Katie Pike

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.).

Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7-year follow-up of the ORACLE II trial

BACKGROUND The ORACLE II trial compared the use of erythromycin and/or amoxicillin-clavulanate (co-amoxiclav) with that of placebo for women in spontaneous preterm labour and intact membranes, without overt signs of clinical infection, by use of a factorial randomised design. The aim of the present study--the ORACLE Children Study II--was to determine the long-term effects on children after exposure to antibiotics in this clinical situation. METHODS We assessed children at age 7 years born to the 4221 women who had completed the ORACLE II study and who were eligible for follow-up with a structured parental questionnaire to assess the childs health status. Functional impairment was defined as the presence of any level of functional impairment (severe, moderate, or mild) derived from the mark III Multi-Attribute Health Status classification system. Educational outcomes were assessed with national curriculum test results for children resident in England. FINDINGS Outcome was determined for 3196 (71%) eligible children. Overall, a greater proportion of children whose mothers had been prescribed erythromycin, with or without co-amoxiclav, had any functional impairment than did those whose mothers had received no erythromycin (658 [42.3%] of 1554 children vs 574 [38.3%] of 1498; odds ratio 1.18, 95% CI 1.02-1.37). Co-amoxiclav (with or without erythromycin) had no effect on the proportion of children with any functional impairment, compared with receipt of no co-amoxiclav (624 [40.7%] of 1523 vs 608 [40.0%] of 1520; 1.03, 0.89-1.19). No effects were seen with either antibiotic on the number of deaths, other medical conditions, behavioural patterns, or educational attainment. However, more children whose mothers had received erythromycin or co-amoxiclav developed cerebral palsy than did those born to mothers who received no erythromycin or no co-amoxiclav, respectively (erythromycin: 53 [3.3%] of 1611 vs 27 [1.7%] of 1562, 1.93, 1.21-3.09; co-amoxiclav: 50 [3.2%] of 1587 vs 30 [1.9%] of 1586, 1.69, 1.07-2.67). The number needed to harm with erythromycin was 64 (95% CI 37-209) and with co-amoxiclav 79 (42-591). INTERPRETATION The prescription of erythromycin for women in spontaneous preterm labour with intact membranes was associated with an increase in functional impairment among their children at 7 years of age. The risk of cerebral palsy was increased by either antibiotic, although the overall risk of this condition was low. FUNDING UK Medical Research Council.

Childhood outcomes after prescription of antibiotics to pregnant women with preterm rupture of the membranes: 7-year follow-up of the ORACLE I trial

BACKGROUND The ORACLE I trial compared the use of erythromycin and/or amoxicillin-clavulanate (co-amoxiclav) with that of placebo for women with preterm rupture of the membranes without overt signs of clinical infection, by use of a factorial randomised design. The aim of the present study--the ORACLE Children Study I--was to determine the long-term effects on children of these interventions. METHODS We assessed children at age 7 years born to the 4148 women who had completed the ORACLE I trial and who were eligible for follow-up with a structured parental questionnaire to assess the childs health status. Functional impairment was defined as the presence of any level of functional impairment (severe, moderate, or mild) derived from the mark III Multi-Attribute Health Status classification system. Educational outcomes were assessed with national curriculum test results for children resident in England. FINDINGS Outcome was determined for 3298 (75%) eligible children. There was no difference in the proportion of children with any functional impairment after prescription of erythromycin, with or without co-amoxiclav, compared with those born to mothers who received no erythromycin (594 [38.3%] of 1551 children vs 655 [40.4%] of 1620; odds ratio 0.91, 95% CI 0.79-1.05) or after prescription of co-amoxiclav, with or without erythromycin, compared with those born to mothers who received no co-amoxiclav (645 [40.6%] of 1587 vs 604 [38.1%] of 1584; 1.11, 0.96-1.28). Neither antibiotic had a significant effect on the overall level of behavioural difficulties experienced, on specific medical conditions, or on the proportions of children achieving each level in reading, writing, or mathematics at key stage one. INTERPRETATION The prescription of antibiotics for women with preterm rupture of the membranes seems to have little effect on the health of children at 7 years of age. FUNDING UK Medical Research Council.

Thoracic Epidural Anesthesia Improves Early Outcomes in Patients Undergoing Off-pump Coronary Artery Bypass Surgery: A Prospective, Randomized, Controlled Trial

Background:The aim of this two-center, open, randomized, controlled trial was to evaluate the impact of thoracic epidural anesthesia on early clinical outcomes in patients undergoing off-pump coronary artery bypass surgery. Methods:Two hundred and twenty-six patients were randomized to either general anesthesia plus epidural (GAE) (n = 109) or general anesthesia only (GA) (n = 117). The primary outcome was length of postoperative hospital stay. Secondary outcomes were: arrhythmia, inotropic support, intubation time, perioperative myocardial infarction, neurologic events, intensive care stay, pain scores, and analgesia requirement. Results:Baseline characteristics were similar in the two groups. One patient died in the GAE group. Median postoperative stay was significantly reduced in the GAE, compared with the GA, group (5 days, interquartile range [5–6] vs. 6 days, interquartile range [5–7], hazard ratio = 1.39, 95% CI [1.06–1.82]; P = 0.017). The incidence of arrhythmias and the median intubation time were both significantly lower in the GAE, compared with the GA, group (odds ratio = 0.41, 95% CI [0.22–0.78], P = 0.006 and hazard ratio = 1.73, 95% CI [1.31–2.27], P < 0.001, respectively). Patients in the GAE group were more likely to need vasoconstrictors intraoperatively than in the GA group (odds ratio = 2.50, 95% CI [1.22–5.12]; P = 0.012). The GAE, compared with GA, group reported significantly lower levels of impairment for all pain domains and reduced morphine usage (odds ratio = 0.07, 95% CI [0.03–0.17]; P < 0.001). Conclusion:In patients undergoing off-pump coronary artery bypass surgery, the addition of thoracic epidural to general anesthesia significantly reduces the incidence of postoperative arrhythmias and improves pain control and overall quality of recovery, allowing earlier extubation and hospital discharge.

Outcomes at 7 years for babies who developed neonatal necrotising enterocolitis: the ORACLE Children Study.

Background Within the ORACLE Children Study Cohort, the authors have evaluated long-term consequences of the diagnosis of confirmed or suspected neonatal necrotising enterocolitis (NEC) at age of 7 years. Methods Outcomes were assessed using a parental questionnaire, including the Health Utilities Index (HUI-3) to assess functional impairment, and specific medical and behavioural outcomes. Educational outcomes for children in England were explored using national standardised tests. Multiple logistic regression was used to explore independent associates of NEC within the cohort. Results The authors obtained data for 119 (77%) of 157 children following proven or suspected NEC and compared their outcomes with those of the remaining 6496 children. NEC was associated with an increase in risk of neonatal death (OR 14.6 (95% CI 10.4 to 20.6)). At 7 years, NEC conferred an increased risk of all grades of impairment. Adjusting for confounders, risks persisted for any HUI-3 defined functional impairment (adjusted OR 1.55 (1.05, 2.29)), particularly mild impairment (adjusted OR 1.61 (1.03, 2.53)) both in all NEC children and in those with proven NEC, which appeared to be independent. No behavioural or educational associations were confirmed. Following NEC, children were more likely to suffer bowel problems than non-NEC children (adjusted OR 3.96 (2.06, 7.61)). Conclusions The ORACLE Children Study provided opportunity for the largest evaluation of school age outcome following neonatal NEC and demonstrates significant long-term consequences of both gut function (presence of stoma, admission for bowel problems and continuing medical care for gut-related problems) and motor, sensory and cognitive outcomes as measured using HUI-3.

Randomised, double-blind, placebo-controlled trial to determine whether steroids reduce the incidence and severity of nephropathy in Henoch-Schönlein Purpura (HSP)

Background The long-term prognosis of Henoch-Schönlein Purpura (HSP) is predominantly determined by the extent of renal involvement. There is no consensus as to whether treatment with prednisolone at presentation can prevent or ameliorate the progression of nephropathy in HSP. Methods Children under 18 years of age with new-onset HSP were randomly assigned to receive prednisolone or placebo for 14 days. The primary outcomes were (a) the presence of proteinuria at 12 months (defined as urine protein : creatinine ratio (UP : UC) >20 mg/mmol) and (b) the need for additional treatment (defined as the presence of hypertension requiring treatment or renal biopsy anomalies or the need for treatment of renal disease) during the 12 month study period. Results 352 children were randomised. Of those patients with laboratory UP : UC results available at 12 months, 18/123 (15%) patients on prednisolone and 13/124 (10%) patients on placebo had UP : UC >20 mg/mmol. There was no significant difference in the proportion of patients with UP : UC >20 mg/mmol at 12 months between the treatment groups (OR (prednisolone/placebo)=1.46, 95% CI 0.68 to 3.14, n=247), even after adjusting for baseline proteinuria and medications known to affect proteinuria (adjusted OR=1.29, 95% CI 0.58 to 2.82, n=247). Similarly, there was no significant difference in the time needed for additional treatment between the two groups (hazard ratio (HR) (prednisolone/placebo)=0.53, 95% CI 0.18 to 1.59, n=323). Conclusions This is the largest trial of the role of steroids in children with HSP. We found no evidence to suggest that early treatment with prednisolone reduces the prevalence of proteinuria 12 months after disease onset in children with HSP. Trial registration Number ISRCTN71445600

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.

A multi-centre randomised controlled trial of Transfusion Indication Threshold Reduction on transfusion rates, morbidity and healthcare resource use following cardiac surgery: study protocol.

Thresholds for red blood cell transfusion following cardiac surgery vary by hospital and surgeon. The TITRe2 multi-centre randomised controlled trial aims to randomise 2000 patients from 17 United Kingdom centres, and tests the hypothesis that a restrictive transfusion threshold will reduce postoperative morbidity and health service costs compared to a liberal threshold. Patients consent to take part in the study pre-operatively but are only randomised if their haemoglobin falls below 9 g/dL during their post-operative hospital stay. The primary outcome is a binary composite outcome of any serious infectious or ischaemic event in the first three months after randomisation. Many challenges have been encountered in the set-up and running of the study.

Risk profile and outcomes of aortic valve replacement in octogenarians

AIM To investigate the patient characteristics, relationship between the Logistic EuroSCORE (LES) and the observed outcomes in octogenarians who underwent surgical aortic valve replacement (AVR). METHODS Two hundred and seventy three octogenarians underwent AVR between 1996 and 2008 at Bristol Royal Infirmary. Demographics, acute outcomes, length of hospital stay and mortality were obtained. The LES was calculated to characterize the predicted operative risk. Two groups were defined: LES ≥ 15 (n = 80) and LES < 15 (n = 193). RESULTS In patients with LES ≥ 15, 30 d mortality was 14% (95% CI: 7%-23%) compared with 4% (95% CI: 2%-8%) in the LES < 15 group (P < 0.007). Despite the increase in number of operations from 1996 to 2008, the average LES did not change. Only 5% of patients had prior bypass surgery. The LES identified a low risk quartile of patients with a very low mortality (4%, n = 8, P < 0.007) at 30 d. The overall surgical results for octogenarians were excellent. The low risk group had an excellent outcome and the high risk group had a poor outcome after surgical AVR. CONCLUSION It may be better treated with transcatheter aortic valve implantation.

Characteristics of children with cerebral palsy in the ORACLE children study

Aims  We have identified an excess of children with cerebral palsy (CP) born to women who received antibiotic treatment for spontaneous preterm labour (SPL). This nested study investigated the profile of impairment among children with CP in the ORACLE Children Study (OCS), and contrasted outcomes with those in 4Child, a population CP registry.