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1.
Dis Colon Rectum ; 65(1): 93-99, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34882631

RESUMO

BACKGROUND: There is limited evidence on the efficacy of acupuncture in bowel dysfunction treatment. OBJECTIVE: The aim of this pilot study was to investigate the potential value of acupuncture in the treatment of low anterior resection syndrome. DESIGN: This was an open-design pilot study. SETTINGS: This was a single-center study. PATIENTS: Nine (5 female) patients with major low anterior resection syndrome were included. INTERVENTIONS: All patients underwent acupuncture by a trained specialist once a week for 10 weeks. MAIN OUTCOME MEASURES: Bowel function was assessed by using the low anterior resection syndrome score and the Memorial Sloan-Kettering Cancer Center bowel function instrument before the procedure, just after finishing the course of acupuncture, and 6 months after the treatment. RESULTS: The average age was 56.44 (50-65; SD ±5.4). Median age was 56 years. At the end of the procedure, all patients reported significant improvement in low anterior resection syndrome symptoms: the average low anterior resection syndrome score before acupuncture was 39 (±2.7), after acupuncture it was 30.3 (±10.6), and 6 months after acupuncture it was 7.22 (±10.244; p < 0.000). The average Memorial Sloan-Kettering Cancer Center bowel function instrument score before acupuncture was 55.33 (±11.55), after the procedure it was 60 (±14.97), and 6 months later it was 70.22 (±12.2; p < 0.000). LIMITATIONS: The small sample size and the fact that this is a single-center nonblinded study are limitations of this work. CONCLUSIONS: Acupuncture may be effective in low anterior resection syndrome treatment and needs further evaluation. The procedure is safe and feasible. See Video Abstract at http://links.lww.com/DCR/B700. REGISTRATION: ClinicalTrials.gov: NCT03916549. EL PAPEL DE LA ACUPUNTURA TRADICIONAL EN EL TRATAMIENTO DEL SNDROME DE RESECCIN ANTERIOR BAJA UN ESTUDIO PILOTO: ANTECEDENTES:Existe evidencia limitada sobre la eficacia de la acupuntura para el tratamiento de la disfunción intestinal.OBJETIVO:El objetivo de este estudio piloto fue investigar el valor potencial de la acupuntura en el tratamiento del síndrome de resección anterior baja.DISEÑO:Este fue un estudio piloto de diseño abiertoAJUSTES:Este fue un estudio en un solo centroPACIENTES:Fueron incluidos nueve pacientes con síndrome de resección anterior baja (muy sintomáticos), cinco de ellos eran mujeresINTERVENCIONES:Todos los pacientes fueron tratados con acupuntura, una vez a la semana durante diez semanas por un especialista capacitado.PRINCIPALES MEDIDAS DE RESULTADO:La función intestinal fue evaluada, antes del procedimiento, justo al finalizar el ciclo de acupuntura y a los seis meses, utilizando la puntuación (score) para el síndrome de resección anterior baja y el instrumento de función intestinal del Memorial Sloan-Kettering Cancer Center.RESULTADOS:La edad media fue 56,44 (50 - 65) (DE ± 5,4). Edad mediana 56 años. Al final del procedimiento, todos los pacientes manifestaron una mejoría significativa de los síntomas del síndrome de resección anterior baja: La puntuación promedio del síndrome de resección anterior baja antes de la acupuntura fue 39 (± 2,7), después de - 30,3 (± 10,6) y 6 meses después de 7,22 (± 10,244) (p <0,000). El puntaje promedio del instrumento de función intestinal del Memorial Sloan-Kettering Cancer Center antes de la acupuntura fue 55.33 (± 11.55), después del procedimiento 60 (± 14.97) y 6 meses después 70.22 (± 12.2) (p <0,000).LIMITACIONES:Tamaño de muestra pequeño, estudio no cegado en un solo centro.CONCLUSIONES:La acupuntura puede ser eficaz en el tratamiento del síndrome de resección anterior baja, pero es necesario continuar evaluando su utilidad. El procedimiento es seguro y factible. Consulte Video Resumen en http://links.lww.com/DCR/B700.


Assuntos
Terapia por Acupuntura/métodos , Defecação/fisiologia , Incontinência Fecal/terapia , Complicações Pós-Operatórias/fisiopatologia , Neoplasias Retais/cirurgia , Idoso , Incontinência Fecal/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Projetos Piloto , Estudos Prospectivos , Segurança , Síndrome , Resultado do Tratamento
2.
Antimicrob Agents Chemother ; 65(11): e0116821, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34460301

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) infections of surgically implanted subcutaneous vascular catheters (SISVCs) cause serious morbidity in patients with chronic illnesses. Previous in vitro and murine models demonstrated the synergistic interaction of equimolar concentrations of meropenem/piperacillin/tazobactam (MPT) (VIO-001) against MRSA infection. We investigated the pharmacokinetics (PK) and efficacy of VIO-001 for the treatment of MRSA bacteremia in immunocompetent rabbits with SISVCs. In PK studies, we determined that optimal dosing to achieve a time above 4× MIC (T>4×MIC) of a duration of 3 to 3.30 h required a 1-h infusion with every-4-h (Q4h) dosing. Study groups in efficacy experiments consisted of MPT combinations of 100/150/100 mg/kg of body weight (MPT100), 200/300/200 mg/kg (MPT200), and 400/600/400 mg/kg (MPT400); vancomycin (VAN) at 15 mg/kg; and untreated controls (UC). The inoculum of MRSA isolate USA300-TCH1516 (1 × 103 organisms) was administered via the SISCV on day 1 and locked for 24 h. The 8-day therapy started at 24 h postinoculation. There was a significant reduction of MRSA in blood cultures from the SISVCs in all treatment groups, with full clearance on day 4, versus UCs (P < 0.05). Consistent with the clearance of SISVC-related infection, full eradication of MRSA was achieved in lungs, heart, liver, spleen, and kidneys at the end of the study versus UC (P < 0.01). These results strongly correlated with time-kill data, where MPT in the range of 4/6/4 µg/ml to 32/48/32 µg/ml demonstrated a significant 6-log decrease in the bacterial burden versus UC (P < 0.01). In summary, VIO-001 demonstrated a favorable PK/pharmacodynamic (PD) profile and activity against SISCV MRSA infection, bacteremia, and disseminated infection. This rabbit model provides a new system for understanding new antimicrobial agents against MRSA SISVC-related infection, and these data provide a basis for future clinical investigation.


Assuntos
Antibacterianos/farmacocinética , Bacteriemia , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Dispositivos de Acesso Vascular , Animais , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Meropeném , Testes de Sensibilidade Microbiana , Combinação Piperacilina e Tazobactam/farmacocinética , Combinação Piperacilina e Tazobactam/uso terapêutico , Coelhos , Infecções Estafilocócicas/tratamento farmacológico , Distribuição Tecidual
3.
Artigo em Inglês | MEDLINE | ID: mdl-32015048

RESUMO

Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) is an emerging global public health threat that causes life-threatening pneumonia and bacteremia. Ceftazidime-avibactam (CZA) represents a promising advance for the treatment of serious infections caused by KPC-Kp We investigated the pharmacokinetics and efficacy of ceftazidime-avibactam in the treatment of experimental KPC-Kp pneumonia in persistently neutropenic rabbits. For single-dose and multidose (administration every 8 h) pharmacokinetics, rabbits received ceftazidime-avibactam intravenous infusions at 60/15, 90/22.5, and 120/30 mg/kg of body weight. Ceftazidime mean area under the concentration-time curves (AUCs) ranged from 287 to 608 µg·h/ml for a single dose and from 300 to 781 µg·h/ml for multiple doses. Avibactam AUCs ranged from 21 to 48 µg·h/ml for a single dose and from 26 to 48 µg·h/ml for multiple doses. KPC-Kp pneumonia was established by direct endotracheal inoculation. Treatments consisted of ceftazidime-avibactam at 120/30 mg/kg every 6 h, a polymyxin B (PMB) loading dose of 2.5 mg/kg followed by 1.5 mg/kg every 12 h q12h, or no treatment (untreated controls [UC]). There were significant reductions in the residual bacterial burden, lung weights, and pulmonary hemorrhage scores in CZA- and PMB-treated rabbits for a 7-day or a 14-day (P ≤ 0.01) course in comparison with those in the UC. These results corresponded to significant decreases in the bacterial burden in bronchoalveolar lavage fluid after a 7-day or a 14-day treatment (P ≤ 0.01). The outcomes demonstrated an improved response at 14 days versus that at 7 days. There was significantly prolonged survival in rabbits treated with CZA for 14 days in comparison with that in the PMB-treated or UC rabbits (P ≤ 0.05). This study demonstrates that ceftazidime-avibactam displays linear dose-proportional exposures simulating those seen from human plasma pharmacokinetic profiles, is active for the treatment of experimental KPC-Kp pneumonia in persistently neutropenic rabbits, and provides an experimental foundation for the treatment of severely immunocompromised patients with this life-threatening infection.


Assuntos
Antibacterianos/uso terapêutico , Compostos Azabicíclicos/uso terapêutico , Ceftazidima/uso terapêutico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Inibidores de beta-Lactamases/uso terapêutico , Animais , Antibacterianos/farmacocinética , Compostos Azabicíclicos/farmacocinética , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Carga Bacteriana/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Ceftazidima/farmacocinética , Combinação de Medicamentos , Farmacorresistência Bacteriana Múltipla/genética , Feminino , Testes de Sensibilidade Microbiana , Neutropenia , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Coelhos , Inibidores de beta-Lactamases/farmacocinética , beta-Lactamases/metabolismo
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