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2.
J Biomed Mater Res B Appl Biomater ; 110(1): 103-114, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34128323

RESUMEN

Surgical site infections (SSIs) are a persistent clinical challenge. Local antimicrobial delivery may reduce the risk of SSI by increasing drug concentrations and distribution in vulnerable surgical sites compared to what is achieved using systemic antimicrobial prophylaxis alone. In this work, we describe a comprehensive in vivo evaluation of the safety and efficacy of poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylamide-co-Jeffamine M-1000 acrylamide) [PNDJ], an injectable temperature-responsive hydrogel carrier for antimicrobial delivery in surgical sites. Biodistribution data indicate that PNDJ is primarily cleared via the liver and kidneys following drug delivery. Antimicrobial-loaded PNDJ was generally well-tolerated locally and systemically when applied in bone, muscle, articulating joints, and intraperitoneal space, although mild renal toxicity consistent with the released antimicrobials was identified at high doses in rats. Dosing of PNDJ at bone-implant interfaces did not affect normal tissue healing and function of orthopedic implants in a transcortical plug model in rabbits and in canine total hip arthroplasty. Finally, PNDJ was effective at preventing recurrence of implant-associated MSSA and MRSA osteomyelitis in rabbits, showing a trend toward outperforming commercially available antimicrobial-loaded bone cement and systemic antimicrobial administration. These studies indicate that antimicrobial-loaded PNDJ hydrogels are well-tolerated and could reduce incidence of SSI in a variety of surgical procedures.


Asunto(s)
Hidrogeles , Infección de la Herida Quirúrgica , Resinas Acrílicas , Animales , Antibacterianos/farmacología , Perros , Hidrogeles/farmacología , Conejos , Ratas , Infección de la Herida Quirúrgica/prevención & control , Temperatura , Distribución Tisular
3.
Eur J Orthop Surg Traumatol ; 31(7): 1485-1492, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33649991

RESUMEN

BACKGROUND: The purpose of this study was to determine the angular tolerance of the S1 and S2 segments to accommodate a transiliosacral screw across both sacroiliac joints. HYPOTHESIS: We hypothesized that the angular tolerance for transiliosacral screw placement would be more constrained than the angular tolerance for iliosacral fixation in pelves where a safe osseous corridor was measured. MATERIALS AND METHODS: The cortical boundaries of the S1 and S2 sacral segments in 433 pelvic CTs were digitally mapped. A straight-line path was placed within each osseous corridor and extended across both SI joints past the outer iliac cortices. The diameter of the path was increased until it breached the cortex, geometrically determining maximum diameter (Dmax). Angular tolerance for screw placement was calculated with trigonometric analysis of the Dmax value of the corridor, and the average distance from the termination of the osseous corridor to the site of percutaneous insertion. Gender, age, and BMI were evaluated as independent predictors using binomial logistic regression. RESULTS: The transiliosacral angular tolerance for the S1 and S2 osseous corridors was 1.53 ± 0.57 degrees and 1.02 ± 0.33 degrees, respectively. 68.9% of S1 corridors and 81.1% of S2 corridors had a safe zone (corridor diameter ≥ 10 mm) for transiliosacral placement, 48.3% of the pelves had a safe zone for both corridors, while 5.1% had no safe zones. Females had a less frequent Dmax ≥ 10 mm at S1, 52% vs 67% (p = 0.001), and at S2, 64% vs 86% (p < 0.001). DISCUSSION: In conclusion, the angular tolerance of 1.53 and 1.03 degrees for the S1 and S2 segments, respectively, creating a narrow interval for safe passage of the trans-iliac and trans-sacral, with approximately 31.1% of patients not having a viable corridor for screw passage. A correlation exist between S1 and S2 corridors with Dmax ≥ 10 mm and the resulting increase in angular tolerance for safe passage of a transilioscral screw. LEVEL OF EVIDENCE IV: Level Retrospective Cohort.


Asunto(s)
Tornillos Óseos , Sacro , Femenino , Fijación Interna de Fracturas , Humanos , Ilion/cirugía , Pelvis , Estudios Retrospectivos , Sacro/cirugía
4.
Eur J Orthop Surg Traumatol ; 31(2): 235-243, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32797351

RESUMEN

BACKGROUND: Subtrochanteric femur fractures associate with a relatively high complication rate and are traditionally treated operatively with a period of limited weight bearing. Transitioning from extramedullary to intramedullary implants, there are increasing biomechanical and clinical data to support early weight bearing. This multicenter retrospective study examines the effect of postoperative weight bearing as tolerated (WBAT) for subtrochanteric femur fractures. We hypothesize that WBAT will result in a decreased length of stay (LOS) without increasing the incidence of re-operation. METHODS: This study assesses total LOS and postoperative LOS after intramedullary fixation for subtrochanteric fractures between postoperative weight bearing protocols across 6 level I trauma centers (n = 441). Analysis techniques consisted of multivariable linear regression and nonparametric comparative tests. Additional subanalyses were performed, targeting mechanism of injury (MOI), Winquist-Hansen fracture comminution, 20-year age strata, and injury severity score (ISS). RESULTS: Total LOS was shorter in WBAT protocol within the overall sample (7.4 vs 9.7 days; p < 0.01). Rates of re-operation were similar between the two groups (10.6% vs 10.5%; p = 0.99). Stratified analysis identified patients between ages 41-80, WH comminution 2-3, high MOI, and ISS between 6-15 and 21-25 to demonstrate a significant reduction in LOS as a response to WBAT. CONCLUSION: An immediate postoperative weight bearing as tolerated protocol in patients with subtrochanteric fractures reduced length of hospital stay with no significant difference in reoperation and complication rates. If no contraindication exists, immediate weight bearing as tolerated should be considered for patients with subtrochanteric femur fractures treated with statically locked intramedullary nails. LEVEL OF EVIDENCE: Therapeutic Level III.


Asunto(s)
Fijación Intramedular de Fracturas , Fracturas de Cadera , Adulto , Anciano , Anciano de 80 o más Años , Clavos Ortopédicos , Fijación Intramedular de Fracturas/efectos adversos , Fracturas de Cadera/cirugía , Humanos , Tiempo de Internación , Persona de Mediana Edad , Estudios Retrospectivos , Soporte de Peso
5.
West J Emerg Med ; 19(5): 827-833, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-30202495

RESUMEN

INTRODUCTION: Patients with malignancy represent a particular challenge for the emergency department (ED) given their higher acuity, longer ED length of stay, and higher admission rate. It is unknown if patients with malignancies and hyperlactatemia are at increased risk of mortality. If serum lactic acid could improve detection of at-risk patients with cancer, it would be useful in risk stratification. There is also little evidence that "alarm" values of serum lactate (such as >/=4 mmol/L) are appropriate for the population of patients with cancer. METHODS: This was a continuous retrospective cohort study of approximately two years (2012-2014) at a single, tertiary hospital ED; 5,440 patients had serum lactic acid measurements performed in the ED. Of the 5,440 patients in whom lactate was drawn, 1,837 were cancer patients, and 3,603 were non-cancer patients. Cumulative unadjusted mortality (determined by hospital records and an external death tracking system) was recorded at one day, three days, seven days, and 30 days. We used logistic regression to examine the risk of mortality 30 days after the ED visit after adjusting for confounders. RESULTS: In an unadjusted analysis, we found no statistically significant difference in the mortality of cancer vs. non-cancer patients at one day and three days. Significant differences in mortality were found at seven days (at lactate levels of <2 and 4+) and at 30 days (at all lactate levels) based on cancer status. After adjusting for age, gender, and acuity level, 30-day mortality rates were significantly higher at all levels of lactic acid (<2, 2-4, 4+) for patients with malignancy. CONCLUSION: When compared with non-cancer patients, cancer patients with elevated ED lactic acid levels had an increased risk of mortality at virtually all levels and time intervals we measured, although these differences only reached statistical significance in later time intervals (Day 7 and Day 30). Our results suggest that previous work in which lactate "cutoffs" are used to risk-stratify patients with respect to outcomes may be insufficiently sensitive for patients with cancer. Relatively low serum lactate levels may serve as a marker for serious illness in oncologic patients who present to the ED.


Asunto(s)
Servicio de Urgencia en Hospital , Ácido Láctico/sangre , Neoplasias/mortalidad , Anciano , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo
8.
J Am Osteopath Assoc ; 117(1): 7-15, 2017 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-28055097

RESUMEN

CONTEXT: Direct oral anticoagulants (DOACs) may be as effective as, and at times safer than, warfarin. Because DOACs do not require regular serum level monitoring, patients' interaction with the health care system may be reduced. To the authors' knowledge, although studies have evaluated warfarin adherence, few studies have evaluated the real-world adherence to DOACs. OBJECTIVE: To evaluate whether a difference exists between medication adherence of patients taking DOACs vs patients taking warfarin. METHODS: The electronic medical records of the Anticoagulation Clinic database at Mayo Clinic in Scottsdale, Arizona, were reviewed. Inclusion criteria were adults taking DOACs and a matching cohort taking warfarin between January 1, 2011, and December 30, 2013. The Morisky Medication Adherence Scale-8 item, a validated medication adherence tool, was used to evaluate adherence in both cohorts, and the qualitative covariates were analyzed using ordinal logistic regression. RESULTS: Of 324 surveys that were sent, 110 patients (34.0%) responded. Most patients took DOACs for atrial fibrillation, and few took DOACs for venous thromboembolism. Overall, 60 of 66 patients (90.9%) in the DOAC group and 42 of 44 patients (95.5%) in the warfarin group reported medium or high adherence. Difference in adherence scores between the 2 groups was not statistically significant (P=.8). CONCLUSION: Similar adherence was noted between DOACs and warfarin regardless of the frequency of serum level monitoring.


Asunto(s)
Anticoagulantes/uso terapéutico , Fibrilación Atrial/psicología , Cumplimiento de la Medicación , Tromboembolia Venosa/psicología , Warfarina/uso terapéutico , Anciano , Fibrilación Atrial/complicaciones , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/prevención & control , Tromboembolia Venosa/complicaciones
9.
Future Sci OA ; 2(2): FSO123, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28031970

RESUMEN

BACKGROUND: This study evaluated referral patterns for preoperative evaluations of patients with poorly controlled diabetes mellitus (DM) and determined whether intervals between evaluations and surgery day were associated with preoperative glucose levels. RESULTS/METHODOLOGY: In this retrospective analysis of DM patients with a hemoglobin A1c level greater than 8.0%, of the 163 patients who underwent preoperative medical evaluation, only 45% were evaluated by endocrinology. Patients who had surgery earlier than 10 days after the preoperative medical evaluation had preoperative glucose levels 18% higher than those of patients who waited more than 10 days. Preoperative outpatient contact with endocrinology was not associated with preoperative glucose level (p = 0.90). CONCLUSION: For poorly controlled DM, more than 10 days are needed to achieve preoperative glycemic control.

10.
Can J Urol ; 23(5): 8465-8470, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27705732

RESUMEN

INTRODUCTION: To examine the infectious outcomes after the insertion of the temporary prostatic urethral stent (TPUS) in benign prostatic hyperplasia (BPH) patients. MATERIAL AND METHODS: Between November 2007 and September 2012, ninety TPUS were used in 33 patients with BPH at our institution. All patients had negative urine cultures prior to the first stent insertion. TPUS were sent for cultures at time of removal or exchange. Stents were removed at the time of definite surgical intervention, at 4-6 weeks, or when patients elected another course of treatment. Colonization was defined as asymptomatic positive stent culture. Infection was defined as symptomatic positive stent culture requiring treatment. Infection and colonization rates are reported. Logistic regression was used to examine the predictors of infection at any point. Predictors examined were age, body mass index, history of prostate cancer, diabetes mellitus, hyperlipidemia, coronary artery disease, neurologic disorder, erectile dysfunction and the sequence of stent placement. RESULTS: The majority of the subjects, 72% (24/33) had 1-2 stents, 9.0% (3/33) had 3-4 stents, 6.0% (2/33) had 5-6 stents, and 12% (4/33) of patients had more than 6 stents. From the 69 available culture results, the symptomatic infection rate was 16% (11/69) (95% CI: 8.2%-26.7%). The colonization rate was 58% (40/69) (95% CI: 45.5%-69.7%). None of the predictors examined were identified as a predictor of infection. There was no colonization detected when stents were removed in the first 20 days. CONCLUSION: Infection rates with TPUS in BPH patients are acceptable and early removal may prevent colonization.


Asunto(s)
Infecciones Relacionadas con Catéteres , Remoción de Dispositivos/métodos , Técnicas Microbiológicas/métodos , Stents , Ureterostomía , Urinálisis/métodos , Derivación Urinaria , Anciano , Anciano de 80 o más Años , Arizona , Infecciones Relacionadas con Catéteres/diagnóstico , Infecciones Relacionadas con Catéteres/etiología , Infecciones Relacionadas con Catéteres/microbiología , Intervención Médica Temprana/métodos , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Valor Predictivo de las Pruebas , Hiperplasia Prostática/complicaciones , Hiperplasia Prostática/cirugía , Factores de Riesgo , Stents/efectos adversos , Stents/microbiología , Ureterostomía/efectos adversos , Ureterostomía/instrumentación , Ureterostomía/métodos , Derivación Urinaria/instrumentación , Derivación Urinaria/métodos
11.
J Orthop Trauma ; 30(11): e375-e376, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27327961

RESUMEN

The technique of placing an oblique screw in the terminal hole of a plate to increase screw pullout strength is widely taught in the operating room. The origin of this technique is unclear; however, it may have been used simply as a means to identify radiographs and misinterpreted to have some biomechanical benefit. The objective of this study was to measure the structural effect of oblique terminal screw placement (OTSP) during plate osteosynthesis. Foam blocks and limited contact dynamic compression plates and screws were used along with a custom fixture device. The terminal screw was placed in either an oblique (30-degree angle outward) or perpendicular fashion. A load was applied perpendicular to the plate in cantilever bending until failure. The oblique screw construct was significantly weaker than the perpendicular screw construct (399N vs. 465N, P < 0.001), independent of the block of material used. Post hoc analysis showed that the screw angle (P < 0.001) was a significant determinant of the load required to cause screw pullout. OTSP led to a decrease in pullout strength compared with a perpendicular screw in a deformable foam medium similar in density to osteoporotic bone. In patients with poor bone quality, OTSP may create a suboptimal fracture fixation construct.


Asunto(s)
Placas Óseas , Tornillos Óseos , Huesos/fisiología , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Implantación de Prótesis/métodos , Materiales Biomiméticos , Fuerza Compresiva , Análisis de Falla de Equipo , Fricción , Humanos , Diseño de Prótesis , Estrés Mecánico , Resistencia a la Tracción
12.
J Shoulder Elbow Surg ; 25(10): 1643-8, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27106116

RESUMEN

BACKGROUND: Efficacy of tranexamic acid (TXA) remains unproven in the setting of shoulder arthroplasty. The purpose of this study was to determine the effects of TXA on perioperative blood loss and drain output in patients undergoing primary total shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (RTSA). METHODS: We conducted a retrospective comparison of 77 TSAs and 94 RTSAs performed in 168 patients. TXA was administered intravenously in 35 TSA and 42 RTSA patients. Changes in hemoglobin (Hgb), hematocrit (Hct), drain output, and total blood loss were reviewed with univariate analysis and additional multivariate regression examining the cofactors of age, body mass index, American Society of Anesthesiologists status, and gender of each patient. RESULTS: Use of TXA in TSA led to a significant decrease in total blood loss (679 mL vs. 910 mL; P < .001), change in Hgb (1.8 mg/dL vs. 2.6 mg/dL; P < .001), and drop in Hct (5.2 vs. 7.0; P < .001). Similarly, RTSA also had significantly less total blood loss with the use of TXA (791 mL vs. 959 mL; P < .001), change in Hgb (2.3 mg/dL vs. 2.9 mg/dL; P < .001), and change in Hct (6.4 vs. 8.3; P < .001). TXA also significantly decreased drain output in both TSA (99 mL vs. 235 mL; P < .001) and RTSA (180 mL vs. 370 mL; P < .001). CONCLUSIONS: Use of TXA perioperatively among patients undergoing primary shoulder arthroplasty can decrease perioperative blood loss, change in Hgb and Hct, and postoperative drain output.


Asunto(s)
Antifibrinolíticos/uso terapéutico , Artroplastía de Reemplazo de Hombro/efectos adversos , Pérdida de Sangre Quirúrgica/prevención & control , Ácido Tranexámico/uso terapéutico , Anciano , Anciano de 80 o más Años , Antifibrinolíticos/administración & dosificación , Estudios de Cohortes , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Ácido Tranexámico/administración & dosificación , Resultado del Tratamiento
13.
J Prim Care Community Health ; 7(2): 135-8, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26763305

RESUMEN

Health care services that increase costs but fail to improve health are of low value. Limiting low-value services has potential to decrease health care expenditures by eliminating waste. We examined the opinions of Continuing Medical Education attendees about the "Choosing Wisely" campaign and decreasing use of potentially unnecessary services of low value. We compared our attendees' responses to those of participants who completed a survey a year earlier. Respondents acknowledged waste of resources as a common and serious problem and noted frequent opportunities to address low-value services with their patients. They also reported limited ability to successfully reduce unnecessary services in daily clinical care. Lack of familiarity with "Choosing Wisely" may be related.


Asunto(s)
Actitud del Personal de Salud , Gastos en Salud/normas , Uso Excesivo de los Servicios de Salud/prevención & control , Garantía de la Calidad de Atención de Salud , Adulto , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Garantía de la Calidad de Atención de Salud/economía , Escalas de Valor Relativo
14.
Urology ; 88: 155-60, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26582082

RESUMEN

OBJECTIVE: To assess patient-reported functional and quality-of-life (QoL) outcomes associated with various surgical treatments for benign prostate hyperplasia (BPH). MATERIALS AND METHODS: An independent third-party survey was sent to all patients who underwent any surgical treatment for BPH at our institution from January 2007 through January 2013. Overall satisfaction and urinary and sexual outcomes were evaluated using Sexual Health Inventory for Men (SHIM), International Prostate Symptoms Score (IPSS) for urinary function, and International Continence Society-Short Form (ICSmaleSF) questionnaires. RESULTS: Four hundred and seventy-nine respondents (response rate, 55.6%) had undergone holmium laser enucleation of the prostate (HoLEP; n = 214), transurethral resection of the prostate (n = 210), holmium laser ablation of the prostate (n = 21), photoselective vaporization (n = 18), transurethral incision of the prostate (n = 9), and open simple prostatectomy (n = 7). Postoperatively, Sexual Health Inventory for Men scores were not different. However, total IPSS varied significantly among surgical techniques (P < .001). Mean (standard deviation) IPSS was lowest for open simple prostatectomy (4.0 [2.6]), followed by HoLEP (5.8 [5.4]). For individual domains, significant differences were in intermittency (P < .001), weak stream (P = .003), straining (P < .001), and QoL (P = .001). In all these domains, HoLEP had the lowest scores. Regarding International Continence Society-Short Form, we observed a significant difference favoring transurethral resection of the prostate in incontinence (P < .001) and favoring HoLEP in voiding (P = .02) and QoL domains (P = .03). Most patients were satisfied with their surgical intervention, independent of the procedure type. Regret was least in patients who underwent HoLEP (P = .02). CONCLUSION: Patients generally expressed satisfaction with various interventions for BPH. However, those who underwent HoLEP had the best outcomes.


Asunto(s)
Autoevaluación Diagnóstica , Hiperplasia Prostática , Calidad de Vida , Humanos , Masculino , Satisfacción del Paciente , Prostatectomía/métodos , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/cirugía , Estudios Retrospectivos , Sexualidad , Micción
15.
Analyst ; 141(1): 352, 2016 Jan 07.
Artículo en Inglés | MEDLINE | ID: mdl-26626370

RESUMEN

Correction for 'Biophysical separation of Staphylococcus epidermidis strains based on antibiotic resistance' by Paul V. Jones et al., Analyst, 2015, 140, 5152-5161.

16.
J Orthop Trauma ; 29(12): e499-503, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26053466

RESUMEN

OBJECTIVES: The goal of this study was to examine the factors that affect career satisfaction in orthopaedic traumatologists. We hypothesize that the level of stress and career satisfaction in orthopaedic traumatology would be affected by increased number of call nights and work hours. DATA SOURCES: A 30-question survey was emailed to members of the OTA. The survey evaluated 5 critical areas: training/experience, practice characteristics, demands, stress management strategies, and satisfaction. STUDY SELECTION: After approval by the OTA research committee, all active and associate US members of the OTA were contacted. DATA EXTRACTION: The survey was open to the OTA members from July through November of 2012. DATA SYNTHESIS: Of 1031 members of the OTA, 263 members responded for an overall response rate of 25.5%. Most respondents were fellowship-trained (218, 82.9%) and predominantly young (<5 years in practice, 34.4%) or established surgeons (>15 years in practice, 28.5%). Most surgeons were married (229, 87.1%) and have not been divorced (226, 85.9%). Career satisfaction was statistically improved by belonging to larger practice (P = 0.016), decreased by work for more hours per week (P = 0.001), and improved by taking more call (P = 0.014). CONCLUSIONS: Career satisfaction among orthopaedic trauma surgeons was extremely high. Our results indicate that young surgeons may improve their job satisfaction and potentially prolong their career by limiting the numbers of hours worked, taking a consistent number of calls and joining a larger group. LEVEL OF EVIDENCE: Prognostic Level V. See Instructions for Authors for a complete description of levels of evidence.


Asunto(s)
Perfil Laboral , Satisfacción en el Trabajo , Ortopedia , Cirujanos/estadística & datos numéricos , Traumatología , Carga de Trabajo/estadística & datos numéricos , Adulto , Distribución por Edad , Anciano , Femenino , Humanos , Masculino , Estado Civil/estadística & datos numéricos , Persona de Mediana Edad , Ortopedia/estadística & datos numéricos , Encuestas y Cuestionarios , Traumatología/estadística & datos numéricos , Estados Unidos , Recursos Humanos , Lugar de Trabajo/estadística & datos numéricos
17.
Hepatology ; 62(4): 1004-12, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26096332

RESUMEN

UNLABELLED: Interferon (IFN)-free regimens are needed to treat hepatitis C virus (HCV) infection. Combined simeprevir (SMV) and sofosbuvir (SOF) with or without ribavirin (RBV) results in high sustained virological response (SVR) rates along with minimal adverse events (AEs) in patients with hepatitis C genotype 1 (HCV GT1). The aim of this study was to report on the virological response, safety, and tolerability of SOF and SMV with or without RBV in compensated and decompensated patients with cirrhosis with HCV GT1 infection. Patients treated with standardized clinical protocol utilizing SMV+SOF with or without RBV at three transplant centers were retrospectively reviewed. A total of 119 patients (61% male, 87% white, 69% subtype 1a, 30% Child-Pugh-Turcott [CPT]-B liver cirrhosis [LC], and 82% were treatment experienced) received treatment and were followed for a median of 38 weeks (range, 12-58). Sustained virological response (SVR) at week 12 (SVR12) was achieved in 78% (92 of 118) of patients (95% confidence interval: 69-85). Lower pretreatment Model for End Stage Liver Disease (MELD) score was a predictor of SVR12 (P = 0.018). Baseline viral load, previous treatment status, RBV use, or GT1 subtype did not impact SVR 12. The majority of patients with SVR12 showed stability or improvement in MELD score. Treatment was very well tolerated with mild degrees of AEs. CONCLUSIONS: The regimen of SMV+SOF with or without RBV for 12 weeks was very well tolerated and resulted in high SVR12 rates (78%) in HCV GT1 patients with LC. SVR12 was inversely related to pretreatment MELD. SVR12 had favorable short-term impact on MELD score. Long-term impact on disease stability is yet to be determined. Longer treatment duration or the use of different regimen may still be needed in this population.


Asunto(s)
Antivirales/administración & dosificación , Hepatitis C/tratamiento farmacológico , Ribavirina/administración & dosificación , Simeprevir/administración & dosificación , Sofosbuvir/administración & dosificación , Combinación de Medicamentos , Femenino , Genotipo , Hepacivirus/clasificación , Hepacivirus/genética , Hepatitis C/complicaciones , Humanos , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
18.
Analyst ; 140(15): 5152-61, 2015 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-26086047

RESUMEN

Electrophoretic and dielectrophoretic approaches to separations can provide unique capabilities. In the past, capillary and microchip-based approaches to electrophoresis have demonstrated extremely high-resolution separations. More recently, dielectrophoretic systems have shown excellent results for the separation of bioparticles. Here we demonstrate resolution of a difficult pair of targets: gentamicin resistant and susceptible strains of Staphylococcus epidermidis. This separation has significant potential implications for healthcare. This establishes a foundation for biophysical separations as a direct diagnostic tool, potentially improving nearly every figure of merit for diagnostics and antibiotic stewardship. The separations are performed on a modified gradient insulator-based dielectrophoresis (g-iDEP) system and demonstrate that the presence of antibiotic resistance enzymes (or secondary effects) produces a sufficient degree of electrophysical difference to allow separation. The differentiating factor is the ratio of electrophoretic to dielectrophoretic mobilities. This factor is 4.6 ± 0.6 × 10(9) V m(-2) for the resistant strain, versus 9.2 ± 0.4 × 10(9) V m(-2) for the susceptible strain. Using g-iDEP separation, this difference produces clear and easily discerned differentiation of the two strains.


Asunto(s)
Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis/aislamiento & purificación , Antibacterianos/farmacología , Separación Celular/instrumentación , Farmacorresistencia Microbiana , Conductividad Eléctrica , Electroforesis/instrumentación , Gentamicinas/farmacología , Humanos , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus epidermidis/efectos de los fármacos
19.
Clin Orthop Relat Res ; 473(7): 2262-9, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25804880

RESUMEN

BACKGROUND: Liposomal amphotericin B is locally delivered to treat fungal orthopaedic infections but little is known about local tissue toxicity, if any, that might be associated with local delivery. QUESTIONS/PURPOSES: (1) Is liposomal amphotericin B cytotoxic in vitro? (2) Is locally delivered liposomal amphotericin B toxic to tissue in vivo? METHODS: Mouse fibroblasts (BA LB/3T3 A31) and osteoblasts (MC3T3) were exposed to two formulations of amphotericin B (liposomal and deoxycholate) at concentrations of 0, 1, 5, 10, 100, 500, and 1000 µg/mL. Cell viability was determined by MTT assay after 1, 3, and 5 hours of exposure and a proliferation assay after 1, 4, and 7 days of exposure and then after 3 recovery days without drug. Tissue exposure occurred by local delivery of liposomal amphotericin B, 200 or 800 mg/batch antifungal-loaded bone cement (ALBC), or amphotericin B deoxycholate, 800 mg/batch ALBC in rat paraspinal muscles. White blood cell count (WBC) and serum amphotericin B levels were obtained on Days 1 and 3. Rats were euthanized at 2 and 4 weeks and semiqualitative histopathology was performed. RESULTS: Liposomal amphotericin B is cytotoxic in vitro but not toxic to tissues in vivo. All cells survived concentrations up to 1000 µg/mL for 5 hours, 100% ± 0%, but none survived ≥ 100 µg/mL for 7 days, 0% ± 0%. Fibrosis was seen adjacent to ALBC without inflammation or necrosis, indistinguishable from controls for both liposomal amphotericin B doses. Amphotericin B serum levels were all less than 1 µg/mL and WBC counts were all normal. CONCLUSIONS: In vitro cytotoxicity to liposomal amphotericin B occurred but no adverse tissue reaction was seen in vivo. CLINICAL RELEVANCE: Local delivery of liposomal amphotericin B in ALBC was well tolerated by mouse tissue; however, clinical studies are needed to confirm this finding in humans.


Asunto(s)
Anfotericina B/toxicidad , Antifúngicos/toxicidad , Animales , Cementos para Huesos , Células Cultivadas , Fibroblastos/efectos de los fármacos , Ratones , Osteoblastos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley
20.
Clin Orthop Relat Res ; 473(7): 2253-61, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25649197

RESUMEN

BACKGROUND: High-dose antimicrobial-loaded bone cement (ALBC) is recommended to treat orthopaedic infections. Elution characteristics from prefabricated ALBC spacers and how they compare with hand-mixed ALBC are not well described. QUESTIONS/PURPOSES: (1) How does antimicrobial release from prefabricated spacers compare with release from hand-mixed ALBC over time? (2) Is antimicrobial release uniform across the surface of prefabricated ALBC spacers? (3) Do variations exist between different prefabricated spacer components? (4) Do textured surfaces release more antimicrobial than smooth surfaces? METHODS: Six prefabricated ALBC spacer components, two hip and four knee, and three hand-mixed ALBC formulations were studied in this comparative laboratory study. Gentamicin was eluted from 41 discrete sites over the surfaces of six spacer components and compared with elution from 15 ALBC specimens, five from each of three hand-mixed formulations. Elution was compared between spacer sites, components, and surface texture. Statistical analysis was performed by analysis of variance and Tukey's multiple-comparison test or t-test. RESULTS: Gentamicin release was highest in the first 24 hours for both prefabricated ALBC spacers and hand-mixed ALBC. Elution decreased over 7 days similarly for both. At Day 7, prefabricated ALBC spacers eluted more than hand-mixed 1 g ALBC (1 g ALBC: 1.49 ± 0.34, prefabricated: 3.59 ± 1.48, mean difference = 2.1 [0.2-4.0], p = 0.04) but eluted less than 5 g ALBC (9.21 ± 1.31, mean difference = -5.6 [-3.5 to -7.7], p < 0.001) and less than 10 g ALBC (35.8 ± 1.69, mean difference = -32.2 [-29.8 to -34.6], p < 0.001). Release varied from 2.7 to 9.9 µg/mm(2) over the surface of the spacers and from 3.5 to 5.5 µg/mm(2) between components with no component different than the others (Tukey). Release from textured surfaces was inconsistent. CONCLUSIONS: Antimicrobial release from prefabricated ALBC spacers is consistent with low-dose ALBC. Variation across the surface and between components is small compared with changes in antimicrobial load. CLINICAL RELEVANCE: Antimicrobial release from prefabricated ALBC spacers is consistent with local antimicrobial delivered from other low-dose ALBC formulations.


Asunto(s)
Antibacterianos/administración & dosificación , Cementos para Huesos , Portadores de Fármacos , Gentamicinas/administración & dosificación , Infecciones Relacionadas con Prótesis/prevención & control , Diseño de Prótesis
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