Association between frailty and short- and long-term outcomes among critically ill patients: a multicentre prospective cohort study

Background:

Frailty is a multidimensional syndrome characterized by loss of physiologic and cognitive reserves that confers vulnerability to adverse outcomes. We determined the prevalence, correlates and outcomes associated with frailty among adults admitted to intensive care.

Methods:

We prospectively enrolled 421 critically ill adults aged 50 or more at 6 hospitals across the province of Alberta. The primary exposure was frailty, defined by a score greater than 4 on the Clinical Frailty Scale. The primary outcome measure was in-hospital mortality. Secondary outcome measures included adverse events, 1-year mortality and quality of life.

Results:

The prevalence of frailty was 32.8% (95% confidence interval [CI] 28.3%–37.5%). Frail patients were older, were more likely to be female, and had more comorbidities and greater functional dependence than those who were not frail. In-hospital mortality was higher among frail patients than among non-frail patients (32% v. 16%; adjusted odds ratio [OR] 1.81, 95% CI 1.09–3.01) and remained higher at 1 year (48% v. 25%; adjusted hazard ratio 1.82, 95% CI 1.28–2.60). Major adverse events were more common among frail patients (39% v. 29%; OR 1.54, 95% CI 1.01–2.37). Compared with nonfrail survivors, frail survivors were more likely to become functionally dependent (71% v. 52%; OR 2.25, 95% CI 1.03–4.89), had significantly lower quality of life and were more often readmitted to hospital (56% v. 39%; OR 1.98, 95% CI 1.22–3.23) in the 12 months following enrolment.

Interpretation:

Frailty was common among critically ill adults aged 50 and older and identified a population at increased risk of adverse events, morbidity and mortality. Diagnosis of frailty could improve prognostication and identify a vulnerable population that might benefit from follow-up and intervention.Frailty is a term widely used to describe a multidimensional syndrome characterized by the loss of physiologic and cognitive reserves that gives rise to heightened vulnerability to adverse outcomes.^1,2 Adverse events associated with frailty include incident falls, susceptibility to acute illness, perioperative complications, unplanned hospital admissions, disability, need for institutional care, and death.^3–10 Frailty has substantial implications for quality of life, functional autonomy and health services utilization, but it has not been evaluated in critically ill patients.The development of critical illness may lead to frailty in vulnerable patients. Critical illness may also be a key factor impeding recovery and functional autonomy in those already considered to be frail.¹¹ We hypothesized that frailty would identify vulnerable patients who are less likely to tolerate critical illness, who are more susceptible to complications and death, and who are less likely to fully recover after critical illness over the short or long term. We further hypothesized that this information would translate into more accurate prognostication, which might improve decision-making for frail patients and their families. To test these hypotheses, we performed a prospective multicentre study in an unselected cohort of critically ill patients.     

Association between statin therapy and outcomes in critically ill patients: a nested cohort study

Background

The effect of statin therapy on mortality in critically ill patients is controversial, with some studies suggesting a benefit and others suggesting no benefit or even potential harm. The objective of this study was to evaluate the association between statin therapy during intensive care unit (ICU) admission and all-cause mortality in critically ill patients.

Methods

This was a nested cohort study within two randomised controlled trials conducted in a tertiary care ICU. All 763 patients who participated in the two trials were included in this study. Of these, 107 patients (14%) received statins during their ICU stay. The primary endpoint was all-cause ICU and hospital mortality. Secondary endpoints included the development of sepsis and severe sepsis during the ICU stay, the ICU length of stay, the hospital length of stay, and the duration of mechanical ventilation. Multivariate logistic regression was used to adjust for clinically and statistically relevant variables.

Results

Statin therapy was associated with a reduction in hospital mortality (adjusted odds ratio [aOR] = 0.60, 95% confidence interval [CI] 0.36-0.99). Statin therapy was associated with lower hospital mortality in the following groups: patients >58 years of age (aOR = 0.58, 95% CI 0.35-0.97), those with an acute physiology and chronic health evaluation (APACHE II) score >22 (aOR = 0.54, 95% CI 0.31-0.96), diabetic patients (aOR = 0.52, 95% CI 0.30-0.90), patients on vasopressor therapy (aOR = 0.53, 95% CI 0.29-0.97), those admitted with severe sepsis (aOR = 0.22, 95% CI 0.07-0.66), patients with creatinine ≤100 μmol/L (aOR = 0.14, 95% CI 0.04-0.51), and patients with GCS ≤9 (aOR = 0.34, 95% CI 0.17-0.71). When stratified by statin dose, the mortality reduction was mainly observed with statin equipotent doses ≥40 mg of simvastatin (aOR = 0.53, 95% CI 0.28-1.00). Mortality reduction was observed with simvastatin (aOR = 0.37, 95% CI 0.17-0.81) but not with atorvastatin (aOR = 0.80, 95% CI 0.84-1.46). Statin therapy was not associated with a difference in any of the secondary outcomes.

Conclusion

Statin therapy during ICU stay was associated with a reduction in all-cause hospital mortality. This association was especially noted in high-risk subgroups. This potential benefit needs to be validated in a randomised, controlled trial.     

Generic quality of life assessment in dementia patients: a prospective cohort study

Background  

Quality of life (QoL) is increasingly used to characterize the impact of disease and the efficacy of interventions.     

Actual exclusive breastfeeding rates and determinants among a cohort of children living in Gampaha district Sri Lanka: A prospective observational study

Background

Exclusive breastfeeding (EBF) during the early months of life reduce infant morbidity and mortality. Current recommendation in Sri Lanka is to continue exclusive breastfeeding up to six months of age. Exclusive breastfeeding rates are generally assessed by the 24 recall method which overestimates the actual rates. The objective of this study was to determine actual exclusive breast feeding rates in a cohort of Sri Lankan children and to determine the reasons that lead to cessation of breastfeeding before six months of age.

Methods

From a cohort of 2215 babies born in Gampaha district, 500 were randomly selected and invited for the study. They were followed up at two (n?=?404), four (n?=?395) and six (n?=?286) months. An interviewer administered questionnaire asked about feeding history and socio-demographic characteristics. Child health development record was used to assess the growth.

Results

Exclusive breastfeeding rates at two, four and six months were 98.0%, 75.4% and 71.3% respectively. The main reasons to stop exclusive breastfeeding between two to four months was concerns regarding weight gain and between four to six months were mothers starting to work. Majority of the babies that were not exclusively breastfed still continued to have breast milk. Mothers above 30 years had lower exclusive breastfeeding rates compared to younger mothers. Second born babies had higher rates than first borns. There was no significant association between maternal education and exclusive breastfeeding rates.

Conclusions

Exclusive breastfeeding rates were high among this cohort of children. A decrease in EBF was noted between two and four months. EBF up to six months does not cause growth failure. Mothers starting to work and concerns regarding adequacy of breast milk were the major reasons to cease EBF. The actual exclusive breastfeeding rates up to six months was 65.9%.

     

Association between muscular strength and mortality in men: prospective cohort study

Objective To examine prospectively the association between muscular strength and mortality from all causes, cardiovascular disease, and cancer in men.Design Prospective cohort study.Setting Aerobics centre longitudinal study.Participants 8762 men aged 20-80.Main outcome measures All cause mortality up to 31 December 2003; muscular strength, quantified by combining one repetition maximal measures for leg and bench presses and further categorised as age specific thirds of the combined strength variable; and cardiorespiratory fitness assessed by a maximal exercise test on a treadmill.Results During an average follow-up of 18.9 years, 503 deaths occurred (145 cardiovascular disease, 199 cancer). Age adjusted death rates per 10 000 person years across incremental thirds of muscular strength were 38.9, 25.9, and 26.6 for all causes; 12.1, 7.6, and 6.6 for cardiovascular disease; and 6.1, 4.9, and 4.2 for cancer (all P<0.01 for linear trend). After adjusting for age, physical activity, smoking, alcohol intake, body mass index, baseline medical conditions, and family history of cardiovascular disease, hazard ratios across incremental thirds of muscular strength for all cause mortality were 1.0 (referent), 0.72 (95% confidence interval 0.58 to 0.90), and 0.77 (0.62 to 0.96); for death from cardiovascular disease were 1.0 (referent), 0.74 (0.50 to 1.10), and 0.71 (0.47 to 1.07); and for death from cancer were 1.0 (referent), 0.72 (0.51 to 1.00), and 0.68 (0.48 to 0.97). The pattern of the association between muscular strength and death from all causes and cancer persisted after further adjustment for cardiorespiratory fitness; however, the association between muscular strength and death from cardiovascular disease was attenuated after further adjustment for cardiorespiratory fitness.Conclusion Muscular strength is inversely and independently associated with death from all causes and cancer in men, even after adjusting for cardiorespiratory fitness and other potential confounders.     

Acute kidney injury biomarkers for patients in a coronary care unit: a prospective cohort study

Background

Renal dysfunction is an established predictor of all-cause mortality in intensive care units. This study analyzed the outcomes of coronary care unit (CCU) patients and evaluated several biomarkers of acute kidney injury (AKI), including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18) and cystatin C (CysC) on the first day of CCU admission.

Methodology/Principal Findings

Serum and urinary samples collected from 150 patients in the coronary care unit of a tertiary care university hospital between September 2009 and August 2010 were tested for NGAL, IL-18 and CysC. Prospective demographic, clinical and laboratory data were evaluated as predictors of survival in this patient group. The most common cause of CCU admission was acute myocardial infarction (80%). According to Acute Kidney Injury Network criteria, 28.7% (43/150) of CCU patients had AKI of varying severity. Cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p<0.05) between patients with AKI versus those without AKI. For predicting AKI, serum CysC displayed an excellent areas under the receiver operating characteristic curve (AUROC) (0.895±0.031, p<0.001). The overall 180-day survival rate was 88.7% (133/150). Multiple Cox logistic regression hazard analysis revealed that urinary NGAL, serum IL-18, Acute Physiology, Age and Chronic Health Evaluation II (APACHE II) and sodium on CCU admission day one were independent risk factors for 6-month mortality. In terms of 6-month mortality, urinary NGAL had the best discriminatory power, the best Youden index, and the highest overall correctness of prediction.

Conclusions

Our data showed that serum CysC has the best discriminative power for predicting AKI in CCU patients. However, urinary NGAL and serum IL-18 are associated with short-term mortality in these critically ill patients.     

Severe imported falciparum malaria: a cohort study in 400 critically ill adults

Background

Large studies on severe imported malaria in non-endemic industrialized countries are lacking. We sought to describe the clinical spectrum of severe imported malaria in French adults and to identify risk factors for mortality at admission to the intensive care unit.

Methodology and Principal Findings

Retrospective review of severe Plasmodium falciparum malaria episodes according to the 2000 World Health Organization definition and requiring admission to the intensive care unit. Data were collected from medical charts using standardised case-report forms, in 45 French intensive care units in 2000–2006. Risk factors for in-hospital mortality were identified by univariate and multivariate analyses.Data from 400 adults admitted to the intensive care unit were analysed, representing the largest series of severe imported malaria to date. Median age was 45 years; 60% of patients were white, 96% acquired the disease in sub-Saharan Africa, and 65% had not taken antimalarial chemoprophylaxis. Curative quinine treatment was used in 97% of patients. Intensive care unit mortality was 10.5% (42 deaths). By multivariate analysis, three variables at intensive care unit admission were independently associated with hospital death: older age (per 10-year increment, odds ratio [OR], 1.72; 95% confidence interval [95%CI], 1.28–2.32; P = 0.0004), Glasgow Coma Scale score (per 1-point decrease, OR, 1.32; 95%CI, 1.20–1.45; P<0.0001), and higher parasitemia (per 5% increment, OR, 1.41; 95%CI, 1.22–1.62; P<0.0001).

Conclusions and Significance

In a large population of adults treated in a non-endemic industrialized country, severe malaria still carried a high mortality rate. Our data, including predictors of death, can probably be generalized to other non-endemic countries where high-quality healthcare is available.     

The value of joint ultrasonography in predicting arthritis in seropositive patients with arthralgia: a prospective cohort study

Background

The value of joint ultrasonography (US) in the prediction of clinical arthritis in individuals at risk of developing rheumatoid arthritis (RA) is still a point of debate, due to varying scanning protocols and different populations. We investigated whether US abnormalities assessed with a standard joint protocol can predict development of arthritis in seropositive patients with arthralgia.

Methods

Anti-citrullinated protein antibodies and/or rheumatoid factor positive patients with arthralgia, but without clinical arthritis were included. US was performed at baseline in 16 joints: bilateral metacarpophalangeal 2–3, proximal interphalangeal 2–3, wrist and metatarsophalangeal (MTP) joints 2–3 and 5. Images were scored semi-quantitatively for synovial thickening and for positive signs on power Doppler (PD). Association between US abnormalities and arthritis development at the joint and at the patient level was evaluated. Also, we investigated the added value of US over clinical parameters.

Results

Out of 163 patients who underwent US examination, 51 (31%) developed clinical arthritis after a median follow-up time of 12 (interquartile range 5–24) months, of which 44 (86%) satisfied the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA. US revealed synovial thickening and PD in at least one joint in 49 patients (30%) and 7 patients (4%), respectively. Synovial thickening was associated with both development and timing of clinical arthritis in any joint (patient level) when MTP joints were excluded from the US assessment (odds ratio 6.6, confidence interval (CI) 1.9–22), and hazard ratio 3.4, CI 1.6–6.8, respectively, with a mean time to arthritis of 23 versus 45?months when synovial thickening was present versus not present). There was no association between US and arthritis development at the joint level. Predictive capacity was highest in the groups with an intermediate and high risk of developing arthritis based on a prediction rule with clinical parameters.

Conclusions

Synovial thickening on US predicted clinical arthritis development at the patient level in seropositive patients with arthralgia when MTPs were excluded from the US assessment. Positive PD signs were infrequently seen in these at-risk individuals and was not predictive. In patients at intermediate risk of RA, US may help to identify those at higher risk of developing arthritis.

     

Enzymatic changes in myosin regulatory proteins may explain vasoplegia in terminally ill patients with sepsis

The current study was conducted with the hypothesis that failure of maintenance of the vascular tone may be central to failure of the peripheral circulation and spiralling down of blood pressure in sepsis. Namely, we examined the balance between expression of myosin light chain (MLC) phosphatase and kinase, enzymes that regulate MLCs dephosphorylation and phosphorylation with a direct effect on pharmacomechanical coupling for smooth muscle relaxation and contraction respectively. Mechanical recordings and enzyme immunoassays of vascular smooth muscle lysates were used as the major methods to examine arterial biopsy samples from terminally ill sepsis patients. The results of the present study provide evidence that genomic alteration of expression of key regulatory proteins in vascular smooth muscles may be responsible for the relentless downhill course in sepsis. Down-regulation of myosin light chain kinase (MLCK) and up-regulation of MLCK may explain the loss of tone and failure to mount contractile response in vivo during circulation. The mechanical studies demonstrated the inability of the arteries to develop tone when stimulated by phenylephrine in vitro. The results of our study provide indirect hint that control of inflammation is a major therapeutic approach in sepsis, and may facilitate to ameliorate the progressive cardiovascular collapse.     

Association between postnatal catch-up growth and obesity in childhood: prospective cohort study

ObjectiveTo identify predictors of postnatal catch-up growth from birth to two years and its relation to size and obesity at five years.DesignRegional prospective cohort study.SettingAvon longitudinal study of pregnancy and childhood, United Kingdom.Subjects848 full term singletons from a 10% random sample of the Avon longitudinal study of pregnancy and childhood.ResultsSize at birth was representative of the national reference. Overall, 30.7% (260 of 848) of infants showed a gain in SD score for weight greater than 0.67 SD scores between zero and two years, indicating clinically significant catch-up growth. These children had lower weight, length, and ponderal index at birth than other children, and were more often from primiparous pregnancies. They also had taller fathers than other children, and their mothers had lower birth weights and were more likely to smoke during pregnancy. Children who showed catch-up growth between zero and two years were heavier, taller, and fatter (body mass index, percentage body fat, and waist circumference) at five years than other children.ConclusionsIn this contemporary well nourished cohort, catch-up growth was predicted by factors relating to intrauterine restraint of fetal growth. Children who showed catch-up growth between zero and two years were fatter and had more central fat distribution at five years than other children. Mechanisms that signal and regulate early catch-up growth in the postnatal period may influence associations between small size at birth and risks for disease in adulthood.     

Randomised controlled trial of effects of coordinating care for terminally ill cancer patients.

OBJECTIVES--To measure effects on terminally ill cancer patients and their families of coordinating the services available within the NHS and from local authorities and the voluntary sector. DESIGN--Randomised controlled trial. SETTING--Inner London health district. PATIENTS--Cancer patients were routinely notified from 1987 to 1990. 554 patients expected to survive less than one year entered the trial and were randomly allocated to a coordination or a control group. INTERVENTION--All patients received routinely available services. Coordination group patients received the assistance of two nurse coordinators, whose role was to ensure that patients received appropriate and well coordinated services, tailored to their individual needs and circumstances. MAIN OUTCOME MEASURES--Patients and carers were interviewed at home on entry to the trial and at intervals until death. Interviews after bereavement were also conducted. Outcome measures included the presence and severity of physical symptoms, psychiatric morbidity, use of and satisfaction with services, and carers'' problems. Results from the baseline interview, the interview closest to death, and the interview after bereavement were analysed. RESULTS--Few differences between groups were significant. Coordination group patients were less likely to suffer from vomiting, were more likely to report effective treatment for it, and less likely to be concerned about having an itchy skin. Their carers were more likely to report that in the last week of life the patient had had a cough and had had effective treatment for constipation, and they were less likely to rate the patient''s difficulty swallowing as severe or to report effective treatment for anxiety. Coordination group patients were more likely to have seen a chiropodist and their carers were more likely to contact a specialist nurse in a night time emergency. These carers were less likely to feel angry about the death of the patient. CONCLUSIONS--This coordinating service made little difference to patient or family outcomes, perhaps because the service did not have a budget with which it could obtain services or because the professional skills of the nurse-coordinators may have conflicted with the requirements of the coordinating role.