Orphan Drug Label Expansions: Analysis Of Subsequent Rare And Common Indication Approvals.

The Orphan Drug Act of 1983 was enacted to provide financial incentives to stimulate drug development for rare diseases. In recent years, concerns have been raised regarding these orphan drugs, including how many are being approved for both rare and common diseases and the number of subsequent indication approvals. Policy makers have suggested modifications to the Orphan Drug Act's incentives to address these concerns.

Multimodal job interview simulator for training of autistic individuals.

Autistic individuals face difficulties in finding and maintaining employment, and studies have shown that the job interview is often a significant barrier to obtaining employment. Prior computer-based job interview training interventions for autistic individuals have been associated with better interview outcomes. These previous interventions, however, do not leverage the use of multimodal data that could give insight into the emotional underpinnings of autistic individuals' challenges in job interviews.

An Analysis of Antibacterial Drug Development Trends in the United States, 1980-2019.

We present a longitudinal analysis of investigational new drug applications (INDs) for new, systemic antibacterial drugs under active development between 1980 and 2019, evaluating the characteristics of these investigational drugs and the outcomes of these drug development programs. The number of INDs in active development declined by two-thirds, from 39 active INDs at its peak in 1987 to a low 13 in 2001, with decreased development of new cephalosporin, quinolone, and macrolide drugs and reduced participation from large pharmaceutical firms. Antibacterial drug development activity rebounded substantially from 2002 to 2009, primarily led by involvement of small pharmaceutical companies.

An Analysis of Follow-On Development in New Drug Classes, January 1986-June 2018.

Follow-on drugs-new medicines approved within an established drug class-provide incremental treatment improvements, additional choices for clinicians and patients, and potential price competition. We examine the timing, quantity, and product characteristics of within-class drug approvals for new drug classes approved by the US Food and Drug Administration since January 1986. We find that nearly two-thirds of first-in-class drugs do not face a subsequent follow-on product.

Investigating the landscape of US orphan product approvals.

Background: The Orphan Drug Act was enacted in 1983 to encourage the development of drugs for rare diseases. Previous research has attempted to examine the impact of the Act by assessing either the number of orphan designations that have been granted or the number of new orphan drugs approved for marketing. This study provides a more in-depth understanding of the effect of the Orphan Drug Act by investigating all types of drug approvals with an orphan designation, along with multiple characteristics of the drugs, over the entire 35 years of the Act.

Evaluation of Pre-marketing Factors to Predict Post-marketing Boxed Warnings and Safety Withdrawals.

Introduction: An important goal in drug regulation is understanding serious safety issues with new drugs as soon as possible. Achieving this goal requires us to understand whether information provided during the Food and Drug Administration (FDA) drug review can predict serious safety issues that are usually identified after the product is approved. However, research on this topic remains understudied.

Trends In Orphan New Molecular Entities, 1983-2014: Half Were First In Class, And Rare Cancers Were The Most Frequent Target.

The Orphan Drug Act was enacted in 1983 to stimulate drug development for rare diseases. How well this law has accomplished that goal is an important public health question. This study examined the characteristics of the 209 orphan drugs approved as new molecular entities in the period 1983-2014.

Scientific and regulatory reasons for delay and denial of FDA approval of initial applications for new drugs, 2000-2012.

Importance: Some new drug applications fail because of inadequate drug performance and others are not approved because the information submitted to the US Food and Drug Administration (FDA) is unsatisfactory to make that determination. Resubmission of failed applications is costly, delaying marketing approval and the availability of new drugs to patients.

Objective: To identify the reasons that FDA marketing approval for new drugs was delayed or denied.

An improved approach to measuring drug innovation finds steady rates of first-in-class pharmaceuticals, 1987-2011.

For more than a decade, industry analysts and policy makers have raised concerns about declining pharmaceutical innovation, citing declining numbers of new molecular entities (NMEs) approved in the United States each year. Yet there is little consensus on whether this is the best measure of "innovation." We examined NME approvals during 1987-2011 and propose the three distinct subcategories of NMEs--first-in-class, advance-in-class, and addition-to-class--to provide more nuanced and informative insights into underlying trends.

Using Campylobacter spp. and Escherichia coli data and Bayesian microbial risk assessment to examine public health risks in agricultural watersheds under tile drainage management.

Human campylobacteriosis is the leading bacterial gastrointestinal illness in Canada; environmental transmission has been implicated in addition to transmission via consumption of contaminated food. Information about Campylobacter spp. occurrence at the watershed scale will enhance our understanding of the associated public health risks and the efficacy of source water protection strategies.

Quantitative multi-year elucidation of fecal sources of waterborne pathogen contamination in the South Nation River basin using bacteroidales microbial source tracking markers.

Over a seven-year period (2004-2010) 1095 water samples were obtained from the South Nation River basin at multiple watershed monitoring sites (Ontario, Canada). Real-time PCR using Bacteroidales specific markers was used to identify the origin (human (10% prevalence), ruminant (22%), pig (~2%), Canada goose (4%) and muskrat (7%)) of fecal pollution. In parallel, the distribution of fecal indicator bacteria and waterborne pathogens (Cryptosporidium oocysts, Giardia cysts, Escherichia coli O157:H7, Salmonella enterica and Campylobacter spp.

Distribution of selected virulence genes and antibiotic resistance in Enterococcus species isolated from the South Nation River drainage basin, Ontario, Canada.

Aims: Isolate and characterize water enterococci from the South Nation River drainage basin, an area dominated by agriculture.

Methods And Results: A total of 1558 enterococci were isolated from 204 water samples from the South Nation River obtained over a 3-year period. PCR was used to identify isolates to the species level and characterize them for carriage of 12 virulence determinants.

Frequency of virulence genes and antibiotic resistances in Enterococcus spp. isolates from wastewater and feces of domesticated mammals and birds, and wildlife.

Enterococci are gastrointestinal tract residents and also an important cause of nosocomial infections. To understand which species, virulence determinants, and antibiotic resistances are prevalent in enterococci shed by various hosts groups, a total of 1460 strains isolated from 144 fecal samples obtained from wastewater, domesticated mammals and birds, and wildlife were characterized. Identification of isolates to the species level showed that Enterococcus faecalis was dominant in domesticated mammals and birds and wildlife feces, whereas Enterococcus faecium was dominant among wastewater isolates, and that no single Enterococcus species could be associated with a specific host group.

Economic issues with follow-on protein products.

The economic effects of the possible introduction of 'follow-on' protein products have been the subject of recent debate. Here, we aim to explore the economic issues surrounding this debate using three measures: total sales, product complexity and patent expiry. Our analysis shows that the sales of therapeutic protein products are concentrated in a relatively small number of branded products, which may be the most attractive targets for follow-on development.

Growth with high planktonic biomass in Shewanella oneidensis fuel cells.

Shewanella oneidensis MR-1 grew for over 50 days in microbial fuel cells, incompletely oxidizing lactate to acetate with high recovery of the electrons derived from this reaction as electricity. Electricity was produced with lactate or hydrogen and current was comparable to that of electricigens which completely oxidize organic substrates. However, unlike fuel cells with previously described electricigens, in which cells are primarily attached to the anode, at least as many of the S.

Lack of electricity production by Pelobacter carbinolicus indicates that the capacity for Fe(III) oxide reduction does not necessarily confer electron transfer ability to fuel cell anodes.

The ability of Pelobacter carbinolicus to oxidize electron donors with electron transfer to the anodes of microbial fuel cells was evaluated because microorganisms closely related to Pelobacter species are generally abundant on the anodes of microbial fuel cells harvesting electricity from aquatic sediments. P. carbinolicus could not produce current in a microbial fuel cell with electron donors which support Fe(III) oxide reduction by this organism.

The Desulfitobacterium genus.

Desulfitobacterium spp. are strictly anaerobic bacteria that were first isolated from environments contaminated by halogenated organic compounds. They are very versatile microorganisms that can use a wide variety of electron acceptors, such as nitrate, sulfite, metals, humic acids, and man-made or naturally occurring halogenated organic compounds.

Molecular analysis of Desulfitobacterium frappieri pcp-1 involved in reductive dehalogenation of pentachlorophenol.

Desulfitobacterium are Gram positive, spore-forming, strictly anaerobic bacteria, that belong to the Firmicutes, Clostridia, Clostridiales, and Peptococcaceae. Most known members of the genus Desulfitobacterium have the ability to dechlorinate several halogenated compounds by a mechanism of reductive dehalogenation and use them as electron acceptors to generate energy (halorespiration). Desulfitobacteria are therefore perfect candidates to be used in bioremediation treatments of environment polluted with halogenated compounds.

Desulfitobacterium hafniense is present in a high proportion within the biofilms of a high-performance pentachlorophenol-degrading, methanogenic fixed-film reactor.

We developed a pentachlorophenol (PCP)-degrading, methanogenic fixed-film reactor by using broken granular sludge from an upflow anaerobic sludge blanket reactor. This methanogenic consortium was acclimated with increasing concentrations of PCP. After 225 days of acclimation, the reactor was performing at a high level, with a PCP removal rate of 1,173 muM day(-1), a PCP removal efficiency of up to 99%, a degradation efficiency of approximately 60%, and 3-chlorophenol as the main chlorophenol residual intermediate.

Strategies for augmenting the pentachlorophenol degradation potential of UASB anaerobic granules.

Anaerobic degradation of pentachlorophenol (PCP) is an example of a process that may benefit from enrichment or bioaugmentation. In one approach, enrichment acceleration was attempted by applying an on-line control-based selective stress strategy to a native anaerobic upflow sludge bed (UASB) system; this strategy linked PCP loading rate to methane production. As a result, the reactor biomass potential for PCP complete dechlorination reached a rate of 4 mg g(-1) volatile suspended solid (VSS) day(-1) within a period of 120 days.