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Journal of the American Heart... Sep 2022Background Lowering low-density lipoprotein cholesterol (LDL-C) levels decreases major cardiovascular events and is recommended for patients at elevated cardiovascular... (Meta-Analysis)
Meta-Analysis
Network Meta-Analysis of Randomized Trials Evaluating the Comparative Efficacy of Lipid-Lowering Therapies Added to Maximally Tolerated Statins for the Reduction of Low-Density Lipoprotein Cholesterol.
Background Lowering low-density lipoprotein cholesterol (LDL-C) levels decreases major cardiovascular events and is recommended for patients at elevated cardiovascular risk. However, appropriate doses of statin therapy are often insufficient to reduce LDL-C in accordance with current guidelines. In such cases, treatment could be supplemented with nonstatin lipid-lowering therapy. Methods and Results A systematic literature review and network meta-analysis were conducted on randomized controlled trials of nonstatin lipid-lowering therapy added to maximally tolerated statins, including statin-intolerant patients. The primary objective was to assess relative efficacy of nonstatin lipid-lowering therapy in reducing LDL-C levels at week 12. Secondary objectives included the following: LDL-C level reduction at week 24 and change in non-high-density lipoprotein cholesterol and apolipoprotein B at week 12. There were 48 randomized controlled trials included in the primary network meta-analysis. All nonstatin agents significantly reduced LDL-C from baseline versus placebo, regardless of background therapy. At week 12, evolocumab, 140 mg every 2 weeks (Q2W)/420 mg once a month, and alirocumab, 150 mg Q2W, were the most efficacious regimens, followed by alirocumab, 75 mg Q2W, alirocumab, 300 mg once a month, inclisiran, bempedoic acid/ezetimibe fixed-dose combination, and ezetimibe and bempedoic acid used as monotherapies. Primary end point results were generally consistent at week 24, and for other lipid end points at week 12. Conclusions Evolocumab, 140 mg Q2W/420 mg once a month, and alirocumab, 150 mg Q2W, were consistently the most efficacious nonstatin regimens when added to maximally tolerated statins to lower LDL-C, non-high-density lipoprotein cholesterol, and apolipoprotein B levels and facilitate attainment of guideline-recommended risk-stratified lipoprotein levels.
Topics: Anticholesteremic Agents; Apolipoproteins; Cholesterol; Cholesterol, LDL; Dicarboxylic Acids; Double-Blind Method; Ezetimibe; Fatty Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Network Meta-Analysis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36073669
DOI: 10.1161/JAHA.122.025551 -
Emergency Medicine Australasia : EMA Aug 2022Recreational nitrous oxide (N O) use is widespread, and complications associated with its use are increasingly common. We sought to identify risk factors, clinical... (Review)
Review
Recreational nitrous oxide (N O) use is widespread, and complications associated with its use are increasingly common. We sought to identify risk factors, clinical features and outcomes in individuals presenting with effects of chronic N O abuse to develop an approach to clinical assessment and management. A systemic literature review was completed with searches conducted across EMBASE, MEDLINE, PSYCINFO and Cochrane databases. Our search strategy identified 612 studies, 105 met inclusion criteria, and 10 were added via hand search. Subjects from 24 case series and 91 case reports were typically in their 20s, using over 100 bulbs daily for several months. Neurological presentations, including sensory change, gait disturbance or weakness, were characteristic. Serum Vitamin B12 was normal or raised in 133 out of 243 case series subjects and 37 out of 84 reports. Serum homocysteine and methylmalonic acid were usually raised. Macrocytosis and anaemia were not commonly seen. MRI findings were abnormal with dorsal column change where specified, typically involving the cervical spine. Nerve conduction studies mostly reported a sensorimotor polyneuropathy. B12 replacement was the treatment of choice and partial recovery was most reported. This review highlights the dose-dependent nature of chronic N O toxicity and recognises functional B12 deficiency as the cause. As B12 is often normal, homocysteine and methylmalonic acid are important biomarkers of disease. An approach to diagnosis is offered but requires validation in prospective studies. Research exploring B12 and methionine therapy is required to refine management.
Topics: Homocysteine; Humans; Methylmalonic Acid; Nitrous Oxide; Prospective Studies; Vitamin B 12; Vitamin B 12 Deficiency
PubMed: 35695047
DOI: 10.1111/1742-6723.13997 -
Neuropsychological Rehabilitation Sep 2022This study aimed to (1) describe the scope of research related to the Dynamic Comprehensive Model of Awareness (DCMA) (Toglia & Kirk, 2000); (2) identify themes and... (Review)
Review
This study aimed to (1) describe the scope of research related to the Dynamic Comprehensive Model of Awareness (DCMA) (Toglia & Kirk, 2000); (2) identify themes and support for key model postulates; and (3) suggest future research directions related to this model. Using PRISMA scoping guidelines, 366 articles were reviewed, and 54 articles met our inclusion criteria. Selected studies were clustered into three themes: (1) the relationship between general and online self-awareness (50%); (2) interventions based on the model (41%); and (3) factors contributing to self-awareness (9%). Most studies were conducted with participants with acquired brain injury (BI) and traumatic BI (68%), most used a cross-sectional design (50%), and most intervention studies utilized a single-subject design (18%), followed by an experimental design (9%). This review provides evidence for the wide application of the across varying ages and populations. The need for a multidimensional assessment approach is recognized; however, stronger evidence that supports a uniform assessment of online self-awareness is needed. The intervention studies frequently described the importance of direct experience in developing self-awareness; however, few studies compared how intervention methods to influence general versus online self-awareness, or how cognitive capacity, self-efficacy, psychological factors, and context, influence the development of self-awareness.
Topics: Brain Injuries; Brain Injuries, Traumatic; Cross-Sectional Studies; Humans; Maleates; Perception
PubMed: 35583377
DOI: 10.1080/09602011.2022.2075017 -
Multiple Sclerosis and Related Disorders Apr 2022The risk of SARS-CoV-2 infection and severity with disease modifying therapies (DMTs) in multiple sclerosis (MS) remains unclear, with some studies demonstrating...
BACKGROUND
The risk of SARS-CoV-2 infection and severity with disease modifying therapies (DMTs) in multiple sclerosis (MS) remains unclear, with some studies demonstrating increased risks of infection with B-cell-depleting (anti-CD20) therapies and severity, while others fail to observe an association. Most existing studies are limited by a reliance on 'numerator' data (i.e., COVID-19 cases) only.
OBJECTIVE
To assess the risks of COVID-19 by DMT, this study aimed to assess both 'numerator' (patients with SARS-CoV-2 infection) and 'denominator' data (all patients treated with DMTs of interest) to determine if any DMTs impart an increased risk of SARS-CoV-2 infection or disease severity.
METHODS
We systematically reviewed charts and queried patients during clinic encounters in the NYU MS Comprehensive Care Center (MSCCC) for evidence of COVID-19 in all patients who were on the most commonly used DMTs in our clinic (sphingosine-1-phosphate receptor (S1P) modulators (fingolimod/siponimod), rituximab, ocrelizumab, fumarates (dimethyl fumarate/diroximel fumarate), and natalizumab). COVID-19 status was determined by clinical symptoms (CDC case definition) and laboratory testing where available (SARS-CoV-2 PCR, SARS-CoV-2 IgG). Multivariable analyses were conducted to determine predictors of infection and severe disease (hospitalization or death) using SARS-CoV-2 infected individuals per DMT group and all individuals on a given DMT as denominator.
RESULTS
We identified 1,439 MS patients on DMTs of interest, of which 230 had lab-confirmed (n = 173; 75.2%) or suspected (n = 57; 24.8%) COVID-19. Infection was most frequent in those on rituximab (35/138; 25.4%), followed by fumarates (39/217; 18.0%), S1P modulators (43/250; 17.2%), natalizumab (36/245; 14.7%), and ocrelizumab (77/589; 13.1%). There were 14 hospitalizations and 2 deaths. No DMT was found to be significantly associated with increased risk of SARS-CoV-2 infection. Rituximab was a predictor of severe SARS-CoV-2 infection among patients with SARS-CoV-2 infection (OR 6.7; 95% CI 1.1-41.7) but did not reach statistical significance when the entire patient population on DMT was used (OR 2.8; 95% CI 0.6-12.2). No other DMT was associated with an increased risk of severe COVID-19.
CONCLUSIONS
Analysis of COVID-19 risk among all patients on the commonly used DMTs did not demonstrate increased risk of infection with any DMT. Rituximab was associated with increased risk for severe disease.
Topics: COVID-19; Dimethyl Fumarate; Humans; Multiple Sclerosis; Natalizumab; Rituximab; SARS-CoV-2
PubMed: 35398713
DOI: 10.1016/j.msard.2022.103735 -
Multiple Sclerosis and Related Disorders May 2022Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating disorder of the central nervous system. The clinical presentation supported by characteristic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Multiple sclerosis (MS) is a chronic autoimmune inflammatory demyelinating disorder of the central nervous system. The clinical presentation supported by characteristic findings on MRI forms the backbone of the current diagnostic criteria. This study was aimed to investigate the efficacy based on MRI outcomes of FDA approved disease-modifying therapies (DMTs) for relapsing-remitting MS (RRMS).
MATERIALS AND METHODS
We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs) of DMTs. The outcome measures were the mean number of T2 [new/enlarging lesions], new T1 [gadolinium-enhancing (Gd+) T1 and hypointense T1] lesions in brain MRI performed at 12 months or 24 months. We performed a network meta-analysis using the frequentist approach in STATA version 16.0.
RESULTS
We identified 26 RCTs for final analysis. Interferon β-1a and placebo were the most common comparison treatment. Ocrelizumab was more effective in reducing the number of Gd+T1 lesions. Dimethyl fumarate 480 mg was relatively better in reducing the number of new T2 lesions. The treatment ranking showed that ocrelizumab and dimethyl fumarate 480 mg were more efficacious (1 and 0.9 in SUCRA, respectively) for reducing the number of new Gd+T1/hypointense lesions; dimethyl fumarate 480 mg/720 mg and natalizumab were more efficacious (1.0, 0.9 and 0.8 in SUCRA, respectively) to reduce the number of new T2 lesions.
CONCLUSION
Ocrelizumab, dimethyl fumarate 480/720 mg and natalizumab demonstrated favourable MRI outcomes in patients with the RRMS.
Topics: Dimethyl Fumarate; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Network Meta-Analysis
PubMed: 35381534
DOI: 10.1016/j.msard.2022.103760 -
BMJ Open Feb 2022Bempedoic acid (BA) is a novel oral low-density lipoprotein cholesterol lowering drug. This systematic review and meta-analysis aims to assess efficacy and safety for... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Bempedoic acid (BA) is a novel oral low-density lipoprotein cholesterol lowering drug. This systematic review and meta-analysis aims to assess efficacy and safety for clinical outcomes in high cardiovascular (CV) risk patients.
DATA SOURCES
MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Embase, ClinicalTrials.gov, Clinical Trial Results and the American College of Cardiology web site were searched.
STUDY SELECTION
Randomised controlled trials (RCTs) of BA versus placebo in high CV risk patients reporting clinical outcomes were included.
MAIN OUTCOMES AND MEASURES
Primary efficacy outcomes were major adverse cardiovascular events (MACE), all-cause mortality, CV mortality and non-fatal myocardial infarction (MI). Safety outcomes included new onset or worsening of diabetes mellitus (DM), muscular disorders, gout and worsening of renal function.
RESULTS
Six RCTs with a total of 3956 patients and follow-ups of four to 52 weeks were identified. Heterogeneity mainly derived from differing follow-up duration and baseline CV risk. No difference in MACE (OR 0.84; 95% CI 0.61 to 1.15), all-cause mortality (OR 2.37; CI 0.80 to 6.99) and CV mortality (OR 1.66; CI 0.45 to 6.04) for BA versus placebo was observed. BA showed beneficial trends for non-fatal MI (OR 0.57; CI 0.32 to 1.00) and was associated with a lower risk of new-onset or worsening of DM (OR 0.68; CI 0.49 to 0.94), but higher risk of gout (OR 3.29; CI 1.28 to 8.46) and a trend for muscular disorders (OR 2.60; CI 1.15 to 5.91) and worsening of renal function (OR 4.24; CI 0.98 to 18.39).
CONCLUSION
BA in high CV risk patients showed no significant effects on major CV outcomes in short-term follow-up. Unfavourable effects on muscular disorders, renal function and gout sound a note of caution. Hence, further studies with longer term follow-up in carefully selected populations are needed to clarify the risk/benefit ratio of this novel therapy.
Topics: Cholesterol, LDL; Dicarboxylic Acids; Fatty Acids; Humans; Treatment Outcome
PubMed: 35210334
DOI: 10.1136/bmjopen-2021-048893 -
Oral Diseases Apr 2023To assess the efficacy of topical sialogogue spray containing malic acid 1% for treating xerostomia. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the efficacy of topical sialogogue spray containing malic acid 1% for treating xerostomia.
METHODS
We searched PubMed, Cochrane Library, Embase, ClinicalTrials.gov and Web of Science databases. Literature search, screening, study selection, data collection, data extraction and assessment of bias risk were independently conducted by two reviewers. The study appraisal was performed by Cochrane Collaboration's tool for assessing bias risk. The systematic review registration number was PROSPERO-CRD42021241322. All statistical analyses were performed using Review Manager version 5.4.
RESULTS
Five original articles involving 244 patients with xerostomia who received topical sialogogue spray (malic acid 1%) or placebo for two weeks were included in this review. Based on the questionnaire survey, the topical sialogogue spray (malic acid 1%) improved the symptoms of dry mouth significantly better than the placebo, which was reflected in the Dry Mouth Questionnaire (DMQ), Xerostomia Inventory (XI) and Visual Analogue Scale (VAS) scores. Regarding the increase in unstimulated and stimulated saliva flow rates, the intervention group was also better than the placebo group after a two-week course of treatment.
CONCLUSIONS
Although the included studies are limited, our results show that topical sialogogue spray (malic acid 1%) is an effective method for the treatment of xerostomia. Additional randomised controlled trials in the future are needed to provide high-quality evidence of this therapy and to improve clinical practice guidelines.
Topics: Humans; Xerostomia; Malates; Surveys and Questionnaires
PubMed: 34954846
DOI: 10.1111/odi.14116 -
Human Genetics Jul 2022Inherited disorders of cobalamin (cbl) metabolism (cblA-J) result in accumulation of methylmalonic acid (MMA) and/or homocystinuria (HCU). Clinical presentation includes... (Review)
Review
Inherited disorders of cobalamin (cbl) metabolism (cblA-J) result in accumulation of methylmalonic acid (MMA) and/or homocystinuria (HCU). Clinical presentation includes ophthalmological manifestations related to retina, optic nerve and posterior visual alterations, mainly reported in cblC and sporadically in other cbl inborn errors.We searched MEDLINE EMBASE and Cochrane Library, and analyzed articles reporting ocular manifestations in cbl inborn errors. Out of 166 studies a total of 52 studies reporting 163 cbl and 24 mut cases were included. Ocular manifestations were found in all cbl defects except for cblB and cblD-MMA; cblC was the most frequent disorder affecting 137 (84.0%) patients. The c.271dupA was the most common pathogenic variant, accounting for 70/105 (66.7%) cases. One hundred and thirty-seven out of 154 (88.9%) patients presented with early-onset disease (0-12 months). Nystagmus and strabismus were observed in all groups with the exception of MMA patients while maculopathy and peripheral retinal degeneration were almost exclusively found in MMA-HCU patients. Optic nerve damage ranging from mild temporal disc pallor to complete atrophy was prevalent in MMA-HCU.and MMA groups. Nystagmus was frequent in early-onset patients. Retinal and macular degeneration worsened despite early treatment and stabilized systemic function in these patients. The functional prognosis remains poor with final visual acuity < 20/200 in 55.6% (25/45) of cases. In conclusion, the spectrum of eye disease in Cbl patients depends on metabolic severity and age of onset. The development of visual manifestations over time despite early metabolic treatment point out the need for specific innovative therapies.
Topics: Amino Acid Metabolism, Inborn Errors; Homocystinuria; Humans; Macular Degeneration; Methylmalonic Acid; Mutation; Retina; Retinal Degeneration; Vitamin B 12
PubMed: 34652574
DOI: 10.1007/s00439-021-02350-8 -
European Journal of Preventive... Jul 2021Bempedoic acid is a novel oral drug, which has been increasingly researched to play an important role in the treatment of hypercholesterolemia recently. However, results... (Meta-Analysis)
Meta-Analysis
AIM
Bempedoic acid is a novel oral drug, which has been increasingly researched to play an important role in the treatment of hypercholesterolemia recently. However, results from original studies were inconsistent and inconclusive. We aimed to conduct a meta-analysis to quantitatively appraise the efficacy and safety of bempedoic acid.
METHODS
PubMed, Embase, Web of Science and Scopus were searched from inception to 30 January 2020. We included randomized controlled trials that compared the efficacy and safety of bempedoic acid with placebo in patients with hypercholesterolemia. Results from trials were presented as mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) and were pooled by random or fixed effects model. The risk of bias and heterogeneity among trials were also assessed and analyzed.
RESULTS
Pooled analysis of 10 eligible trials showed that bempedoic acid treatment resulted in greater lowering of the low-density lipoprotein cholesterol level than the placebo group (mean difference -23.16%, 95% CI -26.92% to -19.04%). We also found that improvements in lipid parameters and biomarkers were still maintained at weeks 24 and 52 from the long-term trials. As for safety, bempedoic acid did not increase the risk of overall adverse events (OR 1.02, 95% CI 0.88 to 1.18). However, the incidence of adverse events leading to discontinuation was higher in the bempedoic acid group (OR 1.44, 95% CI 1.14 to 1.82).
CONCLUSIONS
Available evidence from randomized controlled trials suggests that bempedoic acid provides a well-tolerated and effective therapeutic option for lipid lowering in patients with hyperlipidemia.
Topics: Dicarboxylic Acids; Fatty Acids; Humans; Hypercholesterolemia; Hyperlipidemias; Hypolipidemic Agents; Randomized Controlled Trials as Topic
PubMed: 34298558
DOI: 10.1177/2047487320930585 -
Journal of Dietary Supplements 2022Although the ergogenic mechanisms of supplementation with citrulline malate are well known, unclear findings regarding variables of muscle strength have been recorded.... (Meta-Analysis)
Meta-Analysis
Although the ergogenic mechanisms of supplementation with citrulline malate are well known, unclear findings regarding variables of muscle strength have been recorded. Such misleading findings in the literature illustrate the need for well-conducted meta-analysis research to elucidate the possible ergogenic impact, which could have major practical consequences for athletes and recreational practitioners seeking to optimize gains in muscle strength. The objective of this systematic review was to summarize the existing literature that evaluated the effects of citrulline malate supplementation on muscle strength outcomes from resistance exercise in resistance-trained individuals. A systematic electronic search in Medline and Scientific Electronic Library Online (SciELO) was completed in August 2020 identifying randomized controlled trials investigating the effect of citrulline malate supplementation on muscle strength in resistance-trained adults. A subsequent meta-analysis was performed. The meta-analysis involved four studies and 138 assessments (69 in citrulline-malate and 69 in placebo groups). We did not observe an overall effect favoring citrulline-malate supplementation (SMD = 0.13 [-0.21; 0.46]). Considering the lower (SMD = 0.06 [-0.47; 0.60]) and upper (SMD = 0.17 [-0.26; 0.60]) limbs, a non-significant overall effect was identified. The mean effects were similar for "limbs" (upper vs lower) [ = 0.763]. Accordingly, our findings suggest that citrulline malate supplementation does not improve muscle strength in healthy and resistance-trained individuals (PROSPERO registration number: CRD42020159338).
Topics: Adult; Humans; Citrulline; Malates; Dietary Supplements; Randomized Controlled Trials as Topic; Muscle Strength; Performance-Enhancing Substances; Muscle, Skeletal; Resistance Training
PubMed: 34176406
DOI: 10.1080/19390211.2021.1939473