Julia M. Cruz

Education of Physicians-in-Training Can Decrease the Risk for Vascular Catheter Infection

Vascular catheter infection is a substantial cause of morbidity and death in hospitalized patients. It has been estimated that 50 000 to 100 000 bloodstream infections related to vascular devices occur yearly in the United States; 90% of these infections originate from central venous catheters (CVCs) (1). The attributable mortality rate for CVC-related bloodstream infections ranges from 14% to 28% (2-6). The attributable cost of such infections has been estimated to be as high as

Interrupted versus Continuous Chemotherapy in Patients with Metastatic Breast Cancer

29 000 per episode (4). Various interventions, including skin preparation with chlorhexidine (7), use of vascular catheters with anti-infective coatings (8, 9), and use of maximum barrier precautions during catheter insertion, have been shown to reduce risk for catheter-related infections (10, 11). Currently, the optimal strategy for minimizing risk for vascular catheter infection is unclear. In 1993, the infection control committee at Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina, adopted the recommendations of Raad and colleagues (11) and established a policy that called for use of maximum sterile barriers (including a full-size sterile drape, sterile gown, sterile gloves, and a mask) when inserting CVCs. Despite conventional bedside and didactic instruction by critical care medicine faculty over a 2-year period, compliance of physicians-in-training was poor (<20%, according to informal surveys). Unpublished observations during a previous investigation suggested that procedures for CVC insertion varied widely and that a new educational approach was necessary. A multidisciplinary group developed and implemented a 1-day hands-on course to teach basic procedures and infection control practices to physicians completing their first postgraduate year (PGY-1) and third-year medical students. The details of this approach, which nurses call a skills fair, form the substance of our report. Methods Description of the Course The course was organized as follows. Infection control practitioners and a hospital epidemiologist taught 1 hour of basic infection control principles. Content included handwashing, isolation and appropriate use of barrier garments, and handling of patients with resistant organisms and varicella. Occupational Safety and Health Administration (OSHA) considerations for blood and body fluids and tuberculosis were taught in a separate hour-long session on a different day. Thereafter, medical students and PGY-1 physicians rotated through a series of 1-hour stations, at which they received 5 to 15 minutes of didactic instruction followed by hands-on instruction that was overseen by one to three faculty members. Faculty were selected because of their roles in supervising and teaching procedures in patient care settings. The course director observed each instructor for an entire session to ensure that the appropriate content was being delivered. At the hands-on stations, participants received training in 1) blood draws through vascular lines [taught by oncology catheter care nurses], 2) arterial puncture for obtaining an arterial blood gas [taught by respiratory therapists], 3) insertion of arterial catheters and CVCs [taught by critical care medicine faculty and fellows and trauma faculty], 4) urinary catheter insertion [taught by nurse instructors], 5) lumbar puncture [taught by an oncologist], 6) peripheral venous catheter insertion [taught by nurse instructors], and 7) phlebotomy (taught by faculty from the School of Medical Technology at Wake Forest University Baptist Medical Center). At all stations, mannequins were used to simulate patients; urinary catheterization was taught with male and female mannequins. All participants practiced phlebotomy on each other. Participants started peripheral intravenous lines first on mannequins and then on another participant. All of the hands-on sessions employed the same devices and supplies used in the hospital. Fifteen-minute breaks were given in the morning and in the afternoon, and a 1-hour lunch was provided. The PGY-1 physicians were divided into two large groups of approximately 50 persons, each of which was taught on a different day as part of the orientation for new interns. The medical students were taught on a separate day. Each hands-on station had 7 to 16 participants per small group session. In the second year of the course, most of the didactic instruction that preceded the hands-on sessions was done by videotape. A member of our infection control department reviewed the content of each didactic session to ensure its consistency with existing infection control policies. Content of courses on vascular catheters included use of povidone-iodine for skin preparation, avoidance of antibiotic ointment at the insertion site, and use of clear plastic dressings. Participants were also instructed to change dressings and intravenous tubing every 3 days and not to adhere to fixed schedules for changing CVCs. Of note, the hospitals infection control policy on vascular catheters did not change substantially during the study period, with the exception of the educational intervention; in particular, antibiotic-coated catheters were not used. Data Collection Previous Experience with Procedures During each hands-on session, PGY-1 physicians were asked to estimate the number of previous procedures that they had performed during medical school. Course Evaluation At the end of each 1-day course, an evaluation was given to each participant. Participants were asked to rate various factors, including each instructor, on a scale of 1 to 5 (1=poor; 5=excellent). Use of Full-Size Sterile Drapes The purchasing department provided data on the use of full-size sterile drapes. During the baseline year, a locally prepared sterile sheet was used. After the first course, a commercially available, full-size sterile drape (Kimberly-Clark, Roswell, Georgia) was used in all areas of the hospital in which CVCs were inserted. The purchasing department also monitored the number of CVCs inserted before and after each course was taught. Full-size sterile drapes were separate from the CVC kits during the preintervention and postintervention periods. Eight months before the first course (4 months into the baseline period), 140 physicians at all levels of training completed an anonymous survey of the perceived need for use of full-size sterile drapes. Before the first course, immediately after the first course, and 6 months after the first course, the participating group of PGY-1 physicians completed subsequent anonymous surveys. The same PGY-1 physicians were also surveyed about whether CVC insertion required povidone-iodine skin preparation, sterile gowns, sterile towels, and sterile gloves. Catheter-Related Infection To determine whether improved compliance with use of full-size sterile drapes or improvements in other areas of vascular catheter insertion were associated with reduced risk for catheter-related infection, precourse and postcourse surveillance for such infection was performed in six general medicine-surgery intensive care units and the associated step-down unit. We focused on insertion of CVCs and arterial catheters because at our institution, physicians-in-training perform essentially all of these procedures. In addition, we examined primary bloodstream infections because more than 90% of such infections in intensive care units probably originate from CVCs (12-14). Nosocomial primary bloodstream infections were identified on the basis of Centers for Disease Control and Prevention (CDC) surveillance definitions (15). In a primary bloodstream infection, a pathogen is isolated from a blood culture or cultures and is not related to infection at another site, unless that site is a vascular catheter (15). Catheter-related infections were defined as meeting definition three of the CDC Cardiovascular System Infection criteria for arterial or venous infection (15). Fulfillment of this definition required the presence of fever (temperature>38 C), pain, erythema, or heat at the catheter site plus the presence of a negative blood culture or absence of any blood cultures and the presence of a positive roll-plate culture of the catheter. For the positive roll-plate culture, we substituted a positive sonication culture ( 100 colony-forming units/mL) (16). Blood cultures were done by using the Wampole Isolator (Wampole Laboratories, Cranbury, New Jersey) and were predominately drawn only through a peripheral vein or as paired cultures through a peripheral vein and through a catheter. Catheter and bloodstream isolates were not molecularly typed. In the seven study units, use of CVCs was high ([central line days/patient days] 100%=73%). Because of this, we concluded that patient-days could serve as a surrogate of device-days, even though the latter would probably be more accurate under other circumstances (12). Other Procedure Considerations The frequency of blood and body fluid exposures among PGY-1 physicians was evaluated during the year before and the year after the first course. These data were obtained from our employee health service, which has had a formalized reporting program for 6 years. We did not measure changes in practice or outcomes related to lumbar punctures because the number of procedures performed was small and the complication rate is low; this made our sample size inadequate for demonstrating differences. In addition, we did not monitor procedures that are not performed primarily by physicians (that is, arterial punctures, urinary catheter insertions, blood draws through lines, peripheral line insertions, and phlebotomy). Statistical Analysis Proportions were compared by using the two-tailed chi-square test or the Fisher exact test. The rates of catheter-related infection were compared by using the incidence density ratio of the preintervention and postintervention periods, which were obtained by using the z test statistic (17). A P value less than 0.05 was consid

Reducing distress in cancer patients with an orientation program.

BACKGROUND Chemotherapy for metastatic breast cancer is palliative, and the optimal duration of therapy is unknown. We designed a trial to determine whether continuous treatment is superior to stopping treatment after a brief induction period and resuming treatment when the disease progresses. METHODS We treated 250 women with metastatic breast cancer with six courses of cyclophosphamide, doxorubicin, and fluorouracil given every three weeks. At the completion of this induction period, women whose disease either regressed or remained stable were randomly assigned to receive either continued treatment with cyclophosphamide, methotrexate, and fluorouracil (maintenance therapy) or no further treatment (observation) followed by treatment with cyclophosphamide, methotrexate, and fluorouracil when disease progression became evident (reinduction). RESULTS The combined rate of complete and partial responses after initial therapy was 30 percent (71 of 233 patients who could be evaluated; 95 percent confidence interval, 25 percent to 37 percent). In another 42 percent (98 patients), the disease remained stable. A total of 145 patients were randomized. Seventy-one were randomly assigned to the maintenance-therapy group, and 74 to the observation group. The median time to progression was 9.4 months for patients in the maintenance-therapy group and 3.2 months for patients in the observation group (P less than 0.001). After reinduction therapy, the median time to progression was 3.5 months. The median length of survival from the time of initial therapy was 14.8 months for all 250 patients; it was 21.1 months for the 71 patients in the maintenance-therapy group and 19.6 months for the 74 patients in the observation group (P = 0.67). Maintenance therapy was the most important determinant of the time before progression (P less than 0.001), but it was not associated with prolonged survival. The changes in performance status were similar in the patients in both groups, but nausea, vomiting, and mucositis were significantly more frequent in the maintenance-therapy group. CONCLUSIONS In patients with breast cancer who received induction chemotherapy for 18 weeks, subsequent continuous chemotherapy was associated with a significant prolongation of the time before progression as compared with those receiving no further therapy; overall survival, however, was not significantly different in the two groups.

Amelioration of vincristine neurotoxicity by glutamic acid

The purpose of this study was to test a brief orientation program for reducing anxiety, depressive symptoms, and overall distress in cancer patients at their initial clinic visit. One hundred and fifty consecutively referred patients seen in an oncology outpatient clinic were randomly assigned to an intervention or usual care control group. The intervention group received a clinic tour, general information about clinic operations, and a question and answer session with an oncology counselor. Outcome measures included the State‐Trait Anxiety Inventory (STAI), the Brief Profile of Mood States (POMS), the Center for Epidemiologic Studies‐Depression (CES‐D) Scale, and an oncology clinic questionnaire which were administered at the initial clinic visit and follow‐up. There were no statistically significant clinical or demographic differences between groups at initial assessment. At follow‐up, the intervention group had lower state anxiety, lower overall distress, and fewer patients reporting depressive symptoms. Patients in the intervention group demonstrated significantly more knowledge about clinic operations and greater satisfaction with care. These data provide evidence that anxiety, distress and depressive symptoms can be reduced with an orientation program. This finding has particular relevance in the early stages of diagnosis where patients may suffer symptoms of anxiety and depression.

Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association.

Neurotoxicity is the principal limiting side effect of the widely used antitumor agent, vincristine. Following evaluation of glutamic acid as a potential modifier of vincristine toxicity in preclinical studies in mice and a preliminary clinical trial, a prospective, double-blind, placebo-controlled, randomized trial was conducted by the Piedmont Oncology Association. Of 87 patients entered into the study, 84 were evaluable, including 42 patients who were randomly assigned to receive vincristine 1.0 mg/m2 weekly for six doses and 42 patients who were assigned to receive glutamic acid 500 mg orally three times daily plus vincristine. The following neurotoxic signs and symptoms were evaluated before each dose of vincristine: reflex changes, paresthesias, constipation, strength, and mental changes. Loss of the Achilles tendon reflex, an objective parameter, was noted in 19 percent of patients receiving glutamic acid and 42 percent of control subjects (p = 0.03). Development of moderate to severe paresthesias, a subjective parameter, occurred in 19 percent of the glutamic acid group and 36 percent of the placebo group (p = 0.09). Overall moderate neurotoxicity (6 units or more), determined by adding the grade of each neurotoxic parameter for the weekly clinic visit in which maximum neurotoxicity occurred, was observed in 21 percent of patients receiving glutamic acid and 43 percent of those in the control group (p = 0.04). Hematologic and gastrointestinal side effects occurred with similar frequency in the two groups. The administration of glutamic acid has decreased vincristine-induced neurotoxicity without any attendant side effects.

A prospective, randomized, double-blind controlled trial of acetaminophen and diphenhydramine pretransfusion medication versus placebo for the prevention of transfusion reactions

One hundred thirty-eight patients with recurrent or metastatic breast cancer were randomized to receive megestrol acetate 40 mg orally four times daily or tamoxifen 10 mg orally twice a day. Upon treatment failure patients were crossed over to the alternate treatment. Eligibility required that either the estrogen receptor (ER) or progesterone receptor (PR) be positive or that both values be unknown, and that the patients be at least 2 years post-spontaneous menopause or over 50 years of age. Pretreatment characteristics including performance status (PS), disease-free interval (DFI), receptor status, and prior treatment were similar for both groups. Only three patients had previous hormonal therapy while one third had prior chemotherapy. Objective response was determined using strict International Union Against Cancer (UICC) criteria. Seventeen of 61 patients achieved complete response (CR) or partial response (PR) on megestrol (28%) while 20 of 64 patients achieved CR or PR on tamoxifen (31%). Responses of skin and bone lesions were similar for both agents; however, more patients with visceral disease responded to tamoxifen. Response did not correlate with the level of ER or PR but was correlated with age. Both unadjusted and adjusted analysis of time to progression and adjusted analysis (for pretreatment variables) of survival showed significant differences favoring tamoxifen. Six of 44 patients (14%) crossed from megestrol to tamoxifen achieved CR or PR while only two of 38 patients (5%) crossed from tamoxifen to megestrol achieved response. Only one of the original patients randomized to megestrol remains on study, while 12 patients still remain on tamoxifen. These data indicate similar response rates for megestrol and tamoxifen; however, time to progression and overall survival significantly favor tamoxifen when used as first-line therapy in this trial.

Prospective evaluation of changes in computed cranial tomography in patients with small cell lung carcinoma treated with chemotherapy and prophylactic cranial irradiation.

BACKGROUND: Acetaminophen and diphenhydramine are commonly used as pretransfusion medications to prevent transfusion reactions. The purpose of this study was to prospectively compare the risk of transfusion reactions in hematology/oncology patients who receive acetaminophen with diphenhydramine or placebo before transfusion.

Tamoxifen versus high-dose oral medroxyprogesterone acetate as initial endocrine therapy for patients with metastatic breast cancer: a Piedmont Oncology Association study.

Computed cranial tomographic scans were performed as part of the pretreatment evaluation and at six- to nine-month intervals posttreatment in 13 patients with small cell lung carcinoma. All patients received 3,000 rad of prophylactic cranial irradiation delivered over two weeks in ten treatment fractions in conjunction with multiagent chemotherapy. Posttreatment scans documented an extraordinarily high frequency of abnormalities including cerebral atrophy (100%), ventricular dilatation (70%), and decreased coefficient of absorption in the white matter (15%). Unexplained neurologic abnormalities developed in four of six patients living at least 15 months after institution of therapy. As the number of long-term survivors of this type of lung cancer increases, the need for prospective comprehensive neuropsychologic assessment to determine the clinical significance of these changes is needed.

High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association

PURPOSE To determine in a prospective randomized trial whether high-dose orally administered medroxy-progesterone acetate (MPA) was superior to tamoxifen in patients with recurrent or metastatic breast cancer who had received no prior endocrine therapy in either the adjuvant or advanced setting. PATIENTS AND METHODS Patients initially received either tamoxifen 20 mg/d orally or MPA 1 g/d orally. At the time of disease progression, patients were crossed over to the other regimen. Eligibility required patients to be age > or = 18 years, performance status 0 to 3, and estrogen receptor (ER)- or progesterone receptor (PR)-positive or unknown. RESULTS One hundred eighty-two eligible patients were entered and 166 were assessable for response. Complete plus partial response rates for tamoxifen and MPA were 17% and 34%, respectively (P = .01). Patients with bone metastases had a significantly higher partial response rate with MPA compared with tamoxifen (33% v 13%). Median time to treatment failure was 5.5 months for tamoxifen and 6.3 months for MPA (P = .48). The median survival duration was 24 months for tamoxifen and 33 months for MPA (P = .09). Multivariate analysis showed that treatment significantly influenced response rate, but not time to treatment failure or survival. After treatment failure following MPA, six of 42 patients (14%) treated with tamoxifen responded, compared with six of 49 (12%) treated with MPA following tamoxifen. Both agents were associated with minimal toxicity, but 35% of patients on MPA gained more than 20 lb as opposed to only 2% on tamoxifen. CONCLUSION In this trial, initial treatment with MPA of endocrine-naive metastatic breast cancer patients was associated with a significantly higher response rate but not with improvement in time to treatment failure or survival, when compared with initial treatment with tamoxifen. Further randomized trials in patients with bone metastases are warranted to determine if high-dose progestin therapy is superior to tamoxifen in these patients.

Bone Marrow Cytogenetic Abnormalities of Aplastic Anemia

One hundred seventy-two patients with advanced breast cancer were randomized to receive oral standard-dose megestrol acetate (MA), 160 mg/d or high-dose MA, 800 mg/d. All but two patients had one prior trial of tamoxifen therapy for either metastatic disease (74%) or as adjuvant treatment (26%). Pretreatment characteristics were similar for both arms. High-dose MA resulted in a superior complete plus partial response rate (27% v 10%, P = .005), time to treatment failure (median, 8.0 v 3.2 months, P = .019), and survival (median, 22.4 v 16.5 months, P = .04) when compared with standard-dose therapy. These differences remained significant after adjustment for other covariates. Thirty-four patients were given high-dose MA after failure of standard-dose MA treatment, and none responded. Weight gain was the most distressing side effect, with 13% of standard-dose and 43% of high-dose patients gaining more than 20 lbs. Four major cardiovascular events occurred in patients receiving high-dose treatment and one in patients given standard doses. Other toxicity was modest. High-dose MA may represent a significant improvement in secondary endocrine therapy for advanced breast cancer patients refractory to initial endocrine treatment, but its use on a regular basis should be reserved until these results are confirmed by other clinical trials.