Atypical presentation of COVID-19 in older patients is associated with frailty but not with adverse outcomes.

PURPOSE: Older patients with COVID-19 can present with atypical complaints, such as falls or delirium. In other diseases, such an atypical presentation is associated with worse clinical outcomes. However, it is not known whether this extends to COVID-19. We aimed to study the association between atypical presentation of COVID-19, frailty and adverse outcomes, as well as the incidence of atypical presentation. METHODS: We conducted a retrospective observational multi-center cohort study in eight hospitals in the Netherlands. We included patients aged ≥ 70 years hospitalized with COVID-19 between February 2020 until May 2020. Atypical presentation of COVID-19 was defined as presentation without fever, cough and/or dyspnea. We collected data concerning symptoms on admission, demographics and frailty parameters [e.g., Charlson Comorbidity Index (CCI) and Clinical Frailty Scale (CFS)]. Outcome data included Intensive Care Unit (ICU) admission, discharge destination and 30-day mortality. RESULTS: We included 780 patients, 9.5% (n = 74) of those patients had an atypical presentation. Patients with an atypical presentation were older (80 years, IQR 76-86 years; versus 79 years, IQR 74-84, p = 0.044) and were more often classified as severely frail (CFS 6-9) compared to patients with a typical presentation (47.6% vs 28.7%, p = 0.004). Overall, there was no significant difference in 30-day mortality between the two groups in univariate analysis (32.4% vs 41.5%; p = 0.173) or in multivariate analysis [OR 0.59 (95% CI 0.34-1.0); p = 0.058]. CONCLUSIONS: In this study, patients with an atypical presentation of COVID-19 were more frail compared to patients with a typical presentation. Contrary to our expectations, an atypical presentation was not associated with worse outcomes.

Characteristics and outcomes of older patients hospitalised for COVID-19 in the first and second wave of the pandemic in The Netherlands: the COVID-OLD study.

BACKGROUND: as the coronavirus disease of 2019 (COVID-19) pandemic progressed diagnostics and treatment changed. OBJECTIVE: to investigate differences in characteristics, disease presentation and outcomes of older hospitalised COVID-19 patients between the first and second pandemic wave in The Netherlands. METHODS: this was a multicentre retrospective cohort study in 16 hospitals in The Netherlands including patients aged ≥ 70 years, hospitalised for COVID-19 in Spring 2020 (first wave) and Autumn 2020 (second wave). Data included Charlson comorbidity index (CCI), disease severity and Clinical Frailty Scale (CFS). Main outcome was in-hospital mortality. RESULTS: a total of 1,376 patients in the first wave (median age 78 years, 60% male) and 946 patients in the second wave (median age 79 years, 61% male) were included. There was no relevant difference in presence of comorbidity (median CCI 2) or frailty (median CFS 4). Patients in the second wave were admitted earlier in the disease course (median 6 versus 7 symptomatic days; P < 0.001). In-hospital mortality was lower in the second wave (38.1% first wave versus 27.0% second wave; P < 0.001). Mortality risk was 40% lower in the second wave compared with the first wave (95% confidence interval: 28-51%) after adjustment for differences in patient characteristics, comorbidity, symptomatic days until admission, disease severity and frailty. CONCLUSIONS: compared with older patients hospitalised in the first COVID-19 wave, patients in the second wave had lower in-hospital mortality, independent of risk factors for mortality.The better prognosis likely reflects earlier diagnosis, the effect of improvement in treatment and is relevant for future guidelines and treatment decisions.

Frailty is associated with in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands: the COVID-OLD study.

BACKGROUND: During the first wave of the coronavirus disease 2019 (COVID-19) pandemic, older patients had an increased risk of hospitalisation and death. Reports on the association of frailty with poor outcome have been conflicting. OBJECTIVE: The aim of the present study was to investigate the independent association between frailty and in-hospital mortality in older hospitalised COVID-19 patients in the Netherlands. METHODS: This was a multicentre retrospective cohort study in 15 hospitals in the Netherlands, including all patients aged ≥70 years, who were hospitalised with clinically confirmed COVID-19 between February and May 2020. Data were collected on demographics, co-morbidity, disease severity and Clinical Frailty Scale (CFS). Primary outcome was in-hospital mortality. RESULTS: A total of 1,376 patients were included (median age 78 years (interquartile range 74-84), 60% male). In total, 499 (38%) patients died during hospital admission. Parameters indicating presence of frailty (CFS 6-9) were associated with more co-morbidities, shorter symptom duration upon presentation (median 4 versus 7 days), lower oxygen demand and lower levels of C-reactive protein. In multivariable analyses, the CFS was independently associated with in-hospital mortality: compared with patients with CFS 1-3, patients with CFS 4-5 had a two times higher risk (odds ratio (OR) 2.0 (95% confidence interval (CI) 1.3-3.0)) and patients with CFS 6-9 had a three times higher risk of in-hospital mortality (OR 2.8 (95% CI 1.8-4.3)). CONCLUSIONS: The in-hospital mortality of older hospitalised COVID-19 patients in the Netherlands was 38%. Frailty was independently associated with higher in-hospital mortality, even though COVID-19 patients with frailty presented earlier to the hospital with less severe symptoms.

Missed diagnosis of pulmonary embolism with age-adjusted d-dimer cut-off value.

Pulmonary embolism (PE) is a potentially severe diagnosis with high short-term mortality. Recently, age-adjusted cut-off values (age × 10 µg/l) of D-dimer were introduced to improve the diagnostic workup in older patients. In clinical practice, PE is considered 'ruled out' in patients with a non-high clinical probability and a normal D-dimer. However, all diagnostic tests have a small false-negative rate. This small probability of misdiagnosis might be easily overlooked by clinicians when using simplified dichotomized flow charts. This case illustrates a normal D-dimer (age-adjusted) but with a PE. We recommend clinicians using the D-dimer test-either conventional or age-adjusted in a rule-out strategy to be aware of the-albeit small probability of a false-negative result.

Validation of the Oudega diagnostic decision rule for diagnosing deep vein thrombosis in frail older out-of-hospital patients.

OBJECTIVE: We aimed to validate the Oudega diagnostic decision rule-which was developed and validated among younger aged primary care patients-to rule-out deep vein thrombosis (DVT) in frail older outpatients. METHODS: In older patients (>60 years, either community dwelling or residing in nursing homes) with clinically suspected DVT, physicians recorded the score on the Oudega rule and d-dimer test. DVT was confirmed with a composite reference standard including ultrasonography examination and 3-month follow-up. The proportion of patients with a very low probability of DVT according to the Oudega rule (efficiency), and the proportion of patients with symptomatic venous thromboembolism during 3 months follow-up within this 'very low risk' group (failure rate) was calculated. RESULTS: DVT occurred in 164 (47%) of the 348 study participants (mean age 81 years, 85% residing in nursing homes). The probability of DVT was very low in 69 patients (Oudega score ≤3 points plus a normal d-dimer test; efficiency 20%) of whom four had non-fatal DVT (failure rate 5.8%; 2.3-14%). With a simple revised version of the Oudega rule for older suspected patients, 43 patients had a low risk of DVT (12% of the total population) of whom only one had DVT (failure rate 2.3%; 0.4-12%). CONCLUSIONS: In older suspected patients, application of the original Oudega rule to exclude DVT resulted in a higher failure rate as compared to previous studies. A revised and simplified Oudega strategy specifically developed for elderly suspected patients resulted in a lower failure rate though at the expense of a lower efficiency.

Accuracy of the Wells clinical prediction rule for pulmonary embolism in older ambulatory adults.

OBJECTIVES: To determine whether the Wells clinical prediction rule for pulmonary embolism (PE), which produces a point score based on clinical features and the likelihood of diagnoses other than PE, combined with normal D-dimer testing can be used to exclude PE in older unhospitalized adults. DESIGN: Prospective cohort study. SETTING: Primary care and nursing homes. PARTICIPANTS: Older adults (≥60) clinically suspected of having a PE (N = 294, mean age 76, 44% residing in a nursing home). MEASUREMENTS: The presence of PE was confirmed using a composite reference standard including computed tomography and 3-month follow-up. The proportion of individuals with an unlikely risk of PE was calculated according to the Wells rule (≤4 points) plus a normal qualitative point-of-care D-dimer test (efficiency) and the presence of symptomatic PE during 3 months of follow-up within these patients (failure rate). RESULTS: Pulmonary embolism occurred in 83 participants (28%). Eighty-five participants had an unlikely risk according to the Wells rule and a normal D-dimer test (efficiency 29%), five of whom experienced a nonfatal PE during 3 months of follow-up (failure rate = 5.9%, 95% confidence interval (CI) = 2.5-13%). According to a refitted diagnostic strategy for older adults, 69 had a low risk of PE (24%), two of whom had PE (failure rate = 2.9%, 95% CI = 0.8-10%). CONCLUSION: The use of the well-known and widely used Wells rule (original or refitted) does not guarantee safe exclusion of PE in older unhospitalized adults with suspected PE. This may lead to discussion among professionals as to whether the original or revised Wells rule is useful for elderly outpatients.

Decisions to withhold diagnostic investigations in nursing home patients with a clinical suspicion of venous thromboembolism.

BACKGROUND: This study aimed to gather insights in physicians' considerations for decisions to either refer for- or to withhold additional diagnostic investigations in nursing home patients with a suspicion of venous thromboembolism. METHODS: Our study was nested in an observational study on diagnostic strategies for suspected venous thromboembolism in nursing home patients. Patient characteristics, bleeding-complications and mortality were related to the decision to withhold investigations. For a better understanding of the physicians' decisions, 21 individual face-to-face in-depth interviews were performed and analysed using the grounded theory approach. RESULTS: Referal for additional diagnostic investigations was forgone in 126/322 (39.1%) patients with an indication for diagnostic work-up. 'Blind' anticoagulant treatment was initiated in 95 (75.4%) of these patients. The 3 month mortality rates were higher for patients in whom investigations were withheld than in the referred patients, irrespective of anticoagulant treatment (odds ratio 2.45; 95% confidence interval 1.40 to 4.29) but when adjusted for the probability of being referred (i.e. the propensity score), there was no relation of non-diagnosis decisions to mortality (odds ratio 1.75; 0.98 to 3.11). In their decisions to forgo diagnostic investigations, physicians incorporated the estimated relative impact of the potential disease; the potential net-benefits of diagnostic investigations and whether performing investigations agreed with established management goals in advance care planning. CONCLUSION: Referral for additional diagnostic investigations is withheld in almost 40% of Dutch nursing home patients with suspected venous thromboembolism and an indication for diagnostic work-up. We propose that, given the complexity of these decisions and the uncertainty regarding their indirect effects on patient outcome, more attention should be focused on the decision to either use or withhold additional diagnostic tests.

Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis.

OBJECTIVE: To review the diagnostic accuracy of D-dimer testing in older patients (>50 years) with suspected venous thromboembolism, using conventional or age adjusted D-dimer cut-off values. DESIGN: Systematic review and bivariate random effects meta-analysis. DATA SOURCES: We searched Medline and Embase for studies published before 21 June 2012 and we contacted the authors of primary studies. STUDY SELECTION: Primary studies that enrolled older patients with suspected venous thromboembolism in whom D-dimer testing, using both conventional (500 µg/L) and age adjusted (age × 10 µg/L) cut-off values, and reference testing were performed. For patients with a non-high clinical probability, 2 × 2 tables were reconstructed and stratified by age category and applied D-dimer cut-off level. RESULTS: 13 cohorts including 12,497 patients with a non-high clinical probability were included in the meta-analysis. The specificity of the conventional cut-off value decreased with increasing age, from 57.6% (95% confidence interval 51.4% to 63.6%) in patients aged 51-60 years to 39.4% (33.5% to 45.6%) in those aged 61-70, 24.5% (20.0% to 29.7% in those aged 71-80, and 14.7% (11.3% to 18.6%) in those aged >80. Age adjusted cut-off values revealed higher specificities over all age categories: 62.3% (56.2% to 68.0%), 49.5% (43.2% to 55.8%), 44.2% (38.0% to 50.5%), and 35.2% (29.4% to 41.5%), respectively. Sensitivities of the age adjusted cut-off remained above 97% in all age categories. CONCLUSIONS: The application of age adjusted cut-off values for D-dimer tests substantially increases specificity without modifying sensitivity, thereby improving the clinical utility of D-dimer testing in patients aged 50 or more with a non-high clinical probability.

Need for tailored strategies to diagnose venous thrombo-embolism in older primary care patients. Extension of a keynote presentation at the 2012 Wonca Europe conference.

Venous thrombo-embolism (VTE, pulmonary embolism and deep vein thrombosis) is common in the elderly and short-term mortality risk increases with age. Hence, notably in older patients, accurately diagnosing VTE can be lifesaving. However, most clinically suspected individuals turn out to have no VTE after imaging examination. Therefore, many physicians would feel reluctant to refer older patients as this can be very burdensome for these patients. Consequently, it is possible that elderly patients are often not referred for diagnostic work-up (risk of under diagnosis), or that treatment for VTE is initiated without confirmation by further testing (risk of overtreatment). Moreover, anticoagulation treatment of VTE is associated with a higher bleeding risk in the elderly. This bleeding risk might even outweigh the potential benefits in some of these patients. Therefore, availability of an accurate diagnostic strategy to safely exclude, and timely diagnose VTE without the need of burdening referrals in many patients might better serve the needs of older patients. Such strategies have been derived and validated in both primary and secondary care patients suspected of VTE. However, the generalizability of these strategies to older patients may be hampered, and their accuracy has never been tested in elderly populations; this in spite of the high prevalence of VTE and the potential for misdiagnosis and thus mistreatment in these patients. Therefore, we advocate validation and adaptation of current diagnostic strategies for VTE for application in elderly patients.

Non-diagnosis decisions and non-treatment decisions in elderly patients with cardiovascular diseases, do they differ?--A systematic review.

The growth in the number of possible medical interventions in the past decennia necessitates physicians to consider whether to use them. Contrary to decisions to withhold treatment, little is known about "non-diagnosis decisions" (NDD) although their consequences seem to be more uncertain. Hence, we hypothesized that "determinants" and "reasons" for NDD are different from those that are associated with non-treatment decisions (NTD). We performed a systematic review on research on physicians' decisions to withhold or withdraw diagnostic or therapeutic interventions. A total of 11,773 unique citations published either in Medline, Embase, or the Cochrane databases were screened, of which 45 articles,--including 4 articles describing NDD in elderly patients suspected of cardiovascular diseases, were considered relevant and analysed in detail. "Determinants" and "reasons" for NDD and NTD were extracted, categorized into predefined categories, and compared with each other. Besides several similarities, we found various differences between NDD and NTD. The proportionality of an intervention (ie, the risk or burden of an intervention opposed to that of no intervention) was associated with NTD but not with NDD. Physician and care institution related characteristics, such as age of the physician or the employment of physician extenders, were more frequently associated with NDD than with NTD. Furthermore, the presence of non-resuscitate directives was correlated with NDD but not with NTD. This systematic review shows that there is little information on NDD in the current literature. Yet, there is not enough evidence to conclude whether NDD can be seen as a separate entity distinct from NTD. More research focusing on NDD seems needed.

Validation of two age dependent D-dimer cut-off values for exclusion of deep vein thrombosis in suspected elderly patients in primary care: retrospective, cross sectional, diagnostic analysis.

OBJECTIVE: To determine whether the use of age adapted D-dimer cut-off values can be translated to primary care patients who are suspected of deep vein thrombosis. DESIGN: Retrospective, cross sectional diagnostic study. SETTING: 110 primary care doctors affiliated with three hospitals in the Netherlands. PARTICIPANTS: 1374 consecutive patients (936 (68.1%) aged >50 years) with clinically suspected deep vein thrombosis. MAIN OUTCOME MEASURES: Proportion of patients with D-dimer values below two proposed age adapted cut-off levels (age in years × 10 µg/L in patients aged >50 years, or 750 µg/L in patients aged ≥ 60 years), in whom deep vein thrombosis could be excluded; and the number of false negative results. RESULTS: Using the Wells score, 647 patients had an unlikely clinical probability of deep vein thrombosis. In these patients (at all ages), deep vein thrombosis could be excluded in 309 (47.8%) using the age dependent cut-off value compared with 272 (42.0%) using the conventional cut-off value of 500 µg/L (increase 5.7%, 95% confidence interval 4.1% to 7.8%). This exclusion rate resulted in 0.5% and 0.3% false negative cases, respectively (increase 0.2%, 0.004% to 8.6%).The increase in exclusion rate by using the age dependent cut-off value was highest in the oldest patients. In patients older than 80 years, deep vein thrombosis could be safely excluded in 22 (35.5%) patients using the age dependent cut-off value compared with 13 (21.0%) using the conventional cut-off value (increase 14.5%, 6.8% to 25.8%). Compared with the age dependent cut-off value, the cut-off value of 750 µg/L had a similar exclusion rate (307 (47.4%) patients) and false negative rate (0.3%). CONCLUSIONS: Combined with a low clinical probability of deep vein thrombosis, use of the age dependent D-dimer cut-off value for patients older than 50 years or the cut-off value of 750 µg/L for patients aged 60 years and older resulted in a considerable increase in the proportion of patients in primary care in whom deep vein thrombosis could be safely excluded, compared with the conventional cut-off value of 500 µg/L.

Quality of life of elderly patients with antipsychotic-induced parkinsonism: a cross-sectional study.

OBJECTIVES: Antipsychotic-induced parkinsonism (AIP) is one of the most common adverse effects of haloperidol. The purpose of this study was to investigate the association between AIP and quality of life of elderly patients treated with haloperidol. DESIGN: Cross-sectional study design. SETTING: Eleven nursing homes, geriatric departments of 2 hospitals, and 3 mental health care centers in the Netherlands. PARTICIPANTS: Participants were 140 elderly patients aged 65 years and older treated for at least 5 days with haloperidol. MEASUREMENTS: The presence of AIP was determined with the Simpson Angus Scale. Quality of life was scored with the QUALIDEM scale. Multivariate linear regression analysis was used to assess whether the presence of AIP and quality of life were correlated. The data of patients with advanced dementia were analyzed separately. RESULTS: Of the 140 included patients, 65 (46%) were diagnosed with AIP. Patients with AIP scored lower than patients without AIP on the QUALIDEM subscales "positive affect," "negative affect," "social relations," "social isolation," and "having something to do." In patients with advanced dementia, quality of life was not significantly different in patients with or without AIP. CONCLUSION: The presence of AIP is negatively associated with the quality of life of elderly patients treated with haloperidol.

Requests for euthanasia: origin of suffering in ALS, heart failure, and cancer patients.

In The Netherlands, relatively more patients (20%) with amyotrophic lateral sclerosis (ALS) die due to euthanasia or physician-assisted suicide (EAS) compared with patients with cancer (5%) or heart failure (0.5%). We wanted to gain insight into the reasons for ALS patients requesting EAS and compare these with the reasons of cancer and heart failure patients. Knowing disease-specific reasons for requesting EAS may improve palliative care in these vulnerable patients. The data used in the present study were derived from the Support and Consultation in Euthanasia in The Netherlands (SCEN) evaluation study. This study provided consultation reports and questionnaires filled out by the attending physicians from 3,337 consultations conducted by SCEN physicians in situations where a patient requested EAS. For this study we selected data on all ALS patients (n = 51), all heart failure patients (n = 61), and a random sample of 73 cancer patients. The most frequently reported reasons for unbearable suffering were: fear of suffocation (45%) and dependency (29%) in ALS patients, pain (46%) and fatigue (28%) in cancer patients, and dyspnea (52%) and dependency (37%) in heart failure patients. Somatic complaints were reported more frequently as a reason for EAS by cancer patients [odds ratio (OR) 0.20, 95% confidence interval (CI) 0.09-0.46] and heart failure patients [OR 0.16, 95% CI 0.05-0.46] than by ALS patients. ALS patients should be helped in a timely fashion to cope with psychosocial symptoms, e.g., by informing them about the low risk of suffocation in the terminal phase and the possible means of preventing this.