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1.
Comput Math Methods Med ; 2022: 2233138, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060654

RESUMO

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.


Assuntos
Carboprosta , Cesárea , Ocitocina , Carboprosta/uso terapêutico , Cesárea/efeitos adversos , Estudos de Coortes , Combinação de Medicamentos , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Recém-Nascido , Ocitocina/uso terapêutico , Hemorragia Pós-Parto/etiologia , Hemorragia Pós-Parto/prevenção & controle , Gravidez , Resultado do Tratamento , Trometamina
2.
Int J Chron Obstruct Pulmon Dis ; 17: 1975-1986, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36065315

RESUMO

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.


Assuntos
Pneumonia , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Corticosteroides , Agonistas de Receptores Adrenérgicos beta 2 , Broncodilatadores , Quimioterapia Combinada , Humanos , Antagonistas Muscarínicos , Nebulizadores e Vaporizadores , Pneumonia/induzido quimicamente , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/epidemiologia
3.
J Assoc Physicians India ; 70(8): 11-12, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36082731

RESUMO

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.


Assuntos
Doença da Artéria Coronariana , Doença Arterial Periférica , Aspirina/efeitos adversos , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Humanos , Doença Arterial Periférica/complicações , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Rivaroxabana/efeitos adversos
4.
BMJ Open ; 12(9): e062096, 2022 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115671

RESUMO

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.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Claritromicina/uso terapêutico , Quimioterapia Combinada , Seguimentos , Furazolidona/uso terapêutico , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Humanos , Resultado do Tratamento , Ureia
5.
Cochrane Database Syst Rev ; 9: CD009887, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36066395

RESUMO

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.


Assuntos
Dioxolanos , Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Anticonvulsivantes/efeitos adversos , Criança , Dioxolanos/efeitos adversos , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Quimioterapia Combinada , Epilepsias Parciais/tratamento farmacológico , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Convulsões/tratamento farmacológico
8.
PLoS One ; 17(9): e0273249, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36083995

RESUMO

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.


Assuntos
Antimaláricos , Artemisininas , Malária Falciparum , Malária , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Burkina Faso , Criança , Resistência a Medicamentos , Quimioterapia Combinada , Humanos , Malária/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Nigéria/epidemiologia , Plasmodium falciparum
9.
Clin Appl Thromb Hemost ; 28: 10760296221124902, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36112808

RESUMO

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.


Assuntos
Aspirina , Inibidores da Agregação Plaquetária , Anticoagulantes/uso terapêutico , Aspirina/efeitos adversos , Ponte de Artéria Coronária/efeitos adversos , Quimioterapia Combinada , Hemorragia/etiologia , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Retrospectivos
10.
Dis Markers ; 2022: 4829750, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118673

RESUMO

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.


Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Compostos Benzidrílicos , Glicemia , LDL-Colesterol , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quimioterapia Combinada , Glucosídeos , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/uso terapêutico
12.
Int J Mol Sci ; 23(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36077436

RESUMO

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.


Assuntos
Hepatite C Crônica , Hepatite C , Antivirais/efeitos adversos , Quimioterapia Combinada , Hepacivirus , Hepatite C/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Humanos , Masculino , Medicina de Precisão , Proteínas Recombinantes/farmacologia , Ribavirina/efeitos adversos , Resultado do Tratamento
13.
Artigo em Inglês | MEDLINE | ID: mdl-36074445

RESUMO

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.


Assuntos
Hepatite C Crônica , Sofosbuvir , Adulto , Antivirais/efeitos adversos , Estudos de Coortes , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Ribavirina/uso terapêutico , Falha de Tratamento , Resultado do Tratamento
15.
Int J Chron Obstruct Pulmon Dis ; 17: 1883-1895, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36003323

RESUMO

Purpose: GOLD 2019 proposed a novel treatment decision tool for follow-up based on the predominant trait (exacerbation or dyspnea) of patients, alongside treatment escalation and de-escalation strategies. This study was designed to provide an up-to-date snapshot of patient and disease characteristics, treatment pathways, and healthcare resource use (HRU) in COPD in real life, and comprehensively examine patients considering GOLD 2019 recommendations. Patients and Methods: This mixed design, observational, multicenter (14 pulmonology clinics) study included all patients with a documented COPD diagnosis (excluding asthma-COPD overlap [ACO]) for ≥12 months, aged ≥40 years at diagnosis who had a COPD-related hospital visit, spirometry test and blood eosinophil count (BEC) measurement under stable conditions within the 12 months before enrollment between February and December 2020. Data were collected cross-sectionally from patients and retrospectively from hospital medical records. Results: This study included 522 patients (GOLD group A: 17.2%, B: 46.4%, C: 3.3%, D: 33.1%), of whom 79.5% were highly symptomatic and 36.2% had high risk of exacerbation. Exacerbations (n = 832; 46.6% moderate, 25.5% severe) were experienced by 57.5% of patients in the previous 12 months. Inter-rater agreement between investigators and patients regarding the reason for visit was low (κ coefficient: 0.338, p = 0.001). Inhaled treatment was modified in 88 patients at index, mainly due to symptomatic state (31.8%) and exacerbations (27.3%); treatment was escalated (57.9%, mainly switched to LABA+LAMA+ICS), inhaler device and/or active ingredient was changed (36.4%) or treatment was de-escalated (5.7%). 27% had ≥1 hospital overnight stay over 12 months. Emergency department visits and days with limitation of daily activities were higher in group D (p < 0.001). Conclusion: Despite being on-treatment, many patients with COPD experience persistent symptoms and exacerbations requiring hospital-related HRU. A treatable trait approach and holistic disease management may improve outcomes by deciding the right treatment for the right patient at the right time.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Corticosteroides , Agonistas de Receptores Adrenérgicos beta 2 , Broncodilatadores , Progressão da Doença , Quimioterapia Combinada , Humanos , Antagonistas Muscarínicos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos Retrospectivos
16.
PLoS One ; 17(8): e0272151, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35947601

RESUMO

BACKGROUND: Leprosy neuropathy is the most common peripheral neuropathy of infectious etiology worldwide; it is characterized as asymmetric and focal multiple mononeuropathy. Semmes-Weinstein monofilament (SWM) test is a simple method to assess sensory nerve function. METHODS AND FINDINGS: In this prospective cohort study, a dermatologist carried out hands and feet tactile sensation test with SWM in 107 multibacillary leprosy patients at diagnosis and in 76 patients at the end of treatment from 2016 to 2019. At diagnosis, 81/107 (75.7%) patients had some degree of functional disability, and 46 (43%) of them had altered SWM-test in the hands and 94 (87.9%) of them in the feet. After one year of multibacillary multidrug therapy, the disability decreasing to 44/76 patients (57.9%) and decreasing of the percentual of patients with altered SWM-test to 18% for the hands, and to 28.7% for the feet. At the end of treatment, the number of SMW-test points presented improvement in the hands of 22 (28.9%) patients, and in the feet of 47 (61.8%). In the hands, by SWM-test, only the radial nerve point demonstrated a significant asymmetry, while in the feet, the difference between the sum of altered SWM-test points showed significant asymmetry between both sides, highlighting the tibial nerve for the establishment of asymmetric leprosy neuropathy. In Spearman's correlation analysis, a positive correlation with statistical significance was observed between the number of hands and feet SWM altered points at diagnosis and the degree of disability at diagnosis (0.69) and at the end of the treatment (0.80). CONCLUSION: The patterns of hands and feet tactile sensation at diagnosis and their consequent modifications with the anti-leprosy drugs define the bacterial etiology of neuropathy, an important tool for the clinical diagnosis and follow up of the disease, highlighting the tibial nerve findings, the most affected nerve among leprosy patients by SWM-test, with significant asymmetry and focality impairments.


Assuntos
Hanseníase , Doenças do Sistema Nervoso Periférico , Quimioterapia Combinada , Humanos , Hansenostáticos , Hanseníase/complicações , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Doenças do Sistema Nervoso Periférico/diagnóstico , Doenças do Sistema Nervoso Periférico/etiologia , Estudos Prospectivos , Sensação , Tato
17.
J Stroke Cerebrovasc Dis ; 31(9): 106683, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35914511

RESUMO

OBJECTIVE: Whether aspirin platelet reactivity affects platelet function and clinical outcomes with different antiplatelet therapies in patients with mild stroke or transient ischemic attack (TIA) remains unclear. We conducted a subgroup analysis of the PRINCE trial. MATERIALS AND METHODS: Patients with mild stroke or TIA were randomized into aspirin+ticagrelor, or aspirin+clopidogrel groups; aspirin reaction units (ARU) were measured at the baseline and after 7 ± 2 days to assess response to treatment. High on-treatment platelet reactivity (HPR) was defined as ≥550 ARU (poor response to aspirin). The platelet functions of ticagrelor and clopidogrel were measured using the VerifyNow P2Y12 assay for P2Y12 reaction units (PRU); HPR to P2Y12 was defined as >208 PRU (poor response to P2Y12). Clinical outcomes included stroke and clinical vascular and bleeding events after 90 days. RESULTS: Among 628 enrolled patients, 69 (11%) were poor aspirin responders. After 7 ± 2 days, the proportion of poor P2Y12 responders for ticagrelor versus clopidogrel significantly reduced in poor (2.6% versus 27.4%) and good (14.3% versus 29.4%) aspirin responders. There were significant interactions between treatment groups, and between treatment groups and aspirin platelet reactivity for poor P2Y12 responders (P = 0.01). After 90 ± 7 days, there were no significant interactions between treatment groups and aspirin platelet reactivity for new stroke risk (good aspirin responders: 5.5% versus 8.8%, hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.32 to 1.16; P = 0.13; poor aspirin responders: 8.6% versus 8.8%, HR: 0.97, 95% CI: 0.20-4.81; P = 0.97; P for interaction = 0.60). Major bleeding was less frequent in poor than good aspirin responders (ticagrelor/aspirin: 0.4%/0%; clopidogrel/aspirin: 1.4%/0%). CONCLUSIONS: In patients with minor stroke or TIA, clopidogrel, and particularly ticagrelor, decreased platelet function in poor versus good aspirin responders. The poor platelet reactivity of aspirin could not sufficiently reduce the risk of recurrent stroke with ticagrelor or clopidogrel; however, HPR (poor aspirin response) may have a protective effect on clinically relevant major bleeding.


Assuntos
Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Aspirina/efeitos adversos , Clopidogrel/efeitos adversos , Quimioterapia Combinada , Humanos , Ataque Isquêmico Transitório/induzido quimicamente , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Acidente Vascular Cerebral/induzido quimicamente , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Ticagrelor/efeitos adversos , Resultado do Tratamento
18.
Trials ; 23(1): 666, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35978342

RESUMO

BACKGROUND: The standard treatment regimen for drug-sensitive tuberculosis (TB), comprising four companion drugs, requires a minimum duration of 6 months, and this lengthy treatment leads to poor adherence and increased toxicity. To improve rates of adherence, reduce adverse events, and lower costs, a simplified and shortened treatment regimen is warranted. METHODS: This study is a multicenter, open-label randomized clinical trial of non-inferiority design that compares a new regimen with the conventional regimen for drug-sensitive pulmonary TB. The investigational group will use a regimen of high-dose rifampicin (30 mg/kg/day) with isoniazid and pyrazinamide, and the treatment will be maintained for 12 weeks after the achievement of negative conversion of sputum culture. The control group will be treated for 6 months with a World Health Organization-endorsed regimen consisting of isoniazid, rifampicin (10 mg/kg/day), ethambutol, and pyrazinamide. The primary endpoint is the proportion of unfavorable outcomes at 18 months after randomization. Secondary outcomes include time to unfavorable treatment outcome, time to culture conversion on liquid medium, treatment success rate at the end of treatment, proportion of recurrence at 18 months after randomization, time to recurrence after treatment completion, and adverse events of grade 3 or higher during the treatment. We predict a 10% unfavorable outcome for the control group, and 0% difference from the investigational group. Based on 80% verification power and a 2.5% one-sided significance level for a non-inferiority margin of 6%, 393 participants per group are required. Considering the 15% dropout rate, a total of 926 participants (463 in each group) will be recruited. DISCUSSION: This study will inform on the feasibility of the treatment regimen using high-dose rifampicin with a shortened and individualized treatment duration for pulmonary TB. TRIAL REGISTRATION: ClinicalTrials.gov NCT04485156 . Registered on July 24, 2020.


Assuntos
Rifampina , Tuberculose Pulmonar , Antituberculosos/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Humanos , Isoniazida/efeitos adversos , Estudos Multicêntricos como Assunto , Pirazinamida/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Rifampina/efeitos adversos , Resultado do Tratamento , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico
19.
Nat Med ; 28(8): 1672-1678, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35953719

RESUMO

Global guidelines for the management of high-cardiovascular-risk patients include aggressive goals for low-density lipoprotein cholesterol (LDL-C). Statin therapy alone is often insufficient to reach goals and nonstatin options have limitations. Here, we tested the lipid-lowering effects of the cholesteryl ester transfer protein (CETP) inhibitor drug obicetrapib in a randomized, double-blind, placebo-controlled trial in dyslipidaemic patients (n = 120, median LDL-C 88 mg dl-1) with background high-intensity statin treatment (NCT04753606). Over the course of 8 weeks, treatment with 5 mg or 10 mg obicetrapib resulted in a significant decrease as compared with placebo in median LDL-C concentration (by up to 51%; P < 0.0001), the primary trial outcome. As compared with placebo, obicetrapib treatment also significantly (P < 0.0001) decreased apolipoprotein B (by up to 30%) and non-high-density lipoprotein cholesterol (non-HDL-C) concentration (by up to 44%), and significantly (P < 0.0001) increased HDL-C concentration (by up to 165%; the secondary trial outcomes) and had an acceptable safety profile. These results support the potential of obicetrapib to address an unmet medical need for high-cardiovascular-risk patients.


Assuntos
Dislipidemias , Inibidores de Hidroximetilglutaril-CoA Redutases , Colesterol , Proteínas de Transferência de Ésteres de Colesterol/uso terapêutico , LDL-Colesterol , Método Duplo-Cego , Quimioterapia Combinada , Dislipidemias/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Resultado do Tratamento
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