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1.
Artigo em Inglês | MEDLINE | ID: mdl-32178607

RESUMO

This report summarises Australian spontaneous surveillance data for adverse events following immunisation (AEFI) for 2018 reported to the Therapeutic Goods Administration and describes reporting trends over the 19-year period 1 January 2000 to 31 December 2018. There were 4221 AEFI records for vaccines administered in 2018, an annual AEFI reporting rate of 16.9 per 100,000 population. There was a 2.9% increase in the overall AEFI reporting rate in 2018 compared to 2017. This slight increase in reported adverse events in 2018 was likely due to new additions to the National Immunisation Program schedule, namely meningococcal ACWY vaccination for children aged 12 months, enhanced immunogenicity trivalent influenza vaccines for adults aged ≥65 years, and state- and territory-funded seasonal influenza vaccination programs for children aged 6 months to <5 years. AEFI reporting rates for most individual vaccines in 2018 were similar to 2017. The most commonly reported adverse events were injection site reaction (34%), pyrexia (15%), rash (15%), vomiting (8%), headache (6%) and pain (6%). Two deaths were reported to the TGA but no clear causal relationship with vaccination was found.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Programas de Imunização , Vacinação/efeitos adversos , Adolescente , Adulto , Idoso , Austrália/epidemiologia , Criança , Pré-Escolar , Exantema/induzido quimicamente , Febre/induzido quimicamente , Humanos , Esquemas de Imunização , Lactente , Vacinas contra Influenza , Reação no Local da Injeção , Masculino , Adulto Jovem
3.
PLoS One ; 15(1): e0227796, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929600

RESUMO

BACKGROUND: Intravenous immunoglobulin (IVIG) therapy is used in the treatment of various diseases, and IVIG-related adverse effects (IVIG-AEs) vary from mild to severe. However, the mechanisms underlying IVIG-AEs and the potential predictive factors are not clear. This study investigated whether certain IVIG-AEs can be predicted before IVIG administration. STUDY DESIGN AND METHODS: This retrospective cohort study at the Division of Neurology, Saitama Children's Medical Center included patients enrolled from 2008 to 2018 who were < 18 years old and received IVIG for the first time. IVIG-AEs were classified according to the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: A total of 104 patients fulfilled the inclusion criteria. The rate of IVIG-AEs was 37.5% (39/104). The most frequent IVIG-AEs were fever (41.0% [16/39]) and headache (38.5% [15/39]). AEs were below grade 2 in all except one patient and there were no grade 4 AEs. High serum total protein (TP) level was significantly related to the occurrence of IVIG-AEs (odds ratio, 14.8; 95% confidence interval, 2.4-90.5; P < 0.01). The optimal cutoff TP level was 6.7 g/dL. Although low WBC count and immunoglobulin G level may be predictive risk factors of IVIG-AEs, it was not confirmed in this study. CONCLUSION: IVIG-AEs occurred in 37.5% of cases, and most were mild. TP was the best predictive risk factor of IVIG-AEs before IVIG administration. These results may aid in elucidating the mechanism underlying IVIG-AEs.


Assuntos
Imunoglobulinas Intravenosas/efeitos adversos , Criança , Pré-Escolar , Exantema/induzido quimicamente , Feminino , Febre/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Incidência , Lactente , Masculino , Náusea/induzido quimicamente , Fatores de Proteção , Estudos Retrospectivos , Vômito/induzido quimicamente
4.
Br J Anaesth ; 124(1): 44-62, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31653394

RESUMO

Most cases of serotonin toxicity are provoked by therapeutic doses of a combination of two or more serotonergic drugs, defined as drugs affecting the serotonin neurotransmitter system. Common serotonergic drugs include many antidepressants, antipsychotics, and opioid analgesics, particularly fentanyl, tramadol, meperidine (pethidine), and methadone, but rarely morphine and other related phenanthrenes. Symptoms of serotonin toxicity are attributable to an effect on monoaminergic transmission caused by an increased synaptic concentration of serotonin. The serotonin transporter (SERT) maintains low serotonin concentrations and is important for the reuptake of the neurotransmitter into the presynaptic nerve terminals. Some opioids inhibit the reuptake of serotonin by inhibiting SERT, thus increasing the plasma and synaptic cleft serotonin concentrations that activate the serotonin receptors. Opioids that are good inhibitors of SERT (tramadol, dextromethorphan, methadone, and meperidine) are most frequently associated with serotonin toxicity. Tramadol also has a direct serotonin-releasing action. Fentanyl produces an efflux of serotonin, and binds to 5-hydroxytryptamine (5-HT)1A and 5-HT2A receptors, whilst methadone, meperidine, and more weakly tapentadol, bind to 5-HT2A but not 5-HT1A receptors. The perioperative period is a time where opioids and other serotonergic drugs are frequently administered in rapid succession, sometimes to patients with other serotonergic drugs in their system. This makes the perioperative period a relatively risky time for serotonin toxicity to occur. The intraoperative recognition of serotonin toxicity is challenging as it can mimic other serious syndromes, such as malignant hyperthermia, sepsis, thyroid storm, and neuroleptic malignant syndrome. Anaesthetists must maintain a heightened awareness of its possible occurrence and a readiness to engage in early treatment to avoid poor outcomes.


Assuntos
Analgésicos Opioides/efeitos adversos , Anestesiologistas , Serotoninérgicos/efeitos adversos , Síndrome da Serotonina/terapia , Febre/induzido quimicamente , Humanos , Complicações Intraoperatórias/induzido quimicamente , Síndrome da Serotonina/diagnóstico
5.
BMC Cancer ; 19(1): 1217, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842789

RESUMO

BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) is increasingly been used to prevent febrile neutropenia (FN) associated with the administration of chemotherapy for various cancers. The most common adverse effects of G-CSF are bone pain and injection-site reactions and aortitis has rarely been reported. We report herein a rare case of G-CSF associated with aortitis in a woman with advanced breast cancer. CASE PRESENTATION: A 72-year-old woman with estrogen receptor-negative human epidermal growth factor 2-positive breast cancer with distant metastases in the lung was admitted. Her treatment was initiated with docetaxel in combination with trastuzumab and pertuzumab followed by the supportive use of a long-acting G-CSF, pegfilgrastim. After administration of pegfilgrastim on day 5, the patient had an intermittent fever (body temperature up to 39.6 °C) on day 9 which continued irrespective of taking levofloxacin. She visited our outpatient clinic on day 13 with no objective symptoms other than fever. Laboratory tests revealed a high neutrophil count (15,000/µl) and a high C-reactive protein (CRP) level (46.35 mg/dl) without any other abnormalities. There was no response upon administration of antimicrobial agents. An 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) revealed thickening of the wall of the descending thoracic aorta and left pleural effusion. Therefore, thoracic aortitis induced by pegfilgrastim was suspected. On day 19, the fever resolved spontaneously followed by a gradual reduction in the neutrophil count and CRP level. In the follow-up CT, the aortic wall thickness and pleural effusion had disappeared. CONCLUSIONS: G-CSF may cause aortitis due to stimulation of the production of inflammatory cytokines. In case of high continuous fever after administration of pegfilgrastim, aortitis should be suspected unless there are other infectious findings.


Assuntos
Aortite/induzido quimicamente , Neoplasias da Mama/tratamento farmacológico , Neutropenia Febril Induzida por Quimioterapia/prevenção & controle , Filgrastim/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Polietilenoglicóis/efeitos adversos , Idoso , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aortite/diagnóstico por imagem , Docetaxel , Feminino , Febre/induzido quimicamente , Filgrastim/uso terapêutico , Fluordesoxiglucose F18 , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Polietilenoglicóis/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Trastuzumab
6.
BMJ Case Rep ; 12(9)2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31570359

RESUMO

A 20-year-old college student presented with high grade, intermittent fever for 10 days associated with blood stained loose stools after taking tablet levamisole for 17 days for vitiligo vulgaris. He was febrile, had a toxic appearance and appeared pale. Investigations showed neutropaenia with thrombocytopaenia. Blood cultures were sterile and stool cultures did not grow any enteric pathogens. His bone marrow examination was suggestive of an aplastic anaemia. He was administered empirical antibiotics, granulocyte colony stimulating factor and platelet transfusions. However, his fever and blood stained stools persisted. A repeat bone marrow examination after 2 weeks still revealed a hypoplastic marrow. Hence, a diagnosis of a levamisole induced bone marrow failure was made. While being worked up for an allogeneic stem cell transplantation, he developed neutropaenic enterocolitis and refractory septic shock with carbapenem resistant Klebsiella pneumoniae and succumbed to his illness.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Levamisol/efeitos adversos , Choque Séptico/induzido quimicamente , Vitiligo/tratamento farmacológico , Adjuvantes Imunológicos/administração & dosagem , Diarreia/induzido quimicamente , Evolução Fatal , Febre/induzido quimicamente , Fator Estimulador de Colônias de Granulócitos , Humanos , Levamisol/administração & dosagem , Masculino , Neutropenia/induzido quimicamente , Transfusão de Plaquetas , Choque Séptico/fisiopatologia , Adulto Jovem
7.
J Vet Emerg Crit Care (San Antonio) ; 29(6): 686-689, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31637843

RESUMO

OBJECTIVE: To describe the clinical characteristics of acute chlorfenapyr toxicity in 3 dogs from a single household. CASE SUMMARY: A 4-year-old neutered female Labrador Retriever was presented with severe hyperthermia (42.6°C [108.6°F]). Emergency management consisting of fluid resuscitation, active cooling, general anesthesia, gastric lavage, activated charcoal administration, and intravenous lipid emulsion was started immediately on the suspicion of toxin exposure. The dog developed symptoms following peracute death in 2 other small breed dog housemates. All dogs had a rapid onset of gastrointestinal signs, neurologic signs, and panting. The dog made a rapid and complete recovery and was discharged 48 hours later. Examination of gastric contents collected from the deceased dogs identified the presence of chlorfenapyr. NEW OR UNIQUE INFORMATION PROVIDED: This is the first reported case of chlorfenapyr toxicity in dogs. Previous case reports in human medicine have reported a variable mortality rate, although 1 of 3 dogs described here made a complete recovery. Chlorfenapyr should be considered in cases of suspected toxicity with similar presenting signs.


Assuntos
Doenças do Cão/induzido quimicamente , Piretrinas/toxicidade , Animais , Carvão Vegetal/uso terapêutico , Cães , Emulsões Gordurosas Intravenosas/uso terapêutico , Evolução Fatal , Feminino , Febre/induzido quimicamente , Febre/terapia , Febre/veterinária , Envenenamento
8.
Biomed Res ; 40(4): 153-161, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31413236

RESUMO

Cold-inducible RNA-binding protein (CIRBP) plays important roles in protection against harmful effects of cold temperature. We previously found that several splicing variants of CIRBP mRNA are constitutively expressed in the heart of non-hibernating euthermic hamsters and that one of the variants is predominantly expressed with remarkable reduction in the expression of other variants in hibernating hypothermic hamsters. The aim of this study was to determine whether the regulation of alternative splicing is a common function in a non-hibernator, the mouse. The expression of CIRBP mRNA was assessed by RT-PCR. In euthermic control mice, several splicing variants of CIRBP mRNA were detected in various organs. When hypothermia was induced in mice by using isoflurane anesthesia, the short form variant, which encodes full-length functional CIRBP, was predominantly detected. Keeping body temperature of anesthetized mice at 37°C prevented changes in the splicing pattern. Exposure of mice to a low temperature did not change the splicing pattern, suggesting that endogenous neuronal and/or humoral pathways activated in response to cold stimuli applied to the body surface play minor roles. In agreement with this, the shift in alternative splicing was reproduced in isolated leukocytes in vitro when they were incubated at 28°C. Since application of a TRPM8 or TRPA1 agonist at 37°C failed to promote the shift in the splicing pattern, it seems likely that cold-sensitive channels are not involved in the splicing regulation. Therefore, it is probable that a substantial reduction of temperature is a major cause of the regulation of alternative splicing of CIRBP transcripts. The regulatory system of CIRBP expression at the level of alternative splicing, which was originally discovered in the hibernating hamster, commonly exists in non-hibernators such as mice.


Assuntos
Processamento Alternativo , Febre/metabolismo , RNA Mensageiro/biossíntese , Proteínas de Ligação a RNA/biossíntese , Animais , Temperatura Corporal , Cricetinae , Febre/induzido quimicamente , Febre/patologia , Hibernação , Masculino , Camundongos
9.
J Therm Biol ; 84: 245-249, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31466760

RESUMO

Leukotrienes mediate several inflammatory events such as neutrophil chemoattraction, leukocyte adhesion, and central-release of cytokines and fever. However, there is no information available about their putative role in lipopolysaccharide (LPS) tolerance. The rational of the present study was to find out if central leukotrienes are involved in the development of LPS tolerance. Thus, we inhibited central leukotriene synthesis in tolerant rats using a pharmacological tool, i.e., a selective inhibitor of leukotriene synthesis MK-886 injected into the third ventricle (3V) of rats. Body core temperature (Tb) was measured using a datalogger placed inside the abdominal cavity. A low-dose of LPS (100 µg/kg ip) was given for 4 consecutive days to induce LPS tolerance. At day 4, rats received a microinjection of MK-886 into the 3V immediately before LPS, whereas control groups were treated with vehicle (saline). We observed that LPS failed to induce plasma cytokines surges, increased hypothalamic PGE2 levels and fever 3 days post LPS treatment, aptly characterizing the tolerance. When MK-886 was given to control rats treated with saline, no significant change in Tb was observed. However, a full LPS-induced fever was observed in tolerant rats pretreated with MK-886, which was associated with an enhancement in the hypothalamic PGE2 levels, that were not accompanied by plasma cytokines (IL-1ß, and IL-6) and PGE2 surges. These data are consistent with the notion that central leukotrienes play a role in fever tolerance to LPS.


Assuntos
Febre/imunologia , Leucotrienos/imunologia , Animais , Temperatura Corporal , Dinoprostona/imunologia , Febre/induzido quimicamente , Hipotálamo/imunologia , Lipopolissacarídeos , Masculino , Ratos Wistar
10.
J Therm Biol ; 84: 36-44, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31466775

RESUMO

It is still an open question as to whether or not aseptic injuries affect the generation of fever due to exogenous pyrogens including bacterial products. Therefore, in the present paper we have investigated the course of endotoxin fever in rats induced with lipopolysaccharide (LPS; given intraperitoneally in a dose of 50 µg/kg) 48 h after subcutaneous administration of turpentine oil (TRP; 0.1 mL per rat) that causes aseptic necrosis of tissues. We found that febrile response was significantly augmented in the animals pre-treated with turpentine compared to control rats (pre-treated with saline), and that observed excessive elevation of body temperature (Tb) was accompanied by enhanced release of fever mediators: interleukin-6 (IL-6) and prostaglandin E2 (PGE2) into plasma. Moreover, we found that sensitization to pyrogenic effects of lipopolysaccharide was associated with the increase in plasma level of high mobility group box 1 protein (HMGB1), one of the best-known damage-associated molecular patterns (DAMP), which was recently discovered as inflammatory mediator. Since the injection of anti-HMGB1 antibodies weakened observed hyperpyrexia in the animals pre-treated with turpentine, we conclude that HMGB1 is a plasma-derived factor released in the course of aseptic injury that enhances pyrogenic effects of LPS.


Assuntos
Febre/sangue , Proteína HMGB1/sangue , Animais , Dinoprostona/sangue , Febre/induzido quimicamente , Membro Posterior/patologia , Interleucina-6/sangue , Lipopolissacarídeos , Masculino , Necrose , Pirogênios , Ratos Wistar , Terebintina/farmacologia
11.
Pharmacol Biochem Behav ; 185: 172762, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31445057

RESUMO

RATIONALE: The majority of synthetic cathinone research has used only male subjects, and as a result there are few studies assessing the impact of biological sex on their effects. OBJECTIVES: The current work extends the characterization of the second-generation synthetic cathinone, α-PVP, by investigating how biological sex impacts α-PVP's aversive and rewarding effects important to its use and potential abuse. METHODS: A combined conditioned taste avoidance/conditioned place preference preparation was utilized in which adult male and female Sprague Dawley rats were injected with 1.5, 3 or 6 mg/kg of racemic α-PVP or vehicle (saline) (IP). Following a 24-day washout period, rats were then tested for thermoregulatory effects of α-PVP using subcutaneous microchips to measure body temperature changes over the course of 8 h. This was followed 21 days later by assessments for α-PVP-induced locomotor activity and stereotypies over a 1-h session. RESULTS: Dose-dependent conditioned taste avoidance was evident in both males and females, although females displayed weaker avoidance at 3 mg/kg compared to males. Males displayed a dose-dependent conditioned place preference, while females did not form a place preference at any dose. α-PVP elicited dose- and time-dependent hyperthermia, with males displaying a faster on-set and delayed off-set compared to females. α-PVP also produced dose- and time-dependent increases in locomotor activity (F > M) and stereotypies (M > F). CONCLUSIONS: As described, males displayed greater rewarding (as indexed by place preference conditioning) and aversive (as indexed by taste avoidance, hyperthermia and stereotypies) effects of α-PVP. Although comparisons between males and females in α-PVP self-administration have not been reported, these data suggest that males may be more likely to use the drug. The implications for sex differences in human use of α-PVP were discussed.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Febre/induzido quimicamente , Locomoção/efeitos dos fármacos , Pentanonas/farmacologia , Pirrolidinas/farmacologia , Paladar/efeitos dos fármacos , Animais , Temperatura Corporal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Condicionamento Clássico , Relação Dose-Resposta a Droga , Feminino , Masculino , Atividade Motora/efeitos dos fármacos , Pentanonas/administração & dosagem , Pirrolidinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Recompensa , Fatores Sexuais
12.
Artigo em Inglês | MEDLINE | ID: mdl-31315166

RESUMO

This report summarises Australian passive surveillance data for adverse events following immunisation (AEFI) for 2017 reported to the Therapeutic Goods Administration and describes reporting trends over the 18-year period 1 January 2000 to 31 December 2017. There were 3,878 AEFI records for vaccines administered in 2017; an annual AEFI reporting rate of 15.8 per 100,000 population. There was a 12% increase in the overall AEFI reporting rate in 2017 compared with 2016. This increase in reported adverse events in 2017 compared to the previous year was likely due to the introduction of the zoster vaccine (Zostavax®) provided free for people aged 70­79 years under the National Immunisation Program (NIP) and also the state- and territory-based meningococcal ACWY conjugate vaccination programs. AEFI reporting rates for most other individual vaccines in 2017 were similar to 2016. The most commonly reported reactions were injection site reaction (34%), pyrexia (17%), rash (15%), vomiting (8%) and pain (7%). The majority of AEFI reports (88%) described non-serious events. Two deaths were reported that were determined to have a causal relationship with vaccination; they occurred in immunocompromised people contraindicated to receive the vaccines.


Assuntos
Doenças do Sistema Imunitário/epidemiologia , Vacinação/efeitos adversos , Vacinas/efeitos adversos , Adolescente , Adulto , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Austrália/epidemiologia , Criança , Pré-Escolar , Exantema/induzido quimicamente , Exantema/epidemiologia , Feminino , Febre/induzido quimicamente , Febre/epidemiologia , Vacina contra Herpes Zoster , Humanos , Programas de Imunização , Lactente , Reação no Local da Injeção/epidemiologia , Masculino , Pessoa de Meia-Idade , Dor/induzido quimicamente , Dor/epidemiologia , Vigilância da População , Vacinação/normas , Vacinação/estatística & dados numéricos , Vacinas/administração & dosagem , Vômito/induzido quimicamente , Vômito/epidemiologia , Adulto Jovem
13.
Support Care Cancer ; 27(10): 3667-3679, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31222393

RESUMO

Febrile neutropenia (FN) is an inflammatory response causing fever that may develop during cancer therapy-induced neutropenia. FN may herald life-threatening infectious complications and should therefore be considered a medical emergency. Patients presenting with FN are routinely subjected to careful history taking and physical examination including X-rays and microbiological evaluations. Nevertheless, an infection is documented clinically in only 20-30% of cases, whereas a causative microbial pathogen is not identified in over 70% of FN cases. The oral cavity is generally only visually inspected. Although it is recognized that ulcerative oral mucositis may be involved in the development of FN, the contribution of infections of the periodontium, the dentition, and salivary glands may be underestimated. These infections can be easily overlooked, as symptoms and signs of inflammation may be limited or absent during neutropenia. This narrative review is aimed to inform the clinician on the potential role of the oral cavity as a potential source in the development of FN. Areas for future research directed to advancing optimal management strategies are discussed.


Assuntos
Antineoplásicos/efeitos adversos , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/microbiologia , Boca/microbiologia , Estomatite/microbiologia , Antineoplásicos/uso terapêutico , Dentição , Feminino , Febre/induzido quimicamente , Febre/microbiologia , Humanos , Masculino , Boca/patologia , Neoplasias/tratamento farmacológico , Periodonto/microbiologia , Glândulas Salivares/microbiologia , Estomatite/patologia
14.
Arthritis Rheumatol ; 71(11): 1955-1963, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31161734

RESUMO

OBJECTIVE: To assess long-term efficacy and safety of canakinumab and the response to vaccination in children ages ≤5 years with cryopyrin-associated periodic syndrome (CAPS). METHODS: CAPS patients (ages ≤5 years) received 2 mg/kg canakinumab subcutaneously every 8 weeks; patients with neonatal-onset multisystem inflammatory disease (NOMID) received a starting dose of 4 mg/kg in this open-label trial. Efficacy was evaluated using physician global assessment of disease activity and serum levels of C-reactive protein (CRP) and amyloid A (SAA). Adverse events (AEs) were recorded. Vaccination response was evaluated using postvaccination antibody titers at 4 and 8 weeks after immunization. RESULTS: Of the 17 patients enrolled, 12 (71%) had Muckle-Wells syndrome, 4 (24%) had NOMID, and 1 (6%) had familial cold autoinflammatory syndrome. All 17 patients had a complete response to canakinumab. Disease activity improved according to the physician global assessment, and for 65% of the patients autoinflammatory disease was characterized as "absent" at the end of the study. Median CRP levels decreased over time. No such change was evident in SAA levels. During the extension study, postvaccination antibody titers increased above protective levels in 16 (94%) of 17 assessable vaccinations. Ten of the patients (59%) had AEs suspected to be related to canakinumab; 8 (47%) experienced at least 1 serious AE (SAE). None of the AEs or SAEs required interruption of canakinumab therapy. CONCLUSION: Our findings indicate that canakinumab effectively maintains efficacy through 152 weeks and appears to have no effect on the ability to produce antibodies against standard childhood non-live vaccines. The safety profile of canakinumab was consistent with previous studies, supporting long-term use of canakinumab for CAPS in children ≤5 years of age.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Síndromes Periódicas Associadas à Criopirina/tratamento farmacológico , Formação de Anticorpos/imunologia , Proteína C-Reativa/metabolismo , Pré-Escolar , Síndromes Periódicas Associadas à Criopirina/imunologia , Síndromes Periódicas Associadas à Criopirina/metabolismo , Diarreia/induzido quimicamente , Feminino , Febre/induzido quimicamente , Humanos , Lactente , Recém-Nascido , Masculino , Nasofaringite/induzido quimicamente , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/etiologia , Proteína Amiloide A Sérica/metabolismo , Resultado do Tratamento , Vacinas/uso terapêutico
15.
J Dermatol ; 46(8): 716-719, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31180164

RESUMO

Pyrexia is the most common adverse event in patients with melanoma or other solid organ malignancies that are treated with the combination of dabrafenib and trametinib (combi-DT). Given the expanded indication for combi-DT, management of pyrexia is a high priority. No previous case series has revealed which blood markers reflect the course of pyrexia and there is no consensus on the management strategy for pyrexia. The current case series study describes the utility of neutrophil count (NC), neutrophil ratio (NR) and C-reactive protein (CRP) in 11 patients with metastatic melanoma and BRAF V600 mutations who experienced pyrexia during combi-DT in our department. We also described the clinical course of pyrexia episodes that were managed with the concomitant use of oral prednisolone and immediate withdrawal of combi-DT. Consequently, the analysis of 37 pyrexia episodes in 11 patients showed that the differences in NC, NR and CRP at the onset of pyrexia were significantly different from those at pyretolysis (P = 0.01, 0.006 and 0.03, respectively). Additionally, in the 24 pyrexia episodes treated with the concomitant use of oral prednisolone and the immediate withdrawal of combi-DT, the mean duration of pyrexia and the mean time to restart combi-DT were 3 and 6 days, respectively. Therefore, the blood markers that reflect the course of pyrexia during combi-DT may be helpful for the appropriate management of pyrexia; also, our management strategy for pyrexia successfully reduced the duration of pyrexia and did not require a long-term drug holiday. Further large-scale studies are required to verify our results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Proteína C-Reativa/análise , Febre/diagnóstico , Imidazóis/efeitos adversos , Neutrófilos , Oximas/efeitos adversos , Piridonas/efeitos adversos , Pirimidinonas/efeitos adversos , Administração Oral , Adulto , Idoso , Biomarcadores/sangue , Estudos de Viabilidade , Feminino , Febre/sangue , Febre/induzido quimicamente , Febre/tratamento farmacológico , Humanos , Contagem de Leucócitos , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
Eur J Cancer Care (Engl) ; 28(5): e13125, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31222826

RESUMO

OBJECTIVE: To examine risk of emergency hospital admission and survival following adjuvant chemotherapy for early breast cancer. METHODS: Linked data from New South Wales population-based and clinical cancer registries (2008-2012), hospital admissions, official death records and pharmaceutical benefit claims. Women aged ≥18 years receiving adjuvant chemotherapy for early-stage operable breast cancer in NSW public hospitals were included. Odds ratios (OR) for emergency hospitalisation within 6 months following chemotherapy initiation were estimated using logistic regression and survival using Kaplan-Meier and Cox proportional hazards methods. RESULTS: A total of 3,950 women were included and 30.6% were hospitalised. The most common principal diagnosis at admission was neutropenia (30.8%). Women receiving docetaxel/carboplatin/trastuzumab (TCH) and docetaxel/cyclophosphamide (TC) were the most frequently hospitalised. After adjustment for demographic and clinical factors, the increased risk of hospitalisation for TCH and TC remained compared with doxorubicin/cyclophosphamide 3-weekly (OR 1.71, 95% confidence interval [CI] 1.24-2.37 and OR 1.47, 95% CI 1.17-1.85 respectively). Five-year overall survival was similar for women who were (92.2%, 95% CI 90.7-93.8) and were not hospitalised (93.1%, 95% CI 92.1-94.1). CONCLUSION: Emergency hospitalisations following chemotherapy for early breast cancer were relatively common, especially following docetaxel-containing protocols. Further examination of reasons for admission is needed to inform actions to improve patient safety.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Febre/epidemiologia , Hospitalização/estatística & dados numéricos , Neutropenia/epidemiologia , Taxa de Sobrevida , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Quimioterapia Adjuvante , Neutropenia Febril Induzida por Quimioterapia/epidemiologia , Neutropenia Febril Induzida por Quimioterapia/etiologia , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Docetaxel/administração & dosagem , Emergências , Feminino , Febre/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , New South Wales/epidemiologia , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Trastuzumab/administração & dosagem
17.
Eur J Pharmacol ; 858: 172495, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31238065

RESUMO

Hyperthermia is most dangerous clinical symptom of acute MDMA administration, and a key factor related to potentially life-threatening MDMA-induced complications. MDMA induces a consistently faster onset of brain hyperthermia when compared to a delayed and moderate hyperthermia in the body, and the most harmful effects of MDMA are related to its modulation of neural functions. The primary focus of this study was to investigate the effects of minocycline, a centrally acting tetracycline derivative on MDMA-induced brain hyperthermia at high ambient temperature. However, we also simultaneously recorded body temperature, heart rate, and locomotor activity changes, allowing us to gain a better understanding of the mechanisms underlying the MDMA-induced hyperthermic response. We also investigated the effects of MDMA at normal ambient temperature to provide further evidence as to the importance of environmental factors on the intensity of MDMA's temperature effects. At normal ambient temperature, MDMA (10 mg/kg, i.p.) induced a significant brain and body hypothermia for the first 90 min following drug administration, and significantly increased heart rate and locomotor activity compared to saline controls. At high ambient temperature however, MDMA (10 mg/kg, i.p.) induced a robust and extended brain and body hyperthermia, as well as significantly increased heart rate and locomotor activity. A 3-day minocycline (50 mg/kg, i.p.) pre-treatment significantly attenuated MDMA-induced increases in brain temperature, body temperature, heart rate, and locomotor activity. Our findings indicate that minocycline is more effective in attenuating the exacerbated MDMA-induced hyperthermic response in the brain compared to the body at high ambient temperature.


Assuntos
Encéfalo/efeitos dos fármacos , Febre/induzido quimicamente , Febre/tratamento farmacológico , Minociclina/farmacologia , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , Animais , Temperatura Corporal/efeitos dos fármacos , Encéfalo/fisiopatologia , Febre/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley
20.
Medicine (Baltimore) ; 98(22): e15868, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145343

RESUMO

BACKGROUND: Benralizumab, a humanized, anti-interleukin-5 (anti-IL-5) receptor α monoclonal antibody that directly and rapidly depletes eosinophils, has shown significant efficacy in reducing asthma exacerbations and improving lung function in moderate to severe eosinophilic asthma patients. However, there is some controversy regarding the adverse events (AEs) of benralizumab and a comprehensive analysis of these AEs has not been performed. This study aimed to assess the incidence of these AEs in published randomized controlled trials (RCTs). METHODS: We searched for RCTs in the Embase, PubMed and Cochrane databases that compared benralizumab with placebo in moderate to severe eosinophilic asthma patients. The outcome was the incidence of AEs during the observation period. RESULTS: Eight RCTs were analyzed in this study. Patients treated with benralizumab had a lower risk of overall AEs (risk ratio (RR) 0.94; 95% confidence interval (CI) 0.90-0.98), serious adverse events (SAEs) (RR 0.82; 95% CI 0.68-0.98), asthma exacerbation (RR 0.72, 95% CI 0.61-0.85), bronchitis (RR 0.76, 95% CI 0.59-0.96) and sinusitis (RR 0.64, 95% CI 0.48-0.85), but had a higher risk of headache (RR 1.42, 95% CI 1.07-1.87) and pyrexia (RR 2.26, 95% CI 1.32-3.87) than patients treated with placebo. No increased incidence of death, hypersensitivity, injection-site reactions, nasopharyngitis, rhinitis, upper respiratory tract infection, influenza, cough, nausea, back pain or arthralgia was observed with benralizumab compared with placebo. CONCLUSIONS: Benralizumab reduced the risk of SAEs, asthma exacerbation, bronchitis and sinusitis, and aggravated the risk of headache and pyrexia. Other AEs were comparable between the benralizumab group and placebo group. Therefore, benralizumab is a relatively safe drug, but vigilance regarding AEs is imperative during long-term treatment.


Assuntos
Antiasmáticos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Asma/tratamento farmacológico , Eosinofilia Pulmonar/tratamento farmacológico , Adolescente , Adulto , Idoso , Criança , Método Duplo-Cego , Feminino , Febre/induzido quimicamente , Cefaleia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto Jovem
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