Cost-Effectiveness of Performing Reference Ultrasonography in Patients with Deep Vein Thrombosis.

BACKGROUND: The diagnosis of recurrent ipsilateral deep vein thrombosis (DVT) with compression ultrasonography (CUS) may be hindered by residual intravascular obstruction after previous DVT. A reference CUS, an additional ultrasound performed at anticoagulant discontinuation, may improve the diagnostic work-up of suspected recurrent ipsilateral DVT by providing baseline images for future comparison. OBJECTIVES: To evaluate the cost-effectiveness of routinely performing reference CUS in DVT patients. METHODS: Patient-level data (n = 96) from a prospective management study (Theia study; NCT02262052) and claims data were used in a decision analytic model to compare 12 scenarios for diagnostic management of suspected recurrent ipsilateral DVT. Estimated health care costs and mortality due to misdiagnosis, recurrent venous thromboembolism, and bleeding during the first year of follow-up after presentation with suspected recurrence were compared. RESULTS: All six scenarios including reference CUS had higher estimated 1-year costs (€1,763-€1,913) than the six without reference CUS (€1,192-€1,474). Costs were higher because reference CUS results often remained unused, as 20% of patients (according to claims data) would return with suspected recurrent DVT. Estimated mortality was comparable in scenarios with (14.8-17.9 per 10,000 patients) and without reference CUS (14.0-18.5 per 10,000). None of the four potentially most desirable scenarios included reference CUS. CONCLUSION: One-year health care costs of diagnostic strategies for suspected recurrent ipsilateral DVT including reference CUS are higher compared to strategies without reference CUS, without mortality benefit. These results can inform policy-makers regarding use of health care resources during follow-up after DVT. From a cost-effectiveness perspective, the findings do not support the routine application of reference CUS.

Validity of a screening method for delirium risk in older patients admitted to a general hospital in the Netherlands.

OBJECTIVE: Delirium is an impactful, frequently occurring complication in older hospital patients. Consequently, risk stratification of delirium was included in a set of mandatory safety measures in general hospitals in the Netherlands. This risk stratification contains three consensus-based questions that have not been validated. Therefore, we evaluated their predictive performance and examined whether other routinely collected patient data can improve the prediction of delirium. METHOD: Using data from a continuous data registry from a general hospital, the prediction of the three questions was compared with the occurrence of delirium in 3786 older patients. Regression models were fitted that included other patient-related delirium risk factors. The performance was expressed by discrimination and calibration. RESULTS: Delirium occurrence was 16.8%. The three questions, a regression model with the three questions, a full model and a reduced model - including the three questions, age, use of glasses, number of medications and Katz-ADL - showed sensitivities of 0.88, 0.88, 0.92 and 0.91 and specificities of 0.52, 0.52, 0.53 and 0.54, when treated as dichotomous models respectively. The three risk models had C-statistics of 0.81, 0.86 and 0.86, with excellent p-values of the U-statistics. CONCLUSION: The three risk-stratification questions show promising results but substantial overprediction (49% predicting positive). Further validation should be done outside the Netherlands, given the potential bias as a result of clinical activities following the risk stratification. The reduced model shows excellent calibration performance, indicating good prediction in each individual patient. In clinical practice, this advantage adds to clinical reasoning.

The Six-Item Cognitive Impairment Test Is Associated with Adverse Outcomes in Acutely Hospitalized Older Patients: A Prospective Cohort Study.

AIM: The study aim was to investigate whether cognitive impairment, measured by the Six-Item Cognitive Impairment Test (6-CIT), is an independent predictor of adverse outcomes in acutely hospitalized older patients. METHODS: This was a prospective multicenter study including acutely hospitalized patients aged 70 years and older. Multivariable logistic regression was used to investigate whether impaired cognition (6-CIT ≥11 points) was an independent predictor of 90-day adverse outcome, a composite measure of functional decline and mortality. Secondary endpoints were hospital length of stay, new institutionalization, and in-hospital mortality. RESULTS: In total, 196 (15.6%) of 1,252 included patients had a 6-CIT ≥11. Median age was 80 years (interquartile range 74-85). Patients with impaired cognition had higher rates of 90-day adverse outcome (41.7% compared to 30.3% in 1,056 not cognitively impaired patients, p = 0.009). Impaired cognition was a predictor of 90-day adverse outcome with a crude odds ratio (OR) of 1.64 (95% CI 1.13-2.39), but statistical significance was lost when fully corrected for possible confounders (OR 1.44, 95% CI 0.98-2.11). For all secondary outcomes, impaired cognition was an independent predictor. CONCLUSIONS: In the acute hospital setting, the 6-CIT is associated with 90-day adverse outcome and is an independent predictor of hospital length of stay, new institutionalization, and in-hospital mortality.

Increasing value and reducing waste by optimizing the development of complex interventions: Enriching the development phase of the Medical Research Council (MRC) Framework.

BACKGROUND: In recent years there has been much emphasis on 'research waste' caused by poor question selection, insufficient attention to previous research results, and avoidable weakness in research design, conduct and analysis. Little attention has been paid to the effect of inadequate development of interventions before proceeding to a full clinical trial. OBJECTIVE: We therefore propose to enrich the development phase of the MRC Framework by adding crucial elements to improve the likelihood of success and enhance the fit with clinical practice METHODS: Based on existing intervention development guidance and synthesis, a comprehensive iterative intervention development approach is proposed. Examples from published reports are presented to illustrate the methodology that can be applied within each element to enhance the intervention design. RESULTS: A comprehensive iterative approach is presented by combining the elements of the MRC Framework development phase with essential elements from existing guidance including: problem identification, the systematic identification of evidence, identification or development of theory, determination of needs, the examination of current practice and context, modelling the process and expected outcomes leading to final element: the intervention design. All elements are drawn from existing models to provide intervention developers with a greater chance of producing an intervention that is well adopted, effective and fitted to the context. CONCLUSION: This comprehensive approach of developing interventions will strengthen the internal and external validity, minimize research waste and add value to health care research. In complex interventions in health care research, flaws in the development process immediately impact the chances of success. Knowledge regarding the causal mechanisms and interactions within the intended clinical context is needed to develop interventions that fit daily practice and are beneficial for the end-user.

HELP! Problems in executing a pragmatic, randomized, stepped wedge trial on the Hospital Elder Life Program to prevent delirium in older patients.

BACKGROUND: A pragmatic, stepped wedge trial design can be an appealing design to evaluate complex interventions in real-life settings. However, there are certain pitfalls that need to be considered. This paper reports on the experiences and lessons learned from the conduct of a cluster randomized, stepped wedge trial evaluating the effect of the Hospital Elder Life Program (HELP) in a Dutch hospital setting to prevent older patients from developing delirium. METHODS: We evaluated our trial which was conducted in eight departments in two hospitals in hospitalized patients aged 70 years or older who were at risk for delirium by reflecting on the assumptions that we had and on what we intended to accomplish when we started, as compared to what we actually realized in the different phases of our study. Lessons learned on the design, the timeline, the enrollment of eligible patients and the use of routinely collected data are provided accompanied by recommendations to address challenges. RESULTS: The start of the trial was delayed which caused subsequent time schedule problems. The requirement for individual informed consent for a quality improvement project made the inclusion more prone to selection bias. Most units experienced major difficulties in including patients, leading to excluding two of the eight units from participation. This resulted in failing to include a similar number of patients in the control condition versus the intervention condition. Data on outcomes routinely collected in the electronic patient records were not accessible during the study, and appeared to be often missing during analyses. CONCLUSIONS: The stepped wedge, cluster randomized trial poses specific risks in the design and execution of research in real-life settings of which researchers should be aware to prevent negative consequences impacting the validity of their results. Valid conclusions on the effectiveness of the HELP in the Dutch hospital setting are hampered by the limited quantity and quality of routine clinical data in our pragmatic trial. Executing a stepped wedge design in a daily practice setting using routinely collected data requires specific attention to ethical review, flexibility, a spacious time schedule, the availability of substantial capacity in the research team and early checks on the data availability and quality. TRIAL REGISTRATION: Netherlands Trial Register, identifier: NTR3842 . Registered on 24 January 2013.

Prediction of 90-day mortality in older patients after discharge from an emergency department: a retrospective follow-up study.

BACKGROUND: Older people frequently attend the emergency department (ED) and have a high risk of poor outcome as compared to their younger counterparts. Our aim was to study routinely collected clinical parameters as predictors of 90-day mortality in older patients attending our ED. METHODS: We conducted a retrospective follow-up study at the Leiden University Medical Center (The Netherlands) among patients aged 70 years or older attending the ED in 2012. Predictors were age, gender, time and way of arrival, presenting complaint, consulting medical specialty, vital signs, pain score and laboratory testing. Cox regression analyses were performed to analyse the association between these predictors and 90-day mortality. RESULTS: Three thousand two hundred one unique patients were eligible for inclusion. Ninety-day mortality was 10.5 % for the total group. Independent predictors of mortality were age (hazard ratio [HR] 1.06, 95 % confidence interval [95 % CI] 1.04-1.08), referral from another hospital (HR 2.74, 95 % CI 1.22-6.11), allocation to a non-surgical specialty (HR: 1.55, 95 % CI 1.13-2.14), increased respiration rate (HR up to 2.21, 95 % CI 1.25-3.92), low oxygen saturation (HR up to 1.96, 95 % CI 1.19-3.23), hypothermia (HR 2.27, 95 % CI 1.28-4.01), fever (HR 0.43, 95 % CI 0.24-0.75), high pain score (HR 1.55, 95 % CI 1.03-2.32) and the indication to perform laboratory testing (HR 3.44, 95 % CI 2.13-5.56). CONCLUSIONS: Routinely collected parameters at the ED can predict 90-day mortality in older patients presenting to the ED. This study forms the first step towards creating a new and simple screening tool to predict and improve health outcome in acutely presenting older patients.

The development, implementation and evaluation of a transitional care programme to improve outcomes of frail older patients after hospitalisation.

BACKGROUND: fragmented healthcare systems are poorly suited to treat the increasing number of older patients with multimorbidity. OBJECTIVE: to report on the development, implementation and evaluation of a regional transitional care programme, aimed at improving the recovery rate of frail hospitalised older patients. METHODS: the programme was drafted in co-creation with organisations representing older adults, care providers and knowledge institutes. Conducting an action research project, the incidence of adverse outcomes within 3 months after hospital admission, and long-term care expenses (LTCE) were compared between samples in 2010-11 (pre-programme) and 2012-13 (post-programme) in frail and non-frail patients. Hospitalised patients aged ≥70 years were included in four hospitals in the targeted region. RESULTS: developed innovations addressed (i) improved risk management; (ii) delivery of integrated, function-oriented care; (iii) specific geriatric interventions; and (iv) optimisation of transfers. The incidence of adverse outcomes was compared in 813 and 904 included patients respectively in the two samples. In frail patients, the incidence of adverse outcomes decreased from 49.2% (149/303) in the pre-programme sample to 35.5% (130/366) in the post-programme sample. The risk ratio (RR), adjusted for heterogeneity between hospitals, was 0.72 (95% CI: 0.60-0.87). In non-frail patients the incidence of adverse outcomes remained unchanged (RR: 1.02, 95% CI: 0.76-1.36). LTCE were similar in the two samples. CONCLUSIONS: by involving stakeholders in designing and developing the transitional care programme, commitment of healthcare providers was secured. Feasible innovations in integrated transitional care for frail older patients after hospitalisation were sustainably implemented from within healthcare organisations.

Predicting mortality in acutely hospitalized older patients: a retrospective cohort study.

Acutely hospitalized older patients have an increased risk of mortality, but at the moment of presentation this risk is difficult to assess. Early identification of patients at high risk might increase the awareness of the physician, and enable tailored decision-making. Existing screening instruments mainly use either geriatric factors or severity of disease for prognostication. Predictive performance of these instruments is moderate, which hampers successive interventions. We conducted a retrospective cohort study among all patients aged 70 years and over who were acutely hospitalized in the Acute Medical Unit of the Leiden University Medical Center, the Netherlands in 2012. We developed a prediction model for 90-day mortality that combines vital signs and laboratory test results reflecting severity of disease with geriatric factors, represented by comorbidities and number of medications. Among 517 patients, 94 patients (18.2 %) died within 90 days after admission. Six predictors of mortality were included in a model for mortality: oxygen saturation, Charlson comorbidity index, thrombocytes, urea, C-reactive protein and non-fasting glucose. The prediction model performs satisfactorily with an 0.738 (0.667-0.798). Using this model, 53 % of the patients in the highest risk decile (N = 51) were deceased within 90 days. In conclusion, we are able to predict 90-day mortality in acutely hospitalized older patients using a model with directly available clinical data describing disease severity and geriatric factors. After further validation, such a model might be used in clinical decision making in older patients.

Optimal screening for increased risk for adverse outcomes in hospitalised older adults.

BACKGROUND: Screening for frailty might help to prevent adverse outcomes in hospitalised older adults. OBJECTIVE: To identify the most predictive and efficient screening tool for frailty. DESIGN AND SETTING: Two consecutive observational prospective cohorts in four hospitals in the Netherlands. SUBJECTS: Patients aged ≥70 years, electively or acutely hospitalised for ≥2 days. METHODS: Screening instruments included in the Dutch Safety Management Programme [VeiligheidsManagementSysteem (VMS)] on four geriatric domains (ADL, falls, undernutrition and delirium) were used and the Identification of Seniors At Risk, the 6-item Cognitive Impairment Test and the Mini-Mental State Examination were assessed. Three months later, adverse outcomes including functional decline, high-healthcare demand or death were determined. Correlation and regression tree analyses were performed and predictive capacities were assessed. RESULTS: Follow-up data were available of 883 patients. All screening instruments were similarly predictive for adverse outcome (predictive power 0.58-0.66), but the percentage of positively screened patients (13-72%), sensitivity (24-89%) and specificity (35-91%) highly differed. The strongest predictive model for frailty was scoring positive on ≥3 VMS domains if aged 70-80 years; or being aged ≥80 years and scoring positive on ≥1 VMS domains. This tool classified 34% of the patients as frail with a sensitivity of 68% and a specificity of 74%. Comparable results were found in the validation cohort. CONCLUSIONS: The VMS-tool plus age (VMS+) offers an efficient instrument to identify frail hospitalised older adults at risk for adverse outcome. In clinical practice, it is important to weigh costs and benefits of screening given the rather low-predictive power of screening instruments.

The association between waist circumference and risk of mortality considering body mass index in 65- to 74-year-olds: a meta-analysis of 29 cohorts involving more than 58 000 elderly persons.

BACKGROUND: For the elderly, the association between waist circumference (WC) and mortality considering body mass index (BMI) remains unclear, and thereby also the evidence base for using these anthropometric measures in clinical practice. This meta-analysis examined the association between WC categories and (cause-specific) mortality within BMI categories. Furthermore, the association of continuous WC with lowest and increased mortality risks was examined. METHODS: Age- and smoking-adjusted relative risks (RRs) of mortality associated with WC-BMI categories and continuous WC (including WC and WC(2)) were calculated by the investigators and pooled by means of random-effects models. RESULTS: During a 5-year-follow-up of 32 678 men and 25 931 women, we ascertained 3318 and 1480 deaths, respectively. A large WC (men: ≥102 cm, women: ≥88 cm) was associated with increased all-cause mortality RRs for those in the 'healthy' weight {1.7 [95% confidence interval (CI): 1.2-2.2], 1.7 (95% CI: 1.3-2.3)}, overweight [1.1(95% CI: 1.0-1.3), 1.4 (95%: 1.1-1.7)] and obese [1.1 (95% CI: 1.0-1.3), 1.6 (95% CI: 1.3-1.9)] BMI category compared with the 'healthy' weight (20-24.9 kg/m(2)) and a small WC (<94 cm, men; <80 cm, women) category. Underweight was associated with highest all-cause mortality RRs in men [2.2 (95% CI: 1.8-2.8)] and women [2.3 (95% CI: 1.8-3.1]. We found a J-shaped association for continuous WC with all-cause, cardiovascular (CVD) and cancer, and a U-shaped association with respiratory disease mortality (P < 0.05). An all-cause (CVD) mortality RR of 2.0 was associated with a WC of 132 cm (123 cm) in men and 116 cm (105 cm) in women. CONCLUSIONS: Our results showed increased mortality risks for elderly people with an increased WC-even across BMI categories- and for those who were classified as 'underweight' using BMI. The results provide a solid basis for re-evaluation of WC cut-points in ageing populations.

Optimal cutoff values for high-risk waist circumference in older adults based on related health outcomes.

The authors aimed to explore optimal cutoffs for high-risk waist circumference (WC) in older adults to assess the health risks of obesity. Prospective data from 4,996 measurements in 2,232 participants aged ≥70 years were collected during 5 triennial measurement cycles (1992/1993-2005/2006) of a population-based cohort study, the Longitudinal Aging Study Amsterdam (Amsterdam, the Netherlands). Cross-sectional associations of WC with pain, mobility limitations, incontinence, knee osteoarthritis, cardiovascular disease, and diabetes were studied. Generalized estimating equations models were fitted with restricted cubic spline functions in order to carefully study the shapes of the associations. Model fits for applying different cutoffs to categorize WC in the association with all outcomes were tested using the quasi-likelihood under the Independence Criterion (QIC). On the basis of the spline regression curves, potential WC cutoffs of approximately 109 cm in men and 98 cm in women were proposed. Based on the model fit, cutoffs between 100 cm and 106 cm were equally applicable in men but should not be higher. In women, the QIC confirmed an optimal cutoff of 99 cm.

Obesity in older adults is associated with an increased prevalence and incidence of pain.

Cross-sectional studies suggest an association between BMI and pain. This prospective study investigated the associations of measured BMI and waist circumference with prevalent and incident pain in older adults. The study included participants of the Longitudinal Aging Study Amsterdam, aged 55-85 years at baseline (1992-1993). Pain was assessed using a subscale of the Nottingham Health Profile at baseline (N = 2,000), after 3 years (N = 1,478) and 6 years (N = 1,271) of follow-up. The overall prevalence of pain was 32.7% at baseline and increased significantly with higher quartiles of BMI or waist circumference. After adjustment for age, education, depression, smoking, physical activity, and chronic diseases, multiple logistic regression analyses showed odds ratios (ORs (95% confidence interval)) for prevalent pain of 2.16 (1.32-3.54) in men and 1.93 (1.26-2.95) in women comparing the highest with the lowest quartile of BMI. Of the participants without pain at baseline, those in the highest quartile of BMI had a twofold increased odds for incident pain after 3 years of follow-up. After 6 years of follow-up, ORs for incident pain were 2.34 (1.17-4.72) in men and 2.78 (1.36-5.70) in women. Additional adjustment for weight change did not change these associations. Similar results were found for the associations between waist circumference and pain. Exploring the reversed causal relation, analyses showed no significant associations between prevalent pain and weight gain. In conclusion, the prevalence of pain is higher among obese older men and women compared to their normal-weight peers. Furthermore, obese older adults are at increased odds to develop pain.