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OBJECTIVE: The study aimed to reach a consensus on the most relevant patient-reported outcomes (PROs), the corresponding measures (PROMs), and measurement frequency during severe asthma patient follow-up. METHODS: Two Delphi rounds were conducted. The questionnaire was developed based on a systematic literature review, a focus group with patients, and a nominal group with experts. It assessed PROs' relevance and the appropriateness (A) and feasibility (F) of PROMs using a Likert scale (1=totally agree; 9=totally disagree). The consensus was established when ≥75% of participants agreed (1-3) or disagreed (7-9). RESULTS: Sixty-three professionals (25 hospital pharmacists, 14 allergists, 13 pulmonologists, and 11 nurses) and 5 patients answered the Delphi questionnaire. A consensus was reached on all PROs regarding their relevance. Experts agreed on the use of ACT (A:95.24%; F:95.24%), mini AQLQ (A:93.65; F:79.37%), mMRC dyspnea scale (A:85.71%; F:85.71%), TAI (A:92.06%; F:85.71%), MMAS (A:75.40%; F:82%), and the dispensing register (A:96.83%; F:92.06%). Also considered suitable were: SNOT-22 (A:90.48%; F:73.80%), PSQI (A:82.54; F:63.90%), HADS (A:82.54; F:64%), WPAI (A:77.78%; F:49.20%), TSQM-9 (A:79.37; F:70.50%) and knowledge of asthma questionnaire (A:77%; F:68.80%); however, their use in clinical practice was considered unfeasible. Panelists also agreed on the appropriateness of EQ-5D, which was finally included despite being considered unfeasible (A: 84.13%; F:67.20%) in clinical practice. Agreement was reached on using ACT, TAI, mMRC, and a dispensing register every three months; mini-AQLQ and MMAS every six months; and EQ-5D every twelve months. CONCLUSION: This consensus paves the way toward patient-centered care, promoting the development of strategies supporting routine assessment of PROs in severe asthma management.
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Asma , Consenso , Técnica Delphi , Medidas de Resultados Relatados pelo Paciente , Humanos , Asma/terapia , Asma/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Índice de Gravidade de Doença , Inquéritos e Questionários , Qualidade de Vida , IdosoRESUMO
BACKGROUND: Due to the recent introduction of new biologic drugs for chronic migraine, a global evaluation in real clinical practice is necessary. OBJECTIVE: The objective was to evaluate the effectiveness and safety in real clinical practice of drugs targeting the calcitonin gene-related peptide receptor (CGRPr) in patients with chronic migraine. METHODS: Single-center, restrospective study (2019-2022), including patients with chronic migraine treated with erenumab, galcanezumab, or fremanezumab. Effectiveness variables were recorded, namely, number of migraine headache days per month (MHD), Migraine Disability Assessment Scale (MIDAS) score, and Headache Impact Test-6 (HIT-6) score, assessing changes at week 12, 24 from baseline. Toxicity was recorded following the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 criteria. RESULTS: In all, 104 patients were included (46.2% erenumab, 41.3% galcanezumab, 12.5% fremanezumab). A reduction in MHD, MIDAS, and HIT-6 was achieved at weeks 12 and 24 with erenumab (p75% at week 24 than those intensified; P = 0.041). There was no difference in efficacy (P = 0.154) or improvement in quality of life (P = 0.783, P = 0.150), but there was greater toxicity (P < 0.001) among nonresponders with erenumab 70 mg versus erenumab 140 mg. CONCLUSIONS: The results confirm the effectiveness and safety of anticalcitonin gene-related peptide (CGRP) drugs in real clinical practice. However, the study shows little benefit from erenumab intensification, with similar effectiveness and worse tolerability than the standard dose.
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Transtornos de Enxaqueca , Qualidade de Vida , Humanos , Transtornos de Enxaqueca/tratamento farmacológicoRESUMO
Acute inflammation is a key component of the immune system's response to pathogens, toxic agents, or tissue injury, involving the stimulation of defense mechanisms aimed to removing pathogenic factors and restoring tissue homeostasis. However, uncontrolled acute inflammatory response may lead to chronic inflammation, which is involved in the development of many diseases, including cancer. Nowadays, the need to find new potential therapeutic compounds has raised the worldwide scientific interest to study the marine environment. Specifically, microalgae are considered rich sources of bioactive molecules, such as carotenoids, which are natural isoprenoid pigments with important beneficial effects for health due to their biological activities. Carotenoids are essential nutrients for mammals, but they are unable to synthesize them; instead, a dietary intake of these compounds is required. Carotenoids are classified as carotenes (hydrocarbon carotenoids), such as α- and ß-carotene, and xanthophylls (oxygenate derivatives) including zeaxanthin, astaxanthin, fucoxanthin, lutein, α- and ß-cryptoxanthin, and canthaxanthin. This review summarizes the present up-to-date knowledge of the anti-inflammatory and anticancer activities of microalgal carotenoids both in vitro and in vivo, as well as the latest status of human studies for their potential use in prevention and treatment of inflammatory diseases and cancer.
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Anti-Inflamatórios/química , Antineoplásicos/química , Carotenoides/química , Microalgas , Animais , Organismos AquáticosRESUMO
Curcumin (Cur) is an anti-inflammatory polyphenol that can be complexed with polymeric cyclodextrin (CD) to improve solubility and bioavailability. The aim of the present work was to prepare a CurCD hydrogel to treat inflammatory skin conditions. Epichlorohydrin-ß-CD (EpißCD) was used as polymeric CD. To characterize the binary system, solid-state and in-solution studies were performed. Afterwards, an experimental design was performed to optimize the hydrogel system. Finally, the CurEpißCD hydrogel system was tested for anti-inflammatory activity using a HaCat psoriasis cell model. Co-grinded Cur/EpißCD binary system showed a strong interaction and Curcumin solubility was much improved. Its combination with Pluronic® F-127/hyaluronate hydrogel demonstrated an improvement in release rate and Curcumin permeation. After testing its anti-inflammatory activity, the system showed a significant reduction in IL-6 levels. Hydrogel-containing CurEpißCD complex is a great alternative to treat topical inflammatory diseases.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Curcumina/administração & dosagem , Portadores de Fármacos/química , Epicloroidrina/química , beta-Ciclodextrinas/química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Linhagem Celular , Curcumina/química , Curcumina/farmacologia , Liberação Controlada de Fármacos , Humanos , Psoríase/tratamento farmacológico , SolubilidadeRESUMO
Ultraviolet (UV) radiation harms the skin, causing oxidative damage, inflammation, and disruption of the skin's barrier function. There is considerable interest in identifying new natural ingredients with antioxidant and anti-inflammatory properties to serve as adjuvants in sunscreens. The flavonoid morin (1) can undergo structural modifications to enhance its biological properties. The aim of this study was to synthesize two new morin-Schiff base derivatives, morin oxime (2) and morin semicarbazone (3), comparing their photoprotective effects with that of the parent compound on UVB-exposed HaCaT keratinocytes. The chemical structure of the novel compounds was revealed based on spectroscopic data analysis. Our findings demonstrated that derivatives 2 and 3 enhanced the light absorption capability in the UV-visible (vis) range compared to 1. Tested compounds exhibited a higher scavenger capacity than Trolox. Moreover, pre-treatment with all compounds protected HaCaT cells from UVB-induced cell death. Compound 3 demonstrated the strongest antioxidant effect, reducing reactive oxygen species (ROS) generation and, subsequently, malondialdehyde (MDA) levels. Additionally, compounds 2 and 3 exhibited greater anti-inflammatory effects than compound 1, significantly reducing interleukin (IL)-6 production levels at all tested concentrations. These findings have demonstrated, for the first time, a promising photoprotective activity of two new Schiff base derivatives and suggest their use as natural sunscreen ingredients.
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The alteration of the gut microbiota mediated by proton pump inhibitor (PPI) drugs could be involved in the clinical response associated with immunotherapy [immunocheckpoint inhibitors (ICIs)] in cancer patients. Due to the current controversy in the scientific evidence, it has been proposed to evaluate the correlation between the concomitant use of PPIs and the effectiveness of immunotherapy in a real clinical practice setting. Single-center retrospective cohort study that included patients treated with anti-PD-1 or anti-CTLA4, including nivolumab, pembrolizumab, atezolizumab, or the combination ipilimumab-nivolumab in metastatic neoplastic disease. The clinical effectiveness of ICI, measured in progression-free survival (PFS) and overall survival (OS), was compared between the PPI-use versus PPI-no-use group. PPI-use group was associated with lower PFS [hazard ratio (HR):1.89 (1.38-2.59), P<0.001] and OS [HR: 2.02 (1.45-2.82), P<0.001] versus PPI-no-use group. However, this difference was not observed for pembrolizumab PFS [HR: 1.38 (0.93-2.39), P=0.160] and OS [HR: 1.41 (0.81-2.44), P=0.187]. The study showed significantly lower PFS and OS in the chronic PPI-use group (P<0.001), recent PPI-use group (P<0.001) and concomitant PPI-use group (P=0.001, 0.007) versus PPI-no-use group. However, late PPI use >30 days after the onset of ICI has no significant effect on the efficacy of treatment [HR: 0.92 (0.49-1.70), P=0.791; HR: 1.10 (0.59-2.05), P=0.756]. The concomitant use of PPIs in immunotherapy is associated with worse clinical outcomes compared with the group without PPI use. In addition, the study shows how the late use of PPIs does not have a significant effect on clinical benefit.
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OBJECTIVE: The purpose of this systematic review is to analyze the published data on the efficacy and safety of doses higher than 180 mg/m2 of irinotecan recommended in the drug's summary of product characteristics in metastatic colorectal cancer patients with genotypes UGT1A1*1/*1 or *1/*28 who are treated with the FOLFIRI regimen. METHOD: A systematic review of the literature was carried out in Medline and Embase searching for articles published up to December 2021. The methods used were based on the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The criteria for the inclusion of studies were previously defined based on the two secondary goals addressed in this review: 1) To analyze the magnitude of the differences in clinical responses and 2) To study the magnitude of the differences in adverse effects of irinotecan at high doses, as compared to the doses described in the summary of product characteristics corresponding to the FOLFIRI regimen in patients with metastatic colorectal cancer with genotypes UGT1A1*1/* 1 or *1/*28. RESULTS: The search yielded a total of 985 references, of which 13 were selected for analysis. Seven evaluated both efficacy and safety and six only safety. With regard to the studies that evaluated both efficacy and safety, six out of seven (85.7%) were in favor of increasing irinotecan dose according to the objective response rate and progression-free survival. Two of them even recommended dose increases based on overall survival. Irinotecan safety studies suggest that doses higher than 180 mg/m2 are tolerated by most UGT1A1*1/*1 and *1/*28 patients. CONCLUSIONS: The present systematic review shows the advisability of considering adjusting the dose of irinotecan when used as part of the FOLFIRI regimen based on the polymorphisms of the UGT1A1 gene as this may increase the likelihood of an adequate clinical response.
OBJETIVO: El objetivo de la presente revisión sistemática es analizar los datos publicados sobre la eficacia y seguridad de las dosis superiores a los 180 mg/m2 de irinotecán recomendadas en la ficha técnica en pacientes con cáncer colorrectal metastásico tratados con el esquema FOLFIRI y con genotipo UGT1A1*1/*1 y *1/*28.Método: Se realizó una revisión sistemática mediante una búsqueda bibliográfica en Medline y Embase de los artículos publicados hasta diciembre de 2021. Los métodos utilizados se basaron en los recomendados según Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Los criterios para la inclusión de los estudios se definieron previamente en base a los dos objetivos secundarios que aborda esta revisión: 1) Analizar la magnitud de la diferencia de la respuesta clínica y 2) estudiar la magnitud de la diferencia de los efectos dversos a irinotecán a dosis altas, en comparación con las dosis descritas en la ficha técnica para el esquema FOLFIRI en pacientes con cáncer colorrectal metastásico con el genotipo UGT1A1*1/*1 o *1/*28. RESULTADOS: La estrategia de búsqueda reportó un total de 98 referencias, de las que 13 fueron seleccionadas para el análisis, 7 (53,8%) evaluando tanto eficacia como seguridad y 6 (46,2%) únicamente seguridad. En relación con los estudios que evaluaron eficacia y seguridad, 6 (85,7%) se mostraron favorables al aumento de dosis en términos de tasa de respuesta objetiva y supervivencia libre de progresión e, incluso, en 2 de ellos en supervivencia global. Los estudios que evaluaron seguridad apuntan a que dosis de irinotecán superiores a 180 mg/m2 son toleradas por la mayor parte de los pacientes UGT1A1*1/*1 y *1/*28. CONCLUSIONES: La presente revisión sistemática muestra la conveniencia de valorar el ajuste de dosis de irinotecán dentro del esquema FOLFIRI en función de los polimorfismos del gen UGT1A1, con un potencial aumento de las probabilidades de una adecuada respuesta clínica.
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Camptotecina , Neoplasias Colorretais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fluoruracila/efeitos adversos , Genótipo , Glucuronosiltransferase/genética , Glucuronosiltransferase/uso terapêutico , Humanos , Irinotecano/efeitos adversos , Leucovorina/efeitos adversosRESUMO
BACKGROUND: People attending drug treatment centres have a high burden of hepatitis C virus (HCV) and face barriers to diagnosis and treatment. Dried blood spot (DBS) testing has been proposed to simplify diagnosis, but many patients remain untreated. In this retrospective study, we evaluated the reasons for non-retention in care in an intervention using on-site DBS testing and the effect of telemedicine and decentralized care compared to standard of care among people attending drug treatment centres who were lost to follow-up. METHODS: In a first phase, retention in care, adherence to treatment, and predictive factors in the DBS testing program of patients in drug treatment centres were analyzed and compared to a cohort of patients treated at the hospital outpatient clinic. Subsequently, in a second phase we evaluated in patients lost to follow-up from drug treatment centres the efficacy of one-step testing and telemedicine linked to a decentralized dispensation of HCV treatment or standard of care. RESULTS: Among 512 patients attending drug treatment centres, 467 (91.2%) agreed to be tested and 53.4% (237 patients/444 valid tests) tested positive (46 ± 9 years, 87.3% male) for HCV antibodies. After excluding patients negative for RNA or under surveillance, 178 patients were scheduled to meet with a specialist. Overall, 44 patients did not attend and 25 did not complete the pre-treatment evaluation. The only factor associated with retention in care was patient's knowledge of HCV infection. Treated patients attending drug treatment centres (n = 68) compared to the hospital outpatient clinic cohort (n = 135) had lower rates of treatment adherence. Among the patients who attended drug treatment centres that were lost to follow-up (n = 69), the proportion of patients who completed the program was significantly higher among those assisted by telemedicine than by standard of care (62.5% vs. 24.3%, p = 0.002). CONCLUSION: Although there was a high participation rate in a DBS testing program in drug treatment centres, non-retention in care is a challenge. Importantly, telemedicine linked to a decentralized dispensation of HCV treatment re-engages patients and may be effective for HCV microelimination.
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Hepatite C , Retenção nos Cuidados , Telemedicina , Feminino , Hepacivirus , Hepatite C/tratamento farmacológico , Humanos , Masculino , Estudos Retrospectivos , Centros de Tratamento de Abuso de SubstânciasRESUMO
OBJECTIVE: To describe our experience of administering bevacizumab doses at 0.5 mg/kg/min. The main objective of the study was to evaluate the safety of this regimen of administration. Secondary endpoints were to evaluate the cost saving and satisfaction of patients with the reduction in treatment delivery time. METHODS: The study included all patients who received bevacizumab therapy during 18 months. Time savings was calculated comparing time of normal-administration regimen (90-60-30 min) versus time with the new administration rate (0.5 mg/kg/min). Finally, importance of the reduction in the treatment delivery time for patients was surveyed. RESULTS: A total of 713 infusions (73 patients) were included in the study. Just one grade 1-HSR was observed and no high-grade HSRs occurred during the study period. The new infusion rate saved 14 980 min which means a saving of 26 940.30 (17 960.20 per year). A convenience sample of patients (25 patients) was interviewed, with an averaged in the importance of time savings by 8.8 points on the visual analogue scale. CONCLUSIONS: Our results show how this infusion rate of bevacizumab can be administered safely with benefit both for the patients and for the health systems by economic savings.
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BACKGROUND AND OBJECTIVES: Evaluate the relationship between the presence of polymorphisms in genes involved in the pharmacodynamics of irinotecan (UGT1A, SLCO1B1, ABCB1 and ABCC2) and the safety of irinotecan in the treatment of metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Prospective observational, single-centre study of 30 months duration, which included patients diagnosed with mCRC treated with FOLFIRI was carried out. Toxicity was evaluated in each treatment cycle according to the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0 NCI. Genomic DNA was obtained with a peripheral blood sample from an extraction method based on alkaline lysis. Genetic characterisation was performed using the LigthCycler®480 platform and allele-specific HybProbe® fluorescent probes. Analysed polymorphisms were: UGT1A1*28, UGT1A1*60, UGT1A7*1,*2,*3,*4, UGT1A7*12, UGT1A9*22, SLCO1B1 (rs11045879), ABCC2 (rs717620) and ABCB1 (rs1045642). RESULTS: Thirty-four patients were included (73.5% were male, mean age 59.9 years [27-81]) in the study. Polymorphisms rs8175347, rs17868323, rs3832043, rs11692021 and rs7577677 were associated with a higher incidence of adverse effects. Furthermore, it was observed that those patients with wild-type in UGT family genes analysed have lower rates of toxicity associated with irinotecan treatment than those with certain mutated allele (P=.010). CONCLUSIONS: These results suggest that the presence of certain polymorphisms in the UGT1A family of genes is related to the development of toxicity during treatment with irinotecan.