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1.
Lancet ; 395(10218): 132-141, 2020 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-31836199

RESUMO

BACKGROUND: Standard-of-care treatment for patients with newly diagnosed multiple myeloma includes combination therapies for patients who are not eligible for autologous stem-cell transplantation. At the primary analysis for progression-free survival of the phase 3 ALCYONE trial, progression-free survival was significantly longer with daratumumab in combination with bortezomib, melphalan, and prednisone (D-VMP) versus bortezomib, melphalan, and prednisone (VMP) alone in patients with transplant-ineligible, newly diagnosed multiple myeloma. Here we report updated efficacy and safety results from a prespecified, interim, overall survival analysis of ALCYONE with more than 36 months of follow-up. METHODS: ALCYONE was a multicentre, randomised, open-label, active-controlled, phase 3 trial that enrolled patients between Feb 9, 2015, and July 14, 2016, at 162 sites in 25 countries across North America, South America, Europe, and the Asia-Pacific region. Patients were eligible for inclusion if they had newly diagnosed multiple myeloma and were ineligible for high-dose chemotherapy with autologous stem-cell transplantation, because of their age (≥65 years) or because of substantial comorbidities. Patients were randomly assigned in a 1:1 ratio and by permuted block randomisation to receive D-VMP or VMP. An interactive web-based randomisation system was used. Randomisation was stratified by International Staging System disease stage, geographical region, and age. There was no masking to treatment assignments. All patients received up to nine 6-week cycles of subcutaneous bortezomib (1·3 mg/m2 of body surface area on days 1, 4, 8, 11, 22, 25, 29, and 32 of cycle one and on days 1, 8, 22, and 29 of cycles two through nine), oral melphalan (9 mg/m2 once daily on days 1 through 4 of each cycle), and oral prednisone (60 mg/m2 once daily on days 1 through 4 of each cycle). Patients in the D-VMP group also received intravenous daratumumab (16 mg/kg of bodyweight, once weekly during cycle one, once every 3 weeks in cycles two through nine, and once every 4 weeks thereafter as maintenance therapy until disease progression or unacceptable toxicity). The primary endpoint was progression-free survival, which has been reported previously. Results presented are from a prespecified interim analysis for overall survival. The primary analysis population (including for overall survival) was the intention-to-treat population of all patients who were randomly assigned to treatment. The safety population included patients who received any dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02195479. FINDINGS: 706 patients were randomly assigned to treatment groups (350 to the D-VMP group, 356 to the VMP group). At a median follow-up of 40·1 months (IQR 37·4-43·1), a significant benefit in overall survival was observed for the D-VMP group. The hazard ratio (HR) for death in the D-VMP group compared with the VMP group was 0·60 (95% CI 0·46-0·80; p=0·0003). The Kaplan-Meier estimate of the 36-month rate of overall survival was 78·0% (95% CI 73·2-82·0) in the D-VMP group and 67·9% (62·6-72·6) in the VMP group. Progression-free survival, the primary endpoint, remained significantly improved for the D-VMP group (HR 0·42 [0·34-0·51]; p<0·0001). The most frequent adverse events during maintenance daratumumab monotherapy in patients in the D-VMP group were respiratory infections (54 [19%] of 278 patients had upper respiratory tract infections; 42 [15%] had bronchitis, 34 [12%] had viral upper respiratory tract infections), cough (34 [12%]), and diarrhoea (28 [10%]). INTERPRETATION: D-VMP prolonged overall survival in patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation. With more than 3 years of follow-up, the D-VMP group continued to show significant improvement in progression-free survival, with no new safety concerns. FUNDING: Janssen Research & Development.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Bortezomib/administração & dosagem , Melfalan/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Prednisona/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Ásia , Bortezomib/efeitos adversos , Intervalo Livre de Doença , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Europa (Continente) , Feminino , Humanos , Quimioterapia de Manutenção , Masculino , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , América do Norte , Prednisona/efeitos adversos , América do Sul , Análise de Sobrevida , Resultado do Tratamento
2.
Medicine (Baltimore) ; 98(50): e18249, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852092

RESUMO

RATIONALE: Cancer and chemotherapy individually confer hypercoagulability and increased risks of thrombosis. Most thromboembolic complication after breast cancer chemotherapy was venous thrombosis after multiagent chemotherapy. Arterial thrombosis is extremely rare in early breast cancer patients receiving adjuvant chemotherapy. PRESENTING CONCERNS: A 55-year-old woman with right breast cancer presented to the emergency department with sudden pain, numbness, and swelling in her left hand. She underwent breast conserving surgery and sentinel lymph node biopsy 2 months before the visit. She received the second cycle of adjuvant Adriamycin-cyclophosphamide chemotherapy 5 days before. INTERVENTIONS: Computed tomography angiography revealed acute arterial thrombosis in the left brachial, radial, and ulnar arteries. Unfractionated heparin was initiated immediately, followed by brachial and radial-ulnar thrombectomy, restoring perfusion to the extremity. The postoperative course was uncomplicated; she was discharged on warfarin at a daily dose of 4 mg. OUTCOMES: Chemotherapy was discontinued. Anticoagulation with warfarin was continued. She subsequently received adjuvant endocrine therapy with an aromatase inhibitor and adjuvant radiotherapy. MAIN LESSONS: Despite the low risks of arterial thrombosis in breast cancer, it is a devastating complication with significant morbidity and mortality. Thromboprophylaxis should be considered in those at risk. Immediate anticoagulant therapy and surgical intervention should be considered in affected cases.


Assuntos
Artéria Braquial , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversos , Artéria Radial , Trombose/induzido quimicamente , Artéria Ulnar , Doença Aguda , Neoplasias da Mama/diagnóstico , Quimioterapia Adjuvante/efeitos adversos , Angiografia por Tomografia Computadorizada , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Trombectomia/métodos , Trombose/diagnóstico , Trombose/cirurgia , Ultrassonografia Doppler
3.
J Drugs Dermatol ; 18(9): 924-927, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524349

RESUMO

Acne is primarily an inflammatory disease. Anti-inflammatory dose doxycycline (40mg: 30mg immediate release and 10mg delayed release beads) is approved for the treatment of rosacea but with demonstrated efficacy for acne. Fixed combination adapalene 0.3% and benzoyl peroxide 2.5% gel is a once-daily formulation approved for the topical management of acne vulgaris. It has both anti-inflammatory and anti-comedogenic properties. Options for management of severe acne are somewhat limited; many patients are not candidates for or refuse treatment with isotretinoin. Systemic antibiotics may be indicated; acne treatment guidelines emphasize antibiotic stewardship in light of increasing concerns about antibiotic resistance and call for the judicious use of conventional systemic antibiotics. This single-center, open label pilot study involving 20 subjects with severe acne assessed the effects of combination treatment using anti-inflammatory dose doxycycline plus adapalene 0.3% and benzoyl peroxide 2.5% gel on IGA scores as well as inflammatory lesion, non-inflammatory lesion, and nodule counts. By week 12, 95% of subjects had at least a 2-grade improvement in IGA scores. Reductions in inflammatory and non-inflammatory lesion counts were statistically significant beginning at week 4 and continuing through week 12. By week 4, the percentage of patients with 0 nodules was 70%, compared to baseline of 20%. Further improvements were seen through week 12. Treatment was well-tolerated with no serious treatment-related adverse events. Combination treatment with anti-inflammatory dose doxycycline plus combination adapalene 0.3% and benzoyl peroxide 2.5% gel is safe and effective for management of severe acne. J Drugs Dermatol. 2019;18(9):924-927.


Assuntos
Acne Vulgar/tratamento farmacológico , Combinação Adapaleno e Peróxido de Benzoil/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Doxiciclina/administração & dosagem , Combinação Adapaleno e Peróxido de Benzoil/efeitos adversos , Administração Cutânea , Administração Oral , Adolescente , Adulto , Criança , Fármacos Dermatológicos/efeitos adversos , Relação Dose-Resposta a Droga , Doxiciclina/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Géis , Humanos , Masculino , Projetos Piloto , Resultado do Tratamento , Adulto Jovem
4.
PLoS Negl Trop Dis ; 13(9): e0007709, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31479442

RESUMO

BACKGROUND: Leprosy has a global presence; more than 180 thousand new cases were registered in 2013, 15% of which were found in the Americas. The elderly are a very susceptible demographic in terms of developing illnesses, mainly because of characteristics natural to the senescence of the human organism. This study's goals were to analyze leprosy in an elderly population from a hyperendemic region of the Brazilian Amazon in a historical series from 2004 to 2013 and to determine the clinical and epidemiological profile of a series of leprosy cases of elderly people in the period spanning from 2009 to 2013. METHODS: To achieve these goals, an observational, longitudinal, retrospective and descriptive study was put together to analyze leprosy in elderly people from data acquired from the Notification Aggravations Information System. Furthermore, a profile of the disease from a retrospective cohort based on data collected from medical records was developed. RESULTS: The number of new cases and the leprosy detection rate decreased across the observed period but remained stable among the elderly. The trend for the next ten years indicates decreases in the number of cases and in the detection rate in the general population and an increase in only the elderly. The overall profile was characterized by a predominance of males (64.32%), the multibacillary clinical form (87.57%), Type 1 reaction episodes (37.50%) and some physical incapacity at diagnosis (49.19%). The risk of reaction was greater in the first six months of multidrug therapy, and the positive result from the skin smear was associated with the greater chance of reactional condition development. CONCLUSIONS: The resulting data demonstrate that leprosy amongst the elderly deserves attention because of the increased susceptibility to disability in this age group, with their higher risk of reaction and their greater level of co-morbidity.


Assuntos
Quimioterapia Combinada/estatística & dados numéricos , Hansenostáticos/uso terapêutico , Hanseníase/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Estudos de Coortes , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Hansenostáticos/efeitos adversos , Hanseníase/diagnóstico , Hanseníase/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Índice de Gravidade de Doença
5.
N Engl J Med ; 381(12): 1103-1113, 2019 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-31475793

RESUMO

BACKGROUND: There are limited data from randomized trials evaluating the use of antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease. METHODS: In a multicenter, open-label trial conducted in Japan, we randomly assigned 2236 patients with atrial fibrillation who had undergone percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) more than 1 year earlier or who had angiographically confirmed coronary artery disease not requiring revascularization to receive monotherapy with rivaroxaban (a non-vitamin K antagonist oral anticoagulant) or combination therapy with rivaroxaban plus a single antiplatelet agent. The primary efficacy end point was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause; this end point was analyzed for noninferiority with a noninferiority margin of 1.46. The primary safety end point was major bleeding, according to the criteria of the International Society on Thrombosis and Hemostasis; this end point was analyzed for superiority. RESULTS: The trial was stopped early because of increased mortality in the combination-therapy group. Rivaroxaban monotherapy was noninferior to combination therapy for the primary efficacy end point, with event rates of 4.14% and 5.75% per patient-year, respectively (hazard ratio, 0.72; 95% confidence interval [CI], 0.55 to 0.95; P<0.001 for noninferiority). Rivaroxaban monotherapy was superior to combination therapy for the primary safety end point, with event rates of 1.62% and 2.76% per patient-year, respectively (hazard ratio, 0.59; 95% CI, 0.39 to 0.89; P = 0.01 for superiority). CONCLUSIONS: As antithrombotic therapy, rivaroxaban monotherapy was noninferior to combination therapy for efficacy and superior for safety in patients with atrial fibrillation and stable coronary artery disease. (Funded by the Japan Cardiovascular Research Foundation; AFIRE UMIN Clinical Trials Registry number, UMIN000016612; and ClinicalTrials.gov number, NCT02642419.).


Assuntos
Fibrilação Atrial/tratamento farmacológico , Doença das Coronárias/terapia , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/uso terapêutico , Idoso , Aspirina/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Ponte de Artéria Coronária , Doença das Coronárias/complicações , Quimioterapia Combinada/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Intervenção Coronária Percutânea , Inibidores da Agregação de Plaquetas/efeitos adversos , Modelos de Riscos Proporcionais , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Rivaroxabana/efeitos adversos
6.
N Engl J Med ; 381(14): 1309-1320, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31475798

RESUMO

BACKGROUND: Patients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear. METHODS: In this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria. RESULTS: A total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P = 0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P = 0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P = 0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02). CONCLUSIONS: In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.).


Assuntos
Aspirina/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Aspirina/efeitos adversos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Feminino , Seguimentos , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Hemorragia/mortalidade , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação de Plaquetas/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Ticagrelor/efeitos adversos , Resultado do Tratamento
8.
J Vet Intern Med ; 33(5): 1977-1987, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31397009

RESUMO

BACKGROUND: Dogs with immune-mediated disease are often coadministered glucocorticoids and aspirin, but ulcerogenic effects of current protocols are unknown. OBJECTIVES: To compare gastrointestinal changes among dogs administered aspirin, prednisone, and combination treatment. ANIMALS: Twenty-four healthy research dogs. METHODS: Double-blinded, placebo-controlled randomized trial of dogs administered placebo, aspirin (2 mg/kg q24h), prednisone (2 mg/kg q24h), or combination treatment PO for 28 days. Clinical signs were recorded daily, with laboratory work performed at baseline and day 28. Gastrointestinal mucosal hemorrhages, erosions, and ulcers were numerated for endoscopic studies performed on days 0, 14, and 28; endoscopic mucosal lesion scores were calculated. Results were compared using mixed model repeated-measures analyses of variance and generalized estimating equation proportional odds models. P < .05 was considered significant. RESULTS: Gastric mucosal lesion scores differed by treatment-by-time (F[6, 40] = 4.4, P = .002), treatment (F[3, 20] = 7.1, P = .002), and time (F[2, 40] = 18.9, P < .001). Post hoc analysis revealed increased scores in the aspirin (day 14 only), prednisone, and prednisone/aspirin groups during treatment. Ulcers were identified on 14 studies, representing 10 dogs. Dogs receiving prednisone and prednisone/aspirin had 11.1 times (95% CI, 1.7-73.6) and 31.5 times (95% CI, 3.5-288.0) higher odds, respectively, of having endoscopic mucosal lesion scores ≥4 than dogs receiving placebo (P ≤ .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Gastrointestinal bleeding occurs commonly in dogs administered aspirin, prednisone, or prednisone/aspirin treatment, with higher lesion scores for dogs receiving combination treatment. Even severe lesions are not accompanied by clinical signs.


Assuntos
Aspirina/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Hemorragia Gastrointestinal/veterinária , Prednisona/efeitos adversos , Administração Oral , Animais , Aspirina/administração & dosagem , Cães , Método Duplo-Cego , Feminino , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/patologia , Hemorragia Gastrointestinal/induzido quimicamente , Masculino , Prednisona/administração & dosagem
9.
Am J Health Syst Pharm ; 76(16): 1211-1217, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369116

RESUMO

PURPOSE: Results of a study to determine whether obesity is associated with acute kidney injury (AKI) among patients receiving combination therapy with piperacillin-tazobactam and vancomycin are reported. METHODS: A retrospective, single-center cohort study of patients who received combination therapy for at least 48 hours was conducted using data from the University of Kentucky Center for Clinical and Translational Science's Enterprise Data Trust. Patients with chronic kidney disease, baseline creatinine clearance of less than 30 mL/min, cystic fibrosis, or missing height or weight information were excluded. RESULTS: A total of 8,125 patients were included in the cohort. Among the variables evaluated, total body weight of 91 kg or more was the variable most predictive of AKI. Patients with a weight of 91 kg or higher were more likely than lower-weight patients to have diabetes (39% versus 21%, p < 0.00001), hypertension (64% versus 47%, p < 0.00001), and heart failure (15% versus 13%, p = 0.007). The median daily vancomcyin dose was lower in patients with a weight of less than 91 kg (2,000 mg versus 3,000 mg, p < 0.00001); however, weight-based doses were lower in patients weighing 91 kg or more (25.5 mg/kg/day versus 27.9 mg/kg/day, p < 0.00001). AKI was more common in patients weighing 91 kg or more (24% versus 18%, p < 0.00001; adjusted odds ratio, 1.46 [95% confidence interval, 1.28-1.66]). CONCLUSION: Increased total body weight increased the rate of AKI among patients concurrently treated with piperacillin-tazobactam and vancomycin independent of clinically important confounders, with an important breakpoint occurring at 91 kg.


Assuntos
Lesão Renal Aguda/epidemiologia , Antibacterianos/efeitos adversos , Obesidade/epidemiologia , Combinação Piperacilina e Tazobactam/efeitos adversos , Vancomicina/efeitos adversos , Lesão Renal Aguda/induzido quimicamente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Peso Corporal , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Kentucky/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
10.
Anticancer Res ; 39(8): 4305-4314, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366522

RESUMO

BACKGROUND/AIM: Risk factors for chemotherapy-induced nausea and vomiting (CINV) with anthracycline-containing regimen for breast cancer patients remain unknown. The risk factors for CINV with FEC100 were investigated. PATIENTS AND METHODS: Data on CINV events and patient backgrounds of 180 patients were collected from the first cycle of FEC100 treatment. In this regimen, patients were administered various antiemetics (ADs). The combinations of ADs were classified into four categories, while body mass index (BMI) was stratified into three categories. Risk factors were selected based on patient characteristics and combination of ADs. Risks for CINV were analyzed by univariate and multivariate analyses. RESULTS: In the univariate analysis of nausea, BMI was a significant factor, while BMI and combination of ADs were significant in vomiting. In the multivariate analysis concerning nausea, BMI was a significant factor. In the analysis concerning vomiting, the combination of ADs and BMI were significant. CONCLUSION: BMI was the most important risk factor for nausea and vomiting, while the combination of ADs was for vomiting.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Náusea/epidemiologia , Vômito/epidemiologia , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/complicações , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/patologia , Fatores de Risco , Vômito/induzido quimicamente , Vômito/patologia
11.
Am J Health Syst Pharm ; 76(16): 1204-1210, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31369115

RESUMO

PURPOSE: Results of a study of rates of acute kidney injury (AKI) in pediatric patients treated with vancomycin plus piperacillin-tazobactam or vancomycin plus alternative antipseudomonal ß-lactams (APBLs) are reported. METHODS: A retrospective, single-center cohort study was performed. Pediatric patients were included in the study cohort if they received combination therapy for at least 48 hours, had documented baseline and follow-up serum creatinine levels, and had a documented serum vancomycin trough concentration. The primary outcome was the frequency of AKI, defined as a 50% or greater increase in serum creatinine concentration from baseline or an increase of at least 0.5 mg/dL from baseline. The secondary outcome was time to AKI onset. RESULTS: A total of 474 patients were included. Among 100 patients who received vancomycin plus piperacillin-tazobactam, the rate of AKI was higher than the rate in the group treated with vancomycin plus alternative APBLs (27% versus 7%, p < 0.0001). The median time to AKI onset was shorter in the piperacillin-tazobactam group versus the alternative APBL group (3.8 versus 7.9 days, p = 0.0065). Patients who were administered piperacillin-tazobactam were almost 6 times as likely to develop AKI (odds ratio [OR], 5.955; 95% confidence interval [CI], 2.774-12.784), and patients who had a maximum vancomycin trough concentration greater than 20 mg/L were 7.5 times as likely to develop AKI (OR, 7.552; 95% CI, 3.625-15.734). CONCLUSION: Pediatric patients treated with concomitant vancomycin and piperacillin-tazobactam had a higher rate of AKI, with faster AKI onset, than those who received vancomycin in combination with other APBLs.


Assuntos
Lesão Renal Aguda/epidemiologia , Antibacterianos/efeitos adversos , Combinação Piperacilina e Tazobactam/efeitos adversos , Sepse/tratamento farmacológico , Vancomicina/efeitos adversos , Lesão Renal Aguda/sangue , Lesão Renal Aguda/induzido quimicamente , Antibacterianos/administração & dosagem , Criança , Creatinina/sangue , Relação Dose-Resposta a Droga , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Masculino , Combinação Piperacilina e Tazobactam/administração & dosagem , Estudos Retrospectivos , Fatores de Tempo , Vancomicina/administração & dosagem
12.
Medicine (Baltimore) ; 98(28): e16403, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305450

RESUMO

BACKGROUND: Thoracic epidural analgesia is the preferred method for postoperative analgesia following thoracic surgery. However, intravenous patient-controlled analgesia (IVPCA) may be an effective alternative. This study was conducted because few scientific reports exist comparing fentanyl-based IVPCA including a low dose of ketamine (fk-IVPCA) with thoracic patient-controlled epidural analgesia (t-PCEA) for the treatment of postoperative pain after video-assisted thoracic surgery (VATS). METHODS: This prospective, and randomized study included 70 patients randomized into fk-IVPCA and t-PCEA groups. Pain at rest and during movement, successful and unsuccessful triggers after pressing the PCA device button, the need for rescue analgesia, drug-related adverse events, and patient satisfaction were recorded for 48 hours postoperatively. RESULTS: No significant differences in the intensity of pain at rest or during movement were observed between the 2 groups within 48 hours postoperatively. The number of unsuccessful PCA triggers in the t-PCEA group 0 to 4 hours after surgery was significantly higher than that in the fk-IVPCA group. However, the numbers of successful PCA triggers in the fk-IVPCA group at 4 to 12 and 0 to 24 hours after surgery were significantly higher than those in the t-PCEA group. The incidence of analgesic-related side effects and patient satisfaction were similar in both groups. CONCLUSIONS: Compared with t-PCEA, the addition of a subanesthetic dose of ketamine to fentanyl-based IVPCA resulted in similar pain control after VATS with no increase in the incidence of drug-related adverse effects. The results confirm that both multimodal intravenous analgesia and epidural analgesia can provide sufficient pain control and are safe strategies for treating acute post-thoracotomy pain.


Assuntos
Analgesia Epidural , Analgesia Controlada pelo Paciente , Analgésicos/administração & dosagem , Fentanila/administração & dosagem , Ketamina/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Administração Intravenosa , Analgesia Epidural/efeitos adversos , Analgesia Controlada pelo Paciente/efeitos adversos , Analgesia Controlada pelo Paciente/métodos , Analgésicos/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Feminino , Fentanila/efeitos adversos , Humanos , Ketamina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Movimento , Manejo da Dor/efeitos adversos , Manejo da Dor/métodos , Satisfação do Paciente , Cirurgia Torácica Vídeoassistida , Toracotomia , Resultado do Tratamento
13.
Int J Clin Pharmacol Ther ; 57(10): 489-499, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31272527

RESUMO

BACKGROUND AND OBJECTIVES: Statin/ezetimibe fixed-dose combination is often used as statin monotherapy; however, no study has analyzed its adverse effect (AE) signals. We comparatively analyzed the AE status of statin and statin/ezetimibe fixed-dose combination and compared the signal information using a 12-year AE reporting database. MATERIALS AND METHODS: We used data from the Korea Adverse Events Reporting System database from 2005 to 2016. Drug-AE pairs corresponded to drugs and AEs for analysis of demographic characteristics, causality, number, and type of serious AEs. Metrics, including proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) were used to detect signals. Signals were compared with drug labels in the USA and Korea. RESULTS: Of the 4,569 AE cases identified, 4,130 and 442 were of statin and statin/ezetimibe fixed-dose combination, respectively. There were no statistically significant differences in AE report characterization for statin and the statin/ezetimibe fixed-dose combination. The number of AE signal detections for statin, statin/ezetimibe fixed-dose combination, and both, based on PRR and ROR, was 16, 4, and 2, respectively, and the number of cases not included on the label was 3, 2, and 0, respectively. The number of AE signals that only met IC indicators was greater in statin/ezetimibe fixed-dose combination (33) than in statin (4), and 12 of the 33 cases in statin/ezetimibe fixed-dose combination were not included on the drug label. CONCLUSION: The combination of statin and ezetimibe exhibited greater AE signal detection than statin alone, and the inclusion of AEs on the drug label was insufficient.


Assuntos
Ezetimiba/administração & dosagem , Ezetimiba/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Anticolesterolemiantes , Bases de Dados Factuais , Quimioterapia Combinada/efeitos adversos , Humanos , República da Coreia
14.
J Dermatol ; 46(9): 770-776, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31270853

RESUMO

The efficacy of lauromacrogol injection therapy and intralesional triamcinolone for infantile hemangiomas (IH) has been well documented recently, but with an increase in serious or rare adverse reactions. The aim of this study is to investigate the safety concerns regarding intralesional injection of lauromacrogol combined with triamcinolone for IH and to study its effect on infant growth and development. A total of 1039 IH patients who were subjected to intralesional injection of lauromacrogol combined with triamcinolone in the Plastic Surgery Department of Shandong Provincial Hospital between 1 January 2015 and 31 May 2018 were enrolled in this study. When the dose of lauromacrogol and triamcinolone was less than 3.5 and 2.0 mg/kg respectively, no serious side-effects were observed. The adverse event rate reported was 7.7%. Among the 405 patients not subjected to propranolol before the last injection, the study included three modes of treatment response: regression (82.7%), stabilization (13.8%) and failure (3.5%). By comparing height and weight to the reference standards and also by comparisons between the same-sex groups, our results confirmed that there was no significant effect on children's height and weight, regardless of whether the injection therapy was combined with oral propranolol at the appropriate dose and with more than 4-week intervals. Intralesional injection of lauromacrogol combined with triamcinolone in the treatment of IH was highly safe and effective.


Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Hemangioma/tratamento farmacológico , Polidocanol/efeitos adversos , Soluções Esclerosantes/efeitos adversos , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Estatura/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Lactente , Injeções Intralesionais , Masculino , Polidocanol/administração & dosagem , Propranolol/administração & dosagem , Propranolol/efeitos adversos , Estudos Retrospectivos , Soluções Esclerosantes/administração & dosagem , Resultado do Tratamento , Triancinolona/administração & dosagem , Triancinolona/efeitos adversos
15.
Yakugaku Zasshi ; 139(7): 1055-1061, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31257252

RESUMO

Linezolid (LZD), an antimicrobial agent against methicillin-resistant Staphylococcus aureus, demonstrates good bone and joint penetration, and is used for prosthetic bone and joint infections. Recently, we observed vomiting in several patients administered LZD. However, there are few reports on the incidence rate of, and risk factors for, LZD-induced nausea and vomiting. In this study, we aimed to verify the relationship between LZD administration and vomiting. Patients administered LZD at the Department of Orthopedic Surgery of Hokkaido University Hospital between November 2008 and December 2017 were enrolled in the study. The primary endpoint was the comparison of the vomiting rate between patients administered LZD (LZD group) and those administered other antibiotics (non-LZD group). For the secondary endpoint, to verify the risk factors of vomiting, a univariate logistic regression analysis was performed. In total, 130 patients were included in this study; 77 patients in the LZD group, and 53 in the non-LZD group. Vomiting occurred in 18 patients in the LZD group and 4 patients in the non-LZD group (23.4% and 7.5%, respectively); this was significantly higher in the LZD group. In the univariate logistic regression analysis, LZD administration, gender (female), age ≥65 years, renal impairment (creatinine clearance <60 mL/min) and concomitant use of rifampicin were extracted as potential risk factors of vomiting. The results of this study reveal a possible relationship between LZD administration and vomiting.


Assuntos
Antibacterianos/efeitos adversos , Linezolida/efeitos adversos , Náusea/induzido quimicamente , Vômito/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Náusea/epidemiologia , Rifampina/administração & dosagem , Rifampina/efeitos adversos , Fatores de Risco , Vômito/epidemiologia , Adulto Jovem
16.
J Drugs Dermatol ; 18(7): 642-648, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31329402

RESUMO

Background: Pigmentation disorders are therapeutically challenging to treat, requiring complicated regimens. Objectives: Alternatives to hydroquinone (HQ) are desired. We evaluated the efficacy and tolerability of a non-HQ multi-action skin tone corrector (ETCS) developed to inhibit melanin production and improve skin quality. Design and Methods: Twice-daily use of ETCS and ETCS + AHA-Ret, a retinoid-based alpha hydroxy acid cream, was evaluated in subjects with mild to severe dyschromia. Digital images were obtained at baseline, 4, 8, and 12 weeks and included assessment of dyschromia, erythema, fine lines/wrinkles, pores, texture, and global improvement. Melanin Index (MI) measurements were obtained at baseline, 4, 8, and 12 weeks. Subject self-assessments were obtained over the course of the study. Adverse Events (AEs) were collected throughout the study. An extension study evaluated use over 16-weeks. Results: Significant mean reductions from baseline occurred in dyschromia for ETCS (n=42) and ETCS + AHA-Ret (n=10) over 12 weeks (P<0.0001, each). Significant mean reductions from baseline in MI were achieved in both groups at every timepoint (ETCS: P<0.0001; ETCS + AHA-Ret: P<0.02, 4 weeks; P<0.0001, 8 and 12 weeks). Substantial improvements were demonstrated in global improvement, fine lines/wrinkles, erythema, pores, and texture at 12 weeks. Reductions from baseline occurred in dyschromia and MI (P<0.0001, each) at 16 weeks. High levels of subject satisfaction were reported with nearly all subjects reporting reduced appearance of uneven skin tone/discoloration and lightened darker patches, and improvement in overall skin tone. Mild, transient AEs were reported with no discontinuations due to an AE. Conclusions: Twice daily use of ETCS led to early, significant reductions in dyschromia and melanin index. Combination use with a retinoid-based, AHA cream in the evening demonstrated enhanced reductions. ETCS effectively reduced hyperpigmentation, improved overall skin appearance, and was highly tolerable. J Drugs Dermatol. 2019;18(7):642-648.


Assuntos
Fármacos Dermatológicos/efeitos adversos , Hiperpigmentação/tratamento farmacológico , Melaninas/antagonistas & inibidores , Creme para a Pele/administração & dosagem , Preparações Clareadoras de Pele/administração & dosagem , Adulto , Idoso , Fármacos Dermatológicos/administração & dosagem , Combinação de Medicamentos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Melaninas/metabolismo , Pessoa de Meia-Idade , Retinoides/administração & dosagem , Retinoides/efeitos adversos , Envelhecimento da Pele/efeitos dos fármacos , Creme para a Pele/efeitos adversos , Creme para a Pele/química , Preparações Clareadoras de Pele/efeitos adversos , Preparações Clareadoras de Pele/química , Pigmentação da Pele/efeitos dos fármacos , Resultado do Tratamento
17.
Am J Health Syst Pharm ; 76(11): 804-809, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31361811

RESUMO

PURPOSE: There are limited data on the effect of ceftriaxone on methotrexate clearance, with results of some studies indicating altered methotrexate pharmacokinetics with the administration of ceftriaxone. We describe 2 possible cases demonstrating an interaction between methotrexate and ceftriaxone, resulting in profound neutropenia. SUMMARY: The decision to continue methotrexate therapy in the setting of surgery or during treatment of an active infection continues to be a topic of debate due to perceived negative effects on the healing process. Methotrexate is typically administered at a lower dose for inflammatory arthritis than for hematologic indications, thus having less immunosuppression potential. However, if methotrexate is continued during treatment of infection, drug interactions along with effects on the healing process should be considered. Ceftriaxone is commonly considered safe for long-term therapy due to its favorable adverse effect and drug interaction profile. Ceftriaxone is partially eliminated via organic anion transporters in the kidneys, leading to potential competition with methotrexate clearance in the renal tubules. Clinicians using these drugs concurrently should be aware of the potential for development of neutropenia and monitor patients receiving this combination closely. CONCLUSION: Two patients receiving ceftriaxone therapy in the setting of a joint infection developed profound neutropenia after resuming oral methotrexate therapy for inflammatory arthritis.


Assuntos
Artrite Infecciosa/tratamento farmacológico , Artrite Psoriásica/tratamento farmacológico , Ceftriaxona/farmacologia , Metotrexato/farmacologia , Neutropenia/induzido quimicamente , Idoso , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Artrite Infecciosa/imunologia , Artrite Infecciosa/microbiologia , Artrite Psoriásica/imunologia , Ceftriaxona/uso terapêutico , Relação Dose-Resposta a Droga , Interações de Medicamentos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Humanos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Propionibacterium acnes/isolamento & purificação , Staphylococcus aureus/isolamento & purificação
18.
Mycoses ; 62(10): 969-978, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31355956

RESUMO

This randomised, double-blind, placebo-controlled trial assessed the efficacy, safety and tolerability of voriconazole+anidulafungin (combination) or voriconazole+placebo (monotherapy) for invasive aspergillosis (IA; NCT00531479). We present a post hoc analysis of Korean and non-Korean patients with IA (including baseline positive serum galactomannan [GM]). Immunocompromised patients ≥ 16 years with IA were randomised 1:1, combination or monotherapy, for ≥ 2 weeks' treatment. The primary endpoint was 6- and 12-week all-cause mortality (Korean modified intent-to-treat [mITT] population). Overall, 454 patients enrolled (Koreans: 56 [combination: 28, monotherapy: 28], non-Koreans: 398 [combination: 200, monotherapy: 198]). The mITT population comprised 40 Koreans (combination: 23; monotherapy: 17) and 237 non-Koreans (combination: 112; monotherapy: 125). Week 6 treatment difference in mortality rate between combination and monotherapy was -6.4% in non-Koreans. This reduction was more marked in Koreans (-22.4%). Week 12 difference in all-cause mortality between combination and monotherapy was -17.7% (Koreans) and -20.2% at Week 6 (Koreans; positive baseline GM). Week 6 mortality (Koreans [mITT]; baseline GM >0.5-2.0) was 0/13 (combination) and 2/6 (monotherapy). Serious adverse events were numerically higher for combination than monotherapy (Koreans: 57.1%, 46.4%; non-Koreans: 49.5%, 46.0%). In Koreans, combination therapy was associated with marginally better outcomes than monotherapy and more so than in non-Koreans.


Assuntos
Anidulafungina/uso terapêutico , Antifúngicos/uso terapêutico , Neoplasias Hematológicas/complicações , Aspergilose Pulmonar Invasiva/tratamento farmacológico , Voriconazol/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anidulafungina/efeitos adversos , Antifúngicos/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Método Duplo-Cego , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Placebos/administração & dosagem , Análise de Sobrevida , Resultado do Tratamento , Voriconazol/efeitos adversos , Adulto Jovem
19.
PLoS Med ; 16(6): e1002839, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31233507

RESUMO

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) provides antifilarial medications to hundreds of millions of people annually to treat filarial infections and prevent elephantiasis. Recent trials have shown that a single-dose, triple-drug treatment (ivermectin with diethylcarbamazine and albendazole [IDA]) is superior to a two-drug combination (diethylcarbamazine plus albendazole [DA]) that is widely used in LF elimination programs. This study was performed to assess the safety of IDA and DA in a variety of endemic settings. METHODS AND FINDINGS: Large community studies were conducted in five countries between October 2016 and November 2017. Two studies were performed in areas with no prior mass drug administration (MDA) for filariasis (Papua New Guinea and Indonesia), and three studies were performed in areas with persistent LF despite extensive prior MDA (India, Haiti, and Fiji). Participants were treated with a single oral dose of IDA (ivermectin, 200 µg/kg; diethylcarbamazine, 6 mg/kg; plus albendazole, a fixed dose of 400 mg) or with DA alone. Treatment assignment in each study site was randomized by locality of residence. Treatment was offered to residents who were ≥5 years of age and not pregnant. Adverse events (AEs) were assessed by medical teams with active follow-up for 2 days and passive follow-up for an additional 5 days. A total of 26,836 persons were enrolled (13,535 females and 13,300 males). A total of 12,280 participants were treated with DA, and 14,556 were treated with IDA. On day 1 or 2 after treatment, 97.4% of participants were assessed for AEs. The frequency of all AEs was similar after IDA and DA treatment (12% versus 12.1%, adjusted odds ratio for IDA versus DA 1.15, 95% CI 0.87-1.52, P = 0.316); 10.9% of participants experienced mild (grade 1) AEs, 1% experienced moderate (grade 2) AEs, and 0.1% experienced severe (grade 3) AEs. Rates of serious AEs after DA and IDA treatment were 0.04% (95% CI 0.01%-0.1%) and 0.01% (95% CI 0.00%-0.04%), respectively. Severity of AEs was not significantly different after IDA or DA. Five of six serious AEs reported occurred after DA treatment. The most common AEs reported were headache, dizziness, abdominal pain, fever, nausea, and fatigue. AE frequencies varied by country and were higher in adults and in females. AEs were more common in study participants with microfilaremia (33.4% versus 11.1%, P < 0.001) and more common in microfilaremic participants after IDA than after DA (39.4% versus 25.6%, P < 0.001). However, there was no excess of severe or serious AEs after IDA in this subgroup. The main limitation of the study was that it was open-label. Also, aggregation of AE data from multiple study sites tends to obscure variability among study sites. CONCLUSIONS: In this study, we observed that IDA was well tolerated in LF-endemic populations. Posttreatment AE rates and severity did not differ significantly after IDA or DA treatment. Thus, results of this study suggest that IDA should be as safe as DA for use as a MDA regimen for LF elimination in areas that currently receive DA. TRIAL REGISTRATION: Clinicaltrials.gov registration number: NCT02899936.


Assuntos
Antiparasitários/administração & dosagem , Antiparasitários/efeitos adversos , Filariose Linfática/tratamento farmacológico , Administração Massiva de Medicamentos/efeitos adversos , Administração Massiva de Medicamentos/métodos , Adulto , Análise por Conglomerados , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Filariose Linfática/diagnóstico , Filariose Linfática/epidemiologia , Fadiga/induzido quimicamente , Fadiga/epidemiologia , Feminino , Seguimentos , Cefaleia/induzido quimicamente , Cefaleia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Medicine (Baltimore) ; 98(18): e15330, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045772

RESUMO

RATIONALE: Although intrathecal opioid infusion has been used for decades for the treatment of severe pain, myoclonus as one of the complications of this therapeutic modality is now beginning to be recognized more. PATIENTS CONCERNS: Here, we report three patients who developed myoclonus after dose adjustment in intrathecal drug delivery system for the treatment of refractory cancer pain. DIAGNOSIS: Spinal myoclonus is a sudden, brief, shock-like muscle contractions originating from the central nervous system. In our cases, it occurred after opioid administration via intrathecal delivery system with no abnormality found in laboratory or imaging examinations. INTERVENTIONS: Spinal myoclonus can be treated effectively by reducing the dose or infusion rate as described in case 1, or changing from an intrathecal to systemic administration in case 2, or correcting infusion and bolus parameters mistakes in case 3. OUTCOMES: All patients recovered quickly after stopping or decreasing the intrathecal drug infusion. LESSONS: Prevention is more important than treatment as for spinal myoclonus. Pain management teams should be aware of this distressing complication. Dose of intrathecal drugs should not exceed the recommended maximal daily doses by guidelines and patient education is important for successful intrathecal analgesic therapy.


Assuntos
Morfina/efeitos adversos , Mioclonia/induzido quimicamente , Neoplasias/tratamento farmacológico , Ropivacaina/efeitos adversos , Doenças da Coluna Vertebral/induzido quimicamente , Conscientização , Dor do Câncer/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Injeções Espinhais/métodos , Pessoa de Meia-Idade , Morfina/administração & dosagem , Mioclonia/prevenção & controle , Metástase Neoplásica , Neoplasias/complicações , Manejo da Dor/métodos , Dor Intratável/tratamento farmacológico , Ropivacaina/administração & dosagem , Doenças da Coluna Vertebral/fisiopatologia , Doenças da Coluna Vertebral/prevenção & controle
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