Improved Postoperative Outcomes after Prehabilitation for Colorectal Cancer Surgery in Older Patients: An Emulated Target Trial.

BACKGROUND: The aim of this study was to assess the effect of a multimodal prehabilitation program on perioperative outcomes in colorectal cancer patients with a higher postoperative complication risk, using an emulated target trial (ETT) design. PATIENTS AND METHODS: An ETT design including overlap weighting based on propensity score was performed. The study consisted of all patients with newly diagnosed colorectal cancer (2016-2021), in a large nonacademic training hospital, who were candidate to elective colorectal cancer surgery and had a higher risk for postoperative complications defined by: age ≥ 65 years and or American Society of Anesthesiologists score III/IV. Intention-to-treat (ITT) and per-protocol analyses were performed to evaluate the effect of prehabilitation compared with usual care on perioperative complications and length of stay (LOS). RESULTS: Two hundred fifty-one patients were included: 128 in the usual care group and 123 patients in the prehabilitation group. In the ITT analysis, the number needed to treat to reduce one or more complications in one person was 4.2 (95% CI 2.6-10). Compared with patients in the usual care group, patients undergoing prehabilitation had a 55% lower comprehensive complication score (95% CI -71 to -32%). There was a 33% reduction (95% CI -44 to -18%) in LOS from 7 to 5 days. CONCLUSIONS: This study showed a clinically relevant reduction of complications and LOS after multimodal prehabilitation in patients undergoing colorectal cancer surgery with a higher postoperative complication risk. The study methodology used may serve as an example for further larger multicenter comparative effectiveness research on prehabilitation.

Implementation of prehabilitation in colorectal cancer surgery: qualitative research on how to strengthen facilitators and overcome barriers.

PURPOSE: Prehabilitation is increasingly offered to patients with colorectal cancer (CRC) undergoing surgery as it could prevent complications and facilitate recovery. However, implementation of such a complex multidisciplinary intervention is challenging. This study aims to explore perspectives of professionals involved in prehabilitation to gain understanding of barriers or facilitators to its implementation and to identify strategies to successful operationalization of prehabilitation. METHODS: In this qualitative study, semi-structured interviews were performed with healthcare professionals involved in prehabilitation for patients with CRC. Prehabilitation was defined as a preoperative program with the aim of improving physical fitness and nutritional status. Parallel with data collection, open coding was applied to the transcribed interviews. The Ottawa Model of Research Use (OMRU) framework, a comprehensive interdisciplinary model guide to promote implementation of research findings into healthcare practice, was used to categorize obtained codes and structure the barriers and facilitators into relevant themes for change. RESULTS: Thirteen interviews were conducted. Important barriers were the conflicting scientific evidence on (cost-)effectiveness of prehabilitation, the current inability to offer a personalized prehabilitation program, the complex logistic organization of the program, and the unawareness of (the importance of) a prehabilitation program among healthcare professionals and patients. Relevant facilitators were availability of program coordinators, availability of physician leadership, and involving skeptical colleagues in the implementation process from the start. CONCLUSIONS: Important barriers to prehabilitation implementation are mainly related to the intervention being complex, relatively unknown and only evaluated in a research setting. Therefore, physicians' leadership is needed to transform care towards more integration of personalized prehabilitation programs. IMPLICATIONS FOR CANCER SURVIVORS: By strengthening prehabilitation programs and evidence of their efficacy using these recommendations, it should be possible to enhance both the pre- and postoperative quality of life for colorectal cancer patients during survivorship.

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.

Trajectories and prognostic factors for recovery after hip fracture: a longitudinal cohort study.

PURPOSE: The aim of this study was to determine recovery trajectories and prognostic factors for poor recovery in frail and non-frail patients after hip fracture. METHODS: Patients with a hip fracture aged 65 years and older admitted to a hospital in the Netherlands from August 2015 to November 2016 were asked to complete questionnaires at one week and one, three, six, 12, and 24 months after injury. The questionnaires included the ICEpop CAPability measure for older people, Health Utility Index, and the Hospital Anxiety Depression Scale. Latent class trajectory analysis was used to determine trajectories of recovery. Patient and injury characteristics for favourable and unfavourable outcome were compared with logistic regression. RESULTS: In total, 696 patients were included of which 367 (53%) patients were frail. Overall, recovery trajectories in frail patients were worse compared to trajectories in non-frail patients. In frail patients, poor recovery was significantly associated with dementia. Lower age was a prognostic factor for good recovery. Immobility, loneliness and weight loss were prognostic for respectively poor capability and symptoms of anxiety and depression. In non-frail patients, recovery after hip fracture was associated with loneliness and the type of hip fracture. CONCLUSION: Although frailty is associated with poor recovery in older patients with hip fracture, a large proportion of frail patients show good recovery. Loneliness determines poor recovery with anxiety and depressive symptoms. TRAIL REGISTRATION: ClinicalTrials.gov identifier: NCT02508675 (July 27, 2015).

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.

Age-related systemic treatment and survival of patients with metachronous metastases from colorectal cancer.

BACKGROUND: Although the spectrum of systemic treatment for metastatic colorectal cancer (mCRC) has widened, there is a paucity of evidence for the feasibility and optimal use of these systemic agents in elderly patients. The present study provides real world data on the age-related systemic treatment and survival of CRC patients with non-resectable metachronous metastases. METHODS: All consecutive patients with non-resectable metastases from primary resected CRC were extracted from the Eindhoven area of the Netherlands Cancer Registry (NCR). Patients receiving palliative systemic therapy were enrolled (n = 385). Systemic treatment and survival were analyzed according to age at diagnosis of metastases. RESULTS: Patients aged ≥75 years more often received first-line single-agent chemotherapy than their younger counterparts (63% vs. 32%, p < .0001). First-line single-agent chemotherapy was often prescribed without additional targeted therapy (78%). Advanced age (≥75 years) was associated with a lower probability of receiving all active cytotoxic agents compared to patients aged <60 years at time of diagnosis of metastases (odds ratio (OR) 0.2, 95% CI 0.10-0.77). In a multivariable Cox regression analysis with adjustment for age and other relevant prognostic factors, the total number of received systemic agents was the only predictor of death (hazard ratio (HR) 0.7, 95% CI 0.61-0.81). CONCLUSION: The beneficial effect of treatment with all active systemic agents on survival (simultaneously or sequentially prescribed) should be taken into account when considering systemic therapy in patients with mCRC. In light of our results, future studies are warranted to clarify the role of potential targeted therapy in elderly mCRC patients, who are often not candidates for combination chemotherapy and treatment with all active cytotoxic agents.

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.

Assessment and treatment of malnutrition in Dutch geriatric practice: consensus through a modified Delphi study.

OBJECTIVE: scientific evidence regarding the optimal management of malnutrition in geriatric patients is scarce. Our aim was to develop a consensus statement for geriatric hospital practice concerning six elements: (i) definition of malnutrition, (ii) screening and assessment, (iii) treatment and monitoring, (iv) roles and responsibilities of involved health care professionals, (v) communication and coordination of care between hospital and community health care professionals, (vi) quality indicators for malnutrition management. DESIGN: a modified Delphi study. METHODS: eleven geriatricians with special interest in malnutrition participated. In four rounds the experts rated the relevance of 204 statements, which were based on a literature review, on a five-point Likert scale. From the responses, means and 95% CIs were calculated. Consensus was defined as a lower 95% confidence limit ≥4.0. RESULTS: the panel reached consensus that malnutrition should be considered a geriatric syndrome. The nutritional status should be assessed using the Mini Nutritional Assessment combined with comprehensive geriatric assessment. Nutritional interventions should be combined with interventions targeting underlying factors. Specific goals for nutritional therapy and ways to achieve them were agreed upon. According to the experts, malnutrition is best managed by a multidisciplinary team for whom roles and responsibilities were specified. At discharge written information about the nutritional problem, treatment plan and goals should be provided to the patient, caregiver and community health care professionals. CONCLUSION: this study shows that a qualitative study based on a modified Delphi technique can result in national consensus on essential ingredients for a practical malnutrition guideline for geriatric patients.

[Prehabilitation before surgery: in all cases?] / Prehabilitatie voorafgaand aan iedere operatie?

While the concept of prehabilitation sounds logical and study results are promising, so far there is no unequivocal answer to the question whether prehabilitation is (cost-)effective. Therefore, positioning prehabilitation as standard care is not yet on the agenda. To achieve this multicenter research should be stimulated through national coordination and research funding in order to clarify the (cost-)effectiveness of prehabilitation.

Technical efficiency evaluation of colorectal cancer care for older patients in Dutch hospitals.

BACKGROUND: Preoperative colorectal cancer care pathways for older patients show considerable practice variation between Dutch hospitals due to differences in interpretation and implementation of guideline-based recommendations. This study aims to report this practice variation in preoperative care between Dutch hospitals in terms of technical efficiency and identifying associated factors. METHODS: Data on preoperative involvement of geriatricians, physical therapists and dieticians and the clinicians' judgement on prehabilitation implementation were collected using quality indicators and questionnaires among colorectal cancer surgeons and specialized nurses. These data were combined with registry-based data on postoperative outcomes obtained from the Dutch Surgical Colorectal Audit for patients aged ≥75 years. A two-stage data envelopment analysis (DEA) approach was used to calculate bias-corrected DEA technical efficiency scores, reflecting the extent to which a hospital invests in multidisciplinary preoperative care (input) in relation to postoperative outcomes (output). In the second stage, hospital care characteristics were used in a bootstrap truncated regression to explain variations in measured efficiency scores. RESULTS: Data of 25 Dutch hospitals were analyzed. There was relevant practice variation in bias-corrected technical efficiency scores (ranging from 0.416 to 0.968) regarding preoperative colorectal cancer surgery. The average efficiency score of hospitals was significantly different from the efficient frontier (p = <0.001). After case-mix correction, higher technical efficiency was associated with larger practice size (p = <0.001), surgery performed in a general hospital versus a university hospital (p = <0.001) and implementation of prehabilitation (p = <0.001). CONCLUSION: This study showed considerable variation in technical efficiency of preoperative colorectal cancer care for older patients as provided by Dutch hospitals. In addition to higher technical efficiency in high-volume hospitals and general hospitals, offering a care pathway that includes prehabilitation was positively related to technical efficiency of hospitals offering colorectal cancer care.

Frailty screening by Geriatric-8 and 4-meter gait speed test is feasible and predicts postoperative complications in elderly colorectal cancer patients.

INTRODUCTION: Identification of frail older colorectal cancer patients might help to select those prone to adverse events and may lead to adjustment of treatment plans. However, the prognostic validity of screening for frailty is unknown. METHODS: This retrospective study evaluates colorectal cancer patients ≥70 years who underwent elective surgery between May 2016 and December 2018. The Geriatric-8 (G8) and 4-m gait speed test (4MGST) were used as frailty screening tools. According to hospital guidelines, patients were referred to a geriatrician when screening was indicative for frailty (G8 ≤ 14 and/or 4MGST < 1 m/s). Patients were categorized as fit, vulnerable or frail by comprehensive geriatric assessment (CGA). The clinical implications and prognostic validity of frailty screening and CGA were evaluated. RESULTS: 149 patients were included, of whom 132 (89%) were screened for frailty. Frailty was suspected in 40% of screened patients (n = 53) of whom 89% (n = 47) was referred for CGA. A higher complication rate was seen in patients with G8 ≤ 14 and/or 4MGST < 1 m/s compared to those with G8 > 14 and 4MGST ≥1 m/s (respectively 62% versus 28%,p < 0.001). Pneumonia (21% versus 6%, p = 0.013) and cardiac complications (11% versus 4%, p = 0.093) were more prevalent in patients with G8 ≤ 14 and/or 4MGST < 1 m/s. CGA identified frail patients as a group with a high complication rate of 68%. CONCLUSION: Screening for frailty with subsequent referral for CGA is feasible in older colorectal cancer patients. Our study suggests that screening for frailty by G8 + 4MGST can identify patients with higher risk for postoperative complications.

[American guideline for geriatric oncology; applicable to Dutch clinical practice?] / Amerikaanse richtlijn voor geriatrische oncologie.

American guideline for geriatric oncology; applicable to Dutch clinical practice? The American Society of Clinical Oncology (ASCO) has recently issued a guideline for geriatric oncology that provides guidance regarding the practical assessment and management of vulnerabilities in older patients undergoing chemotherapy. The recommendations are discussed and a practical framework for implementation in Dutch oncology practice is described.

Comprehensive geriatric assessment and its clinical impact in oncology.

Comprehensive geriatric assessment (CGA) is a process that consists of a multidimensional data-search and a process of analyzing and linking patient characteristics creating an individualized intervention-plan, carried out by a multidisciplinary team. In general, the positive health care effects of CGA are established, but in oncology both CGA and the presence of geriatric syndromes still have to be implemented to tailor oncological therapies to the needs of elderly cancer patients. In this paper the conceptualization of geriatric syndromes, their relationship to CGA and results of clinical studies using CGA in oncology are summarized. Geriatric syndromes are associated with increased vulnerability and refer to highly prevalent, mostly single symptom states (falls, incontinence, cognitive impairment, dizziness, immobility or syncope). Multifactorial analysis is common in geriatric syndromes and forms part of the theoretical foundation for using CGA. In oncology patients, we reviewed the value of CGA on the following endpoints: recognition of health problems, tolerance to chemotherapy and survival. Most studies performed CGA to identify prognostic factors and did not include an intervention. The ability of CGA to detect relevant health problems in an elderly population is reported consistently but no randomized studies are available. CGA should explore the pre-treatment presence of (in)dependence in Instrumental Activities of Daily Living (IADL), poor or moderately poor quality of life, depressive symptoms and cognitive decline, and thereby may help to predict survival. However, if scored by the Charlson comorbidity-index, comorbidities are not convincingly related to survival. The few studies that included a CGA-linked intervention show inconsistent results with regard to survival but compared to usual care quality of life is improved in the surviving period. Functional performance scores and dependency at home appeared to be independent predictive factors for toxicity, similar to depressive symptoms and polypharmacy. Overall, CGA implements/collects information additional to chronological age and Performance Score. So far in oncology there are no prognostic validation studies reported using geriatric syndromes or information based on CGA in its decision making strategies.

Comorbidity in older surgical cancer patients: influence on patient care and outcome.

Evidence is scarce about the influence of comorbidity on outcome of surgery, whereas this information is highly relevant for estimating the surgical risk of cancer patients, and for optimising pre-, peri- and postoperative care. In this paper, the prognostic role of increasing age and comorbid conditions in patients diagnosed with stage I-III colorectal, stage I-II NSCLC or stage I-III breast cancer between 1995 and 2004 in the southern part of the Netherlands is summarised. Almost all patients with stage I-III colon cancer or rectal cancer underwent surgery regardless of age or comorbidity. In contrast, the resection rate among elderly patients with stage I-II NSCLC was clearly lower than among younger patients and was significantly lower when COPD, cardiovascular diseases or diabetes were present. Among patients with stage I-III breast cancer, those aged 80 or older underwent less surgery, and the resection rate appeared to be lower when cardiovascular diseases or diabetes were present. Among patients with resected colorectal cancer, postoperative morbidity and mortality were higher among those undergoing emergency surgery, and also among those with reduced pulmonary function, cardiovascular disease or neurological comorbidity. Among those with resected NSCLC, postoperative morbidity and mortality were related to reduced pulmonary function or cardiovascular disease. Since surgery for breast cancer is low risk, elective surgery, morbidity and mortality were not higher for elderly or those with comorbidity. Among patients with colorectal or breast cancer, comorbidity in general, cardiovascular diseases, COPD, diabetes (only colon and breast cancer) and venous thromboembolism had a negative effect on overall survival, whereas the effect of comorbidity on survival of stage I-II NSCLC was less clear. Elderly and those with comorbidity (especially cardiovascular diseases and COPD) among colorectal cancer and NSCLC patients had more postoperative morbidity and mortality. Prospective randomised studies are needed for refining selection criteria for surgery in elderly cancer patients and for anticipation and prevention of complications.

Step by step development of clinical care pathways for older cancer patients: necessary or desirable?

Medical and nursing staff in oncology for older cancer patients are confronted with a range of problems including co-morbidity, poly-pharmacy, cognitive impairments, emotional problems, functional limitations, sensory impairment and a lack of social support. Comprehensive geriatric assessment identifies many of the existing problems and can be used to estimate life expectancy and tolerance of treatment. However, health care providers have to interpret and apply the medical and nursing information and must deal with specific problems and care needs throughout the continuum of cancer care. Imperfect interdisciplinary communication, cooperation and patient-provider communication may further complicate the care actually delivered. A clinical care pathway aims to improve continuity, increase multidisciplinary tuning and deliver appropriate patient education, treatment and care for vulnerable older cancer patients. This paper gives an overview of common problems in older cancer patients and addresses communication barriers through the development of clinical care pathways in geriatric oncology.

Prognostic impact of increasing age and co-morbidity in cancer patients: a population-based approach.

This large population-based study focuses on the prognostic role of increasing age and co-morbidity in cancer patients diagnosed in the southern Netherlands. Data of patients diagnosed between 1995 and 2002 and recorded in the population-based Eindhoven Cancer Registry were used. Older patients (with serious co-morbidity) with non-small cell lung cancer or prostate cancer underwent surgery less often than younger patients. Elderly with stage III colon cancer, small cell lung cancer, FIGO II or III ovarian cancer or non-Hodgkin's lymphoma (NHL) received (adjuvant) chemotherapy less often, probably because of the higher rate of haematological complications. Administration of adjuvant radiotherapy decreased with age and co-morbidity in patients with rectal cancer, limited small cell lung cancer or breast cancer. In general, elderly did not suffer from more complications than younger patients, except for cardiac complications (colorectal cancer and NHL) and postoperative death (non-small cell lung cancer). For most tumours relative survival was lower for the elderly, except for patients with colon cancer, prostate cancer or indolent NHL. Co-morbidity had an independent prognostic effect, except for tumours with a very poor prognosis. Future prospective studies should investigate whether the guidelines for cancer treatment should be adjusted for elderly with serious co-morbidity.

Cognitive impairment as determinant for sub-optimal control of oral anticoagulation treatment in elderly patients with atrial fibrillation.

BACKGROUND AND OBJECTIVE: Atrial fibrillation is an indication for oral anticoagulation treatment. Maintaining the International Normalized Ratio (INR) within the therapeutic range minimises thromboembolic and bleeding complications. We have investigated whether cognitive capacity affects control of anticoagulation in elderly patients with atrial fibrillation. PATIENTS AND METHODS: A retrospective study was conducted to investigate the association between cognitive impairment and control of anticoagulation. Patients > or =70 years of age with atrial fibrillation using acenocoumarol (nicoumalone) as anticoagulant were included. All patients were monitored by the Anticoagulation Clinic in the Midden-Brabant region in the Netherlands. The cognitive function of all patients was assessed using the Mini-Mental State Examination (MMSE) on the index date. INR values were obtained from the year preceding the index date. Patients with an MMSE score <23 were defined as cognitively impaired. The primary outcome of the study was the incidence of an INR value within the therapeutic range of 2.0-3.4 during < or =70% of treatment time in the year prior to the cognitive function assessment. The secondary endpoint was the number of patients with an INR <2.0 or > or =6.0 at least once during this year. Logistic regression analysis was used to evaluate the association between cognitive function and control of anticoagulation. RESULTS: A total of 152 patients were included in the study. An MMSE score <23 was associated with an inadequate INR control (odds ratio [OR] 2.77; 95% CI 1.13, 6.74). After correction for hospital admission and change of possibly interacting medication (both also associated with inadequate INR control), this association remained statistically significant. Significantly more patients with an MMSE score <23 had one or more INR values of six or higher (OR 3.06; 95% CI 1.14, 8.18). CONCLUSION: In elderly people with atrial fibrillation using oral anticoagulation, an MMSE score <23 is independently associated with an inadequate INR control, mainly because of an increased number of supratherapeutic INR values. This finding should be taken into account when making decisions about use of oral anticoagulants in the elderly.