Global COVID-19 pandemic and reporting behavior - An analysis of the Food and Drug Administration adverse events reporting system.

PURPOSE: To describe the characteristics of adverse event reporting in the United States (US) Food and Drug Administration Adverse Event Reporting System (FAERS) before and after the outbreak of the COVID-19 pandemic. METHODS: We included all FAERS reports from the US and Canada from November 7, 2019 to July 15, 2020 and divided the study period into three equal time intervals (pre-pandemic, first pandemic, second pandemic). We focused on methotrexate, a broadly used drug unrelated to COVID-19, and (hydroxy)chloroquine, another broadly used drug implicated in COVID-19 treatment. Using descriptive statistics, we compared reporting characteristics before and after the COVID-19 outbreak. RESULTS: During the study period, 366 998 cases (60% female, median age: 59 years) were submitted to FAERS. The daily median number of reports (1796 in the pre-pandemic, 1810 in the second pandemic time interval) and other characteristics remained stable. The daily median number of reports for methotrexate decreased from 28 in the pre-pandemic to 15 in the second pandemic time interval, with no considerable differences in other characteristics. The daily median number of reports for (hydroxy)chloroquine increased slightly from 1 in the pre-pandemic to 3 in the second pandemic time interval, while there were also changes in the demographics of cases and an increase in the proportion of cases reported by health professionals. CONCLUSIONS: The overall reporting to FAERS did not change after the outbreak of the COVID-19 pandemic. However, some stimulated reporting was observed for (hydroxy)chloroquine, highlighting the need for caution when conducting pharmacovigilance analyses with substances related to COVID-19.

Treating epistaxis - who cares for a bleeding nose? A secondary data analysis of primary and secondary care.

BACKGROUND: The primary objective was to describe outpatient treatment of epistaxis among different physicians based on a large patient population over a period of 10 years. The secondary objective was to evaluate the value of the practice fee as an instrument of allocation in patients with epistaxis. METHODS: Anonymized statutory health insurance data (AOK Lower Saxony) of patients with a diagnosis of epistaxis treated between 2007 and 2016 were examined. Demographic data, accompanying diagnoses, medication and involved medical groups (general practitioners (GP), pediatricians, ear, nose and throat (ENT) specialists or other) were analyzed. Furthermore, we assessed whether the use of specialist groups changed after abolition of the practice fee in 2013. RESULTS: Epistaxis was responsible for 302,782 cases (160,963 patients). The distribution of cases was slightly in favor of ENT specialists vs. GP (119,170 vs. 110,352). The cases seen by GP and ENT specialists were comparable with regard to age and sex distribution. Hypertension, atrial fibrillation/flutter and an antithrombotic therapy were slightly more common among cases consulting a GP. The GP recorded more co-diagnoses than the ENT. The use of outpatient care and the proportions of the involved physicians scarcely fluctuated during the study period. Overall, 23,118 patients (14.4%) were diagnosed by both, GP and ENT during a relatively short time period. The practice fee remuneration had no impact on the consultation of the physician groups. CONCLUSION: The outpatient treatment of epistaxis constitutes a considerable medical and economic burden in Germany. Strengthening the primary medical sector (GP-centered care) is necessary to reach the goal of initially directing patients to primary care, providing specialists more time for severe cases and reducing the impact on public health balance sheets.

Use of oral anticoagulants in German nursing home residents: drug use patterns and predictors for treatment choice.

AIMS: Information on utilization of oral anticoagulants (OACs) in nursing homes is scarce. This study aimed to (i) describe OAC use in German nursing home residents, (ii) examine factors influencing whether treatment is initiated with vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs) and (iii) assess which conditions predict switching to NOAC instead of continuing VKA. METHODS: Using claims data (2010-2014), we studied a cohort of new nursing home residents aged ≥65 years receiving OAC. Further, OAC use in patients with atrial fibrillation (AF) was examined over the years. RESULTS: Overall, 16 804 patients (median age: 85 years, 75% female, 44% with renal disease) were included. The majority received phenprocoumon as first OAC (58.0%), followed by rivaroxaban (28.1%). Over the study period, NOAC use increased substantially. Initiating NOAC instead of VKA was predicted by a previous stroke (adjusted odds ratio: 1.76; 95% confidence interval: 1.49-2.08). In contrast, renal disease predicted VKA initiation (0.66; 0.59-0.75) as did the presence of a prosthetic heart valve. Switching from VKA to NOAC was predicted by a stroke (2.55; 2.00-3.24), bleeding events and a recent hospitalization. During 2010-2014, the proportion of AF patients with a CHADS2 score ≥2 receiving OAC increased from 27% to 46%. CONCLUSIONS: NOACs are increasingly used in German nursing homes, both for initial anticoagulation but also in VKA pre-treated patients. Switching from VKA to NOAC was substantially influenced by aspects such as intended higher effectiveness and safety but probably also practicability due to less blood monitoring.

Extent and risks of antidepressant off-label use in children and adolescents in Germany between 2004 and 2011.

PURPOSE: So far, only little is known about antidepressant off-label use in pediatric patients. This is the first study examining the prevalence and the risks of off-label antidepressant prescriptions in minors over time in Germany and analyzing patterns regarding age, sex, drug class, and type of off-label use. METHODS: We used claims data of about two million individuals (<18 y) to calculate the share of off-label antidepressant prescriptions for the years 2004 to 2011, stratified by age, sex, and drug class. Off-label prescriptions were analyzed regarding underlying diagnoses, the prescribing doctor's specialty, and the type of off-label use. Incidence rates of adverse events were calculated for off- and on-label use, and the risk of suicidal events associated with off- or on-label use was examined in a nested case-control study. RESULTS: The prevalence of off-label prescriptions decreased from 58.0% to 40.9%. Selective serotonin reuptake inhibitors were more frequently prescribed off-label than tricyclic antidepressants (37.7% vs 17.5% in 2011). The most common type of off-label use was off-label use by age, followed by off-label use by indication, and off-label use by contraindication. Adverse events were rare with no significant differences between on- and off-label use. CONCLUSIONS: Although off-label antidepressant use in minors decreased over time, it is still common. However, this rather indicates a lack of approved drugs for the treatment of depression in this population than inappropriate medical treatment. This is supported by the fact that off-label use was not associated with a higher risk of adverse events than on-label use.

Outpatient antidepressant drug use in children and adolescents in Germany between 2004 and 2011.

PURPOSE: Recent studies on the utilization of antidepressant drugs in minors are scarce, methodologically limited, and do not factor in off-label use sufficiently. Beyond that, little is known about the short treatment durations that have been observed for many young antidepressant users. The present study examined antidepressant use in pediatric patients aged 0 to 17 years over time, investigated changes regarding the prescribed drugs, analyzed underlying diagnoses, and assessed the rate of off-label use. METHODS: We used claims data of roughly two million individuals to calculate annual prevalence and incidence rates of antidepressant prescriptions for the years 2004 to 2011. Analyses were stratified by age, sex, and drug type. For antidepressant users, numbers of prescriptions, frequencies of disorders/diseases, and specialties of the prescribing physicians were examined. The share of off-label prescriptions was calculated for each year. RESULTS: The prescription prevalence of antidepressants ranged between 1.7 and 2.1 per 1000 minors. The use of tricyclic antidepressants decreased from 0.9 to 0.6 prescriptions per 1000 minors, while the use of selective serotonin reuptake inhibitors increased from 0.5 to 1.1. Of the patients with an antidepressant prescription, 46.4% only received one prescription. Depression was by far the most frequent diagnosis among all antidepressant users as well as among subjects with only one prescription. In 2011, 36.3% of all prescriptions were off-label. CONCLUSIONS: The high proportion of single prescriptions, even in patients with a diagnosed depression, and the high rate of off-label use are particularly noteworthy and should be further investigated in future studies. Copyright © 2016 John Wiley & Sons, Ltd.

Outpatient antipsychotic drug use in children and adolescents in Germany between 2004 and 2011.

Studies from different countries showed increasing use of antipsychotics in pediatric patients. However, these studies were methodologically limited and could not assess underlying diagnoses and off-label use sufficiently. This is the first study to examine antipsychotic prescriptions in a representative sample of minors over a long period, looking at changes regarding substances and drug classes, underlying diagnoses, and the rate of off-label use. Claims data of about two million pediatric subjects were used to calculate annual prevalences and incidence rates of antipsychotic prescriptions for the years 2004-2011. Analyses were stratified by sex, age, and drug type. Numbers of prescriptions, frequencies of diseases/disorders, the prescribing physicians' specialties, and the share of off-label prescriptions were examined. During the study period, the prevalence of antipsychotic prescriptions ranged between 2.0 and 2.6 per 1000 minors. Antipsychotic prescriptions in children younger than 6 years decreased from 2.42 per 1000 subjects in 2004 to 0.48 in 2011. Among antipsychotic users, 47.0 % had only one prescription and hyperkinetic disorder was, by far, the most frequent diagnosis. The annual share of off-label prescriptions varied between 61.0 and 69.5 %. Antipsychotics were mainly prescribed to manage aggressive and impulsive behaviors in hyperkinetic disorder patients. This explains the high share of off-label prescriptions but raises concerns, since efficacy and safety of antipsychotics in this indication have not been sufficiently investigated. The decreasing antipsychotic use in younger children and the high proportion of antipsychotic users with one-time prescriptions are striking and should be further investigated in the future.

Pro re nata (as needed) medication in nursing homes: the longer you stay, the more you get?

PURPOSE: Injudicious pro re nata (PRN) or as needed prescribing can lead to polypharmacy, potentially harmful drug interactions and total drug doses exceeding the maximum recommended. Despite the known risks and the widespread administration, there is a paucity of current research examining the use of PRN drugs in nursing homes. Therefore, we examined characteristics of PRN drug use and potential predictors in nursing homes. METHODS: The multicentre cross-sectional study included a heterogeneous sample of 21 nursing homes in Northwestern Germany comprising 852 residents. Descriptive statistics and multivariable regression models were used to analyse and present the collected data. RESULTS: Nearly three quarters (74.9 %) of all residents were treated with at least one PRN medication. On average, each resident was prescribed 2.5 ± 2.3 PRN drugs. On average, residents with no PRN prescriptions stayed since 2.4 ± 2.9 years in the nursing home. Residents with five and more PRN prescriptions were on average since 4.8 ± 4.3 years in the nursing home. In a multivariable analysis, length of stay above the median of 2.1 years (OR 2.4; 95 % CI 1.8, 3.2) and polypharmacy with five or more long-term drugs (OR 2.1; 95 % CI 1.5, 2.9) were associated with a higher number of PRN prescriptions. Most commonly used PRN drug was acetaminophen, which was prescribed to 289 (33.9 %) residents. CONCLUSIONS: The high prevalence of PRN medication should be taken into account when considering polypharmacy and inappropriate drug prescribing or using screening tools like the STOPP/START (screening tool of older persons' potentially inappropriate prescriptions/screening tool to alert doctors to right) criteria in nursing homes. Physicians should regularly reconsider the need of each PRN drug on the medication schedule. Moreover, the high prevalence of PRN medication and the association with length of stay highlights the importance of an accurate documentation.

Antidepressant drug use and off-label prescribing in children and adolescents in Germany: results from a large population-based cohort study.

The off-label use of drugs in children and adolescents is widespread. In Germany, the use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressants (OADs) is not licensed for the treatment of depressive disorders in children and adolescents except for fluoxetine, which was approved in 2006. Against this background, antidepressant drug (ATD) use with a particular focus on off-label prescribing was characterised in a retrospective cohort study including cross-sectional analyses based on claims data of 2,599,685 patients up to 17 years of age. Prevalence of ATD use was 1.84 (95% CI 1.78-1.90) per 1,000 children in 2004, 1.57 (95% CI 1.52-1.62) in 2005 and 1.66 (95% CI 1.61-1.72) in 2006. More than half of all children treated with ATDs (51.29%) received only one single prescription of an ATD during the study period. Of all prescribed ATDs, 11,172 (42.09%) were tricyclic antidepressants 9,179 (34.58%) were SSRIs, 4,371 (16.47%) were St John's wort preparations and 1,821 (6.86%) were OADs. Around half of all children and adolescents who were treated with ATDs were diagnosed with depressive disorders (56.30%). Overall, 13,035 (49.11%) of all ATDs were prescribed off-label. Off-label use by age (40.18%) was found to be more common than off-label use by indication (16.63%) with 7.70% of off-label use occurring in both categories. Specialist treatment by hospital-based physicians increased the risk (odds ratio: 2.26, 95% CI 2.05-2.48) of receiving an off-label prescription compared to treatment by general practitioners. In summary, off-label use of ATDs in children and adolescents was substantial in Germany.

Trends in antipsychotic use among children and adolescents in Germany: a study using 2011-2020 nationwide outpatient claims data.

Introduction: We aimed to provide an update on trends in antipsychotic (AP) use among children and adolescents in Germany. Materials and methods: Based on nationwide outpatient claims data from Germany, we conducted a cross-sectional study. For each year from 2011 to 2020, we determined the prevalence of AP use, defined as the proportion of children and adolescents with at least one AP dispensation. We evaluated trends in AP use by age, sex, and AP class (typical vs. atypical). Additionally, we assessed trends in the specialty of AP prescribers and the frequency of psychiatric diagnoses among AP users. Results: Overall, data from more than 12 million children and adolescents were included for each calendar year (2011: 12,488,827; 2020: 13,330,836). From 2011 to 2020, the overall prevalence of pediatric AP use increased from 3.16 to 3.65 per 1,000, due to an increase in use of both typical APs (from 1.16 to 1.35 per 1,000) and atypical APs (from 2.35 to 2.75 per 1,000). The largest increase in AP use was found among 15- to 19-year-old females, with an increase from 3.88 per 1,000 in 2011 to 7.86 per 1,000 in 2020 (+103%), mainly due to rising quetiapine use (from 1.17 to 3.46 per 1,000). Regarding prescribers' specialty, the proportion of APs prescribed by child and adolescent psychiatrists increased during the studied period (2011: 24.8%; 2020: 36.4%), whereas prescriptions by pediatricians (2011: 26.0%; 2020: 19.9%) and general practitioners (2011: 18.0%; 2020: 12.4%) decreased. Risperidone was the most commonly used AP in males, and quetiapine was the leading AP in females, each with the highest prevalence in 15- to 19-year-olds. In male risperidone users in this age group, the most frequent diagnosis was attention-deficit/hyperactivity disorder (50.4%), while in female quetiapine users it was depression (82.0%). Discussion: Use of APs among children and adolescents in Germany has continued to increase over the last decade. The sharp increase in AP use among 15- to 19-year-old females, which is largely due to an increased use of quetiapine, is remarkable. Potential reasons for this increase-e.g., limited access to psychosocial treatments-should be carefully analyzed. Also, the introduction of more restrictive prescribing guidelines might be considered.

Nurse-Filled versus Pharmacy-Filled Medication Organization Devices-Survey on Current Practices and Views of Home Care Nursing Services.

Medication organization devices (MODs) are widely used among home care nursing services. However, current practices such as the responsibility for filling MODs, different MOD types used and requirements of home care nursing services are largely unknown. The study aimed at analyzing home care nursing services' current practices regarding MOD use, investigating their requirements and determining whether different practices met these requirements. A survey was administered online to German home care nursing services in February 2021. The importance of requirements and the extent of satisfaction were measured using a five-point scale. Attitudes towards disposable, pharmacy-filled MODs were recorded as free text. In total, 690 nursing services responded (67.5% privately owned and 34.5% based in large cities), 92.2% filled MODs themselves and used predominantly reusable, rigid MODs. Pharmacies filling MODs used primarily disposable MODs. Satisfaction with current practices was generally high. Respondents filling MODs themselves were more satisfied with nurses' medication knowledge, but less satisfied with cost effectiveness than those who had pharmacies fill MODs. Of all respondents filling MODs themselves who expressed an opinion on disposable, pharmacy-filled MODs, 50.9% were skeptical, primarily due to fear of losing flexibility. However, no difference in satisfaction with flexibility was found between respondents filling MODs themselves and those using pharmacy-filled MODs. In conclusion, employment of MODs in the professional care setting is a complex task with nursing services as key constituents. There is potential for improvement in the inter-professional collaboration between pharmacies and home care nursing services on the use of MODs. Measures for improvement have to address home care nursing services' requirements with respect to flexibility and medication knowledge.

Antidepressant drug use and regional prescribing patterns in Germany: results from a large population-based study.

OBJECTIVE: To consider antidepressant prescribing on a population level with a focus on regional prescribing patterns in Germany. BASIC METHODS: Based on data from about 70 million individuals covered by all statutory health insurance funds in Germany in 2010, the prevalence of antidepressant use (overall, for drug classes and individual drugs) was calculated stratified by age and sex. Regional analyses were performed on a state and also on a district level. MAIN RESULTS: The study population comprised 68 427 464 (female: 53.0%) persons, of which 5 052 293 (7.4%) were prescribed at least one antidepressant. The most frequently prescribed drug class was tricyclic antidepressants whereas on a substance level citalopram was most commonly used. Antidepressant prescribing was lowest in children and adolescents (0.2%) and most common in persons aged 70 years and older (13.4%). Women more often received antidepressants than men (9.7% vs. 4.8%). Prevalence of antidepressant use varied between 8.7% (Saarland) and 6.3% (Saxony-Anhalt) and was generally highest in the southwestern and lowest in the eastern states. Accordingly, districts with the highest prevalence were located in the southwestern states. PRINCIPAL CONCLUSIONS: Antidepressant use in Germany varied considerably by age and sex and also on a state and district level.

Health Services Use and Costs in Individuals with Autism Spectrum Disorder in Germany: Results from a Survey in ASD Outpatient Clinics.

Autism spectrum disorders (ASD) are associated with high services use, but European data on costs are scarce. Utilisation and annual costs of 385 individuals with ASD (aged 4-67 years; 18.2% females; 37.4% IQ < 85) from German outpatient clinics were assessed. Average annual costs per person were 3287 EUR, with psychiatric inpatient care (19.8%), pharmacotherapy (11.1%), and occupational therapy (11.1%) being the largest cost components. Females incurred higher costs than males (4864 EUR vs. 2936 EUR). In a regression model, female sex (Cost Ratio: 1.65), lower IQ (1.90), and Asperger syndrome (1.54) were associated with higher costs. In conclusion, ASD-related health costs are comparable to those of schizophrenia, thus underlining its public health relevance. Higher costs in females demand further research.

Tyrosine kinase inhibitors targeting vascular endothelial growth factor and the risk of aortic dissection-A pharmacovigilance analysis.

There are concerns by the United States Food and Drug Administration (FDA) regarding a potential link between tyrosine kinase inhibitors targeting vascular endothelial growth factor (VEGF-TKIs) and the risk of aortic dissection. Elevation of blood pressure induced by VEGF-TKIs has been discussed as part of the pathomechanism. To address this important safety issue, we conducted a large pharmacovigilance study assessing the risk of aortic dissection reporting associated with the use of VEGF-TKIs, thereby exploring the role of blood pressure. We queried the FDA Adverse Event Reporting System from 2004 to 2019 for reports including VEGF-TKIs and aortic dissection and estimated reporting odds ratios (RORs) and 95% confidence intervals (CIs) of aortic dissection associated with the use of VEGF-TKIs. Secondary analyses stratified by the strength of blood pressure elevation (≥10 mmHg vs. <10 mmHg increased systolic or diastolic bloods pressure) and pre-existing arterial hypertension. There were 81 reports of aortic dissection related to VEGF-TKIs during the study period. VEGF-TKIs were associated with an increased risk of aortic dissection reporting (ROR, 4.31; 95% CI, 3.43 to 5.42). The risk was higher among compounds strongly increasing blood pressure (ROR, 5.33; 95% CI, 3.88 to 7.32) than among compounds moderately increasing blood pressure (ROR, 2.79; 95% CI, 1.83 to 4.27). Pre-existing arterial hypertension did not modify the association. Overall, our study showed an increased risk of aortic dissection reporting associated with the use of VEGF-TKIs. Blood pressure elevation seems to play a role in the pathophysiology of this adverse effect.

Regional Differences in Opioid Prescribing in Germany - Results of an Analysis of Health Insurance Data of 57 Million Adult People.

BACKGROUND: Regional variations of opioid use have been reported from many countries. The objective of this study was to examine opioid prescribing patterns in Germany including low- and high-potency opioids (LPO and HPO) focusing on regional differences. METHODS: Data source was the "Information system for health care data" comprising statutory health insurance funds data for about 70 million Germans of all ages. For 2010, we received aggregated data (by age, sex, federal state and district) of Germans (18+) who had been prescribed at least one opioid including the number of prescribed packages. For each stratum, we further received the number of insured persons. We calculated LPO and HPO prevalences and the mean number of prescribed packages. RESULTS: Among 57 million adult Germans (mean age: 50.2 years, 53.8% female), opioid prevalences were 38.7 per 1000 persons for LPOs and 12.8 for HPOs. Prevalences rose with increasing age and were higher in women than in men. On average, LPO users were prescribed fewer packages than HPO users (3.5 vs 7.0). LPO use was highest in the eastern states ranging from 32.9 per 1000 persons (Hamburg) to 47.2 (Saxony-Anhalt). HPOs were most often prescribed in the North and in the East with prevalences varying between 10.6 per 1000 persons (Baden-Württemberg) and 16.9 (Mecklenburg-Western Pomerania). On the district level, prevalences varied by the factors 2.6 and 3.2 for LPOs and HPOs, respectively. CONCLUSION: We found large regional variations in opioid prescribing which probably cannot only be attributed to differences in patient characteristics.

Drug interactions with oral anticoagulants in German nursing home residents: comparison between vitamin K antagonists and non-vitamin K antagonist oral anticoagulants based on two nested case-control studies.

BACKGROUND: Vitamin K antagonists (VKAs) are susceptible to drug-drug interactions. Non-VKA oral anticoagulants (NOACs) have a decreased sensitivity to pharmacokinetic interactions and might be therefore considered superior in patients treated with multiple drugs. The objective of this study was to compare the risk of serious bleeding associated with interacting drugs in German nursing home residents treated with VKA or NOAC. METHODS: Using claims data of new nursing home residents aged ≥ 65 years (2010-2014) we conducted separate nested case-control analyses within two cohorts of patients treated with VKA or NOAC, respectively. Cases were defined as patients hospitalized for serious bleeding. For each case, up to 20 controls were selected by risk-set sampling. Conditional logistic regression was used to obtain confounder-adjusted odds ratios (aORs) and 95% confidence intervals (CI) for the risk of bleeding associated with VKA or NOAC use and interacting drugs compared with the use of the respective oral anticoagulant alone. RESULTS: Among 127,227 new nursing home residents, 16,804 patients received oral anticoagulation. Based on 372 cases and 7281 matched controls, the highest risk of bleeding in VKA users was observed for the concomitant use of antibiotics (aOR 3.00; CI 2.11-4.27) vs. VKA use alone, followed by non-steroidal anti-inflammatory drugs (1.66; 1.13-2.43). Among 243 NOAC cases and 4776 matched controls, elevated risks for bleeding were observed for the use of heparins (2.05; 1.25-3.36) and platelet inhibitors (1.92; 1.36-2.72). CONCLUSIONS: Concomitant medication needs to be prescribed cautiously and monitored closely in nursing home residents treated with oral anticoagulants.

Pro Re Nata Drug Use in Nursing Home Residents: A Systematic Review.

OBJECTIVES: In addition to routinely administered long-term medication, complex drug regimens of nursing home residents often include as needed or pro re nata (PRN) medication. However, there has been no systematic evaluation of the frequency and concomitants of PRN medication in nursing homes. The main objective of this systematic review was to provide a current assessment of PRN drug use in nursing homes. DESIGN: A systematic literature search was performed. Data were identified from 4 electronic bibliographic databases: MEDLINE, Embase, CINAHL, and Scopus. Studies were included if they reported quantitative data on PRN drug use in nursing home residents. RESULTS: Our search strategy resulted in 484 hits, of which 27 articles satisfied the inclusion criteria. The mean number of PRN drugs ranged between 0.4 and 4.9 per resident with a median of 2.5. The proportion of residents prescribed at least 1 PRN drug was between 48.4% and 97.4% (median = 74.9). Administration of prescribed PRN medication was rather low as the proportion of residents with administered PRN drugs ranged from 28% to 55%. Frequently prescribed PRN drugs were analgesics, laxatives, and sedatives. Advanced age, dementia, a higher number of regularly scheduled medications, and length of stay in the nursing home were associated with higher use of PRN drugs. CONCLUSIONS/IMPLICATIONS: Although not regularly administered, PRN drug use in nursing home residents should be taken into account as part of complex drug regimens. In that sense, there seems to be an inadequate number of studies reporting on it. When screening tools like the Beers Criteria are adapted, PRN drugs should be included.

Combined use of drugs inhibiting the renin-angiotensin system: prescribing patterns and risk of acute kidney injury in German nursing home residents.

BACKGROUND/AIMS: In 2012, the European Medicines Agency reviewed the safety of dual renin-angiotensin system (RAS) blockade because of potentially increased risks for inter alia acute kidney injury (AKI). Since residents of nursing homes are particularly vulnerable to adverse drug outcomes, the aims of our study were to describe RAS-inhibiting drug use in German nursing home residents and examine the risk of AKI associated with dual RAS blockade. METHODS: Based on claims data, a nested case-control study within a cohort of RAS-inhibiting drug users was conducted. Using conditional logistic regression, confounder-adjusted odds ratios (aORs) and 95% confidence intervals (CI) were obtained for the risk of AKI associated with dual RAS blockade. Subgroup analyses were performed in patients with diabetes or chronic kidney disease and both comorbidities. RESULTS: Of all 127,227 nursing home residents, the study cohort included 64,567 (50.7%) who were treated with at least one RAS-inhibiting drug. More than three quarters of the study population were female (77.1%). Mean age was 86.0 ± 6.8 years. Most residents were treated with angiotensin-converting enzyme inhibitors (77.8%), followed by angiotensin II receptor blockers (21.6%) and aliskiren (0.2%). Annual prevalence of dual RAS blockade declined from 9.6 (95% CI 7.8-11.8) in 2010 to 4.7 (95% CI 4.0-5.4) per 1,000 users in 2014. In the overall cohort, AKI was not significantly associated with dual RAS blockade (aOR 1.99; 0.77-5.17). However, significantly increased aORs were observed when considering patients with diabetes (3.47; 1.27-9.47), chronic kidney disease (4.74; 1.24-18.13) or both (11.17; 2.65-47.15). CONCLUSIONS: Prescribing of drugs inhibiting the RAS is common in German nursing homes. Though the prevalence of dual RAS blockade declined, our study showed an increased risk of AKI in patients with diabetes and/or chronic kidney disease. Therefore, cautious use is warranted in these vulnerable patients.

Antipsychotic drug use in nursing home residents with and without dementia: keep an eye on the pro re nata medication.

Behavioral and psychological symptoms of dementia often lead to the prescription of antipsychotics, especially in nursing homes, but their use remains controversial. This study aimed to assess antipsychotic drug use in residents with dementia compared with those without dementia. Data were obtained through the cross-sectional 'inappropriate medication in patients with renal insufficiency in nursing homes' (IMREN) study including data from 21 nursing homes. Descriptive statistics were used and factors associated with the prescription of antipsychotics were identified by logistic regression. Overall, 57.5% of the 837 residents had a diagnosis of dementia and 47.0% of residents with dementia and 19.5% of those without dementia received antipsychotics. 35.9% of all antipsychotics in residents with dementia were prescribed as pro re nata (PRN) compared with 23.0% for residents without dementia. Typical antipsychotics were prescribed more commonly than atypical ones. The adjusted logistic regression showed a significant association between the prescription of antipsychotics and dementia (odds ratio: 3.58, 95% confidence interval: 2.45-5.25) as well as severe care dependency (odds ratio: 1.68, 95% confidence interval: 1.10-2.55). Despite safety warnings, antipsychotics are still frequently prescribed to residents with dementia. Almost half received antipsychotics and about a third of the antipsychotics are prescribed as PRN. Further studies should assess the use of PRN antipsychotics and guidelines for PRN prescriptions are clearly needed.

Inappropriate Medication in Non-Hospitalized Patients With Renal Insufficiency: A Systematic Review.

OBJECTIVES: Renal insufficiency is common among older patients and, accordingly, renally excreted drugs may require an adjustment in dosage for them. Rates of non-adherence to renal dosing guidelines range from 19% to 70% across all settings, with the highest rate occurring in outpatient care. However, there is a paucity of research in this field. The main objective of this systematic review is to assess how often drugs are inappropriately prescribed in non-hospitalized patients with renal insufficiency. DESIGN: A systematic literature search was performed. Data were identified from three electronic databases: PubMed, CINAHL, and Scopus. Studies were included if they reported quantitative data on inappropriate drug use with respect to renal function in non-hospitalized patients. RESULTS: Our search strategy resulted in 2,403 hits, of which 18 articles satisfied the criteria for inclusion. Mean estimated glomerular filtration rate ranged from 36.0 to 60.4 mL/min. Prevalence of renally inappropriate drug use ranged from 1% to 37% in outpatient settings other than nursing homes, and from 6% to 43% in nursing homes. Eight of the studies we included identified predictors for use of drugs inappropriate for kidney function. Most frequently determined risk factors were increasing age and a high number of prescribed drugs. CONCLUSION: Lack of dose adjustment for renal impairment seems to be a common problem, even in outpatients. However, the differences in methodologies used in these studies hampered any direct comparison. Accepted and comparable standards regarding the drugs included in the studies as well as estimation of renal function would be beneficial.

Data Collection of Medication - Impact of Autocompletion in eCRFs on Efficiency and Data Quality.

OBJECTIVE: Openclinica Input Completion (OIC) was developed to increase the efficiency to enter drugs in eCRF in OpenClinica®. The aim of the study was to evaluate the impact on efficiency and data quality as well as usability. METHODS: 20 participants were asked to input 15 drugs with the new tool and by hand. RESULTS: The mean input time got decreased from 16:12m to 3:59m. 31 of 300 (10%) of manual entered medication data sets had one or more errors versus 10 of 300 (3,3%) data sets entered with OIC. CONCLUSION: OIC was able to increase efficiency and data quality. We conclude that new additions to the graphical user interface in electronical Case-Report-Form (eCRF) systems should be validated before usage in research projects.