Development of a Generic Physiologically Based Kinetic Model for the Prediction of Internal Exposure to Organophosphate Pesticides.

Since their introduction into agriculture, the toxicity of organophosphate (OP) pesticides has been widely studied in animal models. However, next generation risk assessment (NGRA) intends to maximize the use of novel approach methodologies based on in vitro and in silico methods. Therefore, this study describes the development and evaluation of a generic physiologically based kinetic (PBK) model for acute exposure to OP pesticides in rats and humans using quantitative structure property relationships and data from published in vitro studies. The models were evaluated using in vivo studies from the literature for chlorpyrifos, diazinon, fenitrothion, methyl-parathion, ethyl-parathion, dimethoate, chlorfenvinphos, and profenofos. Evaluation was performed by comparing simulated and in vivo observed time profiles for blood, plasma, or urinary concentrations and other toxicokinetic parameters. Of simulated concentration-time profiles, 87 and 91% were within a 5-fold difference from observed toxicokinetic data from rat and human studies, respectively. Only for dimethyl-organophosphates further refinement of the model is required. It is concluded that the developed generic PBK model provides a new tool to assess species differences in rat and human kinetics of OP pesticides. This approach provides a means to perform NGRA for these compounds and could also be adopted for other classes of compounds.

Standard protocols for plant health scientific assessments.

In accordance with the EFSA Strategy 2027 outlining the need for fit-for-purpose protocols for EFSA generic scientific assessments, the EFSA Panel on Plant Health (PLH Panel) developed standard protocols to harmonise the problem formulation process and outputs for mandates addressing recurrent scientific questions. Three types of recurring EFSA plant health mandates require generic scientific assessments: (i) pest categorisation; (ii) commodity risk assessment for the purpose of derogation to provisions of the EU plant health law and (iii) quantitative pest risk assessment. The three standard protocols are tailored to the appropriate level of detail and build on the existing guidance documents laying out the methods for conducting risk assessment in the plant health domain. To develop a standard protocol for pest categorisation, the PLH Panel adapted the latest version of the standard template reporting the evidence needs and the assessment questions to conclude whether a pest fulfils the criteria for being considered a potential quarantine pest for the EU. To develop a standard protocol for commodity risk assessment, the PLH Panel adapted the procedure and standard templates used for commodity risk assessment of high risk plants. To develop a standard protocol for quantitative pest risk assessments (qPRA), the Panel reviewed the existing guidance document on qPRA and the qPRAs published by the PLH Panel. The hierarchy of assessment questions and sub-questions used were identified and extracted. Based on this, a hierarchically organised IT-tool was formulated as protocol for the planning and documentation of future qPRAs.

Generic and Hearing-Specific Quality of Life in Older Adult Cochlear Implant Users.

Background This study aimed to evaluate the quality of life (QOL) of older adults using cochlear implants (CIs) by focusing on how individual characteristics and speech perception are related to generic QOL ratings and utilizing the Health Utilities Index Mark III (HUI3) for assessment. Methodology A cross-sectional study was conducted with 19 participants aged ≥60 years, who were within one to five years post-implant activation. Data were obtained through self-administered questionnaires, including the HUI3 for generic QOL assessment and disease-specific indexes. Speech perception tests and chart reviews provided personal characteristic data. Statistical analysis was performed using the Mann-Whitney U-test, one-way analysis of variance, and Pearson's correlation coefficient. Results In total, 18 patients responded to the study. This study revealed that the generic QOL in older adult CI users was lower than that in the general older adult population. There was no significant association between QOL and variables such as sex, duration of implant usage, or age. However, a longer duration of hearing loss before receiving an implant was associated with higher generic QOL scores. Additionally, a strong correlation was observed between the hearing-related QOL score and utility scores. Conclusions Longer pre-implantation hearing loss correlated with better post-implantation QOL. Additionally, a reduced QOL, specifically within the hearing attribute, a subdomain of the HUI3, was associated with a lower overall generic QOL. The results suggest that generic QOL cannot be evaluated based on hearing ability alone and that cochlear implantation does not completely improve generic QOL. This study represents an important first step in understanding the QOL of older adult CI users from a variety of backgrounds.

Use and Cost Patterns of Antihypertensive Medications in the United States From 1996 to 2021.

BACKGROUND: Antihypertensive medication use patterns have likely been influenced by changing costs and accessibility over the past 3 decades. This study examines the relationships between patent exclusivity loss, medication costs, and national health policies on antihypertensive medication use. METHODS: Using 1996 to 2021 Medical Expenditure Panel Survey data of US adults with hypertension taking at least 1 antihypertensive medication, we conducted a cross-sectional analysis. We explored the associations between patent exclusivity loss, per-pill costs, and Medicare Part D enactment on medication use over time, focusing on the most commonly used medications (lisinopril, amlodipine, losartan, hydrochlorothiazide, and metoprolol). RESULTS: The unweighted sample comprised 50 095 US adults (mean age, 62 years; 53% female). The survey-weighted number of adults taking antihypertensive medications increased from 22 million (95% CIs, 20-23 million) to 55 million (95% CI, 51-60 million) between 1996 and 2021. Loss of patent exclusivity led to increased medication fills, notably for lisinopril, amlodipine, and losartan, which all exhibited within-class dominance. However, per-pill cost decreases coinciding with Medicare Part D did not increase the number of individuals treated or the use of specific antihypertensive medications or classes. CONCLUSIONS: The increase in antihypertensive medication use over the past decades highlights the significant impact of loss of patent exclusivity on the uptake in the use of specific medications. These findings underscore the complexity of factors influencing medication use, beyond cost reductions alone, and suggest that policies need to consider multiple facets to effectively improve antihypertensive medication accessibility and utilization.

Pricing dynamics of anti-seizure medications in the U.S.

BACKGROUND: The median cost of anti-seizure medications (ASM) in the United States (U.S.) nearly doubled per person between 2006 and 2021. This increase, combined with shifts in ASM usage and the impact of the COVID-19 pandemic on drug supply chains amid rising inflation, underscored the urgent need to scrutinize ASM pricing dynamics. This study aimed to analyze the complex dynamics of ASM pricing in the U.S. over the past decade (2013-2023); this included how the entry of generic ASMs influenced the pricing of brand-name counterparts and what impacted price variations across different ASM formulations (e.g., significant inflation, the COVID-19 pandemic). METHODS: This study utilized National Average Drug Acquisition Cost (NADAC) data from November 2013 to July 2023. We adjusted ASM prices for inflation using the Consumer Price Index for Medicinal Drugs - Seasonally Adjusted (CPI-MDS). Statistical analyses included fixed effects regressions and multivariable regression analysis to evaluate the impact of inflation, the number of medication labelers, and the COVID-19 pandemic on ASM prices. RESULTS: Our study analyzed 23 ASMs approved by the U.S. Food and Drug Administration (FDA), which encompassed 223 oral formulations:112 brand-name and 111 generics. From 2013-2016 to 2020-2023, accounting for standard deviations (SD), the average price of brand-name ASMs increased from $8.71 (SD 5.9) to $15.43 (SD 10.7), while generic ASMs saw a slight decrease from $1.39 (SD 1.8) to $1.26 (SD 1.6). Consequently, the price gap between brand-name and generic ASMs surged from 1452.39 % to 3399.26 %. The proportion of matched brand-name and generic ASMs with a price difference of 1000 %-9999 % increased from 32.88 % (2013-2016) to 41.43 % (2020-2023), while those exceeding 10,000 % rose from 16.44 % to 20 % in the same period. Generic immediate-release (IR) formulations were significantly less expensive than extended-release (ER) or delayed-release (DR) counterparts, with cost differences reaching up to 7751.20 %. The number of medication labelers was inversely related to generic ASM prices, which decreased by 5.45 % (p = 0.001) with each additional generic labeler, while brand-name ASM prices increased by 2.46 % (p < 0.001) with each additional generic labeler. The COVID-19 pandemic led to a 24.4 % increase in brand-name ASM prices and a 23.1 % decrease in generic ASM prices. CONCLUSIONS: The findings reveal an expanding price disparity between brand-name and generic oral ASMs. An inverse relationship was observed between the number of medication labelers and generic ASM prices, with additional labelers driving down generic prices. However, introducing more generic labelers led to a significant increase in brand-name ASM prices. Furthermore, following patent expirations, brand-name ASM prices rose-a trend explained by the "generics paradox," where, contrary to expectations, brand prices do not decrease and may even increase when generics enter the market. These findings underscore the need for targeted interventions in drug pricing policies to manage the rising costs associated with epilepsy treatment. To ensure equitable access to ASMs, stakeholders must understand and address the factors driving these pricing dynamics.

Pharmacoeconomic implications of preference toward reference- versus generic-brand antidepressants in primary care.

BACKGROUND: The prevalence of depression is gradually increasing worldwide with an increasing utilization of antidepressants. Nevertheless, despite their lower costs, generic-brand antidepressants were reported to be less prescribed. We aimed to examine the costs of reference- versus generic-brand antidepressant prescriptions in primary care practice. METHODS: This cross-sectional study included electronic prescriptions for adult patients that contained antidepressants (World Health Organization's Anatomical Therapeutic Chemical (ATC) code: N06A), which were generated by a systematically selected sample of primary care doctors (n = 1431) in Istanbul in 2016. We examined the drug groups preferred, the reference- versus generic-brand status, and pharmacotherapy costs. FINDINGS: The majority of the prescriptions were prescribed for women (71.8%), and the average age of the patients was 53.6 ± 16.2 years. In prescriptions with a depression-related indication (n = 40 497), the mean number and cost of drugs were 1.5 ± 1.0 and 22.7 ± 26.4 United States Dollar ($) per prescription, respectively. In these prescriptions, the mean number and cost of antidepressants per encounter were 1.1 ± 0.2 and $17.0 ± 13.2, respectively. Reference-brand antidepressants were preferred in 58.2% of depression-related prescriptions, where the mean cost per prescription was $18.3 ± 12.4. The mean cost per prescription of the generics, which constituted 41.8% of the antidepressants in prescriptions, was $15.1 ± 11.4. We found that if the generic version with the lowest cost was prescribed instead of the reference-brand, the mean cost per prescription would be $12.9 ± 11.2. CONCLUSIONS: Our study highlighted the substantial pharmacoeconomic impact of generic-brand antidepressant prescribing, whose preference over reference-brands could reduce the cost of antidepressant medication treatment by 17.5% in primary care, which could be approximately doubled if the cheapest generic antidepressant had been prescribed.

Confirmatory analysis of the 13-MD and ranking of its meta-dimensions and items.

Background: The 13-MD is a new generic instrument developed to measure general health-related quality of life (GHRQoL). This instrument considers all aspects of health (i.e., physical, mental, and social) in a balanced way. A previous study led to minor changes in the original version of the 13-MD. The objective of this study was to confirm the validity of the modified 13-MD. Methods: Validity was assessed with recent data from the general population of Quebec, Canada. The meta-dimensions and items composing the 13-MD were also subjected to a ranking procedure, which allowed to determine the most important aspects for respondents. Results: A total of 1337 French-speaking participants were recruited with 1099 completing the 13-MD for validation purposes and 1084 completing the ranking procedure. The 13-MD showed very satisfactory results and confirmed to be a valid instrument. The ranking of the meta-dimensions revealed that "Well-being" received the most points, followed by "Sleep and energy" and "Body functioning." Conclusion: These results will be very useful in the continuous improvement of the 13-MD, ultimately leading to the valuation stage (i.e., development of a value set).

Correlation between prescription volumes of generic antiepileptic drugs and the number of clinical epileptologists across prefectural regions in Japan: A descriptive study using a national claims database.

PURPOSE: Although generic drugs are essential in reducing medical costs, their use in epilepsy therapy remains a subject of ongoing debate. In this study, we analysed prescription trends of generic drugs using data from the National Database of Health Insurance Claims and Specific Health Checkups (NDB) Open Data Japan. METHODS: The number of generic drug prescriptions from 2017-2021 was extracted from the NDB Open Data Japan, with data for each medication stratified by prefectural region, sex, and age, allowing for the analysis of the impact of each factor. We analysed the correlation between the prescription volumes of generic antiseizure medications (ASMs) and the number of clinical epileptologists registered with the Japan Epilepsy Society per 100,000 population. RESULTS: In 2021, the prescription volume of generic ASMs was 49 %, whereas that for other pharmacological agents was between 70-80 %. Notably, for children < 15 years of age, generics made up approximately 20 % of prescriptions, which was significantly less than that in other age groups. Analysis by prefecture revealed a negative correlation between prescription volumes of ASMs and the number of clinical epileptologists across prefectural regions in Japan (R = -0.47, p < 0.01). CONCLUSION: Our findings indicate that the higher the proportion of clinical epileptologists in each prefecture, the lower the number of prescribed generic ASMs. Clinical epileptologists in Japan therefore prescribe antiseizure agents in accordance with the Japanese epilepsy treatment guidelines that do not recommend the use of generic agents.

Phylogenetic and Comparative Analysis of Cryptochironomus, Demicryptochironomus and Harnischia Inferred from Mitogenomes (Diptera: Chironomidae).

(1) Background: Mitochondrial genomes have been extensively employed as a crucial marker in numerous dipteran families for understanding phylogenetics and systematics relations, thereby playing a pivotal role in molecular biology studies. The phylogenetic relationship of the Harnischia generic complex remains contentious due to the paucity of taxonomic and molecular data. Specifically, the evolutionary relationships among Cryptochironomus, Demicryptochironomus, and Harnischia are still unclear. (2) Methods: In this study, Polypedilum and Endochironomus were used as outgroups to analyze phylogenetic relationships among Cryptochironomus, Demicryptochironomus, and Harnischia, mitogenomes of four Cryptochironomus, two Demicryptochironomus, two Harnischia, and two Cladopelma were newly sequenced. Subsequently, we conducted a thorough analysis of the nucleotide composition, sequence length, and evolutionary rate. (3) Results: All mitogenomes exhibited structural conservation, with all genes consistently arranged in the identical order as that of the ancestral mitogenome. Nucleotide composition varied significantly among different genes, and the control region displayed the highest A + T content. All protein-coding genes undergo rigorous purification selection, with the ATP8 gene exhibiting the most rapid evolutionary rate among them. Utilizing Bayesian Inference (BI) and Maximum Likelihood (ML) methods across various databases, we reconstructed the phylogenetic relationships among the genera within the Harnischia generic complex, drawing insights from an analysis of 14 mitochondrial genomes. (4) Conclusions: Our results showed that the monophyly of the genera Harnischia was well supported in all topologies; Cryptochironomus is sister to Demicryptochironomus.

Cost savings from medication reviews in community pharmacies for nursing home residents in Estonia: a case study.

BACKGROUND: The aim of this study is to assess the cost savings from medication reviews conducted for individuals living in nursing homes in Estonia. Medication reviews performed as part of the automated dose dispensing (ADD) service by community pharmacies might help identify suboptimal medicine regimens. METHODS: We use a case study approach to identify suboptimal use of medication in treatment plans and estimate the potential cost saving from medication reviews. To achieve this, we assess 101 treatment plans submitted for medication review by nursing homes in Estonia between 2021 and 2023. Additionally, we run OLS regressions to identify the most important determinants of medication cost savings. RESULTS: We estimate an average direct cost saving of €43.62 per patient per year, which corresponds to 8.27% of the average annual medication costs. If medication reviews were conducted for all elderly individuals over 75 years old who use six or more prescription medicines, nearly 2% of Estonia's pharmaceutical budget could be saved. Regression analysis indicates that the most significant contributors to these cost savings are suboptimal use of generics, incorrect dosages (too high), and the elimination of incorrect medications. CONCLUSIONS: Our study suggests that annual medication reviews conducted as part of the ADD service might help reduce medication expenditure when offered to a wider public.

Strategic behavior and entry deterrence by branded drug firms: the case of authorized generic drugs.

Pharmaceutical firms that market brand-name drugs lose substantial market share to generic manufacturers after patent expiration. As a response to the threat of generic competition, branded manufacturers pursue defensive strategies. One such strategy is the launch of authorized generic drugs. Authorized generic drugs are produced by branded manufacturers to compete against other generic drug entrants. Such competition may lower the expected profits of generic drug manufacturers and hence deter future generic drug entry. This paper models and empirically examines whether the introduction of authorized generic drugs changes the independent generic firms' decisions on entering the market. We use an instrumental variable approach to evaluate the effect of authorized generic drugs on the responses of generic manufacturers. The results show that the entry of authorized generic drugs deters and delays the entry of generic drugs.

Development of a health state classification system for the PedsQL™ 4.0 Generic Core Scales for preference-based valuation in Australia.

OBJECTIVES: Pediatric Quality of Life InventoryTM Version 4.0 Generic Core Scales (PedsQL GCS), comprising 23 items covering four sub-scales (physical, emotional, social, and school functioning), is a widely applied generic measure of childhood health-related quality of life, but does not provide health utilities for cost-effectiveness-based decision-making. This study aimed to develop a reduced item version of PedsQL GCS amenable to health utility derivation in Australia. METHODS: Data sources were two cohorts of the Longitudinal Study of Australian Children, including proxy responses for all PedsQL GCS versions (Toddlers, Young Children, Children, Teens), and the CheckPoint sample containing child self-report to the Children version. Three analytic samples were: CheckPoint sample (n=1,874); Mallinson sample containing one measurement per child from one of the Young Children, Children or Teens versions (n=7,855); and Toddlers sample (n=7,401). Exploratory and confirmatory factor analyses assessed dimensionality. Psychometric analyses used Rasch and classical criteria on three randomly selected subsamples (n=500) per sample. Item selection prioritised psychometric performance in CheckPoint sample, also considering performance in other samples and conceptual content. RESULTS: Dimensionality assessments did not generate an alternative empirical structure for the measure, and psychometric analyses were conducted on the original four sub-scales. The selected items were: 'Get aches and pains' for physical functioning; 'Feel sad/blue' for emotional functioning; 'Other kids not friends' for social functioning; and 'Keeping up with school work' for school functioning. CONCLUSIONS: The final four-item set, pending further psychometric validation and valuation, can generate health utilities from the widely used PedsQL GCS to inform cost-effectiveness-based decision-making.

Generic competition and prices for azelastine-fluticasone nasal spray.

KEY POINTS: The original manufacturer of azelastine‒fluticasone (AZ‒FL) prevented generic availability until 2020 via patent enforcement. Following generic availability of AZ‒FL, Medicare utilization increased and spending decreased. Retail prices for generic AZ‒FL remain high due to markup by manufacturers and pharmacies.

Generic phosphate affinity constants of the CD-MUSIC-eSGC model to predict phosphate adsorption and dominant speciation on iron (hydr)oxides.

Estimating the availability of phosphorus in soils and sediments is complicated by the diverse mineralogical properties of iron (hydr)oxides that control the environmental fate of phosphorus. Despite various surface complexation models have been developed, lack of generic phosphate affinity constants (logKPO4s) for iron (hydr)oxides hinders the prediction of phosphate adsorption to iron (hydr)oxides in nature. The aim of this work is to derive generic logKPO4s for the Charge Distribution-Multisite Complexation extended-Stern-Gouy-Chapman (CD-MUSIC-eSGC) model using a large phosphate adsorption database and previously derived generic protonation parameters. The optimized logKPO4s of goethite, hematite and ferrihydrite are located in a much narrower range than those in the RES3T database. Specifically, the logKPO4 ranges of FeOPO3, FeOPO2OH, FeOPO(OH)2, (FeO)2PO2, and (FeO)2POOH complexes were 17.40-18.00, 24.20-27.40, 27.90-29.80, 26.50-29.60, and 30.70-33.40, respectively. A simplified CD-MUSIC-eSGC model with species FeOPO2OH and (FeO)2PO2 and generic logKPO4 values 26.0 ± 0.9 and 27.9 ± 0.8, respectively, provides an accurate prediction of phosphate adsorption and dominant speciation to the iron (hydr)oxides at environmental pH and phosphate levels. For ferrihydrite at low pH and high phosphate levels the species FeOPO(OH)2 and (FeO)2POOH cannot be neglected. The simplified model expands the application boundaries of CD-MUSIC-eSGC model in predicting the phosphate adsorption on natural iron (hydr)oxides without laborious characterization.

Bioequivalence and Safety of Generic Glecaprevir/Pibrentasvir Compared to a Branded Product: A Randomized, Crossover Study in Healthy Volunteers.

This was an open-label, randomized, single-dose, 2-period, crossover clinical trial with an adaptive design to evaluate the bioequivalence and comparative pharmacokinetics of generic glecaprevir/pibrentasvir versus the brand name product in healthy White male and female volunteers under fed conditions. Safety profiles were also assessed. A total of 56 healthy adult volunteers were enrolled and randomly assigned in a 1:1 ratio to receive a single dose of either the generic or reference formulation. After a 7-day washout period, subjects received the alternate product. Blood samples were collected at pre-specified time points up to 48 hours post-dosing. Plasma concentrations of glecaprevir and pibrentasvir were determined using a validated high-performance liquid chromatography-tandem mass spectrometry method. The geometric mean ratios of the test to the reference formulation for maximum plasma concentration (Cmax) and area under the concentration-time curve from drug administration to the last measurable concentration (AUC0-t) fell within the predefined bioequivalence range of 80%-125%. Both formulations demonstrated comparable pharmacokinetic profiles for glecaprevir and pibrentasvir, and can be considered bioequivalent. No adverse events were reported, and both formulations were well tolerated by all participants.

A generic error-related potential classifier based on simulated subjects.

Error-related potentials (ErrPs) are brain signals known to be generated as a reaction to erroneous events. Several works have shown that not only self-made errors but also mistakes generated by external agents can elicit such event-related potentials. The possibility of reliably measuring ErrPs through non-invasive techniques has increased the interest in the brain-computer interface (BCI) community in using such signals to improve performance, for example, by performing error correction. Extensive calibration sessions are typically necessary to gather sufficient trials for training subject-specific ErrP classifiers. This procedure is not only time-consuming but also boresome for participants. In this paper, we explore the effectiveness of ErrPs in closed-loop systems, emphasizing their dependency on precise single-trial classification. To guarantee the presence of an ErrPs signal in the data we employ and to ensure that the parameters defining ErrPs are systematically varied, we utilize the open-source toolbox SEREEGA for data simulation. We generated training instances and evaluated the performance of the generic classifier on both simulated and real-world datasets, proposing a promising alternative to conventional calibration techniques. Results show that a generic support vector machine classifier reaches balanced accuracies of 72.9%, 62.7%, 71.0%, and 70.8% on each validation dataset. While performing similarly to a leave-one-subject-out approach for error class detection, the proposed classifier shows promising generalization across different datasets and subjects without further adaptation. Moreover, by utilizing SEREEGA, we can systematically adjust parameters to accommodate the variability in the ErrP, facilitating the systematic validation of closed-loop setups. Furthermore, our objective is to develop a universal ErrP classifier that captures the signal's variability, enabling it to determine the presence or absence of an ErrP in real EEG data.

Understanding the acceptance of online tourism programs: Perspectives of generic learning outcomes and theory of planned behavior.

The integration of information technology, particularly the Internet, with the tourism industry has laid a solid foundation for the widespread popularity of online tourism. Online tourism offers numerous advantages such as being unconstrained by time, space, and region, having low costs, and providing strong interactive features, making it increasingly popular worldwide. Nevertheless, not all individuals are willing to adopt online tourism, and the factors and mechanisms that influence online tourism require further investigation. This study aims to examine the factors that influence the intention to adopt online tourism by integrating the Technology Acceptance Model (TAM), the Theory of Planned Behavior (TPB), and the Generic Learning Outcomes (GLOs). Using the Yunyou Dunhuang Online Program (), the current study invited tourists to participate in the online tourism experience, and collected 536 pieces of data. The results of structural equation modeling reveal that: (1) attitude toward using and perceived usefulness positively predict behavioral intention to use; (2) perceived ease of use, perceived usefulness, and subjective norm significantly and positively predict attitude toward using; (3) perceived ease of use significantly and positively predicted perceived usefulness, while knowledge and understanding, activity, behavior, and progression had no significant effect on perceived usefulness; (4) knowledge and understanding positively predicted perceived ease of use, while activity, behavior, and progression had no significant effect on perceived ease of use. This study explores the factors influencing online tourism adoption intention in a comprehensive way. The findings hold practical significance for the design of online tourism programs for intangible cultural heritage, providing theoretical guidance for cultural heritage and development.

Relative contribution of comorbid diseases to health-related quality of life in patients with Parkinson's disease.

BACKGROUND: Multimorbidity is common in elderly people, and one of the major consequences of multimorbidity is low health-related quality of life (HRQoL). The aim of this study was to investigate the frequency of comorbid diseases in patients with Parkinson's disease (PD) and to analyze their relative importance in HRQoL. The aim was also to examine agreement between the generic 15D questionnaire and the PD-specific Parkinson's Disease Questionnaire (PDQ-8) to further validate 15D in the evaluation of HRQoL in patients with PD. METHODS: Patients with PD (N = 551) filled a questionnaire on comorbid diseases, and the 15D questionnaire yielding a 15-dimensional health profile and a score representing the overall HRQoL. Self-organizing map was used for an unsupervised pattern recognition of the health profiles. Relative importance analysis was used to evaluate the contribution of 16 comorbid diseases to the 15D score. The agreement between 15D and PDQ-8 questionnaires was studied in a subset of 81 patients that were examined clinically. RESULTS: 533 patients (96.7%) reported comorbid diseases. The most affected dimensions in the 15D questionnaire were secretion, usual activities, discomfort and symptoms, and sexual activity. Self-organizing map identified three patterns of health profiles that included patients with high, low or transition HRQoL. The transition subgroup was similar to low HRQoL subgroup in non-motor dimensions. Sixteen comorbid diseases explained 33.7% of the variance in the 15D score. Memory deficit, depression, heart failure, and atrial fibrillation had the highest relative importance. The intraclass correlation coefficient between the generic 15D and the PD-specific PDQ-8 was 0.642 suggesting moderate reliability. CONCLUSIONS: The most marked differences in HRQoL were in the dimensions of secretion, usual activities, and sexual activity. Pattern detection of 15D health dimensions enabled the detection of a subgroup with disproportionately poor HRQoL in non-motor dimensions. The comorbid diseases affecting most to HRQoL were memory deficit and depression. The generic 15D questionnaire can be used in the evaluation of HRQoL in PD patients.

Which factor reduces pharmaceutical expenditure, number of entrants or price variance? Updated generic drug markets in South Korea.

BACKGROUND: Introducing more generics has been a successful strategy for lowering pharmaceutical prices and expenditure. However, the effect of the strategy depends on the pricing schemes for generics. We aimed to update the South Korean generic markets in terms of effective competition, and to examine the effects of number of manufacturers and price variance on pharmaceutical expenditure. METHODS: We constructed balanced panel data provided by the Health Insurance Review and Assessment Service covering 726 reimbursed substances from 2019 to 2023. We developed original indicators to analyze the generic markets: the maximum-minimum price variance (MMPV) and the maximum-weighted price variance (MWPV). Panel regression with fixed and time-fixed effects was used. RESULTS: Over the study period, the number of manufacturers increased from 17.81 in 2019 to 20.98 in 2020 and then decreased to 18.70 in 2023. The MMPV increased from 204.70 in 2019 to 230.07 in 2022 and then decreased slightly to 225.34 in 2023. The MWPV increased from 59.70 in 2019 to 72.58 in 2023. Two types of segmented markets were noteworthy: low use of low-cost generics with sufficient manufacturers and high use of low-cost generics with insufficient manufacturers. In the fixed and time-fixed effects panel analyses, the MWPV presented a negative association with the number of manufacturers and a positive association with the MMPV. CONCLUSIONS: A newly introduced tiered pricing scheme, designed to differentiate generic prices, was associated with a decrease in the number of manufacturers and an increase in price dispersion. The pricing schemes for generics should be designed with price variance in mind and limit the number of too many generics in South Korea.

Comparable efficacy and safety of generic and branded imatinib for patients with chronic myeloid leukemia in China.

Background: Generics imatinib became an alternative treatment option for chronic myeloid leukemia (CML) patients in China. However, clinicians and patients alike harbor concerns regarding the long-term safety of generic imatinib. Objectives: Patients with chronic phase CML receiving frontline imatinib treatment. Design: A retrospective study was used to evaluate the blood concentration, effectiveness, and safety of generic in 170 CML patients. Methods: Imatinib plasma concentrations were detected by high-performance liquid chromatography-tandem mass spectrometry. Results: Among the 170 patients, 73 (42.9%) patients treated with branded imatinib as first-line therapy, while 22 (12.9%) switched to generic imatinib during treatment due to economic considerations. No significant differences in trough concentrations between branded and generic imatinib (1549.9 ± 648.8 ng/mL vs 1479.0 ± 507.0 ng/mL; p = 0.95). During the 2-year follow-up, there were no significant differences in molecular response rates (major molecular response (MMR): 33.3% vs 37.0%; deep molecular response: 56.9% vs 42.9%, p = 0.17) between the branded and generic imatinib. Both groups showed similar rates of switching to second-generation tyrosine kinase inhibitor (11.8% vs 15.1%, p = 0.56). Furthermore, there were no significant differences in event-free survival or failure-free survival between branded and generic imatinib. Twenty-two (12.9%) switched to generic imatinib during treatment, 68.2% maintained their level of response, 27.3% improved, and only one patient (4.5%) lost MMR. There were no significant differences in the incidence of various adverse events. Conclusion: Generic imatinib are equally effective and safe compared to branded molecules, both for newly diagnosed patients and those who switch from branded.