Non-Hodgkin lymphoma.

Lancet. 2012 Jul 24;

Authors: Shankland KR, Armitage JO, Hancock BW

Abstract

Lymphomas are solid tumours of the immune system. Hodgkin's lymphoma accounts for about 10% of all lymphomas, and the remaining 90% are referred to as non-Hodgkin lymphoma. Non-Hodgkin lymphomas have a wide range of histological appearances and clinical features at presentation, which can make diagnosis difficult. Lymphomas are not rare, and most physicians, irrespective of their specialty, will probably have come across a patient with lymphoma. Timely diagnosis is important because effective, and often curative, therapies are available for many subtypes. In this Seminar we discuss advances in the understanding of the biology of these malignancies and new, available treatments.

PMID: 22835603 [PubMed - as supplied by publisher]

Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): a multicentre, randomised open-label trial.

Lancet. 2012 Jun 16;379(9833):2262-9

Authors: Aschner P, Chan J, Owens DR, Picard S, Wang E, Dain MP, Pilorget V, Echtay A, Fonseca V, EASIE investigators

Abstract

BACKGROUND: In people with type 2 diabetes, a dipeptidyl peptidase-4 (DPP-4) inhibitor is one choice as second-line treatment after metformin, with basal insulin recommended as an alternative. We aimed to compare the efficacy, tolerability, and safety of insulin glargine and sitagliptin, a DPP-4 inhibitor, in patients whose disease was uncontrolled with metformin.

METHODS: In this comparative, parallel, randomised, open-label trial, metformin-treated people aged 35-70 years with glycated haemoglobin A(1c) (HbA(1c)) of 7-11%, diagnosis of type 2 diabetes for at least 6 months, and body-mass index of 25-45 kg/m(2) were recruited from 17 countries. Participants were randomly assigned (1:1) to 24-week treatment with insulin glargine (titrated from an initial subcutaneous dose of 0÷2 units per kg bodyweight to attain fasting plasma glucose of 4÷0-5÷5 mmol/L) or sitagliptin (oral dose of 100 mg daily). Randomisation (via a central interactive voice response system) was by random sequence generation and was stratified by centre. Patients and investigators were not masked to treatment assignment. The primary outcome was change in HbA(1c) from baseline to study end. Efficacy analysis included all randomly assigned participants who had received at least one dose of study drug and had at least one on-treatment assessment of any primary or secondary efficacy variable. This trial is registered at ClinicalTrials.gov, NCT00751114.

FINDINGS: 732 people were screened and 515 were randomly assigned to insulin glargine (n=250) or sitagliptin (n=265). At study end, adjusted mean reduction in HbA(1c) was greater for patients on insulin glargine (n=227; -1÷72%, SE 0÷06) than for those on sitagliptin (n=253; -1÷13%, SE 0÷06) with a mean difference of -0÷59% (95% CI -0÷77 to -0÷42, p<0÷0001). The estimated rate of all symptomatic hypoglycaemic episodes was greater with insulin glargine than with sitagliptin (4÷21 [SE 0÷54] vs 0÷50 [SE 0÷09] events per patient-year; p<0÷0001). Severe hypoglycaemia occurred in only three (1%) patients on insulin glargine and one (<1%) on sitagliptin. 15 (6%) of patients on insulin glargine versus eight (3%) on sitagliptin had at least one serious treatment-emergent adverse event.

INTERPRETATION: Our results support the option of addition of basal insulin in patients with type 2 diabetes inadequately controlled by metformin. Long-term benefits might be expected from the achievement of optimum glycaemic control early in the course of the disease.

FUNDING: Sanofi.

PMID: 22683131 [PubMed - indexed for MEDLINE]

Short-term versus long-term antiarrhythmic drug treatment after cardioversion of atrial fibrillation (Flec-SL): a prospective, randomised, open-label, blinded endpoint assessment trial.

Lancet. 2012 Jun 15;

Authors: Kirchhof P, Andresen D, Bosch R, Borggrefe M, Meinertz T, Parade U, Ravens U, Samol A, Steinbeck G, Treszl A, Wegscheider K, Breithardt G

Abstract

BACKGROUND: Antiarrhythmic drugs prolong the atrial action potential and refractory period, and thereby prevent recurrent atrial fibrillation after cardioversion. The atrial action potential normalises after 2-4 weeks of sinus rhythm, suggesting that antiarrhythmic drugs might not be needed beyond that period. Therefore, we investigated whether short-term antiarrhythmic drug treatment after cardioversion is non-inferior to long-term treatment. METHODS: We enrolled patients in a prospective, randomised, open-label, blinded endpoint assessment trial between May 4, 2007, and March 12, 2010, at 44 centres in Germany. Eligible patients were adults with persistent atrial fibrillation undergoing planned cardioversion. After successful cardioversion, patients were randomly assigned in permuted blocks of six per centre to: no antiarrhythmic drug treatment (control); treatment with flecainide (200-300 mg per day) for 4 weeks (short-term treatment); or flecainide for 6 months (long-term treatment). The primary endpoint was time to persistent atrial fibrillation or death. Patients and clinicians were unmasked to group assignment and treatment. The primary outcome was assessed in a core laboratory, members of which were masked to treatment group. Patients were monitored for 6 months by daily telemetric electrocardiograph (ECG) and centrally adjudicated Holter ECG recordings whenever atrial fibrillation was noted in two consecutive ECGs. Analyses were per protocol. This trial is registered, number ISRCTN62728742. FINDINGS: After assay sensitivity was established with 4-week follow-up data from 242 patients showing that flecainide was superior to no treatment (Kaplan-Meier survival 70÷2%vs 52÷5%; p=0÷0160), the trial continued to compare short-term versus long-term treatment. The primary outcome occurred in 120 (46%) of 261 patients receiving short-term treatment and in 103 (39%) of 263 patients receiving long-term treatment (event-free survival 48÷4% [95% CI 41÷9-55÷0] vs 56÷4% [49÷1-63÷6]; Kaplan-Meier estimate of difference 7÷9% [-1÷9 to 17÷7]; p=0÷2081 for non-inferiority; margin prespecified at 12%). In a post-hoc landmark analysis of patients who had not reached the primary endpoint in the first month, long-term treatment was superior to short-term treatment (Kaplan-Meier estimate of difference 14÷3% [5÷1-23÷6]; hazard ratio 0÷31 [0÷18-0÷56]; p=0÷0001). INTERPRETATION: Short-term antiarrhythmic drug treatment after cardioversion is less effective than is long-term treatment, but can prevent most recurrences of atrial fibrillation. FUNDING: The German Federal Ministry of Education and Research, Deutsche Forschungsgemeinschaft, 3M Medica, and MEDA Pharmaceuticals.

PMID: 22713626 [PubMed - as supplied by publisher]