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Journal of the American Heart... Feb 2024There is debate over whether statins increase risk of hemorrhagic stroke, so we assessed current evidence, including data from new statin trials and trials of nonstatin... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is debate over whether statins increase risk of hemorrhagic stroke, so we assessed current evidence, including data from new statin trials and trials of nonstatin low-density lipoprotein-cholesterol (LDL-C)- and triglyceride-lowering therapies.
METHODS AND RESULTS
We performed a systematic review of large randomized clinical trials (≥1000 patients with ≥2 years follow-up) of LDL-C-lowering therapy (statin, ezetimibe, and PCSK-9 [proprotein convertase subtilisin/kexin type 9] inhibitor) and triglyceride-lowering therapy (omega-3 supplements and fibrate) that reported hemorrhagic stroke as an outcome. We searched MEDLINE, Embase, and Cochrane Library up to July 2, 2021 and updated a meta-analysis of cardiovascular statin trials published in 2012. Among our several subgroup analyses, we looked at difference depending on stroke status and also depending on age. We identified 37 trials for LDL-C lowering (284 301 participants) and 11 for triglyceride lowering (120 984 participants). Overall, we found a higher risk of hemorrhagic stroke for LDL-C lowering, risk ratio (RR) 1.16 (95% CI, 1.01-1.32, =0.03). For statins (33 trials, 216 258 participants), RR=1.17 (95% CI, 1.01-1.36); for PCSK-9 inhibitors (2 trials, 46 488 participants), RR=0.86 (95% CI, 0.43-1.74); and for ezetimibe (2 trials, 21 555 participants), RR=1.14 (95% CI, 0.64-2.03). In statin trials of patients with previous stroke/transient ischemic attack, RR was 1.46 (95% CI, 1.05-2.04), and in trials with mean age ≥65 years old, RR=1.34 (95% CI, 1.04-1.73) (=0.14 and =0.23 respectively); for triglyceride lowering (11 trials, 120 984 participants), RR=1.05 (95% CI, 0.86-1.30).
CONCLUSIONS
We found evidence for a small increased risk of hemorrhagic stroke events with LDL-C-lowering therapies but no clear evidence for triglyceride-lowering therapies.
REGISTRATION
URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42021275363.
Topics: Humans; Aged; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Anticholesteremic Agents; Cholesterol, LDL; Hemorrhagic Stroke; Cardiovascular Diseases; Randomized Controlled Trials as Topic; Ezetimibe; Stroke; Triglycerides
PubMed: 38323514
DOI: 10.1161/JAHA.123.030714 -
BMC Medicine Jul 2021Light-to-moderate alcohol consumption has been reported to be cardio-protective among apparently healthy individuals; however, it is unclear whether this association is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Light-to-moderate alcohol consumption has been reported to be cardio-protective among apparently healthy individuals; however, it is unclear whether this association is also present in those with disease. To examine the association between alcohol consumption and prognosis in individuals with pre-existing cardiovascular disease (CVD), we conducted a series of meta-analyses of new findings from three large-scale cohorts and existing published studies.
METHODS
We assessed alcohol consumption in relation to all-cause mortality, cardiovascular mortality, and subsequent cardiovascular events via de novo analyses of 14,386 patients with a previous myocardial infarction, angina, or stroke in the UK Biobank Study (median follow-up 8.7 years, interquartile range [IQR] 8.0-9.5), involving 1640 deaths and 2950 subsequent events, and 2802 patients and 1257 deaths in 15 waves of the Health Survey for England 1994-2008 and three waves of the Scottish Health Survey 1995, 1998, and 2003 (median follow-up 9.5 years, IQR 5.7-13.0). This was augmented with findings from 12 published studies identified through a systematic review, providing data on 31,235 patients, 5095 deaths, and 1414 subsequent events. To determine the best-fitting dose-response association between alcohol and each outcome in the combined sample of 48,423 patients, models were constructed using fractional polynomial regression, adjusting at least for age, sex, and smoking status.
RESULTS
Alcohol consumption was associated with all assessed outcomes in a J-shaped manner relative to current non-drinkers, with a risk reduction that peaked at 7 g/day (relative risk 0.79, 95% confidence interval 0.73-0.85) for all-cause mortality, 8 g/day (0.73, 0.64-0.83) for cardiovascular mortality and 6 g/day (0.50, 0.26-0.96) for cardiovascular events, and remained significant up to 62, 50, and 15 g/day, respectively. No statistically significant elevated risks were found at higher levels of drinking. In the few studies that excluded former drinkers from the non-drinking reference group, reductions in risk among light-to-moderate drinkers were attenuated.
CONCLUSIONS
For secondary prevention of CVD, current drinkers may not need to stop drinking. However, they should be informed that the lowest risk of mortality and having another cardiovascular event is likely to be associated with lower levels of drinking, that is up to approximately 105g (or equivalent to 13 UK units, with one unit equal to half a pint of beer/lager/cider, half a glass of wine, or one measure of spirits) a week.
Topics: Alcohol Drinking; Cardiovascular Diseases; Female; Health Surveys; Humans; Male; Morbidity; Myocardial Infarction
PubMed: 34311738
DOI: 10.1186/s12916-021-02040-2 -
JAMA Network Open Nov 2021The currently recommended method for screening for retinopathy of prematurity (ROP) is binocular indirect ophthalmoscopy, which requires frequent eye examinations... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The currently recommended method for screening for retinopathy of prematurity (ROP) is binocular indirect ophthalmoscopy, which requires frequent eye examinations entailing a heavy clinical workload. Weight gain-based algorithms have the potential to minimize the need for binocular indirect ophthalmoscopy and have been evaluated in different setups with variable results to predict type 1 or severe ROP.
OBJECTIVE
To synthesize evidence regarding the ability of postnatal weight gain-based algorithms to predict type 1 or severe ROP.
DATA SOURCES
PubMed, MEDLINE, Embase, and the Cochrane Library databases were searched to identify studies published between January 2000 and August 2021.
STUDY SELECTION
Prospective and retrospective studies evaluating the ability of these algorithms to predict type 1 or severe ROP were included.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data. This meta-analysis was performed according to the Cochrane guidelines and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines.
MAIN OUTCOMES AND MEASURES
Ability of algorithms to predict type 1 or sever ROP was measured using statistical indices (pooled sensitivity, specificity, and summary area under the receiver operating characteristic curves, as well as pooled negative likelihood ratios and positive likelihood ratios and diagnostic odds ratios).
RESULTS
A total of 61 studies (>37 000 infants) were included in the meta-analysis. The pooled estimates for sensitivity and specificity, respectively, were 0.89 (95% CI, 0.85-0.92) and 0.57 (95% CI, 0.51-0.63) for WINROP (Weight, IGF-1 [insulinlike growth factor 1], Neonatal, ROP), 1.00 (95% CI, 0.88-1.00) and 0.60 (95% CI, 0.15-0.93) for G-ROP (Postnatal Growth and ROP), 0.95 (95% CI, 0.71-0.99) and 0.52 (95% CI, 0.36-0.68) for CHOP ROP (Children's Hospital of Philadelphia ROP), 0.99 (95% CI, 0.73-1.00) and 0.49 (95% CI, 0.03-0.74) for ROPScore, 0.98 (95% CI, 0.94-0.99) and 0.35 (95% CI, 0.22-0.51) for CO-ROP (Colorado ROP). The original PINT (Premature Infants in Need of Transfusion) ROP study reported a sensitivity of 0.98 (95% CI, 0.91-0.99) and a specificity of 0.36 (95% CI, 0.30-0.42). The pooled negative likelihood ratios were 0.19 (95% CI, 0.13-0.27) for WINROP, 0.0 (95% CI, 0.00-0.32) for G-ROP, 0.10 (95% CI, 0.02-0.53) for CHOP ROP, 0.03 (95% CI, 0.00-0.77) for ROPScore, and 0.07 (95% CI, 0.03-0.16) for CO-ROP. The pooled positive likelihood ratios were 2.1 (95% CI, 1.8-2.4) for WINROP, 2.5 (95% CI, 0.7-9.1) for G-ROP, 2.0 (95% CI, 1.5-2.6) for CHOP ROP, 1.9 (95% CI, 1.1-3.3) for ROPScore, and 1.5 (95% CI, 1.2-1.9) for CO-ROP.
CONCLUSIONS AND RELEVANCE
This study suggests that weight gain-based algorithms have adequate sensitivity and negative likelihood ratios to provide reasonable certainty in ruling out type 1 ROP or severe ROP. Given the implications of missing even a single case of severe ROP, algorithms with very high sensitivity (close to 100%) and low negative likelihood ratios (close to zero) need to be chosen to safely reduce the number of unnecessary examinations in infants at lower risk of severe ROP.
Topics: Algorithms; Birth Weight; Early Diagnosis; Female; Forecasting; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Neonatal Screening; Philadelphia; Prognosis; Prospective Studies; Retinopathy of Prematurity; Retrospective Studies; Risk Assessment; Risk Factors; Sensitivity and Specificity; Weight Gain
PubMed: 34812847
DOI: 10.1001/jamanetworkopen.2021.35879 -
European Heart Journal. Cardiovascular... Apr 2021Safety and efficacy of antithrombotic regimens in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) may differ based on clinical... (Meta-Analysis)
Meta-Analysis
Safety and efficacy of double vs. triple antithrombotic therapy in patients with atrial fibrillation with or without acute coronary syndrome undergoing percutaneous coronary intervention: a collaborative meta-analysis of non-vitamin K antagonist oral anticoagulant-based randomized clinical trials.
AIMS
Safety and efficacy of antithrombotic regimens in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) may differ based on clinical presentation. We sought to compare double vs. triple antithrombotic therapy (DAT vs. TAT) in AF patients with or without acute coronary syndrome (ACS) undergoing PCI.
METHODS AND RESULTS
A systematic review and meta-analysis was performed using PubMed to search for non-vitamin K antagonist oral anticoagulant (NOAC)-based randomized clinical trials. Data on subgroups of ACS or elective PCI were obtained by published reports or trial investigators. A total of 10 193 patients from four NOAC trials were analysed, of whom 5675 presenting with ACS (DAT = 3063 vs. TAT = 2612) and 4518 with stable coronary artery disease (SCAD; DAT = 2421 vs. TAT = 2097). The primary safety endpoint of ISTH major bleeding or clinically relevant non-major bleeding was reduced with DAT compared with TAT in both ACS (12.2% vs. 19.4%; RR 0.63, 95% CI 0.56-0.71; P < 0.0001; I2 = 0%) and SCAD (14.6% vs. 22.0%; RR 0.68, 95% CI 0.55-0.85; P = 0.0008; I2 = 66%), without interaction (P-int = 0.54). Findings were consistent for secondary bleeding endpoints, including intra-cranial haemorrhage. In both subgroups, there was no difference between DAT and TAT for all-cause death, major adverse cardiovascular events, or stroke. Myocardial infarction and stent thrombosis were numerically higher with DAT vs. TAT consistently in ACS and SCAD (P-int = 0.60 and 0.86, respectively). Findings were confirmed by multiple sensitivity analyses, including a separate analysis on dabigatran regimens and a restriction to PCI population.
CONCLUSIONS
DAT, compared with TAT, is associated with lower bleeding risks, including intra-cranial haemorrhage, and a small non-significant excess of cardiac ischaemic events in both patients with or without ACS.
Topics: Acute Coronary Syndrome; Anticoagulants; Atrial Fibrillation; Fibrinolytic Agents; Humans; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic
PubMed: 33119069
DOI: 10.1093/ehjcvp/pvaa116 -
Frontiers in Psychiatry 2021Schizophrenia is a destructive neuropsychiatric disease with a median prevalence of 4.0 per 1,000 during the whole life. Genome-wide association studies have shown the...
Schizophrenia is a destructive neuropsychiatric disease with a median prevalence of 4.0 per 1,000 during the whole life. Genome-wide association studies have shown the role of copy number variants (generally deletions) and certain alleles of common single nucleotide polymorphisms in the pathogenesis of schizophrenia. This disorder predominantly follows the polygenic inheritance model. Schizophrenia has also been linked with various alterations in the transcript and protein content of the brain tissue. Recent studies indicate that alterations in non-coding RNAs (ncRNAs) signature underlie a proportion of this dysregulation. High throughput microarray investigations have demonstrated momentous alterations in the expression of long non-coding RNAs (lncRNA) and microRNAs (miRNAs) in the circulation or post-mortem brain tissues of patients with schizophrenia compared with control samples. While Gomafu, PINT, GAS5, TCONS_l2_00021339, IFNG-AS1, FAS-AS1, PVT1, and TUG1 are among down-regulated lncRNAs in schizophrenia, MEG3, THRIL, HOXA-AS2, Linc-ROR, SPRY4-IT1, UCA1, and MALAT1 have been up-regulated in these patients. Moreover, several miRNAs, such as miR-30e, miR-130b, hsa-miR-130b, miR-193a-3p, hsa-miR-193a-3p, hsa-miR-181b, hsa-miR-34a, hsa-miR-346, and hsa-miR-7 have been shown to be dysregulated in blood or brain samples of patients with schizophrenia. Dysregulation of these transcripts in schizophrenia not only provides insight into the pathogenic processes of this disorder, it also suggests these transcripts could serve as diagnostic markers for schizophrenia. In the present paper, we explore the changes in the expression of miRNAs and lncRNAs in patients with schizophrenia.
PubMed: 34220567
DOI: 10.3389/fpsyt.2021.640463