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1.
Hepatology ; 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33345307

RESUMO

BACKGROUND & AIMS: Porto-sinusoidal vascular liver disease (PSVD) is a rare cause of portal hypertension. PSVD is still often misdiagnosed as cirrhosis, emphasizing the need to improve PSVD diagnosis strategies. Data on liver stiffness measurement (TE-LSM) using transient elastography, in PSVD are limited. The aim of this study was to evaluate the accuracy of TE-LSM to discriminate PSVD from cirrhosis in patients with signs of portal hypertension. APPROACH & RESULTS: Retrospective multicenter study comparing TE-LSM in patients with PSVD, according to VALDIG criteria, to patients with compensated biopsy-proven cirrhosis related to alcohol (n=117), hepatitis C virus (HCV) infection (n=110) or non-alcoholic fatty liver disease (NAFLD) (n=46). All patients had at least one sign of portal hypertension among gastroesophageal varices, splenomegaly, porto-systemic collaterals, history of ascites or platelet count < 150 x 109 /L. The 77 patients with PSVD included in the test cohort had lower median TE-LSM [7.9 kilopascals (kPa)] than the patients with alcohol-, HCV- and NAFLD-related cirrhosis (33.8 kPa, 18.2 kPa, and 33.6 kPa, respectively; p<0.001). When compared to cirrhosis, a cut-off value of 10 kPa had a specificity of 97% for the diagnosis of PSVD, with a 85% positive predictive value. A cut-off value of 20 kPa had a sensitivity of 94% for ruling-out PSVD, with a 97% negative predictive value. 94% of the patients were well-classified. Even better results were obtained in a validation cohort including 78 PSVD patients. CONCLUSIONS: This study including a total of 155 patients with PSVD and 273 patients with cirrhosis demonstrates that TE-LSM <10 kPa strongly suggests PSVD in patients with signs of portal hypertension. Conversely, when TE-LSM is >20 kPa, PSVD is highly unlikely.

2.
JAMA Netw Open ; 3(12): e2029050, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33301017

RESUMO

Importance: The survival benefit of corticosteroids in septic shock remains uncertain. Objective: To estimate the individual treatment effect (ITE) of corticosteroids in adults with septic shock in intensive care units using machine learning and to evaluate the net benefit of corticosteroids when the decision to treat is based on the individual estimated absolute treatment effect. Design, Setting, and Participants: This cohort study used individual patient data from 4 trials on steroid supplementation in adults with septic shock as a training cohort to model the ITE using an ensemble machine learning approach. Data from a double-blinded, placebo-controlled randomized clinical trial comparing hydrocortisone with placebo were used for external validation. Data analysis was conducted from September 2019 to February 2020. Exposures: Intravenous hydrocortisone 50 mg dose every 6 hours for 5 to 7 days with or without enteral 50 µg of fludrocortisone daily for 7 days. The control was either the placebo or usual care. Main Outcomes and Measures: All-cause 90-day mortality. Results: A total of 2548 participants were included in the development cohort, with median (interquartile range [IQR]) age of 66 (55-76) years and 1656 (65.0%) men. The median (IQR) Simplified Acute Physiology Score (SAPS II) was 55 [42-69], and median (IQR) Sepsis-related Organ Failure Assessment score on day 1 was 11 (9-13). The crude pooled relative risk (RR) of death at 90 days was 0.89 (95% CI, 0.83 to 0.96) in favor of corticosteroids. According to the optimal individual model, the estimated median absolute risk reduction was of 2.90% (95% CI, 2.79% to 3.01%). In the external validation cohort of 75 patients, the area under the curve of the optimal individual model was 0.77 (95% CI, 0.59 to 0.92). For any number willing to treat (NWT; defined as the acceptable number of people to treat to avoid 1 additional outcome considering the risk of harm associated with the treatment) less than 25, the net benefit of treating all patients vs treating nobody was negative. When the NWT was 25, the net benefit was 0.01 for the treat all with hydrocortisone strategy, -0.01 for treat all with hydrocortisone and fludrocortisone strategy, 0.06 for the treat by SAPS II strategy, and 0.31 for the treat by optimal individual model strategy. The net benefit of the SAPS II and the optimal individual model treatment strategies converged to zero for a smaller number willing to treat, but the individual model was consistently superior than model based on the SAPS II score. Conclusions and Relevance: These findings suggest that an individualized treatment strategy to decide which patient with septic shock to treat with corticosteroids yielded positive net benefit regardless of potential corticosteroid-associated side effects.

3.
BMJ Open ; 10(12): e040931, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33268422

RESUMO

INTRODUCTION: The benefits and risks of low-dose hydrocortisone in patients with septic shock have been investigated in numerous randomised controlled trials and trial-level meta-analyses. Yet, the routine use of this treatment remains controversial. To overcome the limitations of previous meta-analyses inherent to the use of aggregate data, we will perform an individual patient data meta-analysis (IPDMA) on the effect of hydrocortisone with or without fludrocortisone compared with placebo or usual care on 90-day mortality and other outcomes in patients with septic shock. METHODS AND ANALYSIS: To assess the benefits and risks of hydrocortisone, with or without fludrocortisone for adults with septic shock, we will search major electronic databases from inception to September 2020 (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Latin American Caribbean Health Sciences Literature), complimented by a search for unpublished trials. The primary analysis will compare hydrocortisone with or without fludrocortisone to placebo or no treatment in adult patients with septic shock. Secondary analyses will compare hydrocortisone to placebo (or usual care), hydrocortisone plus fludrocortisone to placebo (or usual care), and hydrocortisone versus hydrocortisone plus fludrocortisone. The primary outcome will be all cause mortality at 90 days. We will conduct both one-stage IPDMA using mixed-effect models and machine learning with targeted maximum likelihood analyses. We will assess the risk of bias related to unshared data and related to the quality of individual trial. ETHICS AND DISSEMINATION: This IPDMA will use existing data from completed randomised clinical trials and will comply with the ethical and regulatory requirements regarding data sharing for each of the component trials. The findings of this study will be submitted for publication in a peer-review journal with straightforward policy for open access. PROSPERO REGISTRATION NUMBER: CRD42017062198.

4.
J Biopharm Stat ; : 1-16, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33222634

RESUMO

Dose-finding trials aim to determine a safe dose to be tested in larger trials for efficacy. In oncology, designs generally assume conventional monotonic increasing dose-toxicity relationships, mostly with binary outcomes (e.g., dose-limiting toxicity or not), measured in the first cycle of therapy or for a fixed number of cycles. However, with new anti-cancer agents such as molecularly targeted therapies and immunotherapies, late-onset toxicities have become more frequent. Designs with prolonged observation windows and censored endpoints analyzed using survival models, appear particularly suited to these settings. Moreover, in this setting, the observation of the late-onset toxicity endpoint could be precluded by trial discontinuation due to death, progression, patient withdrawal, or physician discretion, defining a competing event to toxicity. We propose extensions of the Continual Reassessment Method (CRM) dose-finding design using survival working models for right-censored endpoints and for handling treatment discontinuation in the toxicity observation window, namely the Survival-CRM (Surv-CRM) and the informative survival-CRM (iSurv-CRM). We also developed a benchmark approach for its evaluation. In a simulation study, we compared the performance of the Surv-CRM and iSurv-CRM, to those of the Time-to-event (TITE)-CRM and the nonparametric benchmark. The performance of the proposed methods was consistent with the complexity of scenarios as assessed by the nonparametric benchmark. Without treatment discontinuations, the Surv-CRM provides proportions of correct dose selection close to those of the TITE-CRM with fewer observed toxicities and patients assigned to overtoxic dose levels. In the presence of treatment discontinuation, the iSurv-CRM outperforms the TITE-CRM in identifying the correct dose level.

5.
Blood Adv ; 4(22): 5607-5615, 2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33180899

RESUMO

Chimeric antigen receptor (CAR) T-cell therapy has emerged as an option for relapsed/refractory aggressive B-cell lymphomas that have failed 2 lines of therapy. Failures usually occur early after infusion. The purpose of our study was to identify factors that may predict failure, particularly early progression (EP), within the first month after infusion. Characteristics of 116 patients were analyzed at the time of decision (TD) to use commercial CAR (axicabtagene ciloleucel, n = 49; tisagenlecleucel n = 67) and at the time of treatment (TT), together with total metabolic tumor volume (TMTV) at TT. With a median follow-up of 8.2 months, 55 patients failed treatment; 27 (49%) were early progressors. The estimated 12-month progression-free survival (PFS) and overall survival (OS) were 47.2% (95% confidence interval [CI], 38.0-58.6) and 67.0% (95% CI, 57-79), respectively. Univariate analyses for PFS and OS identified Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage III/IV disease, extranodal (EN) sites ≥2, elevated lactate dehydrogenase (LDH), increased C-reactive protein (CRP), high International Prognostic Index at TD and at TT, as well as increased CRP, bulky mass, and high TMTV at TT, as risk factors. Multivariate analyses for PFS, EP, and OS identified elevated LDH and EN sites ≥2 at TD and the same predictors at TT (ie, increased CRP, EN sites ≥2, and TMTV >80 mL). In summary, risk factors identified for early progression at TD and at TT were EN involvement (≥2 sites) and lymphoma burden (LDH, TMTV).

7.
Ann Intensive Care ; 10(1): 128, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32997260

RESUMO

INTRODUCTION: About 30% of patients with Guillain-Barré syndrome become ventilator dependent, of whom roughly 75% develop pneumonia. This trial aimed at assessing the impact of early mechanical ventilation (EMV) on pneumonia occurrence in GBS patients. We hypothesize that EMV will reduce the incidence of pneumonia. METHODS: This was a single centre, open-label, randomized controlled trial performed on two parallel groups. 50 intensive care unit adults admitted for Guillain-Barré syndrome and at risk for acute respiratory failure. Patients were randomized to early mechanical ventilation via face-mask or endotracheal intubation owing to the presence or absence of impaired swallowing (experimental arm), or to conventional care (control arm). The primary outcome was the incidence of pneumonia up to intensive care unit discharge (or 90 days, pending of which occurred first). FINDINGS: Twenty-five patients were randomized in each group. There was no significant difference between groups for the incidence of pneumonia (10/25 (40%) vs 9/25 (36%), P = 1). There was no significant difference between groups for the time to onset of pneumonia (P = 0.50, Gray test). During follow-up, there were 16/25 (64%) mechanically ventilated patients in the control group, and 25/25 (100%) in the experimental arm (P < 000·1). The time on ventilator was non-significantly shorter in the experimental arm (14 [7; 29] versus 21.5 [17.3; 35.5], P = 0.10). There were no significant differences between groups for length of hospital stay, neurological scores, the proportion of patients who needed tracheostomy, in-hospital death, or any serious adverse events. CONCLUSIONS: In the present study including adults with Guillain-Barré syndrome at high risk of respiratory failure, we did not observe a prevention of pneumonia with early mechanical ventilation. TRIAL REGISTRATION: ClinicalTrials.gov under the number NCT00167622. Registered 9 September 2005, https://clinicaltrials.gov/ct2/show/NCT00167622?cond=Guillain-Barre+Syndrome&cntry=FR&draw=2&rank=1.

8.
Blood ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32871585

RESUMO

A multistage model instructed by a large dataset (knowledge bank [KB] algorithm) has recently been developed to improve outcome prediction and tailor therapeutic decision, including hematopoietic stem cell transplantation (HSCT) in AML. We assessed the performance of the KB in guiding HSCT decision in first complete remission (CR1) in 656 AML patients younger than 60 years from the ALFA-0702 trial (NCT00932412). KB predictions of Overall Survival (OS) were superior to those of European LeukemiaNet (ELN) 2017 risk stratification (C-index 68.9 versus 63.0). Among patients reaching CR1, HSCT in CR1, as a time-dependent covariate was detrimental in those with favorable ELN 2017 risk and those with negative NPM1 MRD (interaction tests P=0.01 and P=0.02, respectively). Using KB simulations of survival at 5 years in a scenario without HSCT in CR1 (KB score), we identified in a similar time-dependent analysis a significant interaction between the KB score and HSCT, with HSCT in CR1 being detrimental only in patients with a good prognosis based on KB simulations (KB score ≥40, interaction test P=0.01). We could finally integrate ELN 2017, NPM1 MRD and KB scores to sort 545 CR1 patients into 278 (51.0%) HSCT candidates and 267 (49.0%) chemo-only candidates. In both time-dependent and 6-month landmark analyses, HSCT significantly improved OS in HSCT candidates while it significantly shortened OS in chemo-only candidates. Integrating KB predictions with ELN 2017 and MRD may thus represent a promising approach to optimize HSCT timing in younger AML patients.

9.
BMC Med Educ ; 20(1): 313, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943030

RESUMO

BACKGROUND: The evaluation process of French medical students will evolve in the next few years in order to improve assessment validity. Script concordance testing (SCT) offers the possibility to assess medical knowledge alongside clinical reasoning under conditions of uncertainty. In this study, we aimed at comparing the SCT scores of a large cohort of undergraduate medical students, according to the experience level of the reference panel. METHODS: In 2019, the authors developed a 30-item SCT and sent it to experts with varying levels of experience. Data analysis included score comparisons with paired Wilcoxon rank sum tests and concordance analysis with Bland & Altman plots. RESULTS: A panel of 75 experts was divided into three groups: 31 residents, 21 non-experienced physicians (NEP) and 23 experienced physicians (EP). Among each group, random samples of N = 20, 15 and 10 were selected. A total of 985 students from nine different medical schools participated in the SCT examination. No matter the size of the panel (N = 20, 15 or 10), students' SCT scores were lower with the NEP group when compared to the resident panel (median score 67.1 vs 69.1, p < 0.0001 if N = 20; 67.2 vs 70.1, p < 0.0001 if N = 15 and 67.7 vs 68.4, p < 0.0001 if N = 10) and with EP compared to NEP (65.4 vs 67.1, p < 0.0001 if N = 20; 66.0 vs 67.2, p < 0.0001 if N = 15 and 62.5 vs 67.7, p < 0.0001 if N = 10). Bland & Altman plots showed good concordances between students' SCT scores, whatever the experience level of the expert panel. CONCLUSIONS: Even though student SCT scores differed statistically according to the expert panels, these differences were rather weak. These results open the possibility of including less-experienced experts in panels for the evaluation of medical students.

10.
Biol Blood Marrow Transplant ; 26(11): 2115-2120, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32738501

RESUMO

Ruxolitinib, a selective Janus kinase (JAK)1/2 inhibitor, has recently been proposed for steroid-refractory chronic graft-versus host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT), particularly in severe skin cGVHD. Lung function impairment is common in severe skin cGVHD through concomitant bronchiolitis obliterans syndrome (BOS) or restrictive lung disease (RLD) from skin sclerosis. To date, no treatment has shown a benefit on lung function in this context. We retrospectively assessed the effect of ruxolitinib on lung function in a cohort of 70 patients diagnosed with sclerotic-type skin cGVHD between March 2015 and April 2018. Among these patients, 36 received ruxolitinib. To handle confounding by indication bias, exposure groups were matched on the propensity score to receive ruxolitinib, incorporating age, myeloablative conditioning, total body irradiation, BOS, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and tobacco use at the time of cohort entry, as well as the time from transplantation. The 1:1 matching used a greedy-matching algorithm with replacement, with a caliper of 0.10. FVC and FEV1 trajectories during follow-up were compared in the matched samples, using linear mixed-effects models. The median duration of follow-up of the 46 matched patients was 58 months (interquartile range, 32 to 84 months). Ten patients had an RLD (6 exposed, 4 unexposed), and 13 patients were diagnosed with BOS (8 exposed, 5 unexposed). FEV1 decreased significantly over time independent of exposure to ruxolitinib (P < .0001). The FEV1 trajectory was similar in the exposed patients and the unexposed patients (P = .11). In conclusion, ruxolitinib administration did not demonstrate any improvement in the course of respiratory function in allogeneic HSCT recipients with sclerotic-type skin cGVHD.

11.
Medicina (Kaunas) ; 56(8)2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32784811

RESUMO

Background and objectives: Hip fracture is a major public health issue. Those fractures lead to high costs and a decrease in quality of life. A national French survey was conducted, with the objectives to firstly assess the current management of hip fracture and its prevention, both in the osteoporotic and cancer settings, and secondly to evaluate the opinions of physicians on the potential use of minimally invasive implantable devices to prevent hip fracture in alternative of surgery. Materials and methods: This national survey was conducted in France between April and July 2017. Questionnaires were sent to orthopedic surgeons, interventional radiologists, oncologists, and rheumatologists. Completed questionnaires were analyzed and compared according to two indications: orthopedics-traumatology and oncology. Factors associated with these responses were assessed using univariable analyses, based on chi-square tests or an exact Fisher test, as appropriate. Results: A total of 182 questionnaires were completed and further analyzed. Physicians have highlighted the need for a low re-fracture rate and to improve life expectancy for more than 1 year (50% for responders of the orthopedics-traumatology questionnaire and 80% for the responders interested in both indications), as well as quality of life (12.5% and 31%, respectively), but with no significant differences in the oncologic indication. Most of the experts were willing to use or prescribe implantable devices for prevention (63% in orthopedics-traumatology and 93% in oncology), although limited clinical experience (54 and 58%) and surgical risk (around 30% in each indication) were considered as limits. Conclusions: Prevention of hip fracture remains a concern for physicians. More clinical experience with implantable devices, in particular in cancer patients, is needed, but implemented in a strategy to maximize patient recovery while reducing costs.

12.
Front Med (Lausanne) ; 7: 372, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671084

RESUMO

The severe respiratory distress syndrome linked to the new coronavirus disease (COVID-19) includes unbearable dyspneic suffering which contributes to the deterioration of the prognosis of patients in intensive care unit (ICU). Patients are put on mechanical ventilation to reduce respiratory suffering and preserve life. Despite this mechanical ventilation, most patients continue to suffer from dyspnea. Dyspnea is a major source of suffering in intensive care and one of the main factors that affect the prognosis of patients. The development of innovative methods for its management, especially non-drug management is more than necessary. In recent years, numerous studies have shown that transcranial direct current stimulation (tDCS) could modulate the perception of acute or chronic pain. In the other hand, it has been shown that the brain zones activated during pain and dyspnea are close and/or superimposed, suggesting that brain structures involved in the integration of aversive emotional component are shared by these two complex sensory experiences. Therefore, it can be hypothesized that stimulation by tDCS with regard to the areas which, in the case of pain have activated one or more of these brain structures, may also have an effect on dyspnea. In addition, our team recently demonstrated that the application of tDCS on the primary cortical motor area can modulate the excitability of the respiratory neurological pathways. Indeed, tDCS in anodal or cathodal modality reduced the excitability of the diaphragmatic cortico-spinal pathways in healthy subjects. We therefore hypothesized that tDCS could relieve dyspnea in COVID-19 patients under mechanical ventilation in ICU. This study was designed to evaluate effects of two modalities of tDCS (anodal and cathodal) vs. placebo, on the relief of dyspnea in COVID-19 patients requiring mechanical ventilation in ICU. Trial Registration: This protocol is derived from the tDCS-DYSP-REA project registered on ClinicalTrials.gov NCT03640455. It will however be registered under its own NCT number.

14.
Biom J ; 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32627864

RESUMO

Cluster analysis, commonly used to explore large biomedical datasets, can be challenging, notably due to missing data or left-censored data induced by the sensitivity limits of the biochemical measurement method. Usually, complete-case analysis, simple imputation, or stochastic simple imputation are applied before clustering. More recently, consensus methods following multiple imputation have been proposed. However, they ignore left-censoring and do not allow the number of clusters to vary across the partitions of each imputed dataset. Here, we developed a consensus-based clustering algorithm in which left-censored data are taken into account using a modified multiple imputation method and the number of clusters is estimated for each imputed dataset. A simulation study was conducted to assess the performance in terms of the number of clusters, the percentage of unclassified observations, and the adjusted Rand index. The simulation results showed that the investigated method works well compared to several alternative approaches. A real-world application in breast cancer patients showed that the proposed method may reveal novel clusters of patients.

16.
Transplant Proc ; 52(10): 2980-2987, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32499142

RESUMO

BACKGROUND: Respiratory complications of solid organ transplant (SOT) are a diagnostic and therapeutic challenge when requiring intensive care unit (ICU) admission. We aimed at describing this challenge in a prospective cohort of SOT recipients admitted in the ICU. METHODS: In this post hoc analysis of an international cohort of immunocompromised patients admitted in the ICU for an acute respiratory failure, we analyzed all SOT recipients and compared their severity, etiologic diagnosis, prognosis, and outcome according to the performance of an invasive diagnostic strategy (encompassing a fiber-optic bronchoscopy and bronchoalveolar lavage), the type of transplanted organ, and the need of invasive ventilation at day 1. RESULTS: Among 1611 patients included in the primary study, 142 were SOT recipients (kidney, n = 73; 51.4%; lung, n = 33; 23.2%; liver, n = 29; 20.4%; heart, n = 7; 4.9%). Lung transplant recipients were younger than other SOT recipients, and severity did not differ across type of received organ. An invasive diagnostic strategy was more frequently performed in lung transplant recipients with a trend toward a higher rate of bacterial etiology in lung than kidney transplant recipients. Overall ICU survival of SOT recipients was 75.4%. Invasive diagnostic strategy, type of transplanted organ, and need of invasive mechanical ventilation at day 1 did not affect ICU prognosis. CONCLUSIONS: ICU management of hypoxemic acute respiratory failure in SOT recipients translated into a low ICU mortality rate, whatever the transplanted organ or the acute respiratory failure cause. The post-ICU burden of acute respiratory failure SOT recipients remains to be investigated.

17.
Ann Hematol ; 99(7): 1615-1625, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32483668

RESUMO

Ibrutinib treatment has been shown to increase survival in patients with B cell malignancies. Real-life data suggest a large part of discontinuations are due to toxicities, impairing ibrutinib efficacy. We aimed to assess the impact of a pharmaceutical care program on the efficacy and safety of ibrutinib. This single-center, cohort, observational study enrolled patients with B cell malignancies. Patients were either assigned to the program or to receive usual care, based on physician decision. The program was conducted by clinical pharmacists specializing in oncology and included patient education for management of toxicities, adherence monitoring, interventions to reduce drug-drug interactions, and follow-up of transition from hospital to community. Between February 2014 and May 2017, we enrolled 155 patients, including 42 (27%) who were allocated to the program group and 113 (73%) to the usual care group. The effect of the program was beneficial in terms of time to treatment failure (p = 0.0005). The 30-month progression-free and overall survivals were significantly superior in the program group (respectively p = 0.002 and p = 0.004). Grade 3 or higher adverse events occurred more frequently for patients in the usual care group (15%) than program group (8%). A pharmaceutical care program provides a personalized environment for outpatient monitoring and control of the key risks associated with oral anticancer agents. This study shows evidence that management of ibrutinib treatment by clinical pharmacists results in significant improvement in survival and better tolerance than usual care.


Assuntos
Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Assistência Farmacêutica/normas , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Melhoria de Qualidade , Tempo para o Tratamento/normas , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Eficiência Organizacional , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Assistência Farmacêutica/organização & administração , Assistência Farmacêutica/tendências , Farmacêuticos/organização & administração , Farmacêuticos/normas , Análise de Sobrevida , Fatores de Tempo , Tempo para o Tratamento/organização & administração , Tempo para o Tratamento/tendências , Falha de Tratamento
18.
J Clin Oncol ; 38(23): 2647-2657, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32574117

RESUMO

PURPOSE: We report a multicenter controlled trial comparing renal recovery and tolerance profile of doublet versus triplet bortezomib-based regimens in patients with initial myeloma cast nephropathy (CN) and acute kidney injury (AKI) without need for dialysis. METHODS: After symptomatic measures and high-dose dexamethasone, patients were randomly assigned to receive bortezomib plus dexamethasone (BD), or BD plus cyclophosphamide (C-BD). In patients with < 50% reduction of serum free light chains (sFLCs) after 3 cycles, chemotherapy was reinforced with either cyclophosphamide (BD group) or thalidomide (C-BD group). RESULTS: Ninety-two patients were enrolled in each group. At random assignment, characteristics of the 2 groups were similar, including median age (68 years) and serum creatinine level (305.5 and 273.5 µmol/L in BD and C-BD group, respectively). At 3 months, renal response rate (primary end point) was not different (41 v 47 responders in the BD and C-BD groups, respectively; relative risk [RR], 0.87; P = .46). Very good partial response (free light chain reduction ≥ 90%) or more was achieved in 36 and 47 patients, respectively (RR, 0.76; P = .10). After 1 cycle of chemotherapy, 69 in the BD group and 67 patients in the C-BD group had achieved sFLC level ≤ 500 mg/L. Serious adverse events were recorded in 30 and 40 patients, respectively. At 12 months, 19 patients had died (9 in the BD group v 10 in the C-BD group), including 10 (6 in the BD group and 4 in the C-BD group) from myeloma progression and 3 (0 in the BD group and 3 in the C-BD group) from infection. Within median follow-up of 27 months, 43 and 42 patients switched to new therapy, respectively. Overall, 50 patients (24 in the BD group and 26 in the C-BD group) had died. CONCLUSION: This randomized study did not show any benefit of C-BD compared with BD on renal recovery of patients with initial CN not requiring dialysis. Adding cyclophosphamide did not sufficiently improve the efficacy-toxicity balance. Patients with myeloma with AKI are fragile, and indication for doublet or triplet regimen should be adapted to frailty.

19.
J Clin Med ; 9(5)2020 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-32429507

RESUMO

BACKGROUND: We aimed to estimate the prevalence of cancer patients who presented to Emergency Departments (EDs), report their chief complaint and identify the predictors of 30-day all-cause mortality. PATIENTS AND METHODS: we undertook a prospective, cross-sectional study during three consecutive days in 138 EDs and performed a logistic regression to identify the predictors of 30-day mortality in hospitalized patients. RESULTS: A total of 1380 cancer patients were included. The prevalence of cancer patients among ED patients was 2.8%. The most frequent reasons patients sought ED care were fatigue (16.6%), dyspnea (16.3%), gastro-intestinal disorders (15.1%), trauma (13.0%), fever (12.5%) and neurological disorders (12.5%). Patients were admitted to the hospital in 64.9% of cases, of which 13.4% died at day 30. Variables independently associated with a higher mortality at day 30 were male gender (Odds Ratio (OR), 1.63; 95% CI, 1.04-2.56), fatigue (OR, 1.65; 95% CI, 1.01-2.67), poor performance status (OR, 3.00; 95% CI, 1.87-4.80), solid malignancy (OR, 3.05; 95% CI, 1.26-7.40), uncontrolled malignancy (OR, 2.27; 95% CI, 1.36-3.80), ED attendance for a neurological disorder (OR, 2.38; 95% CI, 1.36-4.19), high shock-index (OR, 1.80; 95% CI, 1.03-3.13) and oxygen therapy (OR, 2.68; 95% CI, 1.68-4.29). CONCLUSION: Cancer patients showed heterogeneity among their reasons for ED attendance and a high need for hospitalization and case fatality. Malignancy and general health status played a major role in the patient outcomes. This study suggests that the emergency care of cancer patients may be complex. Thus, studies to assess the impact of a dedicated oncology curriculum for ED physicians are warranted.

20.
Chest ; 158(3): 986-998, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32387523

RESUMO

BACKGROUND: Randomized controlled trials (RCTs) in patients with hypoxemic acute respiratory failure (ARF) often failed to show survival benefits and resulted in varying clinical end points. RESEARCH QUESTION: This methodologic review was conducted of published RCTs on ARF, with a careful attention to whether the study results were positive or negative. STUDY DESIGN AND METHODS: MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science were searched for published RCTs in adult patients with ARF between January 1995 and December 2019. The objective was to investigate sources of heterogeneity and factors associated with a positive RCT (ie, with a significant difference on the primary end point). To determine the importance of the primary end point choice, end points were classified as follows: (1) respiratory event end points (corresponding to modification of the ventilation support); (2) physiologic/clinical end points (corresponding to oxygenation or clinical parameters); and (3) mortality. The Cochrane risk-of-bias tool was used to assess study quality. RESULTS: Seventy-four RCTs were included (57% were single-center RCTs) comparing mainly oxygenation/ventilation strategies (95%) in patients with various ARF causes (62%); studies were stopped prematurely in 20% of the trials. A standardized management of ARF was observed in 24 (32%) trials. Twenty-two distinct primary end points have been used, the first of which were those based on respiratory events (44 RCTs [49%]), namely intubation in 76% of the cases. Physiologic/clinical end points have been used in 21 trials (29%) and mortality in nine (12%). Overall, 42 (57%) RCTs were positive, 52% in studies with respiratory event end points, 76% in studies with physiologic/clinical end points, and 33% in studies with mortality end points. Adjusted for study quality (Cochrane risk-of-bias tool), factors associated with a positive RCT included clinically based primary end points (OR, 8.40; 95% CI, 1.35-65.79), the use of standardized ARF management (OR, 4.55; 95% CI, 1.02-22.88), and single-center trials (OR, 3.85; 95% CI, 1.25-13.11). INTERPRETATION: The typology of published RCTs in patients with ARF could be used to frame future trial designs in this field and guide clinicians and researchers toward optimal research transfer to the bedside.

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