Hospital physicians' and older patients' agreement with individualised STOPP/START-based medication optimisation recommendations in a clinical trial setting.

OBJECTIVE: To evaluate the agreement of hospital physicians and older patients with individualised STOPP/START-based medication optimisation recommendations from a pharmacotherapy team. METHODS: This study was embedded within a large European, multicentre, cluster randomised controlled trial examining the effect of a structured medication review on drug-related hospital admissions in multimorbid (≥ 3 chronic conditions) older people (≥ 70 years) with polypharmacy (≥ 5 chronic medications), called OPERAM. Data from the Dutch intervention arm of this trial were used for this study. Medication review was performed jointly by a physician and pharmacist (i.e. pharmacotherapy team) supported by a Clinical Decision Support System with integrated STOPP/START criteria. Individualised STOPP/START-based medication optimisation recommendations were discussed with patients and attending hospital physicians. RESULTS: 139 patients were included, mean (SD) age 78.3 (5.1) years, 47% male and median (IQR) number of medications at admission 11 (9-14). In total, 371 recommendations were discussed with patients and physicians, overall agreement was 61.6% for STOPP and 60.7% for START recommendations. Highest agreement was found for initiation of osteoporosis agents and discontinuation of proton pump inhibitors (both 74%). Factors associated with higher agreement in multivariate analysis were: female gender (+ 17.1% [3.7; 30.4]), ≥ 1 falls in the past year (+ 15.0% [1.5; 28.5]) and renal impairment i.e. eGFR 30-50 ml/min/1.73 m2; (+ 18.0% [2.0; 34.0]). The main reason for disagreement (40%) was patients' reluctance to discontinue or initiate medication. CONCLUSION: Better patient and physician education regarding the benefit/risk balance of pharmacotherapy, in addition to more precise and up-to-date medical records to avoid irrelevant recommendations, will likely result in higher adherence with future pharmacotherapy optimisation recommendations. CLINICAL TRIAL REGISTRATION: Trial Registration Number NCT02986425.

[Polypharmacy in elderly patients]. / Polyfarmacie bij ouderen.

Polypharmacy is increasing with age. With increasing numbers of medication, the risk of the use of potential inappropriate medication is also increasing. In this article we suggest using the WHO-6-step for rational prescribing. We also describe methods and instruments (amongst others: the systemic tool to reduce inappropriate prescribing)physicians can use in assessing the appropriateness of the medication already used by their patients. Finally we describe how, based on recent Dutch guidelines, deprescribing can be done.

Clinically relevant potential drug-drug interactions in intensive care patients: A large retrospective observational multicenter study.

PURPOSE: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. MATERIALS & METHODS: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. RESULTS: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. CONCLUSIONS: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients.

['You tell me, you are the doctor'; patients on long-term psychiatric residences about their medication]. / 'Zegt u het maar, u bent de dokter'; patiënten op langdurige psychiatrische verblijfsafdelingen over hun medicatie.

BACKGROUND: In an era of patient centered care, the question rises whether practitioners of these patients are sufficiently aware of their treatment preferences.
AIM: To study the opinion and knowledge of older, long-term psychiatric patients about their medication and health priorities.
METHOD: Patients were interviewed with the Patient's Attitudes Towards Deprescribing questionnaire. Furthermore patients were asked to name their medication by heart, their health priorities and preferences in medication changes. These preferences were compared with those of their practitioners.
RESULTS: 47 patients (median age 67 years, median 11 drugs) were interviewed. The mean percentage of spontaneously recalled drugs was 37%. Though 64% believed all used drugs were necessary, 77% would like to deprescribe if the doctor said it was possible. Preferences in deprescribing of patients and doctors didn't correspond in about 80%.
CONCLUSION: Most of old psychiatric patients are willing to deprescribe, but await initiative of their doctor. They can recall little of their currently used drugs. Preferences in deprescribing of the patient and doctor do often not match. We recommend to include a patient interview about the need for education and treatment preferences in the annual medication reviews in order to deprescribe and deliver more patient centered care.

[Periodical medication review: bigger and better?] / De periodieke medicatiebeoordeling.

The Netherlands' practice guideline 'Polypharmacy in older people' (2012) proposed selecting patients who would benefit from a periodical medication review. The guideline committee made it clear that firm evidence supporting selection was lacking, and recent studies evaluating the effects of medication review on relevant patient-related outcomes have failed to show a positive effect on almost any of these outcomes. Regulatory authorities have advised expanding the target population for medication review. We have to conclude, however, that rather than implementing medication reviews across a broad population of older people, many with a low risk of adverse events, it may be more cost-effective to limit this potentially useful but time-consuming intervention to a more select population who would benefit the most from it.

[Multidose drug dispensing: what does it really involve?] / Medicatie op rol, wat komt er bij kijken?

- Multidose drug dispensing (MDD) systems are individualised forms of distribution that give structure to medication use. - Starting to use a multidose drug dispensing system must be initiated in joint discussion with the patient, once alternatives such as dosing schemes or automatic repeat-prescription services have been considered. The patient's autonomy and self-management are central.- Studies have shown positive effects of individualised forms of distribution on intermediary outcome measures such as HbA1c, LDL cholesterol, blood pressure and adherence. - Changes in medication should preferably be implemented when the pharmacist orders a new multidose drug dispensing system. It is difficult for the pharmacist to determine whether an immediate change is necessary if the indication and other possible reasons for change are not known. - The prescriber should preferably enquire whether the patient has a multidose dispensing system and should state the moment or the reason for the change on the prescription.- Pharmacotherapy in patients using a multidose drug dispensing system should be reviewed annually.

[Medication review in the mental health care service: experiences on long-stay units]. / Medicatiebeoordeling in de ggz: praktijkervaring op afdelingen voor langdurig verblijf.

BACKGROUND: Medication review is a recurrent, structured and critical evaluation of pharmacotherapy by patient, physician and pharmacist. The Dutch Health Care Inspectorate considers medication review to be a way of improving the quality and safety of drug treatment. However, little is known about the costs, effectiveness and feasibility of medication review in the practice of mental health care. AIM: To obtain an impression of the costs and benefits of a first medication review in a clinical mental health care setting with chronic patients. METHOD: In 2013, the mental health organisation Yulius enrolled 70 hospitalised chronic patients for a first medication review. A detailed record was kept of the prescribed medication, medication changes, and the time invested. RESULTS: More than half of the proposed changes in medication were eventually implemented; 20% of these changes were made during a planned evaluation after three months. The number of drugs prescribed decreased after medication review; the reduction applied more often to somatic medication than to psychotropic medication. Costs relating to medication reviews seemed to be at least in balance with the benefits. CONCLUSION: In the group of patients with severe mental disorder, medication review seems to provide a good opportunity to assess the rationality of pharmacotherapy in a multidisciplinary approach. The time invested appears to be offset by the benefits of medication review.

The Association Between Potentially Inappropriate Prescribing and Medication-Related Hospital Admissions in Older Patients: A Nested Case Control Study.

INTRODUCTION: Medication-related problems can cause serious adverse drug events (ADEs) that may lead to hospitalization of the patient. There are multiple screening methods to detect and reduce potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs). Whether this will result in less medication-related hospitalizations is unknown. The study objective was to assess the risk of preventable medication-related hospital admissions associated with potentially inappropriate prescribing, using the Beers 2012 and the Screening Tool of Older Person's Prescriptions and the Screening Tool to Alert doctors to Right Treatment (STOPP & START) 2008 criteria. DESIGN, SETTING AND PARTICIPANTS: A nested case-control study was conducted with a subset of Dutch participants from the Hospital Admissions Related to Medication (HARM) study. Cases were defined as patients aged ≥65 years with a potentially preventable medication-related hospital admission. For each case, one control was selected, matched for age and sex. The primary determinant was the presence of one or more PIMs according to the Beers 2012 and STOPP 2008 criteria. The secondary determinant was the presence of one or more PIMs and PPOs according to the STOPP & START 2008 criteria. The strength of the association between inappropriate prescribing and medication-related hospital admission was evaluated with multivariate logistic regression and expressed as odds ratios (ORs) with 95 % confidence intervals (CIs). RESULTS: The prevalence of Beers 2012 criteria PIMs in the total cohort was 44.4 %. The prevalence of STOPP & START 2008 criteria PIMs and PPOs were, respectively, 34.1 and 57.7 %. STOPP 2008 criteria PIMs were associated with preventable medication-related hospital admissions [OR adjusted for number of drugs and comorbidities (ORadj) 2.30, 95 % CI 1.30-4.07], whereas there was no association with Beers 2012 criteria PIMs (ORadj 1.49, 95 % CI 0.90-2.47). STOPP PIMs and START PPOs together were also associated with preventable medication-related hospital admissions (ORadj 3.47, 95 % CI 1.70-7.09). CONCLUSION: Our study shows that patients with potentially inappropriate prescribing detected with the STOPP & START 2008 criteria are at risk of preventable medication-related hospital admissions. The STOPP & START 2008 criteria can be used to identify older people at risk of medication-related problems.

[Discontinuing medication in elderly: a checklist may be useful]. / Stoppen van medicatie bij ouderen.

Elderly patients are at an increased risk of developing adverse drug events due to polypharmacy, co-morbidity and changes in physiology. Often, pharmacotherapy in frail elderly patients is initiated based on randomized trials from which this population has been excluded. In such cases, the question when to stop a medication may be as important as when to start it. It is important to consider whether the patient is using Potentially Inappropriate Medications (PIM) that should be stopped. Checklists can be helpful in detecting PIM. A recent study has shown that Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) criteria can identify clinically relevant PIM much better than the Beers criteria often used. These outcomes indicate that patient safety can be improved if clinicians use checklists such as the STOPP.

The course of behavioral problems in elderly nursing home patients with dementia when treated with antipsychotics.

BACKGROUND: Although antipsychotic treatment of behavioral problems in dementia is common, studies investigating the course of these symptoms in nursing homes are scarce. Our primary objective is therefore to describe the course of behavioral problems during antipsychotic treatment in a large sample of elderly nursing home patients with dementia. METHODS: The course of behavioral problems during antipsychotic treatment was studied by comparing the characteristics of patients before, during and after antipsychotic treatment. The study was conducted using the VURAIDB, a database with over 40,000 assessments of over 10,000 nursing home residents in the Netherlands. We used the Challenging Behavior Profile (CBP) to measure an overall behavior score. RESULTS: In total, 556 patients starting with antipsychotics were studied. Of these, 101 (18.2%) improved and 260 (46.8%) deteriorated at three months on the behavior score, compared with their scores before therapy (z = -7.955; P<0.0001). Patients with severe challenging behavior showed improvement more often than patients with mild disturbances. The course of behavioral symptoms after withdrawal was evaluated in 520 patients. Of these patients, 352 (68%) remained stable or improved at 3 months compared with their scores before withdrawal (z = -0.697; p = 0.486), this figure was 58% at 6 months after withdrawal (z = -2.77; p = 0.006). CONCLUSIONS: During treatment of nursing home residents with dementia with antipsychotics the severity of most behavioral problems continues to increase in most patients, with only one out of six patients showing improvement. After withdrawal of antipsychotics, behavioral problems remained stable or improved in 58% of patients.

[Cardiac effects of cholinesterase inhibitors: a reason for restraint?]. / Cardiale neveneffecten van cholinesteraseremmers: een reden tot terughoudendheid in voorschrijven?

Cholinesterase inhibitors are prescribed in the treatment of mild to moderate Alzheimer's dementia. Little is known about the cardiac safety of these drugs. We present two different cases in which cardiac events occurred during the use of a cholinesterase inhibitor. The pathophysiology, the effects of these drugs on the heart, information about the reports of side effects in pharmacovigilance databases and known literature are discussed. Although cardiac risks of cholinesterase inhibitors seem small, we advise to monitor cardiac effects of cholinesterase inhibitors carefully in patients with existing cardiac disease, especially in those using concomitant drugs known to interact with the cardiac risks of cholinesterase inhibitors.

Risk of cerebrovascular events in elderly users of antipsychotics.

It has been shown that elderly patients with dementia treated with atypical and conventional antipsychotics have a twofold increased risk of cerebrovascular adverse events (CVAEs). To investigate the temporal relationship between exposure to antipsychotics and the risk of CVAE, a case-control analysis nested within a cohort of 26,157 community-dwelling patients (mean age 76 +/- 9.7) with at least one antipsychotic prescription was conducted. Data were used from Dutch community pharmacies and hospital discharge records. Five hundred and eighteen cases of hospital admission for CVAE were identified. For each case, four randomly selected controls matched by sex and age were sampled from the cohort. To evaluate the temporal relationship between antipsychotic use and the occurrence of CVAE, two measures were used: the first being a current, recent or past user, and the second for the current users, the duration of use up to the index date. In addition, the cumulative exposure was assessed. Current and recent exposure to antipsychotics were associated with an increased risk of CVAE compared with non-users (odds ratio [OR] 1.7, CI 1.4-2.2). A strong temporal relationship was found; the OR for a history of use less than a week is 9.9 (5.7-17.2). The risk decreases in time and is comparable to non-users after 3 months of use (OR 1.0, CI 0.7-1.3). Cumulative exposure was not associated with an increase in risk. The risk of CVAE in elderly patients associated with antipsychotics is elevated especially during the first weeks of treatment. This risk decreases over time and is back on base level after 3 months of treatment. Chronic use is not associated with CVAE.

[Symptomatic treatment in patients with dementia: light, but not melatonin, is probably worthwhile]. / Symptomatische behandeling bij patiënten met dementie: licht mogelijk wel, maar melatonine niet zinvol.

A recent study in the JAMA described the effects of long-term daily treatment with whole-day bright light in elderly patients with dementia, with or without the addition of melatonin (2.5 mg daily), on cognition, mood, behavioural symptoms, activities of daily living and sleep. It was concluded that light has a modest benefit in improving some cognitive and non-cognitive symptoms of dementia. The effects of melatonin were negligible. Despite the small effects found of this study, the outcomes can be used in clinical practice since other small studies also show a trend towards positive effects of bright light in dementia patients. Since current pharmacotherapy for behavioural problems in dementia has very modest effects at the risk of serious adverse effects, non-pharmacological interventions must be encouraged. Increasing light intensity in the living rooms of patients with dementia is an easy and cheap intervention with possible positive effects on at least some patients.

[Metformin-related lactic acidosis in an 85-year-old woman]. / Lactaatacidose bij een 85-jarige vrouw door behandeling met metformine.

An 85-year-old woman presented at the emergency ward. She had had shortness of breath for several days and no bowel movements for 3 days. On the day ofhospitalisation she experienced sudden abdominal pain and collapsed as she went to the toilet. She was being treated for multiple conditions, including type-2 diabetes. She appeared to have lactic acidosis. At first, the symptoms were not attributed to metformin because she was receiving a low dose and serum-creatinine concentrations were within the normal range (98 micromol/l). Bowel ischaemia was suspected and surgery was performed but no defects were found. She was subsequently treated for metformin-related lactic acidosis but died shortly thereafter due in part to postoperative complications. Lactic acidosis is a rare side effect of metformin. In this patient, the retrospectively calculated glomerular filtration rate (GFR) was extremely low (23 ml/min). The serum-creatinine concentration was normal because the patient's body weight was low (40 kg). Impaired renal function is a risk factor for metformin-related lactic acidosis. Renal function can appear to be normal when measured by serum-creatinine concentration in older patients with reduced muscle mass, but calculation of GFR often reveals impairment. Metformin is contraindicated in patients with poor renal function. The increasing use of metformin in older patients for the treatment of diabetes mellitus warrants renewed attention to this severe side effect.

[The Beers List as an aid to prevent adverse drug reactions in elderly patients]. / De beers-lijst als hulpmiddel om ernstige geneesmiddelbijwerkingen bij ouderen te voorkomen.

Elderly patients are highly susceptible for developing adverse drug reactions (ADR) that can lead to hospitalisation or death. Most of these ADR can be prevented if doctors adjust their prescriptions. Beers et al. have developed a list of drugs that should not be prescribed to elderly patients since they are known for their association with serious ADR. In The Netherlands, 20% of elderly patients receive drugs that are in the so-called Beers list. Although the Beers list has not been adjusted to the Dutch situation, avoidance of these drugs may reduce drug-related hospital admittance. Development of an improved list of drugs that should not be prescribed to elderly patients is needed that is applicable to The Netherlands.

[Increased risk of stroke during the use of olanzapine or risperidone in patients with dementia]. / Toegenomen kans op een beroerte na gebruik van olanzapine of risperidon bij patiënten met dementie.

Post-hoc analysis by the pharmaceutical company Eli Lilly of 5 randomised clinical trials concerning the efficacy ofolanzapine in patients with dementia, has shown that patients taking olanzapine have a risk of experiencing a cerebrovascular accident which is 3 times higher than patients taking placebo. This increased risk has also been found in patients with dementia who take risperidone. Details concerning this relationship cannot be obtained from the sparse information supplied by the producers of risperidone and olanzapine. The pathophysiological mechanisms by which atypical antipsychotics may lead to cerebrovascular accidents are not well understood. Atypical antipsychotics are often prescribed for conditions in which evidence of the efficacy of this group of medications is lacking. This association between antipsychotics and cerebrovascular accidents emphasises the need for a stricter and evidence-based prescription policy for antipsychotics. In cases of adverse drug reaction, more openness on the part of pharmaceutical companies is desirable.

[Antipsychotic medication as a cause of deep hypothermia]. / Antipsychotica als oorzaak van diepe hypothermie.

Two patients were presented at our hospital with hypothermia following dose adjustment of antipsychotic medication. The first patient, a mentally retarded 45-year-old man developed a temperature of 31.7 degrees C several days after starting of levomepromazine. The second patient, an 41-year-old schizophrenic man, whose risperidone dose had been increased following a psychotic crisis, developed deep hypothermia (temperature 29.7 degrees C) and severe respiratory insufficiency requiring pressure support ventilation. Both patients were admitted to the ICU and recovered completely. Antipsychotics influence hypothalamic thermoregulation and may induce hypothermia by stimulating dopamine (mainly D2) receptors and blocking 5-HT2 receptors. Furthermore, antipsychotics may reduce the shivering capability and can cause peripheral vasodilatation and reduced shunting by blocking skin alpha 1 receptors. Hypothermia can be a lethal condition. When a patient's clinical condition deteriorates following the start of antipsychotic medication, the presence of hypothermia should be excluded.

[Continuous subcutaneous infusion in palliative care, an undervalued method]. / Continue subcutane infusie in de palliatieve zorg, een ondergewaardeerde methode.

Three patients, 2 men aged 55 and 54 years and a woman aged 86 years, were admitted to hospital for treatment of symptoms resulting from terminal disease (pain, agitation, nausea etc.). In all three patients, continuous subcutaneous infusion (CSI) of medication was successfully used to control the symptoms. Compared with intravenous infusion, the technique of CSI is easy to learn and is associated with fewer complications. Its reliability and ease-of-use make it a technique that can be used not only in a hospital setting, but also in general practice and nursing homes. Medication used in palliative care (e.g. morphine, haloperidol, metoclopramide, levomepromazine, midazolam) can often be administered safely by CSI. In palliative care, where goals should be accomplished with minimal burden to the patient, CSI must be considered the technique of choice in patients who are unable to swallow their medication.