Dry mouth: saliva substitutes which adsorb and modify existing salivary condition films improve oral lubrication

Clinical Oral Investigations - The aims of this study are to assess different saliva substitutes for their efficacy to lubricate the oral cavity, and to relate this oral lubrication to the ability...     

Stress Testing Versus CT Angiography in Patients With Diabetes and Suspected Coronary Artery Disease

Background

The optimal noninvasive test (NIT) for patients with diabetes and stable symptoms of coronary artery disease (CAD) is unknown.

Quality of Regional Nodal Irradiation Plans in Breast Cancer Patients Across a Large Network—Can We Translate Results From Randomized Trials Into the Clinic?

PurposeRegional nodal irradiation (RNI) improved disease-free survival by 3% to 5% in 2 large randomized trials, but this small absolute advantage relies on accurate contouring and dose delivery. We audited our network to determine compliance on regional nodal coverage, contouring, and dosimetric parameters with respect to accepted guidelines.Methods and MaterialsIn our network, we have established a clinical pathway for patients with node-positive breast cancer that guides indications for RNI and dosimetric goals. We reviewed records of 183 patients with nodal macrometastases after upfront surgery or involved nodes of any size after neoadjuvant chemotherapy. Radiation treatment plans were examined to determine lymph node volumes treated, whether nodes were contoured, quality of nodal contours, and whether target coverage and normal organ dosimetric constraints were met when RNI was delivered.ResultsDespite the presence of macrometastases on sentinel lymph node biopsy, no lymph nodes were treated in 2.2% (4 of 183). Of 179 patients who received nodal irradiation, 18 received radiation to axillary levels 1 and 2 only, and 161 patients received RNI. Overall, regional nodes were not treated despite strong indications in 7.6% (14 of 183). Treated nodes were not contoured for 2.2% (4 of 179), and lymph node contours were unacceptable in 15.4% (27 of 175). Of patients receiving RNI, 14.9% (24 of 161) did not have adequate nodal target volume coverage, mean heart dose was >4 Gy for 3.1% (5 of 161), and lung V20 Gy was >35% for 8.7% (14 of 161).ConclusionsAdherence to indications for regional nodal treatment was high, but nodes were either not contoured or had unacceptable contour quality in 18% of plans, and coverage was inadequate in 15%. Because the small disease-free survival advantage seen in trials may be decreased with these deviations, routine clinical practice requires detailed peer review to fully translate results of clinical trials.     

Effect of lacosamide on ethanol induced conditioned place preference and withdrawal associated behavior in mice: Possible contribution of hippocampal CRMP-2

BackgroundExcessive consumption of ethanol is known to activate the mTORC1 pathway and to enhance the Collapsin Response Mediator Protein-2 (CRMP-2) levels in the limbic region of brain. The latter helps in forming microtubule assembly that is linked to drug taking or addiction-like behavior in rodents. Therefore, in this study, we investigated the effect of lacosamide, an antiepileptic drug and a known CRMP-2 inhibitor, which binds to CRMP-2 and inhibits the formation of microtubule assembly, on ethanol-induced conditioned place preference (CPP) in mice.MethodsThe behavior of mice following ethanol addiction and withdrawal was assessed by performing different behavioral paradigms. Mice underwent ethanol-induced CPP training with alternate dose of ethanol (2 g/kg, po) and saline (10 ml/kg, po). The effect of lacosamide on the expression of ethanol-induced CPP and on ethanol withdrawal associated anxiety and depression-like behavior was evaluated. The effect of drug on locomotor activity was also assessed and hippocampal CRMP-2 levels were measured.ResultsEthanol-induced CPP was associated with enhanced CRMP-2 levels in the hippocampus. Lacosamide significantly reduced the expression of ethanol-induced CPP and alleviated the levels of hippocampal CRMP-2 but aggravated withdrawal-associated anxiety and depression in mice.ConclusionThe present study demonstrated the beneficial effect of lacosamide in attenuation of expression of ethanol induced conditioned place preference via reduction of hippocampal CRMP-2 level. These findings suggest that lacosamide may be investigated further for ethanol addiction but not for managing withdrawal.     

Premature Ticagrelor Discontinuation in Secondary Prevention of Atherosclerotic CVD: JACC Review Topic of the Week

Ticagrelor is a cornerstone of modern antithrombotic therapy alongside aspirin in patients with acute coronary syndrome and after percutaneous coronary intervention. Adverse effects such as bleeding and dyspnea have been associated with premature ticagrelor discontinuation, which may limit any potential advantage of ticagrelor over clopidogrel. The randomized trials of ticagrelor captured adverse events, offering the opportunity to more precisely quantify these effects across studies. Therefore, a meta-analysis of 4 randomized clinical trials of ticagrelor conducted between January 2007 and June 2017 was performed to quantify the incidence and causes of premature ticagrelor discontinuation. Among 66,870 patients followed for a median 18 months, premature ticagrelor discontinuation was seen in 25%; bleeding was the most common cause of discontinuation followed by dyspnea. Versus the comparators, the relative risk of dyspnea-related discontinuation during follow-up was 6.4-fold higher, the relative risk of bleeding was 3.2-fold higher, and the relative risk of discontinuation due to any adverse event was 59% higher for patients receiving ticagrelor. Understanding these potential barriers to adherence to ticagrelor is crucial for informed patient-physician decision making and can inform future efforts to improve ticagrelor adherence. This review discusses the incidence, causes, and biological mechanisms of ticagrelor-related adverse effects and offers strategies to improve adherence to ticagrelor.