A systematic review and evidence-based guideline for diagnosis and treatment of Menkes disease.

Menkes disease is a rare X-linked neurodegenerative disorder caused by defect in copper metabolism. Parenteral copper supplementation has been used as a potential disease-modifying treatment of Menkes disease for decades. However, recent evidence suggests its efficacy only when treatment is started within days after birth, which also has important implications related to the techniques that enable early diagnosis. We aim at proposing a guideline for prenatal and neonatal diagnosis and for disease-modifying treatment of Menkes disease, guided by a systematic review of the literature, and built in conjunction with medical experts, methodologists and patient representatives. Thirteen articles were used for our recommendations that were based on GRADE system. Reviewed evidence suggests that prenatal genetic diagnosis in families with previous diagnosis of Menkes disease is feasible; analysis of plasma catecholamine levels is accurate for neonatal diagnosis of Menkes disease; treatment with copper-histidine is effective to increase survival and reduce neurologic burden of the disease if initiated in the neonatal period; and, treatment indication should not be guided by patient's genotype. In conclusion, our guideline can contribute to standardize some aspects of the clinical care of patients with Menkes disease, especially reducing disease burden and mortality and providers' and families' anxiety.

Systematic Review of Economic Evaluations of Units Dedicated to Acute Coronary Syndromes.

BACKGROUND: Dedicated units for the care of acute coronary syndrome (ACS) have been submitted to economic evaluations; however, the results have not been systematically presented. OBJECTIVE: To identify and summarize economic outcomes of studies on hospital units dedicated to the initial care of patients with suspected or confirmed ACS. METHODS: A systematic review of literature to identify economic evaluations of chest pain unit (CPU), coronary care unit (CCU), or equivalent units was done. Two search strategies were used: the first one to identify economic evaluations irrespective of study design, and the second one to identify randomized clinical trials that reported economic outcomes. The following databases were searched: MEDLINE, EMBASE, CENTRAL, and National Health Service (NHS)Economic Evaluation Database. Data extraction was performed by two independent reviewers. Costs were inflated to 2012 values. RESULTS: Search strategies retrieved five partial economic evaluations based on observational studies, six randomized clinical trials that reported economic outcomes, and five model-based economic evaluations. Overall, cost estimates based on observational studies and randomized clinical trials reported statistically significant cost savings of more than 50% with the adoption of CPU care instead of routine hospitalization or CCU care for suspected low-to-intermediate risk patients with ACS (median per-patient cost US $1,969.89; range US $1,002.12-13,799.15). Model-based economic evaluations reported incremental cost-effectiveness ratios below US $ 50,000/quality-adjusted life-year for all comparisons between intermediate care unit, CPU, or CCU with routine hospital admissions. This finding was sensible to myocardial infarction probability. CONCLUSIONS: Published economic evaluations indicate that more intensive care is likely to be cost-effective in comparison to routine hospital admission for patients with suspected ACS.

A telomerase em células-tronco hematopoéticas: [revisão] / Telomerase in hematopoietic stem cells: [review]

A proliferação das células-tronco hematopoéticas sofre a perda dos telômeros a cada divisão celular. Alguns autores discordam quanto à perda ou não do potencial proliferativo e capacidade de auto-renovação das células mais diferenciadas. Revisaremos aqui o papel da telomerase na biologia do sistema hematopoético, na diferenciação normal ou maligna, assim como no envelhecimento das células-tronco hematopoéticas. A constante renovação celular requerida pela hematopoese confere às células-tronco embrionárias, assim como à maioria das células tumorais, um aumento da capacidade proliferativa marcada pela detecção da enzima telomerase e possível manutenção dos telômeros. Estudos clínicos se farão necessários para esclarecer melhor a atividade da telomerase em células-tronco hematopoéticas, seu possível uso como marcador de diagnóstico e seu uso a fim de propósitos prognósticos.

Hematopoietic stem cell proliferation leads to telomere length decreases at each cellular division. Some authors disagree about the telomere influence on the reduction of the proliferative potential and capacity of self renewal. Here we review telomerase function in the biology of the hematopoietic system, in normal or differentiation and its influence on the ageing of hematopoietic stem cells. The constant cellular renewal required to maintain the hematopoietic system, provides embryonic stem cells, as well as malignant cells, an increased proliferative capacity. This is marked by the detection of telomerase enzyme activity and possible telomere maintenance. Clinical trials will be required to clarify telomerase activity in hematopoietic stem cells, its possible use as a diagnostic marker and its use for prognostic purposes.