Medical Writing Competency Model - Section 1: Functions, Tasks, and Activities.

This article provides Section 1 of the 2017 Edition 2 Medical Writing Competency Model that describes the core work functions and associated tasks and activities related to professional medical writing within the life sciences industry. The functions in the Model are scientific communication strategy; document preparation, development, and finalization; document project management; document template, standard, format, and style development and maintenance; outsourcing, alliance partner, and client management; knowledge, skill, ability, and behavior development and sharing; and process improvement. The full Model also includes Section 2, which covers the knowledge, skills, abilities, and behaviors needed for medical writers to be effective in their roles; Section 2 is presented in a companion article. Regulatory, publication, and other scientific writing as well as management of writing activities are covered. The Model was developed to aid medical writers and managers within the life sciences industry regarding medical writing hiring, training, expectation and goal setting, performance evaluation, career development, retention, and role value sharing to cross-functional partners.

Medical Writing Competency Model - Section 2: Knowledge, Skills, Abilities, and Behaviors.

This article provides Section 2 of the 2017 Edition 2 Medical Writing Competency Model that describes the knowledge, skills, abilities, and behaviors that professional medical writers need in order to perform effectively within the life sciences industry. What a medical writer should know, what they should be able to do, and how they should use this knowledge and these skills to facilitate their primary work function is a focus. Regulatory, publication, and other scientific writing as well as management of writing activities are covered. The full Model also includes Section 1, which covers the core work functions and associated tasks and activities related to professional medical writing within the life sciences industry; Section 1 is included in a companion article. The Model was developed to aid medical writers and managers within the life sciences industry regarding medical writing hiring, training, expectation and goal setting, performance evaluation, career development, retention, and role value sharing to cross-functional partners.

Describing the Endpoint: Consistency Across Protocols, Study Reports, Postings, and Publications.

Endpoints are the cornerstone of clinical trial design and are the critical elements for evaluating the success of a clinical study. Endpoints are communicated in clinical protocols, study reports, study registration and result posting sites, as well as publications. It is, therefore, important that endpoints are presented consistently, correctly, and completely. The FDAAA Final Rule expectations of describing endpoints in specific terms provides a way to keep this consistency across all documents.

A systematic review of osteoporosis medication adherence and osteoporosis-related fracture costs in men.

BACKGROUND AND OBJECTIVE: Male osteoporosis is an increasingly important public health concern. Although several medications are approved for the treatment of osteoporosis, medication non-adherence and the associated consequences are not well documented in male populations. Our objective was to identify and summarize the current knowledge related to osteoporotic medication adherence, the potential implications of non-adherence to the medication, and the cost of osteoporosis-related fractures and health-resource utilization in men. METHODS: Two separate systematic searches were conducted concurrently: one to identify literature reporting male-specific adherence to anti-osteoporotic medication and the clinical consequence of non-adherence in men, and the other to identify literature reporting the cost and resource burden of osteoporosis-related fractures in men. The PubMed, MEDLINE, EMBASE, and Cochrane databases were searched using a date range of 1 January 1998 to 30 June 2012, and citations were screened based on pre-defined criteria. RESULTS: The percentage of males adherent to bisphosphonates [medication possession ratio (MPR) >0.8] over a 1-year period ranged from 32% to 64%. The data imply worse clinical outcomes with treatment non-adherence. Costs and resource use associated with osteoporosis-related fractures in men are high, with hip fractures generating the most cost. CONCLUSIONS: One-third to two-thirds of men are not adherent to bisphosphonates. Non-adherence is associated with increased fracture risk. Estimates of direct and indirect osteoporosis-related fracture costs are also substantial in men, and may even be more costly than in women. More robust data would better inform disease management initiatives that could improve adherence to medication and outcomes in men with osteoporosis.

Osteoporotic fractures: a systematic review of U.S. healthcare costs and resource utilization.

Osteoporotic fractures are costly in terms of both the dollar amount and healthcare utilization. The objective of this review was to systematically synthesize published evidence regarding direct costs associated with the treatment of osteoporosis-related fractures in the U.S. We conducted a systematic literature review of published studies that used claims databases and economic studies reporting costs associated with osteoporosis-related fractures in the U.S. Studies published between 1990 and 2011 were systematically searched in PubMed (primary source), Ovid HealthSTAR, EMBASE and the websites of large agencies. Data concerning study design, patient population and cost components assessed were extracted with qualitative assessment of study methods, limitations and conclusions. Cost assessment included direct medical and hospitalization (inpatient) costs. The cost differences by age and gender were examined. Of the 33 included studies, 26 reported an estimated total medical cost and hospital resource use associated with osteoporotic fractures. These studies indicated that, in the year following a fracture, medical and hospitalization costs were 1.6-6.2 higher than pre-fracture costs and 2.2-3.5 times higher than those for matched controls. Analysis of the hospitalization costs by osteoporotic fracture type resulted in hip fractures identified as the most expensive fracture type (unit cost range $US 8358-32195), while wrist and forearm fractures were the least expensive (unit cost range $US 1885-12136). Although incremental fracture costs were generally lower in the elderly than in the younger population, total costs were highest for the older (≥65 years of age) population. Total healthcare costs for fractures were highest for the older female population, but unit fracture costs in women were not consistently found to be higher than for men. The qualitative assessment of the included studies demonstrated that the design and reporting of individual studies were of good quality. However, the findings of this review and comparisons across studies were limited by differences in methodologies used by the different studies to derive costs, the populations included in the studies used and the fracture assessment. Despite the variability in estimates, the literature indicates that osteoporosis-related fractures are associated with high total medical and hospitalization costs in the U.S. The variability in the cost estimates highlights the importance of comparing the methodologies and the types of costs used when choosing an appropriate unit cost for economic modelling.

Engineering of vault nanocapsules with enzymatic and fluorescent properties.

One of the central issues facing the emerging field of nanotechnology is cellular compatibility. Nanoparticles have been proposed for diagnostic and therapeutic applications, including drug delivery, gene therapy, biological sensors, and controlled catalysis. Viruses, liposomes, peptides, and synthetic and natural polymers have been engineered for these applications, yet significant limitations continue to prevent their use. Avoidance of the body's natural immune system, lack of targeting specificity, and the inability to control packaging and release are remaining obstacles. We have explored the use of a naturally occurring cellular nanoparticle known as the vault, which is named for its morphology with multiple arches reminiscent of cathedral ceilings. Vaults are 13-MDa ribonucleoprotein particles with an internal cavity large enough to sequester hundreds of proteins. Here, we report a strategy to target and sequester biologically active materials within the vault cavity. Attachment of a vault-targeting peptide to two proteins, luciferase and a variant of GFP, resulted in their sequestration within the vault cavity. The targeted proteins confer enzymatic and fluorescent properties on the recombinant vaults, both of which can be detected by their emission of light. The modified vaults are compatible with living cells. The ability to engineer vault particles with designed properties and functionalities represents an important step toward development of a biocompatible nanocapsule.

Postentry neutralization of adenovirus type 5 by an antihexon antibody.

Antibodies against hexon, the major coat protein of adenovirus (Ad), are an important component of the neutralizing activity in serum from naturally infected humans and experimentally infected animals. The mechanisms by which antihexon antibodies neutralize the virus have not been defined. As a model system, murine monoclonal antibodies raised against Ad type 5 (Ad5) were screened for antihexon binding and neutralization activity; one monoclonal antibody, designated 9C12, was selected for further characterization. The minimum ratio of 9C12 to Ad5 required for neutralization was 240 antibody molecules per virus particle, or 1 antibody per hexon trimer. Analysis of antibody-virus complexes by dynamic light scattering and negative-stain electron microscopy (EM) showed that the virus particles were coated with electron-dense material but not aggregated at neutralizing ratios. Cryo-EM image reconstruction of the antibody-virus complex showed that the surface of the virus particle was covered by a meshwork of 9C12 antibody density, consistent with bivalent binding at multiple sites. Confocal analysis revealed that viral attachment, cell entry, and intracellular transport to the nuclear periphery still occur in the presence of neutralizing levels of 9C12. A model is presented for neutralization of Ad by an antihexon antibody in which the hexon capsid is cross-linked by antibodies, thus preventing virus uncoating and nuclear entry of viral DNA.

Cryoelectron microscopy imaging of recombinant and tissue derived vaults: localization of the MVP N termini and VPARP.

The vault is a highly conserved ribonucleoprotein particle found in all higher eukaryotes. It has a barrel-shaped structure and is composed of the major vault protein (MVP); vault poly(ADP-ribose) polymerase (VPARP); telomerase-associated protein 1 (TEP1); and small untranslated RNA (vRNA). Although its strong conservation and high abundance indicate an important cellular role, the function of the vault is unknown. In humans, vaults have been implicated in multidrug resistance during chemotherapy. Recently, assembly of recombinant vaults has been established in insect cells expressing only MVP. Here, we demonstrate that co-expression of MVP with one or both of the other two vault proteins results in their co-assembly into regularly shaped vaults. Particles assembled from MVP with N-terminal peptide tags of various length are compared. Cryoelectron microscopy (cryoEM) and single-particle image reconstruction methods were used to determine the structure of nine recombinant vaults of various composition, as well as wild-type and TEP1-deficient mouse vaults. Recombinant vaults with MVP N-terminal peptide tags showed internal density that varied in size with the length of the tag. Reconstruction of a recombinant vault with a cysteine-rich tag revealed 48-fold rotational symmetry for the vault. A model is proposed for the organization of MVP within the vault with all of the MVP N termini interacting non-covalently at the vault midsection and 48 copies of MVP forming each half vault. CryoEM difference mapping localized VPARP to three density bands lining the inner surface of the vault. Difference maps designed to localize TEP1 showed only weak density inside of the caps, suggesting that TEP1 may interact with MVP via a small interaction region. In the absence of atomic-resolution structures for either VPARP or TEP1, fold recognition methods were applied. A total of 21 repeats were predicted for the TEP1 WD-repeat domain, suggesting an unusually large beta-propeller fold.

Flexibility of the adenovirus fiber is required for efficient receptor interaction.

The adenovirus (Ad) fiber protein mediates Ad binding to the coxsackievirus and Ad receptor (CAR) and is thus a major determinant of viral tropism. The fiber contains three domains: an N-terminal tail that anchors the fiber to the viral capsid, a central shaft region of variable length and flexibility, and a C-terminal knob domain that binds to cell receptors. Ad type 37 (Ad37), a subgroup D virus associated with severe ocular infections, is unable to use CAR efficiently to infect host cells, despite containing a CAR binding site in its fiber knob. We hypothesized that the relatively short, inflexible Ad37 fiber protein restricts interactions with CAR at the cell surface. To test this hypothesis, we analyzed the infectivity and binding of recombinant Ad particles containing modified Ad37 or Ad5 fiber proteins. Ad5 particles equipped with a truncated Ad5 fiber or with a chimeric fiber protein comprised of the Ad5 knob fused to the short, rigid Ad37 shaft domain had significantly reduced infectivity and attachment. In contrast, placing the Ad37 knob onto the long, flexible Ad5 shaft allowed CAR-dependent virus infection and cell attachment, demonstrating the importance of the shaft domain in receptor usage. Increasing fiber rigidity by substituting the predicted flexibility modules in the Ad5 shaft with the corresponding regions of the rigid Ad37 fiber dramatically reduced both virus infection and cell attachment. Cryoelectron microscopy (cryo-EM) single-particle analysis demonstrated the increased rigidity of this chimeric fiber. These studies demonstrate that both length and flexibility of the fiber shaft regulate CAR interaction and provide a molecular explanation for the use of alternative receptors by subgroup D Ad with ocular tropism. We present a molecular model for Ad-CAR interactions at the cell surface that explains the significance of fiber flexibility in cell attachment.