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1.
Comput Math Methods Med ; 2020: 1391583, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33029193

RESUMO

Purpose: We aimed to analyze and evaluate the safety signals of ribavirin-interferon combination through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS), so as to provide reference for the rationale use of these agents in the management of relevant toxicities emerging in patients with novel coronavirus pneumonia (COVID-19). Methods: Reports to the FAERS from 1 January 2004 to 8 March 2020 were analyzed. The proportion of report ratio (PRR), reporting odds ratio (ROR), and Bayesian confidence interval progressive neural network (BCPNN) method were used to detect the safety signals. Results: A total of 55 safety signals were detected from the top 250 adverse event reactions in 2200 reports, but 19 signals were not included in the drug labels. All the detected adverse event reactions were associated with 13 System Organ Classes (SOC), such as gastrointestinal, blood and lymph, hepatobiliary, endocrine, and various nervous systems. The most frequent adverse events were analyzed, and the results showed that females were more likely to suffer from anemia, vomiting, neutropenia, diarrhea, and insomnia. Conclusion: The ADE (adverse drug event) signal detection based on FAERS is helpful to clarify the potential adverse events related to ribavirin-interferon combination for novel coronavirus therapy; clinicians should pay attention to the adverse reactions of gastrointestinal and blood systems, closely monitor the fluctuations of the platelet count, and carry out necessary mental health interventions to avoid serious adverse events.


Assuntos
Infecções por Coronavirus/tratamento farmacológico , Interferons/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Ribavirina/efeitos adversos , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Algoritmos , Teorema de Bayes , Mineração de Dados , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Interferons/administração & dosagem , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Razão de Chances , Pandemias , Segurança do Paciente , Ribavirina/administração & dosagem , Adulto Jovem
2.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
Yakugaku Zasshi ; 140(7): 923-928, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32612057

RESUMO

Riluzole, a drug used in the management of amyotrophic lateral sclerosis (ALS), is associated with a high incidence of liver failure. It is imperative to determine risk factors and severity of liver injury in patients taking riluzole to devise an appropriate treatment regimen. We, therefore, studied risk factors for liver injury in ALS patients who were prescribed riluzole at Kitasato University East Hospital from 1999 to 2015. Of the 222 patients enrolled in this study, 113 and 109 patients were diagnosed with mild to moderate (grade 1 or 2) and without (grade 0) liver injury, respectively. Prediction of risk factors was determined using binary logistical regression analyses. The results showed that 50.9% (n=113) of ALS patients developed mild to moderate liver injury; 71.7% and 53.1% of patients were concurrently using CYP1A2 inhibitors (p=0.005) and diclofenac (p=0.032), respectively; 55.8% of patients with liver injury had a history of smoking (p=0.011). Multivariate analyses revealed that the concurrent use of CYP1A2 inhibitors [odds ratio (OR) 2.152, 95% confidence interval (CI) 1.225-3.780, p=0.008] and history of smoking (OR 1.938, 95% CI 1.125-3.340, p=0.017) were independent risk factors for liver injury in patients receiving riluzole. In conclusion, treatment of ALS patients with riluzole, smoking habits, and concurrent use of CYP1A2 inhibitors are independent liver injury risk factors. Further studies on liver injury are warranted in ALS patients treated with riluzole to comprehensively understand the underlying mechanisms of riluzole-associated liver toxicity.


Assuntos
Esclerose Amiotrófica Lateral/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Riluzol/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores do Citocromo P-450 CYP1A2/efeitos adversos , Inibidores do Citocromo P-450 CYP1A2/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Riluzol/uso terapêutico , Fatores de Risco , Fumar/efeitos adversos
9.
Yakugaku Zasshi ; 140(7): 943-947, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32612060

RESUMO

Concomitant therapy with acetaminophen (APAP) and low-dose aspirin is often used in clinical settings; however, it is unclear whether this combination is involved in the progression of chronic kidney disease (CKD). We hypothesized that concomitant therapy with APAP and low-dose aspirin may cause CKD progression. We carried out a retrospective 6-year cohort study that included all patients who received low-dose aspirin from January 2011 to December 2016 at Kaetsu Hospital. Primary outcome was defined as CKD progression at the end of the study compared with baseline. Among the 441 patients treated during the study period, we identified 89 cases of CKD progression. Multivariate regression analysis showed that exposure to APAP>50 g [odds ratio (OR), 2.68, 95% confidence interval (CI), 1.08-6.70], age increase by 1 year (OR, 1.05, 95% CI, 1.02-1.08), and diabetes mellitus (OR, 2.40, 95% CI, 1.41-4.08) had positive associations with CKD progression. Our findings suggested that concomitant therapy with APAP and low-dose aspirin increased the risk of CKD progression. Therefore, we recommend more thorough monitoring of serum creatinine when patients are on such concomitant therapy. Moreover, it is important to advise users of low-dose aspirin to avoid unnecessary use of APAP, in order to reduce the risk of CKD progression.


Assuntos
Acetaminofen/efeitos adversos , Aspirina/efeitos adversos , Insuficiência Renal Crônica/induzido quimicamente , Acetaminofen/administração & dosagem , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aspirina/administração & dosagem , Biomarcadores , Creatinina/sangue , Complicações do Diabetes , Progressão da Doença , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/prevenção & controle , Estudos Retrospectivos , Fatores de Risco
10.
Drug Saf ; 43(7): 657-660, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32495148

RESUMO

INTRODUCTION: Hydroxychloroquine was recently promoted in patients infected with COVID-19 infection. A recent experimental study has suggested an increased toxicity of hydroxychloroquine in association with metformin in mice. OBJECTIVE: The present study was undertaken to investigate the reality of this putative drug-drug interaction between hydroxychloroquine and metformin using pharmacovigilance data. METHODS: Using VigiBase®, the WHO pharmacovigilance database, we performed a disproportionality analysis (case/non-case study). Cases were reports of fatal outcomes with the drugs of interest and non-cases were all other reports for these drugs registered between 1 January 2000 and 31 December 2019. Data with hydroxychloroquine (or metformin) alone were compared with the association hydroxychloroquine + metformin. Results are reported as ROR (reporting odds ratio) with their 95% confidence interval. RESULTS: Of the 10,771 Individual Case Safety Reports (ICSR) involving hydroxychloroquine, 52 were recorded as 'fatal outcomes'. In comparison with hydroxychloroquine alone, hydroxychloroquine + metformin was associated with an ROR value of 57.7 (23.9-139.3). In comparison with metformin alone, hydroxychloroquine + metformin was associated with an ROR value of 6.0 (2.6-13.8). CONCLUSION: Our study identified a signal for the association hydroxychloroquine + metformin that appears to be more at risk of fatal outcomes (particularly by completed suicides) than one of the two drugs when given alone.


Assuntos
Infecções por Coronavirus , Interações Medicamentosas , Quimioterapia Combinada , Hidroxicloroquina , Metformina , Pandemias , Pneumonia Viral , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/mortalidade , Feminino , Humanos , Hidroxicloroquina/farmacocinética , Hidroxicloroquina/uso terapêutico , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/uso terapêutico , Masculino , Metformina/farmacocinética , Metformina/uso terapêutico , Pessoa de Meia-Idade , Farmacovigilância , Pneumonia Viral/diagnóstico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia
11.
PLoS One ; 15(5): e0232473, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32357195

RESUMO

BACKGROUND: Two-drug regimens (2DR) to treat HIV infection have the potential to reduce long-term toxicity and increase therapeutic options for people living with HIV (PLHIV). Prior phase III trials, SWORD-1 and SWORD-2, as well as GEMINI-1 and GEMINI-2, have demonstrated that a dolutegravir-based 2DR is as effective as three- or four-drug regimens among virologically suppressed patients. Limited information exists, however, on patient and provider experiences with 2DR to inform roll-out and integration into routine clinical care. METHODS: We conducted 39 in-depth interviews with PLHIV currently on 2DR in the context of routine care and 8 of their clinical care providers in the United States (U.S.) and Spain. Participants included 33 male and 6 female PLHIV and 8 providers. Interview topics explored perceptions of and experiences with 2DR compared to prior anti-retroviral regimens (ARVs), side effects, patient satisfaction, and clinical performance. Interviews were audio-recorded, transcribed and analyzed using thematic content analysis. RESULTS: Participants viewed 2DR as a significant and positive advance, in terms of its ability to effectively treat HIV with reduced toxicity and essentially no reported side effects. Patients noted the central role providers played in the decision to switch to a 2DR regimen and, among U.S. participants, the importance of insurance coverage making this preferred option feasible. Patients and providers agreed that a 2DR regimen would be appropriate for any PLHIV regardless of whether they were treatment naïve or had significant experience with ARVs. CONCLUSIONS: Participants' experiences with a 2DR regimen were positive with no participants, reporting side effects and all reporting continued viral suppression. Providers valued the reduced toxicity offered by 2DR and served as the primary gateway to a transition to 2DR for patients in both settings. This study provides a foundation for further research on the transition to 2DR regimens in other populations and contexts including low- and middle-income settings.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Adulto , Idoso , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/economia , Atitude do Pessoal de Saúde , Estudos Transversais , Tomada de Decisões , Custos de Medicamentos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/economia , Quimioterapia Combinada/psicologia , Feminino , Infecções por HIV/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Preferência do Paciente , Espanha , Estados Unidos
12.
Yakugaku Zasshi ; 140(5): 751-754, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32378679

RESUMO

In the hospital, antibiotics are widely used to treat infections. We report a case of acute kidney injury (AKI) caused by an antibiotic drug combination. A 30-year-old Japanese male presented with lung metastases, pneumothorax, empyema, and methicillin-resistant Staphylococcus aureus (MRSA) infection. The patient received a combination of vancomycin and piperacillin/tazobactam, which resulted in elevated vancomycin trough concentration and subsequently in AKI. Renal function was restored upon vancomycin and piperacillin/tazobactam cessation. Though this patient had AKI most likely due to the combined use of two agents as has been reported in many cases, vancomycin trough concentration showed an unexpected abnormal increase when halting vancomycin treatment. This is the first report indicating a drug-drug interaction between vancomycin and piperacillin/tazobactam with unexpected abnormal vancomycin trough concentration, leading to AKI, additionally we think that there was a situation that he stressed against the kidney by a history of medications caused renal dysfunction and co-administration. We suggest that when using vancomycin in combination with piperacillin/tazobactam, the trough concentration of vancomycin must be confirmed simultaneously with renal function and evaluation, and that the combination of these two drugs should be minimized.


Assuntos
Lesão Renal Aguda/etiologia , Antibacterianos/efeitos adversos , Combinação Piperacilina e Tazobactam/efeitos adversos , Vancomicina/administração & dosagem , Vancomicina/efeitos adversos , Vancomicina/sangue , Adulto , Antibacterianos/administração & dosagem , Interações Medicamentosas , Quimioterapia Combinada/efeitos adversos , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina , Combinação Piperacilina e Tazobactam/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico
13.
Ann Cardiol Angeiol (Paris) ; 69(3): 107-114, 2020 May.
Artigo em Francês | MEDLINE | ID: covidwho-78184

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells with angiotensin receptors, leading to pneumonia linked to COVID-19. The virus has a double impact on the cardiovascular system, the infection will be more intense if the host has cardiovascular co-morbidities and the virus can cause life-threatening cardiovascular lesions. Therapies associated with COVID-19 may have adverse cardiovascular effects. Therefore, special attention should be given to cardiovascular protection during COVID-19 infection.


Assuntos
Betacoronavirus/patogenicidade , Doenças Cardiovasculares/complicações , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Azitromicina/efeitos adversos , Azitromicina/uso terapêutico , Betacoronavirus/imunologia , Cardiomiopatias/virologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/prevenção & controle , Transtornos Cerebrovasculares/virologia , Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Comorbidade , Doença das Coronárias/complicações , Doença das Coronárias/prevenção & controle , Doença das Coronárias/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Interações Medicamentosas , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Metilprednisolona/efeitos adversos , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Fatores de Risco , Internalização do Vírus/efeitos dos fármacos
14.
Ann Cardiol Angeiol (Paris) ; 69(3): 107-114, 2020 May.
Artigo em Francês | MEDLINE | ID: mdl-32303363

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells with angiotensin receptors, leading to pneumonia linked to COVID-19. The virus has a double impact on the cardiovascular system, the infection will be more intense if the host has cardiovascular co-morbidities and the virus can cause life-threatening cardiovascular lesions. Therapies associated with COVID-19 may have adverse cardiovascular effects. Therefore, special attention should be given to cardiovascular protection during COVID-19 infection.


Assuntos
Betacoronavirus/patogenicidade , Doenças Cardiovasculares/complicações , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Azitromicina/efeitos adversos , Azitromicina/uso terapêutico , Betacoronavirus/imunologia , Cardiomiopatias/virologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/prevenção & controle , Transtornos Cerebrovasculares/virologia , Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Comorbidade , Doença das Coronárias/complicações , Doença das Coronárias/prevenção & controle , Doença das Coronárias/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Interações Medicamentosas , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Metilprednisolona/efeitos adversos , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Fatores de Risco , Internalização do Vírus/efeitos dos fármacos
16.
PLoS One ; 15(4): e0231102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32287280

RESUMO

BACKGROUND: Our preliminary data showed a slight decrease of estimated glomerular filtration rate (eGFR) after direct-acting antivirals (DAAs) treatment in chronic hepatitis C (CHC). However, long-term outcome of renal evolution after DAAs has not been well documented. AIM: To assess the renal function under DAAs treatment in CHC patients of an Asian population at 6 months and 1 year after complete treatment. METHODS: A cohort of 1536 CHC patients who received therapies with DAAs were analyzed. Serial eGFR levels at 24 weeks after treatment (SVR24) and 48 weeks after treatment (SVR48) were evaluated. We compared eGFR at baseline, SVR12, SVR24 and SVR48, and defined renal function deterioration as decrease of eGFR >25% from baseline to SVR24 and SVR48. RESULTS: Overall, there was decline of eGFR from SVR12 to SVR48 in all patients (84.30 ± 27.00 -> 73.20 ± 28.67 mL/min/1.73m2, p<0.001). This trend of decline was similar in all groups. Multivariate analysis for deterioration in renal function from baseline to SVR24 showed liver transplantation, hypertension and baseline eGFR < 60 mL/min/1.73m2 were independent risk factors. Multivariate analysis for persistent deterioration in renal function from baseline to SVR48 showed liver transplantation, baseline eGFR < 60 mL/min/1.73m2 and DCV/ASV use were independent predictive factors. CONCLUSIONS: There is a trend of decline in eGFR at 1-year after DAAs treatment regardless of baseline renal function or DAAs. Liver transplantation and baseline eGFR < 60 mL/min/1.73m2 were independent predictive factors of persistent deterioration in renal function from baseline to SVR48. Close monitoring renal function in these patients was suggested.


Assuntos
Antivirais/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Hepatite C Crônica/terapia , Rim/efeitos dos fármacos , Transplante de Fígado/efeitos adversos , Idoso , Quimioterapia Combinada/efeitos adversos , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resposta Viral Sustentada , Taiwan , Fatores de Tempo
18.
PLoS Negl Trop Dis ; 14(3): e0008106, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32176703

RESUMO

Lymphatic filariasis has remained endemic in Fiji despite repeated mass drug administration using the well-established and safe combination of diethylcarbamazine and albendazole (DA) since 2002. In certain settings the addition of ivermectin to this combination (IDA) remains a safe strategy and is more efficacious. However, the safety has yet to be described in scabies and soil-transmitted helminth endemic settings like Fiji. Villages of Rotuma and Gau islands were randomised to either DA or IDA. Residents received weight-based treatment unblinded with standard exclusions. Participants were actively found and asked by a nurse about their health daily for the first two days and then asked to seek review for the next five days if unwell. Anyone with severe symptoms were reviewed by a doctor and any serious adverse event was reported to the Medical Monitor and Data Safety Monitoring Board. Of 3612 enrolled and eligible participants, 1216 were randomised to DA and 2396 to IDA. Age and sex in both groups were representative of the population. Over 99% (3598) of participants completed 7 days follow-up. Adverse events were reported by 600 participants (16.7%), distributed equally between treatment groups, with most graded as mild (93.2%). There were three serious adverse events, all judged not attributable to treatment by an independent medical monitor. Fatigue was the most common symptom reported by 8.5%, with headache, dizziness, nausea and arthralgia being the next four most common symptoms. Adverse events were more likely in participants with microfilaremia (43.2% versus 15.7%), but adverse event frequency was not related to the presence of scabies or soil-transmitted helminth infection. IDA has comparable safety to DA with the same frequency of adverse events experienced following community mass drug administration. The presence of co-endemic infections did not increase adverse events. IDA can be used in community programs where preventative chemotherapy is needed for control of lymphatic filariasis and other neglected tropical diseases.


Assuntos
Albendazol/efeitos adversos , Antiparasitários/efeitos adversos , Dietilcarbamazina/efeitos adversos , Inseticidas/efeitos adversos , Ivermectina/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Albendazol/administração & dosagem , Antiparasitários/administração & dosagem , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/tratamento farmacológico , Dietilcarbamazina/administração & dosagem , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Filariose Linfática/tratamento farmacológico , Feminino , Fiji , Helmintíase/tratamento farmacológico , Humanos , Lactente , Inseticidas/administração & dosagem , Ivermectina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Doenças Negligenciadas/tratamento farmacológico , População Rural , Escabiose/tratamento farmacológico , Resultado do Tratamento , Adulto Jovem
19.
Int J Hematol ; 112(2): 234-237, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32207051

RESUMO

Immunoglobulin light chain amyloidosis (AL) is a plasma cell disorder characterized by accumulation of misfolded proteins, which can induce organ damage. Venetoclax is active in multiple myeloma patients, in particular those with t(11;14) translocation. t(11;14) translocation is the most common cytogenetic abnormality in AL patients; venetoclax may thus be a useful additional treatment option for this disease. However, a recent trial in multiple myeloma patients (BELLINI) reported increased mortality associated with venetoclax versus placebo in combination with bortezomib and dexamethasone. In this report, we describe an AL patient who had suffered from recurrent infection during previous treatment, but who responded to and tolerated well single-agent venetoclax for more than 1 year. The present report indicates that venetoclax monotherapy may be active and safe for refractory AL amyloidosis.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Fragilidade , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Sulfonamidas/administração & dosagem , Adulto , Compostos Bicíclicos Heterocíclicos com Pontes/efeitos adversos , Cromossomos Humanos Par 11/genética , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Humanos , Amiloidose de Cadeia Leve de Imunoglobulina/genética , Masculino , Segurança , Sulfonamidas/efeitos adversos , Translocação Genética , Resultado do Tratamento
20.
Cochrane Database Syst Rev ; 2: CD010316, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32026465

RESUMO

BACKGROUND: This is the first update of a review originally published in 2017. Starting with one drug and starting with a combination of two drugs are strategies suggested in clinical guidelines as initial treatment of hypertension. The recommendations are not based on evidence about clinically relevant outcomes. Some antihypertensive combinations have been shown to be harmful. The actual harm-to-benefit balance of each strategy is unknown. OBJECTIVES: To determine if there are differences in clinical outcomes between monotherapy and combination therapy as initial treatment for primary hypertension. SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to April 2019: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 2005), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We used no language restrictions. We also searched clinical studies repositories of pharmaceutical companies, reviews of combination drugs on the US Food and Drug Administration and European Medicines Agency websites, and lists of references in reviews and clinical practice guidelines. SELECTION CRITERIA: We included randomised, double-blind trials with at least 12 months' follow-up in adults with primary hypertension (systolic blood pressure/diastolic blood pressure 140/90 mmHg or higher, or 130/80 mmHg or higher if participants had diabetes), which compared combination of two first-line antihypertensive drugs with monotherapy as initial treatment. Trials had to include at least 50 participants per group and report mortality, cardiovascular mortality, cardiovascular events, or serious adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, evaluated the risk of bias, and performed data entry. The primary outcomes were mortality, serious adverse events, cardiovascular events, and cardiovascular mortality. Secondary outcomes were withdrawals due to drug-related adverse effects, reaching blood pressure control (as defined in each trial), and blood pressure change from baseline. Analyses were based on the intention-to-treat principle. We summarised data on dichotomous outcomes as risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS: This update included one new study in which a subgroup of participants met our inclusion criteria. As none of the four included studies focused solely on people initiating antihypertensive treatment, we asked investigators for data for this subgroup. One study (PREVER-treatment 2016) used a combination of thiazide-type diuretic/potassium-sparing diuretic; as the former is not indicated in monotherapy, we analysed this study separately. The three original trials in the main comparison (monotherapy: 335 participants; combination therapy: 233 participants) included outpatients, mostly European and white people. Two trials only included people with type 2 diabetes; the remaining trial excluded people treated with diabetes, hypocholesterolaemia, or cardiovascular drugs. The follow-up was 12 months in two trials and 36 months in one trial. It is very uncertain whether combination therapy versus monotherapy reduces total mortality (RR 1.35, 95% CI 0.08 to 21.72), cardiovascular mortality (zero events reported), cardiovascular events (RR 0.98, 95% CI 0.22 to 4.41), serious adverse events (RR 0.77, 95% CI 0.31 to 1.92), or withdrawals due to adverse effects (RR 0.85, 95% CI 0.53 to 1.35); all outcomes had 568 participants, and the evidence was rated as of very low certainty due to serious imprecision and for using a subgroup that was not defined in advance. The confidence intervals were extremely wide for all important outcomes and included both appreciable harm and benefit. The PREVER-treatment 2016 trial, which used a combination therapy with potassium-sparing diuretic (monotherapy: 84 participants; combination therapy: 116 participants), included outpatients. This trial was conducted in Brazil and had a follow-up of 18 months. The number of events was very low and confidence intervals very wide, with zero events reported for cardiovascular mortality and withdrawals due to adverse events. It is very uncertain if there are differences in clinical outcomes between monotherapy and combination therapy in this trial. AUTHORS' CONCLUSIONS: The numbers of included participants, and hence the number of events, were too small to draw any conclusion about the relative efficacy of monotherapy versus combination therapy as initial treatment for primary hypertension. There is a need for large clinical trials that address the review question and report clinically relevant endpoints.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão Essencial/tratamento farmacológico , Anti-Hipertensivos/efeitos adversos , Doenças Cardiovasculares/mortalidade , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
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