Factors Influencing Preferences and Responses Towards Drug Safety Communications: A Conjoint Experiment Among Hospital-Based Healthcare Professionals in the Netherlands.

INTRODUCTION: Healthcare professionals (HCPs) are informed about new drug safety issues through Direct Healthcare Professional Communications (DHPCs). The influence of DHPC content on the impact of the communication is unclear. OBJECTIVES: The aim of this study was to assess the effect of content elements 'frequency of the safety issue', 'seriousness of the safety issue', 'need to take action', 'life span of drug involved' and 'type of evidence supporting the safety issue' on hospital-based HCPs' preferences and responses towards DHPCs. METHODS: A survey study including a conjoint experiment was performed among hospital-based HCPs in the Netherlands. Hypothetical DHPCs varying on the five content elements were constructed. Each respondent received eight out of 16 hypothetical DHPCs and was asked about (1) importance to be informed (fixed-point scale), (2) preferred communication timing (multiple options) and (3) their stated actions (multiple options). Associations were tested using generalized linear mixed models. RESULTS: In total, 178 HCPs participated. DHPCs concerning more frequent or serious safety issues, or requiring action, were associated with a higher perceived importance to be informed and a preference for immediate communication. Periodic communication was preferred for DPHCs concerning less frequent or serious safety issues. The most commonly stated action was to discuss the DHPC with colleagues. Monitoring was common when this was recommended. High frequency and seriousness were associated with more prescribing-related actions. CONCLUSION: Frequency and seriousness of the safety issue and the recommended action are likely to influence the impact of DHPCs. The timing of communication could be tailored depending on the content, where less urgent safety issues might be communicated periodically.

Drug Safety Issues Covered by Lay Media: A Cohort Study of Direct Healthcare Provider Communications Sent between 2001 and 2015 in The Netherlands.

BACKGROUND: Some drug safety issues communicated through direct healthcare professional communications (DHPCs) receive substantial media coverage, while others do not. OBJECTIVES: The objective of this study was to assess the extent of coverage of drug safety issues that have been communicated through DHPCs in newspapers and social media. A secondary aim was to explore which determinants may be associated with media coverage. METHODS: Newspaper articles covering drug safety issues communicated through 387 DHPCs published between 2001 and 2015 were retrieved from LexisNexis Academic™. Social media postings were retrieved from Coosto™ for drugs included in 220 DHPCs published between 2010 and 2015. Coverage of DHPCs by newspapers and social media was assessed during the 2-month and 14-day time periods following issuance of the DHPC, respectively. Multivariate logistic regression was used to assess potential DHPC- and drug-related determinants of media coverage. RESULTS: 41 (10.6%) DHPC safety issues were covered in newspaper articles. Newspaper coverage was associated with drugs without a specialist indication [adjusted odds ratio 5.32; 95% confidence interval (2.64-10.73)]. Negative associations were seen for time since market approval [3-5 years 0.30; (0.11-0.82), 6-11 years 0.18; (0.06-0.58)] and year of the DHPC [0.88; (0.81-0.96)]. In the social media, 180 (81.8%) drugs mentioned in 220 DHPCs were covered. Social media coverage was associated with drugs without a specialist indication [6.92; (1.56-30.64)], and for DHPCs communicating clinical safety issues [5.46; (2.03-14.66)]. CONCLUSIONS: Newspapers covered a small proportion of DHPC safety issues only. Most drugs mentioned in DHPCs were covered in social media. Coverage in both media were higher for drugs without a specialist indication.

Antibiotics and risk of first-time hospitalization for myocardial infarction: a population-based case-control study.

There is increasing evidence that inflammation plays an important role in atherosclerosis. Such inflammation is likely related to the presence of infectious organisms. Hence, we examined whether the use of antibiotic drugs decreases the risk of first-time myocardial infarction (MI). We identified 6737 cases of first-time hospitalization for MI, and 67,364 age- and gender-matched, population-based controls during 1991-2002, using data from the County Hospital Discharge Registry and the Civil Registration System of North Jutland County, Denmark. All prescriptions for antibiotics prior to the hospitalization for MI were identified through a prescription database. Conditional logistic regression was used to estimate odds ratios (OR) associated with antibiotic use, adjusted for potential confounding factors including previous discharge diagnoses of hypertension, chronic bronchitis and emphysema, alcoholism, liver cirrhosis, or diabetes mellitus and prescriptions for anti-hypertensive drugs, antidiabetic drugs, lipid-lowering agents, high-dose aspirin, platelet inhibitors, oral anticoagulants, or hormone replacement therapy. The use of any one type of antibiotic in the 3 years before hospitalization was not associated with a decreased risk of MI; the adjusted ORs with corresponding 95% confidence intervals were 1.07, 1.00-1.14 for penicillins; 1.15, 1.00-1.33 for macrolides; 0.95, 0.65-1.39 for tetracyclines; 1.25, 0.84-1.87 for quinolones; and 0.95, 0.80-1.12 for sulfonamides. A slight increase in the risk of MI was seen with the use of more than one type of antibiotic in the preceding 3 years (OR = 1.17, 95% CI = 1.09-1.27). Our findings do not support the hypothesis that the use of antibiotics is associated with a lower risk of first-time MI.

Antidepressants and risk of first-time hospitalization for myocardial infarction: a population-based case-control study.

PURPOSE: Several studies have found an increased risk of myocardial infarction among depressed patients. Selective serotonin reuptake inhibitors (SSRIs) appear to lack the arrhythmic adverse effects of tricyclic antidepressants, and are thought to inhibit platelet aggregation. We examined whether use of different antidepressant classes is associated with a lower risk of first-time hospitalization for myocardial infarction, as compared with nonuse. METHODS: We identified 8887 cases of first-time hospitalization for myocardial infarction and 88,862 age- and sex-matched population-based controls during 1994-2002, using data from North Jutland County, Denmark. Cases and controls were stratified according to history of cardiovascular disease. All prescriptions for antidepressants before hospitalization for myocardial infarction were identified using a prescription database. Conditional logistic regression was used to estimate odds ratios of myocardial infarction associated with antidepressant use, adjusted for possible confounding factors. RESULTS: In patients with a history of cardiovascular disease, we found indications of a lower risk of myocardial infarction among those who used SSRIs (adjusted odds ratio [OR] = 0.85; 95% confidence interval [CI]: 0.62 to 1.16), nonselective serotonin reuptake inhibitors (adjusted OR = 0.83; 95% CI: 0.50 to 1.38), and other antidepressants (adjusted OR = 0.55; 95% CI: 0.31 to 0.97). There were no such associations among persons without a history of cardiovascular disease. CONCLUSION: Antidepressant use may be associated with a decreased risk of hospitalization for myocardial infarction among persons with a history of cardiovascular disease, although it remains uncertain whether there are differences by class of antidepressant.

How to estimate the population that is covered by community pharmacies? An evaluation of two methods using drug utilisation information.

PURPOSE: Pharmacy-dispensing data are valuable sources of drug information, but the population that is covered by the pharmacies is often difficult to determine. We evaluated two methods using drug utilisation information to estimate the population size: a drug-use-based extrapolation of a known part of the population and a capture-recapture estimation without any prior knowledge of the population. METHODS: Using pharmacy-dispensing data of three towns with known populations in the Netherlands, we estimated age-and-sex specific population sizes by extrapolating the proportion of drug-using inhabitants. In addition, we applied two-source and three-source capture-recapture models with all combinations of the following drug groups as different sources: anti-asthmatics, analgesics, antibiotics and anti-histamines. RESULTS: Drug-use-based extrapolation resulted in the best estimates with the least variability. All capture-recapture models provided underestimations of the true population. Three-source capture-recapture resulted in better average estimates than two-source capture-recapture, but also had more variability. CONCLUSIONS: If a part of the population is known, and if there is reason to assume that drug utilisation patterns do not vary within the region, it is best to use drug-use-based extrapolation. In all other situations capture-recapture may be considered, with as main limitation that we found all models to underestimate the population considerably.

The effect of hypertension and hypercholesterolemia screening with subsequent intervention letter on the use of blood pressure and lipid lowering drugs.

AIM: To evaluate the effect of a letter intervention that was send to both the participants of a population screening and their general practitioners. We also tested what predicting variables influenced the GP to actually prescribe blood pressure lowering drugs (BPLD) or lipid lowering drugs (LLD). METHOD: The study design was cross sectional, in the PREVEND outpatient clinic in Groningen University Hospital, the Netherlands. We used the clinical data of the 8592 subjects that participated in the first screening of the PREVEND study. Data on drug use was collected from community pharmacies. Drug use was measured the year before and after the screening with the subsequent intervention letter. As control population without intervention, we used the data from the InterAction DataBase (IADB) standardized for the population characteristics of the intervention group. The letter intervention was sent to participants who had shown after screening to have either an elevated blood pressure or plasma cholesterol, and the letter contained the advice to use a BPLD or LLD. Main outcome measures were proportion of patients prescribed BPLD and/or LLD in the year before and after the intervention, and variables that influence the GP to prescribe BPLD and LLD. RESULTS: Data from the community pharmacy were available from 7567 (88%) subjects. 397 participants (5.2%) received a letter with advice to start a BPLD, and 326 participants (4.3%) received a letter with advice to start a LLD. The prevalence of patients who were using BPLD and LLD before the intervention was not significantly different between the intervention and control group, 16.6 (CI 95% 15.8 -17.5) vs 16.0 and 4.8 (4.4-5.3) vs 4.6, respectively. After the letter intervention, the prevalence of BPLD use was higher in the intervention group compared with the control group (19.4 [18, 5-20, 3]vs 17.0%), as was the prevalence of LLD use (7.1[6.5-7.7) vs 5.4%). The same held true for the incidence of BPLD (3.4[3.0-3.8]vs 2.5%) and LLD use (2.1 [1, 6-2, 4]vs 1.0%), respectively, in the year after the intervention. Univariate and multivariate analysis showed that a higher blood pressure and cholesterol level, but not the presence of other cardiovascular risk factors, were associated to with a greater percentage use of a BPLD and a LLD. CONCLUSION: A population survey followed by a letter of intervention to both the patient and GP are effective to improve the use of blood pressure and lipid lowering drugs as a primary prevention in patients with hypertension and hyperlipidemia. Our therapeutic advice however, was followed only in about one of the three subjects with hypertension and one of the four subjects with hyperlipidemia. The levels of blood pressure and plasma total cholesterol are important variables influencing the GP to prescribe a BPLD and/or LLD.

Chlorpromazine equivalents versus defined daily doses: how to compare antipsychotic drug doses?

Classic chlorpromazine (CPZ) equivalents can be used to chart relative antipsychotic potencies of antipsychotic drugs. Values of CPZ equivalents per drug are ambiguous in literature. In drug use evaluation studies, antipsychotic doses are frequently compared by use of the defined daily dose (DDD). The DDD is the assumed average maintenance dose per day for a drug if used for its main indication in adults. The DDD is based on review of the available older and recent literature. In this report, we evaluated discrepancy between CPZ-equivalent values and DDD-equivalent values. We plotted CPZ-equivalent values against DDD-equivalent values and performed linear regression to determine the mean relationship between the 2 methods. About 67% of the DDD-equivalent values demonstrated lower potencies for antipsychotic drug compared with CPZ-equivalent values. The slope of the regression line was 0.68 (r2 = 0.81). Because we found a great discrepancy between these 2 methods of comparing antipsychotic drug doses, we think further research is necessary to develop a standardized way of antipsychotic drug comparison.

Corticosteroid use and its association with microalbuminuria in the adult population.

BACKGROUND: Corticosteroids exhibit a wide range of adverse effects, among which are a number of cardiovascular effects. Microalbuminuria shows a strong correlation with these cardiovascular effects and is an indicator for cardiovascular risk. We now investigate whether use of corticosteroids, either systemic or nonsystemic, is associated with microalbuminuria. METHODS: We used the data of 7010 subjects of an on-going population based study, focussed on the impact of microalbuminuria (PREVEND). Microalbuminuria was defined as urinary albumin excretion of 30-300 mg/24 h, measured as the mean of two 24-h urine collections. Corticosteroid use was measured in the year preceding the albumin measurement using community pharmacy data. RESULTS: After adjusting for age and sex, the odds ratio (OR) for having microalbuminuria was slightly elevated (1.21; 95% CI 1.03-1.41; N=1798) for corticosteroid users. The ORs were lower for subjects using only systemic corticosteroids (1.07; 95% CI 0.67-1.72; N=146), or only local corticosteroids (1.11; 95% CI 0.93-1.32; N=1442). However, the OR for subjects using both systemic and local corticosteroids was raised (1.99; 95% CI 1.42-2.77; N=210). CONCLUSION: Corticosteroid use, and especially use of both systemic and local corticosteroids is associated with microalbuminuria. Based on this investigation we cannot say if this is due to adverse effects of corticosteroids themselves, or effects of the underlying disease.

Drug-induced renal function impairment: a population-based survey.

PURPOSE: The knowledge that drugs can affect renal function is mainly based on experimental studies or case reports. Thus, it has only been investigated in selected populations. Here we describe drug groups associated with altered renal function in the general population. METHODS: To study this, we used baseline data of 8592 subjects of a population-based cohort. Hyper- and hypofiltration were defined as a filtration above or below the 90% confidence interval of age-and-sex-corrected creatinine clearance. Drug use was measured in the year preceding the kidney function measurement. RESULTS: The prevalence of hyperfiltration (4.6% in the general population) was higher among subjects using anti-diabetics (11.7%), dermatological corticosteroids (5.9%) and sex hormones (5.8%), but lower in subjects using anti-thrombotics (2.4%) and diuretics (2.1%). Hypofiltration (4.3% in the general population) was seen more often in users of beta blockers (6.2%), ACE inhibitors (7.1%), statins (7.2%), anti-thrombitics (6.8%), trimethoprim (7.9%), vaccines (9.4%), NSAIDs (5.2%), anti-ulcer agents (6.3%), laxatives (7.7%) and eyedrops (6.7%). CONCLUSIONS: Several drug groups found in this overview were to be expected, since patients with kidney disease often use them (e.g. cardiovascular drugs). Several other drug groups were somewhat unexpected and deserve further attention.

Pharmacy data in epidemiological studies: an easy to obtain and reliable tool.

PURPOSE: The agreement between drug use measured in computerized pharmacy records and patient interviews or questionnaires is generally good. However, most investigations on this subject studied selected populations or subsets. We studied the coverage of Dutch pharmacy data for our study cohort, and the agreement between the different sources. METHODS: We used the data from 8592 subjects of an on-going population-based study, focused on the impact of microalbuminuria (PREVEND). Data on drug use was collected in a questionnaire and at community pharmacies. Drug use was measured in the year preceding the questionnaire. Agreement between the sources was measured using kappa-values, sensitivity and positive predictive value. RESULTS: Pharmacy data could be collected for 7568 (88%) of the study cohort. Pharmacy data and questionnaires showed good agreement for antihypertensives, lipid lowering drugs, oral antidiabetics and oral contraceptives, but poor agreement for nitrates, hormone replacement therapy and painkillers. CONCLUSIONS: Pharmacy data could be collected for a large proportion of our cohort. For chronically used drugs pharmacy data generally agrees well with questionnaires. However, for drugs used for shorter periods, as needed, or also available over-the-counter, the agreement is not so good. Pharmacy data can be a valuable source of drug information in epidemiological studies.

The impact of antihypertensive drug groups on urinary albumin excretion in a non-diabetic population.

AIMS: Microalbuminuria (30-300 mg 24 h-1) is recognized to be independently associated with renal and cardiovascular risk. Antihypertensives may lower microalbuminuria. We questioned whether the use of different antihypertensive drug classes in general practice influences microalbuminuria as related to blood pressure in nondiabetic subjects. METHODS: To study this, we used the data from 6836 subjects of an on-going population based study, focused on the meaning of microalbuminuria (PREVEND). Odds ratios, adjusted for age, sex, blood pressure, cholesterol level, smoking and the use of other antihypertensive or cardiovascular drugs, were calculated to determine the association of drug groups with microalbuminuria. Influence of antihypertensives on the relation between blood pressure and (log) urinary albumin excretion was determined by comparing linear regression lines. RESULTS: Microalbuminuria was significantly associated with the use of dihydropyridine calcium channel blockers (odds ratio: 1.76 [1.22-2.54]), but not with other antihypertensive drug groups. The linear regression line of the relation between blood pressure and (log) urinary albumin excretion was significantly steeper (P = 0.0047) for users of calcium channel blockers, but not for other antihypertensives, compared with subjects using no antihypertensive. Users of a combination of renin-angiotensin system inhibitors and diuretics however, had a less steep regression line (P = 0.037). CONCLUSIONS: This study suggests a disadvantageous effect of dihydropyridine calcium channel blockers on microalbuminuria compared with other antihypertensive drug groups. Thus, if microalbuminuria is causally related to an increased risk for cardiovascular morbidity and mortality, dihydropyridines do not seem to be agents of choice to lower blood pressure. Furthermore, the combination of renin-angiotensin system inhibition and diuretics seems to act synergistically.