RESUMO
BACKGROUND: Onychomycosis (OM) is a common nail infection treated with amorolfine hydrochloride nail lacquer in China. Monitoring drug concentrations and using dermoscopy to evaluate treatment efficacy may provide new insights. OBJECTIVE: The study aims to analyse amorolfine concentrations in nails with mild to moderate OM, assess treatment outcomes using dermoscopy and explore factors influencing drug concentrations and efficacy. METHODS: Patients with mild to moderate OM confirmed by fungal microscopy were enrolled. Amorolfine nail lacquer was applied twice weekly for 36 weeks. Monthly nail samples measured amorolfine concentrations using liquid chromatography. Dermoscopy was performed before and after treatment to evaluate responses. Mixed-effects models and logistic regression analysed factors affecting drug concentrations and outcomes. RESULTS: Ninety-seven nails were included. Amorolfine concentrations increased over time, with higher levels in females, fingernails, 2nd-5th digits and superficial white OM (p < 0.05). Age was a risk factor, while drug concentration and OM type were protective for clinical efficacy (p < 0.05). Peak concentration correlated with clinical (r = 0.487, p = 0.000) and mycological (r = 0.433, p = 0.000) responses. Dermoscopic features improved significantly in successful cases (p < 0.05). LIMITATIONS: In the assessment of fungal efficacy, only fungal microscopy was used, and fungal cultures were not performed. The study was limited by a small sample size and the lack of a longer follow-up to assess relapse. CONCLUSION: Amorolfine concentrations vary with patient and nail characteristics, influencing efficacy. Dermoscopy is valuable for monitoring OM treatment.
Assuntos
Antifúngicos , Morfolinas , Unhas , Onicomicose , Humanos , Onicomicose/tratamento farmacológico , Onicomicose/microbiologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Antifúngicos/uso terapêutico , Antifúngicos/administração & dosagem , Resultado do Tratamento , Morfolinas/uso terapêutico , Morfolinas/administração & dosagem , Unhas/microbiologia , Idoso , Adulto Jovem , Modelos Logísticos , China , Dermoscopia , Análise Multivariada , AdolescenteRESUMO
PURPOSE: Excessive tachycardia in resuscitated septic shock patients can impair hemodynamics and worsen patient outcome. We investigated whether heart rate (HR) control can be achieved without increased vasopressor requirements using the titratable highly selective, ultra-short-acting ß1-blocker landiolol. METHODS: This randomized, open-label, controlled trial was conducted at 20 sites in 7 European countries from 2018 to 2022 and investigated the efficacy and safety of landiolol in adult patients with septic shock and persistent tachycardia. Patients were randomly assigned to receive either landiolol along with standard treatment (n = 99) or standard treatment alone (n = 101). The combined primary endpoint was HR response (i.e., HR within the range of 80-94 beats per minute) and its maintenance without increasing vasopressor requirements during the first 24 h after treatment start. Key secondary endpoints were 28-day mortality and adverse events. RESULTS: Out of 196 included septic shock patients, 98 received standard treatment combined with landiolol and 98 standard treatment alone. A significantly larger proportion of patients met the combined primary endpoint in the landiolol group than in the control group (39.8% [39/98] vs. 23.5% [23/98]), with a between-group difference of 16.5% (95% confidence interval [CI]: 3.4-28.8%; p = 0.013). There were no statistically significant differences between study groups in tested secondary outcomes and adverse events. CONCLUSION: The ultra-short-acting beta-blocker landiolol was effective in reducing and maintaining HR without increasing vasopressor requirements after 24 h in patients with septic shock and persistent tachycardia. There were no differences in adverse events and clinical outcomes such as 28-day mortality vs. standard of care. The results of this study, in the context of previous trials, do not support a treatment strategy of stringent HR reduction (< 95 bpm) in an unselected septic shock population with persistent tachycardia. Further investigations are needed to identify septic shock patient phenotypes that benefit clinically from HR control.
Assuntos
Frequência Cardíaca , Morfolinas , Choque Séptico , Taquicardia , Ureia , Humanos , Choque Séptico/tratamento farmacológico , Choque Séptico/complicações , Choque Séptico/fisiopatologia , Masculino , Feminino , Pessoa de Meia-Idade , Ureia/análogos & derivados , Ureia/uso terapêutico , Ureia/farmacologia , Taquicardia/tratamento farmacológico , Taquicardia/fisiopatologia , Taquicardia/complicações , Idoso , Frequência Cardíaca/efeitos dos fármacos , Morfolinas/uso terapêutico , Morfolinas/farmacologia , Europa (Continente)RESUMO
Membranous nephropathy (MN) is a common pathological type of adult nephrotic syndrome. Up to 20% of patients with MN develop end-stage renal disease (ESRD). Podocytes have an important function in maintaining the glomerular filtration barrier and play a crucial role in the occurrence and development of proteinuria and MN. PI3K/AKT signaling pathway is involved in the entire process of podocyte growth, differentiation, and apoptosis. Kemeng Fang (KMF) is a traditional Chinese medicine formula that has been used to delay kidney injury. However, the therapeutic mechanism of KMF in MN is unclear. Here, the MN rat model was established by axillary, inguinal, and tail vein injections of cationized bovine serum albumin (C-BSA), and then KMF and PI3K inhibitor (LY294002) were administered. The data of liver function, kidney function, blood lipid, renal pathology, podocyte function, expression level of PI3K/AKT signaling pathway, and transcriptomics of rats demonstrated that KMF has a protective effect on the podocytes of MN rats by activating the PI3K/AKT signaling pathway, and it can effectively prevent the progression of MN.
Assuntos
Apoptose , Medicamentos de Ervas Chinesas , Glomerulonefrite Membranosa , Fosfatidilinositol 3-Quinases , Podócitos , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Animais , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/metabolismo , Podócitos/efeitos dos fármacos , Podócitos/metabolismo , Podócitos/patologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Masculino , Ratos Sprague-Dawley , Morfolinas/farmacologia , Morfolinas/uso terapêutico , Cromonas/farmacologia , Modelos Animais de DoençasRESUMO
OBJECTIVE: Thumbtack Needling (TN) has been employed in the treatment of functional constipation (FC), although the existing evidence supporting its effectiveness is limited. This study is to evaluate the efficacy of TN in ameliorating FC. METHOD: A total of 482 eligible patients were recruited and randomly assigned to the TN group or the Mosapride Citrate (MC) group. The TN was buried once for three days, rest for one day after two consecutive burials, followed by a 4-week follow-up. The primary outcome measure was the score for Complete and spontaneous bowel movement score (CSBMs). Secondary outcome measures included the Bristol Stool Form Scale (BSFS), Cleveland Clinic Score (CCS), and the Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL). RESULTS: Out of the 482 patients randomized, 241 were allocated to each group. Of these, 216 patients (89.6 %) in both groups completed the intervention and follow-up. Compared with the baseline, the differences of CSBMs in TN group [1.76(95 % CI, 1.61 to 1.91)] and MC group [1.35(95 % CI, 1.20 to 1.50)] at week 4 meet the threshold for minimal clinically important difference (MCID). However, there were no clinical difference from baseline at week 2 and week 8 in both groups. Mean CSBMs at week 4 was 3.35 ± 0.99 in the TN group and 3 ± 1.03 in the MC group (adjusted difference between groups, 0.37 points [95 % CI, 0.18 to 0.55]; P < 0.001), although differences between the two groups did not meet the MCID threshold. CONCLUSION: Compared with mosapride citrate, thumbtack needling produced a greater improvement in CSBMs, although the difference from control was not clinically significant. GOV IDENTIFIER: ChiCTR2100043684.
Assuntos
Constipação Intestinal , Qualidade de Vida , Humanos , Constipação Intestinal/terapia , Constipação Intestinal/tratamento farmacológico , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Morfolinas/uso terapêutico , Terapia por Acupuntura/métodos , Benzamidas/uso terapêutico , Inquéritos e Questionários , Agulhas , Resultado do TratamentoRESUMO
Cardiac remodeling in rats with post-infarction chronic heart failure caused by anterior transmural myocardial infarction leads to an atypical location of areas of positive and negative cardioelectric potentials on the body surface before the onset of the PII-wave on the ECG in the limb leads, which is a sign of increased heterogeneity of atrial depolarization associated with the appearance of additional excitation focus in the left atrium. A course of therapy with fabomotizole leads to a decrease in the heterogeneity of atrial depolarization at the initial stages of the formation of the cardioelectric field of the atria on the body surface before the onset of the PII-wave, thereby producing an antiarrhythmic effect.
Assuntos
Mapeamento Potencial de Superfície Corporal , Átrios do Coração , Insuficiência Cardíaca , Infarto do Miocárdio , Animais , Ratos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/complicações , Átrios do Coração/efeitos dos fármacos , Átrios do Coração/fisiopatologia , Masculino , Mapeamento Potencial de Superfície Corporal/métodos , Morfolinas/farmacologia , Morfolinas/uso terapêutico , Eletrocardiografia , Ratos Wistar , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Antiarrítmicos/uso terapêutico , Antiarrítmicos/farmacologiaRESUMO
This retrospective cohort study analyzed data from a Japanese health insurance database to assess the effectiveness of baloxavir (n = 4822) for preventing severe events compared with oseltamivir (n = 10,523) in patients with influenza B. The primary endpoint was hospitalization incidence (Days 2-14). The secondary endpoints included intravenous antibacterial drug use, pneumonia hospitalization, heart failure hospitalization, inhalational oxygen requirement, and use of other anti-influenza drugs. The hospitalization incidence was significantly lower with baloxavir (0.15% vs. 0.37%; risk ratio: 2.48, 95% confidence interval: 1.13-5.43). Pneumonia and additional anti-influenza therapy were also less frequent with baloxavir, thus supporting its use. Trial Registration: UMIN Clinical Trials Registry Study ID: UMIN000051382.
Assuntos
Antivirais , Dibenzotiepinas , Vírus da Influenza B , Influenza Humana , Morfolinas , Oseltamivir , Pacientes Ambulatoriais , Piridonas , Triazinas , Humanos , Influenza Humana/tratamento farmacológico , Dibenzotiepinas/uso terapêutico , Oseltamivir/uso terapêutico , Antivirais/uso terapêutico , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Adulto , Piridonas/uso terapêutico , Morfolinas/uso terapêutico , Triazinas/uso terapêutico , Idoso , Vírus da Influenza B/efeitos dos fármacos , Adulto Jovem , Adolescente , Hospitalização/estatística & dados numéricos , Criança , Piridinas/uso terapêutico , Japão/epidemiologia , Pré-Escolar , Resultado do Tratamento , Lactente , Idoso de 80 Anos ou maisRESUMO
Fibroblast Growth Factor Receptors (FGFRs) are emerging as key factors involved in tumorigenesis, tumor microenvironment remodeling and acquired resistance to targeted therapies. Pemigatinib is a Tyrosine-Kinase Inhibitor that selectively targets aberrant FGFR1, FGFR2 and FGFR3. Pemigatinib is now approved for advanced-stage cholangiocarcinoma (CCA) but data suggests that other tumor histotypes exhibit FGFR alterations, thus hypothesizing its potential efficacy in other cancer settings. The present systematic review, based on PRISMA guidelines, aims to synthetize and critically interpret the results of all available preclinical and clinical evidence regarding Pemigatinib use in cancer. In April 2024, an extensive search was performed in PubMed, MEDLINE, and Scopus databases using the keyword "Pemigatinib". Twenty-seven studies finally met all inclusion criteria. The promising results emerging from Pemigatinib preclinical and clinical studies pave the way for Pemigatinib extension to multiple solid cancer settings.
Assuntos
Pirimidinas , Receptores de Fatores de Crescimento de Fibroblastos , Animais , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Terapia de Alvo Molecular/métodos , Morfolinas/farmacologia , Morfolinas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Medicina de Precisão/métodos , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Pirróis/farmacologia , Pirróis/uso terapêutico , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Resultado do Tratamento , /uso terapêuticoRESUMO
BACKGROUND AND OBJECTIVE: Neuropathic pain is a chronic condition characterized by aberrant signaling within the somatosensory system, affecting millions of people worldwide with limited treatment options. Herein, we aim at investigating the potential of a sigma-1 receptor (σ1R) antagonist in managing neuropathic pain. METHODS: A Chronic Constriction Injury (CCI) model was used to induce neuropathic pain. The potential of (+)-MR200 was evaluated following daily subcutaneous injections of the compound. Its mechanism of action was confirmed by administration of a well-known σ1R agonist, PRE084. RESULTS: (+)-MR200 demonstrated efficacy in protecting neurons from damage and alleviating pain hypersensitivity in CCI model. Our results suggest that (+)-MR200 reduced the activation of astrocytes and microglia, cells known to contribute to the neuroinflammatory process, suggesting that (+)-MR200 may not only address pain symptoms but also tackle the underlying cellular mechanism involved. Furthermore, (+)-MR200 treatment normalized levels of the gap junction (GJ)-forming protein connexin 43 (Cx43), suggesting a reduction in harmful intercellular communication that could fuel the chronicity of pain. CONCLUSIONS: This approach could offer a neuroprotective strategy for managing neuropathic pain, addressing both pain symptoms and cellular processes driving the condition. Understanding the dynamics of σ1R expression and function in neuropathic pain is crucial for clinical intervention.
Assuntos
Conexina 43 , Neuralgia , Receptores sigma , Receptor Sigma-1 , Receptores sigma/metabolismo , Receptores sigma/agonistas , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Animais , Masculino , Conexina 43/metabolismo , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Comunicação Celular/efeitos dos fármacos , Dor Crônica/tratamento farmacológico , Dor Crônica/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Ratos Sprague-Dawley , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Nervo Isquiático/lesões , Morfolinas/farmacologia , Morfolinas/uso terapêuticoRESUMO
OBJECTIVES: Immunocompromised patients may experience prolonged shedding of influenza virus potentially leading to severe infections. Alternatives to monotherapy with neuraminidase inhibitors should be evaluated to entirely suppress viral replication and prevent drug-resistant mutations. METHODS: We investigated the clinical and virological evolution in a case of persistent influenza A and human coronavirus OC43 (HCoV-OC43) coinfection in a hematopoietic stem cell transplant recipient after different therapeutic strategies. RESULTS: Successive oseltamivir and zanamivir monotherapies failed to control both infections, with positive results persisting for over 110 days each. This led to the emergence of highly resistant oseltamivir strains due to neuraminidase mutations (E119V and R292K) followed by a deletion (del245-248), while maintaining sensitivity to zanamivir. The intra-host viral diversity data showed that the treatments impacted viral diversity of influenza virus, but not of HCoV-OC43. Considering the patient's underlying condition and the impact of prolonged viral shedding on pulmonary function, eradicating the influenza virus was necessary. A 10-day regimen combining zanamivir and baloxavir-marboxil effectively controlled influenza virus replication and was associated with the clearance of HCoV-OC43, finally resulting in comprehensive respiratory recovery. CONCLUSION: These observations underscore the importance of further investigating combination treatments as the primary approach to achieve influenza eradication in immunocompromised patients.
Assuntos
Antivirais , Dibenzotiepinas , Transplante de Células-Tronco Hematopoéticas , Influenza Humana , Morfolinas , Piridonas , Triazinas , Zanamivir , Humanos , Zanamivir/uso terapêutico , Zanamivir/farmacologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Antivirais/uso terapêutico , Antivirais/farmacologia , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Piridonas/uso terapêutico , Dibenzotiepinas/uso terapêutico , Morfolinas/uso terapêutico , Triazinas/uso terapêutico , Triazinas/farmacologia , Coronavirus Humano OC43/efeitos dos fármacos , Coronavirus Humano OC43/genética , Farmacorresistência Viral/genética , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/genética , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Hospedeiro Imunocomprometido , Masculino , Quimioterapia Combinada , Pessoa de Meia-Idade , Eliminação de Partículas Virais/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , FemininoRESUMO
Fostamatinib is a spleen tyrosine kinase inhibitor indicated for the treatment of chronic immune thrombocytopenia (ITP) unresponsive to a previous treatment. Real-world studies evaluating the utilization and effectiveness of fostamatinib outside the context of a clinical trial are lacking. The objective of this analysis was to evaluate the effectiveness of fostamatinib for the treatment of ITP in a real-world cohort. We conducted a single-center, retrospective, observational study to evaluate the effectiveness of fostamatinib for the treatment of ITP. The primary endpoint was durable response as defined by the American Society of Hematology ITP response criteria. Secondary endpoints included overall response rate, time to response, and safety. Subgroup analysis was performed to assess frequency of durable response in key subgroups of patients based on prior therapies. Thirty-one patients treated with fostamatinib for ITP were included in our analysis. Patients had received a median of four prior lines of therapy. Ten patients (32%) achieved a durable response. Most durable responders maintained their response at 24 months ( n â=â7; 70%). The median time to response was 9âdays. Four patients (13%) discontinued fostamatinib due to an adverse event. Subgroups who had higher rates of durable responses included those who had received two to three prior lines of therapy (40%), splenectomized patients (50%), and those who had not received prior rituximab (55%). Fostamatinib therapy in a real-world population of patients with heavily pretreated ITP led to a durable response in a third of patients, which was maintained for most responders.
Assuntos
Aminopiridinas , Morfolinas , Oxazinas , Púrpura Trombocitopênica Idiopática , Humanos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Oxazinas/uso terapêutico , Morfolinas/uso terapêutico , Aminopiridinas/uso terapêutico , Idoso , Adulto , Resultado do Tratamento , Pirimidinas/uso terapêutico , Doença Crônica , Piridinas/uso terapêutico , Compostos Organofosforados/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Idoso de 80 Anos ou maisAssuntos
Antieméticos , Aprepitanto , Gastrectomia , Laparoscopia , Obesidade Mórbida , Náusea e Vômito Pós-Operatórios , Humanos , Aprepitanto/uso terapêutico , Náusea e Vômito Pós-Operatórios/prevenção & controle , Antieméticos/uso terapêutico , Gastrectomia/efeitos adversos , Obesidade Mórbida/cirurgia , Morfolinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Pandemic influenza poses a recurring threat to public health. Antiviral drugs are vital in combating influenza pandemics. Baloxavir marboxil (BXM) is a novel agent that provides clinical and public health benefits in influenza treatment. METHODS: We constructed a linked dynamic transmission-economic evaluation model combining a modified susceptible-exposed-infected-recovered (SEIR) model and a decision tree model to evaluate the cost-effectiveness of adding BXM to oseltamivir in China's influenza pandemic scenario. The cost-effectiveness was evaluated for the general population from the Chinese healthcare system perspective, although the users of BXM and oseltamivir were influenza-infected persons. The SEIR model simulated the transmission dynamics, dividing the population into four compartments: susceptible, exposed, infected, and recovered, while the decision tree model assessed disease severity and costs. We utilized data from clinical trials and observational studies in the literature to parameterize the models. Costs were based on 2021 CN¥ and not discounted due to a short time-frame of one year in the model. One-way, two-way, and probabilistic sensitivity analyses were also conducted. RESULTS: The integrated model demonstrated that adding BXM to treatment choices reduced the cumulative incidence of infection from 49.49% to 43.26% and increased quality-adjusted life years (QALYs) by 0.00021 per person compared with oseltamivir alone in the base-case scenario. The intervention also amounted to a positive net monetary benefit of CN¥77.85 per person at the willingness to pay of CN¥80,976 per QALY. Sensitivity analysis confirmed the robustness of these findings, with consistent results across varied key parameters and assumptions. CONCLUSIONS: Adding BXM to treatment choices instead of only treating with oseltamivir for influenza pandemic control in China appears to be cost-effective compared with oseltamivir alone. The dual-agent strategy not only enhances population health outcomes and conserves resources, but also mitigates influenza transmission and alleviates healthcare burden.
Assuntos
Antivirais , Análise Custo-Benefício , Dibenzotiepinas , Influenza Humana , Modelos Econômicos , Morfolinas , Oseltamivir , Pandemias , Piridonas , Triazinas , Humanos , Oseltamivir/economia , Oseltamivir/uso terapêutico , Influenza Humana/economia , Influenza Humana/prevenção & controle , Influenza Humana/tratamento farmacológico , Influenza Humana/epidemiologia , Antivirais/economia , Antivirais/uso terapêutico , China/epidemiologia , Piridonas/economia , Piridonas/uso terapêutico , Triazinas/economia , Triazinas/uso terapêutico , Dibenzotiepinas/uso terapêutico , Dibenzotiepinas/economia , Morfolinas/economia , Morfolinas/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida , Saúde Pública/economia , Árvores de Decisões , Tiepinas/uso terapêutico , Tiepinas/economia , Análise de Custo-EfetividadeAssuntos
Bexaroteno , Proteínas Proto-Oncogênicas c-ret , Humanos , Bexaroteno/uso terapêutico , Bexaroteno/farmacologia , Proteínas Proto-Oncogênicas c-ret/genética , Pirazóis/uso terapêutico , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/genética , Antineoplásicos/uso terapêutico , Tetra-Hidronaftalenos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Mutação , Piridinas/uso terapêutico , Proteínas Proto-Oncogênicas c-met/genética , Aprovação de Drogas , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/patologia , Pirimidinas/uso terapêutico , Morfolinas/uso terapêutico , Tiazóis/uso terapêutico , Tiazóis/farmacologia , Éxons , BenzamidasRESUMO
Immune thrombocytopenia is caused by autoantibodies against surface antigens on platelets. Since only about 50â% of cases will allow the identification of glycoprotein-specific antibodies, ITP remains a diagnosis of exclusion. Apart from EDTA-induced pseudo thrombocytopenia, other diseases like secondary thrombocytopenia due to medication, a large number of other disease and hereditary thrombocytopenias must be taken into account. The first-line therapy of ITP includes corticosteroids and intravenous immunoglobulins. The second line consists of thrombopoietin receptor agonists, rituximab, or splenectomy. For further lines of therapy, Fostamatinib and non-steroidal immunosuppressives are available.
Assuntos
Púrpura Trombocitopênica Idiopática , Esplenectomia , Humanos , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/terapia , Diagnóstico Diferencial , Corticosteroides/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Imunossupressores/efeitos adversos , Rituximab/uso terapêutico , Rituximab/efeitos adversos , Morfolinas/uso terapêutico , Morfolinas/efeitos adversosRESUMO
Baloxavir marboxil (baloxavir), approved as an anti-influenza drug in Japan in March 2018, can induce reduced therapeutic effectiveness due to PA protein substitutions. We assessed PA substitutions in clinical samples from influenza-infected children and adults pre- and post-baloxavir treatment, examining their impact on fever and symptom duration. During the 2022-2023 influenza season, the predominant circulating influenza subtype detected by cycling-probe RT-PCR was A(H3N2) (n = 234), with a minor circulation of A(H1N1)pdm09 (n = 10). Of the 234 influenza A(H3N2) viruses collected prior to baloxavir treatment, 2 (0.8%) viruses carry PA/I38T substitution. One virus was collected from a toddler and one from an adult, indicating the presence of viruses with reduced susceptibility to baloxavir, without prior exposure to the drug. Of the 54 paired influenza A(H3N2) viruses collected following baloxavir treatment, 8 (14.8%) viruses carried E23 K/G, or I38 M/T substitutions in PA. Variant calling through next-generation sequencing (NGS) showed varying proportions (6-100 %), a polymorphism and a mixture of PA/E23 K/G, and I38 M/T substitutions in the clinical samples. These eight viruses were obtained from children aged 7-14 years, with a median fever duration of 16.7 h and a median symptom duration of 93.7 h, which were similar to those of the wild type. However, the delayed viral clearance associated with the emergence of PA substitutions was observed. No substitutions conferring resistance to neuraminidase inhibitors were detected in 37 paired samples collected before and following oseltamivir treatment. These findings underscore the need for ongoing antiviral surveillance, informing public health strategies and clinical antiviral recommendations for seasonal influenza.
Assuntos
Substituição de Aminoácidos , Antivirais , Dibenzotiepinas , Farmacorresistência Viral , Vírus da Influenza A Subtipo H3N2 , Influenza Humana , Morfolinas , Piridonas , Triazinas , Proteínas Virais , Humanos , Dibenzotiepinas/uso terapêutico , Dibenzotiepinas/farmacologia , Influenza Humana/tratamento farmacológico , Influenza Humana/virologia , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/efeitos dos fármacos , Vírus da Influenza A Subtipo H3N2/enzimologia , Triazinas/uso terapêutico , Triazinas/farmacologia , Japão , Antivirais/farmacologia , Antivirais/uso terapêutico , Morfolinas/uso terapêutico , Farmacorresistência Viral/genética , Criança , Adulto , Pré-Escolar , Adolescente , Proteínas Virais/genética , RNA Polimerase Dependente de RNA/genética , Feminino , Masculino , Tiepinas/uso terapêutico , Tiepinas/farmacologia , Lactente , Pessoa de Meia-Idade , Estações do Ano , Piridinas/uso terapêutico , Piridinas/farmacologia , Adulto Jovem , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , IdosoAssuntos
Cirurgia Bariátrica , Rivaroxabana , Humanos , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/métodos , Rivaroxabana/uso terapêutico , Rivaroxabana/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Morfolinas/uso terapêutico , Morfolinas/administração & dosagem , Tiofenos/uso terapêutico , Tiofenos/administração & dosagemRESUMO
Diabetes mellitus is a severe endocrine disease that affects more and more people every year. Modern medical chemistry sets itself the task of finding effective and safe drugs against diabetes. This review provides an overview of potential antidiabetic drugs based on three heterocyclic compounds, namely morpholine, piperazine, and piperidine. Studies have shown that compounds containing their moieties can be quite effective in vitro and in vivo for the treatment of diabetes and its consequences.
Assuntos
Hipoglicemiantes , Morfolinas , Piperazina , Piperidinas , Humanos , Piperidinas/química , Piperidinas/farmacologia , Piperidinas/uso terapêutico , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Morfolinas/química , Morfolinas/farmacologia , Morfolinas/uso terapêutico , Piperazina/química , Piperazina/farmacologia , Animais , Piperazinas/química , Piperazinas/farmacologia , Piperazinas/síntese química , Piperazinas/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Relação Estrutura-AtividadeAssuntos
Antieméticos , Aprepitanto , Gastrectomia , Laparoscopia , Obesidade Mórbida , Náusea e Vômito Pós-Operatórios , Humanos , Aprepitanto/uso terapêutico , Náusea e Vômito Pós-Operatórios/prevenção & controle , Antieméticos/uso terapêutico , Gastrectomia/efeitos adversos , Obesidade Mórbida/cirurgia , Morfolinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Immune thrombocytopenia (ITP) is an immune-mediated disease that results in low platelet counts. Despite appropriate treatment, many patients continue to experience refractory disease. Fostamatinib, an oral spleen tyrosine kinase (SYK) inhibitor, has emerged as a promising option for refractory ITP. OBJECTIVE: This meta-analysis aims to evaluate the efficacy and safety of fostamatinib compared to conventional therapy in adults aged ≥ 18 years with refractory ITP. MATERIALS AND METHODS: Literature search was conducted in PubMed, Scopus, Embase, and clinicaltrials.gov databases from inception to March 31, 2024. Randomized controlled trials (RCTs) assessing the safety and efficacy of fostamatinib in adults with refractory ITP were included. Data extraction, risk of bias assessment, and statistical analysis were performed following PRISMA guideline. RESULTS: A total of 495 articles were screened, with three RCTs meeting the inclusion criteria. Fostamatinib therapy demonstrated superior efficacy in achieving stable platelet response by week 24 (ORR 0.80; 95%CI 0.72-0.88), platelet count ≥ 50,000/µL at weeks 12 (ORR 0.80; 95%CI 0.72-0.90) and week 24 (ORR 0.82; 95%CI 0.72-0.90). Additionally, fostamatinib improves platelet counts in subjects with a baseline count of < 15,000/µL. The Number Needed to Treat (NNT) was calculated as 10. Adverse effects include diarrhea (RR 2.32; 95%CI 1.11-4.84), hypertension (RR 2.33; 95%CI 1.00-5.43), and abnormal liver function tests (RR 4.18; 95% CI 1.00-17.48). Interestingly, the occurrences of nausea (RR 1.77; 95% CI 0.33-9.67) and rash (RR 2.28; 95% CI 0.50-10.29) did not achieve statistical significance. CONCLUSION: This meta-analysis provides robust evidence supporting the efficacy of fostamatinib in improving platelet counts and achieving therapeutic goals in adults with refractory ITP. However, fostamatinib's safety profile warrants consideration due to higher rates of diarrhea, hypertension, and abnormal liver function tests.
Assuntos
Aminopiridinas , Morfolinas , Oxazinas , Púrpura Trombocitopênica Idiopática , Piridinas , Pirimidinas , Adulto , Humanos , Aminopiridinas/uso terapêutico , Aminopiridinas/efeitos adversos , Morfolinas/uso terapêutico , Morfolinas/efeitos adversos , Oxazinas/uso terapêutico , Oxazinas/efeitos adversos , Contagem de Plaquetas , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/sangue , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Quinase Syk/antagonistas & inibidores , Resultado do TratamentoRESUMO
INTRODUCTION: This study aims to evaluate the effectiveness of aprepitant in preventing postoperative nausea and vomiting (PONV) following metabolic bariatric surgery (MBS). METHODS: Clinical trials meeting the inclusion criteria were identified through searches of PubMed, Embase, and the Cochrane Library databases, as well as clinical trials registered at clinicaltrials. gov. These trials compared aprepitant with the control or placebo groups among patients who underwent MBS. Meta-analysis was performed using StataSE 17.0 software to calculate the pooled risk ratio (RR) and its 95% confidence interval (CI) to assess the effectiveness of aprepitant in preventing PONV following MBS. RESULTS: A total of five articles comprising six studies including 929 patients undergoing MBS were included. Meta-analysis revealed a significant reduction in the incidence of PONV among patients receiving aprepitant (pooled RR = 0.51, 95% CI: 0.38-0.68, P < 0.05). Subgroup analysis indicated that aprepitant effectively reduced PONV incidence at 0, 6, and 12 h postoperatively in patients with MBS, but did not decrease PONV occurrence at 24 and 48 h postoperatively. CONCLUSION: Aprepitant demonstrated significant clinical efficacy in preventing PONV following MBS, effectively reducing patient discomfort, and improving postoperative recovery. Therefore, aprepitant should be considered a preventive measure in patients undergoing MBS to enhance patient satisfaction and recovery rates. Additionally, to maintain an effective drug concentration, aprepitant should be administered within the first 24 h postoperatively. PROSPERO REGISTRATION: CRD 42024528154.