Video-based teleconsultations in pharmaceutical care – A systematic review

BackgroundIn recent years, telemedicine has gained increasing importance in the delivery of pharmaceutical care. The use of video technologies for remote communication between different parties offers the potential to meet the future challenges which arise from the increase in elderly and chronically ill patients. However, the influence of these technologies on patient-related outcomes in pharmaceutical care is not yet sufficiently known.MethodIn December 2018 a systematic literature search was conducted in the databases Medline, Cochrane Library and PubPharm. Randomized controlled trials were considered, which investigate real-time video conferencing between pharmacists on the one hand and patients or other healthcare providers on the other hand. The influence on patient related outcomes compared to standard care was assessed. The bias potential was evaluated using the Cochrane Risk-of-Bias instrument. A total of 4 randomized controlled trials could be included.ResultsThe studies describe partly complex intervention settings with adults and adolescents suffering from asthma, chronic renal failure, HIV infection, hyperlipidemia, hypertension and/or diabetes. None of the studies considers the interprofessional communication of pharmacists with other service providers. No influence on clinical or psychological endpoints was found. In some cases, an increase in adherence and correct medication use is evident. Healthcare utilization is not influenced. In all studies there is an increased risk of systematic bias.DiscussionTeleconsultations with pharmacists can rather be used to ensure the general provision of pharmaceutical care than to improve patient-related outcomes. Further studies are necessary to fully depict the influence of telemedical interventions in pharmaceutical care.     

Keynote review: Is declining innovation in the pharmaceutical industry a myth?

Increasing the rate of innovation is a requirement to achieve much-needed advances in patient care, as well as to secure the future of the pharmaceutical industry. Currently, there is a perception in the external environment that pharmaceutical R&D is no longer innovative, fails to bring new drugs to market or, at best, produces a rising number of 'me-too' drugs with no advantage over existing treatments. In addition, the cost to discover and develop new medicines (i.e. cost per launch) has risen dramatically in recent years. The quoted development cost per medicine is a reality, and is not disputed here. However, data are provided that demonstrate that with regard to innovation rates, the current perception is wrong - although there have been, and continue to be, fluctuations in drug launches, there has been a steady increase in the number of new chemical entities launched, both in absolute numbers of FDA-approved medicines and in the proportion of priority reviews.     

Non-stoichiometric inhibition in integrated lead finding – a literature review

ABSTRACT

Introduction: Non-stoichiometric inhibition summarizes different mechanisms by which low-molecular weight compounds can reproducibly inhibit high-throughput screening (HTS) and other lead finding assays without binding to a structurally defined site on their molecular target. This disqualifies such molecules from optimization by medicinal chemistry, and therefore their rapid elimination from screening hit lists is essential for productive and effective drug discovery.

Areas covered: This review covers recent literature that either investigates the various mechanisms behind non-stoichiometric inhibition or suggests assays and readouts to identify them. In addition, combination of the various methods to distill promising molecules out of raw primary hit lists step-by-step is considered. Emerging technologies to demonstrate target engagement in cells are also discussed.

Expert opinion: Over the last few years, awareness of non-stoichiometric inhibitors within screening libraries and HTS hit lists has considerably increased, not only in the pharmaceutical industry but also in the academic drug discovery community. This has resulted in a variety of methods to detect and handle such compounds. These range from in silico approaches to flag suspicious compounds, and counterassays to measure non-stoichiometric inhibition, to biophysical methods that positively demonstrate stoichiometric binding. In addition, novel technologies to verify target engagement within cells are becoming available. While still a time- and resource-consuming nuisance, non-stoichiometric inhibitors therefore do not fundamentally jeopardize the discovery of low molecular weight lead and drug candidates. Rather, they should be viewed as a manageable issue that with appropriate expertise can be overcome through integration of the above-mentioned approaches.     

Secondary patents in the pharmaceutical industry: missing the wood for the trees?

Introduction: The critics of the Innovator pharmaceutical industry allege that secondary patents are trivial modifications over the primary patent, which extend its term and delay the entry of the generics in the market place. The protagonists regard secondary patents a result of continuous research and development (R&D), which help them introduce and protect new, differentiated products.

Areas covered: The areas covered are Product life cycle management (PLCM), Drug approval process, Orange book (OB) listed patents, US patent data.

Expert opinion: Our analysis of the patents and products of four innovators viz., AstraZeneca, Takeda, Eisai and Wyeth in the field of proton pump inhibitors (PPI’s) and Merck and Pfizer in the field of Statins shows that secondary patents help innovators sustain competition against other innovators in the specific product segment. The number of secondary patents listed in OB per NCE depends on the innovators interest in exploiting the NCE, the success of R & D effort and product lifecycle management strategy in the wake of market competition. Market entry decisions of innovators are strategic rather than a mere fallout of the secondary patents granted. Entry of another innovator is more unpredictable and hurts the first entrant more vis a vis the entry of generics who can enter the market when the patents protecting a product are no more enforceable, and hence more predictable. Generic entry in the field of PPI’s shows that the term of the primary patent is not extended by the secondary patents.     

Bradykinin receptor antagonists – a review of the patent literature 2005 – 2008

Background: For > 20 years, pharmaceutical companies and academic centers have been developing bradykinin antagonists. The patent literature on these molecules (up to and including 2004) has been analyzed previously in this journal in two review articles. Objective: The aim of this review is to provide an update (from 2005 to early 2009) on the patenting activity in the field of bradykinin antagonists (including patents on their formulation). Where possible, the information from the patents has been supplemented with that from the primary literature, clinical trial databases and company websites in an attempt to give a more complete picture. Conclusions: In the past 4 years, nearly 50 new patents have been filed on bradykinin antagonists – in the case of several filings, only the original source has been considered in this analysis – the vast majority of these (> 93%) on B1 antagonists. However, despite this large amount of work, only one compound, icatibant – a hydrophilic decapeptide selective for the B2 receptor – has reached the market, although it needs to be administered parenterally.     

Marketing activity in the community pharmacy sector – A scoping review

Background

Community pharmacy ownership requires engaging with marketing strategies to influence consumer behaviour. There is a plethora of information from trade journals, expert opinion, and published discussion surrounding this issue. Despite this, evidence relating to the efficacy of marketing activity within the pharmacy sector is scant.

Do phthalates act as obesogens in humans? A systematic review of the epidemiological literature

Introduction: Phthalates, a class of commonly used compounds with widespread human exposure, have been described as obesogens, or chemicals that disrupt lipid metabolism and produce metabolic changes leading to increased risk of type 2 diabetes mellitus (DM) and cardiovascular disease (CVD). This communication provides a systematic review of the available epidemiologic evidence on associations between phthalate ester metabolites in urine or blood and various health endpoints related to overweight/obesity, DM or CVD. Methods: We followed the current methodological guidelines for systematic reviews to identify, retrieve and summarize the relevant epidemiological literature on the relation between phthalates and overweight/obesity, DM, CVD or related biomarkers. Each eligible paper was summarized with respect to methods and results with particular attention to study design and exposure assessment. As quantitative meta-analysis was not feasible, the study results were assessed qualitatively for inter- and intra-study consistency. Results: We identified 26 publications of epidemiologic studies that assessed associations between either urinary or serum phthalate metabolites and outcomes of interest. These studies represented 18 independent data sources. We found no inter- or intra-study consistency for any phthalate metabolite for any of the indicators of overweight/obesity, DM or CVD in children or adults. Most reported associations were not statistically significantly different from the null, some were positive, and others were inverse. All studies except two used cross-sectional analyses and for this reason could not be used to test causal hypotheses. Conclusion: The current epidemiological data do not support or refute the hypothesis that phthalates act as obesogens in humans.     

Do stimulants improve functioning in adults with ADHD?: A review of the literature

ADHD is prevalent in adulthood and stimulant pharmacotherapy is the primary treatment for uncomplicated presentations. ADHD is associated with significant functional impairment in major life roles. Measurement of the efficacy of stimulant treatment for adult ADHD therefore should include assessment of improvement in role function. A literature search was conducted to identify studies that measured change in function with stimulant treatment in adult ADHD using measures other than global clinical impression or global assessment of function ratings. Five studies were identified that met our search criteria. Evidence of functional improvement with stimulant treatment was found with the following validated self-report measures of functional wellbeing employed across these studies: the Medical Outcome Study 36-item Short Form Health Survey; ADHD Impact Module for Adults; Quality of Life Enjoyment and Satisfaction scale—Short Form; Sheehan Disability Scale, and Social Adjustment Scale—Self-Report. We conclude that investigations using self-report scales provide evidence that stimulant treatment translates into measurable improvement in daily function for adults with ADHD. Further investigation could better characterize the mediators and moderators of individual improvement, an important step towards the personalization of treatment for ADHD in adulthood.     

Model-based analysis of high shear wet granulation from batch to continuous processes in pharmaceutical production – A critical review

The manufacturing of pharmaceutical dosage forms, which has traditionally been a batch-wise process, is now also transformed into a series of continuous operations. Some operations such as tabletting and milling are already performed in continuous mode, while the adaptation towards a complete continuous production line is still hampered by complex steps such as granulation and drying which are considered to be too inflexible to handle potential product change-overs. Granulation is necessary in order to achieve good flowability properties and better control of drug content uniformity. This paper reviews modelling and supporting measurement tools for the high shear wet granulation (HSWG) process, which is an important granulation technique due to the inherent benefits and the suitability of this unit operation for the desired switch to continuous mode. For gaining improved insight into the complete system, particle-level mechanisms are required to be better understood, and linked with an appropriate meso- or macro-scale model. A brief review has been provided to understand the mechanisms of the granulation process at micro- or particle-level such as those involving wetting and nucleation, aggregation, breakage and consolidation. Further, population balance modelling (PBM) and the discrete element method (DEM), which are the current state-of-the-art methods for granulation modelling at micro- to meso-scale, are discussed. The DEM approach has a major role to play in future research as it bridges the gap between micro- and meso-scales. Furthermore, interesting developments in the measurement technologies are discussed with a focus towards inline measurements of the granulation process to obtain experimental data which are required for developing good models. Based on the current state of the developments, the review focuses on the twin-screw granulator as a device for continuous HSWG and attempts to critically evaluate the current process. As a result, a set of open research questions are identified. These questions need to be answered in the future in order to fill the knowledge gap that currently exists both at micro- and macro-scale, and which is currently limiting the further development of the process to its full potential in pharmaceutical applications.     

What's new in Nanotoxicology? Brief review of the 2007 literature

The use and commercial potential of engineered nanomaterials is increasing, but questions of occupational and public health safety remain. Here, we review research published in 2007 concerning toxicology of nanomaterials. Articles were selected from the Medline Pubmed database, published or pre-published during 2007, using keywords (nanomaterials or nanoparticles or nanostructures) and (toxicity or health). From the 238 articles, we chose to concentrate mainly on research into carbonaceous (carbon nanotubes [CNTs] and fullerenes) and metallic materials (pure metal, oxides), because of their relevance. The induction of oxidative stress was repeatedly reported, and new information on the movement of nanomaterials through membranes was publicized. Concerning CNTs, information was revealed on DNA damage in vitro and pulmonary and systemic in vivo effects. Several of the reports failed to follow recent expert recommendations concerning good practice for nanotoxicologic research, complicating the integration of the new data into the larger picture of safety of nanomaterials.     

Preventing contrast nephropathy: what is the best strategy? A review of the literature

Patients receiving radiocontrast for diagnostic and interventional procedures are at risk for developing contrast nephropathy (CN). In fact, radiocontrast nephropathy is currently the third leading cause of hospital-acquired renal failure. Understanding that CN has been associated with increased length of hospitalization and mortality, determining the best prevention strategy is of utmost importance. Patients at the greatest risk for developing acute renal failure are patients with diabetes and underlying renal insufficiency. Several therapies have been investigated for the prevention of CN; unfortunately, very few have shown a consistent benefit. Therapies that have been studied include saline hydration, N-acetylcysteine (NAC), theophylline, calcium channel blockers, diuretics, dopamine, endothelin receptor antagonists, atrial natriuretic peptide, angiotensin-converting enzyme inhibitors, and prostaglandin E-1. Using adequate hydration, using low-osmolar dyes, and minimizing the dose of contrast have all been shown to be effective in reducing CN and are considered the standard of care. While trials with many pharmacologic agents have produced conflicting results, intervention with NAC has also been promising. This article reviews the pathophysiology, risk factors, and therapies that are currently available for the prevention of CN.     

Are constipation drugs effective and safe to be used in children? A review of the literature

INTRODUCTION: Functional constipation is a common and often enduring problem in childhood. Although functional constipation is well defined by the Rome III criteria, these criteria have not always been integrated in general practice. Early diagnosis and treatment are key factors with respect to successful long-term outcome, as chronic constipation has a negative effect on the quality of life and is a burden for the public healthcare system. The safety of laxatives used for paediatric-functional constipation is based on well-designed trials carried out mostly in adults. Therefore, we conducted a review of the literature outlining the evidence for the efficacy and safety of laxatives used in chronic paediatric-functional constipation. AREAS COVERED: This review clearly shows a lack of large well-designed placebo-controlled trials in children with constipation. Therefore, any interpretation with regards to the evidence for the effectiveness or safety of laxatives used in children is difficult and we extended the search for side effects to the adult literature. EXPERT OPINION: In adults, new promising drugs are on the virtue of breaking through in the treatment of chronic constipation. Carrying out well-defined placebo-controlled trials in children should be the next step before using these drugs.