Non-dispensing pharmacists integrated into general practices as a new interprofessional model: a qualitative evaluation of general practitioners' experiences and views.

BACKGROUND: A new interprofessional model incorporating non-dispensing pharmacists in general practice teams can improve the quality of pharmaceutical care. However, results of the model are dependent on the context. Understanding when, why and how the model works may increase chances of successful broader implementation in other general practices. Earlier theories suggested that the results of the model are achieved by bringing pharmacotherapeutic knowledge into general practices. This mechanism may not be enough for successful implementation of the model. We wanted to understand better how establishing new interprofessional models in existing healthcare organisations takes place. METHODS: An interview study, with a realist informed evaluation was conducted. This qualitative study was part of the Pharmacotherapy Optimisation through Integration of a Non-dispensing pharmacist in primary care Teams (POINT) project. We invited the general practitioners of the 9 general practices who (had) worked closely with a non-dispensing pharmacist for an interview. Interview data were analysed through discussions about the coding with the research team where themes were developed over time. RESULTS: We interviewed 2 general practitioners in each general practice (18 interviews in total). In a context where general practitioners acknowledge the need for improvement and are willing to work with a non-dispensing pharmacist as a new team member, the following mechanisms are triggered. Non-dispensing pharmacists add new knowledge to current general practice. Through everyday talk (discursive actions) both general practitioners and non-dispensing pharmacists evolve in what they consider appropriate, legitimate and imaginable in their work situations. They align their professional identities. CONCLUSIONS: Not only the addition of new knowledge of non-dispensing pharmacist to the general practice team is crucial for the success of this interprofessional healthcare model, but also alignment of the general practitioners' and non-dispensing pharmacists' professional identities. This is essentially different from traditional pharmaceutical care models, in which pharmacists and GPs work in separate organisations. To induce the process of identity alignment, general practitioners need to acknowledge the need to improve the quality of pharmaceutical care interprofessionally. By acknowledging the aspect of interprofessionality, both general practitioners and non-dispensing pharmacists will explore and reflect on what they consider appropriate, legitimate and imaginable in carrying out their professional roles. TRIAL REGISTRATION: The POINT project was pre-registered in The Netherlands National Trial Register, with Trial registration number NTR-4389.

Effects of non-dispensing pharmacists integrated in general practice on medication-related hospitalisations.

AIMS: To evaluate the effect of non-dispensing pharmacists (NDPs) integrated in general practice on medication-related hospitalisations, drug burden index and costs in patients at high risk of medication problems (being 65 years or older and using 5 or more chronic medications). METHODS: This was a multicentre, nonrandomised, controlled intervention study with pre-post comparison (2013 vs June 2014 to May 2015) in 25 general practices in the Netherlands, comparing NDP-led care (intervention) with 2 current pharmaceutical care models (usual care and usual care plus). In the intervention group, 10 specially trained NDPs were employed in general practices to take integral responsibility for the pharmaceutical care. They provided a broad range of medication therapy management services both on patient level (e.g. clinical medication review) and practice level (e.g. quality improvement projects). In the control groups, pharmaceutical care was provided as usual by general practitioners and community pharmacists, or as usual plus, when pharmacists were additionally trained in performing medication reviews. RESULTS: Overall, 822 medication-related hospitalisations were identified among 11 281 high-risk patients during the intervention period. After adjustment for clustering and potential confounders, the rate ratio of medication-related hospitalisations in the intervention group compared to usual care was 0.68 (95% confidence interval: 0.57-0.82) and 1.05 (95% confidence interval: 0.73-1.52) compared to usual care plus. No differences in drug burden index or costs were found. CONCLUSIONS: In general practices with an integrated NDP, the rate of medication-related hospitalisations is lower compared to usual care. No differences with usual care plus were found.

Comparison of urine and oral fluid as matrices for screening of thirty-three benzodiazepines and benzodiazepine-like substances using immunoassay and LC-MS(-MS).

Benzodiazepines are the most frequently detected medicinal drugs in drivers. The use of benzodiazepines is associated with an increased road accident risk. In this study, the presence of benzodiazepines detected by liquid chromatography-(tandem) mass spectrometry [LC-MS(-MS)] in oral fluid and urine samples obtained from drivers stopped during a roadside survey was compared. In addition, the sensitivity and selectivity of enzyme multiplied immunoassay technique (EMIT II Plus) relative to LC-MS(-MS) was determined for both matrices. A total number of 1,011 urine samples were collected and screened for benzodiazepines using immunoassay (IA) (EMIT II Plus; cutoff 300 ng/mL). In the IA-positive (n = 25) and a group of randomly selected negative urine samples (n = 79), the presence or absence of benzodiazepines was confirmed by LC-MS-MS after deglucuronidation. The corresponding oral fluid samples (n = 101, 3 samples omitted), were analyzed by LC-MS(-MS) and IA (EMIT II Plus; cutoff 10 ng/mL). The presence of benzodiazepines was demonstrated by LC-MS-(MS) in all IA-positive urine samples, but in only four corresponding oral fluid samples. Concentrations in oral fluid were, one substance excepted, lower than in urine. The sensitivity and specificity of EMIT II Plus were better by using urine as matrix for screening of benzodiazepines than by using oral fluid. The results show that benzodiazepines are detectable in oral fluid. More research has to be done to determine the pharmacokinetic profile of the different benzodiazepines in oral fluid and to study the relationship between dose, concentration (in oral fluid and blood), and impairment.

The role of albumin conformation in the binding of diazepam to human serum albumin.

The effect of hydrogen, chloride and calcium ions on the binding of diazepam to human serum albumin has been studied by circular dichroism and equilibrium dialysis. In all cases the molar ellipticity of the diazepam-albumin complex increases with pH over the pH range 5 to 9. Under these conditions the free concentration of diazepam at a constant low drug to protein ratio decreases with pH. This free concentration is higher in the presence of chloride and calcium ions. With a two state conformational model for albumin it was shown, that the pH dependences of molar ellipticity of the diazepam-albumin complex and of the free concentration of diazepam are linked. It was demonstrated that the N-B transition of albumin is involved in the pH dependent binding of diazepam. The consequences of these findings for equilibrium dialysis procedures in determining free plasma levels of diazepam are discussed.

Drug use and the severity of a traffic accident.

Several studies have showed that driving under the influence of alcohol and/or certain illicit or medicinal drugs increases the risk of a (severe) crash. Data with respect to the question whether this also leads to a more severe accident are sparse. This study examines the relationship between the use of alcohol, illicit drugs and/or medicinal drugs and the severity of an accident within a group of drivers that were involved in a crash in The Netherlands. Blood samples of 993 drivers, collected in the period from October 1998 through September 1999, were linked to accident characteristics as available from the National Transport Research Centre. The outcome measure was the severity of the accident. An accident was considered severe when the accident had resulted in hospital admission or death. All the blood samples obtained after the accident were screened for the presence of alcohol, illicit drugs (opiates, amphetamines and amphetamine-like substances, cocaine and metabolites, methadone, cannabinoids) and medicinal drugs (benzodiazepines, barbiturates and tricyclic antidepressants). The strength of the associations between exposure to the different classes of alcohol/drugs/medicines and the severity of the accident was evaluated using logistic regression analysis and were expressed as odds ratios (OR), adjusted for age, gender, time of the day, day of the week and urban area. The most frequently detected drugs were cannabinoids, benzodiazepines and cocaine. Our results showed no clear association between the use of alcohol, illicit drug and/or medicinal drug use and the severity of the accident. Given the process of obtaining blood samples from drivers involved in accidents and the retrospective nature of the study, we cannot rule out the occurrence of selection bias. Therefore, our findings need further confirmation.

Evidence for distinct consecutive steps in the neutral to base transition of human serum albumin.

The neutral to base transition in human serum albumin has been studied by means of circular dichroism and equilibrium dialysis using nitrazepam as the non-covalently bound circular dichroic probe. Spectroscopically two transitions were observed over the pH range 5.5-8.5, whereas dialysis data point to only one transition occurring in the latter part of the pH region studied. Both pH dependences could only be correlated if it is assumed that the neutral to base transition consists of at least two distinct consecutive steps.

Psychomotor performance and real driving performance of outpatients receiving diazepam.

The primary aim of this study was to compare task performance in a laboratory test and real driving performance of outpatients receiving diazepam medication with those of control subjects. Plasma and saliva samples were taken to investigate a level-response relationship. Real driving performance was measured by trained observers. The design of the laboratory test was based on a vigilance task (high attention) directly followed by a simple eye-hand coordination tasks (low attention). Twenty-two males participated in the study. Diazepam was given orally by prescription, mostly as a maintenance dose of 5 mg three times a day. Patients receiving diazepam showed impaired performance in the driving test and the low-attention task. Furthermore, the results indicate no relationship between plasma or saliva levels of diazepam and/or its metabolite N-desmethyldiazepam and real driving performance and/or laboratory task performance.

Clinical pharmacy in primary care and community pharmacy.

The role of the community pharmacist involved in primary care has been undergoing change. In the late 1970s and early 1980s, developments in computerized medication surveillance within the Netherlands enabled pharmacists to react to prescriptions and detect inappropriate pharmacotherapy in community pharmacy sites. This activity became more clinically or patient-oriented in the late 1980s. In the early 1990s, pharmaceutical care was introduced in community pharmacy practice, and emphasis was given to providing patient-centered care and documenting cognitive services. The key features of pharmaceutical care provided in the primary care setting are described based on a review of the literature and on experiences in the Netherlands. Patient outcomes have yet to be shown to be improved by community pharmacy practice; methods for measuring performance are still lacking. Methods to evaluate the extent of integration of community pharmacy services into the clinical team are also lacking but are needed in order to define the future role of community pharmacists in the primary care setting. Integrated care needs to be developed in the Netherlands in order to present the next phase in the process of the "pharmaceutical evolution."

Quantitative analysis of 33 benzodiazepines, metabolites and benzodiazepine-like substances in whole blood by liquid chromatography-(tandem) mass spectrometry.

A quantitative method using high-performance liquid chromatography-mass spectrometry (LC-MS, ion trap) after matrix supported liquid-liquid extraction is described for the simultaneous determination in whole blood of 33 benzodiazepines including metabolites and benzodiazepine-like substances. The limits of detection (LOD) range from 0.0001 to 0.0126 mg/l. Linearity is satisfactory for all compounds. The extraction recoveries for the benzodiazepines in whole blood are between 60 and 91%, desmethyldiazepam, OH-bromazepam and brotizolam excepted. Selectivity, accuracy and precision are satisfactory for clinical and forensic purposes.

Psychoactive substance use and the risk of motor vehicle accidents.

The driving performance is easily impaired as a consequence of the use of alcohol and/or licit and illicit drugs. However, the role of drugs other than alcohol in motor vehicle accidents has not been well established. The objective of this study was to estimate the association between psychoactive drug use and motor vehicle accidents requiring hospitalisation. A prospective observational case-control study was conducted in the Tilburg region of The Netherlands from May 2000 to August 2001. Cases were car or van drivers involved in road crashes needing hospitalisation. Demographic and trauma related data was collected from hospital and ambulance records. Urine and/or blood samples were collected on admission. Controls were drivers recruited at random while driving on public roads. Sampling was conducted by researchers, in close collaboration with the Tilburg police, covering different days of the week and times of the day. Respondents were interviewed and asked for a urine sample. If no urine sample could be collected, a blood sample was requested. All blood and urine samples were tested for alcohol and a number of licit and illicit drugs. The main outcome measures were odds ratios (OR) for injury crash associated with single or multiple use of several drugs by drivers. The risk for road trauma was increased for single use of benzodiazepines (adjusted OR 5.1 (95% Cl: 1.8-14.0)) and alcohol (blood alcohol concentrations of 0.50-0.79 g/l, adjusted OR 5.5 (95% Cl: 1.3-23.2) and >or=0.8 g/l, adjusted OR 15.5 (95% Cl: 7.1-33.9)). High relative risks were estimated for drivers using combinations of drugs (adjusted OR 6.1 (95% Cl: 2.6-14.1)) and those using a combination of drugs and alcohol (OR 112.2 (95% Cl: 14.1-892)). Increased risks, although not statistically significantly, were assessed for drivers using amphetamines, cocaine, or opiates. No increased risk for road trauma was found for drivers exposed to cannabis. The study concludes that drug use, especially alcohol, benzodiazepines and multiple drug use and drug-alcohol combinations, among vehicle drivers increases the risk for a road trauma accident requiring hospitalisation.

The stability of benzodiazepines in saliva.

The stability of some selected benzodiazepines in saliva has been studied. The benzodiazepines nitrazepam and clonazepam were found to be unstable in saliva at room temperature and nitrazepam was converted into 7-aminonitrazepam. The conversion rate of nitrazepam was strongly dependent on the composition of the subject's saliva. Nitro-reduction may complicate the use of saliva in epidemiological studies on drugs and driving. This could occur particularly if saliva drug concentrations are to be used as a quantitative measure of driving performance.

Complications in correlation studies between serum, free serum and saliva concentrations of nitrazepam.

The relation between free serum and saliva concentrations of nitrazepam in healthy male volunteers has been studied. It was found that the average value of free serum concentrations from all volunteers was twice the average value of corresponding saliva concentrations. Sometimes mean values of serum, free serum and saliva concentrations are used in correlation studies. However, the data from individual volunteers showed that there was no correlation between them. Statistics can easily introduce false pictures for correlations between free serum and saliva concentrations of nitrazepam, whereas no correlation could be found on the basis of results from individuals. In response studies such as the effects of drugs on driving performance, the free serum and saliva concentrations of a drug from individual volunteers should therefore be considered. This will complicate the use of saliva in epidemiological studies on drugs and driving.

The role of buffer composition during equilibrium dialysis in determining concentrations of free diazepam in serum.

Serum levels of free diazepam as determined with equilibrium dialysis depend on the composition of the dialyzing buffer with respect to Ca2+ and Cl-. Physiological concentrations of these ions double the obtained free serum levels, in line with data of diazepam containing albumin solutions. The diazepam binding capacity of serum was found to be higher than that of albumin alone, suggesting that albumin is probably not the only diazepam binding protein in serum. Evidence was also found that the diazepam binding to these other serum proteins is dependent on the presence of Ca2+ and Cl-.

Non-response in a pharmacy and patient-based intensive monitoring system: a quantitative study on non-response bias and reasons for non-response.

OBJECTIVE: Worldwide pharmacists play an increasingly important role in pharmacovigilance. Lareb Intensive Monitoring (LIM) in the Netherlands is a new form of active pharmacovigilance where pharmacists play a key role. Patients using drugs which are monitored are identified in the pharmacy and invited to participate in the active monitoring. Not all invited patients participate. This study aimed to investigate non-response bias in LIM, as well as reasons for non-response in order to identify barriers to participation. METHODS: The study population consisted of patients who received a first dispensation of an antidiabetic drug monitored with LIM between 1 July 2010 and 28 February 2011. Possible non-response bias was investigated by comparing age, gender and the number of drugs used as co-medication. Reasons for non-response were investigated using a postal questionnaire. KEY FINDINGS: Respondents were on average 4.5 years younger than non-respondents and used less co-medication. There were no differences regarding gender. The main reason for non-response was that information in the pharmacy was lacking. CONCLUSION: Differences between respondents and non-respondents should be taken into account when analysing and generalising data collected through LIM, as this might contribute to non-response bias. The relatively high response to the postal questionnaire, together with the answers about reasons for non-response, show that patients are willing to participate in a web-based intensive monitoring system, when they are informed and invited in the pharmacy.

Pharmacist-led intervention study to improve drug therapy in asthma and COPD patients.

BACKGROUND: Pharmacists can play an important role in identifying and instructing pulmonary patients on their inhalation techniques in their patient contacts when dispensing inhalation medication. Pharmacy dispensing data can be used to identify inappropriate drug use in asthma and chronic obstructive pulmonary disease (COPD) patients. Recent studies found beneficial effects of pharmacy care services in improving drug adherence of pulmonary patients. However, large-scale and rigorous evaluations on pharmacist-led interventions in community care settings to enhance evidence-based drug treatment in patients with asthma and COPD seems to be lacking and results from studies on pharmacist-led interventions for pharmacotherapy improvements are inconsistent. This study evaluated the effectiveness of pharmacist-led interventions on suboptimal drug use patterns with asthma or COPD medication with substantial numbers of pharmacies and patients involved. SETTING: A prospective cohort study in a group of community pharmacies (intervention group) with a matched control group of Dutch community pharmacies was conducted between May 2011 and February 2012. Algorithms on 19 potential problems with asthma or COPD medication in a national dispensing database were used to signal patients to pharmacists of the intervention group (IG). METHODS: IG pharmacists selected patients for comprehensive care by a structured program. Changes in problems were measured during 10 months in selected and all users of asthma and COPD medication of IG pharmacies and in compared to a control pharmacies (CG) without the structured program. Primary outcome was reduction of oral high dosage corticosteroids or antibiotics (HDT). Secondary outcomes were changes in the persistence of 19 potential problems in the IG compared to CG. RESULTS: In the 107 IG pharmacies, 3,757 patients were selected for comprehensive care from totally 102,497 asthma or COPD patients and compared with 105,507 patients from 105 CG pharmacies. The mean number of HDT decreased in selected IG patients by an additional 0.54 (95 % CI 0.21-0.86) HDT treatments. From the problems with specific COPD and asthma medication, all problems decreased additionally to the CG within the total asthma or COPD population from the IG. Within the selected IG population the following problems decreased additionally for obsolete medication by 35 % (95 % CI 6-54 %), contra-indicated medication by 61 % (95 % CI 38-75 %) and lower use of powder inhalers in elderly patients by 29 % (95 % CI 13-42 %). CONCLUSION: Community pharmacists actively providing comprehensive pharmacy care could improve effective treatment in asthma and COPD patients and thereby decrease the number of prescriptions for exacerbations for these patients.

Medication review practices in European countries.

BACKGROUND: Medication review procedures have been developed in many countries to improve rational and safe medication use. The similarities, comprehensiveness, and effectiveness of these procedures has not been assessed, or compared. OBJECTIVE: The aim of this study was to explore medication review practices in European countries. METHODS: An online survey was sent to 32 European countries (all 28 European Union countries and 4 other European countries) by email to one person in each country known to be aware of medication review practices in their country in May 2011. The informants were identified through Pharmaceutical Group of European Union. To complement and validate the information received through Pharmaceutical Group of European Union, medication review experts involved in Pharmaceutical Care Network Europe were contacted. The survey assessed comprehensiveness of the medication review procedures classified according to 3 types in terms of settings; access to patient clinical information; patient involvement; availability of documentation and information; collaboration with the physician; quality control, and training required. RESULTS: Almost two thirds (64%) of the 25 European countries which responded (response rate 78%) indicated having at least one type of medication review procedure in their country. In the community setting prescription (type I) and adherence (type II) medication reviews were the most common (established in 9 and 11 countries, respectively). More comprehensive type III clinical medication reviews requiring access to clinical patient information were still rare, and just being established in 6 countries. CONCLUSIONS: Medication review procedures are becoming common in health care throughout Europe, however improving their comprehensiveness would require better access to patient information for those professionals conducting clinical medication reviews. In addition to benchmarking, the inventory can enhance cooperation between countries and stakeholders involved in medication review practice development nationally and internationally.

The relation between the blood benzodiazepine concentration and performance in suspected impaired drivers.

Several experimental studies have shown a negative influence of benzodiazepines on driving skills. The objective of this study is to study the relationship between the blood concentration of benzodiazepines and the influence on performance in field sobriety tests. A retrospective case file evaluation was conducted to select cases of drivers, tested positive for benzodiazepines only in the period from January 1999 to December 2004. Drivers were grouped into the categories sub therapeutic, therapeutic or elevated concentrations. The outcome of the tests (walking, walking after turn, nystagmus, Romberg's test, behavior, pupils and orientation) was binomial. A Chi square test was used to assess differences in proportions of the categorized cases. In total 171 cases were included. Observations of behavior (n=137; p<0.01), walking (n=109; p<0.01), walking after turn (n=89; p=0.02) and Romberg's test (n=88; p<0.05) were significantly related to the benzodiazepine concentration. There was no significant relation between benzodiazepine concentration and effect on pupil size, nystagmus or orientation. The results of our study indicate a relation between the concentration of benzodiazepines and the results of some performance tests. More effort is needed to standardize the tests and to determine the sensitivity and selectivity of the tests for benzodiazepines.

The relation between the use of psychoactive substances and the severity of the injury in a group of crash-involved drivers admitted to a regional trauma center.

OBJECTIVE: There is much evidence that driving under the influence of alcohol and/or drugs of abuse is related to an increased accident risk. A remaining question is whether the use of psychoactive substances is also related to clinically more severe accidents. The aim of this study is to explore the relationship between the use of psychoactive substances and the injury severity in a group of crash-involved drivers. METHODS: The study group included all injured car drivers, admitted to the regional trauma center, in the period from May 2000 until August 2001. The outcome of interest was the severity of injury, measured by using the Injury Severity Score (ISS). The determinant was the presence of psychoactive substances in blood and urine samples. Psychoactive substances tested for were alcohol, amphetamines, barbiturates, benzodiazepines, cannabis, methadone, opiates, and tricyclic antidepressants in blood and urine. RESULTS: The number of injured car drivers included in this study was 106. Overall, 43% (46/106) of the drivers tested positive for at least one psychoactive substance. Comparison of the means of the log ISS suggests that there is no significant difference between drivers who tested positive for alcohol and/or drugs, compared to drivers tested negative. CONCLUSION: The results of this study support the hypothesis that there is no clear association between use of psychoactive substances and the severity of crash-related injury.

The Electronic Pharmaceutical Dossier: an effective aid to documenting pharmaceutical care data.

Pharmaceutical care involves decision-making based upon communication and judgements to avoid, initiate maintain or discontinue pharmacotherapy. After establishing patient-pharmacist relationships and implementing collaboration with physicians based upon consensus guidelines, relevant information should be collected and processed in order to determine drug therapy problems and desired treatment outcomes. This paper describes in short the development of a 'care concept' for pharmaceutical care and focuses in particular on the fully integrated functions of a pharmacy automation system (Pharmacom) for documenting relevant data and supporting the processing of drug therapy.

Driving tests with patients.

Mental illness and the use of psychotropic drugs are considered to influence driving skills of patients. However, studies which indicate the relative contributions of these factors are rare. It is emphasized that for measuring the effects of psychotropic drugs on driving performance of patients, real driving tests are needed. Actual driving and psychomotor performance of patients receiving diazepam, and patients and healthy volunteers receiving mebhydrolin were measured to illustrate the use of real driving tests. The results of both studies are discussed in terms of problems associated with the application of these tests. Patient recruitment is considered to be a major problem. To draw conclusions under these circumstances is extremely difficult, but still acceptable in comparison with the limitations and methodological difficulties of the more commonly used laboratory tests. Some guidelines for driving tests with patients are given.