Do newly marketed generic medicines expand markets using descriptive time series analysis and mixed logit models? Korea as an exemplar and its implications

Introduction: There have been concerns in Korea that the availability of cheaper generics can appreciably increase prescribed volumes thereby negating their beneficial effects on overall pharmaceutical expenditure. Objectives: Explore market changes after newly entered generics including market expansion and substitution effects, and to examine factors contributing to the prescribing of newly entered generics using atorvastatin as an exemplar. This is because previous studies have shown market expansion had occurred following generic atorvastatin. Methods: Explore market expansion effects by extracting all statins users from July 2008 to June 2010 from the nationally representative dataset of 2008, combined with the National Health Insurance Claims data, with atorvastatin’s patent expiring in July 2008. The data consisted of medical visit episodes of patients who had been prescribed statins at least once during the observational period. Patients who had been prescribed any statin before the observation period were classified as the previously treated group and those who had not as the newly treated group. Descriptive time series analysis was conducted and the mixed logit model applied to understand factors contributing to generic atorvastatin prescriptions. Results: Market expansion was observed after generic atorvastatin availability with an appreciable increase in number of newly treated patients, whereas substitution effect was found among previously treated patients. Newly treated patients tended to get significantly lower daily doses (p<0.0001). According to the mixed logistic analysis, newly treated patients were more likely to be prescribed generic atorvastatin (OR=2.58; 95% CI, 2.05-3.26) than their counterparts. Clinicians and secondary hospitals were also key drivers of generic atorvastatin (ORs were 10.41 and 9.81, respectively). Conclusions: Newly marketed generic statins in Korea resulted in an expanding market by substantially increasing the number of new patients with clinics and hospitals appreciably using newly marketed generics. However lower doses of statins were prescribed. Policy makers do recognize that generic availability can save costs so should be encouraged. However, this is a concern when generic availability appreciably expands the market, potentially increasing the financial burden. This needs to be addressed. Additionally in Korea, the quality of prescribing should be monitored, especially focusing on clinics and secondary hospital

QCM-D Monitoring of Binding-Induced Conformational Change of Calmodulin

Understanding conformational changes are important when studying a protein such as calmodulin (CaM), which activates various target enzymes and regulates numerous physiological functions. CaM is a highly flexible protein that can transitorily adopt various conformations. A quartz crystal microbalance with dissipation (QCM-D) sensor was used to study binding-induced conformational changes of surface-immobilized CaM. Structural changes of CaM were evaluated using the Voigt’s viscoelastic model with frequency (ΔF) and dissipation change (ΔD). When Apo-CaM layer was incubated in 0.1 mM Ca2+ solution, the layer decreased by approximately 0.56 nm, due to the release of coupled water molecules and conformational change. The application of CaM itself also caused a significantly more compact layer, supporting previous findings that CaM dimerization forms a collapsed structure that exposes a hydrophobic tunnel. The binding characteristics of CaM with peptides derived from proteins in a signal transduction pathway also demonstrated diverse biophysical properties of the CaM complexes. Each peptide showed a unique ΔF/ΔD pattern indicating versatility of CaM configuration to favorably adjust to each target molecule. The study demonstrates that the QCM-D sensor is capable of simultaneously studying binding affinity and plasticity of protein configuration for target binding. The CaM data obtained on hydrated protein layer thickness is complementary to configuration measurements of a single CaM molecule

Early Surgery for Traumatic Spinal Cord Injury: Where Are We Now?

Study Design: Narrative review. Objective: There is a strong biological rationale to perform early decompression after traumatic spinal cord injury (SCI). With an enlarging clinical evidence base, most spine surgeons internationally now favor early decompression for the majority of SCI patients; however, a number of pertinent questions remain surrounding this therapy. Methods: A narrative review evaluating the status of early surgery for SCI. In particular, we addressed the following questions: (1) Which patients stand to benefit most from early surgery? 2) What is the most appropriate time threshold defining early surgery? Results: Although heterogeneity exists, the evidence generally seems to support early surgery. While the best evidence exists for cervical SCI, there is insufficient data to support a differential effect for early surgery depending on neurological level or injury severity. When comparing thresholds to define early versus late surgery-including a later threshold (48-72 hours), an earlier threshold (24 hours), and an ultra-early threshold (8-12 hours)-the 2 earlier time points seem to be associated with the greatest potential for improved outcomes. However, existing prehospital and hospital logistics pose barriers to early surgery in a significant proportion of patients. An overview of recommendations from the recent AOSpine guidelines is provided. Conclusion: In spite of increasing acceptance of early surgery post SCI, further research is needed to (1) identify subgroups of patients who stand to derive particular benefit-in particular to develop more evidence-based approaches for central cord syndrome and (2) investigate the efficacy and feasibility of ultra-early surgery targeting more aggressive timelines

Spoofing prevention via RF power profiling in wireless network-on-chip

With increasing integration in SoCs, the Network-on-Chip (NoC) connecting of cores and accelerators is of paramount importance to provide low-latency and high-throughput communication. Due to limits of scaling of electrical wires, especially for long multi-mm distances on-chip, alternate technologies such as Wireless NoC (WNoC) have shown promise. Since WNoCs can provide low-latency one-hop transfers across the entire chip, there has been a recent surge in research demonstrating their performance and energy benefits. However, little to no work has studied the additional security challenges that are unique to WNoCs. In this work, we study the potential threat of spoofing attacks in WNoCs due to malicious hardware trojans. We introduce Veritas, a drop-in solution aimed at detecting and correcting such spoofing attacks. To this end, our solution exploits the static propagation environment of WNoCs to associate each node to a power profile. We demonstrate that, with small area and power overheads, Veritas works well in a variety of settings.Peer ReviewedPostprint (author's final draft

Guidelines for the management of degenerative cervical myelopathy and spinal cord injury: an introduction to a focus issue

Study Design: Introduction to a guidelines project. Objectives: The objective of this focus issue is to present guidelines that outline how to best manage patients with degenerative cervical myelopathy (DCM) and spinal cord injury (SCI). Topics addressed in this focus issue include: 1) management strategies for patients with mild, moderate and severe DCM; and 2a) timing of surgical decompression; b) the use of methylprednisolone sodium succinate; c) the type and timing of anticoagulation strategies; d) the role of magnetic resonance imaging in clinical decision making and outcome prediction; and e) the type and timing of rehabilitation in patients with SCI. Methods: Systematic reviews were conducted to address key clinical questions and to synthesize the current body of evidence. A multidisciplinary guideline development group used the results of these reviews, along with their clinical expertise, to develop clinical practice guidelines, in a process that adhered to methodology proposed by the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) Working Group. Results: The multidisciplinary guideline development group combined the systematic review findings with their clinical expertise and opinions to formulate recommendations on how to manage patients with DCM and SCI. Conclusions: These guidelines will serve as tools to assist clinicians in their decision making by offering a perspective that combines the available evidence, expertise from a variety of clinicians, and patient values

Can local policies on biosimilars optimize the use of freed resources – experiences from Italy

There is an increasing need to prescribe biosimilars to fund new medicines and increasing medicine volumes. Bertolani and Jommi document successful measures introduced regionally in Italy

Back-Translation Practices in Organizational Research: Avoiding Loss in Translation

As organizational research continues to globalize, scholars increasingly must translate established scales into languages other than those in which the scales were originally developed. In organizational psychology research, back-translation is the dominant procedure for translating scales. Back-translation has notable strengths in maintaining the psychometric properties of an established scale in a translated version. However, cross-cultural methodologists have argued that in its most basic form, back-translation often does not result in translations with acceptable levels of equivalence between original and translated research materials. Fortunately, there are complementary procedures to back-translation that can evaluate and strengthen the extent to which scale translations have achieved equivalence between original and translated versions of scales. But how often organizational researchers use and report these procedures in tandem with back-translation is unclear. This article aims to address this lack of clarity by evaluating the state of the use of back-translation in organizational psychology research by reviewing every study in Journal of Applied Psychology that has employed translation over the past nearly 25 years (k = 333). Our findings suggest that the majority of the time that researchers engage in translation procedures, they report having done so. At the same time, the details of these procedures are commonly underreported, making it unclear whether additional techniques beyond back-translation have been used to examine and demonstrate equivalence between original and translated versions of scales. Based on the results of our review, we develop a set of recommendations for conducting and reporting scale translations in organizational research

The impact of South Korea’s new drug-pricing policy on market competition among off-patent drugs

A new pricing policy was introduced in Korea in April 2012 with the aim of strengthening competition among off-patent drugs by eliminating price gaps between originators and generics. Examine the effect of newly implemented pricing policy. Retrospectively examining the effects through extracting from the National Health Insurance claims data a 30-month panel dataset (January 2011 - June 2013) containing consumption data in four major therapeutic classes (antihypertensives, lipid-lowering drugs, antiulcerants and antidepressants). Proxies for market competition were examined before and after the policy. The new pricing policy didn’t enhance competition among off-patent drugs. In fact, price dispersion significantly decreased as opposed to the expected change. Originator-to-generic utilization increased to 6.12 times (p=0.000) after the new policy. The new pricing policy made no impact on competition among off-patent drugs. Competition in the off-patent market cannot be enhanced unless both supply and demand-side measures are coordinated