Frailty in acute coronary syndromes. A systematic review and narrative synthesis of frailty assessment tools and interventions from randomised controlled trials.

AIM: We aimed to review all randomised controlled trial (RCT) data to explore optimal identification and treatment strategies of frail patients with Acute Coronary Syndromes (ACS). METHODS: The protocol was preregistered (PROSPERO - CRD42021250235). We performed a systematic review including RCT's that 1; used at least one frailty assessment tool to assess frailty and its impact on outcomes in patients diagnosed with ACS and 2; used at least one intervention where change in frailty was measured in patients diagnosed with ACS. The Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE were searched on the 1st April 2021 and updated on 4th July 2023. Owing to low search output results are presented as a narrative synthesis of available evidence. RESULTS: A single RCT used a frailty assessment tool. A single RCT specifically targeted frailty with their intervention. This precluded further quantitative analysis. There was indication of selection bias against frail participants, and a signal of value for physical activity measurement in frail ACS patients. There was a high level of uncertainty and low level of robustness of this evidence. CONCLUSIONS: Data from RCT's alone is inadequate in answering the reviews question. Future RCT's need to address ways to incorporate frail participants, whilst mitigating selection biases. Physical performance aspects of the frailty syndrome appear to be high yield modifiable targets that improve outcomes. Intervention trials should consider using change in frailty status as an outcome measure. Any trials that include frail participants should present data specifically attributable to this group.

The NightLife study - the clinical and cost-effectiveness of thrice-weekly, extended, in-centre nocturnal haemodialysis versus daytime haemodialysis using a mixed methods approach: study protocol for a randomised controlled trial.

BACKGROUND: In-centre nocturnal haemodialysis (INHD) offers extended-hours haemodialysis, 6 to 8 h thrice-weekly overnight, with the support of dialysis specialist nurses. There is increasing observational data demonstrating potential benefits of INHD on health-related quality of life (HRQoL). There is a lack of randomised controlled trial (RCT) data to confirm these benefits and assess safety. METHODS: The NightLife study is a pragmatic, two-arm, multicentre RCT comparing the impact of 6 months INHD to conventional haemodialysis (thrice-weekly daytime in-centre haemodialysis, 3.5-5 h per session). The primary outcome is the total score from the Kidney Disease Quality of Life tool at 6 months. Secondary outcomes include sleep and cognitive function, measures of safety, adherence to dialysis and impact on clinical parameters. There is an embedded Process Evaluation to assess implementation, health economic modelling and a QuinteT Recruitment Intervention to understand factors that influence recruitment and retention. Adults (≥ 18 years old) who have been established on haemodialysis for > 3 months are eligible to participate. DISCUSSION: There are 68,000 adults in the UK that need kidney replacement therapy (KRT), with in-centre haemodialysis the treatment modality for over a third of cases. HRQoL is an independent predictor of hospitalisation and mortality in individuals on maintenance dialysis. Haemodialysis is associated with poor HRQoL in comparison to the general population. INHD has the potential to improve HRQoL. Vigorous RCT evidence of effectiveness is lacking. The NightLife study is an essential step in the understanding of dialysis therapies and will guide patient-centred decisions regarding KRT in the future. TRIAL REGISTRATION: Trial registration number: ISRCTN87042063. Registered: 14/07/2020.

Patient blood management interventions do not lead to important clinical benefits or cost-effectiveness for major surgery: a network meta-analysis.

BACKGROUND: Patient blood management (PBM) interventions aim to improve clinical outcomes by reducing bleeding and transfusion. We assessed whether existing evidence supports the routine use of combinations of these interventions during and after major surgery. METHODS: Five systematic reviews and a National Institute of Health and Care Excellence health economic review of trials of common PBM interventions enrolling participants of any age undergoing surgery were updated. The last search was on June 1, 2019. Studies in trauma, burns, gastrointestinal haemorrhage, gynaecology, dentistry, or critical care were excluded. The co-primary outcomes were: risk of receiving red cell transfusion and 30-day or hospital all-cause mortality. Treatment effects were estimated using random-effects models and risk ratios (RR) with 95% confidence intervals (CIs). Heterogeneity assessments used I2. Network meta-analyses used a frequentist approach. The protocol was registered prospectively (PROSPERO CRD42018085730). RESULTS: Searches identified 393 eligible randomised controlled trials enrolling 54 917 participants. PBM interventions resulted in a reduction in exposure to red cell transfusion (RR=0.60; 95% CI 0.57, 0.63; I2=77%), but had no statistically significant treatment effect on 30-day or hospital mortality (RR=0.93; 95% CI 0.81, 1.07; I2=0%). Treatment effects were consistent across multiple secondary outcomes, sub-groups and sensitivity analyses that considered clinical setting, type of intervention, and trial quality. Network meta-analysis did not demonstrate additive benefits from the use of multiple interventions. No trial demonstrated that PBM was cost-effective. CONCLUSIONS: In randomised trials, PBM interventions do not have important clinical benefits beyond reducing bleeding and transfusion in people undergoing major surgery.

A multicentre randomised controlled trial of Transfusion Indication Threshold Reduction on transfusion rates, morbidity and health-care resource use following cardiac surgery (TITRe2).

BACKGROUND: Uncertainty about optimal red blood cell transfusion thresholds in cardiac surgery is reflected in widely varying transfusion rates between surgeons and cardiac centres. OBJECTIVE: To test the hypothesis that a restrictive compared with a liberal threshold for red blood cell transfusion after cardiac surgery reduces post-operative morbidity and health-care costs. DESIGN: Multicentre, parallel randomised controlled trial and within-trial cost-utility analysis from a UK NHS and Personal Social Services perspective. We could not blind health-care staff but tried to blind participants. Random allocations were generated by computer and minimised by centre and operation. SETTING: Seventeen specialist cardiac surgery centres in UK NHS hospitals. PARTICIPANTS: Patients aged > 16 years undergoing non-emergency cardiac surgery with post-operative haemoglobin < 9 g/dl. Exclusion criteria were: unwilling to have transfusion owing to beliefs; platelet, red blood cell or clotting disorder; ongoing or recurrent sepsis; and critical limb ischaemia. INTERVENTIONS: Participants in the liberal group were eligible for transfusion immediately after randomisation (post-operative haemoglobin < 9 g/dl); participants in the restrictive group were eligible for transfusion if their post-operative haemoglobin fell to < 7.5 g/dl during the index hospital stay. MAIN OUTCOME MEASURES: The primary outcome was a composite outcome of any serious infectious (sepsis or wound infection) or ischaemic event (permanent stroke, myocardial infarction, gut infarction or acute kidney injury) during the 3 months after randomisation. Events were verified or adjudicated by blinded personnel. Secondary outcomes included blood products transfused; infectious events; ischaemic events; quality of life (European Quality of Life-5 Dimensions); duration of intensive care or high-dependency unit stay; duration of hospital stay; significant pulmonary morbidity; all-cause mortality; resource use, costs and cost-effectiveness. RESULTS: We randomised 2007 participants between 15 July 2009 and 18 February 2013; four withdrew, leaving 1000 and 1003 in the restrictive and liberal groups, respectively. Transfusion rates after randomisation were 53.4% (534/1000) and 92.2% (925/1003). The primary outcome occurred in 35.1% (331/944) and 33.0% (317/962) of participants in the restrictive and liberal groups [odds ratio (OR) 1.11, 95% confidence interval (CI) 0.91 to 1.34; p = 0.30], respectively. There were no subgroup effects for the primary outcome, although some sensitivity analyses substantially altered the estimated OR. There were no differences for secondary clinical outcomes except for mortality, with more deaths in the restrictive group (4.2%, 42/1000 vs. 2.6%, 26/1003; hazard ratio 1.64, 95% CI 1.00 to 2.67; p = 0.045). Serious post-operative complications excluding primary outcome events occurred in 35.7% (354/991) and 34.2% (339/991) of participants in the restrictive and liberal groups, respectively. The total cost per participant from surgery to 3 months postoperatively differed little by group, just £182 less (standard error £488) in the restrictive group, largely owing to the difference in red blood cells cost. In the base-case cost-effectiveness results, the point estimate suggested that the restrictive threshold was cost-effective; however, this result was very uncertain partly owing to the negligible difference in quality-adjusted life-years gained. CONCLUSIONS: A restrictive transfusion threshold is not superior to a liberal threshold after cardiac surgery. This finding supports restrictive transfusion due to reduced consumption and costs of red blood cells. However, secondary findings create uncertainty about recommending restrictive transfusion and prompt a new hypothesis that liberal transfusion may be superior after cardiac surgery. Reanalyses of existing trial datasets, excluding all participants who did not breach the liberal threshold, followed by a meta-analysis of the reanalysed results are the most obvious research steps to address the new hypothesis about the possible harm of red blood cell transfusion. TRIAL REGISTRATION: Current Controlled Trials ISRCTN70923932. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 60. See the NIHR Journals Library website for further project information.

Liberal or restrictive transfusion after cardiac surgery.

BACKGROUND: Whether a restrictive threshold for hemoglobin level in red-cell transfusions, as compared with a liberal threshold, reduces postoperative morbidity and health care costs after cardiac surgery is uncertain. METHODS: We conducted a multicenter, parallel-group trial in which patients older than 16 years of age who were undergoing nonemergency cardiac surgery were recruited from 17 centers in the United Kingdom. Patients with a postoperative hemoglobin level of less than 9 g per deciliter were randomly assigned to a restrictive transfusion threshold (hemoglobin level <7.5 g per deciliter) or a liberal transfusion threshold (hemoglobin level <9 g per deciliter). The primary outcome was a serious infection (sepsis or wound infection) or an ischemic event (permanent stroke [confirmation on brain imaging and deficit in motor, sensory, or coordination functions], myocardial infarction, infarction of the gut, or acute kidney injury) within 3 months after randomization. Health care costs, excluding the index surgery, were estimated from the day of surgery to 3 months after surgery. RESULTS: A total of 2007 patients underwent randomization; 4 participants withdrew, leaving 1000 in the restrictive-threshold group and 1003 in the liberal-threshold group. Transfusion rates after randomization were 53.4% and 92.2% in the two groups, respectively. The primary outcome occurred in 35.1% of the patients in the restrictive-threshold group and 33.0% of the patients in the liberal-threshold group (odds ratio, 1.11; 95% confidence interval [CI], 0.91 to 1.34; P=0.30); there was no indication of heterogeneity according to subgroup. There were more deaths in the restrictive-threshold group than in the liberal-threshold group (4.2% vs. 2.6%; hazard ratio, 1.64; 95% CI, 1.00 to 2.67; P=0.045). Serious postoperative complications, excluding primary-outcome events, occurred in 35.7% of participants in the restrictive-threshold group and 34.2% of participants in the liberal-threshold group. Total costs did not differ significantly between the groups. CONCLUSIONS: A restrictive transfusion threshold after cardiac surgery was not superior to a liberal threshold with respect to morbidity or health care costs. (Funded by the National Institute for Health Research Health Technology Assessment program; Current Controlled Trials number, ISRCTN70923932.).

An open randomized controlled trial of median sternotomy versus anterolateral left thoracotomy on morbidity and health care resource use in patients having off-pump coronary artery bypass surgery: the Sternotomy Versus Thoracotomy (STET) trial.

OBJECTIVE: Our objective was to compare off-pump coronary artery bypass surgery carried out via a left anterolateral thoracotomy (ThoraCAB) or via a conventional median sternotomy (OPCAB). BACKGROUND: Recent advances in minimally invasive cardiac surgery have extended the technique to allow complete surgical revascularization on the beating heart via thoracotomy. METHODS: Patients undergoing nonemergency primary surgery were enrolled between February 2007 and September 2009 at 2 centers. The primary outcome was the time from surgery to fitness for hospital discharge as defined by objective criteria. RESULTS: A total of 93 patients were randomized to off-pump coronary artery bypass surgery via a median sternotomy (OPCAB) and 91 to off-pump coronary artery bypass surgery via a left anterolateral thoracotomy (ThoraCAB). The surgery was longer for patients in the ThoraCAB group (median, 4.1 vs 3.3 hours) and there were fewer with more than 3 grafts (2% vs 17%). The median time from surgery to fitness for discharge was 6 days (interquartile range, 4-7) in the ThoraCAB group versus 5 days (interquartile range, 4-7) in the OPCAB group (P = .53). The intubation time was shorter, by on average 65 minutes, in the ThoraCAB group (P = .017), although the time in intensive care was similar (P = .91). Pain scores were similar (P = .97), but more analgesia was required in the ThoraCAB group (median duration, 38.8 vs 35.5 hours, P < .001; tramadol use, 66% vs 49%, P = .024). ThoraCAB was associated with significantly worse lung function at discharge (average difference, -0.25 L, P = .01) but quality of life scores at 3 and 12 months were similar (P = .52). The average total cost was 10% higher with ThoraCAB (P = .007). CONCLUSIONS: ThoraCAB resulted in no overall clinical benefit relative to OPCAB.

Thoracic endovascular repair versus open surgical repair - which is the more cost-effective intervention for descending thoracic aortic pathologies?

OBJECTIVE: Endovascular treatment is increasingly used to treat complicated aortic pathology. The aim of the study was to assess if compared with operative repair, thoracic endovascular repair of aorta (TEVAR) was associated with a cost benefit in management of diseases affecting the descending thoracic aorta. We also compared early and mid-term outcomes between the two groups. METHODS: Clinical characteristics, outcomes and hospitalisation costs of 84 consecutive patients undergoing intervention for conditions affecting the descending thoracic aorta were reviewed retrospectively. Hospitalisation costs were calculated from National Health Service (NHS) reference costs for staff time, consumables, transfusion and length of stay. RESULTS: Apart from a higher frequency of acute type B dissection (16/45 vs 5/39, p = 0.047) in the TEVAR group, the baseline characteristics were similar. TEVAR was associated with significant reductions in morbidity (renal dysfunction 11 (31%) vs 5 (10%) p=0.025; in-hospital death 7 (20%) vs 3 (6%), p = 0.03; median intensive therapy unit (ITU) stay 6 (3-11) vs 1 (1-4), p < 0.0001). TEVAR was associated with significantly increased procedural costs (£2468 (€2961) vs £9581 (€11495) p ≤ 0.0001). This was chiefly attributable to the cost of endovascular stents. There was no significant difference in overall hospitalisation costs. TEVAR was associated with significantly lower freedom from death or re-operation (log rank p=0.048). CONCLUSIONS: TEVAR is associated with reduced morbidity and mortality in the short term. However, no cost benefit was seen with TEVAR even in the short term. In the long term, due to increased risk of re-interventions TEVAR may actually prove to be a more expensive therapeutic option.

Increased mortality, morbidity, and cost associated with red blood cell transfusion after cardiac surgery.

PURPOSE OF REVIEW: Literature since 2006 was reviewed to identify the harms and costs of red blood cell (RBC) transfusion. RECENT FINDINGS: Several studies, in people having various cardiac surgery operations, found strong associations of RBC transfusion with mortality and postoperative morbidity. The effect on mortality was strongest close to the time of operation but extended to 5 years. Morbidity outcomes included serious wound and systemic infections, renal failure, prolonged ventilation, low cardiac index, myocardial infarction, and stroke. RBC transfusion was also strongly associated with increased cardiac intensive care unit and ward postoperative stay, and hence, increased cost of admission; available studies did not consider all resources used and the associated costs. SUMMARY: The harms of RBC transfusion have potentially serious and long-term consequences for patients and are costly for health services. This evidence should shift clinicians' equipoise towards more restrictive transfusion practice. The immediate aim should be to avoid transfusing a small number of RBC units for general malaise attributed to anaemia, a practice that appears to occur in about 50% of transfused patients. Randomized trials comparing restrictive and liberal transfusion triggers are urgently needed to directly compare the benefits and harms from RBC transfusion.

Increased mortality, morbidity, and cost associated with red blood cell transfusion after cardiac surgery.

PURPOSE OF REVIEW: Literature since 2006 was reviewed to identify the harms and costs of red blood cell (RBC) transfusion. RECENT FINDINGS: Several studies, on people having various cardiac surgery operations, found strong associations of RBC transfusion with mortality and postoperative morbidity. The effect on mortality was strongest close to the time of operation but extended to 5 years. Morbidity outcomes included serious wound and systemic infections, renal failure, prolonged ventilation, low cardiac index, myocardial infarction, and stroke. RBC transfusion was also strongly associated with increased intensive care and ward postoperative stay, and hence increased cost of admission; available studies did not consider all resources used and the associated costs. SUMMARY: The harms of RBC transfusion have potentially serious and long-term consequences for patients and are costly for health services. This evidence should shift clinicians' equipoise towards more restrictive transfusion practice. The immediate aim should be to avoid transfusing small numbers of RBC units for general malaise attributed to anaemia, a practice which appears to occur in about 50% of transfused patients. Randomized trials comparing restrictive and liberal transfusion triggers are urgently needed to compare directly the balance of benefits and harms from RBC transfusion.

Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery.

BACKGROUND: Red blood cell transfusion can both benefit and harm. To inform decisions about transfusion, we aimed to quantify associations of transfusion with clinical outcomes and cost in patients having cardiac surgery. METHODS AND RESULTS: Clinical, hematology, and blood transfusion databases were linked with the UK population register. Additional hematocrit information was obtained from intensive care unit charts. Composite infection (respiratory or wound infection or septicemia) and ischemic outcomes (myocardial infarction, stroke, renal impairment, or failure) were prespecified as coprimary end points. Secondary outcomes were resource use, cost, and survival. Associations were estimated by regression modeling with adjustment for potential confounding. All adult patients having cardiac surgery between April 1, 1996, and December 31, 2003, with key exposure and outcome data were included (98%). Adjusted odds ratios for composite infection (737 of 8516) and ischemic outcomes (832 of 8518) for transfused versus nontransfused patients were 3.38 (95% confidence interval [CI], 2.60 to 4.40) and 3.35 (95% CI, 2.68 to 4.35), respectively. Transfusion was associated with increased relative cost of admission (any transfusion, 1.42 times [95% CI, 1.37 to 1.46], varying from 1.11 for 1 U to 3.35 for >9 U). At any time after their operations, transfused patients were less likely to have been discharged from hospital (hazard ratio [HR], 0.63; 95% CI, 0.60 to 0.67) and were more likely to have died (0 to 30 days: HR, 6.69; 95% CI, 3.66 to 15.1; 31 days to 1 year: HR, 2.59; 95% CI, 1.68 to 4.17; >1 year: HR, 1.32; 95% CI, 1.08 to 1.64). CONCLUSIONS: Red blood cell transfusion in patients having cardiac surgery is strongly associated with both infection and ischemic postoperative morbidity, hospital stay, increased early and late mortality, and hospital costs.