Preventing hospital admissions by reviewing medication (PHARM) in primary care: an open controlled study in an elderly population.

WHAT IS KNOWN AND OBJECTIVE: Limited and conflicting evidence exists on the effect of a multicomponent pharmaceutical care intervention (i.e. medication review, involving collaboration between general practitioners (GPs), pharmacists and patients) on medication-related hospitalizations, survival, adverse drug events (ADEs) and quality of life. We aimed to investigate the effect of a multicomponent pharmaceutical care intervention on these outcomes. METHODS: An open controlled multicentre study was conducted within primary care settings. Patients with a high risk on medication-related hospitalizations based on old age, use of five or more medicines, non-adherence and type of medication used were included. The intervention consisted of a patient interview, a review of the pharmacotherapy and the execution and follow-up evaluation of a pharmaceutical care plan. The patient's own pharmacist and GP carried out the intervention. The control group received usual care and was cared for by a GP other than the intervention GP. The primary outcome of the study was the frequency of hospital admissions related to medication within the study period of 12 months for each patient. Secondary outcomes were survival, quality of life and ADEs. RESULTS AND DISCUSSION: 364 intervention and 310 control patients were included. Less medication-related hospital admissions were found in the intervention group (n = 6; 1·6%) than in the control group (n = 10; 3·2%) but the overall effect was not statistically significant (hazard ratio (HR) 0·50, 95% confidence interval (CI) 0·12-1·59). The secondary outcomes were not statistically significantly different either. The study was underpowered, which may explain the negative results. A post hoc analysis showed that the effect of the intervention was statistically significant for patients with five diseases or more: five diseases, HR 0·28 (95% bootstrap CI: 0·056-0·73) and eight diseases, HR 0·11 (95% CI: 0·013-0·34). WHAT IS NEW AND CONCLUSION: A multicomponent pharmaceutical care intervention does not prevent medication-related hospital admissions. Whether this is true for such interventions in general is unknown, because the PHARM study was underpowered. The intervention may significantly reduce medication-related hospitalizations in patients with five or more comorbidities, but this is only based on a post hoc analysis and thus needs confirmation in large controlled trials.

Determinants of DNA yield and purity collected with buccal cell samples.

Buccal cells are an important source of DNA in epidemiological studies, but little is known about factors that influence amount and purity of DNA. We assessed these factors in a self-administered buccal cell collection procedure, obtained with three cotton swabs. In 2,451 patients DNA yield and in 1,033 patients DNA purity was assessed. Total DNA yield ranged from 0.08 to 1078.0 microg (median 54.3 microg; mean 82.2 microg +/- SD 92.6). The median UV 260:280 ratio, was 1.95. Samples from men yielded significantly more DNA (median 58.7 microg) than those from women (median 44.2 microg). Diuretic drug users had significantly lower purity (median 1.92) compared to other antihypertensive drug users (1.95). One technician obtained significantly lower DNA yields. Older age was associated with lower DNA purity. In conclusion, DNA yield from buccal swabs was higher in men and DNA purity was associated with age and the use of diuretics.

Publication trends in newspapers and scientific journals for SSRIs and suicidality: a systematic longitudinal study.

Background In the period 2003-2008, the regulatory authorities issued several warnings restricting the use of selective serotonin re-uptake inhibitors (SSRIs) in paediatrics, in reaction to safety concerns regarding the risk of suicidality. In this study, the SSRIs and suicidality controversy serves as a template to analyse the long-term publication trends regarding the benefit/risk profile of medications. The aim is to ascertain differences (in terms of numbers, categories and timing) between negative and positive newspaper and journal articles on SSRIs and suicidality and to ascertain correlations between changes in the reports and regulatory warnings. Methods A systematic review of scientific articles (Embase) and the Netherlands (NL) and the UK newspapers (LexisNexis) was performed between 2000 and 2010. Categorisation was done by 'effect' (related treatment effect), 'type of article' and 'age group'. The articles' positive-to-negative effect ratio was determined. Differences in distribution of effect categories were analysed across sources, type of article and age group using the Mann-Whitney (two subgroups) or Kruskal-Wallis test (three or more). Findings In total, 1141 articles were categorised: 352 scientific, 224 Dutch and 565 British newspaper articles. Scientific articles were predominantly on research and were positive, whereas newspaper articles were negative (ratios=3.50-scientific, 0.69-NL and 0.94-UK; p<0.001). Articles on paediatrics were less positive in scientific journals and more negative in newspapers (ratios=2.29-scientific, 0.26-NL and 0.20-UK; p<0.001), while articles on adults were positive overall (ratios=10.0-scientific, 1.06-NL and 1.70-UK; p<0.001). In addition, negative-effect reporting trends were exacerbated following regulatory warnings and were generally opinion articles, both in scientific journals and in newspapers (2003/2004 and after 2007). Interpretation The authors found a positive publication tendency inherent in journal research articles. This apparent positive publication bias present in scientific journals, however, does not seem to prevent the dissemination of 'bad' news about medications. The negative tendency present in Dutch and British newspapers was perceivable in the paediatrics group and during the warnings, indicating that national news media have informed the public about this international drug safety controversy on time.

Recruitment of a cohort of lamotrigine users through community pharmacists: differences between patients who gave informed consent and those who did not.

OBJECTIVE: Community pharmacists may function as intermediaries in the recruitment of a population-based cohort of patients using specific drugs. In this study, baseline characteristics and the retention rate of patients that gave informed consent, refused and did not answer were compared. METHODS: A total of 1819 patients using the new antiepileptic drug (AED) lamotrigine were asked to provide informed consent for a retrospective chart study via their individual pharmacist. Four possible reactions resulted from the consent question: active consent, active refusal, passive refusal and non-informed. Patient characteristics and lamotrigine retention rate of the different groups were compared. RESULTS: Pharmacists did not inform a total of 183 patients (10%). Of the remaining patients, a total of 968 (59%) gave consent; 101 (6%) actively refused and 567 (35%) did not respond. Age, burden of illness, psychotropic co-medication and continuation of lamotrigine therapy were related to active consent. Lamotrigine retention rate in patients that gave consent was higher than in other patients. CONCLUSIONS: Patient recruitment with community pharmacists as intermediaries for observational studies on the effects of (new) drugs is feasible, and allows access to a broad population of patients. The recruitment procedure, however, may lead to selection bias.

Evaluation of patient outcomes in an area where prescribing of anticholinergic antidepressants was influenced by academic detailing.

OBJECTIVE: To evaluate, on a patient level, the effect of a "physician-level intervention" that successfully reduced the incidence of anticholinergic antidepressant prescribing. DESIGN: Cross-sectional surveys with questionnaires sent before and after intervention. SETTING: Additional study in an RCT to reduce the prescribing of highly anticholinergic antidepressants in the elderly in the South Holland Islands. PARTICIPANTS: Elderly patients (age 60-95 years) who used antidepressants in 1995 and 1996 in our research area according to a health insurance prescription database. MAIN OUTCOME MEASURES: Prevalence of adverse events related to antidepressant use, severity of depression and quality of life were compared in users living in the intervention and control areas. RESULTS: Prior to our intervention we sent 2,359 questionnaires of which we could use 827 (35%) for analysis. At baseline, there were no statistically significant differences between the intervention and control areas. After the intervention 3,375 questionnaires were sent, of which 939 (28%) could be used. The occurrence of "dry mouth" and "coughing" and the "amount of pain" were lower in the intervention area compared to the control area (p < 0.05). CONCLUSION: We found no indications that adverse events, severity of depression or quality of life were changed in an unfavourable direction, when comparing patients inside and outside the intervention area.

Selective serotonin reuptake inhibitor-induced urinary incontinence.

PURPOSE: Irrespective of its cause, urinary incontinence is a medical condition seriously affecting quality of life and is increasingly recognized. In this study, we examined the association between the use of selective serotonin reuptake inhibitors (SSRIs) and urinary incontinence. METHODS: A retrospective follow-up study among starters with an SSRI was performed to estimate the relative and absolute risk for urinary incontinence associated with SSRI use. Data came from the PHARMO database, which includes information on drug dispensing for approximately 450,000 residents living in eight Dutch cities. All patients initially using an SSRI between 1994 and 1998 were selected. The frequency measures for urinary incontinence were estimated by using prescription sequence analysis, where initiation of spasmolytic drugs or absorbent products was used as a measure for urinary incontinence. Besides crude incidence density calculations, Andersen-Gill's model was used in order to control for possible confounding factors and time varying covariates. RESULTS: A total of 13,531 were identified as first time users of an SSRI. Compared to non-exposure, the incidence density ratio for urinary incontinence during SSRI exposure was 1.75 (95% CI 1.56-1.97). Overall, compared to baseline, SSRI use caused 14 extra cases of urinary incontinence per 1000 patients treated per year; the elderly were more at risk resulting in 60 extra cases per 1000 patients per year. The adjusted relative risk for urinary incontinence due to SSRI use was 1.61 (95% CI 1.42-1.82); the risk for sertraline users was 2.76; 95% CI 1.47-5.21). CONCLUSIONS: Exposure to SSRIs is associated with an increased risk for developing urinary incontinence, which can be explained pharmacologically. Approximately 15 out of 1000 patients treated per year with an SSRI developed urinary incontinence. The elderly and users of sertraline are at the highest risk.

Diffusion of the new antiepileptic drug lamotrigine in Dutch clinical practice.

INTRODUCTION: Lamotrigine is one of the recently introduced antiepileptic drugs (AEDs) licensed in the Netherlands in 1995. The objective of this study was to examine the diffusion of lamotrigine into clinical practice. Three different aspects of this diffusion process were examined: incidence of use, patient characteristics and changes in prescription patterns in the first 5 years following its introduction. METHODS: A retrospective follow-up study has been conducted using drug prescription data from the database of the Dutch Drug Information Project (GIP database). Patients were included who started with lamotrigine, carbamazepine, phenytoin or valproate in the period between January 1996 and December 2000. Incidence of use was calculated for the four drugs. Multiple logistic regression analysis was used to determine differences in baseline characteristics. The Chi-square test was used to analyse changes in the usage patterns of lamotrigine. RESULTS: The study population consisted of a total of 29,718 patients who were prescribed carbamazepine, phenytoin, valproate or lamotrigine for the first time in the study period. Carbamazepine and valproate accounted for the majority of all new prescriptions; the incidence of lamotrigine use remained stable with 4.4 patients per 100,000 per year. Baseline characteristics of lamotrigine differed depending on the patient's age and gender (OR 3.7, 95% CI 3.3-4.2; OR 1.4, 95% CI 1.3-1.5) relative to the conventional AEDs. In a large majority of cases, lamotrigine was used as a second-line or third-line AED. Physicians prescribing lamotrigine were predominantly neurologists, in contrast to prescribers of conventional AEDs. The prevalence of psychotropic medication and migraine-abortive drugs was significantly lower in users of lamotrigine than in users of conventional AEDs. During follow-up, several significant trends were noticed in the prescribing of lamotrigine with regard to age groups, gender, antiepileptic history and off-label use. DISCUSSION: Lamotrigine is prescribed to a population different from that using conventional AEDs. The uptake of lamotrigine in clinical practice is slow, for reasons probably related to characteristics of the drug itself and the prescribers. During the observation period, lamotrigine diffused gradually towards more first-line use as an AED and more off-label use.

Patterns of lamotrigine use in daily clinical practice during the first 5 years after introduction in the Netherlands.

OBJECTIVE: Follow-up data on the long-term effectiveness (efficacy and tolerability) of lamotrigine are limited. A useful though crude measure for effectiveness in daily clinical practice is the treatment retention rate determined from drug dispensing data. This study describes the baseline characteristics, the usage patterns and the retention rate of this antiepileptic drug (AED) in a population-based cohort of lamotrigine users in the Netherlands during the first 5 years after its registration in 1995. Data from this cohort are compared with those from the initial randomized clinical trials (RCTs) in patients with refractory epilepsy. METHODS: This retrospective cohort study used dispensing data from community pharmacies. Baseline characteristics and usage patterns were evaluated for first time users of lamotrigine in this study. Usage patterns were characterized as continued, add-on or discontinued use during the patient observation time window. Cox regression analysis was used to explore possible relationships between baseline characteristics and specific usage patterns defined. The baseline characteristics and discontinuation rates in this cohort study were compared with RCT data reported in medical literature. RESULTS: A total of 3598 lamotrigine users were identified. The mean age of the population was 39 years and 54% were female. On average, patients used two other AEDs at the start of lamotrigine therapy and approximately 6% of the patients had no history of prior AED use. The discontinuation rate was 25% after 1 year, and approximately 32% at the end of the 5-year study. Addition of another drug or discontinuation was seen in more than half of the population 3 years after the start of therapy. Concurrent use of valproic acid was associated with a better retention rate. Absence of AED history, use of antidepressants, or use of migraine abortive drugs resulted in an increased likelihood of discontinuing lamotrigine. The population from RCTs differed from the study cohort with respect to age, concurrent use of AEDs and length of follow-up. CONCLUSION: Data from RCTs cannot easily be extrapolated to daily clinical practice. In this large, observational study, lamotrigine therapy failed in a considerable number of patients, although the mean retention rate was better than previously reported by others. Population-based linkage of health care records can be used to further clarify the effectiveness of lamotrigine.