RESUMO
Hypomyelination and congenital cataract (HCC, OMIM #610532) is a rare autosomal recessive disorder due to FAM126A mutations characterized by congenital cataract, progressive neurologic impairment, and myelin deficiency in the central and peripheral nervous system. We have identified two novel mutations in three affected members of two unrelated families. Two sibs harbouring a microdeletion causing a premature stop in the protein showed the classical clinical and neuroradiologic HCC picture. The third patient carrying a missense mutation showed a relatively mild clinical picture without peripheral neuropathy. A residual amount of hyccin protein in primary fibroblasts was demonstrated by functional studies indicating that missense mutations are likely to have less detrimental effects if compared with splice-site mutations or deletions that cause the full-blown HCC phenotype, including peripheral nervous system involvement.
Assuntos
Catarata/congênito , Catarata/genética , Doença de Charcot-Marie-Tooth/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Mutação , Sequência de Aminoácidos , Encéfalo/metabolismo , Encéfalo/patologia , Catarata/patologia , Doença de Charcot-Marie-Tooth/patologia , Criança , Feminino , Humanos , Lactente , Peptídeos e Proteínas de Sinalização Intracelular/química , Proteínas de Membrana/química , Dados de Sequência Molecular , Linhagem , Alinhamento de SequênciaRESUMO
BACKGROUND AND PURPOSES: To determine the prevalence of SLC2A1 mutations in children with early-onset absence epilepsy (EOAE) and to investigate whether there were differences in demographic and electroclinical data between patients who became seizure-free with anti-epileptic drug (AED) monotherapy (group I) and those who needed add-on treatment of a second AED (group II). METHODS: We reviewed children with EOAE attending different Italian epilepsy centers. All participants had onset of absence seizures within the first 3 years of life but otherwise conformed to a strict definition of childhood absence epilepsy. Mutation analysis of SLC2A1 was performed in each patient. RESULTS: Eighty-four children (57 in group I, 27 in group II) fulfilled the inclusion criteria. No mutation in SLC2A1 was found. There were no statistical differences between the two groups with regard to F/M ratio, age at onset of EOAE, early history of febrile seizures, first-degree family history for genetic generalized epilepsy, duration of AED therapy at 3 years after enrollment, use of AEDs at 3 years, failed withdrawals at 3 years, terminal remission of EOAE at 3 years, and 6-month follow-up EEG data. Mean duration of seizures/active epilepsy was significantly shorter in group I than in group II (P = 0.008). CONCLUSIONS: We demonstrate that in a large series of children with rigorous diagnosis of EOAE, no mutations in SLC2A1 gene are detected. Except for duration of seizures/active epilepsy, no significant differences in demographic and electroclinical aspects are observed between children with EOAE who responded well to AED monotherapy and those who became seizure-free with add-on treatment of a second AED.
Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Tipo Ausência/genética , Transportador de Glucose Tipo 1/genética , Mutação/genética , Anticonvulsivantes/administração & dosagem , Pré-Escolar , Quimioterapia Combinada , Epilepsia Tipo Ausência/tratamento farmacológico , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
INTRODUCTION: Drug-related problems can be caused by potentially inappropriate prescribing (PIP), one of the most used tools for its identification are the STOPP (Older Persons' potentially inappropriate Prescriptions) - START (Screening Tool to Alert doctors to Right Treatment) criteria. The objective of this study is to determine PIP in older adults who receive pharmaceutical care in the Pharmacotherapy Optimization Unit (POU)-Rosario. MATERIALS AND METHODS: Pharmacoepidemiological observational study, which evaluates the quality of medication use. Workplace: POU-Rosario. Population under study: adults over 60 years of age, who received pharmacotherapy follow-up during the period March 2017 to February 2018. PIPs were identified using the STOPP-START criteria, 2014 version; selecting the most appropriate criteria to assess outpatient pharmacotherapy. Prevalence of PIP and amount of PIP per active principle were estimated. RESULTS: 50 patients older than 60 years received pharmacotherapy follow-up in the POU; 47 patients (94.0%) had at least one PIP corresponding to a STOPP criterion; 17 STOPP criteria were found among the 41 initially selected, leading to 145 PIPs identified. And 7 START criteria among the 11 initially selected, leading to 50 PIPs identified. Medications with a higher amount of PIPs: benzodiazepines and proton pump inhibitors. CONCLUSIONS: This study allowed the identification of a high prevalence of PIP. The data obtained show the usefulness of these criteria. The STOPP-START criteria have been included to support decision making during pharmacotherapy follow-up to propose pharmaceutical interventions, in order to enhance pharmacotherapy. These activities contribute to patient safety, a dimension of health quality.
Assuntos
Tratamento Farmacológico , Prescrição Inadequada/prevenção & controle , Prescrição Inadequada/estatística & dados numéricos , Assistência Farmacêutica/normas , Lista de Medicamentos Potencialmente Inapropriados/normas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
BACKGROUND AND PURPOSE: Segmental callosal agenesis is characterized by the absence of the intermediate callosal portion. We aimed to evaluate the structural connectivity of segmental callosal agenesis by using constrained spherical deconvolution tractography and connectome analysis. MATERIALS AND METHODS: We reviewed the clinical-radiologic features of 8 patients (5 males; mean age, 3.9 years). Spherical deconvolution and probabilistic tractography were performed on diffusion data. Structural connectivity analysis, including summary network metrics, modularity analysis, and network consistency measures, was applied in 5 patients and 10 age-/sex-matched controls. RESULTS: We identified 3 subtypes based on the position of the hippocampal commissure: beneath the anterior callosal remnant in 3 patients (type I), beneath the posterior callosal remnant in 3 patients (type II), and between the anterior and posterior callosal remnants in 2 patients (type III). In all patients, the agenetic segment corresponded to fibers projecting to the parietal lobe, and segmental Probst bundles were found at that level. Ectopic callosal bundles were identified in 3 patients. Topology analysis revealed reduced global connectivity in patients compared with controls. The network topology of segmental callosal agenesis was more variable across patients than that of the control connectomes. Modularity analysis revealed disruption of the structural core organization in the patients. CONCLUSIONS: Three malformative subtypes of segmental callosal agenesis were identified. Even the absence of a small callosal segment may impact global brain connectivity and modularity organization. The presence of ectopic callosal bundles may explain the greater interindividual variation in the connectomes of patients with segmental callosal agenesis.
Assuntos
Agenesia do Corpo Caloso/patologia , Adolescente , Agenesia do Corpo Caloso/diagnóstico por imagem , Estudos de Casos e Controles , Criança , Pré-Escolar , Conectoma , Imagem de Tensor de Difusão , Feminino , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Masculino , Vias Neurais/diagnóstico por imagem , Vias Neurais/patologia , Lobo Parietal/diagnóstico por imagem , Lobo Parietal/patologia , Estudos RetrospectivosRESUMO
Introducción: La gestión eficiente del inventario es un desafío para los Servicios de Farmacia Hospitalaria (SFH). Se han reportado resultados favorables en la mejora de procesos hospitalarios utilizando la metodología Lean Six Sigma (LSS). Este trabajo tiene como objetivo implementar la metodología LSS para mejorar el desempeño de tres procesos que influyen en el inventario del SFH en un 70% y alcanzar un mínimo del 90% de stocks correctos.Métodos: El estudio se desarrolló en el SFH del Instituto Modelo de Cardiología Privado S.R.L. Se aplicó metodología DMAIC (definir, medir, analizar, implementar mejoras, controlar) en el proceso de recepción (PR), proceso de dispensación por dosis diaria unitaria (PDDU) y proceso de distribución de insumos a servicios (PDS). Se definieron tres períodos: inicial (08/18-09/18) para calcular el desempeño base medido en número de errores/ciclo, implementación (10/18-12/18) para aplicar mejoras, y consolidación (01/19-03/19) para evaluar consistencia en el tiempo. Se controló mensualmente el inventario del SFH y mediante control estadístico se monitoreó estabilidad y capacidad. Resultados: Comparando el período inicial vs. consolidación los errores disminuyeron: PR de 0,135 errores/recepción a 0,033 errores/recepción, PDDU de 0,064 errores/paciente a 0,008 errores/paciente y PDS de 1,294 errores/pedido a 0,044 errores/pedido respectivamente. En el período de consolidación el 95,95% de stocks fueron correctos vs. el 63,42% del período diagnóstico.Conclusión: La implementación de LSS en un SFH eficientizó la gestión del stock y disminuyó los errores en los procesos de PR, PDDU y PDS, demostrando ser una herramienta muy útil para las organizaciones de salud. (AU)
Introduction: Efficient inventory management is a challenge for Hospital Pharmacy Services (HPS). Positive results have been reported in the improvement of hospital processes using the Lean Six Sigma (LSS) methodology. This work aims to implement the LSS methodology to improve the performance of three processes that influence the inventory of the HPS by 70% and reach a minimum of 90% of correct stocks.Methods: The study was carried out at the HPS of the Instituto Modelo de Cardiología Privado S.R.L. DMAIC methodology (define, measure, analyse, improve, control) was applied in the receiving process (RP), the unit dose daily drug distribution system (UDDDDS) and the supply distribution to hospital services process (SDHSP). Three periods were defined: initial (08/18-09/18) to calculate the base performance measured in number of defects/cycle, implementation (10/18-12/18) to apply improvements, and consolidation (01/19-03/19) to evaluate consistency over time. The inventory of the SPH was checked monthly and the stability and capacity of each process was monitored with statistical control techniques.Results: Comparing the initial period vs. consolidation the defects decreased: RP from 0.135 defects/reception to 0.033 defects/reception, UDDDDS from 0.064 defects/patient to 0.008 defects/patient and SDHSP from 1.294 defects/order to 0.044 defects/order respectively. In the consolidation period 95.95% of stocks were correct vs. 63.42% of the diagnostic period.Conclusion: The implementation of LSS in an HPS efficient the stock management and reduced errors in the processes of RP, UDDDDS and SDHSP, proving to be a very useful tool for health care organizations. (AU)
Assuntos
Humanos , 34002 , FarmáciaRESUMO
The Authors describe three infants with visceral leishmaniasis in whom bioptic research (in marrow, spleen and liver) has not demonstrated presence of leishmania. They remark this unusual aspect of visceral leishmaniasis in infant and debate the epidemiological, diagnostic, and therapeutic aspects of these cases.
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Leishmaniose Visceral/diagnóstico , Animais , Antiprotozoários/uso terapêutico , Feminino , Humanos , Lactente , Leishmania donovani/isolamento & purificação , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/imunologia , Masculino , Meglumina/uso terapêutico , Antimoniato de Meglumina , Compostos Organometálicos/uso terapêuticoRESUMO
The Authors carried out retrospective research into bacterial enteritis observed during the past 5 years (Jan. 1982-Dec. 1986) in Pediatric Clinic R of Palermo. The pathogenic agents more frequently isolated were minor salmonellas, followed by E. Coli and shigellas. The first ones showed an incidence almost constant during the five years, while the second and third ones presented epidemic tops in 1982 and 1985. Inside the salmonellas' group it was evidenced a prevalence of S.T. Murium (44.71%), of S. Corvallis (21.13%) and of S. Enteridis (11.38%) and inside the shigellas' group S. Sonnei was more evident (80.43%). A higher incidence of bacterial enteritis appeared: during the period summer-autumn, in patients under one year or undernourished, in those coming from lower social classes, not breast-fed or wrongly fed. An accurate analyses of symptoms has not allowed an aetiological diagnosis, and clinical course of illness was always favourable. The therapy more often used was rehydration, associated with antibiotics only in very serious cases.
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Infecções Bacterianas/epidemiologia , Enterite/etiologia , Fatores Etários , Antibacterianos/uso terapêutico , Bactérias/isolamento & purificação , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/terapia , Criança , Pré-Escolar , Enterite/tratamento farmacológico , Enterite/epidemiologia , Fezes/microbiologia , Hidratação , Humanos , Lactente , Estudos Retrospectivos , Estações do Ano , Fatores SocioeconômicosAssuntos
Caveolina 3/genética , Aberrações Cromossômicas , Deleção Cromossômica , Análise Mutacional de DNA , Genes Recessivos/genética , Cãibra Muscular/genética , Debilidade Muscular/genética , Doenças Musculares/genética , Adulto , Biópsia , Creatina Quinase/sangue , Eletromiografia , Éxons/genética , Feminino , Triagem de Portadores Genéticos , Genótipo , Humanos , Contração Muscular/genética , Cãibra Muscular/diagnóstico , Debilidade Muscular/diagnóstico , Músculo Esquelético/patologia , Doenças Musculares/diagnóstico , Exame Neurológico , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único/genética , Receptores de Ocitocina/genéticaRESUMO
OBJECTIVES: To describe the medication errors in the medication use cycle in a general public hospital, and to identify intervention strategies in relation to the detection and prevention of these errors. METHODS: Descriptive study with cross-sectional design. General public hospital of 190 beds, in Rosario (Argentina). Daily and systematic data collection of the circuit of use of medicines during May 2009. Once the errors were identified and classified, an interdisciplinary group sequentially applied different quality management tools to recognize and weigh causes, and propose solutions. (Flowchart, Cause Effect Diagram, Brainstorming, Nominal Group and Matrix Decision). RESULTS: Information on 60 patients was retrieved during the study period, with 506 medication errors detected. The impact indicators showed the following values: 8.4 errors/patient and 88.6 errors/100 patients-day. From the causes identified, two were defined as relevant: "Double prescription" and "Lack of clear policy". Of the various solutions proposed, an intervention strategy was defined to include a differently designed form for "prescription/indication/administration" in the clinical history which could be updated daily, with a duplicate to Pharmacy for the distribution, as well as a Standard Operating Procedure to standardize this new way of working. CONCLUSION: This work achieved, through quality management, the commitment of a team of health professionals to seek and make changes for patient safety, and to improve the quality of services provided by the hospital.
Assuntos
Erros de Medicação/prevenção & controle , Segurança do Paciente/normas , Gestão da Qualidade Total , Estudos Transversais , Árvores de Decisões , Hospitais Públicos , Humanos , Erros de Medicação/classificaçãoRESUMO
The dietary habits of 174 infants under 6 months old and suffering from enteritis were analysed revealing a high incidence of feeding errors (almost always feeding with artificial formulas, wrong concentration of milk powder, failure to sterilise the bottle and the water used to dilute the milk, too early administration of undiluted, unboiled bottled cow's milk, too early and incorrect weaning). Such mistakes appeared to be linked to the poor economic and sociocultural conditions of the families concerned. It is claimed that dietary errors conditioned by the poor economic and sociocultural conditions encountered may have favoured the onset of enteritis and that the adequate prophylaxis of acute infantile enteritis will depend on improving people's dietary habits and living conditions.
Assuntos
Enterite/etiologia , Alimentos Infantis/efeitos adversos , Doença Aguda , Animais , Humanos , Lactente , Recém-Nascido , Leite/efeitos adversos , Fatores SocioeconômicosRESUMO
BACKGROUND: Glycogen storage disease type IV (GSD-IV) is a clinically heterogeneous autosomal recessive disorder due to glycogen branching enzyme (GBE) deficiency and resulting in the accumulation of an amylopectin-like polysaccharide. The typical presentation is liver disease of childhood, progressing to lethal cirrhosis. The neuromuscular form of GSD-IV varies in onset (perinatal, congenital, juvenile, or adult) and severity. OBJECTIVE: To identify the molecular bases of different neuromuscular forms of GSD-IV and to establish possible genotype/phenotype correlations. METHODS: Eight patients with GBE deficiency had different neuromuscular presentations: three had fetal akinesia deformation sequence (FADS), three had congenital myopathy, one had juvenile myopathy, and one had combined myopathic and hepatic features. In all patients, the promoter and the entire coding region of the GBE gene at the RNA and genomic level were sequenced. RESULTS: Nine novel mutations were identified, including nonsense, missense, deletion, insertion, and splice-junction mutations. The three cases with FADS were homozygous, whereas all other cases were compound heterozygotes. CONCLUSIONS: This study expands the spectrum of mutations in the GBE gene and confirms that the neuromuscular presentation of GSD-IV is clinically and genetically heterogeneous.