Investigating covariate-by-centre interaction in survival data.

In survival analysis, assessing the existence of potential centre effects on the baseline hazard or on the effect of fixed covariates on the baseline hazard, such as treatment-by-centre interaction, is a frequent clinical concern in multicentre studies. Survival models with random effects on the baseline hazard and/or on the effect of the covariates of interest have been largely applied, for instance, to investigate potential centre effects. We aimed to develop a procedure to routinely test for multiple random effects in survival analyses.

Natural History of Cardiac and Respiratory Involvement, Prognosis and Predictive Factors for Long-Term Survival in Adult Patients with Limb Girdle Muscular Dystrophies Type 2C and 2D.

Background: Type 2C and 2D limb girdle muscular dystrophies (LGMD) are a group of autosomal recessive limb girdle muscular dystrophies manifested by proximal myopathy, impaired respiratory muscle function and cardiomyopathy. The correlation and the prognostic impact of respiratory and heart impairment are poorly described. We aimed to describe the long-term cardiac and respiratory follow-up of these patients and to determine predictive factors of cardio-respiratory events and mortality in LGMD 2C and 2D.

Recurrent NRAS mutations in pulmonary Langerhans cell histiocytosis.

The mitogen-activated protein kinase (MAPK) pathway is constantly activated in Langerhans cell histiocytosis (LCH). Mutations of the downstream kinases BRAF and MAP2K1 mediate this activation in a subset of LCH lesions. In this study, we attempted to identify other mutations which may explain the MAPK activation in nonmutated BRAF and MAP2K1 LCH lesions.

CAESAR: a new tool to assess relatives' experience of dying and death in the ICU.

Purpose: To develop an instrument designed specifically to assess the experience of relatives of patients who die in the intensive care unit (ICU).

Methods: The instrument was developed using a mixed methodology and validated in a prospective multicentre study. Relatives of patients who died in 41 ICUs completed the questionnaire by telephone 21 days after the death, then completed the Hospital Anxiety and Depression Scale, Impact of Event Scale-Revised and Inventory of Complicated Grief after 3, 6, and 12 months.

Impact of the condolence letter on the experience of bereaved families after a death in intensive care: study protocol for a randomized controlled trial.

Background: As intensive care mortality is high, end of life is a subject of major concern for intensivists. In this context, relatives are particularly vulnerable and prone to post-ICU syndrome, in the form of high levels of anxiety, depression, post-traumatic stress, and complicated grief. Grieving families suffer from a feeling of abandonment and evoke the need to get back in touch with the team to ask questions and remove doubts, but very few actually do.

A multiple imputation approach for MNAR mechanisms compatible with Heckman's model.

Standard implementations of multiple imputation (MI) approaches provide unbiased inferences based on an assumption of underlying missing at random (MAR) mechanisms. However, in the presence of missing data generated by missing not at random (MNAR) mechanisms, MI is not satisfactory. Originating in an econometric statistical context, Heckman's model, also called the sample selection method, deals with selected samples using two joined linear equations, termed the selection equation and the outcome equation.

Pre-treatment with oral hydroxyurea prior to intensive chemotherapy improves early survival of patients with high hyperleukocytosis in acute myeloid leukemia.

Acute myeloid leukemia with high white blood cell count (WBC) is a medical emergency. A reduction of tumor burden with hydroxyurea may prevent life-threatening complications induced by straight chemotherapy. To evaluate this strategy, we reviewed medical charts of adult patients admitted to our institution from 1997 to 2011 with non-promyelocytic AML and WBC over 50 G/L.

Extrathoracic investigation in adult patients with isolated pulmonary langerhans cell histiocytosis.

Background: An important objective on diagnosis of patients with Langerhans cell histiocytosis (LCH) is to determine the extent of disease. However, whether systematic extrathoracic investigation is needed in adult patients with clinically isolated pulmonary LCH (PLCH) has not been evaluated.

Methods: In this prospective, multicentre study, 54 consecutive patients with newly diagnosed clinically isolated PLCH were systematically evaluated at inclusion by bone imaging and blood laboratory testing to search for subclinical extrapulmonary LCH involvement.

Natural Killer Lymphocytes Are Dysfunctional in Kidney Transplant Recipients on Diagnosis of Cancer.

Background: The incidence of cancer is increased after solid organ transplantation. Natural killer (NK) cells are key effectors of the tumor immune response.

Methods: We conducted a cross sectional multicentre matched case-control study including 42 kidney transplant recipients (KTRs) on diagnosis of cancer and 41 KTRs without cancer.

Standard or accelerated methotrexate, vinblastine, doxorubicin and cisplatin as neoadjuvant chemotherapy for locally advanced urothelial bladder cancer: Does dose intensity matter?

Background: There is continuing controversy regarding the optimal regimen for neoadjuvant chemotherapy (NAC) in bladder cancer.

Patients And Methods: We performed a retrospective analysis of 241 consecutive bladder cancer patients who received a combination of methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) using a standard (52 patients) or an accelerated schedule (189 patients) as NAC before radical cystectomy in 17 centres of the French GEnito-urinary TUmour Group from March 2004-May 2013.

Results: The median age was 62 years.

Rituximab and risk of second primary malignancies in patients with non-Hodgkin lymphoma: a systematic review and meta-analysis.

Background: Addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy improves response rates and survival in patients with B-cell non-Hodgkin lymphoma (NHL). However, rituximab induces a transient B-cell depletion and a dose-dependent T-cell inactivation that could impair T-cell immunosurveillance. The impact of rituximab on second primary malignancy (SPM) risk remains unclear so far.

Effect of lenalidomide treatment on clonal architecture of myelodysplastic syndromes without 5q deletion.

Non-del(5q) transfusion-dependent low/intermediate-1 myelodysplastic syndrome (MDS) patients achieve an erythroid response with lenalidomide in 25% of cases. Addition of an erythropoiesis-stimulating agent could improve response rate. The impact of recurrent somatic mutations identified in the diseased clone in response to lenalidomide and the drug's effects on clonal evolution remain unknown.

Acute kidney injury in critically ill patients with haematological malignancies: results of a multicentre cohort study from the Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologie.

Background: Cancer patients are at high risk for acute kidney injury (AKI), which is associated with high morbidity and mortality. We sought to appraise the incidence, risk factors, and outcome of AKI in a large multicentre cohort study of critically ill patients with haematological malignancies.

Methods: We used a retrospective analysis of a prospectively collected database.

Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis-stimulating agent-refractory lower-risk MDS without 5q deletion.

After failure of erythropoiesis-stimulating agents (ESAs), lenalidomide (LEN) yields red blood cell (RBC) transfusion independence (TI) in 20-30% of lower-risk non-del5q myelodysplastic syndrome (MDS). Several observations suggest an additive effect of ESA and LEN in this situation. We performed a randomized phase III study in 131 RBC transfusion-dependent (TD, median transfusion requirement six RBC units per 8 weeks) lower-risk ESA-refractory non-del5q MDS.

Changing use of noninvasive ventilation in critically ill patients: trends over 15 years in francophone countries.

Purpose: Over the last two decades, noninvasive ventilation (NIV) has been proposed in various causes of acute respiratory failure (ARF) but some indications are debated. Current trends in NIV use are unknown.

Methods: Comparison of three multicenter prospective audits including all patients receiving mechanical ventilation and conducted in 1997, 2002, and 2011 in francophone countries.

Effect of Noninvasive Ventilation vs Oxygen Therapy on Mortality Among Immunocompromised Patients With Acute Respiratory Failure: A Randomized Clinical Trial.

Importance: Noninvasive ventilation has been recommended to decrease mortality among immunocompromised patients with hypoxemic acute respiratory failure. However, its effectiveness for this indication remains unclear.

Objective: To determine whether early noninvasive ventilation improved survival in immunocompromised patients with nonhypercapnic acute hypoxemic respiratory failure.

Acute respiratory failure in patients with hematological malignancies: outcomes according to initial ventilation strategy. A groupe de recherche respiratoire en réanimation onco-hématologique (Grrr-OH) study.

Background: In patients with hematological malignancies and acute respiratory failure (ARF), noninvasive ventilation was associated with a decreased mortality in older studies. However, mortality of intubated patients decreased in the last years. In this study, we assess outcomes in those patients according to the initial ventilation strategy.

A Bayesian Hybrid Adaptive Randomisation Design for Clinical Trials with Survival Outcomes.

Background: Response-adaptive randomisation designs have been proposed to improve the efficiency of phase III randomised clinical trials and improve the outcomes of the clinical trial population. In the setting of failure time outcomes, Zhang and Rosenberger (2007) developed a response-adaptive randomisation approach that targets an optimal allocation, based on a fixed sample size.

Objectives: The aim of this research is to propose a response-adaptive randomisation procedure for survival trials with an interim monitoring plan, based on the following optimal criterion: for fixed variance of the estimated log hazard ratio, what allocation minimizes the expected hazard of failure? We demonstrate the utility of the design by redesigning a clinical trial on multiple myeloma.

Ceramic-on-ceramic THA Implants in Patients Younger Than 20 Years.

Background: Poor survival of THA implants in very young patients has been attributed to use of cemented implants, wear of conventional polyethylene, and the presence of morphologic deformities in the proximal femur or in the acetabulum. Few studies have reported the long-term results of ceramic-on-ceramic implants in THAs in patients younger than 20 years.

Question/purposes: We determined: (1) the proportion of patients who experienced complications related to the ceramic bearing (squeaking, fracture); (2) the survivorship free from loosening and free from revision for any reason; (3) whether patients with osteonecrosis had inferior survivorship compared with patients whose surgical indication was all other diagnoses including sequelae of pediatric hip disorders (developmental dysplasia of the hip, Legg-Calvé-Perthes disease, slipped capital femoral epiphysis); and (4) clinical function.

Prognostic value of kidney biopsy in myeloma cast nephropathy: a retrospective study of 70 patients.

Background: Light chain myeloma cast nephropathy (MCN) is the major cause of renal failure in multiple myeloma and strongly impacts patient survival. The role of kidney biopsy in the management of MCN is unclear.

Methods: Renal pathological findings were retrospectively studied in 70 patients with multiple myeloma and MCN.

Bortezomib produces high hematological response rates with prolonged renal survival in monoclonal immunoglobulin deposition disease.

Monoclonal immunoglobulin deposition disease (MIDD) is a rare complication of plasma cell disorders, defined by linear Congo red-negative deposits of monoclonal light chain, heavy chain, or both along basement membranes. While renal involvement is prominent, treatment strategies, such as the impact of novel anti-myeloma agents, remain poorly defined. Here we retrospectively studied 49 patients with MIDD who received a median of 4.