A Systematic Literature Review on the Assessment of Palatability and Swallowability in the Development of Oral Dosage Forms for Pediatric Patients.

BACKGROUND: Palatability and swallowability of oral dosage forms are important considerations in the development of medications for pediatric populations. As a result of recent legislation, the number of pharmaceutical products being developed with formulations for children is increasing. However, there are limited recommendations and published literature regarding appropriate palatability and swallowability assessment scales in pediatric patients. OBJECTIVE: This systematic literature review aimed to identify and evaluate tools currently utilized to assess palatability and swallowability in clinical trials for pediatric oral dosage forms and identify any potential relationships between palatability and treatment adherence. Literature databases were searched for clinical trials that evaluated palatability of oral dosage forms targeted for pediatric patients. The searches were limited to papers in the English language from January 2008 to March 2013. RESULTS: A total of 137 citations were identified, with 27 articles included in the final full-text analysis. CONCLUSIONS: Various limitations to this systematic review exist, primarily focused on the unavailability of published, early phase development data related to palatability. However, based on results of this review, palatability is often assessed in clinical trials of pediatric dosage forms through the utilization of 2 unvalidated, yet widely accepted, visual scales. There is no standard statistical methodology for analyzing the results of these scales or the cross-comparison of results across studies. Limited evidence regarding a correlation between palatability and treatment adherence in pediatric patients was identified.

Industry Survey on Current Practices in the Assessment of Palatability and Swallowability in the Development of Pediatric Oral Dosage Forms.

An industry-based survey was conducted by the Global Alliance for Pediatric Therapeutics in February 2013 to determine and evaluate the current industry practices in the assessment of palatability and swallowability during the development of pediatric oral solid dosage forms, including the design and statistical analysis of such studies. In addition, the survey was designed to identify areas where regulatory guidance is most needed. The survey was distributed to 6 research-based pharmaceutical companies and to members of the American Academy of Pediatrics' Provisional Section on Advances in Therapeutics and Technology. In general, while all responding companies have experience developing pediatric medicines, there was no consistent approach among respondents to the assessment of organoleptic properties of solid dosage forms, including excipients. In the direct assessment of palatability in pediatric patients in clinical trials, the survey identified that a variety of methods is used across companies, including visual analogue scales, simple and complex hedonic scales, and simplistic Likert-type scales. No assessment method identified was acknowledged as validated or with any statistical correlates, with many respondents stating that scales used in the pharmaceutical industry are adapted from the significant work conducted in the food service industry. Based on findings from the industry survey, the authors believe that there is an opportunity for consensus of the assessment of palatability and swallowability in the development of pediatric oral solid dosage forms.

Comparison of serotonin toxicity with concomitant use of either linezolid or comparators and serotonergic agents: an analysis of Phase III and IV randomized clinical trial data.

OBJECTIVES AND METHODS: The present study's objective was to evaluate serotonin toxicity with concomitant use of linezolid or comparators and serotonergic agents from 20 Phase III and IV comparator-controlled clinical studies on treatment of various Gram-positive infections. All reported adverse events were evaluated for serotonin toxicity using exact and surrogate terms consistent with Sternbach Criteria and Hunter Serotonin Toxicity Criteria. RESULTS: Baseline demographics and co-morbidities were similar between linezolid and comparator groups. No patients in either group were reported to have adverse events identified as serotonin toxicity. Among the patients receiving at least one serotonergic agent, 9 of the 2208 (0.41%) linezolid patients and 3 of the 2057 (0.15%) comparator patients met the Sternbach Criteria [risk ratio (RR) 2.79; 95% confidence interval (95% CI) 0.76-10.31]; 3 (0.14%) of the linezolid patients and 1 (0.05%) of the comparator patients met the Hunter Serotonin Toxicity Criteria (RR 2.79; 95% CI 0.29-26.85). No patients met both criteria. Most patients meeting criteria for serotonin toxicity had past or present co-morbidities that may have contributed to or overlapped with reported adverse events. CONCLUSIONS: While the potential exists for serotonin toxicity to occur with concomitant use of linezolid and serotonergic agents, the risk appears to be low. Based on the large database of Phase III and IV studies included in our analysis, we did not find enough evidence to conclude that linezolid-induced serotonin toxicity was different from that of comparators.

Design of near-field irregular diffractive optical elements by use of a multiresolution direct binary search method.

A multiresolution direct binary search iterative procedure is used to design small dielectric irregular diffractive optical elements that have subwavelength features and achieve near-field focusing below the diffraction limit. Designs with a single focus or with two foci, depending on wavelength or polarization, illustrate the possible functionalities available from the large number of degrees of freedom. These examples suggest that the concept of such elements may find applications in near-field lithography, wavelength-division multiplexing, spectral analysis, and polarization beam splitters.

Disease-specific diagnosis of coinfecting tickborne zoonoses: babesiosis, human granulocytic ehrlichiosis, and Lyme disease.

To determine whether a unique group of clinical and laboratory manifestations characterize certain major deer tick-transmitted human pathogens in North America, we compared the symptoms, short-term complications, and laboratory test results of New England residents who became ill due to > or =1 of these pathogens. Patients completed a uniformly structured questionnaire and submitted blood samples for serologic and polymerase chain reaction (PCR) testing after developing symptoms of Lyme disease, human babesiosis, or human granulocytic ehrlichiosis (HGE). Complete blood count with thin blood smear, PCR, and immunoglobulin M antibody tests helped differentiate the acute manifestations of these diseases. Physicians should consider use of tests designed to diagnose babesiosis and HGE in patients with Lyme disease who experience a prolonged flulike illness that fails to respond to appropriate antiborrelial therapy.