A dosimetric study of radionuclide therapy for bone marrow ablation

In a phase I clinical trial, six multiple myeloma patients, who were non-responsive to conventional therapy and were scheduled for bone marrow transplantation, received Holmium-166 ($\sp{166}$Ho) labeled to a bone seeking agent, DOTMP (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene-phosphonic acid), for the purpose of bone marrow ablation. The specific aims of my research within this protocol were to evaluate the toxicity and efficacy of $\sp{166}$Ho DOTMP by quantifying the in vivo pharmacokinetics and radiation dosimetry, and by correlating these results to the biologic response observed. The reproducibility of pharmacokinetics from multiple injections of $\sp{166}$Ho DOTMP administered to these myeloma patients was demonstrated from both blood and whole body retention. The skeletal concentration of $\sp{166}$Ho DOTMP was heterogenous in all six patients: high in the ribs, pelvis, and lumbar vertebrae regions, and relatively low in the femurs, arms, and head.^ A novel technique was developed to calculate the radiation dose to the bone marrow in each skeletal ROI, and was applied to all six $\sp{166}$Ho DOTMP patients. Radiation dose estimates for the bone marrow calculated using the standard MIRD "S" factors were compared with the average values derived from the heterogenous distribution of activity in the skeleton (i.e., the regional technique). The results from the two techniques were significantly different; the average of the dose estimates from the regional technique were typically 30% greater. Furthermore, the regional technique provided a range of radiation doses for the entire marrow volume, while the MIRD "S" factors only provided a single value. Dose volume histogram analysis of data from the regional technique indicated a range of dose estimates that varied by a factor of 10 between the high dose and low dose regions. Finally, the observed clinical response of cells and abnormal proteins measured in bone marrow aspirates and peripheral blood samples were compared with radiation dose estimates for the bone marrow calculated from the standard and regional technique. The results showed the regional technique values correlated more closely to several clinical response parameters. (Abstract shortened by UMI.) ^

Barriers and facilitators to nurses' acceptance of and implications for injury rates of an IV catheter safety device

This study has the purpose of determining the barriers and facilitators to nurses' acceptance of the Johnson and Johnson Protectiv®* Plus IV catheter safety needle device and implications for needlestick injuries at St. Luke's Episcopal Hospital, Houston, Texas. A one-time cross-sectional survey of 620 responding nurses was conducted by this researcher during December, 2000. The study objectives were to: (1) describe the perceived (a) organizational and individual barriers and facilitators and (b) acceptance of implementation of the IV catheter device; (2) examine the relative importance of these predictors; (3) describe (a) perceived changes in needlestick injuries after implementation of the device; (b) the reported incidence of injuries; and (c) the extent of underreporting by nurses; and (4) examine the relative importance of (a) the preceding predictors and (b) acceptance of the device in predicting perceived changes in needlestick injuries. Safety climate and training were evaluated as organizational factors. Individual factors evaluated were experience with the device, including time using it and frequency of use, and background information, including nursing unit, and length of time as a nurse in this hospital and in total nursing career. The conceptual framework was based upon the safety climate model. Descriptive statistics and multiple and logistic regression were utilized to address the study objectives. ^ The findings showed widespread acceptance of the device and a strong perception that it reduced the number of needlesticks. Acceptance was notably predicted by adequate training, appropriate time between training and device use, solid safety climate, and short length of service, in that order. A barrier to acceptance was nurses' longtime of use of previous needle technologies. Over four-fifths of nurses were compliant in always using the device. Compliance had two facilitators: length of time using device and, to a lesser extent, safety climate. Rates of compliance tended to be lower among nurses in units in which the device was frequently used. ^ High quality training and an atmosphere of caring about nurse safety stand out as primary facilitators that other institutions would need to adopt in order to achieve maximum success in implementing safety programs involving utilization of new safety devices. ^

Long-term central venous catheter-related candidemia: A new approach towards diagnosis and management

A case-series analysis of approximately 811 cancer patients who developed Candidemia between 1989 and 1998 and seen at M. D. Anderson Cancer Center, was studied to assess the impact and timing of central venous catheter (CVC) removal on the outcome of fungal bloodstream infections in cancer patients with primary catheter-related Candidemia as well as secondary infections. ^ This study explored the diagnosis and the management of vascular catheter-associated fungemia in patients with cancer. The microbiologic and clinical factors were determined to predict catheter-related Candidemia. Those factors included, in addition to basic demographics, the underlying malignancy, chemotherapy, neutropenia, and other salient data. Statistical analyses included univariate and multivariate logistic regression to determine the outcome of Candidemia in relation to the timing of catheter removal, type of species, and to identify predictors of catheter-related infections. ^ The conclusions of the study aim at enhancing our mastery of issues involving CVC removal and potentially will have an impact on the management of nosocomial bloodstream infections related to timing of CVC removal and the optimal duration of treatment of catheter-related Candidemia. ^

Effect of the emergence of community acquired methicillin resistant Staphylococcus aureus on microbial resistance patterns seen during a seven year study of minocycline/rifampin catheter use

Background. Health care associated catheter related blood stream infections (CRBSI) represent a significant public health concern in the United States. Several studies have suggested that precautions such as maximum sterile barrier and use of antimicrobial catheters are efficacious at reducing CRBSI, but there is concern within the medical community that the prolonged use of antimicrobial catheters may be associated with increased bacterial resistance. Clinical studies have been done showing no association and a significant decrease in microbial resistance with prolonged minocycline/rifampin (M/R) catheter use. One explanation is the emergence of community acquired methicillin resistant Staphylococcus aureus (MRSA), which is more susceptible to antibiotics, as a cause of CRBSI.^ Methods. Data from 323 MRSA isolates cultured from cancer patients at The University of Texas MD Anderson Cancer center from 1997-2007 displaying MRSA infection were analyzed to determine whether there is a relationship between resistance to minocycline and rifampin and prolonged wide spread use of minocycline (M/R) catheters. Analysis was also conducted to determine whether there was a significant change in the prevalence community acquired MRSA (CA-MRSA) during this time period and if this emergence act as a confounder masquerading the true relationship between microbial resistance and prolonged M/R catheter use.^ Results. Our study showed that the significant (p=0.008) change in strain type over time is a confounding variable; the adjusted model showed a significant protective effect (OR 0.000281, 95% CI 1.4x10 -4-5.5x10-4) in the relationship between MRSA resistance to minocycline and prolonged M/R catheter use. The relationship between resistance to rifampin and prolonged M/R catheter use was not significant.^ Conclusion. The emergence of CA-MRSA is a confounder and in the relationship between resistance to minocycline and rifampin and prolonged M/R catheter use. However, despite the adjustment for the more susceptible CA-MRSA the widespread use of M/R catheters does not promote microbial resistance. ^

Cost-effectiveness analysis of stereotactic body radiotherapy and radiofrequency ablation for medically inoperable liver metastases from colorectal cancer

This report describes the development of a Markov model for comparing percutaneous radiofrequency ablation (RFA) and stereotactic body radiation therapy (SBRT) in terms of their cost-utility in treating isolated liver metastases from colorectal cancer. The model is based on data from multiple retrospective and prospective studies, available data on different utility states associated with treatment and complications, as well as publicly available Medicare costs. The purpose of this report is to establish a well-justified model for clinical management decisions. In comparison with SBRT, RFA is the most cost-effective treatment for this patient population. From the societal perspective, SBRT may be an acceptable alternative with an ICER of $28,673/QALY. ^

The prevention of catheter related bloodstream infections in a pediatric population

Catheter related bloodstream infections are a significant barrier to success in many inpatient healthcare facilities. The goal of this study was to analyze and determine if an evidence based methodology to reduce the number of catheter related bloodstream infections in a pediatric inpatient healthcare facility had significant impact on the infection rate. Catheter related bloodstream infection rates were compared before and after program implementation. The patient population was selected based upon a recommendation in the 2010 National Healthcare Safety Network report on device related infections. This report indicated a need for more data on pediatric populations requiring admission to a long term care facility. The study design is a retrospective cohort study. Catheter related bloodstream infection data was gathered between 2008 and 2011. In October of 2008 a program implementation began to reduce the number of catheter related bloodstream infections. The key components of this initiative were to implement a standardized catheter maintenance checklist, introduce the usage of a chlorhexadine gluconate based product for catheter maintenance and skin antisepsis, and a multidisciplinary education plan that focused on hand hygiene and aseptic technique. The catheter related bloodstream infection rate in 2008 was 21.21 infections per 1000 patient-line days. After program implementation the 2009 catheter related bloodstream infection rate dropped to 1.11 per 1000 patient-line days. The infection rates in 2010 and 2011 were 2.19 and 1.47 respectively. Additionally, this study demonstrated that there was a potential cost savings of $620,000 to $1,240,000 between 2008 and 2009. In conclusion, an evidence based program based upon CDC guidelines can have a significant impact on catheter related bloodstream infection rates. ^

Bacteremia and mortality within 30 days of catheter-associated bacteriuria

Background: The distinction between catheter-associated asymptomatic bacteriuria (CAABU) and catheter-associated urinary tract infection (CAUTI) has only recently been widely appreciated. Our aims were to describe the relationship between CAUTI/CAABU and subsequent bacteremia and to investigate whether CAUTI/CAABU and antimicrobial use was associated with either bacteremia or mortality within 30 days. ^ Methods: Our study design was retrospective cohort. Patients with a urinary catheter and a positive urine culture between October 2010 and June 2011 at a large tertiary care facility were included. A multivariable model for analysis was constructed which controlled for age, race, Charlson co-morbidity score, catheter type and duration, category of organism,antimicrobials and classification of the catheter-associated bacteriuria as CAUTI or CAABU. ^ Results: Data from 444 catheter associated urine culture episodes in 308 unique patients were included in the analysis. Overall mortality was 21.1% (61 of 308 patients) within 30 days. Among the 444 urine culture episodes, 402 (90.5%) of these episodes were associated with antibiotic use. 52 (11.7%) of episodes were associated with bacteremia, but only 3 episodes of bacteremia (0.7% of 444 CAB episodes) were caused by an organism from the urinary tract. One of these episodes was CAABU and the other 2 were CAUTI. Bacteremia within 30 days was associated with having CAUTI rather than CAABU and having an indwelling urinary catheter rather than a condom catheter. The variables which were found to be significant for mortality within 30 days were a higher Charlson co-morbidity score and the presence of Candida in the urine culture. Use of antimicrobial agents to treat the bacteriuria was not associated with an increase or decrease in either bacteremia or mortality. ^ Conclusions: Our findings call into question the practice of giving antimicrobial agents to treat bacteriuria in an inpatient population with nearly universal antimicrobial use. A better practice may be targeted treatment of bacteriuria in patients with risk factors predictive of bacteremia and mortality.^

Subclavian vein catheter -related infection and hospital costs associated with exchange via a guidewire

An observational study was conducted in a SICU to determine the frequency of subclavian vein catheter-related infection at 72 hours, to identify the hospital cost of exchange via a guidewire and the estimated hospital cost-savings of a 72 hour vs 144 hour exchange policy.^ An overall catheter-related infection ($\geq$15 col. by Maki's technique (1977)) occurred in 3% (3/100) of the catheter tips cultured. Specific infections rates were: 9.7% (3/31) for triple lumen catheters, 0% (0/30) for Swan-Ganz catheters, 0% (0/30) for Cordes catheters, and 0% (0/9) for single lumen catheters.^ An estimated annual hospital cost-savings of $35,699.00 was identified if exchange of 72 hour policy were changed to every 144 hours.^ It was recommended that a randomized clinical trial be conducted to determine the effect of changing a subclavian vein catheter via a guidewire every 72 hours vs 144 hours. ^