled antibiotics modestly reduced the proportion of patients experiencing exacerbations (risk ratio [RR], 0.85) and exacerbation frequency (RR, 0.78). Severe exacerbations were also decreased (RR, 0.48), and there was a slight increase in the time to the first exacerbation (hazard ratio [HR], 0.80). Additionally, quality of life showed modest improvements as measured by the Quality of Life Questionnaire-Bronchiectasis (mean difference, 2.51) and the St. George Respiratory Questionnaire (mean difference, -3.13). Bacterial load was consistently reduced, although FEV1 did not change meaningfully with treatment. The rate of adverse effects was similar to placebo (odds ratio [OR], 0.99), but antibiotic resistance appeared more likely to increase with treatment.

Implications for Practice: Inhaled antibiotics appear to be a beneficial treatment for adults with bronchiectasis, as they can reduce both exacerbation rates and severity while also improving quality of life. However, the increased risk of antibiotic resistance is a concern, indicating the need for careful patient selection and monitoring during treatment. These findings support the use of inhaled antibiotics in appropriate cases, particularly for those at high risk of exacerbations.

Reference: Cordeiro, R., Choi, H., Haworth, C. S., & Chalmers, J. D. (2024). The Efficacy and Safety of Inhaled Antibiotics for the Treatment of Bronchiectasis in Adults. CHEST Journal, 166(1), 61-80. DOI: https://doi.org/10.1016/j.chest.2024.01.045.

 


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.

 


Meta-Analysis: Effects of extracorporeal CO2 removal on gas exchange and ventilator settings in critically ill adults – Crit Care

27 May, 2024 | 20:28h | UTC

Summary: Study Design and Population: This systematic review and meta-analysis included 49 studies (3 RCTs, 46 observational studies) involving 1672 critically ill adults undergoing extracorporeal carbon dioxide removal (ECCO2R) for respiratory failure between January 2000 and March 2022.

Main Findings: ECCO2R significantly reduced PaCO2, plateau pressure, and tidal volume, while increasing pH across all patient groups. Adverse event rate was 19%. The three RCTs did not show mortality benefits but indicated longer ICU and hospital stays.

Implications for Practice: ECCO2R improves gas exchange and reduces ventilation invasiveness, especially in ARDS and lung transplant patients. However, due to the lack of mortality benefits and increased adverse events, further studies are needed to identify patient groups that could benefit most from ECCO2R.

 

Reference (link to free full-text):

Stommel AM et al. (2024). Effects of extracorporeal CO2 removal on gas exchange and ventilator settings: a systematic review and meta-analysis. Critical Care, 28(146). DOI: 10.1186/s13054-024-04927-x.

 


Systematic Review: Daratumumab enhances survival in newly diagnosed multiple myeloma patients ineligible for transplant – Cochrane Library

4 May, 2024 | 13:46h | UTC

Study Design and Population:
This Cochrane review evaluates four open-label, two-arm randomized controlled trials involving 1,783 adults with newly diagnosed multiple myeloma ineligible for autologous stem cell transplant. The studies were conducted globally, mainly in middle- and high-income countries, with participants aged between 69 to 74 years. Adding Daratumumab, a CD38-targeting monoclonal antibody, to standard antineoplastic therapy was compared to standard antineoplastic therapy alone.

 

Main Findings:
Daratumumab significantly improved overall survival with a hazard ratio of 0.64 and increased progression-free survival with a hazard ratio of 0.48, based on moderate-certainty evidence from the studies. Quality of life showed a slight improvement, although the evidence was of low certainty. Treatment-related serious adverse events were more common in the daratumumab group, with a risk ratio of 1.18. However, there was no significant increase in adverse events of CTCAE grade ≥3, except for a higher risk of infections.

 

Implications for Practice:
The addition of daratumumab to standard antineoplastic therapy offers a potential benefit in overall survival and disease progression control for patients with multiple myeloma who are ineligible for transplant. These benefits must be weighed against the increased risk of serious adverse events and infections. Future studies could provide further insights, particularly into the long-term quality of life and management of side effects.

 

Reference (link to abstract – $ for full-text):

Langer P et al. (2024). Daratumumab and antineoplastic therapy versus antineoplastic therapy only for adults with newly diagnosed multiple myeloma ineligible for transplant. Cochrane Database of Systematic Reviews, Issue 5. DOI: 10.1002/14651858.CD013595.pub2.

 


Systematic Review: Effects of ACE inhibitors and ARBs on kidney and cardiovascular outcomes in diabetic patients – Cochrane Library

4 May, 2024 | 13:32h | UTC

Study Design and Population:

This systematic review and meta-analysis evaluated the effectiveness of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in managing cardiovascular and kidney outcomes in adults with diabetes and kidney disease. It included data from 109 randomized controlled trials totaling 28,341 participants, comparing the impact of ACEi and ARBs, either alone or in combination, against each other, placebo, or no treatment.

 

Main Findings:

The analysis revealed that ACEi may reduce the risk of kidney failure (RR 0.61, 95% CI 0.39 to 0.94) but generally has little effect on all-cause mortality and cardiovascular death compared to placebo, with low certainty of evidence. Similarly, ARBs showed potential in preventing kidney failure (RR 0.82, 95% CI 0.72 to 0.94) and the progression from microalbuminuria to macroalbuminuria. The effects on cardiovascular outcomes remained uncertain and showed minimal difference compared to placebo or no treatment.

 

Implications for Practice:

While ACEi and ARBs may aid in preventing kidney failure in patients with diabetic kidney disease, their broader impacts on mortality and cardiovascular health remain uncertain. This underscores the necessity for further rigorous research to verify these findings and better determine the optimal therapeutic strategies. Clinicians should weigh these results against individual patient profiles considering the overall low certainty of the evidence.

 

Reference (link to abstract – $ for full-text):

Natale, P. et al. (2024). Comparative Efficacy of ACE Inhibitors and ARB on Kidney and Cardiovascular Outcomes in Diabetic Kidney Disease. Cochrane Database of Systematic Reviews. DOI: 10.1002/14651858.CD006257.pub2.

 


Systematic Review: Comparing antibiotic treatment vs. appendectomy for the initial treatment of uncomplicated appendicitis – Cochrane Library

4 May, 2024 | 13:09h | UTC

Study Design and Population:

This Cochrane review analyzed 13 randomized controlled trials involving 3,358 participants to compare the efficacy of antibiotic treatment versus appendectomy in managing uncomplicated acute appendicitis. The included studies predominantly involved adult participants and utilized broad-spectrum antibiotics, with interventions ranging from open to predominantly laparoscopic appendectomy. Data collection spanned from hospital admission to up to seven years, with studies conducted across various global regions, including Asia, Europe, and North America.

 

Main Findings:

The primary outcomes revealed that antibiotic treatment might slightly increase the risk of unsuccessful treatment with 76 additional unsuccessful cases per 1,000 individuals compared to surgery, though these results did not reach clinical significance. Antibiotics reduced wound infections but possibly increased the average hospital stay by half a day. About 30.7% of participants treated with antibiotics required an appendectomy within one year. Secondary outcomes showed very uncertain evidence on antibiotics’ effect on intra-abdominal abscess or reoperation rates, and a slight increase in negative appendectomy rates was observed.

 

Implications for Practice:

The findings suggest that while antibiotics could serve as an initial treatment to avoid surgery in two-thirds of cases annually, a significant portion may still require surgical intervention. This information is crucial for clinicians in making informed treatment decisions, particularly considering patient preferences and the risk of surgery. Further research is needed to explore long-term outcomes and identify patient subgroups that may benefit most from either treatment.

 

Reference (link to abstract – $ for full-text):

Doleman B, Fonnes S, Lund JN, et al. (2024). Appendectomy versus antibiotic treatment for acute appendicitis. Cochrane Database of Systematic Reviews, (April 29), CD015038.pub2. DOI: https://doi.org/10.1002/14651858.CD015038.pub2.

 


M-A: Neoadjuvant chemoimmunotherapy enhances event-free survival in resectable NSCLC with low PD-L1 expression

28 Apr, 2024 | 20:20h | UTC

This meta-analysis evaluated the impact of neoadjuvant chemoimmunotherapy versus chemotherapy on resectable non-small cell lung cancer (NSCLC) patients, particularly focusing on those with tumor PD-L1 levels below 1%. The study synthesized data from 43 trials, encompassing 5431 patients, to assess clinical outcomes such as overall and event-free survival, alongside major and complete pathological responses. Findings highlighted that neoadjuvant chemoimmunotherapy significantly improved event-free survival (hazard ratio, 0.74; 95% CI, 0.62-0.89) compared to chemotherapy alone, particularly in patients with low PD-L1 expression, though overall survival benefits were not observed. The pooled analysis from randomized clinical trials showed favorable outcomes across all examined endpoints, supporting the superiority of neoadjuvant chemoimmunotherapy in these settings.

 

Reference (link to free full-text):

Sorin, M., Prosty, C., Ghaleb, L., et al. (2024). Neoadjuvant Chemoimmunotherapy for NSCLC A Systematic Review and Meta-Analysis. JAMA Oncology. doi:10.1001/jamaoncol.2024.0057.

 


Meta-Analysis: Efficacy of MRI in prostate cancer screening for reducing unnecessary biopsies

28 Apr, 2024 | 20:13h | UTC

This meta-analysis evaluated the effectiveness of incorporating magnetic resonance imaging (MRI) into prostate cancer screening pathways, compared to prostate-specific antigen (PSA)–only screening strategies. Analyzing data from 80,114 men across 12 studies, the findings demonstrate that MRI-based screening, particularly when using a sequential approach and a PI-RADS score ≥3 cutoff for biopsy, significantly increases the odds of detecting clinically significant prostate cancers (OR, 4.15) while reducing unnecessary biopsies (OR, 0.28) and detection of clinically insignificant cancers (OR, 0.34). Implementing a higher PI-RADS score of ≥4 further decreased the detection of insignificant cancers and biopsies performed, without impacting the detection rate of significant cancers. These results support the integration of MRI into screening programs to enhance diagnostic precision and reduce patient harm.

 

Reference (link to abstract – $ for full-text):

Tamás Fazekas et al. (2024). Magnetic Resonance Imaging in Prostate Cancer Screening:  A Systematic Review and Meta-Analysis. JAMA Oncol, Published online April 5, 2024. DOI: 10.1001/jamaoncol.2024.0734

 


M-A: Cardiovascular benefits of SGLT2 inhibitors in patients without diabetes

22 Mar, 2024 | 11:07h | UTC

Study Design and Population: This meta-analysis investigated the cardiovascular (CV) outcomes associated with sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients without diabetes mellitus (DM). By systematically reviewing online databases, the authors identified and included six randomized controlled trials (RCTs) in their analysis. These trials compared SGLT2i with placebo/control in a total of 12,984 participants, who were followed for an average duration of 17.7 months. The study population comprised mainly patients with heart failure (HF), chronic kidney disease, or myocardial infarction, with a mean age of 64 years, where 72% were men and the mean hemoglobin A1C level was 5.7%.

Main Findings: The use of SGLT2i was associated with a significant reduction in composite CV death or hospitalization for HF, with an odds ratio (OR) of 0.77 (95% confidence interval [CI], 0.68 to 0.87, p < 0.0001), primarily due to a decrease in hospitalization for HF (OR 0.70, 95% CI 0.60 to 0.81, p < 0.00001). No significant differences were observed in CV death, all-cause death, or major adverse CV events when comparing SGLT2i to placebo. Notably, serious adverse events were lower with the use of empagliflozin compared to placebo.

Implications for Practice: This meta-analysis highlights the significant CV benefits of SGLT2i treatment in reducing CV death or hospitalization for HF in patients without DM, compared with placebo. These findings suggest the potential for broader use of SGLT2i in populations without diabetes to improve cardiovascular outcomes.

Reference: Sahib Singh et al. (2024). Cardiovascular Outcomes With Empagliflozin and Dapagliflozin in Patients Without Diabetes. The American Journal of Cardiology, Published: February 29, 2024. DOI: https://doi.org/10.1016/j.amjcard.2024.02.039. Access the study here: [Link]


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

20 Mar, 2024 | 17:54h | UTC

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

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

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

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


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