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GeroScience Feb 2024Balancing stroke prevention and risk of bleeding in patients with atrial fibrillation (AF) is challenging. Direct oral anticoagulants (DOACs) are by now considered... (Meta-Analysis)
Meta-Analysis
Safety outcomes of direct oral anticoagulants in older adults with atrial fibrillation: a systematic review and meta-analysis of (subgroup analyses from) randomized controlled trials.
Balancing stroke prevention and risk of bleeding in patients with atrial fibrillation (AF) is challenging. Direct oral anticoagulants (DOACs) are by now considered standard of care for treating patients with AF in international guidelines. Our objective was to assess the safety of long-term intake of DOACs in older adults with AF. We included RCTs in elderly (≥ 65 years) patients with AF. A systematic search in MEDLINE and EMBASE was performed on 19 April 2022. For determination of risk of bias, the RoB 2 tool was applied. We pooled outcomes using random-effects meta-analyses. The quality of evidence was assessed using GRADE. Eleven RCTs with a total of 63,374 patients were identified. Two RCTs compared apixaban with either warfarin or aspirin, four edoxaban with either placebo, aspirin, or vitamin K antagonists (VKAs), two dabigatran with warfarin and three rivaroxaban with warfarin. DOACs probably reduce mortality in elderly patients with AF (HR 0.89 95%CI 0.77 to 1.02). Low-dose DOACs likely reduce bleeding compared to VKAs (HR ranged from 0.47 to 1.01). For high-dose DOACS the risk of bleeding varied widely (HR ranged from 0.80 to 1.40). We found that low-dose DOACs probably decrease mortality in AF patients. Moreover, apixaban and probably edoxaban are associated with fewer major or clinically relevant bleeding (MCRB) events compared to VKAs. For dabigatran and rivaroxaban, the risk of MCRB varies depending on dose. Moreover, subgroup analyses indicate that in the very old (≥ 85) the risk for MCRB events might be increased when using DOACs.Registration: PROSPERO: CRD42020187876.
Topics: Humans; Aged; Atrial Fibrillation; Warfarin; Rivaroxaban; Dabigatran; Randomized Controlled Trials as Topic; Anticoagulants; Hemorrhage; Aspirin; Pyridines; Thiazoles
PubMed: 37261677
DOI: 10.1007/s11357-023-00825-2 -
Pharmaceutics Oct 2023The clinical outcomes of antiretroviral drugs may be modified through drug interactions; thus, it is important to update the drug interactions in people living with HIV... (Review)
Review
BACKGROUND
The clinical outcomes of antiretroviral drugs may be modified through drug interactions; thus, it is important to update the drug interactions in people living with HIV (PLHIV).
AIM
To update clinically relevant drug interactions in PLHIV on antiretroviral therapy with novel drug interactions published from 2017 to 2022.
METHODS
A systematic review in Medline/PubMed database from July 2017 to December 2022 using the Mesh terms antiretroviral agents and drug interactions or herb-drug interactions or food-drug interactions. Publications with drug interactions in humans, in English or Spanish, and with full-text access were retrieved. The clinical relevance of drug interactions was grouped into five levels according to the gravity and probability of occurrence.
RESULTS
A total of 366 articles were identified, with 219 (including 87 citation lists) were included, which allowed for the identification of 471 drug interaction pairs; among them, 291 were systematically reported for the first time. In total 42 (14.4%) and 137 (47.1%) were level one and two, respectively, and 233 (80.1%) pairs were explained with the pharmacokinetic mechanism. Among these 291 pairs, protease inhibitors (PIs) and ritonavir/cobicistat-boosted PIs, as well as integrase strand transfer inhibitors (InSTIs), with 70 (24.1%) and 65 (22.3%) drug interaction pairs of levels one and two, respectively, were more frequent.
CONCLUSIONS
In PLHIV on antiretroviral therapy, we identify 291 drug interaction pairs systematically reported for the first time, with 179 (61.5%) being assessed as clinically relevant (levels one and two). The pharmacokinetic mechanism was the most frequently identified. PIs, ritonavir/cobicistat-boosted PIs, and InSTIs were the antiretroviral groups with the highest number of clinically relevant drug interaction pairs (levels one and two).
PubMed: 37896248
DOI: 10.3390/pharmaceutics15102488 -
Alternative Therapies in Health and... Apr 2024Heart failure with preserved ejection fraction (HFpEF) is a prevalent and clinically significant condition characterized by limited treatment options. In this context,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Heart failure with preserved ejection fraction (HFpEF) is a prevalent and clinically significant condition characterized by limited treatment options. In this context, the objective of this meta-analysis is to evaluate the effectiveness of sacubitril/valsartan compared to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in managing HFpEF.
METHODS
A systematic search of relevant studies was conducted in PubMed, Embase, Web of Science, and Cochrane Library. Randomized controlled trials comparing sacubitril/valsartan to ACEIs or ARBs in HFpEF patients were included. Inclusion criteria: LVEF>45%, NYHA II-IV, Sac/Val vs ACEI/ARB, RCTs, treatment duration >3 months, sample size ≥25 per group. Exclusion criteria: Animal studies, unclear/missing data, poor quality, case studies/expert opinions.Hospitalization for heart failure and cardiovascular mortality were the primary outcomes, while the additional results included mortality from all causes, improvement of NYHA class, modifications in NT-proBNP, and with LVEF.
RESULTS
Sacubitril/valsartan substantially reduced heart failure hospitalization rates compared to ACEIs and ARBs, according to a total of six studies involving 5,201 participants (Relative Risk, 0.78; 95% CI, 0.65 to 0.85; P = .001). Nonetheless, there were no significant improvements in mortality due to cardiovascular disease (Relative Risk, 0.94; 95% CI, 0.79-1.12; P = .563). Sacubitril/valsartan did not affect total mortality from all causes significantly (Relative Risk, 0.95; 95% CI, 0.84-1.09; P = .453), but it did enhance NYHA classification (Relative Risk, 1.25; 95% CI, 1.10-1.43; P = .001). NT-proBNP levels decreased substantially (Weighted Mean Difference, -266.67; 95% CI, -525.86 to -7.47), whereas there had been little major shift in LVEF (Weighted Mean Difference, 1.49; 95% CI, -1.33 to 4.21; P = .342).
CONCLUSIONS
Sacubitril/valsartan may provide superior benefits in reducing heart failure hospitalization rates, NT-proBNP levels, and improving NYHA classification in patients with HFpEF compared to ACEIs and ARBs. Sacubitril/valsartan might be considered as a preferred treatment option for HFpEF patients due to its benefits in reducing heart failure hospitalization rates and improving symptom severity.
Topics: Humans; Valsartan; Heart Failure; Biphenyl Compounds; Aminobutyrates; Drug Combinations; Stroke Volume; Angiotensin Receptor Antagonists; Tetrazoles; Aged; Angiotensin-Converting Enzyme Inhibitors
PubMed: 37917889
DOI: No ID Found -
Archives of Gerontology and Geriatrics Nov 2023The risk-to-benefit ratio of cardioprotective medications in frail older adults is uncertain. The objective was to systematically review prescribing of... (Review)
Review
AIMS
The risk-to-benefit ratio of cardioprotective medications in frail older adults is uncertain. The objective was to systematically review prescribing of guideline-recommended cardioprotective medications following myocardial infarction (MI) in people who are frail.
DATA SOURCES
Ovid Medline, PubMed and Cochrane were searched from inception to October 2022 for studies that reported prescribing of one or more cardioprotective medication classes post-MI or acute coronary syndromes in people with frailty.
STUDY SELECTION
We included observational studies that reported prescribing of cardioprotective medications post-MI stratified by frailty status.
RESULTS
Overall, 16 cohort studies published from 2013 to 2022 that used seven different frailty scales were included. Prescribing of all cardioprotective medication classes following MI was lower in frail compared to non-frail people, with absolute rates of prescribing varying substantially across studies. Median prescribing in frail and non-frail people, respectively, was 88.9% (IQR 81.5-96.2) and 93.1% (IQR 92.0-98.9) for aspirin; 68.1% (IQR 61.9-91.2) and 86.7% (IQR 79.5-92.8) for P2Y12-inhibitors; 83.1% (IQR 76.9-91.3) and 94.0% (IQR 87.1-95.9) for lipid-lowering therapy; 67.9% (IQR 60.6-74.0) and 74.7% (IQR 71.3-84.5) for angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers; and 74.1% (IQR 69.2-79) and 77.6% (IQR 71.8-85.9) for beta-blockers.
CONCLUSION
People who were frail were less likely to be prescribed guideline recommended medication classes post-MI than those who were non-frail. Further research is needed into treatment benefits and risks in frail people to avoid unnecessarily withholding treatment in this high-risk population, while also minimising potential for medication related harm.
Topics: Humans; Aged; Frailty; Myocardial Infarction; Acute Coronary Syndrome; Angiotensin-Converting Enzyme Inhibitors; Risk Factors
PubMed: 37356114
DOI: 10.1016/j.archger.2023.105106 -
BMC Infectious Diseases Jan 2024There is no systematic review on the prevalence of HIV drug resistance (HIVDR) in Iran. We aimed to estimate the prevalence of HIVDR among people living with HIV (PLHIV)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is no systematic review on the prevalence of HIV drug resistance (HIVDR) in Iran. We aimed to estimate the prevalence of HIVDR among people living with HIV (PLHIV) in Iran. We assessed HIVDR prevalence in antiretroviral therapy (ART) naïve PLHIV (i.e., those without a history of ART) and PLHIV receiving ART.
METHOD
We systematically searched Scopus, PubMed, Web of Science, Embase, Iranian databases (Iranian Medical Research Information System, Magiran, and Scientific Information Database), the references of studies, and Google Scholar until March 2023. A random-effects model was used to calculate a point estimate and 95% confidence interval (95% CI) for the prevalence of HIVDR in PLHIV.
RESULTS
Among 461 potential publications, 22 studies were included in the meta-analysis. The pooled prevalence of acquired HIVDR in PLHIV receiving ART was 34% (95% CI: 19, 50) for nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), 27% (95% CI: 15, 41) for non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 9% (95% CI: 3, 18) for protease inhibitors (PIs). The pooled prevalence of acquired HIVDR in treatment failure PLHIV was 50% (95% CI: 31, 69) for NRTIs, 49% (95% CI: 29, 69) for NNRTIs, 11% (95% CI: 2, 24) for PIs, and 1% (95% CI: 0, 4) for integrase inhibitors (INIs). The pooled prevalence of transmitted HIVDR in ART-naïve people was 3% (95% CI; 1, 6) for NRTIs, 5% (95% CI: 2, 9) for NNRTIs, and 0 for PIs and INIs.
CONCLUSION
The prevalence of HIVDR was relatively high in both ART-naïve PLHIV and those receiving ART. Without universal pretreatment HIVDR testing and more frequent routine HIV viral load testing among PLHIV who are on ART, the HIVDR prevalence might increase in PLHIV in Iran.
Topics: Humans; Iran; Reverse Transcriptase Inhibitors; Prevalence; HIV-1; Drug Resistance, Viral; HIV Infections; Anti-HIV Agents; Mutation
PubMed: 38166733
DOI: 10.1186/s12879-023-08916-3 -
Renal Failure Dec 2024To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by... (Meta-Analysis)
Meta-Analysis
Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis.
OBJECTIVE
To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis.
METHODS
PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software.
RESULTS
A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59-5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (β-MG). Importantly, the sensitivity analysis confirmed the study's stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or β-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias.
CONCLUSIONS
The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.
Topics: Humans; Diabetic Nephropathies; Angiotensin-Converting Enzyme Inhibitors; Renin-Angiotensin System; Drug Therapy, Combination; Angiotensin Receptor Antagonists; Astragalus Plant; Randomized Controlled Trials as Topic; Drugs, Chinese Herbal; Treatment Outcome; Creatinine; Glycated Hemoglobin; Proteinuria
PubMed: 38836372
DOI: 10.1080/0886022X.2024.2359033 -
PloS One 2024Due to the inconsistent findings from various studies, the role of gene polymorphisms in the renin-angiotensin system in influencing the development of cardiomyopathy... (Meta-Analysis)
Meta-Analysis
Due to the inconsistent findings from various studies, the role of gene polymorphisms in the renin-angiotensin system in influencing the development of cardiomyopathy remains unclear. In this study, we conducted a systematic review and meta-analysis to summarize the findings regarding the impact of angiotensin converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T, and angiotensin II Type 1 receptor (AGTR1) A1166C gene polymorphisms in patients with cardiomyopathy. We performed a comprehensive search of several electronic databases, including PubMed, Embase, the Cochrane Library, and Web of Science, covering articles published from the time of database creation to April 17, 2023. Studies on the assessment of genetic polymorphisms in genes related to the renin-angiotensin system in relation to cardiomyopathy were included. The primary outcome was cardiomyopathy. Risk of bias was assessed using the Newcastle-Ottawa Scale scale. The meta-analysis includes 19 studies with 4,052 cases and 5,592 controls. The ACE I/D polymorphisms were found to be associated with cardiomyopathy (allelic model D vs I: OR = 1.29, 95CI% = 1.08-1.52; dominant model DD+ID vs II: OR = 1.43, 95CI% = 1.01-2.02; recessive model DD vs ID+II: OR = 0.79, 95CI% = 0.64-0.98). AGT M235T polymorphism and cardiomyopathy were not significantly correlated (allelic model T vs M: OR = 1.26, 95CI% = 0.96-1.66; dominant model TT+MT vs MM: OR = 1.30, 95CI% = 0.98-1.73; recessive model TT vs MT+MM: OR = 0.63, 95CI% = 0.37-1.07). AGTR1 polymorphism and cardiomyopathy were not significantly associated under allelic model A vs C (OR = 0.69, 95CI% = 0.46-1.03) and recessive model AA vs CA+CC (OR = 0.89, 95CI% = 0.34-2.30), but under the dominant model AA+CA vs CC (OR = 0.51, 95CI% = 0.38-0.68). The current meta-analysis reveals that polymorphisms in ACE I/D may be a genetic risk factor for cardiomyopathy. There is an association between AGTR1 gene polymorphisms and risk of cardiomyopathy under the specific model.
Topics: Humans; Renin-Angiotensin System; Risk Factors; Polymorphism, Genetic; Peptidyl-Dipeptidase A; Angiotensinogen; Cardiomyopathies; Receptor, Angiotensin, Type 1
PubMed: 38166133
DOI: 10.1371/journal.pone.0295626 -
Environmental Science and Pollution... Jan 2024This study presents a systematic review of the scientific and technological production related to the use of systems based on UV, HO, and Cl for the elimination of... (Review)
Review
Systematic analysis of the scientific-technological production on the use of the UV, HO, and/or Cl systems in the elimination of bacteria and associated antibiotic resistance genes.
This study presents a systematic review of the scientific and technological production related to the use of systems based on UV, HO, and Cl for the elimination of antibiotic-resistant bacteria (ARB) and genes associated with antibiotic resistance (ARGs). Using the Pro Know-C (Knowledge Development Process-Constructivist) methodology, a portfolio was created and analyzed that includes 19 articles and 18 patents published between 2011 and 2022. The results show a greater scientific-technological production in UV irradiation systems (8 articles and 5 patents) and the binary combination UV/HO (9 articles and 4 patents). It was emphasized that UV irradiation alone focuses mainly on the removal of ARB, while the addition of HO or Cl, either individually or in binary combinations with UV, enhances the removal of ARB and ARG. The need for further research on the UV/HO/Cl system is emphasized, as gaps in the scientific-technological production of this system (0 articles and 2 patents), especially in its electrochemically assisted implementation, have been identified. Despite the gaps identified, there are promising prospects for the use of combined electrochemically assisted UV/HO/Cl disinfection systems. This is demonstrated by the effective removal of a wide range of contaminants, including ARB, fungi, and viruses, as well as microorganisms resistant to conventional disinfectants, while reducing the formation of toxic by-products.
Topics: Hydrogen Peroxide; Angiotensin Receptor Antagonists; Water Purification; Chlorine; Angiotensin-Converting Enzyme Inhibitors; Drug Resistance, Microbial; Bacteria; Disinfection; Ultraviolet Rays
PubMed: 38165540
DOI: 10.1007/s11356-023-31435-2 -
Orphanet Journal of Rare Diseases Feb 2024Alpha 1 Antitrypsin Deficiency (AATD) is a largely underrecognized genetic condition characterized by low Alpha 1 Antitrypsin (AAT) serum levels, resulting from... (Review)
Review
BACKGROUND
Alpha 1 Antitrypsin Deficiency (AATD) is a largely underrecognized genetic condition characterized by low Alpha 1 Antitrypsin (AAT) serum levels, resulting from variations in SERPINA1. Many individuals affected by AATD are thought to be undiagnosed, leading to poor patient outcomes. The Z (c.1096G > A; p.Glu366Lys) and S (c.863A > T; p.Glu288Val) deficiency variants are the most frequently found variants in AATD, with the Z variant present in most individuals diagnosed with AATD. However, there are many other less frequent variants known to contribute to lung and/or liver disease in AATD. To identify the most common rare variants associated with AATD, we conducted a systematic literature review with the aim of assessing AATD variation patterns across the world.
METHODS
A systematic literature search was performed to identify published studies reporting AATD/SERPINA1 variants. Study eligibility was assessed for the potential to contain relevant information, with quality assessment and data extraction performed on studies meeting all eligibility criteria. AATD variants were grouped by variant type and linked to the geographical region identified from the reporting article.
RESULTS
Of the 4945 articles identified by the search string, 864 contained useful information for this study. Most articles came from the United States, followed by the United Kingdom, Germany, Spain, and Italy. Collectively, the articles identified a total of 7631 rare variants and 216 types of rare variant across 80 counties. The F (c.739C > T; p.Arg247Cys) variant was identified 1,281 times and was the most reported known rare variant worldwide, followed by the I (c.187C > T; p.Arg63Cys) variant. Worldwide, there were 1492 Null/rare variants that were unidentified at the time of source article publication and 75 rare novel variants reported only once.
CONCLUSION
AATD goes far beyond the Z and S variants, suggesting there may be widespread underdiagnosis of patients with the condition. Each geographical region has its own distinctive variety of AATD variants and, therefore, comprehensive testing is needed to fully understand the true number and type of variants that exist. Comprehensive testing is also needed to ensure accurate diagnosis, optimize treatment strategies, and improve outcomes for patients with AATD.
Topics: Humans; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; Germany; Italy; Lung; Spain
PubMed: 38388492
DOI: 10.1186/s13023-024-03069-1 -
American Journal of Cardiovascular... Jan 2024Elevated circulating cholesterol levels in patients with acute coronary syndrome (ACS) increase morbidity and mortality. Recent studies reported that PCSK9 inhibitors... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Elevated circulating cholesterol levels in patients with acute coronary syndrome (ACS) increase morbidity and mortality. Recent studies reported that PCSK9 inhibitors (PCSK9i) have a beneficial effect on various domains of patients' lipid profiles and cardiovascular and mortality outcomes. Here, we aim to further investigate the efficacy and safety of PCSK9i in patients with ACS or who experienced recent episodes.
METHODS
We comprehensively searched PubMed, Scopus, Web of Science and Cochrane CENTRAL to identify all randomized controlled trials comparing PCSK9i versus placebo. Data were extracted and analysed using Stata/MP version 17.0.
RESULTS
Eleven studies (n = 24,732) were included in this meta-analysis. In terms of efficacy outcomes, compared with the control group, PCSK9i significantly decreased levels of LDL-C, TC, TG, Lp (a) and Apo-B, with the following values, respectively: Cohen's d of - 1.25, 95% confidence interval (CI - 1.64 to - 0.87); Cohen's d of - 1.32, 95% CI (- 1.83 to - 0.81); Cohen's d of - 0.26, 95% CI (- 0.37 to - 0.14); Cohen's d of - 0.70, 95% CI (- 1.15 to - 0.26); and Cohen's d of - 1.46, 95% CI (- 1.97 to - 0.94). The levels of HDL-C and Apo-A1 increased by: Cohen's d 0.27, 95% CI (0.16-0.39) and Cohen's d of 0.30, 95% CI (0.17-0.42), respectively. Regarding safety outcomes, PCSK9i was associated with lower odds of myocardial infarction (MI) and cerebrovascular events with the following values, respectively: OR = 0.87, 95% CI (0.78-0.97) and OR = 0.71, 95% CI (0.52-0.98).
CONCLUSIONS
PCSK9i was associated with better lipid profile and quality of life of patients and can be recommended as an optimal treatment strategy. Further trials should study combinations of PCSK9i with other lipid-lowering drugs.
Topics: Humans; Acute Coronary Syndrome; Anticholesteremic Agents; Cholesterol, LDL; Hypercholesterolemia; PCSK9 Inhibitors; Proprotein Convertase 9; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 38241002
DOI: 10.1007/s40256-023-00621-5