Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study.

BACKGROUND: Metastatic colorectal cancer (mCRC) is commonly treated with 5-fluorouracil, folinic acid, and oxaliplatin or irinotecan. The multitargeted kinase inhibitor, regorafenib, was combined with chemotherapy as first- or second-line treatment of mCRC to assess safety and pharmacokinetics (primary objectives) and tumor response (secondary objective). PATIENTS AND METHODS: Forty-five patients were treated every 2 weeks with 5-fluorouracil 400 mg/m(2) bolus then 2400 mg/m(2) over 46 h, folinic acid 400 mg/m(2), and either oxaliplatin 85 mg/m(2) or irinotecan 180 mg/m(2). On days 4-10, patients received regorafenib 160 mg orally once daily. RESULTS: The median duration of treatment was 108 (range 2-345 days). Treatment was stopped for adverse events or death (17 patients), disease progression (11 patients), and consent withdrawal or investigator decision (11 patients). Six patients remained on regorafenib at data cutoff (two without chemotherapy). Drug-related adverse events occurred in 44 patients [grade ≥ 3 in 32 patients: mostly neutropenia (17 patients) and leukopenia, hand-foot skin reaction, and hypophosphatemia (four patients each)]. Thirty-three patients achieved disease control (partial response or stable disease) for a median of 126 (range 42-281 days). CONCLUSION: Regorafenib had acceptable tolerability in combination with chemotherapy, with increased exposure of irinotecan and SN-38 but no significant effect on 5-fluorouracil or oxaliplatin pharmacokinetics.

[Neurological complication after a vertical infraclavicular brachial plexus block. Case report of possible differential diagnoses of a neurological deficit]. / Neurologische Komplikation nach einer vertikalen infraklavikulären Plexusblockade: Fallbericht über mögliche Differenzialdiagnosen eines neurologischen Defizits.

A 72-year-old man with an obliteration of the brachial artery received a vertical infraclavicular block (VIP) for vascular surgery but 20 h after the operation a complete paresis of the affected extremity occurred. A new vascular obliteration could be excluded. During the diagnostic examination the patient noticed a snapping noise in the cervical column when moving his head and an abrupt recovery of the neurological deficits occurred. The radiological diagnostic provided no indication of cerebral ischemia or lesions of the brachial plexus. An additional diagnostic finding was a profound herniated vertebral disc with compression of the myelon. Fortunately, the neurological deficits completely returned to normal.

Neurobehavioral test performance in the third National Health and Nutrition Examination Survey.

The third National Health and Nutrition Examination Survey (NHANES III) contained three computerized neurobehavioral tests from the Neurobehavioral Evaluation System (NES): simple reaction time, symbol-digit substitution and serial digit learning. The neurobehavioral data that were collected came from a nationally representative sample of adults 20-59 years old. Performance on the tests was related to sex, age, education level, family income and race-ethnicity. Performance decreased as age increased, and increased as education level and family income increased. Differences in performance between sexes, levels of education and racial-ethnic groups tended to decrease as family income increased. The relationship between age and performance on the symbol-digit substitution test varied by education level and by racial-ethnic group. The relationship between age and performance on the serial digit learning test varied by racial-ethnic group. Questionnaire variables that were related to performance on one or more of the tests included the reported amount of last night's sleep, energy level, computer or video game familiarity, alcoholic beverages within the last 3 h and effort. Persons who took the tests in English or Spanish performed differently on the symbol-digit substitution and serial digit learning tests. Performance on all the tests decreased as test room temperature increased.

Hantavirus infection--southwestern United States: interim recommendations for risk reduction. Centers for Disease Control and Prevention.

This report provides interim recommendations for prevention and control of hantavirus infections associated with rodents in the southwestern United States. It is based on principles of rodent and infection control and contains specific recommendations for reducing rodent shelter and food sources in and around the home, recommendations for eliminating rodents inside the home and preventing them from entering the home, precautions for preventing hantavirus infection while rodent-contaminated areas are being cleaned up, prevention measures for persons who have occupational exposure to wild rodents, and precautions for campers and hikers.

Effects of elemental mercury exposure at a thermometer plant.

This study compares 84 mercury-exposed workers at a thermometer manufacturing facility with 79 unexposed workers for evidence of chronic mercury toxicity. Personal breathing-zone air concentrations of mercury ranged from 25.6 to 270.6 micrograms/m3 for thermometer workers. Urinary mercury levels in the study population ranged from 1.3 to 344.5 micrograms/g creatinine, with eight (10%) participants exceeding 150 micrograms/g creatinine and three workers exceeding 300 micrograms/g creatinine, which indicates increased absorption of mercury among the thermometer workers. All urine mercury levels in the comparison group were compatible with normal background levels in unexposed adults (less than 10 micrograms/g creatinine). Thermometer plant workers reported more symptoms than did controls; in general, these differences were not statistically significant and could not be specifically associated with mercury exposure. Static tremor, abnormal Romberg test, dysdiadochokinesia, and difficulty with heel-to-toe gait were more prevalent among thermometer workers than control workers, which could not be associated with recent mercury exposure; there was some suggestion of an association with chronic exposure. There were no intergroup differences for the standard clinical tests of renal function except for a significantly higher mean specific gravity among the thermometer workers. A positive correlation was found, however, between urinary N-acetyl-b-D-glucosaminidase (NAG) and urinary mercury. There was no consistent evidence for intergroup differences in proximal renal tubule function, as measured by urinary beta 2-microglobulin (B2M) or retinol binding protein (RBP).

Development of a standard questionnaire for occupational health research.

Direct surveys of groups of workers can provide valuable occupational health surveillance data, but this requires consistent collection of data. As part of efforts to improve the standardization of such methodology, NIOSH is developing a standard occupational health questionnaire. This questionnaire will be designed to collect demographic and occupational history information in addition to information about the presence of a spectrum of work-related conditions. The questionnaire will have a modular structure and will consist of a core questionnaire and a series of condition-specific modules.

Investigation of occupational cancer clusters: theory and practice.

Local and federal government agencies are often asked to investigate apparent clusters of cancer in communities or workplaces. Often these investigations cannot utilize the methods that have been developed for evaluation of disease clusters because the clusters are too small, and the populations to be studied and the periods of time to be covered are determined in an a posteriori manner. Still, government investigators are called upon to render an official opinion of the apparent clusters. Application of a theoretical approach to cluster analysis must give way to a more pragmatic approach. A review of 61 investigations of apparent clusters conducted by the National Institute for Occupational Safety and Health (NIOSH) during the period 1978-84 showed that most of the clusters contained five or fewer cases and had no plausible occupational etiology. Despite the few clusters that were identified, these investigations generally provided a service to workers and employers who were concerned about occupational cancer.