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1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(5): 1654-1663, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31607328

RESUMO

OBJECTIVE: To compare the effects of intravenous and subcutaneous injection of bortezomib on incidence and relative risk of peripheral neuropathy in patients with multiple myeloma(MM). METHODS: The electronic database of PubMed, Embase, Cochrance library, CNKI and related meeting records were searched by computers. The data were derived all from a matched randomized controlled studies. The incidence, relative risk(RR) and 95% confidence interval of peripheral neuropathy caused by intravenous and subcustaneous injections were calculated by the statistical methods. RESULTS: Four RCT studies were selected for meta-analysis, with a total of 911 patients (479 cases and 432 cases in the subcutaneous injection and intravenous injection groups, respectively). The incidence of peripheral neuropathy in the intravenous injection group was 41.4% (95% CI=0.137-0.692, P=0.003), and the incidence of >2 grade of peripheral neuropathy was 15.6% (95% CI=0.005-0.308, P=0.043). The corresponding incidence rates of the subcutaneous injection group were 16% (95% CI=0.021-0.299, P=0.024) and 3.4% (95% CI=-0.011-0.080, P=0.141) respectively. Compared with the intravenous injection group, the RR of peripheral neuropathy and the relative risk of peripheral neuropathy above grade 2 were 0.525, 95% CI=0.297-0.928 (P=0.027) and 0.376, 95% CI=0.196-0.722 (P=0.003) respectively. CONCLUSION: Subcutaneous injection of bortezomib at therapeutic doses significantly reduces the incidence of peripheral neuropathy compared with intravenous injection.


Assuntos
Bortezomib/efeitos adversos , Mieloma Múltiplo , Doenças do Sistema Nervoso Periférico , Antineoplásicos , Humanos , Incidência , Injeções Subcutâneas , Doenças do Sistema Nervoso Periférico/induzido quimicamente
2.
Zhonghua Shao Shang Za Zhi ; 35(10): 726-732, 2019 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-31658543

RESUMO

Objective: To preliminarily investigate the influence of recombinant human growth hormone (rhGH) on the immune function of younger children with severe burn injuries. Methods: A total of 30 younger children with severe burn injuries, conforming to the study criteria, were admitted to our hospital from July 2016 to July 2018. They were enrolled in the prospective, randomized, double-blinded, controlled trial and divided into group rhGH [n=15, 10 boys and 5 girls, aged (22±10) months] and control group [n=15, 8 boys and 7 girls, aged (21±7) months] according to the random number table. The patients in control group received anti-shock, anti-infection, and wound caring therapies, etc. On the basis of above-mentioned treatment, the patients in group rhGH were subcutaneously injected with rhGH once every night before bedding, with a dosage of 0.2 IU·kg(-1)·d(-1), from the 3rd day post injury for 7 consecutive days. Before and on the 3rd and 7th day of rhGH treatments, the fasting peripheral venous blood was collected from patients in both groups. Blood glucose level was detected by glucometer. Percentages of CD4(+) T lymphocytes, CD8(+) T lymphocytes, CD3(+) T lymphocytes, CD19(+) B lymphocytes, and ratio of CD4(+) T lymphocytes to CD8(+) T lymphocytes were determined by flow cytometer. Mass concentration of serum immune globulin (Ig) A, IgG, and complement C3 were detected by enzyme-linked immunosorbent assay. Data were processed with Fisher's exact probability test, independent sample t test, analysis of variance for repeated measurement and Bonferroni correction, and Mann-Whitney U test. Results: (1) The blood glucose levels of children in the two groups were similar before and on the 3rd and 7th day of rhGH treatment (t=0.474, 1.652, 1.997, P>0.05). The glucose levels of children in group rhGH on the 3rd and 7th day of rhGH treatment [(6.9±1.0) and (7.7±1.1) mmol/L] were significantly higher than (5.9±0.9) mmol/L before rhGH treatment (P<0.05). The glucose level of children in control group on the 7th day of rhGH treatment was significantly higher than that before rhGH treatment (P<0.05). (2) The percentages of CD4(+) T lymphocytes of children in group rhGH before rhGH treatment and on the 7th day of rhGH treatment were (35.1±2.0)% and (38.5±2.2)%, which were close to (36.2±2.0)% and (33.6±2.2)% in control group, respectively (t=0.371, 1.553, P>0.05). The percentages of CD4(+) T lymphocytes of children in group rhGH on the 7th day of rhGH treatment[(44.7±2.2)%] was significantly higher than (36.5±2.2)% in control group (t=2.624, P<0.05). The percentage of CD4(+) T lymphocytes of children in group rhGH on the 7th day of rhGH treatment was significantly higher than that before rhGH treatment (P<0.05). The percentages of CD4(+) T lymphocytes of children in control group on the 3rd and 7th day of rhGH treatment were both close to the percentage before rhGH treatment (P>0.05). (3) The percentage of CD8(+) T lymphocytes of children in group rhGH on the 3rd day of rhGH treatment was significantly lower than that in control group (t=2.107, P<0.05). (4) The ratio of CD4(+) T lymphocytes to CD8(+) T lymphocytes of children in group rhGH on the 7th day of rhGH treatment (2.36±0.20) was significantly higher than 1.72±0.20 in control group (t=2.285, P<0.05). The ratio of CD4(+) T lymphocytes to CD8(+) T lymphocytes of children in group rhGH on the 7th day of rhGH treatment was significantly higher than 2.04±0.19 before rhGH treatment (P<0.05). (5) The percentages of CD3(+) T lymphocytes and CD19(+) B lymphocytes of children in the two groups were similar before and on the 3rd and 7th day of rhGH treatment (t=1.913, 0.552, 1.327, 1.465, 1.587, 0.407, P>0.05). The percentages of CD3(+) T lymphocytes of children in group rhGH on the 3rd and 7th day of rhGH treatment were significantly higher than the percentage before rhGH treatment (P<0.05). (6) The mass concentration of serum IgA, complement C3, and IgG of children in the two groups was similar before and on the 3rd and 7th day of rhGH treatment (t=-1.596, -0.100, 1.263, -0.220, 1.378, 1.631, Z=0.228, 0.519, 1.182, P>0.05). The mass concentration of serum IgA and complement C3 of children in group rhGH on the 3rd and 7th day of rhGH treatment was significantly higher than that before rhGH treatment(P<0.05). Conclusions: rhGH has little effect on humoral immunity of younger children with severe burn injuries with limited influence on CD19(+) B lymphocyte, mass concentration of serum IgA, IgG, and complement C3. It may improve the cellular immunity function mainly through promoting the release of CD4(+) T lymphocyte, reducing the release of CD8(+) T lymphocyte. It can be used in clinical treatment of younger children with severe burn injuries.


Assuntos
Queimaduras/terapia , Hormônio do Crescimento Humano/administração & dosagem , Linfócitos T/imunologia , Queimaduras/imunologia , Queimaduras/metabolismo , Criança , Pré-Escolar , Feminino , Hormônio do Crescimento Humano/uso terapêutico , Humanos , Lactente , Injeções Subcutâneas , Masculino , Estudos Prospectivos , Proteínas Recombinantes , Linfócitos T/metabolismo , Resultado do Tratamento
3.
Toxicol Lett ; 317: 120-129, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31580884

RESUMO

PEGylation is considered a safe mechanism to enhance the pharmacokinetics (PK) and pharmacodynamics (PD) of biotherapeutics. Previous studies using PEGylation as a PK enhancement tool have reported benign PEG-related vacuolation in multiple tissues. This paper establishes a threshold for PEG burden beyond which there are alterations in tissue architecture that could potentially lead to dysfunction. As part of the nonclinical safety assessment of Compound A, a 12 kDa protein conjugated to a 40 kDa branched PEG molecule, monkeys were dosed subcutaneously twice weekly for 3 months at protein doses resulting in weekly PEG doses of 8, 24, 120, or 160 mg/kg. Consistent with previous reports with PEGylated biomolecules, Compound A administration resulted in intracellular vacuoles attributed to the PEG moiety in macrophages in numerous tissues and epithelial cells in the choroid plexus and kidney. Vacuolation occurred at all doses with dose-dependent severity and no evidence of recovery up to 2 months after dosing cessation. The vacuolation was considered nonadverse at PEG doses ≤120 mg/kg/week. However, at 160 mg/kg/week PEG, the vacuolation in choroid plexus, pituitary gland, kidney, and choroid of the eye was considered adverse due to significant alterations of tissue architecture that raised concern for the possibility of compromised tissue function. To our knowledge, this is the first report of potentially adverse cellular consequences of PEG accumulation in tissues other than kidney. Furthermore, the lack of reversibility of vacuolation coupled with the lack of a biomarker for intracellular PEG accumulation highlights a potential risk that should be weighed against the benefits of PK/PD enhancement for long-term administration of PEGylated compounds at high doses.


Assuntos
Células Epiteliais/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Polietilenoglicóis/toxicidade , Proteínas/toxicidade , Vacúolos/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Esquema de Medicação , Composição de Medicamentos , Células Epiteliais/patologia , Feminino , Injeções Subcutâneas , Macaca fascicularis , Macrófagos/patologia , Masculino , Polietilenoglicóis/administração & dosagem , Proteínas/administração & dosagem , Medição de Risco , Fatores de Tempo , Vacúolos/patologia
4.
N Engl J Med ; 381(13): 1215-1226, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31553834

RESUMO

BACKGROUND: Biologic therapies are widely used in patients with ulcerative colitis. Head-to-head trials of these therapies in patients with inflammatory bowel disease are lacking. METHODS: In a phase 3b, double-blind, double-dummy, randomized trial conducted at 245 centers in 34 countries, we compared vedolizumab with adalimumab in adults with moderately to severely active ulcerative colitis to determine whether vedolizumab was superior. Previous exposure to a tumor necrosis factor inhibitor other than adalimumab was allowed in up to 25% of patients. The patients were assigned to receive infusions of 300 mg of vedolizumab on day 1 and at weeks 2, 6, 14, 22, 30, 38, and 46 (plus injections of placebo) or subcutaneous injections of 40 mg of adalimumab, with a total dose of 160 mg at week 1, 80 mg at week 2, and 40 mg every 2 weeks thereafter until week 50 (plus infusions of placebo). Dose escalation was not permitted in either group. The primary outcome was clinical remission at week 52 (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). To control for type I error, efficacy outcomes were analyzed with a hierarchical testing procedure, with the variables in the following order: clinical remission, endoscopic improvement (subscore of 0 to 1 on the Mayo endoscopic component), and corticosteroid-free remission at week 52. RESULTS: A total of 769 patients underwent randomization and received at least one dose of vedolizumab (383 patients) or adalimumab (386 patients). At week 52, clinical remission was observed in a higher percentage of patients in the vedolizumab group than in the adalimumab group (31.3% vs. 22.5%; difference, 8.8 percentage points; 95% confidence interval [CI], 2.5 to 15.0; P = 0.006), as was endoscopic improvement (39.7% vs. 27.7%; difference, 11.9 percentage points; 95% CI, 5.3 to 18.5; P<0.001). Corticosteroid-free clinical remission occurred in 12.6% of the patients in the vedolizumab group and in 21.8% in the adalimumab group (difference, -9.3 percentage points; 95% CI, -18.9 to 0.4). Exposure-adjusted incidence rates of infection were 23.4 and 34.6 events per 100 patient-years with vedolizumab and adalimumab, respectively, and the corresponding rates for serious infection were 1.6 and 2.2 events per 100 patient-years. CONCLUSIONS: In this trial involving patients with moderately to severely active ulcerative colitis, vedolizumab was superior to adalimumab with respect to achievement of clinical remission and endoscopic improvement, but not corticosteroid-free clinical remission. (Funded by Takeda; VARSITY ClinicalTrials.gov number, NCT02497469; EudraCT number, 2015-000939-33.).


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Adalimumab/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Indução de Remissão/métodos
5.
J Drugs Dermatol ; 18(9): 870-877, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524342

RESUMO

BACKGROUND: ATX-101 (deoxycholic acid) causes adipocytolysis when injected into subcutaneous fat. OBJECTIVE: Evaluate the long-term safety and efficacy of ATX-101 for submental fat (SMF) reduction. METHODS: Adults (N=165) with moderate-to-extreme SMF received ≤6 treatments of open-label ATX-101 (2 mg/cm2) and were evaluated up to 12 months after last treatment. Efficacy end points included improvements in SMF based on clinician or subject assessment, patient-reported outcomes, downtime (via subject questionnaire), and skin laxity. Safety was evaluated throughout the study. RESULTS: Twelve weeks after last treatment, most subjects achieved a ≥1-grade improvement in SMF based on clinician (86.8%) or subject (83.8%) evaluation; at 12 months, 90.4% and 80.7% of these responders, respectively, maintained the response. Overall, 84.9% of subjects were satisfied with the appearance of their face/chin. At 12 months, 82.9% of subjects had unchanged, and 10.1% had improved, skin laxity relative to 12 weeks after last treatment. Adverse events were mild to moderate and mainly involved the treatment area. During the 7 days after the first treatment, 13.3% of subjects missed work and 33.9% missed social/leisure activities. Following subsequent treatments, 2.4%­6.0% of subjects missed work and 10.0%­15.7% missed social/leisure activities. CONCLUSION: The safety and efficacy of ATX-101 were sustained over 12 months. ClinicalTrials.gov identifier, NCT01426373 J Drugs Dermatol. 2019;18(9):870-877.


Assuntos
Técnicas Cosméticas , Ácido Desoxicólico/administração & dosagem , Lipólise/efeitos dos fármacos , Gordura Subcutânea/efeitos dos fármacos , Adulto , Queixo , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Gordura Subcutânea/metabolismo , Resultado do Tratamento
6.
J Drugs Dermatol ; 18(9): 880-886, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524343

RESUMO

BACKGROUND: Poly-L-lactic acid (PLLA) is increasingly used for a range of indications, from HIV lipodystrophy to gluteal augmentation; however, there is no clear consensus on appropriate product preparation and use. OBJECTIVE: To establish current practices for PLLA reconstitution and usage in the USA. METHODS AND MATERIALS: A 19-question survey pertaining to the reconstitution and use of PLLA was distributed to members of the American Board of Cosmetic Surgery and American Board of Facial Cosmetic Surgery and at several cosmetic conferences. 410 questionnaires were returned anonymously over a 3-month period. The results were collated and analyzed. RESULTS: The commonest indication for PLLA was HIV lipodystrophy (46.8%), followed by gluteal augmentation (42.4%). For the face, the majority used a dilution of 9-10 mL (60.4%). For the gluteal region, the majority used a dilution greater than 21 mL (51.3%). Most respondents reconstituted PLLA in sterile water (59.8%) more than 21 hours before use (51.0%) and added lidocaine to the solution (94.7%). Most physicians used topical anesthetic cream (83.2%), manual agitation (85.8%) and recommended self-massage post-treatment (99.6%). CONCLUSION: There is considerable variation in PLLA reconstitution and use. Further well-designed studies are needed to establish the safest, most effective ways to use this product. J Drugs Dermatol. 2019;18(9):880-886.


Assuntos
Técnicas Cosméticas/estatística & dados numéricos , Preenchedores Dérmicos/administração & dosagem , Revisão de Uso de Medicamentos/estatística & dados numéricos , Poliésteres/administração & dosagem , Anestésicos Locais , Nádegas , Preenchedores Dérmicos/efeitos adversos , Composição de Medicamentos/métodos , Composição de Medicamentos/estatística & dados numéricos , Face , Humanos , Injeções Subcutâneas , Médicos/estatística & dados numéricos , Poliésteres/efeitos adversos , Padrões de Prática Médica/estatística & dados numéricos , Envelhecimento da Pele/efeitos dos fármacos , Soluções , Solventes , Inquéritos e Questionários/estatística & dados numéricos
7.
J Drugs Dermatol ; 18(9): 896-902, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524345

RESUMO

OBJECTIVE: Vascular events are among the most dreaded complications of safe soft tissue filler injections. The aim of the present study is to present a practical guide for regional facial soft tissue filler injections, which is founded in anatomy and considers safety as its first priority. MATERIAL AND METHODS: The study sample consisted of 20 fresh (non-embalmed) hemi-faces from 10 Caucasian body donors (7 females, 3 males) with a mean age of 83.5±6.8 years and a mean BMI of 25.3±4.3 kg/m2. Injections of the upper, middle and lower faces of the body donors were performed using a commercially available hyaluronic acid based soft tissue filler. RESULTS: The results of the layer by layer dissections revealed that the injected material was separated from crucial neuro-vascular structures by fascial and/or muscular planes, which were not permeated by the product. Utilizing a single cutaneous access point per facial region, safe planes can be reached. CONCLUSION: This study provides a practical guide for safe soft tissue filler injections for the upper, middle, and lower face. Using cadaveric dissections and dyed product revealed that the targeted facial planes are separated either by fascial planes or by muscular tissue from arterial vasculature. J Drugs Dermatol. 2019;18(9):896-902.


Assuntos
Técnicas Cosméticas/normas , Preenchedores Dérmicos/efeitos adversos , Face/irrigação sanguínea , Guias de Prática Clínica como Assunto , Idoso , Idoso de 80 Anos ou mais , Preenchedores Dérmicos/administração & dosagem , Dissecação , Embalsamamento , Feminino , Humanos , Injeções Subcutâneas/efeitos adversos , Masculino , Pele/irrigação sanguínea
8.
J Drugs Dermatol ; 18(9): 929-935, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524350

RESUMO

Injectable poly-L-lactic acid (PLLA) is a biodegradable synthetic polymer that stimulates collagen production, leading to gradual volume restoration. The treatment of sagging skin in body areas is still a big challenge, as there are few aesthetic procedures aiming to improve it. This article provides recommendations on the use of PLLA in the treatment of skin laxity in off-face areas, as the neck, décolletage, arms, abdomen, buttocks, and thighs, including the patient selection, product preparation, and injection techniques. The use of PLLA is a promising method for the treatment of skin laxity in corporal areas, improving body contour and appearance. Further investigation is needed to better understand the efficacy and durability of PLLA in non-facial indications and to provide the best evidence for optimal patient outcomes. J Drugs Dermatol. 2019;18(9):929-935.


Assuntos
Celulose/administração & dosagem , Técnicas Cosméticas/normas , Elasticidade/efeitos dos fármacos , Ácido Láctico/administração & dosagem , Manitol/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Fatores Etários , Celulose/efeitos adversos , Técnicas Cosméticas/efeitos adversos , Estética , Feminino , Humanos , Injeções Subcutâneas/efeitos adversos , Ácido Láctico/efeitos adversos , Manitol/efeitos adversos , Pessoa de Meia-Idade , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Rejuvenescimento , Pele/efeitos dos fármacos , Pele/metabolismo
9.
J Drugs Dermatol ; 18(9): 940-942, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524352

RESUMO

Prurigo nodularis (PN) is a disease in which chronic scratching and picking of the skin due to intense pruritis results in papulonodules, notably in areas that are accessible to the patient. The pathophysiology is hypothesized to be mediated by a Th2 helper cell response, similar to that seen in atopic dermatitis, therefore, treatment of PN with dupilumab would be expected to elicit a therapeutic response. We demonstrated that treatment of PN with dupilumab significantly decreased pruritis and the size and number of new lesions after 2 months of treatment. J Drugs Dermatol. 2019;18(9):940-942.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Prurigo/tratamento farmacológico , Prurido/tratamento farmacológico , Adulto , Feminino , Humanos , Injeções Subcutâneas , Prurigo/diagnóstico , Prurigo/patologia , Prurido/diagnóstico , Prurido/patologia , Pele/efeitos dos fármacos , Pele/patologia , Resultado do Tratamento
10.
J Drugs Dermatol ; 18(9): 943-945, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524993

RESUMO

Raynaud's phenomenon is an exaggerated physiological response of blood vessels in the distal extremities to emotional stress and cold. It can be idiopathic or secondary to a connective tissue disorder, such as scleroderma or systemic lupus erythematosus. Treatment for Raynaud's phenomenon consists primarily of lifestyle modifications; if unsuccessful, pharmacotherapy with dihydropyridine calcium channel blockers can be added. Botulinum toxin (BTX-A) is a neurotoxic protein produced by Clostridium botulinum spores. While most widely known for its cosmetic use, BTX-A has many therapeutic utilities due to its ability to inhibit multiple neurotransmitters. In this report, we present a patient with Raynaud's phenomenon refractory to standard therapies whose symptoms resolved after treatment with BTX-A. Follow-up with the patient after one and five years showed no relapse or recurrence of symptoms. J Drugs Dermatol. 2019;18(9):943-945.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Neurotoxinas/administração & dosagem , Doença de Raynaud/tratamento farmacológico , Pele/patologia , Resistência a Medicamentos , Feminino , Dedos , Humanos , Injeções Subcutâneas , Necrose/tratamento farmacológico , Necrose/etiologia , Doença de Raynaud/complicações , Pele/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
11.
J Drugs Dermatol ; 18(9): 947-949, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524994

RESUMO

Bullous pemphigoid (BP) is a rare blistering skin disease that is commonly treated with corticosteroids and immunosuppressive agents. Here, we present a 74-year-old woman with severe BP following a leg fracture who was successfully treated with omalizumab. We started her on a regimen of omalizumab 300 mg subcutaneously every 4 weeks, and within a week she reported significantly decreased pain and faster healing time of lesions. Incidentally, bilateral erythematous, non-blistering dermatitis developed 5 centimeters distal to the injection sites within a week of her first injection and resolved spontaneously in 2 days. She continues to tolerate the omalizumab injections well after 28 months of treatment and has not developed the injection site dermatitis since the first administration. Omalizumab appears to be a promising treatment modality for BP even when associated with transient injection site reactions, but further studies investigating the mechanisms by which omalizumab reduces bullae in BP are needed. J Drugs Dermatol. 2019;18(9):947-949.


Assuntos
Imunossupressores/administração & dosagem , Reação no Local da Injeção/etiologia , Omalizumab/administração & dosagem , Penfigoide Bolhoso/tratamento farmacológico , Idoso , Feminino , Humanos , Imunossupressores/efeitos adversos , Injeções Subcutâneas , Omalizumab/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
12.
Exp Parasitol ; 206: 107768, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31539540

RESUMO

Canine leishmaniosis due to Leishmania infantum is a widespread zoonotic disease. Although aminosidine can be an effective treatment, current therapeutic recommendations do not advocate its use, mainly due to concerns regarding the potential nephrotoxicity and ototoxicity of this drug. The aim of this randomized, blinded, controlled study was to evaluate the nephrotoxicity and ototoxicity of aminosidine-allopurinol combination and compare it with that of meglumine antimonate-allopurinol combination in non-azotemic dogs with leishmaniosis. Forty dogs with leishmaniosis were randomly assigned to be treated with either aminosidine at 15 mg/kg, subcutaneously, once daily for 28 days (group A) or with meglumine antimonate at 100 mg/kg, subcutaneously, once daily for 28 days (group B). In addition to either drug, dogs in both groups were administered allopurinol at 10 mg/kg per os twice daily for 2 months. Kidney function was evaluated through measurement of serum creatinine, urea nitrogen, inorganic phosphorus, and cystatin-c concentrations and complete urinalysis, including protein-to-creatinine ratio, at baseline and after 14, 28, and 60 days from the beginning of the treatment. At the same time points, vestibular and auditory functions were evaluated through neurological examination and brainstem auditory evoked response (BAER) recordings of wave I, wave V, inter-wave I-V latencies, and minimum hearing thresholds. None of the dogs developed clinicopathological evidence of kidney disease during the study. Serum creatinine concentration increased >0.3 mg/dl over baseline in 2 dogs in group A and in 5 dogs in group B. Parameters of kidney function were not significantly different or were improved compared to baseline and the only difference between the two groups was the lower concentration of serum creatinine in group A. None of the dogs developed peripheral vestibular syndrome or hearing impairment. At the end of the study, parameters of auditory function were not significantly different or were improved compared to baseline and there were no differences between the two groups. The results of this study show that the nephrotoxicity and ototoxicity of aminosidine, when administered to non-azotemic dogs with leishmaniosis at 15 mg/kg subcutaneously once daily for 28 days along with allopurinol, is minimal and does not differ from that of meglumine antimonate.


Assuntos
Alopurinol/efeitos adversos , Doenças do Cão/tratamento farmacológico , Audição/efeitos dos fármacos , Rim/efeitos dos fármacos , Leishmaniose Visceral/veterinária , Paromomicina/efeitos adversos , Alopurinol/administração & dosagem , Alopurinol/uso terapêutico , Animais , Cóclea/efeitos dos fármacos , Creatinina/sangue , Doenças do Cão/parasitologia , Cães , Método Duplo-Cego , Combinação de Medicamentos , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Perda Auditiva/induzido quimicamente , Perda Auditiva/veterinária , Injeções Subcutâneas/veterinária , Leishmania infantum , Leishmaniose Visceral/tratamento farmacológico , Masculino , Antimoniato de Meglumina/administração & dosagem , Antimoniato de Meglumina/efeitos adversos , Antimoniato de Meglumina/uso terapêutico , Exame Neurológico/veterinária , Paromomicina/administração & dosagem , Paromomicina/uso terapêutico , Distribuição Aleatória , Vestíbulo do Labirinto/efeitos dos fármacos
13.
Soins Pediatr Pueric ; 40(310): 27-30, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31543231

RESUMO

Studies and the experience of caregivers in paediatric hospital departments reveal the difficulties encountered by families and children when the treatment of a chronic disease requires injections to be administered by the family at home. Many treatments in paediatrics are administered by subcutaneous injection which means parents need to perform this procedure on their child, often for organisational reasons. However, injecting medication into one's child is not easy for the parent, even when the technique is mastered.


Assuntos
Injeções Subcutâneas/psicologia , Relações Pais-Filho , Pais/psicologia , Criança , Humanos
14.
N Engl J Med ; 381(13): 1201-1214, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31553833

RESUMO

BACKGROUND: The efficacy of ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, as induction and maintenance therapy in patients with ulcerative colitis is unknown. METHODS: We evaluated ustekinumab as 8-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 mg [320 patients] or a weight-range-based dose that approximated 6 mg per kilogram of body weight [322]) or placebo (319). Patients who had a response to induction therapy 8 weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks [172 patients] or every 8 weeks [176]) or placebo (175). The primary end point in the induction trial (week 8) and the maintenance trial (week 44) was clinical remission (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). RESULTS: The percentage of patients who had clinical remission at week 8 among patients who received intravenous ustekinumab at a dose of 130 mg (15.6%) or 6 mg per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P<0.001 for both comparisons). Among patients who had a response to induction therapy with ustekinumab and underwent a second randomization, the percentage of patients who had clinical remission at week 44 was significantly higher among patients assigned to 90 mg of subcutaneous ustekinumab every 12 weeks (38.4%) or every 8 weeks (43.8%) than among those assigned to placebo (24.0%) (P = 0.002 and P<0.001, respectively). The incidence of serious adverse events with ustekinumab was similar to that with placebo. Through 52 weeks of exposure, there were two deaths (one each from acute respiratory distress syndrome and hemorrhage from esophageal varices) and seven cases of cancer (one each of prostate, colon, renal papillary, and rectal cancer and three nonmelanoma skin cancers) among 825 patients who received ustekinumab and no deaths and one case of cancer (testicular cancer) among 319 patients who received placebo. CONCLUSIONS: Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis. (Funded by Janssen Research and Development; UNIFI ClinicalTrials.gov number, NCT02407236.).


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Ustekinumab/uso terapêutico , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Quimioterapia de Indução , Infusões Intravenosas , Injeções Subcutâneas , Quimioterapia de Manutenção , Masculino , Gravidade do Paciente , Indução de Remissão/métodos , Ustekinumab/administração & dosagem , Ustekinumab/efeitos adversos
16.
Medicine (Baltimore) ; 98(32): e16683, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31393369

RESUMO

Interferon-alpha (IFN-α) is currently the preferred antiviral treatment for children with chronic hepatitis B (CHB) aged >1-year-old. However, the evidence regarding the exact efficacy and safety in the real world is not sufficient. This study aimed to investigate the efficacy of IFN-α therapy in children with CHB and to provide a theoretical basis for practically identifying ideal antiviral therapies for CHB children.Clinical manifestations, baseline characteristics, related laboratory tests, and adverse events were retrospectively analyzed in children with CHB who visited the Children's Hospital of Fudan University, were treated with IFN-α and were followed up from January 2003 to October 2018.A total of 18 immune-active patients without advanced fibrosis were enrolled, and their average age at the start of treatment was 4.45 ±â€Š2.75 years old. IFN α-2b was administered subcutaneously by body surface area (BSA) category, based on 3 MU/m, for a median 48 weeks. Before treatment, the alanine aminotransferase (ALT) range was 81 to 409 U/L (median 158 U/L). The median hepatitis B virus (HBV)-DNA load was 9.89 × 10 IU/mL, and the HBV-DNA load varied from 3.10 × 10 to 4.56 × 10 IU/mL. The ALT levels of 17 children became normal at an average of 12 weeks during treatment, and those of 1 child became normal at 6 weeks after IFN-α withdrawal. Sixteen (88.9%, 16/18) children became HBV-DNA negative (<10 IU/mL) at an average of 24 weeks during treatment, while 1 became negative at 96 weeks after IFN-α withdrawal and 1 remained HBV-DNA positive. HBV e antigen (HBeAg) seroconversion occurred in 13 of 14 (92.9%, 13/14) HBeAg-positive patients at an average of 12 weeks during treatment. HBV s antigen (HBsAg) loss or seroconversion occurred in 4 (22.2%, 4/18) patients at an average of 21 weeks during treatment. Only mild flu-like symptoms and transient neutropenia appeared in some children at the early treatment stage. No severe abnormal results were observed in other laboratory parameters.The antiviral monotherapy of 48 weeks of IFN-α was well tolerated and good responded, which was associated with higher rates of HBeAg seroconversion and HBsAg clearance in the children in this study than in previously reported adults and pediatric patients.


Assuntos
Antivirais/administração & dosagem , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Adolescente , Antivirais/farmacologia , Criança , Pré-Escolar , China , Estudos de Coortes , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Interferon-alfa/farmacologia , Masculino , Soroconversão/efeitos dos fármacos , Carga Viral/efeitos dos fármacos
17.
N Engl J Med ; 381(6): 531-542, 2019 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-31390500

RESUMO

BACKGROUND: Familial chylomicronemia syndrome is a rare genetic disorder that is caused by loss of lipoprotein lipase activity and characterized by chylomicronemia and recurrent episodes of pancreatitis. There are no effective therapies. In an open-label study of three patients with this syndrome, antisense-mediated inhibition of hepatic APOC3 mRNA with volanesorsen led to decreased plasma apolipoprotein C-III and triglyceride levels. METHODS: We conducted a phase 3, double-blind, randomized 52-week trial to evaluate the safety and effectiveness of volanesorsen in 66 patients with familial chylomicronemia syndrome. Patients were randomly assigned, in a 1:1 ratio, to receive volanesorsen or placebo. The primary end point was the percentage change in fasting triglyceride levels from baseline to 3 months. RESULTS: Patients receiving volanesorsen had a decrease in mean plasma apolipoprotein C-III levels from baseline of 25.7 mg per deciliter, corresponding to an 84% decrease at 3 months, whereas patients receiving placebo had an increase in mean plasma apolipoprotein C-III levels from baseline of 1.9 mg per deciliter, corresponding to a 6.1% increase (P<0.001). Patients receiving volanesorsen had a 77% decrease in mean triglyceride levels, corresponding to a mean decrease of 1712 mg per deciliter (19.3 mmol per liter) (95% confidence interval [CI], 1330 to 2094 mg per deciliter [15.0 to 23.6 mmol per liter]), whereas patients receiving placebo had an 18% increase in mean triglyceride levels, corresponding to an increase of 92.0 mg per deciliter (1.0 mmol per liter) (95% CI, -301.0 to 486 mg per deciliter [-3.4 to 5.5 mmol per liter]) (P<0.001). At 3 months, 77% of the patients in the volanesorsen group, as compared with 10% of patients in the placebo group, had triglyceride levels of less than 750 mg per deciliter (8.5 mmol per liter). A total of 20 of 33 patients who received volanesorsen had injection-site reactions, whereas none of the patients who received placebo had such reactions. No patients in the placebo group had platelet counts below 100,000 per microliter, whereas 15 of 33 patients in the volanesorsen group had such levels, including 2 who had levels below 25,000 per microliter. No patient had platelet counts below 50,000 per microliter after enhanced platelet-monitoring began. CONCLUSIONS: Volanesorsen lowered triglyceride levels to less than 750 mg per deciliter in 77% of patients with familial chylomicronemia syndrome. Thrombocytopenia and injection-site reactions were common adverse events. (Funded by Ionis Pharmaceuticals and Akcea Therapeutics; APPROACH Clinical Trials.gov number, NCT02211209.).


Assuntos
Apolipoproteína C-III/antagonistas & inibidores , Hiperlipoproteinemia Tipo I/tratamento farmacológico , Oligonucleotídeos/uso terapêutico , RNA Mensageiro/antagonistas & inibidores , Trombocitopenia/induzido quimicamente , Triglicerídeos/sangue , Adulto , Idoso , Análise de Variância , Apolipoproteína C-III/sangue , Apolipoproteína C-III/genética , Método Duplo-Cego , Feminino , Humanos , Hiperlipoproteinemia Tipo I/sangue , Injeções Subcutâneas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oligonucleotídeos/administração & dosagem , Oligonucleotídeos/efeitos adversos , Contagem de Plaquetas , Adulto Jovem
18.
J Drugs Dermatol ; 18(8): 804-813, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31424712

RESUMO

Dupilumab, a monoclonal antibody that blocks the shared receptor subunit for interleukin (IL)-4 and IL-13, is currently approved for the treatment of adults with inadequately controlled moderate-to-severe atopic dermatitis (AD). The efficacy and safety of dupilumab for AD among racial subgroups is unknown. This post hoc analysis from three phase 3 trials assessed the efficacy and safety of dupilumab vs placebo by racial subgroup (White, Asian, Black/African American). Data from LIBERTY AD SOLO 1 (NCT02277743), SOLO 2 (NCT02277769), and CHRONOS (NCT02260986) were pooled. Outcomes included mean and percent change from baseline to week 16 in the key therapeutic domains Eczema Area and Severity Index (EASI), Peak Pruritus Numerical Rating Scale (NRS), Dermatology Life Quality Index (DLQI), and Patient-Oriented Eczema Measure, as well as Investigator's Global Assessment and pain or discomfort assessed by the European Quality of Life-5 Dimensions 3 level questionnaire. A total of 2,058 patients (White n=1,429, Asian n=501, Black/African American n=128) were included in the current analysis. Baseline demographics and disease characteristics were balanced between treatment groups and racial subgroups. In the three trials, dupilumab significantly (P<0.0001) improved all assessed outcomes compared with placebo in the White and Asian subgroups. In the smaller Black/African American subgroup, dupilumab significantly (P<0.0001) improved EASI endpoints and mean changes in Peak Pruritus NRS and DLQI vs placebo, with positive numeric trends favoring dupilumab in all other endpoints. Dupilumab was generally well tolerated, with an acceptable safety profile in all racial subgroups. Serious adverse events occurred more frequently with placebo; treatment discontinuations due to adverse events were rare in all treatment groups. Significant clinical improvement and a favorable benefit-risk profile can be achieved with dupilumab treatment in patients of White, Asian, and Black/African American racial subgroups with moderate-to-severe AD inadequately controlled with topical medications. ClinicalTrials.gov identifiers: NCT02277743, NCT02277769, NCT02260986


Assuntos
Anticorpos Monoclonais/administração & dosagem , Dermatite Atópica/tratamento farmacológico , Adulto , Afro-Americanos/estatística & dados numéricos , Anticorpos Monoclonais/efeitos adversos , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Dermatite Atópica/diagnóstico , Método Duplo-Cego , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Placebos/efeitos adversos , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
19.
J Drugs Dermatol ; 18(8): 822-823, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31424714

RESUMO

Guttate psoriasis is an acute subtype of plaque psoriasis characterized by eruption of small, scaly plaques, and papules, 5 to 10 mm in size over the trunk and proximal extremities.1 It often arises in children and young adults concomitantly with or shortly after a streptococcal throat infection or tonsillitis. Patients with chronic plaque psoriasis can also experience guttate flares following streptococcal throat infections.1,2 Controlling guttate psoriasis with topical corticosteroids is difficult to achieve due to numerous widespread lesions. Other treatment options include phototherapy and short term use of cyclosporine or methotrexate, as guttate variants of psoriasis can remit with these treatments.1,2 Guselkumab, an inhibitor of the p19 cytokine subunit of interleukin-23 and interleukin-39, produces dramatic resolutions of plaque psoriasis with long lasting effects.3 This case report describes a patient with a guttate variant of plaque psoriasis that resolved after a single administration of guselkumab and continues to remain clear more than 6 months after treatment with guselkumab.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Psoríase/tratamento farmacológico , Feminino , Humanos , Injeções Subcutâneas , Resultado do Tratamento , Adulto Jovem
20.
Lancet ; 394(10203): 1030-1040, 2019 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-31427046

RESUMO

BACKGROUND: Antibodies targeting calcitonin gene-related peptide (CGRP) or its receptor have shown efficacy in the prevention of migraine attacks. We investigated the efficacy and tolerability of fremanezumab, a fully humanised CGRP antibody, in patients with migraine who had previously not responded to two to four classes of migraine preventive medications. METHODS: The randomised, double-blind, placebo-controlled, parallel-group, phase 3b FOCUS trial was done at 104 sites (including hospitals, medical centres, research institutes, and group practice clinics) across Belgium, the Czech Republic, Denmark, Finland, France, Germany, Italy, the Netherlands, Poland, Spain, Sweden, Switzerland, the UK, and the USA. We enrolled participants aged 18-70 years with episodic or chronic migraine who had documented failure to two to four classes of migraine preventive medications in the past 10 years. Failure was defined as no clinically meaningful improvement after at least 3 months of therapy at a stable dose, as per the treating physician's judgment; discontinuation because of adverse events that made treatment intolerable; or treatment contraindicated or unsuitable for the preventive treatment of migraine for the patient. Participants were randomly assigned (1:1:1) by electronic interactive response technology to subcutaneously administered quarterly fremanezumab (month 1, 675 mg; months 2 and 3: placebo), monthly fremanezumab (month 1: 225 mg in episodic migraine and 675 mg in chronic migraine; months 2 and 3: 225 mg in both migraine subgroups), or matched monthly placebo for 12 weeks. The primary outcome was mean change from baseline in the monthly average number of migraine days during the 12-week treatment period. This trial is registered with ClinicalTrials.gov, number NCT03308968, and is now completed. FINDINGS: Between Nov 10, 2017, and July 6, 2018, 838 participants with episodic (329 [39%]) or chronic (509 [61%]) migraine were randomly assigned to placebo (n=279), quarterly fremanezumab (n=276), or monthly fremanezumab (n=283). Reductions from baseline in monthly average migraine days over 12 weeks were greater versus placebo (least-squares mean [LSM] change -0·6 [SE 0·3]) with quarterly fremanezumab (LSM change -3·7 [0·3]; LSM difference vs placebo -3·1 [95% CI -3·8 to -2·4]; p<0·0001) and with monthly fremanezumab (LSM change -4·1 [0·34]; LSM difference vs placebo -3·5 [-4·2 to -2·8]; p<0·0001). Adverse events were similar for placebo and fremanezumab. Serious adverse events were reported in four (1%) of 277 participants with placebo, two (<1%) of 276 with quarterly fremanezumab, and four (1%) of 285 with monthly fremanezumab. INTERPRETATION: Fremanezumab was effective and well tolerated in patients with difficult-to-treat migraine who had previously not responded to up to four classes of migraine preventive medications. FUNDING: Teva Pharmaceuticals.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Transtornos de Enxaqueca/prevenção & controle , Adolescente , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Peptídeo Relacionado com Gene de Calcitonina/agonistas , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
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