Vancomycin administration: the impact of multidisciplinary interventions

BACKGROUND: The clinical microbiology team observed that patients were not receiving all prescribed doses of vancomycin. Ward staff was confused about ordering and interpreting vancomycin therapeutic drug monitoring (TDM) levels. AIM: To audit the incidence of vancomycin dose omission. To implement a series of interventions to improve vancomycin dose administration, and to repeat the audit process to assess these interventions. METHODS: Three prospective audits were conducted to assess the impact of vancomycin TDM on administration of vancomycin. After the first audit, a number of changes in the TDM process were undertaken. After review of the second audit, a senior pharmacist coordinated ward-based pharmacists in assisting staff to interpret levels, and TDM interpretative charts were designed for drug charts. Following the third audit, feedback to hospital management and a plan for ongoing education were undertaken. RESULTS: There was a significant reduction in the number of vancomycin doses held inappropriately in the third (10% (78/782) of prescribed doses) when compared to the first audit (16% (161/1007) of doses) (p<0.01). Of doses that were held inappropriately, there was a significant decrease in doses held for no apparent reason in audit 3 (16% (27/170) of prescribed doses) when compared to audit 1 (25% (69/282) of doses) (p<0.05). CONCLUSIONS: The interventions resulted in a 37.5% reduction in inappropriately held vancomycin doses over a one-year period; 10% of doses are still being held inappropriately. This study highlights the difficulties in identifying barriers to change and changing healthcare worker behaviour.     

Paradoxical scintigraphy bone scan findings with malignancy‐associated extreme hypercalcemia

We report the first case of extreme hypercalcemia (Ca ²⁺ >6.0 mmol/L) as the initial presentation of de novo metastatic breast cancer. Following treatment and stabilization of the patient, imaging revealed a large breast mass and widespread osseous metastases. Whole body bone scintigraphy demonstrated significant extra osseous uptake of radiotracer in the lungs, liver, and kidneys—a rare phenomenon secondary to profound hypercalcemia. Biopsy revealed estrogen receptor (ER) positive breast carcinoma, for which the patient was treated.     

A novel problem,a tested solution: A case of an infected left ventricular titanium plug

Persistent infection of left ventricular-assisted devices are challenging to treat. We describe a case of a middle-aged man who presented with cardiogenic shock and profound heart failure from sarcoid myocarditis, necessitating the placement of a left ventricular assist device. After recovery of cardiac function, the device was decommissioned but complicated by infection in the implant bed, chest wall, and of the titanium plug left in situ. This to our knowledge is the first report of an infected titanium plug and we describe an option of using a latissimus dorsi flap using its vascularized tissues to treat the infected plug. This is another example where a multidisciplinary approach can yield rewarding results in cases such as these.     

Myeloma in patients younger than age 50 years presents with more favorable features and shows better survival: an analysis of 10 549 patients from the International Myeloma Working Group

We analyzed the presenting features and survival in 1689 patients with multiple myeloma aged younger than 50 years compared with 8860 patients 50 years of age and older. Of the total 10 549 patients, 7765 received conventional therapy and 2784 received high-dose therapy. Young patients were more frequently male, had more favorable features such as low International Staging System (ISS) and Durie-Salmon stage as well as less frequently adverse prognostic factors including high C-reactive protein (CRP), low hemoglobin, increased serum creatinine, and poor performance status. Survival was significantly longer in young patients (median, 5.2 years vs 3.7 years; P < .001) both after conventional (median, 4.5 years vs 3.3 years; P < .001) or high-dose therapy (median, 7.5 years vs 5.7 years; P = .04). The 10-year survival rate was 19% after conventional therapy and 43% after high-dose therapy in young patients, and 8% and 29%, respectively, in older patients. Multivariate analysis revealed age as an independent risk factor during conventional therapy, but not after autologous transplantation. A total of 5 of the 10 independent risk factors identified for conventional therapy were also relevant for autologous transplantation. After adjusting for normal mortality, lower ISS stage and other favorable prognostic features seem to account for the significantly longer survival of young patients with multiple myeloma with age remaining a risk factor during conventional therapy.     

Neuropeptide Y enhances the release of luteinizing hormone (LH) induced by LH-releasing hormone

Depending upon the steroid hormonal milieu, centrally administered neuropeptide Y (NPY) exerts differential effects on the release of LH. Ovarian hormones also effect the concentrations of NPY in hypothalamic nuclei, and some of the changes are similar to those caused by LHRH. The present studies tested whether NPY acts directly on the pituitary gland, either alone or in combination with LHRH, to modify LH secretion. Hemipituitary fragments obtained from ovariectomized rats were incubated in medium 199, and the in vitro effects on LH release of LHRH, NPY, or the two peptides together were assessed. As expected, LHRH (10(-9)-10(-7) M) produced a dose-dependent release of LH, whereas NPY alone had a lesser stimulatory effect at concentrations of 10(-7) or 10(-6) M. On the other hand, 10(-6) M NPY significantly enhanced LH release in response to 10(-9) M LHRH. A potentiation by NPY of the LHRH-induced LH response was observed in an anterior pituitary cell culture system. Cells from the pituitaries of ovariectomized rats were dispersed and cultured for 3 days in medium 199 with BSA, gentamicin, horse serum, and fetal calf serum. During a 3-h incubation, NPY alone (10(-9)-10(-7) M) failed to affect LH release, but significantly potentiated the release induced by 10(-9) or 10(-8) M LHRH. These findings are in accord with the hypothesis that hypothalamic NPY neurons may participate in the regulation of LH secretion in the rat and indicate that one of the mechanisms of its action may be to increase the pituitary LH response to LHRH.     

Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels

To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.     

Two-year trends in physical performance following supervised exercise among community-dwelling older veterans

The extent to which exercise can delay the normal decline in physical performance associated with aging is unknown. We examined the impact of 2 years of supervised exercise on cardiovascular fitness, flexibility, and strength in a group of elderly (age 65-74) veterans. Seventy-five patients exercised 3 days/week for 90-minute sessions emphasizing aerobic, flexibility, and strength development. Thirty-six (47%) completed 2 years of a voluntary supervised exercise program (n = 16-25 with complete data). Over a 2-year follow-up period, cardiovascular outcome variables improved significantly: metabolic equivalents increased 20% (7.4 +/- 2.2 to 9.0 +/- 2.4, P less than 0.001) and submaximal heart rate decreased 7% (131.4 +/- 14.8 to 121.0 +/- 18.5 beats/minute, P = 0.06). Resting heart rate decreased 8% (68.5 +/- 8.0 to 63.6 +/- 8.4 beats/minute, P = 0.02) but this difference did not reach statistical significance. Flexibility, measured by hamstring length, improved 11% (57.5 +/- 15.1 to 64.0 +/- 11.1 degrees, P = 0.02). Strength variables did not improve. The study indicates that improvements in cardiovascular function and flexibility achieved by the elderly in the early stages of an exercise program can be maintained for at least 2 years.     

Sex steroid control of gonadotropin secretion in the human male. I. Effects of testosterone administration in normal and gonadotropin-releasing hormone-deficient men

The precise sites of action of the negative feed-back effects of gonadal steroids in men remain unclear. To determine whether testosterone (T) administration can suppress gonadotropin secretion directly at the level of the pituitary, the pituitary responses to physiological doses of GnRH were assessed in six men with complete GnRH deficiency, whose pituitary-gonadal function had been normalized with long term pulsatile GnRH delivery, before and during a 4-day continuous T infusion (15 mg/day). Their responses were compared with the effects of identical T infusions on spontaneous gonadotropin secretion and the response to a 100-micrograms GnRH bolus in six normal men. Both groups were monitored with 15 h of frequent blood sampling before and during the last day of the T infusion. In the GnRH-deficient men, the first three GnRH doses were identical and were chosen to produce LH pulses with amplitudes in the midphysiological range of our normal men (i.e. a physiological dose), while the last four doses spanned 1.5 log orders (7.5, 25, 75, and 250 ng/kg). The 250 ng/kg dose was always administered last because it is known to be pharmacological. In the GnRH-deficient men, mean LH (P less than 0.02) and FSH (P less than 0.01) levels as well as LH pulse amplitude (P less than 0.05) decreased significantly during T infusion, demonstrating a direct pituitary-suppressive effect of T and/or its metabolites. Mean LH levels were suppressed to a greater extent in the normal than in the GnRH-deficient men (58 +/- 15% vs. 28 +/- 7%; P less than 0.05). In addition, LH frequency decreased significantly (P less than 0.01) during T administration in the normal men. These latter two findings suggest that T administration also suppresses hypothalamic GnRH release. T was unable to suppress gonadotropin secretion in one GnRH-deficient and one normal man. In both groups, the suppressive effect of T administration was present only in response to physiological doses of GnRH. Because the pituitary- and hypothalamus-suppressive effects of T could be mediated by its aromatization to estrogens, five GnRH-deficient and five normal men underwent identical T infusions with concomitant administration of the aromatase inhibitor testolactone (TL; 500 mg, orally, every 6 h). As an additional control, four GnRH-deficient and four normal men received TL alone. TL administration completely prevented the effect of T administration to suppress gonadotropin secretion in both the normal and GnRH-deficient men, and mean LH levels increased significantly in both the GnRH-deficient (P less than 0.01) and the normal (P less than 0.001) men who received TL alone. The increase in mean LH levels was greater (P less than 0.01) in the normal men who received TL alone than in the normal men who received T plus TL, thus revealing a direct effect of androgens in normal men. Measurements of T and estradiol production rates in three men demonstrated that TL effectively blocked aromatization.(ABSTRACT TRUNCATED AT 400 WORDS)     

Continuous absence of metaphase-defined cytogenetic abnormalities,especially of chromosome 13 and hypodiploidy,ensures long-term survival in multiple myeloma treated with Total Therapy I: interpretation in the context of global gene expression

Metaphase cytogenetic abnormalities (CAs), especially of chromosome 13 (CA 13), confer a grave prognosis in multiple myeloma even with tandem autotransplantations as applied in Total Therapy I, which enrolled 231 patients between 1989 and 1994. With a median follow-up of almost 9 years, the prognostic implications of all individual CAs, detected prior to treatment and at relapse, were investigated. Among all CAs and standard prognostic factors examined prior to therapy, only hypodiploidy and CA 13 (hypo-13 CA), alone or in combination, were associated with shortest event-free survival and overall survival (OS). The shortest postrelapse OS was observed with hypo-13 CA, which was newly detected in 18 of all 28 patients presenting with this abnormality at relapse. Superior prognosis was associated with the absence of any CA at both diagnosis and relapse (10-year OS, 40%). The lack of independent prognostic implications of other CAs points to a uniquely aggressive behavior of hypo-13 CA (present in 16% of patients at diagnosis). With the use of microarray data in 146 patients enrolled in Total Therapy II, overexpression of cell cycle genes distinguished CA from no CA, especially in cases of del(13) detected by interphase fluorescence in situ hybridization (FISH). FISH 13, resulting in a haploinsufficiency of RB1 and other genes mapping to chromosome 13, as well as activation of IGF1R, appears to have an amplifying effect on cell cycle gene expression, thus providing a molecular explanation for the dire outcome of patients with CA 13 compared with those with other CAs.