CAM-ICU may not be the optimal screening tool for early delirium screening in older emergency department patients: a prospective cohort study

Objectives: Delirium is a frequent problem among older patients in the emergency department (ED) and early detection is important to prevent its associated adverse outcomes. Several screening tools for delirium have been proposed for the ED, such as the 6-Item Cognitive Impairment Test (6-CIT) and the Confusion Assessment Method-ICU (CAM-ICU). Previous validation of the CAM-ICU for use in the ED showed varying results, possibly because it was administered at different or unknown time points. The aim was to study the prevalence of delirium in older ( ≥ 70 years) ED patients using the CAM-ICU and 6-CIT.

Participants and methods: A prospective cohort study was carried out in one tertiary care and one secondary care hospital in the Netherlands. Patients aged 70 years and older attending the ED were included. Delirium screening was performed within 1 h after ED registration using the CAM-ICU. The 6-CIT was determined for comparison using a cut-off point of at least 14 points indicating possible delirium.

Results: A total of 997 patients were included in the study, with a median age of 78 years (interquartile range 74-84). Delirium as assessed with CAM-ICU was positive in only 13 (1.3%, 95% confidence interval: 0.8-2.2) patients. Ninety-five (9.5% 95% confidence interval: 7.9-11.5) patients had 6-CIT more than or equal to 14.

Conclusion: We found a delirium prevalence of 1.3% using the CAM-ICU, which was much lower than the expected prevalence of around 10% as being frequently reported in the literature and what we found when using the 6-CIT. On the basis of these results, caution is warranted to use the CAM-ICU for early screening in the ED.


Association Between Levothyroxine Treatment and Thyroid-Related Symptoms Among Adults Aged 80 Years and Older With Subclinical Hypothyroidism

It is unclear whether levothyroxine treatment provides clinically important benefits in adults aged 80 years and older with subclinical hypothyroidism.To determine the association of levothyroxine treatment for subclinical hypothyroidism with thyroid-related quality of life in adults aged 80 years and older.Prospectively planned combined analysis of data involving community-dwelling adults aged 80 years and older with subclinical hypothyroidism. Data from a randomized clinical trial were combined with a subgroup of participants aged 80 years and older from a second clinical trial. The trials were conducted between April 2013 and May 2018. Final follow-up was May 4, 2018.Participants were randomly assigned to receive levothyroxine (n = 112; 52 participants from the first trial and 60 from the second trial) or placebo (n = 139; 53 participants from the first trial and 86 from the second trial).Co-primary outcomes were Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire scores for the domains of hypothyroid symptoms and tiredness at 1 year (range, 0-100; higher scores indicate worse quality of life; minimal clinically important difference, 9).Of 251 participants (mean age, 85 years; 118 [47%] women), 105 were included from the first clinical trial and 146 were included from the second clinical trial. A total of 212 participants (84%) completed the study. The hypothyroid symptoms score decreased from 21.7 at baseline to 19.3 at 12 months in the levothyroxine group vs from 19.8 at baseline to 17.4 at 12 months in the placebo group (adjusted between-group difference, 1.3 [95% CI, −2.7 to 5.2]; P = .53). The tiredness score increased from 25.5 at baseline to 28.2 at 12 months in the levothyroxine group vs from 25.1 at baseline to 28.7 at 12 months in the placebo group (adjusted between-group difference, −0.1 [95% CI, −4.5 to 4.3]; P = .96). At least 1 adverse event occurred in 33 participants (29.5%) in the levothyroxine group (the most common adverse event was cerebrovascular accident, which occurred in 3 participants [2.2%]) and 40 participants (28.8%) in the placebo group (the most common adverse event was pneumonia, which occurred in 4 [3.6%] participants).In this prospectively planned analysis of data from 2 clinical trials involving adults aged 80 years and older with subclinical hypothyroidism, treatment with levothyroxine, compared with placebo, was not significantly associated with improvement in hypothyroid symptoms or fatigue. These findings do not support routine use of levothyroxine for treatment of subclinical hypothyroidism in adults aged 80 years and Identifier: NCT01660126; Netherlands Trial Register: NTR3851


Systematic Review: Components of a Comprehensive Geriatric Assessment in Inflammatory Bowel Disease-A Potentially Promising but Often Neglected Risk Stratification

Background: The population of older patients with inflammatory bowel disease [IBD] is increasing. Patient age does not fully account for poor outcomes and its clinical utility for risk stratification is limited. Comprehensive geriatric assessment [CGA], comprising a somatic, functional, mental, and social assessment or frailty, could be a predictor tool.

Aims: To systematically review literature on the kind of components of a CGA being used in adult IBD patients and the association of these components with adverse health outcomes.

Methods: An electronic literature search was performed on January 16, 2018, using PubMed, Embase, Web of Science, the Cochrane Library, CENTRAL, Emcare, and PsycINFO. Longitudinal studies relating somatic, functional, mental, and social assessment or frailty to adverse health outcomes during follow-up in IBD patients were included. The Newcastle-Ottawa scale was used to assess individual study quality.

Results: Of 4080 identified citations, 27 studies were included, reporting 169 associations. Median sample size was 108 patients (interquartile range [IQR] 60-704). No studies performed subgroup analyses on older patients, and the highest mean age reported was 52.7 years. Somatic and functional assessments were used in three studies, mental in 24, and social in five. No study assessed cognitive status, functional performance, or frailty. In 62 associations [36.7%], components of a CGA were significantly associated with adverse health outcome measurements.

Conclusions: Components of a CGA were associated with adverse health outcomes in IBD patients, but older patients were under-represented. More studies among older patients with IBD are warranted to further establish the clinical impact of a CGA.

Keywords: Crohn’s disease; comprehensive geriatric assessment; ulcerative colitis.


Vital signs and impaired cognition in older emergency department patients: The APOP study

Background/Objectives Cognitive impairment is a frequent problem among older patients attending the Emergency Department (ED) and can be the result of pre-existing cognitive impairment, delirium, or neurologic disorders. Another cause can also be acute disturbance of brain perfusion and oxygenation, which may be reversed by optimal resuscitation. This study aimed to assess the relationship between vital signs, as a measure of acute hemodynamic changes, and cognitive impairment in older ED patients. Design Prospective cohort study Setting ED’s of two tertiary care and two secondary care hospitals in the Netherlands. Participants 2629 patients aged 70-years and older Measurements Vital signs were measured at the moment of ED arrival as part of routine clinical care. Cognition was measured using the Six-Item Cognitive Impairment Test (6-CIT). Results The median age of patients was 78 years (IQR 74–84). Cognitive impairment was present in 738 patients (28.1%). When comparing lowest with highest quartiles, a systolic blood pressure of <129 mmHg (OR 1.30, 95% confidence interval (95%CI) 0.98–1.73)was associated with increased risk of cognitive impairment. A higher respiratory rate (>21/min) was associated with increased risk of impaired cognition (OR 2.16, 95% CI 1.58–2.95) as well as oxygen saturation of <95% (OR 1.64, 95%CI 1.24–2.19). Conclusion Abnormal vital signs associated with decreased brain perfusion and oxygenation are also associated with cognitive impairment in older ED patients. This may partially be explained by the association between disease severity and delirium, but also by acute disturbance of brain perfusion and oxygenation. Future studies should establish whether normalization of vital signs will also acutely improve cognition.


Erythrocyte sedimentation rate as an independent prognostic marker for mortality: a prospective population-based cohort study

Background: A very high erythrocyte sedimentation rate (ESR) is usually an indication of underlying pathology. Additionally, a moderately elevated ESR may also be attributable to biological ageing. Whether the ESR is a prognostic factor for mortality, regardless of age, has been scarcely investigated. Therefore, the objective was to analyse the association between elevated ESR levels and the risk of mortality in a prospective cohort of the general population.

Methods: We studied data from the Rotterdam Study (1990-2014). ESR levels were measured at baseline and individuals were followed until death or end of study. Associations between moderately (20-50 mm h-1 ) and markedly (>50 mm h-1 ) elevated ESR levels and all-cause mortality were assessed using multivariate Cox proportional hazard models.

Results: In total, 5226 participants were included, and the mean age was 70.3 years. During a median follow-up time of 14.9 years, 3749 participants died (71.7%). After adjustment, both a moderately elevated ESR and a markedly elevated ESR were associated with a significantly higher risk of overall mortality [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.12-1.35 and HR 1.89, 95% CI 1.38-2.60, respectively]. Although the ESR becomes higher with age, in a group aged above 75 years, without any comorbidities, an ESR > 20 mm h-1 remained associated with a significantly increased risk of mortality (HR 1.29, 95%CI 1.01-1.64).

Conclusion: An elevated ESR is an independent prognostic factor for mortality. Despite the fact that ESR increases with age, it remains associated with an increased risk of mortality and warrants close follow-up.

Keywords: ageing; erythrocyte sedimentation rate; general population; low-grade inflammation; mortality.


Geriatric assessment and 1-year mortality in older patients with cancer in the head and neck region: A cohort study

Background: The aim is to describe the association of functional capacity and cognitive functioning with 1-year mortality in older patients with cancer in the head and neck region.

Methods: We performed a cohort study in which all patients aged 70 years and older received a geriatric screening before treatment. Main outcome was 1-year mortality.

Results: A total of 102 patients were included. Median age was 78.7 years (interquartile range [IQR], 72.3-84.5), 25% were cognitive impaired, 40% were malnourished, and 28.4% used a walking device. Overall, 1-year mortality was 42.3%. Male sex (hazard ratio [HR], 4.30; 95% confidence interval [CI], 1.35-13.67), malnutrition (HR, 2.55; 95% CI, 1.19-5.16), and using a walking device (HR, 2.80; 95% CI 1.13-6.93) were associated with higher mortality risk, independent of stage and comorbidities.

Conclusion: In older patients with head and neck cancer, the mortality rates are high. Nutritional status and mobility are determinants of 1-year mortality, independent of tumor stage, age, and comorbidity.

Keywords: cognitive disorders; geriatric oncology; head and neck cancer; physical functioning; social functioning.


Assessment of the Relationship Between Genetic Determinants of Thyroid Function and Atrial Fibrillation: A Mendelian Randomization Study

Importance: Increased free thyroxine (FT4) and decreased thyrotropin are associated with increased risk of atrial fibrillation (AF) in observational studies, but direct involvement is unclear.

Objective: To evaluate the potential direct involvement of thyroid traits on AF.

Design, setting, and participants: Study-level mendelian randomization (MR) included 11 studies, and summary-level MR included 55 114 AF cases and 482 295 referents, all of European ancestry.

Exposures: Genomewide significant variants were used as instruments for standardized FT4 and thyrotropin levels within the reference range, standardized triiodothyronine (FT3):FT4 ratio, hypothyroidism, standardized thyroid peroxidase antibody levels, and hyperthyroidism. Mendelian randomization used genetic risk scores in study-level analysis or individual single-nucleotide polymorphisms in 2-sample MR for the summary-level data.

Conclusions and relevance: Genetically increased FT3:FT4 ratio and hyperthyroidism, but not FT4 within the reference range, were associated with increased AF, and increased thyrotropin within the reference range and hypothyroidism were associated with decreased AF, supporting a pathway involving the pituitary-thyroid-cardiac axis.


The association between intravenous fluid resuscitation and mortality in older emergency department patients with suspected infection.

Objective: Recent studies suggest that hypotension thresholds in current guidelines might be too low for older patients due to arterial stiffening, possibly leading to insufficient fluid resuscitation. We compared intravenous (IV) fluid volumes that older (≥ 70 years) and younger (< 70 years) patients with suspected infection with similar initial systolic blood pressure (SBP) received in the emergency department (ED) and investigated whether this was associated with in-hospital mortality in older patients. Methods: This was an observational multicenter study using an existing database in which consecutive ED patients hospitalized with suspected infection were prospectively included. We first compared the fluid volumes older and younger ED patients received per initial SBP category. Patients were then stratified into two SBP categories (≤ or > 120 mmHg; 120 has been suggested to be a better threshold) and thereafter into three fluid volume categories: 0-1 L, 1-2 L, or > 2 L. In each SBP and fluid category, case-mix-adjusted in-hospital mortality was compared between older and younger patients, using multivariable logistic regression analysis.

Results: The included 981 (37%) older and 1678 (63%) younger ED patients received similar IV fluid volumes per initial SBP category. Older patients with an initial SBP > 120 mmHg had a higher adjusted OR of 2.06 (95% CI 1.02-4.16), in the 0-1 L category, while this association was not found in the higher fluid categories of 1-2 L or > 2 L. In the SBP ≤ 120 mmHg category, this association was also absent.

Conclusion: This hypothesis-generating study suggests that older patients with suspected infection may need higher fluid volumes than younger patients, when having a seemingly normal initial SBP.

Keywords: Emergency medicine; Fluid resuscitation; Geriatrics; Infectious diseases; Sepsis; Systolic blood pressure.


Study protocol: a randomised controlled trial on the clinical effects of levothyroxine treatment for subclinical hypothyroidism in people aged 80 years and over

Subclinical hypothyroidism is common in older people and its contribution to health and disease needs to be elucidated further. Observational and clinical trial data on the clinical effects of subclinical hypothyroidism in persons aged 80 years and over is inconclusive, with some studies suggesting harm and some suggesting benefits, translating into equipoise whether levothyroxine therapy provides clinical benefits. This manuscript describes the study protocol for the Institute for Evidence-Based Medicine in Old Age (IEMO) 80-plus thyroid trial to generate the necessary evidence base.


Optimization of the APOP screener to predict functional decline or mortality in older emergency department patients: Cross-validation in four prospective cohorts

Introduction: Many screening instruments to predict adverse health outcomes in older patients visiting the emergency department (ED) have been developed, but successful implementation has been hampered because they are insufficiently validated or not tailored for the intended use of everyday clinical practice. The present study aims to refine and validate an existing screening instrument (the APOP screener) to predict 90-day functional decline or mortality in older ED patients.

Methods: Consecutive older patients (≥70 years) visiting the EDs of four hospitals were included and prospectively followed. First, an expert panel used predefined criteria to decide which independent predictors (including demographics, illness severity and geriatric parameters) were suitable for refinement of the model predicting functional decline or mortality after 90 days. Second, the model was cross-validated in all four hospitals and predictive performance was assessed. Additionally, a pilot study among triage nurses experiences and clinical usability of the APOP screener was conducted.

Results: In total 2629 older patients were included, with a median age of 79 years (IQR 74-84). After 90 days 805 patients (30.6%) experienced functional decline or mortality. The refined prediction model included age, gender, way of arrival, need of regular help, need help in bathing/showering, hospitalization the prior six months and impaired cognition. Calibration was good and cross-validation was successful with a pooled area under the curve of 0.71 (0.69-0.73). In the top 20% patients predicted to be at highest risk in total 58% (95%CI 54%-62%) experienced functional decline or mortality. Triage nurses found the screener well suited for clinical use, with room for improvement.

Conclusion: In conclusion, optimization of the APOP screener resulted in a short and more simplified screener, which adequately identifies older ED patients at highest risk for functional decline or mortality. The findings of the pilot study were promising for clinical use.

Keywords: Adverse outcomes; Emergency medical services; Older patients; Optimization; Screening.