RESUMO
OBJECTIVE: To evaluate the association of a combined exposure to antenatal steroids and prophylactic indomethacin with the outcome of spontaneous intestinal perforation (SIP) among neonates born at <26 weeks of gestation or <750 g birth weight. STUDY DESIGN: We conducted a retrospective study of preterm infants admitted to Canadian Neonatal Network units between 2010 and 2018. Infants were classified into 2 groups based on receipt of antenatal steroids; the latter subgrouped as recent (≤7 days before birth) or latent (>7 days before birth) exposures. The co-exposure was prophylactic indomethacin. The primary outcome was SIP. Multivariable logistic regression analysis was used to calculate aORs. RESULTS: Among 4720 eligible infants, 4121 (87%) received antenatal steroids and 1045 (22.1%) received prophylactic indomethacin. Among infants exposed to antenatal steroids, those who received prophylactic indomethacin had higher odds of SIP (aOR 1.61, 95% CI 1.14-2.28) compared with no prophylactic indomethacin. Subgroup analyses revealed recent antenatal steroids exposure with prophylactic indomethacin had higher odds of SIP (aOR 1.67, 95% CI 1.15-2.43), but latent antenatal steroids exposure with prophylactic indomethacin did not (aOR 1.24, 95% CI 0.48-3.21), compared with the respective groups with no prophylactic indomethacin. Among those not exposed to antenatal steroids, mortality was lower among those who received prophylactic indomethacin (aOR 0.45, 95% CI 0.28-0.73) compared with no prophylactic indomethacin. CONCLUSIONS: In preterm neonates of <26 weeks of gestation or birth weight <750 g, co-exposure of antenatal steroids and prophylactic indomethacin was associated with SIP, especially if antenatal steroids was received within 7 days before birth. Among those unexposed to antenatal steroids, prophylactic indomethacin was associated with lower odds of mortality.
Assuntos
Lesões Encefálicas , Perfuração Intestinal , Canadá , Feminino , Idade Gestacional , Humanos , Indometacina/efeitos adversos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Perfuração Intestinal/induzido quimicamente , Perfuração Intestinal/epidemiologia , Perfuração Intestinal/prevenção & controle , Gravidez , Estudos Retrospectivos , EsteroidesRESUMO
BACKGROUND: The last decade has seen the increasing use of biological medicines in combination with chemotherapy containing 5-fluorouracil/oxaliplatin or irinotecan for the treatment of metastatic colorectal cancer (mCRC). These combinations have resulted in increased progression-free survival (PFS) in patients with mCRC; however, there are remaining concerns over the extent of their effect on overall survival (OS). Published studies to date suggest no major differences between the three currently available monoclonal antibodies (MoAbs); however, there are differences in costs. In addition, there is rising litigation in Brazil in order to access these medicines as they are currently not reimbursed. OBJECTIVE: The aim was to investigate the comparative effectiveness and safety of three MoAbs (bevacizumab, cetuximab and panitumumab) associated with fluoropyrimidine-based chemotherapy regimens and compared to fluoropyrimidine-based chemotherapy alone in patients with mCRC, through an updated systematic review and meta-analysis of concurrent or non-concurrent observational cohort studies, to guide authorities and the judiciary. METHOD: A systematic review and meta-analysis was performed based on cohort studies published in databases up to November 2017. Effectiveness measures included OS, PFS, post-progression survival (PPS), Response Evaluation Criteria In Solid Tumors (RECIST), response rate, metastasectomy and safety. The methodological quality of the studies was also evaluated. RESULTS: A total of 21 observational cohort studies were included. There were statistically significant and clinically relevant benefits in patients treated with bevacizumab versus no bevacizumab mainly around OS, PFS, PPS and the metastasectomy rate, but not for the disease control rates. However, there was an increase in treatment-related toxicities and concerns with the heterogeneity of the studies. CONCLUSION: The results pointed to an advantage in favor of bevacizumab for OS, PFS, PPS, and metastasectomy. Although this advantage may be considered clinically modest, bevacizumab represents a hope for increased survival and a chance of metastasectomy for patients with mCRC. However, there are serious adverse events associated with its use, especially severe hypertension and gastrointestinal perforation, that need to be considered.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Análise Custo-Benefício , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Bevacizumab/economia , Bevacizumab/uso terapêutico , Brasil , Cetuximab/economia , Cetuximab/uso terapêutico , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Honorários Farmacêuticos , Fluoruracila/economia , Fluoruracila/uso terapêutico , Humanos , Hipertensão/induzido quimicamente , Hipertensão/epidemiologia , Incidência , Perfuração Intestinal/induzido quimicamente , Perfuração Intestinal/epidemiologia , Irinotecano/economia , Irinotecano/uso terapêutico , Oxaliplatina/economia , Oxaliplatina/uso terapêutico , Panitumumabe/economia , Panitumumabe/uso terapêutico , Mecanismo de Reembolso/legislação & jurisprudência , Critérios de Avaliação de Resposta em Tumores SólidosRESUMO
ABSTRACT Objective: The advent of multikinase inhibitor (MKI) therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The aim of this manuscript is to communicate rare adverse events that occurred in less than 5% of patients in clinical trials in a subset of patients treated in our hospital. Subjects and methods: Out of 760 patients with thyroid cancer followed up with in our Division of Endocrinology, 29 (3.8%) received treatment with MKIs. The median age at diagnosis of these patients was 53 years (range 20-70), and 75.9% of them were women. Sorafenib was prescribed as first-line treatment to 23 patients with differentiated thyroid cancer and as second-line treatment to one patient with advanced medullary thyroid cancer (MTC). Vandetanib was indicated as first-line treatment in 6 patients with MTC and lenvatinib as second-line treatment in two patients with progressive disease under sorafenib treatment. Results: During the follow-up of treatment (mean 13.7 ± 7 months, median 12 months, range 6-32), 5/29 (17.2%) patients presented rare adverse events. These rare adverse effects were: heart failure, thrombocytopenia, and squamous cell carcinoma during sorafenib therapy and squamous cell carcinoma and oophoritis with intestinal perforation during vandetanib treatment. Conclusions: About 3 to 5 years after the approval of MKI therapy, we learned that MKIs usually lead to adverse effects in the majority of patients. Although most of them are manageable, we still need to be aware of potentially serious and rare or unreported adverse effects that can be life-threatening.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Piperidinas/efeitos adversos , Quinazolinas/efeitos adversos , Carcinoma/tratamento farmacológico , Carcinoma Medular/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Antineoplásicos/efeitos adversos , Ooforite/induzido quimicamente , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos , Trombocitopenia/induzido quimicamente , Fatores de Tempo , Neoplasias da Glândula Tireoide/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Seguimentos , Estimativa de Kaplan-Meier , Sorafenibe/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Perfuração Intestinal/induzido quimicamenteRESUMO
OBJECTIVE: The advent of multikinase inhibitor (MKI) therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The aim of this manuscript is to communicate rare adverse events that occurred in less than 5% of patients in clinical trials in a subset of patients treated in our hospital. SUBJECTS AND METHODS: Out of 760 patients with thyroid cancer followed up with in our Division of Endocrinology, 29 (3.8%) received treatment with MKIs. The median age at diagnosis of these patients was 53 years (range 20-70), and 75.9% of them were women. Sorafenib was prescribed as first-line treatment to 23 patients with differentiated thyroid cancer and as second-line treatment to one patient with advanced medullary thyroid cancer (MTC). Vandetanib was indicated as first-line treatment in 6 patients with MTC and lenvatinib as second-line treatment in two patients with progressive disease under sorafenib treatment. RESULTS: During the follow-up of treatment (mean 13.7 ± 7 months, median 12 months, range 6-32), 5/29 (17.2%) patients presented rare adverse events. These rare adverse effects were: heart failure, thrombocytopenia, and squamous cell carcinoma during sorafenib therapy and squamous cell carcinoma and oophoritis with intestinal perforation during vandetanib treatment. CONCLUSIONS: About 3 to 5 years after the approval of MKI therapy, we learned that MKIs usually lead to adverse effects in the majority of patients. Although most of them are manageable, we still need to be aware of potentially serious and rare or unreported adverse effects that can be life-threatening.
Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Medular/tratamento farmacológico , Carcinoma/tratamento farmacológico , Piperidinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinas/efeitos adversos , Sorafenibe/efeitos adversos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto , Idoso , Feminino , Seguimentos , Insuficiência Cardíaca/induzido quimicamente , Humanos , Perfuração Intestinal/induzido quimicamente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Ooforite/induzido quimicamente , Compostos de Fenilureia/efeitos adversos , Quinolinas/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Trombocitopenia/induzido quimicamente , Fatores de Tempo , Adulto JovemRESUMO
Central nervous system dopaminergic mechanisms have been implicated in the cytokine response to stress and sepsis. We here describe the effects of haloperidol or clozapine in the treatment of sepsis induced by cecal ligation and puncture. Male Wistar rats were subjected to the CLP procedure were treated with haloperidol or clozapine and plasma cytokines, myeloperoxidase activity, markers of organ injury and survival was analyzed. The addition of haloperidol or clozapine to basic support did not diminished hepatic, renal, pancreatic or muscular damage observed after sepsis. Neither haloperidol, nor clozapine, modulates pro and antiinflammatory cytokines after sepsis induction. In addition, haloperidol treatment did not diminished myeloperoxidase activity in the kidney, lung or liver, or altered BALF markers of lung damage or inflammatory infiltration. Our data did not support a role of haloperidol or clozapine as an immunomodulator agent in the treatment of sepsis in an animal model of peritonitis.
Assuntos
Antagonistas de Dopamina/uso terapêutico , Peritônio/patologia , Sepse/tratamento farmacológico , Animais , Biomarcadores/sangue , Clozapina/farmacologia , Clozapina/uso terapêutico , Modelos Animais de Doenças , Antagonistas de Dopamina/farmacologia , Haloperidol/farmacologia , Haloperidol/uso terapêutico , Inflamação , Perfuração Intestinal/induzido quimicamente , Perfuração Intestinal/patologia , Masculino , Infiltração de Neutrófilos/efeitos dos fármacos , Ratos , Ratos Wistar , Sepse/induzido quimicamenteRESUMO
OBJECTIVES: To investigate the effect of hydrocortisone treatment on survival without bronchopulmonary dysplasia (BPD) and to study whether serum cortisol concentrations predict the response. STUDY DESIGN: We performed a randomized, placebo-controlled trial on infants with gestation < or =30 weeks, body weight of 501 to 1250 g, and respiratory failure. Hydrocortisone was started before 36 hours of age and given for 10 days at doses from 2.0 to 0.75 mg/kg per day. Shortly before hydrocortisone treatment, basal and stimulated (ACTH, 0.1 microg/kg) serum cortisols were measured. RESULTS: The study was discontinued early, because of gastrointestinal perforations in the hydrocortisone group (4/25 vs 0/26, P = .05); 3 of the 4 had received indomethacin/ibuprofen. The incidence of BPD (28% vs placebo 42%, P = 0.28) tended to be lower, and patent ductus arteriosus (36% vs 73%, P = .01) was lower in the hydrocortisone group. The hydrocortisone-treated infants with serum cortisol concentrations above the median had a high risk of gastrointestinal perforation. In infants with cortisol values below the median, hydrocortisone treatment increased survival without BPD. CONCLUSIONS: Serum cortisol concentrations measured shortly after birth may identify those very high-risk infants who may benefit from hydrocortisone supplementation.
Assuntos
Anti-Inflamatórios/uso terapêutico , Displasia Broncopulmonar/prevenção & controle , Hidrocortisona/sangue , Hidrocortisona/uso terapêutico , Mortalidade Infantil , Anti-Inflamatórios/efeitos adversos , Feminino , Finlândia , Humanos , Hidrocortisona/efeitos adversos , Recém-Nascido , Perfuração Intestinal/induzido quimicamente , Masculino , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
Se presenta un paciente masculino de 64 años de edad, con historia de dolor abdominal de 15 horas de evolución, quien refiere un cuadro inespecífico inicialmente, para luego convertirse en un abdomen agudo quirúrgico con peritonitis, sin historia de fiebre y sin elevación de glóbulos blancos. Antecedente de tener diagnóstico de Mieloma Múltiple y recibiendo tratamiento con dexametasona por 14 meses. Se documenta por laparotomía exploradora perforación única de colon sigmoides y peritonitis difusa, sin evidencia de lesión diverticular subyacente ni causa infecciosa o isquémica en el colon perforado. Se maneja con resección de colon sigmoides y colostomía con bolsa de Hartmann. Ante la falta de evidencia de otra causa aparente, esta perforación se atribuye al uso prolongado de esteroides y se analiza el caso con respecto a la literatura disponible hasta el momento
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Abdome Agudo , Dor Abdominal , Colo Sigmoide , Colostomia , Dexametasona , Perfuração Intestinal/induzido quimicamente , PeritoniteAssuntos
Dexametasona/efeitos adversos , Glucocorticoides/efeitos adversos , Transtornos do Crescimento/induzido quimicamente , Recém-Nascido de muito Baixo Peso , Perfuração Intestinal/induzido quimicamente , Gastropatias/induzido quimicamente , Dexametasona/uso terapêutico , Método Duplo-Cego , Glucocorticoides/uso terapêutico , Humanos , Recém-Nascido , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Three preterm infants exposed antenatally to indomethacin developed a characteristic syndrome consisting of edema and hydrops with a bleeding disorder at birth, oliguric renal failure during the first 3 postnatal days, and acute pneumoperitoneum resulting from localized ileal perforation(s) at the end of the first week of life. Despite the value of indomethacin for arresting preterm labor, the physician must take into account the potential hazards of drug toxicity.
Assuntos
Líquido Amniótico , Doenças do Íleo/induzido quimicamente , Indometacina/efeitos adversos , Doenças do Prematuro/induzido quimicamente , Perfuração Intestinal/induzido quimicamente , Nefropatias/induzido quimicamente , Tocólise/efeitos adversos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Gravidez , SíndromeRESUMO
Between 1980 and 1984, of 107 patients receiving 16 mg/d of dexamethasone for spinal cord compression, three (2.8%) developed gastrointestinal (GI) perforation and two (1.9%) GI bleeding; of 226 being tapered from 100 mg/d of dexamethasone, perforation occurred in six (2.7%) and GI bleeding in eight (3.5%). Of 125 patients with GI perforations treated between 1979 and 1986, 41 (33%) were on steroids, 24 for neurologic disease. Median duration of steroid therapy was 24 days; 20 (91%) of the neurologic patients perforated within 30 days. The steroid group had more free peritoneal involvement (p less than 0.00001), but fewer signs and symptoms of peritonitis (p less than 0.000001) than the nonsteroid group. Seventeen patients were receiving steroids for cord compression; they had significantly more rectosigmoid perforations (p less than 0.014) and associated constipation (p less than 0.000001) than the 108 remaining patients. GI perforation is a less well-recognized complication of steroid therapy in neurologic patients than is GI bleeding though it occurs as frequently, is more difficult to diagnose, and far more serious. In steroid-treated patients, prevention of constipation might avert this serious complication, while early diagnosis will improve the outcome.