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1.
Nat Commun ; 11(1): 4915, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004811

RESUMO

A phenotype of Escherichia coli and Klebsiella pneumoniae, resistant to piperacillin/tazobactam (TZP) but susceptible to carbapenems and 3rd generation cephalosporins, has emerged. The resistance mechanism associated with this phenotype has been identified as hyperproduction of the ß-lactamase TEM. However, the mechanism of hyperproduction due to gene amplification is not well understood. Here, we report a mechanism of gene amplification due to a translocatable unit (TU) excising from an IS26-flanked pseudo-compound transposon, PTn6762, which harbours blaTEM-1B. The TU re-inserts into the chromosome adjacent to IS26 and forms a tandem array of TUs, which increases the copy number of blaTEM-1B, leading to TEM-1B hyperproduction and TZP resistance. Despite a significant increase in blaTEM-1B copy number, the TZP-resistant isolate does not incur a fitness cost compared to the TZP-susceptible ancestor. This mechanism of amplification of blaTEM-1B is an important consideration when using genomic data to predict susceptibility to TZP.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Escherichia coli/tratamento farmacológico , Proteínas de Escherichia coli/genética , Escherichia coli/genética , beta-Lactamases/genética , Antibacterianos/uso terapêutico , Cromossomos Bacterianos/genética , Elementos de DNA Transponíveis/genética , DNA Bacteriano/genética , Quimioterapia Combinada/métodos , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Amplificação de Genes , Regulação Bacteriana da Expressão Gênica , Genoma Bacteriano/genética , Humanos , Testes de Sensibilidade Microbiana , Piperacilina/farmacologia , Piperacilina/uso terapêutico , Polimorfismo de Fragmento de Restrição , RNA Ribossômico 16S/genética , Tazobactam/farmacologia , Tazobactam/uso terapêutico , Sequenciamento Completo do Genoma
2.
Int J Antimicrob Agents ; 56(2): 106020, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32862840

RESUMO

The emergence of SARS-coronavirus-2 (SARS-CoV-2) has led to a global pandemic disease referred to as coronavirus disease 19 (COVID-19). Hydroxychloroquine (CLQ-OH)/azithromycin (ATM) combination therapy is currently being tested for the treatment of COVID-19, with promising results. However, the molecular mechanism of action of this combination is not yet established. Using molecular dynamics (MD) simulations, this study shows that the drugs act in synergy to prevent any close contact between the virus and the plasma membrane of host cells. Unexpected molecular similarity is shown between ATM and the sugar moiety of GM1, a lipid raft ganglioside acting as a host attachment cofactor for respiratory viruses. Due to this mimicry, ATM interacts with the ganglioside-binding domain of SARS-CoV-2 spike protein. This binding site shared by ATM and GM1 displays a conserved amino acid triad Q-134/F-135/N-137 located at the tip of the spike protein. CLQ-OH molecules are shown to saturate virus attachment sites on gangliosides in the vicinity of the primary coronavirus receptor, angiotensin-converting enzyme-2 (ACE-2). Taken together, these data show that ATM is directed against the virus, whereas CLQ-OH is directed against cellular attachment cofactors. We conclude that both drugs act as competitive inhibitors of SARS-CoV-2 attachment to the host-cell membrane. This is consistent with a synergistic antiviral mechanism at the plasma membrane level, where therapeutic intervention is likely to be most efficient. This molecular mechanism may explain the beneficial effects of CLQ-OH/ATM combination therapy in patients with COVID-19. Incidentally, the data also indicate that the conserved Q-134/F-135/N-137 triad could be considered as a target for vaccine strategies.


Assuntos
Azitromicina/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Gangliosídeo G(M1)/metabolismo , Hidroxicloroquina/farmacologia , Pneumonia Viral/tratamento farmacológico , Glicoproteína da Espícula de Coronavírus/metabolismo , Ligação Viral/efeitos dos fármacos , Sequência de Aminoácidos , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/metabolismo , Sítios de Ligação/efeitos dos fármacos , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Humanos , Simulação de Dinâmica Molecular , Pandemias , Peptidil Dipeptidase A/metabolismo , Ligação Proteica/efeitos dos fármacos , Domínios Proteicos/efeitos dos fármacos , Alinhamento de Sequência
3.
Medicine (Baltimore) ; 99(35): e21395, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871865

RESUMO

BACKGROUND: Obsessive-compulsive disorder is common, chronic mental disorder, which is characterized by recurrent, unwanted, or intrusive thoughts and repetitive behaviors or mental action. Acupuncture and moxibustion, as a popular form of complementary and alternative therapy, have the advantages of low side effects, high safety, and low cost. The research showed that acupuncture and moxibustion have a good clinical efficacy on obsessive-compulsive disorder. However, there is no literature to systematically evaluate the efficacy and safety of acupuncture and moxibustion in treating obsessive-compulsive disorder. Thus, this study is aimed to evaluate the efficacy and safety of acupuncture and moxibustion for obsessive-compulsive disorder patients, providing reliable evidence for clinical application. METHODS: Randomized controlled trials of acupuncture and moxibustion combined with western medicine for the treatment of obsessive-compulsive disorder will be searched in the databases including PubMed, EMBASE, the Cochrane library, Web of science, China National Knowledge Infrastructure(CNKI), WanFang, the Chongqing VIP Chinese Science and Technology Periodical Database, and China biomedical literature database (CBM) from inception to June, 2020. In addition, Baidu, Google Scholar, International Clinical Trials Registry Platform, and Chinese Clinical Trials Registry will be searched to obtain the gray literature and relevant data that have not yet been published. Two qualified researchers will extract data and assess the risk of bias from included studies dependently. Statistical analysis is performed in RevMan 5.3 software. RESULTS: The efficacy and safety of acupuncture and moxibustion combined with western medicine for obsessive-compulsive disorder will be assessed based on the total effective rate, Hamilton Anxiety Scale score, Hamilton Rating Scale for Depression score, Clinical Global Impression score, side effects, and so on. CONCLUSIONS: The proposed systematic review and meta-analysis of acupuncture and moxibustion combined with western medicine for treating obsessive-compulsive disorder is expected to provide reliable evidence for clinical application. 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/CDGTW.


Assuntos
Terapia por Acupuntura/métodos , Moxibustão/efeitos adversos , Transtorno Obsessivo-Compulsivo/psicologia , Transtorno Obsessivo-Compulsivo/terapia , Terapia por Acupuntura/economia , China/epidemiologia , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Moxibustão/economia , Transtorno Obsessivo-Compulsivo/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento
4.
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
5.
N Z Med J ; 133(1520): 61-72, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32994594

RESUMO

AIM: In the PRACTICAL study, as-needed budesonide/formoterol reduced the rate of severe exacerbations compared with maintenance budesonide plus as-needed terbutaline. In a pre-specified analysis we analysed the efficacy in Maori and Pacific peoples, populations with worse asthma outcomes. METHOD: The PRACTICAL study was a 52-week, open-label, parallel group, randomised controlled trial of 890 adults with mild to moderate asthma, who were randomised to budesonide/formoterol Turbuhaler 200/6mcg one actuation as required or budesonide Turbuhaler 200mcg one actuation twice daily and terbutaline Turbuhaler 250mcg two actuations as required. The primary outcome was rate of severe exacerbations. The analysis strategy was to test an ethnicity-treatment interaction term for each outcome variable. RESULTS: Seventy-two participants (8%) identified as Maori, 36 participants (4%) as Pacific ethnicity. There was no evidence that ethnicity was an effect modifier for severe exacerbations (P interaction 0.70). CONCLUSION: The reduction in severe exacerbation risk with budesonide-formoterol reliever compared with maintenance budesonide was similar in Maori and Pacific adults compared with New Zealand European/Other.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Combinação Budesonida e Fumarato de Formoterol/uso terapêutico , Quimioterapia Combinada/métodos , Administração por Inalação , Adulto , Antiasmáticos/administração & dosagem , Asma/fisiopatologia , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Budesonida/administração & dosagem , Budesonida/uso terapêutico , Combinação Budesonida e Fumarato de Formoterol/administração & dosagem , Estudos de Casos e Controles , Progressão da Doença , Grupos Étnicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nebulizadores e Vaporizadores/normas , Nova Zelândia/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Terbutalina/administração & dosagem , Terbutalina/uso terapêutico , Resultado do Tratamento
6.
N Z Med J ; 133(1520): 120-124, 2020 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-32994602

RESUMO

Spontaneous bleeding in the head and neck region is exceedingly rare, particularly in the absence of trauma or an underlying disorder. We describe a case of an atraumatic lingual haematoma in an 88-year-old male presenting with threatened airway obstruction. The only risk factor our patient had was Aspirin use. Our patient was able to be managed conservatively with observation in the hospital's high dependency unit (HDU) and intravenous steroid (Dexamethasone) and antibiotic (Amoxicillin + Clavulanic acid) therapy. We discuss this case to highlight the importance of recognising an impending airway emergency in the setting of deep space bleeding or swelling.


Assuntos
Obstrução das Vias Respiratórias/etiologia , Hematoma/complicações , Língua/patologia , Administração Intravenosa , Idoso de 80 Anos ou mais , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/uso terapêutico , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Quimioterapia Combinada/métodos , Hematoma/tratamento farmacológico , Humanos , Masculino , Língua/irrigação sanguínea , Resultado do Tratamento
7.
Medicine (Baltimore) ; 99(34): e21952, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846865

RESUMO

BACKGROUND: Sodium cantharidinate/vitamin B6 (SC/VB6) injection, a famous insect-derived traditional Chinese medicine preparation, has been widely applied as a promising adjunctive drug for hepatocellular carcinoma (HCC). However, its exact clinical efficacy and safety is still not well investigated. In this study, we aimed to summarize the efficacy of SC/VB6 injection on survival, liver function, immune function, and quality of life (QoL) in patients with HCC through the meta-analysis. METHODS: All available randomized controlled trials (RCTs) and high-quality prospective cohort studies that investigated the efficacy and safety of SC/VB6 for patients with HCC were searched from ten electronic databases including PubMed, Google Scholar, Cochrane Library, Excerpt Medica Database (Embase), Medline, Web of Science (WOS), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (CSJ), and Wanfang Database. Papers in Chinese or English published from January 2000 to July 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 researchers. The clinical outcomes including overall survival (OS), QoL, liver function, immune function, and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and the quality of the clinical trials was also evaluated. RESULTS: The results of this study will be published in a peer-reviewed journal, and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for HCC patients. CONCLUSION: Our study will draw an objective conclusion of the efficacy of SC/VB6 on survival, liver function, immune function, and QoL in patients with HCC. INPLASY REGISTRATION NUMBER: INPLASY202070121.


Assuntos
Cantaridina/análogos & derivados , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/patologia , Vitamina B 6/farmacologia , Complexo Vitamínico B/farmacologia , Cantaridina/administração & dosagem , Cantaridina/farmacologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/psicologia , China/epidemiologia , Quimioterapia Combinada/métodos , Humanos , Sistema Imunitário/efeitos dos fármacos , Injeções/métodos , Fígado/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Sobrevida , Resultado do Tratamento , Vitamina B 6/administração & dosagem , Complexo Vitamínico B/administração & dosagem
8.
Transplantation ; 104(8): 1686-1694, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732848

RESUMO

BACKGROUND: It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with calcineurin inhibitor (CNI) have excluded hypersensitized recipients from enrollment. METHODS: To shed light on this issue, we examined 71 consecutive patients with a baseline calculated panel reactive antibody (cPRA) ≥50% that underwent kidney transplantation from June 2013 to December 2016 in our unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 38), or mTORi (either everolimus or sirolimus, n = 33, target trough levels 3-8 ng/mL). RESULTS: Demographic and immunological risk profiles were similar, and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection (hazard ratio [confidence interval], 0.32 [0.11-0.90], P = 0.031 at univariable analysis and 0.34 [0.11-0.95], P = 0.040 at multivariable analysis). There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de novo donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/mL for MPA and mTORi group respectively, P = 0.277). CONCLUSIONS: This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.


Assuntos
Dessensibilização Imunológica/métodos , Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto , Idoso , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Dessensibilização Imunológica/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Everolimo/administração & dosagem , Everolimo/efeitos adversos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Humanos , Imunossupressores/efeitos adversos , Isoanticorpos/imunologia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Estudos Retrospectivos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Serina-Treonina Quinases TOR/imunologia , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Resultado do Tratamento
10.
Cochrane Database Syst Rev ; 8: CD009716, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32813275

RESUMO

BACKGROUND: Stroke is a leading cause of morbidity and mortality worldwide. Antiplatelet agents are considered to be the cornerstone for secondary prevention of stroke, but the role of using multiple antiplatelet agents early after stroke or transient ischaemic attack (TIA) to improve outcomes has not been established. OBJECTIVES: To determine the effectiveness and safety of initiating, within 72 hours after an ischaemic stroke or TIA, multiple antiplatelet agents versus fewer antiplatelet agents to prevent stroke recurrence. The analysis explores the evidence for different drug combinations. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched 6 July 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 7 of 12, 2020) (last searched 6 July 2020), MEDLINE Ovid (from 1946 to 6 July 2020), Embase (1980 to 6 July 2020), ClinicalTrials.gov, and the WHO ICTRP. We also searched the reference lists of identified studies and reviews and used the Science Citation Index Cited Reference search for forward tracking of included studies. SELECTION CRITERIA: We selected all randomised controlled trials (RCTs) that compared the use of multiple versus fewer antiplatelet agents initiated within 72 hours after stroke or TIA. DATA COLLECTION AND ANALYSIS: We extracted data from eligible studies for the primary outcomes of stroke recurrence and vascular death, and secondary outcomes of myocardial infarction; composite outcome of stroke, myocardial infarction, and vascular death; intracranial haemorrhage; extracranial haemorrhage; ischaemic stroke; death from all causes; and haemorrhagic stroke. We computed an estimate of treatment effect and performed a test for heterogeneity between trials. We analysed data on an intention-to-treat basis and assessed bias for all studies. We rated the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 15 RCTs with a total of 17,091 participants. Compared with fewer antiplatelet agents, multiple antiplatelet agents were associated with a significantly lower risk of stroke recurrence (5.78% versus 7.84%, risk ratio (RR) 0.73, 95% confidence interval (CI) 0.66 to 0.82; P < 0.001; moderate-certainty evidence) with no significant difference in vascular death (0.60% versus 0.66%, RR 0.98, 95% CI 0.66 to 1.45; P = 0.94; moderate-certainty evidence). There was a higher risk of intracranial haemorrhage (0.42% versus 0.21%, RR 1.92, 95% CI 1.05 to 3.50; P = 0.03; low-certainty evidence) and extracranial haemorrhage (6.38% versus 2.81%, RR 2.25, 95% CI 1.88 to 2.70; P < 0.001; high-certainty evidence) with multiple antiplatelet agents. On secondary analysis of dual versus single antiplatelet agent therapy, benefit for stroke recurrence (5.73% versus 8.06%, RR 0.71, 95% CI 0.62 to 0.80; P < 0.001; moderate-certainty evidence) was maintained as well as risk of extracranial haemorrhage (1.24% versus 0.40%, RR 3.08, 95% CI 1.74 to 5.46; P < 0.001; high-certainty evidence). The composite outcome of stroke, myocardial infarction, and vascular death (6.37% versus 8.77%, RR 0.72, 95% CI 0.64 to 0.82; P < 0.001; moderate-certainty evidence) and ischaemic stroke (6.30% versus 8.94%, RR 0.70, 95% CI 0.61 to 0.81; P < 0.001; high-certainty evidence) were significantly in favour of dual antiplatelet therapy, whilst the risk of intracranial haemorrhage became less significant (0.34% versus 0.21%, RR 1.53, 95% CI 0.76 to 3.06; P = 0.23; low-certainty evidence). AUTHORS' CONCLUSIONS: Multiple antiplatelet agents are more effective in reducing stroke recurrence but increase the risk of haemorrhage compared to one antiplatelet agent. The benefit in reduction of stroke recurrence seems to outweigh the harm for dual antiplatelet agents initiated in the acute setting and continued for one month. There is lack of evidence regarding multiple versus multiple antiplatelet agents. Further studies are required in different populations to establish comprehensive safety profiles and long-term outcomes to establish duration of therapy.


Assuntos
Ataque Isquêmico Transitório/prevenção & controle , Inibidores da Agregação de Plaquetas/uso terapêutico , Prevenção Secundária/métodos , Acidente Vascular Cerebral/prevenção & controle , Viés , Causas de Morte , Intervalos de Confiança , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Análise de Intenção de Tratamento , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/epidemiologia , Infarto do Miocárdio/epidemiologia , Razão de Chances , Inibidores da Agregação de Plaquetas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo
11.
PLoS One ; 15(8): e0236264, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32750060

RESUMO

BACKGROUND: Extensively drug-resistant tuberculosis (XDR TB) is a very serious form of tuberculosis that is burdened with a heavy mortality toll, especially before the advent of new TB drugs. The Democratic Republic of the Congo (DRC) is among the countries most affected by this new epidemic. METHODS: A retrospective analysis was performed of the records of all patients with pre- and extensively drug-resistant tuberculosis hospitalized from January 1, 2015 to December 31, 2017 and monitored for at least 6 months to one year after the end of their treatment in Kinshasa; an individualized therapeutic regimen with bedaquiline for 20 months was built for each patient. The adverse effects were systematically monitored. RESULTS: Of the 40 laboratory-confirmed patients, 32 (80%) patients started treatment, including 29 preXRB and 3 XDR TB patients. In the eligible group, 3 patients (9.4%) had HIV-TB coinfections. The therapeutic success rate was 53.2%, and the mortality rate was 46.8% (15/32); there were no relapses, failures or losses to follow-up. All coinfected HIV-TB patients died during treatment. The cumulative patient survival rate was 62.5% at 3 months, 53.1% at 6 months and 53.1% at 20 months. The most common adverse events were vomiting, Skin rash, anemia and peripheral neuropathy. CONCLUSION: The new anti-tuberculosis drugs are a real hope for the management of Drug Resistant tuberculosis patient and other new therapeutic combinations may improve favorable outcomes.


Assuntos
Antituberculosos/administração & dosagem , Diarilquinolinas/administração & dosagem , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Adolescente , Adulto , Idoso , Anemia/induzido quimicamente , Anemia/epidemiologia , Antituberculosos/efeitos adversos , Efeitos Psicossociais da Doença , República Democrática do Congo/epidemiologia , Diarilquinolinas/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Exantema/induzido quimicamente , Exantema/epidemiologia , Tuberculose Extensivamente Resistente a Medicamentos/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Vômito/induzido quimicamente , Vômito/epidemiologia , Adulto Jovem
12.
Hum Reprod ; 35(8): 1781-1796, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32712670

RESUMO

STUDY QUESTION: Does HIV protease inhibitor (PI)-based combination antiretroviral therapy (cART) initiated at periconception affect key events in early pregnancy, i.e. decidualization and spiral artery remodeling? SUMMARY ANSWER: Two PIs, lopinavir and darunavir, currently offered as cART options in HIV-positive pregnancies were evaluated, and we found that lopinavir-based cART, but not darunavir-based cART, impaired uterine decidualization and spiral artery remodeling in both human ex vivo and mouse in vivo experimental models. WHAT IS KNOWN ALREADY: Early initiation of cART is recommended for pregnant women living with HIV. However, poor birth outcomes are frequently observed in HIV-positive pregnancies exposed to PI-based cART, especially when it is initiated prior to conception. The correlation between early initiation of PI-cART and adverse birth outcomes is poorly understood, due to lack of data on the specific effects of PI-cART on the early stages of pregnancy involving uterine decidualization and spiral artery remodeling. STUDY DESIGN, SIZE, DURATION: Lopinavir and darunavir were evaluated in clinically relevant combinations using an ex vivo human first-trimester placenta-decidua explant model, an in vitro human primary decidual cell culture system, and an in vivo mouse pregnancy model. The first-trimester (gestational age, 6-8 weeks) human placenta-decidua tissue was obtained from 11 to 15 healthy women undergoing elective termination of pregnancy. C57Bl/6 female mice (four/treatment group) were administered either lopinavir-cART, darunavir-cART or water by oral gavage once daily starting on the day of plug detection until sacrifice. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human: Spiral artery remodeling was assessed by immunohistochemical analysis of first-trimester placenta-decidua explant co-culture system. Trophoblast migration was measured using a placental explant culture. A primary decidual cell culture was used to evaluate the viability of immune cell populations by flow cytometry. Soluble factors, including biomarkers of decidualization and angiogenesis, were quantified by ELISA and Luminex assay using decidua-conditioned media. Mouse: In the mouse pregnancy model, gestational day 6.5 or 9.5 implantation sites were used to assess decidualization, spiral artery remodeling and uterine natural killer (uNK) cell numbers by immunohistochemistry. Transcription factor STAT3 was assayed by immunohistochemistry in both human decidua and mouse implantation sites. MAIN RESULTS AND THE ROLE OF CHANCE: Lopinavir-cART, but not darunavir-cART, impaired uterine decidualization and spiral artery remodeling in both experimental models. Lopinavir-cART treatment was also associated with selective depletion of uNK cells, reduced trophoblast migration and defective placentation. The lopinavir-associated decidualization defects were attributed to a decrease in expression of transcription factor STAT3, known to regulate decidualization. Our results suggest that periconceptional initiation of lopinavir-cART, but not darunavir-cART, causes defective maturation of the uterine endometrium, leading to impairments in spiral artery remodeling and placentation, thus contributing to the poor birth outcomes. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The human first-trimester placenta/decidua samples could only be obtained from healthy females undergoing elective termination of pregnancy. As biopsy is the only way to obtain first-trimester decidua from pregnant women living with HIV on PI-cART, ethics approval and participant consent are difficult to obtain. Furthermore, our animal model is limited to the study of cART and does not include HIV. HIV infection is also associated with immune dysregulation, inflammation, alterations in angiogenic factors and complement activation, all of which could influence decidual and placental vascular remodeling and modify any cART effects. WIDER IMPLICATIONS OF THE FINDINGS: Our findings provide mechanistic insight with direct clinical implications, rationalizing why the highest adverse birth outcomes are reported in HIV-positive pregnancies exposed to lopinavir-cART from conception. We demonstrate that dysregulation of decidualization is the mechanism through which lopinavir-cART, but not darunavir-cART, use in early pregnancy leads to poor birth outcomes. Although lopinavir is no longer a first-line regimen in pregnancy, it remains an alternate regimen and is often the only PI available in low resource settings. Our results highlight the need for reconsidering current guidelines recommending lopinavir use in pregnancy and indicate that lopinavir should be avoided especially in the first trimester, whereas darunavir is safe to use and should be the preferred PI in pregnancy.Further, in current times of the COVID-19 pandemic, lopinavir is among the top drug candidates which are being repurposed for inclusion in clinical trials world-over, to assess their therapeutic potential against the dangerous respiratory disease. Current trials are also testing the efficacy of lopinavir given prophylactically to protect health care workers and people with potential exposures. Given the current extraordinary numbers, these might include women with early pregnancies, who may or may not be cognizant of their gestational status. This is a matter of concern as it could mean that women with early pregnancies might be exposed to this drug, which can cause decidualization defects. Our findings provide evidence of safety concerns surrounding lopinavir use in pregnancy, that women of reproductive age considering participation in such trials should be made aware of, so they can make a fully informed decision. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by funding from the Canadian Institutes of Health Research (CIHR) (PJT-148684 and MOP-130398 to L.S.). C.D. received support from CIHR Foundation (FDN143262 to Stephen Lye). S.K. received a TGHRI postdoctoral fellowship. The authors declare that there are no conflicts of interest. L.S. reports personal fees from ViiV Healthcare for participation in a Women and Transgender Think Tank.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Lopinavir/efeitos adversos , Placentação/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Animais , Betacoronavirus/efeitos dos fármacos , Células Cultivadas , Ensaios Clínicos como Assunto , Técnicas de Cocultura , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Darunavir/efeitos adversos , Decídua/irrigação sanguínea , Decídua/citologia , Decídua/efeitos dos fármacos , Modelos Animais de Doenças , Reposicionamento de Medicamentos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Implantação do Embrião/efeitos dos fármacos , Endométrio/irrigação sanguínea , Endométrio/efeitos dos fármacos , Feminino , Humanos , Exposição Materna/efeitos adversos , Camundongos , Pandemias , Pneumonia Viral/virologia , Gravidez , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Cultura Primária de Células , Trofoblastos , Remodelação Vascular/efeitos dos fármacos
13.
Medicine (Baltimore) ; 99(28): e20887, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664082

RESUMO

BACKGROUND: Dry eye symptom threatens human health and causes a larger burden of disease, the study aims to systematically compare the therapeutic effect of Lycium-rehmannia pills combined with topical eye drops and pure western medicine (western medicine eye drops) on dry eye symptom, to provide a reflection and enlightenment for clinical treatment. METHOD: PubMed, The Cochrane Library, EMbase, MEDLINE, CBM, WanFang, VIP, and CNKI databases were searched manually and automatically by the computer until March 2019 and relevant randomized controlled trials (RCTs) were selected. Article selection and data extraction were conducted by 2 researchers independently, then RevMan 5.3 was applied for meta-analysis. RESULT: Fifteen randomized controlled trials were included, including 1222 patients (eyes = 2382). The meta-analysis results showed that Lycium-rehmannia pills combined with western medicine were superior to the control group in terms of therapeutic efficiency [OR = 4.38, 95% confidence interval (CI) (3.26, 5.89), P < .00001]. There were controversial results that the study group was better than the control group in Basic Schirmer test [MD, 2.46, 95% CI (1.49, 3.44), P < .00001], tear break up time [MD, 3.79, 95% CI (3.57, 4.01), P < .00001], and Fluorescein test [MD, -1.29, 95% CI (-1.42, -1.15), P < .00001], but Lycium-rehmannia pills combined with western medicine could not reduce the incidence of adverse reactions, including eyelid inflammation [OR = 1.00, 95% CI (0.37, 2.72), P = 1.00] and congestion symptom [OR = 0.55, 95% CI (0.18, 1.65), P = .28]. CONCLUSION: Lycium-rehmannia pills combined with western medicine is better than the control group of therapeutic efficiency in the treatment of dry eye symptom. Due to the quantity and quality limitations of the literature, there were controversial results that the study group was better than the control group in Basic Schirmer test, Tear break up time, Fluorescein test, and reduced adverse reactions, including inflammation of the eyelids and congestion. The above conclusion needs more clinical trials to test and verify.


Assuntos
Síndromes do Olho Seco/tratamento farmacológico , Lycium/efeitos adversos , Plantas Medicinais/efeitos adversos , Rehmannia/efeitos adversos , Lágrimas/efeitos dos fármacos , Administração Tópica , Adulto , Quimioterapia Combinada/métodos , Doenças Palpebrais/epidemiologia , Doenças Palpebrais/patologia , Feminino , Humanos , Incidência , Inflamação/epidemiologia , Inflamação/patologia , Masculino , Medicina Tradicional Chinesa/métodos , Pessoa de Meia-Idade , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/uso terapêutico , Avaliação de Resultados em Cuidados de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Lágrimas/fisiologia
14.
BMJ Case Rep ; 13(7)2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32690571

RESUMO

A 45-year-old man presented with acute sinusitis. He was treated with a 10-day course of trimethoprim/sulfamethoxazole, and a subsequent 14-day course of amoxicillin-clavulanate with no improvement in symptoms. Culture of purulent nasal secretions revealed the rare enterobacter Cedecea lapagei The patient had complete resolution of his symptoms after a 14-day course of gentamicin/dexamethasone nasal rinses. Emerging pathogens have been a timeless concern for physicians, as witnessed by the current SARS-CoV-2 outbreak. C. lapagei has been reported to cause human infection only a dozen times since its discovery, all in severely compromised patients. This is the first documented case of sinusitis reported with C. lapagei and may portend a rising prevalence of disease burden in the general population. This case demonstrates the necessity of obtaining cultures when standard antibiotics result in treatment failure.


Assuntos
Dexametasona/administração & dosagem , Infecções por Enterobacteriaceae/tratamento farmacológico , Gentamicinas/administração & dosagem , Sinusite/tratamento farmacológico , Doença Aguda , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Dexametasona/uso terapêutico , Quimioterapia Combinada/métodos , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/complicações , Gentamicinas/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Sinusite/microbiologia , Resultado do Tratamento , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
15.
Scott Med J ; 65(3): 72-75, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32638647

RESUMO

Cytokine storm is a life-threatening complication of Covid-19 infection. Excessive cytokines are the products of hyperactive immune inflammatory response mounted by the host against the virus. There is no agreed treatment for cytokine storm. Three therapeutic agents with proven immune-modulatory properties in regular use in a wide range of inflammatory disorders (high dose intravenous immunoglobulin, Rituximab and thalidomide) are proposed for the treatment of cytokine storm. Safety and efficacy of the proposed treatment should be assessed by randomised controlled clinical trials. The use of the proposed treatment is expected to reduce the mortality rate and alter the overall management of the pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Rituximab/uso terapêutico , Talidomida/uso terapêutico , Administração Intravenosa , Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/etiologia , Quimioterapia Combinada/métodos , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Pandemias , Pneumonia Viral/complicações , Rituximab/administração & dosagem , Talidomida/administração & dosagem
16.
Cochrane Database Syst Rev ; 7: CD005583, 2020 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-32628791

RESUMO

BACKGROUND: Gastric cancer is the third most common cause of cancer death worldwide. Individuals infected with Helicobacter pylori have a higher likelihood of developing gastric cancer than individuals who are not infected. Eradication of H. pylori in healthy asymptomatic individuals in the general population may reduce the incidence of gastric cancer, but the magnitude of this effect is unclear. OBJECTIVES: To assess the effectiveness of eradication of H. pylori in healthy asymptomatic individuals in the general population in reducing the incidence of gastric cancer. SEARCH METHODS: We identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 1), MEDLINE (1946 to February 2020), and EMBASE (1974 to February 2020). We handsearched reference lists from trials selected by electronic searching to identify further relevant trials. We handsearched published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) between 2001 and 2019. We contacted members of the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group and experts in the field and asked them to provide details of outstanding clinical trials and any relevant unpublished materials. SELECTION CRITERIA: We analysed randomised controlled trials comparing at least one week of H. pylori therapy with placebo or no treatment in preventing subsequent development of gastric cancer in otherwise healthy and asymptomatic H. pylori-positive adults. Trials had to follow up participants for at least two years and needed to have at least two participants with gastric cancer as an outcome. We defined gastric cancer as any gastric adenocarcinoma, including intestinal (differentiated) or diffuse (undifferentiated) type, with or without specified histology. DATA COLLECTION AND ANALYSIS: We collected data on incidence of gastric cancer, incidence of oesophageal cancer, deaths from gastric cancer, deaths from any cause, and adverse effects arising due to therapy. MAIN RESULTS: Six trials met all our eligibility criteria and provided extractable data in the previous version. Following our updated search, one new RCT was identified, meaning that seven trials were included in this updated review. In addition, one previously included trial provided fully published data out to 10 years, and another previously included trial provided fully published data out to 22 years of follow-up. Four trials were at low risk of bias, one trial was at unclear risk, and two trials were at high risk of bias. Six trials were conducted in Asian populations. In preventing development of subsequent gastric cancer, H. pylori eradication therapy was superior to placebo or no treatment (RR 0.54, 95% confidence interval (CI) 0.40 to 0.72, 7 trials, 8323 participants, moderate certainty evidence). Only two trials reported the effect of eradication of H. pylori on the development of subsequent oesophageal cancer. Sixteen (0.8%) of 1947 participants assigned to eradication therapy subsequently developed oesophageal cancer compared with 13 (0.7%) of 1941 participants allocated to placebo (RR 1.22, 95% CI 0.59 to 2.54, moderate certainty evidence). H. pylori eradication reduced mortality from gastric cancer compared with placebo or no treatment (RR 0.61, 95% CI 0.40 to 0.92, 4 trials, 6301 participants, moderate certainty evidence). There was little or no evidence in all-cause mortality (RR 0.97, 95% CI 0.85 to 1.12, 5 trials, 7079 participants, moderate certainty evidence). Adverse events data were poorly reported. AUTHORS' CONCLUSIONS: We found moderate certainty evidence that searching for and eradicating H. pylori reduces the incidence of gastric cancer and death from gastric cancer in healthy asymptomatic infected Asian individuals, but we cannot necessarily extrapolate this data to other populations.


Assuntos
Antibacterianos/uso terapêutico , Infecções Assintomáticas/terapia , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Neoplasias Gástricas/prevenção & controle , Antiulcerosos/uso terapêutico , Carcinoma de Células Escamosas/epidemiologia , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Neoplasias Esofágicas/epidemiologia , Humanos , Incidência , Lesões Pré-Cancerosas/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/mortalidade
17.
Cochrane Database Syst Rev ; 7: CD001416, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32715463

RESUMO

BACKGROUND: The majority of people with epilepsy have a good prognosis, and their seizures can be well controlled with the use of a single antiepileptic agent, but up to 30% develop dug-resistant epilepsy, especially those with focal seizures. In this review, we summarised the evidence from randomised controlled trials (RCT) of zonisamide, used as an add-on treatment for focal epilepsy uncontrolled by one or more concomitant antiepileptic drug. This is an updated version of the Cochrane review previously published in 2018. OBJECTIVES: To evaluate the efficacy and tolerability of zonisamide, when used as an add-on treatment for people with focal epilepsy uncontrolled by one or more concomitant antiepileptic drugs. SEARCH METHODS: For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (September 2019). In addition, we contacted Eisai Limited (makers and licensees of zonisamide) and experts in the field, to seek any ongoing or unpublished studies. SELECTION CRITERIA: Randomised controlled trials, in which add-on zonisamide was compared with placebo or another antiepileptic drug in people with focal epilepsy, uncontrolled by one or more concomitant antiepileptic drugs. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, extracted data, assessed for risk of bias using the Cochrane 'Risk of bias' tool, and assessed the certainty of the evidence, using the GRADE approach. The primary outcome was at least a 50% reduction in total seizure frequency; the secondary outcomes were (1) tolerability; and (2) adverse effects. We used an intention-to-treat approach for our primary analyses. We estimated summary risk ratios (RRs) for each outcome. We displayed a summary of the estimates of effects and certainty of the evidence for each outcome in a 'Summary of findings' table. MAIN RESULTS: We did not find any new studies since the last version of this review. We included eight studies (1636 participants) from previous versions of this review. The overall RR with 95% confidence interval (CI) for at least a 50% reduction in seizure frequency for 300 mg to 500 mg/day of zonisamide compared to placebo was 1.90 (95% CI 1.63 to 2.22; 7 trials, 1371 participants; moderate-certainty evidence). The RR for 50% reduction in seizure frequency compared to placebo for any dose of zonisamide (100 mg to 500 mg/day) was 1.86 (95% CI 1.60 to 2.17; 7 trials, 1429 participants; moderate-certainty evidence). The number needed to treat for an additional beneficial outcome was six (95% CI 4.1 to 6.8). Two trials provided evidence of a dose-response relationship for this outcome. The RR for treatment withdrawal for 300 mg to 500 mg/day of zonisamide compared to placebo was 1.59 (95% CI 1.18 to 2.13; 6 trials, 1099 participants; moderate-certainty evidence), and for 100 mg to 500 mg/day was 1.44 (95% CI 1.08 to 1.93; 6 trials, 1156 participants; moderate-certainty evidence). The number needed to treat for an additional harmful outcome was 15 (95% CI 9.3 to 36.7). The following adverse effects were more likely to be associated with zonisamide than with placebo: ataxia (RR 3.85, 99% CI 1.36 to 10.93; 4 trials, 734 participants; low-certainty evidence); somnolence (RR 1.52, 99% CI 1.00 to 2.31; 8 trials, 1636 participants; moderate-certainty evidence); agitation (RR 2.35, 99% CI 1.05 to 5.27; 4 trials, 598 participants; low-certainty evidence); and anorexia (RR 2.74, 99% CI 1.64 to 4.60; 6 trials, 1181 participants; low-certainty evidence). Across the eight studies, we rated risk of bias domains at low or unclear risk of bias, apart from two studies, which we rated at high risk of attrition bias. Five of the eight studies were sponsored by the drug companies that produced zonisamide. AUTHORS' CONCLUSIONS: When used as an add-on treatment in people with focal epilepsy, uncontrolled by one or more concomitant antiepileptic drugs, moderate-certainty evidence found that zonisamide was more successful than placebo at reducing the frequency of seizures by at least 50%. We were unable to identify minimum effective and maximum tolerated doses. The included trials evaluated a maximum stable-dose phase of 18 weeks, so results cannot be used to confirm longer periods of efficacy in seizure control. The results cannot be extrapolated to monotherapy, or to people with other seizure types or epilepsy syndromes.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Zonisamida/uso terapêutico , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Quimioterapia Combinada/métodos , Humanos , Análise de Intenção de Tratamento , Números Necessários para Tratar , Ensaios Clínicos Controlados Aleatórios como Assunto , Falha de Tratamento , Zonisamida/administração & dosagem , Zonisamida/efeitos adversos
18.
Scott Med J ; 65(3): 72-75, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: covidwho-636014

RESUMO

Cytokine storm is a life-threatening complication of Covid-19 infection. Excessive cytokines are the products of hyperactive immune inflammatory response mounted by the host against the virus. There is no agreed treatment for cytokine storm. Three therapeutic agents with proven immune-modulatory properties in regular use in a wide range of inflammatory disorders (high dose intravenous immunoglobulin, Rituximab and thalidomide) are proposed for the treatment of cytokine storm. Safety and efficacy of the proposed treatment should be assessed by randomised controlled clinical trials. The use of the proposed treatment is expected to reduce the mortality rate and alter the overall management of the pandemic.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Rituximab/uso terapêutico , Talidomida/uso terapêutico , Administração Intravenosa , Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/etiologia , Quimioterapia Combinada/métodos , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Pandemias , Pneumonia Viral/complicações , Rituximab/administração & dosagem , Talidomida/administração & dosagem
19.
Cancer Discov ; 10(10): 1514-1527, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32699031

RESUMO

Among 2,186 U.S. adults with invasive cancer and laboratory-confirmed SARS-CoV-2 infection, we examined the association of COVID-19 treatments with 30-day all-cause mortality and factors associated with treatment. Logistic regression with multiple adjustments (e.g., comorbidities, cancer status, baseline COVID-19 severity) was performed. Hydroxychloroquine with any other drug was associated with increased mortality versus treatment with any COVID-19 treatment other than hydroxychloroquine or untreated controls; this association was not present with hydroxychloroquine alone. Remdesivir had numerically reduced mortality versus untreated controls that did not reach statistical significance. Baseline COVID-19 severity was strongly associated with receipt of any treatment. Black patients were approximately half as likely to receive remdesivir as white patients. Although observational studies can be limited by potential unmeasured confounding, our findings add to the emerging understanding of patterns of care for patients with cancer and COVID-19 and support evaluation of emerging treatments through inclusive prospective controlled trials. SIGNIFICANCE: Evaluating the potential role of COVID-19 treatments in patients with cancer in a large observational study, there was no statistically significant 30-day all-cause mortality benefit with hydroxychloroquine or high-dose corticosteroids alone or in combination; remdesivir showed potential benefit. Treatment receipt reflects clinical decision-making and suggests disparities in medication access.This article is highlighted in the In This Issue feature, p. 1426.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Uso de Medicamentos/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Neoplasias/mortalidade , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Fatores Etários , Idoso , Alanina/análogos & derivados , Alanina/uso terapêutico , Betacoronavirus/patogenicidade , Tomada de Decisão Clínica , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Seguimentos , Glucocorticoides/uso terapêutico , Mortalidade Hospitalar , Humanos , Hidroxicloroquina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Resultado do Tratamento , Estados Unidos/epidemiologia
20.
PLoS One ; 15(7): e0235376, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32629460

RESUMO

AIM: To develop a statistical model to identify determinants of glycemic control. MATERIALS AND METHODS: A database was extracted from patients' records with at least one glycated hemoglobin (HbA1c) analysis and with antidiabetic therapy established and stabilized. A logistic regression model was designed to identify the statistical significance of factors associated with glycemic control. RESULTS: Higher probability of success (HbA1c ≤8% [64 mmol/mol]) was found for those who were older in age, those who were men, and those with higher education levels. Increased values for the following variables were associated with the poorest glycemic control: number of years of T2DM since diagnosis, number of antidiabetic medicines, body mass index, low-density lipoprotein cholesterol, triglycerides, systolic blood pressure and number of diabetes consultations in the last twelve months. The following pharmacotherapeutic treatments were associated with glycemic control (in decreasing order of the results): oral antidiabetic drugs; oral antidiabetic drugs and insulin; insulin. Patients using metformin and a dipeptidyl peptidase-4 inhibitors have a higher probability of success than do patients using metformin and a sulfonylurea, and patients using insulin and metformin have a higher probability of success than do patients using insulin alone. CONCLUSIONS: Sociodemographic, clinical and therapeutic parameters can strongly affect glycemic control. Studies based on real-life patient data provide important information on the development of more effective glycemic control.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobina A Glicada/análise , Hipoglicemiantes/uso terapêutico , Modelos Biológicos , Fatores Etários , Idoso , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Hemoglobina A Glicada/efeitos dos fármacos , Humanos , Hipoglicemiantes/farmacologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Fatores Socioeconômicos , Fatores de Tempo , Resultado do Tratamento
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