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1.
J Hepatol ; 75(6): 1355-1366, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34333100

RESUMO

BACKGROUND & AIMS: Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model. METHODS: In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses. RESULTS: In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD. CONCLUSIONS: In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed. LAY SUMMARY: While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model.


Assuntos
Doença Hepática Terminal/classificação , Doença Hepática Terminal/etiologia , Mortalidade/tendências , Adulto , Idoso , Estudos de Coortes , Doença Hepática Terminal/mortalidade , Seguimentos , Humanos , Itália , Pessoa de Meia-Idade , Modelos Biológicos , Prognóstico , Índice de Gravidade de Doença , Fatores de Tempo , Estudos de Validação como Assunto
2.
J Viral Hepat ; 28(8): 1190-1199, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33896097

RESUMO

Real-world evidence on the course of Hepatitis C Virus (HCV) chronic liver disease after Sustained Virologic Response (SVR) obtained with direct-acting antiviral drugs (DAAs) are still limited, and the effects on mortality remain unclear. We evaluated the post-treatment survival of 4307 patients in the RESIST-HCV cohort (mean age 66.3 ± 11.6 years, 56.9% males, 24.7% chronic hepatitis, 66.9% Child-Pugh A cirrhosis and 8.4% Child-Pugh B cirrhosis) treated with DAAs between March 2015 and December 2016 and followed for a median of 73 weeks (range 16-152). Proportional cause-specific hazard regression for competing risks was used to evaluate the survival and to assess the predictors of liver and cardiovascular death. Overall, 94.7% of patients achieved SVR while 5.3% were HCV RNA-positive at last follow-up. Sixty-three patients (1.4%) died during the observation period. SVR was associated with a decreased risk of liver mortality (hazard ratio,HR0.09, beta -2.37, p < .001). Also, platelet count (HR 0.99, beta-0.01, p = .007) and albumin value (HR 0.26, beta -1.36 p = .001) were associated with liver mortality by competing risk analysis. SVR was associated with a reduced risk of cardiovascular mortality regardless of presence of cirrhosis (HR 0.07, beta-2.67, p < .001). Presence of diabetes (HR 3.45, beta 1.24, p = .014) and chronic kidney disease class ≥3 (HR 3.60, beta 1.28, p = 0.016) were two factors independently associated with higher risk of cardiovascular mortality. Patients with SVR to a DAA therapy have a better liver and cardiovascular survival, and the effects of HCV eradication are most evident in patients with compensated liver disease.


Assuntos
Doenças Cardiovasculares , Hepatite C Crônica , Hepatite C , Idoso , Antivirais/uso terapêutico , Doenças Cardiovasculares/epidemiologia , Feminino , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade
3.
J Hepatol ; 71(2): 265-273, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30959157

RESUMO

BACKGROUND & AIMS: The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV), following successful treatment of early hepatocellular carcinoma (HCC), has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation. METHODS: We prospectively enrolled 163 consecutive patients with HCV-related cirrhosis and a first diagnosis of early Barcelona Clinic Liver Cancer stage 0/A HCC, who had achieved a complete radiologic response after curative resection or ablation and were subsequently treated with DAAs. DAA-untreated patients from the ITA.LI.CA. cohort (n = 328) served as controls. After propensity score matching, outcomes of 102 DAA-treated (DAA group) and 102 DAA-untreated patients (No DAA group) were compared. RESULTS: In the DAA group, 7/102 patients (6.9%) died, HCC recurred in 28/102 patients (27.5%) and hepatic decompensation occurred in 6/102 patients (5.9%), after a mean follow-up of 21.4 months. OS was significantly higher in the DAA group compared to the No DAA group (hazard ratio [HR] 0.39; 95% CI0.17-0.91; p = 0.03). HCC recurrence was not significantly different between the DAA and No DAA groups (HR0.70; 95% CI0.44-1.13; p = 0.15). A significant reduction in the rate of hepatic decompensation was observed in the DAA group compared with the No DAA group (HR0.32; 95% CI0.13-0.84; p = 0.02). In the DAA group, sustained virologic response was a significant predictor of OS (HR 0.02; 95% CI 0.00-0.19; p <0.001), HCC recurrence (HR 0.25; 95% CI 0.11-0.57; p <0.001) and hepatic decompensation (HR 0.12; 95% CI 0.02-0.38; p = 0.02). CONCLUSIONS: In patients with HCV-related cirrhosis who had been successfully treated for early HCC, DAAs significantly improved OS compared with No DAA treatment. LAY SUMMARY: We aimed to determine whether direct-acting antivirals (DAAs) significantly improve overall survival in patients with hepatitis C virus-related compensated cirrhosis and a first diagnosis of hepatocellular carcinoma (HCC) which has been successfully treated with curative resection or ablation. Using propensity-score matched patients, we found that DAAs improved overall survival and reduced the risk of hepatic decompensation. However, the risk of HCC recurrence was not significantly reduced.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/mortalidade , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Cirrose Hepática/complicações , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Hepatite C/virologia , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Pontuação de Propensão , Estudos Prospectivos , Taxa de Sobrevida , Resposta Viral Sustentada
4.
Am J Gastroenterol ; 114(8): 1275-1282, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31135449

RESUMO

INTRODUCTION: The Baveno VI consensus guidelines and an expanded algorithm suggest that transient elastography (TE) and platelet (PLT) count can be used to identify patients with cirrhosis who can avoid esophagogastroduodenoscopy (EGD). The primary aims of this study were to assess the ability of a simple algorithm, which uses only laboratory parameters, to predict medium/large esophageal varices (EV) in patients with hepatitis C virus (HCV) and cirrhosis from the Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) cohort and to compare the performance of the algorithm with Baveno VI and Expanded Baveno VI criteria. The secondary aim was to assess the role of TE in ruling out large EV. METHODS: In total, 1,381 patients with HCV-associated cirrhosis who had EGD and TE within 1 year of starting treatment with direct-acting antivirals were evaluated. Using multivariate logistic analysis, laboratory variables were selected to determine which were independently associated with medium/large EV to create the RESIST-HCV criteria. These criteria were tested in a training cohort with patients from a single center (Palermo) and validated with patients from the 21 other centers of the RESIST-HCV program (validation cohort). RESULTS: In the entire cohort, medium/large EV were identified in 5 of 216 patients (2.3%) using the Baveno VI criteria and 13 of 497 patients (2.6%) using the Expanded Baveno VI criteria. PLT count and albumin level were independently associated with medium/large EV. The best cut-off values were a PLT count greater than 120 × 10 cells/µL and serum albumin level greater than 3.6 g/dL; negative predictive values (NPVs) were 97.2% and 94.7%, respectively. In the training cohort of 326 patients, 119 (36.5%) met the RESIST-HCV criteria and the NPV was 99.2%. Among 1,055 patients in the validation cohort, 315 (30%) met the RESIST-HCV criteria and the NPV was 98.1%. Adding TE to the RESIST-HCV criteria reduced the avoided EGDs for approximately 25% of patients and the NPV was 98.2%. DISCUSSION: The "easy-to-use" RESIST-HCV algorithm avoids EGD for high-risk EV screening for more than 30% of patients and has the same performance criteria as TE. Using these criteria simplifies the diagnosis of portal hypertension.


Assuntos
Varizes Esofágicas e Gástricas/diagnóstico , Hepatite C Crônica/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Albumina Sérica/metabolismo , Idoso , Algoritmos , Técnicas de Imagem por Elasticidade , Endoscopia do Sistema Digestório , Varizes Esofágicas e Gástricas/etiologia , Feminino , Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/prevenção & controle , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Hepatite C Crônica/metabolismo , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Contagem de Plaquetas , Reprodutibilidade dos Testes
5.
J Hepatol ; 68(3): 563-576, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29111320

RESUMO

The clinical course of cirrhosis is mostly determined by the progressive increase of portal hypertension, hyperdynamic circulation, bacterial translocation and activation of systemic inflammation. Different disease states, encompassing compensated and decompensated cirrhosis and a late decompensated state, are related to the progression of these mechanisms and may be recognised by haemodynamic or clinical characteristics. While these disease states do not follow a predictable sequence, they correspond to varying mortality risk. Acute-on-chronic liver failure may occur either in decompensated or in compensated cirrhosis and is always associated with a high short-term mortality. The increasing severity of these disease states prompted the concept of clinical states of cirrhosis. A multistate approach has been considered to describe the clinical course of the disease. Such an approach requires the assessment of the probabilities of different outcomes in each state, which compete with each other to occur first and mark the transition towards a different state. This requires the use of competing risks analysis, since the traditional Kaplan-Meier analysis should only be used in two-state settings. Accounting for competing risks also has implications for prognosis and treatment efficacy research. The aim of this review is to summarise relevant clinical states and to show examples of competing risks analysis in multistate models of cirrhosis.


Assuntos
Cirrose Hepática , Progressão da Doença , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/fisiopatologia , Prognóstico , Medição de Risco
6.
Curr Oncol ; 31(3): 1504-1514, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38534947

RESUMO

The aim of this study was to present our preliminary experience with transarterial radioembolization (TARE) using Yttrium-90 (90Y), compare the cancer-specific survival (CSS) of patients with hepatocellular carcinoma (HCC) and colorectal cancer (CRC) liver metastases undergoing TARE, and investigate the influence of additional treatments on CSS. Our database was interrogated to retrieve patients who had undergone TARE using Yttrium-90 (90Y) glass or resin microspheres. Kaplan-Meier curves and the log-rank test were employed to conduct survival analysis for the different groups (p < 0.05). Thirty-nine patients were retrieved (sex: 27 M, 12 F; mean age: 63.59 ± 15.66 years): twenty-three with hepatocellular carcinoma (HCC) and sixteen with CRC liver metastasis. Globally, the patients with HCC demonstrated a significantly longer CSS than those with CRC liver metastasis (22.64 ± 2.7 vs. 7.21 ± 1.65 months; p = 0.014). Among the patients with CRC liver metastasis, those receiving TARE and additional concomitant treatments (n = 10) demonstrated a longer CSS than the CRC patients receiving only TARE (9.97 ± 2.21 vs. 2.59 ± 0.24 months; p = 0.06). In the HCC group, there was a trend of a longer CSS in patients (n = 8) receiving TARE and additional treatments (27.89 ± 3.1 vs. 17.69 ± 3.14 months; p = 0.15). Patients with HCC seem to achieve a longer survival after TARE compared to patients with CRC liver metastases. In patients with CRC liver metastases, the combination of TARE and additional concomitant treatments may improve survival.


Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Humanos , Pessoa de Meia-Idade , Idoso , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Radioisótopos de Ítrio
7.
Front Immunol ; 15: 1397890, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38799474

RESUMO

Objective: Inflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF. Methods: The risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still's disease patients and Behçet's disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression. Results: 580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet's disease patients and 497 Still's disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still's disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet's disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (ß1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (ß1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (ß1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (ß1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (ß1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (ß1 = 2.089, 95% CI. 0.7-3.5, p=0.002). Conclusions: The risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.


Assuntos
Febre Familiar do Mediterrâneo , Neoplasias , Sistema de Registros , Humanos , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/epidemiologia , Neoplasias/epidemiologia , Neoplasias/etiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Fatores de Risco , Estudos de Coortes , Adulto Jovem , Fibromialgia/epidemiologia , Fibromialgia/etiologia , Síndrome de Behçet/epidemiologia , Síndrome de Behçet/complicações
9.
Dig Liver Dis ; 55(6): 704-713, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36586769

RESUMO

The use of artificial intelligence is rapidly increasing in medicine to support clinical decision making mostly through diagnostic and prediction models. Such models derive from huge databases (big data) including a large variety of health-related individual patient data (input) and the corresponding diagnosis and/or outcome (labels). Various types of algorithms (e.g. neural networks) based on powerful computational ability (machine), allow to detect the relationship between input and labels (learning). More complex algorithms, like recurrent neural network can learn from previous as well as actual input (deep learning) and are used for more complex tasks like imaging analysis and personalized (bespoke) medicine. The prompt availability of big data makes that artificial intelligence can provide rapid answers to questions that would require years of traditional clinical research. It may therefore be a key tool to overcome several major gaps in the model of advanced chronic liver disease, mostly transition from mild to clinically significant portal hypertension, the impact of acute decompensation and the role of further decompensation and treatment efficiency. However, several limitations of artificial intelligence should be overcome before its application in clinical practice. Assessment of the risk of bias, understandability of the black boxes developing the models and models' validation are the most important areas deserving clarification for artificial intelligence to be widely accepted from physicians and patients.


Assuntos
Inteligência Artificial , Hepatopatias , Humanos , Aprendizado de Máquina , Redes Neurais de Computação , Algoritmos , Hepatopatias/diagnóstico por imagem
12.
Ann Intern Med ; 154(7): 464-71, 2011 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-21464348

RESUMO

BACKGROUND: The systemic capillary leak syndrome (SCLS) is a rare disease characterized by life-threatening attacks of capillary hyperpermeability. OBJECTIVE: To describe the clinical characteristics, laboratory findings, treatments, and outcomes of patients with SCLS who were not previously reported in the literature. DESIGN: Case series. SETTING: Patients referred to a European multicenter SCLS registry between January 1997 and July 2010. PATIENTS: 28 patients with SCLS. MEASUREMENTS: Frequency, severity of attacks, and vital status were assessed every 6 months, from diagnosis to the end of the study. RESULTS: 13 men and 15 women referred to the registry who were not previously reported in the literature had 252 attacks. Median age at disease onset was 49.1 years (range, 5.4 to 77.7 years), and median annual frequency of attacks was 1.23 (range, 0.13 to 21.18) per patient. Monoclonal IgG gammopathy was observed in 25 patients (89%). Preventive treatment included intravenous immunoglobulin (n = 18), terbutaline (n = 9), and aminophylline (n = 10). Eight patients died (29%); 1-year survival was 89%, and 5-year survival was 73%. Death was directly related to SCLS attacks in 6 of 8 cases (75%). In 10 patients with a prediagnosis period greater than 6 months who received preventive treatment, the annual frequency of attacks after diagnosis decreased by a median of 1.55 (range, 0.14 to 8.84) per patient. Five years after diagnosis, survival was 85% in 23 patients who had received prophylactic treatment and 20% in 5 patients who had not. LIMITATION: The benefits of preventive treatment could not be precisely ascertained because of the small sample size and because most patients received several treatments. CONCLUSION: Clinical experience with these 28 patients with SCLS suggests that prophylactic treatment with ß(2)-agonists or intravenous immunoglobulin may reduce the frequency and severity of attacks and may improve survival. PRIMARY FUNDING SOURCE: Université Pierre et Marie Curie, Paris, France.


Assuntos
Síndrome de Vazamento Capilar , Adolescente , Agonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Bloqueadores dos Canais de Cálcio/uso terapêutico , Síndrome de Vazamento Capilar/diagnóstico , Síndrome de Vazamento Capilar/epidemiologia , Síndrome de Vazamento Capilar/terapia , Criança , Pré-Escolar , Quimioterapia Combinada , Europa (Continente)/epidemiologia , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Resultado do Tratamento , Adulto Jovem
13.
J Allergy Clin Immunol Pract ; 10(11): 2889-2895, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35870726

RESUMO

BACKGROUND: The systemic capillary leak syndrome (SCLS), also known as Clarkson disease, is a very rare condition characterized by recurrent life-threatening episodes of vascular hyperpermeability in the presence of a monoclonal gammopathy. Extended intravenous immunoglobulin (IVIG) treatment is associated with fewer recurrences and improved survival, but the optimal treatment dosage and duration remain unknown. OBJECTIVE: We aim to evaluate the safety of IVIG tapering and withdrawal in patients with SCLS. METHODS: We conducted a retrospective multicenter study including all adult patients with monoclonal gammopathy-associated SCLS from the EurêClark registry who received at least 1 course of IVIG. The primary end point was overall survival according to IVIG withdrawal. RESULTS: Fifty-nine patients of mean ± SD age 51 ± 13 years were included. Overall cumulative probabilities of 2-, 5-, 10- and 15-year survival were 100%, 85%, 72%, 44%, respectively. The IVIG was withdrawn at least once in 18 patients (31%; W+ group) and never in 41 patients (69%; W- group). Cumulative probabilities of 10-year survival in W+ versus W- groups were 50% and 83% (log rank test, P = .02), respectively. Relapse rate and the median number of relapses in the W+ versus the W- groups were 72% versus 58% (P = 0.3) and 2.5 (0.3-4) versus 1 (0-2) (P = .03), respectively. The IVIG tapering was not statistically associated with increased person-year incidence of attacks using a mixed linear model. CONCLUSIONS: The IVIG withdrawal was associated with increased mortality and higher rate of recurrence in SCLS patients. The IVIG tapering might be cautiously considered in stable SCLS patients.


Assuntos
Síndrome de Vazamento Capilar , Paraproteinemias , Adulto , Humanos , Pessoa de Meia-Idade , Síndrome de Vazamento Capilar/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Paraproteinemias/complicações , Estudos Retrospectivos , Incidência
14.
Front Med (Lausanne) ; 9: 980679, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36160138

RESUMO

Objective: The present manuscript aims to describe an international, electronic-based, user-friendly and interoperable patient registry for monogenic autoinflammatory diseases (mAIDs), developed in the contest of the Autoinflammatory Diseases Alliance (AIDA) Network. Methods: This is an electronic platform, based on the Research Electronic Data Capture (REDCap) tool, used for real-world data collection of demographics, clinical, laboratory, instrumental and socioeconomic data of mAIDs patients. The instrument has flexibility, may change over time based on new scientific acquisitions, and communicate potentially with other similar registries; security, data quality and data governance are corner stones of the platform. Results: AIDA project will share knowledge and expertise on mAIDs. Since its start, 118 centers from 24 countries and 4 continents have joined the AIDA project. Fifty-nine centers have already obtained the approval from their local Ethics Committees. Currently, the platform counts 337 users (122 Principal Investigators, 210 Site Investigators, 2 Lead Investigators, and 3 data managers). The Registry collects baseline and follow-up data using 3,748 fields organized into 21 instruments, which include demographics, patient history, symptoms, trigger/risk factors, therapies, and healthcare information for mAIDs patients. Conclusions: The AIDA mAIDs Registry, acts both as a research tool for future collaborative real-life studies on mAIDs and as a service to connect all the figures called to participate. On this basis, the registry is expected to play a pivotal role in generating new scientific evidence on this group of rare diseases, substantially improving the management of patients, and optimizing the impact on the healthcare system. NCT05200715 available at https://clinicaltrials.gov.

15.
Pharmacoepidemiol Drug Saf ; 19(11): 1113-23, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20848397

RESUMO

PURPOSE: Treatment of patients with chronic hepatitis C with alpha-interferon and ribavirin usually produces adverse events within the first 3 months. We aimed to assess safety and predictors of discontinuation or dose modification of these drugs. METHODS: Observational study of 312 patients with predominantly genotype 1 chronic hepatitis C treated openly along 5 years in a clinical practice setting. RESULTS: Eighty-four percent of patients experienced at least one adverse event (853 events in total, 3.3 per patient on average). Incidence rate was higher during the first 90 days and decreased thereafter (<5%). Discontinuation rates at 30 and 90 days and at end of treatment were 2, 4 and 8%, respectively. Seventy percent of discontinuation cases were due to adverse events rather than to laboratory abnormalities. Serious adverse events were rare (<1%). Dose modifications were made in 158 patients (51%) on 237 occasions. After adjusting for covariates, older age was a predictor of early discontinuation, whereas HCV genotypes 1-4 and daily ribavirin dose of 1000 mg or more were predictors of dose modification. CONCLUSIONS: The majority of real-world patients with chronic hepatitis C tolerate acceptably dual therapy and very few discontinue it. Subjective decisions on dose reduction of either compound appears to have a major impact on adherence of patients. There is a need to better define, collect and analyse clinical features which may predict adverse events and safety-related decisions during therapy of chronic hepatitis C.


Assuntos
Antivirais/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Ribavirina/efeitos adversos , Adulto , Fatores Etários , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Humanos , Incidência , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Ribavirina/administração & dosagem , Ribavirina/uso terapêutico
17.
Hepatol Int ; 12(Suppl 1): 34-43, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28681347

RESUMO

The clinical course of cirrhosis has been typically described by a compensated and a decompensated state based on the absence or, respectively, the presence of any of bleeding, ascites, encephalopathy or jaundice. More recently, it has been recognized that increasing portal hypertension and several major clinical events are followed by a marked worsening in prognosis, and disease states have been proposed accordingly in a multistate model. The development of multistate models implies the assessment of the probabilities of more than one possible outcome from each disease state. This requires the use of competing risks analysis which investigates the risk of several competing outcomes. In such a situation, the Kaplan-Meier risk estimates and the Cox regression may be not appropriate. Clinical states of cirrhosis presently considered as suitable for a comprehensive multistate model include: in compensated cirrhosis, early (mild) portal hypertension with hepatic venous pressure gradient (HVPG) >5 and <10 mmHg, clinically significant portal hypertension (HVPG ≥ 10 mmHg) without gastro-esophageal varices (GEV), and GEV; in decompensated cirrhosis, a first variceal bleeding without other decompensating events, any first non-bleeding decompensation and any second decompensating event; and in a late decompensation state, refractory ascites, sepsis, renal failure, recurrent encephalopathy, profound jaundice, acute on chronic liver failure, all predicting a very short survival. In this review, we illustrate how competing risks analysis and multistate models may be applied to cirrhosis.


Assuntos
Varizes Esofágicas e Gástricas/complicações , Hemorragia Gastrointestinal/complicações , Encefalopatia Hepática/complicações , Hipertensão Portal/complicações , Cirrose Hepática/classificação , Cirrose Hepática/complicações , Ascite/complicações , Ascite/epidemiologia , Ascite/mortalidade , Ascite/fisiopatologia , Progressão da Doença , Varizes Esofágicas e Gástricas/epidemiologia , Varizes Esofágicas e Gástricas/mortalidade , Varizes Esofágicas e Gástricas/fisiopatologia , Hemorragia Gastrointestinal/epidemiologia , Hemorragia Gastrointestinal/mortalidade , Hemorragia Gastrointestinal/fisiopatologia , Encefalopatia Hepática/epidemiologia , Encefalopatia Hepática/mortalidade , Encefalopatia Hepática/fisiopatologia , Humanos , Hipertensão Portal/epidemiologia , Hipertensão Portal/mortalidade , Hipertensão Portal/fisiopatologia , Icterícia/complicações , Icterícia/epidemiologia , Icterícia/mortalidade , Icterícia/fisiopatologia , Cirrose Hepática/epidemiologia , Cirrose Hepática/fisiopatologia , Modelos Teóricos , Pressão na Veia Porta/fisiologia , Valor Preditivo dos Testes , Prognóstico , Recidiva , Insuficiência Renal/complicações , Insuficiência Renal/epidemiologia , Insuficiência Renal/mortalidade , Insuficiência Renal/fisiopatologia , Medição de Risco , Sepse/complicações , Sepse/epidemiologia , Sepse/mortalidade , Sepse/fisiopatologia , Índice de Gravidade de Doença
18.
Am J Med ; 130(10): 1219.e19-1219.e27, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28602874

RESUMO

BACKGROUND: Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome. METHODS: We conducted a cohort analysis of all patients included in the European Clarkson disease (EurêClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months. RESULTS: Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality. CONCLUSIONS: We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first line in prevention therapy.


Assuntos
Síndrome de Vazamento Capilar/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Paraproteinemias/diagnóstico por imagem , Síndrome de Vazamento Capilar/etiologia , Síndrome de Vazamento Capilar/mortalidade , Síndrome de Vazamento Capilar/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paraproteinemias/complicações , Paraproteinemias/mortalidade , Paraproteinemias/patologia , Análise de Sobrevida , Terbutalina/uso terapêutico , Teofilina/uso terapêutico
19.
Intern Emerg Med ; 11(2): 251-60, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26910239

RESUMO

The interest in prognosis research has been steadily growing during the past few decades because of its impact on clinical decision making. However, since the methodology of prognosis research is still incompletely defined, the quality of published prognosis studies is largely unsatisfactory. Seven major domain for risk of bias in prognosis research have been identified, including study participation, attrition, selection of candidate predictors, outcome definition, confounding factors, analysis, and interpretation of results. The methodology for performing prognostic studies is currently aimed at avoiding such potential biases. Amongst methodologic requirements in prognosis research, the following should be considered most relevant: beforehand publication of the study protocol including the full statistical plan; inclusion of patients at a similar point along the course of the disease; rationale and biological plausibility of candidate predictors; complete information; control of overfitting and underfitting; adequate data handling and analysis; publication of the original data. Validation and analysis of the impact that prediction models have on patient management, are key steps for translation of prognosis research into clinical practice. Finally, transparent reporting of prognostic studies is essential for assessing reliability, applicability and generalizability of study results, and recommendations are now available for this aim.


Assuntos
Viés , Avaliação de Resultados em Cuidados de Saúde/organização & administração , Prognóstico , Humanos
20.
Expert Rev Anticancer Ther ; 16(12): 1291-1302, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27730841

RESUMO

INTRODUCTION: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death with an increasing prevalence worldwide. Early diagnosis of HCC is important since observational studies have reported that, in patients undergoing surveillance, cancer is diagnosed at an earlier stage with increased chances of curative therapies. Anyway, despite the extensive use of screening for HCC, its effectiveness is still a controversial topic since supporting evidence is not unequivocal and some issues need to be explored. Areas covered: The aim of this paper is to review main literature data supporting performance and effectiveness of screening for early detection of hepatocellular carcinoma. Expert commentary: Clinical benefit of screening for HCC is controversial and there are no sufficient data supporting its effectiveness in reducing cancer specific mortality. Since it is unlikely that RCTs will be performed in the future, surveillance should be still reasonably recommended in all at-risk population, until potential data against its effectiveness will be provided. In the future additional and more effective non-invasive tests will be needed, as well as proper surveillance intervals and risk threshold for surveillance enrollment must be assessed and refined by prospective studies.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Programas de Rastreamento/métodos , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Detecção Precoce de Câncer/métodos , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Estadiamento de Neoplasias , Vigilância da População , Ensaios Clínicos Controlados Aleatórios como Assunto
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