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1.
Artigo em Inglês | MEDLINE | ID: mdl-34360043

RESUMO

The purpose of this study is to investigate physicians' knowledge, attitudes and practice of generic medicine substitutions in China. We conducted a cross-sectional online questionnaire survey on physicians from secondary or tertiary hospitals in China from 2020 December to 2021 April. Descriptive statistical and ordered logistic regression were used for analysis. A total of 1225 physicians were included in the final analysis, and only 330 (26.94%) of them scored 4 or above in the knowledge part, which means that the physicians have a good knowledge of generic substitutions. Of the total, 586 (47.83%) agreed or strongly agreed that generic drugs could be substituted for originator drugs and 585 (47.75%) always or often prescribed generic medicines. The percentage of physicians with a positive attitude toward or that practice prescribing generic medicine is below 50%, which needs to be improved in China. Physicians' knowledge, their attitude toward generic substitution, if familiar with the policy of generic substitution, and incentives for prescribing generic medicines are influencing factors for the practice of generic substitution. Our studies show that the practice of generic substitution by physicians could be improved by several measures in China. We suggested that the physicians should be taught more about the bulk-buy policy and the generic-originator equivalence evaluation policy. Moreover, government incentives to promote generic substitution should be established. Our study also suggested that physicians with less working experience and female physicians should learn more about generic substitution.


Assuntos
Substituição de Medicamentos , Médicos , Atitude do Pessoal de Saúde , Estudos Transversais , Medicamentos Genéricos , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Padrões de Prática Médica , Inquéritos e Questionários
3.
Aliment Pharmacol Ther ; 54(5): 678-688, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34223654

RESUMO

BACKGROUND: Biologics account for a significant cost in inflammatory bowel disease (IBD) management; however, switching from infliximab originator to its biosimilars has enabled cost saving without compromising disease control. The effects on IBD activity and infliximab trough levels of a second switch to another biosimilar are, however, uncertain. AIMS: To assess the effects on disease activity and infliximab trough levels associated with switching from infliximab biosimilar CT-P13 to another biosimilar SB2 and compare outcomes in those switching for the first and second time. METHODS: IBD patients on CT-P13, including some previously switched from originator, were prospectively followed during a switch to SB2. C-reactive protein (CRP), trough infliximab level and clinical disease activity indices were collected at baseline, Infusion 3 or 4 ('early' after switch), and 1 year. RESULTS: One hundred eighty-six patients (n = 99 second switch) on stable infliximab dosing underwent switching. Compared with baseline, there was no significant change in CRP, clinical disease activity scores or median trough infliximab level at the early time point among first-switch (baseline vs early: 5.7 vs 6.6 µg/mL, P = 0.05) and second-switch (4.3 vs 4.9 µg/mL, P = 0.07) patients nor at 1 year (median infliximab trough levels, baseline vs 1 year, in first-switch [5.7 vs 5.7 µg/mL, P = 0.37] and second-switch [4.3 vs 4.7 µg/mL, P = 0.06] patients). The proportion of patients in clinical remission did not significantly change at the early (92% vs 91% at baseline, P = 0.75) or 1 year (95% vs 91% at baseline, P = 0.16) time points. There was no significant difference in time to loss of response between patients switching for the first or second time (P = 0.69). CONCLUSIONS: Switching from one infliximab biosimilar to another had no adverse impact on infliximab trough levels, and clinical and biochemical disease activity, regardless of whether switching for the first or second time.


Assuntos
Medicamentos Biossimilares , Doenças Inflamatórias Intestinais , Preparações Farmacêuticas , Medicamentos Biossimilares/efeitos adversos , Substituição de Medicamentos , Fármacos Gastrointestinais/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento
4.
Isr Med Assoc J ; 23(6): 344-349, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34155846

RESUMO

BACKGROUND: There is a lack of real-life clinical data for biosimilar etanercept, an anti-TNF blocking fusion protein. We describe the comparable efficacy and safety of originator and biosimilar etanercept in rheumatoid arthritis (RA) patients in a real-life clinical setting. Our data confirm that a biosimilar etanercept can be safely used as first-line treatment as well as in patients switched from a previous originator compound. OBJECTIVES: To compare the efficacy and safety of originator and biosimilar etanercept in a cohort of RA patients attending two Italian hospitals. METHODS: The study involved 81 consecutive adult RA patients treated for at least 6 months with originator or biosimilar etanercept and considered their clinical and laboratory data, concomitant medications, and adverse events at baseline, and after 3 and 6 months of treatment. RESULTS: Group 1 included 51 patients taking originator etanercept; group 2 included 30 taking biosimilar etanercept, including 19 who had been switched from the reference product. Despite a significant baseline difference in clinical disease activity, one-way analysis of variance showed that the two groups were clinically comparable after 6 months of treatment, and the same was true when only those receiving etanercept as first-line biological treatment were considered. Nine patients discontinued the treatment due to inefficacy or adverse events, which were never serious and were only reported in group 1. CONCLUSIONS: The efficacy and safety profiles of originator and biosimilar etanercept are comparable in RA patients in a real-life clinical setting. Further studies are needed to confirm these preliminary findings.


Assuntos
Artrite Reumatoide , Medicamentos Biossimilares , Substituição de Medicamentos/métodos , Etanercepte , Preferência do Paciente , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Medicamentos Biossimilares/administração & dosagem , Medicamentos Biossimilares/efeitos adversos , Sedimentação Sanguínea/efeitos dos fármacos , Proteína C-Reativa/análise , Pesquisa Comparativa da Efetividade , Análise Custo-Benefício , Monitoramento de Medicamentos/métodos , Etanercepte/administração & dosagem , Etanercepte/efeitos adversos , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Gravidade do Paciente , Segurança do Paciente , Resultado do Tratamento
5.
Medicine (Baltimore) ; 100(25): e26450, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160440

RESUMO

RATIONALE: The guidelines recommended gefitinib as a first-line targeted treatment for stage IV non-small-cell lung cancer (NSCLC) patients with EGFR mutations. However, resistance to gefitinib ensues invariably and there is little evidence as for the effectiveness of subsequent salvage treatment for patients without T790m mutation. The case is to evaluate the efficacy of erlotinib, another EGFR-TKI, after failed first-line use of gefitinib. PATIENT CONCERNS: We described a 55-year-old man with good performance status (PS). DIAGNOSES: He was histopathologically diagnosed stage IV lung adenocarcinoma with EGFR mutations in November 2018. INTERVENTIONS: He was administrated with gefitinib daily (250 mg) for activating epidermal growth factor receptor (EGFR) mutations (exon 19 deletions,19del), and combined with platinum-based dual-drug chemotherapy. During the target treatments, the optimal efficacy evaluation was partial remission (PR) with a 12-month progression-free survival (PFS) time. Later, the intracranial progression of the patient rendered the treatment change to erlotinib. OUTCOMES: It is surprising that the tumor lesion in brain as well as lung relieved obviously. His progression-free survival (PFS)was nearly 11 months, and the overall survival (OS)was>36 months up to now. The adverse events were tolerable. LESSIONS: This case manifests that re-biopsy of advanced or recurrent NSCLC is beneficial to make a better therapeutic regimen, and erlotinib can be used as a salvage treatment after gefitinib failure.


Assuntos
Neoplasias Encefálicas/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Cloridrato de Erlotinib/uso terapêutico , Neoplasias Pulmonares/terapia , Recidiva Local de Neoplasia/terapia , Terapia de Salvação/métodos , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Quimiorradioterapia/métodos , Resistencia a Medicamentos Antineoplásicos , Substituição de Medicamentos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Cloridrato de Erlotinib/farmacologia , Gefitinibe/farmacologia , Gefitinibe/uso terapêutico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Radioterapia de Intensidade Modulada , Critérios de Avaliação de Resposta em Tumores Sólidos
6.
Medicine (Baltimore) ; 100(25): e26481, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160460

RESUMO

ABSTRACT: Botulinum toxin A is considered an effective treatment for involuntary facial movements. We examined whether treatment efficacy maintained or changed over time with two products, Botox and Dysport, in patients with hemifacial spasm, facial synkinesis and benign essential blepharospasm.We retrospectively investigated 87 consecutive patients (51 women, 36 men) who had undergone treatment for ≥6 years. Long-term effects, as well as side effects of Botox or Dysport local injections were evaluated. The first three treatments were considered the titration period and not taken into account when testing for dose changes.Mean treatment duration was 10 years (range 6-11, SD 1.0), 2441 treatments were administered, 1162 with Botox and 1279 with Dysport, the two brands were interchanged as needed. Good to full improvement was seen in 90% of patients both with both brands. Injection doses and treatment responses were consistent during the study with both drugs. No major side effects were reported, and relatively few minor adverse events were reported, with clear reduction from the titration period (6.1%), to the remainder of the study (3.9%).Botulinum toxin (BTX-A) is a satisfactory long-term treatment without need for dose increase over. Both Botox and Dysport were effective when used interchangeably.


Assuntos
Blefarospasmo/tratamento farmacológico , Toxinas Botulínicas Tipo A/administração & dosagem , Espasmo Hemifacial/tratamento farmacológico , Fármacos Neuromusculares/administração & dosagem , Sincinesia/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Blefarospasmo/fisiopatologia , Relação Dose-Resposta a Droga , Substituição de Medicamentos , Músculos Faciais/efeitos dos fármacos , Músculos Faciais/inervação , Músculos Faciais/fisiopatologia , Feminino , Seguimentos , Espasmo Hemifacial/fisiopatologia , Humanos , Injeções/métodos , Assistência de Longa Duração/métodos , Masculino , Pessoa de Meia-Idade , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Estudos Retrospectivos , Sincinesia/fisiopatologia , Resultado do Tratamento , Adulto Jovem
7.
Medicine (Baltimore) ; 100(23): e26137, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34114997

RESUMO

RATIONALE: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased morbidity, especially stroke and heart failure. There is also increasing awareness that atrial fibrillation is a major cause of embolic events which in 75% of cases are complicated by cerebrovascular accidents. PATIENT CONCERNS: A 50-year-old woman with mitral bioprosthesis under warfarin for nonvalvular atrial fibrillation was referred to our Coronary Intensive Care Unit due to acute myocardial infarction without evidence of significant coronary artery stenosis. DIAGNOSES: Cardiovascular examination showed an irregular pulse and a grade II diastolic murmur was audible at the apical area. The patient underwent coronary angiography showing absence of obstructive coronary artery disease. We decided to replace Warfarin with direct oral anticoagulants as anticoagulant therapy. INTERVENTIONS: Transoesophageal echocardiography revealed a thrombus in left atrial appendage that was treated by replacing warfarin with an oral direct thrombin inhibitor. OUTCOMES: At 2-month follow-up, the therapy showed to be effective for thrombus resolution. LESSONS: Our case demonstrated how AF has high risk of thromboembolic complications, not only in terms of stroke but also of myocardial infarction and death.The use of direct oral anticoagulants in AF patients with bioprosthetic heart valves is still debated due to an unclear definition of "nonvalvular" AF.


Assuntos
Apêndice Atrial/diagnóstico por imagem , Fibrilação Atrial , Substituição de Medicamentos/métodos , Inibidores do Fator Xa/administração & dosagem , Trombose , Varfarina/uso terapêutico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Bioprótese , Ecocardiografia Transesofagiana/métodos , Feminino , Próteses Valvulares Cardíacas , Humanos , Pessoa de Meia-Idade , Valva Mitral/cirurgia , Trombose/diagnóstico por imagem , Trombose/tratamento farmacológico , Trombose/fisiopatologia , Resultado do Tratamento
9.
Endocr Pract ; 27(9): 941-947, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34111556

RESUMO

OBJECTIVE: To compare bone mineral density (BMD) changes after 12 months of treatment with denosumab or bisphosphonates in postmenopausal women with severe osteoporosis after stopping teriparatide therapy. METHODS: We retrospectively analyzed 140 postmenopausal women (mean age, 74.2 years) with severe osteoporosis who had been treated with teriparatide for 18 to 24 months at our outpatient clinic in a tertiary endocrine center between 2006 and 2015. After stopping teriparatide therapy, they continued treatment with a bisphosphonate (alendronate, risedronate, ibandronate, or zoledronic acid) or denosumab while receiving daily vitamin D and calcium. BMD at the lumbar spine (LS), total hip (TH), and femoral neck (FN) was measured by dual energy x-ray absorptiometry when teriparatide therapy was discontinued (baseline) and after 12 months of further treatment. Multivariate linear regression models were used to identify the predictors of BMD gain. RESULTS: After stopping teriparatide therapy, 70 women continued treatment with bisphosphonates and 70 received denosumab. LS, but not TH or FN, BMD gain was significantly greater in the denosumab group than in the bisphosphonates group at 12 months. Multivariate analysis showed that BMD gain at the LS was negatively associated with bisphosphonate versus denosumab treatment and positively associated with baseline serum total procollagen type I N-terminal propeptide. BMD gains at the FN were predicted by higher baseline serum urate levels. BMD gains at the TH and FN were negatively associated with pretreatment BMD gains at the same site. CONCLUSION: Twelve months after stopping teriparatide therapy, sequential denosumab treatment appeared to yield higher additional LS BMD gain on average compared with bisphosphonates treatment.


Assuntos
Conservadores da Densidade Óssea , Denosumab , Difosfonatos , Osteoporose Pós-Menopausa , Idoso , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Difosfonatos/uso terapêutico , Substituição de Medicamentos , Feminino , Humanos , Osteoporose Pós-Menopausa/tratamento farmacológico , Estudos Retrospectivos , Teriparatida/uso terapêutico
10.
Medicine (Baltimore) ; 100(26): e26449, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190169

RESUMO

RATIONALE: Anaplastic lymphoma kinase (ALK) inhibitors have been approved for patients with ALK-rearrangement lung cancer. The effect is superior to the standard first-line therapy of pemetrexed plus platinum-based chemotherapy. However, ALK inhibitors are associated with rare and sometimes fatal adverse events. Organizing pneumonitis (OP) is a rare and serious adverse event usually caused by ceritinib, and it is easily misdiagnosed as infectious pneumonia, metastasis, or cancer progression. PATIENT CONCERNS: A 56-year-old female presented with chest tightness and dyspnea for more than 10 days. She was previously healthy with no significant medical history. Workup including chest computed tomography (CT), pathological examination of a biopsy specimen, and next-generation sequencing was consistent with a diagnosis of IVA ALK-rearrangement lung adenocarcinoma. She was treated with pemetrexed plus platinum-based chemotherapy and crizotinib concurrently, followed by maintenance therapy with crizotinib alone and she had an almost complete response. However, about 26 months after beginning treatment she developed multiple brain metastases. Crizotinib was discontinued and she was begun on ceritinib. After about 3 months the brain metastases had almost complete response. After 5 months of ceritinib, however, multiple patchy lesions appeared in the bilateral upper lungs. DIAGNOSES: Treatment with antibiotics had no effect and blood and sputum cultures are negative. A CT-guided biopsy of the upper lung was performed, and pathological hematoxylin-eosin staining and immunohistochemical studies were consistent with OP. INTERVENTIONS: Ceritinib was discontinued, she was begun on prednisone 0.5 mg/kg orally every day, and regular follow-up is necessary. OUTCOMES: CT of the chest 2 and 4 weeks after beginning prednisone showed the lung lesions to be gradually resolving, and she was continued on prednisone for 2 months and gradually reduced the dose of prednisone every 2 weeks. No related adverse events were occurred in patient. LESSONS: OP must be differentiated from infectious pneumonia, metastasis, or cancer progression. The mechanism of OP is still unknown and needs further research. Biopsy plays a role in making a diagnosis of OP. In our patient, discontinuing ceritinib and treating her with prednisone resulted in a good outcome.


Assuntos
Adenocarcinoma de Pulmão , Quinase do Linfoma Anaplásico , Pneumonia em Organização Criptogênica , Neoplasias Pulmonares , Prednisona/administração & dosagem , Pirimidinas , Sulfonas , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/fisiopatologia , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Quinase do Linfoma Anaplásico/genética , Antineoplásicos/uso terapêutico , Biópsia/métodos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Crizotinibe/uso terapêutico , Pneumonia em Organização Criptogênica/induzido quimicamente , Pneumonia em Organização Criptogênica/patologia , Pneumonia em Organização Criptogênica/terapia , Substituição de Medicamentos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/fisiopatologia , Pessoa de Meia-Idade , Pemetrexede/uso terapêutico , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Sulfonas/administração & dosagem , Sulfonas/efeitos adversos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
11.
Transplant Proc ; 53(5): 1589-1598, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34020796

RESUMO

BACKGROUND: Leukopenia is a common complication after kidney transplantation. The etiology is multifactorial, with medication adverse effects and cytomegalovirus infection as main causes. Optimal strategies to prevent or treat posttransplant leukopenia remain unknown. We aimed to identify risk factors for leukopenia and to investigate the benefit of switching the immunosuppressive therapy to hydrocortisone as a continuous infusion. METHODS: We retrospectively evaluated all patients with leukopenia after kidney transplantation between 2007 and 2017 at our center relative to age- and sex-matched controls. RESULTS: Leukopenia was associated with the degree of rejection therapy before leukopenia, the immunosuppressive therapy before transplantation, and an induction therapy with rabbit antithymocyte globulin. Patients with leukopenia exhibited increased mortality, an increased incidence of bacterial and viral infections, and more acute rejections. Switching to hydrocortisone as a continuous infusion in patients with severe leukopenia decreased the duration of leukopenia and the incidence of subsequent viral infections, especially with cytomegalovirus. CONCLUSION: Leukopenia is a risk factor for infectious complications and mortality, and it is associated with acute rejection. Switching immunosuppressive therapy to hydrocortisone as a continuous infusion is a safe approach to reduce the duration of leukopenia and the incidence of viral infections.


Assuntos
Imunossupressão/métodos , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Leucopenia/tratamento farmacológico , Complicações Pós-Operatórias/tratamento farmacológico , Adulto , Estudos de Casos e Controles , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/terapia , Substituição de Medicamentos , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressão/efeitos adversos , Leucopenia/imunologia , Leucopenia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Fatores de Risco
12.
Ann Hematol ; 100(7): 1723-1732, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33942128

RESUMO

Data on clinical use of ponatinib are limited. This prospective registry aimed to evaluate outcomes of ponatinib treatment in routine practice over 3 years (2016-2019) in Belgium (NCT03678454). Patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) were treated with ponatinib per current label. Fifty patients (33 CML and 17 Ph+ ALL) were enrolled. Fifty-five percent of CML and 29% of Ph+ ALL patients had received ≥3 prior tyrosine kinase inhibitors (TKIs). Reasons for starting ponatinib were intolerance (40%), relapse or refractoriness (28%) to previous TKIs, progression (16%), or T315I mutation (16%). Median follow-up was 15 months for CML and 4.5 months for Ph+ ALL patients. Best response was a major molecular response in 58% of CML and 41% of Ph+ ALL patients. Of 20 patients who started ponatinib due to intolerance to previous TKIs, 9 (64%) CML and 4 (67%) Ph+ ALL achieved a major molecular response. Three-year estimates of overall survival were 85.3% and 85.6%, respectively, in CML and Ph+ ALL patients; estimated progression-free survival was 81.6% and 48.9%. Adverse reactions were reported in 34 patients (68%); rash (26%) and dry skin (10%) were most common. Reported cardiovascular adverse reactions included vascular stenosis (3), arterial hypertension (2), chest pain (1), palpitations (1), and vascular occlusion (1). This Belgian registry confirms results from the PACE clinical trial and supports routine ponatinib use in CML and Ph+ ALL patients who are resistant or intolerant to previous TKIs or with the T315I mutation.


Assuntos
Antineoplásicos/uso terapêutico , Imidazóis/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Piridazinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Bélgica , Doenças Cardiovasculares/induzido quimicamente , Erupção por Droga/etiologia , Substituição de Medicamentos , Feminino , Seguimentos , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Humanos , Ictiose/induzido quimicamente , Imidazóis/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Piridazinas/efeitos adversos , Sistema de Registros , Terapia de Salvação , Resultado do Tratamento , Adulto Jovem
13.
Cardiovasc Toxicol ; 21(9): 687-694, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34018126

RESUMO

Several medicines, including cancer therapies, are known to alter the electrophysiological function of ventricular myocytes resulting in abnormal prolongation and dispersion of ventricular repolarization (quantified by multi-lead QTc measurement). This effect could be amplified by other concomitant factors (e.g., combination with other drugs affecting the QT, and/or electrolyte abnormalities, such as especially hypokalemia, hypomagnesaemia, and hypocalcemia). Usually, this condition results in higher risk of torsade de point and other life-threatening arrhythmias, related to unrecognized unpaired cardiac ventricular repolarization reserve (VRR). Being VRR a dynamic phenomenon, QT prolongation might often not be identified during the 10-s standard 12-lead ECG recording at rest, leaving the patient at increased risk for life-threatening event. We report the case of a 49-year woman, undergoing tamoxifen therapy for breast cancer, which alteration of ventricular repolarization reserve, persisting also after correction of concomitant recurrent hypokalemia, was evidenced only after manual measurements of the corrected QT (QTc) interval from selected intervals of the 12-lead ECG Holter monitoring. This otherwise missed finding was fundamental to drive the discontinuation of tamoxifen, shifting to another "safer" therapeutic option, and to avoid the use of potentially arrhythmogenic antibiotics when treating a bilateral pneumonia in recent COVID-19.


Assuntos
Antibacterianos/uso terapêutico , Arritmias Cardíacas/diagnóstico , Neoplasias da Mama/tratamento farmacológico , COVID-19/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Eletrocardiografia , Antagonistas de Estrogênios/efeitos adversos , Sistema de Condução Cardíaco/efeitos dos fármacos , Tamoxifeno/efeitos adversos , Potenciais de Ação , Antibacterianos/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/fisiopatologia , COVID-19/complicações , COVID-19/diagnóstico , Substituição de Medicamentos , Feminino , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco
14.
Ann Hematol ; 100(7): 1667-1675, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33988739

RESUMO

The aim of this study is to collect paroxysmal nocturnal hemoglobinuria (PNH) patient data from hematology centers all over Turkey in order to identify clinical features and management of PNH patients. Patients with PNH were evaluated by a retrospective review of medical records from 19 different institutions around Turkey. Patient demographics, medical history, laboratory findings, and PNH-specific information, including symptoms at the diagnosis, complications, erythrocyte, and granulocyte clone size, treatment, and causes of death were recorded. Sixty patients (28 males, 32 females) were identified. The median age was 33 (range; 17-77) years. Forty-six patients were diagnosed as classic PNH and 14 as secondary PNH. Fatigue and abdominal pain were the most frequent presenting symptoms. After eculizumab became available in Turkey, most of the patients (n = 31/46, 67.4%) were switched to eculizumab. Three patients with classic PNH underwent stem cell transplantation. The median survival time was 42 (range; 7-183 months) months. This study is the first and most comprehensive review of PNH cases in Turkey. It provided us useful information to find out the differences between our patients and literature, which may help us understand the disease.


Assuntos
Hemoglobinúria Paroxística/epidemiologia , Adolescente , Adulto , Idoso , Aloenxertos , Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças da Medula Óssea/complicações , Substituição de Medicamentos , Feminino , Hemoglobinúria Paroxística/tratamento farmacológico , Hemoglobinúria Paroxística/etiologia , Hemoglobinúria Paroxística/terapia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Análise de Sobrevida , Avaliação de Sintomas , Trombofilia/etiologia , Resultado do Tratamento , Turquia/epidemiologia , Adulto Jovem
15.
CMAJ Open ; 9(2): E364-E375, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33863794

RESUMO

BACKGROUND: Oral anticoagulants are commonly used high-risk medications, but little is known about their safety in transition from hospital to home. Our objective was to measure the rates of hemorrhage and thromboembolic events among older adults receiving oral anticoagulant treatment early after hospital discharge compared to later. METHODS: We conducted a retrospective population-based cohort study among Ontario residents aged 66 years or more who started, continued or resumed oral anticoagulant therapy at hospital discharge between September 2010 and March 2015. We calculated the rates of hemorrhage and thromboembolic events requiring hospital admission or an emergency department visit over a 1-year follow-up period, stratified by the first 30 days after discharge and the remainder of the year. We used multivariable regression models, adjusting for covariates, to estimate the effect of sex, prevalent versus incident use, and switching anticoagulants on events. RESULTS: A total of 123 139 patients (68 408 women [55.6%]; mean age 78.2 yr) were included. About one-quarter (32 563 [26.4%]) had a Charlson Comorbidity Index score of 2 or higher. The rates of hemorrhage and thromboembolic events per 100 person-years were highest during the first 30 days after hospital discharge (25.8, 95% CI 24.8-26.8 and 19.3, 95% CI 18.4-20.2, respectively), falling to 15.7 (95% CI 15.3-16.1) and 6.9 (95% CI 6.6-7.1), respectively, during the subsequent 11 months. Multivariable analysis showed that patients whose anticoagulant was switched in hospital and men had more hemorrhages and thromboembolic events in follow-up. INTERPRETATION: The first few weeks following hospital discharge represent a very high-risk period for adverse events related to oral anticoagulant treatment among older adults. The results support an intervention trial addressing anticoagulation management in the early postdischarge period.


Assuntos
Assistência ao Convalescente , Anticoagulantes , Fibrilação Atrial , Hemorragia , Risco Ajustado/métodos , Acidente Vascular Cerebral , Tromboembolia , Administração Oral , Assistência ao Convalescente/métodos , Assistência ao Convalescente/normas , Assistência ao Convalescente/estatística & dados numéricos , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Substituição de Medicamentos/efeitos adversos , Substituição de Medicamentos/métodos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/diagnóstico , Hemorragia/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Ontário/epidemiologia , Alta do Paciente/normas , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Tromboembolia/induzido quimicamente , Tromboembolia/diagnóstico , Tromboembolia/epidemiologia , Suspensão de Tratamento/estatística & dados numéricos
16.
Diabetes Res Clin Pract ; 176: 108828, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33894280

RESUMO

AIMS: To identify patient-specific factors associated with early metformin treatment modification among type 2 diabetes patients before and after implementation of the updated 2015 NICE (National Institute for Health and Care Excellence) guideline. METHODS: We conducted a population-based cohort study using data from the Clinical Practice Research Datalink GOLD database (2009-2016). Patients ≥ 18 years, newly treated with metformin only, during the period of valid data collection were included. The first prescription defined start of follow-up. Determinants of treatment modification in two cohorts (before and after implementation of the updated guideline) were studied by time-dependent Cox proportional hazards regression. RESULTS: After implementation of the updated guideline, patients were less likely to receive sulphonylureas (62.3% vs 41.3%) or thiazolidediones (4.7% vs 2.2%) and more likely to receive dipeptidyl peptidase-4 inhibitors (15.8% vs 27.1%) or sodium-glucose cotransporter-2 inhibitors (0.8% vs 9.9%). Some determinants influenced general practitioners' prescribing differently after implementation of the updated guideline compared to before, including a high body mass index and heart failure. CONCLUSIONS: Our results indicate that a first step towards tailored prescribing has been made. However, not all determinants that are important to consider when prescribing second-line glucose-lowering agents were of influence on general practitioners' prescribing.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Uso de Medicamentos/estatística & dados numéricos , Fidelidade a Diretrizes/estatística & dados numéricos , Hipoglicemiantes , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Substituição de Medicamentos/normas , Substituição de Medicamentos/estatística & dados numéricos , Endocrinologia/história , Endocrinologia/métodos , Endocrinologia/normas , Feminino , História do Século XXI , Humanos , Hipoglicemiantes/classificação , Hipoglicemiantes/normas , Hipoglicemiantes/uso terapêutico , Ciência da Implementação , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Estudos Retrospectivos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Adulto Jovem
17.
Clin Pharmacol Ther ; 110(2): 443-451, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33811324

RESUMO

Negative clinical outcomes after switching from brand to generic antidepressants have raised concerns regarding therapeutic equivalency. This research aims to estimate the prevalence of switching and to identify predictors for generic to brand switching for various antidepressants. This retrospective cohort study utilized data from a 10% random sample of enrollees in the IQVIA PharMetrics Plus claims database from 2007-2015. The base cohort consisted of commercially insured patients who were prescribed escitalopram, duloxetine, or venlafaxine extended release (ER) anytime from the year prior to the generic launch through December 2014. The primary outcome was defined as a switch from generic to a brand within 14 days of sustained generic use in a 1-year follow-up period. Adjusted logistic regression and generalized estimating equations for repeated measures estimated the drug specific and overall odds of switch-to-brand among brand initiators relative to generic initiators, respectively. A total of 102,831 unique patients across 3 drug products contributed to the final analytic sample. The overall prevalence of switch from generic to brand was 0.74%. Across all three antidepressants, brands initiators were more likely to experience a switch-to-brand: escitalopram (odds ratio (OR): 14.41, 95% confidence interval (CI): 11.14-18.64), duloxetine (OR: 8.08, 95% CI: 4.85-13.41) and venlafaxine ER (OR: 16.46, 95% CI: 11.56-23.46). The pooled odds of a switch-to-brand in brand vs. generic initiators was 13.77 (95% CI: 11.35-16.71). This study suggests a low overall switch-to-brand prevalence and may support therapeutic equivalence between brand and generic antidepressants. Initiating with a brand product was the strongest predictor for switching back to brand and suggests that patient experience may play a role in drug utilization.


Assuntos
Antidepressivos/uso terapêutico , Medicamentos Genéricos , Equivalência Terapêutica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Bases de Dados Factuais , Transtorno Depressivo/tratamento farmacológico , Substituição de Medicamentos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
18.
Seizure ; 91: 515-519, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33840583

RESUMO

INTRODUCTION: This paper reviews the potential legal ramifications of prescribing or dispensing generics for people with epilepsy (PWE) and the international perspective. SPECIAL CONSIDERATIONS: Anti-seizure medications (ASM) control ~70% of seizures. Generic alternatives must respect -20% to +25% of the bioequivalence of the 'parent' medication but are not tested, one against another. The first generic may reflect -20% and the next +25%, almost halving or doubling the bioequivalence. While doctors in some countries, prescribing ASM, have the option to deny generic substitution, this may not always be respected by the 'learned intermediary'. Use of trade name, be it of a specific generic or the parent compound, obviates the potential for substitution, especially if prohibiting substitution. LEGAL CONSEQUENCES ATTACHED TO BRAND SUBSTITUTION: Patients given a generic substitute, without warning of potential risks who experience serious consequences, may litigate for medical negligence. This responsibility rests with the provision and failure to warn, be it doctor, pharmacist or institution. Where a pharmacist ignores a doctor's instruction, there is also the potential of professional misconduct. INTERNATIONAL PERSPECTIVE: In the USA, litigation against manufacturers failed but litigating against prescribers or dispensers remains possible. While generic substitution is preferred, US doctors retain the right to reject brand substitution. Other jurisdictions likewise advocate generics, some mandating the same, but most offer the option to refuse brand substitution. CONCLUSIONS: Generic substitution, particularly for PWE, has the potential for serious harm. There is a duty of care to warn of such risks. It is the responsibility of the provider to so warn, thereby achieving informed consent.


Assuntos
Substituição de Medicamentos , Medicamentos Genéricos , Medicamentos Genéricos/uso terapêutico , Medicina Legal , Humanos , Equivalência Terapêutica , Reino Unido , Estados Unidos
19.
Medicine (Baltimore) ; 100(16): e25300, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33879661

RESUMO

ABSTRACT: During the last years there has been an increasing availability of drugs (biologics and small molecules) with different mechanisms of action (MoA) in psoriatic arthritis (PsA). New issues about treatment strategies have arisen. The main aim of this study is to verify if there is a difference in terms of clinical efficacy (i.e. retention rate) between cycling (i.e. treating patients with the same MoA after the failure of the previous one) or swap (i.e choosing drugs with a MoA different from the failed previous one) strategies in PsA.In this mono-centric medical records review study, PsA patients treated with biologics, apremilast or tofacitinib were enrolled. Every prescription was clustered in three groups: cycling (CG), swap (SG) or first line group (1LG). Kaplan-Meier analysis and Cox test estimated and compared drugs' retention rate in CG, SG and 1LG. P < .05 was considered statistically significant.One hundred eighty-three PsA patients were enrolled (9967 patient-months). In CG and 1LG the more prescribed drugs were tumor necrosis factor inhibitor (respectively 99% and 89%), in SG interleukin 17 inhibitor (60%). There were no differences in terms of sex, age, disease duration, and retention rate between CG and SG. The 18-months retention rate of 1LG, SG and CG was 77%, 60%, and 51% respectively. The CG retention rate was lower than in 1LG (P = .03).The findings of this study suggest that in PsA the swap strategy gives no remarkable advantage compared to cycling. However, patients undergoing swap strategy may experience the same failure rate observed in naives.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/administração & dosagem , Substituição de Medicamentos/métodos , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Análise por Conglomerados , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Piperidinas/administração & dosagem , Modelos de Riscos Proporcionais , Pirimidinas/administração & dosagem , Talidomida/administração & dosagem , Talidomida/análogos & derivados , Resultado do Tratamento
20.
Front Immunol ; 12: 614715, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33841397

RESUMO

The extended interval dosing (EID) of natalizumab has been suggested to be associated with a reduced risk of progressive multifocal leukoencephalopathy (PML) and short-term preservation of efficacy but its long-term effectiveness remain unknown. We aimed to determine the long-term effectiveness and safety of natalizumab in an EID setting in a cohort of patients with multiple sclerosis (MS) treated for more than 7 years. We conducted an observational retrospective cohort study, including 39 (34 female, 5 male) patients with clinically definite relapsing-MS, initially treated with standard interval dosing (SID) of natalizumab (mean time 54 months [SD29]) who were then switched to EID, every 8 weeks (mean time 76 months [SD13]). The main outcome measures included the following: i) annualized relapse rate (ARR), ii) radiological activity, iii) disability progression, and iv) NEDA-3 no evidence of disease activity index. EID preserved ARR, radiological activity, and prevented disability worsening during follow-up. The proportion of patients maintaining their NEDA-3 status after 24, 48, and 72 months of natalizumab administration in EID was 94%, 73%, and 70%, respectively. Stratified analysis according to history of drug therapy showed that the EID of natalizumab was slightly more effective in naïve patients than in those previously treated with other immunosuppressive drugs. No cases of PML or other severe adverse reactions were reported. In conclusion, long-term therapy with natalizumab in an EID setting following an SID regimen maintained its disease-modifying activity, and was safe and well tolerated for over 7 years. These encouraging observational results need to be confirmed in controlled clinical trials.


Assuntos
Fatores Imunológicos/administração & dosagem , Esclerose Múltipla/tratamento farmacológico , Natalizumab/administração & dosagem , Adulto , Antirreumáticos , Gerenciamento Clínico , Suscetibilidade a Doenças , Substituição de Medicamentos , Feminino , Humanos , Imunossupressores , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/etiologia , Prognóstico , Radiografia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
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