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Use of tobacco products in any form is unsafe, and nearly all tobacco product use begins during adolescence. CDC and the Food and Drug Administration (FDA) analyzed data from the 2024 National Youth Tobacco Survey to determine tobacco product use among U.S. middle school (grades 6-8) and high school (grades 9-12) students. In 2024, current (previous 30-day) use of any tobacco product was reported by 10.1% of high school students (representing 1.58 million students) and 5.4% of middle school students (representing 640,000 students). Among all students, e-cigarettes were the most commonly reported tobacco product currently used (5.9%), followed by nicotine pouches (1.8%), cigarettes (1.4%), cigars (1.2%), smokeless tobacco (1.2%), other oral nicotine products (1.2%), heated tobacco products (0.8%), hookahs (0.7%), and pipe tobacco (0.5%). During 2023-2024, among all students, the estimated number who reported current use of any tobacco product decreased from 2.80 to 2.25 million students; e-cigarette use decreased (from 2.13 to 1.63 million students); and hookah use decreased (from 290,000 to 190,000 students). Among high school students, current use of any tobacco product decreased from 12.6% to 10.1% of students, and e-cigarette use decreased from 10.0% to 7.8%. Among middle school students, no statistically significant changes occurred. Evidence-based strategies can help prevent initiation and promote cessation of tobacco product use among U.S. youths. [ABSTRACT FROM AUTHOR]

The article comments on a paper by professor Bryan E. Denham on the magazine reporting of the history of patent medicine in the U.S., including topics on the role of muckraking magazines in exposing deceptive advertising, the implementation of Pure Food and Drug Act, and the importance of labeling.

Although studies in mass communication and investigative journalism have examined associations between newspaper reporting and policy formation, little research has focused on the policy influence of magazine coverage. In addition, given research questions that implicitly or explicitly conclude with policy implementation, studies have tended to analyze materials prior to the passage of legislation with little attention paid to subsequent reporting. This monograph examines magazine coverage of patent medicines before and after the Pure Food and Drug Act of 1906 became law. Patent medicines, which appeared in the form of cure-alls, headache remedies, and soothing syrups, emerged long before the federal government regulated substances such as morphine and cocaine, and nostrums often included these substances in addition to alcohol. Near the turn of the 20th century, magazine journalists began to draw attention to the hazards associated with patent medicines, building an agenda for policy reform. The Pure Food and Drug Act of 1906 required manufacturers to list habit-forming substances and the quantities of those substances on product labels, and sales showed an appreciable decline; however, companies continued to profit. An examination of magazine articles showed that, in addition to patent-medicine manufacturers, newspapers received significant criticism for advancing industry interests through advertising. As a partial result of outlandish claims made in advertisements, problems with patent medicines continued after implementation of the Pure Food and Drug Act. Government officials and the U.S. Supreme Court were among those who undermined the 1906 law. Implications for investigative journalism, history, and public policy are discussed. [ABSTRACT FROM AUTHOR]

The article comments on the paper by professor Bryan Denham on the history of patent medicine in the U.S., including topics on the enactment of 1906 Pure Food and Drug Act, native and political advertising, and the advertising of hemp products.

Abstract: Understanding the role of food science education in developing undergraduate students’ intentions to implement Good Manufacturing Practices (GMPs) may be a key strategy in developing the workforce's implementation of GMPs and other food safety programs. Previous research has demonstrated the effects of educational interventions on planned food safety behaviors in various settings; however, none have studied GMPs interventions and college students. This study applied the Theory of Planned Behavior (TPB) to evaluate the effects of a game‐based e‐learning module on undergraduate students’ planned behaviors concerning GMPs. Forty‐four participants were recruited from 42 food science clubs across the United States to complete a game‐based e‐learning module and pre‐ and posttest survey instruments. We compared changes in pre‐ and posttest scores using paired Wilcoxon signed rank tests and explored the role of GMP‐related knowledge and TPB constructs (attitudes, subjective norms, and perceived behavioral controls) in predicting students’ intentions to implement GMPs using multiple linear regression. We modeled pretest scores, posttest scores, and changes in scores while controlling for student demographic factors (for example, year in college, gender, and so on). Only participants’ knowledge and perceived behavioral controls significantly increased (P < 0.05) after completing the game‐based e‐learning module. Posttest regression models explained twice as much variance than pretest models (up to 54% total). Changes in intentions to implement GMPs were predicted by changes in subjective norms, perceived behavioral controls, and knowledge, as well as previous enrollment in food safety courses and interest in working in the food industry. The only predictive variables for both pre‐ and posttest scores were subjective norms, previous enrollment in food safety courses and interest in working in the food industry (P < 0.05). A discussion of how these results provide insights for food safety educators to optimize their teaching impacts was presented. [ABSTRACT FROM AUTHOR]

Abstract Lumbar intervertebral body fusion devices (L-IBFDs) are intended to provide stability to promote fusion in patients with a variety of lumbar pathologies. Different L-IBFD designs have been developed to accommodate various surgical approaches for lumbar interbody fusion procedures including anterior, lateral, posterior, and transforaminal lumbar interbody fusions (ALIF, LLIF, PLIF, and TLIF, respectively). Due to design differences, there is a potential for mechanical performance differences between ALIF, LLIF, PLIF, and TLIF devices. To evaluate this, mechanical performance and device dimension data were collected from 124 Traditional 510(k) submissions to the FDA for L-IBFDs cleared for marketing from 2007 through 2016. From these submissions, mechanical test results were aggregated for seven commonly performed tests: static and dynamic axial compression, compression-shear, and torsion testing per ASTM F2077 , and subsidence testing per ASTM F2267. The Kruskal-Wallis test and Wilcoxon signed-rank test were used to determine if device type (ALIF, LLIF, PLIF, TLIF) had a significant effect on mechanical performance parameters (static testing: stiffness and yield strength; dynamic testing: runout load; subsidence testing: stiffness [Kp]). Generally, ALIFs and LLIFs were found to be stiffer, stronger, and had higher subsidence resistance than PLIF and TLIF designs. These results are likely due to the larger footprints of the ALIF and LLIF devices. The relative mechanical performance and subsidence resistance can be considered when determining the appropriate surgical approach and implant for a given patient. Overall, the mechanical performance data presented here can be utilized for future L-IBFD development and design verification. [ABSTRACT FROM AUTHOR]

The article offers information on the drugs Erenumab, Benralizumab, and Tezacaftor/ivacaftor, which are approved for marketing by the U.S. Food and Drug Administration Topics include estimated number of Americans who experience migraine headaches, medications that are used most often in the treatment of acute migraine attacks, and the effectiveness of erenumab. Also mentioned are the indications and administration of Benralizumab and Tezacaftor/ivacaftor.

The article focuses on the laws governing drugs in the U.S. Topics discussed icnlude changes to state and federal drug sentencing laws; substance use patterns and sentencing policies in the country; and enactment of Food and Drug Act, Marijuana Tax Act, and Harrison Narcotics Tax Act for preventing the same.

The soft tissue thermal index defined in the Output Display Standard is not applicable to eye exposures because of unique eye properties such as high ultrasound absorption in the lens and orbital fat. To address this potential safety issue, the U.S. Food and Drug Administration has recommended a maximum exposure level for ophthalmic exams of 50 mW/cm2 (derated spatial-peak temporal-average intensity, ISPTA.3) based on a model of ultrasound propagation in the eye. To gain a better understanding of actual temperature rise as a function of ISPTA.3, an ex vivo experimental study within the porcine lens was performed. Both temperature and acoustic pressure were measured simultaneously in the lens using a fiberoptic probe. At ISPTA.3 = 50 mW/cm2, the maximum and average temperature rises over 133 measurements were 0.23°C and 0.09°C, respectively. A 1.5°C temperature rise was not obtained until ISPTA.3 ≈ 435 mW/cm2. The data indicate that operating below the Food and Drug Administration guidance level should result in relatively low heating in ophthalmic exposures. [ABSTRACT FROM AUTHOR]

The article offers information on the history, purpose and significance of marijuana prohibition under the provisions of the Controlled Substances Act of 1970 and the Food, Drug, and Cosmetic Act of 1906. It analyzes the attempt of the U.S. States to legalize the use of marijuana under the Tenth Amendment of the Constitution.

The article focuses on the existence of a fundamental right to be free from governmental intrusion into food choices within the penumbral rights established by the U.S Supreme Court. Topics discussed include a history of the evolution of food regulation in the U.S, the Federal Food, Drug, and Cosmetic Act of 1938 and the U.S Pure Food and Drug Act of 1906 for regulation of food. Other topics include trends in government paternalism and the food safety issues in the U.S.

Abstract: The compliance of a cross section of commercial and institutional caterings in Ghana to the PNDC Law 305B Sections 1, 6 and 7 was studied with the use of purposively sampled food workers in the two set ups. Both commercial and institutional caterings had considerable number of hygiene trained personnel in supervisory position in compliance with section 6 of the Food Law. Sections 1 and 7 on the sale of unwholesome food through lack of available control measures on handling non conforming raw materials and the preparation of food under unsanitary conditions respectively needed much improvement in both set ups. It was recommended that an introduction to the Food Law in Ghana should be added to enforced food hygiene training for food handlers that commensurate with their activities. [Copyright &y& Elsevier]

The article reflects on the development history and current use of regulatory science in the U.S. It reflects on the first act the U.S. Pure Food and Drug Act passed by the U.S. Food and Drug Administration in 1906 which was later modified in 1938 as the U.S. Food, Drug and Cosmetic Act of 1938 which required manufactured to given premarket notification to regulators about the safety of product. It talks about Kefauver–Harris Amendments to 1938 Act and on use of term "regulatory science".

The article focuses on the U.S. Drug Amendments of 1962, which amended the U.S. Food and Drug Act of 1906. Topics include the enactment of the U.S. Federal Food, Drug, and Cosmetic Act of 1938, the development of the U.S. Food and Drug Administration (FDA), and the U.S. Drug Efficacy Study Implementation (DESI) Program.

Abstract: Background: Erectile dysfunction (ED) has been a prevalent disease worldwide. The mainstay of treatment for ED focused on oral medications such as phosphodiesterase-5 (PDE-5) inhibitors or other medical aids with variable acceptance. Trazodone is a second-generation antidepressant approved by the U.S. Food and Drug Administration in 1981. Some evidence has suggested that trazodone may be helpful in improving ED, especially for problems dealing with male arousal. Although controversial, trazodone can sometimes be used for ED as an off-label medication for urological patients. By using a nationwide health insurance database, we attempted to estimate and thereafter analyze the existence and extent of off-label use of trazodone for ED in Taiwan. Methods: The 1/500 randomly sampled outpatient visits dataset and the 1/1 million randomly selected dataset issued in 2000 in the National Health Insurance Research Database were used to estimate the total number of visits and the urological visits involving trazodone prescriptions. The refill rate, patient age at first prescription, and the diagnoses assigned to the prescription visits were also gathered and analyzed. Results: The prescription visits in urological clinics consisted exclusively of male patients (99.0 ± 1.3%, p < 0.001). The use of trazodone was more prevalent and regular among the elderly (p < 0.001), which happens to parallel the trend of incidence rates of ED. Starting in 1998, the prescription rate for trazodone increased rapidly, but then slowed, equalized, and topped out in 2003. One of the reasons for this marked change in prescriptions rates in Taiwan may be the increased awareness of ED as a treatable disease under the promotion and marketing of three PDE-5 inhibitors. ED-related diagnoses assigned to the prescription visits accounted for 55% of total visits, whereas anxiety/depression-associated diagnoses were the bases of less than 13%, and those attributed to insomnia accounted for 2.3% of visits. Conclusion: Despite the fact that trazodone was not officially approved for patients with urological conditions, this medication has been used as an ED treatment in Taiwan at least since 1997; the prescriptions of trazodone were more prevalent among the elderly, and this trend increased, then evened out, and eventually reached its maximum point in 2003, correlating with the introduction of PDE-5 inhibitors. [Copyright &y& Elsevier]

The article presents a speech by attorney Richard M. Cooper which was delivered at the Food and Drug Law Institute's 56th Annual Conference on April 23, 2013. Cooper addresses various issues including the U.S. Food, Drug, and Cosmetic Act and the 1906 Pure Food and Drugs Law, as well as the nation's Food and Drug Administration (FDA). FDA approvals for drugs and devices are also mentioned, along with the FDA Alumni Association.

Introduction: In 2010, the U.S. Food and Drug Administration (FDA) developed 36 proposed health warnings for cigarette packages, from which 9 were subsequently selected for implementation. The current study aimed to evaluate the perceived efficacy of the 36 proposed FDA warnings. Methods: Web-based surveys were conducted with 783 adult smokers and 510 youth in United States. Participants were randomized to view and rate two sets of 6–7 warnings, each set corresponding to one of nine health effect statements required under the Tobacco Control Act. Warnings included all 36 FDA-proposed warnings and additional warnings for comparison. Results: Youth and adults rated individual warnings similarly; in all cases where differences were found, youth perceived warnings as more effective. Comparisons on specific elements indicated that warnings were perceived as more effective if they were: full color (vs. black and white), featured real people (vs. comic book style), contained graphic images (vs. nongraphic), and included a telephone “quitline” number or personal information. Few sociodemographic differences were observed in overall perceived effectiveness: younger respondents, non-White respondents, and smokers intending to quit rated warnings higher. Conclusions: Seven of the nine health warnings selected by the FDA for implementation were among the proposed warnings rated as most effective in the current study. However, the warning(s) added for comparison were rated higher than the FDA-selected warning for five of the nine sets, suggesting some warnings could be improved for greater impact. The findings support the inclusion of a telephone “quitline” number and reinforce the importance of depicting “real” people and health effects. [ABSTRACT FROM AUTHOR]

Abstract: Various regulatory authorities like International Conference on Harmonization (ICH), US Food and Drug Administration, Canadian Drug and Health Agency are emphasizing on the purity requirements and the identification of impurities in active pharmaceutical drugs. Qualification of the impurities is the process of acquiring and evaluating data that establishes biological safety of an individual impurity; thus, revealing the need and scope of impurity profiling of drugs in pharmaceutical research. As no stability-indicating method is available for identification of degradation products of trandolapril, a new angiotensin converting enzyme inhibitor (ACEI), under stress testing, the development of an accurate method is needed for quantification and qualification of degradation products. Ultra high performance liquid chromatography (UPLC) coupled to electrospray tandem mass spectrometry was used for the rapid and simultaneous analysis of trandolapril and its degradation products. Chromatographic separation was achieved in less than 4min, with improved peak resolution and sensitivity. Thanks to this method, the kinetics of trandolapril degradation under various operating conditions and the characterization of the structure of the by-products formed during stress testing have been determined. Thereafter, a mechanism of trandolapril degradation in acid and neutral conditions, including all the identified products, was then proposed. [Copyright &y& Elsevier]

This study examines how an integrated program of marketing communication (including advertising and public relations) addressed the purity of patent flour, a consumable attacked by the pure food movement and other health advocates for corrupt and contaminated production processes. Targeted to homemakers and commercial bakers alike, the promotional materials studied here examine the Gold Medal and Pillsbury brands from 1880 to 1930, a period that saw the rise of national brands, the growth of national advertising, the passage of the Pure Food and Drug Act of 1906, and the educational and regulatory efforts of the FDA. It was found that these companies responded to those criticisms and developed a long-term campaign that tapped into contemporary cultural concerns not only to sell product but also to educate consumers about purity, health values, and domestic success. In the process, these promotions also sought to build on a bond of trust in the product to trust in the brand and the company itself through traditional ad placements in targeted media and through initiatives that reached into consumers' homes and kitchens. [ABSTRACT FROM AUTHOR]

Treatment decisions made in clinical practice, based on current guidelines, often conflict with decisions by third-party payors that restrict the ability of patients with primary immunodeficiency disease (PI) to adhere to appropriate treatment. This is seen by many physicians as potentially placing the health of patients at risk. Key treatment decisions challenged by third-party payors and discussed here include dosing, product safety, and routes of administration. Data on safety issues emphasize that IgG products are not generic drugs and each of the products currently licensed by the Food and Drug Administration (FDA) must be regarded as an individual therapy, given the products' different manufacturing processes and stabilizing ingredients. The issue of switching patients to a different product needs careful consideration as evidence shows that infusion-related adverse events in many patients are frequently related to this activity. Decisions regarding the route of therapy should also be individualized to the patient, weighing such factors as side effects, adherence with therapy, and lifestyle. [ABSTRACT FROM AUTHOR]

Abstract: In this study the mutagenic, recombinagenic, carcinogenic and anticarcinogenic potential of orlistat was assessed using the somatic mutation and recombination test (SMART) and the epithelial tumor detection test (wts). The experiments were conducted on Drosophila melanogaster. In the assessment using SMART, larvae, descendants from the standard (ST) cross and the high bioactivation (HB) cross, were treated chronically with three orlistat concentrations. The results revealed a recombinagenic effect, associated with orlistat, in the descendants of the HB cross, at all three levels of concentration. Homologous recombination can function as a determinant at different stages of carcinogenesis. For verification, larvae from the wts test, descendants of the wts/TM3 virgin female and mwh/mwh male cross, were treated with the same three orlistat concentrations separately and in association with mitomicin C (0.1mM). The results did not, however, provide evidence that orlistat has carcinogenic potential nor was it associated with the reduction of tumors induced by mitomicin C in D. melanogaster. [Copyright &y& Elsevier]

Zinc oxide (ZnO) is an inorganic compound widely used in everyday applications. ZnO is currently listed as a generally recognized as safe (GRAS) material by the Food and Drug Administration and is used as food additive. The advent of nanotechnology has led the development of materials with new properties for use as antimicrobial agents. Thus, ZnO in nanoscale has shown antimicrobial properties and potential applications in food preservation. ZnO nanoparticles have been incorporated in polymeric matrices in order to provide antimicrobial activity to the packaging material and improve packaging properties. This review presents the main synthesis methods of ZnO nanoparticles, principal characteristics and mechanisms of antimicrobial action as well as the effect of their incorporation in polymeric matrices. Safety issues such as exposure routes and migration studies are also discussed. [ABSTRACT FROM AUTHOR]

Abstract: Antibody microarrays with enzyme-linked immunosorbent technology are used for quantitative, simultaneous and high-throughput analysis of multiple proteins in a single probe. Kinetic detection can significantly improve precision and quantification range of microarray measurements. Here we present the open source software Kinetic Operating Microarray Analyzer (KOMA) that enables calibration and high-throughput analysis of quantitative microarray data collected using a time-resolved kinetic detection protocol of the enzymatic signal. This tool can also be helpful for analyzing data from any other analytical assays employing enzymatic signal amplification, in which a broader range of quantification is reached by the time-resolved recording of readouts. KOMA is open for download at http://www.uni-heidelberg.de/fakultaeten/biowissenschaften/ipmb/biologie/woelfl/Research.html together with a set of test raw data and requires R version 2.12 and Java RE version 6.0. [Copyright &y& Elsevier]

Purpose: To explore the comparative performance of the recently proposed bioequivalence (BE) approaches, FDA and EMA, by the FDA working group on highly variable drugs and the EMA, respectively; to compare the impact of the GMR-constraint on the two approaches; and to provide representative plots of % BE acceptance as a function of geometric mean ratio, sample size and variability. Methods: Simulated BE studies and extreme GMR versus CV plots were used. Three sequence, three period crossover studies with two treatments were simulated using four levels of within-subject variability. Results: The FDA and EMA approaches were identical when variability was <30%. In all other cases, the FDA method was more permissive than EMA. The major discrepancy was observed for variability values >50%. The GMR-constraint was necessary for FDA, especially for drugs with high variabilities. For EMA, the GMR-constraint only became effective when sample size was large and variability was close to 50%. Conclusions: A significant discrepancy in the performances of FDA and EMA was observed for high variability values. The GMR-constraint was essential for FDA, but it was of minor importance in case of the EMA. [ABSTRACT FROM AUTHOR]

A new rapid method for the determination of actinides in food samples has been developed at the Savannah River Site Environmental Lab (Aiken, SC, USA) that can be used for emergency response or routine food samples. If a radiological dispersive device or improvised nuclear device event occurs, there will be a urgent need for rapid analyzes of many different environmental matrices, as well as food samples, to support dose mitigation and protect general populations from radioactivity that may enter the food chain. The recent accident at Fukushima nuclear power plant in March, 2011 reinforces the need to have rapid analyzes for radionuclides in environmental and food samples. The new method to determine actinides in food samples utilizes a furnace ashing step, a rapid sodium hydroxide fusion method, a lanthanum fluoride matrix removal step, and a column separation process with stacked TEVA, TRU, and DGA resin cartridges. The furnace ashing and rapid fusion steps are performed in relatively inexpensive, reusable zirconium crucibles. Alpha emitters are prepared using rare earth micro precipitation for counting by alpha spectrometry. The method showed high chemical recoveries and effective removal of interferences. The determination of actinides in food samples can be performed in less than 8 h for 10 g samples with excellent quality for emergency samples using short count times. Larger food samples (100 g) may be processed in 24 h or less. The rapid fusion technique is a rugged sample digestion method that ensures that any refractory actinide particles are effectively digested. This method can be used to meet the derived intervention level guidelines recommended by the U.S. Food and Drug Administrations. [ABSTRACT FROM AUTHOR]

Calcium-sensing receptors (CaSR) are integral to regulation of systemic Ca2+ homeostasis. Altered expression levels or mutations in CaSR cause Ca2+ handling diseases. CaSR is regulated by both endogenous allosteric modulators and allosteric drugs, including the first Food and Drug Administration-approved allosteric agonist, Cinacalcet HCl (Sensipar®). Recent studies suggest that allosteric modulators not only alter function of plasma membrane-localized CaSR, but regulate CaSR stability at the endoplasmic reticulum. This brief review summarizes our current understanding of the role of membrane-permeant allosteric agonists in cotranslational stabilization of CaSR, and highlights additional, indirect, signalling-dependent role(s) for membrane-impermeant allosteric drugs. Overall, these studies suggest that allosteric drugs act at multiple cellular organelles to control receptor abundance and hence function, and that drug hydrophobicity can bias the relative contributions of plasma membrane and intracellular organelles to CaSR abundance and signalling. LINKED ARTICLES This article is part of a themed section on the Molecular Pharmacology of G Protein-Coupled Receptors (GPCRs). To view the other articles in this section visit . To view the 2010 themed section on the same topic visit [ABSTRACT FROM AUTHOR]

The US campaign for ‘pure food’ from the 1880s through 1906 featured a diverse coalition of groups with quite different ways of defining the problem, identifying the relevant actors, and balancing political and consumerist tactics. This paper examines how these differences in framing, rather than undermining cooperation or impeding success, helped to broaden the coalition for pure food and to win passage of the 1906 Food and Drug Act. It pays particular attention to the ways in which women's groups acted as frame brokers, translating pure food issues into a maternalist language and, in so doing, contributing both new support and new tactics to the campaign. The case study is used to address more general issues in the relationship between framing and (1) coalition-building and (2) tactical repertoires. [ABSTRACT FROM PUBLISHER]

The article presents information on the U.S. State Court of Appeals case International Dairy Foods Association v. Boggs in which it was held mandatory for the U.S. Food and Drug Administration (FDA) to label milk from cows which are being treated with recombinant Bovine Somatotropin (rBST). It discusses a brief history of the FDA's authority under the U.S. Pure Food and Drug Act of 1906. It also provides information on the FDA's approval of rBST and the challenges against its decision.

Abstract: The aim of this study was to demonstrate the usefulness of the size exclusion chromatography with evaporative light scattering detection (SEC-ELSD) method in the identification and quantitative analysis of polydimethylsiloxanes (PDMS). The process of validation for the method was conducted, and the values obtained were compared with the acceptance criteria. Particularly important was the conclusion that SEC-ELSD method showed a high specificity for PDMS. PDMS is an organosilicon polymer and for this reason, it does not exist as a concrete chemical species. Depending on the length of the chain, PDMS can be toxic for organism. So far, the SEC-ELSD method has not been applied for the control of pharmaceutical products containing such PDMS as dimeticone or simeticone. The safety of use and effectiveness of such pharmaceutical products relies on the control of their quality. Therefore, the analytical methods and procedures that meet acceptance criteria for qualitative and quantitative analysis of the PDMS should be used. In the case of the analysis of pharmaceutical products, the acceptance criteria are established and recommended by, for example, the Pharmacopoeias, the U.S. Food and Drug Administration (FDA), the International Conference on Harmonisation (ICH) and the World Health Organization (WHO). The progress of knowledge, however, requires the development of new analytical tools which are able to solve incoming problems. In the case of pharmaceutical formulations containing PDMS, which are used not only by adults but also by children, it is necessary to use analytical methods which are characterized by a high specificity. [Copyright &y& Elsevier]

Faught E. Vigabatrin therapy for refractory complex partial seizures: review of clinical trial experience in the United States. Acta Neurol Scand: 2011: 124 (Suppl. 192): 29-35. © 2011 John Wiley & Sons A/S. Vigabatrin is an antiepileptic drug used in more than 50 countries as adjunctive therapy for the treatment of refractory complex partial seizures (rCPS) in adults. First approved in the United Kingdom in 1989, vigabatrin was approved for use in the United States by the Food and Drug Administration in 2009. Although most clinical trials of vigabatrin have been conducted in Europe, three major trials, including two pivotal trials, were conducted in the United States. These trials have demonstrated efficacy and tolerability findings similar to those observed from the European trials. Results of the US trials have demonstrated vigabatrin to be an effective and generally well-tolerated therapy for rCPS in adults, with an optimal dosage of 3 g/day for most patients, and an onset of response generally within 2 weeks. This review focuses on the design and results of the three major US trials of vigabatrin in adults with rCPS. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) involves the activation of a photosensitizing drug, which preferentially localizes to diseased skin, by irradiation with light to cause selective cytotoxic damage. Since its discovery in the early 20th century and the development of topical photosensitizers 2 decades ago, PDT is increasingly being used in dermatology for a wide range of neoplastic, inflammatory, and infectious cutaneous conditions. Topical 5-aminolevulinic acid and methyl aminolevulinic acid, the most commonly used agents in PDT, have received Food and Drug Administration approval for the treatment of actinic keratoses, and many second-generation photosensitizers are under investigation. Compared with conventional therapies, PDT has the advantage of being noninvasive and capable of field treatment. It is also associated with quicker recovery periods and excellent cosmetic results. Because of these benefits, PDT is being evaluated as a potential treatment option for many dermatologic conditions and has been shown to be effective for certain nonmelanoma skin cancers. Although research is still limited, PDT might also have a therapeutic benefit for cutaneous T-cell lymphoma, acne, psoriasis, leishmaniasis, and warts, among others. This article is a review of the clinical applications of PDT in dermatology and summarizes the current evidence in literature describing its efficacy, safety, and cosmetic outcome. [ABSTRACT FROM AUTHOR]

Despite a sharp increase in the expenditures for drug research and development (R&D) in the past decade, the declining trend in the number of new drugs approved annually by the US Food and Drug Administration continues. This growing disparity between R&D investment and new drug approvals results in part from the deficiency in promising therapeutic targets and leads to a stagnation exacerbated by the lack of advanced drug discovery tools for harvesting the 'high-hanging fruits' such as inhibitors of protein-protein interactions (PPIs). Small peptide inhibitors of PPIs can be of high affinity and specificity, promising an important class of therapeutic agents that target PPIs involved in a great variety of biological processes. However, susceptibility to proteolytic degradation in vivo still remains a major hurdle that limits their therapeutic potential. This limitation can be overcome by mirror-image phage display, a technique that allows, through phage-expressed peptide library screening against the D-enantiomer of a target protein, for the identification of proteolysis-resistant D-peptide inhibitors of PPIs. Recent advances in total protein synthesis via native chemical ligation have significantly expanded the scope of molecular targets for mirror-image phage display. This concise review focuses on the latest development in the combined use of mirror-image phage display and native chemical ligation for D-peptide based anticancer drug discovery. [ABSTRACT FROM AUTHOR]

Abstract: Magnetic resonance imaging (MRI) studies of tissue engineered constructs prior to implantation clearly demonstrate the utility of the MRI technique for studying the bone formation process. To test the utility of our MRI protocols for explant studies, we present a novel test platform in which osteoblast-seeded scaffolds were implanted on the chorioallantoic membrane of a chick embryo. Scaffolds from the following experimental groups were examined by high-resolution MRI: (a) cell-seeded implanted scaffolds (CIM), (b) unseeded implanted scaffolds (UCIM), (c) cell-seeded scaffolds in static culture (CIV) and (d) unseeded scaffolds in static culture (UCIV). The reduction in water proton transverse relaxation times and the concomitant increase in water proton magnetization transfer ratios for CIM and CIV scaffolds, compared to UCIV scaffolds, were consistent with the formation of a bone-like tissue within the polymer scaffold, which was confirmed by immunohistochemistry and fluorescence microscopy. However, the presence of angiogenic vessels and fibrotic adhesions around UCIM scaffolds can confound MRI findings of bone deposition. Consequently, to improve the specificity of the MRI technique for detecting mineralized deposits within explanted tissue engineered bone constructs, we introduce a novel contrast agent that uses alendronate to target a Food and Drug Administration-approved MRI contrast agent (Gd-DOTA) to bone mineral. Our contrast agent termed GdALN was used to uniquely identify mineralized deposits in representative samples from our four experimental groups. After GdALN treatment, both CIM and CIV scaffolds, containing mineralized deposits, showed marked signal enhancement on longitudinal relaxation time-weighted (T1W) images compared to UCIV scaffolds. Relative to UCIV scaffolds, some enhancement was observed in T1W images of GdALN-treated UCIM scaffolds, subjacent to the dark adhesions at the scaffold surface, possibly from dystrophic mineral formed in the fibrotic adhesions. Notably, residual dark areas on T1W images of CIM and UCIM scaffolds were attributable to blood inside infiltrating vessels. In summary, we present the efficacy of GdALN for sensitizing the MRI technique to the deposition of mineralized deposits in explanted polymeric scaffolds. [Copyright &y& Elsevier]

Summary: During a recent Food and Drug Administration workshop on clinical trials to evaluate new TB drugs, questions were raised regarding the use of bacteriologic endpoints such as treatment failure and relapse as measures of improvement in health status and long term outcome after treatment. FDA scientists asked how patients’ clinical signs and symptoms changed during therapy, noting that while such information is usually collected during clinical trials, it is not often reported. We analyzed data from an international phase 3 TB treatment trial that included systematic assessments of symptoms. The percentage of subjects with self-reported symptoms at baseline ranged from 30% for dyspnea to 81% for cough, with 51% reporting fever. During therapy, fever, sweats, and dyspnea decreased most rapidly, with near resolution by the end of therapy. Chest pain and cough resolved more slowly; 13% of subjects reported cough at six months. Symptom resolution during treatment did not differ between those who relapsed and those who did not. Among those with microbiological relapse, symptoms returned with significant increases in the proportion with fever, cough, and chest pain. At the time of relapse, cough was the most frequent symptom, occurring in 75% of subjects who relapsed but only 12% of those who did not. Our data support the continued use of bacteriologic endpoints based on sputum culture as surrogate measures of the relief of symptoms, improvement in health status and favorable long term treatment outcome in TB drug trials. [ABSTRACT FROM AUTHOR]

Background: Continuous-flow left ventricular assist devices (LVADs) such as the HeartMate II have become the therapy of choice in patients with end-stage heart failure. The aim of this study is to report the outcomes in patients receiving the HeartMate II LVAD at a single center and review the lessons learned from this experience. Methods: From June 2005 to June 2010, 130 consecutive patients received the HeartMate II LVAD. Of these, 102 were bridge-to-transplant (BTT), 17 destination therapy, and 11 exchanges for failed HeartMate XVE. This study focuses on the 102 BTT patients. The HeartMate II was approved by the US Food and Drug Administration (FDA) as BTT in April 2008 and 64 patients received this device as BTT since that date. We review our experience with the device as BTT and report on patient survival and adverse events as well as the impact of FDA approval on outcomes. Results: Overall, mean age was 52.6 ± 12.8 years; 26 (25.5%) were female. Disease etiology was ischemic in 58, nonischemic in 36, and other in 8. Overall, 30-day, 6-month, and 1-year survival for the BTT patients was 95.1%, 83.5%, and 78.8%, respectively. The 6-month survival in 38 patients in the clinical trial (pre-FDA) was 88.8% and was not statistically significant compared with the 76.2% 6-month survival in the 64 patients in the post-FDA approval period (p value = 0.1). Major adverse events among the 102 BTT patients included right ventricular failure in 5 (4.9%), LVAD driveline infections in 25 (24.5%), neurologic events in 10 (9.8%), and gastrointestinal bleeding in 18 (17.6%) patients. In addition, 1 patient (0.98%) had pump thrombus requiring device replacement. Conclusions: Despite significant morbidity, use of the HeartMate II LVAD as BTT provides excellent hemodynamic support and is associated with excellent survival and low mortality. In addition, there needs to be improvement and focused strategies in the areas of gastrointestinal bleeding, driveline infections, and adverse neurologic events for these devices to be able to provide a real long-term alternative to heart transplantation. [ABSTRACT FROM AUTHOR]

Abstract: In August 2010, the World Health Organization and the Korea Food & Drug Administration jointly organized the first implementation workshop of WHO guidelines on evaluating similar biotherapeutic products (SBPs) at the global level. The objective of the Workshop was to facilitate implementation of the newly adopted WHO Guidelines into the practice of national regulatory authorities (NRAs). WHO Guidelines were recognized by the workshop participants as a tool for harmonizing regulatory requirements worldwide. By reviewing and practicing several case studies, better understanding and consensus on the principles of clinical trial designs were reached. However, variations in terms of the national requirements for quality, safety and efficacy of these products revealed diversity in the regulatory expectations in different countries and regions. In addition, lack of terminology for the products developed as copy products (so called "me too" products) with a partial comparability to an RBP, led to a great diversity in evaluating as well as naming these products. The workshop participants proposed the following actions: a) NRAs should make efforts to build their capacities for regulation of SBPs; b) WHO should revise WHO Guidelines for assuring the quality of products prepared by recombinant DNA technology (WHO TRS 814) and continue monitoring progress with the implementation of the Guidelines on evaluating SBPs. Publication of the outcome of the Workshop was recognized as another action that WHO should coordinate. [Copyright &y& Elsevier]

Purpose: We describe the safety of sipuleucel-T using an integrated analysis of 4 randomized, controlled studies in patients with prostate cancer. Materials and Methods: Adverse events, survival data and laboratory evaluations were examined for common, rare and latent events. Results: In 5% or more of sipuleucel-T cases some adverse events were reported at a rate at least twice that in controls, including chills in 53.1%, pyrexia in 31.3%, headache in 18.1%, myalgia in 11.8%, influenza-like illness in 9.7% and hyperhidrosis in 5.0%. These events generally occurred within 1 day of infusion, were grade 1 or 2 in severity and resolved in 2 days or less. The incidence of serious adverse events reported was 24.0% in sipuleucel-T cases and 25.1% in controls. Grade 3 or greater adverse events were reported within 1 day of infusion in 40 of 601 sipuleucel-T cases (6.7%) and 7 of 303 controls (2.3%). The incidence rate of reported cerebrovascular events was 3.5% for sipuleucel-T cases and 2.6% in controls. Conclusions: Sipuleucel-T therapy in patients with prostate cancer has a side effect profile that is characterized by mild to moderate, short-term, reversible adverse events. There was no evidence of a treatment related increase in autoimmune complications or secondary malignancies after treatment with sipuleucel-T. Sipuleucel-T can be administered safely in the outpatient setting. [ABSTRACT FROM AUTHOR]

This study at a commercial hatchery was required by the U.S. Food and Drug Administration to provide independent substantiation of the results of previous laboratory dose-confirmation studies on the use of copper sulfate (CuSO4) to control fungus (Saprolegnia spp.) on the eggs of channel catfish, Ictalurus punctatus. The study compared an untreated control group of eggs to eggs treated with 10 mg/L CuSO4 in a flow-through system; mean water temperature was 23.5°C. Eggs were treated once daily until the embryos reached the eyed stage (5 treatments). Hatching was complete by day 11, and fry were counted to determine the percentage of survival in each treatment. Fungus was identified by polymerase chain reaction (PCR) as Saprolegnia spp. The mean survival in the control treatments was 4% and 40% in the CuSO4 treatments; the latter survival was significantly higher, but still lower than normal. This study confirms that 10 mg/L CuSO4 is an effective treatment to control fungus on catfish eggs when used daily until the eggs are eyed. However, continued treatment of eggs until hatching occurs may be warranted based on fungal growth rates observed after treatments were discontinued. [ABSTRACT FROM PUBLISHER]

Chronic constipation and IBS-C are two of the most common functional bowel disorders encountered by primary care providers and gastroenterologists, affecting up to 27% of the population in Western countries [1-4]. The treatment of these disorders is often empiric and most current therapies are indicated for episodic constipation. Over time, most patients become refractory to one or more laxatives. Lubiprostone (Amitiza) has been approved by the US Food and Drug Administration (FDA) for the treatment of chronic-idiopathic constipation [6]. It is an oral bicyclic fatty acid that selectively activates type 2 chloride channels in the apical membrane of the intestinal epithelial cells, hence stimulating chloride secretion, along with passive secretion of sodium and water, inducing peristalsis and laxation, without stimulating gastrointestinal smooth muscle. Several trials have shown it to be effective in the treatment of chronic idiopathic constipation, and recently also IBS-C. It has little systemic absorption and almost free of any serious adverse effects, however, occasionally can cause nausea. Based on the available evidence, it is reasonable to conclude that lubiprostone should be added to the short list of evidence-based pharmacotherapies for chronic constipation and IBS-C. Given the overlap between chronic constipation and IBS-C, clinicians can consider two strategies when deciding on the initial dose of lubiprostone. Based on current product labeling, it is recommended that 8 μg bid be started in patients with IBS-C whereas 24 μg bid be used in those with chronic constipation. Thus far, lubiprostone offers a novel approach to our therapeutic armamentarium, however, there is a need for more drugs with different mechanisms of action, in order to treat constipation that is often multifunctional. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to examine the frequency and causes of surgical explantation of patent foramen ovale (PFO) closure devices. Background: PFO has been linked with cryptogenic strokes, recurrent transient neurologic deficits, sleep apnea, decompression illness, and migraines. Several randomized trials are in progress to determine whether PFO closure is preferable to medical management in the treatment of patients with cryptogenic strokes or migraine. The majority of PFO closures are performed off-label, because there is no U.S. Food and Drug Administration approval for use of any device to close a PFO. As data are accumulating on the benefits of implanting PFO closure devices, it is also important to examine complications that might occur. Methods: We performed a database review to identify the frequency and causes of PFO device explantation, examining 18 PFO closure centers in Europe and the United States. Results: Of the 13,736 percutaneous PFO device implantations performed over the past 9 years at these 18 institutions, 38 devices (0.28% [95% confidence interval: 0.20% to 0.37%]) required surgical removal. There were a wide range of causes cited for these removals. The most common cause for explantation was chest pain (n = 14), often determined to be secondary to nickel allergy to the PFO device. Other causes for explantation included persistence of a residual shunt (n = 12), the presence of thrombus on the device (n = 4), pericardial effusion (n = 2), perforation of the atrium or aortic root (n = 2), recurrent strokes (n = 1), the development of endocarditis (n = 1), and undocumented reasons (n = 2). Conclusions: The vast majority of PFO closure procedures are performed safely with minimal complications. However, there is a small (0.28%) incidence of severe long-term problems associated with PFO closure that might require surgical removal of the device. In addition, the frequency of surgical explantation was found to be device-dependent; some of these devices seem to be safer than others. [Copyright &y& Elsevier]

Abstract: Background: The lack of post Food and Drug Administration (FDA)-approval acceptance studies among males aged 18–26 years is problematic relative to the design of human papillomavirus (HPV) vaccine promotion programs designed to target males. Accordingly this study identified correlates of intention to receive the HPV vaccine among young men. Methods: Young men (n =150) were recruited from two university campuses in the southern United States. Men completed an audio computer-assisted self administered interview assessing their beliefs, attitudes, and intent to receive the vaccine, newly approved for males. Bivariate associations between various measures and men''s intent to be vaccinated in the next 12 months were assessed using t-tests. Measures achieving bivariate significance were entered into a regression model. Results: In the regression model, those reporting oral–genital sex were more likely to have positive intent (β=0.32, t =4.20, P =0.0001). Those classified as having a relatively higher perceived susceptibility to HPV were more likely to have positive intent (β=0.19, t =2.53, P =0.013). Finally, intent was associated with agreement/disagreement to the statement that “the HPV vaccine is so new that I should wait awhile before deciding about getting vaccinated” (β=0.19, t =2.49, P =0.014). Those not agreeing were more likely to have positive intent. Conclusion: Young men who have had oral–genital sex and those with greater perceptions of susceptibility to HPV may have greater intent to receive the HPV vaccine. A barrier reducing their intention for vaccination may be the relatively new introduction of this vaccine to the male population. [Copyright &y& Elsevier]

Title VIII of the Food and Drug Administration Amendments Act (FDAAA) has required basic results reporting from interventional clinical studies in a tabular format since September 27, 2008, on the US government website ClinicalTrials.gov. The State of Maine also required study results posting (including adverse event data), as of December 8, 2008. In addition to the already existing Protocol Registration System (PRS), the National Library of Medicine has developed a Results Registration System (RRS) with an entry application on the website that prepopulates table shells for results entry on the basis of the information in the PRS. Participant Flow, Baseline Characteristics, Outcome Measures, and Reported Adverse Events are the main modules of the RRS. At UCB we have entered results from more than 30 studies in RRS. This article reports our first experiences with basic results reporting from the perspective of a midsized pharmaceutical company, describes the challenges faced in establishing processes to enable results entry, and provides recommendations to improve the current RRS. [ABSTRACT FROM AUTHOR]

The path of scientific change is unforeseeable and may be marked by abrupt shifts in course. When these shifts occur, our criminal justice system is ill-equipped to respond expeditiously; it thus lags behind scientific frontiers. In an age where science-dependent prosecutions are proliferating, this failure is of particular concern. Because it is fully constructed by and dependent on medical expertise, Shaken Baby Syndrome (SBS) raises in stark form the problems that arise when science outpaces law--most troublingly, the prospect that we are imprisoning people who have committed no crime. The trajectory of SBS in the criminal courts reveals fundamental limitations of our system's ability to absorb forensic advances in a manner consistent with the administration of justice. The law may ultimately align itself with the latest scientific thinking, but it is doing so slowly, arbitrarily, and in a wholly unreasoned (and unstudied)fashion. In the interim, we are witnessing patterned injustice. This Article constructs a conceptual framework that describes and critiques how criminal justice evolves in the wake of scientific change. It thus begins the process of reforming institutions, laws, and practices to better account for the tentative nature of scientific orthodoxy. By priming the system to deal more effectively with epistemic contingency, we affirm our commitment to protecting the innocent. [ABSTRACT FROM AUTHOR]

The unmet need for improved multiple myeloma (MM) therapy has stimulated clinical development of monoclonal antibodies (mAbs) targeting either MM cells or cells of the bone marrow (BM) microenvironment. In contrast to small-molecule inhibitors, therapeutic mAbs present the potential to specifically target tumor cells and directly induce an immune response to lyse tumor cells. Unique immune-effector mechanisms are only triggered by therapeutic mAbs but not by small molecule targeting agents. Although therapeutic murine mAbs or chimeric mAbs can cause immunogenicity, the advancement of genetic recombination for humanizing rodent mAbs has allowed large-scale production and designation of mAbs with better affinities, efficient selection, decreasing immunogenicity, and improved effector functions. These advancements of antibody engineering technologies have largely overcome the critical obstacle of antibody immunogenicity and enabled the development and subsequent Food and Drug Administration (FDA) approval of therapeutic Abs for cancer and other diseases. [ABSTRACT FROM AUTHOR]

Abstract: In this review we would like to aim at pharmaceuticals engineered on the nanoscale, i.e. pharmaceuticals where the nanomaterial plays the pivotal therapeutic role or adds additional functionality to the previous compound. Those cases would be considered as nanopharmaceuticals. The development of inorganic systems is opening the pharmaceutical nanotechnology novel horizons for diagnosis, imaging and therapy mainly because of their nanometer-size and their high surface area to volume ratios which allow for specific functions that are not possible in the micrometer-size particles. This review will focus on pharmaceutical forms that are based on inorganic nanoparticles where the nanosize of the inorganic component provides unique characteristics to the pharmaceutical form. Several examples of these systems that are either in pre-clinical investigation and under examination by the Food and Drug Administration (FDA) or that have been already approved by the FDA and are in clinical practice today like Gastromark®, NanoTherm®, Colloidal Gold for Lateral Flow tests, HfO-NPs, BioVant™ will be described and reviewed. [Copyright &y& Elsevier]