High refill-adherence to adalimumab is associated with low disease activity in patients with inflammatory bowel disease.

PURPOSE: Adalimumab has evolved to one of the more affordable first-line biologics for the treatment of inflammatory bowel disease (IBD), since its patent expired. However, poor adherence to adalimumab is a concern and may limit its effectiveness. It is plausible that good adherence improves treatment outcomes in IBD patients, but evidence is scarce. The aim of this study was to assess whether high refill-adherence (medication possession ratio (MPR) ≥ 80%) to adalimumab is associated with less active disease in IBD patients. METHODS: In this retrospective study, the MPR was used to assess refill-adherence of IBD patients using adalimumab. Disease activity was defined as a composite endpoint determined by endoscopy findings, laboratory results, validated questionnaires and clinical assessment by a gastroenterologist. Logistic regression was used to determine the association between high refill-adherence (MPR ≥ 80%) and disease activity. RESULTS: IBD was in remission in 72 of the 113 included patients and 41 had active disease at the time of the most recent prescription. Out of the patients who were in remission, 86.1% were adherent vs. 75.6% in patients with active disease. High refill-adherence was significantly associated with lower odds of active disease after adjustment for confounders: adjusted odds ratio 0.297, 95% confidence interval 0.099-0.892. CONCLUSION: High refill-adherence to adalimumab therapy was associated with less active disease in IBD patients. Our results confirm the relevance of good adherence to adalimumab for achieving optimal treatment results, which may limit the need for switching to more expensive biologics.

Optimizing pharmacotherapy and deprescribing strategies in older adults living with multimorbidity and polypharmacy: EuGMS SIG on pharmacology position paper.

Inappropriate polypharmacy is highly prevalent among older adults and presents a significant healthcare concern. Conducting medication reviews and implementing deprescribing strategies in multimorbid older adults with polypharmacy are an inherently complex and challenging task. Recognizing this, the Special Interest Group on Pharmacology of the European Geriatric Medicine Society has compiled evidence on medication review and deprescribing in older adults and has formulated recommendations to enhance appropriate prescribing practices. The current evidence supports the need for a comprehensive and widespread transformation in education, guidelines, research, advocacy, and policy to improve the management of polypharmacy in older individuals. Furthermore, incorporating deprescribing as a routine aspect of care for the ageing population is crucial. We emphasize the importance of involving geriatricians and experts in geriatric pharmacology in driving, and actively participating in this transformative process. By doing so, we can work towards achieving optimal medication use and enhancing the well-being of older adults in the generations to come.

Anticholinergic Drug Use on Admission and the Risk of In-Hospital Falls in Older Hospitalized Patients.

Purpose: In-hospital falls, especially among older patients, are a major and underestimated problem. Several studies have suggested a possible association between anticholinergic drug use and falls, but the results are inconclusive and studies focusing on in-hospital falls are scarce. The aim of the present study was to investigate whether anticholinergic drug exposure on admission is associated with in-hospital falls. Patients and Methods: This retrospective chart review study was conducted in the Erasmus MC University Medical Center, Rotterdam, the Netherlands. Patients aged 65 years and older, who were acutely admitted to the geriatric ward between 2012 and 2015, were included. Anticholinergic drug exposure was determined with the Anticholinergic Risk Scale (ARS), the Anticholinergic Cognitive Burden scale (ACB) and the list of Chew. Logistic regression was used to investigate the possible association between anticholinergic drug exposure and in-hospital falls. Analyses were adjusted for age, sex, fall history, fall as reason for admission, number of drugs on admission, use of a mobility aid and delirium. Results: A total of 905 patients were included, of which 94 patients experienced one or more in-hospital falls. Each additional anticholinergic drug in use, according to the ARS, was associated with an increased odd of experiencing a fall (OR = 1.49, 95% CI: 1.06-2.10). Other measures, ie anticholinergic drug use (yes/no) and different categories of anticholinergic drug burden, measured with the ARS, ACB and list of Chew, were all not associated with in-hospital falls. Conclusion: Anticholinergic drug exposure on admission is possibly not a main risk factor for in-hospital falls among older patients.

Anticholinergic Drug Burden and Delirium: A Systematic Review.

OBJECTIVES: To investigate the association between anticholinergic drug burden (ADB), measured with anticholinergic drug scales, and delirium and delirium severity. DESIGN: Systematic review. SETTING AND PARTICIPANTS: All available studies. METHODS: A systematic literature search was performed in Medline, Embase, PsycINFO, Web of Science, CINAHL, Cochrane library, and Google Scholar. Studies evaluating the association between ADB (measured as a total score) and delirium or delirium severity, published in English, were eligible for inclusion. RESULTS: Sixteen studies, including 148,756 persons, were included. Fifteen studies investigated delirium. ADB was measured with the Anticholinergic Risk Scale (ARS, n = 5), the Anticholinergic Cognitive Burden Scale (ACB, n = 6), the list of Chew (n = 1), the Anticholinergic Drug Scale (ADS, n = 5), a modified version of the ARS (n = 1), and a modified version of the ACB (n = 1). A high ADB, measured with the ARS, was associated with delirium (5/5). Also with the modified version of the ARS and ACB, an association was found between a high ADB and delirium during 3-month (1/1) and 1-year follow-up (1/1), respectively. When ADB was assessed with other scales, the results were inconclusive, with only 1 positive association for the ACB (1/6) and ADS (1/5) each. The possible association between ADB and delirium severity has also been investigated (ADS n = 2, Summers Drug Risk Number n = 1). One study found an association between a high ADB, measured with the ADS, and an increase in severity of delirium. CONCLUSIONS AND IMPLICATIONS: ADB assessed with the ARS is consistently associated with delirium. The association found between the modified versions of the ARS and ACB and delirium needs confirmation. When ADB was assessed with other scales, the findings were inconclusive. The current findings suggest that the ARS might be a useful tool to identify patients at increased risk for delirium.

Antipsychotics and Lorazepam During Delirium: Are We Harming Older Patients? A Real-Life Data Study.

BACKGROUND: Delirium affects approximately one out of three older hospitalized patients and is associated with poor clinical outcomes. Approaches used to manage delirium consist of non-pharmacological and pharmacological interventions. Antipsychotics and lorazepam are commonly used to treat symptoms of delirium, but conflicting data exist on the effect of these drugs on the outcomes of delirium. OBJECTIVE: The aim of this study was to investigate whether the use of antipsychotics, with or without lorazepam, increases the risk of prolonged hospital stay, post-discharge institutionalization, and in-hospital mortality in older patients with delirium. METHODS: In this retrospective chart review study, we included acutely ill patients aged ≥ 65 years who were admitted to a geriatric ward and diagnosed with delirium. Patients were stratified into three groups based on whether or not they received antipsychotics and lorazepam to manage delirium: (0) no antipsychotics; (1) antipsychotics only; and (2) antipsychotics plus lorazepam. Length of hospital stay (LOS) and frequencies of post-discharge institutionalization and in-hospital mortality were compared. RESULTS: In total, 212 patients with delirium were included (mean age 81.9 ± 5.6 years); 40 did not receive antipsychotics (18.9%), 123 received antipsychotics only (58.0%) and 49 received antipsychotics and lorazepam (23.1%). There was a trend to a longer LOS in patients who received both antipsychotics and lorazepam (median LOS group 0 = 8.0 days, group 1 = 10.0 days, and group 2 = 12.0 days). Furthermore, trends to a higher incidence of post-discharge institutionalization and in-hospital mortality were observed in patients who received both treatments (institutionalization group 0 = 45.0%, group 1 = 59.3%, group 2 = 81.6%; and in-hospital mortality group 0 = 7.5%, group 1 = 10.6%, group 2 = 16.3%). CONCLUSION: The use of antipsychotics, with or without lorazepam, during delirium is associated with increased risks of poor outcomes. These findings suggest that clinicians should be cautious about routine prescribing of these drugs to older patients with delirium. Further investigation is needed to clarify this association.

Delirium: A Frequent Manifestation in COVID-19 Older Patients.

The authors report a high prevalence of delirium in COVID-19 old patients admitted in an academic hospital. During the recent COVID-19 period, delirium was present in 38% of old patients admitted with delirium at the COVID ward of the Erasmus MC University Medical Center of Rotterdam. We do not know in which patients COVID-19 can cause delirium; however, considering the high prevalence of delirium in COVID-19 old patients and the potential serious consequences, attention is needed in order to reduce disability and mortality in this vulnerable category of patients.

Differences in potential biomarkers of delirium between acutely ill medical and elective cardiac surgery patients.

BACKGROUND/AIMS: The pathophysiology of delirium is poorly understood. Increasing evidence suggests that different pathways might be involved in the pathophysiology depending on the population studied. The aim of the present study was to investigate potential differences in mean plasma levels of neopterin, amino acids, amino acid ratios and homovanillic acid between two groups of patients with delirium. METHODS: Data from acutely ill medical patients aged 65 years and older, and patients aged 70 years and older undergoing elective cardiac surgery, were used. Differences in biomarker levels between the groups were investigated using univariate ANOVA with adjustments for age, sex, comorbidities, C-reactive protein (CRP) and the estimated glomerular filtration rate (eGFR), where appropriate. Linear regression analysis was used to identify potential determinants of the investigated biochemical markers. RESULTS: Eighty patients with delirium were included (23 acutely ill medical patients and 57 elective cardiac surgery patients). After adjustment, higher mean neopterin levels (93.1 vs 47.3 nmol/L, P=0.001) and higher phenylalanine/tyrosine ratios (1.39 vs 1.15, P=0.032) were found in acutely ill medical patients when compared to elective cardiac surgery patients. CRP levels were positively correlated with neopterin levels in acutely ill medical patients, explaining 28.4% of the variance in neopterin levels. eGFR was negatively correlated with neopterin in elective cardiac surgery patients, explaining 53.7% of the variance in neopterin levels. CONCLUSION: In this study, we found differences in mean neopterin levels and phenylalanine/tyrosine ratios between acutely ill medical and elective cardiac surgery patients with delirium. Moreover, our findings may suggest that in acutely ill medical patients, neopterin levels are mainly determined by inflammation/oxidative stress whereas in elective cardiac surgery patients, neopterin levels are mainly driven by renal function/fluid status. These findings suggest that the markers and pathways that might be involved in the pathophysiology of delirium may differ between specific groups of patients.

Increased neutrophil-lymphocyte ratio in delirium: a pilot study.

AIM: Delirium is a common and severe complication among older hospitalized patients. The pathophysiology is poorly understood, but it has been suggested that inflammation and oxidative stress may play a role. The aim of this pilot study was to investigate levels of the neutrophil-lymphocyte ratio (NLR) - a marker of systemic inflammation and oxidative stress - in patients with and without delirium. METHODS: This pilot study was performed within a retrospective chart review study that included acutely ill patients, 65 years and older, who were admitted to the ward of geriatrics of the Erasmus University Medical Center. All patients in whom the differential white blood cell (WBC) counts as well as the C-reactive protein (CRP) level were determined within 24 h after admission were included in the present study. Differences in NLR between patients with and without delirium were investigated using univariate analysis of variance, with adjustments for age, sex, comorbidities, CRP level, and total WBC count. RESULTS: Eighty-six patients were included. Thirteen patients were diagnosed with delirium. In adjusted models, higher mean NLR values were found in patients with, than in those without, delirium (9.10 vs 5.18, P=0.003). CONCLUSION: In this pilot study, we found increased NLR levels in patients with delirium. This finding might suggest that an inadequate response of the immune system and oxidative stress may play a role in the pathogenesis of delirium. Further studies are needed to confirm the association between NLR and delirium.

Anticholinergic drug exposure is associated with delirium and postdischarge institutionalization in acutely ill hospitalized older patients.

Several studies investigated the possible association between anticholinergic drugs and diverse clinical outcomes in older persons, but the results are inconsistent. The aim of this study was to investigate whether anticholinergic drug exposure is associated with delirium on admission, length of hospital stay, postdischarge institutionalization and in-hospital mortality in acutely ill hospitalized older patients. In this observational chart review study, we included acutely ill patients aged 65 and older who were admitted to the geriatric ward of the Erasmus University Medical Center, Rotterdam, The Netherlands, between 2012 and 2015 (n = 905). Anticholinergic drug exposure on admission was defined as the use of anticholinergic drugs, total number of anticholinergic drugs and anticholinergic drug burden score (ADB), quantified with the Anticholinergic Risk Scale (ARS), the Anticholinergic Cognitive Burden scale (ACB) and the list of Chew et al. (Chew). Logistic regression analyses were performed to investigate possible associations between anticholinergic drug exposure and the aforementioned outcomes. Analyses were adjusted for age, sex, comorbidities, non-anticholinergic drugs and delirium, where appropriate. Moderate and high ADB measured with the ARS were associated with delirium on admission with odds ratios (OR) of 1.70 (95% confidence interval (CI) = 1.16-2.49) and 1.83 (95% CI = 1.06-3.15), respectively. High ADB measured with the ARS was also associated with postdischarge institutionalization (OR = 2.43, 95% CI = 1.24-4.75). No associations were found using the ACB and Chew. Future studies are warranted to investigate the clinical usefulness of the ARS in reducing complications in older persons.

Potential Influence of Aspirin on Neopterin and Tryptophan Levels in Patients with a Delirium.

In an in vitro study, it was found that aspirin might decrease neopterin production and tryptophan degradation. The aim of the present study was to evaluate the possible association between aspirin use and mean neopterin and tryptophan levels in patients with and without a delirium and whether the use of aspirin is associated with a decreased prevalence of delirium. Neopterin and tryptophan levels were determined previously in acutely ill admitted patients aged ≥65 years. The possible influence of aspirin on mean levels of neopterin and tryptophan was investigated with univariate analysis of variance in adjusted models. Eighty-three patients were included; 22 had a delirium. In patients without a delirium (no aspirin (n = 31) versus aspirin (n = 27)), mean neopterin levels were 47.0 nmol/L versus 43.6 nmol/L (p = 0.645) and tryptophan levels were 33.1 µmol/L versus 33.9 µmol/L (p = 0.816). In patients with a delirium (no aspirin (n = 13) versus aspirin (n = 9)), mean neopterin levels were 77.8 nmol/L versus 71.1 nmol/L (p = 0.779) and tryptophan levels were 22.4 µmol/L versus 27.3 µmol/L (p = 0.439). No difference was found in the distribution of aspirin users between patients with and without a delirium. In this study, we found that the use of aspirin had no significant effect on mean levels of neopterin and tryptophan. However, the raw data suggest that there might be a potential influence in patients with a delirium. Aspirin use was not associated with a decreased prevalence of delirium.

Disturbed Serotonergic Neurotransmission and Oxidative Stress in Elderly Patients with Delirium.

BACKGROUND: Oxidative stress and disturbances in serotonergic and dopaminergic neurotransmission may play a role in the pathophysiology of delirium. AIMS: In this study, we investigated levels of amino acids, amino acid ratios and levels of homovanillic acid (HVA) as indicators for oxidative stress and disturbances in neurotransmission. METHODS: Plasma levels of amino acids, amino acid ratios and HVA were determined in acutely ill patients aged ≥65 years admitted to the wards of Internal Medicine and Geriatrics of the Erasmus University Medical Center and the ward of Geriatrics of the Havenziekenhuis, Rotterdam, The Netherlands. Differences in the biochemical parameters between patients with and without delirium were investigated by analysis of variance in models adjusted for age, gender and comorbidities. RESULTS: Of the 86 patients included, 23 had delirium. In adjusted models, higher mean phenylalanine/tyrosine ratios (1.34 vs. 1.14, p = 0.028), lower mean tryptophan/large neutral amino acids ratios (4.90 vs. 6.12, p = 0.021) and lower mean arginine levels (34.8 vs. 45.2 µmol/l, p = 0.022) were found in patients with delirium when compared to those without. No differences were found in HVA levels between patients with and without delirium. CONCLUSION: The findings of this study suggest disturbed serotonergic neurotransmission and an increased status of oxidative stress in patients with delirium.

Neopterin: a potential biomarker for delirium in elderly patients.

BACKGROUND/AIMS: The diagnosis of delirium is not supported by specific biomarkers. In a previous study, high neopterin levels were found in patients with a postoperative delirium. In the present study, we investigated levels of neopterin, interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1) in acutely ill admitted elderly patients with and without a delirium. METHODS: Plasma/serum levels of neopterin, IL-6 and IGF-1 were determined in patients aged ≥65 years admitted to the wards of Internal Medicine and Geriatrics. Differences in biomarker levels between patients with and without a delirium were investigated by the analysis of variance in models adjusted for age, gender, comorbidities and eGFR (when appropriate). RESULTS: Eighty-six patients were included; 23 of them with a delirium. In adjusted models, higher mean levels of neopterin (70.5 vs. 45.9 nmol/l, p = 0.009) and IL-6 (43.1 vs. 18.5 pg/ml, p = 0.034) and lower mean levels of IGF-1 (6.3 vs. 9.3 nmol/l, p = 0.007) were found in patients with a delirium compared to those without. CONCLUSIONS: The findings of this study suggest that neopterin might be a potential biomarker for delirium which, through oxidative stress and activation of the immune system, may play a role in the pathophysiology of delirium.