Self-medication in Poland: the pharmacist’s advisory role in Warsaw

Background

Easy access favours the informative role that pharmacists play in Poland with regard to the proper use of medicinal products as well as preventing illness and promoting health.

Objective

The aim of the present study was to define situations in which patients ask a pharmacist for advice and to identify the most important factors that affect the patients’ decisions in seeking advice from a pharmacist.

Method

n all, 101 patients (69 women, 32 men) aged 19–67 years participated in the study. The study was conducted using a structured interview research method. Patients were asked to answer a set of closed-ended questions related to their habits regarding the purchase of medicines and the factors that affected their decision to seek the advice of a pharmacist.

Main outcome measure

Factors determining the choice to contact a pharmacy.

Results

Patients seldom asked pharmacists for advice: 77 of the patients “rarely” or “never” went to a pharmacy to consult the pharmacist. When patients did ask the pharmacist for advice, it was mainly concerning the choice of over-the-counter medicines. The most important reason for patients visiting a pharmacy for advice was the large number of pharmacies in Poland and their ease of access; the long queues of people in busy pharmacies and the lack of confidentiality in the pharmacy were considered negative factors.

Conclusion

The current advisory role of pharmacists in Poland seems of minimal importance to the public.     

Autophagy in the liver: cell’s cannibalism and beyond

Chronic liver disease and its progression to liver failure are induced by various etiologies including viral infection, alcoholic and nonalcoholic hepatosteatosis. It is anticipated that the prevalence of fatty liver disease will continue to rise due to the growing incidence of obesity and metabolic disorder. Evidence is accumulating to indicate that the onset of fatty liver disease is causatively linked to mitochondrial dysfunction and abnormal lipid accumulation. Current treatment options for this disease are limited. Autophagy is an integral catabolic pathway that maintains cellular homeostasis both selectively and nonselectively. As mitophagy and lipophagy selectively remove dysfunctional mitochondria and excess lipids, respectively, stimulation of autophagy could have therapeutic potential to ameliorate liver function in steatotic patients. This review highlights our up-to-date knowledge on mechanistic roles of autophagy in the pathogenesis of fatty liver disease and its vulnerability to surgical stress, with an emphasis on mitophagy and lipophagy.     

Advancements in the treatment of agitation in Alzheimer’s disease

Introduction: Neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD) are associated with significant negative outcomes for patients and their caregivers. Agitation, one of the most distressing NPS, lacks well-established long-term interventions that are both effective and safe. While non-pharmacological interventions are the suggested first-line treatment, it isn’t effective in managing symptoms for every patient. In such cases, clinicians turn to the use of pharmacological interventions. Traditionally, these interventions consist of off-label use of antipsychotics, sedative/hypnotics, anxiolytics, acetylcholinesterase inhibitors, memantine and antidepressants, where the efficacy doesn’t necessarily outweigh the associated risks.

Areas covered: Gains made in understanding the neurobiological mechanisms underlying agitation have fueled several recent clinical trials. A comprehensive literature search for published articles evaluating pharmacologic interventions for agitation in AD was done. A review of some of these clinical trials was completed: dextromethorphan/quinidine, scyllo-inositol, brexpiprazole, prazosin, cannabinoids, dronabinol and citalopram show promise in treating agitation.

Expert opinion: Neurobiological findings and enhanced trial designs have re-ignited the area of pharmacological treatment of NPS. Although further research is needed to fully determine the safety, tolerability and efficacy of these treatments, the mission to finding effective treatments for NPS such as agitation in patients with dementia is well underway.     

Boron’s journey: advances in the study and application of pharmacokinetics

Introduction: Boron-containing compounds (BCCs) are attractive chemical entities in drug development. Some of these compounds have been used in the treatment of human disease, and studies on their pharmacodynamics suggest that they employ multiple forms of activity. However, less is known about the pharmacokinetic profile of these molecules.

Areas covered: The herein compiled reported data is presented in accordance with the classical ‘ADME’ system for identifying the scope of BCCs in the respective fields. Our analysis suggests that these compounds have several distinct ways to move within the human body, and that the specific structural features of each molecule account for its distinct pharmacokinetic profile. These insights should be useful for designing BCCs with a desired effect.

Expert opinion: Increasing knowledge about the pharmacokinetics of BCCs is providing a broader understanding about the design of new release systems and potential drugs, as well as probable protein transporters that could be related to key roles in physiological processes. These transporters may be involved in sodium transport, hormone release and regulation of the cell cycle. The shared features among groups of BCCs are being identified in order to apply these insights to the design of advantageous compounds.     

Comparison of Finkelstein’s Method With the Conventional Approach for Interval-Censored Data Analysis

Interval-censored time-to-event data occurs frequently in randomized clinical trials. Many new methods for analysis of interval-censored time-to-event data have been proposed in the last two decades. However, most of these methods either rely on assumptions that are hard to verify in practice or are computationally challenging. As a result, none of them has been accepted by the pharmaceutical industry as a standard method. Taking advantage of modern computational power, we did an extensive simulation to compare the performance of conventional imputation-based analysis methods for such data with an existing nonparametric interval-censored data analysis method by Finkelstein (1986) in a typical setting for confirmatory clinical trials. The simulation results clearly favor the nonparametric method, which provides credible inference even under extreme conditions. This helps ease a key concern of the regulatory agency and paves the way for wide acceptance of interval-censored clinical endpoint as a primary endpoint in confirmatory trials. An approximate formula for event size calculation is provided for the design of clinical trials with such an endpoint.     

Modeling of Bounded Outcome Scores with Data on the Boundaries: Application to Disability Assessment for Dementia Scores in Alzheimer’s Disease

Mixed-effects beta regression (BR), boundary-inflated beta regression (ZOI), and coarsening model (CO) were investigated for analyzing bounded outcome scores with data at the boundaries in the context of Alzheimer’s disease. Monte Carlo simulations were conducted to simulate disability assessment for dementia (DAD) scores using these three models, and each set of simulated data were analyzed by the original simulation model. One thousand trials were simulated, and each trial contained 250 subjects. For each subject, DAD scores were simulated at baseline, 13, 26, 39, 52, 65, and 78 weeks. The simulation-reestimation exercise showed that all the three models could reasonably recover their true parameter values. The bias of the parameter estimates of the ZOI model was generally less than 1%, while the bias of the CO model was mainly within 5%. The bias of the BR model was slightly higher, i.e., less than or in the order of 20%. In the application to real-world DAD data from clinical studies, examination of prediction error and visual predictive check (VPC) plots suggested that both BR and ZOI models had similar predictive performance and described the longitudinal progression of DAD slightly better than the CO model. In conclusion, the investigated three modeling approaches may be sensible choices for bounded outcome scores with data on the edges. Prediction error and VPC plots can be used to identify the model with best predictive performance.     

Novel pharmaceuticals in the treatment of psychosis in Parkinson’s disease

Parkinson’s disease (PD) affects 10 million people worldwide. Half will develop psychosis, the majority experiencing hallucinations rather than delusions. Emergence of psychosis increases the likelihood of institutionalization and mortality. Where pharmacological treatment is warranted, options are limited. Most currently licensed atypical antipsychotics are ineffective or worsen motor symptoms in people with PD. This review of provides an overview of the current landscape of treatments and the opportunities in emerging research. Clozapine is the only licensed antipsychotic with proven efficacy, although the associated side effects limit its use. With recent advances in understanding the role of serotonin, rational drug design approaches have delivered a novel pharmacological treatment with recently proven efficacy in clinical trials of people with PD and psychosis. Pimavanserin represents an important addition to treatment.     

Octreotide’s Role in the Management of Sulfonylurea-Induced Hypoglycemia

The objective is to evaluate the evidence regarding octreotide's efficacy as a treatment for sulfonylurea-induced hypoglycemia. A search of PubMed for articles published from 1965 to 2008 using combinations of the terms octreotide, antidote, sulfonylurea, overdose, poisoning, and toxicity was performed. References from identified articles were reviewed for additional sources. Animal studies, case reports, case series, and randomized controlled trials were evaluated. An animal model of sulfonylurea overdose demonstrates that octreotide reduces the number of refractory sulfonylurea-induced hypoglycemic episodes. Published case reports describe the use of octreotide to prevent recurrent hypoglycemia after sulfonylurea overdose. A retrospective case series demonstrates that administration of octreotide decreases the need for supplemental dextrose boluses as well as hypoglycemic events. Two prospective, controlled trials determined that octreotide and supplemental dextrose increase blood glucose concentrations with fewer hypoglycemic events. Based on animal and human data, there is sufficient evidence to recommend the use of octreotide with supplemental dextrose for the treatment of sulfonylurea-induced hypoglycemia.     

Future directions in the treatment of Alzheimer’s disease

Alzheimer’s disease (AD) remains the most common of the neurodegenerative disorders. In the elderly, it represents the most frequently occurring form of dementia, especially if considered alongside concomitant cerebrovascular disease. Current treatment involves the use of acetylcholinesterase inhibitors, which have shown symptomatic benefits in the recognised domains of cognition, function and behaviour. While they may have intrinsic disease-modifying activity, this is yet to be proven, and strategies to alter the fundamental neuropathological changes in AD continue to be sought. Much of the evidence suggests that the accumulation of amyloid-β may play a pivotal role, therefore the bulk of current research is focused on possible intervention along the amyloid pathways. However, the abnormal phosphorylation of tau is also a reasonable target and as the molecular basis of AD is better delineated, more targeted treatment approaches are being proposed. This paper reports on the current data that is setting the future directions for research into AD.     

Economic assessment in the management of non-Hodgkin’s lymphoma

An increasing need for economic evaluations of non-Hodgkin’s lymphoma (NHL) treatments exists. We performed a literature review on the currently available NHL economic evaluations, using PubMed and the Cochrane database. English and Dutch language papers on treatment in adults were selected. A total of 88 publications were found, 44 of which were included. Of these, 6 economic evaluation-specific methodological items are evaluated (study perspective, overhead costs, data sources, charges or prices, sensitivity analysis, presentations of resource use and unit costs), enabling readers to judge the value of these studies. The 11 subjects covered by the economic evaluations are discussed. Many NHL treatments remain to be studied in economic evaluations. Future publications should report on the six methodological items in more detail, and preferably tackle them in the recommended way.     

An update on the advancements in the treatment of agitation in Alzheimer’s disease

Introduction: Neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD) are associated with significant negative outcomes for patients and their caregivers. Agitation, one of the most distressing NPS, lacks safe and effective long term interventions. Nonpharmacological interventions are suggested as first-line treatment, but aren’t effective for every patient, resulting in pharmacological interventions for some patients, consisting of off-label use of antipsychotics, sedative/hypnotics, anxiolytics, acetylcholinesterase inhibitors, memantine, and antidepressants; where efficacy doesn’t necessarily outweigh associated risks.

Areas covered: Gains in understanding neurobiological mechanisms underlying agitation have fueled several recent clinical trials. This article updates our review published in 2014. Comprehensive literature search for published articles from January 2014 to December 2016 evaluating pharmacologic interventions for agitation in AD was done. A review of several clinical trials was completed: dextromethorphan/quinidine, scyllo-inositol, brexpiprazole, prazosin, cannabinoids, citalopram, escitalopram, pimavanserin, ITI-007, ORM-12741 show promise in treating agitation.

Expert opinion: Neurobiological findings, innovative trials designs, statistical approaches, and preliminary paths for regulatory agency acceptance have re-ignited the area of pharmacological treatment of NPS. Though further research is needed to fully determine the safety, tolerability and efficacy of these treatments, the mission to find effective treatments for neuropsychiatric symptoms such as agitation in patients with dementia is well underway.     

The debate over dopamine’s role in reward: the case for incentive salience

Introduction

Debate continues over the precise causal contribution made by mesolimbic dopamine systems to reward. There are three competing explanatory categories: ‘liking’, learning, and ‘wanting’. Does dopamine mostly mediate the hedonic impact of reward (‘liking’)? Does it instead mediate learned predictions of future reward, prediction error teaching signals and stamp in associative links (learning)? Or does dopamine motivate the pursuit of rewards by attributing incentive salience to reward-related stimuli (‘wanting’)? Each hypothesis is evaluated here, and it is suggested that the incentive salience or ‘wanting’ hypothesis of dopamine function may be consistent with more evidence than either learning or ‘liking’. In brief, recent evidence indicates that dopamine is neither necessary nor sufficient to mediate changes in hedonic ‘liking’ for sensory pleasures. Other recent evidence indicates that dopamine is not needed for new learning, and not sufficient to directly mediate learning by causing teaching or prediction signals. By contrast, growing evidence indicates that dopamine does contribute causally to incentive salience. Dopamine appears necessary for normal ‘wanting’, and dopamine activation can be sufficient to enhance cue-triggered incentive salience. Drugs of abuse that promote dopamine signals short circuit and sensitize dynamic mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Such drugs interact with incentive salience integrations of Pavlovian associative information with physiological state signals. That interaction sets the stage to cause compulsive ‘wanting’ in addiction, but also provides opportunities for experiments to disentangle ‘wanting’, ‘liking’, and learning hypotheses. Results from studies that exploited those opportunities are described here.

Conclusion

In short, dopamine’s contribution appears to be chiefly to cause ‘wanting’ for hedonic rewards, more than ‘liking’ or learning for those rewards.     

Rollercoaster ride of kynurenines: steering the wheel towards neuroprotection in Alzheimer’s disease

ABSTRACT

Introduction: Alzheimer’s disease (AD) is associated with cerebral cognitive deficits exhibiting two cardinal hallmarks: accruement of extracellular amyloid plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein. The currently accessible therapeutic armamentarium merely provides symptomatic relief. Therefore, the cry for prospective neuroprotective strategies seems to be the need of the hour.

Areas covered: This review comprehensively establishes correlation between kynurenine pathway (KP) metabolites and AD with major emphasis on its two functionally contrasting neuroactive metabolites i.e. kynurenic acid (KYNA) and quinolinic acid (QUIN) and enlists various clinical studies which hold a potential for future therapeutics in AD. Also, major hypotheses of AD and mechanisms underlying them have been scrutinized with the aim to brush up the readers with basic pathology of AD.

Expert opinion: KP is unique in itself as it holds two completely different domains i.e. neurotoxic QUIN and neuroprotective KYNA and disrupted equilibrium between the two has a hand in neurodegeneration. KYNA has long been demonstrated to be neuroprotective but lately being disparaged for cognitive side effects. But we blaze a trail by amalgamating the pharmacological mechanistic studies of KYNA in kinship with α7nAChRs, NMDARs and GABA which lends aid in favour of KA.     

Recent developments in the pharmacological treatment of Parkinson’s disease

Parkinson’s disease (PD) is a neurodegenerative disorder associated with the loss of dopaminergic neurons in the substantia nigra. The decline of dopamine leads to motor dysfunctions manifested as tremor, rigidity and bradykinesia. The pharmacological treatment of choice for the past 30 years has primarily been the dopamine precursor levodopa. Although it is the most effective treatment available, it is clear that other drugs are needed in order to sustain a therapeutic benefit and to alleviate fluctuations in mobility (i.e., motor fluctuations). Furthermore, there is some evidence that levodopa may hasten the occurrence of motor fluctuations and involuntary movements called dyskinesias. Hence, many clinicians delay the use of levodopa and employ the use of other symptomatic treatments including monoamine oxidase type B (MAO-B) inhibitors and dopamine agonists as first-line therapy in de novo patients. Regardless of treatment, the disease continues to progress as there is still no obvious means of altering disease progression (i.e., no neuroprotective therapy), to restore loss of dopamine (i.e., no restorative therapy) or prevent the disease (i.e. preventative therapy). With disease progression, polypharmacy is common and often employs a combination of antiparkinsonian agents. There have been some key advances in treatment with the advent of MAO-B inhibitors, dopamine agonists and catechol-O-methyltransferase inhibitors; however, the arsenal of drug treatment remains limited. As the mechanism of PD is further elucidated, novel drug treatments will continue to emerge in the areas of preventative, restorative or symptomatic therapy. Despite the purpose of treatment, the ideal pharmacological drug for PD will include the presence of a safe side-effect profile, a simple dosing schedule, the ability to provide symptomatic relief and the potential to alter disease progression. The purpose of this article is to examine upcoming antiparkinsonian drugs in clinical trials based on their pharmacology, safety and efficacy.