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1.
Can J Hosp Pharm ; 77(3): e3560, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39144571

RESUMO

Background: Clostridioides difficile is a pathogen causing diarrheal illness, which can be treated with vancomycin or fidaxomicin. Objective: To evaluate changes in monthly prescription volumes for oral vancomycin and fidaxomicin in Ontario community pharmacies following implementation of the 2017 and 2021 updates to guidelines from the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) and after a 2019 provincial formulary change for vancomycin. Methods: An interrupted time-series analysis was conducted from November 2015 to October 2021 using monthly projected prescription volumes obtained from IQVIA's Compuscript database. Level and slope (trend) changes in prescribing were assessed using segmented linear regression. Results: The volume of vancomycin prescriptions increased by 74 prescriptions per month (95% confidence interval [CI] 16 to 132) following implementation of the 2017 guideline update and by 73 prescriptions per month (95% CI 13 to 133) after the 2019 formulary change; however, no statistically significant changes were observed after implementation of the 2021 guideline update. No significant trend changes were observed for fidaxomicin. Conclusion: Guidelines and formulary changes were correlated with increased volume of vancomycin prescriptions.


Contexte: Le Clostridioides difficile est un agent pathogène provoquant une maladie diarrhéique pouvant être traitée avec de la vancomycine ou de la fidaxomicine. Objectif: Évaluer les changements de volume mensuel des prescriptions de vancomycine et de fidaxomicine par voie orale dans les pharmacies communautaires de l'Ontario après la mise en œuvre des lignes directrices actualisées en 2017 et 2021 de l'Infectious Diseases Society of America (IDSA) et de la Society for Healthcare Epidemiology of America (SHEA) et à la suite d'une modification au régime d'assurance-médicaments pour la vancomycine à l'échelle provinciale en 2019. Méthodologie: Une analyse de séries chronologiques interrompues a été réalisée de novembre 2015 à octobre 2021 à l'aide des volumes mensuels de prescriptions projetés qui ont été obtenus grâce à la base de données Compuscript d'IQVIA. Les changements du volume des prescriptions et de son évolution dans le temps (le niveau et la pente, respectivement) ont été évalués à l'aide d'une régression linéaire segmentée. Résultats: Le volume des prescriptions de vancomycine a augmenté de 74 prescriptions par mois (intervalle de confiance [IC] à 95 % 16­132) après la mise en œuvre des lignes directrices actualisées en 2017; il a augmenté de 73 prescriptions par mois (IC à 95 % 13­133) après la modification du régime d'assurance-médicaments de 2019; cependant, aucun changement statistiquement significatif n'a été observé après la mise en œuvre des lignes directrices actualisées en 2021. Aucun changement significatif de tendance n'a été observé pour la fidaxomicine. Conclusion: Les lignes directrices et les modifications du régime d'assurance-médicaments étaient corrélées à une augmentation du volume des prescriptions de vancomycine.

2.
J Pharm Sci ; 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39153662

RESUMO

The often-perceived limitations of image analysis have for many years impeded the widespread application of such systems as first line characterisation tools. Image analysis has, however, undergone a notable resurgence in the pharmaceutical industry fuelled by developments system capabilities and the desire of scientists to characterize the morphological nature of their particles more adequately. The importance of particle shape as well as size is now widely acknowledged. With the increasing use of modelling and simulations, and ongoing developments though the integration of machine learning and artificial intelligence, the utility of image analysis is increasing significantly driven by the richness of the data obtained. Such datasets provide means to circumvent the requirement to rely on less informative descriptors and enable the move towards the use of whole distributions. Combining the improved particle size and shape measurement and description with advances in modelling and simulations is enabling improved means to elucidate the link between particle and bulk powder properties. In addition to improved capabilities to describe input materials, approaches to characterize single components within multicomponent systems are providing scientists means to understand how their material may change during manufacture thus providing a means to link the behaviour of final dosage forms with the particle properties at the point of action. The aim is to provide an overview of image analysis and update readers with innovations and capabilities to other methods in the small molecule arena. We will also describe the use of AI for the improved analysis using image analysis.

3.
Pharm Dev Technol ; 29(5): 395-414, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38618690

RESUMO

The MCS initiative was first introduced in 2013. Since then, two MCS papers have been published: the first proposing a structured approach to consider the impact of drug substance physical properties on manufacturability and the second outlining real world examples of MCS principles. By 2023, both publications had been extensively cited by over 240 publications. This article firstly reviews this citing work and considers how the MCS concepts have been received and are being applied. Secondly, we will extend the MCS framework to continuous manufacture. The review structure follows the flow of drug product development focussing first on optimisation of API properties. The exploitation of links between API particle properties and manufacturability using large datasets seems particularly promising. Subsequently, applications of the MCS for formulation design include a detailed look at the impact of percolation threshold, the role of excipients and how other classification systems can be of assistance. The final review section focusses on manufacturing process development, covering the impact of strain rate sensitivity and modelling applications. The second part of the paper focuses on continuous processing proposing a parallel MCS framework alongside the existing batch manufacturing guidance. Specifically, we propose that continuous direct compression can accommodate a wider range of API properties compared to its batch equivalent.


Assuntos
Excipientes , Tecnologia Farmacêutica , Excipientes/química , Tecnologia Farmacêutica/métodos , Preparações Farmacêuticas/química , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Indústria Farmacêutica/métodos
4.
Toxicol Sci ; 199(1): 89-107, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38310358

RESUMO

The success and sustainability of U.S. EPA efforts to reduce, refine, and replace in vivo animal testing depends on the ability to translate toxicokinetic and toxicodynamic data from in vitro and in silico new approach methods (NAMs) to human-relevant exposures and health outcomes. Organotypic culture models employing primary human cells enable consideration of human health effects and inter-individual variability but present significant challenges for test method standardization, transferability, and validation. Increasing confidence in the information provided by these in vitro NAMs requires setting appropriate performance standards and benchmarks, defined by the context of use, to consider human biology and mechanistic relevance without animal data. The human thyroid microtissue (hTMT) assay utilizes primary human thyrocytes to reproduce structural and functional features of the thyroid gland that enable testing for potential thyroid-disrupting chemicals. As a variable-donor assay platform, conventional principles for assay performance standardization need to be balanced with the ability to predict a range of human responses. The objectives of this study were to (1) define the technical parameters for optimal donor procurement, primary thyrocyte qualification, and performance in the hTMT assay, and (2) set benchmark ranges for reference chemical responses. Thyrocytes derived from a cohort of 32 demographically diverse euthyroid donors were characterized across a battery of endpoints to evaluate morphological and functional variability. Reference chemical responses were profiled to evaluate the range and chemical-specific variability of donor-dependent effects within the cohort. The data-informed minimum acceptance criteria for donor qualification and set benchmark parameters for method transfer proficiency testing and validation of assay performance.


Assuntos
Glândula Tireoide , Humanos , Glândula Tireoide/efeitos dos fármacos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Células Epiteliais da Tireoide/efeitos dos fármacos , Células Epiteliais da Tireoide/metabolismo , Células Cultivadas , Disruptores Endócrinos/toxicidade , Adulto Jovem , Bioensaio/normas , Bioensaio/métodos , Reprodutibilidade dos Testes , Alternativas aos Testes com Animais/normas , Idoso , Benchmarking
5.
AAPS PharmSciTech ; 25(1): 24, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267745

RESUMO

Previous work demonstrated that roller compaction of a 40%w/w theophylline-loaded formulation resulted in granulate consisting of un-compacted fractions which were shown to constitute between 34 and 48%v/v of the granulate dependent on processing conditions. The active pharmaceutical ingredient (API) primary particle size within the un-compacted fraction was also shown to have undergone notable size reduction. The aim of the current work was to test the hypothesis that the observations may be more indicative of the relative compactability of the API due to the formulation being above the percolation threshold. This was done by assessing the impact of varied API loads in the formulation on the non-granulated fraction of the final granulate and the extent of attrition of API particles within the non-granulated fraction. The influence of processing conditions for all formulations was also investigated. The results verify that the observations, both of this study and the previous work, are not a consequence of exceeding the percolation threshold. The volume of un-compacted material within the granulate samples was observed to range between 34.7 and 65.5% depending on the API load and roll pressure, whilst the API attrition was equivalent across all conditions.


Assuntos
Teofilina , Tamanho da Partícula
7.
J Am Med Dir Assoc ; 25(1): 121-129, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37863111

RESUMO

OBJECTIVES: To examine the associations between COVID-19 pandemic waves (1-4) and prevalent antipsychotic, antidepressant, benzodiazepine, anticonvulsant, and opioid use among assisted living (AL) residents, by setting (dementia care vs other). DESIGN: Population-based, repeated cross-sectional study. SETTING AND PARTICIPANTS: Linked clinical and health administrative databases for residents of all publicly subsidized AL homes (N = 256) in Alberta, Canada, examined from January 2018 to December 2021. Setting-specific quarterly cohorts of residents were derived for pandemic (starting March 1, 2020) and comparable historical (2018/2019 combined) periods. METHODS: The quarterly proportion of residents dispensed an antipsychotic, antidepressant, benzodiazepine, anticonvulsant, or opioid was examined for each setting and period. Log-binomial generalized estimating equations models estimated prevalence ratios (PR) for period (pandemic vs historical quarterly periods), setting (dementia care vs other AL), and period-setting interactions. RESULTS: On March 1, 2020, there were 2874 dementia care and 6611 other AL residents (mean age 82.4 vs 79.9 years, 68.2% vs 66.1% female, 93.5% vs 42.6% with dementia, respectively). Antipsychotic use increased during waves 2 to 4 for residents of both settings, but this increase was significantly greater for dementia care than other AL residents during waves 3 and 4 (eg, wave 3, PR 1.21, 95% CI 1.14-1.27 vs PR 1.12, 95% CI 1.07-1.17, interaction term P = .029). In both settings, there was a significant but modest increase in antidepressant use and a significant decrease in benzodiazepine use during several pandemic waves. For other AL residents only, there was a small statistically significant increase in anticonvulsant use during waves 2 to 4. No significant pandemic effect was observed for prevalent opioid use in either setting. CONCLUSIONS AND IMPLICATIONS: The persistence of the pandemic-associated increase in antipsychotic, antidepressant, and anticonvulsant use in AL residents, and greater increase in antipsychotic use for dementia care settings, raises concerns about the attendant risks for residents, especially those with dementia.


Assuntos
Antipsicóticos , COVID-19 , Demência , Humanos , Feminino , Idoso de 80 Anos ou mais , Masculino , Antipsicóticos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Analgésicos Opioides/uso terapêutico , Pandemias , Casas de Saúde , Estudos Transversais , Psicotrópicos/uso terapêutico , Antidepressivos/uso terapêutico , Benzodiazepinas/uso terapêutico , Alberta , Demência/tratamento farmacológico , Demência/epidemiologia
9.
Pharmaceutics ; 15(8)2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37631368

RESUMO

Hypromellose, a widely used polymer in the pharmaceutical industry, is available in several grades, depending on the percentage of substitution of the methoxyl and hydroxypropyl groups and molecular weight, and in various functional forms (e.g., suitable for direct compression tableting). These differences can affect their physicomechanical properties, and so this study aims to characterise the particle size and mechanical properties of HPMC K100M polymer grades from four different vendors. Eight polymers (CR and DC grades) were analysed using scanning electron microscopy (SEM) and light microscopy automated image analysis particle characterisation to examine the powder's particle morphology and particle size distribution. Bulk density, tapped density, and true density of the materials were also analysed. Flow was determined using a shear cell tester. Flat-faced polymer compacts were made at five different compression forces and the mechanical properties of the compacts were evaluated to give an indication of the powder's capacity to form a tablet with desirable strength under specific pressures. The results indicated that the CR grades of the polymers displayed a smaller particle size and better mechanical properties compared to the DC grade HPMC K100M polymers. The DC grades, however, had better flow properties than their CR counterparts. The results also suggested some similarities and differences between some of the polymers from the different vendors despite the similarity in substitution level, reminding the user that care and consideration should be given when substitution is required.

10.
Diabetes Obes Metab ; 25(12): 3490-3500, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37563767

RESUMO

AIMS: To assess post-initiation predictors of discontinuation of sodium-glucose cotransporter-2 (SGLT2) inhibitors compared to dipeptidyl-peptidase-4 (DPP-4) inhibitors in the United Kingdom. MATERIALS AND METHODS: We conducted a comparative population-based retrospective cohort study using primary care data from the UK Clinical Practice Research Datalink (CPRD) with linked data to hospital and death records. We included new metformin users who initiated either SGLT2 inhibitors or DPP-4 inhibitors between January 2013 and October 2019. The main outcome was treatment discontinuation, defined as the first 90-day gap after the estimated treatment end date. We used a series of extended Cox models to assess which time-dependent predictors were associated with treatment discontinuation. To test if the hazard ratio of discontinuation for each predictor was statistically different between SGLT2 and DPP-4 inhibitors, an exposure-predictor interaction term was added to each model. RESULTS: There were 2550 new users of SGLT2 inhibitors and 8195 new users of DPP-4 inhibitors. Approximately 69% of SGLT2 inhibitor and 74% of DPP-4 inhibitor users had discontinued treatment by the end of follow-up. Occurrence of fractures after treatment initiation was a significant predictor of discontinuation of SGLT2 inhibitors (hazard ratio [HR] 4.13, 95% confidence interval [CI] 2.12-8.06) but not DPP-4 inhibitors (HR 0.93, 95% CI 0.79-1.11). The rate of treatment discontinuation was significantly higher for those with low estimated glomerular filtration rate and minimal contact with the healthcare system. Efficacy endpoints, such as heart failure and glycated haemoglobin level, were not associated with treatment discontinuation. CONCLUSIONS: Our findings reflect some discrepancy between the available evidence and prescribing behaviour for SGLT2 inhibitors.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Estudos de Coortes , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Glucose/uso terapêutico , Hipoglicemiantes/uso terapêutico , Estudos Retrospectivos , Sódio , Transportador 2 de Glucose-Sódio , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
11.
Diabetes Care ; 46(8): 1492-1500, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37315211

RESUMO

OBJECTIVE: Evidence of an increased dementia risk with insulin use in type 2 diabetes is weakened by confounding by indication and disease severity. Herein we reassess this association, while accounting for confounding through design and analysis. RESEARCH DESIGN AND METHODS: Using administrative health care data from British Columbia, Canada, we identified patients diagnosed with type 2 diabetes in 1998-2016. To adjust for confounding by diabetes severity through design, we compared new users of insulin to new users of a noninsulin class, both from a restricted cohort of those who previously received two noninsulin antihyperglycemic classes. We further adjusted for confounding using 1) conventional multivariable adjustment and 2) inverse probability of treatment weighting (IPTW) based on the high-dimensional propensity score algorithm. The hazard ratio [HR] (95% CI) of dementia was estimated using cause-specific hazards models with death as a competing risk. RESULTS: The analytical comparative cohort included 7,863 insulin versus 25,230 noninsulin users. At baseline, insulin users were more likely to have worse health indicators. A total of 78 dementia events occurred over a median (interquartile range) follow-up of 3.9 (5.9) years among insulin users, and 179 events occurred over 4.6 (4.4) years among noninsulin users. The HR (95% CI) of dementia for insulin use versus noninsulin use was 1.68 (1.29-2.20) before adjustment and 1.39 (1.05-1.86) after multivariable adjustment, which was further attenuated to 1.14 (0.81-1.60) after IPTW. CONCLUSIONS: Among individuals with type 2 diabetes previously exposed to two noninsulin antihyperglycemic medications, no significant association was observed between insulin use and all-cause dementia.


Assuntos
Demência , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Estudos de Coortes , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Insulina Regular Humana/uso terapêutico , Demência/epidemiologia , Demência/tratamento farmacológico
13.
Int J Pharm ; 635: 122743, 2023 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-36804520

RESUMO

The aim of this work was to develop approaches to utilize whole particle distributions for both particle size and particle shape parameters to map the full range of particle properties in a curated dataset. It is hoped that such an approach may enable a more complete understanding of the particle landscape as a step towards improving the link between particle properties and processing behaviour. A 1-dimensional principal component analysis (PCA) approach was applied to create a 'morphological distribution landscape'. A dataset of imaged APIs, intermediates and excipients encompassing particle size, particle shape (elongation, length and width) and distribution shape was curated between 2008 and 2022. The curated dataset encompassed over 200 different materials, which included over 150 different APIs, and approximately 3500 unique samples. For the purposes of the current work, only API samples were included. The morphological landscape enables differentiation of materials of equivalent size but varying shape and vice versa. It is hoped that this type of approach can be utilised to better understand the influence of particle properties on pharmaceutical processing behaviour and thereby enable scientists to leverage historical knowledge to highlight and mitigate risks associated to materials of similar morphological nature.


Assuntos
Tamanho da Partícula
14.
FEBS J ; 290(8): 2064-2084, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36401795

RESUMO

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor and functions as a tumour suppressor in different cancer models. In the present study, we report detailed characterization of 11-chloro-7H-benzimidazo[2,1-a]benzo[de]iso-quinolin-7-one (11-Cl-BBQ) as a select modulator of AhR-regulated transcription (SMAhRT) with anti-cancer actions. Treatment of lung cancer cells with 11-Cl-BBQ induced potent and sustained AhR-dependent anti-proliferative effects by promoting G1 phase cell cycle arrest. Investigation of 11-Cl-BBQ-induced transcription in H460 cells with or without the AhR expression by RNA-sequencing revealed activation of p53 signalling. In addition, 11-Cl-BBQ suppressed multiple pathways involved in DNA replication and increased expression of cyclin-dependent kinase inhibitors, including p27Kip1 , in an AhR-dependent manner. CRISPR/Cas9 knockout of individual genes revealed the requirement for both p53 and p27Kip1 for the AhR-mediated anti-proliferative effects. Our results identify 11-Cl-BBQ as a potential lung cancer therapeutic, highlight the feasibility of targeting AhR and provide important mechanistic insights into AhR-mediated-anticancer actions.


Assuntos
Neoplasias Pulmonares , Receptores de Hidrocarboneto Arílico , Humanos , Proteínas de Ciclo Celular/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Pulmão/metabolismo , Neoplasias Pulmonares/genética , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismo , RNA , Proteína Supressora de Tumor p53/genética
15.
Int J Epidemiol ; 52(3): 908-920, 2023 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-36048015

RESUMO

BACKGROUND: Previous studies have shown hypoglycaemia to be associated with an increased risk of dementia; however, there are several design challenges to consider. The objective of this study is to assess the association between hypoglycaemia and dementia while addressing these challenges using a lag period, exposure density sampling (EDS) and inverse probability of treatment weighting (IPTW). METHODS: This was a population-based cohort using data (1996-2018) from British Columbia, Canada. From a cohort of incident type 2 diabetes patients aged 40-70 years, we created a dynamic sub-cohort of hypoglycaemia-exposed (≥1 episode requiring hospitalization or a physician visit) and unexposed individuals using EDS, in which four unexposed individuals per one exposed were randomly selected into risk sets based on diabetes duration and age. Follow-up was until dementia diagnosis, death, emigration or 31 December 2018. Those diagnosed with dementia within 2 years of follow-up were censored. We adjusted for confounding using IPTW and estimated the hazard ratio (HR, 95% CI) of dementia using weighted conditional cause-specific hazards risk models with death as a competing risk. RESULTS: Among 13 970 patients with incident type 2 diabetes, 2794 experienced hypoglycaemia. There were 329 dementia events over a median (interquartile range: IQR) follow-up of 5.03 (5.7) years. IPTW resulted in well-balanced groups with weighted incidence rates (95% CI) of 4.59 (3.52, 5.98)/1000 person-years among exposed and 3.33 (2.58, 3.88)/1000 person-years among unexposed participants. The risk of dementia was higher among those with hypoglycaemia (HR, 1.83; 95% CI 1.31, 2.57). CONCLUSIONS: After addressing several methodological challenges, we showed that hypoglycaemia contributes to an increased risk of all-cause dementia among patients with type 2 diabetes.


Assuntos
Demência , Diabetes Mellitus Tipo 2 , Hipoglicemia , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Estudos de Coortes , Hipoglicemia/epidemiologia , Hipoglicemia/etiologia , Demência/epidemiologia , Colúmbia Britânica/epidemiologia , Fatores de Risco
16.
Br J Clin Pharmacol ; 89(2): 431-439, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-34964156

RESUMO

AIMS: Disproportionality analysis is a common pharmacovigilance tool to detect safety signals of type 2 diabetes medications from spontaneous drug reporting databases. The aim was to demonstrate the impact of using active-comparator restricted disproportionality analysis (ACR-DA), wherein the reference group is restricted to reports with a clinically appropriate active comparator. METHODS: Using reports from the Food and Drug Administration Adverse Event Reporting System, we assessed if sodium/glucose cotransporter 2 (SGLT2) inhibitors are associated with higher reporting of 5 potential adverse events: acute kidney injury, genitourinary tract infections, diabetic ketoacidosis, fractures, and amputations. For each adverse event, we calculated the proportional reporting ratio (PRR) and adjusted reporting odds ratio (aROR [95% confidence interval, CI]) using 3 types of reference groups: no SGLT2 inhibitor (background risk reference), other diabetes drugs (therapeutic class reference), and dipeptidyl peptidase 4 inhibitors (active comparator reference). RESULTS: Based on ACR-DA, we did not detect a safety signal for acute kidney injury (PRR 0.92 [0.81-1.04]; aROR 0.78 [95% CI 0.72-0.85]) or fractures (PRR 0.44[95% CI 0.17-1.15]; aROR 0.74 [95% CI 0.61-0.91]) associated with SGLT2 inhibitors compared to dipeptidyl peptidase 4 inhibitors. However, we detected safety signals for genitourinary tract infections (PRR 2.75[2.02-3.76]; aROR 2.54[2.26-2.86], diabetic ketoacidosis (PRR 63.85[39.37-103.53; aROR 91.49[70.66-118.48]), and amputations (PRR 52.60 [19.66-140.75]; aROR 22.64 [15.32-33.42]. CONCLUSION: The use of the proposed ACR-DA to detect safety signals of type 2 diabetes medications may reduce false positive safety signals through careful selection of the comparator which is expected to reduce channelling bias.


Assuntos
Injúria Renal Aguda , Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Farmacovigilância , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Cetoacidose Diabética/induzido quimicamente , Cetoacidose Diabética/epidemiologia , Cetoacidose Diabética/tratamento farmacológico , Sistemas de Notificação de Reações Adversas a Medicamentos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Doença Crônica , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/tratamento farmacológico , Glucose , Sódio
17.
Can J Diabetes ; 47(2): 153-161, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36481264

RESUMO

OBJECTIVES: Landmark clinical trials have shown the sodium-glucose cotransporter-2 (SGLT-2) inhibitors to have cardiorenal benefits beyond their glucose-lowering effect. Clinical guidelines now recommend their use in patients with chronic kidney disease or heart failure, with or without type 2 diabetes, potentially affecting prescribing patterns among physician specialties. METHODS: Using monthly projected total retail dispensed prescription data from IQVIA's CompuScript database, we assessed trends in prescribing SGLT-2 inhibitors among 6 prescriber specialities from 2015 to 2021 in Canada. We assessed these trends at the class, agent, and dose level using joinpoint regression. RESULTS: From 2015 to 2021, the projected total retail dispensed prescriptions of SGLT-2 inhibitors from all prescribers increased. Relative to other prescribers, >60% of SGLT-2 inhibitor prescriptions were written by general practitioners or family physicians. The percentage of prescriptions from endocrinologists decreased (average annual percent change: mean, -10.8; 95% confidence interval [CI], -12.2% to -9.4%), whereas a dramatic increase was observed for cardiologists (mean, 44.1%, 95% CI, 32.9 to 56.2). The percentage from nephrologists also increased, albeit not statistically significant (mean, 12.4; 95% CI, -0.5 to 27.1). Significant changes in the agent and dose of SGLT-2 inhibitor prescribed were also observed among cardiologists and nephrologists. CONCLUSIONS: Between 2015 and 2021, there was a steady increase in the proportion of SGLT-2 inhibitor prescriptions from cardiologists and nephrologists, reflecting emerging evidence and guideline recommendations.


Assuntos
Diabetes Mellitus Tipo 2 , Médicos , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Hipoglicemiantes/uso terapêutico , Glucose , Sódio/uso terapêutico
18.
Diabetes Care ; 46(2): 331-340, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36516080

RESUMO

OBJECTIVE: Severe hypoglycemia is associated with an increased risk of dementia. We examined if the association is consistently present in mid- and late-life hypoglycemia. RESEARCH DESIGN AND METHODS: Using health care data from Population Data BC, we created a base cohort of patients age ≥40 years with incident type 2 diabetes. Exposure was the first occurrence of severe hypoglycemia (hospitalization or physician visit). We assessed exposure versus no exposure in mid- (age 45-64 years) and late-life (age 65-84 years) cohorts. Index date was the later of the 45th birthday (midlife cohort), 65th birthday (late-life cohort), or diabetes diagnosis. Those with hypoglycemia or dementia before the index date were excluded. Patients were followed from index date until dementia diagnosis, death, emigration, or 31 December 2018. Exposure was modeled as time dependent. We adjusted for confounding using propensity score weighting. Dementia risk was estimated using cause-specific hazards models with death as a competing risk. RESULTS: Of 221,683 patients in the midlife cohort, 1,793 experienced their first severe hypoglycemic event. Over a median of 9.14 years, 3,117 dementia outcomes occurred (32 among exposed). Of 223,940 patients in the late-life cohort, 2,466 experienced their first severe hypoglycemic event. Over a median of 6.7 years, 15,997 dementia outcomes occurred (158 among exposed). The rate of dementia was higher for those with (vs. without) hypoglycemia in both the mid- (hazard ratio 2.85; 95% CI 1.72-4.72) and late-life (2.38; 1.83-3.11) cohorts. CONCLUSIONS: Both mid- and late-life hypoglycemia were associated with approximately double the risk of dementia, indicating the need for prevention throughout the life course of those with diabetes.


Assuntos
Demência , Diabetes Mellitus Tipo 2 , Hipoglicemia , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Estudos de Coortes , Demência/etiologia , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Fatores de Risco
19.
Respir Res ; 23(1): 364, 2022 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-36539784

RESUMO

ß2-agonists provide necessary bronchodilatory action, are recommended by existing clinical practice guidelines and are widely prescribed for patients with these conditions. We examined the risk of all-cause mortality and hospitalization for pneumonia associated with long-or short-acting ß2-agonists (LABA or SABA) or ICS (inhaled corticosteroids)/LABA use. In a nested case-control of 185,407 patients, we found no association between ß2-agonist use and the risk of pneumonia in patients with asthma, COPD, or asthma-COPD overlap. In contrast, new SABA [HR 1.82 (95% CI 1.04-3.20)] or LABA [HR 2.77 (95% CI 1.22-6.31)] use was associated with an increased risk of all-cause mortality compared to ICS use in COPD patients.


Assuntos
Asma , Pneumonia , Doença Pulmonar Obstrutiva Crônica , Humanos , Quimioterapia Combinada , Administração por Inalação , Asma/diagnóstico , Asma/tratamento farmacológico , Asma/induzido quimicamente , Corticosteroides/uso terapêutico , Hospitalização , Pneumonia/induzido quimicamente , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , Hormônios Esteroides Gonadais , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos
20.
AAPS PharmSciTech ; 23(8): 286, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36261755

RESUMO

Computational modeling, machine learning, and statistical data analysis are increasingly utilized to mitigate chemistry, manufacturing, and control failures related to particle properties in solid dosage form manufacture. Advances in particle characterization techniques and computational approaches provide unprecedented opportunities to explore relationships between particle morphology and drug product manufacturability. Achieving this, however, has numerous challenges such as producing and appropriately curating robust particle size and shape data. Addressing these challenges requires a harmonized strategy from material sampling practices, characterization technique selection, and data curation to provide data sets which are informative on material properties. Herein, common sources of error in particle characterization and data compression are reviewed, and a proposal for providing robust particle morphology (size and shape) data to support modeling efforts, approaches for data curation, and the outlook for modeling particle properties are discussed.


Assuntos
Curadoria de Dados , Indústria Farmacêutica , Pós , Tamanho da Partícula , Simulação por Computador
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