scholarly journals Estudo Genético nas Distonias Primárias: Recomendações do Grupo de Neurogenética do Centro Hospitalar São João

2017 ◽  
Vol 30 (4) ◽  
pp. 340
Author(s):  
Ana Monteiro ◽  
João Massano ◽  
Miguel Leão ◽  
Carolina Garrett ◽  
Em nome do Grupo de Neurogenética do Centro Hospitalar São João
Keyword(s):  
Clinical Practice ◽  
Age Of Onset ◽  
Scientific Evidence ◽  
Low Frequency ◽  
Gene Mutations ◽  
Molecular Testing ◽  
International Consensus ◽  
Group A ◽  
Neurogenetic Disorders ◽  
The Cost

The primary dystonias are a particular group of dystonias of presumed genetic origin, with a wide age of onset and variable progression. The diagnosis is, therefore, a challenge and the issue of the genetic investigation presents frequently in clinical practice. In the past few years several gene mutations have been identified as causative of primary dystonias. The choice of molecular testing is complex, given the clinical specificities and low frequency of these entities and the cost of genetic testing. It must follow observation by specialized clinicians highly differentiated in this area and be supported by a rational plan of investigation. The Centro Hospitalar São João Neurogenetics Group, a multidisciplinary team of Neurologists and Geneticists with special interest in neurogenetic disorders, devised consensus recommendations for the investigation of the genetic etiology of the primary dystonias, based on international consensus documents and recent published scientific evidence. This manuscript adopts the new classification system for genetic movement disorders, allowing for its systematic and standardized use in clinical practice.

scholarly journals Investigação de Etiologia Genética nas Demências Neurodegenerativas: Recomendações do Grupo de Neurogenética do Centro Hospitalar São João

2016 ◽  
Vol 29 (10) ◽  
pp. 675
Author(s):  
João Massano ◽  
Miguel Leão ◽  
Carolina Garrett ◽  
On behalf of Grupo de Neurogenética do Centro Hospitalar São João
Keyword(s):  
Alzheimer Disease ◽  
Frontotemporal Dementia ◽  
Scientific Evidence ◽  
Genetic Diagnosis ◽  
Gene Mutations ◽  
Genetic Etiology ◽  
International Consensus ◽  
Group A ◽  
Neurogenetic Disorders ◽  
Neurodegenerative Dementias

In the past few years several gene mutations have been identified as causative of the most frequent neurodegenerative dementias (Alzheimer disease and frontotemporal dementia). These advances, along with the complex phenotype-genotype relationships and the costs associated with genetic testing, have often made it difficult for clinicians to decide with regard to a rational plan for the investigation of the genetic etiology of the degenerative dementias. The Centro Hospitalar São João Neurogenetics Group, a multidisciplinary team of Neurologists and Geneticists with special interest in neurogenetic disorders, devised consensus recommendations for the investigation of the genetic etiology of Alzheimer disease and frontotemporal dementia in clinical practice, based on international consensus documents (currently containing partly outdated information) and published scientific evidence on this topic. Alzheimerdisease may be caused by mutations in PSEN1, PSEN2 and APP. APOE genotyping is not recommended for the diagnostic or genetic counseling purposes in Alzheimer disease. Frontotemporal dementia may be caused by mutations in several genes such as c9orf72, PGRN, MAPT, TBK1, VCP, SQSTM1, and UBQLN2. This paper pragmatically approaches the process of genetic diagnosis in Alzheimer disease and frontotemporal dementia, with specific recommendations for both disorders.

scholarly journals Investigação de Etiologia Genética nas Ataxias Neurodegenerativas: Recomendações do Grupo de Neurogenética do Centro Hospitalar São João, Portugal

2017 ◽  
Vol 30 (6) ◽  
pp. 502
Author(s):  
Tiago Gomes ◽  
Joana Guimaraes ◽  
Miguel Leão ◽  
Em nome do Grupo de Neurogenética do Centro Hospitalar São João
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Scientific Evidence ◽  
Genetic Diagnosis ◽  
Clinical History ◽  
International Consensus ◽  
Neurogenetic Disorders ◽  
Rational Plan ◽  
Rational Process

In recent decades, a long and increasing list of monogenic neurodegenerative ataxias has been identified, allowing for better characterization of the pathophysiology, phenotype and prognosis of this heterogeneous group of disorders, while also revealing potential new therapeutic targets. However, the heterogeneity and complexity of the genotype-phenotype relationships and the high costs of molecular genetics often make it difficult for clinicians to decide on a molecular investigation based on an unbiased rational plan. Clinical history is essential to guide the diagnostic workup, but often the phenotype does not hold enough specificity to allow for predicting the genotype. The Group of Neurogenetics of the Centro Hospitalar São João, a multidisciplinary team of neurologists and geneticists with special interest in neurogenetic disorders, devised consensus recommendations for the investigation of the genetic aetiology of neurodegenerative ataxias in clinical practice, based on international consensus documents (currently containing potentially outdated information) and published scientific evidence on this topic. At the time these recommendations were written, there were around 10 well described autosomal recessive loci and more than 27 autosomal dominant loci for neurodegenerative ataxias. This document covers, in a pragmatic way, the rational process used for the genetic diagnosis of neurodegenerative ataxias, with specific recommendations for the various groups of these heterogeneous diseases, per the Portuguese reality.

Molecular diagnostic testing patterns in patients (pts) with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) in the Connect MDS/AML Registry.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 7553-7553
Author(s):  
Tracy George ◽  
Jay L. Patel ◽  
Mehrdad Abedi ◽  
Christopher R. Cogle ◽  
Harry Paul Erba ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Diagnostic Testing ◽  
Gene Mutations ◽  
Integrated Approach ◽  
Geographic Region ◽  
Molecular Diagnostic ◽  
Molecular Testing ◽  
Factors Associated ◽  
The Impact ◽  
Testing Patterns

7553 Background: MDS and AML diagnosis requires an integrated approach including morphologic, cytogenetic and molecular testing. The WHO classification criteria for MDS and AML diagnosis were updated in 2016; however, the impact on clinical practice is unclear. We investigated molecular testing patterns for pts with MDS or AML treated in academic (AC) or community/government (CO/GOV)-based centers in the Connect MDS/AML Registry. Methods: The Connect MDS/AML Disease Registry (NCT01688011) is a large ongoing, US, multicenter, prospective observational cohort study of pts with MDS (aged ≥ 18 yrs) or AML (aged ≥ 55 yrs). Patient data were collected for this analysis upon enrollment from 12 Dec 2013 to 13 Dec 2019, the analysis cut-off. Differences in molecular testing between MDS and AML pts were evaluated and logistic regression used to assess factors associated with increased molecular testing. Results: As of 13 Dec 2019, 800 MDS pts and 626 AML pts were enrolled; median age was 74 vs 71 yrs, 66.3% vs 61.5% were male, and 73.5% vs 60.2% were insured by Medicare/Medicaid. A greater proportion of AML pts (77.5%) had molecular testing vs MDS pts (29.1%). Of 380 MDS pts enrolled before 2017 (< 2017), 16.8% had molecular testing, increasing to 40.2% in 420 MDS pts enrolled from 2017 onward (≥ 2017). Of 289 AML pts enrolled < 2017, 68.9% had molecular testing, increasing to 84.9% in 337 AML pts enrolled ≥ 2017. Mean number of mutations tested increased between < 2017 and ≥ 2017 from 6.9 to 12.7 in MDS pts and from 6.1 to 10.4 in AML pts. Of the 11 mutations most frequently tested ≥ 2017 in MDS and AML pts, 0% and 36%, respectively, have FDA-approved targeted therapies. Gene mutations tested differed between MDS and AML pts; ASXL1 was most frequently tested in MDS pts (68.2%) and FLT3-ITD in AML pts (89.7%). Testing rates increased between < 2017 and ≥ 2017 for ASXL1 from 48.4% to 75.7% in MDS pts and for FLT3-ITD from 84.4% to 93.4% in AML pts. Factors associated with increased testing were age < 75 (vs ≥ 75) yrs, ELN score ≥ 2 (vs 1) and enrollment at AC site (vs CO/GOV) (all P < 0.01) in AML pts and age < 80 (vs ≥ 80 yrs; P < 0.01), AC site (vs CO/GOV; P < 0.01), and geographic region outside the Midwest ( P = 0.015) in MDS pts. Conclusions: While molecular testing rates have increased since the publication of the WHO 2016 criteria, molecular testing rates for MDS pts remain lower than those for AML pts in real-world clinical practice. Elderly pts and pts enrolled in CO/GOV sites were found to have lower rates of molecular testing in both MDS and AML patient cohorts.

scholarly journals Standardizing nomenclature in regional anesthesia: an ASRA-ESRA Delphi consensus study of abdominal wall, paraspinal, and chest wall blocks

2021 ◽  
Vol 46 (7) ◽  
pp. 571-580
Author(s):  
Kariem El-Boghdadly ◽  
Morné Wolmarans ◽  
Angela D Stengel ◽  
Eric Albrecht ◽  
Ki Jinn Chin ◽  
...  
Keyword(s):  
Education Research ◽  
Clinical Practice ◽  
Abdominal Wall ◽  
Chest Wall ◽  
Round Table Discussion ◽  
Anesthetic Techniques ◽  
Delphi Consensus ◽  
International Consensus ◽  
Strong Consensus ◽  
Regional Anesthetic

BackgroundThere is heterogeneity in the names and anatomical descriptions of regional anesthetic techniques. This may have adverse consequences on education, research, and implementation into clinical practice. We aimed to produce standardized nomenclature for abdominal wall, paraspinal, and chest wall regional anesthetic techniques.MethodsWe conducted an international consensus study involving experts using a three-round Delphi method to produce a list of names and corresponding descriptions of anatomical targets. After long-list formulation by a Steering Committee, the first and second rounds involved anonymous electronic voting and commenting, with the third round involving a virtual round table discussion aiming to achieve consensus on items that had yet to achieve it. Novel names were presented where required for anatomical clarity and harmonization. Strong consensus was defined as ≥75% agreement and weak consensus as 50% to 74% agreement.ResultsSixty expert Collaborators participated in this study. After three rounds and clarification, harmonization, and introduction of novel nomenclature, strong consensus was achieved for the names of 16 block names and weak consensus for four names. For anatomical descriptions, strong consensus was achieved for 19 blocks and weak consensus was achieved for one approach. Several areas requiring further research were identified.ConclusionsHarmonization and standardization of nomenclature may improve education, research, and ultimately patient care. We present the first international consensus on nomenclature and anatomical descriptions of blocks of the abdominal wall, chest wall, and paraspinal blocks. We recommend using the consensus results in academic and clinical practice.

In-line filtration reduced phlebitis associated with peripheral venous cannulation: Focus on cost-effectiveness and patients’ perspectives

2019 ◽  
Vol 21 (2) ◽  
pp. 154-160
Author(s):  
Gianluca Villa ◽  
Rosa Giua ◽  
Timothy Amass ◽  
Lorenzo Tofani ◽  
Cosimo Chelazzi ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Vascular Access ◽  
Cost Effective ◽  
Causative Factor ◽  
Control Group ◽  
Previous Trial ◽  
Venous Cannulation ◽  
Group A ◽  
The Cost ◽  
And Control

Background: In a previous trial, in-line filtration significantly prevented postoperative phlebitis associated with short peripheral venous cannulation. This study aims to describe the cost-effectiveness of in-line filtration in reducing phlebitis and examine patients’ perception of in-hospital vascular access management with and without in-line filtration. Methods: We analysed costs associated with in-line filtration: these data were prospectively recorded during the previous trial. Furthermore, we performed a follow-up for all the 268 patients enrolled in this trial. Among these, 213 patients responded and completed 6 months after hospital discharge questionnaires evaluating the perception of and satisfaction with the management of their vascular access. Results: In-line filtration group required 95.60€ more than the no-filtration group (a mean of € 0.71/patient). In terms of satisfaction with the perioperative management of their short peripheral venous cannulation, 110 (82%) and 103 (76.9%) patients, respectively, for in-line filtration and control group, completed this survey. Within in-line filtration group, 97.3% of patients were satisfied/strongly satisfied; if compared with previous experiences on short peripheral venous cannulation, 11% of them recognised in-line filtration as a relevant causative factor in determining their satisfaction. Among patients within the control group, 93.2% were satisfied/strongly satisfied, although up to 30% of them had experienced postoperative phlebitis. At the qualitative interview, they recognised no difference than previous experiences on short peripheral venous cannulation, and mentioned postoperative phlebitis as a common event that ‘normally occurs’ during a hospital stay. Conclusion: In-line filtration is cost-effective in preventing postoperative phlebitis, and it seems to contribute to increasing patient satisfaction and reducing short peripheral venous cannulation–related discomfort

scholarly journals A Population-Specific Optimized GeneXpert Pooling Algorithm for Chlamydia trachomatis and Neisseria gonorrhoeae To Reduce Cost of Molecular Sexually Transmitted Infection Screening in Resource-Limited Settings

2020 ◽  
Vol 58 (9) ◽  
Author(s):  
Sarah Connolly ◽  
William Kilembe ◽  
Mubiana Inambao ◽  
Ana-Maria Visoiu ◽  
Tyronza Sharkey ◽  
...  
Keyword(s):  
Trichomonas Vaginalis ◽  
Molecular Testing ◽  
Resource Limited Settings ◽  
Syphilis Infection ◽  
Syndromic Management ◽  
Sexually Transmitted ◽  
Factors Associated ◽  
Resource Limited ◽  
The Cost ◽  
Low Prevalence

ABSTRACT The sexually transmitted infections (STIs) chlamydia (CT) and gonorrhea (NG) are often asymptomatic in women and undetected by syndromic management, leading to complications such as pelvic inflammatory disease, infertility, and ectopic pregnancy. Molecular testing, such as the GeneXpert CT/NG assay, is highly sensitive, but cost restraints preclude implementation of these technologies in resource-limited settings. Pooled testing is one strategy to reduce the cost per sample, but the extent of savings depends on disease prevalence. The current study describes a pooling strategy based on identification of sociodemographic and laboratory factors associated with CT/NG prevalence in a high-risk cohort of Zambian female sex workers and single mothers conducted from 2016 to 2019. Factors associated with testing positive for CT/NG via logistic regression modeling included city, younger age, lower education, long-acting reversible contraception usage, Trichomonas vaginalis infection, bacterial vaginosis, and incident syphilis infection. Based on these factors, the study population was stratified into high-, intermediate-, and low-prevalence subgroups and tested accordingly—individually, pools of 3, or pools of 4, respectively. The cost per sample was reduced from $18 to as low as $9.43 in the low-prevalence subgroup. The checklist tool and pooling approach described can be used in a variety of treatment algorithms to lower the cost per sample and increase access to molecular STI screening. This is particularly valuable in resource-limited settings to detect and treat asymptomatic CT/NG infections missed by traditional syndromic management.

scholarly journals Nanopore Targeted Sequencing for Rapid Gene Mutations Detection in Acute Myeloid Leukemia

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 1026 ◽  
Author(s):  
Cumbo ◽  
Minervini ◽  
Orsini ◽  
Anelli ◽  
Zagaria ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Low Cost ◽  
Gene Mutations ◽  
Predictive Biomarkers ◽  
Molecular Testing ◽  
Sequencing Analysis ◽  
Cebpa Mutations ◽  
Targeted Gene Sequencing ◽  
Acute Myeloid

Acute myeloid leukemia (AML) clinical settings cannot do without molecular testing to confirm or rule out predictive biomarkers for prognostic stratification, in order to initiate or withhold targeted therapy. Next generation sequencing offers the advantage of the simultaneous investigation of numerous genes, but these methods remain expensive and time consuming. In this context, we present a nanopore-based assay for rapid (24 h) sequencing of six genes (NPM1, FLT3, CEBPA, TP53, IDH1 and IDH2) that are recurrently mutated in AML. The study included 22 AML patients at diagnosis; all data were compared with the results of S5 sequencing, and discordant variants were validated by Sanger sequencing. Nanopore approach showed substantial advantages in terms of speed and low cost. Furthermore, the ability to generate long reads allows a more accurate detection of longer FLT3 internal tandem duplications and phasing double CEBPA mutations. In conclusion, we propose a cheap, rapid workflow that can potentially enable all basic molecular biology laboratories to perform detailed targeted gene sequencing analysis in AML patients, in order to define their prognosis and the appropriate treatment.

scholarly journals Mutation screening of the thyroid peroxidase gene in a cohort of 55 Portuguese patients with congenital hypothyroidism

2005 ◽  
Vol 152 (2) ◽  
pp. 193-198 ◽  
Author(s):  
Carina Rodrigues ◽  
Paula Jorge ◽  
José Pires Soares ◽  
Isaura Santos ◽  
Regina Salomão ◽  
...  
Keyword(s):  
Congenital Hypothyroidism ◽  
Mutation Screening ◽  
Gene Mutations ◽  
Human Thyroid ◽  
Thyroid Peroxidase ◽  
Molecular Testing ◽  
Missense Mutations ◽  
Human Thyroid Peroxidase ◽  
Iodide Organification Defect ◽  
Organification Defect

Objective: Defects in the human thyroid peroxidase (TPO) gene are reported to be one of the causes of congenital hypothyroidism (CH) due to a total iodide organification defect. The aim of the present study was to determine the nature and frequency of TPO gene mutations in patients with CH, characterised by elevated TSH levels and orthotopic thyroid gland, identified in the Portuguese National Neonatal Screening Programme. Subjects and methods: The sample comprised 55 patients, from 53 unrelated families, with follow-up in the endocrinology clinics of the treatment centres of Porto and Lisbon. Mutation screening in the TPO gene (exons 1–17) was performed by single-strand conformational analysis followed by sequencing of fragments with abnormal migration patterns. Results: Eight different mutations were detected in 13 patients (seven homozygotes and six compound heterozygotes). Novel mutations included three missense mutations, namely 391T > C (S131P), 1274A > G (N425S) and 2512T > A (C838S), as well as the predictable splice mutation 2748G > A (Q916Q/spl?). The undocumented polymorphism 180-47A > C was also detected. Conclusion: The results are in accordance with previous observations confirming the genetic heterogeneity of TPO defects. The proportion of patients in which the aetiology was determined justifies the implementation of this molecular testing in our CH patients with dyshormonogenesis.

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