Class of 2015 Abstract / Objectives: Argatroban is the current drug of choice for type II heparin induced thrombocytopenia. Primarily metabolized by the liver, this direct thrombin inhibitor has a volume of distribution of approximately 174 mLs per kg. While few studies suggested no differences in coagulation parameters or clinical outcomes between obese and non-obese populations receiving argatroban, a recent case report revealed elevated anticoagulation parameters for 20 days post argatroban discontinuation in a morbidly obese female. The purpose of this study is to assess anticoagulation parameters in obese and non-obese patients in an intensive care unit (ICU) setting who received argatroban treatment during their stay. Methods: This is a retrospective, observational, single-centered study. Participants of the study must be adults, at least 18 years of age. Patient must be an inpatient and have received argatroban for either suspected or confirmed heparin-induced thrombocytopenia (HIT). All patients in the study were screened for the above criteria between November 2008 and September 2013. Patients admitted to the cardiac ICU were excluded from the study. Main anticoagulation parameters post discontinuation evaluated were daily international normalized ratio (INR) and activated partial thromboplastin time (aPTT), while safety outcomes included major, minor and non-bleed events. All data were analyzed with STATA 13 with P less than 0.05 being considered as statistically significant. Results: The study included a total of 51 patients, 37 were non-obese with body mass index (BMI) less than 30 kg per m2 (73 percent), and 14 were obese with BMI greater or equal to 30 kg per m2 (27 percent). Among basic demographic data, no differences were found between age, sex, race, height and SOFA scores at baseline between the two groups, BMI less than 30 kg per m2 and BMI greater or equal to 30 kg per m2. (P equals 0.7, 0.21, 1.0, 0.41, 0.51 respectively). However, as expected, weight was the only characteristic that was different at baseline (P less than 0.01). Primary outcome of time of INR to normalization post argatroban administration (2.73 seconds plus or minus 0.27 seconds) as well as safety outcomes including major, minor, and non-bleed adverse events (P equals 0.61) were statistically non-significant between the two groups. Conclusions: In this retrospective, observational, single centered study, no differences were identified between non-obese and obese groups in terms of argatroban administration, primary anticoagulation parameters, and safety outcomes. The length of time required for coagulation parameters to normalize after discontinuation of argatroban therapy for HIT does not appear to be influenced by BMI. Large, multicenter, and random controlled trials are needed to evaluate obesity on pharmacokinetic parameters and clinical outcomes of argatroban.

No description available.

Importance: Polymorphic expression of drug metabolizing enzymes affects the metabolism of antidepressants, and thus can contribute to drug response and/or adverse events. Pregnancy itself can affect CYP2D6 activity with profound variations determined by CYP2D6 genotype. Objective: To investigate the association between CYP2D6 genotype and the risk of antidepressant discontinuation, dosage modification, and the occurrence of maternal CYP2D6, Antidepressants, Depression during pregnancy. Setting: Data from the Organization of Teratology Information Specialists (OTIS) Antidepressants in Pregnancy Cohort, 2006-2010, were used. Women were eligible if they were within 14 completed weeks of pregnancy at recruitment and exposed to an antidepressant or having any exposures considered non-teratogenic. Main Outcomes and Measures: Gestational antidepressant usage was self-reported and defined as continuous/discontinued use, and non-use; dosage modification was further documented. Maternal depression and anxiety were measured every trimester using the telephone interviewer-administered Edinburgh Postnatal Depression Scale and the Beck Anxiety Inventory, respectively. Saliva samples were collected and used for CYP2D6 genotype analyses. Logistic regression models were used to calculate crude and adjusted odds ratios (OR) with 95% confidence intervals. Results: A total of 246 pregnant women were included in the study. The majority were normal metabolizers (NM, n = 204, 83%); 3.3% (n = 8) were ultrarapid metabolizers (UM), 5.7%(n = 14) poor metabolizers (PM), and 8.1%(n= 20) intermediate metabolizers (IM). Among study subjects, 139 women were treated with antidepressants at the beginning of pregnancy, and 21 antidepressant users (15%) discontinued therapy during pregnancy. Adjusting for depressive symptoms, and other potential confounders, the risk of discontinuing antidepressants during pregnancy was nearly four times higher in slow metabolizers (poor or intermediate metabolizers) compared to those with a faster metabolism rate (normal or ultrarapid metabolizers), aOR = 3.57 (95% CI: 1.15-11.11). Predicted CYP2D6 metabolizer status did not impact dosage modifications. Compared with slow metabolizers, significantly higher proportion of women in the fast metabolizer group had depressive symptomin the first trimester (19.81 vs. 5.88%, P = 0.049). Almost 21% of treated women remained depressed during pregnancy (14.4% NM-UM; 6.1% PM-IM). Conclusions and Relevance: Prior knowledge of CYP2D6 genotype may help to identify pregnant women at greater risk of antidepressant discontinuation. Twenty percent of women exposed to antidepressants during pregnancy remained depressed, indicating an urgent need for personalized treatment of depression during pregnancy.

No description available.

Oral cancer drugs are branded and expensive medications that generally do not have generics available. The restrictions of the Medicare Part D program, including the coverage gap and high cost-sharing, and the high cost of oral chemotherapy may lead to patients’ non-adherence to medication. Few studies have examined the cost and utilization of oral anti-cancer medications. This study will be the first to examine the costs associated with the use of oral anti-cancer medications and the impact of cost-sharing and type of prescription drug subsidy on medication discontinuation in the Medicare Part D elderly population. Objectives: To determine the usage and costs of oral cancer treatment in elderly Medicare Part D beneficiaries and to examine the relationship between out of pocket costs and medication discontinuation or delay. Methods: A cross-sectional study of the spending and usage of oral cancer drugs in the Medicare Part D population was conducted. A 5% random sample of 2008 Medicare beneficiaries was used. The study sample included all members of this group who: 1) were 65 years of age and older and 2) filled at least one prescription for imatinib, erlotinib, anastrozole, letrozole, or thalidomide. We examined the average costs patients paid per day, the cost that the Part D plan paid per day, and the total cost that patients paid for the entire year for each drug. The demographic characteristics and type of prescription drug subsidy of Part D beneficiaries who used oral cancer drugs were reported in frequency counts and percentages. We also determined the percentage of enrollees who entered the Part D coverage gap, the time and duration that they fell into the coverage gap, the number of beneficiaries who discontinued treatment and the association between OOP costs and medication discontinuation or delay, controlling for polypharmacy, prescription coverage and socio-demographic factors. Results: Prescription drug subsidy was categorized in four groups: 1) Dual Eligible (DE), 2) full Low Income Subsidy (LIS), 3) partial LIS, and 4) no subsidy. Mean out-of-pocket (OOP) costs per day were between $0.03 and $0.09 for DE beneficiaries, between $0.04 and $0.23 for full LIS beneficiaries, between $1.17 and $6.34 for partial LIS beneficiaries and between $2.93 and $36.84 for beneficiaries who did not receive a subsidy. On average, the beneficiaries who used oral cancer medications were between 75 and 76 years of age. Over half of oral cancer medication users were Caucasian and female. Over two-thirds of oral cancer medication users received no subsidies for their prescription coverage. About 99% of users of the more expensive drugs - imatinib, erlotinib and thalidomide - entered the coverage gap and the majority of these entered the coverage gap at the time of their first fill. In contrast, beneficiaries who filled the less expensive drugs - anastrozole and letrozole - entered the coverage gap later. Less than 7% entered the coverage gap at the time of the first fill of their prescriptions. Beneficiaries who used imatinib, erlotinib, or thalidomide spent approximately a month in the coverage gap. Over the course of a year, the majority of their time was spent in the catastrophic phase. Approximately 33-60% of total oral cancer drug users discontinued their therapies. About 50% of these discontinued during the coverage gap for anastrozole and letrozole and about 80% discontinued during the catastrophic phase for imatinib, erloinib and thalidomide. OOP costs were associated with medication discontinuation for all five oral cancer drugs. The odds of discontinuation and delay increased 101%, 170%, and 264% for each $100 increase in OOP spending for imatinib, erlotinib and thalidomide users, respectively. The odds of discontinuation and delay increased 9%-10%, and 6-8% for every $10 increase in OOP spending for anastrozole and letrozole users, respectively. Conclusions: About 33-60% of all users discontinued their therapies. Beneficiaries receiving subsidies had low OOP costs, averaging between $0.03 and $6.34 per day. Beneficiaries on the more expensive drugs and not having subsidies had high OOP costs, averaging between $15.66 and 36.84 per day. Higher OOP costs were associated with an increased likelihood of discontinuation or delay.

This thesis sought to explore the phenomenon of discontinuing neuroleptic medication for psychosis. It comprises three standalone papers. Papers one and two have been prepared for submission to journals and in accordance with the journal guidelines. Paper one is a systematic literature review synthesising studies investigating the association between neuroleptic discontinuation and functional outcomes. Databases were systematically searched and thirteen studies were included in the review. Evidence regarding the association between discontinuation from neuroleptic medication and functional outcomes was mixed. Findings are limited by the scarcity of evidence, diversity in the study methods and designs used, and methodological and design quality issues. Paper two is a qualitative study exploring personal accounts of making choices about neuroleptic medication, specifically considering decisions to discontinue. Twelve participants were interviewed and a constructivist grounded theory approach was used to analyse transcripts. The findings suggest that making sense of choices relates to a continuation-discontinuation spectrum and involves three interrelated tasks. The tasks are: forming a personal theory of the need for, and acceptability of, neuroleptic medication; negotiating the challenges of forming alliances with others; and weaving a safety net to safeguard wellbeing. A theoretical model explaining the processes involved in the tasks and the mediating factors is presented and discussed. The clinical implications of the findings are discussed with reference to existing literature. Paper three is not intended for publication and is a critical review of the research process, in which the strengths and weaknesses of the systematic review and empirical study are evaluated. Personal and professional reflections on the experience of conducting a systematic review and an empirical qualitative study are discussed and the implications of the research for future clinical practice and research are considered.

Cholinesterase inhibitors (ChEIs) are the first line pharmacotherapy for the symptoms of Alzheimer’s disease (AD). Though ChEIs offer modest cognitive benefits in early AD, literature addressing their continued use in severe AD is scarce. This study assessed the safety of discontinuing ChEIs in institutionalized moderate-severe AD patients. Twenty-six patients were randomized, double-blind to ChEI continuation or placebo for 8-weeks. Vitals, weight (kg) and adverse events (AEs) were monitored biweekly. Chi-square test revealed no significant association between semi-blinded treatment allocation and AE occurrence (χ²=(1,26)=0.99, p=0.32). Groups showed no differences on clinically significant weight loss (χ²=(1,26) =1.9, p=0.17), mean weight loss (F=.531, p= .473), pulse rate (F=.624, p=.437), or side effects (F=.224, p=.640). Preliminary results suggest that either ChEIs are well tolerated or that these drugs are no longer providing therapeutic benefit. Study completion (recruitment of 60 patients and unblinding) will generate more comprehensive data for determination of safe ChEI discontinuation guidelines.

Cholinesterase inhibitors (ChEIs) are the first line pharmacotherapy for the symptoms of Alzheimer’s disease (AD). Though ChEIs offer modest cognitive benefits in early AD, literature addressing their continued use in severe AD is scarce. This study assessed the safety of discontinuing ChEIs in institutionalized moderate-severe AD patients. Twenty-six patients were randomized, double-blind to ChEI continuation or placebo for 8-weeks. Vitals, weight (kg) and adverse events (AEs) were monitored biweekly. Chi-square test revealed no significant association between semi-blinded treatment allocation and AE occurrence (χ²=(1,26)=0.99, p=0.32). Groups showed no differences on clinically significant weight loss (χ²=(1,26) =1.9, p=0.17), mean weight loss (F=.531, p= .473), pulse rate (F=.624, p=.437), or side effects (F=.224, p=.640). Preliminary results suggest that either ChEIs are well tolerated or that these drugs are no longer providing therapeutic benefit. Study completion (recruitment of 60 patients and unblinding) will generate more comprehensive data for determination of safe ChEI discontinuation guidelines.

Die Einführung des polyvalenten Bachelors mit dem berufsfeldspezifischen Profil für das Lehramt an Grund-, Mittel- und Förderschulen sowie das Höhere Lehramt an Gymnasien ("BA-Lehramt") und den entsprechenden lehramtsspezifischen Masterstudiengängen ("MA-Lehramt") war auch mit dem Ziel verbunden, die Abbruch- bzw. Schwundquoten der Studierenden zu reduzieren. Um dieses Ziel erreichen zu können, muss man aus unserer Sicht neben den "reinen Zahlen" vor allem die Gründe kennen, die dazu führen, das Lehramtsstudium abzubrechen. Ein Entgegenwirken ist in erster Linie bei jenen Gründen möglich und wünschenswert, die im Studium bzw. in den Studienbedingungen verankert sind.

No description available.