Discrepancies in corrected calcium versus ionised calcium in a geriatric population: an observational study.

BACKGROUND: Calcium can be measured as ionised (Ca-ionised) or albumin-adjusted total calcium (Ca-albumin). Current clinical guidelines predominantly utilise Ca-albumin, despite Ca-ionised being the gold standard. Discrepancies can occur between these measurement modalities and can lead to clinical dilemmas. It remains unclear how large these discrepancies are in older patients. This study investigated the discrepancies between Ca-ionised and Ca-albumin in geriatric patients. METHODS: This is an observational study of all geriatric patients (n = 876) in the Jeroen Bosch Hospital (January 2018 and January 2021) in whom both Ca-ionised and Ca-albumin were measured. Misclassification of calcaemic state (i.e. low, normal or high) was calculated (percentages), the measure of agreement was described using Cohen's Kappa and for the continuous data Pearson's correlation coefficient was used. Relevant categories of age and renal function were considered for effect modification effects and studied by interaction terms in a regression model. RESULTS: In one-third of the measurements, there was a misclassification. Ca-albumin measurements failed to identify 28% of hypocalcaemia. In 3.5%, hypercalcemia based on Ca-albumin was not confirmed by Ca-ionised. The correlation coefficient between Ca-ionised and Ca-albumin was 0.743 (P = 0.01) and measure of agreement by Kappa was 0.213 (P < 0.001). In the oldest old (≥ 85 years) and patients with eGFR <30 ml/min/1.73 m2 ,the agreement by Kappa was lower, with values of 0.192 and 0.104, respectively. CONCLUSION: There is a discrepancy between Ca-albumin and Ca-ionised in one-third of the geriatric patients, leading to clinical dilemmas. In the oldest old and patients with renal dysfunction, this problem is most pronounced.

Recognition of cognitive dysfunction in hospitalised older patients: a flash mob study.

BACKGROUND: It is important that healthcare professionals recognise cognitive dysfunction in hospitalised older patients in order to address associated care needs, such as enhanced involvement of relatives and extra cognitive and functional support. However, studies analysing medical records suggest that healthcare professionals have low awareness of cognitive dysfunction in hospitalised older patients. In this study, we investigated the prevalence of cognitive dysfunction in hospitalised older patients, the percentage of patients in which cognitive dysfunction was recognised by healthcare professionals, and which variables were associated with recognition. METHODS: A multicentre, nationwide, cross-sectional observational study was conducted on a single day using a flash mob study design in thirteen university and general hospitals in the Netherlands. Cognitive function was assessed in hospitalised patients aged ≥ 65 years old, who were admitted to medical and surgical wards. A Mini-Cog score of < 3 out of 5 indicated cognitive dysfunction. The attending nurses and physicians were asked whether they suspected cognitive dysfunction in their patient. Variables associated with recognition of cognitive dysfunction were assessed using multilevel and multivariable logistic regression analyses. RESULTS: 347 of 757 enrolled patients (46%) showed cognitive dysfunction. Cognitive dysfunction was recognised by attending nurses in 137 of 323 patients (42%) and by physicians in 156 patients (48%). In 135 patients (42%), cognitive dysfunction was not recognised by either the attending nurse or physician. Recognition of cognitive dysfunction was better at a lower Mini-Cog score, with the best recognition in patients with the lowest scores. Patients with a Mini-Cog score < 3 were best recognised in the geriatric department (69% by nurses and 72% by physicians). CONCLUSION: Cognitive dysfunction is common in hospitalised older patients and is poorly recognised by healthcare professionals. This study highlights the need to improve recognition of cognitive dysfunction in hospitalised older patients, particularly in individuals with less apparent cognitive dysfunction. The high proportion of older patients with cognitive dysfunction suggests that it may be beneficial to provide care tailored to cognitive dysfunction for all hospitalised older patients.

Low dose oral haloperidol does not prolong QTc interval in older acutely hospitalised adults: a subanalysis of a randomised double-blind placebo-controlled study.

BACKGROUND: Haloperidol is the most frequently prescribed antipsychotic for delirium symptoms. The risk of QTc prolongation often raises concerns, although the effect of haloperidol on QTc interval has not yet been investigated in a randomised placebo-controlled fixed-dose study. METHODS: A subanalysis of a randomised double-blind placebo-controlled study was conducted to evaluate the effect of prophylactic haloperidol 1 mg or placebo 1 mg orally twice-daily (maximum of 14 doses) on QTc interval in patients aged 70 years and over. Bedside, 12-lead ECGs were recorded before, during and after the one-week intervention period. Automatic QTc measurements were obtained in addition to manual measurements of QT and RR intervals, blinded for treatment status. Manual measurements were corrected (QTc) using Bazett (QTc-B), Framingham (QTc-Fa), Fridericia (QTc-Fi) and Hodges (QTc-H) methods. Mixed model analyses were used to test for differences in longitudinal course of QTc between patients receiving haloperidol and placebo. RESULTS: ECG recordings of 72 patients (haloperidol n = 38) were analysed, 45.8% male. Median (range) haloperidol serum concentration on day 4 was 0.71 (0.32-1.82) µg/L (n = 23). Longitudinal course of mean QTc did not significantly differ between treatment arms for any of the automatic or manually derived QTc values. CONCLUSIONS: Low dose oral haloperidol did not result in QTc prolongation in older acutely hospitalised patients. Results may not be generalizable to patients with existing ECG abnormalities such as atrial fibrillation.

Association Between Urinary Tract Infections and Antipsychotic Drug Use in Older Adults.

Antipsychotic drugs are frequently prescribed to older adults, but they may be associated with serious adverse effects. The objective was to investigate the association between use of antipsychotics in older adults and the risk of urinary tract infections (UTIs).This study was designed as a cohort study.Data were obtained from the Clinical Practice Research Datalink from January 1, 2000, to September 29, 2016.Primary care patients 65 years or older in the United Kingdom with a first prescription for an oral antipsychotic were included in the study.Incidence of UTIs was calculated for periods with and without exposure to antipsychotic drugs in one cohort. Cox proportional hazard regression analysis with Andersen-Gill extension for recurrent events was used to calculate hazard ratios (HRs) with 95% confidence interval (CI).During the study period, 191,827 individuals with a first prescription for an oral antipsychotic drug were identified. Current use of antipsychotics was associated with an increased risk of UTI compared with past use (adjusted HR, 1.31; 95% CI, 1.28-1.34). This effect was strongest in the first 14 days of use (adjusted HR, 1.83; 95% CI, 1.73-1.95) and in individuals who used more than one antipsychotic drug concomitantly (adjusted HR, 1.64; 95% CI, 1.45-1.87). The risk was slightly higher for typical antipsychotics than for atypical antipsychotics. Stratification by sex showed that risk estimates were slightly higher in men than in women.Use of antipsychotics was associated with an increased risk of UTIs in both men and women, particularly in the first weeks after the start of treatment.

Haloperidol versus placebo for delirium prevention in acutely hospitalised older at risk patients: a multi-centre double-blind randomised controlled clinical trial.

Background: because the few randomised placebo-controlled trials investigating the potential role for prophylactic haloperidol in delirium prevention have focused on specific surgical populations, we investigated its efficacy and safety in acutely hospitalised older patients. Methods: this multi-centre, double-blind, stratified, block randomised, placebo-controlled trial was conducted at six Dutch hospitals. Patients age ≥70 years, acutely admitted through the emergency department for general medicine or surgical specialties and at risk for delirium were randomised (n = 245) to haloperidol or placebo 1 mg orally twice-daily (maximum of 14 doses) on top of standard nonpharmacological prevention strategies. The primary outcome was delirium incidence. Other endpoints included delirium severity and duration, drug safety and clinical outcomes. Results: intention-to-treat analysis included 242 participants (calculated sample size n = 390, statistical power of current sample 59%) allocated to haloperidol (n = 118) or placebo (n = 124). In the haloperidol and placebo group, delirium incidence was 19.5 versus 14.5% (OR 1.43, 95% CI 0.72 to 2.78); median (IQR) delirium duration 4 (2, 5) versus 3 (1, 6) days (P = 0.366); maximum DRS-R-98 score 16 (9.8, 19.5) versus 10 (5.5, 22.5) (P = 0.549; 53.7% missing data); hospital LOS 7 (4, 10.3) versus 7 (5, 11.8) days (P = 0.343); 3-month mortality 9.9 versus 12.5% (OR 0.77, 95% CI 0.34 to 1.75), respectively. No treatment-limiting side effects were noted. Conclusions: prophylactic low-dose oral haloperidol did not reduce delirium incidence in acutely hospitalised older patients. Therefore, prophylactic use of haloperidol in this population is not recommended.

Prophylactic Use of Haloperidol and Changes in Glucose Levels in Hospitalized Older Patients.

BACKGROUND: Treatment with antipsychotic drugs has been associated with glucose dysregulation in older outpatients, especially in the early stage of therapy. The underlying mechanism is, however, unclear. The aim of this study was to investigate changes in glucose levels during haloperidol use compared with the use of placebo among older hospitalized patients. METHODS: This substudy was part of a larger multicenter, randomized, double blind, placebo-controlled clinical trial among hospitalized patients aged 70 years and older who had an increased risk of in-hospital delirium. Patients who were admitted to the Jeroen Bosch Hospital in 's-Hertogenbosch between June 2014 and February 2015 were invited to participate in the study. Participating patients were randomized for treatment and given 1 mg of haloperidol or a placebo twice daily for a maximum of 7 consecutive days (14 doses). Exclusion criteria for this substudy were the use of corticosteroids and changes in diabetes medication. Random blood samples to determine glucose levels were collected before day 1 and on day 6 of the study. Student independent sample t test was used to determine differences in glucose changes between both groups. RESULTS: Twenty-nine patients were included (haloperidol, n = 14; placebo, n = 15). The mean glucose level for placebo users was 139.3 mg/dL (SD, 50.1) on day 1 and 140.8 mg/dL (SD, 45.7) on day 6, and the mean glucose level for haloperidol users was 139.9 mg/dL (SD, 71.0) on day 1 and 150.2 mg/dL (SD, 39.1) on day 6. The difference was not statistically significant (P = 0.685). CONCLUSIONS: Short-term prophylactic use of haloperidol was not associated with changes in glucose levels in older hospitalized patients compared with those given a placebo in this small study.

Antipsychotic drug use associated with urinary tract infections in older women.

OBJECTIVES: Antipsychotic drugs are frequently prescribed to elderly patients, but they are associated with serious adverse effects. The objective of the current study was to investigate the association between use of antipsychotics by elderly women and the risk of urinary tract infections (UTIs). COHORT STUDY SETTING: Dispensing data were obtained from the PHARMO Database Network for the period 1998-2008. PARTICIPANTS: Ambulatory Dutch women (≥65 years) with current and past use of antipsychotics. MEASUREMENTS: Incidence rates of UTIs, as defined by use of nitrofurantoin, was calculated within and outside the period of exposure to antipsychotic drugs. Cox proportional hazard regression analysis with Andersen-Gill extension for recurrent events was used to calculate crude and adjusted hazard ratios (HRs). RESULTS: During the study period, 18,541 women with a first prescription of an antipsychotic were identified. Current use of antipsychotics was associated with an increased risk of UTI compared to past use: HR, adjusted for age and history of UTIs, 1.33, 95% CI 1.27-1.39. A strong temporal relationship was found: the risk of being treated for a UTI was higher in the first week after the start of the treatment (adjusted HR 3.03, 95% CI 2.63-3.50) and decreased after 3 months (adjusted HR 1.22, 95% CI 1.17-1.28). Cumulative exposure was not associated with an increased risk of UTIs. There was no difference in effect between conventional and atypical antipsychotics. CONCLUSION: Our results show an increased risk of uncomplicated UTIs during antipsychotic use in older female patients, especially in the first week of treatment.

Rating scales to measure side effects of antipsychotic medication: A systematic review.

INTRODUCTION: Many patients experience side effects during treatment with antipsychotics. This article reviews the clinical use and psychometric characteristics of rating scales used to assess side effects in patients treated with antipsychotics. METHODS: A systematic literature search was performed using the electronic databases PubMed and Embase, with predefined search terms. RESULTS: In total, 52 different scales were used in the 440 articles retrieved. For multiple side effects measured with one scale, the Udvalg for Kliniske Undersøgelser Side Effects Rating Scale for Clinicians was used the most, whereas the Liverpool University Neuroleptic Side Effect Rating Scale had the best psychometric characteristics (Cronbach's α 0.81 and test-retest reliability 0.89). The Simpson Angus Scale was used the most to rate extrapyramidal side effects, although the Maryland Psychiatric Research Center scale had the best characteristics (Cronbach's α 0.80, test-retest reliability 0.92 and inter-rater reliability 0.81-0.90). The Arizona Sexual Experience Scale was used the most to assess sexual dysfunction, but the Antipsychotics and Sexual Functioning Questionnaire and the Nagoya Sexual Functioning Questionnaire had the best characteristics. CONCLUSION: This review will help researchers and clinicians make a purpose-oriented choice of which scale to use. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42014013010.

Efficacy and safety of haloperidol prophylaxis for delirium prevention in older medical and surgical at-risk patients acutely admitted to hospital through the emergency department: study protocol of a multicenter, randomised, double-blind, placebo-controlled clinical trial.

BACKGROUND: Delirium is associated with substantial morbidity and mortality rates in elderly hospitalised patients, and a growing problem due to increase in life expectancy. Implementation of standardised non-pharmacological delirium prevention strategies is challenging and adherence remains low. Pharmacological delirium prevention with haloperidol, currently the drug of choice for delirium, seems promising. However, the generalisability of randomised controlled trial results is questionable since studies have only been performed in selected postoperative hip-surgery and intensive care unit patient populations. We therefore present the design of the multicenter, randomised, double-blind, placebo-controlled clinical trial on early pharmacological intervention to prevent delirium: haloperidol prophylaxis in older emergency department patients (The HARPOON study). METHODS/DESIGN: In six Dutch hospitals, at-risk patients aged 70 years or older acutely admitted through the emergency department for general medicine and surgical specialties are randomised (n = 390) for treatment with prophylactic haloperidol 1 mg or placebo twice daily for a maximum of seven consecutive days. Primary outcome measure is the incidence of in-hospital delirium within seven days of start of the study intervention, diagnosed with the Confusion Assessment Method, and the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for delirium. Secondary outcome measures include delirium severity and duration assessed with the Delirium Rating Scale Revised 98; number of delirium-free days; adverse events; hospital length-of-stay; all-cause mortality; new institutionalisation; (Instrumental) Activities of Daily Living assessed with the Katz Index of ADL, and Lawton IADL scale; cognitive function assessed with the Six-item Cognitive Impairment Test, and the Dutch short form Informant Questionnaire on Cognitive Decline in the Elderly. Patients will be contacted by telephone three and six months post-discharge to collect data on cognitive- and physical function, home residency, all-cause hospital admissions, and all-cause mortality. DISCUSSION: The HARPOON study will provide relevant information on the efficacy and safety of prophylactic haloperidol treatment for in-hospital delirium and its effects on relevant clinical outcomes in elderly at-risk medical and surgical patients. TRIAL REGISTRATION: EudraCT Number: 201100476215; ClinicalTrials.gov Identifier: NCT01530308; Dutch Clinical Trial Registry: NTR3207.

Psychotropic medications, including short acting benzodiazepines, strongly increase the frequency of falls in elderly.

OBJECTIVES: Falls in the elderly are common and often serious. The aim of this study was to examine the association between the use of different classes of psychotropic medications, especially short acting benzodiazepines, and the frequency of falling in elderly. Study design This retrospective cohort study was performed with patients who visited the day clinic of the department of geriatric medicine of the University Medical Center Utrecht in the Netherlands between 1 January 2011 and 1 April 2012. Measurements Frequencies of falling in the past year and medication use were recorded. Logistic regression analysis was performed to assess the relationship between the frequency of falling in the past year and the use of psychotropic medications. RESULTS: During this period 404 patients were included and 238 (58.9%) of them had experienced one or more falls in the past year. After multivariate adjustment, frequent falls remained significantly associated with exposure to psychotropic medications (odds ratio [OR] 1.96; 95% confidence interval [CI] 1.17-3.28), antipsychotics (OR 3.62; 95% CI 1.27-10.33), hypnotics and anxiolytics (OR 1.81; 95% CI 1.05-3.11), short-acting benzodiazepines or Z-drugs (OR 1.94; 95% CI 1.10-3.42) and antidepressants (OR 2.35; 95% CI 1.33-4.16). CONCLUSIONS: This study confirms that taking psychotropic medication, including short-acting benzodiazepines, strongly increases the frequency of falls in elderly. This relation should be explicitly recognized by doctors prescribing for older people, and by older people themselves. If possible such medication should be avoided for elderly patients especially with other risk factors for falling.