Using a pharmacist–community health worker collaboration to address medication adherence barriers

ObjectivePharmacists are positioned to evaluate and educate patients regarding medication adherence; however, opportunities exist to leverage a collaborative approach in eliciting barriers encountered by patients, especially in minority groups. Community health workers (CHWs) are individuals from the communities who form relationships with patients and help increase their access to health care resources. This study aimed to evaluate the effectiveness of a collaboration between CHWs and pharmacists in identifying and addressing medication adherence barriers faced by hypertensive patients.MethodsAfter receiving training in medication therapy management support, CHWs from the South East American Indian Council collaborated with students and pharmacists from the Center for Quality Medication Management at the University of Florida to identify and address medication adherence barriers encountered by hypertensive patients who were mainly Native American or black. The CHWs documented information from the patient interviews during the initial and follow-up visits. The team collaborated to identify intervention opportunities on the basis of the adherence barriers identified. Follow-up visits were conducted to measure progress.ResultsThirty-three hypertensive patients with or without diabetes were included in the study. The pharmacists, in partnership with the CHWs, offered 149 interventions related to medication adherence barriers. The most commonly identified barriers included forgetfulness, adverse effects, and knowledge concerns. By the final visits, 75.6% of the barriers related to antihypertensive medications and 63.9% of the barriers related to antidiabetic medications were resolved. In addition, a paired t test indicated a significant difference in the mean blood pressure values (P = 0.006 for systolic and P = 0.008 for diastolic) recorded at the initial (mean = 136/85.7 mm Hg) and final (mean = 130.1/81.2 mm Hg) visits.ConclusionThe findings of this pilot project support the collaboration between pharmacists and CHWs to help improve medication adherence and patient outcomes. Additional research is recommended to validate these study findings.     

Cannabis use in Switzerland 2015–2045: A population survey based model

BackgroundAlternative cannabis regulation models are discussed and implemented worldwide. A baseline scenario under the assumption of no policy or market changes may prove useful to forecast cannabis use and treatment demand and evaluate changes in legislation.MethodsBased on data of the Continuous Rolling Survey of Addictive Behaviours and Related Risks on cannabis use, age, gender and nationality from 2011 to 2015, we used general estimating equation analysis to model lifetime and 30-days prevalence from 2015 to 2045 in Switzerland accounting for demographic trends.ResultsLifetime prevalence of cannabis use is projected to grow from 28.3% (CI 95% 27.8–28.8) in 2015 to 42.0% (CI 95% 41.0–43.0) in 2045. 30-days prevalence would increase slightly from 2.70% (CI 95% 2.53–2.88) to 3.39% (CI 95% 3.11–3.66). Due to population growth, absolute numbers with past 30-day cannabis use are estimated to increase from 202,784 (CI 95% 189,534–216,035) to 314,302 (CI 95% 288,504–340,100). Among those aged under 30 years no substantial change in lifetime and 30-days prevalence of cannabis use is projected. Larger changes are estimated to occur in the age group 30+. The mean age of past 30-day cannabis users would increase for men with Swiss nationality from 30.3 to 38.7 years.DiscussionPopulation-based survey data and demographic projections can be used to develop baseline scenarios of future cannabis use. Assuming no changes in cannabis legislation, growing absolute numbers of users will likely increase treatment demand. Cannabis use is estimated to increase among the group aged >30 years, which is currently underrepresented in clinical treatment and research. Our findings highlight the need for prospective baseline scenarios to evaluate the impact of legislative changes on cannabis use. Moreover, in Switzerland effective prevention and treatment interventions for cannabis use disorders are required even if cannabis legislation remains unchanged.     

Effects of Aniline–An Aromatic Amine to Some Freshwater Organisms

We determined the acute and chronic toxicity of aniline to tilapia (Oreochromis mossambicus), cladoceran crusatcea (Moina micrura) and oligochaete worm (Branchiura sowerbyi) using static bioassay tests. The 96h LC₅₀ values of aniline for O. mossambicus, M. micrura and B. sowerbyi were 69.4, 0.6 and 586mg l^–1 respectively. Tilapia responded to even low concentrations of aniline: the fish lost appetite at aniline concentrations as low as 0.02mg l^–1. A 90 d outdoor bioassay with tilapia showed that 0.02mg l^–1 aniline reduced fish yield, specific growth rate and food conversion efficiency. Reproductive functions of fish were affected by aniline at a concentration of 0.5mg l^–1 and above. Dissolved oxygen, primary productivity and plankton population of the test medium also were significantly reduced at 2.65 and 6.94mg l^–1 aniline.     

In vitro blood–brain barrier model adapted to repeated-dose toxicological screening

Toxicity to the central nervous system (CNS) is a key feature in the toxicological profile of compounds and there is a growing interest to use in vitro cell assays.The blood–brain barrier (BBB) is a highly restrictive barrier that preserves homeostasis within the brain microenvironment. By modelling the BBB it is possible to investigate whether a compound is likely to compromise its functionality, which would cause unwanted effects on brain cells. These investigations are usually performed using a single exposure to drugs, whereas CNS side effects usually result from repeated exposures.The main objective of this study was to adapt our established BBB model to the evaluation of repeated-dose toxicity at the BBB.Studies were undertaken within the European Predict-IV consortium to study the effect on BBB permeability of 12 selected drugs after 14 days of repeated treatment to a single pre-selected concentration.Compared to single exposure, a 100-fold lower colchicine concentration in 14 days repeated-dose treatment was toxic. This demonstrates the importance to evaluate the BBB toxicity in repeated-dose testing. Finally, the potentiating effects of cyclosporin A on the BBB toxicity of colchicine illustrate the possibility to use in vitro BBB models to make risk assessment of drug–drug interactions.     

An approach based on antioxidant fingerprint–efficacy relationship and TLC bioautography assay to quality evaluation of Rubia cordifolia from various sources

In this work, an approach based on antioxidant fingerprint–efficacy relationships and TLC bioautography assay was developed for quality evaluation of traditional Chinese medicine (TCM). First, chemical fingerprints of 20 batches of different sources of Rubia cordifolia were established by HPLC. The antioxidant activities of these samples were evaluated by 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. Then, five active components from fingerprint peaks were determined by both multiple correlation analysis and TLC bioautography assay. Similarity analysis and hierarchical clustering analysis (HCA) based on these active peaks were chosen to evaluate the quality of R. cordifolia from different sources. The samples with similarities below 0.9 had poorer antioxidant activities and those having stronger activities fell into the same cluster in HCA. Finally, five batches of commercial samples were processed in the same way to verify the feasibility of this method. The results suggested that chemical fingerprinting combined with similarity analysis based on fingerprint–efficacy relationship and TLC bioautography could evaluate the antioxidant activity of R. cordifolia from various sources. The established technique would also provide an easy method of evaluating the quality of other TCMs.     

Assessment of DCE–MRI parameters for brain tumors through implementation of physiologically–based pharmacokinetic model approaches for Gd-DOTA

Dynamic-contrast enhanced magnetic resonance imaging (DCE–MRI) is used for detailed characterization of pathology of lesions sites, such as brain tumors, by quantitative analysis of tracer’s data through the use of pharmacokinetic (PK) models. A key component for PK models in DCE–MRI is the estimation of the concentration–time profile of the tracer in a nearby vessel, referred as Arterial Input Function (AIF). The aim of this work was to assess through full body physiologically-based pharmacokinetic (PBPK) model approaches the PK profile of gadoteric acid (Gd-DOTA) and explore potential application for parameter estimation in DCE-MRI based on PBPK-derived AIFs. The PBPK simulations were generated through Simcyp^® platform and the predicted PK parameters for Gd-DOTA were compared with available clinical data regarding healthy volunteers and renal impairment patients. The assessment of DCE-MRI parameters was implemented by utilizing similar virtual profiles based on gender, age and weight to clinical profiles of patients diagnosed with glioblastoma multiforme. The PBPK–derived AIFs were then used to compute DCE-MRI parameters through the Extended Tofts Model and compared with the corresponding ones derived from image-based AIF computation. The comparison involved: (i) image measured AIF of patients vs AIF of in silico profile, and, (ii) population average AIF vs in silico mean AIFs. The results indicate that PBPK–derived AIFs allowed the estimation of comparable imaging biomarkers with those calculated from typical DCE–MRI image analysis. The incorporation of PBPK models and potential utilization of in silico profiles to real patient data, can provide new perspectives in DCE–MRI parameter estimation and data analysis.     

Is law enforcement of drug-impaired driving cost-efficient? An explorative study of a methodology for cost–benefit analysis

BackgroundRoad users driving under the influence of psychoactive substances may be at much higher relative risk (RR) in road traffic than the average driver. Legislation banning blood alcohol concentrations above certain threshold levels combined with roadside breath-testing of alcohol have been in lieu for decades in many countries, but new legislation and testing of drivers for drug use have recently been implemented in some countries.MethodsIn this article we present a methodology for cost–benefit analysis (CBA) of increased law enforcement of roadside drug screening. This is an analysis of the profitability for society, where costs of control are weighed against the reduction in injuries expected from fewer drugged drivers on the roads. We specify assumptions regarding costs and the effect of the specificity of the drug screening device, and quantify a deterrence effect related to sensitivity of the device yielding the benefit estimates.ResultsThree European countries with different current enforcement levels were studied, yielding benefit–cost ratios in the approximate range of 0.5–5 for a tripling of current levels of enforcement, with costs of about 4000 EUR per convicted and in the range of 1.5 and 13 million EUR per prevented fatality.ConclusionsThe applied methodology for CBA has involved a simplistic behavioural response to enforcement increase and control efficiency. Although this methodology should be developed further, it is clearly indicated that the cost-efficiency of increased law enforcement of drug driving offences is dependent on the baseline situation of drug-use in traffic and on the current level of enforcement, as well as the RR and prevalence of drugs in road traffic.     

An attempt to structurally convert μ-selective morphine toward δ-receptor binding: dimerization based on enkephalin conformation

In order to elucidate the substrate specificities for μ- and δ-opioid receptors, dimerization of the μ-specific morphine molecule was attempted, based on the hypothesis of the possible relationship between the molecular conformation of endogenous enkephalin and its selectivity for each opioid receptor. The NOR2 ([normorphine]NCH₂CH₂N[normorphine]) thus synthesized exhibited agonist activity showing a preference for binding with the δ-opioid receptor, compared with the parent morphine molecule. Antagonist activity was also observed for NOR3 ([normorphine]NCH₂CH₂CH₂N[normorphine]).     

Exploring Inductive Linearization for simulation and estimation with an application to the Michaelis–Menten model

Journal of Pharmacokinetics and Pharmacodynamics - Nonlinear ordinary differential equations (ODEs) are common in pharmacokinetic–pharmacodynamic systems. Although their exact solutions...     

A semi-mechanistic absorption model to evaluate drug–drug interaction with dabigatran: application with clarithromycin

Aim

The aim of this study was to develop a PK/PD model to assess drug–drug interactions between dabigatran and P-gp modulators, using the example of clarithromycin, a strong inhibitor of P-gp.

Methods

Ten healthy male volunteers were randomized to receive in the first treatment period a single 300 mg dose of dabigatran etexilate (DE) and in the second treatment period 500 mg clarithromycin twice daily during 3 days and then 300 mg DE plus 500 mg clarithromycin on the fourth day, or the same treatments in the reverse sequence. Dabigatran plasma concentration and ecarin clotting time (ECT) were measured on 11 blood samples. Models were built using a non-linear mixed effect modelling approach.

Results

The best PK model was based on an inverse Gaussian absorption process with two compartments. The relationship between dabigatran concentration and ECT was implemented as a linear function. No continuous covariate was associated with a significant decrease in the objective function. The concomitant administration of clarithromycin induced a significant change only in DE bioavailability, which increased from 6.5% to 10.1% in the presence of clarithromycin. Clarithromycin increased peak concentration and AUC by 60.2% and 49.1% respectively.

Conclusion

The model proposed effectively describes the complex PK of dabigatran and takes into account drug–drug interactions with P-gp activity modulators, such as clarithromycin.