Prevalence and burden of bipolar disorders in European countries.

A literature search, supplemented by an expert survey and selected reanalyses of existing data from epidemiological studies was performed to determine the prevalence and associated burden of bipolar I and II disorder in EU countries. Only studies using established diagnostic instruments based on DSM-III-R or DSM-IV, or ICD-10 criteria were considered. Fourteen studies from a total of 10 countries were identified. The majority of studies reported 12-month estimates of approximately 1% (range 0.5-1.1%), with little evidence of a gender difference. The cumulative lifetime incidence (two prospective-longitudinal studies) is slightly higher (1.5-2%); and when the wider range of bipolar spectrum disorders is considered estimates increased to approximately 6%. Few studies have reported separate estimates for bipolar I and II disorders. Age of first onset of bipolar disorder is most frequently reported in late adolescence and early adulthood. A high degree of concurrent and sequential comorbidity with other mental disorders and physical illnesses is common. Most studies suggest equally high or even higher levels of impairments and disabilities of bipolar disorders as compared to major depression and schizophrenia. Few data are available on treatment and health care utilization.     

Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm, and dampened 24-hour rest-activity patterns in patients with metastatic colorectal cancer.

PURPOSE: Incapacitating symptom burden in cancer patients contributes to poor quality of life (QOL) and can influence treatment outcomes because of poor tolerance to therapy. In this study, the role of circulating cytokines in the production symptoms in cancer patients is evaluated. EXPERIMENTAL DESIGN: Eighty patients with metastatic colorectal cancer with either normal (group I, n = 40) or dampened (group II, n = 40) 24-hour rest/activity patterns measured by actigraphy were identified. Actigraphy patterns were correlated with QOL indices, serum cortisol obtained at 8:00 a.m. and 4:00 p.m. and with serum levels of transforming growth factor-alpha, tumor necrosis factor-alpha, and interleukin 6 (IL-6) obtained at 8:00 a.m. and analyzed in duplicate by ELISA. Cytokine levels and survival were also correlated. RESULTS: Group II patients had significantly higher pre treatment levels of all three cytokines, displayed significantly poorer emotional and social functioning, had higher fatigue, more appetite loss, and poorer performance status compared with group I patients. Transforming growth factor-alpha (TGF-alpha) and IL-6 were significantly increased in the patients with WHO performance status >1 and in those with appetite loss. Fatigue was significantly associated with elevated TGF-alpha only. IL-6 was increased in those patients with extensive liver involvement and multiple organ replacement, and it was significantly correlated with dampened cortisol rhythm. In a multivariate analysis, IL-6 was correlated with poor treatment outcome. CONCLUSIONS: Significant correlations were found between serum levels of TGF-alpha and IL-6, circadian patterns in wrist activity and serum cortisol and tumor-related symptoms in patients with metastatic colorectal cancer. These data support the hypothesis that some cancer patient's symptoms of fatigue, poor QOL, and treatment outcome are related to tumor or host generated cytokines and could reflect cytokine effects on the circadian timing system. This interplay between cytokine signaling pathways, the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and efferent pathways of the suprachiasmatic nucleus that control circadian physiology, opens the way to new rational interventions for symptom management in cancer patients.     

Enoxaparin for the prevention of venous thromboembolism associated with central vein catheter: a double-blind, placebo-controlled, randomized study in cancer patients.

PURPOSE: The extent of venous thromboembolism (VTE) associated with central vein catheters (CVC) in cancer patients remains unclear. The aim of this study was to evaluate the efficacy and safety of the low molecular weight heparin, enoxaparin, in the prevention of VTE. PATIENTS AND METHODS: In a multicenter, double-blind study, consecutive cancer patients scheduled for CVC insertion were randomly assigned to receive either subcutaneous enoxaparin 40 mg once a day or placebo. Treatment was started 2 hours before CVC insertion and continued for 6 weeks. The primary end points of the study were deep vein thrombosis (DVT), confirmed by venography of the CVC limb performed 6 weeks after randomization, or clinically overt pulmonary embolism, confirmed by objective testing during the study drug administration. Patients were assessed for bleeding complications. RESULTS: Three hundred eighty-five patients were randomized, of which 321 (83.4%) underwent venography. A venography was adequate for adjudication in 155 patients in each treatment group. A DVT was observed in 22 patients (14.1%) treated with enoxaparin and in 28 patients (18.0%) treated with placebo, corresponding to a relative risk of 0.78 (95% CI, 0.47 to 1.31). No major bleeding occurred. Five patients (2.6%) in the enoxaparin group and two patients (1.0%) in the placebo group died during the treatment period. CONCLUSION: In this study, no difference in the rate of CVC-related VTE was detected between patients receiving enoxaparin and patients receiving placebo. The dose of enoxaparin used in this study proved to be safe. Clinical trials evaluating higher enoxaparin doses could optimize the efficacy of this agent for this indication.     

Clinical significance of tumor microsatellite instability and immunohistochemistry for mismatch repair deficiency in colorectal cancers

Referrals to genetics services are becoming increasingly common for patients who are diagnosed with early-onset colorectal cancer (CRC) or patients who have a family history of CRC. Microsatellite instability (MSI) testing and immunohistochemical analysis (IHC) of the patient’s tumor tissue, which assess indirectly the cellular status of DNA mismatch repair, have proven important tools for geneticists and genetic counselors to determine whether or not these individuals may be at risk for an inherited cancer syndrome, Lynch syndrome (a subset of hereditary nonpolyposis colorectal cancer). The application of tumor MSI/ IHC also extends to the group of providers involved in the diagnosis and management of CRC, demonstrating the growing clinical applicability of MSI/IHC testing. This review discusses the clinical utility of MSI/IHC analysis, including its benefits and limitations, and addresses some of the current debates surrounding testing.     

Environmental risk factors and colorectal neoplasia: Recent developments

The vast majority of new cases of colorectal cancer, the second most common cause of death in men and women in the United States, are attributable to environmental rather than genetic causes. Recent research has clarified inconsistencies in the literature and has explored new pathways through which risk factors may act. This review discusses newly published, selected interesting and important findings in colorectal cancer etiology; these include postmenopausal hormone use, nonsteroidal anti-inflammatory drug use, obesity, physical activity, diet, and other confirmed epidemiologic associations. This research provides insight into mechanisms and offers opportunities for prevention.     

Temperature-sensitive hydrogels

Thermo-sensitive polymers are appealing materials for several therapeutic applications, such as in regenerative medicine and in situ drug release. These macromolecules are characterized by the ability to undergo swelling/deswelling processes during temperature change-induced phase transitions. Swelling and shrinking temperatures depend on the specific physicochemical properties, namely salt concentration or pH, of the thermo-sensitive gels as well as the incubation environment. An understanding of the mechanisms underlying the gel-swelling equilibrium and kinetics is necessary for the selection of an appropriate gel in relation to the specific pharmaceutical application. Thermo-sensitive polymers used in medicine include polyacrylamides, polyvinyls, polyethers, polysaccharides, and polyphosphazenes. A few of them have been successfully used as 3-dimentional supports for cell cultivation, allowing for the production of scaffolds with excellent biologic properties for application in regenerative medicine. Stem cells that can undergo specific differentiation under the appropriate stimulation have also been cultivated. The ability of drug/polymer solutions to turn into gels at physiologic temperature has been exploited for local drug delivery. The prolonged in situ presence and slow drug release enhances the therapeutic performance of antibiotics used in urogenital pathologies, anti-inflammatory agents, and anticancer drugs. The reduced toxicity as well as lower fluctuations in peak-to-trough drug concentrations make these systems superior to traditional gels. Thermo-sensitive hydrogels have also been demonstrated to be interesting formulations for the delivery of biotechnological drugs. Proteins and oligonucleotides can be loaded under mild conditions, stabilized, and released at a controlled rate. Finally, thermo-reversible polymers have been investigated for protein conjugation to enhance the physicochemical, biologic, immunologic, and pharmacokinetic properties of biotechnological products.