Chris A. Rogers

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.

Ranibizumab versus Bevacizumab to Treat Neovascular Age-related Macular Degeneration: One-Year Findings from the IVAN Randomized Trial.

PURPOSE To compare the efficacy and safety of ranibizumab and bevacizumab intravitreal injections to treat neovascular age-related macular degeneration (nAMD). DESIGN Multicenter, noninferiority factorial trial with equal allocation to groups. The noninferiority limit was 3.5 letters. This trial is registered (ISRCTN92166560). PARTICIPANTS People >50 years of age with untreated nAMD in the study eye who read ≥ 25 letters on the Early Treatment Diabetic Retinopathy Study chart. METHODS We randomized participants to 4 groups: ranibizumab or bevacizumab, given either every month (continuous) or as needed (discontinuous), with monthly review. MAIN OUTCOME MEASURES The primary outcome is at 2 years; this paper reports a prespecified interim analysis at 1 year. The primary efficacy and safety outcome measures are distance visual acuity and arteriothrombotic events or heart failure. Other outcome measures are health-related quality of life, contrast sensitivity, near visual acuity, reading index, lesion morphology, serum vascular endothelial growth factor (VEGF) levels, and costs. RESULTS Between March 27, 2008 and October 15, 2010, we randomized and treated 610 participants. One year after randomization, the comparison between bevacizumab and ranibizumab was inconclusive (bevacizumab minus ranibizumab -1.99 letters, 95% confidence interval [CI], -4.04 to 0.06). Discontinuous treatment was equivalent to continuous treatment (discontinuous minus continuous -0.35 letters; 95% CI, -2.40 to 1.70). Foveal total thickness did not differ by drug, but was 9% less with continuous treatment (geometric mean ratio [GMR], 0.91; 95% CI, 0.86 to 0.97; P = 0.005). Fewer participants receiving bevacizumab had an arteriothrombotic event or heart failure (odds ratio [OR], 0.23; 95% CI, 0.05 to 1.07; P = 0.03). There was no difference between drugs in the proportion experiencing a serious systemic adverse event (OR, 1.35; 95% CI, 0.80 to 2.27; P = 0.25). Serum VEGF was lower with bevacizumab (GMR, 0.47; 95% CI, 0.41 to 0.54; P<0.0001) and higher with discontinuous treatment (GMR, 1.23; 95% CI, 1.07 to 1.42; P = 0.004). Continuous and discontinuous treatment costs were £9656 and £6398 per patient per year for ranibizumab and £1654 and £1509 for bevacizumab; bevacizumab was less costly for both treatment regimens (P<0.0001). CONCLUSIONS The comparison of visual acuity at 1 year between bevacizumab and ranibizumab was inconclusive. Visual acuities with continuous and discontinuous treatment were equivalent. Other outcomes are consistent with the drugs and treatment regimens having similar efficacy and safety. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosures may be found after the references.

Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial

BACKGROUND Bevacizumab has been suggested to have similar effectiveness to ranibizumab for treatment of neovascular age-related macular degeneration. The Inhibition of VEGF in Age-related choroidal Neovascularisation (IVAN) trial was designed to compare these drugs and different regimens. Here, we report the findings at the prespecified 2-year timepoint. METHODS In a multicentre, 2×2 factorial, non-inferiority randomised trial, we enrolled adults aged at least 50 years with active, previously untreated neovascular age-related macular degeneration and a best corrected distance visual acuity (BCVA) of at least 25 letters from 23 hospitals in the UK. Participants were randomly assigned (1:1:1:1) to intravitreal injections of ranibizumab (0·5 mg) or bevacizumab (1·25 mg) in continuous (every month) or discontinuous (as needed) regimens, with monthly review. Study participants and clinical assessors were masked to drug allocation. Allocation to continuous or discontinuous treatment was masked up to 3 months, at which point investigators and participants were unmasked. The primary outcome was BCVA at 2 years, with a prespecified non-inferiority limit of 3·5 letters. The primary safety outcome was arterial thrombotic event or hospital admission for heart failure. Analyses were by modified intention to treat. This trial is registered, number ISRCTN92166560. FINDINGS Between March 27, 2008, and Oct 15, 2010, 628 patients underwent randomisation. 18 were withdrawn; 610 received study drugs (314 ranibizumab; 296 bevacizumab) and were included in analyses. 525 participants reached the visit at 2 years: 134 ranibizumab in continuous regimen, 137 ranibizumab in discontinuous regimen, 127 bevacizumab in continuous regimen, and 127 bevacizumab in discontinuous regimen. For BCVA, bevacizumab was neither non-inferior nor inferior to ranibizumab (mean difference -1·37 letters, 95% CI -3·75 to 1·01; p=0·26). Discontinuous treatment was neither non-inferior nor inferior to continuous treatment (-1·63 letters, -4·01 to 0·75; p=0·18). Frequency of arterial thrombotic events or hospital admission for heart failure did not differ between groups given ranibizumab (20 [6%] of 314 participants) and bevacizumab (12 [4%] of 296; odds ratio [OR] 1·69, 95% CI 0·80-3·57; p=0·16), or those given continuous (12 [4%] of 308) and discontinuous treatment (20 [7%] of 302; 0·56, 0·27-1·19; p=0·13). Mortality was lower with continuous than discontinuous treatment (OR 0·47, 95% CI 0·22-1·03; p=0·05), but did not differ by drug group (0·96, 0·46-2·02; p=0·91). INTERPRETATION Ranibizumab and bevacizumab have similar efficacy. Reduction in the frequency of retreatment resulted in a small loss of efficacy irrespective of drug. Safety was worse when treatment was administered discontinuously. These findings highlight that the choice of anti-VEGF treatment strategy is less straightforward than previously thought. FUNDING UK National Institute for Health Research Health Technology Assessment programme.

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.).

Conclusions of the corneal transplant follow-up study

AIM On the basis of finalised data from the Corneal Transplant Follow up Study to identify and quantify factors influencing corneal graft outcome in terms of graft survival, rejection, visual acuity, and astigmatism. METHODS Multifactorial analysis of 2777 grafts registered by the UK Transplant Support Service from July 1987 to June 1991. RESULTS Several recipient factors influencing graft survival, rejection, and visual acuity were identified, but no donor factors. Of the operative factors amenable to change, mixed suturing was associated with reduced graft survival, and larger grafts with increased risk of rejection but better visual acuity when surviving. There was increased risk of rejection with poor matching at HLA class I antigens, but mismatched HLA-DR grafts suffered less rejection than those with zero HLA-DR mismatches. Recipient age below 10 years was associated with increased risk of both rejection and graft failure. However, whereas increasing age above 10 years was not associated with differential graft survival, it was significantly associated with decreasing risk of rejection. CONCLUSIONS While confirming possible benefits of HLA-A and B matching, the expense and delay involved in awaiting matched HLA-DR tissue is unlikely to be justified. Other donor factors are unrelated to graft outcome following screening of tissue by eye banks. The highest rates of graft failure and rejection happen in the early postoperative period, and factors influencing visual outcome are also apparent at this stage.

Inadequate Blood Glucose Control Is Associated With In-Hospital Mortality and Morbidity in Diabetic and Nondiabetic Patients Undergoing Cardiac Surgery

Background— Derangement of glucose metabolism after surgery is not specific to patients with diabetes mellitus. We investigated the effect of different degrees of blood glucose control (BGC) on clinical outcomes after cardiac surgery. Methods and Results— We analyzed 8727 adults operated on between April 1996 and March 2004. The highest blood glucose level recorded over the first 60 hours postoperatively was used to classify patients as having good (<200 mg/dL), moderate (200 to 250 mg/dL), or poor (>250 mg/dL) BGC; 7547 patients (85%) had good, 905 (10%) had moderate, and 365 (4%) had poor BGC. Patients with inadequate BGC were more likely to present with advanced New York Heart Association class, congestive heart failure, hypertension, renal dysfunction, and ejection fraction <50% (P≤0.001). We found that 52% of patients with poor, 31% with moderate, and 8% with good BGC had diabetes mellitus. Inadequate BGC, but not diabetes mellitus (P=0.79), was associated with in-hospital mortality (good, 1.8%; moderate, 4.2%; poor, 9.6%; adjusted odds ratio: poor versus good BGC, 3.90 [95% confidence interval, 2.47 to 6.15]; moderate versus good BGC, 1.68 [95% confidence interval, 1.25 to 2.25]). Inadequate BGC also was associated with postoperative myocardial infarction (eg, odds ratio, poor versus good BGC: 2.73 [95% confidence interval, 1.74 to 4.26]) and with pulmonary and renal complications in patients without known diabetes mellitus (eg, odds ratio, poor versus good BGC: 2.27 [95% confidence interval, 1.65 to 3.12] and 2.82 [95% confidence interval, 1.54 to 5.14] respectively). Conclusions— More than 50% of patients with moderate to poor BGC after cardiac surgery were not previously identified as diabetic. Inadequate postoperative BGC is a predictor of in-hospital mortality and morbidity.

DURABILITY OF TERNARY BLEND CONCRETE WITH SILICA FUME AND BLAST-FURNACE SLAG: LABORATORY AND OUTDOOR EXPOSURE SITE STUDIES

In September 1998, a site investigation assessing the durability performance of ternary blend concretes was initiated by an academic-government-industry consortium. Different concretes were cast in the field to assess durability performance in an outdoor exposure setting as well as with standard lab tests. Resistances to the following deterioration mechanisms were assessed: alkali-silica reactivity, chloride ion ingress, and deicer salt scaling. Compressive strength was also measured at various ages. This paper describes this project in detail and presents field observations and lab findings up to 2 years later.

Early and Midterm Clinical Outcome in Patients With Severe Left Ventricular Dysfunction Undergoing Coronary Artery Surgery

BACKGROUND Patients presenting with severe left ventricular (LV) dysfunction undergoing coronary artery surgery are at increased risk of perioperative morbidity and mortality. The present study investigated early and midterm outcomes in a consecutive series of patients with severe LV dysfunction undergoing coronary surgery at our institution. METHODS Data on 5,195 consecutive patients undergoing coronary artery bypass grafting (CABG) alone (in-hospital mortality 1.35%) from April 1996 to August 2002 were prospectively recorded in the Patient Analysis and Tracking System. Two hundred and fifty patients (median age 65 years [interquartile range, 57 to 70]) with preoperative left ventricular ejection fraction less than 30% (74 off pump; 29.6%) were identified and early and midterm clinical outcomes analyzed. Propensity scores were used to take account of the imbalance in the distribution of prognostic factors between the on-pump and off-pump groups. RESULTS Patients undergoing on-pump surgery were less likely to have current congestive heart failure, insulin-dependent diabetes, a history of hypertension, have had gastrointestinal tract surgery or an ulcer, or unstable angina. They had on average lower Parsonnet scores and New York Heart Association and Canadian Cardiovascular Score ratings. However they were more likely to have more extensive coronary artery heart disease and to require more grafts than those undergoing off-pump surgery. After adjustment for consultant team and propensity scores no differences between groups with regard to in-hospital mortality and morbidity were found. The only in-hospital outcome to show a significant difference after adjustment was the need for intraoperative inotropic support, which was higher in the on-pump group (odds ratio 5.1; 95% confidence interval 2.55 to 10.2; p < 0.001)). The median follow-up times for the on- and off-pump groups were 3.4 years and 1.4 years respectively. Three-year survival was higher with on-pump surgery (87% on-pump versus 73% off-pump) but this difference did not reach statistical significance after adjustment for prognostic variables (hazard ratio 0.54, 95% confidence interval 0.22 to 1.26, p = 0.16). CONCLUSIONS In-hospital mortality and morbidity in patients presenting with severe LV dysfunction is low with comparable results with both on- and off-pump coronary artery surgery. Midterm clinical outcome is encouraging and seems to justify surgical revascularization for this high-risk group of patients.

Influence of donor and histocompatibility factors on corneal graft outcome.

The Corneal Transplant Follow-up Study has followed 2311 penetrating keratoplasties for up to 450 days after transplant. A total of 207 failures were observed, including 65 classical rejections and 35 endothelial decompensations. At 12 months, graft survival was 89%, and survival free from rejection was 87%. For surviving grafts, risk of failure reduced from 4.8% in the first 75 days and stabilized after 5 months at 1.2% in each 75-day interval. Risk of rejection initially followed a similar pattern, but then increased after 12 months. Multifactorial analyses accounted for differences in recipient characteristics and interrelationships of donor factors. Donor age, sex, cause of death, and method of corneal storage were not found to influence significantly either time to graft failure or time to first rejection. Grafts in prospectively tissue-typed donor-recipient pairs were generally considered before surgery to be at increased risk of either graft failure or rejection. With due allowance, increasing risk of rejection was associated with increasing numbers of mismatches at HLA-A and HLA-B broad antigens. The opposite was true at HLA-DR broad antigens, where increased risk of rejection was observed with no mismatches.

Corneal Graft Survival and Visual Outcome: A Multicenter Study

PURPOSE The Corneal Transplant Follow-up Study has followed 2385 corneal transplants performed in the United Kingdom and the Republic of Ireland for up to 450 days to quantify factors influencing corneal graft survival and visual outcome 3 and 12 months postoperatively. METHODS Multifactorial analyses of grafts registered by United Kingdom Transplant Support Service from July 1987 to June 1990 were used. Corrected visual acuity of functioning grafts was assessed at 3 and 12 months. RESULTS Of 2385 corneal transplants followed, 214 failures were observed: graft survival was 95% at 3 months and 89% at 1 year. Similar factors affected outcome at each time. Decreased risk of failure was associated with surgeons reporting most grafts, and increased risk was associated with regrafts, patients younger than 10 years of age, nonvisual reasons for grafting, endothelial failure, and deep vascularization. Visual outcome was worse in older patients and was associated with cosmetic reasons for grafting, superficial vascularization preoperatively, and secondary endothelial failure. Visual acuity was better when the other eye had been grafted previously, or when the diagnosis was keratoconus or stromal dystrophy. CONCLUSIONS Primary endothelial failure was associated with high failure rates but good visual results when functioning. Most other factors had similar effects on both outcome measures. Improved outcome under highest-reporting surgeons was slight, and indicated possible differences in postoperative care.