The effect of ICU-tailored drug-drug interaction alerts on medication prescribing and monitoring: protocol for a cluster randomized stepped-wedge trial.

BACKGROUND: Drug-drug interactions (DDIs) can cause patient harm. Between 46 and 90% of patients admitted to the Intensive Care Unit (ICU) are exposed to potential DDIs (pDDIs). This rate is twice as high as patients on general wards. Clinical decision support systems (CDSSs) have shown their potential to prevent pDDIs. However, the literature shows that there is considerable room for improvement of CDSSs, in particular by increasing the clinical relevance of the pDDI alerts they generate and thereby reducing alert fatigue. However, consensus on which pDDIs are clinically relevant in the ICU setting is lacking. The primary aim of this study is to evaluate the effect of alerts based on only clinically relevant interactions for the ICU setting on the prevention of pDDIs among Dutch ICUs. METHODS: To define the clinically relevant pDDIs, we will follow a rigorous two-step Delphi procedure in which a national expert panel will assess which pDDIs are perceived clinically relevant for the Dutch ICU setting. The intervention is the CDSS that generates alerts based on the clinically relevant pDDIs. The intervention will be evaluated in a stepped-wedge trial. A total of 12 Dutch adult ICUs using the same patient data management system, in which the CDSS will operate, were invited to participate in the trial. Of the 12 ICUs, 9 agreed to participate and will be enrolled in the trial. Our primary outcome measure is the incidence of clinically relevant pDDIs per 1000 medication administrations. DISCUSSION: This study will identify pDDIs relevant for the ICU setting. It will also enhance our understanding of the effectiveness of alerts confined to clinically relevant pDDIs. Both of these contributions can facilitate the successful implementation of CDSSs in the ICU and in other domains as well. TRIAL REGISTRATION: Nederlands Trial register Identifier: NL6762 . Registered November 26, 2018.

['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.

[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.

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.

[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.

[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.

[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.

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.

[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.

[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.

Meta-analysis of efficacy and safety of second-generation dihydropyridine calcium channel blockers in heart failure.

Second-generation dihydropyridine calcium channel blockers slightly increase cardiac index, left ventricular ejection fraction, and exercise treadmill tests in patients with chronic heart failure, and do not increase norepinephrine levels; these drugs seem to be safe and beneficial in this category of patients. A 6% reduction in mortality was found, which, although not significantly different from 0%, does indicate that these drugs do not increase mortality in this category of patients.

Cardiac tamponade following sternal puncture in two patients.

Sternal puncture for harvesting bone marrow is a procedure with potentially lethal complications. Both the occurrence of pneumothorax and sternal fracture are reported. We present two patients with a cardiac tamponade following elective sternal puncture. (See Editorial p. 4).

Relationship between internal risk factors for development of decubitus ulcers and the blood flow response following pressure load.

The objective of this study was to investigate the extent to which internal risk factors for the development of decubitus ulcers are related to the blood flow response following the relief of a pressure load. There were 122 nursing home patients (43 men, 69 women, mean age: 81 +/- 8 years; range: 60-97). The following potential, internal risk factors for the development of decubitus ulcers were assessed: chronic disorders (diabetes mellitus, cardiovascular disease [congestive heart failure, history of myocardial infarct or angina pectoris] and cerebrovascular accident), fever, blood pressure, nutritional status, serum hemoglobin concentration, and serum urea and serum creatinine concentrations. Skin temperature response (latency time and total response time) was measured following relief of a 100 kPa test pressure. The presence of cardiovascular disease, cerebrovascular accident, poor nutritional condition, high serum urea and male gender showed a significant relationship with an impaired blood flow response. The delayed latency found showed a similarity to the so-called "no-reflow phenomenon." The association of cardiovascular disease and a cerebrovascular accident with a delay in the blood flow response may result from endothelial damage. A poor nutritional condition may be associated with a deficit of scavengers of oxygen-derived free radicals. The presence of free radicals may damage endothelium during reperfusion, thus influencing the blood flow response. The association of high serum urea with delayed vasodilatation may theoretically be explained by the association of serum urea and impaired kidney functioning, since the kidney is an important organ in the production of vasoactive substances. Serum urea can also be considered a measure for nutritional condition. Gender may function as a substitute for other, unmeasured factors that are related to blood flow response.

[Norton's decubitus risk score in a nursing home]. / De risicoscoring voor decubitus volgens Norton in een verpleeghuis.

Decubitus must be considered an important problem in public health care. In the Netherlands (total population 15 million) the costs of prevention and treatment of decubitus in the hospitals and nursing homes are approximately Dfl. 700 million per year. In order to identify patients at risk for the development of decubitus at an early stage. Norton and colleagues developed a scoring system that includes an assessment of general physical condition, mental status, activity level, mobility and incontinence. In a prospective study in 224 somatic nursing home patients we investigated the relationship between the Norton-score and the appearance of decubitus. The authors conclude that, when using the Norton-score, it is not possible to differentiate patients at risk clearly from patients with no risk. From the five items used by Norton, only mobility and, to a lesser degree, general physical condition, show a significant relation with the occurrence of decubitus ulcers. In order to identify the patients at risk roughly, the physician can suffice with scoring these two items.