bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initiating and Maintaining Patients on Warfarin Anticoagulation: The Importance of Monitoring
Authors: Ezekowitz Michael D. , James Kenneth E. , Radford Martha J. , Rickles Frederick R. , Redmond Nadia 
Published: November 2007

Background: The VA Stroke Prevention in Nonrheumatic Atrial Fibrillation study was a prospective, randomized, double-blind study comparing low-dose warfarin with placebo in patients with nonrheumatic atrial fibrillation. The trial showed a 79% reduction in stroke rate in warfarin randomized patients without an increase in bleeding complications. We examined the need for frequent prothrombin time monitoring (international normalized ratios [INR] were not measured directly) in patients receiving warfarin. Methods and Results: Patients were initiated on 4.0 mg/d warfarin with a goal of main taining the prothrombin time ratio (PTR) within the range of 1.2-1.5 (estimated INR: 1.4-2.8). PTR monitoring was performed weekly during a 12-week induction period and monthly thereafter for a total follow-up of 3 years. Two hundred sixty patients were ran domized to receive warfarin. During the induction period, the proportion of patients whose PTRs were in the desired range increased from 28% at 1 week postrandomization to 65% at 12 weeks postrandomization; the proportion of patients requiring a dose adjustment decreased from 52% to 16% during the same period. During the maintenance period, the mean proportion of patients whose PTRs were within 1.2-1.5 was 60.5% ± 6.2%. Conclusions: Low-dose anticoagulation with warfarin in outpatients should be initiated at the anticipated maintenance dose. This approach reduces the chance of being out of range on the high side. Weekly INR estimation during this phase seems optimal. Considerable dose adjusting was required during the maintenance phase to keep patients within range; monthly INRs are required. Because of the need for dose adjustments, fixed-dose warfarin regimens are unlikely to keep patients in the desired narrow therapeutic range.
Hemostatic and Fibrinolytic Status in Patients With Ovarian Cancer and Benign Ovarian Cysts: Could D-dimer and Antithrombin III Levels Be Included as Prognostic Markers for Survival Outcome?
Authors: Koh Stephen C.L. , Tham Kok-Fun , Razvi Khalil , Oei Pau-Ling , Lim Fang-Kan , Roy A.-C. , Prasad R.N.V. 
Published: November 2007

We determined the hemostatic and fibrinolytic status in 60 patients with ovarian cancer and benign ovarian cysts. Hypercoagulation, increased platelets, and enhanced fibrinolysis were seen in patients with preoperative ovarian cancer compared to patients with benign ovarian cysts. Enhanced thrombin generation, evidenced by increased F1+2 and decreased antithrombin III (ATIII) levels with further enhanced fibrinolysis by elevated D-dimer, was seen in advanced cancer. Ten ovarian cancer patients died within 13 months after diagnosis and another died at 24 months, all from advanced stage of cancer, except one from stage IC cancer who died at 11. months. The survival rates from the disease at 13 months and 24 months were 66.7% and 45%, respectively. Most of the patients had gone through the complete course of chemotherapy, and those patients still alive have been disease free between 13 and 42 months. No statistical relationships for the hemostatic parameters studied in ovarian cancer patients could be found between those who died and those still living 13 and 24 months after diagnosis, except for ATIII and D-dimer levels. Elevated D-dimer levels were associated with those who died within 13 and 24 months from the disease, and the decreased ATIII levels only reached statistical significance by 24 months. It could be suggested that these two parameters might be useful as systemic prognostic markers in survival outcome from the disease for the first 24 months in advanced ovarian cancer, in addition to the known correlation with the International Federation of Gynecology and Obstetrics stage. Key Words: Hemostatic—fibrinolytic—Ovarian cancer.
Cytogenetic monitoring of pharmaceutical staff working with cytostatic drug preparations: A 5-year follow-up
Authors: Peschke Michael , Nagel Sibylle , Haamann Frank , Melzer Simone , Meier Klaus 
Published: November 2007

Introduction. Cytostatic drug preparation in hos pital pharmacies leads to a concentration of expo sure on a few people and requires considerable protective measures. Methods. To prove the efficiency of those standards, 45 people who routinely prepare cyto static drugs were monitored with cytogenetic tests, Micronucleus-rate (MN), and Sister Chroma tid Exchange-rate (SCE), once a year over a period up to 5 years. All participants of the study received a physical examination before they began prepar ing cytostatic drugs. Baseline MN and SCE were performed at the time. Individual comparisons for the tests between pre- and post-exposure, and a comparison between an exposed and an unex posed group were then performed. Results. During the 5-year follow-up there were no hints of genotoxic effects as a result of handling cytostatic drugs. Conclusion. Thus, it appeared that the safety precautions employed at this Institute were ade quate.
Do topotecan concentrations in saliva reflect plasma concentrations?
Authors: van Warmerdam Ljc , Rosing H. , ten Bokkel Huinink WW , Maes Raa , Beijnen JH 
Published: November 2007

Purpose. There is an increasing interest to use saliva as biological fluid for drug monitoring as it reflects adequately, in some cases, drug concentrations in plasma. A great advantage is that it can be obtained conveniently by a noninvasive method. We describe our experience with respect to the practical use of saliva for pharmacokinetic monitoring of the novel anticancer agent topotecan. Patients and Methods. Eighty-one saliva sam ples and corresponding plasma samples were ob tained 2 hours after the end of infusion from 15 patients with either ovarian cancer or small cell lung cancer, receiving 1.5 mg/m 2 per day topotecan for 5 consecutive days every 3 weeks. Saliva was obtained by a citric-acid containing dental cotton roll which stimulated the saliva flow. Results. The plasma topotecan concentrations varied between 3.67 and 24.4 ng/mL, with an intrapa tient (day-to-day) variation of only 9.8%, and an inter patient variation of 27.2%. The saliva concentrations varied between 5.34 and 74.2 ng/mL, with an intrapa tient variation of 25.3%, and an interpatient variation of 53.5%. The mean plasma/saliva topotecan ratio was 0.66 (range 0.21 to 1.58) and was both patient dependent and dependent on the sampling time. The day-to-day variation of the plasma/saliva concentra tion ratio in this daily times five schedule was 27.6%, and the interpatient variation was 45.5%. The saliva concentrations of topotecan were not related to the occurrence of mucositis, which was noted in some patients. Conclusion. Based on the large variability in the plasma/saliva ratios, we conclude that in our investi gational setting saliva is not a reliable matrix for topotecan analysis and that plasma sampling is to be preferred.
The development of a national oncology pharmacy audit database in the United Kingdom of Great Britain and Northern Ireland
Authors: Stanley A.P. , Austin M.C. 
Published: November 2007

Audit has become an important facet of service and patient management over the last 5 to 10 years. The importance of Audit has received particular emphasis in the UK through the endorsement of both its concepts and its practice from the government via the National Health Service Executive and professional bodies such as the Royal Pharmaceutical Society and the General Medical Council. Within specialities, such as pharmacy services to oncology departments, the relative scale of operation makes self or even local peer-reviewed audit inappro priate. There needs to be a more broad based and less isolated comparison of standards, ideally with exter nal peer review. Furthermore because oncology phar macy tends to be run from small, very busy units the audit process would require additional time, re sources, or data collection. An appropriate audit process should, therefore, be based around existing work practices and not require additional resources. Bearing in mind these principles, a collaboration between a group of oncology pharmacists and a specialized health care firm was developed and the JANUS project and the NOPAD (National Oncology Pharmacy Database) established. The scheme relies on computer extraction of core data from existing working records. While being completely anonymous of patients and reporting centre. Data are then pro cessed into the NOPAD database which can be used by a reporting centre to compare their internal audit data to a national core data set, and for academic research into pharmacy practices in oncology phar macy. Furthermore information from the database has to be sold in a "washed out" form to oncology firms to pay for the running costs of the service. Although not universally subscribed to throughout the UK, there has been around an 80% uptake of the concept and further project looking to extend the database to cover support therapies, and/or other therapeutic areas as well as linking this drug usage picture to the UKs cancer registries disease distri bution picture. Some of the background to this unique UK initiative are presented, and the mechanism by whic the project works for UK centres is described.
Pharmaceutical care and the cancer patient
Authors: Ignoffo Robert J. , King Reginald 
Published: November 2007

Purpose. The primary objective of this paper is to discuss pharmaceutical care of the oncology patient in the context of recent recommendations made by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and recent changes in Health Care Reform. Data Sources. We reviewed the literature through a MEDLINE search from 1985 to 1995. We searched the following terms: pharmaceutical care, cancer, patient, and pharmacist. We restricted the search to the English language. We also have incor porated several of our practice guidelines as examples of tools that can be used in the implementation of pharmaceutical care. We also focused on areas that the JCAHO guidelines specify as important pharma ceutical care issues in the cancer patient. Data Extraction. Within the framework of drug prescribing, drug administration, drug monitoring, and patient education, we have provided interven tions that may potentially improve outcomes in can cer patients. Data Synthesis. The advent of managed care will require that the pharmacist be more involved in the care and management of the cancer patient. This activity will necessitate that the pharmacist document the impact of interventions on patient outcomes. Although tumor response and survival are classic outcomes that are assessed in the cancer patient, other outcome indicators may be used to evaluate interventions made by the pharmacist. Conclusions. This review offers strategies for implementing pharmaceutical care in the cancer pa tient. Because we did not present study results on patient outcomes, it is unknown which of these proposed pharmacist interventions are important fac tors in the implementation of pharmaceutical care in this patient population. Although pharmaceutical care is the new paradigm in pharmacy practice, we must perform prospective studies to determine its value to the cancer community.
An evaluation of the stability of granulocyte colony stimulating factor on short-term storage and delivery from an elastomeric infusion system
Authors: Tivnann Helen Ann , Gaines-Gas Rose , Thorpe Robin , Mire-Sluis Anthony Richard 
Published: November 2007

Aim. To evaluate the stability of granulocyte col ony stimulating factor (G-CSF) (lenograstim) on the 14-day storage and delivery from an elastomeric infusion system (infusion device). Methods. Infusion devices were filled with two different concentrations of G-CSF and stored for various times at 4°C under sterile conditions. Samples of G-CSF solution were then released through the infusion device and bioassayed on the G-CSF dependent murine cell line G-NFS-60. Results. There was no statistically significant loss of bioactivity of G-CSF throughout storage and delivery from the devices for the maximum 14-day period tested at either concentration of G-CSF. Conclusion. The devices can be filled with G-CSF and stored at 4°C for up to 14 days under sterile conditions without loss of biological activ ity, suggesting that these devices are compatible with this biological material and suitable for its short-term storage.
Elimination of NQ01 gene expression by vitamin E
Authors: Kolesar Jill M. , Talbert Robert L. , Kuhn John G. 
Published: November 2007

Objective. NQ01 codes for NAD(P)H:Quinone ox idoreductase (NQOR, DT-diaphorase) which cata lyzes the two electron reduction of quinones. NQOR may protect against quinone-mediated carci nogenicity and activate bioreductive alkylating agents. NQ01 gene expression is induced in re sponse to variety of stimuli, including oxidative stress. Gene expression of NQ01 in response to the antioxidant vitamin E was investigated in this case report. Case Summary. Baseline NQ01 gene expression was 7.5 × 10-6 ng NQ01/mL cDNA in one healthy, male (age 46) adult nonsmoking volunteer. The sub ject subsequently began taking vitamin E (α-tocoph erol, Bronson) 400 IU/d. NQ01 gene expression after 30 days of vitamin E administration was undetect able. The volunteer discontinued vitamin E and NQ01 gene expression was 1.46 × 10-6 ng NQ01/mL cDNA after 30 days. Vitamin E was restarted and after 30 and 60 days, NQ01 gene expression was again undetectable. Discussion: In this subject we have demon strated the ability of vitamin E to effectively eliminate NQ01 gene expression in vivo as measured by a quantitative RT-PCR CE-LIF assay. Vitamin E modu lates signal transduction pathways in response to oxidative stress possibly by downregulation of nu clear factor kappa B (NF-kB). NF-κB, in turn, increases the gene transcription of NQ01. We hypothesize that vitamin E decreases the gene expression of NQ01 by this signaling pathway; by decreasing NF-KB, which in turn downregulates NQ01 gene expression. This may be important for oncology patients because as dem onstrated in vitro, decreased NQOR activity results in resistance to mitomycin-C. Conclusion. Treatment with pharmacological doses of vitamin E can result in NQ01 gene expres sion down regulation in vivo when analyzed by RT-PCR CE-LIF. This interaction, role in the signaling. cascade, and its potential influence on an individuals response to chemotherapy represents an important avenue of exploration.
Clinical pharmacokinetics in oncology: Outcome in vancomycin
Authors: Aldaz Pastor Azucena , de la Asunción Inmaculada Tejedor , Gonzalez-Criado Carolina , Idoate Garcia Antonio 
Published: November 2007

The University Clinic of Navarra is a general teaching hospital with a total of 413 beds, 60 of which are oncology beds. Of the specimens analysed in 1994 by the clinical pharmacokinetics unit, 53.2% were per formed in cancer patients and 27.3% were performed in patients receiving vancomycin. Methods. We established 10 criteria governing both the process and the result in assessing the quality of vancomycin pharmacokinetic monitoring in oncological patients. We performed a retrospective assessment of the data-monitoring follow-up sheets of 100 cancer patients treated with vancomycin and whose serum vancomycin levels were monitored by the clinical pharmacokinetics unit between April 1993 and March 1994. Results. Overall, the degree of compliance with the 10 defined criteria was good, even though 100% compliance was achieved only in criterion 5 (use of the kinetic method) and criterion 8 (repetition of monitoring must be justified). The lowest compliance was obtained in criterion 1 (evaluation of the initial medical prescription) and criterion 6 (the serum creatinine and daily fluid balances, parameters en compassed within the clinical assessment of the pa tient). Conclusions. The detailed analyses of the crite ria performance suggest that the process of serum sample extraction in the wards should be improved and the frequency of serum creatinine testing should be increased. Corrective measures have been pro posed, and once they are developed, accepted, and implemented, the criteria will be reevaluated and a further audit performed to determine the usefulness of the changes made.
Liposomal doxorubicin: Doxil®
Authors: Patel J. 
Published: November 2007

Objective: Many cytotoxic chemotherapy agents have a narrow therapeutic index. In fact, in some patients, the onset of serious adverse effects may precede any therapeutic benefit. The use of lipo somes to target drug delivery to the site of action can improve a drug's therapeutic index by increasing its efficacy while minimizing toxicity. Liposomal doxo rubicin (Doxil®, Sequus Pharmaceuticals, Inc.)* is the first liposomal chemotherapy product to be approved in the United States. The purpose of this review is to provide a basic understanding of liposomal drug delivery, describe the unique pharmacokinetic prop erties of liposomal doxorubicin (Doxil®), and, finally, comment on this novel drug's place in therapy. Data Sources: Manual and on-line (Medline) literature searches were performed. Search terms included were the brand and generic names of the product, Kaposi's sarcoma, and liposomes. The med ical information department of Sequus Pharmaceuti cals was contacted. Study Selection: If available, controlled clinical trials with scientific merit were reviewed. Nonran domized studies, case reports, review articles, and letters to editors were considered if appropriate. Conclusions: Liposomal chemotherapy is one of many attempts to improve cytotoxic chemotherapy by maximizing tumor cell kill while minimizing pa tient adverse effects. Liposomal doxorubicin (Doxil®) is the first of such products approved for use in the United States and has a unique formulation and advantageous pharmacokinetic profile. Liposomal doxorubicin (Doxil®) is both a safe and effective agent in the treatment of advanced AIDS-related Ka posi's sarcoma. The efficacy of liposomal doxorubicin (Doxil®) in the treatment of refractory solid tumors such as breast cancer, lung cancer, colorectal cancer, renal cell cancer, ovarian cancer, and sarcoma has not been demonstrated uniformly. Limited data are avail able regarding the cardiotoxicity potential of this agent; currently no definitive conclusions can be made. Further investigation will be needed to find the ideal dose, dose schedule, and monitoring parameters for the use of liposomal doxorubicin (Doxil®) in patients with solid tumors.
Economic evaluation of 4% albumin solution, gelatine, and hydroxyethylamidon for plasma volume expansion in cancer patients
Authors: Pinguet Frédéric , Poujol Sylvain , Martel Pascal , Roch Isabelle , Bressolle Francoise 
Published: November 2007

Purpose. Given the potential advantages of the use of hydroxyethylamidon, the purpose of this cost analysis was to examine the economic consequences of the use of such derivatives compared to albumin and gelatine for fluid resuscitation in patients with various types of cancer. Methods. We report on the economic evalua tion conducted at the Montpellier Anticancer Center between July 1989 and December 1995. Patients with various types of cancer were included in the study. About 310 patients were treated each year. Since January 1991, an economic policy was undertaken to reduce the cost of treatment by volume expanders. Results. During the study period, the pharma ceutical price of these drugs, the number of patients, and the number of days of hospitalization remained relatively stable. From 1991 to 1995 of this economic evaluation, we observed a regular decrease in the utilization of fluid expanders. Indeed, 2370 vials were used in 1990 and only 868 in 1995. In 1991, a new plasma volume expander, hydroxyethylamidon, be came commercially available. Consequently, from 1992, we observed a decrease in the use of 4% albumin; then, from 1993, there was a decrease in the use of gelatine. In 1989, the mean cost of each vial was $46; it was $16 in 1995. This decrease is attrib utable to a progressive substitution of 4% albumin, then of gelatine, by hydroxyethylamidon. During the 24 first months of the present study, the total cost of plasma volume expanders was approximately $180,000 (July 1989 to June 1991); it was $164,000 during the following 54 months (July 1991 to Decem ber 1995). Conclusion. The pharmaceutical economic pol icy and the risk of using blood product have contrib uted to a decrease in the total cost of the different drugs used as plasma volume expanders. To date, the savings realized have been ∼$75,000 annually.
A comparison of the safety and efficacy of ondansetron versus granisetron as prophylaxis against chemo/ radiotherapy-induced nausea and vomiting in bone marrow transplantation patients. A double-blinded, randomized, prospective, pilot study
Authors: Or Reuven , Kupaluchnik Yosef , Drakos Pavlos , Nagler Arnon , Cass Yaakov 
Published: November 2007

Introduction. Nausea and vomiting (N&V) are well known and distressing side effects of chemoradio therapy. Conditioning protocols for patients undergo ing bone marrow transplantation (BMT) consist of highly emetogenic high-dose chemotherapy with or without total body irradiation (TBI). The 5HT3 (sero tonin receptor) antagonists heralded a marked im provement in controlling chemotherapy-induced N&V. Ondansetron and granisetron have been avail able for some time with limited information available concerning their pharmacological and pharmacoeco nomic differences and patient acceptability. Patients and Methods. This pilot study initiated comparison of the two drugs and evaluated the antiemetic efficacy and safety of a single daily dose of ondansetron, 16 mg, plus dexamethasone, 10 mg, compared to granisetron, 3 mg, plus dexamethasone, 10 mg, in patients receiving high dose chemotherapy (±TBI), prior to BMT. The 12-month pilot study was double-blinded, randomized, and prospective. A non- homogenous cohort of 23 patients (10 receiving ondansetron and 13 granisetron) were enrolled. Results. No significant differences in the efficacy of the two protocols were observed. In each arm about 50% of the patients had a complete response, and a similar number had a major response. Side Effects. The most common adverse events reported during the study included diarrhea and head ache. No patients were withdrawn due to side effects. Conclusions. Our preliminary findings suggest that both of these two antiemetic protocols are safe and similarly effective in preventing chemotherapy-induced emesis in patients receiving BMT conditioning. Discussion. Further evaluation in a multicenter study should now be made to compare efficacy, safety, cost-effectiveness, and quality of life parame ters of these two drugs.