Recent developments in the prevention of chemotherapy-induced nausea and vomiting (CINV): a comprehensive review.

The prevention of chemotherapy-induced nausea and vomiting (CINV) has been revolutionized over the past 25 years. Guideline-based treatment means that vomiting can be prevented in the majority, but not in all patients. Therefore, antiemetic research continues with the goal of optimizing CINV control for all patients. This comprehensive review summarizes the research efforts in this field over the past few years. Emerging from this research are two new antiemetic agents, netupitant/palonosetron, the first antiemetic combination agent and rolapitant, a new NK1RA. In addition, studies have evaluated the benefits of olanzapine and ginger, explored optimal combinations of agents for delayed CINV prevention, confirmed that dexamethasone-sparing regimens are effective, and demonstrated the value of NK1RAs in high-dose chemotherapy settings as well as with certain moderately emetogenic chemotherapies such as carboplatin. Research has also validated the correlation between antiemetic guideline adherence and improved CINV control. Finally, regulatory authorities have utilized extreme caution in retiring some 5-HT3RAs or decreasing their maximum dose.

The randomized shortened dental arch study: oral health-related quality of life.

OBJECTIVES: Although the shortened dental arch (SDA) concept is a widely accepted strategy to avoid overtreatment, little is known on its impact on oral health-related quality of life (OHRQoL). This multicenter randomized controlled trial aimed to investigate the OHRQoL for removable partial dental prostheses (RPDP) with molar replacement versus the SDA concept. MATERIAL AND METHODS: In both groups, missing anterior teeth were replaced with fixed dental prosthesis. Two hundred fifteen patients with bilateral molar loss in at least one jaw were included. The Oral Health Impact Profile (OHIP-49) was completed before; 6 weeks (baseline), 6 months, and 12 months after treatment; and thereafter annually until 5 years. RESULTS: Of the initial cohort, 81 patients were assigned to the RPDP group and 71 to the SDA group (age, 34 to 86 years). Before treatment, the median OHIP score was similar in both groups (RPDP, 38.0; SDA, 40.0; n.s.). Results indicate marked improvements in OHRQoL in both groups between pretreatment and baseline (RPDP, 27.0; SDA, 19.0; p ≤ 0.0001) which continued in the RPDP group until the 1-year follow-up (p = 0.0002). These significant reductions in OHIP scores are reflected in its subscales. No further differences were seen within and between groups during the remainder observation period. CONCLUSION: Both treatments show a significant improvement in OHRQoL which continued in the RPDP group until the 1-year follow-up. No significant differences were seen between groups. CLINICAL RELEVANCE: For improving OHRQoL, it is not necessary to replace missing molars with a RPDP.

Treatment of adolescents and young adults (AYA) with cancer in a multidisciplinary setting: on the way to a highly specialized AYA unit.

Further survival improvements of adolescents and young adults (AYA) with cancer are clearly affected by biological characteristics of the malignancies and age-specific needs. Multidisciplinary teams drawing expertice from both pediatric and adult cancer teams as well as clinical trials are required to meet the age specific needs of AYA patients with cancer. In 2011, the first AYA unit was established at the University Hospital Halle (Saale), where patients with newly-diagnosed cancer aged 15-25 are treated interdisciplinary by pediatric and adult oncologists. The enrollment into pediatric or adult clinical trials is controlled by age 18. Over the last 2 years, 19 AYA with cancer have been treated at the unit; and, in turn patients and their relatives reflected a high satisfaction with the offered novel health care approach. In the scope of the future Comprehensive Cancer Center at the University Hospital Halle (Saale), a complete ward is planned for all admitted AYA up to 25 years with cancer. The patients will be treated by a tumor-specialized multidisciplinary team of adult or pediatric oncologists and oncological surgeons. Therefore, we intend to establish a special teaching curriculum for physicians, nurses and psychosocial health care staff. Rather than age, cancer biology of a malignancy, surveillance data of late side effects as well as the age-specific needs of AYA patients will be crucial for best treatment options.

The randomized shortened dental arch study: tooth loss over five years.

OBJECTIVES: The study was designed to provide clinical outcome data for two treatments of the shortened dental arch (SDA). MATERIAL AND METHODS: In a multicenter randomized controlled clinical trial, patients with complete molar loss in one jaw were provided with either a partial removable dental prosthesis (PRDP) retained with precision attachments or treated according to the SDA concept preserving or restoring a premolar occlusion. No implants were placed. The primary outcome was tooth loss. RESULTS: Of 152 treated patients, 132 patients reached the 5-year examination. Over 5 years, 38 patients experienced tooth loss. For the primary outcome tooth loss, the Kaplan-Meier survival rates at 5 years were 0.74 (95% CI 0.64, 0.84) in the PRDP group and 0.74 (95% CI 0.63, 0.85) in the SDA group. For tooth loss in the study jaw, the survival rates at 5 years were 0.88 (95% CI 0.80, 0.95) in the PRDP group and 0.84 (95% CI 0.74, 0.93) in the SDA group. The differences were not significant. No Cox regression models of appropriate fit explaining tooth loss on the patient level could be found. CONCLUSIONS: The overall treatment goals of a sustainable oral rehabilitation and the avoidance of further tooth loss over longer periods were not reliably achievable. The influence of the type of prosthetic treatment on tooth loss might have been overestimated. CLINICAL RELEVANCE: Regarding our results, the patient's view will gain even more importance in the clinical decision between removable and fixed restorations in SDAs.

Modeling Interoperable Information Systems with 3LGM² and IHE.

BACKGROUND: Strategic planning of information systems (IS) in healthcare requires descriptions of the current and the future IS state. Enterprise architecture planning (EAP) tools like the 3LGM² tool help to build up and to analyze IS models. A model of the planned architecture can be derived from an analysis of current state IS models. Building an interoperable IS, i. e. an IS consisting of interoperable components, can be considered a relevant strategic information management goal for many IS in healthcare. Integrating the healthcare enterprise (IHE) is an initiative which targets interoperability by using established standards. OBJECTIVES: To link IHE concepts to 3LGM² concepts within the 3LGM² tool. To describe how an information manager can be supported in handling the complex IHE world and planning interoperable IS using 3LGM² models. To describe how developers or maintainers of IHE profiles can be supported by the representation of IHE concepts in 3LGM². METHODS: Conceptualization and concept mapping methods are used to assign IHE concepts such as domains, integration profiles actors and transactions to the concepts of the three-layer graph-based meta-model (3LGM²). RESULTS: IHE concepts were successfully linked to 3LGM² concepts. An IHE-master-model, i. e. an abstract model for IHE concepts, was modeled with the help of 3LGM² tool. Two IHE domains were modeled in detail (ITI, QRPH). We describe two use cases for the representation of IHE concepts and IHE domains as 3LGM² models. Information managers can use the IHE-master-model as reference model for modeling interoperable IS based on IHE profiles during EAP activities. IHE developers are supported in analyzing consistency of IHE concepts with the help of the IHE-master-model and functions of the 3LGM² tool CONCLUSION: The complex relations between IHE concepts can be modeled by using the EAP method 3LGM². 3LGM² tool offers visualization and analysis features which are now available for the IHE-master-model. Thus information managers and IHE developers can use or develop IHE profiles systematically. In order to improve the usability and handling of the IHE-master-model and its usage as a reference model, some further refinements have to be done. Evaluating the use of the IHE-master-model by information managers and IHE developers is subject to further research.

Chlorinated drinking water is mutagenic and causes 3-methylcholanthrene type induction of hepatic monooxygenase.

Acid/neutral fractions of 4 chlorinated drinking water samples were tested for mutagenicity in the Ames' test and injected intraperitoneally to 10- and 20-day-old Wistar rats at doses of 200 and 100 liters of water/kg body weight. Cytochrome P-450 mediated enzyme activities of ethylmorphine-N-demethylase (EMND), 7-ethoxycoumarin-O-deethylase (ECOD), 7-ethoxyresorufin-O-deethylase (EROD) and 7-pentoxyresorufin-O-dealkylase (PEROD) were determined in the 9000 g supernatant fraction of liver homogenate. EROD was introduced by the concentrates. The induction was related to the mutagenic activity. About 4-fold increase in activity was observed with the most mutagenic sample. PEROD was also slightly enhanced. EMND and ECOD activities were not affected by the lower dose, but the higher dose caused inhibition of 30-40%. Although the extracts were not toxic to bacteria, they were unexpectedly toxic to rats. It is concluded that the samples contained 3-methylcholanthrene (3-MC) type inducer(s).

Influence of 2-acetylaminofluorene (2-AAF) on biotransformation and lipid peroxidation in salivary glands and liver from male rats.

Salivary glands proved to be active in biotransformation. In microsomes of rat salivary glands 7-ethoxyresorufin O-deethylation (EROD) and 7-pentoxyresorufin O-depentylation (PEROD) were detectable, but with much lower activities than in the liver. Beside the well-known induction of EROD or PEROD in the liver by beta-naphthoflavone (BNF) or phenobarbital (PB), respectively, a marked rise in EROD rate of salivary glands was observed after BNF treatment. Administration of 2-AAF caused an increase in EROD rates in liver microsomes, but a decrease in microsomes of salivary glands. This decrease in EROD rate was accompanied by selective cytotoxic damages in the convoluted granulated tubules of the submandibular glands. No cytotoxic damage occurred in the submandibular glands after a combined administration of the inducer BNF and 2-AAF. This indicates relations between these toxic effects of 2-AAF and changes of 2-AAF-metabolism in BNF-induced rats, maybe in the liver and/or in the submandibular glands themselves.

Age dependent different influence of carbon tetrachloride on biotransformation of xenobiotics, glutathione content, lipid peroxidation and histopathology of rat liver.

15- and 60-day-old male rats were treated with different doses of CCl4 orally. 24 h later cytochrome P-450 (P450) concentration, 7-ethoxyresorufin O-deethylation (EROD) and 7-pentoxy-resorufin O-deethylation (PEROD) activities were determined. Whereas P450 and EROD are lowered to the same extent in both ages, PEROD shows a more pronounced inhibition in the livers of younger rats. The formation of endogenous lipid peroxides (measured as thiobarbituric acid reactive substances) is drastically increased only in the livers of young rats. The hepatic glutathione (GSH) content was unaffected by CCl4 treatment whereas oxidized glutathione is more increased in the livers of adult rats. This can be caused by a higher activity of GSH-peroxidase in the livers of adult rats. The changes in NADPH-induced lipid peroxidation and chemiluminescence correlate partially with the changes in P450 and biotransformation reactions. Histopathologically the liver damage is more extensive in suckling rats. The necrosis is localized predominantly in the perivenous tissue, which has normally the highest activities of toxification and detoxification enzymes.

Hemodynamic parameters and renal blood flow following stimulation of renal tubular transport processes by treatment with thyroid hormones.

In adult rats, renal excretion of p-aminohippurate (PAH) can be stimulated by repeated administration of thyroid hormones. Data on renal cortical slices show clearly that a stimulation of active, carrier-mediated tubular transport processes is the most important cause. In vivo experiments also show an influence of treatment with thyroid hormones on various hemodynamic parameters. The diminution of vascular resistance in cortical and medullary regions of the kidney might contribute to the increased PAH excretion in thyroid hormone-treated rats.

Influence of neonatal and postnatal administration of diethylstilbestrol on hepatic monooxygenase activities and lipid peroxidation in adult rats.

Treatment of adult male and female rats with DES caused a significant reduction of cytochrome P450 concentration, ethylmorphine N-demethylation and ethoxycoumarin O-deethylation. These decreases are not modified by a neonatal treatment with this hormone. In contrast to monooxygenase activities the NADPH-induced lipid peroxidation shows only a tendency to decrease if animals received DES as adults. But a decrease of about 50% is observed after "neonatal plus treatment of adults" with DES. The role of formation of reactive oxygen species characterized by chemiluminescence methods in connection with lipid peroxidation is discussed.

[Apropos of a case of laryngeal granular cell tumor]. / A propos d'un cas de tumeur laryngée à cellules granuleuses.

The granular cell tumor, or Abrikossofs tumor, is a benign rare neoplastic disease, which affects the larynx in approximately 6% of all the described locations. Its nervoux origin is admitted by the majority of the specialists and its treatment is only surgical. After describing the histopathology and the clinical characteristics of the lesion, we describe a most unusual atypical endolaryngeal location. In our review we have not found any case described as such.

The NK-1 receptor-antagonist aprepitant in high-dose chemotherapy (high-dose melphalan and high-dose T-ICE: paclitaxel, ifosfamide, carboplatin, etoposide): efficacy and safety of a triple antiemetic combination.

Complete protection from nausea/vomiting is currently achieved in a minority of patients receiving high-dose chemotherapy (HDC). Currently the use of 5-HT3-antagonists and dexamethasone (DEX) represents the standard of care. The role of the NK-1-antagonist aprepitant in HDC remains to be better defined. A total of 64 patients undergoing multiple days of HDC received granisetron, DEX plus aprepitant during chemotherapy. After the end of chemotherapy aprepitant plus DEX was given for a further 2 days. Primary end point was CR defined as no vomiting and no use of rescue medication in the overall phase (day 1 until 5 days after end of chemotherapy). Acute/delayed and overall CR were achieved in 83%/70% and 63%, respectively. Acute and delayed nausea were observed in 20 and 38% of the patients. The tolerability of the aprepitant regimen over 4-5 days was comparable with the 3-day antiemetic regimen. In our study, aprepitant demonstrated good tolerability. Taking into account the methodological constraints of comparing our results with those from the available literature, the addition of aprepitant to the antiemetic treatment regimen may provide improved prevention of chemotherapy-induced nausea and vomiting during HDC.

Concerns for decreased foetal movements in uncomplicated pregnancies--increased risk of foetal growth restriction and stillbirth among women being overweight, advanced age or smoking.

INTRODUCTION: We aimed to determine whether the clinical characteristics of women in uncomplicated pregnancies presenting with decreased foetal movements (DFMs) would help target subgroups of women at the highest risk. Furthermore, we also aimed whether DFMs in complicated pregnancies identified the additional needs for intensified management. METHODS: Singleton third trimester pregnancies (n=2374) presenting with DFMs from June 2004 through October 2005 were prospectively registered in 14 delivery units in Norway. Among pregnancies that were uncomplicated until registration for DFMs, cases with good outcomes (birth weight between 10th and 90th percentile, term delivery and live-born child) were compared with cases with adverse outcomes. RESULTS: In uncomplicated pregnancies, maternal overweight, advanced age and smoking identified subgroups of cases at increased risk of foetal growth restriction and stillbirth. DFMs of longer duration, in particular the perceived absence of movements, identified cases at increased risk of stillbirth, irrespective of other maternal characteristics. When women with complicated pregnancies reported DFMs, additional indications for follow-up were found in 1/3 of cases. CONCLUSIONS: Maternal overweight, advanced age, smoking and the duration of DFMs are the characteristics that help in identifying pregnancies that should be targeted for intensified management. Time matters and knowledge-based information are needed to improve foetal health.

The randomized shortened dental arch study: tooth loss.

The evidence concerning the management of shortened dental arch (SDA) cases is sparse. This multi-center study was aimed at generating data on outcomes and survival rates for two common treatments, removable dental prostheses (RDP) for molar replacement or no replacement (SDA). The hypothesis was that the treatments lead to different incidences of tooth loss. We included 215 patients with complete molar loss in one jaw. Molars were either replaced by RDP or not replaced, according to the SDA concept. First tooth loss after treatment was the primary outcome measure. This event occurred in 13 patients in the RDP group and nine patients in the SDA group. The respective Kaplan-Meier survival rates at 38 months were 0.83 (95% CI: 0.74-0.91) in the RDP group and 0.86 (95% CI: 0.78-0.95) in the SDA group, the difference being non-significant.