RESUMO
Direct oral anticoagulants (DOACs) are used in anticoagulant therapy. The purpose of this study was to evaluate the association of DOAC-induced gastrointestinal (GI) and nervous system hemorrhage using the FDA's Adverse Event Reporting System (FAERS) database and the Japanese Adverse Drug Event Report (JADER) database. We identified and analyzed the reports of hemorrhagic reactions between 2004 and 2016 from the FAERS and JADER databases, and calculated the adjusted reported odds ratio (ROR) using the multiple logistic regression method. Additionally, we used the time-to-onset analysis. In the FAERS database, the adjusted ROR of apixaban, rivaroxaban, and dabigatran for GI hemorrhage was 6.79 (5.84-7.91), 19.58 (18.85-20.34), and 14.51 (13.58-15.51), respectively. In the JADER database, the adjusted ROR of apixaban, rivaroxaban, edoxaban, and dabigatran for GI hemorrhage was 11.80 (9.50-14.64), 11.03 (9.18-13.26), 10.17 (6.95-14.88), and 9.85 (7.23-13.42), respectively. We found that the association of GI hemorrhage with DOACs was affected by sex (female). Additionally, 30% of GI hemorrhage was observed after 30 days. Hemorrhagic reactions of both GI and nervous systems were observed in both the spontaneous reporting system databases. We recommend that female patients who experience symptoms related to GI hemorrhage should be closely monitored and advised to adhere to an appropriate care plan. Additionally, our results show that patients should be closely monitored for hemorrhage even after a month.
Assuntos
Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Administração Oral , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Humanos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/epidemiologia , Japão/epidemiologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estados Unidos/epidemiologia , United States Food and Drug AdministrationRESUMO
Aim: Postpartum depression is a mood disorder that commonly affects women during the early postpartum period. The objective of this study was to analyse the association of postpartum depression with drugs (including contraceptive devices and implants) with spontaneously reported adverse events reported in the US Food and Drug Administration Adverse Event Reporting System database. Design: Retrospective study. Method: Reports of postpartum depression events between 2004-2015 were analysed with a reporting odds ratio (ROR) algorithm. The Medical Dictionary for Regulatory Activities was used to identify postpartum depression. Results: The reporting odds ratios (95% confidence intervals, CI) of levonorgestrel (an intrauterine device with progestogen), etonogestrel (a hormonal contraceptive implant), sertraline and drospirenone (an oral contraceptive) were 12.5 (8.7-18.0), 14.0 (8.5-22.8), 12.2 (6.5-23.1) and 5.4 (2.7-10.9) respectively. Among the drugs in the US Food and Drug Administration Adverse Event Reporting System database, the use of contraceptives or an intrauterine device with progestogen might convey risk for postpartum depression.
RESUMO
Drug-induced photosensitivity (DIP) refers to the development of cutaneous disorders caused by the combined effects of different medications and light. The aim of this study was to obtain new information on drug risk comparisons and on DIP onset profiles, including seasonal variations, for clinically used prescription drugs. We analyzed reports of DIP recorded in the Japanese Adverse Drug Event Report (JADER) database using a reporting odds ratio (ROR). We also used Weibull proportional-hazards models for each drug to examine the patterns of DIP. The JADER database contains 430587 reports recorded from April 2004 to November 2016. The ROR values (95% confidence interval [CI]) of losartan/hydrochlorothiazide (HCTZ), valsartan/HCTZ, and ketoprofen were 214.5 (162.1-283.9), 104.7 (66.3-165.5), and 117.9 (76.6-181.5), respectively. For time-to-onset analysis, the median durations (interquartile range) for DIP caused by losartan/HCTZ, valsartan/HCTZ, and ketoprofen were 56 (41-78), 49 (38-88), and 8 (2-14) days, respectively. The lower limit of the 95% CI for the Weibull shape parameter ß value for losartan/HCTZ was greater than 1. More than half of the reports of DIP onset following the administration of ketoprofen were recorded within 10 d of treatment initiation. The seasonal variation of photosensitivity reactions was shown to follow an annual sinusoidal pattern with a peak in April and May. Based on the results, losartan/HCTZ, valsartan/HCTZ, and ketoprofen should be used carefully in clinical practice to avoid DIP.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Anti-Inflamatórios não Esteroides/efeitos adversos , Transtornos de Fotossensibilidade/epidemiologia , Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Combinação de Medicamentos , Feminino , Humanos , Hidroclorotiazida/efeitos adversos , Incidência , Japão/epidemiologia , Cetoprofeno/efeitos adversos , Losartan/efeitos adversos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Transtornos de Fotossensibilidade/induzido quimicamente , Estações do Ano , Valsartana/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Drug-induced gingival hyperplasia (DIGH) causes problems with chewing, aesthetics, and pronunciation, and leads to the deterioration of the patient's quality of life (QOL). Thus, the aim of this study was to evaluate the incidence of DIGH using spontaneous reporting system (SRS) databases. METHODS: We analyzed reports of DIGH from SRS databases and calculated the reporting odds ratios (RORs) of suspected drugs (immunosuppressants, calcium channel blockers, and anticonvulsants). The SRS databases used were the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) database. With the data, we evaluated the time-to-onset profile and the hazard type using the Weibull shape parameter (WSP). Furthermore, we used the association rule mining technique to discover undetected relationships such as possible risk factors. RESULTS: The FAERS contained 5,821,716 reports. The RORs (95% confidence interval: CI) for cyclosporine, everolimus, sirolimus, mycophenolate mofetil, amlodipine, nifedipine, carbamazepine, clobazam, levetiracetam, phenobarbital, phenytoin, primidone, topiramate, and valproic acid, were 39.4 (95% CI: 30.3-51.2), 4.2 (1.7-10.0), 6.6 (2.5-17.7), 13.1 (7.2-23.2), 94.8 (80.0-112.9), 57.9 (35.7-94.0), 15.1 (10.3-22.3), 65.4 (33.8-126.7), 6.5 (3.6-11.8), 19.7 (8.8-44.0), 65.4 (52.4-82.9), 56.5 (21.1-151.7), 2.9 (1.1-7.7), and 17.5 (12.6-24.4), respectively. The JADER database contained 430,587 reports. The median time-to-onset of gingival hyperplasia values for immunosuppressants, calcium channel blockers, and anticonvulsants use were 71, 262, and 37 days, respectively. Furthermore, the 95% CI of the WSP ß for anticonvulsants was over and excluded 1, which meant that they were wear-out failure type. CONCLUSIONS: Our results suggest that DIGH monitoring of patients administered immunosuppressants, calcium channel blockers, or anticonvulsants is important. We demonstrated the potential risk of DIGH following the long-term use of calcium channel blocker over approximately 260 days. Based on the results of the association rule mining approach, patients with intellectual disability who are administered phenytoin should be monitored carefully. We recommend that patients who experience symptoms related to DIGH should be closely monitored.
RESUMO
Combined estrogen-progestin preparations (CEPs) are associated with thromboembolic (TE) side effects. The aim of this study was to evaluate the incidence of TE using the Japanese Adverse Drug Event Report (JADER) database. Adverse events recorded from April 2004 to November 2014 in the JADER database were obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) website (www.pmda.go.jp). We calculated the reporting odds ratios (RORs) of suspected CEPs, analyzed the time-to-onset profile, and assessed the hazard type using Weibull shape parameter (WSP). Furthermore, we used the applied association rule mining technique to discover undetected relationships such as the possible risk factors. The total number of reported cases in the JADER contained was 338,224. The RORs (95% confidential interval, CI) of drospirenone combined with ethinyl estradiol (EE, Dro-EE), norethisterone with EE (Ne-EE), levonorgestrel with EE (Lev-EE), desogestrel with EE (Des-EE), and norgestrel with EE (Nor-EE) were 56.2 (44.3-71.4), 29.1 (23.5-35.9), 42.9 (32.3-57.0), 44.7 (32.7-61.1), and 38.6 (26.3-56.7), respectively. The medians (25%-75%) of the time-to-onset of Dro-EE, Ne-EE, Lev-EE, Des-EE, and Nor-EE were 150.0 (75.3-314.0), 128.0 (27.0-279.0), 204.0 (44.0-660.0), 142.0 (41.3-344.0), and 16.5 (8.8-32.0) days, respectively. The 95% CIs of the WSP-ß for Ne-EE, Lev-EE, and Nor-EE were lower and excluded 1. Association rule mining indicated that patients with anemia had a potential risk of developing a TE when using CEPs. Our results suggest that it is important to monitor patients administered CEP for TE. Careful observation is recommended, especially for those using Nor-EE, and this information may be useful for efficient therapeutic planning.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Estrogênios/administração & dosagem , Estrogênios/efeitos adversos , Progestinas/administração & dosagem , Progestinas/efeitos adversos , Tromboembolia/induzido quimicamente , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Androstenos/administração & dosagem , Androstenos/efeitos adversos , Criança , Anticoncepcionais Orais Combinados/administração & dosagem , Anticoncepcionais Orais Combinados/efeitos adversos , Bases de Dados Factuais , Desogestrel/administração & dosagem , Desogestrel/efeitos adversos , Etinilestradiol/administração & dosagem , Etinilestradiol/efeitos adversos , Feminino , Humanos , Japão , Levanogestrel/administração & dosagem , Levanogestrel/efeitos adversos , Masculino , Pessoa de Meia-Idade , Noretindrona/administração & dosagem , Noretindrona/efeitos adversos , Norgestrel/administração & dosagem , Norgestrel/efeitos adversos , Razão de Chances , Adulto JovemRESUMO
Tumor necrosis factor-α (TNF-α) inhibitors are increasingly being used as treatment for rheumatoid arthritis (RA). However, the administration of these drugs carries the risk of inducing injection site reaction (ISR). ISR gives rise to patient stress, nervousness, and a decrease in quality of life (QoL). In order to alleviate pain and other symptoms, early countermeasures must be taken against this adverse event. In order to improve understanding of the risk factors contributing to the induction of ISR, we evaluated the association between TNF-α inhibitors and ISR by applying a logistic regression model to age-stratified data obtained from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. The FAERS database contains 7,561,254 reports from January 2004 to December 2015. Adjusted reporting odds ratios (RORs) (95% Confidence Intervals) were obtained for interaction terms for age-stratified groups treated with etanercept (ETN) and adalimumab (ADA). The adjusted RORs for ETN* ≥ 70 and ADA* ≥ 70 groups were the lowest among the age-stratified groups undergoing the respective monotherapies. Furthermore, we found that crude RORs for ETN + methotrexate (MTX) combination therapy and ADA + MTX combination therapy were lower than those for the respective monotherapies. This study was the first to evaluate the relationship between aging and ISR using the FAERS database.
Assuntos
Adalimumab/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Etanercepte/efeitos adversos , Injeções/efeitos adversos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos , United States Food and Drug Administration , Adulto JovemRESUMO
AIM: Polypharmacy is a major problem for elderly patients in developed countries. We investigated whether a multidisciplinary medication review using electronic medical records could reduce the number of drugs administered to elderly patients receiving polypharmacy. METHODS: The present study included 432 elderly patients (188 women, 244 men; 267 patients aged 65-74 years and 165 patients aged ≥75 years) who were admitted to and discharged from the Department of Neurology and Geriatrics, Gifu University Hospital, between 2004 and 2011; those who died at the hospital were excluded. The names, categories, and numbers of orally administered drugs at admission and discharge were examined retrospectively using electronic medical records. The histories of continuous oral immunotherapy use at the hospital, falls during the 2 years before hospital admission and the presence of fall risk factors were also evaluated. P-values <0.05 were considered statistically significant. RESULTS: On average 1.14 ± 3.07 fewer types of drugs were given to patients at discharge than at admission in patients receiving polypharmacy (P < 0.001). However, the number of drugs given to patients undergoing continuous oral immunotherapy increased by 1.67 ± 3.47 (P < 0.001). The number of drugs was reduced in 33.1% of fallers, and 36.3% of non-fallers. In both fallers and non-fallers, there was a reduction in drug categories associated with falls. CONCLUSIONS: Multidisciplinary medication review using electronic medical records could significantly reduce the numbers of drugs taken by elderly inpatients receiving polypharmacy, including drugs associated with falls, in both fallers and non-fallers Geriatr Gerontol Int 2017; 17: 653-658.
Assuntos
Polimedicação , Acidentes por Quedas , Idoso , Idoso de 80 Anos ou mais , Registros Eletrônicos de Saúde , Feminino , Hospitalização , Humanos , Japão , Masculino , Erros de Medicação/prevenção & controle , Padrões de Prática Médica , Estudos RetrospectivosRESUMO
PURPOSE: To evaluate and compare the usefulness of equivalent cross-relaxation rate (ECR) imaging (ECRI) and diffusion-weighted imaging (DWI) in the early prediction of the response of bevacizumab-containing treatments of colorectal liver metastases. METHODS AND MATERIAL: Seven patients received bevacizumab-containing treatments for colorectal liver metastases. Serial magnetic resonance imaging was performed to evaluate responses before and 2 weeks after starting chemotherapy. In the ECRI, we adopted the off-resonance technique for preferential saturation of immobile protons to evaluate the ECR values. A single saturation transfer pulse frequency was used at a frequency of 3.5 ppm downfield from the water resonance. In the DWI, the apparent diffusion coefficient (ADC) value commonly used with two b-values was acquired by using diffusion weightings of 0 and 800 s/mm2. The region of interest of the metastatic lesions in the liver was separately measured by ECRI and DWI. Tumor response was assessed by response evaluation criteria in solid tumors criteria 8 weeks after starting chemotherapy. RESULTS: In this study, we had four responders and three nonresponders. There was a significant difference in the pretreatment ECR values between the responders and nonresponders (P=.01); there was no significant difference in the ADC values between the two groups. Analysis of the percentage difference between the pretreatment and post-treatment values, termed as percentage change, showed that there were no significant differences in the percentage change of the ADC values between both groups; however, the percentage change in the ECR value was significantly greater for the responders than for the nonresponders (-41.6%±17.1% vs. -12.9%±6.9%, respectively; P=.04). CONCLUSION: The pretreatment ECR value and percentage change of the ECR value 2 weeks after starting chemotherapy were useful parameters in the early prediction of response to bevacizumab-containing treatment in colorectal liver metastases.
Assuntos
Bevacizumab/uso terapêutico , Neoplasias Colorretais/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Segunda Neoplasia Primária/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Feminino , Humanos , Fígado/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Segunda Neoplasia Primária/diagnóstico por imagem , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Resultado do TratamentoRESUMO
Long QT syndrome (LQTS) is a disorder of the heart's electrical activity that infrequently causes severe ventricular arrhythmias such as a type of ventricular tachycardia called torsade de pointes (TdP) and ventricular fibrillation, which can be fatal. There have been no previous reports on the time-to-onset for LQTS based on data from spontaneous reporting systems. The aim of this study was to assess the time-to-onset of LQTS according to drug treatment. We analyzed the association between 113 drugs in 37 therapeutic categories and LQTS including TdP using data obtained from the Japanese Adverse Drug Event Report database. For signal detection, we used the reporting odds ratio (ROR). Furthermore, we analyzed the time-to-onset data and assessed the hazard type using the Weibull shape parameter. The RORs (95% confidence interval) for bepridil, amiodarone, pilsicainide, nilotinib, disopyramide, arsenic trioxide, clarithromycin, cibenzoline, donepezil, famotidine, sulpiride, and nifekalant were 174.4 (148.6-204.6), 17.3 (14.7-20.4), 52.0 (43.4-62.4), 13.9 (11.5-16.7), 69.3 (55.3-86.8), 54.2 (43.2-68.0), 4.7 (3.8-5.8), 19.9 (15.9-25.0), 8.1 (6.5-10.1), 3.2 (2.5-4.1), 7.1 (5.5-9.2), and 254.8 (168.5-385.4), respectively. The medians and quartiles of time-to-onset for aprindine (oral) and bepridil were 20.0 (11.0-35.8) and 18.0 (6.0-43.0) days, respectively. The lower 95% confidence interval of the shape parameter ß of bepridil was over 1 and the hazard was considered to increase over time.Our study indicated that the pattern of LQTS onset might differ among drugs. Based on these results, careful long-term observation is recommended, especially for specific drugs such as bepridil and aprindine. This information may be useful for the prevention of sudden death following LQTS and for efficient therapeutic planning.
Assuntos
Aprindina/efeitos adversos , Bepridil/efeitos adversos , Bases de Dados Factuais , Síndrome do QT Longo , Administração Oral , Aprindina/administração & dosagem , Bepridil/administração & dosagem , Feminino , Humanos , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/epidemiologia , Síndrome do QT Longo/fisiopatologia , Masculino , Fatores de TempoRESUMO
"Big data" is a new buzzword. The point is not to be dazzled by the volume of data, but rather to analyze it, and convert it into insights, innovations, and business value. There are also real differences between conventional analytics and big data. In this article, we show some results of big data analysis using open DPC (Diagnosis Procedure Combination) data in areas of the central part of JAPAN: Toyama, Ishikawa, Fukui, Nagano, Gifu, Aichi, Shizuoka, and Mie Prefectures. These 8 prefectures contain 51 medical administration areas called the second medical area. By applying big data analysis techniques such as k-means, hierarchical clustering, and self-organizing maps to DPC data, we can visualize the disease structure and detect similarities or variations among the 51 second medical areas. The combination of a big data analysis technique and open DPC data is a very powerful method to depict real figures on patient distribution in Japan.
Assuntos
Bases de Dados Factuais/estatística & dados numéricos , Análise por Conglomerados , Mineração de DadosRESUMO
OBJECTIVE: This study was designed to investigate pharmacological interaction between magnesium laxative and antacid in patients receiving opioid analgesic. METHODS: Data obtained from a total of 441 eligible patients receiving opioid analgesic for the first time were retrospectively analysed. The incidence of constipation, defined as stool-free interval of 3 days and more within the first week of opioid intake, was compared between patients who took laxative alone and those who received laxative in combination with antacid. KEY FINDINGS: Laxatives were prescribed in 74% of patients, among them 61% received antacids such as proton pump inhibitor and H2 receptor blocker. Magnesia was the most commonly used laxative (89%). Constipation occurred in 21% and 55% of patients with and without laxatives, respectively. Antacids reversed the laxative action of lower doses (<2000 mg/day) but not higher doses (>2000 mg/day) of magnesia without affecting the effects of other laxatives. Therefore, it is suggested that both acid-dependent and acid-independent mechanisms may operate in the laxative action of magnesia, in which the former may be involved in the action of lower doses of magnesia. CONCLUSION: Care should be taken to avoid the unfavourable pharmacological interaction between low doses of magnesia and antacid.
Assuntos
Analgésicos Opioides/efeitos adversos , Antiácidos/efeitos adversos , Constipação Intestinal/tratamento farmacológico , Interações Medicamentosas , Laxantes/farmacologia , Óxido de Magnésio/farmacologia , Neoplasias/tratamento farmacológico , Ácidos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiácidos/uso terapêutico , Antiulcerosos/efeitos adversos , Antiulcerosos/uso terapêutico , Constipação Intestinal/etiologia , Humanos , Laxantes/administração & dosagem , Óxido de Magnésio/administração & dosagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions associated with fatal disorders. Although many causes of SJS/TEN have been proposed, the time-to-onset for SJS/TEN and the relationship between aging and SJS/TEN are still not clear. Therefore, the aim of this study was to determine the relationship between aging and SJS/TEN using the Japanese Adverse Drug Event Report (JADER) database and analyze the time-to-onset profile of SJS/TEN. METHODS: We analyzed reports of SJS/TEN recorded in the JADER database between 2004 and 2015 using an adjusted reporting odds ratio (ROR). We also used Weibull proportional hazards models for each drug to examine the expression patterns of SJS/TEN. We selected the drugs according to the number of the reports associated with SJS/TEN. RESULTS: The JADER contained 330,686 reports from April 2004 to April 2015. The adjusted RORs for patients in the 0-19-, 20-39-, 60-79-, and ≥ 80-year-old groups from all data extracted from the JADER database were 1.33 (95 % confidence interval [CI], 1.21-1.45), 1.78 (95 % CI, 1.65-1.93), 0.71 (95 % CI, 0.66-0.75), and 0.72 (95 % CI, 0.66-0.79), respectively. The adjusted ROR tended to be higher in patients aged 0-19 years, particularly in patients using antipyretic analgesics, such as loxoprofen or acetaminophen. More than half of the cases of SJS/TEN onset following administration of loxoprofen and acetaminophen occurred within 4 days of the initiation of treatment. The median times-to-onset were 3 days for loxoprofen and 2 days for acetaminophen. The scale parameter α values of loxoprofen and acetaminophen were 9.44 and 6.17, respectively. The upper 95 % CIs of shape parameter ß values for the drugs were all less than 1, with the exceptions of those for carbamazepine, ACE inhibitors, and corticosteroids. CONCLUSIONS: Our results suggested that monitoring of younger patients who frequently use antipyretic analgesics is important. These drugs should be used and monitored within the first 2-3 days of treatment in the Japanese population.
RESUMO
We developed a tool that allows a medical facility to offer efficient nursing care with limited human resources by optimizing the distribution of hospital ward nursing tasks. The use of information and communications technology to visualize daily workloads and make use of quantified workload data is important for identifying management elements that allow the efficient allocation of personnel and tasks. The goal of this study was to utilize data from the ward management tool that we developed to consider workflow processes for nursing staff and the relationships between the nursing competence of the nursing staff and the patients' conditions and how these impact on workloads. We found a correlation between workload and staff competence. With respect to the teamwork index and patient condition, structural equation modeling analysis using the intensity of nursing care needs and degree of independent daily living showed that patient condition had a meaningful effect on workload.
Assuntos
Eficiência Organizacional/estatística & dados numéricos , Sistemas de Informação Administrativa/estatística & dados numéricos , Modelos Organizacionais , Recursos Humanos de Enfermagem Hospitalar/estatística & dados numéricos , Admissão e Escalonamento de Pessoal/organização & administração , Carga de Trabalho/estatística & dados numéricos , Análise Fatorial , Humanos , Japão , Quartos de Pacientes/estatística & dados numéricos , Software , Revisão da Utilização de Recursos de Saúde , Fluxo de TrabalhoRESUMO
The Japanese Ministry of Health, Labor, and Welfare lists hand-foot syndrome as a serious adverse drug event. Therefore, we evaluated its association with anticancer drug therapy using case reports in the Japanese Adverse Drug Event Report (JADER) and the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). In addition, we calculated the reporting odds ratio (ROR) of anticancer drugs potentially associated with hand-foot syndrome, and applied the Weibull shape parameter to time-to-event data from JADER. We found that JADER contained 338224 reports from April 2004 to November 2014, while FAERS contained 5821354 reports from January 2004 to June 2014. In JADER, the RORs [95% confidence interval (CI)] of hand-foot syndrome for capecitabine, tegafur-gimeracil-oteracil, fluorouracil, sorafenib, and regorafenib were 63.60 (95%CI, 56.19-71.99), 1.30 (95%CI, 0.89-1.89), 0.48 (95%CI, 0.30-0.77), 26.10 (95%CI, 22.86-29.80), and 133.27 (95%CI, 112.85-157.39), respectively. Adverse event symptoms of hand-foot syndrome were observed with most anticancer drugs, which carry warnings of the propensity to cause these effects in their drug information literature. The time-to-event analysis using the Weibull shape parameter revealed differences in the time-dependency of the adverse events of each drug. Therefore, anticancer drugs should be used carefully in clinical practice, and patients may require careful monitoring for symptoms of hand-foot syndrome.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Antineoplásicos/efeitos adversos , Conjuntos de Dados como Assunto/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Síndrome Mão-Pé/epidemiologia , Síndrome Mão-Pé/etiologia , Síndrome Mão-Pé/prevenção & controle , Humanos , Japão/epidemiologia , Fatores de Tempo , Estados Unidos , United States Food and Drug AdministrationRESUMO
Selective serotonin reuptake inhibitors (SSRIs) are prescribed for the treatment of depression worldwide. SSRIs are suspected to increase the risk of suicidal ideation and behavior (suicidality) in children, adolescents, and young adults. We examined the association between SSRI therapy and suicidality by applying a logistic regression model to age-stratified data from the Food and Drug Administration (FDA) Adverse Event Reporting System database. We attempted to mitigate the effect of patient-related factors by data subsetting. We selected case reports for SSRIs as referred to in the World Health Organization Anatomical Therapeutic Chemical classification code N06AB. The association between SSRIs and "suicidal events" or "self-harm events" was calculated as a reporting odds ratio (ROR) and adjusted for covariates by logistic regression. For subjects <18 years old (y.o.) the adjusted RORs (95% confidence interval) of SSRI therapy with suicidal events were 9.58 (8.97-10.23) in the whole data analysis and 4.64 (4.15-5.19) in the subset analysis; those with self-harm events were 31.40 (27.71-35.58) and 16.31 (13.12-20.29), respectively. Although the adjusted RORs were lower in the subset analyses than in the whole data analyses, both analyses indicated associations between SSRI treatment and suicidal and self-harm events. In both analyses these associations were stronger in the <18 y.o. group than other age groups. Children and adolescents should be closely monitored for the occurrence of suicidality when they are prescribed SSRIs. In addition, we found that data subsetting might mitigate the effect of an intrinsic risk among patients taking the suspected drug.
Assuntos
Depressão/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Suicídio , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Criança , Bases de Dados Factuais , Depressão/complicações , Transtorno Depressivo/complicações , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Comportamento Autodestrutivo , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Suicídio/estatística & dados numéricos , Estados Unidos , United States Food and Drug Administration , Adulto JovemRESUMO
There have been concerns that oseltamivir causes neuropsychiatric adverse events (NPAEs). We analyzed the association of age and gender with NPAEs in patients treated with oseltamivir using a logistic regression model. NPAE data were obtained from the U.S. Food and Drug Administration Adverse Event Reporting System (2004 to 2013). The lower limit of the reporting odds ratio (ROR) 95% confidence interval (CI) of "abnormal behavior" in Japan, Singapore, and Taiwan was ≥1. The effects of the interaction terms for oseltamivir in male patients aged 10-19 years were statistically significant. The adjusted ROR of "abnormal behavior" was 96.4 (95% CI, 77.5-119.9) in male patients aged 10-19 years treated with osletamivir. In female patients, the results of the likelihood ratio test for "abnormal behavior" were not statistically significant. The adjusted NPAE RORs were increased in male and female patients under the age of 20 years. Oseltamivir use could be associated with "abnormal behavior" in males aged 10-19 years. After considering the causality restraints of the current analysis, further epidemiological studies are recommended.
Assuntos
Antivirais/efeitos adversos , Transtornos Mentais/induzido quimicamente , Oseltamivir/efeitos adversos , Adolescente , Adulto , Antivirais/uso terapêutico , Ásia/epidemiologia , Comportamento/efeitos dos fármacos , Sintomas Comportamentais , Criança , Feminino , Humanos , Influenza Humana/tratamento farmacológico , Masculino , Razão de Chances , Oseltamivir/uso terapêutico , Adulto JovemRESUMO
Over-the-counter (OTC) drugs play an important role in self-medication. To ensure patient safety, pharmacists should ask patients to pay attention to possible adverse events (AE) associated with OTC drugs and educate patients about the symptoms related to those AEs. The aims of the present study were as follows: (1) to assess the tendency of AEs to occur with OTC drug use in Japan; (2) to detect a safety signal for OTC drugs using the reporting odds ratio (ROR); and (3) to evaluate clustery features, which include suspected drugs and therapeutic classifications, and safety signal indices (number of reports and the ROR), using cluster analysis. The number of reports of AEs following use of combination cold remedy, antipyretic and analgesic remedy, and herbal medicine was 1007, 566, and 221, respectively. We set the cluster number at five; clustery features obtained were as follows: (1) high reporting rate for skin and subcutaneous tissue disorder AEs was the largest group related to combination cold remedy; (2) high reporting rate for nervous system disorder AEs including dizziness was the second largest group. The same medicinal ingredient may demonstrate similar tendencies of the occurrence of AEs and similar clustery features in the Japanese Adverse Drug Event Report database. Our analysis of AEs associated with OTC drugs may be useful for pharmacists and patients alike. Further studies are required to draw better-informed conclusions.
Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Mineração de Dados , Bases de Dados Factuais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Medicamentos sem Prescrição/efeitos adversos , Análise por Conglomerados , Humanos , Japão/epidemiologiaRESUMO
Clopidogrel is an antiplatelet agent widely used in combination with aspirin to limit the occurrence of cardiovascular (embolic/thrombotic) events. Consensus guidelines recommend proton pump inhibitors (PPIs) as a gastrointestinal (GI) prophylactic measure for all patients receiving dual antiplatelet therapy with clopidogrel and aspirin. The objective of this study was to analyze the effect of the simultaneous use of clopidogrel, aspirin, and PPIs on hemorrhagic and embolic/thrombotic events using the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Reports of hemorrhagic and embolic/thrombotic events between 2004 and 2013 were analyzed with a reporting odds ratio (ROR) algorithm and logistic regression methods. The Medical Dictionary for Regulatory Activities Preferred Terms was used to identify such events. Regarding hemorrhagic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 4.40 (95% confidence interval [CI], 4.02-4.81) and 3.40 (95% CI, 2.84-4.06), respectively. For embolic/thrombotic events, the adjusted RORs of the concomitant use of aspirin and clopidogrel and those of PPIs prescribed with aspirin and clopidogrel were 2.37 (95% CI, 2.16-2.59) and 2.38 (95% CI, 2.00-2.84), respectively. Among patients included in the FAERS database, the concurrent use of aspirin and clopidogrel with PPIs reduced the adjusted ROR of GI hemorrhagic events. PPIs had little influence on the adjusted ROR of embolic/thrombotic events. These results support the use of PPIs as a preventive measure against GI hemorrhagic events for patients receiving clopidogrel and aspirin.
Assuntos
Aspirina/efeitos adversos , Interações Medicamentosas , Embolia/prevenção & controle , Hemorragia Gastrointestinal/prevenção & controle , Inibidores da Bomba de Prótons/efeitos adversos , Trombose/prevenção & controle , Ticlopidina/análogos & derivados , Sistemas de Notificação de Reações Adversas a Medicamentos , Aspirina/uso terapêutico , Clopidogrel , Quimioterapia Combinada , Feminino , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Razão de Chances , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Fatores de Risco , Ticlopidina/efeitos adversos , Ticlopidina/uso terapêutico , Estados Unidos , United States Food and Drug AdministrationRESUMO
Mitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL) deficiency is an autosomal recessive disorder affecting the leucine catabolic pathway and ketone body synthesis, and is clinically characterized by metabolic crises with hypoketotic hypoglycemia, metabolic acidosis and hyperammonemia. In the present study, we initially used PCR with genomic followed by direct sequencing to investigate the molecular genetic basis of HMGCL deficiency in two patients clinically diagnosed with the condition. Although we identified a mutation in each patient, the inheritance patterns of these mutations were not consistent with disease causation. Therefore, we investigated HMGCL using multiplex ligation-dependent probe amplification (MLPA) to determine the copy numbers of all exons. A heterozygous deletion that included exons 2-4 was identified in one of the patients. MLPA revealed that the other patient had two copies for all HMGCL exons. Paternal uniparental isodisomy of chromosome 1 was confirmed in this patient by microarray analysis. These findings indicate that MLPA is useful for the identification of genomic aberrations and mutations other than small-scale nucleotide alterations. To the best of our knowledge, this is the first study describing HMGCL deficiency caused by uniparental disomy.