Continuation of Geriatric Discharge Medication in Primary Care and its Association with Rehospitalizations - A Cohort Study.

Transition of care in geriatric patients is a complex and high risk process, particularly the continuation of discharge medication in primary care. We aimed to determine how general practitioners' management of geriatric patients' discharge medication is associated with rehospitalizations. A prospective monocentric cohort study was done in an acute geriatric inpatient clinic with six-months follow-up. Acutely hospitalized patients ≥ 70 years old with functional impairment and frailty currently taking medications were followed up after hospital discharge and continuation (n=27) or change (n=44) of discharge medication by the General Practitioner was determined. Outcomes were rehospitalizations, days spent at home and time until recurrent rehospitalizations. 71 patients (mean age 82 years, 46 women [65%]) were followed up for six months after hospital discharge. In a negative binomial regression model, the rehospitalization rate after three months was 3.8 times higher in participants whose discharge medication was changed (p = 0.023). The effect did not persist over six months. Patients who were continued on their discharge medication were rehospitalized significantly later and/or less often during the six months observation period, statistically measured by a recurrent events survival model (HR 0.267, p = 0.003). In conclusion, continuation of discharge medication after an acute hospitalization in a specialized geriatric clinic could prevent early rehospitalizations.

High-alert medications for hospitalised paediatric patients - a two-step survey among paediatric clinical expert pharmacists in Germany.

Paediatric patients are more vulnerable to be harmed by medication errors compared to adults due to pharmacokinetic and pharmacodynamic changes in their development, individual dosing calculations, and manipulation of ready to-use products intended for adult patients. According to the Institute of Safe Medication Practices, there are some "drugs that bear a heightened risk of causing significant patient harm when they are used in error"; these drugs are called high-alert medications (HAM). The two-step survey among paediatric clinical expert pharmacists presented here aimed to compile a nation-wide HAM list. To provide detailed guidance, this survey followed a drugbased approach, resulting in specific potential drug related problems (DRPs) and associated recommendations for prevention. In contrast to this approach, in the first round of the survey two drug classes were included that both were rated as HAM (i.e.chemotherapy and parenteral nutrition). Twenty single drugs were identified as HAM, 65% of which were cardiovascular or neurological drugs. The paediatric expert pharmacists mentioned in total 216 potential DRPs; in particular, they identified potential administration-related problems (28% of all DRPs), dosing-related problems (26%), and drug-choice-related problems (18%, e.g.drug confusion and drug monitoring). Moreover, they suggested 275 potential interventions to address these DRPs. Two thirds of all interventions dealt with the preparation by the hospital pharmacy, standardisation of processes (e.g.labelling), and education or training. In conclusion, this survey provided a German paediatric high-alert medication list from a paediatric pharmacist point of view. Moreover, the experts mentioned for the first time specific potential DRPs and associated interventions to guide a local multidisciplinary approach for preventing medication-related harm in children.

Use of electronic adverse drug reaction check to identify inpatients with a high drug-associated risk of falling: a case-control study at the Department of Neurology.

Background: In hospital, falls are frequent adverse events. Certain drugs affect the fall risk, therefore studying prescriptions may reveal perilous combinations and support falls prevention. As neurologic diseases frequently increase fall risk, neurologic patients require special attention concerning fall prevention. Aim: To analyse the performance of the electronic adverse drug reaction check programmes VERIKO® and SCHOLZ Datenbank® in identifying neurologic patients with a high drug-associated fall risk. Method: Falls in the Department of Neurology in 2016 were matched to fall-free control patients of the same age, sex and principal diagnosis. Their estimated fall risk and other risk factors were compared using univariate and a multifactorial conditional logistic regression. Receiver operating characteristic curves visualised the performance of both programmes. R² for a model with and without software was calculated. Results: Eighty-seven matched pairs were analysed. In the univariate analyses, VERIKO risk estimations showed a significant correlation to fall events (OR=1.448, CI=1.061-1.975). Additionally, the number of comorbidities (OR=1.086, CI=1.013-1.164), the Hospital Frailty Risk Score (OR=1.085, CI=1.025-1.149), impaired balance (OR=3.6, CI=1.337-9.696), gait abnormality (OR=4.75, CI=1.616-13.962), presence of delirium (OR=3.4, CI=1.254-9.216) and previous falls (OR=8.0, CI=1.839-34.793) were related to high fall risk. Polypharmacy and the number of potentially inappropriate medications did not correlate with fall events. In the multivariate analysis, the Hospital Frailty Risk Score was associated to fall risk (OR=1.390, 95%-CI=1.049-1.842). Both programmes showed an area under the receiver operating characteristics curves < 0.6 and improved the model performance slightly (ΔR² ≤ 0.0006). Conclusion: VERIKO risk estimations correlated significantly to fall events. Nevertheless, both programmes showed little accuracy in identifying drug-associated fall risk.

The prevalence of 'triple whammy' prescriptions in surgical inpatients and associated pharmacist recommendations.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are beneficial in surgical settings, they may however lead to adverse drug reactions including decreased renal function, a risk, which is exacerbated by combination with other nephrotoxics, and particularly when NSAIDs are given as part of a so-called 'Triple Whammy' (TW) with diuretics and renin-angiotensin system blockers. The objective of this study was to identify the prevalence of TW-prescriptions in a surgical inpatient setting and to document the changes in renal function after pharmacist recommendations. A prospective, observational single centre pilot study was performed using a series of eleven weekly Point-Prevalence Analyses (PPA). Adult surgical inpatients were screened for a TW-prescription by a clinical pharmacist, who made one of two recommendations on identification of a TW: for patients with eGFR > 60 ml/min/1.73m² close monitoring of renal function; for patients with eGFR ≤ 60 ml/min/1.73m² discontinuation of NSAID. A TW was identified in 18 of 317 patients (prevalence 5.7%; mean age 75 years). NSAID discontinuation was recommended for 7/18 patients (39%) and implemented for six (33%). In cases where the NSAID was de-prescribed, an improvement in renal function until the time of discharge was observed, whilst in patients with eGFR > 60 ml/min/1.73m² for whom monitoring was recommended eGFR remained stable. TW-prescriptions were found to be a potential problem in the studied group of older surgical inpatients. Clinical pharmacists are well placed to identify patients who are prescribed a TW, and to advise on the management of these patients.

[Glucose metabolism in older patients]. / Glukosestoffwechsel im fortgeschrittenen Lebensalter.

Current guidelines for specialized treatment of diabetes mellitus in the elderly (>65 years old) are primarily based on epidemiologic studies and geriatric assessment of functional health. Yet, age-dependent alterations of glucose metabolism and homeostasis are highly relevant to the pathophysiology of diabetes in the elderly. In this review, we focus on age-related alterations in metabolic pathways and their relevance for the specialized diabetic care in the elderly. We review the role of increasing insulin resistance, age-related ß­cell dysfunction and incretin secretion. The clinical relevance of these effects will also be discussed in regard to the central geriatric syndrome of sarcopenia and antidiabetic drug therapy.

Comprehensive pharmaceutical care to prevent drug-related readmissions of dependent-living elderly patients: a randomized controlled trial.

BACKGROUND: Elderly patients are vulnerable to adverse drug reactions (ADRs). Drug-related readmissions (DRRs) can be a major consequence of ADR. Therefore, this study aimed to investigate the effects of a ward-based, comprehensive pharmaceutical care service on the occurrence of DRRs as the endpoint in dependent-living elderly patients. METHODS: A randomized, controlled trial was performed at a German University Hospital. Patients fulfilling the following criteria were eligible: admission to a cooperating ward, existing drug therapy at admission, 65 years of age and older, home-care or nursing home residents in ambulatory care, and a minimum hospital stay of three days. Patients received either standard care (control group) or pharmaceutical care (intervention group). Follow-up consultations were conducted for each patient at 1, 8, 26, and 52 weeks after discharge. The time to DRR was defined as the primary outcome measure and was analysed using the log-rank test. The Cox-proportional hazard model was used for risk factor analysis. RESULTS: Sixty patients (n = 31 intervention group, n = 29 control group) participated in the study. For patients in the intervention group, the median time to DRR was prolonged; however, the level of statistical significance was not reached (log-rank test P = 0.068; HR = 3.28, P = 0.086). When the risk factors 'age' or 'length of stay on the ward' were added to the Cox proportional hazard model, patients in the control group exhibited a significantly higher risk of experiencing a DRR than patients of the intervention group (HR = 4.62; P = 0.028 including age and HR = 5.76; P = 0.033 including length of stay on the ward). CONCLUSIONS: Our findings demonstrate the successful implementation of ward-based, comprehensive pharmaceutical care for dependent-living elderly. Despite a low participation rate, which led to an underpowered study, the results provide a preliminary efficacy signal and effect size estimates to power a definitive trial. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01578525 , prospectively registered April 13, 2012.

Clinical decision support systems differ in their ability to identify clinically relevant drug interactions of immunosuppressants in kidney transplant patients.

WHAT IS KNOWN AND OBJECTIVE: In kidney transplant patients, clinically relevant drug-drug interactions (DDIs) with immunosuppressants potentially lead to serious adverse drug events (ADEs). The aim of this study was (i) to show that five clinical decision support systems (CDSSs) differ in their ability to identify clinically relevant potential DDIs (pDDIs) of immunosuppressants in kidney transplant patients and (ii) to compare CDSSs in terms of their ability to identify clinically relevant pDDIs in this context. METHODS: All pDDIs being possible between nine immunosuppressants and 234 comedication drugs were identified for 264 intensive care unit (ICU) kidney transplant patients from 1999 to 2010. For pDDI identification, five CDSSs were used: DRUG-REAX® , ID PHARMA CHECK® , Lexi-Interact, mediQ and Meona. PDDIs from high severity categories were defined as clinically relevant. Classification of pDDIs as clinically relevant/non-clinically relevant by a clinical pharmacist using Stockley's Drug Interactions was employed as benchmark. We analysed inter-rater agreement, sensitivity, specificity, positive predictive value and negative predictive value. RESULTS AND DISCUSSION: Clinical decision support systems generated a total of 759 pDDI alerts. A total of 240 pDDI alerts were in high severity categories. A total of 391 different pDDIs were identified. Only 5% (n = 35) of different pDDIs were identified by all CDSSs. A total of 49 pDDIs were classified as clinically relevant by clinical pharmacists' rating using Stockley's Drug Interactions. Meona (0·72) has the highest inter-rater agreement with the benchmark for clinically relevant pDDIs. ID PHARMA CHECK® and mediQ show highest sensitivities (0·74, respectively). Meona has the highest specificity (0·99) and positive predictive value (0·89). WHAT IS NEW AND CONCLUSION: Five CDSSs differ in their ability to identify clinically relevant pDDIs of immunosuppressants in kidney transplant patients. Data may assist in selecting CDSSs for kidney transplant patients in the ICU. Using CDSSs to identify clinically relevant pDDIs could prevent ADEs and contribute to the overall goal of avoiding patient harm and increasing patient safety.

Serotonergic modulation of resting state default mode network connectivity in healthy women.

The default mode network (DMN) plays a central role in intrinsic thought processes. Altered DMN connectivity has been linked to diminished cerebral serotonin synthesis. Diminished brain serotonin synthesis is further associated with a lack of impulse control and various psychiatric disorders. Here, we investigated the serotonergic modulation of intrinsic functional connectivity (FC) within the DMN in healthy adult females, controlling for the menstrual cycle phase. Eighteen healthy women in the follicular phase (aged 20-31 years) participated in a double-blind controlled cross-over study of serotonin depletion. Acute tryptophan depletion (ATD) and a balanced amino acid load (BAL), used as the control condition, were applied on two separate days of assessment. Neural resting state data using functional magnetic resonance imaging (fMRI) and individual trait impulsivity scores were obtained. ATD compared with BAL significantly reduced FC with the DMN in the precuneus (associated with self-referential thinking) and enhanced FC with the DMN in the frontal cortex (associated with cognitive reasoning). Connectivity differences with the DMN between BAL and ATD in the precentral gyrus were significantly correlated with the magnitude of serotonin depletion. Right medial frontal gyrus and left superior frontal gyrus connectivity differences with the DMN were inversely correlated with trait impulsivity. These findings partially deviate from previous findings obtained in males and underline the importance of gender-specific studies and controlling for menstrual cycle to further elucidate the mechanism of ATD-induced changes within intrinsic thought processes.

Effects of a short-term reduction in brain serotonin synthesis on the availability of the soluble leptin receptor in healthy women.

Serotonin (5-HT) and the hormone leptin have been linked to the underlying neurobiology of appetite regulation with evidence coming from animal and cellular research, but direct evidence linking these two pathways in humans is lacking. We examined the effects of reduced brain 5-HT synthesis due to acute tryptophan depletion (ATD) on levels of soluble leptin receptor (sOb-R), the main high-affinity leptin binding protein, in healthy adults using an exploratory approach. Women, but not men, showed reduced sOb-R concentrations after ATD administration. With females showing reduced baseline levels of central 5-HT synthesis compared to males diminished brain 5-HT synthesis affected the leptin axis through the sOb-R in females, thereby potentially influencing their vulnerability to dysfunctional appetite regulation and co-morbid mood symptoms.

Wide cleft between theory and practice: medical students' perception of their education in patient and medication safety.

In medicine today, future doctors are expected to ensure patient safety. Yet medical students often feel uncertain if they can meet these high expectations. This study aims to quantify the perceptions of medical students regarding the actual quality of their education in the fields of patient safety and, in particular, medication safety. A questionnaire was designed and distributed to about 100 upper-level medical students. The students had to respond to 12 questions regarding the following categories: 1) familiarity with patient safety and/or medication safety; 2) personal experience in high-risk clinical situations; and 3) perceived relevance of knowledge in the area of patient and medication Safety for clinical practice. Of the respondents 42.1% and 36.8% had delved into the topic patient safety and medication safety, respectively. In clinical practice 88.2% of respondents had experienced a high-risk situation for patients. Regarding patient safety and medication safety, respectively, 82.9% and 85.3% of the respondents found these topics to be particularly relevant to their clinical practice. This study has shown that there is a measurable discrepancy between the students' perceived quality of their medical education and their feelings that they are well prepared to cope with severe clinical challenges.

Change in electrodermal activity after acute tryptophan depletion associated with aggression in young people with attention deficit hyperactivity disorder (ADHD).

We investigated the impact of acute tryptophan depletion (ATD) and reduced brain serotonin synthesis on physiological arousal in 15 young people with ADHD participating in an aggression-inducing game. ATD was not associated with altered physiological arousal, as indexed by electrodermal activity (EDA). Baseline aggression was negatively correlated with the mean ATD effect on EDA. In accordance with the low arousal theory related to aggressive behavior, subjects with reduced physiological responsiveness/lower electrodermal reactivity to ATD tended to display elevated externalizing behavior.

Influence of acute tryptophan depletion on verbal declarative episodic memory in young adult females.

Diminished synthesis of the neurotransmitter serotonin (5-HT) in the brain has been linked to disturbed memory processes. The present study investigated the effects of diminished central nervous 5-HT synthesis as achieved by an acute dietary tryptophan depletion (ATD) on verbal declarative episodic memory in young women while controlling for the effects of female sex hormones. Eighteen healthy females (aged 20-31 years) participated in a within-subject repeated measures study, with two separate days of assessment spaced at least one individual menstrual cycle apart. On one day, participants were subjected to ATD, thus lowering central nervous 5-HT synthesis. The other day participants received a tryptophan-balanced amino acid load (BAL = control condition). The study was randomized, counterbalanced and double blind in terms of ATD/BAL administration. Measurements took place in the early follicular phase of the participants' menstrual cycle. Estrogen, FSH and LH levels were assessed at baseline. Verbal declarative episodic memory was assessed using a structured word-learning task. Short-term memory, as indexed by immediate recall, was reduced after ATD intake, whereas delayed recall and recognition after a 25-min delay did not show any differences after intake of ATD or BAL. In young women, verbal short-term memory function was more vulnerable to ATD than consolidation processes. In light of the possible interplay between female sex hormones and 5-HT, further studies comparing different menstrual cycle phases are needed.

Effects of tryptophan depletion on reactive aggression and aggressive decision-making in young people with ADHD.

OBJECTIVE: The neurotransmitter serotonin (5-HT) has been linked to the underlying biological processes related to aggressive behaviour. However, only a few studies on this subject involving young people have been published so far. METHOD: We aimed to investigate the effects of acute tryptophan depletion (ATD) on reactive aggression and decision-time for aggressive responses in a sample of young people with Attention deficit hyperactivity disorder (n = 20), a population at risk for aggressive behaviour. The study design was a double-blind within-subject crossover design. Aggression was assessed using a Point subtraction aggression game (PSAG) with high (HP) and low provocation (LP) trials 2.5 h after the intake of ATD and a tryptophan-balanced control condition. RESULTS: A chi-square comparison was used to identify the effect of ATD on increased aggression after LP. Boys were more likely to respond with an increased aggressive response after HP under ATD as represented by an increased relative risk and odds ratios. Girls had a higher relative risk than boys of an increased point subtraction under ATD after LP. No significant gender differences in decision-time were detected. CONCLUSION: An effect of ATD on increased aggression was found in the whole sample after LP. Research involving larger samples is needed to confirm the present preliminary findings.

Acute tryptophan depletion in accordance with body weight: influx of amino acids across the blood-brain barrier.

Acute tryptophan depletion (ATD) is a method of reducing central nervous serotonin (5-HT) synthesis in humans by administering an amino acid (AA) beverage lacking in tryptophan (TRP), the physiological precursor of 5-HT. However, to date, the use of conventional ATD protocols in children and adolescents was limited due to frequently observed side effects (e.g., vomiting and nausea). This study investigated the effects of diminished central nervous system 5-HT synthesis on plasma concentrations of relevant AAs and TRP influx into the brain in 24 healthy young adults using the ATD procedure Moja-De, a test protocol that has been used in preliminary research in youths. Twenty-four healthy participants received ATD and a TRP-balanced amino acid load (BAL) using a randomized double-blind within-subject crossover design. Plasma concentrations of the relevant AAs that compete with TRP on the same transport system were assessed at baseline and 90, 180, and 240 min after ATD/BAL intake. TRP influx across the blood-brain barrier was calculated using Michaelis-Menten kinetics with a correction for multiple substrate competition, indicating a significant decrease in TRP influx into the central nervous system under Moja-De. ATD Moja-De decreased TRP influx into the brain and central nervous system 5-HT synthesis safely and effectively and was well tolerated, allowing it to be used in children and adolescents. Future research into other secondary, compensatory effects induced by ATD in patients with neuropsychiatric disorders and healthy populations is needed. ATD Moja-De allows this type of research with a focus on a developmental viewpoint.

Effects of serotonin depletion on punishment processing in the orbitofrontal and anterior cingulate cortices of healthy women.

Diminished synthesis of the neurotransmitter serotonin (5-HT) has been linked to disrupted impulse control in aversive contexts. However, the neural correlates underlying a serotonergic modulation of female impulsivity remain unclear. The present study investigated punishment-induced inhibition in healthy young women. Eighteen healthy female subjects (aged 20-31) participated in a double-blinded, counterbalanced, placebo-controlled, within subjects, repeated measures study. They were assessed on two randomly assigned occasions that were controlled for menstrual cycle phase. In a randomized order, one day, acute tryptophan depletion (ATD) was used to reduce 5-HT synthesis in the brain. On the other day, participants received a tryptophan-balanced amino acid load (BAL) as a control condition. Three hours after administration of ATD/BAL, neural activity was recorded during a modified Go/No-Go task implementing reward or punishment processes using functional magnetic resonance imaging (fMRI). Neural activation during No-Go trials in punishment conditions after BAL versus ATD administration correlated positively with the magnitude of central 5-HT depletion in the ventral and subgenual anterior cingulate cortices (ACC). Furthermore, neural activation in the medial orbitofrontal cortex (mOFC) and the dorsal ACC correlated positively with trait impulsivity. The results indicate reduced neural sensitivity to punishment after short-term depletion of 5-HT in brain areas related to emotion regulation (subgenual ACC) increasing with depletion magnitude and in brain areas related to appraisal and expression of emotions (mOFC and dorsal ACC), increasing with trait impulsivity. This suggests a serotonergic modulation of neural circuits related to emotion regulation, impulsive behavior, and punishment processing in females.

Hypotension alters the release of catecholamines in the hypothalamus of the conscious rabbit.

The posterior hypothalamic nucleus of conscious, freely moving rabbits was superfused with CSF through a cannula. Intravenous injection of nitroprusside elicited a fall of the arterial blood pressure and increased the rates of release of endogenous catecholamines in the posterior hypothalamic nucleus, while noradrenaline increased the blood pressure but did not change the release of catecholamines. It is concluded that hypotension leads to a counteracting increase in the release of catecholamines in the posterior hypothalamus.

Optimizing the pharmacotherapy of vascular surgery patients by medication reconciliation.

AIM: Medication errors may occur at any stage during the medication process and can lead to preventable adverse drug events and patients' harm. Pharmacists' support for reconcilable medication has been shown to be effective, rectifying errors and inaccuracies of the drug treatment and in the increase of medication safety. However, none of the previous studies focused on vascular patients. We investigated the nature and frequency of drug-related problems (DRPs) including the amount of potentially inappropriate medication (PIM) prescribed for elderly patients suffering from vascular diseases and the influence of pharmacists in the improvement of cardiovascular medication. METHODS: After the patients' routine admission process, medication reconciliation was performed. Therefore, a pharmacist obtained an accurate medication use history. The patients' drug therapy was critically screened for DRPs and referring to this, intervention was made by the pharmacist and communicated to the physician if necessary. Potentially inappropriate medication in the elderly was reviewed through a retrospective analysis using the Priscus-List. DRPs were documented anonymously and classified. RESULTS: We identified 138 DRPs among 105 patients. Sixty-five patients experienced at least 1 DRP, accordingly 1.3 DRPs per patient. In total, 43 unintended discrepancies between current medication and admission medication were detected with an overall rate of 0.41 per patient; 100 interventions were made of which 56 resulted in explicit recommendations for prescription changes. Drug classes frequently affected by DRPs were antihypertensive in 23.9%, antithrombotic agents in 19.3% and lipid lowering agents in 12.1%. In a retrospective analysis of the home medication, 12 definite PIM were identified in 49 elderly patients. CONCLUSION: DRPs are common in the medication of vascular surgery patients and may be improved by pharmacists.

Hypercholesterolemia and its association with enhanced stem cell mobilization and harvest after high-dose cyclophosphamide+G-CSF.

High-dose chemotherapy with autologous peripheral blood SCT is a common treatment option in several hematological and non-hematological malignancies. So far, prediction of successful stem cell mobilization and harvest is limited. Just recently, hypercholesterolemia was shown to increase mobilization of hematopoietic progenitor cells into the peripheral circulation in mice. On the basis of these results, we performed a retrospective multivariate analysis incorporating a variety of clinical parameters in 83 patients following high-dose cyclophosphamide+G-CSF treatment. Interestingly, we found a significant positive correlation between stem cell mobilization and harvest for plasma cholesterol and lactate dehydrogenase (LDH) only. Patients with hypercholesterolemia showed a substantially higher median peripheral blood CD34(+)-peak (126 vs 47/µL, P=0.003), higher median number of harvested CD34(+)-cells/kg (9.6 vs 7.4 × 10(6)/kg, P<0.001) and a sufficient number for at least one SCT in a remarkably higher proportion (84.9 vs 52.9%, P=0.003) compared with patients with normal cholesterol levels.