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Frontiers in Neurology 2021Although numerous epidemiological studies have investigated the association between -174G/C(rs1800795) polymorphism in the interleukin-6 (IL-6) gene-stimulatory region...
Although numerous epidemiological studies have investigated the association between -174G/C(rs1800795) polymorphism in the interleukin-6 (IL-6) gene-stimulatory region and the risk of ischemic stroke (IS), they failed to reach a unified conclusion. The true relationship between -174G/C(rs1800795) polymorphism and IS remains controversial and unclear. Therefore, in this meta-analysis, we aimed to analyze more precisely the association between -174G/C(rs1800795) single-nucleotide polymorphism (SNP) of IL-6 gene and IS in a larger pooled population. A comprehensive literature search was performed in , and until June 30, 2021. A fixed or random-effects model was utilized based on heterogeneity between studies. The odds ratios (ORs) and 95% confidence intervals (Cis) were calculated in the models of allele comparison (G vs. C), homozygote comparison (GG vs. CC) and (GC vs. CC), dominant (GG vs. GC + CC), hyper dominant (GG + CC vs. GC), and recessive (GG + GC vs. CC) to determine the strength of associations. This meta-analysis included 13 case-control studies in 35 articles with 5,548 individuals. Overall, no significant associations between IL-6 -174G/C(rs1800795) and IS were identified (G vs. C:OR [95% CI] = 0.99 [0.81, 1.21], = 0.91; GG + CC vs. GC:0.97 [0.85, 1.11], = 0.66; GG vs. GC + CC: 1.01 [0.81, 1.25], = 0.94; GC vs. CC: OR [95% CI] = 1.01 [0.68, 1.5], = 0.96; GG vs. CC:0.93 [0.57, 1.51], = 0.76; GG + GC vs. CC:0.97 [0.64, 1.47], = 0.89). In the subgroup analyses by ethnicity or HWE -value, there was a statistically significant association between IL-6 -174G/C(rs1800795) polymorphisms and IS in the alleles model; (G vs. C: LogOR [95% CI] = 0.14 [-0.16,.45], = 0.00), homozygote model (GG vs. CC: LogOR [95% CI] = 0.18 [-0.58,.95], = 0.00) and (GC vs. CC: LogOR [95% CI] = 0.2 [-0.46,.85], = 0.00), dominant model (GG vs. GC + CC: OR [95% CI] = 0.02 [-0.72, 0.77], = 0.00), and recessive model (GG + GC vs. CC: OR [95% CI]= -0.17 [-0.86,.52], = 0.00) of the European population and in the dominant model (GG vs. GC + CC: OR [95% CI] = -0.13 [-0.51, 0.24]) of the Asian population. No statistical significance was identified in both six models of HWE ≥ 0.2 group (both ≥ 0.05). This meta-analysis revealed no correlation between IL-6 -174G/C(rs1800795) polymorphism and IS, whereas the subgroup analysis indicated that the relationship between IL-6 -174G/C(rs1800795) polymorphism and IS susceptibility varied significantly according to ethnicity and geography.
PubMed: 35069427
DOI: 10.3389/fneur.2021.799022 -
Animals : An Open Access Journal From... Dec 2022Aggression among group-housed male mice is a major animal welfare concern often observed at animal facilities. Studies designed to understand the causes of male mice... (Review)
Review
Aggression among group-housed male mice is a major animal welfare concern often observed at animal facilities. Studies designed to understand the causes of male mice aggression have used different methodological approaches and have been heterogeneous, using different strains, environmental enrichments, housing conditions, group formations and durations. By conducting a systematic literature review based on 198 observed conclusions from 90 articles, we showed that the methodological approach used to study aggression was relevant for the outcome and suggested that home cage observations were better when studying home cage aggression than tests provoking aggression outside the home cage. The study further revealed that aggression is a complex problem; one solution will not be appropriate for all animal facilities and all research projects. Recommendations were provided on promising tools to minimize aggression, based on the results, which included what type of environmental enrichments could be appropriate and which strains of male mice were less likely to be aggressive.
PubMed: 36611751
DOI: 10.3390/ani13010143 -
Philosophical Transactions of the Royal... Jan 2023Forest restoration has been proposed as a scalable nature-based solution to achieve global environmental and socio-economic outcomes and is central to many policy... (Review)
Review
Forest restoration has been proposed as a scalable nature-based solution to achieve global environmental and socio-economic outcomes and is central to many policy initiatives, such as the Bonn Challenge. Restored forests contain appreciable biodiversity, improve habitat connectivity and sequester carbon. Incentive mechanisms (e.g. payments for ecosystem services and allocation of management rights) have been a focus of forest restoration efforts for decades. Yet, there is still little understanding of their role in promoting restoration success. We conducted a systematic literature review to investigate how incentive mechanisms are used to promote forest restoration, outcomes, and the biophysical and socio-economic factors that influence implementation and program success. We found that socio-economic factors, such as governance, monitoring systems and the experience and beliefs of participants, dominate whether or not an incentive mechanism is successful. We found that approximately half of the studies report both positive ecological and socio-economic outcomes. However, reported adverse outcomes were more commonly socio-economic than ecological. Our results reveal that achieving forest restoration at a sufficient scale to meet international commitments will require stronger assessment and management of socio-economic factors that enable or constrain the success of incentive mechanisms. This article is part of the theme issue 'Understanding forest landscape restoration: reinforcing scientific foundations for the UN Decade on Ecosystem Restoration'.
Topics: Humans; Ecosystem; Motivation; Forests; Biodiversity; Conservation of Natural Resources
PubMed: 36373914
DOI: 10.1098/rstb.2021.0088 -
Diagnostics (Basel, Switzerland) Jun 2023(1) Background. The anatomical variations of the vertebral arteries (VAs) have a significant impact both in neurosurgery and forensic pathology. The purpose of this... (Review)
Review
(1) Background. The anatomical variations of the vertebral arteries (VAs) have a significant impact both in neurosurgery and forensic pathology. The purpose of this study was to evaluate the variational anatomy of the vertebral artery. We evaluated anatomical aspects regarding the V1 and V2 segments of the VA: origin, course, tortuosity, hypoplasia, and dominance, and established the prevalence of each variation. (2) Methods. We conducted a systematic search in PubMed and Google Scholar databases, up to December 2022. Sixty-two studies, comprising 32,153 vessels, were included in the current meta-analysis. We used a random-effects model with a DerSimonian-Laird estimator. The confidence intervals were set at 95%. The heterogeneity between studies was assessed using I. The funnel plot and Egger's regression test for plot asymmetry were used for the evaluation of publication bias. Statistical significance was considered at < 0.05. (3) Results. The most common site for the origin of both VAs was the subclavian artery. The aortic arch origin of the left VA had a prevalence of 4.81%. Other origins of the right VAs were noted: aortic arch (0.1%), right common carotid artery (0.1%), and brachiocephalic trunk (0.5%). Ninety-two percent of the VAs entered the transverse foramen (TF) of the C6 vertebra, followed by C5, C7, C4, and least frequently, C3 (0.1%). Roughly one out of four (25.9%) VAs presented a sort of tortuosity, the transversal one representing the most common variant. Hypoplasia occurred in 7.94% of the vessels. Left VA dominance (36.1%) is more common, compared to right VA dominance (25.3%). (4) Conclusions. The anatomy of the VA is highly irregular, and eventual intraoperative complications may be life-threatening. The prevalence of VA origin from the subclavian artery is 94.1%, 92.0% of the VAs entered the TF at C6, 26.6% were tortuous, and 7.94% were hypoplastic.
PubMed: 37370931
DOI: 10.3390/diagnostics13122036 -
Alimentary Pharmacology & Therapeutics Apr 2016Microscopic colitis shares certain common clinical manifestations with functional bowel disorders, especially diarrhoea-dominant irritable bowel syndrome (IBS) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Microscopic colitis shares certain common clinical manifestations with functional bowel disorders, especially diarrhoea-dominant irritable bowel syndrome (IBS) and functional diarrhoea. However, the exact relationship between microscopic colitis and functional bowel disorders has not been systematically assessed.
AIM
To conduct a systematic review and meta-analysis on the diagnostic overlap between functional bowel disorders and microscopic colitis.
METHODS
We searched MEDLINE, EMBASE and SCOPUS databases, as well as the abstract books of the major gastroenterology meetings, to investigate the prevalence of microscopic colitis among patients with functional bowel disorders (considering all subtypes of both disorders) and vice versa. Data were pooled with a random-effects model.
RESULTS
Of 227 references identified, data were collected from 26 studies and a total of 5,099 adult patients. The pooled prevalence any type of functional bowel disorders in patients who present diagnostic criteria of microscopic colitis was 39.1% (95% CI: 22.8-56.6%; I : 97%) and was higher for lymphocytic colitis than for collagenous colitis (40.7% vs. 28.4%, respectively; P = 0.58). The prevalence of microscopic colitis in functional bowel disorders patients was 7% (95% CI: 3.6-11.4%), reaching 9.8% (95% CI: 4.4-17.1%; I : 95%) in patients exhibiting diarrhoea-dominant IBS, nonsignificantly higher than microscopic colitis rates among patients with constipation-dominant IBS (1.3%) or mixed-dominant IBS (1.9%).
CONCLUSIONS
There is a significant overlap of symptoms between microscopic colitis and functional bowel disorders, especially in diarrhoeal subtypes. The high proportion of microscopic colitis among diarrhoea-dominant functional syndromes should serve as a call for more active diagnosis in selected patients.
Topics: Adult; Colitis, Collagenous; Colitis, Lymphocytic; Colitis, Microscopic; Constipation; Diarrhea; Humans; Irritable Bowel Syndrome; Prevalence
PubMed: 26913568
DOI: 10.1111/apt.13573 -
Health Technology Assessment... Aug 2016End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
End-stage renal disease is a long-term irreversible decline in kidney function requiring kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation followed by induction and maintenance immunosuppressive therapy to reduce the risk of kidney rejection and prolong graft survival.
OBJECTIVES
To systematically review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect,(®) Novartis Pharmaceuticals) and rabbit antihuman thymocyte immunoglobulin (Thymoglobuline,(®) Sanofi) as induction therapy and immediate-release tacrolimus [Adoport(®) (Sandoz); Capexion(®) (Mylan); Modigraf(®) (Astellas Pharma); Perixis(®) (Accord Healthcare); Prograf(®) (Astellas Pharma); Tacni(®) (Teva); Vivadex(®) (Dexcel Pharma)], prolonged-release tacrolimus (Advagraf,(®) Astellas Pharma); belatacept (BEL) (Nulojix,(®) Bristol-Myers Squibb), mycophenolate mofetil (MMF) [Arzip(®) (Zentiva), CellCept(®) (Roche Products), Myfenax(®) (Teva), generic MMF is manufactured by Accord Healthcare, Actavis, Arrow Pharmaceuticals, Dr Reddy's Laboratories, Mylan, Sandoz and Wockhardt], mycophenolate sodium, sirolimus (Rapamune,(®) Pfizer) and everolimus (Certican,(®) Novartis Pharmaceuticals) as maintenance therapy in children and adolescents undergoing renal transplantation.
DATA SOURCES
Clinical effectiveness searches were conducted to 7 January 2015 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science [via Institute for Scientific Information (ISI)], Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (HTA) (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted to 15 January 2015 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Databases (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and EconLit (via EBSCOhost).
REVIEW METHODS
Titles and abstracts were screened according to predefined inclusion criteria, as were full texts of identified studies. Included studies were extracted and quality appraised. Data were meta-analysed when appropriate. A new discrete time state transition economic model (semi-Markov) was developed; graft function, and incidences of acute rejection and new-onset diabetes mellitus were used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death.
RESULTS
Three randomised controlled trials (RCTs) and four non-RCTs were included. The RCTs only evaluated BAS and tacrolimus (TAC). No statistically significant differences in key outcomes were found between BAS and placebo/no induction. Statistically significantly higher graft function (p < 0.01) and less biopsy-proven acute rejection (odds ratio 0.29, 95% confidence interval 0.15 to 0.57) was found between TAC and ciclosporin (CSA). Only one cost-effectiveness study was identified, which informed NICE guidance TA99. BAS [with TAC and azathioprine (AZA)] was predicted to be cost-effective at £20,000-30,000 per quality-adjusted life year (QALY) versus no induction (BAS was dominant). BAS (with CSA and MMF) was not predicted to be cost-effective at £20,000-30,000 per QALY versus no induction (BAS was dominated). TAC (with AZA) was predicted to be cost-effective at £20,000-30,000 per QALY versus CSA (TAC was dominant). A model based on adult evidence suggests that at a cost-effectiveness threshold of £20,000-30,000 per QALY, BAS and TAC are cost-effective in all considered combinations; MMF was also cost-effective with CSA but not TAC.
LIMITATIONS
The RCT evidence is very limited; analyses comparing all interventions need to rely on adult evidence.
CONCLUSIONS
TAC is likely to be cost-effective (vs. CSA, in combination with AZA) at £20,000-30,000 per QALY. Analysis based on one RCT found BAS to be dominant, but analysis based on another RCT found BAS to be dominated. BAS plus TAC and AZA was predicted to be cost-effective at £20,000-30,000 per QALY when all regimens were compared using extrapolated adult evidence. High-quality primary effectiveness research is needed. The UK Renal Registry could form the basis for a prospective primary study.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42014013544.
FUNDING
The National Institute for Health Research HTA programme.
Topics: Abatacept; Antibodies, Monoclonal; Antilymphocyte Serum; Azathioprine; Basiliximab; Child; Clinical Trials as Topic; Cost-Benefit Analysis; Drug Therapy, Combination; Everolimus; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Models, Economic; Mycophenolic Acid; Recombinant Fusion Proteins; Sirolimus; Tacrolimus; Technology Assessment, Biomedical
PubMed: 27557331
DOI: 10.3310/hta20610 -
PharmacoEconomics Jan 2023Fenfluramine, tradename Fintepla, was appraised within the National Institute for Health and Care Excellence (NICE) single technology appraisal (STA) process as... (Meta-Analysis)
Meta-Analysis Review
Fenfluramine, tradename Fintepla, was appraised within the National Institute for Health and Care Excellence (NICE) single technology appraisal (STA) process as Technology Appraisal 808. Within the STA process, the company (Zogenix International) provided NICE with a written submission and a mathematical health economic model, summarising the company's estimates of the clinical effectiveness and cost-effectiveness of fenfluramine for patients with Dravet syndrome (DS). This company submission (CS) was reviewed by an evidence review group (ERG) independent of NICE. The ERG, Kleijnen Systematic Reviews in collaboration with Maastricht University Medical Centre, produced an ERG report. This paper presents a summary of the ERG report and the development of the NICE guidance. The CS included a systematic review of the evidence for fenfluramine. From this review the company identified and presented evidence from two randomised trials (Study 1 and Study 1504), an open-label extension study (Study 1503) and 'real world evidence' from a prospective and retrospective study. Both randomised trials were conducted in patients up to 18 years of age with DS, whose seizures were incompletely controlled with previous anti-epileptic drugs. A Bayesian network meta-analysis was performed to compare fenfluramine with cannabidiol plus clobazam. There was no evidence of a difference between any doses of fenfluramine and cannabidiol in the mean convulsive seizure frequency (CSF) rate during treatment. However, fenfluramine increased the number of patients achieving ≥ 50% reduction in CSF frequency from baseline compared to cannabidiol. The company used an individual-patient state-transition model (R version 3.5.2) to model cost-effectiveness of fenfluramine. The CSF and convulsive seizure-free days were estimated using patient-level data from the placebo arm of the fenfluramine registration studies. Subsequently, a treatment effect of either fenfluramine or cannabidiol was applied. Utility values for the economic model were obtained by mapping Pediatric Quality of Life Inventory data from the registration studies to EuroQol-5D-3L Youth (EQ-5D-Y-3L). The company included caregiver utilities in their base-case, as the severe needs of patients with DS have a major impact on parents and caregivers. There were several key issues. First, the company included caregiver utilities in the model in a way that when patients in the economic model died, the corresponding caregiver utility was also set to zero. Second, the model was built in R statistical software, resulting in transparency issues. Third, the company assumed the same percentage reduction for convulsive seizure days as was estimated for CSF. Fourth, during the final appraisal committee meeting, influential changes were made to the model that were not in line with the ERG's preferences (but were accepted by the appraisal committee). The company's revised and final incremental cost effectiveness ratio (ICER) in line with committee preferences resulted in fenfluramine dominating cannabidiol. Fenfluramine was recommended as an add-on to other antiepileptic medicines for treating seizures associated with DS in people aged 2 years and older in the National Health Service (NHS).
Topics: Child; Humans; Adolescent; Cannabidiol; Bayes Theorem; Prospective Studies; Quality of Life; Retrospective Studies; State Medicine; Epilepsies, Myoclonic; Cost-Benefit Analysis; Technology Assessment, Biomedical; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic
PubMed: 36301414
DOI: 10.1007/s40273-022-01209-8 -
Medical Science Monitor : International... Aug 2021BACKGROUND Toll-like receptor 4 (TLR4) plays a pivotal role in the innate immune response and is hyperactivated in preeclampsia (PE). Several researchers have published... (Meta-Analysis)
Meta-Analysis
BACKGROUND Toll-like receptor 4 (TLR4) plays a pivotal role in the innate immune response and is hyperactivated in preeclampsia (PE). Several researchers have published conflicting evidence for TLR4 rs4986790 and rs4986791 single nucleotide polymorphisms (SNPs) as risk factors for PE. The present meta-analysis was conducted to obtain a more definitive conclusion about the effects of these SNPs on PE susceptibility. MATERIAL AND METHODS To determine the correlation between rs4986790 and rs4986791 polymorphisms in the TLR4 gene and susceptibility to PE, the PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure, and Chinese WANFANG databases were searched for eligible articles. Statistical analysis was performed with STATA software, version 12.0. Pooled odds ratios with corresponding 95% confidence intervals (CIs) were extracted for assessment of correlation strength. RESULTS We identified 5 studies including 578 cases and 631 controls for the rs4986790 SNP and 4 studies including 469 cases and 457 controls for the rs4986791 SNP, mainly from a White population. The pooled analyses showed no statistical relationship between the polymorphisms rs4986790 and rs4986791 and PE susceptibility in 5 genetic models (all P>0.05). Moreover, the allelic and dominant gene models of rs4986790 and the allelic, heterozygous, and dominant gene models of rs4986791 had high heterogeneity. The sensitivity analysis explored potential sources of heterogeneity and confirmed the findings of this meta-analysis. CONCLUSIONS TLR4 rs4986790 and rs4986791 polymorphisms may not be implicated in PE susceptibility, primarily in a White population. More high-quality studies of genetic associations with PE are warranted.
Topics: Female; Humans; Models, Genetic; Polymorphism, Single Nucleotide; Pre-Eclampsia; Pregnancy; Toll-Like Receptor 4
PubMed: 34334784
DOI: 10.12659/MSM.930438 -
Biomedicines Dec 2022Lafora disease (LD) is a neurodegenerative condition characterized by the accumulation of polyglucosan bodies (PBs) throughout the brain. Alongside metabolic and... (Review)
Review
BACKGROUND
Lafora disease (LD) is a neurodegenerative condition characterized by the accumulation of polyglucosan bodies (PBs) throughout the brain. Alongside metabolic and molecular alterations, neuroinflammation has emerged as another key histopathological feature of LD.
METHODS
To investigate the role of astrocytes and microglia in LD, we performed a systematic review according to the PRISMA statement. PubMed, Scopus, and Web-of-Science database searches were performed independently by two reviewers.
RESULTS
Thirty-five studies analyzing the relationship of astrocytes and microglia with LD and/or the effects of anti-inflammatory treatments in LD animal models were identified and included in the review. Although LD has long been dominated by a neuronocentric view, a growing body of evidence suggests a role of glial cells in the disease, starting with the finding that these cells accumulate PBs. We discuss the potential meaning of glial PB accumulations, the likely factors activating glial cells, and the possible contribution of glial cells to LD neurodegeneration and epilepsy.
CONCLUSIONS
Given the evidence for the role of neuroinflammation in LD, future studies should consider glial cells as a potential therapeutic target for modifying/delaying LD progression; however, it should be kept in mind that these cells can potentially assume multiple reactive phenotypes, which could influence the therapeutic response.
PubMed: 36551859
DOI: 10.3390/biomedicines10123103 -
PloS One 2015To compare efficacy and safety of laparoscopicnephrectomy (LN) versus open nephrectomy (ON) in the management of autosomal dominant polycystic kidney disease (ADPKD), we... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare efficacy and safety of laparoscopicnephrectomy (LN) versus open nephrectomy (ON) in the management of autosomal dominant polycystic kidney disease (ADPKD), we conducted a systematic review and meta-analysis.
METHODS
A systematic search of the electronic databases PubMed, Scopus, and the Cochrane Library was performed up to October 2014. This systematic review was performed based on observational comparative studies that assessed the two techniques. The weighted mean difference (WMD) and risk ratio (RR), with their corresponding 95% confidence interval (CI), were calculated to compare continuous and dichotomous variables, respectively.
RESULTS
Seven studies were identified, including 195 cases (118 LN/77 ON). Although LN was associated with longer operative time (WMD 30.236, 95%CI 14.541 -45.932, P<0.001) and the specimen might not have been resected as heavy as the ON group (WMD -986.516, 95%CI -1883.24--89.795, P = 0.031), patients in this group might benefit from a shorter length of hospital stay (WMD -3.576, 95%CI 4.976--2.176, P <0.001), less estimated blood loss (WMD -180.245, 95%CI -317.939--42.556, P = 0.010), and lower need of transfusion (RR 0.345, 95%CI 0.183-0.650, P = 0.001). The LN group also had less overall complications (RR 0.545, 95%CI 0.329-0.903, P = 0.018). The need of narcotic analgesics between the two groups might have no significant difference (WMD -54.66, 95%CI -129.76-20.44, P = 0.154).
CONCLUSION
LN for giant symptomatic ADPKD was feasible, safe and efficacious. Morbidity was significantly reduced compared with the open approach. For an experienced laparoscopist, LN might be a better alternative.
Topics: Blood Loss, Surgical; Blood Transfusion; Humans; Laparoscopy; Nephrectomy; Operative Time; Polycystic Kidney, Autosomal Dominant; Postoperative Complications; Treatment Outcome
PubMed: 26053633
DOI: 10.1371/journal.pone.0129317