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1.
PLoS Biol ; 18(9): e3000856, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32941420

RESUMO

Antibiotic combination therapies are important for the efficient treatment of many types of infections, including those caused by antibiotic-resistant pathogens. Combination treatment strategies are typically used under the assumption that synergies are conserved across species and strains, even though recent results show that the combined treatment effect is determined by specific drug-strain interactions that can vary extensively and unpredictably, both between and within bacterial species. To address this problem, we present a new method in which antibiotic synergy is rapidly quantified on a case-by-case basis, allowing for improved combination therapy. The novel CombiANT methodology consists of a 3D-printed agar plate insert that produces defined diffusion landscapes of 3 antibiotics, permitting synergy quantification between all 3 antibiotic pairs with a single test. Automated image analysis yields fractional inhibitory concentration indices (FICis) with high accuracy and precision. A technical validation with 3 major pathogens, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, showed equivalent performance to checkerboard methodology, with the advantage of strongly reduced assay complexity and costs for CombiANT. A synergy screening of 10 antibiotic combinations for 12 E. coli urinary tract infection (UTI) clinical isolates illustrates the need for refined combination treatment strategies. For example, combinations of trimethoprim (TMP) + nitrofurantoin (NIT) and TMP + mecillinam (MEC) showed synergy, but only for certain individual isolates, whereas MEC + NIT combinations showed antagonistic interactions across all tested strains. These data suggest that the CombiANT methodology could allow personalized clinical synergy testing and large-scale screening. We anticipate that CombiANT will greatly facilitate clinical and basic research of antibiotic synergy.


Assuntos
Antibacterianos/administração & dosagem , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana/métodos , Algoritmos , Andinocilina/administração & dosagem , Andinocilina/farmacologia , Antibacterianos/farmacologia , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Humanos , Testes de Sensibilidade Microbiana/instrumentação , Nitrofurantoína/administração & dosagem , Nitrofurantoína/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Reprodutibilidade dos Testes , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Trimetoprima/administração & dosagem , Trimetoprima/farmacologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
2.
Medicine (Baltimore) ; 99(32): e21627, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769925

RESUMO

BACKGROUND: Acupoint application combined with western medicine has been used for treating allergic rhinitis widely. However, the efficacy and safety of acupoint application combined with western medicine for allergic rhinitis are unclear. This study aims to evaluate the efficacy and safety of acupoint application combined with western medicine for allergic rhinitis. METHODS: Randomized controlled trials of acupoint application combined with western medicine for allergic rhinitis will be searched in PubMed, EMbase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database from inception to July, 2020. And Baidu Scholar, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain more relevant studies comprehensively. Two researchers will perform data extraction and risk of bias assessment independently. Statistical analysis will be conducted in RevMan 5.3. RESULTS: This study will summarize the present evidence by exploring the efficacy and safety of acupoint application combined with western medicine for the treatment of allergic rhinitis. CONCLUSIONS: The findings of the study will provide helpful evidence for the efficacy and safety of acupoint application combined with western medicine in the treatment of allergic rhinitis, facilitating clinical practice and further scientific studies. ETHICS AND DISSEMINATION: The private information from individuals will not publish. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/NSGJH.


Assuntos
Pontos de Acupuntura , Protocolos Clínicos , Quimioterapia Combinada/normas , Segurança do Paciente/normas , Rinite Alérgica/terapia , Terapia por Acupuntura/métodos , Quimioterapia Combinada/efeitos adversos , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Resultado do Tratamento
4.
J Urol ; 204(5): 969-975, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32519913

RESUMO

PURPOSE: American Urological Association (AUA) antibiotic prophylaxis recommendations may be insufficient for covering organisms commonly found in penile prosthesis infections. In this study we assess the difference between AUA recommended antibiotic prophylaxis and nonstandard prophylaxis in preventing device infections in penile prosthesis surgery performed in diabetic patients. MATERIALS AND METHODS: A multicenter, retrospective cohort study of diabetic patients undergoing primary penile prosthesis surgery was performed between April 2003 and August 2018. Eighteen institutions from the United States, Europe and Korea contributed. The association between antibiotic prophylaxis type and postoperative penile prosthesis infections, device explantations and revision surgeries was assessed. RESULTS: Standard AUA antibiotic prophylaxis was followed in 48.6% (391) of cases while nonstandard prophylaxis was used in 51.4% (413). Common nonstandard antibiotic prophylaxis included vancomycin-gentamycin-fluoroquinolone, clindamycin-fluoroquinolone, and vancomycin-fluoroquinolone among other combinations. Patients who received AUA prophylaxis had significantly more postoperative device infections (5.6% vs 1.9%, p <0.01) and explantations (8.3% vs 2.0%, p <0.001) compared to those who received nonstandard prophylaxis. Patients who received AUA prophylaxis had significantly higher odds of a postoperative device infection (OR 2.8, 95% CI 1.1-7.3) and explantation (OR 3.6, 95% CI 1.4-9.1) compared to those who received nonstandard prophylaxis. CONCLUSIONS: Diabetic men with erectile dysfunction who received standard AUA prophylaxis for penile prosthesis surgery had significantly greater odds of experiencing a postoperative device infection and device explantation compared to patients who received nonstandard prophylaxis. Our study provides a strong rationale for a prospective investigation to establish the most appropriate prophylaxis strategy in penile prosthesis surgery.


Assuntos
Antibioticoprofilaxia/normas , Diabetes Mellitus/imunologia , Disfunção Erétil/cirurgia , Prótese de Pênis/efeitos adversos , Guias de Prática Clínica como Assunto , Implantação de Prótese/efeitos adversos , Infecções Relacionadas à Prótese/epidemiologia , Idoso , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Antibioticoprofilaxia/estatística & dados numéricos , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Quimioterapia Combinada/estatística & dados numéricos , Europa (Continente)/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Implantação de Prótese/instrumentação , Infecções Relacionadas à Prótese/imunologia , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/prevenção & controle , Reoperação/estatística & dados numéricos , República da Coreia/epidemiologia , Estudos Retrospectivos , Sociedades Médicas/normas , Resultado do Tratamento , Estados Unidos/epidemiologia , Urologia/normas
5.
Medicine (Baltimore) ; 99(23): e20473, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32501994

RESUMO

BACKGROUND: In China, heat-clearing and detoxifying Chinese medicines combined with conventional therapy are commonly applied to treat the mild hand, foot, and mouth disease (HFMD). However, there is lack of solid evidence on the efficacy and safety of such therapies. METHODS: We conducted a pooled analysis with individual patient data from 5 strictly randomized controlled clinical trials to assess the efficacy and safety of this combination therapy for mild HFMD. An intention-to-treat analysis was performed. A 2-stage meta-analysis method was adopted to analyze the pooled effect size. RESULTS: In total, 947 patients were included. Compared with conventional therapy, the combination therapy significantly reduced the progression rate of HFMD from mild to severe (odds ratio [OR] 0.43, 95% confidence interval [CI]: 0.22 to 0.83, P = .01). Meanwhile, the healing time of skin rash and oral ulcer in the combination therapy group was significantly shorter than that of conventional therapy. The overall hazard ratio (HR) of healing time of the skin rash or oral ulcer was 1.22 (95%CI: 1.04 to 1.43; P = .02). However, except Jinlianqingre effervescent tablets, the combination therapy cannot shorten the time to fever resolution (HR 1.12, 95%CI: 0.97 to 1.29, P = .14). Because of the heterogeneity, Jinlianqingre effervescent tablets were analyzed separately and the HRs of the time to fever resolution and the healing time of skin rash or oral ulcer were 3.88 (95%CI: 3.19 to 4.72; P < .0001) and 3.79 (95%CI: 2.81 to 5.11; P < .0001), respectively. There were 30 adverse events reported in total; 2 cases were related to Chinese medicines. CONCLUSION: In conclusion, the heat-clearing and detoxifying Chinese medicines on top of conventional therapy can effectively reduce the progressive rate of mild HFMD and improve healing of skin and oral mucosal lesions. More studies are needed for the time to fever resolution.


Assuntos
Quimioterapia Combinada/normas , Medicamentos de Ervas Chinesas/normas , Febre/tratamento farmacológico , Doença de Mão, Pé e Boca/tratamento farmacológico , Quimioterapia Combinada/métodos , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Inativação Metabólica , Razão de Chances
7.
Am J Respir Crit Care Med ; 201(9): e56-e69, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32283960

RESUMO

Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD). It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thoracic Society.Methods: Comprehensive evidence syntheses were performed on all relevant studies that addressed the clinical questions and critical patient-centered outcomes agreed upon by the panel of experts. The evidence was appraised, rated, and graded, and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach.Results: After weighing the quality of evidence and balancing the desirable and undesirable effects, the guideline panel made the following recommendations: 1) a strong recommendation for the use of long-acting ß2-agonist (LABA)/long-acting muscarinic antagonist (LAMA) combination therapy over LABA or LAMA monotherapy in patients with COPD and dyspnea or exercise intolerance; 2) a conditional recommendation for the use of triple therapy with inhaled corticosteroids (ICS)/LABA/LAMA over dual therapy with LABA/LAMA in patients with COPD and dyspnea or exercise intolerance who have experienced one or more exacerbations in the past year; 3) a conditional recommendation for ICS withdrawal for patients with COPD receiving triple therapy (ICS/LABA/LAMA) if the patient has had no exacerbations in the past year; 4) no recommendation for or against ICS as an additive therapy to long-acting bronchodilators in patients with COPD and blood eosinophilia, except for those patients with a history of one or more exacerbations in the past year requiring antibiotics or oral steroids or hospitalization, for whom ICS is conditionally recommended as an additive therapy; 5) a conditional recommendation against the use of maintenance oral corticosteroids in patients with COPD and a history of severe and frequent exacerbations; and 6) a conditional recommendation for opioid-based therapy in patients with COPD who experience advanced refractory dyspnea despite otherwise optimal therapy.Conclusions: The task force made recommendations regarding the pharmacologic treatment of COPD based on currently available evidence. Additional research in populations that are underrepresented in clinical trials is needed, including studies in patients with COPD 80 years of age and older, those with multiple chronic health conditions, and those with a codiagnosis of COPD and asthma.


Assuntos
Corticosteroides/normas , Agonistas de Receptores Adrenérgicos beta 2/normas , Broncodilatadores/normas , Quimioterapia Combinada/normas , Antagonistas Muscarínicos/normas , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Corticosteroides/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Broncodilatadores/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/uso terapêutico , Guias de Prática Clínica como Assunto , Sociedades Médicas/normas , Estados Unidos
10.
Medicine (Baltimore) ; 99(9): e19295, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118743

RESUMO

BACKGROUND: Preoperative chemoradiotherapy (CRT) is one standard option for localized esophageal or gastroesophageal junction (GEJ) cancer patients but an optimal concurrent chemotherapy combination is not established. METHODS: 412 patients with resectable (cT1N1M0 or cT2-4N0-3M0) esophageal or GEJ cancer treated at the MDACC between October 2002 and June 2016 were analyzed. Exposures: CRT with DF or FOX followed by surgery (trimodality; TMT). Main outcomes and measures: Primary endpoints were overall survival (OS) and disease-free survival (DFS). Univariate and multivariate Cox analyses were performed. RESULTS: Of the 412 patients analyzed, 264 (64%) received DF and 148 (36%) FOX. The median age was 60 years, and 95% had adenocarcinoma. The clinical complete response, positron-emission tomography response, and pathologic complete response rates were 73%, 73%, and 30%, respectively. Median follow-up was 60.4 months. Median OS for the entire cohort was 81.6 months (95% confidence interval [CI], 56.3-122.0); 81.6 months (95% CI, 55.9-not estimable) for the DF group and 67.7 months (95% CI, 41.6-not estimable) for the FOX group (P = .24). The median DFS was 45.6 months (95% CI, 33.1-61.7) for the entire cohort; 49.5 months (95% CI, 38.6-70.3) for DF and 33.0 months (95% CI, 18.1-70.4; P = .38) for FOX. Higher tumor location (unfavorable) and clinical complete response (favorable) were prognostic for both OS and DFS in the multivariate analysis. CONCLUSION: At our high-volume center, the outcome of 412 TMT esophageal cancer patients was excellent. Taxane-based chemotherapy produces nonsignificant favorable trend.


Assuntos
Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Quimiorradioterapia/métodos , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Compostos de Platina/uso terapêutico , Taxoides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Hidrocarbonetos Aromáticos com Pontes/normas , Quimiorradioterapia/normas , Quimiorradioterapia/estatística & dados numéricos , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Quimioterapia Combinada/estatística & dados numéricos , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Platina/normas , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Sobrevida , Taxoides/normas , Texas , Resultado do Tratamento
11.
Intern Emerg Med ; 15(2): 327-331, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32040830

RESUMO

The aim of this systematic review was to assess AKI (acute kidney injury) in adult patients, treated with vancomycin (V) + piperacillin/tazobactam (PT) compared to V monotherapy. Studies were found in Pubmed, Web of Science and Scopus databases. Articles not in English, pediatric studies and case reports were excluded. A study is eligible for inclusion if the adjusted Odds ratio (aOR) for AKI in V + PT compared to V monotherapy groups, could be extracted or determined from available data. Six retrospective cohort studies were eligible for inclusion criteria and so they were included in the analysis. All studies separately showed a significant higher risk of developing AKI (OR > 1, p < 0.05) in V + PT group compared to V monotherapy group. Considering the methodological difference of included studies, a random effect model was preferred. The model showed a pooled significant higher risk of developing AKI [OR 2.77 (95% CI 1.94, 3.96), p < 0.0001] in V + PT group compared to V group. Association of V and PT appears to be associated with a greater risk of AKI compared to V in monotherapy. These results may serve as the impetus for further evaluation into true mechanisms behind this additive nephrotoxic effect and its potential implications on mortality.


Assuntos
Lesão Renal Aguda/etiologia , Quimioterapia Combinada/normas , Piperacilina/efeitos adversos , Tazobactam/efeitos adversos , Vancomicina/efeitos adversos , Adulto , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Humanos , Piperacilina/uso terapêutico , Tazobactam/uso terapêutico , Vancomicina/uso terapêutico
12.
Einstein (Sao Paulo) ; 18: eAO4995, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-32074221

RESUMO

OBJECTIVE: To describe antiretroviral treatment regimens prescribed and their compliance with the Clinical Protocol and Therapy Guidelines of the Ministry of Health for the management of HIV infection. METHODS: Observational and descriptive study. Secondary data of the state of Paraná (Brazil) on drugs, treatment regimens, lines of treatment and number of individuals on treatment, from January to June 2018, were accessed at the Antiretroviral Agents Logistic Control System. Combinations of antiretroviral drugs (treatment regimens) were compared according to the current Clinical Protocol and Therapy Guidelines and non-compliances were classified and quantified. RESULTS: In Paraná, 35,127 individuals with HIV were treated with 253 different treatment regimens. Of the prescribed regimens, 19.1% were first-line, 27.4% second-line and 48.5% third-line. Among non-compliances, the most prevalent were absence of association of protease inhibitors and ritonavir (42.8%), low efficacy triple therapy (36.9%), double therapy (26.1%), monotherapy (20.3%), and triple therapy of nucleoside analog reverse transcriptase inhibitors (17.1%). CONCLUSION: Most individuals receiving HIV treatment in the state of Paraná are on treatment regimens established in the current Clinical Protocol and Therapy Guidelines, which contributes to successful therapy. However, associations not provided by the current Clinical Protocol and Therapy Guidelines were identified in the initial treatment lines, which could lead to ineffectiveness, virologic failure and viral resistance.


Assuntos
Antirretrovirais/administração & dosagem , Protocolos Clínicos/normas , Fidelidade a Diretrizes/normas , Adesão à Medicação , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Brasil , Quimioterapia Combinada/normas , Quimioterapia Combinada/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Humanos , Adesão à Medicação/estatística & dados numéricos
14.
Gastroenterology ; 158(5): 1465-1496.e17, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31945351

RESUMO

A subset of patients with ulcerative colitis (UC) present with, or progress to, moderate to severe disease activity. These patients are at high risk for colectomy, hospitalization, corticosteroid dependence, and serious infections. The risk of life-threatening complications and emergency colectomy is particularly high among those patients hospitalized with acute severe ulcerative colitis. Optimal management of outpatients or inpatients with moderate to severe UC often requires the use of immunomodulator and/or biologic therapies, including thiopurines, methotrexate, cyclosporine, tacrolimus, TNF-α antagonists, vedolizumab, tofacitnib, or ustekinumab, either as monotherapy or in combination (with immunomodulators), to mitigate these risks. Decisions about optimal drug therapy in moderate to severe UC are complex, with limited guidance on comparative efficacy and safety of different treatments, leading to considerable practice variability. Therefore, the American Gastroenterological Association prioritized development of clinical guidelines on this topic. To inform the clinical guidelines, this technical review was completed in accordance with the Grading of Recommendations Assessment, Development and Evaluation framework. Focused questions in adult outpatients with moderate to severe UC included: (1) overall and comparative efficacy of different medications for induction and maintenance of remission in patients with or without prior exposure to TNF-α antagonists, (2) comparative efficacy and safety of biologic monotherapy vs combination therapy with immunomodulators, (3) comparative efficacy of top-down (upfront use of biologics and/or immunomodulator therapy) vs step-up therapy (acceleration to biologic and/or immunomodulator therapy only after failure of 5-aminosalicylates, and (4) role of continuing vs stopping 5-aminosalicylates in patients being treated with immunomodulator and/or biologic therapy for moderate to severe UC. Focused questions in adults hospitalized with acute severe ulcerative colitis included: (5) overall and comparative efficacy of pharmacologic interventions for inpatients refractory to corticosteroids, in reducing risk of colectomy, (6) optimal dosing regimens for intravenous corticosteroids and infliximab in these patients, and (7) role of adjunctive antibiotics in the absence of confirmed infections.


Assuntos
Colectomia/normas , Colite Ulcerativa/terapia , Gastroenterologia/normas , Fatores Imunológicos/uso terapêutico , Guias de Prática Clínica como Assunto , Adulto , Assistência Ambulatorial/métodos , Assistência Ambulatorial/normas , Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Fatores Biológicos/uso terapêutico , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/imunologia , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Gastroenterologia/métodos , Glucocorticoides/uso terapêutico , Hospitalização , Humanos , Índice de Gravidade de Doença , Sociedades Médicas/normas , Resultado do Tratamento , Estados Unidos
15.
J Am Acad Dermatol ; 82(3): 575-585.e1, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29438767

RESUMO

BACKGROUND: Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management. OBJECTIVE: We now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations. METHODS: A preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus. RESULTS: The 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion. LIMITATIONS: Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available. CONCLUSIONS: We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus.


Assuntos
Fatores Imunológicos/administração & dosagem , Pênfigo/diagnóstico , Pênfigo/terapia , Plasmaferese , Guias de Prática Clínica como Assunto , Academias e Institutos/normas , Administração Intravenosa , Antígenos CD20/imunologia , Terapia Combinada/métodos , Terapia Combinada/normas , Consenso , Técnica Delfos , Dermatologia/métodos , Dermatologia/normas , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Europa (Continente) , Glucocorticoides/administração & dosagem , Humanos , Pênfigo/imunologia , Rituximab/administração & dosagem , Índice de Gravidade de Doença
16.
Int J Neuropsychopharmacol ; 23(2): 125-131, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31867671

RESUMO

The term polypharmacy was originally coined to refer to problems related to multiple drug consumption and excessive drug use during the treatment of a disease or disorder. In the treatment of schizophrenia, polypharmacy usually refers to the simultaneous use of 2 or more antipsychotic medications or combined (adjunct) medications such as mood stabilizers, antidepressants, anxiolytics, or hypnotics in addition to single or multiple antipsychotics. Two decades ago, antipsychotic polypharmacy was criticized as being more expensive, having unproven efficacy, and causing more side effects. However, in recent years, antipsychotic polypharmacy has become more or less acceptable in the views of clinical practitioners and academic researchers. Results from recent reviews have suggested that the common practice of antipsychotic polypharmacy lacks double-blind or high-quality evidence of efficacy, except for negative symptom reduction with aripiprazole augmentation. We reviewed some representative studies that enrolled large numbers of patients and compared antipsychotic polypharmacy and monotherapy during the past decade. The results revealed that a certain proportion of select patients can benefit from antipsychotic polypharmacy without further negative consequences. Because most of the current treatment guidelines from different countries and organizations prefer monotherapy and discourage all antipsychotic polypharmacy, guidelines regarding the use of antipsychotic polypharmacy in clinical practice should be revised. On the basis of the findings of 2 large-scale studies from Asia and Europe, we also suggest ideal rates of various maintenance treatments of schizophrenia, which are as follows: antipsychotic polypharmacy, 30%; combined mood stabilizer, 15%; combined antidepressant, 10%; combined anxiolytics, 30%; and combined hypnotic, 10%.


Assuntos
Antipsicóticos/uso terapêutico , Quimioterapia Combinada/normas , Polimedicação , Guias de Prática Clínica como Assunto/normas , Esquizofrenia/tratamento farmacológico , Humanos
18.
Medicina (Kaunas) ; 55(11)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752240

RESUMO

Background and Objectives: Neuroinflammation is associated with many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). In this study, we investigate the anti-inflammatory, anti-oxidant, and anti-apoptotic properties of two non-psychoactive phytocannabinoids, cannabigerol (CBG) and cannabidiol (CBD). Materials and Methods: The motoneuron-like cell line NSC-34 differentiated by serum deprivation and with the additional treatment of all-trans retinoic acid (RA) is a valid model to investigate molecular events linked to neurodegeneration in ALS. Results: Pre-treatment with CBG (at 2.5 and 5 µM doses) alone and in combination with CBD (at 2.5 and 5 µM doses) was able to reduce neuroinflammation induced by a culture medium of LPS-stimulated macrophages. In particular, the pre-treatment with CBD at a 5 µM dose decreased TNF-α levels and increased IL10 and IL-37 expression. CBG-CBD association at a 5 µM dose also reduced NF-kB nuclear factor activation with low degradation of the inhibitor of kappaB alpha (IkBα). CBG and CBD co-administered at a 5 µM dose decreased iNOS expression and increased Nrf2 levels. Furthermore, the pre-treatment with the association of two non-psychoactive cannabinoids downregulated Bax protein expression and upregulated Bcl-2 expression. Our data show the anti-inflammatory, anti-oxidant, and anti-apoptotic effects PPARγ-mediated. Conclusions: Our results provide preliminary support on the potential therapeutic application of a CBG-CBD combination for further preclinical studies.


Assuntos
Canabinoides/normas , Quimioterapia Combinada/normas , Inflamação/prevenção & controle , Neurônios/efeitos dos fármacos , Canabidiol/normas , Canabidiol/uso terapêutico , Canabinoides/uso terapêutico , Técnicas de Cultura de Células/métodos , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Humanos , Fatores de Proteção
19.
Kathmandu Univ Med J (KUMJ) ; 17(65): 14-19, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31734672

RESUMO

Background Acne vulgaris has considerable impact on physical and psychological health. Isotretinoin is considered most effective drug available for acne therapy but with limited acceptance because of its adverse effects. Antihistamine inhibits inflammatory mediators, Propionibacterium acne induced itching, reduction of squalene and sebum in sebocyte, reduces anxiety and further lessens hormonal derangement and inhibits mast cell induced fibrosis and scars. Clinical relevance is lacking in the use of antihistamine in the treatment of acne and its potential efficacy needs to be clarified. Objective To evaluate the efficacy and safety of combining isotretinoin and antihistamine compare to isotretinoin alone in patients with moderate to severe acne at week 12. Method One hundred patients with moderate to severe acne were included in this randomised, controlled comparative study. Fifty patients were treated with isotretinoin and 50 patients were treated with additional antihistamine, levocetirizine and assessment was done at baseline, 4, 8 and 12 weeks of treatment. Result At week 12, compared to isotretinoin only group, combination of isotretinoin and levocetirizine group showed more statistically significant decrease in score of global acne grading system (51.0 vs. 38.5%) and acne lesion counts (non-inflammatory lesion: 63.2 vs. 44.5%; inflammatory lesions: 75.9 vs. 62.7%; total lesions: 66.07 vs. 48.7%; all p< 0.05). Flaring up of acne occurred less frequently and adverse effects were more tolerable in levocetirizine group. Conclusion Use of antihistamine with isotretinoin provides synergic effect while minimizing the side effect of isotretinoin and greater clearance of the lesion and scars.


Assuntos
Acne Vulgar/tratamento farmacológico , Antagonistas dos Receptores Histamínicos/uso terapêutico , Isotretinoína/uso terapêutico , Acne Vulgar/complicações , Adolescente , Adulto , Cetirizina/efeitos adversos , Cetirizina/uso terapêutico , Cicatriz/etiologia , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/normas , Feminino , Antagonistas dos Receptores Histamínicos/efeitos adversos , Humanos , Isotretinoína/efeitos adversos , Masculino , Exame Físico , Resultado do Tratamento
20.
Pharmacoepidemiol Drug Saf ; 28(12): 1572-1582, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31482621

RESUMO

PURPOSE: To compare the effectiveness on blood pressure (BP) of initial two-drug therapy versus monotherapy in hypertensive patients. METHODS: Using the Clinical Practice Research Datalink, linked with Hospital Episode Statistics and Office for National Statistics, we identified a cohort of adults with uncontrolled hypertension, initiating one or two antihypertensive drug classes between 2006 and 2014. New users of two drugs and monotherapy were matched 1:2 by propensity score. Main exposure was "as-treated," ie, until first regimen change. Primary and secondary endpoints were systolic and diastolic BP control and major adverse cardiovascular event (MACE), respectively. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazard models. RESULTS: Of 54 523 eligible patients, 3256 (6.0%) were initiated to a two-drug combination. Of these, 2807 were matched to 5614 monotherapy users. Mean exposure duration was 12.7 months, with 76.5% patients changing their initial regimen. Two-drug therapy was associated with a clinically significant BP control increase in all hypertensive patients (HR = 1.17 [95%CI: 1.09-1.26]), more so in patients with grade 2-3 hypertension (HR = 1.28 [1.17-1.41]). An increase of 27% in BP control (HR = 1.27 [1.08-1.49]) was observed in patients initiating an ACEi+CCB combination compared with initiators of either single class. No significant association was found between two-drug therapy and MACE. Several sensitivity analyses confirmed the main findings. CONCLUSIONS: Few patients initiated therapy with two drugs, reflecting UK guidelines' recommendation to start with monotherapy. This study supports the greater effectiveness of two-drug therapy as the initial regimen for BP control.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Idoso , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/normas , Pressão Sanguínea/efeitos dos fármacos , Estudos de Coortes , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Feminino , Humanos , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento , Reino Unido
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