Postoperative risk stratification in oral squamous cell carcinoma.

Postoperative prognostic stratification using the Union for International Cancer Control (UICC) TNM 8th edition staging rules (UICC 8) may identify additional groups of patients who could benefit from adjuvant radiotherapy. Currently, selection for such treatment is not based on all known prognostic factors, and their relative importance may vary depending on the overall risk category. The objective of this study therefore was to evaluate these possibilities. We retrospectively studied 644 patients who had surgery with curative intent for oral squamous cell carcinoma (OSCC) between March 2006 and February 2017. The outcomes of interest were disease-specific survival (DSS) and locoregional recurrence (LRR). Patients were re-staged according to the UICC 8 staging rules. Putative clinical and pathological prognostic variables were evaluated and hazard ratios estimated. Regression analysis was done to identify independent prognostic factors, and iterative analyses identified clinically-relevant risk categories with a minimum of residual prognostic variables. The significance of recognised pathological prognostic factors differed according to the overall risk category. An intermediate risk group comprising patients with pN1 disease as well those with pT3 disease solely on the basis of a depth of invasion (DOI) of more than 10 mm, was identified. A trial to evaluate the benefit or otherwise of adjuvant radiotherapy in this group is now required. Individual prognostic risk factors should be considered within the context of the overall risk category in patients with OSCC.

Descriptive characteristics and in-hospital mortality of critically bleeding patients requiring massive transfusion: results from the Australian and New Zealand Massive Transfusion Registry.

BACKGROUND AND OBJECTIVES: Critically bleeding patients requiring massive transfusion (MT) are clinically challenging, and limited data exist to support management decisions. This study describes patient characteristics, transfusion support and clinical outcomes from the Australian and New Zealand (NZ) Massive Transfusion Registry (ANZ-MTR). MATERIALS AND METHODS: Retrospective, cohort study of all adult patients receiving MT (≥5 units red blood cells [RBC] in 4 h) at participating ANZ-MTR hospitals, 2011-2015. Mortality information was collected from the Australian National Death Index and NZ Ministry of Health. Associations between patient characteristics and outcomes were modelled using logistic regression. RESULTS: A total of 3560 MT cases were identified. For in-hospital deaths, cardiothoracic surgery was the most frequent bleeding context (24·5%) followed by trauma (18·3%). Age (OR = 1·03; 95% CI: 1·02-1·04), more comorbidities (OR = 1·14; 95% CI: 1·09-1·21), larger volume of RBC in first 24 h from MT onset (OR = 1·04; 95% CI: 1·02-1·06), higher platelet to RBC ratio at 4 h (OR = 2·76; 95% CI: 1·14-6·65) and higher activated partial thromboplastin time (OR = 1·02; 95% CI: 1·01-1·03) were associated with in-hospital mortality. CONCLUSION: Patients with more comorbidities, older age, traumatic or surgical bleeding or requiring more blood components had higher in-hospital mortality. These findings provide a basis to evaluate and monitor practice relating to optimal use of blood products, variation in transfusion practices and patient outcomes, and also enable benchmarking of hospital performance for management of MT in specific patient groups.

Evaluation of clinical coding data to determine causes of critical bleeding in patients receiving massive transfusion: a bi-national, multicentre, cross-sectional study.

OBJECTIVES: To evaluate the use of routinely collected data to determine the cause(s) of critical bleeding in patients who receive massive transfusion (MT). BACKGROUND: Routinely collected data are increasingly being used to describe and evaluate transfusion practice. MATERIALS/METHODS: Chart reviews were undertaken on 10 randomly selected MT patients at 48 hospitals across Australia and New Zealand to determine the cause(s) of critical bleeding. Diagnosis-related group (DRG) and International Classification of Diseases (ICD) codes were extracted separately and used to assign each patient a cause of critical bleeding. These were compared against chart review using percentage agreement and kappa statistics. RESULTS: A total of 427 MT patients were included with complete ICD and DRG data for 427 (100%) and 396 (93%), respectively. Good overall agreement was found between chart review and ICD codes (78·3%; κ = 0·74, 95% CI 0·70-0·79) and only fair overall agreement with DRG (51%; κ = 0·45, 95% CI 0·40-0·50). Both ICD and DRG were sensitive and accurate for classifying obstetric haemorrhage patients (98% sensitivity and κ > 0·94). However, compared with the ICD algorithm, DRGs were less sensitive and accurate in classifying bleeding as a result of gastrointestinal haemorrhage (74% vs 8%; κ = 0·75 vs 0·1), trauma (92% vs 62%; κ = 0·78 vs 0·67), cardiac (80% vs 57%; κ = 0·79 vs 0·60) and vascular surgery (64% vs 56%; κ = 0·69 vs 0·65). CONCLUSION: Algorithms using ICD codes can determine the cause of critical bleeding in patients requiring MT with good to excellent agreement with clinical history. DRG are less suitable to determine critical bleeding causes.

Improving outcomes for hospital patients with critical bleeding requiring massive transfusion: the Australian and New Zealand Massive Transfusion Registry study methodology.

BACKGROUND: The Australian and New Zealand (ANZ) Massive Transfusion (MT) Registry (MTR) has been established to improve the quality of care of patients with critical bleeding (CB) requiring MT (≥ 5 units red blood cells (RBC) over 4 h). The MTR is providing data to: (1) improve the evidence base for transfusion practice by systematically collecting data on transfusion practice and clinical outcomes; (2) monitor variations in practice and provide an opportunity for benchmarking, and feedback on practice/blood product use; (3) inform blood supply planning, inventory management and development of future clinical trials; and (4) measure and enhance translation of evidence into policy and patient blood management guidelines. The MTR commenced in 2011. At each participating site, all eligible patients aged ≥18 years with CB from any clinical context receiving MT are included using a waived consent model. Patient information and clinical coding, transfusion history, and laboratory test results are extracted for each patient's hospital admission at the episode level. RESULTS: Thirty-two hospitals have enrolled and 3566 MT patients have been identified across Australia and New Zealand between 2011 and 2015. The majority of CB contexts are surgical, followed by trauma and gastrointestinal haemorrhage. Validation studies have verified that the definition of MT used in the registry correctly identifies 94 % of CB events, and that the median time of transfusion for the majority of fresh products is the 'product event issue time' from the hospital blood bank plus 20 min. Data linkage between the MTR and mortality databases in Australia and New Zealand will allow comparisons of risk-adjusted mortality estimates across different bleeding contexts, and between countries. Data extracts will be examined to determine if there are differences in patient outcomes according to transfusion practice. The ratios of blood components (e.g. FFP:RBC) used in different types of critical bleeding will also be investigated. CONCLUSIONS: The MTR is generating data with the potential to have an impact on management and policy decision-making in CB and MT and provide benchmarking and monitoring tools for immediate application.

Improving red cell transfusion in the elective surgical setting: an improvement collaborative with evaluation.

BACKGROUND & OBJECTIVES: Significant research conducted in New South Wales (NSW) hospitals' indicated that about 30% of red cell transfusions in stable adult patients was inappropriate. Of the total Australian government blood product budget in 2009-2010 (i.e. $878·8 million dollars) was spent on fresh blood products and plasma collection. The Clinical Excellence Commission (CEC) launched a systematic intervention called Blood Watch (BW) aiming to reduce inappropriate red cell transfusions in all NSW hospitals. An evaluation of BW was undertaken to measure the effectiveness of the programme and to estimate the associated potential cost-saving. MATERIALS & METHODS: Through the deterministic linkage of the four population-based administrative databases, three outcome indicators and four process indicators were developed. The analyses were of five elective surgical groups as they were the focus of the interventions. Three-level logistic regression and three-level linear regression were used to explore the time trend of the study process and outcome indicators. Modelling of the possible avoided red cell transfusions was also undertaken using a quadratic regression technique. RESULTS: Overall, there was a 27·4% reduction of the blood usage after the introduction of the BW programme and the reductions were consistent across five elective surgical groups. Such a reduction was associated with annual cost-savings of over $8·5 million. CONCLUSIONS: The BW programme which was based on collaborative improvement methods and implemented at scale led to significant reduction of blood usage, consistently across five elective surgical groups and significant cost-saving.

What factors contribute to hospital variation in obstetric transfusion rates?

BACKGROUND AND OBJECTIVES: To explore variation in red blood cell transfusion rates between hospitals, and the extent to which this can be explained. A secondary objective was to assess whether hospital transfusion rates are associated with maternal morbidity. MATERIALS AND METHODS: Linked hospital discharge and birth data were used to identify births (n = 279 145) in hospitals with at least 10 deliveries per annum between 2008 and 2010 in New South Wales, Australia. To investigate transfusion rates, a series of random-effects multilevel logistic regression models were fitted, progressively adjusting for maternal, obstetric and hospital factors. Correlations between hospital transfusion and maternal, neonatal morbidity and readmission rates were assessed. RESULTS: Overall, the transfusion rate was 1.4% (hospital range 0.6-2.9) across 89 hospitals. Adjusting for maternal casemix reduced the variation between hospitals by 26%. Adjustment for obstetric interventions further reduced variation by 8% and a further 39% after adjustment for hospital type (range 1.1-2.0%). At a hospital level, high transfusion rates were moderately correlated with maternal morbidity (0.59, P = 0.01), but not with low Apgar scores (0.39, P = 0.08), or readmission rates (0.18, P = 0.29). CONCLUSION: Both casemix and practice differences contributed to the variation in transfusion rates between hospitals. The relationship between outcomes and transfusion rates was variable; however, low transfusion rates were not associated with worse outcomes.

Elucidating the clinical characteristics of patients captured using different definitions of massive transfusion.

BACKGROUND AND OBJECTIVES: The type and clinical characteristics of patients identified with commonly used definitions of massive transfusion (MT) are largely unknown. The objective of this study was to define the clinical characteristics of patients meeting different definitions of MT for the purpose of patient recruitment in observational studies. MATERIALS AND METHODS: Data were extracted on all patients who received red blood cell (RBC) transfusions in 2010 at three tertiary Australian hospitals. MT patients were identified according to three definitions: ≥10 units RBC in 24 h (10/24 h), ≥6 units RBC in 6 h (6/6 h) and ≥5 units RBC in 4 h (5/4 h). Clinical coding data were used to assign bleeding context. Data on in-hospital mortality were also extracted. RESULTS: Five hundred and forty-two patients met at least one MT definition, with 236 (44%) included by all definitions. The most inclusive definition was 5/4 h (508 patients, 94%) followed by 6/6 h (455 patients, 84%) and 10/24 h (251 patients, 46%). Importantly, 40-55% of most types of critical bleeding events and 82% of all obstetric haemorrhage cases were excluded by the 10/24 h definition. Patients who met both the 5/4 h and 10/24 h definitions were transfused more RBCs (19 vs. 8 median total RBC units; P < 0·001), had longer ventilation time (120 vs. 55 h; P < 0·001), median ICU (149 vs. 99 h; P < 0·001) and hospital length of stay (23 vs. 18 h; P = 0·006) and had a higher in-hospital mortality rate (23·3% vs. 16·4%; P = 0·050). CONCLUSION: The 5/4 h MT definition was the most inclusive, but combination with the 10/24 h definition appeared to identify a clinically important patient cohort.

Uncontrolled bleeding in surgical patients: the role of recombinant activated factor VIIa.

Recombinant activated factor VII (rFVIIa), developed and effective in managing inhibitors in haemophilia patients, is being widely used off-label as a "panhaemostatic agent" with ongoing controversy as to its benefits and risks in terms of controlling critical haemorrhage and improving patient outcomes. Current insights into haemostatic mechanisms have resulted in a better understanding of the central role of FVII/FVIIa and tissue factor in the localization and initiation of haemostasis. There is a plethora of case reports and series published on the use of rFVIIa in critical life-threatening haemorrhage and in perioperative settings associated with significant blood loss or the potential for catastrophic haemorrhage. Additionally, the literature is replete with reviews for the use of rFVIIa in various clinical settings, but there is a dearth of good evidence from randomized controlled trials for efficacy. Safety, especially from the thrombogenicity perspective, has been a major issue, but turns out to be less of a concern with thrombotic potential needing to be weighed against the anticipated benefits. Although there is some clinical trial and observational data supporting efficacy it has been difficult to recommend clear clinical practice guidelines, especially as clinical outcome data in terms of morbidity and mortality is limited. Some of the best evidence relates to reduction in allogeneic blood transfusion requirements. This in itself is important and probably clinically relevant in view of the accumulating evidence that allogeneic blood transfusion is an independent risk factor for poorer clinical outcome. It is unlikely that there will be adequate randomized clinical trials to better answer the question of efficacy, thus making data from registries of greater importance. Indeed, the process of establishing efficacy, safety and regulation of a therapeutic that is increasingly used off-label is not without significant difficulties.

Patient blood management - a new paradigm for transfusion medicine?

The saving of many lives in history has been duly credited to blood transfusions. What is frequently overlooked is the fact that, in light of a wealth of evidence as well as other management options, a therapy deemed suitable yesterday may no longer be the first choice today. Use of blood has not been based upon scientific evaluation of benefits, but mostly on anecdotal experience and a variety of factors are challenging current practice. Blood is a precious resource with an ever limiting supply due to the aging population. Costs have also continually increased due to advances (and complexities) in collection, testing, processing and administration of transfusion, which could make up 5% of the total health service budget. Risks of transfusions remain a major concern, with advances in blood screening and processing shifting the profile from infectious to non-infectious risks. Most worrying though, is the accumulating literature demonstrating a strong (often dose-dependent) association between transfusion and adverse outcomes. These include increased length of stay, postoperative infection, morbidity and mortality. To this end, a recent international consensus conference on transfusion outcomes (ICCTO) concluded that there was little evidence to corroborate that blood would improve patients' outcomes in the vast majority of clinical scenarios in which transfusions are currently routinely considered; more appropriate clinical management options should be adopted and transfusion avoided wherever possible. On the other hand, there are patients for whom the perceived benefits of transfusion are likely to outweigh the potential risks. Consensus guidelines for blood component therapy have been developed to assist clinicians in identifying these patients and most of these guidelines have long advocated more conservative 'triggers' for transfusion. However, significant variation in practice and inappropriate transfusions are still prevalent. The 'blood must always be good philosophy' continues to permeate clinical practice. An alternative approach, however, is being adopted in an increasing number of centres. Experience in managing Jehovah's Witness patients has shown that complex care without transfusion is possible and results are comparable with, if not better than those of transfused patients. These experiences and rising awareness of downsides of transfusion helped create what has become known as 'patient blood management'. Principles of this approach include optimizing erythropoiesis, reducing surgical blood loss and harnessing the patient's physiological tolerance of anaemia. Treatment is tailored to the individual patient, using a multidisciplinary team approach and employing a combination of modalities. Results have demonstrated reduction of transfusion, improved patient outcomes and patient satisfaction. Significant healthcare cost savings have also followed. Despite the success of patient blood management programmes and calls for practice change, the potential and actual harm to patients caused through inappropriate transfusion is still not sufficiently tangible for the public and many clinicians. This has to change. The medical, ethical, legal and economic evidence cannot be ignored. Patient blood management needs to be implemented as the standard of care for all patients.

Recombinant activated factor VII in critical bleeding: experience from the Australian and New Zealand Haemostasis Register.

BACKGROUND: There has been increasing off-label use of recombinant activated factor VII (rFVIIa/NovoSeven; Novo Nordisk, Bagsvaerd, Denmark) for patients with critical bleeding. Given the lack of high-level evidence, the clinical indications, observed response and adverse events are important to capture. METHODS: The Haemostasis Registry collects retrospective and contemporaneous data on all use of rFVIIa at participating institutions for non-haemophiliac patients with critical bleeding (i.e. off-label use). RESULTS: As of October 2006, 694 cases had been reported into the register from 37 hospitals across Australia and New Zealand. These comprise an array of therapeutic categories, including salvage use in: perioperative cardiothoracic surgery (44%), trauma (16%), medical bleeding (9%), obstetric bleeding (4%) and other types of critical bleeding (28%). Patients received a median (interquartile range) dose of 91 mug/kg (75-103) and 83% of patients received a single dose of rFVIIa. The documented response rate to a single dose of rFVIIa was 69%. The 28-day survival was 68%, but varied with clinical category. The rate of adverse events probably or possibly linked to the use of rFVIIa was 6%, with most of the thromboembolic adverse events occurring in the cardiac surgery group. CONCLUSION: The Haemostasis Registry cannot replace well-designed prospective randomized controlled trials, but in their absence this registry provides a basis for understanding current clinical experience of rFVIIa. Registries continue to be vital in monitoring off-label uses of medications.

Guidelines for the transfusion of red cells.

The following recommendations, which aim at standardising and rationalising clinical indications for the transfusion of red cells in Belgium, were drawn up by a working group of the Superior Health Council. To this end, the Superior Health Council organised an expert meeting devoted to "Guidelines for the transfusion of red cells" in collaboration with the Belgian Hematological Society. The experts discussed the indications for red cell transfusions, the ideal red cell concentrate, the practical issues of administering red cells, and red cell transfusions in patients in a critical condition. The recommendations formulated by the experts were validated by the working group with the purpose of harmonising red cell transfusion in Belgian hospitals.

Clinicians as gatekeepers: what is the best route to optimal blood use?

Maintaining the supply of allogeneic blood has always been a challenge and its optimal use difficult to ensure and monitor. Increasingly, economic pressures and public perceptions have been driving decision making in delivery of sufficient and safe blood components of high quality. On the other hand, many of the assumed benefits of allogenic blood component therapy are being questioned, and the potential hazards of transfusion have been underestimated. Indeed, recent evidence suggests that in many clinical settings there are significant under-recognised hazards of transfusion in which benefit is difficult to confirm. This paper questions the current paradigm, in which there is excessive focus on the supply side of the blood transfusion chain rather than the clinical problem facing patients and clinicians. Blood transfusion should no longer be the default therapeutic decision when evidence for efficacy is lacking and there is clinical uncertainty. The appropriateness of transfusion practices will only improve, not by expecting clinicians to be gatekeepers of the blood supply, but with better patient blood management based on a sound understanding of pathophysiology and better evidence for transfusion efficacy. Evidence-based transfusion medicine should view a patient's own blood as a valuable and unique natural resource that should be conserved and managed appropriately. Altruistically donated allogeneic blood transfusion should only be used as therapy when there is evidence for potential benefit, there are no alternatives, a quality product is available and the risks are appropriately considered and balanced against the benefits.

Therapeutic apheresis.

During the last 30 years in vivo blood cell separation, generally referred to apheresis, has established a central role in both blood donor programmes and therapeutics. The technological advances in apheresis equipment has made procedures safer, faster and more effective. This article will review the use of apheresis in clinical medicine with emphasis on plasma exchange and peripheral blood stem cell collection. Plasma exchange now has a pivotal role in the management of a range of disorders, specially those with autoimmune pathogenesis. However, Plasma exchange should be practised as one component of an integrated and frequently multidisciplinary approach to management. The harvesting of allogeneic or autologous of peripheral blood haemopoietic stem cells is increased and it has become the principle indication for apheresis in many haematology units. A well coordinated protocol approach to this procedure is important if adequate haemopoietic stems cells are to be collected and safely cyropreserved. This requires successful cooperation between medical, nursing and scientific personnel.