Task analysis of information technology-mediated medication management in outpatient care.

AIMS: Educating physicians in the procedural as well as cognitive skills of information technology (IT)-mediated medication management could be one of the missing links for the improvement of patient safety. We aimed to compose a framework of tasks that need to be addressed to optimize medication management in outpatient care. METHODS: Formal task analysis: decomposition of a complex task into a set of subtasks. First, we obtained a general description of the medication management process from exploratory interviews. Secondly, we interviewed experts in-depth to further define tasks and subtasks. SETTING: Outpatient care in different fields of medicine in six teaching and academic medical centres in the Netherlands and the United States. PARTICIPANTS: 20 experts. Tasks were divided up into procedural, cognitive and macrocognitive tasks and categorized into the three components of dynamic decision making. RESULTS: The medication management process consists of three components: (i) reviewing the medication situation; (ii) composing a treatment plan; and (iii) accomplishing and communicating a treatment and surveillance plan. Subtasks include multiple cognitive tasks such as composing a list of current medications and evaluating the reliability of sources, and procedural tasks such as documenting current medication. The identified macrocognitive tasks were: planning, integration of IT in workflow, managing uncertainties and responsibilities, and problem detection. CONCLUSIONS: All identified procedural, cognitive and macrocognitive skills should be included when designing education for IT-mediated medication management. The resulting framework supports the design of educational interventions to improve IT-mediated medication management in outpatient care.

[Hallucinations and vivid dreams by use of metoprolol]. / Hallucinaties en levendige dromen bij metoprololgebruik.

A 71-year-old man had had visual hallucinations and vivid dreams for two years after starting to take metoprolol. When metoprolol was replaced by atenolol the patient's symptoms disappeared within five days. Side-effects of beta-blockers on the central nervous system are relatively uncommon. The mechanisms underlying these side-effects are not fully understood. Lipophilic beta-blockers can cross the blood-brain barrier, whereas hydrophilic beta-blockers cannot. Doctors need to be alerted to the varying side-effects of specific beta-blockers.

[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.

[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.

Diagnostic errors; the need to have autopsies.

INTRODUCTION: In geriatric patients, atypical presentation and limitations in diagnostic scope may lead to underdiagnosis. The aim of this study was to establish the frequency, nature and causes of clinical diagnostic errors in a geriatric population. DESIGN: A retrospective study. METHODS: We assessed the accuracy of clinical diagnosis using autopsy results as our gold standard. Factors likely to influence accuracy of clinical diagnosis were identified. We used the (modified) classification of Goldman et al. to define discrepancy. RESULTS: We analysed 93 autopsies of a total of 331 deaths (28%). Discrepancies in major diagnoses were seen in 36 cases (39%). In 17 of these, clinical management might have been different if the diagnosis had been made premortem. These were: pulmonary embolism (4); unrecognised infection (4); intestinal ischaemia (3); ruptured aortic aneurysm (2); malignancy (1); tracheal obstruction (1); intestinal obstruction (1) and acute pancreatitis (1). Discrepancies in minor diagnoses were seen in 46 cases (50%). About one third of these were clinically relevant. Discrepancies occurred more frequently if there was a degree of uncertainty about clinical diagnosis p<0.001). CONCLUSION: Major discrepancies between clinical diagnosis and autopsy findings were seen in 39% of our study population. They occur more often in the case of uncertain clinical diagnosis. Our findings stress the continuing and important role of autopsy in improving clinical practice in geriatric medicine.

[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.

[Clinically relevant drug interactions in the elderly]. / Klinisch relevante geneesmiddeleninteracties bij ouderen.

About 15% of hospital admissions of elderly patients in the Netherlands are caused by adverse effects of drugs. With polypharmacy there is an increased chance of adverse effects occurring. It is not always possible to reduce polypharmacy in the elderly. Polypharmacy is often associated with drug interactions which result in an increased or decreased effect, or the occurrence of adverse effects. Due to changes in the pharmacokinetic and pharmacodynamic properties of drugs in the elderly, the effect of interactions is more clinically relevant. Pharmacokinetic interactions influence absorption, liver metabolism or excretion by the kidneys. In particular, interactions with drugs that have a narrow pharmacotherapeutic spectrum can result in serious adverse effects: anticonvulsives, anti-Parkinson drugs, antipsychotics, coumarin derivates, digitalis preparations, lithium salts, opiates, sulphonylurea derivates, tricyclic antidepressants and verapamil. The most important pharmacodynamic changes in the elderly concern an increased sensitivity of the target organ. This is particularly the case for substances which have an effect on the central nervous system, such as antidepressants and antipsychotics, but also applies to benzodiazepines, coumarin derivatives and digoxin. When an unexpected adverse effect occurs in a patient or a previously effective therapy suddenly fails, it is wise to consider drug interaction as a possible cause.

[Clozapine for the treatment of psychosis in 3 elderly patients with Parkinson's disease]. / Clozapine ter behandeling van psychose bij 3 oude patiënten met de ziekte van Parkinson.

Three patients with Parkinson's disease developed psychosis. None of the three showed any other somatic cause for the psychosis except the Parkinson's disease. The first patient, a 73-year-old male, was initially treated with olanzapine and rivastigmine, without any effect. While treating the second patient, a 75-year-old male who had been suffering from Parkinson's disease for years, the Parkinson medication was first reduced and later on olanzapine and rivastigmine were prescribed, without a lasting effect on the psychotic symptoms. In the third patient, an 85-year-old male, medication reduction was unsuccessful. Finally, all three were treated effectively with clozapine. Psychosis in Parkinson's disease is a serious disorder that is often difficult to treat. In most cases, antipsychotic medication is needed. The atypical antipsychotic clozapine is effective without aggravation of the motor symptoms. Despite the side effects, such as the risk of agranulocytosis, drowsiness and weight gain, clozapine should be considered as a possible treatment.

[Severe parkinsonism due to metoclopramide in a patient with polypharmacy]. / Ernstig parkinsonisme ten gevolge van metoclopramide bij een patiënte met polyfarmacie.

A 73-year-old woman, with tuberculosis of the large intestine, developed nausea as a side effect of the antituberculosis drugs. The nausea was treated with metoclopramide. Subsequently she developed severe medication-induced parkinsonism. As her symptoms initially mimicked a depressive disorder, drug-induced parkinsonism was only considered at a later stage. Due to drug-induced impaired function of the liver and kidney the patient had received a toxic dose of metoclopramide. Treatment with biperiden and withdrawal of the metoclopramide resulted in a reduction of the complaints within 3 months, after which the anti-tuberculosis medication could be reintroduced. Adjusting the dose of metoclopramide could possibly have prevented this severe side effect.

Prolonged outpatient vitamin K antagonist use and risk of venous thromboembolism in patients undergoing total hip or knee replacement.

BACKGROUND: Long-term risk of venous thromboembolism (VTE) following total hip or knee replacement (THR/TKR) compared with controls has not been studied extensively, and the long-term influence of outpatient anticoagulant use on VTE risk remains unknown. The objectives were to evaluate long-term VTE risk following THR/TKR compared with matched controls, and to investigate effect modification by prolonged outpatient vitamin K antagonist use. METHODS: A Danish retrospective nationwide cohort study was conducted. All patients undergoing primary THR/TKR (n = 95,227) between 1998 and 2007 were selected, each matched by age, sex and region with three controls (no THR/TKR). Patients were stratified by prolonged outpatient vitamin K antagonist use in the previous 3 months (in a time-dependent manner). All subjects were followed for VTE, and Cox models were used to calculate disease and medication history adjusted hazard ratios (HRs). RESULTS: Within 6 weeks following surgery, a 13-fold increased risk of VTE was found for THR (adj. HR 12.9; 95% CI 11.2-14.7), and a 14-fold elevated risk for TKR (adj. HR 13.6; 95% CI 11.0-16.7), compared with matched controls. The risk remained substantially increased for at least 4 months following THR/TKR. Within this period, prolonged outpatient vitamin K antagonist use reduced the increase in VTE risk by 69% for THR and 54% for TKR. CONCLUSION: The risk of VTE remains substantially elevated for at least 4 months following THR/TKR; this is well beyond the recommended duration of anticoagulant use. The increase in VTE risk is less pronounced in prolonged outpatient vitamin K antagonist users.

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.

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.

Effect of gastric distension on cardiovascular parameters: gastrovascular reflex is attenuated in the elderly.

Stretching the stomach wall in young healthy subjects causes an increase in muscle sympathetic nerve activity and in blood pressure, the gastrovascular reflex. We compared healthy elderly subjects with healthy young subjects to find out whether the gastrovascular reflex attenuates in normal ageing and we studied whether there was a difference in autonomic function or gastric compliance that could explain this possible attenuation. Muscle sympathetic nerve activity, finger blood pressure and heart rate were continuously recorded during stepwise isobaric gastric distension using a barostat in eight healthy young (6 men and 2 women, 27 +/- 3.2 years, mean +/-s.e.m.) and eight healthy elderly subjects (7 men and 1 woman, 76 +/- 1.5 years). Changes in cardiac output and total peripheral arterial resistance were calculated from the blood pressure signal. The baseline mean arterial pressure and muscle sympathetic nerve activity were higher in the elderly group (both P < 0.05) and muscle sympathetic nerve activity increase during the cold pressor test was lower in the elderly group (P = 0.005). During stepwise gastric distension, the elderly subjects showed an attenuated increase in muscle sympathetic nerve activity compared to the young subjects (P < 0.01). The older group tended to show a higher increase in mean arterial pressure (P = 0.08), heart rate (P = 0.06) and total peripheral arterial resistance (P = 0.09) The cardiac output rose slightly in both groups without significant difference between groups. The fundic compliance did not differ between groups. We conclude that stepwise gastric distension caused an increase in muscle sympathetic nerve activity in both groups, but the increase in the elderly was attenuated.

Antipsychotics and Parkinson's disease: association with disease and drug choice during the first 5 years of antiparkinsonian drug treatment.

OBJECTIVE: Psychosis is a common complication of the drug treatment of Parkinson's disease (PD). Treatment of this complication is difficult as most antipsychotic drugs worsen motor symptoms of PD. Only the atypical antipsychotic clozapine improves psychosis without worsening of parkinsonism. The aim of the present study was to assess the rate of initiation of antipsychotic treatment in patients with PD compared with controls. The quality of pharmacotherapy was determined by assessing which antipsychotic drugs were initiated. METHODS: Data came from the PHARMO database, which includes drug-dispensing information for all residents of six Dutch cities. Selected were all persons aged 55 years and older who used levodopa for at least 180 days and who started antiparkinsonian drugs at least 180 days after entry into PHARMO. These patients were matched to at most three controls for age, gender, pharmacy and time of use. The association between rate of initiation of antipsychotic drug treatment and PD was determined using the Cox proportional hazards model. RESULTS: The study included 271 patients with PD and 748 controls. During follow-up, 38 patients and 25 controls started taking an antipsychotic drug; relative risk was 3.9 (95% confidence interval 2.3, 6.4). Six patients with PD received an atypical agent (16%). Clozapine was given to five patients with PD. No control used clozapine. Haloperidol was most frequently prescribed to the patients (29%) and the controls (36%). CONCLUSION: Patients with PD began taking antipsychotic drugs almost four times more frequently than controls. The quality of pharmacotherapy can be improved by prescribing atypical antipsychotic drugs to patients with PD.

Start of a selective serotonin reuptake inhibitor (SSRI) and increase of antiparkinsonian drug treatment in patients on levodopa.

AIMS: We determined whether the start of selective serotonin reuptake inhibitors (SSRI) in levodopa users was followed by a faster increase of antiparkinsonian drug treatment. METHODS: Selected were all levodopa users of 55 years and older from the PHARMO prescription database. The rate of increase of antiparkinsonian drug treatment was compared using Cox's proportional hazard model for starters of SSRI (n = 15) with starters of tricyclic antidepressants (TCA) (n = 31) and with patients not using antidepressants (n = 304), and was adjusted for age, gender, and duration of levodopa use. RESULTS: The hazard ratio for the SSRI group compared with the TCA group was 4.2 (95% confidence interval 1.4, 12.6) and compared with the second control group was 2.7 (1.2, 5.2). CONCLUSIONS: The start of SSRI therapy in levodopa users is followed by a faster increase of antiparkinsonian drug treatment.

Influence of benzodiazepines on antiparkinsonian drug treatment in levodopa users.

OBJECTIVES: Animal studies showed that benzodiazepines decrease the concentration of dopamine in the striatum. Benzodiazepines may therefore affect the treatment of Parkinson's disease. This study determined whether start of a benzodiazepine in patients on levodopa was followed by a faster increase of antiparkinsonian drug treatment. METHODS: Data came from the PHARMO database, which includes information on drug dispensing for all residents of six Dutch cities. Selected were all patients aged 55 years and older who used levodopa for at least 360 days. The rate of increase of antiparkinsonian drug treatment was compared between starters of a benzodiazepine and controls who did not start a benzodiazepine with the use of Cox's proportional hazard model. RESULTS: Identified were 45 benzodiazepine starters (27 women, mean age 76.4 years) and 169 controls (83 women, 74.3 years). Antiparkinsonian drug treatment increased faster in the benzodiazepine group; relative risk was 1.44 (95% confidence interval 0.80-2.59). CONCLUSION: This study has not found any statistically significant increase in antiparkinsonian drug treatment when a benzodiazepine was started in a small population of chronic levodopa users.