OBJECTIVE: To demonstrate a framework for calculating daily dose distributions for proton therapy in a timeframe amenable to online evaluation using CT-on-Rails.
METHODS: Tasks associated with calculation of daily dose are fully automated. A rigid registration between daily and planning images is used to propagate beams and targets for calculation of daily dose; additionally, risk structures are propagated using deformable registration to facilitate online evaluation. An end-to-end constancy test was carried out using a pelvis phantom containing a simulated target and bladder contour. 97 Daily fan-beam CT data sets associated with 10 clinical patients were processed to demonstrate feasibility and utility of online evaluation. Computing times and dosimetric differences are reported.
RESULTS: The phantom constancy test took 62 s to complete with no notable discrepancies in the registrations or calculated dose. Max doses were identical for target and bladder contours on initial and repeat scans (359 and 310 cGy (RBE) respectively). Total processing time for 97 daily patient images averaged 154.6 s (73.0 - 222.0 s; SD = 31.8 s). On average, dose calculation accounted for 35 % of total processing time. Average differences in D95 for target contours was 1.5 % (SD = 1.6 %) with a max decrease of 5.9 % on a single daily image.
CONCLUSIONS: Daily dose can be automatically calculated in a timeframe amenable to online evaluation using scanner utilities in conjunction with the scripting API of a commercial treatment planning system. Online evaluation of dose in proton therapy is useful to detect clinically relevant changes, guide setup, and facilitate treatment or replanning decisions.

Background: Fingolimod is approved in relapsing-remitting multiple sclerosis (RRMS) with the recommended dose of 0.5 mg daily. To tackle possible adverse events, some clinicians may reduce the dose of fingolimod, mainly in the alternate-day form. We systematically reviewed the literature for efficacy measures of this method. Methods: PubMed (Medline®), Web of Science, Embase, Scopus, and the Cochrane Library databases were searched until April 9, 2021. Clinical studies (other than case reports and case series), in English, were included. Then, publications concerning alternate dose fingolimod (including every other day, every two or three days) were selected. Those studies concerning reduced daily dose (any daily dose less than 0.5 mg/day) were excluded to focus on alternate dosing. Results: Four observational studies were included. Data on Ohtani et al. study were limited. Three other studies were of good quality based on the Newcastle-Ottawa Scale. A total of 296 patients on the standard dose were compared to 276 patients on the alternate dosage. The most common reason for switching to the alternate dose was lymphopenia, followed by elevated liver enzymes. Two studies concluded that the alternate dosing could be a safe, yet effective strategy in patients with intolerable adverse effects of daily dose. However, Zecca et al. warned about the high possibility of disease reactivation. Due to the differences in outcome measures of the studies, meta-analysis was not applicable. Conclusion: This systematic review highlights the ambiguity of evidence on safety and efficacy of alternate dosing of fingolimod, encouraging further research on the subject.

Clozapine is the most effective drug for treatment-resistant schizophrenia, and the dosage and concentration of clozapine in the treatment of mental illness vary greatly in different populations and are affected by many factors.
The serum clozapine concentration of 3734 psychiatric patients was detected, and data on daily dose, sex, age and other medical records were collected for statistical analysis.
The mean daily dose, mean serum concentration and mean C/D (concentration/dose) ratio of clozapine were 191.02 ± 113.47 mg/day, 326.15 ± 235.66 ng/mL and 1.94 ± 1.25 ng/mL per mg/day, respectively. There was difference in daily dose between sexes, and females had higher daily dose (p <0.01), higher serum clozapine concentrations (p < 0.01) and higher C/D ratios (p < 0.01). There were significant differences in daily dose (p < 0.001), serum drug concentration (p < 0.001) and C/D ratio (p < 0.001) among different age groups. The daily dose decreased with age (p for trend < 0.001), and the C/D ratio increased with age (p for trend < 0.001). Inpatients and outpatients had no difference in daily dose, but inpatients had higher serum concentration (p < 0.001) and C/D ratio (p < 0.001). There was no difference in daily dose among different occupations, but there were significant differences in serum concentration (p < 0.001) and C/D ratio (p < 0.001), and unemployed patients may have higher serum concentration and C/D ratio. Duration of disease, comorbidity, marital status, and psychotic type may influence the daily dose and serum concentration.
The effective daily dose and serum concentration of clozapine in the study area may be lower than recommended levels, and women have higher serum concentrations and slower metabolic rates. With increasing age, the daily dose decreases, and the metabolic rate slows. Inpatient status and occupation of patients may influence the serum concentration and metabolic rate of clozapine.

UNASSIGNED: Worldwide, the leading cause of invasive candidiasis and the fourth leading cause of hospital-acquired infections are the Candida species (spp.) group. One of the most important tools in fighting such drug-resistant fungi is the appropriate use of antifungal agents.
UNASSIGNED: The study aimed to determine echinocandins\' general prescribing patterns and how they are associated with the treatment period.
UNASSIGNED: A quantitative, observational, and descriptive was used, and included patients receiving antifungal treatment in a private hospital in Gauteng, South Africa between 01 January 2015 to 31 December 2015.
UNASSIGNED: Of the 146 patient files included, 102 patients (69.9%) received caspofungin and 44 patients (30.1%) were treated with anidulafungin. For the former, 99 (97.1%) patients received a loading dose (LD) of 70 mg, while 200 mg anidulafungin was only prescribed to 30 patients (68.2%). In line with maintenance dose guidelines, the majority (98.1%) of caspofungin-treated patients received 50 mg IV daily, whereas 4 (3.9%) patients were treated at higher doses (70 mg daily). Anidulafungin was administered at various maintenance doses, including 400 mg (2.3% of patients), 200 mg (52.3%), 100 mg (43.2%) and 50 mg (2.3%) IV daily.
UNASSIGNED: Our results can be utilised to produce a hospital-specific algorithm in terms of Candida-infected patients.
UNASSIGNED: These findings contribute to our understanding of prescribing patterns of antifungal agents and the impact thereof on treating Candida spp. Infections.

There are many challenges associated with longitudinally applying therapeutic knowledge in the pharmacy curriculum. This study investigated student participation using the messaging platform, WhatsApp (Meta Platforms, Inc.), as a discussion-based platform for pharmacy students.
The created WhatsApp group chat discussion, \"The Daily Dose,\" was a longitudinal learning experience occurring during pharmacy students\' last year of clinical rotations or third year of didactic learning. Students were asked daily clinical questions in the application and participation was primarily assessed. This study included a pre-survey, discussion participation assessment, and a post-survey. The surveys assessed student self-evaluations of their learning, clinical confidence levels, board preparedness, and program learning experience feedback.
A total of 115 questions were asked and 37 students voluntarily joined. Students participated by responding to 97% of questions. Of the 37 students who joined, 81% were experiential education students and 19% were didactic education students. A moderator needed to prompt for participation for 34% of the questions. The majority of students (95%) learned something new. Experiential education students were more likely to participate than didactic education students. A moderator may be beneficial to keep the discussion active. Students\' self-evaluations of clinical confidence and board preparedness increased after participating in The Daily Dose.
The Daily Dose is an innovative way to engage student discussion and reinforce pharmacy therapeutic knowledge. This tool could be expanded to use with multiple pharmacy learners.

The literature considers children both a risk group for administering probiotic strains and one of the populations that can most benefit from it. Due to the health benefits associated to probiotic supplementation, this scope review sought to formulate a critical evaluation of how Lacticaseibacillus rhamnosus GG, carried in food and non-food matrices, and experimental design may affect the health promotion of infants and children. In this study, a literature search was conducted in three scientific databases: PubMed, Web of Science, and SciELO to retrieve research, published in English or Spanish, which administered L. rhamnosus GG to infants and children with any disease or in eutrophic condition. Three reviewers with an expert supervision screened 540 articles, published between 2001 and 2022, which were retrieved from the databases. The data extracted was compiled and shown in this scoping review. In total, was included, after criteria observation, 44 articles in this review. Intestinal disorders were the most frequent outcome in these studies (36.4%) and capsules, the most common vehicle for administering the probiotic strain (40.9%). Probiotic strain dose ranged from 105 to 1012 cfu/dose of L. rhamnosus GG and intervention length extended from one to more than 6 months. Food matrix showed health effects in 57.1% of the clinical trials and non-food matrix 46.7%, which indicates that the health-promoting effect of the probiotic GG strain may be equivalent between the two forms of delivery. However, the highly heterogeneous experimental designs prevent further analysis and a systematic review and meta-analysis is recommended to address just the outcomes of studies and achieve data homogeneity in order to determine which vehicle is the most suitable for health promoting.

Tacrolimus is a major immunosuppressor against post-transplant rejection in kidney transplant recipients. However, the narrow therapeutic index of tacrolimus and considerable variability among individuals are challenges for therapeutic outcomes. The aim of this study was to compare different machine learning and deep learning algorithms and establish individualized dose prediction models by using the best performing algorithm. Therefore, among the 10 commonly used algorithms we compared, the TabNet algorithm outperformed other algorithms with the highest R2 (0.824), the lowest prediction error [mean absolute error (MAE) 0.468, mean square error (MSE) 0.558, and root mean square error (RMSE) 0.745], and good performance of overestimated (5.29%) or underestimated dose percentage (8.52%). In the final prediction model, the last tacrolimus daily dose, the last tacrolimus therapeutic drug monitoring value, time after transplantation, hematocrit, serum creatinine, aspartate aminotransferase, weight, CYP3A5, body mass index, and uric acid were the most influential variables on tacrolimus daily dose. Our study provides a reference for the application of deep learning technique in tacrolimus dose estimation, and the TabNet model with desirable predictive performance is expected to be expanded and applied in future clinical practice.

Warfarin\'s complex dosing is a significant barrier to measurement of its exposure in observational studies using population databases. Using population-based administrative data (1996-2019) from British Columbia, Canada, we developed a method based on statistical modeling (Random Effects Warfarin Days\' Supply (REWarDS)) that involves fitting a random-effects linear regression model to patients\' cumulative dosage over time for estimation of warfarin exposure. Model parameters included a minimal universally available set of variables from prescription records for estimation of patients\' individualized average daily doses of warfarin. REWarDS estimates were validated against a reference standard (manual calculation of the daily dose using the free-text administration instructions entered by the dispensing pharmacist) and compared with alternative methods (fixed window, fixed tablet, defined daily dose, and reverse wait time distribution) using Pearson\'s correlation coefficient (r), the intraclass correlation coefficient, and the root mean squared error. REWarDS-estimated days\' supply showed strong correlation and agreement with the reference standard (r = 0.90 (95% confidence interval (CI): 0.90, 0.90); intraclass correlation coefficient = 0.95 (95% CI: 0.94, 0.95); root mean squared error = 8.24 days) and performed better than all of the alternative methods. REWarDS-estimated days\' supply was valid and more accurate than estimates from all other available methods. REWarDS is expected to confer optimal precision in studies measuring warfarin exposure using administrative data.

OBJECTIVE: To describe the different insulin therapy patterns and insulin daily doses in children and adolescents (aged 1-17 years) with type 1 diabetes.
METHODS: This cross-sectional study based on the longitudinal prescription (LRx) database (IQVIA) included children and adolescents who received at least two insulin prescriptions of the same drug from 1 January 2016 to 31 December 2019. The study outcomes included the proportion of patients with insulin pumps and multiple daily injection therapy, human insulin and insulin analogue use, as well as insulin daily doses. A multivariable linear regression model was used to study the association between age, sex, insulin drugs, and daily dose.
RESULTS: A total of 22 512 children and adolescents (mean age: 13.5 years, 47.1% female) were included. The proportion of patients using insulin pump therapy decreased with age, from 72.6% (females) and 73.0% (males) in the age group of younger than 6 years to 30.8% (females) and 26.1% (males) in adolescents. Insulin aspart was the most common short-acting insulin, with the proportion of users increasing from 56% in the age group of younger than 6 years to 69%-70% in the 13-17 years age group. The daily dose of insulin pump therapy was 10 units lower than multiple daily injection (MDI) (P < .001).
CONCLUSIONS: We found a marked age dependency for pump use, with a strong increase observed in the youngest age group. Insulin aspart was the most frequently used analogue insulin. A higher total daily insulin dose was shown in patients on MDI versus insulin pump, along with a significant age dependency.

There have been concerns that antipsychotics increase the incidence of hyperglycemic progression. Many factors have been suggested to contribute to the risk of antipsychotic-induced hyperglycemic progression, including the type, daily dose, and number of antipsychotics; however, few studies have examined these relationships. This study aimed to examine the affect of antipsychotic treatment-associated factors on hyperglycemic progression, after adjustment for the affect of background factors suggested to be associated with hyperglycemic progression. This was a nationwide, multicenter, prospective cohort study examining the incidence of hyperglycemic progression during a 12 mo period following the initiation of newly prescribed antipsychotic medication. Demographic data, medication history, and blood test values were collected from 631 study participants with normal blood glucose levels at baseline for 12 mo. The primary endpoint (incidence of hyperglycemic progression) was defined as progression from normal to prediabetic or probable diabetic status, and was evaluated based on the Japanese monitoring guidance in patients with schizophrenia. To further examine the affect of antipsychotics on glucose metabolism over time, we examined changes in HbA1c levels 3, 6, and 12 mo after the initiation of treatment with each antipsychotic. We found that treatment with zotepine and clozapine was associated with a significantly high incidence of hyperglycemic progression. Furthermore, changes in HbA1c levels 6 mo after the initiation of zotepine treatment were significantly higher than those following blonanserin and haloperidol treatments. In contrast, there was no significant difference in the change in total cholesterol, triglycerides, HDL cholesterol, and BMI during the same period. Moreover, the \"daily dose\" and \"number\" of antipsychotics did not show an association with the incidence of hyperglycemic progression. However, in a post hoc analysis in which the antipsychotics were divided into two groups according to the strength of blockade of H1, M1, M3, and 5-HT2C receptors, the incidence of hyperglycemic progression was higher in the medium- and high-daily dose groups than in the low-daily dose group in the antipsychotic group with strong blockade of these receptors. Our study indicated that the type of antipsychotic had a greater affect on the incidence of hyperglycemic progression than the daily dose of antipsychotics or their number. Among these, zotepine was most likely to increase the incidence of hyperglycemic progression, suggesting the need for caution when these antipsychotics are prescribed.