Drug monitoring detects under- and overdosing in patients receiving 5-fluorouracil-containing chemotherapy-results of a prospective, multicenter German observational study.

INTRODUCTION: Body surface area (BSA)-based dosing of 5-fluorouracil (5-FU) results in marked inter-individual variability in drug levels, whereas determination of plasma 5-FU concentration and area under the curve (AUC) is a more precise dosing method but has not been integrated into clinical routine. We conducted a multicenter, prospective study to study 5-FU AUC distributions and assess clinical factors predicting therapeutic dosing in patients receiving BSA-dosed 5-FU. METHODS: Between June 2017 and January 2018, a total of 434 patients receiving continuous, infusional BSA-dosed 5-FU from 37 sites in Germany were included. Plasma 5-FU concentration and AUC were measured in venous blood samples at steady state. The primary objective was to determine 5-FU AUC distributions in relation to the target range, which is defined as 20-30 mg × h/l. The second objective was to explore clinical parameters that correlate with achievement of 5-FU AUC target range. RESULTS: The primary tumor was mainly located in the gastrointestinal tract (96.3%), with colorectal cancer being the most common (71.2%) tumor entity. 5-FU was administered as monotherapy (8.1%) or as part of FOLFOX (33.2%), FOLFIRI (26.3%), or other regimens (12.4%). Treatment setting was adjuvant (31.3%) or metastatic (64.5%). The median AUC was 16 mg × h/l. Only 20.3% of patients received 5-FU treatment within the target range, whereas the majority of patients (60.6%) were underdosed and 19.1% of patients were overdosed. In the univariate logistic regression, treatment setting was the only clinical parameter that significantly correlated with achievement of the target range. Patients treated in the metastatic setting had a 2.1 (95% confidence interval 1.186-3.776, P = 0.011) higher odds to reach the target range compared with patients treated in the adjuvant setting. CONCLUSIONS: The majority of patients received suboptimal doses of 5-FU using BSA dosing. Therapeutic drug monitoring of 5-FU is an option for optimized individualized cancer therapy and should be integrated into the clinical practice.

[Laryngeal amyloidosis: a clinical case and review of literature]. / Amyloïdose laryngée: revue de la littérature et cas clinique.

Amyloidosis consists of different forms of systemic or isolated organ lesions characterised by fibrillary protein deposits in extra-cellular tissue. The isolated involvement of the larynx is the most frequent form in the ENT sphere. We present a clinical case of a 67 year-old woman addressed for a sub-acute laryngitis resistant to conservative treatment, and finally diagnosed with laryngeal amyloidosis. We reviewed its physiopathology, the scientific literature as well as the different possibilities of management. Laryngeal amyloidosis is rare. A thorough additional work-up for the research of multifocal or systemic forms is highly recommended. The treatment aims at a minimal invasive endoscopic surgery with functional organ preservation.

[An update on bone anchored hearing aids]. / Appareils auditifs à ancrage osseux.

Hearing loss represents a hidden handicapwith various repercussions on development and social life. In the majority of cases, classical hearing aids address most hearing losses. However, the enhancement required for severe deafness frequently involves sound distortions which are very uncomfortable for patients. With the advent of bone anchored hearing aids, conductive hearing losses as well as mixed hearing losses are now better rehabilitated. Recently their indications have been expanded to profound to severe sensorineural hearing loss. The emergence of new materials as well as subcutaneous implants has lead to lessen skin complications and has diminished the aesthetic discomfort of this type of hearing devices.

Thermodynamic modeling of chromium: strong and weak magnetic coupling.

As chromium is a decisive ingredient for stainless steels, a reliable understanding of its thermodynamic properties is indispensable. Parameter-free first-principles methods have nowadays evolved to a state allowing such thermodynamic predictions. For materials such as Cr, however, the inclusion of magnetic entropy and higher order contributions such as anharmonic entropy is still a formidable task. Employing state-of-the-art ab initio molecular dynamics simulations and statistical concepts, we compute a set of thermodynamic properties based on quasiharmonic, anharmonic, electronic and magnetic free energy contributions from first principles. The magnetic contribution is modeled by an effective nearest-neighbor Heisenberg model, which itself is solved numerically exactly by means of a quantum Monte Carlo method. We investigate two different scenarios: a weak magnetic coupling scenario for Cr, as usually presumed in empirical thermodynamic models, turns out to be in clear disagreement with experimental observations. We show that instead a mixed Hamiltonian including weak and strong magnetic coupling provides a consistent picture with good agreement to experimental thermodynamic data.

Severe pulmonary toxicity in patients with advanced-stage Hodgkin's disease treated with a modified bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, and gemcitabine (BEACOPP) regimen is probably related to the combination of gemcitabine and bleomycin: a report of the German Hodgkin's Lymphoma Study Group.

PURPOSE: To investigate a new effective, nonleukemogenic polychemotherapy regimen, BAGCOPP (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone, gemcitabine) in a phase I/II dose-escalation study in patients with advanced-stage Hodgkin' s disease (HD). PATIENTS AND METHODS: Patients in clinical stages IIB with risk factors III and IV were enrolled in this nonrandomized, multicenter trial aimed at defining the maximum-tolerated dose of gemcitabine within a modified escalated BEACOPP regimen. Gemcitabine was given at a starting dose of 800 mg/m(2) on days 1 and 4 of each cycle. RESULTS: Twenty-seven patients (eight female, 19 male) were enrolled with a median age of 33 years (range, 19 to 65 years). Due to a higher than expected hematotoxicity, the day-4 application of gemcitabine was omitted after 14 patients were included and 59 cycles were given. A total of eight patients developed lung toxicity, mainly pneumonitis (six of eight), which led to the termination of the study. With a median follow-up of 27 months, 25 patients are in continuing complete remission. CONCLUSION: The substitution of etoposide by gemcitabine in the escalated BEACOPP schema is not feasible and leads to severe pulmonary toxicity. This toxicity is probably related to the concomittant application of gemcitabine and bleomycin.

Comparative analyses of bone marrow micrometastases in breast and gastric cancer.

This study is a comparative analysis of the prevalence, absolute number and aggregation status of bone marrow micro-metastases (BMM) between breast (n=234) and gastric (n=102) cancer patients based on a standardized number of 1 X 10(6) bone marrow-derived cells per patient. Additionally, expression of the epithelial cell adhesion molecule E-cadherin was analyzed on disseminated tumor cells. A positive BMM status was demonstrated in 88/234 breast and 45/102 gastric cancer patients. The presence of CK18+ cells positively correlated with parameters of advanced tumor progression in breast, but not in gastric cancer. Interestingly, 25.2% of the node-negative patients already had micrometastatic cells in the bone marrow at diagnosis. Regarding the absolute number of CK18+ cells and the frequency of CK18+ cell clusters, no significant difference was found between the 2 tumor types. However, clusters consisting of more than 10 CK18+ cells (type II clusters) were present exclusively in breast cancer patients. Additionally, co-expression of CK18 and E-cadherin was detectable in 15/21 micrometastases-positive breast but in only 1/9 gastric cancer patients. While prevalence of micrometastatic cells in bone marrow is discussed as an early indicator for systemic disease, aggregation status and a certain antigen profile might be indicative for site-specific differences in the manifestation pattern of solid metastases.

Diagnosis of group A streptococcal pharyngitis in a private clinic: comparative evaluation of an optical immunoassay method and culture.

We compared the sensitivity and specificity of the Strep A Optical ImmunoAssay (OIA) method with our routine trypticase soy agar with 5% sheep blood (TSA) culture technique and with a broth-enhanced culture in the diagnosis of group A beta-hemolytic streptococcal infection. Compared with broth-enhanced culture, the Strep A OIA had a sensitivity and specificity of 94.8% and 98.8%, respectively; TSA culture had a sensitivity and specificity of 92.5% and 99.4%, respectively. The Strep A OIA, which takes 10 minutes to perform, offered sensitivity and specificity equivalent to that of TSA culture in the diagnosis of group A beta-hemolytic streptococcal pharyngitis.

Pediatricians' diagnostic approach to pharyngitis and impact of CLIA 1988 on office diagnostic tests.

OBJECTIVE: To determine the factors associated with an optimal diagnostic approach to a child with pharyngitis, characterize office laboratory methods for throat swab culture and group A streptococcal rapid antigen testing, and assess the potential impact of the Clinical Laboratory Improvement Amendments (CLIA) of 1988 on the performance of these tests. DESIGN AND SETTING: Mailed survey to all board-certified primary care pediatricians from seven western states with telephone follow-up for nonrespondents. OUTCOME MEASURES: Differences in practice characteristics and use of office laboratory tests for physicians who usually (> 80%) diagnose pharyngitis using a recommended approach vs those who follow this approach less often (< 50%); characteristics of physicians who indicate that they intend to discontinue office throat culture because of CLIA and those who will continue to perform this test also are compared. RESULTS: Responses from 531 pediatricians were analyzed. Forty-four percent diagnosed pharyngitis appropriately for more than 80% of patients, and 17% did so for fewer than 50%. Optimal diagnosis was significantly more common among physicians who cultured throat swabs in their office (relative risk, 1.40; 95% confidence interval, 1.19 to 1.66) and less common among solo practitioners (relative risk, 0.71; 95% confidence interval, 0.56 to 0.88). Factors that may decrease the sensitivity of office throat culture include short duration of incubation (59%), lack of quality control (51%), and limited education of the persons reading results (6%). With implementation of CLIA, 24% of pediatricians reported that they already have discontinued or will discontinue office throat culture, and 23% have discontinued or will discontinue antigen detection testing for group A streptococci. Those most likely to stop office culture include solo practitioners and practitioners who do not currently perform quality control of culture methods. CONCLUSIONS: Office culture for group A streptococci is strongly associated with an optimal diagnostic approach. Implementation of CLIA regulations may substantially decrease the number of physicians who perform this test. The balance between potential improvements in the quality of office culture with CLIA implementation and the decreased availability of this test needs to be assessed.

Health risk changes with a low-cost individualized health promotion program: effects at up to 30 months.

BACKGROUND AND PURPOSE: Health promotion programs are increasingly important components of health care in an era of predominantly chronic illness preceded by identified health risk behaviors. We report a large and relatively long experience with a low-cost intervention delivered through the mail and using sequential time-oriented risk appraisal and personalized recommendations, each six months, together with self-management materials. METHODS: We performed a prospective, longitudinal, observational study of 103,937 consecutive program participants observed for at least six months and up to 30 months. The primary study endpoint is overall health risk score, with secondary analysis of individual risk behaviors. A concurrent comparison group utilizes the initial scores of new participants by calendar time over the study period. RESULTS: Strong overall positive effects were observed, with improvement in computed health risk scores over 18 months of 14.7% (p less than .0001) in those 65 and over and 18.4% (p<.0001) in those under 65. At 30 months, improvement was 18.8% (p less than .0001) and 25.7% (p less than .0001), respectively. There was improvement in self-report scores for all targeted health risk behaviors, except for pounds over ideal weight, including smoking; dietary fat, salt, and fiber; alcohol; exercise; cholesterol; and reported stress. There was progressive improvement approximating 5% each six-month period. Results were consistent across age groups 16-35, 36-50, 51-65, and over 65 and over different educational level. Results could not be accounted for by sequential changes in initial health habits of participants over time. DISCUSSION: (ABSTRACT TRUNCATED AT 250 WORDS)

[Detection of tumor cells in bone marrow: a deciding aid for adjuvant therapy in node negative patients with breast cancer. Concept for a multicenter study and results of the pilot phase]. / Tumorzellnachweis im Knochenmark: Entscheidungshilfe zur adjuvanten Therapie bei nodal-negativen Patientinnen mit Mammacarcinom. Konzept einer Multicenterstudie und Ergebnisse der Pilotphase.

In node-negative breast cancer some 30% of patients will suffer a tumor relapse, despite primary curative therapeutic intervention. An adjuvant therapy is therefore in discussion, especially in presence of risk factors. Immunocytochemical staining of cytokeratin-positive cells in bone marrow aspirates with monoclonal antibodies offers a chance to detect tumorcell dissemination at an early stage of single tumor cells. In 103 consecutive patients 50% showed a positive bone marrow aspirate, in node negative patients still 34%. Based on the literature and tumor biology this method may be valid in selecting node-negative breast cancer patients for adjuvant therapy. In a prospective multi-center trial the prognostic value will be evaluated in regard to other prognostic factors. Additionally the benefit of an adjuvant therapy will be studied in a randomized prospective trial.

Periodontal probe use in general practice in Florida.

Use of the periodontal probe in 134 Florida dental practices was studied. Results indicated that 62% of the practices performed a complete recorded periodontal probing for new patients. Recall patients received a complete recorded periodontal probing in 57% of the practices at a mean frequency of 12.7 months. Selected site probing was performed in 22% of the offices as part of the new patient examination, and in 34% of the offices as part of the recall examination. In the examinations in 57% of the practices, changes in pocket depths were detected that could suggest changes in connective tissue levels.