2012 Iowa Drug Control Strategy

Drug use is a preventable behavior; drug addiction is a treatable disease; and a balanced approach of proven and promising prevention, treatment and enforcement is required to protect Iowans from drugs now and in the future. Drug abuse itself is a two-faceted problem, affected by both the available supply of and the demand for illegal drugs and other substances of abuse. Any strategy dealing with both the supply of and demand for drugs of abuse must be three-fold and involve these coordinated components: 1) Prevention strategies to discourage the initial human demand for drugs, 2) Treatment for those who already abuse or are addicted to drugs, in order to halt their drug-seeking behavior, and 3) Law enforcement actions to decrease the supply of illegal drugs and bring to treatment those who otherwise would not seek help. It is with these three approaches in mind that the Governor’s Office of Drug Control Policy presents the 2012 Iowa Drug Control Strategy. Mark J. Schouten Director, Governor’s Office of Drug Control Policy

Polypharmacy as predictor of drug cost, length of hospital stay and mortality rate in nursing homes : a retrospective analysis of pharmacy medication records

Background and objectives: Polypharmacy (PP) is a typical con-sequence of multiple chronic conditions in elderly patients. PP is commonly defined as the use of multiple concurrent drug therapies although a standard definition is not used. The aims of this study were to assess the PP rate among nursing home (NH) residents using the data of the pharmacy medication records and to investigate the threshold level of PP as predictor of drug cost, length of hospital stay and mortality rate

Brain metastasis: opportunity for drug development?

PURPOSE OF REVIEW: Brain metastases are a common clinical problem, and only limited treatment options exist. We review recent advances in medical brain metastasis research with a focus on the most common tumor types associated with secondary brain colonization: melanoma, breast cancer and lung cancer. We speculate on opportunities for drug development in patients with brain metastases, both as a treatment of established disease and as an adjuvant and prophylactic strategy. RECENT FINDINGS: BRAF inhibitors and the immunomodulatory anticytotoxic T-lymphocyte-associated antigen 4 antibody ipilimumab have shown clinically meaningful activity in melanoma patients with brain metastases. In breast cancer, current studies on drug treatment of brain metastases are mainly focusing on human epidermal growth factor receptor 2 targeting agents such as lapatinib. Emerging data seem to implicate a potential role of targeted agents including antiangiogenic compounds, pazopanib, and epithelial growth factor receptor inhibitors for prevention of brain metastasis formation in breast cancer or nonsmall cell lung cancer. SUMMARY: Novel drugs are beginning to enter clinical practice for selected patients with brain metastases. The promising findings from recent studies may fuel more research on brain metastases and their optimal drug treatment.

Controlled expression of recombinant proteins in Physcomitrella patens by a conditional heat-shock promoter: a tool for plant research and biotechnology.

The ability to express tightly controlled amounts of endogenous and recombinant proteins in plant cells is an essential tool for research and biotechnology. Here, the inducibility of the soybean heat-shock Gmhsp17.3B promoter was addressed in the moss Physcomitrella patens, using beta-glucuronidase (GUS) and an F-actin marker (GFP-talin) as reporter proteins. In stably transformed moss lines, Gmhsp17.3B-driven GUS expression was extremely low at 25 degrees C. In contrast, a short non-damaging heat-treatment at 38 degrees C rapidly induced reporter expression over three orders of magnitude, enabling GUS accumulation and the labelling of F-actin cytoskeleton in all cell types and tissues. Induction levels were tightly proportional to the temperature and duration of the heat treatment, allowing fine-tuning of protein expression. Repeated heating/cooling cycles led to the massive GUS accumulation, up to 2.3% of the total soluble proteins. The anti-inflammatory drug acetyl salicylic acid (ASA) and the membrane-fluidiser benzyl alcohol (BA) also induced GUS expression at 25 degrees C, allowing the production of recombinant proteins without heat-treatment. The Gmhsp17.3B promoter thus provides a reliable versatile conditional promoter for the controlled expression of recombinant proteins in the moss P. patens.

Predictors of onset of cannabis and other drug use in male young adults: results from a longitudinal study.

BACKGROUND: The use of cannabis and other illegal drugs is particularly prevalent in male young adults and is associated with severe health problems. This longitudinal study explored variables associated with the onset of cannabis use and the onset of illegal drug use other than cannabis separately in male young adults, including demographics, religion and religiosity, health, social context, substance use, and personality. Furthermore, we explored how far the gateway hypothesis and the common liability to addiction model are in line with the resulting prediction models. METHODS: The data were gathered within the Cohort Study on Substance Use Risk Factors (C-SURF). Young men aged around 20 years provided demographic, social, health, substance use, and personality-related data at baseline. Onset of cannabis and other drug use were assessed at 15-months follow-up. Samples of 2,774 and 4,254 individuals who indicated at baseline that they have not used cannabis and other drugs, respectively, in their life and who provided follow-up data were used for the prediction models. Hierarchical logistic stepwise regressions were conducted, in order to identify predictors of the late onset of cannabis and other drug use separately. RESULTS: Not providing for oneself, having siblings, depressiveness, parental divorce, lower parental knowledge of peers and the whereabouts, peer pressure, very low nicotine dependence, and sensation seeking were positively associated with the onset of cannabis use. Practising religion was negatively associated with the onset of cannabis use. Onset of drug use other than cannabis showed a positive association with depressiveness, antisocial personality disorder, lower parental knowledge of peers and the whereabouts, psychiatric problems of peers, problematic cannabis use, and sensation seeking. CONCLUSIONS: Consideration of the predictor variables identified within this study may help to identify young male adults for whom preventive measures for cannabis or other drug use are most appropriate. The results provide evidence for both the gateway hypothesis and the common liability to addiction model and point to further variables like depressiveness or practising of religion that might influence the onset of drug use.

Orthopedic implant used as drug delivery system: clinical situation and state of the research.

A partial review is proposed on the existing literature for the research performed in orthopedic implant used as drug delivery system. In the first part, an evaluation is given on the clinical need to deliver a drug in the surrounding of an implant. Secondly, a review of the clinical situation is developed for implants already used as drug delivery system. Experimental works performed for local delivery are reported. In particular, a description is given on the in vitro and in vivo studies where the implant is coated with different proteins or drugs. Finally, a conclusion is proposed on the next step in the development of orthopedic implant as drug delivery system mentioning also the industrial situation.

Agency Fact Sheet, Department of the Governor's Office of Drug Control Policy, FY2007

This document produced by the Iowa Department of Administrative Services has been developed to provide a multitude of information about executive branch agencies/department on a single sheet of paper. The facts provides general information, contact information, workforce data, leave and benefits information and affirmative action data.

Prediction of Infant Drug Exposure Through Breastfeeding: Population PK Modeling and Simulation of Fluoxetine Exposure.

The likelihood of significant exposure to drugs in infants through breast milk is poorly defined, given the difficulties of conducting pharmacokinetics (PK) studies. Using fluoxetine (FX) as an example, we conducted a proof-of-principle study applying population PK (popPK) modeling and simulation to estimate drug exposure in infants through breast milk. We simulated data for 1,000 mother-infant pairs, assuming conservatively that the FX clearance in an infant is 20% of the allometrically adjusted value in adults. The model-generated estimate of the milk-to-plasma ratio for FX (mean: 0.59) was consistent with those reported in other studies. The median infant-to-mother ratio of FX steady-state plasma concentrations predicted by the simulation was 8.5%. Although the disposition of the active metabolite, norfluoxetine, could not be modeled, popPK-informed simulation may be valid for other drugs, particularly those without active metabolites, thereby providing a practical alternative to conventional PK studies for exposure risk assessment in this population.

Simultaneous quantification of selective serotonin reuptake inhibitors and metabolites in human plasma by liquid chromatography-electrospray mass spectrometry for therapeutic drug monitoring.

A simple and sensitive liquid chromatography-electrospray ionization mass spectrometry method was developed for the simultaneous quantification in human plasma of all selective serotonin reuptake inhibitors (citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) and their main active metabolites (desmethyl-citalopram and norfluoxetine). A stable isotope-labeled internal standard was used for each analyte to compensate for the global method variability, including extraction and ionization variations. After sample (250μl) pre-treatment with acetonitrile (500μl) to precipitate proteins, a fast solid-phase extraction procedure was performed using mixed mode Oasis MCX 96-well plate. Chromatographic separation was achieved in less than 9.0min on a XBridge C18 column (2.1×100mm; 3.5μm) using a gradient of ammonium acetate (pH 8.1; 50mM) and acetonitrile as mobile phase at a flow rate of 0.3ml/min. The method was fully validated according to Société Française des Sciences et Techniques Pharmaceutiques protocols and the latest Food and Drug Administration guidelines. Six point calibration curves were used to cover a large concentration range of 1-500ng/ml for citalopram, desmethyl-citalopram, paroxetine and sertraline, 1-1000ng/ml for fluoxetine and fluvoxamine, and 2-1000ng/ml for norfluoxetine. Good quantitative performances were achieved in terms of trueness (84.2-109.6%), repeatability (0.9-14.6%) and intermediate precision (1.8-18.0%) in the entire assay range including the lower limit of quantification. Internal standard-normalized matrix effects were lower than 13%. The accuracy profiles (total error) were mainly included in the acceptance limits of ±30% for biological samples. The method was successfully applied for routine therapeutic drug monitoring of more than 1600 patient plasma samples over 9 months. The β-expectation tolerance intervals determined during the validation phase were coherent with the results of quality control samples analyzed during routine use. This method is therefore precise and suitable both for therapeutic drug monitoring and pharmacokinetic studies in most clinical laboratories.

Agency Fact Sheet, Department of Governor Office of Drug Control Policy, FY2008

This document produced by the Iowa Department of Administrative Services has been developed to provide a multitude of information about executive branch agencies/department on a single sheet of paper. The facts provides general information, contact information, workforce data, leave and benefits information and affirmative action data.

Agency Fact Sheet, Office of Governor of Drug Control Policy, FY2009

This document produced by the Iowa Department of Administrative Services has been developed to provide a multitude of information about executive branch agencies/department on a single sheet of paper. The facts provides general information, contact information, workforce data, leave and benefits information and affirmative action data.

Suivi thérapeutique de l'imatinib = Therapeutische Drug-Monitoring von Imatinib

Monitoring spielt eine wichtige Rolle zur Therapieevaluierung und Behandlungsentscheidung - solange es auf der Basis der Messung von entsprechenden klinischen oder validierten Surrogat-Markern stattfindet. Im Hinblick auf die Imatinib-Therapie scheint das «Therapeutische Drug-Monitoring» (TDM) ein nützlicher Ansatz zum Therapie-Monitoring der CML-Behandlung zu sein, welches die Plasmakonzentration des Arzneimittels als Marker zur Therapieüberwachung verwendet. Imatinib-Plasmakonzentrationen variieren beträchtlich von Patient zu Patient unter dem gleichen Dosierungsschema, aufgrund der interindividuell unterschiedlichen Pharmakokinetik des Arzneimittels. Für die Plasmaexposition wurde gezeigt, dass sie mit dem klinischen Outcome von CML-Patienten korreliert - sowohl im Bezug auf das Therapieansprechen als auch auf das Nebenwirkungsprofil. Es ist noch unklar, ob das TDM von Imatinib nur im Falle von klinischen Problemen Verwendung finden sollte oder ob CML-Patienten bereits von einem systematischen, präventiven «Routine»-Monitoring zur Therapieindividualisierung - zur Steuerung der Plasmakonzentration in einen therapeutischen Bereich - profitieren könnten, welches in letzter Zeit immer häufiger empfohlen wird. Um diese Fragestellung zu beantworten, nimmt eine prospektive, randomisiert kontrollierte Schweizer Studie CML-Patienten auf, die seit weniger als 5 Jahren mit Imatinib behandelt werden, und bietet das TDM zudem für alle Patienten im Falle von klinischen Problemen an.