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1.
Emerg Infect Dis ; 27(4): 1220-1222, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33522478

RESUMO

Coronavirus disease (COVID-19) symptoms can be mistaken for vaccine-related side effects during initial days after immunization. Among 4,081 vaccinated healthcare workers in Israel, 22 (0.54%) developed COVID-19 from 1-10 days (median 3.5 days) after immunization. Clinicians should not dismiss postvaccination symptoms as vaccine-related and should promptly test for COVID-19.


Assuntos
/efeitos adversos , Pessoal de Saúde/estatística & dados numéricos , Vacinação , Adulto , Rotas de Resultados Adversos , /epidemiologia , /métodos , /administração & dosagem , Diagnóstico Diferencial , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Feminino , Humanos , Israel/epidemiologia , Masculino , Vacinação/efeitos adversos , Vacinação/métodos , Vacinação/estatística & dados numéricos
2.
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
3.
BMJ ; 372: m4931, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514507

RESUMO

OBJECTIVE: To evaluate the association between human papillomavirus (HPV) vaccination and serious adverse events in adolescent girls in South Korea. DESIGN: Cohort study. SETTING: A large linked database created by linking the Korea Immunization Registry Information System and the National Health Information Database, between January 2017 and December 2019. PARTICIPANTS: 441 399 girls aged 11-14 years who had been vaccinated in 2017: 382 020 had been vaccinated against HPV and 59 379 had not been vaccinated against HPV. MAIN OUTCOME MEASURES: Outcomes were 33 serious adverse events, including endocrine, gastrointestinal, cardiovascular, musculoskeletal, haematological, dermatological, and neurological diseases. A cohort design was used for the primary analysis and a self-controlled risk interval design for the secondary analysis; both analyses used a risk period of one year after HPV vaccination for each outcome. Incidence rate and adjusted rate ratios were estimated using Poisson regression in the primary analysis, comparing the HPV vaccinated group with the HPV unvaccinated group, and adjusted relative risks were estimated using conditional logistic regression in the secondary analysis. RESULTS: Among the 33 predefined serious adverse events, no associations were found with HPV vaccination in the cohort analysis, including Hashimoto's thyroiditis (incidence rate per 100 000 person years: 52.7 v 36.3 for the vaccinated and unvaccinated groups; adjusted rate ratio 1.24, 95% confidence interval 0.78 to 1.94) and rheumatoid arthritis (incidence rate per 100 000 person years: 168.1 v 145.4 for the vaccinated and unvaccinated groups; 0.99, 0.79 to 1.25), with the exception of an increased risk observed for migraine (incidence rate per 100 000 person years: 1235.0 v 920.9 for the vaccinated and unvaccinated groups; 1.11, 1.02 to 1.22). Secondary analysis using self-controlled risk intervals confirmed no associations between HPV vaccination and serious adverse events, including migraine (adjusted relative risk 0.67, 95% confidence interval 0.58 to 0.78). Results were robust to varying follow-up periods and for vaccine subtypes. CONCLUSIONS: In this nationwide cohort study, with more than 500 000 doses of HPV vaccines, no evidence was found to support an association between HPV vaccination and serious adverse events using both cohort analysis and self-controlled risk interval analysis. Inconsistent findings for migraine should be interpreted with caution considering its pathophysiology and the population of interest.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Vacinas contra Papillomavirus/efeitos adversos , Adolescente , Criança , Estudos de Coortes , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Feminino , Humanos , Infecções por Papillomavirus/prevenção & controle , Sistema de Registros , República da Coreia/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle
4.
Drug Saf ; 44(1): 95-105, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33354753

RESUMO

INTRODUCTION: Evidence-based clinical data on coronavirus disease 2019 (COVID-19) pharmacotherapies are scarce. OBJECTIVE: This study documented and characterized COVID-19 cases reported in individuals receiving treatment with Pfizer pharmaceutical products and cases that reported use of Pfizer pharmaceutical products for COVID-19 treatment. METHODS: This retrospective observational review leveraged the Pfizer safety database containing adverse event data collected in association with use of Pfizer products between 1 October, 2019, and 25 June, 2020; the database includes worldwide adverse event data from various sources. Selected Medical Dictionary for Drug Regulatory Activities (MedDRA®) Preferred Terms and subsequent clinical review were used to characterize COVID-19 cases. RESULTS: Over 1500 relevant cases were identified over an 8-month period. In cases that reported COVID-19, immunosuppressant/immunomodulating agents, followed by anticoagulant/antithrombic agents and corticosteroids, were the most frequently reported agents. The frequent reporting of immunosuppressant/immunomodulating agents among cases of COVID-19 suggests increased vulnerability to infection among treated patients, either because of immunosuppressive effects of certain agents or the nature of the underlying treated condition. In cases involving off-label pharmacotherapy use for the treatment of COVID-19-related conditions, the most frequently reported therapeutic classes included antibiotics, antimalarial agents, antivirals/antiretroviral agents, immunosuppressant/immunomodulating agents, corticosteroids, anticoagulants, and immunoglobulin/interferons. The most frequently reported pharmacotherapeutic agents were azithromycin and chloroquine/hydroxychloroquine, followed by lopinavir-ritonavir, ceftriaxone, and tofacitinib. The most frequently reported clinical adverse events associated with azithromycin (as sole therapy or combined with chloroquine/hydroxychloroquine) include electrocardiogram QT prolonged, drug interaction, hepatitis, diarrhea, and hepatitis acute. Regarding cardiac-related events, 19% (120/645) of azithromycin cases reported events associated with QT prolongation/torsade de pointes (which included seven fatal cardiac events). The most frequently reported clinical adverse events associated with other commonly used agents are also presented. CONCLUSIONS: This pharmacovigilance surveillance study provides a unique characterization of cases in which a broad range of pharmaceutical products was reported in relation to COVID-19.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/tendências , Indústria Farmacêutica/tendências , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Saúde Global/tendências , Farmacovigilância , Sistemas de Notificação de Reações Adversas a Medicamentos/normas , Anticoagulantes/efeitos adversos , Antimaláricos/efeitos adversos , Antivirais/efeitos adversos , Bases de Dados Factuais/normas , Bases de Dados Factuais/tendências , Indústria Farmacêutica/normas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Saúde Global/normas , Humanos , Imunossupressores/efeitos adversos , Estudos Retrospectivos
5.
Trials ; 21(1): 1028, 2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33353566

RESUMO

BACKGROUND: Randomised controlled trials (RCTs) provide valuable information and inform the development of harm profiles of new treatments. Harms are typically assessed through the collection of adverse events (AEs). Despite AEs being routine outcomes collected in trials, analysis and reporting of AEs in journal articles are continually shown to be suboptimal. One key challenge is the large volume of AEs, which can make evaluation and communication problematic. Prominent practice is to report frequency tables of AEs by arm. Visual displays offer an effective solution to assess and communicate complex information; however, they are rarely used and there is a lack of practical guidance on what and how to visually display complex AE data. METHODS: In this article, we demonstrate the use of two plots identified to be beneficial for wide use in RCTs, since both can display multiple AEs and are suitable to display point estimates for binary, count, or time-to-event AE data: the volcano and dot plots. We compare and contrast the use of data visualisations against traditional frequency table reporting, using published AE information in two placebo-controlled trials, of remdesivir for COVID-19 and GDNF for Parkinson disease. We introduce statistical programmes for implementation in Stata. RESULTS/CASE STUDY: Visualisations of AEs in the COVID-19 trial communicated a risk profile for remdesivir which differed from the main message in the published authors' conclusion. In the Parkinson's disease trial of GDNF, the visualisation provided immediate communication of harm signals, which had otherwise been contained within lengthy descriptive text and tables. Asymmetry in the volcano plot helped flag extreme events that were less obvious from review of the frequency table and dot plot. The dot plot allowed a more comprehensive representation by means of a more detailed summary. CONCLUSIONS: Visualisations can better support investigators to assimilate large volumes of data and enable improved informal between-arm comparisons compared to tables. We endorse increased uptake for use in trial publications. Care in construction of visual displays needs to be taken as there can be potential to overemphasise treatment effects in some circumstances.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Apresentação de Dados , Visualização de Dados , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Fator Neurotrófico Derivado de Linhagem de Célula Glial/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Projetos de Pesquisa/normas , Monofosfato de Adenosina/efeitos adversos , Alanina/efeitos adversos , Antiparkinsonianos/efeitos adversos , Antivirais/efeitos adversos , Gráficos por Computador , Confiabilidade dos Dados , Análise de Dados , Monitoramento de Medicamentos/métodos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Medicine (Baltimore) ; 99(52): e23861, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33350780

RESUMO

ABSTRACT: We examined whether the age of patients with rheumatoid arthritis was associated with adverse events (AEs) caused by biologic disease-modifying antirheumatic drugs (bDMARDs).Patients with rheumatoid arthritis using bDMARDs from Showa University Hospital, Showa University Northern Yokohama Hospital, and Showa University Koto Toyosu Hospital from January 2005 to December 2017 were eligible for this retrospective cohort study. The maximum observation period was determined to be 1 year. Outcomes in patients older and younger than 75 years were compared. The primary outcome was the rate of drug discontinuation because of AEs caused by bDMARDs. Univariate and multivariate analyses were performed using Pearson's chi-squared test and logistic regression analysis, respectively.A total of 416 patients were enrolled; median (interquartile range [IQR]): 60.0 (44.3 - 71.0) years and 84.6% women; patients ≥ 75 years were 67/416 (16.1%). The rates of drug discontinuation because of AEs caused by bDMARDs were 10.5% (7/67) in patients 75 years and older and 10.9% (38/349) in those younger than 75 years (relative risk 0.95, 95% confidential interval 0.45-2.24). In logistic regression analysis adjusted for covariates, the rate of drug discontinuation showed no significant difference between the patients ≥ 75 years and the those < 75 years (adjusted odds ratio 0.70, 95% confidential interval 0.29-1.75, P = .45).The rate of drug discontinuation because of AEs caused by bDMARDs was not significantly different between patients 75 years and older and patients younger than 75 years.


Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide , Produtos Biológicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Suspensão de Tratamento/estatística & dados numéricos , Fatores Etários , Idoso , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Produtos Biológicos/administração & dosagem , Estudos de Coortes , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Estudos Retrospectivos , Medição de Risco
7.
Lancet Oncol ; 21(10): e463-e476, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002442

RESUMO

Immunotherapy represents a paradigm shift in oncology treatment. The goal of immunotherapy is to overcome immunosuppression induced by a tumour and its microenvironment, thereby allowing the immune system to target and kill cancer cells. The immunotherapy era began when the first immune checkpoint inhibitor, ipilimumab, was approved for use almost a decade ago. This therapeutic approach is associated with distinct types of response, including processes such as pseudoprogression (ie, increased tumour burden via radiology, which is not accompanied by clinical deterioration) and hyperprogression (ie, rapid progression of the disease as a result of immunotherapy). In this Review, we focus on therapeutic approaches for patients who progress on immunotherapy. We review the different types of clinical responses associated with immunotherapy and describe treatment options for this population.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Imunoterapia/efeitos adversos , Neoplasias/terapia , Algoritmos , Antineoplásicos Imunológicos/efeitos adversos , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Humanos , Critérios de Avaliação de Resposta em Tumores Sólidos , Terapia de Salvação
10.
BMC Geriatr ; 20(1): 346, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32928134

RESUMO

BACKGROUND: Drug-induced liver injury (DILI) represents an increasing morbidity in the general population, but more so in the elderly cohort of patients. Despite this, the concept of its prevention through prospective analysis has largely remained unexamined. We evaluated the utility of recently validated adverse drug reactions (ADR) avoidability tool in a cohort of elderly patients with DILI. METHODS: We examined 38 DILI-drug pairs from n=38 patients in a prospective cohort of patients presenting with adverse drug reactions to a Weill Cornell-affiliated tertiary hospital between February 2019 and January 2020. DILI outcomes were adjudicated by the updated Roussel Uclaf Causality Assessment Method (RUCAM). Two clinical pharmacologists and two general physicians utilized the Liverpool adverse drug reactions avoidability tool (LAAT) and the modified Hallas tools to rate the preventability of DILI-drug pairs. Inter-rater, exact agreement proportions, as well as intraclass correlation coefficients were generated and expressed as ordinal outcomes. RESULTS: The cases examined for the determination of DILI avoidability had probability likelihood of "probable" or "highly probable" by the updated RUCAM scale. Examination of the 38 DILI-drug pairs (n= 38 patients) resulted in a total of 152 ordinal outcome decisions. We found about 32.3% (50/152) and 34.2% (52/152) of DILI-drug pairs were rated as "avoidable" ("probable" or "definite") by the LAAT and the modified Hallas tools respectively. The overall median Krippendorf's kappa with the LAAT was 0.61 (SE 0.12, CI 0.36, 0.85) and for modified Hallas tool was 0.53 (SE 0.18; CI 0.16, 0.89). The inter-rater correlation coefficient (ICC) for the LAAT and modified Hallas were 0.50 [0.32, 0.65] and 0.63 [0.48, 0.76] respectively. Exact pairwise agreement was present in 30/38 (IQR 29.5, 34.5), and 28/38 (IQR 27.5-35.5) of DILI-ADR pairs using the LAAT and modified Hallas tools respectively. CONCLUSION: We found a significant proportion of drug-induced liver injury adjudicated by the updated RUCAM scale in elderly hospitalized cohort of patients were avoidable with significant implication for therapeutic commissioning as well as cost effectiveness interventions in this cohort of patients.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Clínicos Gerais , Fígado/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Feminino , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
Neurology ; 95(3): e239-e246, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32601123

RESUMO

OBJECTIVE: To determine whether systematic screening for adverse effects of antiepileptic drugs (AEDs) reduces toxicity burden and improves health-related quality of life in patients with epilepsy. METHODS: Consecutive patients with uncontrolled seizures aged ≥16 years and a high Adverse Event Profile (AEP) score were randomized to 2 groups and followed up for 18 months at 11 referral centers. AEP scores were made available to treating physicians at all visits in the intervention group, but not in the control group. Co-primary endpoints were changes in AEP scores and Quality of Life Inventory for Epilepsy-31 (QOLIE-31) scores. RESULTS: Of 809 enrolled patients able to complete the AEP questionnaire, 222 had AEP scores ≥45 and were randomized to the intervention (n = 111) or control group (n = 111). A total of 206 patients completed the 18-month follow-up. Compared with baseline, AEP scores decreased on average by 7.2% at 6 months, 12.1% at 12 months, and 13.8% at 18 months in the intervention group (p < 0.0001), and by 7.7% at 6 months, 9.2% at 12 months, and 12.0% at 18 months in controls (p < 0.0001). QOLIE-31 scores also improved from baseline to final visit, with a mean 20.7% increase in the intervention group and a mean 24.9% increase in the control group (p < 0.0001). However, there were no statistically significant differences in outcomes between groups for the 2 co-primary variables. CONCLUSIONS: Contrary to findings from a previous study, systematic screening for adverse effects of AEDs using AEP scores did not lead to a reduced burden of toxicity over usual physician treatment. ITALIAN MEDICINES AGENCY AIFA IDENTIFIER: FARM52K2WM_003. CLINICALTRIALSGOV IDENTIFIER: NCT03939507 (registered retrospectively in 2019; the study was conducted during the 2006-2009 period and registration of clinical trials was not a widely established practice when this study was initiated). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the additional collection of formal questionnaires regarding adverse effects of AEDs does not reduce toxicity burden over usual physician treatment.


Assuntos
Anticonvulsivantes/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Epilepsia/tratamento farmacológico , Programas de Rastreamento/métodos , Adolescente , Adulto , Idoso , Epilepsia/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Programas de Rastreamento/tendências , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
16.
Int. j. psychol. psychol. ther. (Ed. impr.) ; 20(2): 211-222, jun. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-196866

RESUMO

No disponible


The use of psychedelic drugs for the treatment of some mental disorders is increasing. However, their use is associated to certain risks, being the most important the exacerbation of mental disorders, mainly psychosis or bipolar disorder. While both 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin are on the Phase-III of the process of drug commercialization, there are not enough screening strategies in order to ensure the safety of patients who will receive those treatments. This article presents the development and validation of a test that assesses the risk of developing psychotic or bipolar disorders using two samples of 156 and 510 participants. The Graded Response Model from Item Response Theory was used. The final version of the test, composed by 30 items, shows very satisfactory psychometric indices, allowing its use as a screening tool in experimental or clinical settings


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Alucinógenos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , 3,4-Metilenodioxianfetamina/efeitos adversos , Psilocibina/efeitos adversos , Processos Psicoterapêuticos , Transtornos Mentais/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Fatores de Risco , Psicoterapia/métodos
17.
Aliment Pharmacol Ther ; 51(11): 1130-1138, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32383253

RESUMO

BACKGROUND: Medications can affect gastrointestinal tract motility. However, their effects on oesophageal motility in particular are often not as widely known or may be underestimated. AIM: To review the effect of existing medication use on high-resolution oesophageal manometry (HRM) in a 'real-world' setting. METHODS: Adult patients with upper gut symptoms and normal endoscopy or imaging who had HRM over a 22-month period were analysed. Achalasia and major disorders of peristalsis were excluded. All medications taken within 24 hours of the procedure were prospectively recorded and compared with HRM results, controlling for age, gender and proton pump inhibitor use. RESULTS: A total of 502 patients (323 female, mean age 51) were recruited. Of these, 41.2% had normal oesophageal HRM, while 41.4% had ineffective oesophageal motility (IOM) and 7.6% had oesophagogastric junction outflow obstruction (OGJOO). Serotonin/norepinephrine reuptake inhibitors (SNRI) and opioids were associated with significantly higher resting lower oesophageal sphincter pressure. Benzodiazepines and opioids were associated with elevated integrated relaxation pressure. SNRI and inhaled beta-agonists were associated with increased distal contractile index, whereas calcium channel blockers were associated with a lower distal contractile index. Odds ratio of being on anticholinergics was higher in IOM patients vs normal (3.6, CI 1.2-10.8). Odds ratio for anticholinergics, inhaled beta-agonists, anticonvulsants, SNRIs and opioids (trend) were all > 3 for OGJOO patients vs normal. CONCLUSION: Many medication classes are associated with abnormal HRM variables and diagnoses such as OGJOO and IOM; some of these associations are probably causal. These possible links should be taken into consideration during manometry interpretation.


Assuntos
Antidepressivos/efeitos adversos , Antagonistas Colinérgicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Doenças do Esôfago/induzido quimicamente , Doenças do Esôfago/epidemiologia , Adulto , Idoso , Estudos de Coortes , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Acalasia Esofágica/induzido quimicamente , Acalasia Esofágica/diagnóstico , Acalasia Esofágica/epidemiologia , Doenças do Esôfago/diagnóstico , Transtornos da Motilidade Esofágica/induzido quimicamente , Transtornos da Motilidade Esofágica/diagnóstico , Transtornos da Motilidade Esofágica/epidemiologia , Feminino , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Masculino , Manometria/métodos , Pessoa de Meia-Idade , Contração Muscular , Peristaltismo/efeitos dos fármacos , Inibidores da Bomba de Prótons/efeitos adversos , Estudos Retrospectivos
18.
BMC Bioinformatics ; 21(1): 163, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349656

RESUMO

BACKGROUND: While clinical trials are considered the gold standard for detecting adverse events, often these trials are not sufficiently powered to detect difficult to observe adverse events. We developed a preliminary approach to predict 135 adverse events using post-market safety data from marketed drugs. Adverse event information available from FDA product labels and scientific literature for drugs that have the same activity at one or more of the same targets, structural and target similarities, and the duration of post market experience were used as features for a classifier algorithm. The proposed method was studied using 54 drugs and a probabilistic approach of performance evaluation using bootstrapping with 10,000 iterations. RESULTS: Out of 135 adverse events, 53 had high probability of having high positive predictive value. Cross validation showed that 32% of the model-predicted safety label changes occurred within four to nine years of approval (median: six years). CONCLUSIONS: This approach predicts 53 serious adverse events with high positive predictive values where well-characterized target-event relationships exist. Adverse events with well-defined target-event associations were better predicted compared to adverse events that may be idiosyncratic or related to secondary target effects that were poorly captured. Further enhancement of this model with additional features, such as target prediction and drug binding data, may increase accuracy.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Biologia Computacional/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Algoritmos , Humanos
19.
PLoS One ; 15(5): e0232990, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32384097

RESUMO

BACKGROUND: Underlying medical causes of obesity (endocrine disorders, genetic obesity disorders, cerebral or medication-induced obesities) are thought to be rare. Even in specialized pediatric endocrinology clinics, low diagnostic yield is reported, but evidence is limited. Identifying these causes is vital for patient-tailored treatment. OBJECTIVES: To present the results of a systematic diagnostic workup in children and adolescents referred to a specialized pediatric obesity center. METHODS: This is a prospective observational study. Prevalence of underlying medical causes was determined after a multidisciplinary, systematic diagnostic workup including growth charts analysis, extensive biochemical and hormonal assessment and genetic testing in all patients. RESULTS: The diagnostic workup was completed in n = 282 patients. Median age was 10.8 years (IQR 7.7-14.1); median BMI +3.7SDS (IQR +3.3-+4.3). In 54 (19%) patients, a singular underlying medical cause was identified: in 37 patients genetic obesity, in 8 patients cerebral and in 9 patients medication-induced obesities. In total, thirteen different genetic obesity disorders were diagnosed. Obesity onset <5 years (p = 0.04) and hyperphagia (p = 0.001) were indicators of underlying genetic causes, but only in patients without intellectual disability (ID). Patients with genetic obesity with ID more often had a history of neonatal feeding problems (p = 0.003) and short stature (p = 0.005). BMI-SDS was not higher in patients with genetic obesity disorders (p = 0.52). Patients with cerebral and medication-induced obesities had lower height-SDS than the rest of the cohort. CONCLUSIONS: To our knowledge, this is the first study to report the results of a systematic diagnostic workup aimed at identifying endocrine, genetic, cerebral or medication-induced causes of pediatric obesity. We found that a variety of singular underlying causes were identified in 19% of the patients with severe childhood obesity. Because of this heterogeneity, an extensive diagnostic approach is needed to establish the underlying medical causes and to facilitate disease-specific, patient-tailored treatment.


Assuntos
Obesidade Pediátrica/etiologia , Adolescente , Instituições de Assistência Ambulatorial , Encefalopatias/complicações , Criança , Pré-Escolar , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Doenças do Sistema Endócrino/complicações , Feminino , Testes Genéticos , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/complicações , Masculino , Países Baixos , Obesidade Pediátrica/diagnóstico , Obesidade Pediátrica/genética , Fenótipo , Estudos Prospectivos
20.
Tunis Med ; 98(2): 123-130, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32395801

RESUMO

BACKGROUND: Cardiac arrest (CA) is a public health problem, with various etiologies and a fatal issue in 90-95% of cases. Toxin-induced cardiac arrests (TICA) are poorly described. Scarcity of national data prompted us to carry-out this study. AIM: To determine TICA frequency in a Tunisian reference center in toxicology and its hospital prognosis, and to describe its clinical and therapeutic aspects Methods : Data were collected retrospectively over an 8-years period. We included patients admitted for post-CA care with highly suspected or confirmed TICA. Clinical and toxicological data were recorded. RESULTS: We recorded 21 cases of TICA, which represented 48.8% of CA. A single toxic agent was incriminated in 90% of cases. Main causative agents identified in our series were pesticides and betablockers: chloralosed (n = 6), carbamate inhibitor of cholinesterase (n = 5), acebutolol (n = 4) and organophosphate (n = 2). One case of opiates and cocaine poisoning was reported. Median duration of "no flow" was 0 minutes. Mean duration of "low flow" was 13.74±9.15 minutes. An initial shockable rhythm was noted only in three patients. Mortality rate was 76% (16/21). Four of the five survivors had a Cerebral Performance Category Scale (CPC) 1, only one patient survived with a CPC 3. Factors associated with mortality were : the duration of "low flow" (p=0.02) and APACHE II score (p=0.014). APACHE II≥29 was the only independent factor (OR=2.0, 95%CI [1.07;3.71]). CONCLUSION: TICA were most frequently provoked by pesticides, mortality was high and was independently predicted by APACHE II score.


Assuntos
Cardiotoxicidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Parada Cardíaca/induzido quimicamente , Parada Cardíaca/diagnóstico , Parada Cardíaca/terapia , Toxinas Biológicas/toxicidade , Antagonistas Adrenérgicos beta/toxicidade , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/epidemiologia , Cardiotoxicidade/etiologia , Cardiotoxicidade/terapia , Cocaína/envenenamento , 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/terapia , Parada Cardíaca/epidemiologia , Mortalidade Hospitalar , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Mortalidade , Organofosfatos/toxicidade , Praguicidas/toxicidade , Estudos Retrospectivos , Fatores de Risco , Toxinas Biológicas/classificação , Resultado do Tratamento , Tunísia/epidemiologia
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