Standard Intravenous Research Articles

P-877. Effectiveness of Oral Step-down Antibiotic Therapy in Uncomplicated Enterococcus faecalis Bloodstream Infection

Abstract Background The transition from intravenous (IV) to oral antibiotic therapy is a common strategy in the management of uncomplicated bloodstream infection (BSI). However, the role of oral step-down therapy in uncomplicated Enterococcus faecalis BSI has not been defined. This retrospective cohort study examines the effectiveness of oral step-down antibiotics compared to standard IV therapy in uncomplicated E. faecalis BSI. Risk factors for treatment failure in uncomplicated Enterococcus faecalis bloodstream infection (BSI) *Early clinical failure criteria include systolic blood pressure <100 mmHg or vasopressor use, heart rate >100 beats/minute, respiratory rate ≥ 22 breaths/minute or mechanical ventilation, altered mental status, white blood cell count >12,000/mm3. Methods Adults with uncomplicated E. faecalis BSI admitted to 10 Prisma Health hospitals in South Carolina from January 2021 to June 2023 were evaluated. Clinically insignificant positive blood cultures, polymicrobial, recurrent, persistent, and complicated BSI were excluded. Deaths within 7 days were excluded to mitigate immortal time bias. Multivariate Cox proportional hazards regression examined the risk of treatment failure (all-cause mortality or recurrence) within 90-day. Wilcoxon rank sum test compared hospital length of stay (HLOS) between the two groups. Results Of 476 screened patients, 131 with uncomplicated E. faecalis BSI were included in the analysis. The median age was 70 years, 84 (64%) were men, and 46 (35%) had a urinary source of infection. Eighty-seven patients (66%) received standard IV therapy and 44 (34%) were transitioned to oral step-down therapy. Median antibiotic treatment durations were 15 and 14 days, respectively. Patients in the oral step-down group received 6 days of IV antibiotics followed by 8 days of oral therapy, most commonly oral aminopenicillins (33/44; 75%). In the multivariate Cox model, oral step-down therapy was not associated with increased risk of treatment failure compared to standard IV therapy (hazard ratio 0.91, 95% confidence intervals 0.31-2.63; Table). HLOS was 7 days in the oral step-down group and 11 days in the standard IV group (p< 0.001). Conclusion Transitioning patients with uncomplicated E. faecalis BSI from IV to oral step-down antibiotic therapy appears to be a promising strategy with shorter HLOS and no significant increase in the risk of treatment failure. These results should be confirmed in larger multicenter studies prior to routine implementation in clinical practice. Disclosures All Authors: No reported disclosures

Intra-articular Injection of a B Cell Depletion Antibody Enhances Local Exposure to the Joint-Draining Lymph Node in Mice with Collagen-Induced Arthritis.

Changes to the number, type, and function of immune cells within the joint-draining lymphatics is a major contributor to the progression of inflammatory arthritis. In particular, there is a significant expansion in pathogenic B cells in the joint-draining lymph node (jdLN). These B cells appear to clog the lymphatic sinuses in the lymph node, inhibit lymph flow, and therefore, reduce the clearance of inflammatory fluid and cells from the joint. Taken together, there is potential to treat inflammatory arthritis more effectively, as well as reduce off-target side effects, with localized delivery of B-cell depleting therapies to the jdLNs. We recently reported that joint-draining lymphatic exposure of biologic disease-modifying anti-rheumatic drugs (DMARDs), including the B cell depletion antibody rituximab, is increased in healthy rats following intra-articular (IA) compared to subcutaneous (SC) or intravenous (IV) administration. This suggests that IA administration of B cell depleting antibodies may increase delivery to target cells in the jdLN and increase the effectiveness of B cell depletion compared to standard SC or IV administration. However, whether enhanced local delivery of DMARDs to the jdLN is also achieved after IA injection in the setting of inflammatory arthritis, where there is inflammation in the joint and jdLN B cell expansion is unknown. We, therefore, assessed the lymph node distribution, absorption and plasma pharmacokinetics, and B cell depletion at different sites after IA, SC, or IV administration of a fluorescently labeled mouse anti-CD20 B cell depleting antibody (Cy5-αCD20) in healthy mice compared to mice with collagen-induced arthritis (CIA). The absorption and plasma pharmacokinetics of Cy5-αCD20 appeared unaltered in mice with CIA whereas distribution of Cy5-αCD20 to the jdLNs was generally increased in mice with CIA, regardless of the route of administration. However, IA administration led to greater and more specific exposure to the jdLNs. Consistent with increased Cy5-αCD20 in the jdLNs of CIA compared to healthy mice, there was a greater reduction in jdLN weight and a trend toward greater jdLN B cell depletion at 24 h compared to 4 h after IA compared to SC and IV administration. Taken together, this data supports the potential to improve local efficacy of B cell depletion therapies through a jdLN-directed approach which will enable a reduction in dose and systemic toxicities.

Is Topical Vancomycin an Option? A Randomized Controlled Trial to Determine the Safety of the Topical Use of Vancomycin Powder in Preventing Postoperative Infections in Total Knee Arthroplasty, as Compared With Standard Postoperative Antibiotics

BackgroundThe demand for total knee arthroplasties (TKAs) is expected to rise in the coming decades, increasing the burden of periprosthetic joint infections (PJIs). The use of intrawound vancomycin powder (VP) has proven to be effective in reducing the incidence of PJIs after spinal surgery. That said, its effectiveness in TKA remains unclear. This trial aims to examine the efficacy of intrawound vancomycin powder first versus standard postoperative antibiotics in preventing PJIs after TKA. MethodsThis study was a double-blinded, noninferiority, randomized controlled trial. All participants received standard preoperative intravenous (IV) antibiotics (Cefazolin/Vancomycin) within 60 minutes of skin incision. Patients in the treatment group received 1 gram of VP applied intraoperatively by the orthopedic surgeon (500 mg directly on the prosthesis, 500 mg above the closed joint capsule). These patients did not receive postoperative antibiotics. Patients in the control group received standard postoperative IV antibiotics. The primary outcome was the incidence of acute surgical site infection within 42 days of procedure. ResultsThere were 80 patients randomized to the treatment group and 85 patients randomized to the control. Groups were matched with respect to baseline characteristics, including average age (66 versus 64), BMI (35.7 versus 33.4), and diabetics (16 versus 13). The trial was halted at 1 year as a significantly greater proportion (P = .03) of patients in the treatment group (n = 3, 3.75%) were diagnosed with PJIs compared to the control (n = 0). ConclusionOur trial demonstrated the intrawound application of VP to be inferior to standard postoperative IV antibiotics in reducing the incidence of PJIs after TKA.

1843. Intravenous versus Partial Oral Antibiotic Therapy in the Treatment of Uncomplicated Bloodstream Infection due to Streptococcus species

Abstract Background Effectiveness of oral antibiotics for transition of therapy in uncomplicated bloodstream infections (BSI) due to Streptococcus species remains unclear. This retrospective cohort study examines effectiveness of partial oral antibiotic regimens in patients with uncomplicated BSI due to Streptococcus species compared to standard intravenous (IV) only therapy. Methods Adult patients with uncomplicated BSI due to Streptococcus species from April 2016 through June 2020 in 7 hospitals within Prisma Health in South Carolina were evaluated. Patients who died within 7 days of BSI were excluded to reduce the impact of survival bias. Multivariate Cox proportional hazards regression was used to examine time to treatment failure, defined as a composite of all-cause mortality and BSI recurrence within 90 days. Results A total of 222 patients with Streptococcus species BSI were included in the analysis. Overall, the median age was 62 years, and 116 (52.3%) were men. Beta-hemolytic streptococci (87; 39.2%) were the most common bloodstream isolates, followed by S. pneumoniae (76; 34.2%) and viridans group streptococci (59; 26.6%). Among this cohort, 99 patients received only IV antibiotics, and the remaining 123 received partial oral therapy. The median duration of therapy in both groups was 14 days, and median duration of IV antibiotics prior to oral transition was 4 days. Most patients in the partial oral group were transitioned to either oral beta-lactams (62; 50.4%) or fluoroquinolones (47; 38.2%). Of the IV only group, 46 (46.5%) required outpatient IV antibiotics. Treatment failure rates were 12.0% and 4.4% in the IV only and partial oral therapy groups, respectively (p=0.04). After adjustments for age, chronic comorbidities, and initial response to therapy within the first 72-96 hours, there was no difference in the risk of treatment failure in the partial oral compared to IV only group (hazards ratio 0.55, 95% CI 0.19-1.64; p=0.28). Conclusion Transitioning patients from IV to oral antibiotics may be a reasonable strategy in the management of uncomplicated BSI due to Streptococcus species. Partial oral therapy does not seem to have a higher treatment failure rate than standard IV only therapy and may spare many patients from outpatient IV antibiotics. Disclosures All Authors: No reported disclosures.

Evaluating the Use of Dalbavancin for Off-Label Indications.

(1) Background: Dalbavancin is a long-acting lipoglycopeptide antibiotic approved for skin and soft-tissue infections. Post-marketing experience suggests dalbavancin is being used for off-label indications that normally require long-term intravenous (IV) antibiotics; however, data assessing this off-label usage are limited. The purpose of this study was to evaluate the real-world efficacy, safety, and financial impact of off-label dalbavancin use. (2) Methods: This is a retrospective, observational study conducted within a 4-hospital health system. Adult patients who received dalbavancin from January 2018 to January 2021 for an off-label indication were included. The primary outcome was clinical success at 90 days. Secondary outcomes included safety (nephrotoxicity and hepatotoxicity). A pharmacoeconomic analysis was performed by comparing the cost of dalbavancin to the anticipated cost of patient stay if standard IV therapy was given. (3) Results: Forty-eight patients met study criteria. Indications included osteomyelitis (54%), endocarditis (23%), bacteremia (15%), and prosthetic joint infection (8%). The predominant organism was S. aureus (60%), with 42% caused by methicillin-resistant S. aureus. Overall, 41 (85%) patients achieved clinical success at 90 days, including 85% with osteomyelitis, 82% with endocarditis, and 86% with bacteremia. There were no instances of nephrotoxicity or hepatotoxicity. Estimated cost avoidance per patient was USD 5313 and USD 1683 if traditional IV therapy would have been completed in the hospital and skilled nursing facility, respectively. (4) Conclusion: Dalbavancin was associated with a relatively high success rate for the treatment of off-label indications and may be a cost-effective alternative to traditional IV antibiotic therapy.

Partial oral antibiotic treatment for bacterial brain abscess: an open-label randomized non-inferiority trial (ORAL)

BackgroundThe advised standard treatment for bacterial brain abscess following surgery is 6 to 8 weeks of intravenous (IV) antibiotic treatment, but an early switch to oral antibiotic treatment has been suggested to be equally effective.MethodsThis investigator-initiated, international, multi-center, parallel group, open-label, randomized (1:1 allocation) controlled trial will examine if oral treatment after 2 weeks of IV antibiotic therapy is non-inferior to standard 6–8 weeks of IV antibiotics for bacterial brain abscess in adults (≥ 18 years of age). The study will be conducted at hospitals across Denmark, the Netherlands, France, Australia, and Sweden. Exclusion criteria are severe immunocompromise or impaired gastro-intestinal absorption, pregnancy, device-related brain abscesses, and brain abscess caused by nocardia, tuberculosis, or Pseudomonas spp. The primary objective is a composite endpoint at 6 months after randomization consisting of all-cause mortality, intraventricular rupture of brain abscess, unplanned re-aspiration or excision of brain abscess, relapse, or recurrence. The primary endpoint will be adjudicated by an independent blinded endpoint committee. Secondary outcomes include extended Glasgow Outcome Scale scores and all-cause mortality at end of treatment as well as 3, 6, and 12 months since randomization, completion of assigned treatment, IV catheter associated complications, durations of admission and antibiotic treatment, severe adverse events, quality of life scores, and cognitive evaluations. The planned sample size is 450 patients for a one-sided alpha of 0.025 and a power of 90% to exclude a difference in favor of standard treatment of more than 10%. Date of initiation of first study center was November 3, 2020, with active recruitment for 3 years and follow-up for 1 year of all patients.DiscussionThe results of this study may guide future recommendations for treatment of bacterial brain abscess. If early transition to oral antibiotics proves non-inferior to standard IV treatment, this will provide considerable health and costs benefits.Trial registrationClinicalTrials.gov NCT04140903, first registered 28.10.2019. EudraCT number: 2019-002845-39, first registered 03.07.2019

346 Ultra Long Versus Standard Long Peripheral Intravenous Catheters: A Randomized Controlled Trial of Ultrasound-Guided Catheter Survival

Ultrasound-guided intravenous (IV) catheters have dismal dwell time with most IVs failing prior to completion of therapy. Catheter length in vein is a variable directly related to catheter survival. We investigate the survival of an ultra long peripheral IV compared to standard long peripheral IV placed under ultrasound (US)-guidance. We conducted a single site, 2-arm, nonblinded, randomized controlled trial of catheter survival. Adult patients presenting to the emergency department (ED) with a history of difficult vascular access were recruited to participate. Patients were randomized to receive either a standard long 4.78 cm length 20 gauge US-guided IV catheter or the intervention ultra long 6.35 cm length 20 gauge US-guided IV catheter. The primary outcome was catheter survival. All functional catheters removed with less than 24 hours dwell time were excluded from the survival analysis. Any catheter failure regardless of dwell time was included in the survival analysis. Secondary outcomes included evaluation of insertion parameters including first-stick success and time to insertion as well as complications including thrombosis and infection. 270 patients were enrolled. 194 patients were included in the survival analysis with 99 in the standard long IV group and 95 in the ultra long IV group. Kaplan-Meier estimate of catheter median survival time was 135.88 hours (5.66 days) [95% CI 115-310] for the ultra long IV catheters compared to 77.67 hours (3.23 days) [95% CI 63-102] for the standard long IV catheters (Log-rank Test: p = 0.008). IVs with greater than 3.1 cm of the catheter residing in vein had a median survival of 128.90 hours (5.37 days) [95% CI 96-504] compared to 76.55 hours (3.18 days) [95% CI 63-115] for IVs with less than 3.1 cm in the vein (p=0.04). This study supports the use of ultra long IV catheters over the standard length options for upper arm insertions as these catheters have a favorable survival profile for difficult access ED patients. The improved survival is related to the amount of catheter residing in the vein with greater than 3.1 cm catheter in vein yielding the best longevity. Further, as ultra long catheters have similar insertion characteristics and no additional education/training is needed for insertion competency, adoption of these catheters can occur seamlessly at any ED.

Standard long IV catheters versus extended dwell catheters: A randomized comparison of ultrasound-guided catheter survival

IntroductionEstablishing peripheral intravenous (IV) access is a vital step in providing emergency care. Ten to 30% of Emergency Department (ED) patients have difficult vascular access (DVA). Even after cannulation, early failure of US-guided IV catheters is a common complication. The primary goal of this study was to compare survival of a standard long IV catheter to a longer extended dwell catheter. MethodsThis study was a prospective, randomized comparative evaluation of catheter longevity. Two catheters were used in the comparison: [1] a standard long IV catheter, the 4.78 cm 20 gauge Becton Dickinson (BD); and [2] a 6 cm 3 French (19.5 gauge) Access Scientific POWERWAND™ extended dwell catheter (EDC). Adult DVA patients in the ED with vein depths of 1.20 cm–1.60 cm and expected hospital admissions of at least 24 h were recruited. Results120 patients were enrolled. Ultimately, 70 patients were included in the survival analysis, with 33 patients in the EDC group and 37 patients in the standard long IV group. EDC catheters had lower rates of failure (p = 0.0016). Time to median catheter survival was 4.04 days for EDC catheters versus 1.25 days for the standard long IV catheter. Multivariate survival analysis also showed a significant survival benefit for the EDC catheter (p = 0.0360). ConclusionA longer extended dwell catheter represents a viable and favorable alternative to the standard longer IVs used for US-guided cannulation of veins >1.20 cm in depth. These catheters have significantly improved survival rates with similar insertion success characteristics.

Neuropathy and efficacy of once weekly subcutaneous bortezomib in multiple myeloma and light chain (AL) amyloidosis.

IntroductionRandomized studies have shown that bortezomib (BTZ) can be given weekly via intravenous (IV) route or twice weekly via subcutaneous (SC) route with lower neuropathy risk and no loss of anti-myeloma efficacy compared to original standard IV twice weekly schedule. Weekly SC should therefore yield the best therapeutic index and is widely used but has not been compared to established administration schedules in the context of a clinical trial.MethodsComprehensive electronic medical record review was done for disease control and neuropathy symptoms of 344 consecutive patients who received their first BTZ-containing regimen for myeloma or AL amyloidosis before or after we changed to SC weekly in December 2010. Univariate and multivariable analyses were carried out that adjusted for age, underlying disease, concurrently used anticancer agents, underlying conditions predisposing to neuropathy, and number of prior regimens compared SC weekly to other schedules.ResultsFifty-three patients received BTZ SC weekly, 17 SC twice weekly, 127 IV weekly and 147 IV twice weekly. Risk for neuropathy of any grade was higher with other schedules compared to SC weekly (44.3% vs. 26.9%, p = 0.001) while response rate was similar (72.1% vs. 76.6%, respectively, p = 0.15). Multivariable analyses upheld higher neuropathy risk (Odds ratio 2.45, 95% CI 1.26–4.76, p = 0.008) while the likelihood of not achieving a response (= partial response or better) was comparable (Odds ratio 1.25, 95% CI 0.58–2.71, p = 0.56) for other schedules compared to SC weekly, respectively. Lower neuropathy risk translated into longer treatment duration when BTZ was started SC weekly (p = 0.001).ConclusionsWeekly SC BTZ has activity comparable to other schedules and causes low rates of neuropathy.

Extravasation Risk Using Ultrasound‐guided Peripheral Intravenous Catheters for Computed Tomography Contrast Administration

Ultrasound-guided intravenous catheter (USGIV) insertion is increasingly being used for administration of intravenous (IV) contrast for computed tomography (CT) scans. The goal of this investigation was to evaluate the risk of contrast extravasation among patients receiving contrast through USGIV catheters. A retrospective observational study of adult patients who underwent a contrast-enhanced CT scan at a tertiary care emergency department during a recent 64-month period was conducted. The unadjusted prevalence of contrast extravasation was compared between patients with an USGIV and those with a standard peripheral IV inserted without ultrasound. Then, a two-stage sampling design was used to select a subset of the population for a multivariable logistic regression model evaluating USGIVs as a risk factor for extravasation while adjusting for potential confounders. In total, 40,143 patients underwent a contrasted CT scan, including 364 (0.9%) who had contrast administered through an USGIV. Unadjusted prevalence of extravasation was 3.6% for contrast administration through USGIVs and 0.3% for standard IVs (relative risk = 13.9, 95% confidence interval [CI] = 7.9 to 24.6). After potential confounders were adjusted for, CT contrast administered through USGIVs was associated with extravasation (adjusted odds ratio = 8.6, 95% CI = 4.6 to 16.2). No patients required surgical management for contrast extravasation; one patient in the standard IV group was admitted for observation due to extravasation. Patients who received contrast for a CT scan through an USGIV had a higher risk of extravasation than those who received contrast through a standard peripheral IV. Clinicians should consider this extravasation risk when weighing the risks and benefits of a contrast-enhanced CT scan in a patient with USGIV vascular access.

Use of a pressure wire to evaluate right heart pressures in a pre-liver transplant recipient through a peripheral IV.

Use of a pressure wire to evaluate right heart pressures in a pre-liver transplant recipient through a peripheral IV.

Novel Technique for Rebubbling DMEK Grafts at the Slit Lamp Using Intravenous Extension Tubing.

To describe a novel technique for rebubbling DMEK grafts at the slit lamp using a cannula coupled to a syringe with intravenous (IV) extension tubing. We present a retrospective case series of eyes that underwent rebubbling using a novel technique at the slit lamp. The rebubbling apparatus is assembled using a standard 43-inch IV extension tube, a 5-cc luer lock syringe, and a 27-gauge cannula. The cannula is screwed onto one end of the extension tubing, and a 5-cc syringe that has been filled with air is screwed onto the opposite end. With the patient seated at the slit lamp, the cannula is positioned in the anterior chamber by the surgeon with one hand while the other hand operates the syringe and the joystick. We performed 5 rebubbling procedures at the slit lamp using a standard syringe and cannula. Despite suboptimal ergonomics with this approach, all of these cases achieved sufficient air fills without any complications. Four rebubbling procedures were subsequently performed at the slit lamp using our novel rebubbling technique. All of these cases also attained sufficient air fills without complications, but they were noted to be much easier to perform by the surgeon. Using IV extension tubing to couple a syringe to a cannula for rebubbling DMEK grafts at the slit lamp is ergonomically superior to the conventional alternative of using a standard cannula on a syringe. The technique is also simple and inexpensive to adopt.

Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer.

Ovarian cancer tends to be chemosensitive and confine itself to the surface of the peritoneal cavity for much of its natural history. These features have made it an obvious target for intraperitoneal (IP) chemotherapy. Chemotherapy for ovarian cancer is usually given as an intravenous (IV) infusion repeatedly over five to eight cycles. Intraperitoneal chemotherapy is given by infusion of the chemotherapeutic agent directly into the peritoneal cavity. There are biological reasons why this might increase the anticancer effect and reduce some systemic adverse effects in comparison to IV therapy. To determine if adding a component of the chemotherapy regime into the peritoneal cavity affects overall survival, progression-free survival, quality of life (QOL) and toxicity in the primary treatment of epithelial ovarian cancer. We searched the Gynaecological Cancer Review Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2011, MEDLINE (1951 to May 2011) and EMBASE (1974 to May 2011). We updated these searches in February 2007, August 2010, May 2011 and September 2015. In addition, we handsearched and cascade searched the major gynaecological oncology journals up to May 2011. The analysis was restricted to randomised controlled trials (RCTs) assessing women with a new diagnosis of primary epithelial ovarian cancer, of any FIGO stage, following primary cytoreductive surgery. Standard IV chemotherapy was compared with chemotherapy that included a component of IP administration. We extracted data on overall survival, disease-free survival, adverse events and QOL and performed meta-analyses of hazard ratios (HR) for time-to-event variables and relative risks (RR) for dichotomous outcomes using RevMan software. Nine randomised trials studied 2119 women receiving primary treatment for ovarian cancer. We considered six trials to be of high quality. Women were less likely to die if they received an IP component to chemotherapy (eight studies, 2026 women; HR = 0.81; 95% confidence interval (CI): 0.72 to 0.90). Intraperitoneal component chemotherapy prolonged the disease-free interval (five studies, 1311 women; HR = 0.78; 95% CI: 0.70 to 0.86). There was greater serious toxicity with regard to gastrointestinal effects, pain, fever and infection but less ototoxicity with the IP than the IV route. Intraperitoneal chemotherapy increases overall survival and progression-free survival from advanced ovarian cancer. The results of this meta-analysis provide the most reliable estimates of the relative survival benefits of IP over IV therapy and should be used as part of the decision making process. However, the potential for catheter related complications and toxicity needs to be considered when deciding on the most appropriate treatment for each individual woman. The optimal dose, timing and mechanism of administration cannot be addressed from this meta-analysis. This needs to be addressed in the next phase of clinical trials.

Subcutaneous administration of bortezomib significantly decreased and delayed the development of peripheral neuropathy in patients with newly diagnosed multiple myeloma

Bortezomib (btz) is the major and potent agent in multiple myeloma (MM) treatment and intravenous (IV) injection is its standard administration route. However, peripheral neuropathy (PN) always limited the use of btz. Subcutaneous (SC) administration is an important alternative. The primary outcome of our previous study showed that SC administration of btz significantly decreased and delayed the development of PN in patients with newly diagnosed MM (NDMM) and relapse/refractory MM (RRMM). Here, we amplified the cohorts and extended follow up to further confirm our previous primary outcome in patients with NDMM. This retrospective, historical control study was undertaken at a single centre in China. Patients with NDMM were assigned to receive up to nine 21-day cycles of Btz based regimens, including PAd/VDd/BCd (btz 1.3 mg/m2 , on days 1, 4, 8 and 11; adriamycin 9 mg/m2 on days 1-4; or PLD 30mg/m2 on days 1, or CTX 500mg/m2 on days 1, 8, 15, and dexamethasone 20 mg/day on days 1, 2, 4, 5, 8, 9, 11 and 12). Btz was administered by SC injection or IV infusion. Then the efficacy and safety of SC versus IV btz were compared. 330 NDMM patients were received Btz based treatment. 151 received a median of 5 cycles of SC btz (SC group) from 2012.3 to 2014.12. 179 cases were treated with a median 3 cycles of IV btz (historical control IV group) from 2008.5 to 2012.2. The overall response rate (ORR, >1⁄4PR) was 97.4% and 97.2% in these two groups, with 37.7% and 36.3% achieved CR respectively, indication the efficacy was very comparable. SC group had better safety profile. Most of any grade adverse events (AE) were less common with SC than with IV administration, including thrombocytopenia, neutropenia, anaemia. The most importance was PN of any grade (32.1% vs 58.1%; p1⁄40$01) was significantly decreased with SC btz. Especially severe PN (grade 3/4) was also significantly decreased (5.3% vs 18.4%, p1⁄40.013). Notably, the incidence and seriousness of diarrhea were lower (any grade, 9.8% vs 15.7%, >1⁄4grade 3, 0.9% vs 4.7%, respectively), so were constipation, and intestinal obstruction, which may be related to the neuropathy toxicity of btz. The time of developing PN was delayed in SC group. Median dosage of btz when PN developed was 15.6 mg/m2 in SC group and 10.4mg/m2 in IV group. The efficacy of SC btz in patients with NDMM was comparable with standard IV administration. SC btz was locally well tolerated. It significantly decreased and delayed the development of PN. PO-143 Melphalan 140mg/m“2” significantly reduces 5 year progression free survival in multiple myeloma patients receiving a peripheral blood autologous stem cell transplant compared with melphalan 200mg/m“2” C. Attwood, E. Nicholson, R. Chakraverty, A. Fielding, P. Kottaridis, D. Hughes, A. Mehta, W. Stewart, C. Kyriakou, S. Worthington, S. Grace, A. Wechalekar, S. MacKinnon Royal Free Hospital, London

Fludarabine, cyclophosphamide and rituximab as first-line treatment in patients with newly diagnosed follicular lymphoma.

Fludarabine-based regimens are highly effective as first-line therapy in patients with follicular lymphoma. Nevertheless, noticeable haematological toxicity has been reported using fludarabine-based regimens. To analyse the combination of low-dose oral fludarabine and cyclophosphamide plus rituximab (FCR) as induction therapy, followed by rituximab as maintenance therapy. We retrospectively analysed 73 patients diagnosed with low-grade follicular lymphoma treated with two different schemes: attenuated oral (AO) and standard intravenous (SIV) FCR. Overall response rate (ORR) was 95% (complete response rate, CRR 79.5%, partial response, PR 15.4%). CRR was 84.6% in AO vs. 61.9% in SIV (P=0.058). 44.4% of patients underwent maintenance therapy. Grade 3-4 toxicities included neutropenia: 65.4%; anaemia: 39.7%; thrombocytopenia: five patients; infectious complications: six patients. There were no treatment-related deaths. 6.8% had a secondary malignancy. Progression-free survival (PFS) was 84.6% at 12yr. The following variables influenced PFS in multivariate analysis: Hb<12g/dL [HR 4.7 (95% CI 1.18-18.6)], response after induction [HR 4.9 (95% CI 1.01-24)] for PR vs. CR and [HR 21.27 (95% CI 4.33-104)] for SD/DP vs. CR. OS was 83.1% at 12yr. The following variables significantly influenced OS in multivariate analysis: not receiving rituximab as maintenance therapy (HR 10.7 (95% CI 1.4-82.5), increased levels of β2-microglobulin [HR 5.2 (95% CI 1.16-23.7)]. FCR allowed us to obtain a high response rate, which translated into promising progression free and overall survival with an acceptable and manageable toxicity profile, especially with the attenuated oral scheme.

Evaluation of Fluid Bolus Administration Rates Using Ruggedized Field Intravenous Systems

The purpose of this study was to evaluate 2 ruggedized field intravenous (IV) systems currently in use by US military medics and to determine their effect on fluid bolus administration rates. A series of 500 mL fluid boluses consisting of either Lactated Ringer's solution or Hextend were delivered to 2 artificial intravenous training arms using a standard 18G catheter (control) and 2 separate ruggedized field IV systems. Fluid boluses were delivered under both gravity force and pressure infusion (constant 300 mm Hg), and total bolus times were recorded. Using Lactated Ringer's solution, the standard IV system took a mean time of 9:33 minutes (95% CI: 9:13-9:54) to deliver a 500 mL fluid bolus whereas the 2 ruggedized field systems took mean times of 14:50 minutes (95% CI: 14:00-15:40) and 12:20 minutes (95% CI: 11:54-12:45). Using Hextend, the mean bolus time for the control system was 24:39 minutes (95% CI: 22:47-26:32). The 2 ruggedized field systems required an average of 49:32 minutes (95% CI: 48:07-50:58) and 39:46 minutes (95% CI: 37:30-42:01) to deliver an equivalent bolus. Pressure infusion significantly increased flow rate in all systems. Ruggedized field IV systems can significantly delay fluid bolus rates. In instances where ruggedized field systems are deemed necessary, pressure infusion devices should be considered to overcome the constrictive effects of the ruggedized system.

Three ongoing intraperitoneal chemotherapy trials in ovarian cancer

Three ongoing intraperitoneal chemotherapy trials in ovarian cancer

Intracoronary versus intravenous bolus abciximab application in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: 6-month effects on infarct size and left ventricular function

Administration of abciximab during primary percutaneous coronary intervention (PCI) reduces major adverse cardiac events (MACE) in patients with ST-elevation myocardial infarction (STEMI). Intracoronary (IC) abciximab bolus application during PCI results in high local drug concentration, improved perfusion, reduction of infarct size, and less microvascular obstruction early after infarction. Aim of this study was to investigate whether the early benefits of an IC abciximab administration in STEMI patients undergoing PCI are sustained at 6 months. We performed 6-month follow-up of 154 STEMI patients undergoing PCI, who were randomised to either IC (n = 77) or intravenous (IV) (n = 77) bolus abciximab administration with subsequent 12-h intravenous infusion. The primary endpoint was infarct size at 6-month follow-up as assessed by delayed enhancement magnetic resonance imaging. Clinical end points were MACEs within 6 months after infarction. The median infarct size after 6 months was significantly reduced in the IC abciximab group (16.7 vs. 24.1%, p = 0.002). A significant recovery of LV function was only observed in the IC abciximab group (p < 0.001), and IC abciximab group patients had significantly less adverse remodelling as compared to standard IV abciximab treatment (p = 0.03). These beneficial effects also translated into a strong trend towards a reduced MACE rate in the IC abciximab group at 6-month follow-up (10 vs. 21%, p = 0.07). Intracoronary abciximab application in STEMI patients undergoing PCI is superior to standard IV treatment with respect to infarct size, recovery of LV function and reverse remodelling 6 months after infarction.

The feasibility of carboplatin-based intraperitoneal chemotherapy in ovarian cancer

Objective To reduce toxicities in cisplatin-based intraperitoneal (IP) chemotherapy, we substituted carboplatin for cisplatin. The purpose of this study was to provide preliminary toxicity data of carboplatin-based IP chemotherapy and to evaluate the feasibility of this chemotherapy regimen in patients with ovarian cancer after primary debulking surgery. Study design The toxicity data of 19 primary ovarian cancer patients (IP group) who underwent carboplatin-based IP and intravenous (IV) combination chemotherapy (IP carboplatin AUC 5 on day 1, IV paclitaxel 175 mg/m 2 on day 2, and IP paclitaxel 60 mg/m 2 on day 8) after primary debulking surgery were retrospectively analyzed and compared to 34 patients (IV group) who were treated with standard platinum-based IV chemotherapy during the same period. Results The toxicity data in a total of 118 cycles were analyzed. Grade 3 or 4 leukopenia, neutropenia, and pain were more common in the IP group than the IV group. There were seven catheter-related complications. Fourteen patients (73.7%) were able to complete six cycles or more of IP chemotherapy. Survival results in the IP group were compared with those from the IV group; a prolonged progression-free survival was observed (26.6 vs. 20.7 months; p = 0.038). Compared to the previous results with cisplatin-based IP chemotherapy, there was no significant difference in hematologic events. However, gastrointestinal, neurologic, and metabolic events in this study were definitely lower compared to those of cisplatin-based IP chemotherapy. Conclusions Carboplatin-based IP and IV combination chemotherapy is feasible in patients with ovarian carcinoma after primary debulking surgery.

Quality of Life in Operable Colon Cancer Patients Receiving Oral Compared With Intravenous Chemotherapy: Results From National Surgical Adjuvant Breast and Bowel Project Trial C-06

We compared health-related quality of life (HRQL), symptoms, and convenience of care (COC) in patients with stage II/III carcinoma of the colon who received either oral uracil/ftorafur (UFT) plus leucovorin (LV) or standard intravenous (IV) fluorouracil (FU) plus LV as adjuvant chemotherapy. We measured HRQL with the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) questionnaire, Short Form-36 Vitality Scale (SF-36), and a Quality of Life Rating Scale (QLRS) at baseline, once during chemotherapy, and at 1 year. We used the Symptom Distress Scale (SDS) and treatment-specific Symptom Checklist (SCL) to assess symptoms and a modified Burden of Care form to assess COC at baseline, on day 1 of each treatment cycle, and at 1 year. Repeated measures analyses controlling for demographic variables and baseline scores were used for statistical comparisons. The study accrued 1,608 patients, 803 to the FU arm and 805 to the UFT arm. There were no differences between the arms in overall FACT-C scores, FACT-C scores within the subscales of colon-specific, physical, emotional, social, and functional health, or QLRS scores. Patients taking UFT reported substantially higher COC. Statistically significant but small differences were observed for SF-36, favoring FU, and for SDS and SCL, both favoring UFT. Patients perceive adjuvant treatment with UFT + LV as more convenient than standard IV treatment with FU + LV. Both regimens are well tolerated and do not differ in their impact on HRQL.