The lived experience of depression: a bottom-up review co-written by experts by experience and academics.

We provide here the first bottom-up review of the lived experience of depression, co-written by experts by experience and academics. First-person accounts within and outside the medical field were screened and discussed in collaborative workshops involving numerous individuals with lived experience of depression, family members and carers, representing a global network of organizations. The material was enriched by phenomenologically informed perspectives and shared with all collaborators in a cloud-based system.

Investigational Bruton's tyrosine kinase inhibitors for the treatment of rheumatoid arthritis.

Introduction: The Tec family of non-receptor tyrosine kinases comprises five members. The cellular expression and function of these kinases has implicated them as potential drug targets for the treatment of both malignant and autoimmune diseases. Most attention has focused on inhibitors of BTK kinase with ibrutinib already approved for the treatment of mantle cell lymphoma and chronic lymphocytic leukaemia.

Humira: the impending patent battles over adalimumab biosimilars.

The world's top selling drug, adalimumab (AbbVie's Humira), generated sales in excess of US$13 billion in 2015. The primary product patent expires in 2016 in the USA and 2018 in Europe. This has resulted in a rush by companies to develop adalimumab biosimilars and Amgen submitted regulatory filings for its product ABP-501 in late 2015 in both the USA and Europe.

Developments in inhaled combination therapies: patent activity 2013-2014.

Introduction: Since the 1970s, the treatment options for asthma and chronic obstructive pulmonary disease have increasingly relied upon the use of inhaled drug formulations, generally from handheld inhaler devices. The introduction of combinations of a corticosteroid with a long-acting β2 agonist has dramatically transformed the accepted treatment paradigm. This has led to a dramatic increase in the development of novel combinations of inhaled drugs, including long-acting muscarinic antagonists with long-acting β2 agonists, as well as triple combinations, and of devices for their delivery.

Evaluation of US20150011555. An inhaled IP receptor agonist for the treatment of pulmonary arterial hypertension.

Introduction: Pulmonary arterial hypertension (PAH) is a rare disease for which IP receptor agonists provide one of the main classes of treatment. Currently available agents tend to lack receptor selectivity.

Areas Covered: Four salts of 7-(2,3-di-p-tolyl-7,8-dihydropyrido[2,3-b]pyrazin-5(6H)-yl)heptanoic acid, crystalline forms and compositions of each of these salts, and their use to treat conditions mediated by IP receptor activation, in particular PAH, are claimed.

Evaluation of WO-2014132220, selective PDGFR inhibitors for the treatment of pulmonary arterial hypertension.

Introduction: Pulmonary arterial hypertension (PAH) is a rare disease currently treated by a range of vasodilator agents and/or endothelin antagonists. Inhibition of platelet derived growth factor receptor (PDGFR) kinases has been suggested to provide an additional therapeutic modality, and clinical studies with the non-selective PDGFR inhibitor imatinib appear to validate this hypothesis. However, side-effects associated with a lack of selectivity suggest clinical utility requires the identification and development of selective PDGFR inhibitors.

Investigational p38 inhibitors for the treatment of chronic obstructive pulmonary disease.

Introduction: The p38 protein kinases, in particular p38α and p38β, regulate the production of multiple inflammatory mediators. Consequentially, considerable effort has been focused on trying to develop p38 inhibitors for the treatment of inflammatory diseases. Some 20 p38 inhibitors have progressed to clinical development, mostly for the treatment of rheumatoid arthritis, but with little success.

Respivert's multikinase inhibitors, an evaluation of WO2014033446 to WO2014033449.

These four patent applications all claim that N-aryl-N'-pyrazol-5-yl urea derivatives , related to RV-568, which are inhibitors of p38, Syk and Src kinases. All four applications claim their use in the treatment of inflammatory diseases, notably asthma and chronic obstructive pulmonary disease. The four applications are primarily differentiated by the claimed substitution of the pyrazole ring.

Evaluation of WO2014075392 and WO2014075393, Merck's first PI3Kδ inhibitor filings.

Introduction: There is considerable interest in the development of selective PI3Kδ inhibitors for the treatment of inflammatory diseases and haematological cancers. Merck has no previous filings in this field but licensed Exelixis' programme, including its lead compound XL-499, in December 2011.

Areas Covered: Both applications claim novel 9-alkyl-6,8-disubstituted purine derivatives as selective δ inhibitors for the treatment of asthma, obstructive airways disease, arthritis and cancer.

Complications associated with the prehospital use of laryngeal tubes--a systematic analysis of risk factors and strategies for prevention.

Objective: With the increasing spread of laryngeal tubes (LT) in emergency medicine, complications and side-effects are observed. We sought to identify complications associated with the use of LTs in emergency medicine, and to develop strategies to prevent these incidents.

Methods: In a prospective clinical study, all patients who had their airways managed in the field with a LT and who were admitted through the emergency department of the Frankfurt University Hospital during a 6 year period were evaluated using anonymised data collection sheets.

Inducible tyrosine kinase inhibitors: a review of the patent literature (2010 - 2013).

Introduction: The non-receptor tyrosine kinase, inducible tyrosine kinase (Itk), plays an important role in thymus(T)-cell signalling and the production of pro-inflammatory cytokines. Itk, and the other Tec family members, Rlk and Tec, are viewed as attractive drug targets for new agents for the treatment of autoimmune and inflammatory diseases. Interest in Itk inhibitors is still modest compared to other kinases such as the Janus kinase (JAK) family or Syk.

Selective JAK inhibitors in development for rheumatoid arthritis.

Introduction: The JAK kinases are a family of four tyrosine receptor kinases that play a pivotal role in cytokine receptor signalling pathways via their interaction with signal transducers and activators of transcription proteins. Selective inhibitors of JAK kinases are viewed as of considerable potential as disease-modifying anti-inflammatory drugs for the treatment of rheumatoid arthritis.

Areas Covered: This article provides a review of the clinical development and available clinical results for those JAK inhibitors currently under investigation.

The use of salt-inducible kinase inhibitors to treat autoimmune and inflammatory diseases: evaluation of WO2013136070.

Novel methods for the treatment of inflammatory and autoimmune diseases comprising the administration of salt-inducible kinase inhibitors are claimed. One novel inhibitor (HG-9-91-01) and the use of 2,4-diaminopyrimidine and 2,6-diaminopyrimidine derivatives are claimed. The use of such inhibitors upregulates the level of the anti-inflammatory cytokine IL-10 in macrophages.

A retrospective analysis of the effect of intraoperative opioid dose on cancer recurrence after non-small cell lung cancer resection.

Preclinical studies have demonstrated that opioid receptor agonists increase the rate of non-small cell lung cancer (NSCLC) growth and metastasis. Following institutional review board approval, we retrieved data on 901 patients who underwent surgery for NSCLC at MD Anderson Cancer Center. Comprehensive demographics, intraoperative data, and recurrence-free survival (RFS) and overall survival (OS) at 3 and 5 years were obtained.

A retrospective evaluation of the use of video-capable double-lumen endotracheal tubes in thoracic surgery.

Objective: The objective of this study was to evaluate whether the use of a video double-lumen tube reduced the need for fiberoptic bronchoscopy for (1) verification of initial tube placement and for (2) reverification of correct placement after repositioning for thoracotomy.

Design: A single-center retrospective study.

Setting: Thoracic surgery in a medical university hospital.

Spleen tyrosine kinase inhibitors: a review of the patent literature 2010 - 2013.

Introduction: The non-receptor tyrosine kinase, spleen tyrosine kinase (Syk), is primarily expressed in haematopoietic cells and appears to be particularly important in B cells. Syk is involved in signal transduction processes and appears to regulate allergic, inflammatory and autoimmune responses. It also appears to play a significant role in the development of haematological malignancies.

Novel picolinamide-based cystic fibrosis transmembrane regulator modulators: evaluation of WO2013038373, WO2013038376, WO2013038381, WO2013038386 and WO2013038390.

Cystic fibrosis (CF) is a genetic disease caused by defects in the CF transmembrane regulator (CFTR) gene, which encodes an epithelial chloride channel. The most common mutation, Δ508CFTR, produces a protein that is misfolded and does not reach the cell membrane. The discovery that partial chloride channel function could be restored by exposure to exogenous chemical stimuli led to the search for selective CFTR modulators.

Evaluation of WO2013117503 and WO2013117504: the use of PI3K inhibitors to treat cough or idiopathic pulmonary fibrosis.

Two applications claim the use of the closely related, broad spectrum phosphatidylinositol 3-kinase inhibitors 2,4-difluoro-N-{2-(methoxy)-5-[4-(4-pyridazinyl)-6-quinolinyl]-3-pyridinyl}benzenesulfonamide (GSK-2126458) and 2,4-difluoro-N-{2-(methoxy)-5-[4-(4-morpholino)-6-quinazolinyl]-3-pyridinyl}benzenesulfonamide for the treatment of idiopathic pulmonary fibrosis and cough, respectively. Some in vitro data are presented in support of these claimed utilities. Since the filing of these applications, GSK-2126458 has commenced a dose-finding Phase I study in patients with idiopathic pulmonary fibrosis.

Evaluation of WO2013116562A, an orally active PI3Kδ inhibitor for the treatment of asthma.

(S)-4-amino-6-((1-(5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)ethyl)amino)pyrimidine-5-carbonitrile is claimed as a highly selective, PI3Kδ inhibitor. It is claimed to be useful in the treatment of asthma and appears intended for oral administration. It is shown to be well absorbed after oral administration and to have reasonable metabolic stability.