Small Number Of Doses Research Articles

Preference of young adults for COVID-19 vaccination in the United Kingdom: a discrete choice experiment

ABSTRACT Objectives To determine preferences for COVID-19 vaccinations in the young adult population in the United Kingdom (UK). Method A discrete choice experiment survey was conducted in UK young adults. Participants were asked to choose between two hypothetical vaccines the one they preferred the most. Vaccines were defined by five attributes (effectiveness, risk of side effects, duration of protection, number of doses, confidence in available evidence), identified following a systematic literature review and qualitative interviews with 13 young adults. A random parameters logit model, a latent class model, and subgroup analyses were used to identify preferences. Results One hundred and forty-nine respondents were included (70% women, mean age 23 years). All five attributes significantly influenced respondents’ vaccination decisions. Respondents valued higher effectiveness, lower risk of side effects, longer protection duration, and a smaller number of doses. Based on the range of levels of each attribute, vaccine effectiveness was the most important attribute (relative importance 34%), followed by risk of side effects (32%), and duration of vaccine protection (22%). Conclusions The five investigated vaccine attributes appear to play an important role in young adults’ decision-making process. Results of this study may help health authorities designing appropriate strategies in future vaccines campaigns in the younger UK population.

Global antibiotic dosing strategies in hospitalised children: Characterising variation and implications for harmonisation of international guidelines.

Paediatric global antibiotic guidelines are inconsistent, most likely due to the limited pharmacokinetic and efficacy data in this population. We investigated factors underlying variation in antibiotic dosing using data from five global point prevalence surveys. Data from 3,367 doses of the 16 most frequent intravenous antibiotics administered to children 1 month-12 years across 23 countries were analysed. For each antibiotic, we identified standard doses given as either weight-based doses (in mg/kg/day) or fixed daily doses (in mg/day), and investigated the pattern of dosing using each strategy. Factors underlying observed variation in weight-based doses were investigated using linear mixed effects models. Weight-based dosing (in mg/kg/day) clustered around a small number of peaks, and all antibiotics had 1-3 standard weight-based doses used in 5%-48% of doses. Dosing strategy was more often weight-based than fixed daily dosing for all antibiotics apart from teicoplanin, which had approximately equal proportions of dosing attributable to each strategy. No strong consistent patterns emerged to explain the historical variation in actual weight-based doses used apart from higher dosing seen in central nervous system infections, and lower in skin and soft tissue infections compared to lower respiratory tract infections. Higher dosing was noted in the Americas compared to the European region. Antibiotic dosing in children clusters around a small number of doses, although variation remains. There is a clear opportunity for the clinical, scientific and public health communities to consolidate behind a consistent set of global antibiotic dosing guidelines to harmonise current practice and prioritise future research.

Adsorption of Vi Capsular Antigen of Salmonella Typhi in Chitosan-Poly (Methacrylic Acid) Nanoparticles.

The development of a nanoparticulate system for the carrier antigen is now an important tool in the vaccination process, since a smaller number of doses is necessary for effective immunization. Thus, in this work a nanoparticulate system using polymers of chitosan and poly (methacrylic acid) (CS–PMAA) to adsorb the Vi antigen of Salmonella Typhi was developed. CS–PMAA nanoparticles with different proportions of chitosan and poly (methacrylic acid) were obtained and reached sizes from 123.9 ± 2.48 to 234.9 ± 2.66 nm, and spherical shapes were seen in transmission microscopy. At pH 7.2, the nanoparticles had a cationic surface charge that contributed to the adsorption of the Vi antigen. Qualitative analyses of the isolated Vi antigen were performed using Fourier-transform infrared spectroscopy, which indicated the presence of all the characteristic bands of the capsular polysaccharide, and nuclear magnetic resonance, which showed signals for the five hydrogens and the N-acetyl and O-acetyl groups which are characteristic of the Vi antigen structure. In the adsorption kinetics study, the Vi capsular antigen, contained in a phosphate buffer solution of pH 7.2, experienced 55% adsorption on the 1–1% (CS–PMAA) nanoparticles. The adsorption kinetics results showed the ability of the nanoparticulate system to adsorb the Vi antigen.

Opioid prescription patterns for pediatric orthopaedic fracture patients

BackgroundWhile hospitalizations attributed to opioid poisonings are increasing in the pediatric population, the patterns of prescribing behaviors of health care providers remains unclear. The aims of this study were to identify the opioid prescribing patterns of an orthopaedic team for post-surgical pediatric orthopaedic fracture patients, and to examine whether patient demographics, injury type, and type of providers were associated with the opioid prescribing patterns at discharge. MethodsA retrospective chart review was performed among all patients aged 0–18 years undergoing surgery for elbow, forearm, wrist, femur, tibia and ankle fractures between 2014 and 2016 at a large children's hospital. Inclusion criteria were patients with isolated operative fractures involving the elbow, forearm, wrist, femur, tibia or ankle who received an opioid prescription at discharge prescribed by a member of the orthopaedic team. Exclusion criteria included patients discharged without opioids or patients discharged with opioid prescriptions from another medical team. Response1000 unique patients (546 male) were identified, with average age of 7.9 years. The most common fracture was elbow (67.2%), followed by femur (12.4%), ankle (9.4%), forearm (5.8%), wrist (4.6%), and tibia (1.6%). Average dose of opioids prescribed was 28.4 (SD = 11.5) per patient. All prescriptions followed recommended guidelines for each medication. Patients who were older (p < 0.0001) or heavier (p < 0.0001) were prescribed a significantly greater average number of opioid doses. Nurse practitioners wrote 57.0% of the discharge prescriptions, followed by residents (23.0%) and physician assistants (14.5%). Attending surgeons accounted for only 5.5% of prescriptions. Residents and physician assistants prescribed significantly higher average doses than nurse practitioners and attending surgeons (p < 0.0001). Patients receiving liquid opioids received a statistically significant (p < 0.001) smaller number of doses than patients receiving tablets. ConclusionsPediatric orthopaedic trauma patients appear to be receiving generic numbers of opioid pain medication doses after fracture surgery due to universal rather than injury-specific prescribing patterns. Further study is required to determine the appropriate number of doses per injury type.

A Flexible Bayesian Approach for Modeling Monotonic Dose–Response Relationships in Drug Development Trials

Clinical trials often involve comparing 2–4 doses or regimens of an experimental therapy with a control treatment. These studies might occur early in a drug development process, where the aim might be to demonstrate a basic level of proof (the so-called proof of concept (PoC) studies), at a later stage, to help establish a dose or doses that should be used in phase III trials (dose-finding), or even in confirmatory studies, where the registration of several doses might be considered. When a small number of doses are examined, the ability to implement parametric modeling is somewhat limited. As an alternative, in this paper, a flexible Bayesian model is suggested. In particular, we draw on the idea of using Bayesian model averaging (BMA) to exploit an assumed monotonic dose–response relationship, without using strong parametric assumptions. The approach is exemplified by assessing operating characteristics in the design of a PoC study examining a new treatment for psoriatic arthritis and a post hoc data analysis involving three confirmatory clinical trials, which examined an adjunctive treatment for partial epilepsy. Key difficulties, such as prior specification and computation, are discussed. A further extension, based on combining the flexible modeling with a classical multiple comparisons procedure, known as MCP–MOD, is examined. The benefit of this extension is a potential reduction in the number of simulations that might be needed to investigate operating characteristics of the statistical analysis.

Development of a low-dose fast-dissolving tablet formulation of Newcastle disease vaccine for low-cost backyard poultry immunisation

The immunisation of backyard poultry is critical for maintaining healthy flocks to provide nutrition and income for low-resource farmers worldwide. A vaccine presentation for flocks of less than 50 birds...

Study on the Dosing Accuracy of Commonly Used Disposable Insulin Pens

Improved patient comfort and optimal glycemic control have led to the widespread use of insulin pens, particularly in Europe. Most of the former studies on the dose accuracy of insulin pens included only a small number of doses and pens. In extension to our previous large-scale study testing the dosing accuracy following a randomized dosing sequence with each pen, the present study was more directed toward the dose accuracy for one specific dose dispensed repeatedly with the same pen. This is the first study providing detailed comparative data on the accuracy of repeated dose delivery with prefilled disposable insulin pens at low, middle, and high doses, dispensed over the entire pen volume. In total, 15 previously unused insulin pens from two lots of each pen type (SoloSTAR(®) [sanofi-aventis, Paris, France], FlexPen(®) [Novo Nordisk A/S, Bagsværd, Denmark], Next Generation FlexPen [Novo Nordisk], and KwikPen™ [Eli Lilly, Indianapolis, IN]) were used to deliver 5-unit (low), 30-unit (middle), and 60-unit (high) doses, respectively, dispensed four times from each pen in a nonrandomized manner. Actual doses were determined gravimetrically taking the density of the respective insulin into account and were evaluated according to the guidelines (DIN EN ISO 11608-1:2000) of the International Organization for Standardization (ISO). All tested insulin pens met the requirements for accuracy with none of the single values being outside the defined range of the ISO recommendations (1±1 units, 30±1.5 units, and 60±3 units, respectively). The present study demonstrated a consistent and accurate dose delivery at all dosage levels for all tested insulin pens, with no clinically relevant differences among the products.

Educational needs of patients with rheumatoid arthritis

Only three patients received pain assessment within 4 h of admission. No patients were assessed regularly regarding the location and intensity of their pain. More than one third of patients did not receive any PRN analgesics. Patients of 80 years of age or older received a smaller number of doses of PRN analgesics than their younger counterparts. The number of doses of PRN analgesics received by patients following pain assessment was significantly greater than that received by patients without pain assessment. More than 60% of nurses reported that they were aware of the method of assessing pain in the elderly, and more than three quarters said that ‘‘administration of analgesia around-the-clock’’ is better than ‘‘administration as required’’. Of the barriers for optimal pain management, the one that created the most challenge was ‘‘difficulty communicating with patients’’.

Hypothesis Testing and Bayesian Estimation using a Sigmoid E max Model Applied to Sparse Dose-Response Designs

Application of a sigmoid E max model is described for the assessment of dose-response with designs containing a small number of doses (typically, three to six). The expanded model is a common E max model with a power (Hill) parameter applied to dose and the ED 50 parameter. The model will be evaluated following a strategy proposed by Bretz et al. (2005). The sigmoid E max model is used to create several contrasts that have high power to detect an increasing trend from placebo. Alpha level for the hypothesis of no dose-response is controlled using multiple comparison methods applied to the p-values obtained from the contrasts. Subsequent to establishing drug activity, Bayesian methods are used to estimate the dose-response curve from the sparse dosing design. Bayesian estimation applied to the sigmoid model represents uncertainty in model selection that is missed when a single simpler model is selected from a collection of non-nested models. The goal is to base model selection on substantive knowledge and broad experience with dose-response relationships rather than criteria selected to ensure convergence of estimators. Bayesian estimation also addresses deficiencies in confidence intervals and tests derived from asymptotic-based maximum likelihood estimation when some parameters are poorly determined, which is typical for data from common dose-response designs.

Contributions of negative reinforcement processes to compulsive drug use

Addictive drugs such as opiate can produce physical dependence after a very small number of doses. consequently, to stave off or alleviate the withdrawal distress precipitated by dependence, the addicted person resort to self- drug administration. however, the withdrawal relief theory of drug addiction posits that an aversive condition is terminated by drug administration. this model explains the negative reinforcement processes of addiction. concisely, the present review examined the major tenets of negative reinforcement theories of addiction and the way the tenets contribute to compulsive drug use. this is supported by a body of theoretical and empirical evidence substantiating the contribution of negative reinforcement processes in drug motivation.IFE PsychologIA Vol. 13(2) 2005: 183-195

Polymer drug delivery may overcome poor patient compliance in TB

Will it be possible to deliver an entire course of antituberculosis chemotherapy via biodegradable polymer implants? It looks like the answer is yes. This may require a small number of doses, or a single implant may be enough. Either way, this new approach to tuberculosis treatment could prove extremely useful in reducing noncompliance. Details of research into this new approach were presented at the Global Conference on Lung Health [Mainz, Germany; June 1994].

The study of the distribution of dose in radiotherapy with the aid of electronic computers.

SUMMARY The authors comment on the utilization of electronic computers as a means of obtaining, quickly and efficiently, the distribution of dose in radiotherapy, with consequent facilitation of the planning procedure. The authors describe the plan of operation and its flow chart. During recent years, electronic computers have been the object of studies with a view to using them in the planning of teleradiation treatment. In this respect much work was done by Tsien, by Professor Theodor Sterling and associates of the University of Cincinnatti, by research workers from the University of Gothenburg, by Dr. Ruheri Perez-Tamayo and companions from the Penrose Cancer Hospital, and by Dr. J. Laughlin and collaborators of the New York Memorial Hospital. As we know, the planning of radiotherapy for deep lesions is quite complex, due to the slight difference in sensitivity between the malignant tissues which should be destroyed and the circumjacent healthy ones, which are often vital and more sensitive than the blastoma itself, and which should be protected. It is up to the radiotherapist, after exhaustively studying the structure and location of the tumour and its relations with the surrounding tissues, to divide the amount of radiation into several “entrance doors”– fields situated at various places on the surface of the body and which, from different angles, shed their rays in the direction of the neoplasia. In determining the openings of the diaphragm, the angles of incidence, and the weights of the contributions from each field, he should concentrate on the region aimed at, the sum of the destructive effects of such radiation beams, since their doses are summable. In order to know the distribution of the dose throughout the irradiated region, it is necessary to verify the values of the sums of the various beams in a sufficiently large number of points and situated not only on the tumour but also on the adjacent healthy structures. Sometimes, once the disposition is known (the isodose curves having been made), points. of overdosage, distortions, deviations and other defects are noted. It is up to the radiotherapist to analyse and find the cause of error and to make a new distribution, thus reinitiating the planning process and studying the new procedure. If it is true that the intensity diminishes-in relation to the distance of the source, the distribution of the amount of radiation in one beam is, however, complex: it depends on the dimensions of the source, on the collirnation device, on the distance source-skin, on the medium, on the spectral composition of the radiation. On a plane perpendicular to the axis the dose varies up to more than 20%, since the radiation emission is not isotropic and the distance to the source is greater on the borders, the diffusion is quantitatively different in the centre and on the limits of the field, and the more peripheral rays go through a greater thickness of filter, as they go through it at an oblique angle. Consequently, the action of the various beams on the region treated produces a distribution of dose which is difficult to calculate and entails a great deal of work. Lack of means capable of making the calculations quickly leads the radiotherapist to the repetition of pre-established techniques (often without the required exactitude), giving rise to the error resulting from the alterations proper to each case, of the dimensions of the patient and of the lesion and its relations with adjacent tissues. The alternative, the solution by graphic method starting from curves traced on transparent paper, is an exceedingly slow process, tiring, and not very exact, for it is impossible to calculate in this way more than a small number of doses in spaced points. Electronic computers fulfil the need for performing these complicated and slow mathematical operations in short periods of time. The utilization of the computer makes it possible to determine, within a short time, the dose in a great number of points; it gives the specialist the opportunity to make several studies for the same case and select the most convenient planning, thus perfecting the techniques; it also brings about greater safety, both in the number of points calculated and in the precision of the results.

The natural history of ragweed hay fever: A twenty-year study of 120 patients

This paper shows what happens to a group of 120 patients with ragweed hay fever during the twenty-odd years after they have applied for treatment. In each year the number of patients under treatment has diminished, partly because some have moved away, but mostly because the symptoms have improved enough to make further treatment unnecessary. The average number of doses given each year per patient under treatment has been reduced steadily from 10 doses in 1945 to 8 doses in 1950, 7.5 in 1955, 6.3 in 1960, and now to 4.9 doses in 1963. “Clearance” of hay fever has occurred each year in an increasing proportion of the cases. One cannot say that the so-called specific treatment with pollen extract relieves every patient, nor can one say that this treatment has an effect which is permanent, even if the immediate result of that treatment is to abolish all the symptoms of hay fever for that year. However, the method of treating “old” well-known patients with a small number of doses given close to the tolerance level is useful for hay fever.