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1.
Lancet ; 394(10215): 2173-2183, 2019 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-31810609

RESUMO

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/sangue , Medição de Risco/métodos , Adulto , Idoso , Austrália/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos/epidemiologia
2.
Injury ; 50(10): 1671-1677, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31690405

RESUMO

INTRODUCTION: Early coagulation support (ECS) includes prompt infusion of tranexamic acid, fibrinogen concentrate, and packed red blood cells for initial resuscitation of major trauma patients. The aim of this study was to determine the effects, in terms of blood product consumption, length of stay, and in-hospital mortality, of the ECS protocol, compared to the massive transfusion protocol (MTP) in the treatment of major trauma patients. PATIENTS AND METHODS: A retrospective analysis was conducted using the registry data of two Italian trauma centres. Adult major trauma patients with, or at risk of, active bleeding who were managed according to the MTP during the years 2011-2012, or the ECS protocol during the years 2013-2014 and were considered at risk of multiple transfusions, were enrolled. The primary endpoint was to determine whether the ECS protocol reduces the use of blood products in the acute management of trauma patients. Secondary endpoints were the outcome measures of length of stay in ICU, length of stay in hospital, and mortality at 24-hours and 28-days after hospital admission. RESULTS: Among the 518 major trauma patients admitted to the trauma centres during the study period, 235 patients (118 in the pre-ECS period and 117 in the ECS period) matched one of the inclusion criteria and were enrolled in the study. Compared with the pre-ECS period, the ECS period showed a reduction in the average consumption of packed red blood cells (-1.87 units, 95% confidence interval [CI], -2.40, -1.34), platelets (-1.28 units; 95% CI, -1.64, -0.91), and fresh frozen plasma (-1.69; 95% CI, -2.14, -1.25) in the first 24-hours. Furthermore, during the ECS period, we recorded a 10-day reduction in the hospital length of stay (-10 days, 95% CI, -11.6, -8.4) and a non-significant 28-day mortality increase. CONCLUSIONS: The ECS protocol was effective in reducing blood product consumption compared to the MTP and confirmed the importance of early fibrinogen administration as a strategy of rapid coagulation. This novel approach may be adopted in real-life management of major trauma patients.

3.
Transl Lung Cancer Res ; 8(5): 584-592, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31737495

RESUMO

Background: Routine testing of baseline EGFR T790M mutation may have important clinical impact but many discordant data have been reported regarding the diagnostic, prognostic and predictive role of this marker. In this study we aimed to assess T790M frequency in 164 untreated EGFR-mutated NSCLCs using methods with different sensitivity as well as to analyze the relationship between baseline T790M mutation status, patient's clinicopathologic features and tyrosine kinase inhibitors (TKI) treatment outcomes. Methods: We compared the diagnostic performance, sensitivity and specificity of three methods, namely MALDI-TOF mass spectrometry (MS), Allele-Specific Real Time PCR (AS-PCR), droplet digital PCR (ddPCR). Ultra-deep next generation sequencing (NGS) validation of T790M-mutant NSCLCs was performed using SiRe® panel. Results: Baseline T790M occurred in 17% of the tumors. Intermediately sensitive techniques such as MALDI-TOF MS (detection limit of T790M ≥5%) allow to detect T790M in 2% of cases exhibiting mutant-allele fractions ranging from 11.5% to 17%. Median overall survival (OS) in these patients was poor (7.3 months) and progression free survival (PFS) was of 3.3 months in patients treated with a 1st generation EGFR TKI. The remaining T790M-positive cases showed very low mutant-allele fractions ranging from 0.07% to 0.38% and required highly sensitive methods such as ddPCR and NGS to be identified. All these cases showed a concurrent sensitizing EGFR mutation (mainly exon 19 deletion), and clinicopathological features similar to those observed in EGFR mutant cancers. Median OS of these patients was 27 months while median PFS after TKI treatment was 20 months. Conclusions: Routine test of baseline EGFR T790M may have an important role in the prediction to EGFR TKI therapy response and should be performed using highly sensitive and quantitative methods, such as ddPCR and NGS, in order to reliably distinguish NSCLCs with high or very low T790M mutant-allele fraction.

4.
Data Brief ; 27: 104768, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31763415

RESUMO

This article provides additional data on the application of early coagulation support protocol in the management of major trauma patients. Data come from a retrospective analysis reported in the article "Early coagulation support protocol: a valid approach in real-life management of major trauma patients. Results from two Italian centres" [1]. Data contain information about the relationship between differences in resource use and mortality outcomes, and patient demographic and clinical features at presentation. Furthermore, a comparison between resource consumption, the probability of multiple transfusions and the mortality outcomes among propensity-score matched patients is reported.

5.
JAMA Cardiol ; : 1-10, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31664431

RESUMO

Importance: Risk stratification for coronary heart disease (CHD) remains challenging because of the complex causative mechanism of the disease. Metabolomic profiling offers the potential to detect new biomarkers and improve CHD risk assessment. Objective: To evaluate the association between circulating metabolites and incident CHD in a large European cohort. Design, Setting, and Participants: This population-based study used the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) case-cohort to measure circulating metabolites using a targeted approach in serum samples from 10 741 individuals without prevalent CHD. The cohort consisted of a weighted, random subcohort of the original cohort of more than 70 000 individuals. The case-cohort design was applied to 6 European cohorts: FINRISK97 (Finland), Monitoring of Trends and Determinants in Cardiovascular Diseases/Cooperative Health Research in the Region of Augsburg (MONICA/KORA; Germany), MONICA-Brianza and Moli-Sani (Italy), DanMONICA (Denmark), and the Scottish Heart Health Extended Cohort (United Kingdom). Main Outcomes and Measures: Associations with time to CHD onset were assessed individually by applying weighted and adjusted Cox proportional hazard models. The association of metabolites with CHD onset was examined by C indices. Results: In 10 741 individuals (4157 women [38.7%]; median [interquartile range] age, 56.5 [49.2-62.2] years), 2166 incident CHD events (20.2%) occurred over a median (interquartile range) follow-up time of 9.2 (4.5-15.0) years. Among the 141 metabolites analyzed, 24 were significantly associated with incident CHD at a nominal P value of .05, including phosphatidylcholines (PCs), lysoPCs, amino acids, and sphingolipids. Five PCs remained significant after correction for multiple testing: acyl-alkyl-PC C40:6 (hazard ratio [HR], 1.13 [95% CI, 1.07-1.18]), diacyl-PC C40:6 (HR, 1.10 [95% CI, 1.04-1.15]), acyl-alkyl-PC C38:6 (HR, 1.11 [95% CI, 1.05-1.16]), diacyl-PC C38:6 (HR, 1.09 [95% CI, 1.04-1.14]) and diacyl-PC C38:5 (HR, 1.10 [95% CI, 1.05-1.16]). Lower levels of these metabolites were associated with increased risk of incident CHD. The strength of the associations competes with those of classic risk factors (C statistics: acyl-alkyl-PC C40:6, 0.756 [95% CI, 0.738-0.774], diacyl-PC C40:6, 0.754 [95% CI, 0.736-0.772], acyl-alkyl-PC C38:6, 0.755 [95% CI, 0.736-0.773], diacyl-PC C38:6, 0.754 [95% CI, 0.736-0.772]), diacyl-PC C38:5, 0.754 [95% CI, 0.736-0.772]). Adding metabolites to a base risk model including classic risk factors high-sensitivity C-reactive protein and high-sensitivity troponin I did not improve discrimination by C statistics. Conclusions and Relevance: Five PCs were significantly associated with increased risk of incident CHD and showed comparable discrimination with individual classic risk factors. Although these metabolites do not improve CHD risk assessment beyond that of classic risk factors, these findings hold promise for an improved understanding of the pathophysiology of CHD.

6.
Int J Epidemiol ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31620789

RESUMO

BACKGROUND: An increasing number of observational studies combine large sample sizes with low participation rates, which could lead to standard inference failing to control the false-discovery rate. We investigated if the 'empirical calibration of P-value' method (EPCV), reliant on negative controls, can preserve type I error in the context of survival analysis. METHODS: We used simulated cohort studies with 50% participation rate and two different selection bias mechanisms, and a real-life application on predictors of cancer mortality using data from four population-based cohorts in Northern Italy (n = 6976 men and women aged 25-74 years at baseline and 17 years of median follow-up). RESULTS: Type I error for the standard Cox model was above the 5% nominal level in 15 out of 16 simulated settings; for n = 10 000, the chances of a null association with hazard ratio = 1.05 having a P-value < 0.05 were 42.5%. Conversely, EPCV with 10 negative controls preserved the 5% nominal level in all the simulation settings, reducing bias in the point estimate by 80-90% when its main assumption was verified. In the real case, 15 out of 21 (71%) blood markers with no association with cancer mortality according to literature had a P-value < 0.05 in age- and gender-adjusted Cox models. After calibration, only 1 (4.8%) remained statistically significant. CONCLUSIONS: In the analyses of large observational studies prone to selection bias, the use of empirical distribution to calibrate P-values can substantially reduce the number of trivial results needing further screening for relevance and external validity.

8.
BMC Oral Health ; 19(1): 101, 2019 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170969

RESUMO

BACKGROUND: Until now, a few studies have addressed the accuracy of intraoral scanners (IOSs) in implantology. Hence, the aim of this in vitro study was to assess the accuracy of 5 different IOSs in the impressions of single and multiple implants, and to compare them. METHODS: Plaster models were prepared, representative of a partially edentulous maxilla (PEM) to be restored with a single crown (SC) and a partial prosthesis (PP), and a totally edentulous maxilla (TEM) to be restored with a full-arch (FA). These models were scanned with a desktop scanner, to capture reference models (RMs), and with 5 IOSs (CS 3600®, Trios3®, Omnicam®, DWIO®, Emerald®); 10 scans were taken for each model, using each IOS. All IOS datasets were loaded into a reverse-engineering software where they were superimposed on the corresponding RMs, to evaluate trueness, and superimposed on each other within groups, to determine precision. A statistical analysis was performed. RESULTS: In the SC, CS 3600® had the best trueness (15.2 ± 0.8 µm), followed by Trios3® (22.3 ± 0.5 µm), DWIO® (27.8 ± 3.2 µm), Omnicam® (28.4 ± 4.5 µm), Emerald® (43.1 ± 11.5 µm). In the PP, CS 3600® had the best trueness (23 ± 1.1 µm), followed by Trios3® (28.5 ± 0.5 µm), Omnicam® (38.1 ± 8.8 µm), Emerald® (49.3 ± 5.5 µm), DWIO® (49.8 ± 5 µm). In the FA, CS 3600® had the best trueness (44.9 ± 8.9 µm), followed by Trios3® (46.3 ± 4.9 µm), Emerald® (66.3 ± 5.6 µm), Omnicam® (70.4 ± 11.9 µm), DWIO® (92.1 ± 24.1 µm). Significant differences were found between the IOSs; a significant difference in trueness was found between the contexts (SC vs. PP vs. FA). In the SC, CS 3600® had the best precision (11.3 ± 1.1 µm), followed by Trios3® (15.2 ± 0.8 µm), DWIO® (27.1 ± 10.7 µm), Omnicam® (30.6 ± 3.3 µm), Emerald® (32.8 ± 10.7 µm). In the PP, CS 3600® had the best precision (17 ± 2.3 µm), followed by Trios3® (21 ± 1.9 µm), Emerald® (29.9 ± 8.9 µm), DWIO® (34.8 ± 10.8 µm), Omnicam® (43.2 ± 9.4 µm). In the FA, Trios3® had the best precision (35.6 ± 3.4 µm), followed by CS 3600® (35.7 ± 4.3 µm), Emerald® (61.5 ± 18.1 µm), Omnicam® (89.3 ± 14 µm), DWIO® (111 ± 24.8 µm). Significant differences were found between the IOSs; a significant difference in precision was found between the contexts (SC vs. PP vs. FA). CONCLUSIONS: The IOSs showed significant differences between them, both in trueness and in precision. The mathematical error increased in the transition from SC to PP up to FA, both in trueness than in precision.


Assuntos
Projeto Auxiliado por Computador , Técnica de Moldagem Odontológica , Coroas , Modelos Dentários , Imagem Tridimensional , Maxila
9.
Eur J Prev Cardiol ; 26(17): 1877-1885, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31109187

RESUMO

AIMS: The aim of this study was to investigate the independent associations of occupational (OPA) and sport physical activity (SpPA) and job strain on the incidence of coronary heart disease (CHD) events, and to explore their interplay. METHODS: The study sample included 3310 25-64-year-old employed men, free of CHD at baseline, recruited in three population-based and one factory-based cohorts. OPA and SpPA, and job strain were assessed by the Baecke and the Job Content Questionnaires, respectively. We estimated the associations between different domains of physical activity and job strain with CHD, adjusting for major risk factors using Cox models. RESULTS: During follow-up (median=14 years), 120 CHD events, fatal and non-fatal, occurred. In the entire sample, a higher CHD risk was found for high job strain (hazard ratio=1.55, 95% confidence interval: 1.05-2.31). The joint effect of low OPA and high job strain was estimated as a hazard ratio of 2.53 (1.29-4.97; reference intermediate OPA with non-high strain). With respect to intermediate OPA workers, in stratified analysis when SpPA is none, low OPA workers had a hazard ratio of 2.13 (95% confidence interval: 1.19-3.81), increased to 3.95 (1.79-8.78) by the presence of high job strain. Low OPA-high job strain workers take great advantage from SpPA, reducing their risk up to 90%. In contrast, the protective effect of SpPA on CHD in other OPA-job strain categories was modest or even absent, in particular when OPA is high. CONCLUSIONS: Our study shows a protective effect of recommended and intermediate SpPA levels on CHD risk among sedentary male workers. When workers are jointly exposed to high job strain and sedentary work their risk further increases, but this group benefits most from regular sport physical activity.

10.
Oral Dis ; 25(6): 1634-1644, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31066953

RESUMO

OBJECTIVE: The purpose of this case-control study was to compare the pharmacological anamnesis collected from a group of 150 burning mouth syndrome (BMS) patients with that of a control group of 150 patients matched for age and sex. MATERIALS AND METHODS: The patients' medical histories were reviewed, and data on drug therapy were collected. Drugs were classified on the basis of pharmacological effects; the classes were antihypertensives (i.e., ACE inhibitors/ARBs, calcium antagonists, diuretics and beta-blockers), antiaggregants, anticoagulants, antidiabetics, vitamin D integrators, bisphosphonates, psychotropics (i.e., anxiolytics and antidepressants), gastroprotectors, statins, thyroid hormone substitutes, corticosteroids and immunosuppressants. RESULTS: The BMS patients and the controls were matched for age (mean age: 69 years) and sex (128 females and 22 males). Antihypertensives, especially ACE inhibitors/ARBs (OR = 0.37, CI: 0.22-0.63, p = 0.0002) and beta-blockers (OR = 0.36, CI: 0.19-0.68 p = 002), revealed an inverse association with the presence of BMS, whereas anxiolytics (OR = 3.78, CI: 2.12-6.75 p < 0.0001), but neither antidepressants nor antipsychotics, were significantly associated with BMS. There were no correlations with other drug classes. CONCLUSION: Our study highlighted that ACE inhibitors, ARBs and beta-blockers were in inverse relation to BMS and found that anxiolytics, but neither antidepressants nor antipsychotics, were linked to the presence of the syndrome.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Antidepressivos/efeitos adversos , Antipsicóticos/efeitos adversos , Síndrome da Ardência Bucal , Antagonistas Adrenérgicos beta/administração & dosagem , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Antidepressivos/administração & dosagem , Antipsicóticos/administração & dosagem , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
Stroke ; 50(3): 610-617, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30786848

RESUMO

Background and Purpose- NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a risk factor for atrial fibrillation and a marker of cardiac function used in the detection of heart failure. Given the link between cardiac dysfunction and stroke, NT-proBNP is a candidate marker of stroke risk. Our aim was to evaluate the association of NT-proBNP with stroke and to determine the predictive value beyond a panel of established risk factors. Methods- Based on the Biomarkers for Cardiovascular Risk Assessment in Europe-Consortium, we analyzed data of 58 173 participants (50% men; mean age 52 y) free of stroke from 6 community-based cohorts. NT-proBNP measurements were performed in the central Biomarkers for Cardiovascular Risk Assessment in Europe laboratory. The outcomes considered were total stroke and subtypes of stroke (ischemic/hemorrhagic). Results- During a median follow-up time of 7.9 years, we observed 1550 stroke events (1176 ischemic). Increasing quarters of the NT-proBNP distribution were associated with increasing risk of stroke ( P for trend <0.0001; multivariable Cox regression analysis adjusted for risk factors and cardiac diseases). Individuals in the highest NT-proBNP quarter (NT-proBNP >82.2 pg/mL) had 2-fold (95% CI, 75%-151%) greater risk of stroke than individuals in the lowest quarter (NT-proBNP <20.4 pg/mL). The association remained unchanged when adjusted for interim coronary events during follow-up, and though it was somewhat heterogeneous across cohorts, it was highly homogenous according to cardiovascular risk profile or subtypes of stroke. The addition of NT-proBNP to a reference model increased the C-index discrimination measure by 0.006 ( P=0.0005), yielded a categorical net reclassification improvement of 2.0% in events and 1.4% in nonevents and an integrated discrimination improvement of 0.007. Conclusions- In European individuals free of stroke, levels of NT-proBNP are positively associated with risk of ischemic and hemorrhagic stroke, independently from several other risk factors and conditions. The addition of NT-proBNP to variables of established risk scores improves prediction of stroke, with a medium effect size.


Assuntos
Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Adulto , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Biomarcadores , Isquemia Encefálica/sangue , Isquemia Encefálica/epidemiologia , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Humanos , Hemorragias Intracranianas/sangue , Hemorragias Intracranianas/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Fatores Sexuais , Resultado do Tratamento
12.
Clin Colorectal Cancer ; 18(2): e251-e260, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30638691

RESUMO

BACKGROUND: Approximately 10% of metastatic colorectal cancer (mCRC) cases will harbor the BRAF p.V600E mutation (BRAF-mCRC) and have been associated with a poor prognosis. Although they are usually considered a unique clinical entity, biologic heterogeneity has been described. We performed an extensive clinicopathologic study of a multicenter series of BRAF-mCRC to highlight differences between tumors with microsatellite instability (MSI) and microsatellite stable tumors, focusing on both inflammatory profiles and neuroendocrine differentiation. METHODS: We included 59 BRAF-mCRC cases and collected the clinical data (ie, surgery, treatment, and follow-up). We evaluated MSI status, budding, lympho-angioinvasion, neuroinvasion, extent of active stroma, CD3+ and CD8+ intratumoral and peritumoral lymphocytes, programmed cell death ligand 1, p53, Ki-67, synaptophysin, and CDX2 expression. RESULTS: The 22 MSI BRAF-mCRC cases were associated with the right side (P < .0001), an expansive grown pattern (P < .01), programmed cell death ligand 1 expression (P < .0001), high CD8 T-cell content (P = .0001), and lymph node metastases (P < .029). The 37 MSS BRAF-mCRC cases were characterized by a greater stromal component (P = .0002), pulmonary metastases (P = .095), and p53 and synaptophysin immunoreactivity (P = .004 and P = .001, respectively). Univariate analysis demonstrated that MSI and a high CD8 T-cell content were associated with a 34% (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.34-1.28; P = .2) and 33% (HR, 0.67; 95% CI, 0.45-0.99; P = .04) reduction in the risk of death, respectively. The combined presence of MSI and CD8 T-cell content decreased the hazard of mortality ≤ 63% (HR, 0.37; 95% CI, 0.14-0.97; P = .2), which was slightly reduced after multivariate analysis. CONCLUSION: A simultaneous evaluation of MSI, CD8 T-cell content, and neuroendocrine markers could allow for the identification of subsets of BRAF-mCRC with a different prognosis and potential eligibility for specific treatments.

13.
Head Neck ; 2019 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31889395

RESUMO

BACKGROUND: Post therapeutic surveillance of head and neck neoplasms is a still debated issue in the current literature: although different works tried to establish frequency, modality, and efficacy of a routine follow-up, little evidence has been produced, in particular considering only sinonasal malignancies. METHODS: A retrospective review of patients treated for sinonasal malignancies in a single tertiary center and followed through a regular program of follow-up was carried out. Rate of recurrence, location, timing, diagnosis, and salvage treatment were the main data analyzed. RESULTS: Of note, 417 patients were included in the study and 117 experienced at least one relapse. Staging, histological type, and previous treatment represent the main clinical factors to be considered to stratify patient's risk of recurrence. CONCLUSION: A regular post therapeutic surveillance can provide an early recurrence detection for patients treated for sinonasal malignancies, offering opportunity for salvage treatment in a high percentage of patients.

14.
G Ital Med Lav Ergon ; 41(4): 333-336, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32126604

RESUMO

SUMMARY: Aims. Some categories of workers are more vulnerable to the detrimental effect of job strain on cardiovascular risk. We investigate allostatic load, the physiological "wear and tear" resulting from adaptation to chronic stress, as a candidate pathway to explain such vulnerability. Methods. We selected 25-64 years old salaried workers participants to three population-based cohorts. We defined allostatic load (AL) as the sum of z-scores of 9 selected biomarkers; occupational classes (OCs) from the Erikson- Goldthorpe-Portocarero schema; and job strain (JS) according to Karasek's demand-control model. We adopted the Oaxaca- Blinder decomposition to disentangle the OC gradient in AL into the differential exposure (attributable to different JS prevalence across OCs) and the differential vulnerability (attributable to a different effect of JS on AL across OCs) components. Results. In the n=2010 workers (62% men, 34% manuals), OCs, but not JS categories, were associated with AL, independently of age and gender (p-value: 0.02). In the overall sample, JS did not have an effect on the OC gradient in AL. Conversely, in workers with sleep impairment, depression, or not engaged into physical activity, JS had a positive differential vulnerability coefficient of 0.63 (95%CI 0.05 to 1.21). Conclusions. In manual workers with impaired capacity of response, job strain is associated with a disproportional allostatic load accumulation.

15.
Biomed Res Int ; 2018: 5325032, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30112398

RESUMO

Aim: To compare the outcome of digital versus analog procedures for the restoration of single implants. Methods: Over a two-year period (2014-2016), all patients who had been treated in a dental center with a single implant were randomly assigned to receive either a monolithic zirconia crown, fabricated with digital workflow (test group), or a metal-ceramic crown, fabricated with analog workflow (control group). All patients were followed for 1 year after the delivery of the final crown. The outcomes were success, complications, peri-implant marginal bone loss (PIMBL), patient satisfaction, and time and cost of the treatment. Results: 50 patients (22 males, 28 females; mean age 52.6±13.4 years) were randomly assigned to one of the groups (25 per group). Both workflows showed high success (92%) and low complication rate (8%). No significant differences were found in the mean PIMBL between test (0.39±0.29mm) and control (0.54±0.32mm) groups. Patients preferred digital impressions. Taking the impression took half the time in the test group (20±5min) than in the control (50±7min) group. When calculating active working time, workflow in the test group was more time-efficient than in the control group, for provisional (70±15min versus 340±37min) and final crowns (29±9min versus 260±26min). The digital procedure presented lower costs than the analog (€277.3 versus €392.2). Conclusions: No significant clinical or radiographic differences were found between digital and analog procedures; however, the digital workflow was preferred by patients; it reduced active treatment time and costs. The present study is registered in the ISRCTN (http://www.isrctn.com/ISRCTN36259164) with number 36259164.


Assuntos
Projeto Auxiliado por Computador , Coroas , Planejamento de Prótese Dentária , Adulto , Idoso , Implantes Dentários para Um Único Dente , Porcelana Dentária , Falha de Restauração Dentária , Feminino , Seguimentos , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
16.
Arch Public Health ; 76: 31, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29988313

RESUMO

Background: Population-based registries implement the comprehensive collection of all disease events that occur in a well-characterized population within a certain time period and represent the preferred tools for disease monitoring at a population level. Main characteristics of a Population-based registry are to provide answers to defined research questions, also related to clinical and health policy purposes, assuring completeness of event identification, and implementing a process of case adjudication (validation) according to standardised diagnostic criteria. Methods: The application of a standard methodology results in the availability of reliable and comparable data and facilitates the transferability of health information for research and evidence-based health policies. Although registries are extremely useful, they require considerable resources to be implemented and maintained, high cost and efforts, to produce stable and reliable indicators. Results: Thanks to available health information and information technology, current administrative databases on hospital admissions and discharges, medication use, in-patient care utilization, surgical operations, drug dispensations, ticket exemption and invasive procedures are increasingly available. They represent basic sources of information for implementing Population-based registries.Main strengths and limitations of Population-based registries are described taking into consideration the example of cardiovascular diseases, as well as future challenges and opportunities for implementing Population-based registries at European level. Conclusions: The integration of population-based registries and current administrative health databases may help to complete the picture of the disease rebuilding the evolution of the disease as a continuum from the onset to the possible consequent complications.

17.
Int J Public Health ; 63(6): 723-732, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29802415

RESUMO

OBJECTIVES: The prognostic utility of lifestyle risk factors and job-related conditions (LS&JRC) for cardiovascular disease (CVD) risk stratification remains to be clarified. METHODS: We investigated discrimination and clinical utility of LS&JRC among 2532 workers, 35-64 years old, CVD-free at the time of recruitment (1989-1996) in four prospective cohorts in Northern Italy, and followed up (median 14 years) until first major coronary event or ischemic stroke, fatal or non-fatal. From a Cox model including cigarette smoking, alcohol intake, occupational and sport physical activity and job strain, we estimated 10-year discrimination as the area under the ROC curve (AUC), and clinical utility as the Net Benefit. RESULTS: N = 162 events occurred during follow-up (10-year risk: 4.3%). The LS&JRC model showed the same discrimination (AUC = 0.753, 95% CI 0.700-0.780) as blood lipids, blood pressure, smoking and diabetes (AUC = 0.753), consistently across occupational classes. Among workers at low CVD risk (n = 1832, 91 CVD events), 687 were at increased LS&JRC risk; of these, 1 every 15 was a case, resulting in a positive Net Benefit (1.27; 95% CI 0.68-2.16). CONCLUSIONS: LS&JRC are as accurate as clinical risk factors in identifying future cardiovascular events among working males. Our results support initiatives to improve total health at work as strategies to prevent cardiovascular disease.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Saúde do Trabalhador , Adulto , Emprego/psicologia , Feminino , Humanos , Itália/epidemiologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco
18.
Eur J Vasc Endovasc Surg ; 55(5): 633-639, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29506942

RESUMO

OBJECTIVES: Prevalence data on abdominal aortic aneurysm (AAA) in women, subjects younger than 65 years and in subgroups carrying specific risk factors are scarce. AAA prevalence was evaluated in an Italian population including women and younger subjects, stratifying for the presence of cardiovascular disease (CVD) risk factors and CVD risk score. MATERIALS AND METHODS: A population based cross-sectional study was conducted between 2013 and 2016. Men aged 50-75 and women aged 60-75 years, resident in the city of Varese (northern Italy), were randomly selected from the civil registry. A vascular surgeon performed an abdominal aortic ultrasound scan at four sites using the leading edge to leading edge method. CVD risk score was computed using the ESC-SCORE algorithm. The age and gender specific prevalence was estimated, stratifying by the presence of CVD and cardiovascular risk factors. RESULTS: Among the 3755 subjects with a valid ultrasound measurement, 63 subjects with an AAA were identified (5 referred for surgical intervention), among whom 34 were not previously known (30 men 1.3%, 95% CI 0.9-1.8; 4 women 0.3%, 95% CI 0.1-0.8). Considering age classes in men only, the highest prevalence of screen detected AAA was found in subjects aged 65-70 (1.2%; 95% CI 0.4-2.5) and 70-75 (2.5%; 95% CI 1.4-4.0) years. Among 65-75 year old men, the highest AAA prevalence was found in subjects with a previous myocardial infarction (MI 4.9%, 95% CI 2.0-9.9) and in ever-smokers reporting more than 15 pack years of smoking (4.1%, 95% CI 2.5-6.3). Among the younger subjects, those having an ESC-SCORE higher than 5% or a previous CVD (MI or stroke) showed a prevalence of 1.4% (95% CI 0.3-4.2; prevalence including subaneurysms 6.7%, 95% CI 3.7-11.0%). CONCLUSIONS: In the study population, both a general screening program in 65-75 year old men and an approach targeted to subgroups at higher risk merit evaluation in a cost-effectiveness study. In 50-64 year old men, strategies for population selection should consider CVD risk stratification tools.


Assuntos
Aneurisma da Aorta Abdominal/epidemiologia , Programas de Rastreamento , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Prevalência , Medição de Risco , Fatores de Risco , Fumar/epidemiologia , Ultrassonografia
19.
Int J Qual Health Care ; 30(5): 344-350, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29474652

RESUMO

Background: Hospital-based registries provide a key contribution in assessing the quality of care in acute myocardial infarction (MI) patients, although some concern on selection bias of included cases has recently arisen. We investigated the feasibility of a retrospective, population-based registry of MIs in monitoring the quality of care. Methods: We identified all the hospitalizations with a diagnosis of acute MI among 35-79 years old residents in the Varese province, Northern Italy, in 2007-2008. Information needed to define performance according to the American Heart Association set was extracted from hospital case histories. To characterize our approach, we focus on data completeness for critical event times and eligibility criteria, and on the analysis of ST-elevated MI (STEMI) patients according to received reperfusion treatment. Results: Exact time of hospital admission and of percutaneous coronary angioplasty (PCI) procedure was available in 96% and 77% of MIs, with no difference between non-transferred (n = 1399) and inter-hospital transferred (n = 300) patients. Data completeness for eligibility to action/treatment criteria was >90% for each performance measure except statin prescription at discharge (76%). About 45% of STEMI experienced a delay in PCI-capable hospital arrival, and only one every three ST-elevated MI patients received primary PCI; these were more likely to be younger male cases with less comorbidities than un-treated patients. Conclusions: Complementary to clinical registries, the retrospective population-based is a feasible approach which allows monitoring the entire pattern of care of all hospitalized MI patients independent of their clinical characteristics.


Assuntos
Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/cirurgia , Garantia da Qualidade dos Cuidados de Saúde/métodos , Sistema de Registros , Adulto , Idoso , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Reperfusão Miocárdica/estatística & dados numéricos , Transferência de Pacientes/estatística & dados numéricos , Intervenção Coronária Percutânea/estatística & dados numéricos , Estudos Retrospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia
20.
Heart ; 104(14): 1165-1172, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29440185

RESUMO

OBJECTIVES: We investigate the independent and interacting long-term associations of occupational physical activity (OPA) and sport physical activity (SpPA) with the incidence of coronary heart disease (CHD) and cardiovascular diseases (CVD; CHD plus ischaemic stroke) in North Italian male workers. METHODS: 3574 employed men aged 25-64 years, free of CVD at baseline, recruited in three population-based and one factory-based cohorts, were included in the analysis. The Baecke Questionnaire was used to assess OPA and SpPA in 'minutes per week' of moderate or vigorous PA. We estimated the associations between different domains of PA and the endpoints, adjusting for major CVD risk factors, using Cox models. RESULTS: During a median follow-up of 14 years, 135 and 174 first CHD and CVD events, fatal and non-fatal, occurred. Compared with the intermediate OPA tertile, the HRs for CHD among low and high OPA workers were 1.66 (95% CI 1.06 to 2.59) and 1.18 (0.72 to 1.94), respectively (P value=0.07). Decreasing trends in CHD and CVD rates across increasing levels of SpPA were also found, with an HR for CVD of 0.68 (0.46 to 0.98) for intermediate/recommended SpPA compared with poor SpPA. We also found a statistically significant SpPA-OPA interaction, and the protective effect of SpPA was only found among sedentary workers, for both endpoints. Conversely, high OPA workers with intermediate/recommended SpPA levels had increased CHD and CVD rates compared with the poor SpPA category. CONCLUSIONS: Our results provide further evidence on the health paradox of OPA, with higher CVD rates among workers with intense PA at work. Moreover, the protective effect on CVDs of SpPA is prominent in sedentary workers, but it attenuates and even reverses in moderate and strenuous OPA workers.


Assuntos
Doença das Coronárias/epidemiologia , Exercício , Saúde do Trabalhador , Esportes , Acidente Vascular Cerebral/epidemiologia , Adulto , Estudos de Coortes , Seguimentos , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Risco , Comportamento Sedentário
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