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1.
BMC Anesthesiol ; 24(1): 123, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561654

RESUMO

BACKGROUND: Glycopyrrolate-neostigmine (G/N) for reversing neuromuscular blockade (NMB) causes fewer changes in heart rate (HR) than atropine-neostigmine (A/N). This advantage may be especially beneficial for elderly patients. Therefore, this study aimed to compare the cardiovascular effects of G/N and A/N for the reversal of NMB in elderly patients. METHODS: Elderly patients aged 65-80 years who were scheduled for elective non-cardiac surgery under general anesthesia were randomly assigned to the glycopyrrolate group (group G) or the atropine group (group A). Following the last administration of muscle relaxants for more than 30 min, group G received 4 ug/kg glycopyrrolate and 20 ug/kg neostigmine, while group A received 10 ug/kg atropine and 20 ug/kg neostigmine. HR, mean arterial pressure (MAP), and ST segment in lead II (ST-II) were measured 1 min before administration and 1-15 min after administration. RESULTS: HR was significantly lower in group G compared to group A at 2-8 min after administration (P < 0.05). MAP was significantly lower in group G compared to group A at 1-4 min after administration (P < 0.05). ST-II was significantly depressed in group A compared to group G at 2, 3, 4, 5, 6, 7, 8, 9, 11, 13, 14, and 15 min after administration (P < 0.05). CONCLUSIONS: In comparison to A/N, G/N for reversing residual NMB in the elderly has a more stable HR, MAP, and ST-II within 15 min after administration.


Assuntos
Sistema Cardiovascular , Recuperação Demorada da Anestesia , Bloqueio Neuromuscular , Idoso , Humanos , Neostigmina/farmacologia , Glicopirrolato , Atropina/farmacologia
2.
Actas dermo-sifiliogr. (Ed. impr.) ; 115(4): 356-357, Abr. 2024. tab
Artigo em Espanhol | IBECS | ID: ibc-ADZ-18

RESUMO

La hiperhidrosis se caracteriza por excesiva sudoración, habitualmente secundaria a disfunción autonómica con hipersecreción de las glándulas sudoríparas ecrinas. La hiperhidrosis primaria focal es la forma más frecuente, y afecta axilas, palmas, plantas y/o cara. Frecuentemente genera un gran impacto en la calidad de vida y en la actividad social. Su tratamiento es complejo. Los antitranspirantes tópicos son recomendados en primer lugar en la mayoría de casos de hiperhidrosis leve. Múltiples ensayos clínicos y estudios prospectivos avalan la eficacia y tolerabilidad de los anticolinérgicos orales y tópicos. En casos moderado/graves, el glicopirronio tópico, el cual ha sido evaluado en al menos 8 ensayos clínicos con más de 2.000 pacientes en total, podría ser considerado la primera línea farmacológica en la hiperhidrosis axilar mal controlada con antitranspirantes tópicos; seguido por inyecciones de toxina botulínica, sistemas de microondas y por anticolinérgicos orales. En este artículo revisamos el rol de los anticolinérgicos tópicos en el manejo de la hiperhidrosis focal en adultos y niños.(AU)


Hyperhidrosis, or excessive sweating, is characterized by overactivity of the eccrine sweat glands, usually associated with dysfunction of the autonomic nervous system. Primary focal hyperhidrosis is the most common form and can affect the axillae, palms, soles, and/or face, often leading to significantly impaired quality of life and social functioning. Treatment is complex. Topical antiperspirants are normally recommended as the first-line treatment for mild hyperhidrosis. Multiple clinical trials and prospective studies support the efficacy and tolerability of oral and topical anticholinergics in the management of hyperhidrosis. Topical glycopyrronium, which has been investigated in at least 8 clinical trials enrolling more than 2000 patients, is probably the first-line pharmacological treatment for axillary hyperhidrosis in patients with moderate to severe disease poorly controlled with topical antiperspirants. Second-line treatments include botulinum toxin injections, microwave treatment, and oral anticholinergics. We review the use of topical anticholinergics in the management of focal hyperhidrosis in adults and children.(AU)


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Antagonistas Colinérgicos/administração & dosagem , Hiperidrose/tratamento farmacológico , Glicopirrolato , Iontoforese , Toxinas Botulínicas Tipo A , Dermatologia , Dermatopatias
3.
Actas dermo-sifiliogr. (Ed. impr.) ; 115(4): T356-T367, Abr. 2024. tab
Artigo em Inglês | IBECS | ID: ibc-ADZ-19

RESUMO

La hiperhidrosis se caracteriza por excesiva sudoración, habitualmente secundaria a disfunción autonómica con hipersecreción de las glándulas sudoríparas ecrinas. La hiperhidrosis primaria focal es la forma más frecuente, y afecta axilas, palmas, plantas y/o cara. Frecuentemente genera un gran impacto en la calidad de vida y en la actividad social. Su tratamiento es complejo. Los antitranspirantes tópicos son recomendados en primer lugar en la mayoría de casos de hiperhidrosis leve. Múltiples ensayos clínicos y estudios prospectivos avalan la eficacia y tolerabilidad de los anticolinérgicos orales y tópicos. En casos moderado/graves, el glicopirronio tópico, el cual ha sido evaluado en al menos 8 ensayos clínicos con más de 2.000 pacientes en total, podría ser considerado la primera línea farmacológica en la hiperhidrosis axilar mal controlada con antitranspirantes tópicos; seguido por inyecciones de toxina botulínica, sistemas de microondas y por anticolinérgicos orales. En este artículo revisamos el rol de los anticolinérgicos tópicos en el manejo de la hiperhidrosis focal en adultos y niños.(AU)


Hyperhidrosis, or excessive sweating, is characterized by overactivity of the eccrine sweat glands, usually associated with dysfunction of the autonomic nervous system. Primary focal hyperhidrosis is the most common form and can affect the axillae, palms, soles, and/or face, often leading to significantly impaired quality of life and social functioning. Treatment is complex. Topical antiperspirants are normally recommended as the first-line treatment for mild hyperhidrosis. Multiple clinical trials and prospective studies support the efficacy and tolerability of oral and topical anticholinergics in the management of hyperhidrosis. Topical glycopyrronium, which has been investigated in at least 8 clinical trials enrolling more than 2000 patients, is probably the first-line pharmacological treatment for axillary hyperhidrosis in patients with moderate to severe disease poorly controlled with topical antiperspirants. Second-line treatments include botulinum toxin injections, microwave treatment, and oral anticholinergics. We review the use of topical anticholinergics in the management of focal hyperhidrosis in adults and children.(AU)


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Antagonistas Colinérgicos/administração & dosagem , Hiperidrose/tratamento farmacológico , Glicopirrolato , Iontoforese , Toxinas Botulínicas Tipo A , Dermatologia , Dermatopatias
4.
Artigo em Inglês | MEDLINE | ID: mdl-38435125

RESUMO

Purpose: The TRITRIAL study assessed the effects of beclometasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) fixed combination in patients with chronic obstructive pulmonary disease (COPD) in a real-world setting, focusing on patient's experience and perspective through the use of patients reported outcomes. Patients and Methods: TRITRIAL was a multicenter, prospective, observational study conducted on patients with moderate-severe COPD treated with BDP/FF/G fixed therapy for 12 months. The main objective was to evaluate the impact of BDP/FF/G on health status through the COPD Assessment Test (CAT) score. Additional assessments included adherence and satisfaction, measured by the TAI-10/12 questionnaire and a specifically designed eight-item questionnaire, quality of life through the EQ-5D-5L test, sleep quality through the COPD and Asthma Sleep Impact Scale (CASIS), as well as safety and disease-related outcomes. Results: Data from 655 patients were analyzed in the study. The mean total CAT score significantly improved (from 22.8 at baseline to 18.1 at 6 months and 16.5 at 12 months; p < 0.0001), as well as all the eight CAT sub-items, which decreased on average by 0.5-0.9 points during the study. Adherence and usability of the inhaler also improved during the study, with a decrease in poor compliance (from 30.1% to 18.3%) and an increase in good compliance (from 51.8% to 58.3%) according to the TAI score. Patients also benefited from significantly improved quality of life (EQ Index from 0.70 to 0.80; EQ-5D VAS score from 55.1 to 63.1) and sleep quality (CASIS score from 41.1 to 31.8). Finally, patients reported a significant reduction in exacerbation during the study. Conclusion: TRITRIAL showed that the BDP/FF/G fixed combination is effective and safe in patients with moderate-severe COPD and poorly controlled disease, improving patients' HRQoL, sleep quality, adherence and inhaler usability and reducing COPD symptoms and the risk of exacerbation in a real-life setting.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Humanos , Beclometasona/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Glicopirrolato/efeitos adversos , Estudos Prospectivos , Nível de Saúde , Fumarato de Formoterol/efeitos adversos , Fumaratos , Itália
5.
J Clin Anesth ; 93: 111344, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38007845

RESUMO

STUDY OBJECTIVE: Perioperative neuromuscular blocking agents are pharmacologically reversed to minimize complications associated with residual neuromuscular block. Neuromuscular block reversal with anticholinesterases (e.g., neostigmine) require coadministration of an anticholinergic agent (e.g., glycopyrrolate) to mitigate muscarinic activity; however, sugammadex, devoid of cholinergic activity, does not require anticholinergic coadministration. Single-institution studies have found decreased incidence of post-operative urinary retention associated with sugammadex reversal. This study used a multicenter database to better understand the association between neuromuscular block reversal technique and post-operative urinary retention. DESIGN: Retrospective cohort study utilizing large healthcare database. SETTING: Non-profit, non-governmental and community and teaching hospitals and health systems from rural and urban areas. PATIENTS: 61,898 matched adult inpatients and 95,500 matched adult outpatients. INTERVENTIONS: Neuromuscular block reversal with sugammadex or neostigmine plus glycopyrrolate. MEASUREMENTS: Incidence of post-operative urinary retention by neuromuscular block reversal agent and the independent association of neuromuscular block reversal technique and risk of post-operative urinary retention. MAIN RESULTS: The incidence of post-operative urinary retention was 2-fold greater among neostigmine with glycopyrrolate compared to sugammadex patients (5.0% vs 2.4% inpatients; 0.9% vs 0.4% outpatients; both p < 0.0001). Multivariable logistic regression identified reversal with neostigmine to be independently associated with greater risk of post-operative urinary retention (inpatients: odds ratio, 2.20; 95% confidence interval, 2.00 to 2.41; p < 0.001; outpatients: odds ratio, 2.57; 95% confidence interval, 2.13 to 3.10; p < 0.001). Post-operative urinary retention-related visits within 2 days following discharge were five-fold higher among those reversed with neostigmine than sugammadex among inpatients (0.05% vs. 0.01%, respectively; p = 0.018) and outpatients (0.5% vs. 0.1%; p < 0.0001). CONCLUSION: Though this study suggests that neuromuscular block reversal with neostigmine can increase post-operative urinary retention risk, additional studies are needed to fully understand the association.


Assuntos
Bloqueio Neuromuscular , Fármacos Neuromusculares não Despolarizantes , Retenção Urinária , Adulto , Humanos , Neostigmina/efeitos adversos , Sugammadex/efeitos adversos , Bloqueio Neuromuscular/efeitos adversos , Bloqueio Neuromuscular/métodos , Retenção Urinária/induzido quimicamente , Retenção Urinária/epidemiologia , Glicopirrolato , Estudos Retrospectivos , Inibidores da Colinesterase/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Hospitais
6.
Food Funct ; 14(24): 10941-10954, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-38009324

RESUMO

Tropomyosin (TM) is the major allergen in shrimp that is known to be the primary trigger for shrimp-induced food allergy. Our previous reports suggest that glycation could reduce the allergenicity of TM and the reduction of allergenicity is largely dependent on the sources of saccharides. This investigation aimed to investigate the glycation of TM by glucose and maltotriose as well as the effects of glycation on the allergenicity of TM. Compared to TM, the IgG-binding capacity and IgE-binding capacity of tropomyosin glycated by glucose (TM-G) was greatly reduced with a longer glycation time, the release of allergic mediators from RBL-2H3 mast cells was reduced in a time-dependent manner, and weaker allergic reactions were induced in BALB/c mice. Conversely, tropomyosin glycated by maltotriose (TM-MTS) exhibited a stronger allergenicity after 48 hours of glycation due to the generation of neoallergens that were derived from the advanced glycation end products (AGEs). In conclusion, glucose could be used to desensitize the shrimp TM-induced food allergy via glycation, which could significantly reduce the allergenicity and alleviate allergic symptoms. This work could provide a novel approach to reduce the allergenicity of shrimp tropomyosin and prevent the shrimp tropomyosin-induced food allergy.


Assuntos
Hipersensibilidade Alimentar , Penaeidae , Camundongos , Animais , Produtos Finais de Glicação Avançada , Glucose , Alérgenos , Tropomiosina , Glicopirrolato , Camundongos Endogâmicos BALB C
8.
Pulm Pharmacol Ther ; 83: 102270, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38008396

RESUMO

Inhaled corticosteroids, along with beta2-agonists and anti-muscarinics, represent the cornerstone of asthma treatment. Although the advent of monoclonal antibodies has dramatically changed severe asthma management, there are still patients ineligible or with poor response to biologics. Moreover, high costs associated with monoclonal antibodies prescription are still an open issue, leading clinicians to carefully assess cost-benefit ratio before their administration. From this perspective, the use of single-inhaler Beclometasone Dipropionate/Formoterol Fumarate/Glycopyrronium in patients with severe asthma could not only improve their clinical and functional performance, but also postpone biologic prescription, with positive repercussions on healthcare costs.


Assuntos
Antiasmáticos , Asma , Produtos Biológicos , Humanos , Fumarato de Formoterol/uso terapêutico , Beclometasona/uso terapêutico , Glicopirrolato/uso terapêutico , Antiasmáticos/uso terapêutico , Administração por Inalação , Combinação de Medicamentos , Asma/tratamento farmacológico , Nebulizadores e Vaporizadores , Anticorpos Monoclonais/uso terapêutico , Produtos Biológicos/uso terapêutico , Broncodilatadores/uso terapêutico
9.
Int J Chron Obstruct Pulmon Dis ; 18: 2245-2256, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37849918

RESUMO

Purpose: Triple therapy to prevent exacerbations from chronic obstructive pulmonary disease (COPD) is associated with improved health compared to single and dual-agent therapy in some populations. This study assessed the benefits of prompt administration of budesonide/glycopyrrolate/formoterol fumarate (BGF) following a COPD exacerbation. Patients and methods: EROS was a retrospective analysis of people with COPD using the MORE2 Registry®. Inclusion required ≥1 severe, ≥2 moderate, or ≥1 moderate exacerbation while on other maintenance treatment. Within 12 months following the index exacerbation, ≥1 pharmacy claim for BGF was required. Primary outcomes were the rate of COPD exacerbations and healthcare costs for those that received BGF promptly (within 30 days of index exacerbation) versus delayed (31-180 days) and very delayed (181-365 days). The effect of each 30-day delay in initiation of BGF was estimated using a multivariable negative binomial regression model. Results: 2409 patients were identified: 434 prompt, 1187 delayed, and 788 very delayed. The rate (95% CI) of total exacerbations post-index increased as time to BGF initiation increased: prompt 1.52 (1.39-1.66); delayed 2.00 (1.92-2.09); and very delayed 2.30 (2.20-2.40). Adjusting for patient characteristics, each 30-day delay in receiving BGF was associated with a 5% increase in the average number of subsequent exacerbations (rate ratio, 95% CI: 1.05, 1.01-1.08; p<0.05). Prompt initiation of BGF was also associated with lower post-index annualized COPD-related costs ($5002 for prompt vs $7639 and $8724 for the delayed and very delayed groups, respectively). Conclusion: Following a COPD exacerbation, promptly initiating BGF was associated with a reduction in subsequent exacerbations and reduced healthcare utilization and costs.


Assuntos
Broncodilatadores , Doença Pulmonar Obstrutiva Crônica , Humanos , Broncodilatadores/efeitos adversos , Glicopirrolato/efeitos adversos , Fumarato de Formoterol/efeitos adversos , Estudos Retrospectivos , Combinação de Medicamentos , Inaladores Dosimetrados , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Método Duplo-Cego , Budesonida/efeitos adversos , Nebulizadores e Vaporizadores , Administração por Inalação
10.
J Int Med Res ; 51(10): 3000605231202144, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37795584

RESUMO

OBJECTIVES: To compare the urine output and estimated glomerular filtration rate (eGFR) of patients postoperatively administered sugammadex or glycopyrrolate 7 days following kidney transplantation (KT). METHODS: We retrospectively enrolled 134 consecutive patients who underwent KT under general anesthesia. Their urine output and eGFR were recorded every 24 hours between postoperative day (POD) 1 and 7. We used regression analysis to evaluate the relationship between the reversal agent administered and the outcomes of the participants. RESULTS: The urine output and eGFR of the participants did not differ between the two groups. Multivariate analysis showed that body mass index (BMI) (odds ratio (OR) 1.21; 95% confidence interval (CI) 1.05-1.40), diabetes mellitus (OR 3.14; 95% CI 1.07-9.16), neurovascular disease (OR 7.00; 95% CI 1.61-30.42), and the duration of surgery (OR 1.01; 95% CI 1.00-1.01) were associated with lower urine output on POD 7. In addition, only BMI (OR 1.25; 95% CI 1.09-1.42) was associated with low eGFR on POD 7. CONCLUSIONS: The urine output and eGFR of patients administered sugammadex or glycopyrrolate following KT did not differ 7 days later. Moreover, glycopyrrolate does not affect urine output or eGFR on POD 7, according to multivariate regression analysis.


Assuntos
Glicopirrolato , Transplante de Rim , Humanos , Estudos Retrospectivos , Transplante de Rim/efeitos adversos , Sugammadex , Taxa de Filtração Glomerular , Rim
11.
Respir Res ; 24(1): 244, 2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37803368

RESUMO

BACKGROUND: This study, in patients with symptomatic chronic obstructive pulmonary disease (COPD), explored switching therapy from non-extrafine high-dose inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA; fluticasone propionate/salmeterol [FP/SLM]) to extrafine medium-dose beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium (BDP/FF/G), both via dry-powder inhaler. Functional Respiratory Imaging, a quantitative computed tomography method with 3D reconstructions of pulmonary anatomy, was used to assess airway geometry and lung function. METHODS: Patients receiving a stable ICS/LABA regimen for ≥ 8 weeks were switched to FP/SLM 500/50 µg, one inhalation twice-daily (high-dose ICS) for 6 weeks. After baseline assessments (Visit 2 [V2]), therapy was switched to BDP/FF/G 100/6/10 µg, two inhalations twice-daily (medium-dose ICS) for 6 weeks, followed by V3. The primary endpoints were percentage changes in specific image-based airway volume (siVaw) and resistance (siRaw) from baseline to predose at V3 (i.e., chronic effects), assessed at total lung capacity (TLC) in central and distal lung regions. Secondary endpoints included siVaw and siRaw changes from pre-dose to post-dose at V2, and from pre-dose to post-dose at V3 at TLC (i.e., acute effects), and chronic and acute changes in siVaw and siRaw at functional residual capacity (FRC). Pre-dose forced expiratory volume in 1 s (FEV1) and COPD Assessment Test (CAT) were also assessed. RESULTS: There were no significant changes in pre-dose siVaw or siRaw at TLC from baseline to V3, although at FRC there was a significant decrease in mean siRaw in the distal airways (- 63.6%; p = 0.0261). In addition, in the distal airways there were significant acute effects at TLC on mean siVaw and siRaw (siVaw: 39.8% and 62.6%; siRaw: - 51.1% and - 57.2%, V2 and V3, respectively; all p < 0.001) and at FRC at V2 (siVaw: 77.9%; siRaw: - 67.0%; both p < 0.001). At V3, the mean change in pre-dose FEV1 was 62.2 mL (p = 0.0690), and in CAT total score was - 3.30 (p < 0.0001). CONCLUSIONS: In patients with symptomatic COPD receiving high-dose ICS/LABA, adding a long-acting muscarinic antagonist while decreasing the ICS dose by switching to medium-dose extrafine BDP/FF/G was associated with improved airway indices, especially in the distal airways, together with improvements in respiratory health status. Trial registration ClinicalTrials.gov (NCT04876677), first posted 6th May 2021.


Assuntos
Glicopirrolato , Doença Pulmonar Obstrutiva Crônica , Humanos , Fumarato de Formoterol , Beclometasona , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Antagonistas Muscarínicos , Administração por Inalação , Combinação Fluticasona-Salmeterol , Combinação de Medicamentos , Agonistas de Receptores Adrenérgicos beta 2 , Broncodilatadores
12.
Syst Rev ; 12(1): 158, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37674180

RESUMO

BACKGROUND: Autonomy-supporting interventions, such as self-determination theory and guided self-determination interventions, may improve self-management and clinical and psychosocial outcomes in people with diabetes. Such interventions have never been systematically reviewed assessing both benefits and harms and concurrently controlling the risks of random errors using trial sequential analysis methodology. This systematic review investigates the benefits and harms of self-determination theory-based interventions compared to usual care in people with diabetes. METHODS: We used the Cochrane methodology. Randomized clinical trials assessing interventions theoretically based on guided self-determination or self-determination theory in any setting were eligible. A comprehensive search (latest search April 2022) was undertaken in CENTRAL, MEDLINE, Embase, LILACS, PsycINFO, SCI-EXPANDED, CINAHL, SSCI, CPCI-S, and CPCI-SSH to identify relevant trials. Two authors independently screened, extracted data, and performed risk-of-bias assessment of included trials using the Cochrane risk-of-bias tool 1.0. Our primary outcomes were quality of life, all-cause mortality, and serious adverse events. Our secondary outcomes were diabetes distress, depressive symptoms, and nonserious adverse events not considered serious. Exploratory outcomes were glycated hemoglobin and motivation (autonomy, controlled, amotivation). Outcomes were assessed at the end of the intervention (primary time point) and at maximum follow-up. The analyses were conducted using Review Manager 5.4 and Trial Sequential Analysis 0.9.5.10. Certainty of the evidence was assessed by GRADE. RESULTS: Our search identified 5578 potentially eligible studies of which 11 randomized trials (6059 participants) were included. All trials were assessed at overall high risk of bias. We found no effect of self-determination theory-based interventions compared with usual care on quality of life (mean difference 0.00 points, 95% CI -4.85, 4.86, I2 = 0%; 225 participants, 3 trials, TSA-adjusted CI -11.83, 11.83), all-cause mortality, serious adverse events, diabetes distress, depressive symptoms, adverse events, glycated hemoglobulin A1c, or motivation (controlled). The certainty of the evidence was low to very low for all outcomes. We found beneficial effect on motivation (autonomous and amotivation; low certainty evidence). CONCLUSIONS: We found no effect of self-determination-based interventions on our primary or secondary outcomes. The evidence was of very low certainty. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020181144.


Assuntos
Diabetes Mellitus , Qualidade de Vida , Humanos , Diabetes Mellitus/terapia , Hemoglobinas Glicadas , Glicopirrolato , MEDLINE
13.
Int J Chron Obstruct Pulmon Dis ; 18: 2039-2054, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37731774

RESUMO

Purpose: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with significant morbidity and mortality and increased economic healthcare burden for patients with COPD. Long-acting muscarinic antagonist (LAMA)/long-acting ß2-agonist (LABA) dual therapy is recommended for patients receiving mono-bronchodilator therapy who experience exacerbations or ongoing breathlessness. This study compared two single-inhaler LAMA/LABA dual therapies, umeclidinium/vilanterol (UMEC/VI) and indacaterol/glycopyrronium (IND/GLY), on moderate-to-severe exacerbation rates in patients with COPD in England. Patients and Methods: This retrospective cohort study used linked primary care electronic health record data (Clinical Practice Research Datalink-Aurum) and secondary care data (Hospital Episode Statistics) to assess outcomes for patients with COPD who had a first prescription for single-inhaler UMEC/VI or IND/GLY (index date) between 1 January 2015 and 30 September 2019 (indexing period). Analyses compared UMEC/VI and IND/GLY on moderate-to-severe, moderate, and severe exacerbations, healthcare resource utilization (HCRU), and direct costs at 6, 12, 18, and 24 months, and time-to-first on-treatment exacerbation up to 24 months post-index date. Following inverse probability of treatment weighting (IPTW), non-inferiority and superiority of UMEC/VI versus IND/GLY were assessed. Results: In total, 12,031 patients were included, of whom 8753 (72.8%) were prescribed UMEC/VI and 3278 (27.2%) IND/GLY. After IPTW, for moderate-to-severe exacerbations, weighted rate ratios were <1 at 6, 12, and 18 months and equal to 1 at 24 months for UMEC/VI; around the null value for moderate exacerbations and <1 at all timepoints for severe exacerbations. UMEC/VI showed lower HCRU incidence rates than IND/GLY for all-cause Accident and Emergency visits and COPD-related inpatient stays and associated all-cause costs at 6 months post-indexing. Time-to-triple therapy was similar for both treatments. Conclusion: UMEC/VI demonstrated non-inferiority to IND/GLY in moderate-to-severe exacerbation reduction at 6, 12 and 18 months. These results support previous findings demonstrating similarity between UMEC/VI and IND/GLY on reduction of moderate-to-severe exacerbations.


Assuntos
Glicopirrolato , Doença Pulmonar Obstrutiva Crônica , Humanos , Glicopirrolato/efeitos adversos , Estudos Retrospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Antagonistas Muscarínicos/efeitos adversos , Inglaterra
14.
Med Biol Eng Comput ; 61(11): 3021-3034, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37582979

RESUMO

The current study aims to simulate fatigue microdamage accumulation in glycated cortical bone with increased advanced glycation end-products (AGEs) using a phase field fatigue framework. We link the material degradation in the fracture toughness of cortical bone to the high levels of AGEs in this tissue. We simulate fatigue fracture in 2D models of cortical bone microstructure extracted from human tibias. The results present that the mismatch between the critical energy release rate of microstructural features (e.g., osteons and interstitial tissue) can alter crack initiation and propagation patterns. Moreover, the high AGEs content through the increased mismatch ratio can cause the activation or deactivation of bone toughening mechanisms under cyclic loading. The fatigue fracture simulations also show that the lifetime of diabetic cortical bone samples can be dependent on the geometry of microstructural features and the mismatch ratio between the features. Additionally, the results indicate that the trapped cracks in cement lines in the diabetic cortical microstructure can prevent further crack growth under cyclic loading. The present findings show that alterations in the materials heterogeneity of microstructural features can change the fatigue fracture response, lifetime, and fragility of cortical bone with high AGEs contents. Cortical bone models are created from microscopy images taken from the cortical cross-section of human tibias. Increased glycation contents in the cortical bone sample can change the crack growth trajectories.


Assuntos
Osso Cortical , Diabetes Mellitus , Fraturas Ósseas , Fraturas de Estresse , Humanos , Fenômenos Biomecânicos , Osso Cortical/diagnóstico por imagem , Produtos Finais de Glicação Avançada , Glicopirrolato , Estresse Mecânico
15.
Pulm Pharmacol Ther ; 83: 102245, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37607661

RESUMO

INTRODUCTION: The climate crisis poses an immediate threat to human health and well-being, demanding urgent adaptions across sectors, including healthcare. The development of pressurized metered dose inhalers (MDIs) with greater sensitivity to the climate emergency using novel propellants with lower global warming potentials (GWPs), but comparable pharmacokinetic (PK) parameters to currently marketed MDIs, is a vital step toward reducing the impact of healthcare for respiratory disorders on climate change. This study evaluated the relative bioavailabilities of the individual components of a fixed-dose combination of budesonide/glycopyrrolate/formoterol fumarate (BGF) 160/9/4.8 µg per actuation between three different propellant formulations. METHODS: Healthy male participants (aged 18-60 years) were randomized into a single-blind, three-period, single-dose, single-center, crossover study (NCT04600505). The PK and safety and tolerability profiles of BGF MDI formulated with two novel propellants with low GWP (hydrofluoroolefin-1234ze [HFO]; hydrofluorocarbon-152a [HFC]) were compared with BGF MDI formulated with the propellant used in the currently marketed reference product (hydrofluoroalkane-134a [HFA]). The study included a screening period, three treatment periods (with 3- to 7-day washout periods between each dose), and a follow-up. The primary PK parameters assessed were maximum observed plasma concentration (Cmax), area under the plasma concentration curve (AUC) from time zero extrapolated to infinity (AUCinf), and AUC from time zero to the time of the last quantifiable analyte concentration (AUClast). The study was not powered to statistically demonstrate bioequivalence. RESULTS: Forty-seven participants completed the study, and 24 participants were evaluable for PK assessments. Systemic exposure, based on geometric mean ratios (90% confidence interval), to each BGF component from the test propellants delivered in a standard MDI was comparable with the reference propellant for AUClast (HFO vs. HFA: budesonide, 107.30 [94.53, 121.90]; glycopyrrolate, 106.10 [86.18, 130.60]; formoterol, 98.13 [86.44, 111.40]; HFC vs. HFA: budesonide, 98.80 [84.59, 115.40]; glycopyrrolate, 99.71 [80.84, 123.00]; formoterol, 107.00 [88.82, 128.90]); AUCinf (where evaluable) and Cmax followed the same trend. There were no serious adverse events or adverse events leading to treatment discontinuation. No new safety signals were observed. CONCLUSIONS: Systemic BGF component exposure was similar for both test propellants (HFO and HFC) compared with the HFA reference propellant, with an acceptable safety profile in the studied population. Therefore, both novel low GWP propellants show strong potential as candidates for development of MDIs with greater sensitivity to the climate crisis, a vital step toward ameliorating the detrimental impact of healthcare on the environment. Further investigation in larger studies is warranted.


Assuntos
Broncodilatadores , Glicopirrolato , Humanos , Masculino , Administração por Inalação , Disponibilidade Biológica , Budesonida/farmacocinética , Estudos Cross-Over , Método Duplo-Cego , Combinação de Medicamentos , Fumarato de Formoterol , Aquecimento Global , Inaladores Dosimetrados , Método Simples-Cego , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade
16.
J Pharm Biomed Anal ; 234: 115553, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37399700

RESUMO

A novel simple, specific, sensitive, accurate and precise reversed phase high performance liquid chromatographic method (RP-HPLC/UV) was developed and validated for the simultaneous estimation of Glycopyrronium bromide (GLY), Indacaterol acetate (IND) and Mometasone furoate (MOF) in pure form, in laboratory prepared mixtures and in pharmaceutical dosage form. Experimental design methodology was applied by using Plackett-Burman and face-centered composite designs to achieve the best resolution with minimum experimental trials. The designed model was statistically analyzed, graphically presented by surface plots and the relationships between coefficients of the derived polynomial equations were interpreted. Chromatographic separation was achieved on Inertsil ODS C18 column (250 ×4.6 mm, 5 µm) at ambient temperature using a mobile phase composed of methanol: 0.1% glacial acetic acid (pH4) in a gradient elution at a flow rate 1 mL /min. UV detection was carried out at 233 nm. Response was found to be linear in the concentration range of 20-120 µg /mL with regression coefficient (r2 = 0.999) for GLY, 50-300 µg /mL with regression coefficient (r2 = 0.9995) for IND and 50-300 µg /mL with regression coefficient (r2 = 0.9998) for MOF. The method was validated as per ICH guidelines and satisfactory results were achieved. The method was successfully applied for the analysis of the cited drugs in their fixed dose combination (FDC) pharmaceutical formulation. Statistical comparison between the results obtained by the proposed method and the reference methods for GLY, IND and MOF showed no significant difference. The developed method could be implemented in quality control aspects of the cited drugs. Four green metrics were used to evaluate the new RP-HPLC/UV method's greenness and compare it to other published techniques.


Assuntos
Glicopirrolato , Quinolonas , Furoato de Mometasona , Cromatografia Líquida de Alta Pressão/métodos , Nebulizadores e Vaporizadores
17.
Eur J Clin Pharmacol ; 79(10): 1321-1332, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37507595

RESUMO

OBJECTIVES: This study aimed to quantitatively compare the efficacy and safety of long-acting ß2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) and LABA/inhaled corticosteroid (ICS) fixed-dose combinations (FDCs) in preventing moderate or severe chronic obstructive pulmonary disease (COPD) exacerbations. METHODS: A literature search was performed using public databases. The time course characteristics of the probability of a moderate or severe exacerbation in stable COPD patients treated with LABA/LAMA and LABA/ICS FDCs were described by the parametric survival function. A random-effects model in a single-arm meta-analysis was used to analyze the incidence of serious adverse events (SAEs) and pneumonia. RESULTS: Twenty studies including 23,955 participants were included. The proportion of participants with a history of COPD exacerbation (%) in the previous year and the postbronchodilator forced expiratory volume in the first second (FEV1) (%predicted) were important factors affecting drug efficacy. After adjusting the above factors to median levels of 100% and 45.5%, respectively, the moderate or severe exacerbation rates at 52 weeks for olodaterol/tiotropium, formoterol/budesonide, indacaterol/glycopyrronium, formoterol/glycopyrronium, vilanterol/fluticasone, salmeterol/fluticasone, and vilanterol/umeclidinium were 38.3%, 41.0%, 42.6%, 47.0%, 47.5%, 47.9%, and 53.0%, respectively. In terms of safety, significant differences were observed among drugs containing different LABA/LAMA FDCs. CONCLUSIONS: This study showed that not all LABA/LAMA FDCs were superior to LABA/ICS FDCs in safety and in preventing moderate or severe exacerbations in patients with stable COPD, providing important quantitative information for COPD-related guidelines.


Assuntos
Antagonistas Muscarínicos , Doença Pulmonar Obstrutiva Crônica , Humanos , Administração por Inalação , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Broncodilatadores/uso terapêutico , Combinação de Medicamentos , Fluticasona/uso terapêutico , Fumarato de Formoterol/uso terapêutico , Glicopirrolato/uso terapêutico , Antagonistas Muscarínicos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
18.
Cardiovasc Diabetol ; 22(1): 173, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37438755

RESUMO

BACKGROUND: Hyperglycaemia is frequent in acute ischemic stroke and denotes a bad prognosis, even in the absence of pre-existing diabetes. However, in clinical trials treatment of elevated glucose levels with insulin did not improve stroke outcome, suggesting that collateral effects rather than hyperglycaemia itself aggravate ischemic brain damage. As reactive glucose metabolites, glyoxal and methylglyoxal are candidates for mediating the deleterious effects of hyperglycaemia in acute stroke. METHODS: In 135 patients with acute stroke, we used liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to measure glyoxal, methylglyoxal and several of their glycated amino acid derivatives in serum. Results were verified in a second cohort of 61 stroke patients. The association of serum concentrations with standard stroke outcome scales (NIHSS, mRS) was tested. RESULTS: Glucose, glyoxal, methylglyoxal, and the glyoxal-derived glycated amino acid Nδ-(5-hydro-4-imidazolon-2-yl)ornithine (G-H1) were positively correlated with a bad stroke outcome at 3 months as measured by mRS90, at least in one of the two cohorts. However, the glycated amino acids Nε-carboxyethyllysine (CEL) and in one cohort pyrraline showed an inverse correlation with stroke outcome probably reflecting lower food intake in severe stroke. Patients with a poor outcome had higher serum concentrations of glyoxal and methylglyoxal. CONCLUSIONS: The glucose-derived α-dicarbonyl glyoxal and glycated amino acids arising from a reaction with glyoxal are associated with a poor outcome in ischemic stroke. Thus, lowering α-dicarbonyls or counteracting their action could be a therapeutic strategy for hyperglycaemic stroke.


Assuntos
Antifibrinolíticos , Hiperglicemia , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/diagnóstico , Glioxal , Aldeído Pirúvico , Estudos de Coortes , Hiperglicemia/diagnóstico , Cromatografia Líquida , Espectrometria de Massas em Tandem , Acidente Vascular Cerebral/diagnóstico , Aminoácidos , Glucose , Glicopirrolato
19.
J Aerosol Med Pulm Drug Deliv ; 36(4): 189-209, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37428619

RESUMO

The journey of using anticholinergics in the treatment of asthma started with anticholinergic-containing plants such as Datura stramonium and Atropa belladonna, followed by ipratropium bromide and continued with tiotropium, glycopyrronium, and umeclidinium. Although antimuscarinics were used in the maintenance treatment of asthma over a century ago, after a long time (since 2014), it has been recommended to be used as an add-on long-acting antimuscarinic agent (LAMA) therapy in the maintenance treatment of asthma. The airway tone controlled by the vagus nerve is increased in asthma. Allergens, toxins, or viruses cause airway inflammation and inflammation-related epithelial damage, increased sensory nerve stimulation, ganglionic and postganglionic acetylcholine (ACh) release by inflammatory mediators, intensification of ACh signaling at M1 and M3 muscarinic ACh receptors (mAChRs), and dysfunction of M2 mAChR. Optimal anticholinergic drug for asthma should effectively block M3 and M1 receptors, but have minimal effect on M2 receptors. Tiotropium, umeclidinium, and glycopyrronium are anticholinergic agents with this feature. Tiotropium has been used in a separate inhaler as an add-on treatment to inhaled corticosteroid (ICS)/long-acting ß2-agonist (LABA), and glycopyrronium and umeclidinium have been used in a single inhaler as a combination of ICS/LABA/LAMA in asthma in recent years. Guidelines recommend this regimen as an optimization step for patients with severe asthma before initiating any biologic or systemic corticosteroid therapy. In this review, the history of antimuscarinic agents, their effectiveness and safety in line with randomized controlled trials, and real-life studies in asthma treatment will be discussed according to the current data.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Antagonistas Muscarínicos , Brometo de Tiotrópio , Glicopirrolato , Administração por Inalação , Asma/tratamento farmacológico , Antagonistas Colinérgicos/uso terapêutico , Corticosteroides , Inflamação/tratamento farmacológico , Broncodilatadores/farmacologia , Broncodilatadores/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2 , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
20.
Anesth Prog ; 70(2): 53-57, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37379091

RESUMO

OBJECTIVE: Scientific evidence has rarely, if at all, been reported in the literature demonstrating analytical confirmation of the physical compatibility and stability of glycopyrrolate and rocuronium combined. The purpose of this experiment was to determine if glycopyrrolate and rocuronium are physically compatible. METHODS: Glycopyrrolate and rocuronium were combined in various containers, observed over a 60-minute period, and compared against positive and negative controls. Measured metrics included color change, precipitate formation, Tyndall beam test, turbidity, and pH. Statistical analyses were used to assess significance of data trends. RESULTS: The combination of glycopyrrolate and rocuronium did not result in any color change, precipitate formation, a positive Tyndall beam test, or a significantly positive turbidity and did not result in any significant change in pH, regardless of container. CONCLUSION: Per the protocol used in this study, glycopyrrolate and rocuronium were determined to be physically compatible.


Assuntos
Glicopirrolato , Humanos , Rocurônio
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