Oral antineoplastic agents: how do we care about adherence?

AimsOral therapies, including hormone‐based or targeted therapies, have recently taken an increasing place in cancer treatment. In this context, a state of the art of the available studies dealing with the adherence of adult patients to oral anticancer treatment is warranted. The purpose of this review is to address (i) the association between assessment methods and measured adherence, (ii) the putative factors related to adherence and (iii) new ways of improving adherence to oral cancer therapies.MethodsWe conducted a literature‐based narrative review of studies obtained from Pubmed using medical subject heading terms and free‐text terms combining concepts related to oral anticancer medication and adherence.ResultsThe analysis is based on 48 studies published since 1990, mostly assessing hormone‐based therapy in breast cancer and targeted therapies in chronic myeloid leukaemia. Various methods of adherence were reported including self‐report, medication measurement or combinations of methods. Adherence rates were found to vary from 14% to 100%. Beside patient related‐factors, adherence rate discrepancies were found to be dependent on the method used. Furthermore, there was no consensual definition of adherence even regarding the same methods, some of them tolerating a period of interruption during the treatment period. Finally, several studies addressing persistence found a progressive decrease in adherence with time.ConclusionAdherence to novel oral therapies is a major issue and further research is warranted to standardize adherence assessment in clinical studies better and to define better the most appropriate approaches to improve long term adherence in oncology practice.     

Cardiovascular disorders in patients with congenital portosystemic shunts: 23 years of experience in a tertiary referral centre

Central illustration. Time of occurrence and outcome of cardiovascular disorders in patients (pts) with congenital portosystemic shunt (CPSS). Patients with normal anatomy and those with congenital heart disease (CHD) were distinguished. Heart failure (HF) was the main symptom in both the prenatal and neonatal periods, whereas portopulmonary hypertension (PPH) and hepatopulmonary syndrome (HPS) represented the major concerns beyond the first months of life. CV: cardiovascular; NAS: no additional symptoms; PH: pulmonary hypertension; RD: respiratory distress. ^aFetal diagnosis of CPSS. ^bNeonatal diagnosis of CPSS. ^cDiagnosis of CPSS > 1 month of age

     

Postmortem coronary artery calcium score in cases of myocardial infarction

International Journal of Legal Medicine - Sudden cardiac death (SCD) related to atherosclerotic coronary artery disease (ACAD) resulting in myocardial infarction is the most prevalent cause of...     

Tinzaparin Sodium Pharmacokinetics in Patients with Chronic Kidney Disease: Practical Implications

Low-molecular-weight heparins (LMWHs) are the mainstay of the prophylaxis and treatment of venous thromboembolism (VTE). Due to their renal elimination, the risk of accumulation with the related bleeding risk may represent a limitation for the use of LMWHs in patients with chronic kidney disease (CKD) as the risk of major bleeding is increased in patients with creatinine clearance (CrCl) < 30 mL/min, especially in patients with cancer. LMWH structure and molecular weight (MW) are heterogeneous among available agents. The elimination of tinzaparin, which has the highest mean MW among LMWHs, is less dependent on renal function as it is also metabolized through the reticuloendothelial system. A subcutaneous therapeutic dose of tinzaparin (175 IU/kg) once daily has been shown to cause no accumulation of anti-factor Xa activity in patients with CrCl ≥ 20 mL/min. Clinical experience from randomized controlled studies has shown no significant impact of CKD on bleeding risk in cancer patients receiving treatment doses of tinzaparin. This suggests that in these patients the use of treatment doses of tinzaparin does not require anticoagulation monitoring or dose adjustment.     

Streamlined ion torrent PGM-based diagnostics: BRCA1 and BRCA2 genes as a model

To meet challenges in terms of throughput and turnaround time, many diagnostic laboratories are shifting from Sanger sequencing to higher throughput next-generation sequencing (NGS) platforms. Bearing in mind that the performance and quality criteria expected from NGS in diagnostic or research settings are strikingly different, we have developed an Ion Torrent''s PGM-based routine diagnostic procedure for BRCA1/2 sequencing. The procedure was first tested on a training set of 62 control samples, and then blindly validated on 77 samples in parallel with our routine technique. The training set was composed of difficult cases, for example, insertions and/or deletions of various sizes, large-scale rearrangements and, obviously, mutations occurring in homopolymer regions. We also compared two bioinformatic solutions in this diagnostic context, an in-house academic pipeline and the commercially available NextGene software (Softgenetics). NextGene analysis provided higher sensitivity, as four previously undetected single-nucleotide variations were found. Regarding specificity, an average of 1.5 confirmatory Sanger sequencings per patient was needed for complete BRCA1/2 screening. Large-scale rearrangements were identified by two distinct analyses, that is, bioinformatics and fragment analysis with electrophoresis profile comparison. Turnaround time was enhanced, as a series of 30 patients were sequenced by one technician, making the results available for the clinician in 10 working days following blood sampling. BRCA1/2 genes are a good model, representative of the difficulties commonly encountered in diagnostic settings, which is why we believe our findings are of interest for the whole community, and the pipeline described can be adapted by any user of PGM for diagnostic purposes.