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Journal of Periodontology Jan 2021The peri-implant soft tissue phenotype (PSP) encompasses the keratinized mucosa width (KMW), mucosal thickness (MT), and supracrestal tissue height (STH). Numerous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The peri-implant soft tissue phenotype (PSP) encompasses the keratinized mucosa width (KMW), mucosal thickness (MT), and supracrestal tissue height (STH). Numerous approaches to augment soft tissue volume around endosseous dental implants have been investigated. To what extent PSP modification is beneficial for peri-implant health has been subject of debate in the field of implant dentistry. The aim of this systematic review was to analyze the evidence regarding the efficacy of soft tissue augmentation procedures aimed at modifying the PSP and their impact on peri-implant health.
METHODS
A comprehensive search was performed to identify clinical studies that involved soft tissue augmentation around dental implants and reported findings on KMW, MT, and/or STH changes. The effect of the intervention on peri-implant health was also assessed. Selected articles were classified based on the general type of surgical approach to increase PSP, either bilaminar or an apically positioned flap (APF) technique. A network meta-analysis including only randomized-controlled trials (RCTs) reporting on PSP outcomes was conducted to assess and compare different techniques.
RESULTS
A total of 52 articles were included in the qualitative analysis, and 23 RCTs were included as part of the network meta-analysis. Sixteen RCTs reported the outcomes of PSP modification therapy with bilaminar techniques, whereas 7 involved the use of APF. The analysis showed that bilaminar techniques in combination with soft tissue grafts (connective tissue graft [CTG], collagen matrix [CM], and acellular dermal matrix [ADM]) resulted in a significant increase in MT compared to non-augmented sites. In particular, CTG and ADM were associated with higher MT gain as compared to CM and non-augmented sites. However, no significant differences in KMW were observed across different bilaminar techniques. PSP modification via a bilaminar approach utilizing either CTG or CM showed beneficial effects on marginal bone level stability. APF-based approaches in combination with free gingival graft (FGG), CTG, CM, or ADM showed a significant KMW gain compared to non-augmented sites. However, compared to APF alone, only FGG exhibited a significantly higher KMW gain. APF with any evaluated soft tissue graft was associated with with reduction of probing depth, soft tissue dehiscence and plaque index compared to non-augmented sites compared to non-augmented sites. The evidence regarding the effect of PSP modification via APF-based approaches on peri-implant marginal bone loss or preservation is inconclusive.
CONCLUSIONS
Bilaminar approach involving CTG or ADM obtained the highest amount of MT gain, whereas APF in combination with FGG was the most effective technique for increasing KMW. KMW augmentation via APF was associated with a significant reduction in probing depth, soft tissue dehiscence and plaque index, regardless of the soft tissue grafting material employed, whereas bilaminar techniques with CTG or CM showed beneficial effects on marginal bone level stability.
Topics: Connective Tissue; Dental Implants; Gingiva; Network Meta-Analysis; Phenotype
PubMed: 32710810
DOI: 10.1002/JPER.19-0716 -
International Journal of Infectious... Sep 2022Dengue infection is a growing public health problem, with the number of reported cases increasing in the Americas and worldwide. This review characterized the... (Review)
Review
OBJECTIVES
Dengue infection is a growing public health problem, with the number of reported cases increasing in the Americas and worldwide. This review characterized the epidemiological and economic burden of dengue in Brazil.
METHODS
Embase, MEDLINE, evidence-based review databases, and gray literature sources were searched for published literature and surveillance reports on epidemiology (between 2000 and 2019) and costs (between 2009 and 2019) of dengue in Brazil. Studies were included if they reported data on incidence, seroprevalence, serotype distribution, expansion factors, hospitalization, mortality, or costs. Data were summarized descriptively and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
RESULTS
A total of 344 publications were included (167 peer-reviewed and 177 gray literature). Dengue outbreaks increased in incidence and frequency, with the highest incidence observed in 2015 at 807 cases per 100,000 population. Outbreaks were related to alternating predominant serotypes. Dengue was more frequent in young adults (aged 20-39 years) and in the Midwest. Cost and societal impacts are substantial and varied across regions, age, and public/private delivery of healthcare services.
CONCLUSION
The burden of dengue in Brazil is increasing and likely underestimated. Therefore, developing and implementing new strategies, including vaccination, is essential to reduce the disease burden.
Topics: Brazil; Dengue; Disease Outbreaks; Humans; Seroepidemiologic Studies; Serogroup; Young Adult
PubMed: 35793756
DOI: 10.1016/j.ijid.2022.06.050 -
Journal of Periodontology Nov 2020The periodontal phenotype consists of the bone morphotype, the keratinized tissue (KT), and gingival thickness (GT). The latter two components, overlying the bone,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The periodontal phenotype consists of the bone morphotype, the keratinized tissue (KT), and gingival thickness (GT). The latter two components, overlying the bone, constitute the gingival phenotype. Several techniques have been proposed for enhancing or augmenting KT or GT. However, how phenotype modification therapy (PMT) affects periodontal health and whether the obtained outcomes are maintained over time have not been elucidated. The aim of the present review was to summarize the available evidence in regard to the utilized approaches for gingival PMT and assess their comparative efficacy in augmenting KT, GT and in improving periodontal health using autogenous, allogenic, and xenogeneic grafting approaches.
METHODS
A detailed systematic search was performed to identify eligible randomized clinical trials (RCTs) reporting on the changes in GT and KT (primary outcomes). The selected articles were segregated into the type of approach based on having performed a root coverage, or non-root coverage procedure. A network meta-analysis (NMA) was conducted for each approach to assess and compare the outcomes among different treatment arms for the primary outcomes.
RESULTS
A total of 105 eligible RCTs were included. 95 pertaining to root coverage (3,539 treated gingival recessions [GRs]), and 10 for non-root coverage procedures (699 total treated sites). The analysis on root coverage procedures showed that all investigated techniques (the acellular dermal matrix [ADM], collagen matrix [CM], connective tissue graft [CTG]) are able to significantly increase the GT, compared with treatment with flap alone. However, KT was only significantly increased with the use of CTG or ADM. Early post-treatment GT was found to inversely predict future GR. For non-root coverage procedures, only the changes in KT could be analyzed; all investigated treatment groups (ADM, CM, free gingival graft [FGG], living cellular construct [LCC], in combination with an apically positioned flap [APF]), resulted in significantly more KT than treatment with APF alone. Additionally, the augmented GT was shown to be sustained, and KT displayed an incremental increase over time.
CONCLUSIONS
Within its limitations, it was observed that any graft material was able to significantly enhance GT, while KT in root coverage procedures was significantly enhanced with CTG and ADM, and in non-root coverage procedures, with ADM, CM, FGG, and LCC compared with APF alone. The autogenous soft tissue graft (CTG/FGG) proved to be superior in all comparisons for both outcomes of GT and KT.
Topics: Connective Tissue; Gingiva; Gingival Recession; Humans; Network Meta-Analysis; Phenotype; Tooth Root; Treatment Outcome
PubMed: 32392401
DOI: 10.1002/JPER.19-0715 -
Scientific Reports Nov 2021Molar-Incisor Hypomineralization (MIH) is a qualitative defect of enamel of unknown etiology, affecting one or more permanent molars and may include incisors. This... (Meta-Analysis)
Meta-Analysis
Molar-Incisor Hypomineralization (MIH) is a qualitative defect of enamel of unknown etiology, affecting one or more permanent molars and may include incisors. This condition is a clinical challenge and its prevalence is still uncertain given the recent increase in research. Thus, we aimed to comprehensively estimate the overall prevalence of MIH and associated characteristics. This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). We searched articles using PubMed, MEDLINE, CENTRAL, Web of Science, SciELO, LILACS and TRIP databases, until July 2021. Heterogeneity and publication bias were computed via I test statistics and Egger's significance test, respectively. Random-effects meta-analysis of prevalence were processed. We used the Strength of Recommendation Taxonomy [SORT] to grading the strength of evidence. Overall, 116 observational studies were included, with one study with moderate methodological quality and the remaining of high methodological quality. Subgroup analysis confirmed an influence of not using the 2003 MIH case definition (p = 0.0066). The pooled prevalence of MIH was 13.5% (95% CI 12.0-15.1, I = 98.0%). Affected incisors were seen in 36.6% (95% CI 30.0-43.7, I = 92.5%) of the cases. Lastly, the prevalence of hypomineralization of the second primary molars was observed in 3.6% of the MIH cases (95% CI 1.9-6.8, I = 96.3%). America was the continent with highest prevalence (15.3, 95% CI 12.8-18.3, p < 0.001, I = 96.3%) and Asia had the lowest prevalence (10.7, 95% CI 8.5-13.5, p < 0.001, I = 98.7%), however no continental differences were found. Sample size and year of publication were slight contributing factors to the heterogeneity in the analysis. Overall, these results were classified with a SORT A recommendation.
Topics: Dental Enamel Hypoplasia; Disease Susceptibility; Genetic Predisposition to Disease; Global Health; Humans; Incisor; Molar; Phenotype; Population Surveillance; Prevalence; Risk Factors; Severity of Illness Index; Sex Factors
PubMed: 34789780
DOI: 10.1038/s41598-021-01541-7 -
Applied and Environmental Microbiology Jul 2019spp. are among the most important foodborne pathogens and the third leading cause of human death among diarrheal diseases worldwide. Animals are the primary source of... (Meta-Analysis)
Meta-Analysis
spp. are among the most important foodborne pathogens and the third leading cause of human death among diarrheal diseases worldwide. Animals are the primary source of this pathogen, and animal-based foods are the main transmission route to humans. Thus, understanding the global epidemiology of serovars is key to controlling and monitoring this bacterium. In this context, this study aimed to evaluate the prevalence and diversity of serovars in animal-based foods (beef, pork, poultry, and seafood) throughout the five continents (Africa, the Americas [North and Latin America], Asia, Europe, and Oceania). The meta-analysis consisted of a chemometric assessment (hierarchical cluster analysis and principal component analysis) to identify the main epidemiological findings, including the prevalence and diversity of the serovars in each matrix. Regarding the serovar distribution, Typhimurium presented a cosmopolitan distribution, reported in all four assessed matrices and continents; poultry continues to play a central role in the dissemination of the Enteritidis serovar to humans, and Anatum and Weltevreden were the most frequently found in beef and seafood, respectively. Additionally, we recommended careful monitoring of certain serovars, such as Derby, Agona, Infantis, and Kentucky. Finally, given the scientific data regarding the most frequently reported serovars and which matrices constitute the main vehicles for the transmission of this pathogen, control programs may be improved, and specific interventions may be implemented in an attempt to reduce the risk of this pathogen reaching humans. Salmonellosis is caused by spp. and is the third leading cause of death among food-transmitted diseases. This pathogen is commonly disseminated in domestic and wild animals, and the infection's symptoms are characterized by acute fever, nausea, abdominal pain, and diarrhea. The animals are the primary source of salmonellae, and animal-based foods are the main transmission route to humans. Therefore, data collected from these sources could contribute to future global interventions for effective control and surveillance of along the food chain. In light of this, the importance of our research is in identifying the prevalence of serovars in four animal-based food matrices (pork, poultry, beef, and seafood) and to evaluate the importance that each matrix has as the primary source of this pathogen to humans.
Topics: Animals; Food Microbiology; Prevalence; Salmonella Infections, Animal; Salmonella enterica; Serogroup
PubMed: 31053586
DOI: 10.1128/AEM.00591-19 -
The American Journal of Psychiatry Jan 2023The aim of this study was to catalog and evaluate response biomarkers correlated with autism spectrum disorder (ASD) symptoms to improve clinical trials. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The aim of this study was to catalog and evaluate response biomarkers correlated with autism spectrum disorder (ASD) symptoms to improve clinical trials.
METHODS
A systematic review of MEDLINE, Embase, and Scopus was conducted in April 2020. Seven criteria were applied to focus on original research that includes quantifiable response biomarkers measured alongside ASD symptoms. Interventional studies or human studies that assessed the correlation between biomarkers and ASD-related behavioral measures were included.
RESULTS
A total of 5,799 independent records yielded 280 articles for review that reported on 940 biomarkers, 755 of which were unique to a single publication. Molecular biomarkers were the most frequently assayed, including cytokines, growth factors, measures of oxidative stress, neurotransmitters, and hormones, followed by neurophysiology (e.g., EEG and eye tracking), neuroimaging (e.g., functional MRI), and other physiological measures. Studies were highly heterogeneous, including in phenotypes, demographic characteristics, tissues assayed, and methods for biomarker detection. With a median total sample size of 64, almost all of the reviewed studies were only powered to identify biomarkers with large effect sizes. Reporting of individual-level values and summary statistics was inconsistent, hampering mega- and meta-analysis. Biomarkers assayed in multiple studies yielded mostly inconsistent results, revealing a "replication crisis."
CONCLUSIONS
There is currently no response biomarker with sufficient evidence to inform ASD clinical trials. This review highlights methodological imperatives for ASD biomarker research necessary to make definitive progress: consistent experimental design, correction for multiple comparisons, formal replication, sharing of sample-level data, and preregistration of study designs. Systematic "big data" analyses of multiple potential biomarkers could accelerate discovery.
Topics: Humans; Autism Spectrum Disorder; Biomarkers; Phenotype; Magnetic Resonance Imaging; Research Design
PubMed: 36475375
DOI: 10.1176/appi.ajp.21100992 -
European Journal of Medical Genetics Oct 2021Hereditary Diffuse Gastric Cancer (HDGC) is a cancer predisposing syndrome mainly caused by germline inactivating variants in CDH1, encoding E-cadherin. Early-onset...
Hereditary Diffuse Gastric Cancer (HDGC) is a cancer predisposing syndrome mainly caused by germline inactivating variants in CDH1, encoding E-cadherin. Early-onset diffuse gastric cancer (DGC) and/or invasive lobular breast cancer (LBC) are the main phenotypes in CDH1-associated HDGC. CTNNA1, encoding for α-E-catenin, and E-cadherin-partner in the adherens junction complex, has been recently classified as a HDGC predisposing gene. Nevertheless, little is known about CTNNA1 tumor spectrum in variant carriers and variant-type associated causality. Herein, we systematically reviewed the literature searching for CTNNA1 germline variants carriers, further categorized them according to HDGC clinical criteria (HDGC vs non-HDGC), collected phenotypes, classified variants molecularly and according to CDH1 ACMG/AMP guidelines and performed genotype-phenotype analysis. We found 41 families carrying CTNNA1 germline variants encompassing in total 105 probands and relatives. All probands from 13 HDGC families presented DGC and their average age of onset was 40 ± 17 years; 10/13 (77%) HDGC families carried a pathogenic (P) variant. Most probands from 28 non-HDGC families developed unspecified-BC, as well as most of their relatives; 4/28 (14%) carried a P variant, 16/28 (57%) carried a likely pathogenic (LP) variant, 7/28 (25%) carried variants of unknown significance (VUS) and 1/28 (4%) carried a likely benign variant. Regardless of clinical criteria, 97% (32/33) of probands and relatives from P variant-carrier families had DGC/unspecified-GC. In LP variant-carrier families, 82% (28/34) of probands and relatives had unspecified-BC. Only 2/105 individuals had LBC. A cluster of frameshift and nonsense variants was found in CTNNA1 last exon of non-HDGC families and classified as VUS. In conclusion, current available data confirms an association of CTNNA1 P variants with early-onset DGC, but not with LBC. We demonstrate that in ascertained cohorts, CTNNA1 P variants explain <2% of HDGC families and support the use of ACMG/AMP CDH1 specific variant curation guidelines, while no specific guidelines are developed for CTNNA1 variant classification. Moreover, we demonstrated that truncating variants at the CTNNA1 NMD-incompetent last exon have limited deleteriousness, and that CTNNA1 LP variants have lower actionability than CDH1 LP variants. Current knowledge supports considering only CTNNA1 P variants as clinically actionable in HDGC carrying families.
Topics: Antigens, CD; Cadherins; Gene Frequency; Genetic Predisposition to Disease; Germ-Line Mutation; Heterozygote; Humans; Pedigree; Phenotype; Stomach Neoplasms; alpha Catenin
PubMed: 34425242
DOI: 10.1016/j.ejmg.2021.104316 -
Journal of the European Academy of... Jun 2022Atopic dermatitis is a heterogeneous disease, accompanied by a wide variation in disease presentation and the potential to identify many phenotypes that may be relevant... (Review)
Review
Atopic dermatitis is a heterogeneous disease, accompanied by a wide variation in disease presentation and the potential to identify many phenotypes that may be relevant for prognosis and treatment. We aimed to systematically review previously reported phenotypes of atopic dermatitis and any characteristics associated with them. Ovid EMBASE, Ovid MEDLINE and Web of Science were searched from inception till 12 February 2021 for studies attempting to classify atopic dermatitis. Primary outcomes are atopic dermatitis phenotypes and characteristics associated with them in subsequent analyses. A secondary outcome is the methodological approach used to derive them. In total, 8511 records were found. By focussing only on certain clinical phenotypes, 186 studies were eligible for inclusion. The majority of studies were hospital-based (59%, 109/186) and cross-sectional (76%, 141/186). The number of included patients ranged from seven to 526 808. Data-driven approaches to identify phenotypes were only used in a minority of studies (7%, 13/186). Ninety-one studies (49%) investigated a phenotype based on disease severity. A phenotype based on disease trajectory, morphology and eczema herpeticum was investigated in 56 (30%), 22 (12%) and 11 (6%) studies respectively. Thirty-six studies (19%) investigated morphological characteristics in other phenotypes. Investigated associated characteristics differed between studies. In conclusion, we present an overview of phenotype definitions used in literature for severity, trajectory, morphology and eczema herpeticum, including associated characteristics. There is a lack of uniform and consistent use of atopic dermatitis phenotypes across studies.
Topics: Cross-Sectional Studies; Dermatitis, Atopic; Eczema; Humans; Kaposi Varicelliform Eruption; Phenotype; Severity of Illness Index
PubMed: 35170821
DOI: 10.1111/jdv.18008 -
European Journal of Heart Failure Dec 2022An algorithm for non-invasive diagnosis of amyloid transthyretin cardiac amyloidosis (ATTR-CA) and novel disease-modifying therapies have prompted an active search for... (Meta-Analysis)
Meta-Analysis
AIMS
An algorithm for non-invasive diagnosis of amyloid transthyretin cardiac amyloidosis (ATTR-CA) and novel disease-modifying therapies have prompted an active search for CA. We examined the prevalence of CA in different settings based on literature data.
METHODS AND RESULTS
We performed a systematic search for screening studies on CA, focusing on the prevalence, sex and age distribution in different clinical settings. The prevalence of CA in different settings was as follows: bone scintigraphy for non-cardiac reasons (n = 5 studies), 1% (95% confidence interval [CI] 0%-1%); heart failure with preserved ejection fraction (n = 6), 12% (95% CI 6%-20%); heart failure with reduced or mildly reduced ejection fraction (n = 2), 10% (95% CI 6%-15%); conduction disorders warranting pacemaker implantation (n = 1), 2% (95% CI 0%-4%); surgery for carpal tunnel syndrome (n = 3), 7% (95% CI 5%-10%); hypertrophic cardiomyopathy phenotype (n = 2), 7% (95% CI 5%-9%); severe aortic stenosis (n = 7), 8% (95% CI 5%-13%); autopsy series of 'unselected' elderly individuals (n = 4), 21% (95% CI 7%-39%). The average age of CA patients in the different settings ranged from 74 to 90 years, and the percentage of men from 50% to 100%. Many patients had ATTR-CA, but the average percentage of patients with amyloid light-chain (AL) CA was up to 18%.
CONCLUSIONS
Searching for CA in specific settings allows to identify a relatively high number of cases who may be eligible for treatment if the diagnosis is unequivocal. ATTR-CA accounts for many cases of CA across the different settings, but AL-CA is not infrequent. Median age at diagnosis falls in the eighth or ninth decades, and many patients diagnosed with CA are women.
Topics: Female; Male; Humans; Heart Failure; Amyloidosis; Amyloid; Phenotype; Ventricular Dysfunction, Left; Cardiomyopathies
PubMed: 35509173
DOI: 10.1002/ejhf.2532 -
Brain : a Journal of Neurology Dec 2022Pathogenic variants in the voltage-gated sodium channel gene family lead to early onset epilepsies, neurodevelopmental disorders, skeletal muscle channelopathies,...
Pathogenic variants in the voltage-gated sodium channel gene family lead to early onset epilepsies, neurodevelopmental disorders, skeletal muscle channelopathies, peripheral neuropathies and cardiac arrhythmias. Disease-associated variants have diverse functional effects ranging from complete loss-of-function to marked gain-of-function. Therapeutic strategy is likely to depend on functional effect. Experimental studies offer important insights into channel function but are resource intensive and only performed in a minority of cases. Given the evolutionarily conserved nature of the sodium channel genes, we investigated whether similarities in biophysical properties between different voltage-gated sodium channels can predict function and inform precision treatment across sodium channelopathies. We performed a systematic literature search identifying functionally assessed variants in any of the nine voltage-gated sodium channel genes until 28 April 2021. We included missense variants that had been electrophysiologically characterized in mammalian cells in whole-cell patch-clamp recordings. We performed an alignment of linear protein sequences of all sodium channel genes and correlated variants by their overall functional effect on biophysical properties. Of 951 identified records, 437 sodium channel-variants met our inclusion criteria and were reviewed for functional properties. Of these, 141 variants were epilepsy-associated (SCN1/2/3/8A), 79 had a neuromuscular phenotype (SCN4/9/10/11A), 149 were associated with a cardiac phenotype (SCN5/10A) and 68 (16%) were considered benign. We detected 38 missense variant pairs with an identical disease-associated variant in a different sodium channel gene. Thirty-five out of 38 of those pairs resulted in similar functional consequences, indicating up to 92% biophysical agreement between corresponding sodium channel variants (odds ratio = 11.3; 95% confidence interval = 2.8 to 66.9; P < 0.001). Pathogenic missense variants were clustered in specific functional domains, whereas population variants were significantly more frequent across non-conserved domains (odds ratio = 18.6; 95% confidence interval = 10.9-34.4; P < 0.001). Pore-loop regions were frequently associated with loss-of-function variants, whereas inactivation sites were associated with gain-of-function (odds ratio = 42.1, 95% confidence interval = 14.5-122.4; P < 0.001), whilst variants occurring in voltage-sensing regions comprised a range of gain- and loss-of-function effects. Our findings suggest that biophysical characterisation of variants in one SCN-gene can predict channel function across different SCN-genes where experimental data are not available. The collected data represent the first gain- versus loss-of-function topological map of SCN proteins indicating shared patterns of biophysical effects aiding variant analysis and guiding precision therapy. We integrated our findings into a free online webtool to facilitate functional sodium channel gene variant interpretation (http://SCN-viewer.broadinstitute.org).
Topics: Animals; Channelopathies; Peripheral Nervous System Diseases; Voltage-Gated Sodium Channels; Epilepsy; Phenotype; Mammals
PubMed: 35037686
DOI: 10.1093/brain/awac006