[The conversation with the patient is essential for good pharmacotherapeutic care]. / Het gesprek met de patiënt is essentieel voor goede farmacotherapeutische zorg.

Frail elderly with polypharmacy are at greater risk of preventable medication-related health damage. To improve medication safety, the healthcare field prepared, in consultation with the Dutch Health Care Inspectorate, a number of guidelines and standards containing conditions for safe prescribing. According to these standards the active involvement of patients by health care professionals is essential for good pharmacotherapeutic care. However, two studies with patients show that there is still room for improvement. According to patients, they can be (even) better informed about changes in their medication. Also the caregivers could communicate more clearly who is the central contact point and who is ultimately responsible for the medication. Patients are not sufficiently informed on this. Furthermore, there is uncertainty about how and why medication reviews are performed. More explanation to patients about this is desirable. In addition, patients experience that keeping their medication list up to date and transferring medication data between health care providers could be improved. Finally, a group of patients welcomes the opportunity to co-decide on changes in their medication. In order to prescribe safely, it is crucial that caregivers actively involve patients in pharmacotherapeutic care and really enter into conversation with them about their medication.

Characterization of Apps and Other e-Tools for Medication Use: Insights Into Possible Benefits and Risks.

BACKGROUND: In the past years, an enormous increase in the number of available health-related applications (apps) has occurred, from approximately 5800 in 2011 to over 23,000 in 2013, in the iTunes store. However, little is still known regarding the use, possible effectiveness, and risks of these applications. In this study, we focused on apps and other e-tools related to medicine use. A large subset of the general population uses medicines and might benefit from tools that aid in the use of medicine. OBJECTIVE: The aim of the present study was to gain more insight into the characteristics, possible risks, and possible benefits of health apps and e-tools related to medication use. METHODS: We first made an inventory of apps and other e-tools for medication use (n=116). Tools were coded by two independent researchers, based on the information available in the app stores and websites. Subsequently, for one type of often downloaded apps (aimed at people with diabetes), we investigated users' experiences using an online questionnaire. RESULTS: Results of the inventory show that many apps for medication use are available and that they mainly offer simple functionalities. In line with this, the most experienced benefit by users of apps for regulating blood glucose levels in the online questionnaire was "information quick and conveniently available". Other often experienced benefits were improving health and self-reliance. Results of the inventory show that a minority of the apps for medication use has potentially high risks and for many of the apps it is unclear whether and how personal data are stored. In contrast, online questionnaire among users of apps for blood glucose regulation indicates that they hardly ever experience problems or doubts considering reliability and/or privacy. Although, respondents do mention to experience disadvantages of use due to incomplete apps and apps with poor ease of use. Respondents not using app(s) indicate that they might use them in the future if reliability of the apps and instructions on how to use them are more clear. CONCLUSIONS: This study shows that for apps and e-tools related to medicine use a small subset of tools might involve relatively high risks. For the large group of nonmedical devices apps, risks are lower, but risks lie in the enormous availability and low levels of regulation. In addition, both users and nonusers indicated that overall quality of apps (ease of use, completeness, good functionalities) is an issue. Considering that important benefits (eg, improving health and self-reliance) are experienced by many of the respondents using apps for regulating blood glucose levels, improving reliability and quality of apps is likely to have many profits. In addition, creating better awareness regarding the existence and how to use apps will likely improve proper use by more people, enhancing the profits of these tools.

[Pharmacogenetics in primary health care: implementation and future expectations]. / Farmacogenetica in de eerstelijnszorg: toepassing en toekomstverwachtingen.

Personalised medicine is a targeted approach to the prevention, diagnosis and treatment of disorders on the basis of the specific genetic profile of the patient. Pharmacogenetics research shows that differences in the genetic profile of patients explain the interindividual differences in efficacy and side effects of medicines. Although there are high expectations of personalised medicine and pharmacogenetics in healthcare, both are only used to a limited extent to date. Pharmacogenetics seems particularly important in diseases with a poor prognosis and treatments with potentially serious side effects. Pharmacogenetics testing is reimbursed in the case of serious side effects or unexpected ineffectiveness. 95% of patients in the Netherlands have at least one abnormality in the panel of genes for which guidance is available. The KNMP (Royal Dutch Pharmacists' Association) provides dosing advice based on genotype for 80 medicines, 27 of which are regularly prescribed in primary health care.

[Pharmacotherapeutic care for vulnerable groups with polypharmacy has to get better]. / Farmacotherapeutische zorg voor kwetsbare groepen met polyfarmacie moet beter.

Pharmacotherapeutic care of the elderly and psychiatric patients is complex and risky, because polypharmacy, the chronic use of five or more medications by a patient, is highly prevalent in these groups. Polypharmacy is a risk factor for medication related hospital admissions. The Dutch Health Care Inspectorate (IGZ) adopted 'improving care for the elderly' and 'improving medication safety' as spearheads. In order to provide input to IGZ enforcement policy, RIVM investigated the risks of polypharmacy as well as the measures that might limit these risks. This study shows that over- and undertreatment frequently occur. This may be caused by the fact that a physician sometimes does not know which medicines for a patient were prescribed, changed or stopped by other physicians. It was also found that psychiatric patients often experience side effects or interactions that are specific to psychiatric medicines, sometimes in combination with somatic medication. Various guidelines to improve medication safety are available, but several bottlenecks hamper the implementation, for example in the area of collaboration, direction and transfer of information on medication. But also ICT is insufficiently facilitating and physicians have too little knowledge of polypharmacy in the frail populations. The health care sector is taking various initiatives to remove bottlenecks. IGZ will from 2015 in all health care domains focus on four guidelines that describe the conditions for sensibly prescribing medication to frail people with polypharmacy.

Equivalence considerations for orally inhaled products for local action-ISAM/IPAC-RS European Workshop report.

The purpose of this article is to document the discussions at the 2010 European Workshop on Equivalence Determinations for Orally Inhaled Drugs for Local Action, cohosted by the International Society for Aerosols in Medicine (ISAM) and the International Pharmaceutical Consortium on Regulation and Science (IPAC-RS). The article summarizes current regulatory approaches in Europe, the United States, and Canada, and presents points of consensus as well as ongoing debate in the four major areas: in vitro testing, pharmacokinetic and pharmacodynamic studies, and device similarity. Specific issues in need of further research and discussion are also identified.

Demonstrating Bioequivalence of Locally Acting Orally Inhaled Drug Products (OIPs): Workshop Summary Report.

This March 2009 Workshop Summary Report was sponsored by Product Quality Research Institute (PQRI) based on a proposal by the Inhalation and Nasal Technology Focus Group (INTFG) of the American Association of Pharmaceutical Scientists (AAPS). Participants from the pharmaceutical industry, academia and regulatory bodies from the United States, Europe, India, and Brazil attended the workshop with the objective of presenting, reviewing, and discussing recommendations for demonstrating bioequivalence (BE) that may be considered in the development of orally inhaled drug products and regulatory guidances for new drug applications (NDAs), abbreviated NDAs (ANDAs), and postapproval changes. The workshop addressed areas related to in vitro approaches to demonstrating BE, biomarker strategies, imaging techniques, in vivo approaches to establishing local delivery equivalence and device design similarity. The workshop presented material that provided a baseline for the current understanding of orally inhaled drug products (OIPs) and identified gaps in knowledge and consensus that, if answered, might allow the design of a robust, streamlined method for the BE assessment of locally acting inhalation drugs. These included the following: (1) cascade impactor (CI) studies are not a good 2 predictor of the pulmonary dose; more detailed studies on in vitro/in vivo correlations (e.g., suitability of CI studies for assessing differences in the regional deposition) are needed; (2) there is a lack of consensus on the appropriate statistical methods for assessing in vitro results; (3) fully validated and standardized imaging methods, while capable of providing information on pulmonary dose and regional deposition, might not be applicable to the BE of inhaled products mainly due to the problems of having access to radiolabeled innovator product; (4) if alternatives to current methods for establishing local delivery BE of OIPs cannot be established, biomarkers (pharmacodynamic or clinical endpoints) with a sufficiently steep dose-response need to be identified and validated for all relevant drug classes; and (5) the utility of pharmacokinetic studies for evaluating "local pulmonary delivery" equivalence deserves more attention. A summary of action items for seminars and working groups to address these topics in the future is also presented.

Storage instructions for inhalation capsules: consequences of incorrect storage and adherence in daily practice.

The objective was to study the influence of storage conditions on the quality of inhalation capsules and to investigate patients' knowledge and adherence to storage instructions. Inhalation capsules marketed in the Netherlands were stored at normal (20°C/60% relative humidity) and dry (20°C/25% relative humidity) conditions during 34 days and checked for brittleness. After 1 day of storage at normal conditions, no brittleness was perceived. Longer periods and dry conditions increased the risk of brittleness. Only tiotropium capsules resisted all test situations. Subsequently, patients using inhalation capsules were sent a questionnaire in order to investigate their knowledge and actual behavior regarding storage of the capsules. Adherence to the required storage instructions was achieved by only 31.8% of all patients. Inferior storage locations turned out to be the main problem, 58.7% of the patients applied an incorrect place. Knowledge of the required storage instructions was lacking in 83.6% of all patients. It is concluded that the majority of patients store their inhalation capsules incorrectly and have insufficient knowledge of the appropriate storage conditions. Incorrectly stored capsules may become brittle and cause splintering during inhalation. The feeling of splinters in the mouth/throat may reduce the patient's confidence in the product's quality and affect compliance.

The therapeutic index of locally acting inhaled drugs as a function of their fine particle mass and particle size distribution: a literature review.

The therapeutic index (TI) of locally acting inhaled drug products depends on a number of parameters and processes: the particle size distribution of the inhaled aerosol, the dose-efficacy response curves at the deposition sites, the amount of drug absorbed into the systemic circulation from the lung as well as the gastrointestinal (GI) tract, and the dose-effect curves for the different adverse drug reactions. In this review, we present qualitative scenarios, combining these effects and showing the possible influence of an envisaged change in the particle size distribution in the inhaled dose of a locally acting drug product on the TI. These scenarios are a valuable tool in the development of inhalation drug products. As a surrogate for the inhaled dose in vivo, we use the fine particle mass (FPM), measured by in vitro measurements. Using these scenarios, we reviewed the literature on bronchodilators and corticosteroids for reported associations between a change in the FPM and/or particle size distribution within the FPM, and the TI. We conclude that decreasing the particle size of an inhalation product may alter the TI both in a positive as well as a negative sense. So, smaller particle are not always better.