Medication changes implemented during medication reviews and factors related to deprescribing: Posthoc analyses of a randomized clinical trial in geriatric outpatients with polypharmacy.

AIMS: To provide posthoc analyses of a clinical trial that reported beneficial effects of medication reviews on health-related quality of life. Specifically, to describe the medication changes with a focus on deprescribing and to explore patient- and medication-related factors that may identify patients most likely to benefit from medication reviews. METHODS: Posthoc analyses of data from a pragmatic, nonblinded, randomized clinical trial investigating a medication review intervention (NCT03911934) in 408 geriatric outpatients treated with ≥9 medicines. RESULTS: In the medication review group (n = 196), 26% of the medicines prescribed at baseline were discontinued with 82% still being discontinued after 13 months. The most common reason for discontinuation was lack of indication (72% of discontinuations). The medicines most often discontinued in the medication review group compared with usual care included: metoclopramide (11/15 = 73% discontinued vs. 1/12 = 8% in usual care), acetylsalicylic acid (20/48 = 42% vs. 2/47 = 4%), simvastatin (18/48 = 38% vs. 2/58 = 3%), zopiclone (23/59 = 39% vs. 4/54 = 7%), quinine (9/14 = 64% vs. 6/16 = 38%), citalopram (4/18 = 22% vs. 0/20 = 0%) and tramadol (18/37 = 49% vs. 8/30 = 27%). Factors associated with number of deprescribed medicines included: number of prescribed medicines, Drug Burden Index, patient motivation for medicine changes, and prescriptions of metoclopramide, iron preparations, antidepressants other than selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory drugs, or drugs for urinary incontinence. CONCLUSION: Physician-led medication reviews resulted in persistent deprescribing of medicines in older polypharmacy patients treated with ≥9 medicines. Motivation for having their medicine changed, treatment with more medicines, and a higher burden of sedative and anticholinergic medicines characterized the patients most likely to benefit from physician-led medication reviews.

Effects of a comprehensive medication review intervention on health-related quality of life and other clinical outcomes in geriatric outpatients with polypharmacy: A pragmatic randomized clinical trial.

AIM: To investigate the effects of a comprehensive medication review intervention on health-related quality of life (HRQoL) and clinical outcomes in geriatric outpatients exposed to polypharmacy. METHODS: Pragmatic, nonblinded, randomized clinical trial with follow-up after 4 and 13 months. Participants were geriatric outpatients taking ≥9 medicines. The intervention was an additional consultation with a physician focusing on reviewing medication, informing patients about their medicines and increasing cross-sectoral communication as supplement to and compared with usual care. The primary outcome was change in HRQoL after 4 months measured with the EuroQoL 5-dimension 5-level (EQ-5D-5L) questionnaire. Secondary outcomes were HRQoL after 13 months, mortality, admissions, falls and number of medicines after 4 and 13 months. RESULTS: Of 785 eligible patients, 408 were included (age: mean 80.6 [standard deviation 7.22] years; number of medicines: median 12 [interquartile range 10-14]; females 71%). After 4 months, the adjusted between-group difference in EQ-5D-5L index score was 0.066 in favour of the medication consultation (95% confidence interval 0.01 to 0.12, P = .02). After 4 months, two (1%) participants had died in the medication-consultation group and nine (4%) in the usual-care group (log-rank test, P = .045). The medication consultation reduced the number of medicines by 2.0 (15.8%) after 4 months and 1.3 (10.7%) after 13 months. There were no statistically significant differences in mortality or HRQoL after 13 months, and no differences in falls or admissions. CONCLUSIONS: An additional consultation with medication review and increased communication as supplement to usual geriatric outpatient care improved HRQoL and reduced mortality after 4 months.

Polypharmacy and medication deprescribing: A survey among multimorbid older adults in Denmark.

Polypharmacy is common among multimorbid adults and associated with increased morbidity and mortality. Excessive polypharmacy (ie, ≥10 medicine) is strongly associated with inappropriate medication use, but little is known about attitudes toward deprescribing in patients with excessive polypharmacy. We surveyed 100 Danish individuals aged 65 years and above with ≥10 prescribed medications, using the validated Patients' Attitudes Towards Deprescribing (PATD) instrument. Most participants (81, 81%) thought they took a large number of medications, and 79 (79%) believed that their medications were necessary. Even so, 85 (85%) reported that they would be willing to stop taking one or more of their regular medications if their doctor told them they could, and 11 (11%) felt that they took at least one regular medication that they no longer needed. When presented with visual presentation of various amounts of tablets and capsules, 62 (62%) of participants reported that they would be comfortable taking fewer medications than they did. Forty-two (42%) participants had experience with stopping a regular medication. Almost all participants (92%) wanted to receive follow-up by various means if a medication was discontinued. Forty-one (41%) participants were interested in a consultation at an outpatient clinic specializing in polypharmacy. Overall, the answers to the PATD questionnaire suggest that our cohort of Danish, multimorbid outpatients with extensive polypharmacy have a high confidence in their healthcare providers for medication-related decisions, even though some feel that they are taking more medications than they would like to and feel that some medications may be unnecessary. Our results underline the need for healthcare providers to offer medication reviews in patients with multimorbidity.

Psychotropic medication in a randomly selected group of citizens receiving residential or home care.

INTRODUCTION: Treatment with one or more psychotropic medications (PMs), especially in the elderly, is associated with risk, and the effects of treatment are poorly validated. The aim of this article was to describe the use of PM in a population of citizens receiving either residential care or home care with focus on the prevalence of drug use, the combination of different PMs and doses in relation to current recommendations. METHODS: The medication lists of 214 citizens receiving residential care (122) and home care (92) were collected together with information on age, gender and residential status. RESULTS: Two thirds of the citizens (64.5%) used one or more PMs (antipsychotics 15.9%, antidepressants 43.5%, anxiolytics/hypnotics 27.1% and anti-dementia drugs 16.4%). Citizens treated with antipsychotics were also prescribed antidepressants (52.9%), anxiolytics/hypnotics (35.3%) and anti-dementia drugs (20.9%). Citizens treated with anti-dementia drugs were also prescribed antipsychotics (20.0%) and antidepressants (54.3%). Doses over 20 mg and 10 mg of citalopram and escitalopram, respectively, were given to 28.0% of the citizens treated with these antidepressants. CONCLUSION: Compared to previous studies, we observed improvements with regard to doses and choice of drug, but the use of PMs among the elderly is still not sufficiently in accordance with current recommendations. FUNDING: not relevant. TRIAL REGISTRATION: The Danish Data Protection Agency approved the project with journal number 2007-58-0015.

Is a targeted intensive intervention effective for improvements in hypertension control? A randomized controlled trial.

BACKGROUND: High blood pressure (BP) is one of the most important risk factors for stroke, and antihypertensive therapy significantly reduces the risk of cardiovascular morbidity and mortality. However, achieving a regulated BP in hypertensive patients is still a challenge. OBJECTIVE: To evaluate the impact of an intervention targeting GPs' management of hypertension. METHODS: A cluster randomized trial comprising 124 practices and 2646 patients with hypertension. In the Capital Region of Denmark, the participating GPs were randomized to an intensive or to a moderately intensive intervention group or to a control group and in Region Zealand and Region of Southern Denmark, practices were randomized into a moderately intensive intervention and to a control group. The main outcome measures were change in proportion of patients with high BP and change in systolic BP (SBP) and diastolic BP (DBP) from the first to the second registration. RESULTS: The proportion of patients with high BP in 2007 was reduced in 2009 by ~9% points. The mean SBP was reduced significantly from 2007 to 2009 by 3.61 mmHg [95% confidence interval (CI): -4.26 to -2.96], and the DBP was reduced significantly by 1.99 mmHg (95% CI: -2.37 to -1.61). There was no additional impact in either of the intervention groups. CONCLUSION: There was no impact of the moderate intervention and no additional impact of the intensive intervention on BP.

Multi-dose drug dispensing is a challenge across the primary-secondary care interface.

INTRODUCTION: Multi-dose drug dispensing (MDDD) signifies that the patient's medicine is packed in disposable bags corresponding to the dose that should be taken. The purpose of the present study was to investigate how a hospital MDDD instruction was followed. MATERIAL AND METHODS: All patients receiving MDDD on admission to the acute medical admission ward at Bispebjerg Hospital in the period from 1 January to 30 June 2010 were prospectively included in the study. An audit of the medication lists and hospital case records covering the period from admission to discharge was performed. A proportion of patients received a post-discharge home visit. An interview in both sectors was carried out to determine whether the instructions had been followed. RESULTS: Almost 9% of the patients were receiving MDDD on admission. Information on MDDD was recorded in the physician case record for 3.4% of the patients and in the nurse case record for 12.9% of the patients. Changes in MDDD during hospitalization were made for 58.3% of the patients. General practitioners and/or the community pharmacy were notified of changes in MDDD at discharge for 13.6% of the patients. The post-discharge visits and the interview revealed potential issues of concern regarding patient safety. CONCLUSION: MDDD is frequent. Identification and registration of MDDD is only performed sporadically. Changes in MDDD are frequent, but they are rarely accompanied by information to the general practitioner or the community pharmacy. FUNDING: The project was partly funded by the Ministry of Health and Prevention 2009. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency.

[Medication errors after hospitalisation due to multi-dose drug dispensing in the primary sector]. / Dosisdispensering som årsag til fejlmedicinering ved sektorovergang.

Multi-dose drug dispensing (MDDD) was introduced in Denmark in 2001 in order to minimize medication errors. In May 2010 44.500 Danish citizens received MDDD. We report two cases where MDDD in the primary sector led to medication errors after hospitalisation, the reason partly being difficulties in getting information on MDDD on admission, lack of knowledge on handling MDDD in hospital and inadequate communication between the primary and the secondary sector. These problems has until now been underestimated.

[Changing clinicians' prescription patterns]. / Mulighed for aendring af ordinationsmønster.

In 2005 the Central Drug Committee in co-operation with the hospitals in the county of Copenhagen (H:S) focused on the increasing use of and expenditure derived from three tumour necrosis factor alpha (TNF-alpha) inhibitors. While the three inhibitors are estimated to be equivalent regarding efficacy and safety, eternacept and adalimumab are twice as expensive as infliximab. With a little effort, the Central Drug Committee succeeded in changing clinicians' prescription pattern in a cost-effective manner.

[Patient information leaflets seen through the eyes of patients in a general practice]. / Patienters vurdering af medicinpakningernes indlaegssedler.

INTRODUCTION: The objective was to investigate patients' perception of patient information leaflets, including their readability, comprehensibility and their impact on adherence. MATERIAL AND METHODS: A 14-item questionnaire was prepared and answered by unselected patients in a general practice in Copenhagen. RESULTS: A total of 111 patients were included. Eighty-eight patients (79%) always or often read the patient information leaflets. Among these, 77% attached importance to adverse effects. A mere 13% attached importance to all leaflet information. In all, 21% never or rarely read patient information leaflets, but relied on the doctor or the pharmacist. 62% of the interviewed had no problems reading or understanding the patient information leaflets. Among the 38% with reading problems, 57% had difficulties due to text-size, and 33% found the written language difficult to understand. Thirty-five patients (32%) stated that they had stopped taking medication due to the information about adverse effects. CONCLUSION: The patient information leaflet is an important source of drug information as most patients read the leaflet and nearly a third of the patients stated that information about the adverse effects had made them stop taking their medicine. Future studies should bring into focus the reason for medication adherence, how written information can be made easier to read, comprehensive and correct without contributing to anxiety and non-adherence.

[Application of the medicine profile in an ambulatory setting]. / Anvendelse af den personlige, elektroniske medicinprofil i et ambulatorium.

INTRODUCTION: A person with a digital signature can access his or her own personal electronic medicinal profile (PEM) which can also be accessed by the person's prescribing doctors. The PEM provides an overview and contains an overview of the prescription medicine sold to the patient over the previous two years. MATERIALS AND METHODS: Randomly-selected geriatric ambulatory patients were included. Accordance between physicians' medication records and the PEM was calculated. Moreover, the prescribing ambulatory doctor and the patient's general practitioner were asked if the PEM could contribute with non-recognized information about patients' prescription medicine. RESULTS: We found a 13-20% discrepancy between physicians' medication records and PEMs, involving 50-60% of the patients. In most cases, access to the PEM significantly corrected the discrepancies. Discrepancies were neither correlated to gender, age nor to the amount of prescription medicine. Discrepancies were judged to be serious or influential. CONCLUSION: The PEM provides insight into unrecognized information about patients' prescription medicine and access to the PEM bridges the gap between primary and secondary health care. Easier access to the digital signature, inclusion of over-the-counter drugs, and improved protection against misuse would further improve the PEM and ensure access to updated drug information.

[Combination therapy with acetylsalicylic acid and non-aspirin nonsteroidal anti-inflammatory drugs]. / Kombinationsbehandling med acetylsalicylsyre og nonsteroide antiinflammatoriske laegemidler.

Patients may require both low-dose aspirin (ASA) and a nonsteroidal anti-inflammatory drug (NSAID). This raises the questions of whether NSAIDs may inhibit the cardioprotective effects of low-dose ASA; whether the cardioprotective effect of low-dose ASA can be obtained by NSAIDs: and whether the combination of low-dose ASA and NSAIDs increases the risk of adverse effects. This review attempts to answer these questions.

Thiopurine methyltransferase (TPMT) genotype distribution in azathioprine-tolerant and -intolerant patients with various disorders. The impact of TPMT genotyping in predicting toxicity.

OBJECTIVE: To study the distribution of the thiopurine methyltransferase (TPMT) genotype among azathioprine (Aza)-tolerant and -intolerant patients with various disorders, and to investigate a possible relationship with the Aza metabolite levels. METHODS: Forty-six Aza-tolerant and six Aza-intolerant patients had the TPMT genotype distribution determined using a polymerase chain reaction (PCR) assay and the forty-six Aza-tolerant patients had the Aza metabolite levels determined using a high-pressure liquid chromatography (HPLC) analysis. RESULTS: One non-functional TPMT mutant allele was demonstrated in 2 of the 46 Aza-tolerant patients (4.4%) and one or two non-functional mutant alleles in 2 of the 6 Aza-intolerant patients (33.3%). Of the 4 patients, with one or two non-functional mutant alleles 2 (50%) were intolerant to Aza compared with 4 of the 48 patients (8.3%) with no mutations detected. The time to hepatotoxicity did not differ significantly between the 2 patients with one or two non-functional mutant alleles and the remaining 3 patients ( P=0.5). The TPMT genotype distribution differed slightly in the three different categories of disorders ( P=0.05). The median E-6-TGN level among the 2 TPMT heterozygous patients was 275 pmol/8x10(8) RBC (range 240-310), whereas the remaining 44 patients had a median E-6-TGN level of 110 pmol/8x10(8) RBC (range 0-440) ( P=0.07). CONCLUSION: Although TPMT genotyping cannot be recommended on behalf of the present study, it is to be expected that half of the patients with one or two non-functional TPMT mutant alleles will develop Aza intolerance leading to withdrawal of therapy. Thus, clinicians may anticipate about 5% of the patients to develop intolerance to Aza therapy solely for that reason.

[Drug-induced seizures]. / Laegemiddelinducerede kramper.

Numerous drugs have been suspected to be associated with the occurrence of epileptic seizures. Our information retrieval, however, shows that drug-induced seizures are relatively rare. The risk of seizure seems to be increased, also in patients who are not predisposed to seizure, when taking clozapine, enflurane, theophylline, foscarnet, ganciclovir, and ritonavir. The risk of seizure is greatest in patients predisposed to seizure by use of conventional antipsychotics, olanzapine, risperidone, bupropion, tricyclic antidepressants/selective serotonin reuptake inhibitors, cyclosporin, interferon, corticosteroids, propofol, imipenem, chloroquine, and mefloquine. In case of suspicion of drug-induced seizures, reporting should be made to the Danish Medicines Agency. If the drug has been on the market less than two years, reporting is mandatory.

Effect of growth hormone on hepatic cytochrome P450 activity in healthy elderly men.

OBJECTIVE: Our objective was to study the effect of recombinant human growth hormone (rhGH) on hepatic cytochrome P450 (CYP) activity in 30 healthy elderly men. METHODS: The study was carried out as a randomized, double-blind, placebo-controlled parallel-group study. rhGH or placebo was administered for a period of 12 weeks. CYP activity was measured before, after 12 weeks of rhGH and placebo administration, and at 4 weeks after termination of rhGH and placebo administration with use of the biomarker reactions of CYP1A2 (caffeine), CYP2C19 (mephenytoin), CYP2D6 (sparteine), CYP3A4 (endogenous cortisol metabolism), and antipyrine clearance as common markers of CYP activity. RESULTS: The metabolic ratio of caffeine increased significantly in the group that received growth hormone compared with placebo (median difference, 4.55; 95% confidence interval (CI), 1.64 to 8.60; versus -0.90; 95% CI, -5.70 to 1.36), indicating an induction of CYP1A2. Moreover, the S/R ratio of mephenytoin showed a small but significant increase (median difference, 0.02; 95% CI, 0 to 0.31; versus 0; 95% CI, -0.01 to 0.06), indicating an inhibition of CYP2C19. There were no significant changes of the metabolic ratios of cortisol and sparteine or the antipyrine clearance compared with placebo. CONCLUSIONS: These results indicate that growth hormone induces CYP1A2 and, to a lesser extent, inhibits CYP2C19 in elderly men, but it exerts no effects on CYP2D6 and CYP3A4. Although the induction of CYP1A2 may be of some clinical relevance, the small inhibition of CYP2C19 is probably unimportant.