Management and outcomes in critically ill nonagenarian versus octogenarian patients

Abstract Background Intensive care unit (ICU) patients age 90 years or older represent a growing subgroup and place a huge financial burden on health care resources despite the benefit being unclear. This leads to ethical problems. The present investigation assessed the differences in outcome between nonagenarian and octogenarian ICU patients. Methods We included 7900 acutely admitted older critically ill patients from two large, multinational studies. The primary outcome was 30-day-mortality, and the secondary outcome was ICU-mortality. Baseline characteristics consisted of frailty assessed by the Clinical Frailty Scale (CFS), ICU-management, and outcomes were compared between octogenarian (80–89.9 years) and nonagenarian (> 90 years) patients. We used multilevel logistic regression to evaluate differences between octogenarians and nonagenarians. Results The nonagenarians were 10% of the entire cohort. They experienced a higher percentage of frailty (58% vs 42%; p < 0.001), but lower SOFA scores at admission (6 + 5 vs. 7 + 6; p < 0.001). ICU-management strategies were different. Octogenarians required higher rates of organ support and nonagenarians received higher rates of life-sustaining treatment limitations (40% vs. 33%; p < 0.001). ICU mortality was comparable (27% vs. 27%; p = 0.973) but a higher 30-day-mortality (45% vs. 40%; p = 0.029) was seen in the nonagenarians. After multivariable adjustment nonagenarians had no significantly increased risk for 30-day-mortality (aOR 1.25 (95% CI 0.90–1.74; p = 0.19)). Conclusion After adjustment for confounders, nonagenarians demonstrated no higher 30-day mortality than octogenarian patients. In this study, being age 90 years or more is no particular risk factor for an adverse outcome. This should be considered– together with illness severity and pre-existing functional capacity - to effectively guide triage decisions. Trial registration NCT03134807 and NCT03370692.

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Provision of critical care for the elderly in Europe: a retrospective comparison of national healthcare frameworks in intensive care units

BMJ Open ◽

10.1136/bmjopen-2020-046909 ◽

2021 ◽

Vol 11 (6) ◽

pp. e046909

Author(s):

Bernhard Wernly ◽

Michael Beil ◽

Raphael Romano Bruno ◽

Stephan Binnebössel ◽

Malte Kelm ◽

...

Keyword(s):

Health Economic ◽

Intensive Care ◽

Critically Ill ◽

Admission Policy ◽

Patient Specific ◽

Organ Support ◽

Healthcare Organisation ◽

Economic Data ◽

Clinical Frailty Scale ◽

Link Type

ObjectivesIn Europe, there is a distinction between two different healthcare organisation systems, the tax-based healthcare system (THS) and the social health insurance system (SHI). Our aim was to investigate whether the characteristics, treatment and mortality of older, critically ill patients in the intensive care unit (ICU) differed between THS and SHI.SettingICUs in 16 European countries.ParticipantsIn total, 7817 critically ill older (≥80 years) patients were included in this study, 4941 in THS and 2876 in the SHI systems.Primary and secondary outcomes measuresWe chose generalised estimation equations with robust standard errors to produce population average adjusted OR (aOR). We adjusted for patient-specific variables, health economic data, including gross domestic product (GDP) and human development index (HDI), and treatment strategies.ResultsIn SHI systems, there were higher rates of frail patients (Clinical Frailty Scale>4; 46% vs 41%; p<0.001), longer length of ICU stays (90±162 vs 72±134 hours; p<0.001) and increased levels of organ support. The ICU mortality (aOR 1.50, 95% CI 1.09 to 2.06; p=0.01) was consistently higher in the SHI; however, the 30-day mortality (aOR 0.89, 95% CI 0.66 to 1.21; p=0.47) was similar between THS and SHI. In a sensitivity analysis stratifying for the health economic data, the 30-day mortality was higher in SHI, in low GDP per capita (aOR 2.17, 95% CI 1.42 to 3.58) and low HDI (aOR 1.22, 95% CI 1.64 to 2.20) settings.ConclusionsThe 30-day mortality was similar in both systems. Patients in SHI were older, sicker and frailer at baseline, which could be interpreted as a sign for a more liberal admission policy in SHI. We believe that the observed trend towards ICU excess mortality in SHI results mainly from a more liberal admission policy and an increase in treatment limitations.Trial registration numbersNCT03134807 and NCT03370692.

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Lower serum chloride concentrations are associated with increased risk of mortality in critically ill cirrhotic patients: an analysis of the MIMIC-III database

BMC Gastroenterology ◽

10.1186/s12876-021-01797-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yun Ji ◽

Libin Li

Keyword(s):

Critically Ill ◽

Serum Sodium ◽

Kidney Injury ◽

Icu Mortality ◽

Independent Prognostic Marker ◽

Risk Of Mortality ◽

Serum Chloride ◽

Increased Risk ◽

Cirrhotic Patients ◽

End Stage

Abstract Background Cirrhosis can be complicated by electrolyte abnormalities, but the major focus has been concentrated on the clinical significance of serum sodium levels. Emerging studies have identified hypochloremia as an independent prognostic marker in patients with chronic heart failure and chronic kidney disease. The aim of this study was to investigate whether serum chloride levels were associated with mortality of critically ill cirrhotic patients. Methods Critically ill cirrhotic patients were identified from the Multi-parameter Intelligent Monitoring in Intensive Care III Database. The primary outcome was ICU mortality. Logistic regression was used to explore the association between serum chloride levels and ICU mortality. The area under the receiver operating characteristic curves (AUC) was used to assess the performance of serum chloride levels for predicting ICU mortality. Results A total of 1216 critically ill cirrhotic patients were enrolled in this study. The overall ICU mortality rate was 18.8%. Patients with hypochloremia had a higher ICU mortality than those with non-hypochloremia (34.2% vs. 15.8%; p < 0.001). After multivariable risk adjustment for age, gender, ethnicity, chloride, sodium, Model for End-stage Liver Disease score, Sequential Organ Failure Assessment score, Elixhauser comorbidity index, mechanical ventilation, vasopressors, renal replacement therapy, acute kidney injury, hemoglobin, platelet, and white blood cell, serum chloride levels remained independently associated with ICU mortality (OR 0.94; 95% CI 0.91–0.98; p = 0.002) in contrast to serum sodium levels, which were no longer significant (OR 1.03; 95% CI 0.99–1.08; p = 0.119). The AUC of serum chloride levels (AUC, 0.600; 95% CI 0.556–0.643) for ICU mortality was statistically higher than that of serum sodium levels (AUC, 0.544; 95% CI 0.499–0.590) (p < 0.001). Conclusions In critically ill cirrhotic patients, serum chloride levels are independently and inversely associated with ICU mortality, thus highlighting the prognostic role of serum chloride levels which are largely overlooked.

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Comparison of COVID-19 outcomes in organ transplant recipients (OTr) and non-transplant patients: a study protocol for rapid review

Systematic Reviews ◽

10.1186/s13643-021-01854-8 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Alexis H. Lerner ◽

Elizabeth J. Klein ◽

Anna Hardesty ◽

Orestis A. Panagiotou ◽

Chelsea Misquith ◽

...

Keyword(s):

Meta Analysis ◽

Organ Transplant ◽

Open Science ◽

Rapid Review ◽

Secondary Outcome ◽

Severe Illness ◽

Link Type ◽

Increased Risk ◽

Potential Sources ◽

Measure Of Association

Abstract Background The COVID-19 pandemic has devastated the global community with nearly 4.9 million deaths as of October 2021. While organ transplant (OT) recipients (OTr) may be at increased risk for severe COVID-19 due to their chronic immunocompromised state, outcomes for OTr with COVID-19 remain disputed in the literature. This review will examine whether OTr with COVID-19 are at higher risk for severe illness and death than non-immunocompromised individuals. Methods MEDLINE (via Ovid and PubMed) and EMBASE (via Embase.com) will be searched from December 2019 to October 2021 for observational studies (including cohort and case-control) that compare COVID-19 clinical outcomes in OTr to those in individuals without history of OT. The primary outcome of interest will be mortality as defined in each study, with possible further analyses of in-hospital mortality, 28 or 30-day mortality, and all-cause mortality versus mortality attributable to COVID-19. The secondary outcome of interest will be the severity of COVID-19 disease, most frequently defined as requiring intensive care unit admission or mechanical ventilation. Two reviewers will independently screen all abstracts and full-text articles. Potential conflicts will be resolved by a third reviewer and potentially discussion among all investigators. Methodological quality will be appraised using the Newcastle-Ottawa Scale. If data permit, we will perform random-effects meta-analysis with the Sidik-Jonkman estimator and the Hartung-Knapp adjustment for confidence intervals to estimate a summary measure of association between histories of transplant with each outcome. Potential sources of heterogeneity will be explored using meta-regression. Additional analyses will be conducted to explore the potential sources of heterogeneity (e.g., subgroup analysis) considering least minimal adjustment for confounders. Discussion This rapid review will assess the available evidence on whether OTr diagnosed with COVID-19 are at higher risk for severe illness and death compared to non-immunocompromised individuals. Such knowledge is clinically relevant and may impact risk stratification, allocation of organs and healthcare resources, and organ transplantation protocols during this, and future, pandemics. Systematic review registration Open Science Framework (OSF) registration DOI: 10.17605/osf.io/4n9d7.

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Neuromonitoring of delirium with quantitative pupillometry In sedated mechanically ventilated critically ill patients

10.21203/rs.2.19734/v2 ◽

2020 ◽

Author(s):

Eva Favre ◽

Adriano Bernini ◽

Paola Morelli ◽

Jerôme Pasquier ◽

John-Paul Miroz ◽

...

Keyword(s):

Mechanical Ventilation ◽

Brain Injury ◽

Critically Ill ◽

Critically Ill Patients ◽

Potential Utility ◽

Icu Patients ◽

Mechanically Ventilated ◽

Increased Risk ◽

Infrared Pupillometry ◽

Icu Delirium

Abstract Background. Intensive care unit (ICU) delirium is a frequent secondary neurological complication in critically ill patients undergoing prolonged mechanical ventilation. Quantitative pupillometry is an emerging modality for the neuromonitoring of primary acute brain injury, but its potential utility in patients at risk of ICU delirium is unknown. Methods. This was an observational cohort study of medical-surgical ICU patients, without acute or known primary brain injury, who underwent sedation and mechanical ventilation for at least 48 hours. Starting at day 3, automated infrared pupillometry – blinded to ICU caregivers – was used for repeated measurement of the pupillary function, including quantitative pupillary light reflex (q-PLR, expressed as % pupil constriction to a standardized light stimulus) and constriction velocity (CV, mm/sec). The relationship between delirium, using the CAM-ICU score, and quantitative pupillary variables was examined. Results. A total of 59/100 patients had ICU delirium, diagnosed at a median 8 (5-13) days from admission. Compared to non-delirious patients, subjects with ICU delirium had lower values of q-PLR (25 [19-31] vs. 20 [15-28] %) and CV (2.5 [1.7-2.8] vs. 1.7 [1.4-2.4] mm/sec) at day 3, and at all additional time-points tested ( p <0.05). After adjusting for the SOFA score and the cumulative dose of analgesia and sedation, lower q-PLR was associated with an increased risk of ICU delirium (OR 1.057 [1.007-1.113] at day 3; p =0.03). Conclusions. Sustained abnormalities of quantitative pupillary variables at the early ICU phase correlate with delirium and precede clinical diagnosis by a median 5 days. These findings suggest a potential utility of quantitative pupillometry in sedated mechanically ventilated ICU patients at high risk of delirium.

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An Analysis of 1255 ICU Patients at a Tertiary Military Hospital

Bangladesh Critical Care Journal ◽

10.3329/bccj.v1i1.14368 ◽

2013 ◽

Vol 1 (1) ◽

pp. 40-44

Author(s):

MHM Delwar Hossain ◽

Abdullah Al Maruf

Keyword(s):

Intensive Care Unit ◽

Nursing Care ◽

Ventilatory Support ◽

Military Hospital ◽

Organ Support ◽

Organizational Capability ◽

Icu Mortality ◽

Icu Patients ◽

Medical Discipline ◽

Special Part

An intensive care unit (ICU) is a special part of hospital where expertise medical and nursing care has been provided along with monitoring and organ support. An analysis of 1255 patients was carried out to investigate retrospective review of data from ICU of combined military hospital (CMH) Dhaka. During this study period, the frequency of admission into ICU was more from medical discipline (59.92%) than other disciplines like surgical (37.52%), gynaecological, obstetric and other disciplines (2.55%). The incidence of survival was 53.86% from medical, 69% from surgical and 84.38% from gynaecological, obstetric and other disciplines and mortality was 46.14%, 31% and 15.62% respectively. Occurrence of total ventilatory support provided in all disciplines was 45.34%. In other studies it was found that the ICU mortality varies between 15% to 44% depending on various factors like age, severity of diseases, length of stay and organizational capability of the ICU. The most prevalence of diseases admitted into this ICU was cardiovascular diseases, which were 42.47% and second prevalent diseases were head injury (11.34%). The incidence of immediate mortality within 12 hours was 7.97%.DOI: http://dx.doi.org/10.3329/bccj.v1i1.14368 Bangladesh Crit Care J March 2013; 1: 40-44

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Longitudinal Outcomes in Octogenarian Critically Ill Patients with a Focus on Frailty and Cardiac Surgery

Journal of Clinical Medicine ◽

10.3390/jcm10010012 ◽

2020 ◽

Vol 10 (1) ◽

pp. 12

Author(s):

Aileen Hill ◽

Daren K. Heyland ◽

Rolf Rossaint ◽

Rakesh C. Arora ◽

Daniel T. Engelman ◽

...

Keyword(s):

Cardiac Surgery ◽

Elderly Patients ◽

Critically Ill ◽

Critically Ill Patients ◽

P Value ◽

Clinical Frailty Scale ◽

Icu Patients ◽

Subdistribution Hazard ◽

Discharge Home ◽

Surgical Icu

Cardiac surgery (CSX) can be lifesaving in elderly patients (age ≥ 80 years) but may still be associated with complications and functional decline. Frailty represents a determinant to outcomes in critically ill patients, but little is known about its influence on elderly CSX-patients. This is a secondary exploratory analysis of a multi-center, prospective observational cohort study of 610 elderly patients admitted to the ICU and followed for one year to document long-term outcomes. CSX-ICU-patients (n = 49) were compared to surgical ICU patients (n = 184) with regard to demographics, frailty, and outcomes. Of all surgical patients, 102 (43%) were considered vulnerable or frail. The subdistribution hazard ratio (SHR) of time to discharge home (TTDH) for vulnerable/frail vs. fit/well patients was 0.54 (95% confidence interval (CI), 0.34, 0.86, p = 0.007). The p-value for effect modification between surgery group (CSX vs. surgical ICU patients) and Clinical Frailty Scale (CFS) group was not significant (p = 0.37) suggesting that the observed difference in the CFS effect between the CSX and surgical ICU patients is consistent with random error. A further subgroup analysis shows that among surgical ICU patients, the SHR of time to discharge home (TTDH) for vulnerable/frail vs. fit/well patients was 0.49 (95% CI, 0.29, 0.83) while the corresponding SHR for CSX patients was 0.77 (0.32–1.88). In conclusion, preoperative frailty reduced the rate of discharge to home in both surgical and CSX patients, but a larger sample of CSX patients is needed to adequately address this question in this patient group.

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Safety profile of enhanced thromboprophylaxis strategies for critically ill COVID-19 patients during the first wave of the pandemic: observational report from 28 European intensive care units

Critical Care ◽

10.1186/s13054-021-03543-3 ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Andrea Lavinio ◽

◽

Ari Ercole ◽

Denise Battaglini ◽

Sandra Magnoni ◽

...

Keyword(s):

Intensive Care ◽

Critically Ill ◽

Thromboembolic Events ◽

Icu Mortality ◽

Multi Centre Study ◽

Therapeutic Anticoagulation ◽

Increased Risk ◽

Icu Discharge ◽

Log Odds ◽

Observational Report

Abstract Introduction Critical illness from SARS-CoV-2 infection (COVID-19) is associated with a high burden of pulmonary embolism (PE) and thromboembolic events despite standard thromboprophylaxis. Available guidance is discordant, ranging from standard care to the use of therapeutic anticoagulation for enhanced thromboprophylaxis (ET). Local ET protocols have been empirically determined and are generally intermediate between standard prophylaxis and full anticoagulation. Concerns have been raised in regard to the potential risk of haemorrhage associated with therapeutic anticoagulation. This report describes the prevalence and safety of ET strategies in European Intensive Care Unit (ICUs) and their association with outcomes during the first wave of the COVID pandemic, with particular focus on haemorrhagic complications and ICU mortality. Methods Retrospective, observational, multi-centre study including adult critically ill COVID-19 patients. Anonymised data included demographics, clinical characteristics, thromboprophylaxis and/or anticoagulation treatment. Critical haemorrhage was defined as intracranial haemorrhage or bleeding requiring red blood cells transfusion. Survival was collected at ICU discharge. A multivariable mixed effects generalised linear model analysis matched for the propensity for receiving ET was constructed for both ICU mortality and critical haemorrhage. Results A total of 852 (79% male, age 66 [37–85] years) patients were included from 28 ICUs. Median body mass index and ICU length of stay were 27.7 (25.1–30.7) Kg/m2 and 13 (7–22) days, respectively. Thromboembolic events were reported in 146 patients (17.1%), of those 78 (9.2%) were PE. ICU mortality occurred in 335/852 (39.3%) patients. ET was used in 274 (32.1%) patients, and it was independently associated with significant reduction in ICU mortality (log odds = 0.64 [95% CIs 0.18–1.1; p = 0.0069]) but not an increased risk of critical haemorrhage (log odds = 0.187 [95%CI − 0.591 to − 0.964; p = 0.64]). Conclusions In a cohort of critically ill patients with a high prevalence of thromboembolic events, ET was associated with reduced ICU mortality without an increased burden of haemorrhagic complications. This study suggests ET strategies are safe and associated with favourable outcomes. Whilst full anticoagulation has been questioned for prophylaxis in these patients, our results suggest that there may nevertheless be a role for enhanced / intermediate levels of prophylaxis. Clinical trials investigating causal relationship between intermediate thromboprophylaxis and clinical outcomes are urgently needed.

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Comparison of mortality risk evaluation tools efficacy in critically ill COVID-19 patients

BMC Infectious Diseases ◽

10.1186/s12879-021-06866-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Vaidas Vicka ◽

Elija Januskeviciute ◽

Sigute Miskinyte ◽

Donata Ringaitiene ◽

Mindaugas Serpytis ◽

...

Keyword(s):

Regression Analysis ◽

Critically Ill ◽

Mortality Risk ◽

Multivariate Regression Analysis ◽

Apache Ii ◽

Risk Scores ◽

Icu Mortality ◽

Icu Patients ◽

Point Increase ◽

Number Of Patients

Abstract Background As the COVID-19 pandemic continues, the number of patients admitted to the intensive care unit (ICU) is still increasing. The aim of our article is to estimate which of the conventional ICU mortality risk scores is the most accurate at predicting mortality in COVID-19 patients and to determine how these scores can be used in combination with the 4C Mortality Score. Methods This was a retrospective study of critically ill COVID-19 patients treated in tertiary reference COVID-19 hospitals during the year 2020. The 4C Mortality Score was calculated upon admission to the hospital. The Simplified Acute Physiology Score (SAPS) II, Acute Physiology and Chronic Health Evaluation (APACHE) II, and Sequential Organ Failure Assessment (SOFA) scores were calculated upon admission to the ICU. Patients were divided into two groups: ICU survivors and ICU non-survivors. Results A total of 249 patients were included in the study, of which 63.1% were male. The average age of all patients was 61.32 ± 13.3 years. The all-cause ICU mortality ratio was 41.4% (n = 103). To determine the accuracy of the ICU mortality risk scores a ROC-AUC analysis was performed. The most accurate scale was the APACHE II, with an AUC value of 0.772 (95% CI 0.714–0.830; p < 0.001). All of the ICU risk scores and 4C Mortality Score were significant mortality predictors in the univariate regression analysis. The multivariate regression analysis was completed to elucidate which of the scores can be used in combination with the independent predictive value. In the final model, the APACHE II and 4C Mortality Score prevailed. For each point increase in the APACHE II, mortality risk increased by 1.155 (OR 1.155, 95% CI 1.085–1.229; p < 0.001), and for each point increase in the 4C Mortality Score, mortality risk increased by 1.191 (OR 1.191, 95% CI 1.086–1.306; p < 0.001), demonstrating the best overall calibration of the model. Conclusions The study demonstrated that the APACHE II had the best discrimination of mortality in ICU patients. Both the APACHE II and 4C Mortality Score independently predict mortality risk and can be used concomitantly.

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Disorders of calcium in the critically ill

10.1093/med/9780199600830.003.0253 ◽

2016 ◽

Author(s):

Matthew R. Rosengart

Keyword(s):

Systematic Review ◽

Critical Illness ◽

Critically Ill ◽

Cardiac Arrhythmias ◽

Calcium Concentration ◽

Regulatory Mechanisms ◽

Icu Mortality ◽

Icu Patients ◽

Causal Pathway ◽

And Function

Calcium is vitally important for normal cellular signalling and function. However, its toxicity necessitates that intracellular calcium concentration [Ca2+] be tightly regulated and compartmentalized. Evolutionary pressures have yielded several regulatory mechanisms to maintain intracellular and extracellular ionized calcium concentrations compatible with life. During periods of critical illness these process are commonly overwhelmed, and disorders of calcium homeostasis are highly prevalent among intensive care unit (ICU) patients. Indeed, hypocalcaemia occurs in up to 88% of critically-ill ICU patients suffering from trauma, sepsis, and burns. Contemporary evidence suggests that although hypocalcaemia may be associated with ICU mortality, it is not in the causal pathway. A systematic review concluded there are no data to support the routine parenteral administration of calcium in the management of asymptomatic critical illness-related hypocalcaemia. Asymptomatic hypocalcaemia of critical illness does not necessitate replacement. However, acute, symptomatic hypocalcaemia necessitates parenteral supplementation to prevent tetany, seizures, and cardiac arrhythmias

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Sex-specific prevalence and outcomes of frailty in critically ill patients

Journal of Intensive Care ◽

10.1186/s40560-020-00494-9 ◽

2020 ◽

Vol 8 (1) ◽

Author(s):

Erin Hessey ◽

Carmel Montgomery ◽

Danny J. Zuege ◽

Darryl Rolfson ◽

Henry T. Stelfox ◽

...

Keyword(s):

Risk Factor ◽

Propensity Score ◽

Hospital Mortality ◽

Critically Ill ◽

Invasive Mechanical Ventilation ◽

Important Risk Factor ◽

Organ Support ◽

Icu Mortality ◽

Female Sex ◽

Males And Females

Abstract Background The prevalence of frailty, an important risk factor for short- and long-term outcomes in hospitalized adults, differs by sex. Studies in critically ill adults have also found differences in mortality and organ support rates in males and females. The objective of this study was to determine if these observed differences in mortality and organ support rates can be explained by sex and frailty alone, or if the interaction between sex and frailty is an important risk factor. Methods This is a retrospective multi-centre population-based cohort study of all adult patients (≥ 18 years) admitted to the seventeen intensive care units (ICUs) across Alberta, Canada, between 2016 and 2017. On admission, physicians assigned a Clinical Frailty Scale (CFS) score (1 = very fit, 9 = terminally ill) to all patients. Patients with missing CFS scores or who died within 24 h of ICU admission were excluded. Frailty was defined as CFS ≥ 5. Outcomes included all-cause hospital mortality, ICU mortality, and organ support rates. A propensity score for female sex was generated and 1:1 matching on sex was performed. Multivariable Cox regression or logistic regression, as appropriate, was performed to evaluate the association between sex, frailty, and the sex-frailty interaction term with outcomes. Results Of 15,238 patients included in the cohort, after propensity score matching 11,816 patients remained (mean [standard deviation] age 57.3 [16.9]). In the matched cohort, females had a higher prevalence of frailty than males (32% vs. 27%, respectively) and higher odds of frailty (odds ratio [95% confidence interval (CI)] 1.29 [1.20–1.40]). Though females were less likely to receive invasive mechanical ventilation (hazard ratio [95% CI] 0.78 [0.71–0.86]), the interaction between sex and frailty (i.e., males and females with and without frailty) was not associated with differences in organ support rates. Receipt of dialysis and vasoactive support, as well as hospital mortality and ICU mortality were associated with frailty but were not associated with female sex or the interaction between sex and frailty. Conclusions Although frailty and sex were individually associated with mortality and differences in organ support in the ICU, there does not appear to be a significant interaction between sex and frailty with regards to these outcomes.

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