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.

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.

[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.

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).

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.

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 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.

Primary Anastomosis Versus End-Ostomy in Left-Sided Colonic and Proximal Rectal Cancer Surgery in the Elderly Dutch Population: A Propensity Score Matched Analysis.

BACKGROUND: Primary anastomosis (PA) in left-sided colorectal cancer (CRC) surgery in elderly patients is disputed. The aim of our study was to evaluate the differences in postoperative outcomes after left-sided CRC surgery in elderly patients in The Netherlands, comparing patients with PA and those who underwent end-ostomy (EO). METHOD: Patients aged ≥ 75 years with stage I-III left-sided CRC, diagnosed and surgically treated in 2015-2017 were selected from the Netherlands Cancer Registry (n = 3286). Postoperative outcomes, short-term (30-, 60-, and 90-day) mortality and 3-year overall and relative survival were analyzed, stratified by surgical resection with PA versus EO. Propensity score matching (PSM) and multivariable logistic regression analysis were conducted. RESULTS: Patients with higher age, higher American Society of Anesthesiologists classification and higher tumor stage, a perforation, ileus or tumor located in the proximal rectum, and after open or converted surgery were more likely to receive EO. No difference in anastomotic leakage was seen in PA patients with or without defunctioning stoma (6.2% vs. 7.0%, p = 0.680). Postoperative hospital stay was longer (7.0 vs. 6.0 days, p < 0.0001) and more often prolonged (19% vs. 13%, p = 0.03) in EO patients. Sixty-day mortality (2.9% vs. 6.4%, p < 0.0001), 90-day mortality (3.4% vs. 7.7%, p < 0.0001), and crude 3-year survival (81.2% vs. 58.7%, p < 0.0001) were significantly higher in EO patients, remaining significant after multivariable and PSM analysis. CONCLUSION: There are significant differences between elderly patients after left-sided CRC surgery with PA versus EO in terms of postoperative length of stay, short-term survival, 3-year overall survival, and relative survival at disadvantage of EO patients. This information could be important for decision making regarding surgical treatment in the elderly.

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.

The impact of colorectal surgery on health-related quality of life in older functionally dependent patients with cancer - A longitudinal follow-up study.

BACKGROUND: Older patients who are functionally compromised or frail may be at risk for loss of quality of life (QoL) after colorectal cancer (CRC) surgery. We prospectively studied health-related QoL (HRQoL) and its association with functional dependency on multiple time points before and after CRC surgery. METHODS: Included were patients aged 70 years and older who underwent elective CRC surgery between 2014 and 2015 in combination with an oncogeriatric care path. HRQoL (EORTC QLQ-C30 and CR38) and activities of daily living (ADL, Barthel Index) were measured at four time-points; prior to (T0) and at 3 (T3), 6 (T6), and 12 (T12) months after surgery. Functional dependency was defined as a Barthel Index <19. Using mixed-model regression analysis associations between dependency, time and HRQoL outcomes were tested and corrected for confounders. RESULTS: Response rate was 67% (n = 106) to two or more questionnaires; 26 (25%) patients were functionally dependent. Overall, functionally independent patients experienced a higher HRQoL than dependent patients. Compared to T0, significant and clinically relevant improvements in HRQoL after surgery were observed in functionally dependent patients: better role functioning, a higher global health, a higher summary score, less fatigue and less gastrointestinal problems (p < .05). In functional independent patients, we observed no clinically relevant change in HRQoL. CONCLUSION: Colorectal surgery embedded in geriatric-oncological care has a positive impact on HRQoL in older functionally dependent patients with cancer. Moderate functional dependency should not be considered a generic reason for withholding surgical treatment. Information derived from this study could be used in shared decision making.

Study Protocol of the NVALT25-ELDAPT Trial: Selecting the Optimal Treatment for Older Patients With Stage III Non-small-cell Lung Cancer.

BACKGROUND: Patients aged 75 years or older with stage III non-small-cell lung cancer (NSCLC) are underrepresented in clinical trials, leading to a lack of evidence for selection of the optimal treatment strategy. Information on benefits and harms of concurrent chemoradiotherapy among medically fit elderly patients is largely unknown, and reliable tools are needed to distinguish fit from frail patients for treatment selection. Also, information regarding quality of life during and after treatment is scarce. PATIENTS AND METHODS: This multicenter NVALT25-ELDAPT (Dutch Association of Chest Physicians Trial Number 25 - Elderly with locally advanced Lung cancer: Deciding through geriatric Assessment on the oPtimal Treatment strategy) trial (NCT02284308) consists of a phase III randomized trial in combination with an observational study for all patients who do not participate in the randomized trial. The first aim of this study is to develop a reliable and clinically applicable screening tool to distinguish medically fit from frail patients. All patients ≥ 75 years diagnosed with stage III NSCLC are invited to undergo extensive geriatric assessment (part I). The second aim is to compare treatment tolerance, survival, and quality of life between concurrent and sequential chemoradiotherapy in fit patients (randomized trial, part II). For all patients, overall survival adjusted for quality of life (quality-adjusted survival) is described for each category of fitness and treatment strategy during and after treatment. CONCLUSION: With the results of the NVALT25-ELDAPT trial, treatment selection can be optimized and the best possible outcomes for each individual older patient with stage III NSCLC can be achieved.

Geriatric Assessment for Older Patients with Non-small Cell Lung Cancer: Daily Practice of Centers Participating in the NVALT25-ELDAPT Trial.

INTRODUCTION: Geriatric assessment (GA) for older patients with lung cancer could provide insight into vulnerability, cognitive impairment, and risk of toxicity. Discontinuation and complications of intensive treatment could potentially be prevented in vulnerable and frail patients. This study aimed to evaluate current clinical practice of GA for older patients with lung cancer in the Netherlands and identify potential hurdles for implementation. METHODS: Pulmonologists and radiation oncologists participating in the NVALT25-ELDAPT trial completed an online questionnaire regarding current practice of GA, added value of GA for treatment decision-making and logistic barriers for patients with non-small cell lung cancer. RESULTS: 15 out of 17 centers responded. Three performed GA as standard procedure, three on indication, eight considered a frailty screening step before GA, and one did not perform GA. Suspicion of cognitive problems was mentioned most often as indication for GA and of added value for treatment decision-making, followed by older age, curative-intent treatment, and stage I-III lung cancer. Administered instruments for screening and extensive GA were diverse. Main barriers to implement GA in clinical practice were logistic problems (timescales and availability of trained personnel). CONCLUSION: The use of GA in clinical practice for patients with lung cancer varied widely across centers regarding instruments and domains. Physicians are uniform in their opinion about indications for GA and the added value for treatment decision-making. Research should focus on manageable instruments and important domains to assess for this heterogeneous group of older patients with lung cancer to optimize treatment selection. Trial registration The NVALT25-ELDAPT trial is registered under trial number NCT02284308. Details are available at http://www.eldapt.org (predominantly in Dutch).

Effects of prehabilitation and rehabilitation including a home-based component on physical fitness, adherence, treatment tolerance, and recovery in patients with non-small cell lung cancer: A systematic review.

This systematic review aimed to examine physical fitness, adherence, treatment tolerance, and recovery for (p)rehabilitation including a home-based component for patients with non-small cell lung cancer (NSCLC). PRISMA and Cochrane guidelines were followed. Studies describing (home-based) prehabilitation or rehabilitation in patients with NSCLC were included from four databases (January 2000-April 2016, N=11). Nine of ten rehabilitation studies and one prehabilitation study (437 NSCLC patients, mean age 59-72 years) showed significantly or clinically relevant improved physical fitness. Three (27%) assessed home-based training and eight (73%) combined training at home, inhospital (intramural) and/or at the physiotherapy practice/department (extramural). Six (55%) applied supervision of home-based components, and four (36%) a personalized training program. Adherence varied strongly (9-125% for exercises, 50-100% for patients). Treatment tolerance and recovery were heterogeneously reported. Although promising results of (p)rehabilitation for improving physical fitness were found (especially in case of supervision and personalization), adequately powered studies for home-based (p)rehabilitation are needed.

The mortality reducing effect of aspirin in colorectal cancer patients: Interpreting the evidence.

In 1971 the first study appeared that suggested a relationship between aspirin and cancer. Currently publications on the subject of aspirin and cancer are numerous, with both a beneficial effect of aspirin on cancer incidence and a beneficial effect on cancer survival. This review focusses on the relation between the use of aspirin and improved survival in colorectal cancer patients. Various study designs have been used, with the main part being observational studies and post hoc meta-analyses of cancer outcomes in cardiovascular prevention trials. The results of these studies are unambiguously pointing towards an effect of aspirin on colorectal cancer survival, and several randomised controlled trials are currently ongoing. Some clinicians feel that the current evidence is conclusive and that the time has come for aspirin to be prescribed as adjuvant therapy. However, until this review, not much attention has been paid to the specific types of bias associated with these studies. One of these biases is confounding by indication, because aspirin is indicated for patients as secondary prevention for cardiovascular disease. This review aims to provide perspective on these biases and provide tools for the interpretation of the current evidence. Albeit promising, the current evidence is not sufficient to already prescribe aspirin as adjuvant therapy for colorectal cancer.

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.