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1.
Clin Appl Thromb Hemost ; 28: 10760296221124902, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36112808

RESUMEN

BACKGROUND: Dual antiplatelet therapy (DAPT) is recommended over single antiplatelet therapy (SAPT) in patients following coronary artery bypass grafting (CABG). The compilation of evidence has focused on the efficacy of DAPT to limit risk of graft occlusion, however the safety, especially in the on-pump CABG population, is less well described. The aim of this study was to assess the safety of DAPT versus SAPT after on-pump CABG. METHODS: This was a single-center, retrospective cohort analysis of adult patients following isolated on-pump CABG between January 2012 and December 2019 not on oral anticoagulation at discharge. The primary endpoint was occurrence of a composite bleeding event identified by pre-specified ICD codes. Secondary endpoints consisted of 30-day and 1-year mortalities along with individual bleeding components. RESULTS: Of the 2341 patients included 1250 patients were in the SAPT arm and 1091 patients in the DAPT arm. The study populations differed by age, prior MI, PAD, and CHF status/stage. Bleeding events occurred in a total of 70 patients (3.0%), with 36 patients (2.9%) in the SAPT arm and 34 patients (3.1%) in the DAPT arm (P = .74). 30-day (SAPT 0.7% vs DAPT 0.4%) and 1-year (SAPT 3.3% vs DAPT 2.3%) mortality were not significantly different between groups. The most frequent bleed event was in the gastrointestinal tract. CONCLUSION: In this study, DAPT was not associated with an increase in composite bleeding compared to SAPT. This study could reduce the barrier to prescribing of DAPT given previous efficacy data.


Asunto(s)
Aspirina , Inhibidores de Agregación Plaquetaria , Anticoagulantes/uso terapéutico , Aspirina/efectos adversos , Puente de Arteria Coronaria/efectos adversos , Quimioterapia Combinada , Hemorragia/etiología , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Retrospectivos
2.
Artículo en Inglés | MEDLINE | ID: mdl-36074445

RESUMEN

Despite the high sustained virologic response (SVR) rates of direct-acting antiviral (DAAs) therapy, a small number of patients does not eradicate the virus, and these patients represent a challenge. This study aims to compare the outcomes of three second-line regimens for DAAs-experienced patients with chronic hepatitis C (CHC). This prospective observational study was conducted at the Damanhur Viral Hepatitis Center from January 2017 to February 2020. We included patients with CHC who did not achieve SVR after the complete course of Sofosbuvir/Daclatasvir±Ribavirin (SOF/DAC±RBV). The primary endpoint was SVR-12 after re-treatment. This study included 360 patients (with a mean age of 51.53±11.38 years). Approximately 51.1% of the patients were males, and 65.5% had liver cirrhosis. All patients of group 1 (45 patients) received SOF/VEL/VOX over 12-weeks; SVR-12 was achieved in 44 patients (97.8%). Group 2 (28 patients) received SOF/DAC/RBV over 24-weeks; (one patient was lost during follow-ups and one patient discontinued treatment due to hepatic decompensation). SVR-12 was achieved in 25 patients (96.2%). Group 3 (287 patients) received SOF/Ombitasvir/Paritaprevir/Ritonavir/RBV) over 12-weeks. Eight patients were lost during follow-ups, and one patient discontinued treatment due to grade 4 adverse events. SVR-12 was achieved in 276 patients (99.3%). There was no difference between the groups regarding their age, gender distribution, baseline viral load or comorbidities. Adverse events (thrombocytopenia, anemia, hyperbilirubinaemia and prolonged INR) were significantly higher in group 3, while group 1 did not experience any. The three studied retreatment regimens can be used for DAAs treatment-experienced patients considering availability. The SOF/VEL/VOX combination had the least adverse events.


Asunto(s)
Hepatitis C Crónica , Sofosbuvir , Adulto , Antivirales/efectos adversos , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Ribavirina/uso terapéutico , Insuficiencia del Tratamiento , Resultado del Tratamiento
3.
Int J Mol Sci ; 23(17)2022 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-36077436

RESUMEN

The most commonly used antiviral treatment against hepatitis C virus is a combination of direct-acting antivirals (DAAs) and ribavirin (RBV), which leads to a shortened duration of therapy and a sustained virologic response until 98%. Nonetheless, several dose-related side effects of RBV could limit its applications. This study aims to measure the urinary concentration of RBV and its main metabolites in order to evaluate the drug metabolism ability of HCV patients and to evaluate the adverse effects, such as anemia, with respect to RBV metabolite levels. RBV and its proactive and inactive metabolites were identified and quantified in the urine of 17 HCV males with severe liver fibrosis using proton nuclear magnetic resonance (1H-NMR) at the fourth week (TW4) and at the twelfth week of treatment (EOT). Four prodrug urinary metabolites, including RBV, were identified and three of them were quantified. At both the TW4 and EOT stages, six HCV patients were found to maintain high concentrations of RBV, while another six patients maintained a high level of RBV proactive metabolites, likely due to nucleosidase activity. Furthermore, a negative correlation between the reduction in hemoglobin (Hb) and proactive forms was observed, according to RBV-triphosphate accumulation causing the hemolysis. These findings represent a proof of concept regarding tailoring the drug dose in relation to the specific metabolic ability of the individual, as expected by the precision medicine approach.


Asunto(s)
Hepatitis C Crónica , Hepatitis C , Antivirales/efectos adversos , Quimioterapia Combinada , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Masculino , Medicina de Precisión , Proteínas Recombinantes/farmacología , Ribavirina/efectos adversos , Resultado del Tratamiento
4.
Comput Math Methods Med ; 2022: 2233138, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36060654

RESUMEN

Background: Carboprost tromethamine injection has a high safety factor in clinical application and has a good effect on uterine smooth muscle and vasoconstriction. Carboprost aminobutyriol combined with oxytocin may be beneficial to infant outcome and uterine involution after cesarean section. Objective: To investigate the effects of carboprost tromethamine combined with oxytocin on infant outcome, postpartum hemorrhage, and uterine involution in parturients undergoing cesarean section. Methods: A total of 120 parturients undergone cesarean section in our hospital from February 2019 to April 2021 were selected as the object of study. The parturients were randomly divided into control group (n = 60) and research group (n = 60). The control group was treated with oxytocin, and the research group was treated with carboprost aminobutyriol combined with oxytocin. The amount of maternal bleeding, uterine floor decline index, the end of lochia, poor rate of uterine involution, infant outcome, and the incidence of adverse drug reactions were compared between the two groups. Results: The amount of bleeding in the research group was significantly lower than that in the control group (P < 0.05). The position of the last uterine floor and the index of uterine floor downward movement in the research group were significantly higher than those in the control group (P < 0.05). The disappearance time of bloody lochia and serous lochia in the research group was significantly shorter than that in the control group (P < 0.05). The end time of lochia in the research group was higher than that in the control group, and the rate of uterine involution in the research group was lower than that in the control group (P < 0.05). The neonatal weight and Apgar score in the research group were higher than those in the control group, and the hospitalization rate of neonatal ICU in the research group was significantly lower than that in the control group. The incidence of adverse reactions in the research group was significantly lower than that in the control group (P < 0.05). Conclusion: Carboprost aminobutyriol combined with carbestatin can effectively prevent the occurrence of bleeding after cesarean section, improve uterine involution, and improve neonatal birth quality, which is worth popularizing.


Asunto(s)
Carboprost , Cesárea , Oxitocina , Carboprost/uso terapéutico , Cesárea/efectos adversos , Estudios de Cohortes , Combinación de Medicamentos , Quimioterapia Combinada/efectos adversos , Femenino , Humanos , Recién Nacido , Oxitocina/uso terapéutico , Hemorragia Posparto/etiología , Hemorragia Posparto/prevención & control , Embarazo , Resultado del Tratamiento , Trometamina
5.
Int J Chron Obstruct Pulmon Dis ; 17: 1975-1986, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36065315

RESUMEN

Purpose: Randomized trials report that single-inhaler triple therapy is more effective than dual bronchodilators at reducing exacerbations in patients with chronic obstructive pulmonary disease (COPD). However, this effect may have been influenced by the forced withdrawal of inhaled corticosteroids (ICS) at randomization. We used an adaptive selection new-user design to compare single-inhaler triple therapy with dual bronchodilators in real-world clinical practice. Patients and Methods: We identified a cohort of COPD patients, 40 years or older, treated during 2017-2020, from the United Kingdom's Clinical Practice Research Datalink, a real-world practice setting. ICS-naïve patients initiating single-inhaler triple therapy or dual bronchodilators were compared on the incidence of COPD exacerbation and pneumonia over one year, after adjustment by propensity score weighting. Results: The cohort included 4106 new users of single-inhaler triple therapy and 29,702 of dual bronchodilators. Single-inhaler triple therapy was the first maintenance treatment in 44% of the users and 43% had no COPD exacerbations in the prior year. The adjusted hazard ratio (HR) of a first moderate or severe exacerbation with triple therapy relative to dual bronchodilators was 1.08 (95% confidence interval (CI): 1.00-1.16). Among patients with two or more prior exacerbations the HR was 0.83 (95% CI: 0.74-0.92), while for those with prior asthma diagnosis it was 0.86 (95% CI: 0.70-1.06) and with blood eosinophil count >300 cells/µL it was 0.89 (95% CI: 0.76-1.05). The incidence of severe pneumonia was increased with triple therapy (HR 1.50; 95% CI: 1.29-1.75). Conclusion: In a real-world setting of COPD treatment among ICS-naïve patients, thus unaffected by ICS withdrawal, single-inhaler triple therapy was not more effective than dual bronchodilators at reducing the incidence of exacerbation, except among patients with multiple exacerbations. Single-inhaler triple therapy should be initiated mainly in patients with multiple exacerbations while, for most others, dual bronchodilators are just as effective whilst avoiding the excess risk of severe pneumonias.


Asunto(s)
Neumonía , Enfermedad Pulmonar Obstructiva Crónica , Administración por Inhalación , Corticoesteroides , Agonistas de Receptores Adrenérgicos beta 2 , Broncodilatadores , Quimioterapia Combinada , Humanos , Antagonistas Muscarínicos , Nebulizadores y Vaporizadores , Neumonía/inducido químicamente , Neumonía/diagnóstico , Neumonía/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología
6.
Front Endocrinol (Lausanne) ; 13: 941215, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36111292

RESUMEN

Diabetic kidney disease (DKD) combined with Membranous Nephropathy (MN) was observed in some patients with the increasing of Diabetic patients. However, no treatment guidelines are available for DKD combined with MN. In this study, we for the first time analyzed the safety and efficacy of leflunomide (LEF) combined with low-dose glucocorticoid methylprednisolone (MP) in the treatment of DKD with MN. We retrospectively collected the clinical data of patients with the highest number of DKD combined with MN diagnosed by renal biopsy between December 2016 and December 2020. The inclusion criteria were a history of diabetes for more than 20 months, no glucocorticoid therapy or immunosuppressant therapy for at least 6 months, urine protein level greater than 3.5 g, and a follow-up time of 16 months. In addition to conservative treatment, the patients received LEF monotherapy (LEF, n = 38) or LEF combined with low-dose methylprednisolone (LEF+MP, n = 26). After 16 months of treatment, the complete remission rate was 2.6%, and the remission rate was 15.8% in the LEF group; in the LEF+MP group, the complete remission rate and the remission rate were 23.1% and 34.6%, respectively. At month 16, the urine protein level was lower than the baseline value in both groups (p < 0.05) and was significantly lower in the LEF+MP group than in the LEF group (p < 0.05). Serum albumin levels were higher than the baseline value in both groups (p < 0.05), with no significant between-group difference (p > 0.05). No inter- or intragroup difference in serum creatinine or glycated hemoglobin was observed. During treatment, the relapse rate was lower in the LEF+MP group than in the LEF group (p < 0.05). No irreversible adverse events were observed. In summary, LEF+MP is more effective than LEF monotherapy for DKD combined with MN. Large, long-term, randomized, double-blind, controlled studies are needed to further validate the clinical efficacy of LEF+MP.


Asunto(s)
Nefropatías Diabéticas , Glomerulonefritis Membranosa , Leflunamida , Metilprednisolona , Creatinina , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/tratamiento farmacológico , Quimioterapia Combinada/efectos adversos , Glomerulonefritis Membranosa/complicaciones , Glomerulonefritis Membranosa/tratamiento farmacológico , Hemoglobina A Glucada , Humanos , Inmunosupresores/uso terapéutico , Leflunamida/uso terapéutico , Metilprednisolona/uso terapéutico , Estudios Retrospectivos , Albúmina Sérica
7.
BMJ Open ; 12(9): e062096, 2022 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-36115671

RESUMEN

OBJECTIVES: To explore the outcomes of Helicobacter pylori infection treatments for naïve patients in the real-world settings. DESIGN: A retrospective observational study. SETTING: Single tertiary level academic hospital in China. PARTICIPANTS: We identified patients initially receiving quadruple therapy for H. pylori infection from 2017 to 2020 in whom eradication was confirmed (n=23 470). PRIMARY OUTCOME: Efficacy of different initial H. pylori infection treatments. SECONDARY OUTCOME: Results of urea breath test (UBT) after H. pylori eradication. RESULTS: Among 23 470 patients who received initial H. pylori treatment, 21 285 (90.7%) were treated with amoxicillin-based regimens. The median age of the patients decreased from 2017 to 2020 (45.0 vs 39.0, p<0.0001). The main treatments were therapies containing amoxicillin and furazolidone, which had an eradication rate of 87.6% (14 707/16 784); those containing amoxicillin and clarithromycin had an eradication rate of 85.5% (3577/4182). The date of treatment, age, antibiotic regimen and duration of treatment showed correlations with the failure of H. pylori eradication in a multivariable logistic regression analysis. Finally, positive UBT results after eradication clustered around the cut-off value, in both the 13C-UBT and 14C-UBT. CONCLUSIONS: The major H. pylori infection treatments for naïve patients were those containing amoxicillin and furazolidone, which offered the highest eradication rate. The date of treatment, age, antibiotic regimen and duration of treatment were risk factors for the failure of H. pylori eradication. Additionally, positive UBT results after eradication clustered around the cut-off value.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Claritromicina/uso terapéutico , Quimioterapia Combinada , Estudios de Seguimiento , Furazolidona/uso terapéutico , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Resultado del Tratamiento , Urea
8.
Dis Markers ; 2022: 4829750, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36118673

RESUMEN

Objective: To investigate the efficacy of dapagliflozin for diabetes mellitus complicated by coronary artery diseases and its impact on vascular endothelial function. Methods: Between August 2020 and August 2021, 80 patients with coronary heart disease complicated by type 2 diabetes mellitus were recruited and randomly assigned to receive either dapagliflozin (5 mg daily) plus original oral hypoglycemic agents (dapagliflozin group) or original oral hypoglycemic agents alone (control group). Outcome measures included blood pressure, blood glucose, cholesterol levels, vascular endothelial function, cardiovascular events, and drug-related adverse events. Results: The two groups had similar outcome indices upon admission (P > 0.05). After 20 weeks of medication, the two groups of patients showed similar blood pressure, hemoglobin A1c (HbA1c), and low-density lipoprotein (LDL-C) levels versus those before treatment (P > 0.05), and no significant differences were found in intergroup comparison neither (P > 0.05). Dapagliflozin plus conventional hypoglycemic agents resulted in a significantly higher reactive hyperemia index (RHI) value, fewer cases with abnormal vascular endothelial function, and fewer major cardiovascular events during treatment versus the sole use of conventional hypoglycemic agents (P < 0.05). There was no significant difference in drug-related adverse events between the two groups (P > 0.05). Conclusion: Dapagliflozin improves the vascular endothelial functions of patients with diabetes mellitus complicated by coronary artery disease with a high safety profile and favorable efficacy.


Asunto(s)
Enfermedad de la Arteria Coronaria , Diabetes Mellitus Tipo 2 , Compuestos de Bencidrilo , Glucemia , LDL-Colesterol , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Quimioterapia Combinada , Glucósidos , Hemoglobina A Glucada/análisis , Humanos , Hipoglucemiantes/uso terapéutico
9.
Cochrane Database Syst Rev ; 9: CD009887, 2022 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-36066395

RESUMEN

BACKGROUND: This is an updated version of the Cochrane Review first published in 2014 and last updated in 2020. For nearly 30% of people with epilepsy, current treatments do not control seizures. Stiripentol is an antiepileptic drug (AED) that was developed in France and was approved by the European Medicines Agency (EMA) in 2007 as an adjunctive therapy with valproate and clobazam for the treatment of Dravet syndrome. OBJECTIVES: To evaluate the efficacy and tolerability of stiripentol as add-on treatment for people with drug-resistant focal epilepsy who are taking AEDs. SEARCH METHODS: For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE on 28 March 2022. We contacted the manufacturer of stiripentol and epilepsy experts to identify published, unpublished and ongoing trials. SELECTION CRITERIA: Randomised controlled trials of add-on stiripentol in people with drug-resistant focal epilepsy. DATA COLLECTION AND ANALYSIS: Review authors independently selected trials for inclusion and extracted data. We investigated outcomes including 50% or greater reduction in seizure frequency, seizure freedom, adverse effects, treatment withdrawal and changes in quality of life. MAIN RESULTS: On the basis of our selection criteria, we included no new studies in the present review update. We included only one study from the original review (32 children with focal epilepsy). This study adopted a responder-enriched design and found no clear evidence of a reduction of 50% or more in seizure frequency (risk ratio (RR) 1.51, 95% confidence interval (CI) 0.81 to 2.82; low-certainty evidence) and no clear evidence of seizure freedom (RR 1.18, 95% CI 0.31 to 4.43; low-certainty evidence) when comparing add-on stiripentol with placebo. Stiripentol led to a greater risk of adverse effects considered as a whole (RR 2.65, 95% CI 1.08 to 6.47; low-certainty evidence). When we considered specific adverse effects, CIs were very wide and showed the possibility of substantial increases and small reductions in risks of neurological adverse effects (RR 2.65, 95% CI 0.88 to 8.01; low-certainty evidence). Researchers noted no clear reduction in the risk of study withdrawal (RR 0.66, 95% CI 0.30 to 1.47; low-certainty evidence), which was high in both groups (53.3% in placebo group and 35.3% in stiripentol group; low-certainty evidence). The external validity of this study was limited because only responders to stiripentol (i.e. participants experiencing a decrease in seizure frequency of 50% or greater during an open prerandomisation phase compared with baseline) were included in the randomised, add-on, placebo-controlled, double-blind phase. Furthermore, carry-over and withdrawal effects probably influenced outcomes related to seizure frequency. Very limited information derived from the only included study shows that adverse effects considered as a whole may occur more often with add-on stiripentol than with add-on placebo. AUTHORS' CONCLUSIONS: We have found no new studies since the last version of this review was published. Hence, we have made no changes to the conclusions as presented in previous versions. We can draw no conclusions to support the use of stiripentol as add-on treatment for drug-resistant focal epilepsy. Additional large, randomised, well-conducted trials are needed.


Asunto(s)
Dioxolanos , Epilepsia Refractaria , Epilepsias Parciales , Anticonvulsivantes/efectos adversos , Niño , Dioxolanos/efectos adversos , Epilepsia Refractaria/tratamiento farmacológico , Quimioterapia Combinada , Epilepsias Parciales/tratamiento farmacológico , Humanos , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Convulsiones/tratamiento farmacológico
13.
PLoS One ; 17(9): e0273249, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36083995

RESUMEN

BACKGROUND: Artemisinin-based combination therapies (ACTs) are the recommended treatment for uncomplicated Plasmodium falciparum malaria in all malaria endemic countries. Artemisinin resistance, partner drug resistance, and subsequent ACT failure are widespread in Southeast Asia. The more recent independent emergence of artemisinin resistance in Africa is alarming. In response, triple artemisinin-based combination therapies (TACTs) are being developed to mitigate the risks associated with increasing drug resistance. Since ACTs are still effective in Africa, where malaria is mainly a paediatric disease, the potential deployment of TACTs raises important ethical questions. This paper presents an analysis of stakeholders' perspectives regarding key ethical considerations to be considered in the deployment of TACTs in Africa provided they are found to be safe, well-tolerated and effective for the treatment of uncomplicated malaria. METHODS: We conducted a qualitative study in Burkina Faso and Nigeria assessing stakeholders' (policy makers, suppliers and end-users) perspectives on ethical issues regarding the potential future deployment of TACTs through 68 in-depth interviews and 11 focus group discussions. FINDINGS: Some respondents suggested that there should be evidence of local artemisinin resistance before they consider deploying TACTs, while others suggested that TACTs should be deployed to protect the efficacy of current ACTs. Respondents suggested that additional side effects of TACTs compared to ACTs should be minimal and the cost of TACTs to end-users should not be higher than the cost of current ACTs. There was some disagreement among respondents regarding whether patients should have a choice of treatment options between ACTs and TACTs or only have TACTs available, while ACTs are still effective. The study also suggests that community, public and stakeholder engagement activities are essential to support the introduction and effective uptake of TACTs. CONCLUSION: Addressing ethical issues regarding TACTs and engaging early with stakeholders will be important for their potential deployment in Africa.


Asunto(s)
Antimaláricos , Artemisininas , Malaria Falciparum , Malaria , Antimaláricos/farmacología , Antimaláricos/uso terapéutico , Artemisininas/farmacología , Artemisininas/uso terapéutico , Burkina Faso , Niño , Resistencia a Medicamentos , Quimioterapia Combinada , Humanos , Malaria/tratamiento farmacológico , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/epidemiología , Nigeria/epidemiología , Plasmodium falciparum
14.
Sci Rep ; 12(1): 15698, 2022 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-36127353

RESUMEN

A systematic review and Bayesian network meta-analysis is necessary to evaluate the efficacy and safety of triple therapy with different doses of inhaled corticosteroids (ICS) in stable chronic obstructive pulmonary disease (COPD). We selected 26 parallel randomized controlled trials (41,366 patients) comparing triple therapy with ICS/long-acting beta-agonist (LABA), LABA/long-acting muscarinic antagonist (LAMA), and LAMA in patients with stable COPD for ≥ 12 weeks from PubMed, EMBASE, the Cochrane Library, and clinical trial registries (search from inception to June 30, 2022). Triple therapy with high dose (HD)-ICS exhibited a lower risk of total exacerbation in pre-specified subgroups treated for ≥ 48 weeks than that with low dose (LD)-ICS (odds ratio [OR] = 0.66, 95% credible interval [CrI] = 0.52-0.94, low certainty of evidence) or medium dose (MD)-ICS (OR = 0.66, 95% CrI = 0.51-0.94, low certainty of evidence). Triple therapy with HD-ICS exhibited a lower risk of moderate-to-severe exacerbation in pre-specified subgroups with forced expiratory volume in 1 s < 65% (OR = 0.6, 95% CrI = 0.37-0.98, low certainty of evidence) or previous exacerbation history (OR = 0.6, 95% CrI = 0.36-0.999, very low certainty of evidence) than triple therapy with MD-ICS. Triple therapy with HD-ICS may reduce acute exacerbation in patients with COPD treated with other drug classes including triple therapy with LD- or MD-ICS or dual therapies.


Asunto(s)
Antagonistas Muscarínicos , Enfermedad Pulmonar Obstructiva Crónica , Administración por Inhalación , Corticoesteroides , Agonistas de Receptores Adrenérgicos beta 2 , Teorema de Bayes , Quimioterapia Combinada , Humanos , Antagonistas Muscarínicos/uso terapéutico , Metaanálisis en Red
15.
J Assoc Physicians India ; 70(8): 11-12, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36082731

RESUMEN

Globally, the prevalence of chronic coronary syndrome (CCS) increases with age. In India, there is a rapidly growing burden of coronary artery disease (CAD), which has become the leading cause of morbidity and mortality. Despite recommended medical therapy, patients with CCS are still at risk of ischemic events. Currently, dual antiplatelet therapy (DAPT) is recommended in the form of aspirin and a P2Y12 inhibitor or low dose rivaroxaban in patients with stable CAD and/or peripheral artery disease (PAD). A low dose of rivaroxaban in combination with aspirin is a promising approach; however, for patients who might benefit the most, it still remains a challenge. Clinical trial data on this new drug was certainly very encouraging, with evidence from the COMPASS trial and prespecified subgroups of COMPASS trials suggesting that the addition of rivaroxaban to aspirin was associated with a significantly lower risk of ischemic events, mortality, and tolerable bleeding profile in patients with CCS and high-risk factors. This combination is cost-effective and generally well tolerated in patients with CAD and/or PAD, as well as patients with CCS and multimorbidity or high-risk populations.


Asunto(s)
Enfermedad de la Arteria Coronaria , Enfermedad Arterial Periférica , Aspirina/efectos adversos , Quimioterapia Combinada , Inhibidores del Factor Xa/efectos adversos , Humanos , Enfermedad Arterial Periférica/complicaciones , Enfermedad Arterial Periférica/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/efectos adversos , Rivaroxabán/efectos adversos
17.
Helicobacter ; 27(5): e12922, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35939559

RESUMEN

BACKGROUND: The efficacy and safety of high-dose amoxicillin (AMX) and proton pump inhibitors (PPI) dual therapy raises much more attention in recent years. Comparative studies among the dual therapies are required to explore more suitable regimens. This study compared the efficacy, adverse events, and patient compliance of three different high-dose dual regimens in treatment-naive patients of Helicobacter pylori (H. pylori) infection. MATERIALS AND METHODS: The study was a prospective, multicenter, open-label, randomized controlled trial, including H. pylori-infected treatment-naive patients at 12 tertiary hospitals in China. The eligible subjects received high-dose AMX and esomeprazole (ESO) dual therapy of different regimens. They were randomly assigned to group A (ESO 20 mg plus AMX 750 mg, Qid for 14 days), group B (ESO 40 mg Bid plus AMX 1 g Tid for 14 days), or group C (ESO 20 mg plus AMX 1 g, Tid for 14 days). The eradication rates, adverse events, and patient compliance of the three groups were compared. RESULTS: Between April 2021 and January 2022, a total of 1080 subjects were screened and 945 were randomized. The eradication rates in groups A, B, and C were 88.6% (95% CI 84.5%-91.9%), 84.4% (95% CI 80.0%-88.3%), and 86.7% (95% CI 82.4%-90.2%; p = .315), respectively, based on intention-to-treat analysis; 90.3% (95% CI 86.4%-93.3%), 85.5% (95% CI 81.1%-89.2%), and 87.8% (95% CI 83.6%-91.2%; p = .197), respectively, according to modified intention-to-treat analysis; and 90.4% (95% CI 86.5%-93.5%), 85.8% (95% CI 81.4%-89.5%), and 88.3% (95% CI 84.1%-91.7%; p = .202) in per-protocol analysis. History of antibiotics use in 2 years reduced eradication effect in group B (ESO 40 mg Bid, AMX 1 g Tid). The modified intention-to-treat eradication rates were 81.4% vs 90.0% among those with or without a history of antibiotics use in group B (p = .031). The adverse event rates were 13.7%, 12.7%, and 12.1% in groups A, B, and C, respectively (p = .834). Patient compliance of the three groups was similar. CONCLUSIONS: Two optimized AMX and PPI dual regimens (ESO 40 mg Bid or 20 mg Tid plus AMX 1 g Tid for 14 days) had similar efficacy, safety and compliance as compared with classical dual regimen (ESO 20 mg plus AMX 750 mg Qid for 14 days) in H. pylori-infected treatment-naive patients.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Amoxicilina/farmacología , Antibacterianos/efectos adversos , Quimioterapia Combinada , Esomeprazol/uso terapéutico , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Estudios Prospectivos , Inhibidores de la Bomba de Protones/efectos adversos , Resultado del Tratamiento
18.
Am J Otolaryngol ; 43(5): 103573, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35988360

RESUMEN

PURPOSE: To describe the pharmacokinetics (PK) of ciprofloxacin 0.3 % and fluocinolone acetonide 0.025 % otic solution (CIPRO+FLUO), ciprofloxacin 0.3 % otic solution alone (CIPRO), and fluocinolone acetonide 0.025 % otic solution alone (FLUO) administered into the middle ears of pediatric patients with Acute Otitis Media with Tympanostomy Tubes (AOMT). MATERIALS AND METHODS: We performed a PK analysis of patients who participated in two multicenter, randomized, double-blind AOMT clinical trials (SALVAT studies CIFLOTIII/10IA02 and CIFLOTIII/10IA04). Each patient received 0.25 mL of CIPRO+FLUO, CIPRO, or FLUO twice a day instilled into the ear canal(s) for 7 days to treat AOMT. Blood samples of patients with unilateral AOMT were collected before the administration of the first dose of study medication at Visit 1 (day 1) and within 1-2 h after the last dose on day 7. Blood samples were analyzed to detect ciprofloxacin and fluocinolone acetonide concentrations using two validated liquid chromatography-tandem mass spectrometry (LC-MS-MS) methods, with the lower limit of quantification for ciprofloxacin and fluocinolone acetonide in plasma samples being 1 ng/mL. Thirty randomly selected patients between 10 months and 10 years of age (mean age, 4.4 years) were included in the study. Although all available samples were analyzed, only PK data of the 22 patients with both samples and unilateral disease were considered for study purposes. RESULTS: No detectable concentrations of ciprofloxacin or fluocinolone acetonide in plasma were observed (<1 ng/mL). CONCLUSIONS: These results demonstrated negligible systemic exposure to ciprofloxacin and fluocinolone acetonide following topical otic administration in pediatric patients with AOMT.


Asunto(s)
Ciprofloxacina , Otitis Media , Administración Tópica , Niño , Preescolar , Quimioterapia Combinada , Fluocinolona Acetonida/uso terapéutico , Humanos
19.
N Engl J Med ; 387(8): 715-726, 2022 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-36001712

RESUMEN

BACKGROUND: The cytokine interleukin-6 is involved in the pathogenesis of rheumatoid arthritis. Olokizumab, a humanized monoclonal antibody targeting the interleukin-6 cytokine directly, is being tested for the treatment of rheumatoid arthritis. METHODS: In a 24-week, phase 3, multicenter, placebo- and active-controlled trial, we randomly assigned (in a 2:2:2:1 ratio) patients with rheumatoid arthritis and an inadequate response to methotrexate to receive subcutaneous olokizumab at a dose of 64 mg every 2 or 4 weeks, adalimumab (40 mg every 2 weeks), or placebo; all patients continued methotrexate therapy. The primary end point was an American College of Rheumatology 20 (ACR20) response (≥20% fewer tender and swollen joints and ≥20% improvement in three of five other domains) at week 12, with each olokizumab dose tested for superiority to placebo. We also tested the noninferiority of each olokizumab dose to adalimumab with respect to the percentage of patients with an ACR20 response (noninferiority margin, -12 percentage points in the lower boundary of the 97.5% confidence interval for the difference between groups). RESULTS: A total of 464 patients were assigned to receive olokizumab every 2 weeks, 479 to receive olokizumab every 4 weeks, 462 to receive adalimumab, and 243 to receive placebo. An ACR20 response at week 12 occurred in 44.4% of the patients receiving placebo, in 70.3% receiving olokizumab every 2 weeks (difference vs. placebo, 25.9 percentage points; 97.5% confidence interval [CI], 17.1 to 34.1), in 71.4% receiving olokizumab every 4 weeks (difference vs. placebo, 27.0 percentage points; 97.5% CI, 18.3 to 35.2), and in 66.9% receiving adalimumab (difference vs. placebo, 22.5 percentage points; 95% CI, 14.8 to 29.8) (P<0.001 for the superiority of each olokizumab dose to placebo). Both olokizumab doses were noninferior to adalimumab with respect to the percentage of patients with an ACR20 response at week 12 (difference, 3.4 percentage points [97.5% CI, -3.5 to 10.2] with olokizumab every 2 weeks and 4.5 percentage points [97.5% CI, -2.2 to 11.2] with olokizumab every 4 weeks). Adverse events, most commonly infections, occurred in approximately 70% of the patients who received olokizumab. Antibodies against olokizumab were detected in 3.8% of the patients receiving the drug every 2 weeks and in 5.1% of those receiving it every 4 weeks. CONCLUSIONS: In patients with rheumatoid arthritis who were receiving maintenance methotrexate, olokizumab was superior to placebo and noninferior to adalimumab in producing an ACR20 response at 12 weeks. Larger and longer trials are required to determine the efficacy and safety of olokizumab in patients with rheumatoid arthritis. (Supported by R-Pharm; CREDO2 ClinicalTrials.gov number, NCT02760407.).


Asunto(s)
Adalimumab , Anticuerpos Monoclonales Humanizados , Antirreumáticos , Artritis Reumatoide , Metotrexato , Adalimumab/administración & dosificación , Adalimumab/efectos adversos , Adalimumab/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Método Doble Ciego , Quimioterapia Combinada , Humanos , Interleucina-6/antagonistas & inhibidores , Metotrexato/administración & dosificación , Metotrexato/efectos adversos , Metotrexato/uso terapéutico , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa
20.
Toxins (Basel) ; 14(8)2022 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-36006191

RESUMEN

OnabotulinumtoxinA, targeting the CGRP machinery, has been approved for the last two decades for chronic migraine prevention. The recently approved monoclonal antibodies (mAbs) directed towards the calcitonin gene-related peptide (CGRP) pathway open a new age for chronic migraine control. However, some 40% patients suffering from chronic migraine is still resistant to treatment. The aim of this work is to answer the following PICOS (participants intervention comparator outcome study design) question: Is there evidence of efficacy and safety of the combined administration of anti-CGRP mAbs and onabotulinumtoxinA in chronic migraine? A systematic review and meta-analysis [Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations] was made up to 19 April 2022. The results are encouraging: the combined treatment proved to afford ≥50% monthly headache days (MHDs)/frequency reduction respect to baseline in up to 58.8% of patients; in comparison, anti-CGRP mAbs reduce MHDs of 1.94 days from baseline and botulinum toxin of 1.86 days. Our study demonstrates for the first time that the combination therapy of onabotulinumtoxinA with anti-CGRP mAbs affords a reduction of 2.67 MHDs with respect to onabotulinumtoxinA alone, with moderate certainty of evidence. Adequately powered, good-quality studies are needed to confirm the response to combination therapy in terms of efficacy and safety. PROSPERO registration: CRD42022313640.


Asunto(s)
Anticuerpos Monoclonales , Toxinas Botulínicas Tipo A , Trastornos Migrañosos , Anticuerpos Monoclonales/uso terapéutico , Toxinas Botulínicas Tipo A/uso terapéutico , Péptido Relacionado con Gen de Calcitonina/antagonistas & inhibidores , Quimioterapia Combinada/efectos adversos , Humanos , Trastornos Migrañosos/prevención & control , Resultado del Tratamiento
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