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1.
Zhonghua Er Ke Za Zhi ; 58(1): 41-45, 2020 Jan 02.
Artigo em Chinês | MEDLINE | ID: mdl-31905475

RESUMO

Objective: To evaluate the effectiveness of eradication therapy based on Helicobacter pylori (Hp) susceptibility and CYP2C19 genotype in children with refractory Hp infection. Methods: In this prospective observational cohort study, 156 children with Hp refractory to amoxicillin+clarithromycin+omeprazole triple regimen in Baoding Children's Hospital from December 2017 to May 2018 were enrolled. Ninety-two of them underwent Hp culture and CYP2C19 detection. Seventy-five cases with positive Hp culture were defined as culture successful group and were treated according to Hp susceptibility and CYP2C19 genotype. Seventeen cases with negative Hp culture were defined as culture failed group and were treated only based on the results of CYP2C19 genotype. Sixty-four children who did not have Hp culture and CYP2C19 gene testing were defined as the empirical eradication therapy group and were treated with quadruple regimen (amoxicillin+metronidazole+omeprazole+bismuth). Bacterial resistance, CYP2C19 polymorphism and therapeutic effectiveness between the three groups were compared using chi-square test. Results: Among the 75 positive Hp culture results, 72 (96%) were resistant to clarithromycin, 3 (4%) were resistant to metronidazole, 5 (7%) were resistant to levofloxacin, 5 (7%) were resistant to rifampicin, 1 (1%) was resistant to tetracycline, and none was resistant to amoxicillin and furazolidone. The CYP2C19 polymorphism in 92 patients showed that 43 (47%) were extensive metabolizer (EM), 9 (10%) were poor metabolizer (PM), and 40 (43%) were intermediate metabolizer (IM). In terms of the effectiveness, eradication rate in the culture successful group,culture failed group and empirical eradication therapy group were 99% (74/75), 88% (15/17) and 72% (46/64), respectively (χ(2)=21.325, P<0.05). The eradication rate in the culture successful group was significantly higher than that in empirical eradication therapy group (χ(2)=21.005, P<0.05), while there was no difference between empirical eradication therapy group and culture failed group (χ(2)=1.154, P=0.283). Conclusion: Eradication regimen based on bacterial susceptibility and CYP2C19 genotype should be considered in children with refractory Hp infection.


Assuntos
Citocromo P-450 CYP2C19/genética , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/genética , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Omeprazol/uso terapêutico , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Bismuto/uso terapêutico , Criança , Claritromicina/administração & dosagem , Claritromicina/uso terapêutico , Estudos de Coortes , Resistência a Medicamentos/genética , Feminino , Genótipo , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Metronidazol/uso terapêutico , Omeprazol/administração & dosagem , Polimorfismo Genético , Estudos Prospectivos , Resultado do Tratamento
2.
Adv Exp Med Biol ; 1180: 201-217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31784965

RESUMO

Despite many advances in pharmacotherapy over the past half centurye, only a fraction of patients with Major Depressive Disorder (MDD) can achieve remission after the first or second trial of pharmacotherapy. Those who failed standard antidepressant treatment are termed as Treatment-Resistant Depression (TRD). Pharmacotherapy for TRD is more viable over past 15 years in part due to advances in clinical trials such as the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) and the US Department of Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study. In general, optimizing pharmacotherapy consists of switching to different agents, combination with different antidepressants, or augmentation with different class of psychotropic medications, and the latter is preferred. Augmenting agents with strong evidence include Bupropion, Lithium, Triiodothyronine (T3), Aripiprazole, Brexpiprazole, Quetiapine, and Olanzapine in combination with Fluoxetine. Many works need to be done to further advance this field. These include (1) Establish agreement on a standardized, systematic, and feasible definition of TRD, (2) Establish safety and tolerability beyond acute treatment phase, (3) Establish individual psychosocial and neurobiological marks such as pharmacogenetic variance, and (4) Utilize multi-treatment modules such as combination of psychotherapy and pharmacotherapy in conjunction with brain stimulation therapy such as electroconvulsive therapy, vagus nerve stimulation and transcranial magnetic stimulation; as well as non-traditional therapy such as nutritional supplements, exercise and light therapy.


Assuntos
Transtorno Depressivo Maior/terapia , Antidepressivos/uso terapêutico , Quimioterapia Combinada , Eletroconvulsoterapia , Humanos , Psicoterapia , Estimulação Magnética Transcraniana , Resultado do Tratamento
3.
Pol J Microbiol ; 68(4): 477-491, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31880892

RESUMO

This study explored a potential treatment against methicillin-resistant Staphylococcus aureus (MRSA) infections that combines thioridazine (TZ), an efflux pump inhibitor, and miconazole (MCZ), an autolysis inducer, with the anti-microbial drug cloxacillin (CXN). In vitro, the combination treatment of TZ and MCZ significantly reduced 4096-fold (Σ (FIC) = 0.1 - 1.25) the MIC value of CXN against S. aureus. In vivo, the combination therapy significantly relieved breast redness and swelling in mice infected with either clinical or standard strains of S. aureus. Meanwhile, the number of bacteria isolated from the MRSA135-infected mice decreased significantly (p = 0.0427 < 0.05) after the combination therapy when compared to monotherapy. Moreover, the number of bacteria isolated from the mice infected with a reference S. aureus strain also decreased significantly (p = 0.0191 < 0.05) after the combination therapy when compared to monotherapy. The pathological changes were more significant in the CXN-treated group when compared to mice treated with a combination of three drugs. In addition, we found that combination therapy reduced the release of the bacteria-stimulated cytokines such as IL-6, IFN-γ, and TNF-α. Cytokine assays in serum revealed that CXN alone induced IL-6, IFN-γ, and TNF-α in the mouse groups infected with ATCC 29213 or MRSA135, and the combination of these three drugs significantly reduced IL-6, IFN-γ, and TNF-α concentrations. Also, the levels of TNF-α and IFN-γ in mice treated with a combination of three drugs were significantly lower than in the CXN-treated group. Given the synergistic antibacterial activity of CXN, we concluded that the combination of CXN with TZ, and MCZ could be developed as a novel therapeutic strategy against S. aureus.This study explored a potential treatment against methicillin-resistant Staphylococcus aureus (MRSA) infections that combines thioridazine (TZ), an efflux pump inhibitor, and miconazole (MCZ), an autolysis inducer, with the anti-microbial drug cloxacillin (CXN). In vitro, the combination treatment of TZ and MCZ significantly reduced 4096-fold (Σ (FIC) = 0.1 ­ 1.25) the MIC value of CXN against S. aureus. In vivo, the combination therapy significantly relieved breast redness and swelling in mice infected with either clinical or standard strains of S. aureus. Meanwhile, the number of bacteria isolated from the MRSA135-infected mice decreased significantly (p = 0.0427 < 0.05) after the combination therapy when compared to monotherapy. Moreover, the number of bacteria isolated from the mice infected with a reference S. aureus strain also decreased significantly (p = 0.0191 < 0.05) after the combination therapy when compared to monotherapy. The pathological changes were more significant in the CXN-treated group when compared to mice treated with a combination of three drugs. In addition, we found that combination therapy reduced the release of the bacteria-stimulated cytokines such as IL-6, IFN-γ, and TNF-α. Cytokine assays in serum revealed that CXN alone induced IL-6, IFN-γ, and TNF-α in the mouse groups infected with ATCC 29213 or MRSA135, and the combination of these three drugs significantly reduced IL-6, IFN-γ, and TNF-α concentrations. Also, the levels of TNF-α and IFN-γ in mice treated with a combination of three drugs were significantly lower than in the CXN-treated group. Given the synergistic antibacterial activity of CXN, we concluded that the combination of CXN with TZ, and MCZ could be developed as a novel therapeutic strategy against S. aureus.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/antagonistas & inibidores , Farmacorresistência Bacteriana , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , beta-Lactamas/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Bacteriólise/efeitos dos fármacos , Cloxacilina/farmacologia , Quimioterapia Combinada , Humanos , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Miconazol/farmacologia , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/citologia , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Tioridazina/farmacologia
4.
Medicine (Baltimore) ; 98(50): e18249, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852092

RESUMO

RATIONALE: Cancer and chemotherapy individually confer hypercoagulability and increased risks of thrombosis. Most thromboembolic complication after breast cancer chemotherapy was venous thrombosis after multiagent chemotherapy. Arterial thrombosis is extremely rare in early breast cancer patients receiving adjuvant chemotherapy. PRESENTING CONCERNS: A 55-year-old woman with right breast cancer presented to the emergency department with sudden pain, numbness, and swelling in her left hand. She underwent breast conserving surgery and sentinel lymph node biopsy 2 months before the visit. She received the second cycle of adjuvant Adriamycin-cyclophosphamide chemotherapy 5 days before. INTERVENTIONS: Computed tomography angiography revealed acute arterial thrombosis in the left brachial, radial, and ulnar arteries. Unfractionated heparin was initiated immediately, followed by brachial and radial-ulnar thrombectomy, restoring perfusion to the extremity. The postoperative course was uncomplicated; she was discharged on warfarin at a daily dose of 4 mg. OUTCOMES: Chemotherapy was discontinued. Anticoagulation with warfarin was continued. She subsequently received adjuvant endocrine therapy with an aromatase inhibitor and adjuvant radiotherapy. MAIN LESSONS: Despite the low risks of arterial thrombosis in breast cancer, it is a devastating complication with significant morbidity and mortality. Thromboprophylaxis should be considered in those at risk. Immediate anticoagulant therapy and surgical intervention should be considered in affected cases.


Assuntos
Artéria Braquial , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Artéria Radial , Trombose/induzido quimicamente , Artéria Ulnar , Doença Aguda , Neoplasias da Mama/diagnóstico , Quimioterapia Adjuvante/efeitos adversos , Angiografia por Tomografia Computadorizada , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Trombectomia/métodos , Trombose/diagnóstico , Trombose/cirurgia , Ultrassonografia Doppler
5.
Medicine (Baltimore) ; 98(51): e18458, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31861022

RESUMO

BACKGROUND: Chronic viral hepatitis b and its related complications have caused serious harm to human health and become a worldwide public health problem. Hepatitis b cirrhosis is one of the most common complications in Asia. Traditional Chinese medicine combined with antiviral therapy has become the first choice for clinical treatment of hepatitis b Cirrhosis. Biejia Pill is an effective prescription of traditional Chinese medicine in treating Compensatory period of cirrhosis, and there are more and more clinical reports about its validity in treating Compensatory period of cirrhosis. Therefore, we designed this study protocol to evaluate the adjuvant role of Biejia Pill in the treatment of Compensatory period of cirrhosis. METHOD: Electronic Databases, PubMed, EMBASE database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang, Chinese Scientific Journals Database (VIP) and China Biology Medicine disc, (CBM), will be systematically searched from inception to July 2019. Randomized controlled trials (RCTs) on Biejiajian Pill combined with Entecavir and Entecavir alone against Compensatory period of hepatitis b cirrhosis will be included; inclusion and exclusion criteria will be used to screen the trials. liver fibrosis biomarkers including ECM or its metabolites (serum hyaluronic acid (HA), laminin (LN), procollagen type III (PC-III), and type IV collagen (IV-C)) will be measured as primary outcomes. Liver function, including alanine aminotransferase (ALT) and aspartarte aminotransferase (AST), and improvement of related clinical symptoms will be measured as secondary outcomes. RevMan5 software will be used for literature quality evaluation and data synthesis and analysis. RESULT: To evaluate the efficacy and safety of Biejiajian Pill in combination therapy by observing the outcomes of serum liver fibrosis markers, adverse reactions and liver function. CONCLUSION: This study protocol will be used to evaluate the efficacy and safety of Biejia Pill in combination with entecavir in the treatment of Compensatory period of hepatitis b cirrhosis, as well as the adjuvant treatment of Biejia Pill in combination.PROSPERO registration number: CRD42019135402.


Assuntos
Antivirais/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Guanina/análogos & derivados , Hepatite B/complicações , Cirrose Hepática/tratamento farmacológico , Biomarcadores/sangue , Quimioterapia Combinada , Guanina/uso terapêutico , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Revisão Sistemática como Assunto
6.
Zhonghua Yi Xue Za Zhi ; 99(48): 3781-3785, 2019 Dec 24.
Artigo em Chinês | MEDLINE | ID: mdl-31874514

RESUMO

Objective: To investigate the efficacy, safety and compliance of dual therapy for the first-line eradication of Helicobacter pylori infection through a prospective, single-center and open-label cohort study. Methods: From March 2014 to September 2018, 200 naïve patients with Helicobacter pylori infection and dyspepsia received 14-day dual therapy (rabeprazole 10mg and amoxicillin 500 mg, four times daily orally). Safety and compliance were assessed 1-3 days after eradication. The therapeutic outcome was determined by (13)C-urea breath test 4-8 weeks after eradication. Some patients underwent strain culture, antibiotic sensitivity testing and CYP2C19 polymorphism assay. Results: The eradication rates of dual therapy: intention-to-treat analysis 87.5% (95% confidence interval 82.5%-91.5%), modified intention-to-treat analysis 90.2% (86.1%-94.3%) and per-protocol analysis 91.0% (86.3%-94.7). 21.2% of patients had adverse reactions, the majority were mild to moderate, and only 1.5% of patients discontinued medication because of intolerance to adverse reactions. Patients with good compliance accounted for 96.0%. Variate analyses showed that poor compliance and amoxicillin resistance were the independent risk factors for eradication failure. Conclusions: 14-day dual therapy with rabeprazole and amoxicillin (four times daily) achieved good efficacy, safety and compliance for the first-line eradication of Helicobacter pylori infection.


Assuntos
Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Infecções por Helicobacter , Helicobacter pylori , Inibidores da Bomba de Prótons/uso terapêutico , Rabeprazol/uso terapêutico , Claritromicina , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Humanos , Estudos Prospectivos , Resultado do Tratamento
7.
Medicine (Baltimore) ; 98(51): e18070, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860956

RESUMO

INTRODUCTION: In this study, we presented a rare case of Epstein-Barr virus (EBV) meningoencephalitis presented with meningoencephalitis-like symptoms and diffuse edematous hemorrhage. PATIENT CONCERNS: A 77-year-old male patient was admitted to our hospital with fever, headache, confusion, and unconsciousness for 7 days. Physical examination revealed unconsciousness and stiffness of the neck. DIAGNOSIS: The final diagnosis was EBV meningoencephalitis. INTERVENTIONS: Ganciclovir (two times 350 mg/day, 21 days), methylprednisolone sodium succinate (120 mg, 5 days), and IV immunoglobulins (IV Ig) (0.4 g/kg, 5 days) were given to this patient. OUTCOMES: But the patient's clinical symptoms did not improve, and he was still in a coma. His family refused to be further diagnosed and discharged. After discharge for 2 months, the patient was in a coma. Four months later, the patient died of complications of pulmonary infection. CONCLUSION: The patient is an adult, and imaging was dominated by intracranial diffuse microhemorrhage and edema, which was different from the typical imaging characteristics of EBV encephalitis as previously reported. This specific imaging change may provide new clinical value for the diagnosis of EBV encephalitis.


Assuntos
Infecções por Vírus Epstein-Barr/tratamento farmacológico , Ganciclovir/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Imagem por Ressonância Magnética/métodos , Meningoencefalite/tratamento farmacológico , Metilprednisolona/administração & dosagem , Idoso , Quimioterapia Combinada , Infecções por Vírus Epstein-Barr/diagnóstico por imagem , Seguimentos , Humanos , Masculino , Meningoencefalite/diagnóstico por imagem , Meningoencefalite/virologia , Medição de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
8.
Drugs Today (Barc) ; 55(11): 683-693, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31840683

RESUMO

BRAF V600E mutations are associated with 8-10% of metastatic colorectal cancers (mCRC) and carry a poor prognosis with limited therapeutic options. In contrast to metastatic melanoma, BRAF inhibition alone or in combination with mitogen-activated protein kinase kinase (MEK) inhibitors has shown little utility in the treatment of BRAF V600E-mutant mCRC. This is secondary to upstream activation of the epidermal growth factor receptor (EGFR) pathway and other escape mechanisms. Combining RAF and MEK inhibitors with inhibition of the EGFR pathway through an anti-EGFR receptor antibody (cetuximab) led to the BEACON clinical trial (binimetinib, encorafenib and cetuximab). Trial patients had undergone at least one prior line of chemotherapy. The trial met all its endpoints and is now included in NCCN (National Comprehensive Cancer Network) guidelines. Herein we provide updates in treatment options for patients with BRAF V600E-mutant mCRC, focusing on the practice-changing BEACON-triplet regimen, the first chemotherapy-free combination regimen for mCRC. This combination is being explored frontline in the ANCHOR clinical trial.


Assuntos
Benzimidazóis/uso terapêutico , Carbamatos/uso terapêutico , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Sulfonamidas/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Quimioterapia Combinada , Humanos , Mutação , Metástase Neoplásica , Proteínas Proto-Oncogênicas B-raf/genética
9.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(11): 1305-1311, 2019 Nov 30.
Artigo em Chinês | MEDLINE | ID: mdl-31852646

RESUMO

OBJECTIVE: To assess the efficacy and safety of short- term intensive hypoglycemic therapy with a triple regimen consisting of metformin, sagliptin and dapagliflozin in patients with newly diagnosed type 2 diabetes mellitus with hemoglobin Alc (HbA1c) of 9%-12%. METHODS: We prospectively enrolled 58 patients with newly diagnosed type 2 diabetes, who were treated with metformin combined with sagliptin and dapagliflozin for 12 weeks on the basis of diabetic diet and regular exercise. Blood glucose was monitored during the treatment and the changes in HbA1c, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 hPBG), fasting insulin (FINS), 2-hour postprandial insulin (2 hPINS), fasting C-peptide (F-CP), 2-hour postprandial C-peptide (2 hP-CP), and body weight after treatment as well as the incidence of hypoglycemia and adverse events associated with the treatment were recorded. RESULTS: Two patients withdrew from the study for intolerance of gastrointestinal reactions, and another 2 withdrew for inconvenience of access to the medicines. Fifty-four of the patients finally completed the study, including 34 male and 20 female patients. After 12 weeks of therapy, all the patients showed significant improvements in FBG, 2 hPBG, HbA1c, HOMA-beta and HOMA-IR (P < 0.001) with a mean reduction of HbA1c level by (4.19 ± 1.07)%, and the goal of HbA1c control to below 7.0% was achieved in 83.33% of the patients. The reduction of HbA1c was correlated with FBG (r=0.487, P=0.000), 2 hPBG (r=0.310, P=0.023), and HOMA-ß (r=-0.398, P=0.003). The patients had a mean body weight loss by 2.47±3.38 kg (P < 0.001) and a mean decrease of body mass index (BMI) by 0.90± 1.18 kg/m2 (P < 0.001) after the therapy. The body weight-reducing effect was associated with the patients' baseline body weight (r=0.678, P=0.000), BMI (r=0.818, P=0.000), F-CP (r=0.282, P=0.039) and HOMA-IR (r=0.297, P=0.029). During the therapy 8 patients experienced hypoglycemic symptoms (10 times, 14.81%); 3 patients were diagnosed with hypoglycemia (blood glucose ≤3.9 mmol/L, 3 times), and the overall incidence of hypoglycemia was 5.56%. No serious hypoglycemia or infections of the urinary and reproductive systems occurred in these patients. CONCLUSIONS: Short-term intensive oral hypoglycemic therapy with metformin combined with sagliptin and dapagliflozin is effective for treatment of patients with newly diagnosed type 2 diabetes with HbA1c of 9%-12% and shows a good weight-reducing effect with a low risk of hypoglycemia. The combined therapy can effectively improve ß-cell insulin secretion function, and is suitable for treatment of newly diagnosed type 2 diabetic patients with high blood glucose.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2 , Glucosídeos/uso terapêutico , Metformina/uso terapêutico , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quimioterapia Combinada , Feminino , Hemoglobina A Glicada , Humanos , Hipoglicemiantes , Insulina , Masculino , Resultado do Tratamento
10.
Ther Umsch ; 76(6): 311-316, 2019 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-31762414

RESUMO

The data situation for the use of ICS in asthma is clear. In the case of COPD, on the other hand, where in recent years the pendulum has moved away from ICS towards a dual therapy based on LABA / LAMA, the discussion is open again thanks to new work. However, it would certainly be wrong to recommend ICS as a meaningful therapy for all COPD patients at this point in time, since therapy with ICS is associated with side effects, in particular an increase in the risk of developing pneumonia or osteoporosis. However, there is no doubt that patients with asthma COPD overlap require ICS therapy.


Assuntos
Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2 , Asma , Broncodilatadores/uso terapêutico , Doença Pulmonar Obstrutiva Crônica , Administração por Inalação , Asma/tratamento farmacológico , Quimioterapia Combinada , Humanos , Antagonistas Muscarínicos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico
11.
JAMA ; 322(18): 1780-1788, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31714986

RESUMO

Importance: Additional treatment options are needed for patients who do not achieve sufficient reduction in low-density lipoprotein cholesterol (LDL-C) level with available lipid-lowering therapies. Objective: To assess the efficacy of bempedoic acid vs placebo in patients at high cardiovascular risk receiving maximally tolerated lipid-lowering therapy. Design, Setting, and Participants: Phase 3, randomized, double-blind, placebo-controlled clinical trial conducted at 91 clinical sites in North America and Europe from November 2016 to September 2018, with a final date of follow-up of September 22, 2018. A total of 779 patients with atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or both met randomization criteria, which included LDL-C level 70 mg/dL (1.8 mmol/L) or greater while receiving maximally tolerated lipid-lowering therapy. Interventions: Patients were randomized 2:1 to treatment with bempedoic acid (180 mg) (n = 522) or placebo (n = 257) once daily for 52 weeks. Main Outcomes and Measures: The primary end point was percent change from baseline in LDL-C level at week 12. Secondary measures included changes in levels of lipids, lipoproteins, and biomarkers. Results: Among 779 randomized patients (mean age, 64.3 years; 283 women [36.3%]), 740 (95.0%) completed the trial. At baseline, mean LDL-C level was 120.4 (SD, 37.9) mg/dL. Bempedoic acid lowered LDL-C levels significantly more than placebo at week 12 (-15.1% vs 2.4%, respectively; difference, -17.4% [95% CI, -21.0% to -13.9%]; P < .001). Significant reductions with bempedoic acid vs placebo were observed at week 12 for non-high-density lipoprotein cholesterol (-10.8% vs 2.3%; difference, -13.0% [95% CI, -16.3% to -9.8%]; P < .001), total cholesterol (-9.9% vs 1.3%; difference, -11.2% [95% CI, -13.6% to -8.8%]; P < .001), apolipoprotein B (-9.3% vs 3.7%; difference, -13.0% [95% CI, -16.1% to -9.9%]; P < .001), and high-sensitivity C-reactive protein (median, -18.7% vs -9.4%; difference, -8.7% [asymptotic confidence limits, -17.2% to -0.4%]; P = .04). Common adverse events included nasopharyngitis (5.2% vs 5.1% with bempedoic acid and placebo, respectively), urinary tract infection (5.0% vs 1.9%), and hyperuricemia (4.2% vs 1.9%). Conclusions and Relevance: Among patients at high risk for cardiovascular disease receiving maximally tolerated statins, the addition of bempedoic acid compared with placebo resulted in a significant lowering of LDL-C level over 12 weeks. Further research is needed to assess the durability and clinical effect as well as long-term safety. Trial Registration: ClinicalTrials.gov Identifier: NCT02991118.


Assuntos
Anticolesterolemiantes/uso terapêutico , Aterosclerose/tratamento farmacológico , Ácidos Dicarboxílicos/uso terapêutico , Ácidos Graxos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemia Familiar Combinada/tratamento farmacológico , Idoso , Anticolesterolemiantes/efeitos adversos , Aterosclerose/sangue , Doenças Cardiovasculares/prevenção & controle , LDL-Colesterol/sangue , Ácidos Dicarboxílicos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Ácidos Graxos/efeitos adversos , Feminino , Humanos , Hiperlipidemia Familiar Combinada/sangue , Masculino , Pessoa de Meia-Idade
12.
Orv Hetil ; 160(47): 1856-1863, 2019 Nov.
Artigo em Húngaro | MEDLINE | ID: mdl-31736344

RESUMO

Introduction: The Pan-European Registry on Helicobacter pylori management was conceived in 2013 to monitor eradication practices in Europe for 10 years. Aim: To assess the efficacy of different eradication regimens in a single outpatient clinic of gastroenterology. Method: Between 2013 and 2019, 247 patients were registered in a prospective non-interventional study. The infection was diagnosed either by endoscopy, histology, rapid urease test or 13C-urea breath test. As first-line treatment, the patients received either a 7-day triple regimen (any of PPI + amoxicillin + clarithromycin or tinidazole), 10-day modified sequential treatment (PPI + amoxicillin for 5 days + tinidazole and levofloxacin for 5 days), 10-day quadruple concomitant treatment (PPI + amoxicillin + tetracycline or doxycycline + metronidazole or tinidazole) or bismuth-based quadruple treatment. Bismuth or non-bismuth based quadruple or alternative regimens were given as second- or third-line treatment. Results: The eradication rates on per protocol basis were: 82.7% (95% confidence interval: 68.1-97.4) (first-line regimens), 85.2% (75.4-94.9) (sequential treatment), 95.1% (89.6-100) (concomitant treatment) and 82.6% (69.7-95.9) (bismuth-based quadruple regimen). Second-line regimens achieved 65.2% (48.2-83.0) and third-line therapy 54.5% (19.4-86.6), respectively. Conclusion: The first-line concomitant regimen was superior to triple and not significantly better than the sequential or bismuth-based treatment. Second- and third-line regimens achieved largely suboptimal results. Orv Hetil. 2019; 160(47): 1856-1863.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/isolamento & purificação , Quimioterapia Combinada , Europa (Continente) , Infecções por Helicobacter/diagnóstico , Humanos , Estudos Prospectivos , Sistema de Registros , Resultado do Tratamento
13.
Pan Afr Med J ; 33: 222, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31692792

RESUMO

Introduction: HIV-2, endemic in West Africa, has a natural resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) which makes it difficult to treat it in developing countries. Methods: We conducted a descriptive, longitudinal, prospective study over the period November 2005-June 2017. Virologic failure has been defined as any viral load greater than 50 copies/ml after 6 months of ARV treatment administered twice. Assays for detecting drug-resistance mutations was performed in the protease-coding region and in the reverse transcriptase-coding region. Results: Data from a total of 110 patients were collected. The patients had a median age of 46 years (ranging from 18 to 67) with a sex-ratio F/M of 2.54. At inclusion, viral load could be assessed in 44% of cases with a median of 935cp/ml (ranging from 17 to 144038). Antiretroviral regimen consisted of a combination of 2 NRTIs and 1IP in 94% of cases. The median follow-up was 1200 days (ranging from 1 to 3840); 94 then 76 patients completed their 12-month and 24-month assessments respectively. At 24-month follow-up, 39 patients had virologic failure, reflecting a prevalence of 39% estimated at 33% at 12-month follow-up and at 11% at 24-month follow-up; NRTIs resistance was observed in 45% of patients, IP resistance in 41% of patients while multi-NRTIs resistance and multi-IP resistance in 30% of patients. Conclusion: Currently, there is an urgent need to make available the new therapeutic classes of ARV for second line ART for patients living with HIV-2 with therapeutic failure in resource-limited settings.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/administração & dosagem , HIV-2/isolamento & purificação , Inibidores da Transcriptase Reversa/administração & dosagem , Adolescente , Adulto , Idoso , Farmacorresistência Viral/genética , Quimioterapia Combinada , Feminino , Seguimentos , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Inibidores da Protease de HIV/farmacologia , HIV-2/efeitos dos fármacos , HIV-2/genética , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores da Transcriptase Reversa/farmacologia , Senegal/epidemiologia , Carga Viral , Adulto Jovem
14.
Expert Opin Drug Metab Toxicol ; 15(11): 927-935, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31668105

RESUMO

Introduction: Ritonavir and cobicistat are pharmacoenhancers used to improve the disposition of other HIV antiretrovirals. These drugs are, however, characterized by important pharmacokinetic differences.Areas covered: Here, the authors firstly update the available information on the pharmacokinetics of ritonavir and cobicistat. Subsequently, the review focuses on the description of drug-drug interactions (DDIs) involving cobicistat and comedications that might beneficiate from a shift-back to ritonavir. A MEDLINE Pubmed search for articles published from January 1995 to April 2019 was completed matching the term ritonavir or cobicistat with pharmacokinetics, DDIs, and pharmacology. Moreover, additional studies were identified from the reference list of retrieved articles.Expert opinion: Despite more than 20 years after its introduction on the market, ritonavir still represents a valid option for the treatment of selected HIV-infected patients. The large-scale switch to cobicistat may result in some unexpected DDIs not previously reported for ritonavir. Besides the issue of DDIs, additional advantage of ritonavir over cobicistat is its use in pregnancy, and its availability as single component of pharmaceutical formulations allowing the fine-tuning of antiretroviral regimens in patients with heavy polypharmacy when other unboosted-based therapeutic options cannot be used.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Cobicistat/administração & dosagem , Ritonavir/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Cobicistat/farmacocinética , Interações de Medicamentos , Quimioterapia Combinada , Infecções por HIV/tratamento farmacológico , Humanos , Ritonavir/farmacocinética
15.
Medicine (Baltimore) ; 98(45): e17170, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702607

RESUMO

Reversible cerebral vasoconstriction syndrome (RCVS) is a rare clinical syndrome accompanying with severe headache as its main symptom. Postpartum reversible cerebral vasoconstriction syndrome (PPRCVS) refers to RCVS occurring in the puerperium, in which it has a low incidence, and that is easily missed diagnosed and misdiagnosed in clinical practice.By searching in CNKI and Wanfang databases, 9 published articles reported PPRCVS were found, totally including 12 cases with PPRCVS. The clinical data of these 12 cases were accordingly analyzed and summarized. The characteristics of these cases were compared with those reported in other countries, and eventually the clinical characteristics of Chinese PPRCVS patients were summarized.The clinical characteristics of Chinese PPRCVS patients were basically as same as those found in other countries, while the onset age was earlier, PPRCVS often occurred earlier after delivery, with higher proportions of concomitant symptoms and abnormal laboratory and imaging examinations; moreover, and fewer patients were diagnosed by digital subtraction angiography (DSA).


Assuntos
Angiografia Digital/métodos , Quimioterapia Combinada/métodos , Vasoespasmo Intracraniano/diagnóstico por imagem , Vasoespasmo Intracraniano/tratamento farmacológico , Adulto , Idade de Início , China/epidemiologia , Feminino , Humanos , Incidência , Imagem por Ressonância Magnética , Período Pós-Parto , Vasoespasmo Intracraniano/epidemiologia
16.
Medicine (Baltimore) ; 98(45): e17869, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702652

RESUMO

Nontuberculous mycobacteria (NTM) are important pathogens in humans, and hospital-based studies have shown an increased incidence of NTM infection. However, little is known about the treatment pattern of NTM infection with respect to the number of cases per population in South Korea. This study evaluated the trends in the incidence of NTM infection, respiratory comorbidities, and treatment patterns in South Korea.National claims data from the Health Insurance Review and Assessment service database for the years 2009 to 2015 were reviewed, and codes related to NTM infection, respiratory comorbidities occurring from one year before NTM infection and associated treatments were identified.In total, 52,551 patients were included in the study and the average annual incidence per 100,000 person-years was 12.8. The annual incidence was found to have increased from 6.6 to 26.6 per 100,000 persons. Accompanied comorbidities were tuberculosis (33.7%), followed by bronchial asthma (33.2%), chronic obstructive pulmonary disease (25.6%), and lung cancer (5.8%). A total of 76.6% of patients did not receive any combination treatment within one year after the diagnosis of NTM infection. Macrolide-based treatment was administered to 18.8% of patients.A dramatic increase in the incidence of NTM infection was noted in the population of South Korea. Approximately three-fourth of the patients with NTM infection were clinically observed without treatment for at least 1 year after the identification of NTM infection and most patients who treated NTM infection received macrolide-based combination therapy.


Assuntos
Antibióticos Antituberculose/uso terapêutico , Infecções por Micobactéria não Tuberculosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Comorbidade , Bases de Dados Factuais , Quimioterapia Combinada , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Infecções por Micobactéria não Tuberculosa/epidemiologia , Infecções por Micobactéria não Tuberculosa/terapia , República da Coreia/epidemiologia , Adulto Jovem
17.
Anticancer Res ; 39(11): 5891-5901, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704813

RESUMO

BACKGROUND/AIM: Induction of endoplasmic reticulum (ER) stress is a novel approach to cancer treatment. This study investigated the ability of the clinically feasible combination of the human immunodeficiency virus protease inhibitors lopinavir and ritonavir to induce ER stress killing urological cancer cells. MATERIALS AND METHODS: Renal cancer cells (769-P, 786-O) and bladder cancer cells (UMUC-3, T-24) were used to investigate the ability of the combination to induce ER stress and its mechanism of action. RESULTS: The combination inhibited the growth of both renal and bladder cancer cells synergistically by inducing ER stress. The combination-induced ER stress increased the expression of AMP-activated protein kinase and suppressed the mammalian target of rapamycin pathway. It also increased the expression of a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor and thereby sensitized the cancer cells to TRAIL. CONCLUSION: The combination of lopinavir and ritonavir acts against urological cancer cells by inducing ER stress synergistically.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Inibidores da Protease de HIV/farmacologia , Lopinavir/farmacologia , Ritonavir/farmacologia , Neoplasias Urológicas/tratamento farmacológico , Quimioterapia Combinada , Humanos , Células Tumorais Cultivadas , Neoplasias Urológicas/metabolismo , Neoplasias Urológicas/patologia
18.
Medicine (Baltimore) ; 98(46): e17681, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725610

RESUMO

RATIONALE: Castleman's disease (CD) is a rare lymphoproliferative disease. Compared to unicentric CD, multicentric Castleman disease (MCD) displays poorer prognosis and great variance to different therapies. Though chemotherapy, immunization therapy, and glucocorticoids have been used in the treatment of MCD, its optimal treatment is still controversial. PATIENT CONCERNS: A 47-year-old woman was admitted due to poor appetite, general fatigue, puffiness of face, systemic rash, and abdominal distension. On physical examination, the patient displayed as general lymphadenopathy, splenomegaly, hepatomegaly, and shifting dullness. DIAGNOSES: After biopsy of her swollen lymph node and laboratory tests, her initial diagnosis was hyaline vascular-CD. INTERVENTIONS: She was treated with combination of tocilizumab, lenalidomide, and glucocorticoids. OUTCOMES: This patient achieved complete remission (CR) with all her indexes returned to be normal. Her blood routines and biochemical examinations were still normal during the following period. LESSONS: We reported a case with multicentric Castleman's disease (MCD) which acquired quite good remission after combination treatment with tocilizumab, lenalidomide, and glucocorticoids. Our report provided powerful evidence for displaying the efficiency and safety of target therapy against unicentric Castleman disease.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Glucocorticoides/administração & dosagem , Fatores Imunológicos/administração & dosagem , Lenalidomida/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
19.
Medicine (Baltimore) ; 98(46): e17734, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725614

RESUMO

BACKGROUND: The efficacy of dexketoprofen for migraine attack remains controversial. We conduct a systematic review and meta-analysis to explore the influence of dexketoprofen supplementation versus placebo on pain control in migraine attack patients. METHODS: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through March 2019 for randomized controlled trials (RCTs) assessing the effect of dexketoprofen supplementation versus placebo on pain control for migraine attack patients. This meta-analysis is performed using the random-effect model. RESULTS: Five RCTs involving 794 patients are included in the meta-analysis. Overall, compared with control group for migraine attack, dexketoprofen supplementation is associated with substantially increased pain free at 2 hours (RR = 1.90; 95% CI = 1.43-2.53; P < .0001), pain free at 48 hours (RR = 1.63; 95% CI = 1.07-2.49; P = .02), good or excellent treatment (RR = 1.48; 95% CI = 1.24-1.78; P < .0001) and pain relief at 2 hours (RR = 1.80; 95% CI = 1.17-2.77; P = .007), as well as reduced need for rescue drug (RR = 0.64; 95% CI = 0.43-0.94; P = .02), with no significant increase in adverse events (RR = 1.51; 95% CI = 0.87-2.62; P = .14). CONCLUSION: Dexketoprofen supplementation benefits to improve pain control at 48 hours and reduce the need for rescue drug in migraine attack patients.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Cetoprofeno/análogos & derivados , Transtornos de Enxaqueca/tratamento farmacológico , Manejo da Dor/métodos , Trometamina/administração & dosagem , Adulto , Quimioterapia Combinada , Feminino , Humanos , Cetoprofeno/administração & dosagem , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
20.
Rev Med Suisse ; 15(667): 1854-1858, 2019 Oct 16.
Artigo em Francês | MEDLINE | ID: mdl-31617972

RESUMO

Helicobacter pylori infection is associated with chronic gastric inflammation, peptic ulcer and an increased risk of gastric cancer. Helicobacter eradication traditionally consists of an empirical therapy combining clarithromycine, amoxicillin and proton pump inhibitors. However, this classic therapy needs to be reassessed because of the raising prevalence of clarithromycine resistance. Various alternative eradication treatments have been studied. This article aims to review the recommended alternatives and the different factors to guide the most appropriate first line eradication therapy.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Amoxicilina/farmacologia , Amoxicilina/uso terapêutico , Antibacterianos/farmacologia , Claritromicina/farmacologia , Claritromicina/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Quimioterapia Combinada , Humanos , Inibidores da Bomba de Prótons/farmacologia , Inibidores da Bomba de Prótons/uso terapêutico
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