Prescription Drugs Associated with Reports of Violence Towards Others

CONTEXT: Violence towards others is a seldom-studied adverse drug event and an atypical one because the risk of injury extends to others. OBJECTIVE: To identify the primary suspects in adverse drug event reports describing thoughts or acts of violence towards others, and assess the strength of the association. METHODOLOGY: From the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) data, we extracted all serious adverse event reports for drugs with 200 or more cases received from 2004 through September 2009. We identified any case report indicating homicide, homicidal ideation, physical assault, physical abuse or violence related symptoms. MAIN OUTCOME MEASURES: Disproportionality in reporting was defined as a) 5 or more violence case reports, b) at least twice the number of reports expected given the volume of overall reports for that drug, c) a χ2 statistic indicating the violence cases were unlikely to have occurred by chance (p<0.01). RESULTS: We identified 1527 cases of violence disproportionally reported for 31 drugs. Primary suspect drugs included varenicline (an aid to smoking cessation), 11 antidepressants, 6 sedative/hypnotics and 3 drugs for attention deficit hyperactivity disorder. The evidence of an association was weaker and mixed for antipsychotic drugs and absent for all but 1 anticonvulsant/mood stabilizer. Two or fewer violence cases were reported for 435/484 (84.7%) of all evaluable drugs suggesting that an association with this adverse event is unlikely for these drugs. CONCLUSIONS: Acts of violence towards others are a genuine and serious adverse drug event associated with a relatively small group of drugs. Varenicline, which increases the availability of dopamine, and antidepressants with serotonergic effects were the most strongly and consistently implicated drugs. Prospective studies to evaluate systematically this side effect are needed to establish the incidence, confirm differences among drugs and identify additional common features

Random forest prediction of Alzheimer's disease using pairwise selection from time series data

Time-dependent data collected in studies of Alzheimer's disease usually has missing and irregularly sampled data points. For this reason time series methods which assume regular sampling cannot be applied directly to the data without a pre-processing step. In this paper we use a machine learning method to learn the relationship between pairs of data points at different time separations. The input vector comprises a summary of the time series history and includes both demographic and non-time varying variables such as genetic data. The dataset used is from the 2017 TADPOLE grand challenge which aims to predict the onset of Alzheimer's disease using including demographic, physical and cognitive data. The challenge is a three-fold diagnosis classification into AD, MCI and control groups, the prediction of ADAS-13 score and the normalised ventricle volume. While the competition proceeds, forecasting methods may be compared using a leaderboard dataset selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and with standard metrics for measuring accuracy. For diagnosis, we find an mAUC of 0.82, and a classification accuracy of 0.73. The results show that the method is effective and comparable with other methods.Comment: 6 pages, 1 figure, 6 table

Pathological margins and advanced cutaneous squamous cell carcinoma of the head and neck.

OBJECTIVE:The recommended treatment for cutaneous squamous cell cancer (CuSCC) of the head and neck is Mohs surgical excision or wide local excision. Excision is recommended to a gross surgical margin of 4-6 mm however this is based on limited evidence and specify a goal histologic margin. The objective of this study was therefore to examine the reported histological margin distance following WLE of advanced CuSCC and its association with recurrence and survival. STUDY DESIGN:Retrospective database review. SETTING:All patients included received treatment at UC Davis Department of Otolaryngology-Head and Neck Surgery and/or Radiation Oncology in Sacramento, California. SUBJECTS AND METHODS:The patients included were treated for advanced CuSCC with primary surgery with or without adjuvant therapy. Kaplan Meier survival curves with log rank analysis were then performed to compare 5-year recurrence free survival, and disease-specific survival for patients with different margin distances. RESULTS:Total number of subjects was 92. The overall 5-year DSS and RFS was 68.8 and 51.0% respectively. When the pathological margin distance was ≥5 mm, 5-year disease specific survival was improved when compared to margin distance less than 5 mm (94.7 vs 60.7 p = 0.034). CONCLUSION:The findings of this study suggest that a histologic margin of at least 5 mm may increase survival in advanced head and neck CuSCC patients

Daily report cards as a school-based intervention for children with attention-deficit/hyperactivity disorder

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.This paper describes daily report cards and the evidence relating to their use in schools for children with attention-deficit/hyperactivity disorder (ADHD). This intervention typically involves teachers evaluating a student's behaviour at school against pre-determined targets and parents subsequently providing reinforcement at home for positive reports. Research suggests that the daily report card has been effective in treating a range of ADHD symptoms and improving school outcomes, including academic achievement in some cases. The daily report card also encourages collaboration between teachers and parents, and evidence suggests that the intervention benefits from the inclusion of reinforcement at home. Daily report cards are easy to implement and research finds that teachers consider them an acceptable intervention for ADHD. This paper also considers challenges in using daily report cards, including barriers to their use over the long-term and the risk of stigma for children with a report card. Ideas to address these issues are suggested

Secondary school educational practitioners’ experiences of school attendance problems and interventions to address them: A qualitative study

This is the author accepted manuscript. The final version is available from Taylor & Francis (Routledge) via the DOI in this record.School attendance problems are associated with a range of adverse consequences, and educational practitioners play a role in identifying and responding to attendance problems. This qualitative study explored educational practitioners’ experiences of working with students with attendance problems and interventions to address them. Focus groups were conducted with sixteen practitioners across three secondary schools. Data were analysed using thematic analysis. Attendance problems were considered resource-intensive and emotionally challenging. Practitioners expressed difficulty understanding causes, although individual/family factors were emphasised over school factors. A range of interventions were described, including adaptations to school context and providing emotional support. Views on punitive approaches were mixed. Individualised interventions implemented at the first sign of problems, and a team approach, were considered important. Findings highlight the important role of educational practitioners in identifying attendance problems and implementing interventions. Recommendations include early intervention, team-work, and emotional support for students with, and staff responding to, attendance problems.This work was supported by a PhD studentship from the University of Exeter Medical School, UK

Suicidal Behavior and Depression in Smoking Cessation Treatments

BACKGROUND: Two treatments for smoking cessation--varenicline and bupropion--carry Boxed Warnings from the U.S. Food and Drug Administration (FDA) about suicidal/self-injurious behavior and depression. However, some epidemiological studies report an increased risk in smoking or smoking cessation independent of treatment, and differences between drugs are unknown. METHODOLOGY: From the FDA's Adverse Event Reporting System (AERS) database from 1998 through September 2010 we selected domestic, serious case reports for varenicline (n = 9,575), bupropion for smoking cessation (n = 1,751), and nicotine replacement products (n = 1,917). A composite endpoint of suicidal/self-injurious behavior or depression was defined as a case with one or more Preferred Terms in Standardized MedDRA Query (SMQ) for those adverse effects. The main outcome measure was the ratio of reported suicide/self-injury or depression cases for each drug compared to all other serious events for that drug. RESULTS: Overall we identified 3,249 reported cases of suicidal/self-injurious behavior or depression, 2,925 (90%) for varenicline, 229 (7%) for bupropion, and 95 (3%) for nicotine replacement. Compared to nicotine replacement, the disproportionality results (OR (95% CI)) were varenicline 8.4 (6.8-10.4), and bupropion 2.9 (2.3-3.7). The disproportionality persisted after excluding reports indicating concomitant therapy with any of 58 drugs with suicidal behavior warnings or precautions in the prescribing information. An additional antibiotic comparison group showed that adverse event reports of suicidal/self-injurious behavior or depression were otherwise rare in a healthy population receiving short-term drug treatment. CONCLUSIONS: Varenicline shows a substantial, statistically significant increased risk of reported depression and suicidal/self-injurious behavior. Bupropion for smoking cessation had smaller increased risks. The findings for varenicline, combined with other problems with its safety profile, render it unsuitable for first-line use in smoking cessation

Interactions of C+(2PJ) with rare gas atoms: incipient chemical interactions, potentials and transport coefficients

Accurate interatomic potentials were calculated for the interaction of a singly charged carbon cation, C+, with a single rare gas atom, RG (RG = Ne–Xe). The RCCSD(T) method and basis sets of quadruple-ζ and quintuple-ζ quality were employed; each interaction energy was counterpoise corrected and extrapolated to the basis set limit. The lowest C+(2P) electronic term of the carbon cation was considered, and the interatomic potentials calculated for the diatomic terms that arise from these: 2Π and 2Σ+. Additionally, the interatomic potentials for the respective spin-orbit levels were calculated, and the effect on the spectroscopic parameters was examined. In doing this, anomalously large spin-orbit splittings for RG = Ar–Xe were found, and this was investigated using multi-reference configuration interaction calculations. The latter indicated a small amount of RG → C+ electron transfer and this was used to rationalize the observations. This is taken as evidence of an incipient chemical interaction, which was also examined via contour plots, Birge–Sponer plots and various population analyses across the C+-RG series (RG = He–Xe), with the latter showing unexpected results. Trends in several spectroscopic parameters were examined as a function of the increasing atomic number of the RG atom. Finally, each set of RCCSD(T) potentials was employed, including spin-orbit coupling to calculate the transport coefficients for C+ in RG, and the results were compared with the limited available data