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Scandinavian Journal of Pain Apr 2015Background and aims The development of postoperative chronic pain (POCP) after surgery is a major problem with a considerable socioeconomic impact. It is defined as pain... (Meta-Analysis)
Meta-Analysis Review
Background and aims The development of postoperative chronic pain (POCP) after surgery is a major problem with a considerable socioeconomic impact. It is defined as pain lasting more than the usual healing, often more than 2-6 months. Recent systematic reviews and meta-analyses demonstrate that the N-methyl-D-aspartate-receptor antagonist ketamine given peri- and intraoperatively can reduce immediate postoperative pain, especially if severe postoperative pain is expected and regional anaesthesia techniques are impossible. However, the results concerning the role of ketamine in preventing chronic postoperative pain are conflicting. The aim of this study was to perform a systematic review and a pooled analysis to determine if peri- and intraoperative ketamine can reduce the incidence of chronic postoperative pain. Methods Electronic searches of PubMed, EMBASE and Cochrane including data until September 2013 were conducted. Subsequently, the titles and abstracts were read, and reference lists of reviews and retrieved studies were reviewed for additional studies. Where necessary, authors were contacted to obtain raw data for statistical analysis. Papers reporting on ketamine used in the intra- and postoperative setting with pain measured at least 4 weeks after surgery were identified. For meta-analysis of pain after 1, 3, 6 and 12 months, the results were summarised in a forest plot, indicating the number of patients with and without pain in the ketamine and the control groups. The cut-off value used for the VAS/NRS scales was 3 (range 0-10), which is a generally well-accepted value with clinical impact in view of quality of life. Results Our analysis identified ten papers for the comprehensive meta-analysis, including a total of 784 patients. Three papers, which included a total of 303 patients, reported a positive outcome concerning persistent postsurgical pain. In the analysis, only one of nine pooled estimates of postoperative pain at rest or in motion after 1, 3, 6 or 12 months, defined as a value ≥3 on a visual analogue scale of 0-10, indicated a marginally significant pain reduction. Conclusions Based on the currently available data, there is currently not sufficient evidence to support a reduction in chronic pain due to perioperative administration of ketamine. Only the analysis of postoperative pain at rest after 1 month resulted in a marginally significant reduction of chronic postoperative pain using ketamine in the perioperative setting. Implications It can be hypothesised, that regional anaesthesia in addition to the administration of perioperative ketamine might have a preventive effect on the development of persistent postsurgical pain. An additional high-quality pain relief intra- and postoperatively as well after discharge could be more effective than any particular analgesic method per se. It is an assumption that a low dose infusion ketamine has to be administered for more than 72 h to reduce the risk of chronic postoperative pain.
Topics: Analgesics; Chronic Pain; Humans; Intraoperative Care; Ketamine; Pain, Postoperative; Postoperative Care; Treatment Failure
PubMed: 29911604
DOI: 10.1016/j.sjpain.2014.12.005 -
Journal of Clinical Medicine Nov 2020Alzheimer's disease (AD) is a complex and severe neurodegenerative disease and still lacks effective methods of diagnosis. Dysfunction of the N-methyl-D-aspartate... (Review)
Review
OBJECTIVE
Alzheimer's disease (AD) is a complex and severe neurodegenerative disease and still lacks effective methods of diagnosis. Dysfunction of the N-methyl-D-aspartate receptor (NMDAR) has been found to be involved in synapse dysfunction and neurotoxicity of AD mechanisms. d-Serine, an NMDAR receptor coagonist, is reported as a potential new biomarker for AD. However, the results of serum and cerebrospinal fluid (CSF) d-serine levels are conflicting. We conducted a meta-analysis to investigate the serum and CSF d-serine levels in patients with AD.
METHODS
We searched PubMed, the Cochrane central register of controlled trials, and the Cochrane database of systematic reviews for trials that measured d-serine levels both in patients with AD and in controls. We included controlled trials that analyzed d-serine levels in human samples (e.g., serum and CSF). Studies were pooled using a random-effect model for comparisons between AD and control group. We used effect size (ES; expressed as d-serine levels) in each selected meta-analysis to calculate standardized mean difference (SMD). Positive values indicated increased d-serine levels in AD group. We presented results with 95% confidence intervals (CIs). The heterogeneity of the included trials was evaluated through visually inspecting funnel plots and using the I statistic. Moderators of effects were explored using metaregression.
RESULTS
Seven trials with more than 1186 participants were included in this meta-analysis. d-serine levels in patients with AD were significantly higher than those in controls (SMD = 0.679, 95% CI = 0.335 to 1.022, < 0.001). Subgroup analyses showed that the AD group had significantly higher d-serine levels in serum and CSF compared with the control group (SMD = 0.566 (serum) and 1.008 (CSF); 95% CI = 0.183 to 0.948 (serum) and 0.168 to 1.849 (CSF)). Moreover, a metaregression revealed a significant negative association between ES and mean mini-mental state examination score in AD group (slope = -0.1203, = 0.0004).
CONCLUSIONS
Our results revealed higher d-serine levels in the serum and CSF of patients with AD relative to the controls. Further studies with a larger sample size and longer follow-up are recommended to clarify this association.
PubMed: 33256147
DOI: 10.3390/jcm9123840 -
Frontiers in Endocrinology 2020Still circa 25% to 30% of patients with epilepsy cannot be efficiently controlled with available antiepileptic drugs so newer pharmacological treatment options have been...
Still circa 25% to 30% of patients with epilepsy cannot be efficiently controlled with available antiepileptic drugs so newer pharmacological treatment options have been continuously searched for. In this context, a group of endogenous or exogenous neurosteroids allosterically positively modulating GABA-A receptors may offer a promising approach. Among endogenous neurosteroids synthesized in the brain, allopregnanolone or allotetrahydrodeoxycorticosterone have been documented to exert anticonvulsant activity in a number of experimental models of seizures-pentylenetetrazol-, bicuculline- pilocarpine-, or 6 Hz-induced convulsions in rodents. Neurosteroids can also inhibit fully kindled seizures and some of them have been reported to counteract maximal electroshock-induced convulsions. An exogenous neurosteroid, alphaxalone, significantly elevated the threshold for maximal electroconvulsions in mice but it did not potentiate the anticonvulsive action of a number of conventional antiepileptic drugs against maximal electroshock-induced seizures. Androsterone not only elevated the threshold but significantly enhanced the protective action of carbamazepine, gabapentin and phenobarbital against maximal electroshock in mice, as well. Ganaxolone (a 3beta-methylated analog of allopregnanolone) needs special consideration for two reasons. First, it performed better than conventional antiepileptic drugs, diazepam or valproate, in suppressing convulsive and lethal effects of pentylenetetrazol in pentylenetetrazol-kindled mice. Second, ganaxolone has been evaluated in the randomized, double-blind, placebo-controlled phase 2 trial in patients with intractable partial seizures, taking maximally 3 antiepileptic drugs. The initial results indicate that add-on therapy with ganaxolone resulted in reduced seizure frequency with adverse effect being mainly mild to moderate. Possibly, ganaxolone may be also considered against catamenial seizures. Some positive effects of ganaxolone as an adjuvant were also observed in children with refractory seizures and its use may also prove efficient for the management of neonatal seizures associated with hypoxic injury. Neurosteroids positively modulating GABA-A receptor complex exert anticonvulsive activity in many experimental models of seizures. Their interactions with antiepileptic drugs seem ambiguous in mice. Initial clinical data indicate that ganaxolone may provide a better seizure control in patients with drug-resistant epilepsy.
Topics: Allosteric Regulation; Animals; Anticonvulsants; Epilepsy; GABA-A Receptor Agonists; Humans; Neurosteroids; Seizures; Treatment Outcome
PubMed: 33117274
DOI: 10.3389/fendo.2020.541802 -
Clinical Epigenetics Aug 2023Screening plays a key role in secondary prevention of cervical cancer. High-risk human papillomavirus (hrHPV) testing, a highly sensitive test but with limited... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Screening plays a key role in secondary prevention of cervical cancer. High-risk human papillomavirus (hrHPV) testing, a highly sensitive test but with limited specificity, has become the gold standard frontline for screening programs. Thus, the importance of effective triage strategies, including DNA methylation markers, has been emphasized. Despite the potential reported in individual studies, methylation markers still require validation before being recommended for clinical practice. This systematic review and meta-analysis aimed to evaluate the performance of DNA methylation-based biomarkers for detecting high-grade intraepithelial lesions (HSIL) in hrHPV-positive women.
METHODS
Hence, PubMed, Scopus, and Cochrane databases were searched for studies that assessed methylation in hrHPV-positive women in cervical scrapes. Histologically confirmed HSIL was used as endpoint and QUADAS-2 tool enabled assessment of study quality. A bivariate random-effect model was employed to pool the estimated sensitivity and specificity as well as positive (PPV) and negative (NPV) predictive values.
RESULTS
Twenty-three studies were included in this meta-analysis, from which cohort and referral population-based studies corresponded to nearly 65%. Most of the women analyzed were Dutch, and CADM1, FAM19A4, MAL, and miR124-2 were the most studied genes. Pooled sensitivity and specificity were 0.68 (CI 95% 0.63-0.72) and 0.75 (CI 95% 0.71-0.80) for cervical intraepithelial neoplasia (CIN) 2+ detection, respectively. For CIN3+ detection, pooled sensitivity and specificity were 0.78 (CI 95% 0.74-0.82) and 0.74 (CI 95% 0.69-0.78), respectively. For pooled prevalence, PPV for CIN2+ and CIN3+ detection were 0.514 and 0.392, respectively. Furthermore, NPV for CIN2+ and CIN3+ detection were 0.857 and 0.938, respectively.
CONCLUSIONS
This meta-analysis confirmed the great potential of DNA methylation-based biomarkers as triage tool for hrHPV-positive women in cervical cancer screening. Standardization and improved validation are, however, required. Nevertheless, these markers might represent an excellent alternative to cytology and genotyping for colposcopy referral of hrHPV-positive women, allowing for more cost-effective screening programs.
Topics: Female; Humans; Pregnancy; Uterine Cervical Neoplasms; DNA Methylation; Early Detection of Cancer; Colposcopy; Triage; Papillomavirus Infections; Referral and Consultation; Papillomaviridae; Cell Adhesion Molecule-1
PubMed: 37533074
DOI: 10.1186/s13148-023-01537-2 -
Health Science Reports Sep 2021Benzene is a group I carcinogen, which has been associated with leukemia and myelodysplastic syndrome. Moreover, it has been proposed that polymorphisms in benzene... (Review)
Review
BACKGROUND AND AIMS
Benzene is a group I carcinogen, which has been associated with leukemia and myelodysplastic syndrome. Moreover, it has been proposed that polymorphisms in benzene metabolizing genes influence the outcomes of benzene exposure in the human body. This systematic review aims to elucidate the existent relationship between genetic polymorphisms and the risk of developing adverse health effects in benzene-exposed workers.
METHODS
Three databases were systematically searched until April 2020. The preferred reporting items for systematic reviews and meta-analyses method was used to select articles published between 2005 and 2020. Quality assessment and risk of bias were evaluated by the Newcastle-Ottawa scale.
RESULTS
After full-text evaluation, 36 articles remained out of 645 initially screened. The most studied health effects within the reviewed papers were chronic benzene poisoning, hematotoxicity, altered urinary biomarkers of exposure, micronucleus/chromosomal aberrations, and gene methylation. Furthermore, some polymorphisms on , , , , and , among other genes, showed a statistically significant relationship with an increased risk of developing at least one of these effects on benzene-exposed workers. However, there was no consensus among the reviewed papers on which specific polymorphisms were the ones associated with the adverse health-related outcomes, except for the rs1800566 and the null genotypes. Additionally, the smoking habit was identified as a confounder, demonstrating worse health outcomes in exposed workers that smoked.
CONCLUSION
Though there is a positive relationship between genetic polymorphisms and detrimental health outcomes for benzene-exposed workers, broader benzene-exposed cohorts that take into account the genetic diversity of the population are needed in order to determine which specific polymorphisms incur in health risks.
PubMed: 34295994
DOI: 10.1002/hsr2.327 -
International Journal of Hygiene and... Sep 2021Lead (Pb) is a ubiquitous environmental pollutant and a potent toxic compound. Humans are exposed to Pb through inhalation, ingestion, and skin contact via food, water,... (Review)
Review
Lead (Pb) is a ubiquitous environmental pollutant and a potent toxic compound. Humans are exposed to Pb through inhalation, ingestion, and skin contact via food, water, tobacco smoke, air, dust, and soil. Pb accumulates in bones, brain, liver and kidney. Fetal exposure occurs via transplacental transmission. The most critical health effects are developmental neurotoxicity in infants and cardiovascular effects and nephrotoxicity in adults. Pb exposure has been steadily decreasing over the past decades, but there are few recent exposure data from the general European population; moreover, no safe Pb limit has been set. Sensitive biomarkers of exposure, effect and susceptibility, that reliably and timely indicate Pb-associated toxicity are required to assess human exposure-health relationships in a situation of low to moderate exposure. Therefore, a systematic literature review based on PubMed entries published before July 2019 that addressed Pb exposure and biomarkers of effect and susceptibility, neurodevelopmental toxicity, epigenetic modifications, and transcriptomics was conducted. Finally included were 58 original papers on Pb exposure and 17 studies on biomarkers. The biomarkers that are linked to Pb exposure and neurodevelopment were grouped into effect biomarkers (serum brain-derived neurotrophic factor (BDNF) and serum/saliva cortisol), susceptibility markers (epigenetic markers and gene sequence variants) and other biomarkers (serum high-density lipoprotein (HDL), maternal iron (Fe) and calcium (Ca) status). Serum BDNF and plasma HDL are potential candidates to be further validated as effect markers for routine use in HBM studies of Pb, complemented by markers of Fe and Ca status to also address nutritional interactions related to neurodevelopmental disorders. For several markers, a causal relationship with Pb-induced neurodevelopmental toxicity is likely. Results on BDNF are discussed in relation to Adverse Outcome Pathway (AOP) 13 ("Chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities") of the AOP-Wiki. Further studies are needed to validate sensitive, reliable, and timely effect biomarkers, especially for low to moderate Pb exposure scenarios.
Topics: Adult; Biomarkers; Brain-Derived Neurotrophic Factor; Humans; Infant; Lead; Learning; Saliva
PubMed: 34655857
DOI: 10.1016/j.ijheh.2021.113855 -
European Journal of Anaesthesiology Feb 2015Desflurane's short emergence time supports fast track anaesthesia. Data on the rate of upper airway complications and emergence time when desflurane is used with... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Desflurane's short emergence time supports fast track anaesthesia. Data on the rate of upper airway complications and emergence time when desflurane is used with laryngeal mask airway (LMA) are controversial and limited.
OBJECTIVES
To compare recovery time variables and the rates of upper airway adverse events in patients with an LMA undergoing general surgery with desflurane, sevoflurane, isoflurane or propofol anaesthesia.
DESIGN
A systematic review and meta-analysis of randomised controlled trials (RCTs).
DATA SOURCES
A systematic search for eligible RCTs in Embase (Elsevier) and in PubMed (National Library of Medicine) databases up to September 2013.
ELIGIBILITY CRITERIA
RCTs investigating the rates of cough overall, cough at emergence, laryngospasm, time to eye opening, time to removal of the LMA, time to respond to command and time to state date of birth in patients with an LMA, during emergence from desflurane, sevoflurane, isoflurane or propofol anaesthesia.
RESULTS
Thirteen RCTs were included and analysed. We found a strong interstudy variability. There was no difference in the rates of upper airway events between desflurane and sevoflurane or between desflurane and a control group consisting of all the other anaesthetics combined. Comparing desflurane (n = 284) with all other anaesthetic groups (n = 313), the risk ratio [95% confidence interval (95% CI)] was 1.12 (0.63 to 2.02, P = 0.70). Cough at emergence was only measured in patients receiving desflurane (n = 148) and sevoflurane (n = 146): the risk ratio (95% CI) was 1.49 (0.55 to 4.02, P = 0.43). Laryngospasm was rare and there was no significant difference in its incidence when desflurane (n = 262) was compared with all other anaesthetics combined (n = 289; risk ratio 1.03; 95% CI 0.33 to 3.20, P = 0.96). The times of all emergence variables were significantly faster in the desflurane group than in all other groups.
CONCLUSION
When using an LMA, upper airway adverse reactions in association with desflurane anaesthesia were no different from those noted with sevoflurane, isoflurane or propofol anaesthesia. Emergence from general anaesthesia with desflurane is significantly faster than all the other anaesthetics. Due to interstudy variations and the small size of the trials, further large-scale, multicentre studies are required to confirm or refute the results of this meta-analysis.
Topics: Anesthesia Recovery Period; Anesthesia, General; Anesthetics, Inhalation; Cough; Desflurane; Humans; Isoflurane; Laryngeal Masks; Laryngismus; Methyl Ethers; Propofol; Randomized Controlled Trials as Topic; Sevoflurane
PubMed: 25545286
DOI: 10.1097/EJA.0000000000000183 -
American Journal of Blood Research 2021Acute myeloid leukemia (AML), although genetically and morphologically distinct from other B and T cell ALL subtypes, has one of the most rapidly progressing course and... (Review)
Review
Acute myeloid leukemia (AML), although genetically and morphologically distinct from other B and T cell ALL subtypes, has one of the most rapidly progressing course and worse outcomes. The current diagnostic classification of AML offers best curative intent, the outcomes are not usually those that are expected at the start of therapy. This is partly attributed to the complex mechanism of leukemogenesis and resistance to chemotherapy. The underlying genetic mechanism of resistance is as complex as is the disease etiopathogenesis. Recent advances in therapy of drug resistant AML highlight the role of epigenetic targets. New FDA approved targeted therapy has also provided some evidence at improving outcomes in clinical trials. This review provides a detailed review of FDA approved targets and ongoing clinical trials for targeting CRISPER, CAR-T and other intestinal modalities for approach to epigenetictargets. However, this group of epigenetic targeted therapy needs more validation to prove its clinical efficacy. A systematic review of all published research on these targets, investigational agents and FDA approved targeted therapy summarizes this evidence. It also takes us through a brief review of mechanism of action and targets for therapy.
PubMed: 34824880
DOI: No ID Found -
European Urology Open Science Mar 2022Over the past decade there has been increasing interest in the potential of liquid biopsies and systematic biomarkers in the diagnosis and management of kidney cancer,... (Review)
Review
CONTEXT
Over the past decade there has been increasing interest in the potential of liquid biopsies and systematic biomarkers in the diagnosis and management of kidney cancer, as they may provide a tool for early detection of disease and monitoring of treatment response.
OBJECTIVE
To identify and summarize relevant published data on circulating tumor DNA (ctDNA) in patients with renal cell carcinoma (RCC).
EVIDENCE ACQUISITION
We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement of studies identified in PubMed, MEDLINE, EMBASE, and Cochrane Library up to January 15, 2021. Two reviewers independently screened all articles and performed the data extraction.
EVIDENCE SYNTHESIS
Nineteen studies investigating ctDNA in RCC (1237 patients) were included and analyzed in the final review. The study size and design varied widely, and the studies were divided into five groups according to the method used for ctDNA detection. The outcome data included (1) the sensitivity/specificity if available; (2) the method used for ctDNA detection; and (3) the main findings in the studies.
CONCLUSIONS
The studies highlight that the level of ctDNA in RCC appears to be low. Studies using multiple methods for ctDNA detection indicate that tumor-guided analysis improves the ctDNA detection rate and suggest that cell-free methylated DNA immunoprecipitation and high-throughput sequencing may be a very sensitive method for ctDNA detection in RCC.
PATIENT SUMMARY
We systematically reviewed the literature to identify all relevant studies investigating circulating tumor DNA in patients with kidney cancer to investigate its use and potential in this highly malignant disease. We found that the level of circulating tumor DNA is low in kidney cancer and that very sensitive methods have to be used for detection in this disease.
PubMed: 35106503
DOI: 10.1016/j.euros.2021.12.006 -
The Cochrane Database of Systematic... Mar 2015Electrical cardioversion is an effective procedure for restoring normal sinus rhythm in the hearts of patients with irregular heart rhythms. It is important that the... (Review)
Review
BACKGROUND
Electrical cardioversion is an effective procedure for restoring normal sinus rhythm in the hearts of patients with irregular heart rhythms. It is important that the patient is not fully conscious during the procedure, as it can be painful and distressing. The drug used to make patients unaware of the procedure should rapidly achieve the desired level of sedation, should wear off quickly and should not cause cardiovascular or respiratory side effects.
OBJECTIVES
We aimed to compare the safety, effectiveness and adverse events associated with various anaesthetic or sedative agents used in direct current cardioversion for cardiac arrhythmia in both elective and emergency settings.We sought answers to the following specific questions.• Which drugs deliver the best outcomes for patients undergoing electrical cardioversion?• Does using a particular agent confer advantages or disadvantages?• Is additional analgesic necessary to prevent pain?
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) on 27 March 2014. Our search terms were relevant to the review question and were not limited by outcomes. We also carried out searches of clinical trials registers and forward and backward citation tracking.
SELECTION CRITERIA
We considered all randomized controlled trials and quasi-randomized and cluster-randomized studies with adult participants undergoing electrical cardioversion procedures in the elective or emergency setting.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data, consulting with a third review author for disagreements. We used standard Cochrane methodological procedures, including assessment of risk of bias for all studies.
MAIN RESULTS
We included 23 studies with 1250 participants that compared one drug with one or more other drugs. Of these comparisons, 19 studies compared propofol with another drug. Seven of these compared propofol with etomidate (four of which combined the drugs with remifentanil or fentanyl), five midazolam, six thiopentone and two sevoflurane. Three studies compared etomidate with thiopentone, and three etomidate with midazolam. Two studies compared thiopentone with midazolam, one thiopentone with diazepam and one midazolam with diazepam. Drug doses and the time over which the drugs were given varied between studies. Although all studies were described as randomized, limited information was provided about the methods used for selection and group allocation. A high level of performance bias was observed across studies, as study authors had not attempted to blind the anaesthetist to group allocation. Similarly, study authors had rarely provided sufficient information on whether outcome assessors had been blinded.Included studies presented outcome data for hypotension, apnoea, participant recall, success of cardioversion, minor adverse events of nausea and vomiting, pain at injection site and myoclonus, additional analgesia and participant satisfaction. We did not pool the data from different studies in view of the multiple drug comparisons, differences in definitions and reporting of outcomes, variability of endpoints and high or unclear risk of bias across studies.
AUTHORS' CONCLUSIONS
Few studies reported statistically significant results for our relevant outcomes, and most study authors concluded that both, or all, agents compared in individual studies were adequate for cardioversion procedures. It is our opinion that at present, there is no evidence to suggest that current anaesthetic practice for cardioversion should change.
Topics: Anesthetics; Apnea; Diazepam; Electric Countershock; Etomidate; Fentanyl; Humans; Hypnotics and Sedatives; Hypotension; Mental Recall; Methyl Ethers; Midazolam; Piperidines; Propofol; Randomized Controlled Trials as Topic; Remifentanil; Sevoflurane; Thiopental
PubMed: 25803543
DOI: 10.1002/14651858.CD010824.pub2