Impaired cognition is associated with adverse outcome in older patients in the Emergency Department; the Acutely Presenting Older Patients (APOP) study.

Objective: to investigate whether cognitive impairment, measured early after Emergency Department (ED) arrival and irrespective of its cause, is independently associated with functional decline or mortality after 3 and 12 months in older ED patients. Design and setting: a prospective multi-centre cohort study in all Acutely Presenting Older Patients visiting the Emergency Department (APOP study) of three hospitals in the Netherlands. Participants: 2,130 patients, ≥70 years. Measurements: data on demographics, disease severity and geriatric characteristics were collected during the first hour of the ED visit. Cognition was measured using the 6-Item-Cognitive-Impairment-Test ('6CIT'). Cognitive impairment was defined as 6CIT ≥11, self-reported dementia or the inability to perform the cognition test. The composite adverse outcome after 3 and 12 months was defined as a 1-point decrease in Katz Activities of Daily Living (ADL), new institutionalisation or mortality. Multivariable regression analysis was used to assess whether cognitive impairment independently associates with adverse outcome. Results: of 2,130 included patients, 588 (27.6%) had cognitive impairment at baseline and 654 patients (30.7%) suffered from adverse outcome after 3 months. Cognitive impairment associated with increased risk for adverse outcome (adjusted odds ratio (OR) 1.72, 95%CI 1.37-2.17). After 12 months, 787 patients (36.9%) suffered from adverse outcome. Again, cognitive impairment independently associated with increased risk for adverse outcome (adjusted OR 1.89, 95%CI 1.46-2.46). ORs were similar for patients who were discharged home versus hospitalised patients. Conclusion: cognitive impairment measured during the early stages of ED visit, irrespective of the cause, is independently associated with adverse outcome after 3 and 12 months in older patients.

The APOP screener and clinical outcomes in older hospitalised internal medicine patients.

BACKGROUND: Acutely hospitalised older patients with indications related to internal medicine have high risks of adverse outcomes. We investigated whether risk stratification using the Acutely Presenting Older Patient (APOP) screening tool associates with clinical outcomes in this patient group. METHODS: Patients aged ≥ 70 years who visited the Emergency Department (ED) and were acutely hospitalised for internal medicine were followed prospectively. The APOP screener assesses demographics, physical and cognitive function at ED presentation, and predicts 3-month mortality and functional decline in the older ED population. Patients with a predicted risk ≥ 45% were considered 'high risk'. Clinical outcome was hospital length of stay (LOS), and adverse outcomes were mortality and functional decline, 3 and 12 months after hospitalisation. RESULTS: We included 319 patients, with a median age of 80 (IQR 74-85) years, of whom 94 (29.5%) were categorised as 'high risk' by the APOP screener. These patients had a longer hospital LOS compared to 'low risk' patients 5 (IQR 3-10) vs. 3 (IQR 1-7) days, respectively; p = 0.006). At 3 months, adverse outcomes were more frequent in 'high risk' patients compared to 'low risk' patients (59.6% vs. 34.7%, respectively; p < 0.001). At 12 months, adverse outcomes (67.0% vs. 46.2%, respectively; p = 0.001) and mortality (48.9% vs. 28.0%, respectively; p < 0.001) were greater in 'high risk' compared to 'low risk' patients. CONCLUSION: The APOP screener identifies acutely hospitalised internal medicine patients at high risk for poor short and long-term outcomes. Early risk stratification at admission could aid in individualised treatment decisions to optimise outcomes for older patients.

Occurrence and management of an aberrant free T4 in combination with a normal TSH.

BACKGROUND: Thyroid function tests may show the combination of a normal concentration of serum thyroidstimulating hormone (TSH) and an increased or decreased level of free thyroxine (free T4). How often this occurs is unclear and not everyone is familiar with how it should be adressed. METHODS: We conducted a retrospective cohort study of all adult patients who presented at a non-academic general hospital in the Netherlands between 1 January 2010 and 31 December 2014 and yielded an increased or decreased free T4 in combination with a normal TSH. Exclusion criteria included the use of thyroid medication, pregnancy, a history of thyroid surgery and treatment with radioactive iodine. The medical records of the patients included were retrieved and evaluated. RESULTS: Of the 30,143 combined TSH and free T4 measurements in 23,199 individual patients, 1005 measurements (3.33%) in 775 patients (3.34%) yielded an aberrant free T4 in combination with a normal TSH. 398 patients (1.72%) had a persistent aberrant free T4, 349 (87.7%) of whom had a decreased free T4 and 49 (12.3%) an increased free T4. In 58 of the 398 patients (14.6%) with a persistent abberant free T4 a possible cause was established by the treating physician. However, upon re-examination of medical files a possible causative factor could be identified in 123 patients (30.9%). CONCLUSION: In our study population the prevalence of hyperthyroxinemia or hypothyroxinemia in combination with a normal TSH was 334 per 10.000 patients. When records were thoroughly searched, identification of potential causative factors increased substantially. Clinicians should be encouraged to check for underlying causes.

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.

Optimising the ISAR-HP to screen efficiently for functional decline in older patients.

INTRODUCTION: The Identification of Seniors At Risk-Hospitalised Patients (ISAR-HP) has recently been included in guidelines as a frailty indicator to identify patients for comprehensive geriatric assessment. Previous studies showed that the conventional cut-off score incorrectly classifies a high percentage of patients as high risk. We aimed to optimise the predictive value of ISAR-HP by using different cut-offs in older acutely hospitalised patients. METHODS: A prospective follow-up study was performed in two Dutch hospitals. Acutely hospitalised patients aged ≥ 70 years were included. Demographics, illness severity parameters, geriatric measurements and the ISAR-HP scores were obtained at baseline. The primary outcome was a combined end point of functional decline or mortality during 90-day follow-up. RESULTS: In total 765 acutely hospitalised older patients were included, with a median age of 79 years, of whom 276 (36.1%) experienced functional decline or mortality. The conventional ISAR-HP cut-off of ≥ 2 assigned 432/765 patients (56.5%) as high risk, with a positive predictive value (PPV) of 0.49 (95%CI 0.45-0.54) and a negative predictive value of 0.81 (95%CI 0.76-0.85). Thus, 51% of those whom the ISAR-HP denoted as high risk did not experience the outcome of interest. Raising the cut-off to ≥ 4 assigned 205/765 patients (26.8%) as high risk, with a marginally increased PPV to 0.55 (95%CI 0.48-0.62). CONCLUSION: The ISAR-HP with the conventional cut-off of ≥ 2 incorrectly identifies a large group of patients at high risk for functional decline or mortality and raising the cut-off to 4 only marginally improved performance. Caution is warranted to ensure efficient screening and follow-up interventions.

Predicting adverse health outcomes in older emergency department patients: the APOP study.

BACKGROUND: Older patients experience high rates of adverse outcomes after an emergency department (ED) visit. Early identification of those at high risk could guide preventive interventions and tailored treatment decisions, but available models perform poorly in discriminating those at highest risk. The present study aims to develop and validate a prediction model for functional decline and mortality in older patients presenting to the ED. METHODS: A prospective follow-up study in patients aged ≥ 70, attending the EDs of the LUMC, the Netherlands (derivation) and Alrijne Hospital, the Netherlands (validation) was conducted. A baseline assessment was performed and the main outcome, a composite of functional decline and mortality, was obtained after 90 days of follow-up. RESULTS: In total 751 patients were enrolled in the Leiden University Medical Center of whom 230 patients (30.6%) experienced the composite outcome and 71 patients (9.5%) died. The final model for the composite outcome resulted in an area under the curve (AUC) of 0.73 (95% CI 0.67-0.77) and was experienced in 69% of the patients at highest risk. For mortality the AUC was 0.79 (95% CI 0.73-0.85) and 36% of the patients at highest risk died. External validation in 881 patients of Alrijne Hospital showed an AUC of 0.71 (95% CI 0.67-0.75) for the composite outcome and 0.67 (95% CI 0.60-0.73) for mortality. CONCLUSION: We successfully developed and validated prediction models for 90-day composite outcome and 90-day mortality in older emergency patients. The benefits for patient management by implementing these models with preventive interventions have to be investigated.

Expression of CuZn- and Mn-superoxide dismutase in human colorectal neoplasms.

Decreased intracellular SOD protein levels and activity have been related with malignancy in the past. To investigate their relevance in the carcinogenetic process in the colon, we determined quantitatively CuZn-SOD and Mn-SOD levels and total SOD activity by histochemical means in human normal colorectal mucosa, adenomas, and carcinomas. Protein levels and activity were significantly decreased in carcinomas. CuZn-SOD protein levels, but not Mn-SOD levels or total SOD activity were related with differentiation grade and to a lesser extent with Dukes stage. Moderately differentiated carcinomas and Dukes stage A carcinomas showed lowest levels. Some carcinomas expressed elevated levels of CuZn-SOD and this was an indication of poor survival. It is concluded that decreased SOD expression is not a prognostic marker and seems to be a secondary phenomenon rather than directly linked with the carcinogenetic process.