Patients' Preference for Pharmaceutical Dosage Forms: Does It Affect Medication Adherence? A Cross-Sectional Study in Community Pharmacies.

Background: Dosage forms (DF), which are primarily divided into solid, semisolid, liquid, and gaseous, are among the different factors that influence drug adherence. Thus, the purpose of this study was to evaluate how patients' preferences for pharmaceutical DF affected their adherence to medication in community pharmacies in Gondar town. Methods: A cross-sectional study on community pharmacies was carried out from June 25 to July 27, 2023. The statistical package for social sciences, version 26, was used for data analysis. Factors associated with patient medication discontinuation were found using both bivariate and multivariate logistic regressions. Results: According to our study, the majority of respondents (42.4%) preferred tablet DF. Most respondents (63.9%) DF preference was affected by the size of the medication, in which small-sized were most preferable (59.6%). The oral route of administration was the most preferable (71.2%). The majority of the respondents (59.9%) had a history of discontinuation of medicines. Being male (AOR=2.21, 95% CI: 1.29, 3.79), living in rural areas (AOR=1.98, 95% CI: 1.03, 3.83), types of DF (AOR=4.59, 95% CI: 1.28, 16.52), high frequency of administration (AOR=2.22, 95% CI: 1.08, 4.57), high cost of medication (AOR=3.09, 95% CI: 1.69, 5.68), getting some improvement from illness (AOR=3.29, 95% CI: 1.10, 9.87), and high number of drugs (AOR=3.29, 95% CI: 1.67, 13.85) were significantly associated with medication discontinuation. Conclusion: Our findings showed that tablet dosage forms, oral routes of administration, and once-daily taking of medicines were the most preferred by our respondents. Being male, living in rural areas, types of DF, high frequency of administration, high cost of medication, getting some improvement from illness, and high number of drugs were significantly associated with medication discontinuation. This provides an insight into what to consider when prescribing medicine to enhance patients' adherence and overall therapeutic outcomes.

Sentinel lymph node identification using NIR-II ultrabright Raman nanotags on preclinical models.

Surface-enhanced Raman spectroscopy (SERS) nanotags have garnered much attention as promising bioimaging contrast agent with ultrahigh sensitivity, but their clinical translation faces challenges including biological and laser safety. As breast sentinel lymph node (SLN) imaging agents, SERS nanotags used by local injection and only accumulation in SLNs, which were removed during surgery, greatly reduce biological safety concerns. But their clinical translation lacks pilot demonstration on large animals close to humans. The laser safety requires irradiance below the maximum permissible exposure threshold, which is currently not achievable in most SERS applications. Here we report the invention of the core-shell SERS nanotags with ultrahigh brightness (1 pM limit of detection) at the second near-infrared (NIR-II) window for SLN identification on pre-clinical animal models including rabbits and non-human primate. We for the first time realize the intraoperative SERS-guided SLN navigation under a clinically safe laser (1.73 J/cm2) and identify multiple axillary SLNs on a non-human primate. No evidence of biosafety issues was observed in systematic examinations of these nanotags. Our study unveils the potential of NIR-II SERS nanotags as appropriate SLN tracers, making significant advances toward the accurate positioning of lesions using the SERS-based tracer technique.

Exploring the Role of Pleurotus Ostreatus as an Ointment Formulation in Inducing Wound Healing in Mice Skin.

Background: Natural compounds rich in secondary metabolites have gained attention as alternative therapies for wound healing due to their potential advantages over conventional treatments. Pleurotus ostreatus mushrooms have been identified for their wound-healing properties, including promoting neovascularization, epithelialization, and collagen synthesis. Material and Methods: This study aimed to investigate the wound-healing properties of different doses of topical Extract of Pleurotus ostreatus in albino mice using an excisional wound model. The experimental design involved administering various concentrations of the extract to evaluate its effects on wound closure and histopathological and immunohistochemical parameters. Results: The results revealed significant wound closure and improvements in histopathological and immunohistochemical parameters in mice treated with Pleurotus ostreatus extract. These findings suggest the potential of Pleurotus ostreatus extract as a viable wound healing agent. Conclusion: Pleurotus ostreatus extract demonstrates promising wound-healing capabilities, including promoting wound closure and enhancing histopathological and immunohistochemical parameters in albino mice. Further research is warranted to explore its full therapeutic potential and mechanism of action in wound healing.

Dosing optimization of rituximab for primary membranous nephropathy by population pharmacokinetic and pharmacodynamic study.

Primary membranous nephropathy (PMN) is the most common cause for adult nephrotic syndrome. Rituximab has demonstrated promising clinical efficacy by random controlled trials and the off-label use is widely adopted in PMN. However, the standard dosage is borrowed from B cell lymphoma treatment with far more antigens and is oversaturated for PMN treatment, accompanied with additional safety risk and unnecessary medical cost. More than 15% serious adverse events were observed under standard dosage and low dose therapies were explored recently. Dose optimization by clinical trials is extremely time- and cost-consuming and can be significantly accelerated with the aid of model-informed drug development. Here, we aim to establish the first population pharmacokinetic and pharmacodynamic (PPK/PD) model for rituximab in PMN to guide its dosage optimization. Rituximab pharmacokinetic and pharmacodynamic data from 41 PMN patients in a retrospective study under a newly proposed monthly mini-dose were used to construct quantitative dose-exposure-response relationship via mechanistic target-mediated drug disposition (TMDD) model followed by regression between the reduction of anti-PLA2R titer and time after the treatment. The final model, validated by goodness-of-fit plots, visual predictive checks and bootstrap, was used to recommend the optimized dosing regimen by simulations. The model was well validated for PK/PD prediction. The systemic clearance and half-life are 0.54 L/h and 14.7 days, respectively. Simulation of a novel regimen (6 monthly doses of 100 mg) indicated the comparable ability and superior duration time of CD20+ B cell depletion compared with standard dosage, while the cumulative dosage and safety risk was significantly decreased. We established the first PPK/PD model and provide evidence to support the dosage optimization based on monthly mini-dose. Our study can also efficiently accelerate dosage optimization of novel anti-CD20 antibodies in PMN and other indications.

Ethanol Content of Medications and Its Effect on Blood Alcohol Concentration in Pediatric Patients.

OBJECTIVE: Ethanol is a common excipient used in liquid medications to enhance solubility and inhibit -bacterial growth. While the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have released guidance for how much ethanol is acceptable in medicines, many medications contain more than the recommended amount. The objective of this study was to determine what effect these medications would have on blood alcohol concentration (BAC) for pediatric patients, defined as those medications that would increase the BAC by ≥2.5 mg/dL. METHODS: A list of medications dispensed to pediatric patients from a single hospital over a period of 4 months was obtained. The package inserts of these medications were reviewed to determine ethanol content. Typical doses were used to determine the amount of ethanol pediatric patients weighing 10, 20, and 40 kg would receive. The theoretical BAC was then calculated for each medication containing ethanol. RESULTS: Seven hundred ninety-six medications were dispensed for pediatric patients during the study period, of which 33 contained ethanol. Seven medications would be projected to increase the BAC above 2.5 mg/dL with a normal pediatric dose. CONCLUSION: While most medications do not contain ethanol, we found 7 that contained enough ethanol to potentially raise the BAC above 2.5 mg/dL. Health care practitioners should consider the ethanol content of medications prior to recommending them in children and when assessing overdoses.

Alpha-lipoic Acid: An Antioxidant with Anti-Aging Properties for Disease Therapy.

The anti-aging effects of alpha-lipoic acid (αLA), a natural antioxidant synthesized in human tissues, have attracted a growing interest in recent years. αLA is a short- -chain sulfur-containing fatty acid occurring in the mitochondria of all kinds of eukaryotic cells. Both the oxidized disulfide of αLA and its reduced form (dihydrolipoic acid, DHLA) exhibit prominent antioxidant function. The amount of αLA inside the human body gradually decreases with age resulting in various health disorders. Its lack can be compensated by supplying from external sources such as dietary supplements or medicinal dosage forms. The primary objectives of this study were the analysis of updated information on the latest two-decade research regarding the use of αLA from an anti-aging perspective. The information was collected from PubMed, Wiley Online Library, Scopus, ScienceDirect, SpringerLink, Google Scholar, and clinicaltrials.gov. Numerous in silico, in vitro, in vivo, and clinical studies revealed that αLA shows a protective role in biological systems by direct or indirect reactive oxygen/nitrogen species quenching. αLA demonstrated beneficial properties in the prevention and treatment of many age-related disorders such as neurodegeneration, metabolic disorders, different cancers, nephropathy, infertility, and skin senescence. Its preventive effects in case of Alzheimer's and Parkinson's diseases are of particular interest. Further mechanistic and clinical studies are highly recommended to evaluate the wide spectrum of αLA therapeutic potential that could optimize its dietary intake for prevention and alleviation disorders related to aging.

Corrigendum: Effect of intravenous immunoglobulin therapy on the prognosis of patients with severe fever with thrombocytopenia syndrome and neurological complications.

[This corrects the article DOI: 10.3389/fimmu.2023.1118039.].

A self-management program increases the dosage of inpatient rehabilitation by 26 minutes per day: a process evaluation.

PURPOSE: To evaluate the implementation of a self-management program, My Therapy, designed to increase inpatient rehabilitation therapy dosage via independent practice. MATERIALS AND METHODS: A process evaluation of My Therapy for adult patients admitted for rehabilitation for any condition supervised by physiotherapists and occupational therapists across eight rehabilitation wards compared usual care. Outcomes included reach, dosage, fidelity and adaptation. RESULTS: The mean (SD) age of the process evaluation sample (n = 123) was 73 (11) years with a mean (SD) length of stay of 14.0 (6.6) days. The My Therapy program reached 68% of participants (n = 632/928), and resulted in an average increase in therapy dosage of 26 (95% CI 12 to 40) minutes/day of independent practice. All My Therapy audited programs (n = 28) included body function/structure impairment-based exercises, and half (n = 13/28) included activity/participation-based exercises. On average, participants completed programs 1.8 (SD 1.2) times/day, which were prescribed in accordance with the My Therapy criteria, demonstrating fidelity. There were no between-group differences in daily steps or standing time, however, My Therapy participants spent more time sitting (p ≤ 0.05). Implementation adaptations were minimal. CONCLUSION: A self-management rehabilitation program was implemented with fidelity for two in three rehabilitation patients, resulting in increased therapy dosage with minimal adaptations.

The My Therapy self-management program was implemented with good reach (68% of participants received My Therapy) across four public and private inpatient rehabilitation services.Under My Therapy conditions, the dosage of inpatient rehabilitation therapy participation increased by an average of 26 minutes per day, which will help close the evidence-practice gap between the current rehabilitation dosage of about 1-hour per day, and the recommended rehabilitation dosage of 3-hours per day.My Therapy programs most frequently included impairment-based exercises that were completed in sitting, and did not increase time spent standing and walking.Consideration should be given to prescribing My Therapy (content and dosage) at an optimal level to promote patient functional independence, while maintaining safety.

Effectiveness of a nonweight-based daily dosage of ready-to-use therapeutic food in children suffering from uncomplicated severe acute malnutrition: A nonrandomized, noninferiority analysis of programme data in Afghanistan.

Severe acute malnutrition (SAM) remains a major global public health problem. SAM cases are treated using ready-to-use therapeutic food (RUTF) at a dosage of ∼200 kcal/kg/day per the standard treatment protocol (STD). Emerging evidence on simplifications to the standard protocol, which among other adaptations, includes reducing the daily RUTF dosage, indicates that it is effective and safe for treating children with SAM. In response to a foreseen stock shortage of RUTF, the government of Afghanistan endorsed the temporary use of a modified treatment protocol in which the daily RUTF dosage was prescribed at 1000 kcal/day (irrespective of body weight) until the child achieved moderate acute malnutrition status (weight-for-height z-score ≥ -3 or mid-upper arm circumference [MUAC] ≥ 115 mm), at which point 500 kcal/day was prescribed until cured (modified treatment protocol [MTP]). In this paper, we report the results of this nonweight-based daily RUTF dosage experience. Data of 2042 children with SAM, treated using either the STD protocol (n = 269) or the MTP protocol (n = 1773) from August 2019 to March 2021 in five provinces, were analyzed. The per-protocol analyses confirmed noninferiority of MTP protocol when compared to STD protocol for recovery rate [93.3% vs. 90.2%; ∆ (95% confidence interval, CI) = 3.1 (-0.9; 7.2) %] and length-of-stay [82.6 vs. 75.6 days; ∆ (95% CI) = 6.9 (3.3; 10.5) days], considering the margin of noninferiority of -10% and +14 days, respectively. Weight gain velocity was smaller in the MTP protocol group than in the STD protocol group [3.7 (1.7) vs. 5.2 (2.9) g/kg/day; ∆ (95% CI) = -1.5 (-1.8, -1.2); p < 0.001]. The STD group had a significantly higher mean than the MTP group for absolute MUAC gain [∆ (95% CI) = 1.7 (1.0; 2.3) mm; p < 0.001] and the MUAC velocity [∆ (95% CI) = 0.29 (0.20; 0.37) mm/week; p < 0.001]. Our results confirm the noninferiority of a nonweight-based daily dosage and support the endorsement of this modification as an alternative to the standard protocol in resource-constrained contexts.

Tabletized Nanomedicine: From the Current Scenario to Developing Future Medicine.

The limitations of conventional therapeutic treatments prevailed in the development of nanotechnology-based medical formulations, termed nanomedicine. Nanomedicine is an advanced medicine that often consists of therapeutic agent(s) embedded in biodegradable or biocompatible nanomaterial-based formulations. Among nanomedicine approaches, tablet (oral) nanomedicine is still under development. In tabletized nanomedicine, the dynamic interplay between nanoformulations and the intricate milieu of the gastrointestinal tract simulates a pivotal role, particularly accentuating the influence exerted upon the luminal, mucosal, and epithelial cells. In this work, we document the perspectives and opportunities of nanoformulations toward the development of tabletized nanomedicine. This review also unveils the notion of integrating nanomedicine within a tablet formulation, which facilitates the controlled release of drugs, biomolecules, and agent(s) from the formulation to achieve a better therapeutic response. Finally, an attempt was made to explore current trends in nanomedicine technology such as bacteriophage, probiotic, and oligonucleotide tabletized nanomedicine and the combination of nanomedicine with imaging agents, i.e., nanotheranostics.

Is more always better? Effectiveness of constraint-induced movement therapy in children with high-risk or unilateral cerebral palsy (0-6 years): Systematic review and meta-analysis.

BACKGROUND: While constraint-induced movement therapy is strongly recommended as an intervention for infants with unilateral cerebral palsy, the optimal dosage remains undefined. This systematic review aims to identify the most effective level of intensity of constraint-induced movement therapy to enhance manual function in infants at high risk of asymmetric brain lesions or unilateral cerebral palsy diagnosis. METHODS: This systematic review with meta-analysis encompassed a comprehensive search across four electronic databases to identify articles that met the following criteria: randomised controlled trials, children aged 0-6 with at high risk or with unilateral cerebral palsy, and treatment involving constraint-induced movement therapy for upper limb function. Studies with similar outcomes were pooled by calculating the standardised mean difference score for each subgroup, and subgroups were stratified every 30 h of total intervention dosage (30-60, 61-90, >90 h). Risk of bias was assessed with Cochrane Collaboration's tool. RESULTS: Seventeen studies were included. Meta-analyses revealed significant differences among subgroups. The 30-60 h subgroup showed a weak effect for spontaneous use of the affected upper limb during bimanual performance, grasp function, and parents' perception of how often children use their affected upper limb. Additionally, this subgroup demonstrated a moderate effect for the parents' perception of how effectively children use their affected upper limb. CONCLUSIONS: Using a dosage ranging from 30 to 60 h when applying a constraint-induced movement therapy protocol holds promise as the most age-appropriate and cost-effectiveness approach for improving upper limb functional outcomes and parent's perception.

The application value of a vendor-specific deep learning image reconstruction algorithm in "triple low" head and neck computed tomography angiography.

Background: Head and neck computed tomography angiography (CTA) technology has become the noninvasive imaging method of choice for the diagnosis and long-term follow-up of vascular lesions of the head and neck. However, issues of radiation safety and contrast nephropathy associated with CTA examinations remain concerns. In recent years, deep learning image reconstruction (DLIR) algorithms have been increasingly used in clinical studies, demonstrating their potential for dose optimization. This study aimed to investigate the value of using a DLIR algorithm to reduce radiation and contrast doses in head and neck CTA. Methods: A total of 100 patients were prospectively enrolled and randomly divided into two groups. Group A (50 patients) consisted of those who underwent 70-kVp CTA with a low contrast volume and injection rate and who were classified according to the reconstruction algorithm into subgroups A1 [DLIR at high weighting (DLIR-H)], A2 [DLIR at low weighting (DLIR-L)], and A3 [volume-based adaptive statistical iterative reconstruction with 50% weighting (ASIR-V50%)]. Meanwhile, group B (50 patients) consisted of those who underwent standard radiation and contrast doses at 100 kVp with ASIR-V50% reconstruction. The computed tomography (CT) attenuation, background noise, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and subjective image quality score (SIQS) were statistically compared for several vessels among the four groups. Results: Group A showed significant reductions in contrast dosage, injection rate, and radiation dose of 36.09%, 20.88%, and 47.80%, respectively, compared to group B (all P<0.001). The four groups differed significantly in terms of background noise (all P<0.05) with group A1 having the lowest value. Group A1 also had significantly higher SNR and CNR values compared to group B in all vessels (all P<0.05) except the M1 of the middle cerebral artery for the SNR. Group A1 also had the highest SIQS, followed by the A2, B, and A3 groups. The SIQS showed good agreement between the two reviewers in all groups, with κ values between 0.88 and 1. Conclusions: Compared to the standard-dose protocol using 100 kVp and ASIR-V50%, a protocol of 70 kVp combined with DLIR-H significantly reduces the radiation dose, contrast dose, and injection rate in head and neck CTA while still significantly improving image quality for patients with a standard body size.

Spanish consensus on the management of concomitant antiseizure medications when using cenobamate in adults with drug-resistant focal seizures.

OBJECTIVE: Cenobamate is an antiseizure medication (ASM) associated with high rates of seizure freedom and acceptable tolerability in patients with focal seizures. To achieve the optimal cenobamate dose for maximal potential effectiveness while avoiding or minimizing drug-related adverse events (AEs), the administration of cenobamate with other ASMs must be managed through concomitant ASM load reduction. A panel of Spanish epilepsy experts aimed to provide a Spanish consensus on how to adjust the dose of concomitant ASMs in patients with drug-resistant epilepsy (DRE) in order to improve the effectiveness and tolerability of adjunctive cenobamate. METHODS: A three-stage modified Delphi consensus process was undertaken, including six Spanish epileptologists with extensive experience using cenobamate. Based on current literature and their own expert opinion, the expert panel reached a consensus on when and how to adjust the dosage of concomitant ASMs during cenobamate titration. RESULTS: The expert panel agreed that tailored titration and close follow-up are required to achieve the best efficacy and tolerability when initiating cenobamate in patients receiving concomitant ASMs. When concomitant clobazam, phenytoin, phenobarbital, and sodium channel blockers are taken at high dosages, or when the patient is receiving two or more sodium channel blockers, dosages should be proactively lowered during the cenobamate titration period. Other concomitant ASMs should be reduced only if the patient reports a moderate/severe AE at any stage of the titration period. SIGNIFICANCE: Cenobamate is an effective ASM with a dose-dependent effect. To maximize effectiveness while maintaining the best tolerability profile, co-medication management is needed. The recommendations included herein provide practical guidance for proactive and reactive management of co-medication in cenobamate-treated patients with DRE and a high drug load. PLAIN LANGUAGE SUMMARY: Patients with epilepsy may continue to have seizures even after treatment with several different antiseizure medications (ASMs). Cenobamate is an ASM that can reduce seizures in these patients. In this study, six Spanish experts in epilepsy discussed the best way to use cenobamate in drug-resistant epilepsy. They provide practical guidance on when and how the dose of other ASMs might be adjusted to reduce side effects and optimize the use of cenobamate.

Exploring gonadotropin dosing effects on MII oocyte retrieval in ovarian stimulation.

PURPOSE: Ovarian stimulation with gonadotropins is crucial for obtaining mature oocytes for in vitro fertilization (IVF). Determining the optimal gonadotropin dosage is essential for maximizing its effectiveness. Our study aimed to develop a machine learning (ML) model to predict oocyte counts in IVF patients and retrospectively analyze whether higher gonadotropin doses improve ovarian stimulation outcomes. METHODS: We analyzed the data from 9598 ovarian stimulations. An ML model was employed to predict the number of mature metaphase II (MII) oocytes based on clinical parameters. These predictions were compared with the actual counts of retrieved MII oocytes at different gonadotropin dosages. RESULTS: The ML model provided precise predictions of MII counts, with the AMH and AFC being the most important, and the previous stimulation outcome and age, the less important features for the prediction. Our findings revealed that increasing gonadotropin dosage did not result in a higher number of retrieved MII oocytes. Specifically, for patients predicted to produce 4-8 MII oocytes, a decline in oocyte count was observed as gonadotropin dosage increased. Patients with low (1-3) and high (9-12) MII predictions achieved the best results when administered a daily dose of 225 IU; lower and higher doses proved to be less effective. CONCLUSIONS: Our study suggests that high gonadotropin doses do not enhance MII oocyte retrieval. Our ML model can offer clinicians a novel tool for the precise prediction of MII to guide gonadotropin dosing.