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AIDS and Behavior Jul 2023Optimal adherence to pre-exposure prophylaxis (PrEP) is critical, but challenging. Men who have sex with men and transgender women have high rates of HIV incidence and... (Review)
Review
Optimal adherence to pre-exposure prophylaxis (PrEP) is critical, but challenging. Men who have sex with men and transgender women have high rates of HIV incidence and substance use. Substance use is associated with reduced adherence to other medications, but associations between substance use and adherence to PrEP are less clear. Thus, the current review 1) systematically evaluates the measurement of substance use and PrEP adherence in studies examining both and 2) summarizes reported findings. Peer-reviewed articles published between 2010 - April 2021 examining associations between substance use and PrEP adherence were reviewed. Fifty studies met inclusion criteria. Assessment of substance use (i.e., mostly via self-reports at baseline) and PrEP adherence (i.e., often via tenofovir diphosphate [TFV-DP] concentration levels at follow-up) varied considerably across studies. Many studies used categorical variables (e.g., substance use: yes/no). Studies using TFV-DP levels defined adherence consistently (i.e., TFV-DP ≥ 700 fmol/punch), with slight variations. Qualitative studies (n = 10) indicated that substance use (mainly alcohol) is related to poorer PrEP adherence. While quantitative findings to date are equivocal for alcohol, there is a pattern of findings linking stimulant use with poorer PrEP adherence. This review reveals four methodological gaps, which can be addressed in future research by: 1) use of uniform benchmarks for substance use measures, 2) prospective assessment for substance use, 3) use of continuous outcome variables wherever possible, and 4) more extensive consideration of potential confounders. Addressing these methodological gaps may help us reach more definitive conclusions regarding associations between substance use and PrEP adherence.
Topics: Male; Humans; Female; HIV Infections; Homosexuality, Male; Tenofovir; Pre-Exposure Prophylaxis; Transgender Persons; Sexual and Gender Minorities; Prospective Studies; Medication Adherence; Substance-Related Disorders; Anti-HIV Agents
PubMed: 36538138
DOI: 10.1007/s10461-022-03948-3 -
Brain Injury Jul 2008There has been increasing interest in the role of cholinomimetic agents in the long-term management of cognitive impairment following traumatic brain injury. This paper... (Review)
Review
PRIMARY OBJECTIVE
There has been increasing interest in the role of cholinomimetic agents in the long-term management of cognitive impairment following traumatic brain injury. This paper aims to assess the evidence accumulated thus far.
METHODS
Studies are identified by searching MEDLINE, EMBASE and PsychINFO, contacting experts and pharmaceutical companies and hand searching bibliographies. All study designs are included.
MAIN OUTCOME AND RESULTS
This study identified 25 papers that studied cholinesterase inhibitors, physostigmine and choline in mild-to-severe traumatic brain injury. The outcome with cholinesterase inhibitors and choline is suggestive but not conclusive while physostigmine appears of little benefit. A lack of rigorous studies and a plethora of outcome measures preclude drawing definitive conclusions. Further randomized controlled trials are urgently required.
Topics: Brain Injuries; Cholinesterase Inhibitors; Cognition Disorders; Cytidine Diphosphate Choline; Humans; Lecithins; Neuropsychological Tests; Nootropic Agents; Physostigmine; Surface-Active Agents; Time Factors
PubMed: 18568705
DOI: 10.1080/02699050802132495 -
European Journal of Vascular and... Jan 2022Adenosine diphosphate (ADP) receptor inhibitors such as clopidogrel are known to be less effective at reducing platelet function for some patients because of a... (Meta-Analysis)
Meta-Analysis
A Systematic Review and Meta-Analysis on the Impact of High On-Treatment Platelet Reactivity on Clinical Outcomes for Patients Taking ADP Receptor Inhibitors Following Lower Limb Arterial Endovascular Intervention.
OBJECTIVE
Adenosine diphosphate (ADP) receptor inhibitors such as clopidogrel are known to be less effective at reducing platelet function for some patients because of a phenomenon called high on-treatment platelet reactivity (HTPR). However, the clinical effect of this for patients undergoing endovascular intervention for peripheral arterial disease is unclear. The aim of this study was to assess the impact of ADP receptor inhibitor HTPR on clinical outcomes following lower limb arterial endovascular intervention for peripheral arterial disease.
METHODS
A systematic review and meta-analysis was performed. Primary outcomes included all cause mortality and major bleeding. Secondary outcomes were major adverse cardiovascular events, major adverse limb events, restenosis, and target lesion revascularisation. Outcome quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool.
RESULTS
There were 10 eligible studies including 1 444 patients included in the meta-analysis. The most commonly tested ADP receptor inhibitor was clopidogrel (seven studies). The pooled rate of ADP receptor inhibitor HTPR was 29% (95% CI 27 - 32). The meta-analysis showed that ADP receptor inhibitor HTPR was associated with a greater risk of major adverse limb events (OR 6.25, 95% CI 2.09 - 18.68, p = .001) and a trend towards a higher all cause mortality (OR 1.71, 95% CI 0.99 - 2.94, p = .050) and more major adverse cardiovascular events (OR 4.23, 95% CI 0.46 - 38.92, p = .20) after endovascular intervention. Overall strength of evidence was very low for all outcomes.
CONCLUSION
ADP receptor inhibitor HTPR was associated with worse clinical outcomes after lower limb endovascular intervention for peripheral arterial disease. Prospective studies are required to determine the impact of modifying the antithrombotic regimen on clinical outcomes.
Topics: Cause of Death; Clopidogrel; Endovascular Procedures; Humans; Lower Extremity; Peripheral Arterial Disease; Platelet Activation; Platelet Function Tests; Postoperative Complications; Postoperative Hemorrhage; Purinergic P2 Receptor Antagonists; Treatment Outcome
PubMed: 34844834
DOI: 10.1016/j.ejvs.2021.09.026 -
World Journal of Surgical Oncology Jul 2020The purpose of this study was to explore the efficacy and tolerability of poly ADP-ribose polymerase (PARP) inhibitors in patients with ovarian cancer. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The purpose of this study was to explore the efficacy and tolerability of poly ADP-ribose polymerase (PARP) inhibitors in patients with ovarian cancer.
METHODS
The meta-analysis searched the PubMed, Web of Science, EBSCO, and Cochrane libraries from inception to February 2020 to identify relevant studies. And the main results of this study were long-term prognosis and treatment-related adverse events.
RESULTS
The results showed that the addition of PARP inhibitors could significantly prolong progression-free survival (PFS) and overall survival (OS) for patients with ovarian cancer (HR 0.44, 95% CI 0.34-0.53, p < 0.001; HR, 0.79, 95% CI 0.65-0.94, p < 0.001, respectively). In the BRCA 1/2 mutation patients, the HR of PFS was 0.29 (p < 0.001), and the HR was 0.51 (p < 0.001) in the no BRCA 1/2 mutation patients. The HR of PFS was 0.40 (p < 0.001) in the homologous recombination deficiency (HRD) mutation patients, while the HR was 0.80 (p < 0.001) in the no HRD mutation patients. Moreover, the analysis found that the use of PARP inhibitors did not significantly increase the risk of all grade adverse events (AEs) (RR = 1.04, p = 0.16). But the incidence of grade 3 or higher AEs was increased (RR = 1.87, p = 0.002). In general, the AEs were mainly manifested in the blood system.
CONCLUSIONS
PARP inhibitors can improve the prognosis of ovarian cancer patients with and without genetic mutations (BRCA 1/2 or HRD). Furthermore, PARP inhibitors were tolerable to patients when added to their current therapy, although it inevitably adds the grade 3 and higher AEs.
Topics: Adenosine Diphosphate Ribose; Female; Humans; Ovarian Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; Prognosis
PubMed: 32622363
DOI: 10.1186/s12957-020-01931-7 -
Medicine Nov 2021There is a heated debate on the clinicopathological features and prognostic significance with non-metastasis 23 (NM23) expression in patients with non-small cell lung... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There is a heated debate on the clinicopathological features and prognostic significance with non-metastasis 23 (NM23) expression in patients with non-small cell lung cancer (NSCLC). Thus, we conducted this meta-analysis to evaluate the clinicopathological features and prognostic significance of NM23 for NSCLC patients.
METHODS
Pubmed, Embase, and Web of Science were exhaustively searched to identify relevant studies published prior to March, 2020. Odds radios (ORs) and hazard radios with 95% confidence intervals (CIs) were calculated to summarize the statistics of clinicopathological and prognostic assessments. Q-test and I2-statistic were utilized to assess heterogeneity across the included studies. We also performed subgroup analyses and meta-regression analyses to identify the source of heterogeneity. Publication bias was detected by Begg and Egger tests. Sensitivity analysis was used to value the stability of our results. All the data were analyzed using statistical packages implemented in R version 4.0.5.
RESULTS
Data from a total of 3170 patients from 36 studies were extracted. The meta-analysis revealed that low expression of NM23 was correlated with higher risk of NSCLC (OR = 4.35; 95% CI: 2.76-6.85; P < .01), poorer tumor node metastasis (TNM) staging (OR = 1.39; 95% CI: 1.01-1.90; P = .04), poorer differentiation degree (OR = 1.37; 95% CI: 1.01-1.86; P = .04), positive lymph node metastasis (OR = 1.83; 95% CI: 1.22-2.74; P < .01), lung adenocarcinoma (OR = 1.45; 95% CI: 1.20-1.75; P < .01), and poorer 5-year overall survival (OS) rate (hazard radio = 2.33; 95%CI: 1.32-4.11; P < .01). The subgroup analyses and meta-regression analyses suggested that the "Publication year", "Country", "Sample size", and "Cutoff value" might be the source of heterogeneity in TNM staging, differentiation degree, and lymph node metastasis. Both Begg test and Egger test verified that there were publication bias in 5-year OS rate. Sensitivity analysis supported the credibility of the results.
CONCLUSION
The reduced NM23 expression is strongly associated with higher risk of NSCLC, higher TNM staging, poorer differentiation degree, positive lymph node metastasis, lung adenocarcinoma, and poorer 5-year OS rate in NSCLC patients, which indicated that NM23 could serve as a biomarker predicating the clinicopathological and prognostic significance of NSCLC.
Topics: Adenocarcinoma of Lung; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Humans; Lung Neoplasms; Lymphatic Metastasis; NM23 Nucleoside Diphosphate Kinases; Neoplasm Grading; Neoplasm Staging; Prognosis
PubMed: 34964763
DOI: 10.1097/MD.0000000000027919 -
Platelets 2013The VerifyNow P2Y12 test is a whole-blood, light transmission-based optical detection assay that measures adenosine diphosphate-induced platelet aggregation in a... (Meta-Analysis)
Meta-Analysis Review
The VerifyNow P2Y12 test is a whole-blood, light transmission-based optical detection assay that measures adenosine diphosphate-induced platelet aggregation in a cartridge containing fibrinogen-coated beads. The usefulness of this device to assess the effect of clopidogrel on platelet function was recently highlighted for predicting cardiovascular (CV) events. We therefore performed a meta-analysis to analyze whether adverse clinical outcomes of patients with CV disease increase in association with high on-treatment platelet reactivity (HPR) using the VerifyNow P2Y12 test. We also investigated the effect of the CYP2C19*2 polymorphism on the occurrence of CV events among clopidogrel-treated patients. Relevant studies were searched for in the PubMed database and Cochrane Central Register of Controlled Trials database, and selected if they included data about platelet function assessed using the VerifyNow P2Y12 test or CYP2C19*2 polymorphism in clopidogrel-treated patients with CV disease, and the occurrence of CV events within 6-12 months. In our meta-analysis, 4817 subjects from eight studies and 5307 subjects from seven studies were included for review of platelet function and CYP2C19*2 polymorphism, respectively. Overall, 2237 (46.4%) patients had HPR and these patients had significantly higher odds of CV events compared to patients without HPR (odds ratio(OR) = 3.05, 95% confidence interval: 2.33-3.98, p < 0.001). Heterogeneity among studies was not significant (Cochran's Q-test, p = 0.80 and I(2) = 0%). In the secondary investigation, 1926 (36.3%) patients had at least one CYP2C19*2 allele. Heterogeneity in the OR of the CV events between the CYP2C19*2 allele carriers and non-carriers was observed among the seven studies (Cochran's Q-test, p = 0.01 and I(2) = 56.5%), and the range of the ORs among the seven studies was 0.58-16.6. In conclusion, HPR assessed by VerifyNow P2Y12 test was associated with increased adverse clinical outcomes of clopidogrel-treated patients with CV disease.
Topics: Alleles; Aryl Hydrocarbon Hydroxylases; Cardiovascular Diseases; Cytochrome P-450 CYP2C19; Genotype; Humans; Odds Ratio; Patient Outcome Assessment; Platelet Function Tests; Prognosis; Receptors, Purinergic P2Y12
PubMed: 22757746
DOI: 10.3109/09537104.2012.700969 -
Oncotarget Aug 2017UGT2B15 (uridine diphosphate-glucuronosyltransferase 2B15) catalyzes the conversion of lipophilic C19 steroid androgens such as dihydrotestosterone (DHT) into...
UGT2B15 (uridine diphosphate-glucuronosyltransferase 2B15) catalyzes the conversion of lipophilic C19 steroid androgens such as dihydrotestosterone (DHT) into water-soluble metabolites that can be excreted. Studies of the association between the gene D85Y polymorphism and prostate cancer have yielded contradictory results. We therefore systematically searched in the PubMed, EMBASE, Science Direct/Elsevier, CNKI, and Cochrane Library databases, and identified six relevant studies with which to perform a meta-analysis of the relation between D85Y polymorphism and prostate cancer risk. Our meta-analysis revealed a significant association between D85Y gene polymorphism and prostate cancer in all genetic models (P<0.05). The combined odds ratios and 95% confidence intervals were as follows: additive model, 0.53 and 0.32-0.88; dominant model, 0.51 and 0.33-0.79; recessive model, 0.76 and 0.60-0.96; co-dominant model, 0.55 and 0.35-0.86; and allele model, 0.70 and 0.55-0.89. These results are consistent with the idea that the D85Y enzyme variant reduces the risk of prostate cancer by efficiently metabolizing dihydrotestosterone (DHT), which is associated with prostate cancer progression.
PubMed: 28881775
DOI: 10.18632/oncotarget.17375 -
Indian Journal of Pharmacology 2017Stroke and traumatic brain injury (TBI) are the critical public health and socioeconomic problems throughout the world. At present, citicoline is used as a coadjuvant... (Meta-Analysis)
Meta-Analysis Review
Stroke and traumatic brain injury (TBI) are the critical public health and socioeconomic problems throughout the world. At present, citicoline is used as a coadjuvant for the management of acute ischemic stroke (AIS) and TBI in various countries. This systemic review analyzes the beneficial role of citicoline in AIS and TBI. This systemic review is based on "PubMed" and "Science Direct" search results for citicoline role in stroke and TBI. In this systemic review, we included 12 human trials. A meta-analysis was performed on the basis of neurological evaluation, functional evaluation and Glasgow outcome scale, domestic adaptation evaluation outcomes, and cognitive outcome individually. In neurological evaluation, domestic adaptation evaluation, and cognitive outcomes, there was no significant difference in both the citicoline and placebo groups (odds ratio [OR] = 1.04 [0.9-1.2, = 0.583]; OR = 1.1 [0.94-1.27, = 0.209]; OR = 0.953 [0.75-1.2, = 0.691]). In evaluation of functional outcomes, there was significant difference in both groups and OR was 1.18 (1.04-1.34, = 0.01). Functional outcomes were significantly improved by citicoline, but the positive role of this drug in neurological recovery, domestic adaptation, and cognitive outcomes is still a topic of discussion for future.
Topics: Humans; Brain Injuries, Traumatic; Brain Ischemia; Cognition; Cytidine Diphosphate Choline; Nootropic Agents; Stroke; Treatment Outcome
PubMed: 28458415
DOI: 10.4103/0253-7613.201037 -
Journal of Stroke and Cerebrovascular... Aug 2016Citicoline is a drug approved for the treatment of acute ischemic stroke. Although evidence of its efficacy has been reported, recently published results of a large... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Citicoline is a drug approved for the treatment of acute ischemic stroke. Although evidence of its efficacy has been reported, recently published results of a large placebo-controlled clinical trial did not show differences. This study aims to assess whether starting citicoline treatment within 14 days after stroke onset improves the outcome in patients with acute ischemic stroke, as compared with placebo.
METHODS
A systematic search was performed to identify all published, unconfounded, randomized, double-blind, and placebo-controlled clinical trials of citicoline in acute ischemic stroke.
RESULTS
Ten randomized clinical trials met our inclusion criteria. The administration of citicoline was associated with a significant higher rate of independence, independently of the method of evaluation used (odds ratio [OR] 1.56, 95% confidence interval [CI] = 1.12-2.16 under random effects; OR 1.20, 95% CI = 1.06-1.36 under fixed effects). After studying the cumulative meta-analysis, and with the results obtained with the subgroup of patients who were not treated with recombinant tissue plasminogen activator (rtPA) (OR 1.63, 95% CI = 1.18-2.24 under random effects; OR 1.42, 95% CI = 1.22-1.66 under fixed effects), our hypothesis of dilution of the effect of citicoline was confirmed. When we analyzed the effect of citicoline in patients who were not treated with rtPA and were receiving the highest dose of citicoline started in the first 24 hours after onset, based on more recent trials, there was no heterogeneity, and the size of the effect has an OR of 1.27 (95% CI = 1.05-1.53).
CONCLUSIONS
This systematic review supports some benefits of citicoline in the treatment of acute ischemic stroke. But, on top of the best treatment available (rtPA), citicoline offers a limited benefit.
Topics: Brain Ischemia; Cytidine Diphosphate Choline; Double-Blind Method; Female; Humans; Male; Nootropic Agents; Randomized Controlled Trials as Topic; Stroke
PubMed: 27234918
DOI: 10.1016/j.jstrokecerebrovasdis.2016.04.010 -
Osteoarthritis and Cartilage May 2021To examine and compare the accuracy of conventional radiography (CR) and musculoskeletal ultrasonography (US) in the diagnosis of calcium pyrophosphate (CPP) crystals... (Comparative Study)
Comparative Study Meta-Analysis
The diagnostic value of conventional radiography and musculoskeletal ultrasonography in calcium pyrophosphate deposition disease: a systematic literature review and meta-analysis.
OBJECTIVE
To examine and compare the accuracy of conventional radiography (CR) and musculoskeletal ultrasonography (US) in the diagnosis of calcium pyrophosphate (CPP) crystals deposition disease (CPPD).
DESIGN
A systematic search of electronic databases (PubMed, Embase, and Cochrane), conference abstracts and reference lists was undertaken. Studies which evaluated the accuracy of CR and/or US in the diagnosis of CPPD, using synovial fluid analysis (SFA), histology or classification criteria as reference tests were included. Subgroup analyses by anatomic site and by reference test were performed.
RESULTS
Twenty-six studies were included. Using SFA/histology as reference test, CR and US showed an excellent (CR AUC = 0.889, 95%CI = 0.811-0.967) and an outstanding (US AUC = 0.954, 95%CI = 0.907-1.0) diagnostic accuracy (p < 0.01), respectively. Furthermore, US showed a higher sensitivity (0.85, 95%CI = 0.79-0.90 vs 0.47, 95%CI = 0.40-0.55) and only a little lower specificity (0.87, 95%CI = 0.83-0.91 vs 0.95, 95%CI = 0.92-0.97) than CR. A considerable heterogeneity between the studies was found, with adopted reference test being the main source of heterogeneity. In fact, subgroup analysis showed a significant change in the diagnostic accuracy of CR, but not of US, using Ryan and McCarty criteria or SFA/histology as reference test (CR: AUC = 0.956, 95%CI = 0.925-1.0 vs AUC = 0.889, 95%CI = 0.828-0.950, respectively, p < 0.01) (US: AUC = 0.922, 95%CI = 0.842-1.0 vs AUC = 0.957, 95%CI = 0.865-1.0, respectively, p = 0.08) CONCLUSIONS: Although US is more sensitive and a little less specific than CR for identifying CPP crystals, both these two techniques showed a great diagnostic accuracy and should be regarded as complementary to each other in the diagnostic work-up of patients with CPPD.
Topics: Calcium Pyrophosphate; Chondrocalcinosis; Fascia; Humans; Joints; Ligaments, Articular; Muscle, Skeletal; Radiography; Sensitivity and Specificity; Synovial Fluid; Tendons; Ultrasonography
PubMed: 33577959
DOI: 10.1016/j.joca.2021.01.007