Early identification of long-term poor adherence in ambulatory patients.
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Publications and source records attributed to Eibert R Heerdink.
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BACKGROUND: In the Netherlands, community pharmacists and general practitioners (GPs) collaborate in pharmacotherapy audit meetings (PTAMs) to optimize pharmacotherapy. OBJECTIVE: To identify associations between the quality level of PTAMs and characteristics of pharmacists. METHODS: We used a cross-sectional questionnaire design in a Dutch general practice and community pharmacy setting to estimate the contribution of pharmacists to the quality level of PTAMs. The questionnaire was sent to 123 community pharmacies working closely with 104 GP practices. The outcome variable was the quality level of PTAMs. The questionnaire provided information on 4 topics that were used as independent variables: characteristics of the PTAMs, provision of pharmacotherapy activities, characteristics of the pharmacists, and characteristics of the pharmacies. RESULTS: In total, 109 (88.6%) pharmacists completed the questionnaire, with 103 participating in 62 different PTAMs. Seventeen pharmacists participated in level 1 PTAMs (lowest level), 57 in level 2, 21 in level 3, and 8 in PTAMs at the highest level. The multinomial logistic regression identified only one significant association: pharmacists who participated in the highest quality level reported that they undertake initiatives in PTAMs (OR 2.98; 95% CI 1.07 to 8.26) more frequently compared with pharmacists participating on the lowest level. CONCLUSIONS: In light of existing evidence, the role of pharmacists in PTAMs seems to be important. Pharmacists should create a distinct profile of their expertise, allowing them to professionalize PTAMs by undertaking more initiatives. PTAMs offer pharmacists a great opportunity to become integral members of the prescribing process.
BACKGROUND: Databases are frequently used for pharmacoepidemiological research. However, most of these databases consist either of prescribing, dispensing or administrative data and therefore lack insight in the interaction between the several health professionals around the patient. METHODS: To determine the success rate of linking records from the dispensing database of the Foundation for Pharmaceutical Statistics to the prescribing database of the second Dutch national survey of general practice, conducted by NIVEL (Netherlands Institute for Health Services Research), a deterministic record linkage approach was used with patient and prescription characteristics as matching variables between the two databases. RESULTS: The catchment area included 123 community pharmacies, 90 GP practices and approximately 170,000 unique patients. Overall 110,102 (64.8%) unique patients were linked using the matching variables patient's gender, year of birth, the 4-digit part of the postal code, date of dispensing/prescribing and ATC-code. The final database contains of the 110,102 both prescribing data from 83 GP practices and dispensing data of 112 community pharmacies. CONCLUSION: This study shows that linkage of dispensing to prescribing data is feasible with a combination of patient characteristics, such as gender, year of birth and postal code, and prescription characteristics like prescription date and ATC-code. We obtained a linkage proportion of 64.8% resulting in complete prescribing and dispensing history of 110,102 patients. This offers an opportunity to gain insight in the mechanisms and factors influencing drug utilisation in general practice.
PURPOSE: The aim of this study was to evaluate the effect of the length of the drug free period on incidence measurements as well as on cohort characteristics in users of antidepressants. METHODS: The study population consisted of patients aged 18 years or older who filled a prescription for an antidepressant drug in the Netherlands, between October 2001 and September 2002. One-year incidence of antidepressant drug use was estimated using drug free periods varying in length from 1 month to 9 years. In addition, we evaluated what effect the drug free period has on cohort characteristics by comparing a cohort of first time antidepressant drug users defined using a 9-year drug free period with cohorts using 6, 12 and 24 months drug free period. RESULTS: When using a 6-month drug free period the measured incidence was about 32 per 1,000 individuals (95%CI: 31.3, 32.6) while the measured incidence was 27.5 (95%CI: 26.9, 28.1), 23.5 (95%CI: 22.9, 24.0) and 17.2 (95%CI: 16.7, 17.7) per 1,000 individuals when using a 12-month, 24 month respectively a 9-year drug free period. Furthermore, the prevalence of characteristics in inception cohort studies changes when using different drug free periods. CONCLUSION: Altering the drug free period from a short to a longer one results in decreased incidence. Furthermore, for inception cohorts where first time drug use is an inclusion criterion the drug free period can influence the prevalence of cohort characteristics and for short drug free periods give biased estimates.
PURPOSE: Discontinuation with treatment is a major problem in the treatment of hypertension. The objective of our study was to assess the association between non-compliance and discontinuation in patients who started using antihypertensive monotherapy. METHODS: A nested case-control study within a cohort of new users of antihypertensive drugs between 1st January 1999 and 31st December 2002 was performed. We used data from the PHARMO database, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950,000 subjects. Cases discontinued their use of antihypertensive monotherapy and were not switched to other antihypertensive treatment, controls stayed on their initially prescribed monotherapy. Conditional logistic regression was used to calculate odds ratios (OR) and their 95% confidence intervals (CI). RESULTS: In a cohort of 39,714 new users of antihypertensive drugs, we identified 9111 cases and 9111 matched controls. The percentage of non-compliant patients (compliance < 80%) among cases and controls was 14.0% and 5.8%, respectively [OR 2.86 (95%CI: 2.52-3.24)]. Patients who used less than 90 days had a higher risk on discontinuation [OR 3.10 (95%CI: 2.67-3.59)] than patients who used more than 90 days [OR 2.28 (95%CI: 1.79-2.92)]. The association was generally similar among males and females, among the different types of antihypertensives and among the different age groups. CONCLUSION: In patients who start antihypertensive monotherapy, non-compliance is often followed by discontinuation of this antihypertensive treatment. The pharmacy medication history is a valuable tool for physicians to identify patients who have a high risk on discontinuation with antihypertensive treatment.
AIM: To get more insight into factors that influence compliance with the use of methylphenidate. METHODS: 22 pharmacies detected children who used methylphenidate. Their parents were sent a questionnaire on the use of methylphenidate. In a case-control study, the influence of patient- and drug-related factors on compliance, as reported by parents, was determined. RESULTS: Parents returned 117 (75%) of 157 questionnaires sent out. Of these, 47.8% of the children missed a dose two times a month or more. Forgetting to take the medication (87.9%) was the most important reason. The case-control study showed that children of 16-18 y were more likely to miss doses. Other patient- and drug-related factors did not influence the missing of doses. CONCLUSION: A number of known determinants for compliance do not influence the missing of doses of methylphenidate. With about 80% of the parents reporting that their child missed doses of methylphenidate less than 5 times per month, compliance was quite good for the majority of the children.
BACKGROUND: Multiple-characteristics decision-making (MCDM) models can be used to calculate a score, based on a set of characteristics, for a number of alternative drugs or drug classes to allow comparison between them and thus enhance evidence-based pharmacotherapy. OBJECTIVE: To compare two MCDM models, Simple Additive Weighting (SAW) and Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS), in determining first-line antihypertensive drug class. METHODS: Five different classes of antihypertensive drugs were analyzed: diuretics, beta-adrenoceptor antagonists (beta-blockers), dihydropyridine calcium channel blockers (DHP-CCBs), ACE inhibitors, and angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]). Four characteristics were deemed relevant for the determination of first-line antihypertensive drug class: effectiveness, persistence with treatment as a measure of tolerability, cost, and clinical experience. Weight factors were determined by sending questionnaires to cardiologists, pharmacists, general practitioners (GPs), and internists in The Netherlands. Absolute scores for the characteristics were determined from literature (effectiveness and persistence) and health insurance data (costs and clinical experience). RESULTS: Ninety-two cardiologists (33% of those sent the questionnaire), 90 GPs (31%), 87 internists (31%), and 123 pharmacists (43%) completed the questionnaire. Among all professions, according to both SAW and TOPSIS, ACE inhibitors were ranked as the first-line antihypertensive drug class, typically followed by beta-blockers. CONCLUSION: Both SAW and TOPIS analyses, using weight factors assigned by cardiologists, pharmacists, GPs, and internists from The Netherlands, rank ACE inhibitors as the first choice among antihypertensive drug classes for the treatment of uncomplicated hypertension. Both methods are valuable tools in the development of evidence-based pharmacotherapy.
OBJECTIVE: To determine the doses of haloperidol as a comparator drug in randomized controlled trials (RCTs) with atypical antipsychotics in patients with schizophrenia and to compare these doses with the officially recommended doses for haloperidol in the United States and the United Kingdom. DATA SOURCES: We searched for RCTs conducted and published in English in full before January 2005 in which atypical antipsychotics were compared with haloperidol for the treatment of schizophrenia. We searched for Cochrane Reviews in which 1 of the following atypical antipsychotics was evaluated for the treatment of patients with schizophrenia, schizophreniform psychosis, or other primary psychosis: amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, sertindole, and ziprasidone. For the gap between the end point of inclusion of the studies in the Cochrane Reviews and January 2005, we electronically searched the Cochrane Central Register of Controlled Trials for any further RCTs in which atypical antipsychotics were compared with haloperidol for the same indication. Search terms used were haloperidol and schizophren and haloperidol and psychotic, as well as the names of the selected atypical antipsychotics for the years that were not covered by the Cochrane Reviews. For each study, the required dose and mean dose of haloperidol were compared with officially recommended doses of haloperidol in U.S. (Food and Drug Administration) and U.K. (British National Formulary) guidelines. DATA SYNTHESIS: In all of the included studies (N = 49), the midpoints of the required doses were above the midpoint of the official recommended doses in the United States and United Kingdom for moderately ill patients. In 94% (U.S.) and 80% (U.K.) of the studies, they were above the upper border of the recommended doses. Compared with recommended doses for severely ill patients in both the United Kingdom and United States (range, 6-15 mg daily), in 17 studies (35%) the mean actual used dose was above the upper dose border for severely ill patients (15 mg daily). CONCLUSIONS: Nearly all randomized clinical trials used haloperidol in doses that were higher than the official recommended doses for moderately ill or even severely ill patients. Therefore, it is probable that the results of the RCTs were affected by the high dose of haloperidol, hampering the interpretation of the effects of atypical anti-psychotics in their comparison with haloperidol.
OBJECTIVE: To systematically review the evidence for pharmacologic management of outwardly directed aggressive behavior in general adult psychiatry. DATA SOURCES: Literature searches in PubMed, EMBASE, PsycINFO, and Cochrane libraries from 1966 through March 2005 were used to identify relevant studies. The keywords aggression, violence, anger, and hostility combined with drug therapy, psychotropic drugs, adrenergic beta-antagonists, anticonvulsants, anti-depressants, antipsychotic agents, benzodiazepines, and lithium were searched. Furthermore, the retrieved publications were searched for additional references. STUDY SELECTION: All randomized controlled trials addressing pharmacotherapy for aggression or aggression-related symptoms were included, except studies addressing the "emergency situation" and studies conducted in specialized psychiatric or non-psychiatric settings. DATA EXTRACTION: Evidence synthesis was performed using the "best-evidence principle." Two authors independently adjudicated methodological quality and generalizability to daily clinical practice. DATA SYNTHESIS: Thirty-five randomized controlled trials met the inclusion criteria and were evaluated. On the basis of a best-evidence synthesis model, weak evidence for antiaggressive effects of antipsychotics, anti-depressants, anticonvulsants, and beta-adrenergic-blocking drugs was found. Atypical antipsychotics appeared superior to typical antipsychotics. The use of various outcome measures and insufficient data reporting in the individual studies hampered the quantitative assessment of efficacy across studies. Further limitations of the available randomized controlled trials included small sample sizes, short study duration, and poor generalizability to daily clinical practice setting. CONCLUSIONS: Whereas pharmacotherapy is frequently applied in aggressive patients, only weak evidence of efficacy of various drug classes was found. Consensus about the use of aggression measurement scales in clinical trials is necessary for future research. Furthermore, large-scale trials with more naturalistic designs, as opposed to classical randomized controlled trials with strict inclusion and exclusion criteria, may be advisable in order to obtain results that are more generalizable to daily clinical practice.
BACKGROUND: Generic substitution is an important opportunity to reduce the costs of pharmaceutical care. However, pharmacists and physicians often find that patients and brand-name manufacturers have doubt about the equivalence of the substituted drug. This may be reflected by decreased adherence to therapy. OBJECTIVE: To assess the association between generic substitution and nonadherence to antihypertensive drugs. METHODS: We conducted a matched cohort study between January 1, 1999, and December 31, 2002. Data were obtained from PHARMO, a record linkage system containing drug-dispensing records from community pharmacies and linked hospital discharge records of approximately 950,000 people in The Netherlands. Residents of 30 medium-sized cities who initiated antihypertensive drug therapy were potential subjects. Refill adherence with antihypertensive drugs after substitution was determined; those with refill adherence below 80% were considered nonadherent. RESULTS: Four hundred sixty-three patients with a substitution in therapy and 565 controls, matched on age, gender, therapy start date, duration of use, and generic product code, were identified. Of the patients who switched from brand-name to generic formulations ("substituted"), 13.6% were nonadherent, and of the non-substituted patients (those who did not switch to generic), 18.7% were nonadherent (OR 0.68; 95% CI 0.48 to 0.96). The association was absent in males. None of the patients discontinued the medication. No differences in hospitalizations for cardiovascular disease in the 6 months after the substitution were observed. CONCLUSIONS: Generic substitution of antihypertensive drugs does not lead to lower adherence or more discontinuation and cardiovascular disease-related hospitalizations compared with brand-name therapy. When a less-expensive antihypertensive generic equivalent becomes available, generic substitution should be considered to achieve economic benefits.
BACKGROUND AND OBJECTIVES: In literature, different methods of calculating persistence are used. In this study, the effect of using these different methods on persistence and the association of patients characteristics and persistence are assessed. METHODS: The PHARMO record linkage system was used to calculate persistence with antihypertensive drugs for a cohort of 14,466 new users of antihypertensives. Three different types of methods were used to define the maximum gap allowed between two prescriptions that a patient may have to be defined as a continuous user, one based on a defined number of days (varying from 9-365 days), the second based on the duration of the last prescription (varying from 0.1-4 times the duration), the third based on a combination of both methods, whichever leads to the lowest number of days. RESULTS: Refill persistence varied between 19.7-86.4% (method 1), between 27.9-90.2% (method 2), and between 19.7-86.4% (method 3). Furthermore, patient characteristics associated with persistence differed between and within the three different methods. CONCLUSION: The method used and the variation within a method influenced both persistence and the association between patient characteristics and persistence. Results of persistence studies are highly influenced by the researchers' method of the maximum allowed treatment gap.
The objective of our study was to investigate whether use of antipsychotics is associated with hip/femur fractures and whether pharmacological differences between antipsychotics are related to the occurrence of fractures. A case-control study was conducted, in which cases were defined as patients with a hip/femur fracture. Each patient was matched to one control patient. The association between use of antipsychotics and the occurrence of hip/femur fractures was evaluated using conditional logistic regression. The study included 44,500 patients from 683 general practices from different geographical areas in the UK, registered within the General Practice Research Database (GPRD). Exposure to antipsychotics was categorized as "no use", "current use" and "prior use". Both current and prior use of antipsychotics were associated with an approximately two-fold increased risk of fractures. After adjustment for possible confounders, a small significant effect remained (Odds Ratios (OR) of 1.3). We did not find an association between dose of antipsychotics, or between the degree of blockade of the alpha-1 adrenoceptor or histamine-1 receptor and risk of fractures. The total number of days of antipsychotic use was significantly associated with an increased risk of hip/femur fractures. We conclude that there is a small increased risk of hip/femur fractures associated with the use of antipsychotics. This risk increases with long-term use.
BACKGROUND: Inappropriate (long-term) use of benzodiazepines (BZDs) is a reason for concern. Several studies have suggested that hospitalisation may be a determinant for initiation of BZD use as well as for long-term use. However, the available evidence is conflicting. OBJECTIVE: To determine whether hospitalisation induces initiation of BZD use and subsequent long-term use. METHODS: A retrospective follow-up study was conducted. Randomly, 10,000 patients who had been hospitalised were selected (index date). Non-hospitalised patients, matched on age and gender, were sampled from the same living region and assigned the same index date as the corresponding hospitalised patient. Patients were included if adequate medication data were available from 18 months before to 18 months after the index date. Initiation of BZD use was defined as a prescription for a BZD or BZD-related hypnotic without a prescription for any of these drugs during the prior 6 months. Long-term use was defined as a period of consecutive use for at least 6 months following initiation. RESULTS: In this study, 8,681 hospitalised patients and an equal number of non-hospitalised patients were finally included. Overall, the relative risk for initiation of BZD use was almost twice as high [IDR 1.97 (95%CI 1.84-2.10)] among hospitalised patients as in non-hospitalised patients. This relative risk was most clearly elevated during the time window from 3 months before to 3 months after hospitalisation [IDR 4.81 (95%CI 4.08-5.67)]. The relative risk for long-term use during the entire 36-month observation period was not higher [IDR 1.04 (95%CI 0.95-1.13)] among hospitalised patients than among non-hospitalised patients. Within the time window of 3 months before and after hospitalisation, the relative risk for long-term use was significantly lower for the hospitalised group [RR 0.82 (CI 0.69-0.98)]. CONCLUSION: Our results confirm that hospitalisation is associated with an increased risk for initiation of BZD use; the risk is highest during the 3 months just before and after hospitalisation. However, hospitalisation appeared not to be a determinant for long-term use of BZDs.
OBJECTIVE: To identify socio-demographic characteristics of the first patients receiving a new drug--rofecoxib. OUTCOME MEASUREMENT: Patients starting on rofecoxib or another non-steroidal anti-inflammatory drug (NSAID) and who had not received any NSAIDs the 90 days prior to starting. RESULTS: Starting on rofecoxib was associated with an increasing age (OR in age 80 years and older 8.7; 95% CI 6.7-11.2), a poor self-perceived health (OR=2.4; 95% CI 1.8-3.3), female gender (OR=1.4; 95% CI 1.2-1.6), private insurance (OR=1.3; 1.1-1.5) and previous acetaminophen use (OR=1.3; 1.1-1.7). CONCLUSION: This study noted that specific patient characteristics were associated with getting rofecoxib prescribed shortly after marketing. General practitioners should be aware of selectively prescribing new drugs to specific patients because it may place patients at unintentional and avoidable risk.
OBJECTIVE: To systematically review the impact of interventions by community pharmacists on patients' adherence with chronic medication. DATA SOURCES: A MEDLINE search (1966-November 30, 2003) and a review of reference sections were done to identify all pertinent English- and German-language journal articles. Search terms included compliance, adherence, persistence, discontinuation, pharmacist, and intervention. STUDY SELECTION AND DATA EXTRACTION: From each relevant study, the following data were extracted: study design, country, disease, number of patients, patients' age and gender, type of intervention, duration of follow-up, method of measurement of adherence and adherence rate, and data concerning the quality of the included studies. DATA SYNTHESIS: A total of 162 studies were identified, of which 18 matched our inclusion criteria. Twelve were randomized controlled trials and 6 were non-crossover single-group trials. Eight studies showed significant improvement of adherence at one or more time points. Eight studies did not show any effect, 7 of which were randomized controlled trials. In most studies, adherence rates at baseline were high compared with rates reported in the general population. Counseling, monitoring, and education during weekly or monthly appointments showed some effect. However, these same types of interventions showed no effect in other studies. The overall quality of the included studies was low. CONCLUSIONS: Currently, it is impossible to identify an overall successful adherence-improving strategy performed by pharmacists. More well-designed and well-conducted studies on the effectiveness of interventions by a community pharmacist to improve patient adherence to chronic medication need to be performed.
BACKGROUND: The cyclooxygenase-2 (COX-2) inhibitor rofecoxib was registered in 1999. By 2000, the first reports were published indicating that the agent was possibly associated with an increased risk of myocardial infarction. Since then a surge of data supporting this association has become available. To interpret these data it is essential to ascertain the cardiovascular risk profile of users of rofecoxib relative to other non-steroidal anti-inflammatory drug (NSAID) recipients. OBJECTIVE: To assess differences in cardiovascular risk between starters of rofecoxib versus starters of any other NSAID. SETTING: Data sampled from a representative research network of Dutch general practitioners (GPs) in 2001. DESIGN: New users (starters) of rofecoxib were compared to starters of any other NSAID, unmatched and matched on age, gender, and indication nested in the cohort of the second Dutch National Survey of General Practice. RESULTS: A total of 40.4% of patients starting on rofecoxib had cardiovascular co-morbidity. Patients starting on rofecoxib were twice more likely to have a history of gastrointestinal (GI) morbidity, compared to patients starting on other NSAIDs (OR(adj) = 2.09; 95%CI = 1.65-2.66). These patients were also more likely to have cardiovascular co-morbidity (OR = 1.90; 95%CI = 1.60-2.24) compared to recipients of rofecoxib with no GI co-morbidity. Cardiovascular morbidity was present at the time of rofecoxib exposure in over 61% of carriers of a composite risk profile including age 60 years or older, GI co-morbidity and diagnosis of rheumatoid arthritis and osteoarthritis. CONCLUSIONS: In general, a typical recipient of an NSAID is aged and carrier of a serious cardiovascular risk profile. Selective prescribing of rofecoxib to provide claimed gastroprotection, indirectly and unintentionally resulted in prescribing rofecoxib in a population with high frequencies of cardiovascular morbidities.
OBJECTIVE: With the aim of getting more insight into compliance of children using methylphenidate, we studied the day-to-day use of the drug. In addition, the efficacy and side effects of treatment, stopping, switching to other drugs and the use of additional psychoactive drugs in daily practice were studied. METHOD: On the basis of pharmacy records, the use of methylphenidate by 52 children was studied. Two parameters for compliance were calculated. By means of a questionnaire, parents were asked about their children's compliance with the use of methylphenidate as well as about their experience with treatment. MAIN OUTCOME MEASURE: Compliance, use of methylphenidate in weekends and holidays, self-reported efficacy, side effects, stopping and switching to other drugs. RESULTS: Depending on the parameter calculated, the percentage of children with a good compliance varied from 25 to 47%. About 65% of the children used less or no methylphenidate in the weekends and holidays. Sixty-five percent of the parents reported to pass over a dose once in a while. According to 61% of the parents (n = 28) the efficacy of methylphenidate was good or very good. Nine (33%) of 28 children stopped using methylphenidate. Seven children stopped using the drug because of side-effects or lack of efficacy. Seven children switched to other psychoactive drugs. Fifty-seven percent of all children used additional psychoactive drugs. CONCLUSION: The percentage of children having a good compliance calculated on the basis of pharmacy records is rather low. This is partly the result of the decreased use of methylphenidate in the weekends and holidays.
OBJECTIVE: To assess the proportion of patients starting with antihypertensive drug treatment who continued treatment for at least 10 years. DESIGN: A retrospective cohort study. SETTING: The PHARMO record linkage system containing drug dispensing records from community pharmacies and linked hospital discharge records of approximately 950 000 subjects. PARTICIPANTS: Patients who started using antihypertensive drugs (two or more prescriptions) in 1992 and did not receive a prescription for any antihypertensive drug in the 365 days preceding the first prescription. MAIN OUTCOME MEASURE: Persistence with antihypertensive drugs until 10 years. RESULTS: Among a total of 2325 patients who started using antihypertensive drugs, 39% used continuously during the 10 years of follow-up. Approximately 22% temporarily discontinued and restarted treatment, whereas 39% of patients discontinued permanently. Older patients were more persistent than younger patients [20-39 years: odds ratio (OR) 2.08; 95% confidence interval (CI) 1.52-2.84; 40-59 years: (reference), > or = 60 years: OR 0.69; 95% CI 0.54-0.89]. More patients who started with diuretics (reference) and beta blockers (OR 1.15; 95% CI 0.87-1.52) discontinued compared with those who started with dihydropyridine calcium antagonists (OR 0.54; 95% CI 0.34-0.84), and angiotensin-converting enzyme (ACE) inhibitors (OR 0.38; 95% CI 0.27-0.55). Patients who started with combination therapy (OR 0.29; 95% CI 0.14-0.54 compared with diuretics) or patients who were initially treated by a cardiologist (OR 0.82; 95% CI 0.61-0.97) or internist (OR 0.80; 95% CI 0.62-0.98 compared with general practitioners) also showed higher persistence. CONCLUSION: Long-term persistence in daily practice is low compared with persistence observed in randomized clinical trials and should be considered in the choice of a first-line antihypertensive agent.