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2.
Molecules ; 26(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578679

RESUMO

This study aimed to discover concurrences of adverse drug reactions (ADRs) and derive models of the most frequent items of ADRs based on the SIDER database, which included 1430 marketed drugs and 5868 ADRs. First, common ADRs of organic drugs were manually reclassified according to side effects in the human system and followed by an association rule analysis, which found ADRs of digestive and nervous systems often occurred at the same time with a good association rule. Then, three algorithms, linear discriminant analysis (LDA), support vector machine (SVM) and deep learning, were used to derive models of ADRs of digestive and nervous systems based on 497 organic monomer drugs and to identify key structural features in defining these ADRs. The statistical results indicated that these kinds of QSAR models were good tools for screening ADRs of digestive and nervous systems, which gave the ROC AUC values of 81.5%, 98.9%, 91.5%, 69.5%, 78.4% and 78.8%, respectively. Then, these models were applied to investigate ADRs of 1536 organic compounds with four phase and zero rule-of-five (RO5) violations from the ChEMBL database. Based on the consensus ADRs' predictions of models, 58.1% and 42.6% of compounds were predicted to cause these two ADRs, respectively, indicating the significance of initial assessment of ADRs in early drug discovery.


Assuntos
Algoritmos , Simulação por Computador , Doenças do Sistema Digestório/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Doenças do Sistema Nervoso/induzido quimicamente , Preparações Farmacêuticas/química , Bases de Dados Factuais , Humanos
3.
Psychopharmacology (Berl) ; 238(3): 615-637, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33410989

RESUMO

RATIONALE: Clozapine is the most effective antipsychotic for treatment-refractory schizophrenia for reducing positive psychotic symptoms. It is associated with a reduction in hospitalisation and overall mortality. In spite of this, clozapine remains underutilised due to its complex adverse drug reaction (ADR) profile. OBJECTIVE: This systematic review aims to investigate the association of clozapine and norclozapine serum levels, and peripheral ADRs. METHODS: Studies were searched from four electronic databases (PubMed, EMBASE, PsycINFO and CINAHL) from inception to 12 June 2020. Studies were included if they had adult patients, provided data on steady-state trough clozapine or norclozapine levels and reported on clozapine-associated ADRs. Pregnant women, case reports and series were excluded. RESULTS: A statistically significant correlation was found for clozapine serum levels and triglycerides (n = 70; r = 0.303, 95% CI 0.0119-0.546, p = 0.042), heart rate (n = 137; r = 0.269, 95% CI 0.0918-0.486, p = 0.035), and overall combined ADRs (n = 160; r = 0.264, 95% CI 0.110-0.405, p = 0.001), but not for absolute neutrophil count (n = 223; r = - 0.164, 95% CI - 0.529-0.253, p = 0.444) or total white cell count (n = 18; r = 0.0176, 95% CI - 0.203-0.237, p = 0.878). Interestingly, norclozapine serum levels were found to be statistically correlated to triglycerides (n = 120; r = 0.211, 95% CI 0.0305-0.378, p = 0.022), total cholesterol (n = 120; r = 0.272, 95% CI 0.0948-0.432, p = 0.003) and weight gain (n = 118; r = 0.208, 95% CI 0.0261-0.377, p = 0.025). CONCLUSIONS: Heart rate, triglycerides and combined ADRs are significantly correlated with clozapine levels, and triglycerides, total cholesterol and weight gain with norclozapine levels. Future prospective, randomised controlled studies are needed to identify the cause-effect relationship between clozapine levels and peripheral ADRs.


Assuntos
Antipsicóticos/sangue , Clozapina/análogos & derivados , Clozapina/sangue , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/sangue , Esquizofrenia/tratamento farmacológico , Triglicerídeos/sangue , Adulto , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Clozapina/efeitos adversos , Clozapina/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Gravidez , Esquizofrenia/sangue , Psicologia do Esquizofrênico , Ganho de Peso/efeitos dos fármacos
4.
Ann Hematol ; 100(3): 645-651, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33515047

RESUMO

Management of adult patients with immune thrombocytopenia (ITP) is often unsatisfactory, due to variable efficacy of treatment, risk of life-threatening bleeding if disease control is poor, and side effects associated with treatment. Lack of data on the platelet count threshold associated with bleeding and infection risk associated with ITP treatment limits risk/benefit clinical decision making. We reviewed medical records of all ITP patients who were admitted to our hospital between 2012 and 2017 to evaluate the platelet count threshold for bleeding, infection burden associated with treatment, and real-world efficacy of second-line treatment. We demonstrated fair discrimination between platelet count and occurrence of bleeding, with 15 × 109/L being the optimal cut-off for predicting any bleeding while 20 × 109/L had the highest negative predictive value for severe bleeding. In multivariable analyses, patients who were treated with corticosteroids for at least 2 months were 5.3 times as likely to have an infection. In addition, rituximab response was strongly associated with response to frontline corticosteroids and infection was associated with older age ≥ 65 years and corticosteroid dependence. If corticosteroids are initiated, physicians should aim for the shortest duration of treatment before switching to effective second-line agents for hemostatic platelet counts.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/terapia , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Plaquetas/patologia , Estudos de Coortes , 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/etiologia , Feminino , Seguimentos , Hemorragia/sangue , Hemorragia/diagnóstico , Hemorragia/epidemiologia , Hemorragia/etiologia , Hospitalização/estatística & dados numéricos , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Infecções/epidemiologia , Infecções/etiologia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Púrpura Trombocitopênica Idiopática/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Rituximab/uso terapêutico , Singapura/epidemiologia , Esplenectomia/estatística & dados numéricos , Resultado do Tratamento
6.
Mayo Clin Proc ; 96(1): 242-256, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33413822

RESUMO

Medications to treat disease and extend life in our patients often amass in quantities, resulting in what has been termed "polypharmacy." This imprecise label usually describes the accumulation of 5, and often more, medications. Polypharmacy in advancing age frequently results in drug therapy problems related to interactions, drug toxicity, falls with injury, delirium, and nonadherence. Polypharmacy is associated with resulting increased hospitalizations and higher costs of care for individuals and health care systems. To reduce polypharmacy, we delineate a systematic, consultative approach to identify highest-risk medications and drug-therapy problems. We address strategic reductions (deprescribing) of medications in palliative care, long-term care, and ambulatory older adults. Best practices for reducing opioids, benzodiazepines, and other high-risk medications include education about risk and agreement by patients and their families, advocates, and care teams. Addressing deprescribing should be within the framework of patients' health status as their care and goals transition from longevity to a plan of maintaining alertness, comfort, and satisfaction of quality of life. A team approach to address polypharmacy and avoidance of high-risk therapy is optimal within long-term care. Patients with terminal illnesses or those moving toward a comfort-care emphasis benefit from medication adjustments that are recognized beneficially within each patient's care goals. In caring for older adults, the acknowledgement that complicated regimens and high-risk medications requires a care plan to reduce or prevent medication-related problems and costs that are associated with polypharmacy.


Assuntos
Polimedicação , Idoso , Analgésicos Opioides/efeitos adversos , Antipsicóticos/efeitos adversos , Desprescrições , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Reconciliação de Medicamentos , Instituições de Cuidados Especializados de Enfermagem
7.
Med Clin (Barc) ; 156(6): 277-280, 2021 03 26.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33358536

RESUMO

OBJECTIVE: To characterize health care-related adverse events in patients with SARS-CoV-2 infection who died in a tertiary hospital. METHODS: This is a retrospective, observational study, that included patients who died at HUGTiP hospital between 16 March and 10 April 2020. Data was extracted from the electronic medical record. RESULTS: The median age of the 164 SARS-CoV-2 infected patients who died in the center in the study period was 77.5 years and> 90% of patients had ≥ 1 comorbidity. Forty point two percent of patients had at least ≥ 1 health care-related adverse event. Twenty three point eight of patients had an adverse drug reaction, the leading cause of adverse events in patients who died. Of patients who died in intensive care units, the frequency of problems related to mechanical ventilation was 8.8%. CONCLUSIONS: Although the case fatality rate associated with the adverse events detected was very low, close monitoring of potential health care-related adverse events, especially drug reactions, as the therapeutic management of the disease remains unclear.


Assuntos
Antivirais/efeitos adversos , /terapia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Respiração Artificial/efeitos adversos , Centros de Atenção Terciária , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Terapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Respiração Artificial/mortalidade , Estudos Retrospectivos , Espanha/epidemiologia
8.
Pediatr Blood Cancer ; 68(1): e28714, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32979296

RESUMO

Aerodigestive adverse effects (AD-AE) during intravenous pentamidine (IV-P) infusion for Pneumocystis jiroveci pneumonia prophylaxis are uncommon in retrospective chart review studies. We conducted a survey in patients on IV-P, which included 31 specific questions. Twenty-five patients were included in the analysis; AD-AE were observed in 22 (88%) with recurrence of symptoms in 88% participants with subsequent infusions. Five leading symptoms were congestion (48%), lip tingling (32%), nausea (28%), tongue tingling (24%), vomiting, and throat swelling (17%); multiple symptoms were reported in 72% of the patients. In conclusion, AD-AE of IV-P infusion are common, self-limited, and tend to be recurrent.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Leucemia/terapia , Pentamidina/efeitos adversos , Pneumocystis carinii/efeitos dos fármacos , Pneumonia por Pneumocystis/tratamento farmacológico , Trato Gastrointestinal Superior/patologia , Adolescente , Adulto , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Terapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Infusões Intravenosas , Leucemia/patologia , Masculino , Michigan/epidemiologia , Pentamidina/administração & dosagem , Pneumonia por Pneumocystis/etiologia , Pneumonia por Pneumocystis/patologia , Prognóstico , Autorrelato , Inquéritos e Questionários , Trato Gastrointestinal Superior/efeitos dos fármacos , Adulto Jovem
9.
J Mol Cell Cardiol ; 153: 106-110, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33373642

RESUMO

The coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic as declared by World Health Organization (WHO). In the absence of an effective treatment, different drugs with unknown effectiveness, including antimalarial hydroxychloroquine (HCQ), with or without concurrent administration with azithromycin (AZM), have been tested for treating COVID-19 patients with developed pneumonia. However, the efficacy and safety of HCQ and/or AZM have been questioned by recent clinical reports. Direct effects of these drugs on the human heart remain very poorly defined. To better understand the mechanisms of action of HCQ +/- AZM, we employed bioengineered human ventricular cardiac tissue strip (hvCTS) and anisotropic sheet (hvCAS) assays, made with human pluripotent stem cell (hPSC)-derived ventricular cardiomyocytes (hvCMs), which have been designed for measuring cardiac contractility and electrophysiology, respectively. Our hvCTS experiments showed that AZM induced a dose-dependent negative inotropic effect which could be aggravated by HCQ; electrophysiologically, as revealed by the hvCAS platform, AZM prolonged action potentials and induced spiral wave formations. Collectively, our data were consistent with reported clinical risks of HCQ and AZM on QTc prolongation/ventricular arrhythmias and development of heart failure. In conclusion, our study exposed the risks of HCQ/AZM administration while providing mechanistic insights for their toxicity. Our bioengineered human cardiac tissue constructs therefore provide a useful platform for screening cardiac safety and efficacy when developing therapeutics against COVID-19.


Assuntos
Arritmias Cardíacas/patologia , Azitromicina/efeitos adversos , Cloroquina/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Contração Miocárdica , Miócitos Cardíacos/patologia , Função Ventricular/efeitos dos fármacos , Antibacterianos/efeitos adversos , Antimaláricos/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Células-Tronco Pluripotentes/efeitos dos fármacos , Células-Tronco Pluripotentes/patologia , Engenharia Tecidual/métodos
10.
Biomed Pharmacother ; 133: 111047, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378954

RESUMO

Traditional Chinese medicines (TCMs) are medicines that are widely used in oriental countries under the guidance of ancient Chinese medicinal philosophies. With thousands of years of experiences in fighting against diseases, TCMs are gaining increasing importance in the world. Although the efficacy of TCMs is well recognized in clinic, the toxicity of TCMs has become a serious issue around the world in recent years. In general, the toxicity of TCMs is caused by the toxic medicinal compounds and contaminants in TCMs such as pesticides, herbicides, and heavy metals. Recent studies have demonstrated that gut microbiota can interact with TCMs and thus influence the toxicity of TCMs. However, there is no focused review on gut microbiota and the toxicity of TCMs. Here, we summarized the influences of the gut microbiota on the toxicity of medicinal compounds in TCMs and the corresponding mechanisms were offered. Then, we discussed the relationships between gut microbiota and the TCM contaminants. In addition, we discussed the methods of manipulating gut microbiota to reduce the toxicity of TCMs. At the end of this review, the perspectives on gut microbiota and the toxicity of TCMs were also discussed.


Assuntos
Bactérias/metabolismo , Contaminação de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Medicamentos de Ervas Chinesas/efeitos adversos , Microbioma Gastrointestinal , Intestinos/microbiologia , Medicina Tradicional Chinesa/efeitos adversos , Bactérias/imunologia , Biotransformação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/microbiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Medicamentos de Ervas Chinesas/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Humanos , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Fatores de Risco
11.
PLoS One ; 15(12): e0240276, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33338057

RESUMO

INTRODUCTION: Biological drugs open new possibilities to treat diseases for which drug therapy is limited, but they may be associated with adverse drug reactions (ADRs). OBJECTIVE: To identify the ADRs associated with the use of biological drugs in Colombia. METHODS: This was a retrospective study of ADR reports from 2014 to 2019, contained in the database of Audifarma SA pharmacovigilance program. The ADRs, groups of associated drugs, and affected organs were classified. RESULTS: In total, 5,415 reports of ADRs associated with biological drugs were identified in 78 Colombian cities. A total of 76.1% of the cases corresponded to women. The majority were classified as type A (55.0%) and B (28.9%), and 16.7% were serious cases. The respiratory tract was the most affected organ system (16.8%), followed by the skin and appendages (15.6%). Antineoplastic and immunomodulatory drugs accounted for 70.6% of the reports, and the drugs related to the greatest number of ADRs were adalimumab (12.2%) and etanercept (11.6%). CONCLUSIONS: The reporting of ADRs has increased in recent years and these reactions are mostly classified as tyoe A or B, categorized as serious in almost one-fifth of the reported cases and associated mainly with immunomodulators and antineoplastic agents. This type of study can support decision makers in ways that benefit patient safety and interaction with health systems.


Assuntos
Antineoplásicos/efeitos adversos , Produtos Biológicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Fatores Imunológicos/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Colômbia/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Humanos , Incidência , Masculino , Segurança do Paciente , Farmacovigilância , Doenças Respiratórias/induzido quimicamente , Doenças Respiratórias/epidemiologia , Estudos Retrospectivos , Dermatopatias/induzido quimicamente , Dermatopatias/epidemiologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-33317796

RESUMO

Treatment-related acute gastrointestinal toxicities are a common and often debilitating hurdle encountered in the treatment of cancer patients. While the introduction of targeted therapies such as tyrosine kinase inhibitors has led to improvements in survival outcomes, their use has also been complicated by a high frequency of clinically important adverse effects. Gastrointestinal toxicities such as nausea, vomiting, diarrhoea and hepatotoxicity represent potentially serious adverse events that may necessitate dose reductions, treatment interruptions and cessation of treatment. An improved knowledge of the incidence, pathophysiology, management and prophylaxis of these toxicities is crucial in order to reduce patient morbidity and mortality. In this review, we discuss the main gastrointestinal toxicities associated with chemotherapy and targeted therapies in oncology, outlining their incidence, pathophysiology and expert management guidelines.


Assuntos
Antineoplásicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Gastroenteropatias/induzido quimicamente , Neoplasias/complicações , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Gastroenteropatias/terapia , Humanos , Fatores de Risco
14.
Anticancer Res ; 40(9): 5245-5254, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878813

RESUMO

BACKGROUND/AIM: To determine whether BMI and sarcopenia were related to treatment-limiting toxicity or efficacy of pembrolizumab treatment in melanoma patients. PATIENTS AND METHODS: Medical records for melanoma patients undergoing pembrolizumab treatment at Duke University from January 2014 to September 2018 were reviewed. Pre-treatment measurements such as BMI were collected. Pre-treatment CT imaging was used to determine psoas muscle index (PMI). Patients in the lowest sex-specific tertile of PMI were sarcopenic. Logistic regression measured associations with treatment toxicity and response. Kaplan-Meier analysis assessed progression-free survival (PFS) and overall survival (OS). RESULTS: Among 156 patients, the overall objective response rate was 46.2% and 29 patients (18.6%) experienced treatment-limiting toxicity. Sarcopenia was not significantly associated with toxicity, response, or survival. However, obese patients (BMI >30) experienced higher rates of toxicity (p=0.0007). CONCLUSION: Sarcopenia did not appear to predict clinically relevant outcomes. Obesity, however, represents a readily available predictor of pembrolizumab toxicity.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Índice de Massa Corporal , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Melanoma/complicações , Melanoma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Melanoma/diagnóstico , Melanoma/etiologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Prognóstico , Sarcopenia/complicações , Tomografia Computadorizada por Raios X , Adulto Jovem
15.
PLoS One ; 15(9): e0238285, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32925928

RESUMO

BACKGROUND: Chronic and high dose opioid use may result in adverse events. We analyzed the risk associated with chronic and high dose opioid prescription in a Swiss population. METHODS: Using insurance claims data covering one-sixth of the Swiss population, we analyzed recurrent opioid prescriptions (≥2 opioid claims with at least 1 strong opioid claim) between 2006 and 2014. We calculated the cumulative dose in milligrams morphine equivalents (MED) and treatment duration. Excluded were single opioid claims, opioid use that was cancer treatment related, and opioid use in substitution programs. We assessed the association between the duration of opioid use, prescribed opioid dose, and benzodiazepine use with emergency department (ED) visits, urogenital and pulmonary infections, acute care hospitalization, and death at the end of the episode. RESULTS: In 63,642 recurrent opioid prescription episodes (acute 38%, subacute 7%, chronic 25.8%, very chronic (>360 days) episodes 29%) 18,336 ED visits, 30,209 infections, 19,375 hospitalizations, and 9,662 deaths occurred. The maximum daily MED dose was <20 mg in 15.8%, 20-<50 mg in 16.6%, 50-<100 mg in 21.6%, and ≥100 mg in 46%. Compared to acute episodes (<90 days), episode duration was an independent predictor of ED visits (chronic OR 1.09 (95% CI 1.03-1.15), very chronic (>360 days) OR 1.76 (1.67-1.86)) for adverse effects; infections (chronic OR 1.74 (1.66-1.82), very chronic 4.16 (3.95-4.37)), and hospitalization (chronic: OR 1.22 (1.16-1.29), very chronic OR 1.82 (1.73-1.93)). The risk of death decreased over time (very chronic OR 0.46 (0.43-0.50)). A dose dependent increased risk was observed for ED visits, hospitalization, and death (≥100mg daily MED OR 1.21 (1.13-1.29), OR 1.29 (1.21-1.38), and OR 1.67, 1.50-1.85, respectively). A concomitant use of benzodiazepines increased the odds for ED visits by 46% (OR 1.46, 1.41-1.52), infections by 44% (OR 1.44, 1.41-1.52), hospitalization by 12% (OR 1.12, 1.07-1.1), and death by 45% (OR 1.45, 1.37-1.53). CONCLUSION: The length of opioid use and higher prescribed morphine equivalent dose were independently associated with an increased risk for ED visits and hospitalizations. The risk for infections, ED visits, hospitalizations, and death also increased with concomitant benzodiazepine use.


Assuntos
Analgésicos Opioides/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Hospitalização/estatística & dados numéricos , Revisão da Utilização de Seguros/estatística & dados numéricos , Transtornos Relacionados ao Uso de Opioides/etiologia , Idoso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Masculino , Transtornos Relacionados ao Uso de Opioides/patologia , Prognóstico , Fatores de Risco
16.
Curr Opin Ophthalmol ; 31(5): 403-415, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32740062

RESUMO

PURPOSE OF REVIEW: To compile and report the ocular manifestations of coronavirus disease 2019 (COVID-19) infection and summarize the ocular side effects of investigational treatments of this disease. RECENT FINDINGS: Conjunctivitis is by far the most common ocular manifestation of COVID-19 with viral particles being isolated from tears/secretions of infected individuals. Multiple therapeutic options are being explored across a variety of medication classes with diverse ocular side effects. SUMMARY: Eye care professionals must exercise caution, as conjunctivitis may be the presenting or sole finding of an active COVID-19 infection. While no currently studied therapeutic agents have been found to reliably treat COVID-19, early vaccination trials are progressing and show promise. A video abstract is available for a more detailed summary. VIDEO ABSTRACT: http://links.lww.com/COOP/A36.


Assuntos
Betacoronavirus/isolamento & purificação , Conjuntivite Viral/diagnóstico , Infecções por Coronavirus/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Drogas em Investigação/efeitos adversos , Oftalmopatias/induzido quimicamente , Pneumonia Viral/diagnóstico , Lágrimas/virologia , Conjuntivite Viral/tratamento farmacológico , Conjuntivite Viral/virologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Oftalmopatias/prevenção & controle , Humanos , Pandemias
17.
PLoS One ; 15(8): e0237781, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857798

RESUMO

BACKGROUND: Drug therapy problems (DTPs) are major concerns of healthcare and have been identified to contribute to negative clinical outcomes. The occurrence of DTPs in heart failure patients is associated with worsening of outcomes. The aim of this study was to assess DTPs, associated factors and patient satisfaction among ambulatory heart failure patients at Tikur Anbessa Specialized Hospital (TASH). METHODS: A hospital based prospective cross-sectional study was conducted on 423 heart failure patients on follow up at TASH. Data was collected through patient interview and chart review. Descriptive statistics, binary and multiple logistic regressions were used for analyses and P < 0.05 was used to declare association. RESULTS: Majority of the patients were in NYHA class III (55.6%) and 66% of them had preserved systolic function. DTPs were identified in 291(68.8%) patients, with an average number of 2.51±1.07.per patient. The most common DTPs were drug interaction (27.3%) followed by noncompliance (26.2%), and ineffective drug use (13.7%). ß blockers were the most frequent drug class involved in DTPs followed by angiotensin converting enzyme inhibitors. The global satisfaction was 78% and the overall mean score of treatment satisfaction was 60.5% (SD, 10.5). CONCLUSION: Prevalence of DTPs as well as non-adherence among heart failure patients on follow up is relatively high. Detection and prevention of DTPs along with identifying patients at risk can save lives, help to adopt efficient strategies to closely monitor patients at risk, enhance patient's quality of life and optimize healthcare costs.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Insuficiência Cardíaca/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Adolescente , Antagonistas Adrenérgicos beta/farmacocinética , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Enzima Conversora de Angiotensina/farmacocinética , Estudos Transversais , Interações Medicamentosas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/psicologia , Etiópia/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Adesão à Medicação/psicologia , Pessoa de Meia-Idade , Ambulatório Hospitalar/estatística & dados numéricos , Prevalência , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários/estatística & dados numéricos , Centros de Atenção Terciária/estatística & dados numéricos , Adulto Jovem
19.
Iran J Kidney Dis ; 14(4): 247-255, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32655019

RESUMO

Treatment of coronavirus disease 2019 (COVID-19) among patients with CKD requires special pharmacotherapy considerations that are reviewed here. Literature review was done for several pharmacotherapy aspects in CKD patients including selection and modification of COVID-19 treatment, drug interactions, nephrotoxicity of drugs that are used for treatment of COVID-19 and potential risks/benefits of routine medications of CKD patients during COVID-19 pandemic. CKD patients should be treated according to local or national COVID-19 protocols as other patients. But, there is no data on using remdesivir in patients with severe CKD. Oseltamivir and ribavirin require dose modification in patients with moderate to severe CKD. Nephrolithiasis, CKD, and acute interstitial nephritis have been reported with protease inhibitors. Acute kidney injury has been reported with remdesivir in patients with severe COVID-19. Pharmacokinetic-enhanced protease inhibitors increase the concentration of some drugs such as statins, cinacalcet, steroids, calcineurin inhibitors (CNIs). Some hypothetical benefits and harms have been suggested for statins and renin-angiotensinaldosterone system inhibitors in COVID-19 patients. Continuing guideline-directed administration of these drugs is recommended. Among different immunomodulating/immunosuppressive drugs, hydroxychloroquine and CNIs are the safest ones during COVID-19. Antimetabolites are suggested to be withheld during moderate to severe COVID-19. Fluid therapy and anticoagulant prophylaxis/ treatment need special attention in CKD patients with COVID-19. CKD patients with COVID-19 are treated as other patients, with some dose modifications if needed. Be mindful for management of drug interactions as well as modification of immunosuppressive drugs in patients with moderate to severe COVID-19.


Assuntos
Infecções por Coronavirus , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Pandemias , Pneumonia Viral , Insuficiência Renal Crônica , Betacoronavirus/isolamento & purificação , Comorbidade , Infecções por Coronavirus/classificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Seleção de Pacientes , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Medição de Risco
20.
Tumour Biol ; 42(7): 1010428320938494, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32628088

RESUMO

Radiotherapy and cisplatin lead to cell killing in head and neck squamous cell carcinoma patients, but adverse events and response to treatment are not the same in patients with similar clinicopathological aspects. The aim of this prospective study was to evaluate the roles of TP53 c.215G > C, FAS c.-671A > G, FAS c.-1378G > A, FASL c.-844 C > T, CASP3 c.-1191A > G, and CASP3 c.-182-247G > T single nucleotide variants in toxicity, response rate, and survival of cisplatin chemoradiation-treated head and neck squamous cell carcinoma patients. Genomic DNA was analyzed by polymerase chain reaction for genotyping. Differences between groups of patients were analyzed by chi-square test or Fisher's exact test, multiple logistic regression analysis, and Cox hazards model. One hundred nine patients with head and neck squamous cell carcinoma were enrolled in study. All patients were smokers and/or alcoholics. Patients with FAS c.-671GG genotype, FAS c.-671AG or GG genotype, and FASL c.-844CC genotype had 5.52 (95% confidence interval (CI): 1.42-21.43), 4.03 (95% CI: 1.51-10.79), and 5.77 (95% CI: 1.23-27.04) more chances of presenting chemoradiation-related anemia of grades 2-4, lymphopenia of grade 3 or 4, and ototoxicity of all grades, respectively, than those with the remaining genotypes. FAS c.-671GG genotype was also seen as an independent predictor of shorter event-free survival (hazard ratio (HR): 2.05; P = 0.007) and overall survival (HR: 1.83; P = 0.02) in our head and neck squamous cell carcinoma patients. These findings present, for the first time, preliminary evidence that inherited abnormalities in apoptosis pathway, related to FAS c.-671A > G and FASL c.-844 C > T single nucleotide variants, can alter toxicity and survival of tobacco- and alcohol-related head and neck squamous cell carcinoma patients homogeneously treated with cisplatin chemoradiation.


Assuntos
Proteína Ligante Fas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Receptor fas/genética , Adulto , Idoso , Álcoois/efeitos adversos , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/induzido quimicamente , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Tabaco/efeitos adversos , Proteína Supressora de Tumor p53/genética
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