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1.
JAMA Netw Open ; 4(10): e2129639, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34661663

RESUMO

Importance: Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood. Objective: To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19-associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs. Design, Setting, and Participants: This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age ≥18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included. Exposures: Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy. Main Outcomes and Measures: The main outcome was COVID-19-associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations. Results: A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P < .001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73; P = .004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63; P = .33). Similar findings were obtained in analyses that accounted for potential reporting bias and sensitivity analyses that excluded patients with a COVID-19 diagnosis based on symptoms alone. Conclusions and Relevance: In this cohort study, TNF inhibitor monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory treatment regimens among individuals with IMIDs.


Assuntos
Artrite Reumatoide/tratamento farmacológico , COVID-19/mortalidade , Doenças Inflamatórias Intestinais/tratamento farmacológico , Psoríase/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Artrite Reumatoide/epidemiologia , Comorbidade , Quimioterapia Combinada/efeitos adversos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Psoríase/epidemiologia , Sistema de Registros , Estudos Retrospectivos , SARS-CoV-2
2.
Medicine (Baltimore) ; 100(31): e26622, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397797

RESUMO

BACKGROUND: Several previous randomized controlled trials (RCTs) evaluated the efficacy of metformin combined with simvastatin in the treatment of polycystic ovary syndrome (PCOS), yet the results of the researches are not consistent. It is necessary to conduct a meta-analysis to explore the efficacy and safety of metformin combined with simvastatin in the treatment of PCOS, to provide evidence supports for the treatment of PCOS. METHODS: We searched PubMed, EMbase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Chinese biomedical literature databases online to identify the RCTs evaluating the efficacy of metformin combined with simvastatin in the treatment of PCOS. Standardized mean difference (SMD) and 95% confidence interval (95% CI) were calculated to evaluate the synthesized effects. RESULTS: Nine RCTs with a total of 746 PCOS patients were included. The synthesized results indicated that the combined use of metformin and simvastatin are more beneficial to reduce the total cholesterol (SMD -2.66, 95% CI -3.65 to -1.66), triglycerides (SMD -1.25, 95% CI -2.02 to -0.49), low density lipoprotein (SMD -2.91, 95% CI -3.98 to -1.84), testosterone (SMD -0.64, 95% CI -1.13 to -0.15), fasting insulin (SMD -1.17, 95% CI -2.09 to -0.26) than metformin alone treatment in PCOS patients (all P < .001), and there was no significant difference in the high density lipoprotein (SMD -0.05, 95% CI -0.56-0.46), luteinizing hormone (SMD -0.58, 95% CI -1.66 to -0.50), follicle stimulating hormone (SMD 0.41, 95% CI -0.78-1.59), prolactin (SMD -1.38, 95% CI -2.93-0.17), fasting blood sugar (SMD 0.23, 95% CI -0.52-0.97), and insulin sensitivity index (SMD -0.17, 95% CI -0.48-0.15) between experimental and control groups (all P > .05). CONCLUSIONS: Metformin combined with simvastatin is superior to metformin alone in the treatment of PCOS patients with more advantages in improving the levels of sex hormones, blood lipids, and blood sugar. However, the safety of this therapy still needs to be further explored in clinical studies with high-quality and large samples.


Assuntos
Metformina/uso terapêutico , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Sinvastatina/uso terapêutico , Glicemia/metabolismo , Colesterol/sangue , Quimioterapia Combinada/efeitos adversos , Feminino , Hormônios Esteroides Gonadais/sangue , Humanos , Insulina/sangue , Lipoproteínas LDL/sangue , Metformina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sinvastatina/efeitos adversos , Triglicerídeos/sangue
3.
PLoS Med ; 18(7): e1003709, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34264928

RESUMO

BACKGROUND: Benzodiazepine hypnotics and the related nonbenzodiazepine hypnotics (z-drugs) are among the most frequently prescribed medications for older adults. Both can depress respiration, which could have fatal cardiorespiratory effects, particularly among patients with concurrent opioid use. Trazodone, frequently prescribed in low doses for insomnia, has minimal respiratory effects, and, consequently, may be a safer hypnotic for older patients. Thus, for patients beginning treatment with benzodiazepine hypnotics or z-drugs, we compared deaths during periods of current hypnotic use, without or with concurrent opioids, to those for comparable patients receiving trazodone in doses up to 100 mg. METHODS AND FINDINGS: The retrospective cohort study in the United States included 400,924 Medicare beneficiaries 65 years of age or older without severe illness or evidence of substance use disorder initiating study hypnotic therapy from January 2014 through September 2015. Study endpoints were out-of-hospital (primary) and total mortality. Hazard ratios (HRs) were adjusted for demographic characteristics, psychiatric and neurologic disorders, cardiovascular and renal conditions, respiratory diseases, pain-related diagnoses and medications, measures of frailty, and medical care utilization in a time-dependent propensity score-stratified analysis. Patients without concurrent opioids had 32,388 person-years of current use, 260 (8.0/1,000 person-years) out-of-hospital and 418 (12.9/1,000) total deaths for benzodiazepines; 26,497 person-years,150 (5.7/1,000) out-of-hospital and 227 (8.6/1,000) total deaths for z-drugs; and 16,177 person-years,156 (9.6/1,000) out-of-hospital and 256 (15.8/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (respective HRs: 0.99 [95% confidence interval, 0.81 to 1.22, p = 0.954] and 0.95 [0.82 to 1.14, p = 0.513] and z-drugs (HRs: 0.96 [0.76 to 1.23], p = 0.767 and 0.87 [0.72 to 1.05], p = 0.153) did not differ significantly from that for trazodone. Patients with concurrent opioids had 4,278 person-years of current use, 90 (21.0/1,000) out-of-hospital and 127 (29.7/1,000) total deaths for benzodiazepines; 3,541 person-years, 40 (11.3/1,000) out-of-hospital and 64 (18.1/1,000) total deaths for z-drugs; and 2,347 person-years, 19 (8.1/1,000) out-of-hospital and 36 (15.3/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (HRs: 3.02 [1.83 to 4.97], p < 0.001 and 2.21 [1.52 to 3.20], p < 0.001) and z-drugs (HRs: 1.98 [1.14 to 3.44], p = 0.015 and 1.65 [1.09 to 2.49], p = 0.018) were significantly increased relative to trazodone; findings were similar with exclusion of overdose deaths or restriction to those with cardiovascular causes. Limitations included composition of the study cohort and potential confounding by unmeasured variables. CONCLUSIONS: In US Medicare beneficiaries 65 years of age or older without concurrent opioids who initiated treatment with benzodiazepine hypnotics, z-drugs, or low-dose trazodone, study hypnotics were not associated with mortality. With concurrent opioids, benzodiazepines and z-drugs were associated with increased out-of-hospital and total mortality. These findings indicate that the dangers of benzodiazepine-opioid coadministration go beyond the documented association with overdose death and suggest that in combination with opioids, the z-drugs may be more hazardous than previously thought.


Assuntos
Analgésicos Opioides/efeitos adversos , Benzodiazepinas/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Mortalidade , Medicamentos sob Prescrição/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/administração & dosagem , Benzodiazepinas/administração & dosagem , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Masculino , Medicare , Medicamentos sob Prescrição/administração & dosagem , Estudos Retrospectivos , Estados Unidos
4.
Lancet HIV ; 8(7): e397-e407, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34197772

RESUMO

BACKGROUND: In DISCOVER, a multinational, randomised controlled trial, emtricitabine and tenofovir alafenamide compared with emtricitabine and tenofovir disoproxil fumarate showed non-inferior efficacy for HIV prevention and improved bone mineral density and renal safety biomarkers at week 48. We report outcomes analysed after all participants had completed 96 weeks of follow-up. METHODS: This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in Europe and North America. Adult cisgender men and transgender women who have sex with men, both with a high risk of acquiring HIV as determined by self-reported sexual behaviour or recent sexually transmitted infections, were randomly assigned (1:1) to receive either emtricitabine and tenofovir alafenamide (200/25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine and tenofovir disoproxil fumarate (200/300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). The primary efficacy outcome was incident HIV infection. Incidence of HIV-1 infection per 100 person-years was assessed when the last participant had completed 96 weeks of follow-up. This trial is registered with ClinicalTrials.gov, number NCT02842086. FINDINGS: Between Sept 13, 2016, and June 30, 2017, 5387 participants were randomly assigned to receive emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693), contributing 10 081 person-years of follow-up. At 96 weeks of follow-up, there were eight HIV infections in participants who had received emtricitabine and tenofovir alafenamide (0·16 infections per 100 person-years [95% CI 0·07-0·31]) and 15 in participants who had received emtricitabine and tenofovir disoproxil fumarate (0·30 infections per 100 person-years [0·17-0·49]). Emtricitabine and tenofovir alafenamide maintained its non-inferiority to emtricitabine and tenofovir disoproxil fumarate for HIV prevention (IRR 0·54 [95% CI 0·23-1·26]). Approximately 78-82% of participants reported taking study medication more than 95% of the time across all study visits. Rates of sexually transmitted infections remained high and similar across groups (21 cases per 100 person-years for rectal gonorrhoea and 28 cases per 100 person-years for rectal chlamydia). Emtricitabine and tenofovir alafenamide continued to show superiority over emtricitabine and tenofovir disoproxil fumarate in all but one of the six prespecified bone mineral density and renal biomarkers. There was more weight gain among participants who had received emtricitabine and tenofovir alafenamide (median weight gain 1·7 kg vs 0·5 kg, p<0·0001). INTERPRETATION: Emtricitabine and tenofovir alafenamide is safe and effective for longer-term pre-exposure prophylaxis in cisgender men and transgender women who have sex with men. FUNDING: Gilead Sciences.


Assuntos
Adenina/análogos & derivados , Alanina/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Emtricitabina/uso terapêutico , Infecções por HIV/prevenção & controle , Organofosfonatos/uso terapêutico , Tenofovir/uso terapêutico , Adenina/efeitos adversos , Adenina/uso terapêutico , Adulto , Idoso , Alanina/efeitos adversos , Fármacos Anti-HIV/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Emtricitabina/efeitos adversos , Feminino , Seguimentos , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfonatos/efeitos adversos , Profilaxia Pré-Exposição , Tenofovir/efeitos adversos , Resultado do Tratamento , Adulto Jovem
5.
J S Afr Vet Assoc ; 92(0): e1-e3, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34212736

RESUMO

Etorphine-azaperone is the most commonly used drug combination for chemical immobilisation of free-ranging white rhinoceroses, but causes several profound physiological disturbances, including muscle tremors. The addition of benzodiazepine sedatives, such as midazolam, has been proposed to reduce the muscular rigidity and tremors in immobilised rhinoceroses. Twenty-three free-ranging, sub-adult white rhinoceros bulls were darted and captured using a combination of etorphine plus either azaperone or midazolam. Skeletal muscle tremors were visually evaluated and scored by an experienced veterinarian, and tremor scores and distance run were compared between groups using the Wilcoxon rank sum test. No statistical differences were observed in tremor scores (p = 0.435) or distance run (p = 0.711) between the two groups, and no correlation between these variables was detected (r = -0.628; p = 0.807). Etorphine-midazolam was as effective as etorphine-azaperone at immobilising rhinoceroses, with animals running similar distances. Although the addition of midazolam to the etorphine did not reduce tremor scores compared to azaperone, it might have other beneficial immobilising effects in rhinoceroses, and further investigation is necessary to elucidate possible methods of reducing muscle tremoring during chemical immobilisation of rhinoceroses.


Assuntos
Azaperona/farmacologia , Etorfina/farmacologia , Midazolam/farmacologia , Perissodáctilos , Tremor/veterinária , Animais , Azaperona/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/veterinária , Etorfina/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Hipnóticos e Sedativos/farmacologia , Imobilização , Midazolam/efeitos adversos , Tremor/induzido quimicamente
6.
Sci Rep ; 11(1): 13509, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34188093

RESUMO

Schizophrenia is a chronic mental condition presenting a wide range of symptoms. Although it has a low prevalence compared to other mental conditions, it has a negative impact on social and occupational functions. This study aimed to assess the appropriateness of antipsychotic medications administered to schizophrenic patients and describe current treatment patterns for schizophrenia. A retrospective cohort study was conducted in all patients over the age of 15 with an active diagnosis of schizophrenia and treated with antipsychotics between 2008 and 2013 in the Valencia region. A total of 19,718 patients were eligible for inclusion. The main outcome assessed was inappropriateness of the pharmacotherapeutic management, including polypharmacy use. Altogether, 30.4% of patients received antipsychotic polypharmacy, and 6.8% were prescribed three or more antipsychotics. Overdosage affected 318 individuals (1.6%), and 21.5% used concomitant psychotropics without an associated psychiatric diagnosis. Women and people with a comorbid condition like anxiety or depression were less likely to receive antipsychotic polypharmacy. In contrast, increased polypharmacy was associated with concomitant treatment with other psychoactive drugs, and only in user on maintenance therapy, with more visits to the mental health hospital. Overall, we observed a high level of inappropriateness in antipsychotic prescriptions. Greater adherence to guidelines could maximize the benefits of antipsychotic medications while minimizing risk of adverse effects.


Assuntos
Antipsicóticos , Overdose de Drogas/epidemiologia , Medicamentos sob Prescrição , Esquizofrenia , Adolescente , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medicamentos sob Prescrição/administração & dosagem , Medicamentos sob Prescrição/efeitos adversos , Estudos Retrospectivos , Esquizofrenia/tratamento farmacológico , Esquizofrenia/epidemiologia , Espanha/epidemiologia
7.
J Alzheimers Dis ; 82(3): 1333-1344, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34151816

RESUMO

BACKGROUND: Memantine, an NMDA receptor antagonist, is used for the treatment of Alzheimer's disease. There is a caution to refrain from administrating memantine in combination with some specific drugs such as amantadine or dextromethorphan due to potential interactions that might augment the adverse effects of memantine. OBJECTIVE: This notification has not been validated in real-world data, which we aim to address using a large self-reporting database from Japan. METHODS: We conducted a disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database reported between April 2004 and March 2019 for detecting the neuropsychiatric adverse event (AE) signals associated with memantine and other potentially interactive drugs including amantadine, dextromethorphan, cimetidine, ranitidine, procainamide, quinidine, acetazolamide, citrate, and bicarbonate. Drug-drug interactions between memantine and these drugs were assessed using multiplicative and additive models. RESULTS: There was no statistically robust evidence to support multiplicative or additive interactions between memantine and the aforementioned drugs to increase the reporting of any included neuropsychiatric AEs or AE categories. CONCLUSION: The real-world JADER data did not raise the concern about the interactive increase in the neuropsychiatric AEs in patients with dementia taking memantine in combination with amantadine or dextromethorphan, suggesting there may be no urgent need to prohibit the co-administration of these drugs presently.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/tendências , Bases de Dados Factuais/tendências , Interações Medicamentosas/fisiologia , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Memantina/efeitos adversos , Farmacovigilância , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/psicologia , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/tendências , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/psicologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Estudos Retrospectivos
8.
Medicine (Baltimore) ; 100(25): e26374, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160412

RESUMO

BACKGROUND: Ankylosing spondylitis (AS) is a chronic progressive inflammatory disease of the spine, which mainly invades the sacroiliac joint, spine, and large joints near the trunk, leading to fibrous and skeletal ankylosis and deformity, and can cause damage to the eyes, lung, cardiovascular, kidney and other organs. Chinese herbal formulas (CHF) is an important interventions of Traditional Chinese Medicine (TCM), and CHFs combined with western medicine are widely used in clinical practice to treat AS. METHODS: Eight databases will be systematically retrieved from their inceptions to March 2021. Only randomized controlled trials (RCTs) of CHFs combined with western medicine for AS treatment will meet the inclusion criteria. The primary outcomes we focus on include clinical effectiveness rate, TCM syndrome score, TCM symptom score, Bath ankylosing spondylitis disease activity index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), chest expansion, nocturnal spinal pain, adverse reactions, erythrocyte sedimentation rate (ESR), and C protein response (CRP). The research screening, data extraction, and risk of bias assessment will be performed independently by 2 researchers, and divergence will be solved by a third researcher. Revman 5.3 software will be used for meta-analysis. The confidence of evidence will be graded using grading of recommendations assessment, development, and evaluation (GRADE) algorithm and methodological quality will be assessed adopting risk of bias in systematic reviews (ROBIS). RESULTS: This systematic review (SR) will provide evidence-based medical evidence for AS therapy by CHF combined with western medicine and we will submit the findings of this SR for peer-review publication. CONCLUSIONS: This SR will provide latest and updated summary proof for assessing the effectiveness and safety of CHF combined with western medicine for AS. REGISTRATION NUMBER: INPLASY 202150089.


Assuntos
Anti-Inflamatórios/administração & dosagem , Antirreumáticos/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Imunossupressores/administração & dosagem , Espondilite Anquilosante/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Antirreumáticos/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Espondilite Anquilosante/imunologia , Revisões Sistemáticas como Assunto , Resultado do Tratamento
9.
Medicine (Baltimore) ; 100(25): e26416, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160429

RESUMO

BACKGROUND: Cough variant asthma (CVA) is classified as a distinct form of asthma. As the primary or only symptom, cough is the leading cause for the most prevalent chronic cough among kids. The American College of Clinical Pharmacy, British Thoracic Society, and Chinese guidelines established for diagnosing and treating chronic cough in kids recommend inhaled corticosteroids, combined with leukotriene receptor antagonists when necessary. METHODS: We will conduct a comprehensive search in major databases using keywords to find studies related to the analysis of montelukast sodium and budesonide for treating CVA in kids. Two reviewers will independently assess the quality of the selected research articles and perform data extraction. Next, we will use the RevMan software (version: 5.3) to conduct the statistical analysis of the present study. RESULTS: This study will assess the efficacy and safeness of using montelukast sodium and budesonide to treat kids with CVA by pooling the results of individual studies. CONCLUSION: Our findings will provide vigorous evidence to judge whether montelukast sodium and budesonide therapy is an efficient form of therapy for CVA patients. ETHICS AND DISSEMINATION: Ethics approval is not needed for the present meta-analysis. OSF REGISTRATION NUMBER: May 17, 2021.osf.io/cuvjz (https://osf.io/cuvjz/).


Assuntos
Asma/tratamento farmacológico , Tosse/tratamento farmacológico , Glucocorticoides/administração & dosagem , Antagonistas de Leucotrienos/administração & dosagem , Acetatos/administração & dosagem , Acetatos/efeitos adversos , Administração por Inalação , Asma/diagnóstico , Asma/imunologia , Budesonida/administração & dosagem , Budesonida/efeitos adversos , Criança , Doença Crônica/tratamento farmacológico , Tosse/diagnóstico , Tosse/imunologia , Ciclopropanos/administração & dosagem , Ciclopropanos/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Glucocorticoides/efeitos adversos , Humanos , Antagonistas de Leucotrienos/efeitos adversos , Metanálise como Assunto , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulfetos/administração & dosagem , Sulfetos/efeitos adversos , Revisões Sistemáticas como Assunto , Resultado do Tratamento
10.
Clin Interv Aging ; 16: 1023-1035, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34103905

RESUMO

Purpose: This retrospective observational study investigated the efficacy and safety of vancomycin to treat patients aged 80 years and older. In particular, the associations between vancomycin trough concentration (VTC) and treatment outcomes or nephrotoxicity were explored. Patients and Methods: Patients aged ≥80 years had received ≥3 vancomycin treatments and ≥1 detection of VTC. Treatment outcomes were defined as success or failure. Nephrotoxicity was considered an increase in serum creatinine ≥ 44.2 mmol/L, or 50% above baseline, for ≥2 consecutive days. Univariate and multivariate analyses were performed to identify risk factors for treatment failure and nephrotoxicity. Results: Of 349 patients, 120 (34.4%) experienced treatment failure. For patients with VTCs at <10, 10-15, 15-20, and ≥20 µg/mL, the clinical response rates were, respectively, 77.8, 77.0, 80.5, and 61.0%; the 30-day mortality rates were 2.8, 15.0, 15.3, and 37.8%; and the rates of persistent bacteremia were 16.7, 12.4, 11.9, and 11.0%. The multivariate analysis indicated that blood urea nitrogen ≥11 g/dL and heart failure were independently associated with treatment failure; but not VTC (P = 0.004, 0.016, 0.828, respectively). During vancomycin treatment, 42 (12.0%) patients experienced nephrotoxicity with recovery time 7.5 ± 4.5 days. Fewer than half of patients with nephrotoxicity recovered after suspending vancomycin application. The variables found independently associated with increased nephrotoxicity were: VTC ≥15 µg/mL; treatment duration ≥15 d; and concomitant aminoglycosides administration (P = 0.024, 0.035, 0.029). Conclusion: In patients aged 80 years and older, elevated VTC level was not associated with favorable treatment outcomes. Patients with VTC ≥20 µg/mL appear to suggest a worsened prognosis compared with lower VTCs. The risk of nephrotoxicity increases with elevated VTC, longer treatment time, and concomitant aminoglycoside administration.


Assuntos
Antibacterianos/efeitos adversos , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Vancomicina/efeitos adversos , Idoso , Antibacterianos/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos , Masculino , Pneumonia Estafilocócica/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Vancomicina/uso terapêutico
11.
Medicine (Baltimore) ; 100(23): e25313, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34114978

RESUMO

ABSTRACT: Changes in tryptophan metabolism affect human physiology including the immune system, mood, and sleep and are associated with human immunodeficiency virus (HIV) pathogenesis. This study investigates whether the treatment of HIV-infected individuals with the neurokinin-1 receptor antagonist, aprepitant, alters tryptophan metabolism.This study utilized archival samples from 3 phase 1B clinical trials "Anti-HIV Neuroimmunomodulatory Therapy with Neurokinin-1 Antagonist Aprepitant"-2 double-blinded, placebo-controlled, and 1 open-label study. We tested samples from a total of 57 individuals: 26 combination antiretroviral therapy (cART) naïve individuals receiving aprepitant, 19 cART naïve individuals receiving placebo, and 12 individuals on a ritonavir-containing cART regimen receiving aprepitant. We evaluated the effect of aprepitant on tryptophan metabolism by measuring levels of kynurenine and tryptophan in archival plasma samples and calculating the kynurenine to tryptophan ratio.Aprepitant treatment affected tryptophan metabolism in both cART treated and cART naïve individuals with more profound effects in patients receiving cART. While aprepitant treatment affected tryptophan metabolism in all HIV-infected patients, it only significantly decreased kynurenine to tryptophan ratio in cART treated individuals. Aprepitant treatment offers an opportunity to target inflammation and mood disorders frequently co-existing in chronic HIV infection.


Assuntos
Aprepitanto , Infecções por HIV , Transtornos do Humor , Neuroimunomodulação/efeitos dos fármacos , Ritonavir , Triptofano/metabolismo , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Aprepitanto/administração & dosagem , Aprepitanto/efeitos adversos , Contagem de Linfócito CD4/métodos , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/psicologia , Infecções por HIV/virologia , Humanos , Cinurenina/análise , Masculino , Transtornos do Humor/tratamento farmacológico , Transtornos do Humor/etiologia , Antagonistas dos Receptores de Neurocinina-1/administração & dosagem , Antagonistas dos Receptores de Neurocinina-1/efeitos adversos , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Resultado do Tratamento
12.
Immun Inflamm Dis ; 9(3): 617-621, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33942541

RESUMO

The coronavirus disease (COVID-19), during its course, may involve several organs, including the skin with a petechial skin rash, urticaria and erythematous rash, or varicella-like eruption, representing an additional effect of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as commonly observed in other viral diseases. Considering that symptomatic patients with COVID-19 generally undergo multidrug treatments, the occurrence of a possible adverse drug reaction presenting with cutaneous manifestations should be contemplated. Pleomorphic skin eruptions occurred in a 59-year-old Caucasian woman, affected by a stable form of chronic lymphocytic leukemia, and symptomatic SARS-CoV-2 infection, treated with a combination of hydroxychloroquine sulfate, darunavir, ritonavir, sarilumb, omeprazole, ceftriaxone, high-flow oxygen therapy devices, filgrastim (Zarzio®) as a single injection, and enoxaparin. The patient stopped all treatment but oxygen and enoxaparin were continued and the patient received a high-dose Desametasone with complete remission of dermatological impairment in 10 days. It is very important to differentially diagnose COVID-19 disease-related cutaneous manifestations, where is justified to continue the multidrug antiviral treatment, from those caused by an adverse drug reaction, where it would be necessary to identify the possible culprit drug and to start appropriate antiallergic treatment.


Assuntos
COVID-19 , Exantema , Antivirais/efeitos adversos , COVID-19/complicações , Quimioterapia Combinada/efeitos adversos , Exantema/tratamento farmacológico , Exantema/virologia , Feminino , Humanos , Hidroxicloroquina , Pessoa de Meia-Idade
13.
JAMA ; 325(24): 2466-2479, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34009257

RESUMO

Importance: The benefits and harms of adding long-acting muscarinic antagonists (LAMAs) to inhaled corticosteroids (ICS) and long-acting ß2-agonists (LABAs) for moderate to severe asthma remain unclear. Objective: To systematically synthesize the outcomes and adverse events associated with triple therapy (ICS, LABA, and LAMA) vs dual therapy (ICS plus LABA) in children and adults with persistent uncontrolled asthma. Data Sources: MEDLINE, Embase, CENTRAL, ICTRP, FDA, and EMA databases from November 2017, to December 8, 2020, without language restriction. Study Selection: Two investigators independently selected randomized clinical trials (RCTs) comparing triple vs dual therapy in patients with moderate to severe asthma. Data Extraction and Synthesis: Two reviewers independently extracted data and assessed risk of bias. Random-effects meta-analyses, including individual patient-level exacerbation data, were used. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to assess certainty (quality) of the evidence. Main Outcomes and Measures: Severe exacerbations, asthma control (measured using the Asthma Control Questionnaire [ACQ-7], a 7-item list with each item ranging from 0 [totally controlled] to 6 [severely uncontrolled]; minimal important difference, 0.5), quality of life (measured using the Asthma-related Quality of Life [AQLQ] tool; score range, 1 [severely impaired] to 7 [no impairment]; minimal important difference, 0.5), mortality, and adverse events. Results: Twenty RCTs using 3 LAMA types that enrolled 11 894 children and adults (mean age, 52 years [range, 9-71 years]; 57.7% female) were included. High-certainty evidence showed that triple therapy vs dual therapy was significantly associated with a reduction in severe exacerbation risk (9 trials [9932 patients]; 22.7% vs 27.4%; risk ratio, 0.83 [95% CI, 0.77 to 0.90]) and an improvement in asthma control (14 trials [11 230 patients]; standardized mean difference [SMD], -0.06 [95% CI, -0.10 to -0.02]; mean difference in ACQ-7 scale, -0.04 [95% CI, -0.07 to -0.01]). There were no significant differences in asthma-related quality of life (7 trials [5247 patients]; SMD, 0.05 [95% CI, -0.03 to 0.13]; mean difference in AQLQ score, 0.05 [95% CI, -0.03 to 0.13]; moderate-certainty evidence) or mortality (17 trials [11 595 patients]; 0.12% vs 0.12%; risk ratio, 0.96 [95% CI, 0.33 to 2.75]; high-certainty evidence) between dual and triple therapy. Triple therapy was significantly associated with increased dry mouth and dysphonia (10 trials [7395 patients]; 3.0% vs 1.8%; risk ratio, 1.65 [95% CI, 1.14 to 2.38]; high-certainty evidence), but treatment-related and serious adverse events were not significantly different between groups (moderate-certainty evidence). Conclusions and Relevance: Among children (aged 6 to 18 years) and adults with moderate to severe asthma, triple therapy, compared with dual therapy, was significantly associated with fewer severe asthma exacerbations and modest improvements in asthma control without significant differences in quality of life or mortality.


Assuntos
Corticosteroides/administração & dosagem , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Antiasmáticos/administração & dosagem , Asma/tratamento farmacológico , Antagonistas Muscarínicos/administração & dosagem , Administração por Inalação , Adulto , Antiasmáticos/efeitos adversos , Asma/mortalidade , Asma/fisiopatologia , Criança , Quimioterapia Combinada/efeitos adversos , Volume Expiratório Forçado , Humanos , Nebulizadores e Vaporizadores , Qualidade de Vida , Índice de Gravidade de Doença , Exacerbação dos Sintomas , Xerostomia/induzido quimicamente
14.
Medicine (Baltimore) ; 100(18): e25639, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950941

RESUMO

BACKGROUND: Salvianolate, a common drug for stabilizing heart disease and Angina Pectoris, is considered to be off-label for preventing venous thromboembolism (VTE) or anticoagulation at present. However, many clinical studies have showed that salvianolate can effectively inhibit the deep-vein thrombosis (DVT) incidence, and prevent VTE of perioperative patients in the real world in China. OBJECTIVE: This analysis aimed to evaluate the effectiveness and safety of salvianolate in preventing VTE in perioperative patients. METHODS: Databases of PubMed, Cochrane Library, Embase, CNKI, Wanfang and VIP were searched until July 2019. Literature retrieval, data extraction and quality assessment were independently completed by two researchers and checked with each other. Review Manager 5.2 software was applied for meta-analysis. RESULTS: A total of 429 studies were retrieved, including 11 randomized controlled trials (RCTs) with a total of 1149 subjects. Compared with low molecular weight heparin (LMWH) group alone, salvianolate combined LMWH group had lower DVT incidence in preventing perioperative thrombosis (2.75% and 14.23%, OR: 0.21, 95% CI:[0.08,0.53]; P = .0009). The incidence of adverse reactions of experimental group was similar to that of control group (1.79% and 2.31%, OR: 0.65, 95% CI:[0.18,2.35]. P = .51). Compared with the control group, D-dimer level (D-D), platelet count (PLT), fibrinogen (FIB), whole blood high shear viscosity (WBHSV), and whole blood low shear viscosity (WBLSV) were all significantly decreased (P < .01), and prothrombin time (PT) was significantly increased (P < .05). CONCLUSION: Salvianolate combined LMWH has better effectiveness and the same safety in preventing venous thromboembolism in perioperative patients. However, due to the small number of included literatures, large sample studies are still needed to further verify this conclusion.


Assuntos
Uso Off-Label , Extratos Vegetais/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Tromboembolia Venosa/epidemiologia , China/epidemiologia , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Período Perioperatório/estatística & dados numéricos , Extratos Vegetais/administração & dosagem , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Tempo de Protrombina , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
15.
Medicine (Baltimore) ; 100(20): e25790, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011040

RESUMO

BACKGROUND: It is known that Bi Qi Capsules (BQC) have synergistic effects when combined with Methotrexate, but there is a lack of clinical studies on the long-term efficacy and safety of the combination of the 2 in the treatment of rheumatoid arthritis (RA). Therefore, the purpose of this randomized controlled trial was to evaluate the long-term efficacy and safety of this treatment. METHODS: This was a prospective, double-blind, single-simulation, randomized controlled trial investigating the efficacy and safety of BQC in combination with Methotrexate in the treatment of RA, and was approved by the Clinical Research Ethics Committee of the hospital. Patients were randomized in a 1:1 ratio to either the observation or control group and were respectively followed up for 6 months after receiving 12 weeks of treatment. The observation indexes included: total effective rate, DAS-28 score, inflammatory indexes, and adverse reactions. Finally, the collected data was statistically analyzed by SPSS version 18.0. DISCUSSION: This study evaluated the long-term efficacy of BQC in combination with Methotrexate in the treatment of RA. The trial results of this study will provide new ideas for choosing a combination of Chinese and Western medicine protocols for the treatment of RA. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/U85GX.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Metotrexato/administração & dosagem , Adolescente , Adulto , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Cápsulas , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
16.
J Interv Cardiol ; 2021: 9934535, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34035674

RESUMO

Introduction: This network meta-analysis aimed to evaluate the efficacy and safety of different dual antiplatelet therapies (DAPTs) after percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). Methods: Randomized controlled trials (RCTs) comparing longer-term (>12 months) DAPT (L-DAPT), 12-month DAPT (DAPT 12Mo), 6-month DAPT (DAPT 6Mo), 3-month DAPT followed by aspirin monotherapy (DAPT 3Mo + ASA), 3-month DAPT followed by a P2Y12 receptor inhibitor monotherapy (DAPT 3Mo + P2Y12), or 1-month DAPT with a P2Y12 receptor inhibitor monotherapy (DAPT 1Mo + P2Y12) were searched. Primary endpoints were all-cause mortality, cardiac death, myocardial infarction (MI), major bleeding, any bleeding, definite or probable stent thrombosis (ST), and net adverse clinical events (NACE). This Bayesian network meta-analysis was performed with the random-effects model. Results: Twenty-four RCTs (n = 81339) were included. In comparison with L-DAPT, DAPT 6Mo (OR: 0.50, 95% CI: 0.29-0.83), DAPT 3Mo + P2Y12 (OR: 0.38, 95% CI: 0.18-0.82), DAPT 3Mo + ASA (OR: 0.44, 95% CI: 0.17-0.98), and DAPT 1Mo + P2Y12 (OR: 0.45, 95% CI: 0.14-0.93) were associated with a lower risk of major bleeding. DAPT 3Mo + P2Y12 (OR: 0.58, 95% CI: 0.38-0.88) reduced the risk of any bleeding when compared with DAPT 12Mo. L-DAPT decreased the risk of MI and definite or probable stent ST when compared with DAPT 6Mo. DAPT 3Mo + P2Y12 decreased the risk of NACE in comparison with DAPT 6Mo and DAPT 12Mo. No significant difference in all-cause mortality and cardiac death was observed. In patients with acute coronary syndrome, DAPT 6Mo was comparable to DAPT 12Mo. Conclusion: Short-term (1-3 months) DAPT is noninferior to DAPT 6Mo after DESs implantation, while L-DAPT reduces MI and definite or probable ST rates. DAPT 3Mo + P2Y12 might be a reasonable trade-off in patients with high risk of bleeding accompanied by ischemia.


Assuntos
Reestenose Coronária/prevenção & controle , Quimioterapia Combinada , Stents Farmacológicos , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/farmacologia , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Metanálise em Rede , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Risco Ajustado/métodos
17.
Cochrane Database Syst Rev ; 4: CD007694, 2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33852162

RESUMO

BACKGROUND: Asthma is characterised by chronic inflammation of the airways and recurrent exacerbations with wheezing, chest tightness, and cough. Treatment with inhaled steroids and bronchodilators can result in good control of symptoms, prevention of further morbidity, and improved quality of life. However, an increase in serious adverse events with the use of both regular formoterol and regular salmeterol (long-acting beta2-agonists) compared with placebo for chronic asthma has been demonstrated in previous Cochrane Reviews. This increase was statistically significant in trials that did not randomise participants to an inhaled corticosteroid, but not when formoterol or salmeterol was combined with an inhaled corticosteroid. The confidence intervals were found to be too wide to ensure that the addition of an inhaled corticosteroid renders regular long-acting beta2-agonists completely safe; few participants and insufficient serious adverse events in these trials precluded a definitive decision about the safety of combination treatments. OBJECTIVES: To assess risks of mortality and non-fatal serious adverse events in trials that have randomised patients with chronic asthma to regular formoterol and an inhaled corticosteroid versus regular salmeterol and an inhaled corticosteroid. SEARCH METHODS: We searched the Cochrane Airways Register of Trials, CENTRAL, MEDLINE, Embase, and two trial registries to identify reports of randomised trials for inclusion. We checked manufacturers' websites and clinical trial registers for unpublished trial data, as well as Food and Drug Administration (FDA) submissions in relation to formoterol and salmeterol. The date of the most recent search was  24 February 2021. SELECTION CRITERIA: We included controlled clinical trials with a parallel design, recruiting patients of any age and severity of asthma, if they randomised patients to treatment with regular formoterol versus regular salmeterol (each with a randomised inhaled corticosteroid) and were of at least 12 weeks' duration. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion in the review, extracted outcome data from published papers and trial registries, and applied GRADE rating for the results. We sought unpublished data on mortality and serious adverse events from study sponsors and authors. The primary outcomes were all cause mortality and non-fatal serious adverse events. We chose not to calculate an average result from all the formulations of formoterol and inhaled steroid, as the doses and delivery devices are too diverse to assume a single class effect. MAIN RESULTS: Twenty-one studies in 11,572 adults and adolescents and two studies in 723 children met the eligibility criteria of the review. No data were available for two studies; therefore these were not included in the analysis. Among adult and adolescent studies, seven compared formoterol and budesonide to salmeterol and fluticasone (N = 7764), six compared formoterol and beclomethasone to salmeterol and fluticasone (N = 1923), two compared formoterol and mometasone to salmeterol and fluticasone (N = 1126), two compared formoterol and fluticasone to salmeterol and fluticasone (N = 790), and one compared formoterol and budesonide to salmeterol and budesonide (N = 229). In total, five deaths were reported among adults, none of which was thought to be related to asthma. The certainty of evidence for all-cause mortality was low, as there were not enough deaths to permit any precise conclusions regarding the risk of mortality on combination formoterol versus combination salmeterol. In all, 201 adults reported non-fatal serious adverse events. In studies comparing formoterol and budesonide to salmeterol and fluticasone, there were 77 in the formoterol arm and 68 in the salmeterol arm (Peto odds ratio (OR) 1.14, 95% confidence interval (CI) 0.82 to 1.59; 5935 participants, 7 studies; moderate-certainty evidence). In the formoterol and beclomethasone studies, there were 12 adults in the formoterol arm and 13 in the salmeterol arm with events (Peto OR 0.94, 95% CI 0.43 to 2.08; 1941 participants, 6 studies; moderate-certainty evidence). In the formoterol and mometasone studies, there were 18 in the formoterol arm and 11 in the salmeterol arm (Peto OR 1.02, 95% CI 0.47 to 2.20; 1126 participants, 2 studies; moderate-certainty evidence). One adult in the formoterol and fluticasone studies in the salmeterol arm experienced an event (Peto OR 0.05, 95% CI 0.00 to 3.10; 293 participants, 2 studies; low-certainty evidence). Another adult in the formoterol and budesonide compared to salmeterol and budesonide study in the formoterol arm had an event (Peto OR 7.45, 95% CI 0.15 to 375.68; 229 participants, 1 study; low-certainty evidence). Only 46 adults were reported to have experienced asthma-related serious adverse events. The certainty of the evidence was low to very low due to the small number of events and the absence of independent assessment of causation. The two studies in children compared formoterol and fluticasone to salmeterol and fluticasone. No deaths and no asthma-related serious adverse events were reported in these studies. Four all-cause serious adverse events were reported: three in the formoterol arm, and one in the salmeterol arm (Peto OR 2.72, 95% CI 0.38 to 19.46; 548 participants, 2 studies; low-certainty evidence). AUTHORS' CONCLUSIONS: Overall, for both adults and children, evidence is insufficient to show whether regular formoterol in combination with budesonide, beclomethasone, fluticasone, or mometasone has a different safety profile from salmeterol in combination with fluticasone or budesonide. Five deaths of any cause were reported across all studies and no deaths from asthma; this information is insufficient to permit any firm conclusions about the relative risks of mortality on combination formoterol in comparison to combination salmeterol inhalers. Evidence on all-cause non-fatal serious adverse events indicates that there is probably little to no difference between formoterol/budesonide and salmeterol/fluticasone inhalers. However events for the other formoterol combination inhalers were too few to allow conclusions. Only 46 non-fatal serious adverse events were thought to be asthma related; this small number in addition to the absence of independent outcome assessment means that we have very low confidence for this outcome. We found no evidence of safety issues that would affect the choice between salmeterol and formoterol combination inhalers used for regular maintenance therapy by adults and children with asthma.


Assuntos
Antiasmáticos/efeitos adversos , Asma/tratamento farmacológico , Fumarato de Formoterol/administração & dosagem , Glucocorticoides/efeitos adversos , Xinafoato de Salmeterol/administração & dosagem , Administração por Inalação , Adolescente , Adulto , Antiasmáticos/administração & dosagem , Asma/mortalidade , Beclometasona/administração & dosagem , Beclometasona/efeitos adversos , Broncodilatadores/administração & dosagem , Broncodilatadores/efeitos adversos , Budesonida/administração & dosagem , Budesonida/efeitos adversos , Criança , Doença Crônica , Quimioterapia Combinada/efeitos adversos , Fluticasona/administração & dosagem , Fluticasona/efeitos adversos , Fumarato de Formoterol/efeitos adversos , Glucocorticoides/administração & dosagem , Humanos , Furoato de Mometasona/administração & dosagem , Furoato de Mometasona/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Xinafoato de Salmeterol/efeitos adversos
18.
Int J Antimicrob Agents ; 57(5): 106347, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33892107

RESUMO

At the emergency department of the Robert-Debré children's hospital in Paris, France, artenimol/piperaquine (AP) has been the first-line antimalarial treatment since September 2012. Most children receive the first dose at the hospital and return home if, after 1 hour's observation, there have been no episodes of vomiting. Here we report the case of two children, aged 11 years and 5 years, respectively, in whom the entire cumulative 3 days' treatment course combined was accidentally administered instead of just the first-day treatment dose. Serum piperaquine levels were measured between Hour 40 (H40) and Day 29 (D29) post-ingestion for the first patient, and between H17 and D7 for the second patient. Corrected QT (QTc) values were measured between H12 and D20 for the first patient and between H17 and H64 for the second patient. Despite reports of adverse electrophysiological events, AP overdose occurred without consequence on the QTc interval or clinical cardiac state in these two children.


Assuntos
Antimaláricos/efeitos adversos , Artemisininas/efeitos adversos , Overdose de Drogas/diagnóstico , Quinolinas/administração & dosagem , Cardiotoxicidade , Criança , Pré-Escolar , Quimioterapia Combinada/efeitos adversos , Humanos , Malária Falciparum , Paris
19.
Drug Saf ; 44(6): 635-644, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33864232

RESUMO

INTRODUCTION AND OBJECTIVE: Ivermectin (IVM) and doxycycline (DOXY) have demonstrated in-vitro activity against SARS-CoV-2, and have a reasonable safety profile. The objective of this systematic review was to explore the evidence in the literature on the safety and efficacy of their use as monotherapy and combination therapy in COVID-19 management. METHODS: After prospectively registering the study protocol with the Open Science Framework, we searched PubMed, Google Scholar, clinicaltrials.gov, various pre-print servers and reference lists for relevant records published until 16 February, 2021 using appropriate search strategies. Baseline features and data pertaining to efficacy and safety outcomes were extracted separately for IVM monotherapy, DOXY monotherapy, and IVM + DOXY combination therapy. Methodological quality was assessed based on the study design. RESULTS: Out of 200 articles screened, 19 studies (six retrospective cohort studies, seven randomised controlled trials, five non-randomised trials, one case series) with 8754 unique patients with multiple stages of COVID-19 were included; four were pre-prints and one was an unpublished clinicaltrials.gov document. The comparator was standard care and 'hydroxychloroquine + azithromycin' in seven and three studies respectively, and two studies were placebo controlled; six studies did not have a comparator. IVM monotherapy, DOXY monotherapy and IVM + DOXY were explored in eight, five and five studies, respectively; one study compared IVM monotherapy and IVM + DOXY with placebo. While all studies described efficacy, the safety profile was described in only six studies. Efficacy outcomes were mixed with some studies concluding in favour of the intervention and some studies displaying no significant benefit; barring one study that described 9/183 patients with erosive esophagitis and non-ulcer dyspepsia with IVM + DOXY (without causality assessment details), there were no new safety signals of concern with any of the three interventions considered. The quality of studies varied widely, with five studies having a 'good' methodological quality. CONCLUSIONS: Evidence is not sufficiently strong to either promote or refute the efficacy of IVM, DOXY, or their combination in COVID-19 management. SYSTEMATIC REVIEW PROTOCOL REGISTRATION DETAILS: Open Science Framework: https://osf.io/n7r2j .


Assuntos
COVID-19/tratamento farmacológico , Doxiciclina/farmacologia , Ivermectina/farmacologia , SARS-CoV-2/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Humanos , Resultado do Tratamento
20.
J Am Soc Nephrol ; 32(6): 1465-1473, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33766811

RESUMO

BACKGROUND: Hyperphosphatemia is associated with cardiovascular morbidity and mortality in patients receiving maintenance dialysis. It is unknown whether combining two therapies with different mechanisms of action-tenapanor, an inhibitor of paracellular phosphate absorption, and phosphate binders-is safe and effective for the management of hyperphosphatemia in patients receiving maintenance dialysis. METHODS: This double-blind phase 3 trial enrolled 236 patients undergoing maintenance dialysis with hyperphosphatemia (defined in this trial as serum phosphorus 5.5-10 mg/dl inclusive) despite receiving phosphate binder therapy (sevelamer, nonsevelamer, sevelamer plus nonsevelamer, or multiple nonsevelamer binders). These participants were randomly assigned to receive oral tenapanor 30 mg twice daily or placebo for 4 weeks. The primary efficacy end point was the change in serum phosphorus concentration from baseline to week 4. RESULTS: Of the 236 randomized patients, 235 (99.6%) were included in the full analysis set; this included 116 in the tenapanor plus binder group and 119 in the placebo plus binder group. A total of 228 patients (96.6%) completed the 4-week treatment period. In the full analysis set (mean age 54.5 years, 40.9% women), patients treated with tenapanor plus binder achieved a larger mean change in serum phosphorus concentration from baseline to week 4 compared with placebo plus binder (-0.84 versus -0.19 mg/dl, P<0.001). Diarrhea was the most commonly reported adverse event, resulting in study drug discontinuation in four of 119 (3.4%) and two of 116 (1.7%) patients receiving tenapanor plus binder or placebo plus binder, respectively. CONCLUSIONS: A dual-mechanism treatment using both tenapanor and phosphate binders improved control of hyperphosphatemia in patients undergoing maintenance dialysis compared with phosphate binders alone. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: AMPLIFY, NCT03824587.


Assuntos
Quelantes/uso terapêutico , Hiperfosfatemia/tratamento farmacológico , Isoquinolinas/uso terapêutico , Diálise Renal , Sulfonamidas/uso terapêutico , Adulto , Idoso , Quelantes/efeitos adversos , Diarreia/induzido quimicamente , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Hiperfosfatemia/sangue , Isoquinolinas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Fósforo/sangue , Insuficiência Renal Crônica/terapia , Sevelamer/uso terapêutico , Trocador 3 de Sódio-Hidrogênio/antagonistas & inibidores , Sulfonamidas/efeitos adversos
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