Patient acceptability, safety and access : A balancing act for selecting age-appropriate oral dosage forms for paediatric and geriatric populations

© 2017 Elsevier B.V. All rights reserved.The selection and design of age-appropriate formulations intended for use in paediatric and geriatric patients are dependent on multiple factors affecting patient acceptability, safety and access. The development of an economic and effective product relies on a balanced consideration of the risks and benefits of these factors. This review provides a comprehensive and up-to-date analysis of oral dosage forms considering key aspects of formulation design including dosage considerations, ease of use, tolerability and safety, manufacturing complexity, stability, supply and cost. Patient acceptability has been examined utilising an evidence-based approach to evaluate regulatory guidance and literature. Safety considerations including excipients and potential risk of administration errors of the different dosage forms are also discussed, together with possible manufacturing and supply challenges. Age appropriate drug product design should consider and compare i) acceptability ii) safety and iii) access, although it is important to recognise that these factors must be balanced against each other, and in some situations a compromise may need to be reached when selecting an age-appropriate formulation.Peer reviewedFinal Accepted Versio

Age-appropriate and acceptable paediatric dosage forms: Insights into end-user perceptions, preferences and practices from the Children's Acceptability of Oral Formulations (CALF) Study

A lack of evidence to guide the design of age-appropriate and acceptable dosage forms has been a longstanding knowledge gap in paediatric formulation development. The Children’s Acceptability of Oral Formulations (CALF) study captured end-user perceptions and practices with a focus on solid oral dosage forms, namely tablets, capsules, chewables, orodispersibles, multiparticulates (administered with food) and mini-tablets (administered directly into the mouth). A rigorous development and testing phase produced age-adapted questionnaires as measurement tools with strong evidence of validity and reliability. Overall, 590 school children and adolescents, and 428 adult caregivers were surveyed across hospitals and various community settings. Attitudes towards dosage forms primarily differed based on age and prior use. Positive attitudes to tablets and capsules increased with age until around 14 years. Preference was seen for chewable and orodispersible preparations across ages, while multiparticulates were seemingly less favourable. Overall, 59.6% of school children reported willingness to take 10mm diameter tablets, although only 32.1% of caregivers perceived this size to be suitable. While not to be taken as prescriptive guidance, the results of this study provide some evidence towards rational dosage form design, as well as methodological approaches to help design tools for further evaluation of acceptability within paediatric studies

Acceptability of orodispersible films for delivery of medicines to infants and preschool children

Orodispersible films (ODFs) possess potential to facilitate oral drug delivery to children; however, documentation of their acceptability in this age group is lacking. This study is the first to explore the initial perceptions, acceptability and ease of use of ODFs for infants and preschool children, and their caregivers through observed administration of the type of dosage form. Placebo ODFs were administered to children stratified into aged 6 to 12 months, 1 year, 2 years, 3 years, 4 years and 5 years old and into those with an acute illness or long-term stable condition in hospital setting. Acceptability of the dosage form and end-user views were assessed by (a) direct observation of administration, (b) questionnaires to caregivers and nurses, and (c) age-adapted questionnaires for children aged 3 years and over. The majority of children (78%) aged 3 years and over gave the ODF a positive rating both on verbal and non-verbal scales. Despite little prior experience, 78% of caregivers expressed positive opinion about ODFs before administration. After the ODFs were taken, 79% of infant caregivers and 86% caregivers of preschool children positively rated their child’s acceptance of the ODF. The intraclass correlation coefficient value was 0.92 showing good agreement between ratings of caregivers and nurses. ODFs showed a high degree of acceptability among young children and their caregivers. If drug loading permits, pharmaceutical companies should consider developing pediatric medicines in this format. The methodology described here is useful in assessing the acceptability of active ODF preparations and other dosage forms to children

Patient-centred pharmaceutical design to improve acceptability of medicines : similarities and differences in paediatric and geriatric populations

Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Patient acceptability of a medicinal product is a key aspect in the development and prescribing of medicines. Children and older adults differ in many aspects from the other age subsets of population and require particular considerations in medication acceptability. This review highlights the similarities and differences in these two age groups in relation to factors affecting acceptability of medicines. New and conventional formulations of medicines are considered regarding their appropriateness for use in children and older people. Aspects of a formulation that impact acceptability in these patient groups are discussed, including, for example, taste/smell/viscosity of a liquid and size/shape of a tablet. A better understanding of the acceptability of existing formulations highlights opportunities for the development of new and more acceptable medicines and facilitates safe and effective prescribing for the young and older populationsPeer reviewedFinal Published versio

Improved Methods for the Analysis of Estrogen Residues in Environmental Aqueous Matrices

Improved analytical methods using novel cleanup techniques and inexpensive instrumentation for the determination of residue estrogens in municipal wastewater and swine lagoon wastewater have been developed. Presented approaches are less expensive, less time consuming, yet produce comparable detection limits and extraction efficiencies to existing methods. Chapter I provides an overview on environmental estrogens. Chapter II describes a novel method to quantify five estrogens including estriol, estrone, 17alpha-estradiol, 17beta-estradiol, and 17alpha-ethynylestradiol in influent and effluent municipal wastewater. The method includes sample preparation using solid-phase extraction followed by a “QuEChERS” cleanup, dansylation and LC/MS/MS detection. Hydrophilic-lipophilic balance solid phase extraction (SPE) was used for sample preconcentration and the extract was cleaned up using a dispersive SPE method using MgSO4, PSA and C-18. The resulting extract was then derivatized with dansyl chloride. Separation was achieved on a C-18 column and quantification was accomplished in the positive ion mode using multiple reaction monitoring. The method is capable of detecting below 1 ng/L. Chapter III describes improved approaches to quantify five estrogens and two conjugates, Estrone 3-glucuronide and beta-Estradiol 3-sulfate, in swine lagoon wastewater and storm water runoff. A considerable residue was collected when lagoon wastewater samples were centrifuged therefore both resulting residues and aqueous portions were analyzed separately. Analysis of the aqueous portions was carried out using a similar approach to the method described in Chapter II. However, a simple test-tube liquid-liquid extraction was used as an additional sample clean-up step. A modified QuEChERS method was utilized to efficiently extract the target analytes in the residue. Methods have 0.9 – 2 ng/L detection limits. Chapter IV describes an approach to quantify residue estrogens in municipal wastewater using a comprehensive two-dimensional gas chromatograph (GCxGC). This method requires no further cleanups after SPE and has detection limits ranging from 1.4 – 22.2 ng/L. All presented methods use relatively small initial sample volumes and produce negligible matrix interferences. The developed methods were validated by performing mini surveys on the estrogen levels in environmental aqueous matrices in north Mississippi

Significance of Sustainable Coffee Production in Sri Lanka Aligning with EU Standards for Market Access and Environmental Resilience

Coffee is one of the world's most popular beverages made from the seeds of the tropical coffee plant and global consumption is 2.25 billion cups per day. There is over 70 countries manufacturing coffee and two genre is most important to the coffee industry are Arabica and Robusta. Indeed, the global coffee industry faces significant challenges including fluctuating production costs due to land scarcity, labor unavailability, water scarcity and environmental impacts. This study emphasizes need of manage climate variability , effectively improve production and improve the livelihoods of smallholder farmers while maintaining environmental integrity and sustainability in line with EU standards to gain European market access for Sri Lankan coffee. Indeed, Sri Lankan coffee can access the European market by managing the variables of coffee variety diversification, water management, exploration of new territory, soil conservation, research and development, cooperation and networking and market access

Unsteady Free Convection from Elliptic Tubes at Large Grashof Numbers

This study solves the problem of unsteady free convection from an inclined heated tube both numerically and analytically. The tube is taken to have an elliptic cross-section having a constant heat flux applied to its surface. The surrounding fluid is viscous and incompressible and infinite in extent. The Boussinesq approximation is used to describe the buoyancy force driving the flow. The underlying assumptions made in this work are that the flow remains laminar and two-dimensional for all time. This enables the Navier-Stokes and energy equations to be formulated in terms of the streamfunction, and vorticity. We assume that initially an impulsive heat flux is applied to the surface and that both the tube and surrounding fluid have the same initial temperature. The problem is solved subject to the no-slip and constant heat flux conditions on the surface together with quiescent far-field and initial conditions. An approximate analytical-numerical solution was derived for small times, t and large Grashof numbers, Gr. This was done by expanding the flow variables in a double series in terms of two small parameters and reduces to solving a set of differential equations. The first few terms were solved exactly while the higher-order terms were determined numerically. Flow characteristics presented include average surface temperature plots as well as surface vorticity and surface temperature distributions. The results demonstrate that the approximate analytical-numerical solution is in good agreement with the fully numerical solution for small t and large Gr

Poor-tasting pediatric medicines: Part 1. A scoping review of their impact on patient acceptability, medication adherence, and treatment outcomes

BackgroundMany medicines for children taste bitter and unpleasant, presenting a significant barrier to effective pharmacotherapy. Anecdotally, this issue is widely recognized; however, empirical evidence on the consequences of unpalatable medicines remains scarce and fragmented. The objective of this scoping review was to investigate the impact of poor tasting pediatric medicines on patient acceptability, medication adherence, and/or treatment outcomes.MethodsA literature search was performed in MEDLINE/PubMed, EMBASE and CINAHL from inception to June 2023. Eligibility criteria included interventional or observational studies conducted in children aged 0–18 years (population), administered an unpalatable oral medicine (exposure), with any reported impact on patient acceptability, medication adherence, and treatment effects (outcomes). Study screening and data extraction was completed using a standardized form on Covidence.ResultsAfter searching 2,282 citations and reviewing 429 full-text papers, 225 articles were included in the final analysis. The impact of poor-tasting medicines was observed across 77 diseases or indications, with 156 different unpalatable medicinal products identified. Outcomes were most frequently linked to reduced patient acceptability, with 64% of articles reporting rejection responses, the need for strategies to aid administration (from positive reinforcement to physical restraint and forced administration), and impacts on prescribing practices (e.g., use of non-first line alternative therapies). Medication adherence impacts were reported in 27% of the reviewed studies, where poor taste was reported as a barrier to adherence in chronic diseases and correlated with incomplete dose administration in acute conditions. A small number of studies linked palatability with treatment outcomes, including viral suppression in HIV and seizure control in epilepsy.ConclusionThis review highlights the widespread adverse impact of poor-tasting pediatric medicines on patient experiences and outcomes, though the true extent of the issue may still be underreported. The problem affects children worldwide, across all age groups, and is frequently noted by parents, caregivers, and healthcare professionals in both clinical and domiciliary settings. These findings emphasize the need for the development and prescription of more palatable medicines for children, as well as the advancement of more universal taste-masking strategies to address this widespread problem

Peacemaking: Touch-and-Go? A Critical Analysis of Norway's Facilitation in the Sri Lankan Peace Process (2002-2006)

Civil war peacemaking is a crucial task. The thesis critically examines some of the important features of Norway’s facilitation in Sri Lanka’s Peace Process after signing of the Ceasefire Agreement (CFA) in 2002. Norway’s facilitation for almost six years has showcased challenges and drawbacks for effective peace outcomes. This thesis discusses Norway’s role starting in 2002 until the end of the Geneva talks in 2006 related to various peace engagements. The basic argument in the thesis is to realize how a third party mediation through facilitation can become effective to reinforce a negotiated settlement. The main argument is based on three presumptions in the "Contingency Model" conceptualizing role of international mediation. These three presumptions are detailed in terms of how third-party facilitation likely to be successful upon the facilitator’s ability to remove disputant's power imbalances, the strategic choice for tension reduction and acting on a neutral basis

Teleoperated hand motion tracking Robotic Manipulator with Haptic Feedback

The purpose of this project is to design and develop a remotely operated Robotic Manipulator which can imitate human hand motions captured through a 3D vision sensor and an Inertial Measurement Unit (IMU). The gripper attached at the end of the Robotic Manipulator facilitates the user with gripping objects. Moreover there is a force feedback system at user's end which let the user feel the feedback force exerted on the robot's gripper by the object being gripped. This force feedback is vital in fragile object handling. Main goal of this project is to make Teleoperated Robotic Manipulators more affordable and flexible to use in daily consumer applications. This working model can be further developed to real world applications such as hazardous material handling, daily household activities and disable people assistance.California State University, Northridge. Department of Electrical and Computer Engineering.Includes bibliographical references (pages 64-66