Incidence, course, and management of toxicities associated with cobimetinib in combination with vemurafenib in the coBRIM study.

Background: In the coBRIM phase III trial, the addition of cobimetinib, an MEK inhibitor, to vemurafenib, a BRAF inhibitor, significantly improved progression-free survival [hazard ratio (HR), 0.58; P < 0.0001] and overall survival (HR, 0.70; P = 0.005) in advanced BRAF-mutated melanoma. Here, we report on the incidence, course, and management of key adverse events (AEs) in the coBRIM study. Patients and methods: Patients were randomly assigned 1:1 to receive vemurafenib (960 mg twice a day) and either cobimetinib (60 mg once a day, 21 days on/7 days off) or placebo. In addition to standard safety evaluations, patients underwent regular ophthalmic, cardiac, and dermatologic surveillance examinations. Results: Of 495 patients recruited to the study, 493 patients received treatment and constituted the safety population (cobimetinib combined with vemurafenib, 247; vemurafenib, 246). At data cut-off (30 September 2015), median follow-up was 18.5 months. Nearly every patient experienced an AE. In patients who received cobimetinib combined with vemurafenib, the frequency of grade ≥3 AEs was higher than in patients who received vemurafenib alone (75% versus 61%). Most AEs, including grade ≥3 AEs, occurred within the first treatment cycle. After the first cycle (28 days), the incidence of common AEs (rash, diarrhoea, photosensitivity, elevated creatine phosphokinase, serous retinopathy, pyrexia, and liver laboratory abnormalities) decreased substantially over time. Most AEs were managed conservatively by supportive care measures, dose modifications of study treatment, and, occasionally, permanent treatment discontinuation. Conclusions: These data indicate that most AEs arising from treatment with cobimetinib combined with vemurafenib generally occur early in the treatment course, are mild or moderate and are manageable by patient monitoring, dose modification and supportive care. ClinicalTrials.gov: NCT01689519.

EuroBionet: a pan-European biomonitoring network for urban air quality assessment.

EuroBionet, the 'European Network for the Assessment of Air Quality by the Use of Bioindicator Plants', is an EU-funded cooperative project currently consisting of public authorities and scientific institutes from 12 cities in 8 countries. In 2000, the bioindicator plants tobacco (Nicotiana tabacum Bel W3), poplar (Populus nigra 'Brandaris'), spiderwort (Tradescantia sp. clone 4430), Italian rye grass (Lolium multiflorum italicum) and curly kale (Brassica oleracea acephala) were exposed to ambient air at 90 monitoring sites according to standardised methods. Visible injuries and growth parameters were assessed and the accumulation of toxic substances in leaves determined. The exposure of tobacco resulted in a gradient with low levels of ozone-induced foliar injury in N and NW Europe, and medium to high values in the southern and central regions. The results of heavy metal and sulphur analyses in rye grass samples generally showed low to very low sulphur and low to medium heavy metal concentrations in leaves. In some cities, however, local hot spots of heavy metal contamination were detected. Analyses of the PAH contents in curly kale leaves gave low to medium values, with locally elevated levels at traffic-exposed sites.

Validation of a questionnaire to evaluate the quality of life of nonprofessional caregivers of dependent persons.

AIM OF THE STUDY: To determine the acceptance, validity and reliability of the questionnaire for assessing the type of informal care that caregivers of dependent people give and the effects this care might have on the health of the carer. BACKGROUND: In Spain, the formal health care system provides 12% of the total time dedicated to health care, the remaining 88% is carried out by the informal system within the home environment. The act of caring has effects on various areas of the life of the carer and on family functioning. This makes clear the existing risk when the principal carer becomes a secondary nurse. METHODS: This research was a cross-sectional design, carried out in municipalities in the province of Barcelona (Spain) from January to December 1997. The subjects of the study were 240 caregivers of dependent people. The questionnaire (ICUB97Copyright ) is based on the Virginia Henderson's 14 Needs nursing model. The validity of the content was assessed through the consensus of a group of experts, validity of design by means of comparison with the hypotheses. RESULTS: Test-retest reliability was completed for the three parts of the questionnaire and the kappa index values was 0.89, 0.80 and 0.75 for each part. The higher the level of dependency of the person cared for, the more care tasks the carer had to perform. A correlation coefficient of 0.58 was obtained for the Barthel Index (P < 0.001) and 0.53 on the Philadelphia Index (P < 0.001). The care tasks performed by the carer showing greatest correlation with dependency level were; help with elimination (r=0.73, P < 0.001), help with feeding (r=0.55, P < 0.001) and help in personal development (r=0.55, P=0.001). CONCLUSIONS: This questionnaire provides a reliable and valid instrument for measuring the care given by caregivers to dependent people, to meet their basic needs as well as for assessing the needs of the carers who experience problems by the act of caring. It is therefore important for nursing practice, to have a validated instrument available for identifying the tasks performed by family carers and the effects on their health.

[The consumption of drugs and natural remedies in the older population of a rural area]. / Consumo de medicamentos y remedios naturales en la población anciana de un área rural.

OBJECTIVES: To evaluate the knowledge about medical treatment on people with more than 70 years old, specifically, the understanding, reason for prescription and dosage. To describe the use of natural remedies in the rural environment. To correlate the medication and the natural remedies consumption with health's self-perception. DESIGN: Cross-sectional study. SETTING: Health Center of Santa Eugènia de Berga. Barcelona. PATIENTS: Covered people aged 70 or more, not in an institution, selected by systematic sampling obtained from an updated age and sex register. MEASUREMENTS: A standard questionnaire was used, gathering aspects about medicine and natural remedies consumption and health's self-perception. RESULTS: The average of medicines was 3.08 (SD 2.5) for person. Therapeutics groups most prevalent were cardiovascular and nervous system drugs. The patients remembered correctly the reason of the prescription of the 77% of the medicines and the dosage of the 85%. The 25% of patients needed assistance of some family for to take the medication. We have found statistical significance between health's self-perception and the number of consumed drugs. The 47% of aged population used natural remedies. CONCLUSIONS: The knowledge of medical treatment of our elderly people is satisfactory. We detect in our study a high rate of polymedication. It is necessary, if possible, to rationalize and to reduce the number of drugs. It is useful to revise and to update periodically the elderly people medication. The natural remedies is included on the people's pharmacology and its use is important.

Hyperphosphatasemia: CT assessment.

Hyperphosphatasemia is a rare disorder of uncertain cause. A 39-year-old male exhibiting striking skeletal deformities consisting of enlargement of the skull, enlargement and bowing of the long bones, neurosensorial symptoms and elevated alkaline phosphatase is the subject of this report. In the past, the radiological workup has been limited to plain films. We advocate CT in the assessment of neurological signs and symptoms which may complicate this disease.

Five-day course of granulocyte colony-stimulating factor in patients with prolonged neutropenia after adjuvant chemotherapy for breast cancer is a safe and cost-effective schedule to maintain dose-intensity.

PURPOSE: To analyze the safety and efficacy of a short course of granulocyte colony-stimulating factor (G-CSF) to maintain dose-intensity of subsequent cycles of chemotherapy after a prior episode of prolonged neutropenia, without febrile complications, in patients receiving adjuvant treatment for breast cancer. PATIENTS AND METHODS: Thirty-two patients undergoing adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) or doxorubicin-CMF for stages I to II breast cancer were included after having chemotherapy delays due to neutropenia (absolute neutrophil count [ANC] < 1.5 x 10(9)/L) on day 22. G-CSF was administered subcutaneously on days 15 to 19 of each subsequent cycle. RESULTS: None of the patients included in this study had to be admitted to the hospital for fever and neutropenia. The median percentage of the projected dose-intensity for CMF or doxorubicin-CMF on an intent-to-treat basis was 0.994, which was significantly higher than the delivered dose-intensity before the start of G-CSF treatment (P < .0001). Patients who received concomitant G-CSF and radiotherapy achieved a similar dose-intensity as patients who did not undergo radiotherapy. Seven patients discontinued G-CSF treatment due to musculoskeletal pain. These patients had more subsequent cycle delays because of day 22 neutropenia than the 25 patients who followed the G-CSF schedule (P = .0028). CONCLUSION: A 5-day course of G-CSF in patients with prior chemotherapy delays due to prolonged neutropenia seems to be a safe and cost-effective schedule to maintain CMF or doxorubicin-CMF dose-intensity in the adjuvant treatment of breast cancer.