Dardiotis, Efthimios*
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BACKGROUND: Randomized controlled trials (RCTs) are the best tool to evaluate the effectiveness of clinical interventions. The CONSORT (Consolidated Standards of Reporting Trials) statement is an evidence-based approach to improve the quality of RCTs reporting. OBJECTIVE: To evaluate the reporting quality of published RCTs concerning multiple sclerosis from 2000 to 2015 according to a checklist based on the CONSORT statement. METHODS: Electronic databases were searched for English-language RCTs involving patients with multiple sclerosis (MS). Trials were considered eligible when participants were randomly assigned to at least two medicinal treatment arms and included patients with MS. Quality of reporting was assessed using a 39-item questionnaire based on the CONSORT checklist. Articles were grouped in three 5-year periods and comparisons were made using descriptive statistics. RESULTS AND CONCLUSION: The search identified 102 eligible articles for analysis. 20 of the 38 items of the checklist (52.6%) were addressed in 75% or more of the studies. Reporting of more than 75% of CONSORT items (>75% CONSORT compliance) was increased during the three five-year time periods from 2000 to 2015 (p<0.05). CONCLUSIONS: Quality of reporting in RCTs focusing on multiple sclerosis is showing improvement over time, but still remains unsatisfactory. Further improvement of reporting is necessary to assess the validity of clinical research.
- MeSH
- impakt faktor časopisů MeSH
- lidé MeSH
- periodika jako téma MeSH
- publikování normy MeSH
- randomizované kontrolované studie jako téma normy MeSH
- roztroušená skleróza terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Although transcranial sonography is not yet an established diagnostic modality for dementia screening or differential diagnosis of Alzheimer's disease (AD) from vascular dementia (VaD), intracranial hemodynamic assessment may provide crucial information about the association between cognitive deterioration and vascular risk factors. We conducted a systematic narrative review of available literature through MEDLINE and EMBASE search to identify all available data about the evaluation of VaD patients with transcranial Doppler, and to discuss further the vascular disorders of the cerebral circulation in patients with vascular cognitive impairment. According to the available literature data to date, VaD patients were found to have lower mean flow velocity values in four studies (indicating cerebral hypoperfusion), higher pulsatility indices in three studies (indicating increased downstream vascular resistance), and more severe impairment of cerebrovascular reactivity in five studies (indicating exhausted vasodilatory reserve) compared to AD patients and controls. Microembolic signals were also found to be significantly more common in patients with VaD or AD compared to their age- and gender-matched controls, suggesting that asymptomatic microembolism, apart for being only marker of VaD, could presumably be involved in the genesis of dementia, and in the overlap between VaD and AD. Further studies with larger and carefully selected groups are required to eliminate potential confounders and to set specific cut-off values for the aforementioned hemodynamic parameters in demented patients and dementia subtypes.
- MeSH
- databáze faktografické statistika a číselné údaje MeSH
- kognitivní poruchy diagnóza etiologie MeSH
- lidé MeSH
- mozek patologie MeSH
- mozkový krevní oběh MeSH
- rizikové faktory MeSH
- ultrasonografie dopplerovská transkraniální * MeSH
- vaskulární demence ultrasonografie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
IMPORTANCE: A number of officially approved disease-modifying drugs (DMD) are currently available for the early intervention in patients with relapsing-remitting multiple sclerosis (RRMS). The aim of the present study was to systematically evaluate the effect of DMDs on disability progression in RRMS. METHODS: We performed a systematic review on MEDLINE and SCOPUS databases to include all available placebo-controlled randomized clinical trials (RCTs) of RRMS patients that reported absolute numbers or percentages of disability progression during each study period. Observational studies, case series, case reports, RCTs without placebo subgroups and studies reporting the use of RRMS therapies that are not still officially approved were excluded. Risk ratios (RRs) were calculated in each study protocol to express the comparison of disability progression in RRMS patients treated with a DMD and those RRMS patients receiving placebo. The mixed-effects model was used to calculate both the pooled point estimate in each subgroup and the overall estimates. RESULTS: DMDs for RRMS were found to have a significantly lower risk of disability progression compared to placebo (RR = 0.72, 95%CI: 0.66-0.79; p<0.001), with no evidence of heterogeneity or publication bias. In subsequent subgroup analyses, neither dichotomization of DMDs as "first" and "second" line RRMS therapies [(RR = 0.72, 95% CI = 0.65-0.80) vs. (RR = 0.72, 95% = 0.57-0.91); p = 0.96] nor the route of administration (injectable or oral) [RR = 0.75 (95% CI = 0.64-0.87) vs. RR = 0.74 (95% CI = 0.66-0.83); p = 0.92] had a differential effect on the risk of disability progression. Either considerable (5-20%) or significant (>20%) rates of loss to follow-up were reported in many study protocols, while financial and/or other support from pharmaceutical industries with a clear conflict of interest on the study outcomes was documented in all included studies. CONCLUSIONS: Available DMD are effective in reducing disability progression in patients with RRMS, independently of the route of administration and their classification as "first" or "second" line therapies. Attrition bias needs to be taken into account in the interpretation of these findings.
- MeSH
- imunosupresiva terapeutické užití MeSH
- lidé MeSH
- randomizované kontrolované studie jako téma MeSH
- relabující-remitující roztroušená skleróza farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
IMPORTANCE: A number of genetic loci were found to be associated with dystonia. Quite a few studies have been contacted to examine possible contribution of TOR1A variants to the risk of dystonia, but their results remain conflicting. The aim of the present study was to systematically evaluate the effect of TOR1A gene SNPs on dystonia and its phenotypic subtypes regarding the body distribution. METHODS: We performed a systematic review of Pubmed database to identify all available studies that reported genotype frequencies of TOR1A SNPs in dystonia. In total 16 studies were included in the quantitative analysis. Odds ratios (ORs) were calculated in each study to estimate the influence of TOR1A SNPs genotypes on the risk of dystonia. The fixed-effects model and the random effects model, in case of high heterogeneity, for recessive and dominant mode of inheritance as well as the free generalized odds ratio (ORG) model were used to calculate both the pooled point estimate in each study and the overall estimates. RESULTS: Rs1182 was found to be associated with focal dystonia in recessive mode of inheritance [Odds Ratio, OR (95% confidence interval, C.I.): 1.83 (1.14-2.93), Pz = 0.01]. In addition, rs1801968 was associated with writer's cramp in both recessive and dominant modes [OR (95%C.I.): 5.99 (2.08-17.21), Pz = 0.00009] and [2.48 (1.36-4.51), Pz = 0.003) respectively and in model free-approach [ORG (95%C.I.): 2.58 (1.45-4.58)]. CONCLUSIONS: Our meta-analysis revealed a significant implication of rs1182 and rs1801968 TOR1A variants in the development of focal dystonia and writer's cramp respectively. TOR1A gene variants seem to be implicated in dystonia phenotype.
- MeSH
- databáze faktografické MeSH
- dystonické poruchy genetika patologie MeSH
- dystonie genetika patologie MeSH
- genetická predispozice k nemoci MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- molekulární chaperony genetika MeSH
- odds ratio MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
BACKGROUND: Genetic variants appear to influence, at least to some degree, the extent of brain injury and the clinical outcome of patients who have sustained a traumatic brain injury (TBI). Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase that is implicated in the regulation of blood pressure and cerebral circulation. ACE gene polymorphisms were found to regulate serum ACE enzyme activity. OBJECTIVE: The present study aimed to investigate possible influence of ACE gene region variants on patients' outcome after TBI. PATIENTS AND METHODS: In total, 363 TBI patients prospectively enrolled in the study were genotyped for five tag single nucleotide polymorphisms (SNPs) across the ACE gene. Using logistic regression analyses, tag SNPs and their constructed haplotypes were tested for associations with 6-month Glasgow Outcome Scale scores, after adjustment for age, sex, Glasgow Coma Scale scores at admission, and the presence of a hemorrhagic event in the initial computed tomography scan. RESULTS: Significant effects on TBI outcome were found for three neighboring tag SNPs in the codominant (genotypic) model of inheritance [rs4461142: odds ratio (OR) 0.26, 95% confidence interval (CI) 0.12-0.57, P = 0.0001; rs7221780: OR 2.67, 95% CI 1.25-5.72, P = 0.0003; and rs8066276: OR 3.82, 95% CI 1.80-8.13, P = 0.0002; for the heterozygous variants compared with the common alleles]. None of the constructed common tag SNPs haplotypes was associated with TBI outcome. CONCLUSION: The present study provides evidence of the possible influence of genetic variations in a specific region of the ACE gene on the outcome of TBI patients. This association may have pharmacogenetic implications in identifying those TBI patients who may benefit from ACE inhibition.
- MeSH
- alely MeSH
- angiotensin konvertující enzym genetika MeSH
- demografie MeSH
- dospělí MeSH
- frekvence genu genetika MeSH
- genetické lokusy MeSH
- Glasgowská stupnice kómat MeSH
- haplotypy MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- multivariační analýza MeSH
- poranění mozku genetika MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Α limited number of genetic variants have been linked to the development of intracerebral hemorrhage (ICH). Ιntegrin AV and/or B8-deficient mice were found to develop ICH. The present candidate gene association study was designed to investigate possible influence of integrin AV (ITGAV) and integrin B8 (ITGB8) gene region polymorphisms on the risk of ICH. 1015 participants (250 Greek and 193 Polish patients with primary ICH and 250 Greek and 322 Polish controls) were included in the study. Using logistic regression analyses, 11 tag single nucleotide polymorphisms (SNPs) for ITGAV and 11 for ITGB8 gene were tested for associations with ICH risk, lobar ICH risk and non-lobar ICH after adjustment for age, gender, history of hypertension and country of origin. Linear regression models were used to test the effect of tag SNPs on the ICH age of onset. Correction for multiple comparisons was carried out. The rs7565633 tag SNP of the ITGAV gene was independently associated with the risk of lobar ICH in the codominant model of inheritance [odds ratio (95 % confidence interval (CI)) 0.56 (0.36-0.86), p = 0.0013]. Furthermore, heterozygous individuals of the rs10251386 and the rs10239099 of the ITGB8 gene had significantly lower age of ICH onset compared to the wild-type genotypes [regression coefficient (b) -3.884 (95 % CI -6.519, -1.249), p = 0.0039 and b = -4.502 (95 % CI -7.159, -1.845), p = 0.0009, respectively]. The present study provides preliminary indication for an influence of ITGAV gene tag SNP in the development of lobar ICH and of ITGB8 gene variants in the age of ICH onset.
- MeSH
- beta řetězce integrinu genetika MeSH
- cerebrální krvácení etnologie genetika MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- integrin alfaV genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozková kůra krevní zásobení MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- věk při počátku nemoci MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Polsko epidemiologie MeSH
- Řecko epidemiologie MeSH