Costs and Causes of Oncology Drug Attrition With the Example of Insulin-Like Growth Factor-1 Receptor Inhibitors.

Importance: The development of oncology drugs is expensive and beset by a high attrition rate. Analysis of the costs and causes of translational failure may help to reduce attrition and permit the more appropriate use of resources to reduce mortality from cancer.

Objective: To analyze the causes of failure and expenses incurred in clinical trials of novel oncology drugs, with the example of insulin-like growth factor-1 receptor (IGF-1R) inhibitors, none of which was approved for use in oncology practice.

Should lethal arrhythmias in hypertrophic cardiomyopathy be predicted using non-electrophysiological methods?

While sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) is due to arrhythmias, the guidelines for prediction of SCD are based solely on non-electrophysiological methods. This study aims to stimulate thinking about whether the interests of patients with HCM are better served by using current, 'risk factor', methods of prediction or by further development of electrophysiological methods to determine arrhythmic risk. Five published predictive studies of SCD in HCM, which contain sufficient data to permit analysis, were analysed to compute receiver operating characteristics together with their confidence bounds to compare their formal prediction either by bootstrapping or Monte Carlo analysis.

Performance assessment and economic analysis of a human Liver-Chip for predictive toxicology.

Background: Conventional preclinical models often miss drug toxicities, meaning the harm these drugs pose to humans is only realized in clinical trials or when they make it to market. This has caused the pharmaceutical industry to waste considerable time and resources developing drugs destined to fail. Organ-on-a-Chip technology has the potential improve success in drug development pipelines, as it can recapitulate organ-level pathophysiology and clinical responses; however, systematic and quantitative evaluations of Organ-Chips' predictive value have not yet been reported.

Predictive validity in drug discovery: what it is, why it matters and how to improve it.

Successful drug discovery is like finding oases of safety and efficacy in chemical and biological deserts. Screens in disease models, and other decision tools used in drug research and development (R&D), point towards oases when they score therapeutic candidates in a way that correlates with clinical utility in humans. Otherwise, they probably lead in the wrong direction.

Biopharmaceutical R&D outsourcing: Short-term gain for long-term pain?

Research and development (R&D) outsourcing offers some obvious productivity benefits (e.g., access to new technology, variabilised costs, risk sharing, etc.

Water Accumulation in Amsorb Canister May Cause Inspiratory Flow Obstruction: A Case Report.

A patient received closed-circuit anesthesia from a General Electric Avance S/5 (GE Healthcare, Madison, WI) anesthesia machine during a robotic abdominal procedure. With return of spontaneous ventilation at the end of the procedure, the negative airway pressure alarm began to sound, and a negative airway pressure of 10-15 cm H2O was observed with each breath. Replacing the CO2 absorber resolved the problem.

Patterns and Predictors of Professional Interpreter Use in the Pediatric Emergency Department.

Background And Objectives: Professional interpretation for patients with limited English proficiency remains underused. Understanding predictors of use is crucial for intervention. We sought to identify factors associated with professional interpreter use during pediatric emergency department (ED) visits.

Professional Interpreter Use and Discharge Communication in the Pediatric Emergency Department.

Objective: Families with limited English proficiency (LEP) experience communication barriers and are at risk for adverse events after discharge from the pediatric emergency department (ED). We sought to describe the characteristics of ED discharge communication for LEP families and to assess whether the use of a professional interpreter was associated with provider communication quality during ED discharge.

Methods: Transcripts of video-recorded ED visits for Spanish-speaking LEP families were obtained from a larger study comparing professional interpretation modalities in a freestanding children's hospital.

Evidence for the effectiveness of minimum pricing of alcohol: a systematic review and assessment using the Bradford Hill criteria for causality.

Objectives: To assess the evidence for price-based alcohol policy interventions to determine whether minimum unit pricing (MUP) is likely to be effective.

Design: Systematic review and assessment of studies according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, against the Bradford Hill criteria for causality. Three electronic databases were searched from inception to February 2017.

When Quality Beats Quantity: Decision Theory, Drug Discovery, and the Reproducibility Crisis.

A striking contrast runs through the last 60 years of biopharmaceutical discovery, research, and development. Huge scientific and technological gains should have increased the quality of academic science and raised industrial R&D efficiency. However, academia faces a "reproducibility crisis"; inflation-adjusted industrial R&D costs per novel drug increased nearly 100 fold between 1950 and 2010; and drugs are more likely to fail in clinical development today than in the 1970s.

The Life Sciences Translational Challenge: The European Perspective.

In recent years, concern has been growing that traditional research and development models in the life sciences are unsustainable. Productivity, especially in pharmaceuticals, has plummeted, and too many of the products emerging from increasingly lengthy and costly clinical development offer marginal benefit to patients. Although the phenomenon is global, there are specific and important features of European life sciences that impede the translation of an ever more penetrating understanding of biology into effective treatments.

Financial returns on R&D: looking back at history, looking forward to adaptive licensing.

Investment in R&D for drugs launched in the late 1970s to early 1990s generated good returns for investors. R&D was inexpensive. Clinical trial success rates were high.

Unusual presentation of an intraosseous hemangioma of the maxilla and displaced canine.

Intraosseous hemangiomas are benign vascular malformations which are extremely rare in the maxilla, but have been reported in the mandible, zygoma and orbital region. A 12 years old female presented to the oral and maxillofacial department with an ectopically positioned upper left canine in her zygomatic bone and buccal alveolar expansion between the upper left lateral incisor and upper left first premolar. This case shows the unusual presentation of an intraosseous hemangioma associated with an ectopically migrated upper left canine tooth.

Diagnosing the decline in pharmaceutical R&D efficiency.

The past 60 years have seen huge advances in many of the scientific, technological and managerial factors that should tend to raise the efficiency of commercial drug research and development (RD). Yet the number of new drugs approved per billion US dollars spent on RD has halved roughly every 9 years since 1950, falling around 80-fold in inflation-adjusted terms. There have been many proposed solutions to the problem of declining RD efficiency.

Disc prolapse: evidence of reversal with repeated extension.

Study Design: A basic science study that used a porcine cervical spine model to produce disc prolapse subsequently exposed to an extension protocol.

Objective: This study investigated whether extension or combined extension and side flexion could move the displaced portion of nucleus from the anulus towards the nucleus.

Summary Of Background Data: Previous research has established that repeated flexion can create disc prolapse, the question here is whether repeated extension can reverse the process.

Can Radiofrequency Ablation Be Used as a Treatment Modality for the Management of Pulmonary Metastatic Ameloblastoma?

We report the case of a 59-year-old woman who presented with metastatic ameloblastoma involving the lungs, 20 years after resection of the primary tumor in the mandible. The lesions were debulked on multiple occasions with radiofrequency ablation over an eight-year period with local response. There were no complications related to the procedures.

A four year retrospective study of 1,062 patients presenting with maxillofacial emergencies at a specialist paediatric hospital.

Aims: To examine the nature of maxillofacial injuries that presented to the Birmingham Children's Hospital according to aetiology, incidence and characteristics of patients.

Methods: The maxillofacial unit at Diana Princess of Wales Birmingham Children's Hospital serves a catchment area of 5.2 million.

The direction of progressive herniation in porcine spine motion segments is influenced by the orientation of the bending axis.

Background: It has been shown that disc herniations are a cumulative injury created by repetitive flexion motion while under modest compressive loads. There is a lack of data linking the direction of nucleus tracking to the orientation of the bending motion axis. Our purpose was to determine if the direction that the nucleus tracks through the annulus during progressive herniation is predictable from the direction of bending motion (i.

Lumbar posture--should it, and can it, be modified? A study of passive tissue stiffness and lumbar position during activities of daily living.

Background And Purpose: Physical therapists commonly attempt to reduce and prevent low back pain by "improving" individuals' lumbar posture. To investigate the physical therapy clinical practice of attempting to "improve" lumbar posture, measures of passive tissue stiffness and angular deformation during activities of daily living were used.

Participants: The lumbar spine posture of 150 university students was measured as the inclinometer angle difference between L1 and S1.

Correlations, feature-binding and population coding in primary visual cortex.

To test the hypothesis that correlated neuronal activity serves as the neuronal code for visual feature binding, we applied information theory techniques to multiunit activity recorded from pairs of V1 recording sites in anaesthetised cats while presenting either single or separate bar stimuli. We quantified the roles of firing rates of individual channels and of cross-correlations between recording sites in encoding of visual information. Between 89 and 96% of the information was carried by firing rates; correlations contributed 4-11% extra information.