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Journal of Clinical Hypertension... May 2022Dihydropyridine calcium channel blockers (DHPCCBs) are widely used to treat hypertension and chronic coronary artery disease. One common adverse effect of DHPCCBs is... (Meta-Analysis)
Meta-Analysis
Dihydropyridine calcium channel blockers (DHPCCBs) are widely used to treat hypertension and chronic coronary artery disease. One common adverse effect of DHPCCBs is peripheral edema, particularly of the lower limbs. The side effect could lead to dose reduction or discontinuation of the medication. The combination of DHPCCBs and renin-angiotensin system blockers has shown to reduce the risk of DHPCCBs-associated peripheral edema compared with DHPCCBs monotherapy. We performed the current systematic review and network meta-analysis of randomized controlled trials (RCTs) to estimate the rate of peripheral edema with DHPCCBs as a class and with individual DHPCCBs and the ranking of the reduction of peripheral edema. The effects of renin-angiotensin system blockers on DHPCCBs network meta-analysis were created to analyze the ranking of the reduction of peripheral edema. A total of 3312 publications were identified and 71 studies with 56,283 patients were included. Nifedipine ranked highest in inducing peripheral edema (SUCRA 81.8%) and lacidipine (SUCRA 12.8%) ranked the least. All DHPCCBs except lacidipine resulted in higher relative risk (RR) of peripheral edema compared with placebo. Nifedipine plus angiotensin receptor blocker (SUCRA: 92.3%) did not mitigate peripheral edema and amlodipine plus angiotensin-converting enzyme inhibitors (SUCRA: 16%) reduced peripheral edema the most. Nifedipine ranked the highest and lacidipine ranked the lowest amongst DHPCCBs for developing peripheral edema when used for cardiovascular indications. The second or higher generation of DHPCCBs combination with ACEIs or ARBs or diuretics lowered the chance of peripheral edema development compared to single DHPCCB treatment.
Topics: Antihypertensive Agents; Calcium Channel Blockers; Dihydropyridines; Edema; Humans; Hypertension; Network Meta-Analysis; Nifedipine
PubMed: 35234349
DOI: 10.1111/jch.14436 -
Advances in Therapy Dec 2023A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a Treat & Extend (T&E) regime with intervals up to every 16 weeks (Q16W), relative to other therapies currently in use for treatment of diabetic macular oedema (DME). Of particular interest were anti-vascular endothelial growth factor (VEGF) therapies applied in flexible dosing regimens such as Pro re nata (PRN) and T&E, which are the mainstay in clinical practice.
METHODS
An SLR identifying randomised controlled trials (RCTs) published before August 2021 was conducted, followed by a Bayesian NMA comparing faricimab T&E treatment to aflibercept, ranibizumab, bevacizumab, dexamethasone and laser therapy. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), change in central subfield thickness (CST), injection frequency, ocular adverse events (AE) and all-cause discontinuation, all of which were evaluated at 12 months. Subgroup analyses including patients' naïve to anti-VEGF were conducted where feasible.
RESULTS
Twenty-six studies identified in the SLR were included in the NMA. Most importantly for decision making in clinical practise, faricimab T&E was associated with a statistically greater (95% credible intervals exclude zero) and clinically meaningful decrease in retinal thickness compared to all other flexible dosing regimens (greater retinal drying by 55-125 microns). Anatomical outcomes determine treatment efficacy and retreatment of patients. The NMA also showed a statistically greater increase in mean change in BCVA for faricimab T&E vs. flexible regimens using ranibizumab and bevacizumab (increase of 4.4-4.8 letters) as well as a numerical improvement vs. aflibercept PRN (two letters, 95% credible intervals including zero). Accordingly, the injection frequency was numerically lower versus other treatments using flexible dosing regimens (decrease by 0.92-1.43 injections). The analyses also indicated that the safety profile of faricimab T&E was comparable to those of ranibizumab and aflibercept, which have well-established safety profiles, with similar results for the number of all-cause discontinuations.
CONCLUSION
Faricimab provides a new treatment option in DME with dual-pathway inhibition of VEGF and angiopoeitin-2 (Ang-2). To the authors' knowledge, this is the first indirect comparison of faricimab T&E in DME. The analyses indicate that faricimab T&E is associated with superior retinal drying along with numerically fewer injections compared to all other treatments given in flexible dosing regimens. It also showed superior visual acuity outcomes compared to ranibizumab and bevacizumab.
Topics: Humans; Angiogenesis Inhibitors; Bevacizumab; Diabetic Retinopathy; Intravitreal Injections; Macular Edema; Network Meta-Analysis; Ranibizumab; Vascular Endothelial Growth Factor A
PubMed: 37751021
DOI: 10.1007/s12325-023-02675-y -
Critical Care (London, England) Jan 2021Acute kidney injury (AKI) is a common serious complication in critically ill patients. AKI occurs in up to 50% patients in intensive care unit (ICU), with poor clinical... (Meta-Analysis)
Meta-Analysis
Timing of renal replacement therapy initiation for acute kidney injury in critically ill patients: a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis.
BACKGROUND
Acute kidney injury (AKI) is a common serious complication in critically ill patients. AKI occurs in up to 50% patients in intensive care unit (ICU), with poor clinical prognosis. Renal replacement therapy (RRT) has been widely used in critically ill patients with AKI. However, in patients without urgent indications such as acute pulmonary edema, severe acidosis, and severe hyperkalemia, the optimal timing of RRT initiation is still under debate. We conducted this systematic review of randomized clinical trials (RCTs) with meta-analysis and trial sequential analysis (TSA) to compare the effects of early RRT initiation versus delayed RRT initiation.
METHODS
We searched databases (PubMed, EMBASE and Cochrane Library) from inception through to July 20, 2020, to identify eligible RCTs. The primary outcome was 28-day mortality. Two authors extracted the data independently. When the I values < 25%, we used fixed-effect mode. Otherwise, the random effects model was used as appropriate. TSA was performed to control the risk of random errors and assess whether the results in our meta-analysis were conclusive.
RESULTS
Eleven studies involving 5086 patients were identified. Two studies included patients with sepsis, one study included patients with shock after cardiac surgery, and eight others included mixed populations. The criteria for the initiation of RRT, the definition of AKI, and RRT modalities existed great variations among the studies. The median time of RRT initiation across studies ranged from 2 to 7.6 h in the early RRT group and 21 to 57 h in the delayed RRT group. The pooled results showed that early initiation of RRT could not decrease 28-day all-cause mortality compared with delayed RRT (RR 1.01; 95% CI 0.94-1.09; P = 0.77; I = 0%). TSA result showed that the required information size was 2949. The cumulative Z curve crossed the futility boundary and reached the required information size. In addition, early initiation of RRT could lead to unnecessary RRT exposure in some patients and was associated with a higher incidence of hypotension (RR 1.42; 95% CI 1.23-1.63; P < 0.00001; I = 8%) and RRT-associated infection events (RR 1.34; 95% CI 1.01-1.78; P = 0.04; I = 0%).
CONCLUSIONS
This meta-analysis suggested that early initiation of RRT was not associated with survival benefit in critically ill patients with AKI. In addition, early initiation of RRT could lead to unnecessary RRT exposure in some patients, resulting in a waste of health resources and a higher incidence of RRT-associated adverse events. Maybe, only critically ill patients with a clear and hard indication, such as severe acidosis, pulmonary edema, and hyperkalemia, could benefit from early initiation of RRT.
Topics: Acute Kidney Injury; Critical Illness; Humans; Incidence; Randomized Controlled Trials as Topic; Renal Replacement Therapy; Time Factors; Time-to-Treatment
PubMed: 33407756
DOI: 10.1186/s13054-020-03451-y -
Sports Health Nov 2014The popularity of running barefoot or in minimalist shoes has recently increased because of claims of injury prevention, enhanced running efficiency, and improved...
CONTEXT
The popularity of running barefoot or in minimalist shoes has recently increased because of claims of injury prevention, enhanced running efficiency, and improved performance compared with running in shoes. Potential risks and benefits of running barefoot or in minimalist shoes have yet to be clearly defined.
OBJECTIVE
To determine the methodological quality and level of evidence pertaining to the risks and benefits of running barefoot or in minimalist shoes.
DATA SOURCES
In September 2013, a comprehensive search of the Ovid MEDLINE, SPORTDiscus, and CINAHL databases was performed by 2 independent reviewers.
STUDY SELECTION
Included articles were obtained from peer-reviewed journals in the English language with no limit for year of publication. Final inclusion criteria required at least 1 of the following outcome variables: pain, injury rate, running economy, joint forces, running velocity, electromyography, muscle performance, or edema.
STUDY DESIGN
Systematic review.
LEVEL OF EVIDENCE
Level 3.
DATA EXTRACTION
Two reviewers appraised each article using the Downs and Black checklist and appraised each for level of evidence.
RESULTS
Twenty-three articles met the criteria for this review. Of 27 possible points on the Downs and Black checklist, articles scored between 13 and 19 points, indicating a range of evidence from very limited to moderate. Moderate evidence supports the following biomechanical differences when running barefoot versus in shoes: overall less maximum vertical ground reaction forces, less extension moment and power absorption at the knee, less foot and ankle dorsiflexion at ground contact, less ground contact time, shorter stride length, increased stride frequency, and increased knee flexion at ground contact.
CONCLUSION
Because of lack of high-quality evidence, no definitive conclusions can be drawn regarding specific risks or benefits to running barefoot, shod, or in minimalist shoes.
PubMed: 25364479
DOI: 10.1177/1941738114546846 -
The Cochrane Database of Systematic... Jun 2023Diabetic retinopathy (DR) remains a major cause of sight loss worldwide, despite new therapies and improvements in the metabolic control of people living with diabetes.... (Review)
Review
BACKGROUND
Diabetic retinopathy (DR) remains a major cause of sight loss worldwide, despite new therapies and improvements in the metabolic control of people living with diabetes. Therefore, DR creates a physical and psychological burden for people, and an economic burden for society. Preventing the development and progression of DR, or avoiding the occurrence of its sight-threatening complications is essential, and must be pursued to save sight. Fenofibrate may be a useful strategy to achieve this goal, by reversing diabetes' effects and reducing inflammation in the retina, as well as improving dyslipidaemia and hypertriglyceridaemia. OBJECTIVES: To investigate the benefits and harms of fenofibrate for preventing the development and progression of diabetic retinopathy in people with type 1 (T1D) or type 2 diabetes (T2D), compared with placebo or observation.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, and three trials registers (February 2022).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that included people with T1D or T2D, when these compared fenofibrate with placebo or with observation, and assessed the effect of fenofibrate on the development or progression of DR (or both).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods for data extraction and analysis. Our primary outcome was progression of DR, a composite outcome of 1) incidence of overt retinopathy for participants who did not have DR at baseline, or 2) advancing two or more steps on the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale for participants who had any DR at baseline (or both), based on the evaluation of stereoscopic or non-stereoscopic fundus photographs, during the follow-up period. Overt retinopathy was defined as the presence of any DR observed on stereoscopic or non-stereoscopic colour fundus photographs. Secondary outcomes included the incidence of overt retinopathy, reduction in visual acuity of participants with a reduction in visual acuity of 10 ETDRS letters or more, proliferative diabetic retinopathy, and diabetic macular oedema; mean vision-related quality of life, and serious adverse events of fenofibrate. We used GRADE to assess the certainty of evidence.
MAIN RESULTS
We included two studies and their eye sub-studies (15,313 participants) in people with T2D. The studies were conducted in the US, Canada, Australia, Finland, and New Zealand; follow-up period was four to five years. One was funded by the government, the other by industry. Compared to placebo or observation, fenofibrate likely results in little to no difference in progression of DR (risk ratio (RR) 0.86; 95% confidence interval (CI) 0.60 to 1.25; 1 study, 1012 participants; moderate-certainty evidence) in a population with and without overt retinopathy at baseline. Those without overt retinopathy at baseline showed little or no progression (RR 1.00, 95% CI 0.68 to 1.47; 1 study, 804 participants); those with overt retinopathy at baseline found that their DR progressed slowly (RR 0.21, 95% CI 0.06 to 0.71; 1 study, 208 people; test for interaction P = 0.02). Compared to placebo or observation, fenofibrate likely resulted in little to no difference in either the incidence of overt retinopathy (RR 0.91; 95% CI 0.76 to 1.09; 2 studies, 1631 participants; moderate-certainty evidence); or the incidence of diabetic macular oedema (RR 0.39; 95% CI 0.12 to 1.24; 1 study, 1012 participants; moderate-certainty evidence). The use of fenofibrate increased severe adverse effects (RR 1.55; 95% CI 1.05 to 2.27; 2 studies, 15,313 participants; high-certainty evidence). The studies did not report on incidence of a reduction in visual acuity of 10 ETDRS letters or more, incidence of proliferative diabetic retinopathy, or mean vision-related quality of life.
AUTHORS' CONCLUSIONS
Current, moderate-certainty evidence suggests that in a mixed group of people with and without overt retinopathy, who live with T2D, fenofibrate likely results in little to no difference in progression of diabetic retinopathy. However, in people with overt retinopathy who live with T2D, fenofibrate likely reduces the progression. Serious adverse events were rare, but the risk of their occurrence was increased by the use of fenofibrate. There is no evidence on the effect of fenofibrate in people with T1D. More studies, with larger sample sizes, and participants with T1D are needed. They should measure outcomes that are important to people with diabetes, e.g. change in vision, reduction in visual acuity of 10 ETDRS letters or more, developing proliferative diabetic retinopathy; and evaluating the requirement of other treatments, e.g. injections of anti-vascular endothelial growth factor therapies, steroids.
Topics: Humans; Diabetic Retinopathy; Fenofibrate; Macular Edema; Diabetes Mellitus, Type 1; Retinal Diseases; Diabetes Mellitus, Type 2
PubMed: 37310870
DOI: 10.1002/14651858.CD013318.pub2 -
Current Problems in Cardiology May 2023Monkeypox virus has emerged in different parts of the world with varying clinical symptoms and outcomes. To date, only a few studies have reported cardiac manifestations... (Review)
Review
Monkeypox virus has emerged in different parts of the world with varying clinical symptoms and outcomes. To date, only a few studies have reported cardiac manifestations among monkeypox-infected patients. We aim to systematically evaluate the symptoms, imaging findings, management, and outcomes among monkeypox-induced myocarditis patients. We conducted a systematic literature search in PubMed, Embase, and Scopus from inception till 5th January 2023 by using predefined MESH terms and "AND" and "OR." The following search terms were used: "monkeypox virus" AND "myocarditis." A total of 6 studies with 9 monkeypox-induced myocarditis patients were included in this analysis. The mean age of patients was 33.6 years, with all being male patients. The most common symptoms were fever (89%) and chest pain (100%). Electrocardiogram findings showed 44% of patients had ST-elevation, and 22% had sinus tachycardia. The echocardiographic findings show a mean ejection fraction of 52.14%, while 57% of patients had preserved ejection fraction, and 67% had normal wall motion. Cardiac magnetic resonance findings show 40% of patients had late gadolinium enhancement, and 40% had edema. Management of patients was primarily supportive (33%), and 33% of patients were administered Beta blockers and ACE inhibitors. Overall all patients survived with a good prognosis. Our study's findings show that all cases were reported among male patients with the most common symptoms of chest pain. The overall prognosis was good, with no mortality reported. Infected patients complaining of chest pain should not be ignored, and proper investigation of myocarditis must be considered.
Topics: Humans; Male; Adult; Female; Myocarditis; Contrast Media; Mpox (monkeypox); Gadolinium; Chest Pain
PubMed: 36716982
DOI: 10.1016/j.cpcardiol.2023.101611 -
JACC. Cardiovascular Imaging Nov 2023Quantification of pulmonary edema and congestion is important to guide diagnosis and risk stratification, and to objectively evaluate new therapies in heart failure.... (Review)
Review
Quantification of pulmonary edema and congestion is important to guide diagnosis and risk stratification, and to objectively evaluate new therapies in heart failure. Herein, we review the validation, diagnostic performance, and clinical utility of noninvasive imaging modalities in this setting, including chest x-ray, lung ultrasound (LUS), computed tomography (CT), nuclear medicine imaging methods (positron emission tomography [PET], single photon emission CT), and magnetic resonance imaging (MRI). LUS is a clinically useful bedside modality, and fully quantitative methods (CT, MRI, PET) are likely to be important contributors to a more accurate and precise evaluation of new heart failure therapies and for clinical use in conjunction with cardiac imaging. There are only a limited number of studies evaluating pulmonary congestion during stress. Taken together, noninvasive imaging of pulmonary congestion provides utility for both clinical and research assessment, and continued refinement of methodologic accuracy, validation, and workflow has the potential to increase broader clinical adoption.
Topics: Humans; Pulmonary Edema; Predictive Value of Tests; Lung; Ultrasonography; Heart Failure
PubMed: 37632500
DOI: 10.1016/j.jcmg.2023.06.023 -
Nutrients Nov 2022Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. The evidence connecting dietary intake and DR is emerging, but uncertain. We... (Review)
Review
Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. The evidence connecting dietary intake and DR is emerging, but uncertain. We conducted a systematic review to comprehensively summarize the current understanding of the associations between dietary consumption, DR and diabetic macular edema (DME). We systematically searched PubMed, Embase, Medline, and the Cochrane Central Register of Controlled Trials between January 1967 to May 2022 for all studies investigating the effect of diet on DR and DME. Of the 4962 articles initially identified, 54 relevant articles were retained. Our review found that higher intakes of fruits, vegetables, dietary fibers, fish, a Mediterranean diet, oleic acid, and tea were found to have a protective effect against DR. Conversely, high intakes of diet soda, caloric intake, rice, and choline were associated with a higher risk of DR. No association was seen between vitamin C, riboflavin, vitamin D, and milk and DR. Only one study in our review assessed dietary intake and DME and found a risk of high sodium intake for DME progression. Therefore, the general recommendation for nutritional counseling to manage diabetes may be beneficial to prevent DR risk, but prospective studies in diverse diabetic populations are needed to confirm our findings and expand clinical guidelines for DR management.
Topics: Humans; Diabetic Retinopathy; Macular Edema; Prospective Studies; Risk Factors; Diet, Mediterranean; Eating; Diabetes Mellitus
PubMed: 36501054
DOI: 10.3390/nu14235021 -
Diabetology & Metabolic Syndrome 2019Evidence from observational studies have found a relationship between serum cholesterol and diabetic retinopathy (DR). Apart of the assumption that cholesterolemic... (Review)
Review
Evidence from observational studies have found a relationship between serum cholesterol and diabetic retinopathy (DR). Apart of the assumption that cholesterolemic control has benefits for patients with diabetes with or without retinopathy, the effects of lipid-lowering drugs have not been properly mapped and critically assessed so far. The objective of this study was to evaluate the effects of statins and/or fibrates on prevention and progression of DR. We conducted a Systematic review of randomized controlled trials (RCTs) following the Cochrane Handbook for Systematic Reviews of Interventions and reported in accordance to PRISMA Statement. GRADE approach was used to summarize the certainty of the evidence. Eight RCTs that fulfilled our eligibility criteria were included, assessing the effects of fibrates (n = 4), statins (n = 3) and fibrate plus statins (n = 1) for therapy (n = 8) or prevention (n = 4) of DR. Overall, the main concern regarding risk of bias assessment was due to incomplete outcome data because high rate of losses in five RCTs. Furthermore, the risk of reporting bias was rated unclear due the lack of previously published protocol in seven RCTs. Fibrates seemed to be associated with a 45% risk reduction of macular edema incidence (Relative Risk 0.55, 95% confidence interval of 0.38 to 0.81, 1309 participants, 2 RCTs, I = 0%, low certainty of the evidence). The certainty of evidence for other outcomes was also very low or low, and we are uncertain regarding the effects of fibrates for DR. Overall, adverse events seemed to be similar between fibrate and placebo, but again based on the width of the confidence intervals, an important increase of adverse events cannot be rule out. The combination statin/fibrate did not seem to have benefit for visual acuity but is likely that further studies can modify this estimate since the current evidence is limited. Adverse events and quality of life were not measured or reported. Concluding, this study found eight RCTs, with limited methodological quality, that assessed the effects of fibrates and/or statins for DR. Based on these findings, we are uncertain about the effects of statins for DR. Fibrates seemed to reduce the incidence of macular edema (low certainty evidence) without increase adverse events (low to very low certainty evidence). PROSPERO CRD42016029746.
PubMed: 31719846
DOI: 10.1186/s13098-019-0488-9 -
Cureus Apr 2023COVID-19 vaccination has significantly reduced both the morbidity and mortality rates associated with SARS-CoV-2 infection. Vaccines, especially mRNA vaccines, have been... (Review)
Review
COVID-19 vaccination has significantly reduced both the morbidity and mortality rates associated with SARS-CoV-2 infection. Vaccines, especially mRNA vaccines, have been proposed in several studies to complicate viral myocarditis. Thus, our systematic and meta-analysis review aims to further investigate the possibility of an association between COVID-19 vaccines and myocarditis. We systematically searched PubMed, Web of Science, Scopus, Ovid, and Google Scholar and did a gray search of other databases using the following keywords and terms: "Myocarditis ("Myocarditis" Mesh) OR "Chagas Cardiomyopathy" Mesh) AND "COVID-19 Vaccines" Mesh. The studies were limited to only English articles that reported myocardial inflammation or myocarditis associated with COVID-19 vaccines. Pooled risk ratio with its 95% confidence interval was analyzed by RevMan software (5.4) to perform the meta-analysis. Our study included 671 patients from 44 studies with a mean age of 14-40 years. Nevertheless, myocarditis was noted in a mean of (3.227) days, and 4.19 per million vaccination recipients experienced myocarditis. Most cases were clinically presented with manifestations of cough, chest pain, and fever. Laboratory tests revealed increased C-reactive protein, and troponin with all other cardiac markers in most patients. Cardiac magnetic resonance imaging (MRI) revealed late gadolinium enhancement with myocardial edema and cardiomegaly. Also, electrocardiograms revealed ST-segment elevation in most patients. Furthermore, the incidence of myocarditis was statistically significantly lower in the COVID-19 vaccine group as compared with the control group (RR = 0.15, 95% CI = 0.10-0.23, p-value < 0.00001). No significant association was found between COVID-19 vaccines and the incidence of myocarditis. The study's findings highlight the importance of implementing evidence-based COVID-19 prevention strategies, such as vaccination, to reduce the public health impact of COVID-19 and its associated complications.
PubMed: 37223162
DOI: 10.7759/cureus.37999