Systematic Reviews & Meta-analysis
Systematic Review: Intensive Blood Pressure Targets Do Not Reduce Mortality or Cardiovascular Events in Hypertensive Patients with Chronic Kidney Disease
20 Oct, 2024 | 17:50h | UTCBackground: Chronic kidney disease (CKD) is a significant independent risk factor for cardiovascular disease and mortality, affecting approximately 10% of the global population. Hypertension is prevalent in CKD patients, ranging from 22% to 80% depending on disease stage. While lowering blood pressure is essential in managing CKD, the optimal blood pressure targets remain uncertain, particularly whether lower-than-standard targets provide additional benefits.
Objective: To compare the effects of standard versus lower-than-standard blood pressure targets on mortality and morbidity outcomes in hypertensive patients with CKD.
Methods: A systematic review and meta-analysis of six randomized controlled trials (RCTs) involving 7348 participants were conducted. Studies included adults with hypertension and CKD randomized to lower blood pressure targets (≤130/80 mmHg) versus standard targets (≤140–160/90–100 mmHg) with at least 12 months of follow-up. Primary outcomes were total mortality, total serious adverse events, total cardiovascular events, cardiovascular mortality, and progression to end-stage renal disease (ESRD). Data were analyzed using GRADE methodology to assess the certainty of evidence.
Results: Over a mean follow-up of 3.6 years, lower blood pressure targets likely resulted in little to no difference in total mortality (risk ratio [RR] 0.90; 95% confidence interval [CI], 0.76 to 1.06; moderate-certainty evidence), total serious adverse events (RR 1.01; 95% CI, 0.94 to 1.08; moderate-certainty), and total cardiovascular events (RR 1.00; 95% CI, 0.87 to 1.15; moderate-certainty) compared to standard targets. Lower targets may result in little to no difference in cardiovascular mortality (RR 0.90; 95% CI, 0.70 to 1.16; low-certainty) and progression to ESRD (RR 0.94; 95% CI, 0.80 to 1.11; low-certainty). Participants in the lower target groups achieved greater reductions in systolic and diastolic blood pressure but required more antihypertensive medications.
Conclusions: Intensive blood pressure targets probably do not reduce total mortality, serious adverse events, or cardiovascular events compared to standard targets in hypertensive patients with CKD, and may have little to no effect on cardiovascular mortality or progression to ESRD.
Implications for Practice: Clinicians should consider that lowering blood pressure below standard targets in hypertensive CKD patients may not provide additional benefit in reducing mortality or cardiovascular events. The increased medication burden and potential for adverse effects with intensive targets should be weighed against the lack of demonstrated benefit.
Study Strengths and Limitations: Strengths include the use of individual participant data from six RCTs and a comprehensive analysis using GRADE methodology. Limitations involve the open-label design of the included studies, potential risk of bias, heterogeneity in blood pressure targets and CKD definitions, and limited adverse event reporting.
Future Research: Further high-quality RCTs are needed to determine optimal blood pressure targets in hypertensive CKD patients, including those with varying levels of proteinuria and using out-of-office blood pressure monitoring. Ongoing studies may provide additional evidence in the near future.
Systematic Review: Anifrolumab and Belimumab Improve Disease Control in Systemic Lupus Erythematosus; Voclosporin and Belimumab Effective in Lupus Nephritis
20 Oct, 2024 | 14:26h | UTCBackground: Systemic lupus erythematosus (SLE) management remains challenging due to disease heterogeneity and varying severity. New studies since the 2019 EULAR recommendations necessitate an update to inform clinical practice.
Objective: To analyze new evidence (2018–2022) for SLE management to inform the 2023 update of the European League Against Rheumatism (EULAR) recommendations.
Methods: Systematic literature reviews (SLRs) were conducted in Medline and Cochrane Library databases, covering publications from January 2018 to December 2022. Research focused on five domains: (1) efficacy and safety of SLE treatments, (2) benefits of remission/low disease activity, (3) risks of treatment tapering/withdrawal, (4) management of SLE with antiphospholipid syndrome, and (5) safety of varicella zoster virus (VZV) and SARS-CoV2 immunizations.
Results: A total of 439 relevant articles were identified, predominantly observational studies of low or moderate quality. High-quality randomized controlled trials (RCTs) documented the efficacy of anifrolumab, a type 1 interferon receptor inhibitor, in non-renal SLE, and belimumab and voclosporin, a novel calcineurin inhibitor, in lupus nephritis (LN) when compared with standard care. For specific organ manifestations outside LN, high-quality data were lacking. Multiple observational studies confirmed the benefits of attaining clinical remission or low disease activity, reducing the risk of adverse outcomes. Two RCTs with some concerns found higher relapse rates in patients who discontinued glucocorticoids or immunosuppressants in SLE and LN, respectively; however, observational studies suggest that treatment withdrawal may be feasible in a subset of patients.
Conclusions: Anifrolumab and belimumab achieve better disease control than standard care in extrarenal SLE, while combination therapies with belimumab and voclosporin showed higher response rates in high-quality RCTs in LN. Remission and low disease activity are associated with favorable long-term outcomes. In patients achieving these targets, glucocorticoids and immunosuppressive therapy may be gradually tapered.
Implications for Practice: Clinicians should consider anifrolumab and belimumab for extrarenal SLE, and belimumab and voclosporin for LN. Monitoring and aiming for remission or low disease activity can reduce adverse outcomes. Gradual tapering of glucocorticoids and immunosuppressants may be considered in patients achieving these targets, with careful monitoring for relapse.
Study Strengths and Limitations: Strengths include comprehensive SLRs and inclusion of recent high-quality RCTs. Limitations involve the predominance of low-quality observational studies, lack of high-quality data for specific organ manifestations, and potential bias in treatment withdrawal studies.
Future Research: Further high-quality RCTs are needed to assess treatments for specific organ manifestations outside LN. Long-term studies on tapering and withdrawal strategies of immunosuppressive therapies are necessary to guide safe practice.
Meta-Analysis: Topiramate and CGRP Monoclonal Antibodies Effective in Medication Overuse Headache
13 Oct, 2024 | 14:07h | UTCBackground: Medication overuse headache (MOH) results from frequent intake of acute pain medications, leading to increased headache frequency and severity. There is ongoing debate regarding the necessity and optimal choice of prophylactic drugs in MOH treatment, with previous studies lacking clear guidance.
Objective: To determine the comparative efficacy and safety of available pharmacological therapies for MOH, including their ability to eliminate medication overuse (MO).
Methods: A systematic review and network meta-analysis of randomized controlled trials were conducted, comparing different pharmacological treatments for MOH. Primary outcomes included the responder rate (≥50% reduction in headache frequency), proportion of patients reverting to no medication overuse (nMO), and reductions in monthly headache days and acute medication intake frequency. The certainty of evidence was assessed using the GRADE framework.
Results: Twenty-eight studies involving 5,527 patients were included. Topiramate demonstrated significant benefits in increasing responder rates (odds ratio [OR] 4.93), reducing headache frequency (weighted mean difference [WMD] –5.53), and decreasing acute medication intake frequency (WMD –6.95), but was associated with more adverse events compared to placebo (OR 0.20). Fremanezumab, galcanezumab, and botulinum toxin type A (BTA) were effective in increasing responder rates (ORs 2.57 to 3.46). For reversion to nMO, eptinezumab, fremanezumab, and BTA were superior to placebo (ORs 1.55 to 2.75). Eptinezumab, fremanezumab, erenumab 140 mg, and BTA were more efficacious than erenumab 70 mg without significant differences in safety and tolerability.
Conclusions: Topiramate likely has large beneficial effects on increasing responder rates and reducing headache frequency but is associated with lower safety and greater intolerability. Fremanezumab, galcanezumab, and eptinezumab show promise in increasing responder rates. Eptinezumab has a large beneficial effect on reversion to nMO, with fremanezumab and BTA having smaller effects.
Implications for Practice: Clinicians should balance efficacy and tolerability when selecting pharmacological treatments for MOH. While topiramate is effective, its adverse event profile may limit its use. CGRP monoclonal antibodies, such as eptinezumab and fremanezumab, offer promising efficacy with acceptable safety profiles and may be preferred options for some patients.
Study Strengths and Limitations: Strengths include a comprehensive network meta-analysis of multiple pharmacological therapies and the use of GRADE for assessing evidence certainty. Limitations involve variability among included studies, small sample sizes, and heterogeneity in study populations and methodologies, which may affect the generalizability of the findings.
Future Research: High-quality randomized controlled trials are needed to confirm these findings and directly compare different pharmacological treatments in MOH. Future studies should focus on long-term efficacy, safety of newer therapies, and their impact on patient-centered outcomes.
Meta-analysis: Colchicine Reduces Ischemic Stroke and MACE in Patients with Prior Stroke or Coronary Disease
13 Oct, 2024 | 12:10h | UTCBackground: Colchicine is recommended for secondary prevention in cardiovascular disease, but its efficacy in preventing ischemic stroke and benefits in key patient subgroups remain uncertain. Inflammation plays a significant role in stroke and cardiovascular events, and colchicine’s anti-inflammatory properties may confer additional protective effects.
Objective: To evaluate the efficacy of colchicine for secondary prevention of ischemic stroke and major adverse cardiovascular events (MACE) in patients with prior stroke or coronary disease, and to assess its safety profile across key clinical subgroups.
Methods: A trial-level meta-analysis was conducted, including six randomized controlled trials with a total of 14,934 patients with prior stroke or coronary disease. Trials comparing colchicine with placebo or no colchicine for at least three months were included. The primary efficacy outcomes were ischemic stroke and MACE, defined as a composite of ischemic stroke, myocardial infarction, coronary revascularization, or cardiovascular death. Secondary outcomes included serious safety events and mortality.
Results: Colchicine reduced the risk of ischemic stroke by 27% (1.8%] vs. 186 events [2.5%]; RR 0.73, 95% CI 0.58–0.90; P = .004) and MACE by 27% (505 events [6.8%] vs. 693 events [9.4%]; RR 0.73, 95% CI 0.65–0.81; P < .001). The efficacy was consistent across key subgroups, including sex, age (<70 vs. ≥70 years), diabetes status, and statin use at baseline. Colchicine was not associated with an increase in serious safety outcomes, all-cause mortality (201 deaths [2.7%] vs. 181 deaths [2.4%]; RR 1.09, 95% CI 0.89–1.33; P = .39), cardiovascular death, or non-cardiovascular death.
Conclusions: In patients with prior stroke or coronary disease, colchicine significantly reduces the risk of ischemic stroke and MACE without increasing serious adverse events or mortality. These findings support the use of low-dose colchicine as an effective secondary prevention therapy in a broad cardiovascular patient population.
Implications for Practice: Clinicians should consider incorporating low-dose colchicine into secondary prevention regimens for patients with prior stroke or coronary disease, given its demonstrated efficacy and acceptable safety profile. Its affordability and widespread availability make it a practical option for diverse healthcare settings, including low- and middle-income countries.
Study Strengths and Limitations: Strengths include a large pooled sample size and inclusion of multiple trials across various patient populations, enhancing generalizability. Limitations involve potential performance bias in non-placebo-controlled trials, differences in stroke outcome definitions among studies, and the inability to perform individual patient data analyses.
Future Research: Further studies are needed to evaluate the long-term effects of colchicine on vascular events and cognitive decline in stroke patients, assess safety in patients with renal impairment, and explore its impact on non-cardiovascular mortality.
Meta-Analysis: Oral Anticoagulant Monotherapy Reduced Bleeding Without Increasing Ischemic Events in AF and Stable CAD
9 Oct, 2024 | 11:13h | UTCBackground: Atrial fibrillation (AF) patients with stable coronary artery disease (CAD) often require both oral anticoagulants (OACs) for stroke prevention and antiplatelet therapy for CAD management. However, dual antithrombotic therapy (DAT) increases bleeding risk. The optimal antithrombotic regimen in this population remains unclear.
Objective: To evaluate whether OAC monotherapy reduces major bleeding without increasing ischemic events compared to DAT in patients with AF and stable CAD.
Methods: This meta-analysis followed PRISMA guidelines, pooling data from three randomized controlled trials (RCTs) involving 3,945 patients with AF and stable CAD. The trials included used various OACs (rivaroxaban, edoxaban, or warfarin/DOAC) and compared them with DAT. The primary outcomes were all-cause death, cardiovascular death, and major bleeding. Secondary outcomes included stroke (ischemic and hemorrhagic) and myocardial infarction (MI).
Results: OAC monotherapy significantly reduced the risk of major bleeding compared to DAT (3.4% vs 5.8%; RR: 0.55; 95% CI: 0.32–0.95; p=0.03). There were no significant differences between groups in all-cause death (4.2% vs 5.4%; RR: 0.85; 95% CI: 0.49–1.48; p=0.57), cardiovascular death (2.4% vs 3.0%; RR: 0.84; 95% CI: 0.50–1.41; p=0.50), any stroke event (2.2% vs 3.1%; RR: 0.74; 95% CI: 0.46–1.18; p=0.21), or myocardial infarction (RR: 1.57; 95% CI: 0.79–3.12; p=0.20).
Conclusions: In patients with AF and stable CAD, OAC monotherapy significantly reduces major bleeding risk compared to DAT without increasing the risk of ischemic events or mortality.
Implications for Practice: OAC monotherapy may be a preferable antithrombotic strategy in patients with AF and stable CAD, balancing effective thromboembolic protection with a lower bleeding risk. Clinicians should consider OAC monotherapy to simplify antithrombotic regimens and reduce bleeding complications, especially beyond one year after coronary events or interventions.
Study Strengths and Limitations: Strengths include the inclusion of recent large-scale RCTs and the focus on a clinically relevant patient population. Limitations involve reliance on study-level data, limited number of trials, and potential heterogeneity among included studies. The duration of DAT was not consistently available, and individual patient data meta-analysis may provide more detailed insights.
Future Research: Additional large-scale RCTs and individual patient data meta-analyses are needed to confirm these findings and to determine the optimal duration and type of antithrombotic therapy in patients with AF and stable CAD.
Umbrella Review: 5-Day Antibiotic Courses Effective for Non-ICU Community-Acquired Pneumonia or Exacerbations of COPD
6 Oct, 2024 | 17:12h | UTCBackground: Respiratory tract infections (RTIs) significantly contribute to global disease burden and antibiotic usage. Optimizing antibiotic treatment duration is crucial for antimicrobial stewardship to minimize resistance. Despite evidence supporting shorter antibiotic courses for RTIs, prolonged treatment durations persist in clinical practice.
Objective: To evaluate the current evidence base for optimal antibiotic treatment durations in RTIs and determine whether shorter courses are supported.
Methods: An umbrella review was conducted by searching Ovid MEDLINE, Embase, and Web of Science up to May 1, 2024, without language restrictions. Systematic reviews comparing antibiotic treatment durations for community-acquired pneumonia (CAP), acute exacerbations of chronic obstructive pulmonary disease (AECOPD), hospital-acquired pneumonia (HAP), acute sinusitis, and streptococcal pharyngitis, tonsillitis, or pharyngotonsillitis in adults were included. Pediatric-focused reviews were excluded. Quality assessments utilized the AMSTAR 2 tool for reviews and the Cochrane risk-of-bias tool (version 1) for randomized controlled trials (RCTs). The GRADE approach determined the overall quality of evidence.
Results: Thirty systematic reviews were included, generally of low to critically low quality. For non-ICU CAP (14 reviews), moderate-quality evidence supports a 5-day antibiotic course, with insufficient data for shorter durations. In AECOPD (eight reviews), a 5-day treatment was non-inferior to longer courses regarding clinical and microbiological cure, with similar or fewer adverse events. Evidence for non-ventilator-associated HAP is lacking. In acute sinusitis, shorter regimens appear effective, but further research is needed for patients requiring antibiotics. For pharyngotonsillitis (eight reviews), evidence supports short-course cephalosporin therapy but not short-course penicillin when dosed three times daily.
Conclusions: Evidence supports a 5-day antibiotic treatment duration for non-ICU CAP and AECOPD in clinically improving patients. Implementing this evidence in practice is essential. High-quality RCTs are needed to assess shorter durations for CAP and AECOPD, establish optimal durations for HAP and acute sinusitis, and evaluate short-course penicillin with optimal dosing in pharyngotonsillitis.
Implications for Practice: Clinicians should adopt 5-day antibiotic courses for non-ICU CAP and AECOPD in patients showing clinical improvement, aligning with antimicrobial stewardship objectives to reduce unnecessary antibiotic exposure and resistance development.
Study Strengths and Limitations: Strengths include a comprehensive search and assessment of systematic reviews and meta-analyses. Limitations involve the generally low quality of included reviews and RCTs, with many studies exhibiting unclear or high risk of bias. Heterogeneity in definitions of short-course treatment and variability in patient populations and settings were also noted.
Future Research: High-quality RCTs are required to investigate antibiotic durations shorter than 5 days for CAP and AECOPD, determine optimal treatment lengths for HAP and acute sinusitis, and assess short-course penicillin therapy with optimal dosing schedules in pharyngotonsillitis.
Network Meta-Analysis: Eletriptan, Rizatriptan, Sumatriptan, and Zolmitriptan Most Effective for Acute Migraine Episodes
23 Sep, 2024 | 22:34h | UTCBackground: Migraine, a highly prevalent neurological disorder, is a leading cause of disability, especially among women aged 15 to 49. Effective acute management is critical, with current guidelines recommending non-steroidal anti-inflammatory drugs (NSAIDs) and triptans for moderate to severe episodes. However, the relative efficacy of various drug interventions remains unclear, especially with newer treatments like lasmiditan and gepants entering the market.
Objective: To evaluate and compare the efficacy and tolerability of all licensed oral drugs for the acute treatment of migraine episodes in adults.
Methods: A systematic review and network meta-analysis was conducted, including 137 randomized controlled trials (RCTs) involving 89,445 participants. The study analyzed 17 drug interventions, including NSAIDs, triptans, ditans, and gepants, and compared them with placebo. Primary outcomes included pain freedom at two hours post-dose and sustained pain freedom from two to 24 hours post-dose. Certainty of evidence was assessed using the CINeMA framework, and sensitivity analyses were conducted to confirm the robustness of the findings.
Results: All active interventions outperformed placebo for pain freedom at two hours, with odds ratios ranging from 1.73 (95% CI 1.27 to 2.34) for naratriptan to 5.19 (4.25 to 6.33) for eletriptan. The most effective drugs for sustained pain freedom were eletriptan and ibuprofen. Among head-to-head comparisons, eletriptan was the most effective for pain freedom at two hours, followed by rizatriptan, sumatriptan, and zolmitriptan. Newer drugs like lasmiditan, rimegepant, and ubrogepant were less effective than the triptans and showed adverse effects like dizziness and nausea.
Conclusions: Triptans—specifically eletriptan, rizatriptan, sumatriptan, and zolmitriptan—demonstrated superior efficacy and tolerability profiles compared to newer treatments like lasmiditan and gepants. Given their efficacy, these triptans should be prioritized in acute migraine management. However, triptans are underused, and barriers to access should be addressed to ensure broader utilization. Lasmiditan and gepants may still serve as alternatives for patients contraindicated for triptans due to cardiovascular risks.
Implications for Practice: Clinicians should prioritize triptans, particularly eletriptan, rizatriptan, sumatriptan, and zolmitriptan, in managing acute migraine episodes due to their superior efficacy. Careful consideration is needed when selecting newer drugs like lasmiditan and gepants, as they may be less effective and have higher costs and adverse event risks. Cost-effectiveness and patient cardiovascular profiles should guide decision-making.
Study Strengths and Limitations: Strengths include the comprehensive inclusion of both published and unpublished data, as well as the large sample size and robust methodological framework. Limitations include moderate heterogeneity and low confidence in some comparisons due to reporting biases and imprecise treatment effects in older studies.
Future Research: Future studies should focus on re-evaluating the cardiovascular contraindications of triptans to ensure broader access. Additional research is also needed to assess the cost-effectiveness of newer treatments like lasmiditan and gepants, particularly in patients for whom triptans are unsuitable.
Meta-analysis: Perioperative Colchicine Reduced Postoperative Atrial Fibrillation After CABG
18 Sep, 2024 | 13:33h | UTCBackground: Coronary artery disease (CAD) remains a leading cause of mortality worldwide. Inflammation is a key factor in the development and progression of CAD, and anti-inflammatory therapies have shown potential in improving cardiovascular outcomes. Colchicine, traditionally used to treat gout, has demonstrated efficacy in reducing cardiovascular events in patients with chronic CAD. Previous individual studies have suggested that perioperative colchicine may decrease the incidence of postoperative atrial fibrillation (POAF) in patients undergoing coronary artery bypass grafting (CABG), but a comprehensive analysis is needed to confirm these findings.
Objective: To evaluate the effect of perioperative colchicine administration on the incidence of POAF in patients undergoing isolated CABG surgery through a meta-analysis of randomized controlled trials (RCTs).
Methods: A systematic search was conducted across MEDLINE, Web of Science, and The Cochrane Library to identify RCTs comparing perioperative colchicine administration with standard care in patients undergoing CABG. Inclusion criteria encompassed studies involving isolated CABG patients randomized to receive colchicine or standard care without colchicine. The primary outcome was the incidence of POAF during short-term follow-up.
Results: Five RCTs published between 2014 and 2022 met the inclusion criteria, including a total of 839 patients undergoing isolated CABG. Perioperative colchicine administration was associated with a significant reduction in POAF rates compared to standard care (relative risk [RR], 0.54; 95% confidence interval [CI], 0.40–0.73; p < 0.01). Other outcomes, such as graft patency, myocardial infarction, or long-term mortality, were not uniformly reported and, therefore, not analyzed.
Conclusions: Perioperative administration of colchicine is associated with a significant reduction in the incidence of POAF in patients undergoing CABG surgery.
Implications for Practice: Colchicine may be considered as a prophylactic strategy to reduce POAF in patients undergoing CABG, potentially improving both short- and long-term outcomes. Given the association of POAF with increased perioperative morbidity and long-term adverse events, implementing colchicine could have substantial clinical benefits in this high-risk population.
Study Strengths and Limitations: Strengths of this meta-analysis include the exclusive inclusion of randomized controlled trials and the use of rigorous statistical methods, including sensitivity analysis, which confirmed the robustness of the results. Limitations involve the small number of studies (five RCTs), potential variability in colchicine dosing regimens, and the lack of data on other clinically relevant outcomes.
Future Research: Large-scale, multicenter RCTs are warranted to further assess the effects of colchicine on other important outcomes in CABG patients, such as graft patency, myocardial infarction rates, and long-term mortality. Future studies should also evaluate the risk-benefit profile of colchicine in this patient population to establish its full role in clinical practice.
Reference: Kirov H., Caldonazo T., Runkel A., et al. (2024). Colchicine in Patients with Coronary Disease Undergoing Coronary Artery Bypass Surgery – A Meta-Analysis of Randomized Controlled Trials. The American Journal of Cardiology. DOI: http://doi.org/10.1016/j.amjcard.2024.09.003
Systematic Review: Antidepressants Offer Limited Pain Relief with Potential Harms in Older Adults
17 Sep, 2024 | 11:34h | UTCBackground: Chronic pain is prevalent among older adults and significantly affects their quality of life. Antidepressants are commonly prescribed for pain management in this population across various countries. While several systematic reviews have evaluated the efficacy and safety of antidepressants for pain in adults, none have specifically focused on individuals aged 65 years and older. The efficacy and safety profile of antidepressants for pain relief in older adults remains unclear.
Objective: To assess the efficacy and safety of antidepressant medications compared to all alternatives for the management of non-cancer pain in older adults aged 65 years and above.
Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted. Thirteen databases were searched from inception to February 1, 2024, to identify relevant studies. Trials included compared any antidepressant medication to any alternative (e.g., placebo, other medications, or non-drug therapies) for the treatment of non-cancer pain in older adults. Data extracted included study and participant characteristics, primary efficacy outcomes (pain scores converted to a 0–100 scale), and harms. Estimates for efficacy were pooled using a random-effects model and reported as mean differences with 95% confidence intervals (CIs). The quality of included trials was assessed using the Cochrane risk of bias tool.
Results: Fifteen studies encompassing 1,369 participants met the inclusion criteria. The most frequently studied antidepressants were duloxetine and amitriptyline (six studies each). Pain related to knee osteoarthritis was the most commonly studied condition (six studies). For knee osteoarthritis:
- Immediate Term (0–2 weeks): Antidepressants did not provide a statistically significant reduction in pain compared to alternatives (mean difference [MD], –5.6; 95% CI, –11.5 to 0.3).
- Intermediate Term (≥6 weeks and <12 months): Duloxetine provided a statistically significant, albeit very small, reduction in pain (MD, –9.1; 95% CI, –11.8 to –6.4).
Nearly half of the studies (7 out of 15) reported increased withdrawal of participants in the antidepressant treatment group compared to the comparator group due to adverse events.
Conclusions: For most chronic painful conditions in older adults, the benefits and harms of antidepressant medications are unclear. The available evidence predominantly comes from trials with small sample sizes (less than 100 participants), disclosed industry ties, and trials classified as having unclear or high risk of bias.
Implications for Practice:
- Minimal Benefit: Antidepressants, particularly duloxetine, may offer a very small benefit for pain relief in older adults with knee osteoarthritis over the intermediate term.
- Risk of Harms: The potential harms, including increased adverse events leading to higher withdrawal rates, may outweigh these minimal benefits.
- Clinical Decision-Making: Clinicians should carefully weigh the benefits against the risks when considering prescribing antidepressants for pain in older adults.
- Alternative Strategies: Non-pharmacological interventions and alternative pain management strategies should be prioritized in this population.
Study Strengths and Limitations: Strengths include the comprehensive search strategy across multiple databases and the focus on older adults, a population often underrepresented in clinical trials. Limitations involve the generally low quality of the included trials, small sample sizes, high risk of bias, and inconsistent reporting of pain outcomes and adverse events among studies.
Future Research: Further large-scale, high-quality randomized controlled trials are needed to investigate the efficacy and safety of antidepressants for pain management in older adults. Future studies should also compare antidepressants to non-pharmacological interventions and explore long-term outcomes and optimal dosing regimens in this population.
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 | UTCStudy 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.
Meta-Analysis: High-Dose Psilocybin Shows Small Advantage Over Escitalopram for Depression – The BMJ
24 Aug, 2024 | 16:41h | UTCStudy 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.
Systematic Review: Nasogastric Feeding Increases Diarrhea and Pain Compared to Nasojejunal Feeding in Acute Pancreatitis – BMC Gastroenterol
18 Aug, 2024 | 19:23h | UTCStudy 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.
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 | UTCStudy 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.
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 | UTCStudy 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.
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 | UTCMain 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.
Network Meta-Analysis: Preoperative Chemoradiotherapy and Chemotherapy Equally Improve Survival in Esophagogastric Adenocarcinoma – JAMA Netw Open
17 Aug, 2024 | 19:21h | UTCStudy 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.
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 | UTCStudy 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.
Meta-Analysis: Renal Denervation Modestly Reduces Blood Pressure in Uncontrolled Hypertension – J Am Heart Assoc
17 Aug, 2024 | 16:14h | UTCStudy 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.
Meta-analysis: SSRIs Significantly Reduce Symptoms but Increase Adverse Events in Premenstrual Syndrome – Cochrane Database Syst Rev
17 Aug, 2024 | 16:04h | UTCStudy 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.
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 | UTCStudy 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.
Meta-Analysis: Inhaled Antibiotics Offer Modest Reductions in Exacerbations and Quality of Life Gains in Bronchiectasis – CHEST
11 Aug, 2024 | 13:12h | UTCStudy 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.
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 | UTCStudy 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.
Meta-Analysis: Effects of extracorporeal CO2 removal on gas exchange and ventilator settings in critically ill adults – Crit Care
27 May, 2024 | 20:28h | UTCSummary: 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):
Systematic Review: Daratumumab enhances survival in newly diagnosed multiple myeloma patients ineligible for transplant – Cochrane Library
4 May, 2024 | 13:46h | UTCStudy 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):
Systematic Review: Effects of ACE inhibitors and ARBs on kidney and cardiovascular outcomes in diabetic patients – Cochrane Library
4 May, 2024 | 13:32h | UTCStudy 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):