The impact of health literacy on beliefs about medication in a Dutch medication-using population.

PURPOSE: Medication beliefs are likely contingent on aspects of health literacy: knowledge, motivation, and competences to access, understand, appraise, and apply health information. An association between medication beliefs and health literacy is expected as they both influence self-management. The aim of this study was to examine the association between health literacy and the beliefs about overuse and harmful effects of medication and to examine modifying effects of age, gender, and number of medications on this association. METHODS: The data were collected using the online "Medication panel" of the Dutch Institute for Rational Use of Medicine. A linear regression model was used to examine the association between health literacy and beliefs about medication and the modifying effects of age, gender, and number of medications on this association. RESULTS: Respondents with a lower level of health literacy had more concerns about overuse (ß adj.= -.174, p<.001) and harmful (ß adj.= -.189, p<.001) effects of medication. This study found no modifying effects. CONCLUSIONS: A lower health literacy level is associated with more concerns about the overuse and harmful effects of medication. The results of this study suggest that extra attention should be given to persons with low health literacy level by healthcare professionals, to decrease their concerns about overuse and harmful effects, and improve adherence to self-management behavior.

Predicting Unsuccessful Clozapine Treatment After First Use in Adult Patients With Psychotic Disorders.

PURPOSE/BACKGROUND: Cessation of clozapine therapy and insufficient response may result in relapse of psychotic symptoms and in clinical admissions. However, discontinuation rates are high. Identifying patients at risk for unsuccessful clozapine use might enable clinicians to direct specific attention to them. METHODS/PROCEDURES: Routinely collected data from a large insurance company were used to develop a simple prediction model for unsuccessful clozapine treatment in psychiatric patients 1 year after clozapine was first dispensed by a community pharmacy in the Netherlands. Multivariate logistic regression analyses were performed with the Nagelkerke R statistic as a measure of the predictive value of the model. FINDINGS/RESULTS: A total of 937 patients were dispensed clozapine for the first time by their community pharmacy between January 1, 2011, and December 31, 2015 (index date). Of these, 741 patients had started their clozapine treatment in hospital before the index date (inpatient starters); the remaining 196 patients started clozapine as outpatients on the index date (outpatient starters). In 191 patients (20.4%), clozapine treatment was unsuccessful 1 year after the index date. Unsuccessful treatment was more common among outpatient starters than among inpatient starters (32.1% vs 17.3%). Using backward selection of the variables, a model consisting of 61 variables had the best predictive value overall (Nagelkerke R = 0.301), whereas a model consisting of 52 variables had the best predictive value in outpatient starters (Nagelkerke R = 0.676). IMPLICATIONS/CONCLUSIONS: The likelihood of unsuccessful clozapine treatment after 1 year was higher among patients who started clozapine as outpatients. Despite the use of a diversity of variables and different statistical approaches, it was not possible to make a simple prediction model for unsuccessful clozapine treatment using relatively easily accessible data.

Evaluation of clarity of presentation and applicability of monitoring instructions for patients using lithium in clinical practice guidelines for treatment of bipolar disorder.

OBJECTIVES: Clinical practice guidelines (CPGs) for treatment of bipolar disorder (BD) aim to provide guidance to health care professionals on monitoring of patients using lithium. The aim was to assess the clarity of presentation and applicability of monitoring instructions for patients using lithium in CPGs for treatment of BD. METHODS: CPGs for treatment of BD were selected from acknowledged professional organizations from multiple continents. CPGs were rated on the clarity of presentation and applicability of lithium monitoring instructions using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The applicability of monitoring instructions was assessed according to the Systematic Information for Monitoring (SIM) score. Monitoring instructions were considered applicable when a SIM score of ≥3 was found. RESULTS: The clarity of presentation for six out of the nine CPGs was good (>70%) using the AGREE II tool. Only one CPG scored >70% on applicability. Descriptions of the resource implications and facilitators of and barriers to monitoring were most often missing. All CPGs contained instructions for monitoring of lithium serum levels and renal and thyroid function. Information provided in monitoring instructions (n = 247) was in general applicable to clinical practice (77%) based on the SIM score. Overall, a median SIM score of 3 (interquartile range 3-4) was found. CONCLUSIONS: Improvement of the applicability of CPGs is recommended, and can be achieved by describing the resource implications and facilitators of and barriers to monitoring. In addition, information on critical values and instructions on how to respond to aberrant monitoring parameters are needed. With such improvements, CPGs may better aid health care professionals to monitor patients using lithium.

Development of a nomogram for the estimation of long-term adherence to clozapine therapy using neutrophil fluorescence.

AIMS: Previously, we have reported an association between clozapine use and elevated FL3 neutrophil fluorescence, a flow-cytometric parameter for cell viability. Here, we developed and evaluated a pharmacokinetic-pharmacodynamic model relating FL3-fluorescence to clozapine exposure and derived a nomogram for estimation of long-term adherence. METHODS: Data from 27 patients initiating clozapine were analysed using nonlinear mixed effects modelling. A previously described pharmacokinetic model for clozapine was coupled to a FL3 fluorescence model. For this, an effect compartment with clozapine concentrations as input and a first order decay rate as output was linked with an Emax model to FL3-fluorescence. FL3-fluorescence was simulated for clozapine doses of 50, 150 and 400 mg daily (n = 10 000) to establish the nomogram. Finally, true simulated adherence (% of daily doses taken over 100 days) was compared to nomogram-estimated adherence to evaluate the performance of the nomogram. RESULTS: The half-life of FL3-fluorescence was estimated at 228 h (coefficient of variation 35%). Median absolute prediction errors of the nomogram in case of fully random adherence for 50, 150 and 400 mg ranged from -0.193% to -0.525%. The nomogram performed slightly worse in case of nonrandom adherence (median prediction error up to 5.19%), but was still clinically acceptable. Compliance patterns containing longer drug holidays revealed that the nomogram adequately estimates compliance over approximately the last 3 weeks prior to FL3-measurement. CONCLUSION: Our nomogram could provide information regarding long-term adherence based on prescribed clozapine dose and FL3-fluorescence. Future studies should further explore the clinical value of this biomarker and nomogram.

[Instructions for monitoring clinical parameters in the Summary of Product Characteristics (SmPC) for psychotropic drugs: overview and applicability for clinical practice]. / Instructies voor monitoren van klinische parameters in de registratieteksten van psychofarmaca: overzicht en toepasbaarheid voor de klinische praktijk1.

BACKGROUND: The Summary of Product Characteristics (Smpc) for psychotropic drugs includes instructions for clinical and biomarker monitoring intended to optimise effectiveness and minimise harm.
AIM: To evaluate which monitoring instructions are given in the Smpc and to assess the applicability in clinical practice.
METHOD: The reasons and requirements for monitoring in Smpcs for psychotropic drugs were assessed and somatic parameters were distinguished from non-somatic parameters, thereby the applicability was assessed.
RESULTS: An average of 3.3 instructions per drug label was found. Monitoring was primarily for safety reasons (78%). Requirement was predominantly mandatory (71%). Somatic parameters were most often mentioned (80%). Only 34% of the instructions were determined applicable.
CONCLUSION: Monitoring instructions for psychotropic drugs are aimed at improving safe use. However, most instructions on monitoring do not provide sufficient information to be applicable in clinical practice.

Association between concomitant psychiatric drug use, and patients' beliefs about and persistence with chronic cardiovascular medication.

OBJECTIVE: Psychiatric disorders are associated with an increased risk of cardiovascular diseases and may result in additional risk of non-adherence. No data on the influence of concomitant psychiatric drug use on patients' beliefs and persistence related to cardiovascular medication are available. The objective of this study was to assess to what extent the use of concomitant psychiatric drugs is associated with patients' beliefs about and persistence with chronic cardiovascular medication. METHODS: An observational study in patients using cardiovascular medication was conducted. A mailed questionnaire containing socio-demographical questions and a measure of beliefs about medication (Beliefs about Medicines Questionnaire - specific) was sent to patients selected from fifteen participating pharmacies. Persistence was evaluated based on pharmacy records. RESULTS: Of the 1547 included patients, 551 responded to key questions in the questionnaire and were included for beliefs about medication analysis. In concomitant users of psychiatric drugs significantly higher necessity (17.0 vs. 16.0) and higher concerns (14.3 vs. 13.3), as well as higher proportion of ambivalent (34.5% vs. 25.6%) and lower proportion of indifferent patients (24.1% vs. 33.0%) were found compared with non-users (p < 0.05). 65.2% (n = 1009) of patients were persistent on all their cardiovascular drugs. There was no significant association between concomitant use of psychiatric drugs and non-persistence (OR = 1.2; 95% CI 0.9-1.5). CONCLUSION: Concomitant use of psychiatric drugs was found to be associated with increased beliefs about the necessity of and concerns about cardiovascular medication. Clinicians caring for cardiovascular patients should give additional attention to identifying patients' beliefs about medication among those concomitantly using psychiatric drugs.

Discontinuation of anticoagulant care during admission to a psychiatric hospital.

PURPOSE: Continuation of coumarin therapy is important to prevent thromboembolic events. Continuation of medication, unrelated to the reason for hospital admission, may be at risk due to the patient's psychiatric status and the involvement of several physicians in patient care. METHODS: We performed a retrospective follow-up study of users of orally administered anticoagulants who were admitted to a psychiatric hospital. Information on patient characteristics, anticoagulant use, and International Normalized Ratio (INR) measurements was collected. Discontinuation of anticoagulant care was defined as no anticoagulant dispensing during the first 7 days of hospitalization and/or no INR measurement during hospitalization. Relative risks (RR) of discontinuation, overall and stratified by patient characteristics, was estimated using Cox regression analysis. RESULTS: Of 111 patients, 24.3 % had their anticoagulant care discontinued. For 17.1 %, no anticoagulant was dispensed during the first week, and 13.5 % had no INR measurement during hospitalization. CONCLUSIONS: Admission to a psychiatric hospital leads to discontinuation of anticoagulant care in 24.3 % of patients, with highest risk of discontinuation in patients admitted to nonpsychogeriatric wards. More research is needed to evaluate the clinical impact of this finding.

Lazy sunday afternoons: the negative impact of interruptions in patients' daily routine on adherence to oral antidiabetic medication. A multilevel analysis of electronic monitoring data.

PURPOSE: Considerable variability in adherence over time exists. The aim of this study was to investigate to what extent deviations from the prescribed regimen in type 2 diabetes patients can be explained by characteristics of the individual 'medication intake moments' and the patient. METHODS: Medication intake of 104 non-adherent type 2 diabetes patients from 37 community pharmacies was electronically monitored for 6 months. The primary outcome measures were: (1) whether or not the intake occurred and (2) whether or not the intake occurred within the agreed-upon time period (correct timing). Multilevel logistic regression analyses were performed to account for the nested structure of the data. RESULTS: Medication intakes in the evening and during weekends and holidays were more likely to be incorrectly timed and also more likely to be completely missed. Irrespective of timing, most intakes occurred in the mornings of Monday through Thursday (96 %), and least intakes occurred on Saturday evening (82 %). Correctly timed intakes most often occurred on Monday and Tuesday mornings (61 %) in contrast to Sunday evenings (33 %). A patient's medication regimen was significantly associated with adherence. CONCLUSION: Based on our results, among patients who already have difficulties in taking their oral antidiabetic medication, interruptions in the daily routine negatively influence the intake of their medication. Professionals need to be aware of this variation in adherence within patients. As regular medication intake is important to maintain glycaemic control, healthcare professionals and patients should work together to find strategies that prevent deviations from the prescribed regimen at these problematic dosing times.

Prevalence of medication use for somatic disease in institutionalized psychiatric patients.

INTRODUCTION: Psychiatric patients may use medications for their psychiatric condition as well as for treating concurrent somatic diseases or somatic side effects of psychiatric medicines. The objective of this study was to estimate the prevalence of use of medication for somatic disease in institutionalized psychiatric patients and changes therein during 2006-2010. METHOD: A cross-sectional study in institutionalized psychiatric patients was performed. Medication use for somatic disease on 10 time points between 2006 and 2010 was investigated and stratified by gender, age, psychiatric medication class and the number of different psychiatric medication classes used. RESULTS: The prevalence of use of medication for somatic disease increased from 67.5% in 2006 to 76.9% in 2010. The median number of medications used for somatic disease per patient was 3 between 2006 and 2010. Approximately one-third (34.1%) of the patients received ≥ 3 medications intended for treating somatic disease in 2006 which increased to 46.3% in 2010. In 2010, the prevalence of medication use for somatic disease was highest for analgesics and antirheumatics (34.0%), acid and bowel related medication (25.6%) and anticholinergic medication (24.2%). Medication use for somatic disease was highest in patients ≥ 60 years (95.3%), patients treated with more than one psychiatric medication class (87.5%) and patients treated with mood stabilizers (90.6%). DISCUSSION: Somatic medication use is high in institutionalized psychiatric patients. More attention is needed for co-use of psychiatric and somatic medications to prevent side effects, drug-disease or drug-drug interactions. More research is needed to investigate if somatic care is optimal in institutionalized psychiatric patients.

[Risk factors for inactivity in patients in long-term care with severe mental illness]. / Risicofactoren voor inactiviteit bij patiënten met ernstige psychiatrische aandoeningen in de langdurige zorg.

BACKGROUND: Inactivity is a major problem in long-stay patients with severe mental illness. Very little research has been done into the variables that can predict and explain this inactivity. AIM: To find associations between inactivity and the variables (psychiatric, pharmacological, lifestyle and comorbidity) of patients with severe mental health illness.methods A cross-sectional study was performed at "Zon en Schild", a centre for mental health care in Amersfoort in the Netherlands. The study included 100 long-stay psychiatric patients hospitalized throughout the period February 2011 till July 2011. All of these patients were being treated with antipsychotics and were long-term inpatients at a psychiatric clinic. At the out-patient clinic of "Zon en Schild"; they were screened for inactivity via a subscale of the Nurses"; Observation Scale for Inpatient Evaluation (NOSIE-30). Data were collected and analysed by means of a validated questionnaire, physical examination and patient records. Simple and multiple regression analyses were performed in order to find associated factors associated with inactivity. RESULTS: We found that 31.3% of the variance predicted by the multiple regression analysis model for inactivity was associated with the variables parkinsonism, negative symptoms, metabolic syndrome, diabetes, body-mass index (BMI), first-generation antipsychotics and combination of first- and second-generation antipsychotics. Age (ß=0.235, p=0.04) and a combination therapy involving traditional and atypical antipsychotics (ß=0.317, p=0.04) were significantly associated with inactivity. CONCLUSION: Age and the combination of first- and second-generation antipsychotics were associated with inactivity. Cross-sectional studies do not demonstrate any causal links, but can generate a hypothesis. One possible hypothesis for the surprising link between inactivity and the combination of traditional and atypical antipsychotics is that the combination of antipsychotics promotes and fosters inactivity.key words clinical, epidemiology, inactivity, long-term care, schizophrenia.

Key factors underlying the willingness of patients with cancer to participate in medication redispensing.

BACKGROUND: Redispensing medication unused by patients to other patients could reduce the environmental burden of medication waste. Simultaneously, associated financial loss could be reduced, particularly for expensive medication such as oral anticancer drugs. An important determinant for successful medication redispensing is patient participation. OBJECTIVE(S): To identify key factors underlying the willingness of patients with cancer to participate in the redispensing of unused oral anticancer drugs. METHODS: Semi-structured interviews via telephone or video call were conducted with adult patients diagnosed with cancer from two Dutch hospitals. The interview guide was framed using the COM-B model for behavioural change, to elicit patients' capability, opportunity and motivation to participate in medication redispensing. Questions were related to patients' willingness to accept redispensed medication, reasons thereof, perceived concerns and needs. Inductive thematic analysis was applied. RESULTS: Seventeen patients (aged 38-82 years, 71% female), with nine different types of cancer participated. The majority of participants supported medication redispensing. Four categories of key factors underlying the willingness of patients with cancer to participate in medication redispensing were identified. First, the driver for participation was having positive societal impact, relating to affordability and sustainability of healthcare. Second, having trust in product quality was a requirement, influenced by preconceived beliefs, quality assurance and patients' knowledge of this process. Third, a facilitator for participating in medication redispensing was adequate provision of information. This concerned awareness of medication waste, information about medication redispensing, support from healthcare providers and other patients, and insight into medication dispensing history. Last, a convenient process for returning unused medication to pharmacies would facilitate participation in medication redispensing. CONCLUSIONS: The willingness of patients with cancer to participate in medication redispensing relates to a drive for achieving positive societal impact, provided that medication is of high quality, there is adequate information provision and a convenient process.

Representation of people with intellectual disabilities in randomised controlled trials on antipsychotic treatment for behavioural problems.

BACKGROUND: Behavioural problems are common in people with intellectual disability (ID) and are often treated with antipsychotics. AIM: To establish the frequency and characteristics of people with ID included in randomised controlled trials (RCTs) on antipsychotic treatment for behavioural problems, and to investigate the quality of these RCTs. METHODS: A literature search in EMBASE, PubMed and Cochrane was performed and reviewed. RESULTS: People with ID participated in 27 of the 100 included RCTs. The RCTs were of good quality but smaller compared with trials in patients with dementia or schizophrenia (average sample sizes = 55, 124 and 374). In 13/27 trials no clear definition of ID was given. Over 25 different outcome measures were used to assess behavioural problems. CONCLUSIONS: Studies in which people with ID are included are of a sufficient quality, but of a small size. The heterogeneity in the characteristics of the ID population included as well as in the applied assessment instruments makes performing meta-analyses unfeasible.

The effect of non-adherence to antipsychotic treatment on rehospitalization in patients with psychotic disorders.

BACKGROUND AND AIMS: Many patients with psychotic disorders are non-adherent to antipsychotic (AP) medication(s), potentially contributing to rehospitalization. It is unknown whether non-adherence in different phases of AP use is associated with rehospitalization. The aim of this study was to assess the association between non-adherence to APs and rehospitalization in patients with psychotic disorders. Non-adherence was assessed specifically for the initiation, continued drug use and early discontinuation of AP use. METHODS: A retrospective follow-up study was performed. Adult patients were included at discharge if they suffered from schizophrenia, psychotic, or bipolar I disorder; had been hospitalized in a psychiatric hospital for ⩾7 days; and were treated with oral APs. Patients discharged between January 2006 and December 2009 from Altrecht Mental Health Care were included. Non-adherence was studied in the three phases of medication use: initiation, continued drug use (implementation) and (early) discontinuation after discharge until the end of follow up or until patients were rehospitalized. Cox regression analysis was used to assess the strength of the association between non-adherence for the different phases of AP use and rehospitalization during follow up and expressed as relative risk (RR) with 95% confidence intervals (CI). RESULTS: A total of 417 patients were included. Patients who did not initiate their APs compared with those who did in the first month (RR = 1.62, 95% CI: 1.19-2.19) and between the first and third month after discharge (RR = 1.70, 95% CI: 1.04-2.79) had the highest risk for rehospitalization during follow up. Overall, patients who did not initiate their AP medication within the first year after discharge had a RR of 2.70 (95% CI: 1.97-3.68) for rehospitalization during follow up compared with those that initiated their AP. CONCLUSION: Not initiating APs right after discharge was associated with an increased risk of rehospitalization. Interventions should aim to promote the initiation of APs soon after discharge to minimize the risk of rehospitalization.

Quantifying antibiotic use in paediatrics: a proposal for neonatal DDDs.

The defined daily dose (DDD) as defined by the World Health Organization (WHO) has been the most frequently used unit of measurement to measure antibiotic use. However, measuring antibiotic use in paediatrics is a problem as the WHO DDD methodology is not applicable in children (aged >1 month) due to the large variation in body weight within this population. Based on the narrow range of body weights in the neonatal population, we therefore aimed to develop a set of neonatal DDDs for antibiotics. Eight well-respected (inter)national sources for dosage recommendations of antibiotics in children and neonates were consulted for the assumed maintenance dose of the ten most frequently used antibiotics in neonatal intensive care units in its main indication for neonates. A set of neonatal DDDs for ten commonly used antibiotics in neonates based on an assumed neonatal weight of 2 kg was proposed. Primarily in children DDDs are not applicable to quantify antibiotic use since there is large variation in body weight. In the neonatal population, however, based on its narrow range of body weights and when access to patient level data is not available, neonatal DDDs can be used as a unit of measurement.

Transitions from General Practitioner to Psychiatrist Care (or vice versa) during a first antidepressant treatment episode.

INTRODUCTION: The aim of this study was to investigate how frequently patients transit from general practitioner (GP) to psychiatrist care and vice versa during a first antidepressant episode and antidepressant treatment changes associated with those transitions. METHOD: Antidepressant episodes were constructed for patients (> or =18 years) initiating SSRI use in 2000 (N=10 158). Transition in care within a first treatment episode was investigated. Changes in antidepressant treatment were compared between transiting and non-transiting patients. RESULTS: 6.0% of patients who initiate SSRI use in GP practice transited to psychiatrist care, whereas 39.1% of those initiating use in psychiatrist care transited to GP care. Patients transiting from GP to psychiatrist care were more likely to switch to other antidepressants (RR=6.16, 95% CI: 4.90, 7.75) or to other doses (RR=4.48, 95% CI: 3.76, 5.34) than non-transiting patients. No significant differences in antidepressant treatment were found for patients transiting from psychiatric to GP care. DISCUSSION: Approximately 9% of SSRI initiators transit in care. Transitions from GP to psychiatric care lead to antidepressant treatment changes and could potentially be used in observational studies as a disease severity indicator.

Trials assessing parmacotherapeutic management of aggression in psychiatric patients: comparability with clinical practice.

INTRODUCTION: In a previous review of randomized controlled trials (RCTs) on the pharmacotherapeutic management of aggression, it was shown that there is only weak evidence of effectiveness. In the present study we aim to determine comparability of patients included in these RCTs and patients of psychiatric long-stay wards. METHODS: Exclusion criteria that were used in at least 20% of the RCTs were applied to a sample of aggressive inpatients from clinical practice, in order to find what proportion of these patients would be eligible to participate in the reviewed, high quality RCTs. RESULTS: Only 30% of aggressive psychiatric patients as seen in clinical practice would be eligible to participate in a typical randomized controlled trial based on the most frequently applied exclusion criteria. DISCUSSION: The low comparability of patients included in RCTs with those seen in clinical practice may decrease the generalizability of the findings form RCTs to clinical practice.

Low treatment adherence with antipsychotics is associated with relapse in psychotic disorders within six months after discharge.

OBJECTIVE: The aim of this study was to assess the association between treatment adherence with antipsychotics and schizophrenia relapse on a continuous scale. METHOD: A cohort study with a total of 477 patients with schizophrenia who were recently discharged from an inpatient clinic was performed. RESULTS: In the 160 people who relapsed within the six months after discharge the average medication possession ratio was 0.50. This was 0.59 in the 317 persons who were not readmitted. The resulting hazard ratio for the medication possession ratio on relapse risk was 0.60 (95% confidence interval: 0.42-0.88). CONCLUSION: The found hazard ratio indicates that the risk of relapse is substantially decreased when a patient is properly adherent to the antipsychotic therapy that was prescribed at the inpatient clinic.

Antidepressant use before and after initiation of diabetes mellitus treatment.

AIMS/HYPOTHESIS: Although current literature suggests an association between diabetes and depression, the direction of the association is unclear. We examined the temporal association between diabetes and depression by studying antidepressant and benzodiazepine use around the initiation of diabetes treatment. METHODS: From a pharmacy registry database we selected 49,593 diabetic patients and a random sample of non-diabetic individuals (n = 154,441), all >40 years old. Antidepressant and benzodiazepine use was calculated for the 7 years before and 7 years after the index date. The index date in diabetes patients was defined as the date of initiation of diabetes medication. A random index date was assigned to non-diabetic individuals. Time-specific incidence rate ratios of antidepressant and benzodiazepine use were calculated for intervals of 1 year, 3 months and 1 month. RESULTS: Antidepressant and benzodiazepine use was increased 2 months before and 3 months after the initiation of diabetes treatment compared with non-diabetic individuals. The strongest increase in incidence of antidepressant and benzodiazepine use was seen in the month after initiation of diabetes treatment with incidence rate ratios of 2.4 (95% CI 2.0-3.0) and 3.4 (95% CI 3.0-3.8) respectively, after adjustment for age, sex and Chronic Disease Score. CONCLUSIONS/INTERPRETATION: The increased incidence of antidepressant and benzodiazepine use may be a consequence of the burden of disease, of starting with diabetes medication or of being diagnosed with diabetes. Our findings could also reflect earlier detection by their physician.

Genetic variation in the renin-angiotensin system modifies the beneficial effects of ACE inhibitors on the risk of diabetes mellitus among hypertensives.

The aim of this study was to assess whether the association between angiotensin-converting enzyme (ACE) inhibitor use and the incidence of treated diabetes mellitus is modified by genetic polymorphisms in the renin-angiotensin system (RAS).In a nested case-control study, treated hypertensive patients were genotyped for ACE (insertion (I)/deletion (D)), angiotensinogen (AGT; M235T) and angiotensin II type 1 receptor (AGTR1; A1166C). Cases of newly treated diabetes were identified based on pharmacy records and controls were not yet drug treated for diabetes (case:control ratio 1:10). Self-administered questionnaires and physical examinations were used to assess risk factors for diabetes mellitus. Logistic regression was used to calculate the relative risk of diabetes associated with ACE inhibitor use relative to other antihypertensive treatment, stratified by the RAS genotypes. Among 205 cases and 2050 controls, homozygous 1166A carriers of the AGTR1 gene had a significantly decreased incidence of diabetes associated with current use of ACE inhibitors (odds ratio, OR: 0.47; 95% CI: 0.26-0.84), whereas this incidence was increased among 1166C allele carriers (OR: 1.32; 95% CI: 0.81-2.14). The interaction OR was 3.21 (95% CI: 1.53-6.75). ACE I allele carriers had a significantly reduced incidence of diabetes associated with ACE inhibitors use (OR: 0.63; 95% CI: 0.41-0.98), whereas DD homozygotes had no reduced risk (OR: 0.95; 95% CI: 0.46-1.96). The risk of diabetes associated with ACE inhibitor use was not significantly modified by the AGT-M235T polymorphism. Treatment with ACE inhibitors in hypertensive subjects significantly reduces the occurrence of diabetes in homozygous 1166A carriers of the AGTR1 gene and carriers of the ACE I allele, but not in 1166C allele carriers of the AGTR1 gene and in homozygous ACE D allele carriers.

Changes in outpatient lithium treatment in the Netherlands during 1996-2005.

BACKGROUND: The objectives of the present study were to investigate in outpatients in the Netherlands between 1996 and 2005, changes in 1) the incidence and prevalence of lithium use and 2) lithium use patterns (discontinuation, add-on, and switch). METHODS: Incidence and prevalence of lithium use were determined for each year between 1996 and 2005. In addition, we determined cumulative changes in lithium use (discontinuation, add-on, and switching) at three, six, 12 and 24 months for three separate time-cohorts (1998-1999, 2000-2001 and 2002-2003). Lastly, concomitant use of other drugs used in the treatment of bipolar disorders next to lithium during the 24 months after the first lithium prescription was determined for the three time-cohorts. RESULTS: Incidence of lithium use was constant at approximately 0.2 per 1000 person-years, prevalence increased with 26% from 0.95 to 1.2 per 1000 persons. The percentage of patients receiving an add-on drug used in the treatment of bipolar disorders was constant over the three time-cohorts, with a significant decrease in use of tricyclic antidepressants. Within the patient group that stopped using lithium, more patients switched from lithium to another agent used in the treatment of bipolar disorders over calendar time, and fewer patients discontinued lithium. There was a significant increase in the use of atypical antipsychotics and valproic acid next to lithium. LIMITATIONS: We did not know the specific diagnosis for which lithium treatment was instituted. CONCLUSION: The changes were in line with the increase in alternatives during the last decade and in line with Dutch guidelines.