Early sedation and clinical outcomes of mechanically ventilated patients: a prospective multicenter cohort study

Introduction: Sedation overuse is frequent and possibly associated with poor outcomes in the intensive care unit (ICU) patients. However, the association of early oversedation with clinical outcomes has not been thoroughly evaluated. the aim of this study was to assess the association of early sedation strategies with outcomes of critically ill adult patients under mechanical ventilation (MV).Methods: A secondary analysis of a multicenter prospective cohort conducted in 45 Brazilian ICUs, including adult patients requiring ventilatory support and sedation in the first 48 hours of ICU admissions, was performed. Sedation depth was evaluated after 48 hours of MV. Multivariate analysis was used to identify variables associated with hospital mortality.Results: A total of 322 patients were evaluated. Overall, ICU and hospital mortality rates were 30.4% and 38.8%, respectively. Deep sedation was observed in 113 patients (35.1%). Longer duration of ventilatory support was observed (7 (4 to 10) versus 5 (3 to 9) days, P = 0.041) and more tracheostomies were performed in the deep sedation group (38.9% versus 22%, P=0.001) despite similar PaO2/FiO(2) ratios and acute respiratory distress syndrome (ARDS) severity. in a multivariate analysis, age (Odds Ratio (OR) 1.02; 95% confidence interval (CI) 1.00 to 1.03), Charlson Comorbidity Index >2 (OR 2.06; 95% Cl, 1.44 to 2.94), Simplified Acute Physiology Score 3 (SAPS 3) score (OR 1.02; Cl 95%, 1.00 to 1.04), severe ARDS (OR 1.44; Cl 95%, 1.09 to 1.91) and deep sedation (OR 2.36; Cl 9596, 1.31 to 4.25) were independently associated with increased hospital mortality.Conclusions: Early deep sedation is associated with adverse outcomes and constitutes an independent predictor of hospital mortality in mechanically ventilated patients.Research and Education Institute from Hospital Sirio-Libanes, São PauloD'Or Institute for Research and Education, Rio de Janeiro, BrazilBrazilian Research in Intensive Care NetworkHosp Copa DOr, BR-22031010 Rio de Janeiro, BrazilHosp Sirio Libanes, Res & Educ Inst, BR-01308060 São Paulo, BrazilUniv São Paulo, Fac Med, Hosp Clin, ICU,Emergency Med Dept, BR-05403000 São Paulo, BrazilHosp Sao Camilo Pompeia, ICU, BR-05022000 São Paulo, BrazilCEPETI, BR-82530200 Curitiba, Parana, BrazilHosp Canc I, Inst Nacl Canc, ICU, BR-20230130 Rio de Janeiro, BrazilPasteur Hosp, ICU, BR-20735040 Rio de Janeiro, BrazilIrmandade Santa Casa Misericordia Porto Alegre, RIPIMI, BR-90020090 Porto Alegre, RS, BrazilVitoria Apart Hosp, ICU, BR-29161900 Serra, ES, BrazilHosp Mater Dei, ICU, BR-30140093 Belo Horizonte, MG, BrazilHosp Santa Luzia, ICU, BR-70390902 Brasilia, DF, BrazilHosp Sao Luiz, ICU, BR-04544000 São Paulo, BrazilUniversidade Federal de São Paulo, Anesthesiol Pain & Intens Care Dept, ICU, BR-04024900 São Paulo, BrazilHosp Sao Jose Criciuma, ICU, BR-88801250 Criciuma, BrazilUDI Hosp, ICU, BR-65076820 Sao Luis, BrazilUniv São Paulo, Univ Hosp, ICU, BR-05508000 São Paulo, BrazilUniv São Paulo, Fac Med, Hosp Clin, ICU,Surg Emergency Dept, BR-05403000 São Paulo, BrazilIDOR DOr Inst Res & Educ, BR-22281100 Rio de Janeiro, BrazilInst Nacl Canc, Postgrad Program, BR-20230130 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Anesthesiol Pain & Intens Care Dept, ICU, BR-04024900 São Paulo, BrazilWeb of Scienc

Fatores de risco de paratireoidectomia acidental em tireoidectomia

Incidental parathyroidectomy is a common event in thyroid surgery. The literature shows a finding of parathyroid glands ranging from 6.4% to 31% in pathological specimens of the thyroid gland.Objective: To collect the amount of parathyroid glands found in surgical specimens of thyroidectomy and correlate with the histopathological and demographic variables.Methods: Retrospective study based on pathological reports of thyroidectomy from January 2007 to December 2008.Results: 442 patients were submitted to total thyroidectomy, and 2.93% had parathyroid glands, which corresponded to 13 of this total. The presence of papillary thyroid carcinoma associated with incidental parathyroidectomy was 10.11%, compared to the benign lesion: 1.4%.Conclusion: Papillary thyroid carcinoma was the variable associated with increased number of incidental parathyroidectomy.Metropolitan Univ Santos UNIMES, Sch Med, Santos, SP, BrazilUniv Metropolitana Santos, Santos, SP, BrazilFed Univ Sao Paulo UNIFESP, Sao Paulo, BrazilMetropolitan Univ Santos UNIMES, Dept Otorhinolaryngol & Head & Neck Surg, Santos, SP, BrazilMetropolitan Univ Santos UNIMES, Dept Sci Initiat, Santos, SP, BrazilFed Univ Sao Paulo UNIFESP, Sao Paulo, BrazilWeb of Scienc

Dynamics of brain structure and its genetic architecture over the lifespan

Human brain structure changes throughout our lives. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental, and neurodegenerative diseases. While heritable, specific loci in the genome that influence these rates are largely unknown. Here, we sought to find common genetic variants that affect rates of brain growth or atrophy, in the first genome-wide association analysis of longitudinal changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 10,163 individuals aged 4 to 99 years, on average 3.5 years apart, were used to compute rates of morphological change for 15 brain structures. We discovered 5 genome-wide significant loci and 15 genes associated with brain structural changes. Most individual variants exerted age-dependent effects. All identified genes are expressed in fetal and adult brain tissue, and some exhibit developmentally regulated expression across the lifespan. We demonstrate genetic overlap with depression, schizophrenia, cognitive functioning, height, body mass index and smoking. Several of the discovered loci are implicated in early brain development and point to involvement of metabolic processes. Gene-set findings also implicate immune processes in the rates of brain changes. Taken together, in the world’s largest longitudinal imaging genetics dataset we identified genetic variants that alter age-dependent brain growth and atrophy throughout our lives

Dynamics of Brain Structure and its Genetic Architecture over the Lifespan

Human brain structure changes throughout our lives. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental, and neurodegenerative diseases. While heritable, specific loci in the genome that influence these rates are largely unknown. Here, we sought to find common genetic variants that affect rates of brain growth or atrophy, in the first genome-wide association analysis of longitudinal changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 10,163 individuals aged 4 to 99 years, on average 3.5 years apart, were used to compute rates of morphological change for 15 brain structures. We discovered 5 genome-wide significant loci and 15 genes associated with brain structural changes. Most individual variants exerted age-dependent effects. All identified genes are expressed in fetal and adult brain tissue, and some exhibit developmentally regulated expression across the lifespan. We demonstrate genetic overlap with depression, schizophrenia, cognitive functioning, height, body mass index and smoking. Several of the discovered loci are implicated in early brain development and point to involvement of metabolic processes. Gene-set findings also implicate immune processes in the rates of brain changes. Taken together, in the world’s largest longitudinal imaging genetics dataset we identified genetic variants that alter age-dependent brain growth and atrophy throughout our lives

Genetic variants associated with longitudinal changes in brain structure across the lifespan

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk