Unintentional drowning: Role of medicinal drugs and alcohol

Background: Alcohol is a well-known risk factor in unintentional drownings. Whereas psychotropic drugs, like alcohol, may cause psychomotor impairment and affect cognition, no detailed studies have focused on their association with drowning. Finland provides extensive post-mortem toxicological data for studies on drowning because of its high medico-legal autopsy rates.Methods: Drowning cases, 2000 through 2009, for which post-mortem toxicological analysis was performed, came from the database of the Toxicological Laboratory, Department of Forensic Medicine, University of Helsinki, using the ICD-10 nature-of-injury code T75.1. The data were narrowed to unintentional drowning, using the ICD-10 external-injury codes V90, V92, and W65-74. Each drowning case had its blood alcohol concentration (BAC) and concentrations of other drugs recorded. Evaluation of the contribution of psychotropic drugs to drowning was based on their blood concentration by means of a 6-grade scale.Results: Among victims >= 15 years old, unintentional drownings numbered 1697, of which, 303 (17.9%) were boating-related and 1394 (82.1%) non-boating-related. Among these, 65.0% of boating-related and 61.8% of non-boating-related victims were alcohol-positive (=BAC >= 50 mg/dL). The male-to-female ratio in alcohol-positive drownings was 7.3. At least one psychotropic drug appeared in 453 (26.7%) drowning cases, with some victims' bodies showing up to 7 different drugs. Overall 70 different psychotropic drugs were detectable, with 134 (7.9%) cases both alcohol-negative and psychotropic-drug-positive, of these, 59 (3.5%) were graded 4 to 6, indicating a possible to very probable contribution to drowning. Our findings suggest that psychotropic drugs may play a significant role in drowning, in up to 14.5% of cases, independently or in association with alcohol.Conclusions: Psychotropic drugs alone or in association with alcohol may be an overlooked risk factor in drowning, due to their effects on psychomotor function and cognition. Future studies should also address other mechanisms-for instance drug-induced long-QT syndrome-by which drugs may contribute to drowning

Prognostic and predictive value of clinical and biochemical factors in breast cancer patients with bone metastases receiving "metronomic" zoledronic acid

<p>Abstract</p> <p>Background</p> <p>To assess prognostic and predictive effects of clinical and biochemical factors in our published randomized study of a weekly low dose (metronomic arm) versus a conventional dosage of zoledronic acid (conventional arm) in breast cancer patients with bone metastases.</p> <p>Methods</p> <p>Treatment outcome of 60 patients with bone metastases were used to assess impacts of following potential prognostic factors, estrogen receptor status, lymph node status, 2 year-disease free interval (DFI), numbers of chemotherapy regimens administered, interventions, and serum levels of VEGF, N-telopeptide of type I collagen (NTx), CEA, and CA 15-3.</p> <p>Results</p> <p>In univariate analyses, patients pretreated with 2 or fewer chemotherapy regimens, ER-positive tumors, 3 or fewer lymph nodes, DFI of more than 2 years, serum VEGF of less than 500 pg/mL after 3 months of intervention, serum CEA and CA 15-3 of less than ULN, and baseline serum NTx of less than 18 nM BCE had significantly longer progression free survival (PFS). The multivariate analysis showed that ER positivity (hazard ratio [HR], 0.295; 95% confidence interval [CI], 0.141-0.618; P = 0.001), serum VEGF of less than 500 pg/mL after 3 months of intervention (HR, 2.220; 95% CI, 1.136-4.338; P = 0.020), baseline serum NTx of less than 18 nM BCE (HR, 2.842; 95% CI, 1.458-5.539; P = 0.001), and 2 or fewer chemotherapy regimens received (HR, 7.803; 95% CI, 2.884-21.112; P = 0.000) were associated with a better PFS. When evaluating the predictive effect of the biochemical factors, an interaction between NTx and zoledronic acid intervention was shown (P = 0.005). The HR of weekly low dose versus a conventional dosage of zoledronic acid was estimated to be 2.309 (99% CI, 1.067-5.012) in patients with baseline serum NTx of more than 18 nM BCE, indicating a superiority of weekly low dose of zoledronic acid.</p> <p>Conclusions</p> <p>ER, serum VEGF level after intervention, and numbers of chemotherapy regimens administered are prognostic but not predictive factors in breast cancer patients with bone metastases. Patients with baseline serum NTx of more than 18 nM BCE might benefit more from weekly low-dose of zoledronic acid.</p> <p>Trial registration</p> <p>ClinicalTrials.gov unique identifier: ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00524849">NCT00524849</a></p

Targeted therapies in colorectal cancer: an integrative view by PPPM

In developed countries, colorectal cancer (CRC) is the third most common malignancy, but it is the second most frequent cause of cancer-related death. Clinicians are still faced with numerous challenges in the treatment of this disease, and future approaches which target the molecular features of the disorder will be critical for success in this disease setting. Genetic analyses of many solid tumours have shown that up to 100 protein-encoding genes are mutated. Within CRC, numerous genetic alterations have been identified in a number of pathways. Therefore, understanding the molecular pathology of CRC may present information on potential routes for treatment and may also provide valuable prognostic information. This will be particularly pertinent for molecularly targeted treatments, such as anti-vascular endothelial growth factor therapies and anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy. KRAS and BRAF mutations have been shown to predict response to anti-EGFR therapy. As EGFR can also signal via the phosphatidylinositol 3-kinase (PI3K) kinase pathway, there is considerable interest in the potential roles of members of this pathway (such as PI3K and PTEN) in predicting treatment response. Therefore, a combined approach of new techniques that allow identification of these biomarkers alongside interdisciplinary approaches to the treatment of advanced CRC will aid in the treatment decision-making process and may also serve to guide future therapeutic approaches