Treatment-specific risk of subsequent malignant neoplasms in five-year survivors of diffuse large B-cell lymphoma.

BACKGROUND: The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors. METHODS: Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression. RESULTS: After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin versus ≤2250 mg/m2/≤150 mg/m2, respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab. CONCLUSION: Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up for rituximab-treated patients.

Serum fatty acid chain length associates with prevalent symptomatic end-stage osteoarthritis, independent of BMI.

Higher body mass index (BMI) is associated with osteoarthritis (OA) in both weight-bearing and non-weight-bearing joints, suggesting a link between OA and poor metabolic health beyond mechanical loading. This risk may be influenced by systemic factors accompanying BMI. Fluctuations in concentrations of metabolites may mark or even contribute to development of OA. This study explores the association of metabolites with radiographic knee/hip OA prevalence and progression. A 1H-NMR-metabolomics assay was performed on plasma samples of 1564 cases for prevalent OA and 2,125 controls collected from the Rotterdam Study, CHECK, GARP/NORREF and LUMC-arthroplasty cohorts. OA prevalence and 5 to 10 year progression was assessed by means of Kellgren-Lawrence (KL) score and the OARSI-atlas. End-stage knee/hip OA (TJA) was defined as indication for arthroplasty surgery. Controls did not have OA at baseline or follow-up. Principal component analysis of 227 metabolites demonstrated 23 factors, of which 19 remained interpretable after quality-control. Associations of factor scores with OA definitions were investigated with logistic regression. Fatty acids chain length (FALen), which was included in two factors which associated with TJA, was individually associated with both overall OA as well as TJA. Increased Fatty Acid chain Length is associated with OA.

An international consensus statement on the management of postoperative anaemia after major surgical procedures.

Despite numerous guidelines on the management of anaemia in surgical patients, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in the postoperative period. A number of experienced researchers and clinicians took part in a two-day expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the postoperative period. These statements include: a diagnostic approach to iron deficiency and anaemia in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up that is easy to implement. Available data allow the fulfilment of the requirements of Pillar 1 of Patient Blood Management. We urge national and international research funding bodies to take note of these recommendations, particularly in terms of funding large-scale prospective, randomised clinical trials that can most effectively address the important clinical questions and this clearly unmet medical need.

Vox Sanguinis International Forum on the use of prehospital blood products and pharmaceuticals in the treatment of patients with traumatic haemorrhage.

While specific practices and transported blood products vary around the world, most of the respondents in this International Forum transported at least one blood product for the transfusion to bleeding patients en route to the hospital. The most commonly carried product was RBCs, while the use of whole blood will likely increase given the recent reports of its successful use in the civilian setting, and because of the change in the AABB's Standards regulating its use. It will be interesting to see if plasma use in the prehospital setting becomes more widely used given today's enhanced appreciated of the coagulopathy of trauma and plasma's beneficial effect in reversing it, and if blood products are transported to the scene of injury by more vehicles, that is, not just predominantly in helicopters. It was not surprising that TXA is being widely administered as close to the time of injury as possible given its potential benefit in these patients. This International Forum highlights the importance of focusing attention on prehospital transfusion management with a need to further high­quality research in this area to guide optimal resuscitation strategies.

Towards a systematic approach for (de)implementation of patient blood management strategies.

Despite the increasing availability of evidence in transfusion medicine literature, this evidence does not automatically find its way into practice. This is also applicable to patient blood management (PBM). It may concern the lack of implementation of effective new techniques or treatments, or it may apply to the (over)use of techniques and treatments (e.g. inappropriate transfusions) that have proven to be of limited benefit for patients (low-value care) and could be abandoned (de-implementation). In PBM literature, the implementation of restrictive transfusion thresholds and the de-implementation of inappropriate transfusions are described. However, most implementation strategies were not preceded by the identification of relevant barriers, and the used strategies were not often supported by literature on behavioural changes. In this article, we describe implementation vs de-implementation, highlight the current situation of (de)implementation in PBM and describe a systematic approach for (de)implementation illustrated by an example of a PBM de-implementation study regarding '(cost-) effective patient blood management in total hip and knee arthroplasty'. The systematic approach used for (de)implementation is based on the implementation model of Grol, which consists of the following five steps: the detection of improvement goals, a problem analysis, the selection of (de)implementation strategies, the execution of the (de)implementation strategy and an evaluation. Based on the description of the current situation and the experiences in our de-implementation study, we can conclude that de-implementation may be more difficult than expected as other factors may play a role in effective de-implementation compared to implementation.

International consensus statement on the peri-operative management of anaemia and iron deficiency.

Despite current recommendations on the management of pre-operative anaemia, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in surgical patients. A number of experienced researchers and clinicians took part in an expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the peri-operative period. These statements include: a diagnostic approach for anaemia and iron deficiency in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up. We urge anaesthetists and peri-operative physicians to embrace these recommendations, and hospital administrators to enable implementation of these concepts by allocating adequate resources.

Erythropoietin to reduce allogeneic red blood cell transfusion in patients undergoing total hip or knee arthroplasty.

BACKGROUND AND OBJECTIVES: To determine the value of erythropoietin in reducing allogeneic transfusions, it is important to assess the effects, safety and costs for individual indications. Previous studies neither compared the effects of erythropoietin between total hip and total knee arthroplasty, nor evaluated the safety or costs. We performed a meta-analysis to assess the effects of erythropoietin in total hip and knee arthroplasty separately. Safety and costs were evaluated as secondary outcomes. MATERIALS AND METHODS: A systematic literature search was performed to identify randomized controlled trials evaluating the effect of erythropoietin in total hip and knee arthroplasty until April 2014. Study data were extracted using standardized forms and pooled using a random-effects model. Strength of the evidence was evaluated using Cochrane's Collaboration's tool for risk of bias assessment. RESULTS: Seven studies were included (2439 patients). Erythropoietin significantly reduced exposure to allogeneic transfusion in both hip (RR 0·45; 95%CI 0·33-0·61) and knee (RR 0·38; 95%CI 0·27-0·53) arthroplasty, without differences between indications (P = 0·44). Mean number of transfused red blood cell units was significantly decreased in erythropoietin-treated patients (mean difference -0·57; 95%CI -0·86 to -0·29)(unable to split). No differences in thromboembolic or adverse events were found. Only one study evaluated costs, so that no pooled cost-effectiveness estimates could be given. CONCLUSION: Erythropoietin is effective in both hip and knee arthroplasty and can be considered as safe. However, the decision to use erythropoietin on a routine base should be balanced against its costs, which may be relatively high.

Patient acceptable symptom states after totalhip or knee replacement at mid-term follow-up: Thresholds of the Oxford hip and knee scores.

OBJECTIVES: To define Patient Acceptable Symptom State (PASS) thresholds for the Oxford hip score (OHS) and Oxford knee score (OKS) at mid-term follow-up. METHODS: In a prospective multicentre cohort study, OHS and OKS were collected at a mean follow-up of three years (1.5 to 6.0), combined with a numeric rating scale (NRS) for satisfaction and an external validation question assessing the patient's willingness to undergo surgery again. A total of 550 patients underwent total hip replacement (THR) and 367 underwent total knee replacement (TKR). RESULTS: Receiver operating characteristic (ROC) curves identified a PASS threshold of 42 for the OHS after THR and 37 for the OKS after TKR. THR patients with an OHS ≥ 42 and TKR patients with an OKS ≥ 37 had a higher NRS for satisfaction and a greater likelihood of being willing to undergo surgery again. CONCLUSIONS: PASS thresholds appear larger at mid-term follow-up than at six months after surgery. With- out external validation, we would advise against using these PASS thresholds as absolute thresholds in defining whether or not a patient has attained an acceptable symptom state after THR or TKR. Cite this article: Bone Joint Res 2014;3:7-13.

Hip and knee replacement patients prefer pen-and-paper questionnaires: Implications for future patient-reported outcome measure studies.

OBJECTIVES: Electronic forms of data collection have gained interest in recent years. In orthopaedics, little is known about patient preference regarding pen-and-paper or electronic questionnaires. We aimed to determine whether patients undergoing total hip (THR) or total knee replacement (TKR) prefer pen-and-paper or electronic questionnaires and to identify variables that predict preference for electronic questionnaires. METHODS: We asked patients who participated in a multi-centre cohort study investigating improvement in health-related quality of life (HRQoL) after THR and TKR using pen-and-paper questionnaires, which mode of questionnaire they preferred. Patient age, gender, highest completed level of schooling, body mass index (BMI), comorbidities, indication for joint replacement and pre-operative HRQoL were compared between the groups preferring different modes of questionnaire. We then performed logistic regression analyses to investigate which variables independently predicted preference of electronic questionnaires. RESULTS: A total of 565 THR patients and 387 TKR patients completed the preference question. Of the THR patients, 81.8% (95% confidence interval (CI) 78.4 to 84.7) preferred pen-and-paper questionnaires to electronic questionnaires, as did 86.8% (95% CI 83.1 to 89.8) of TKR patients. Younger age, male gender, higher completed level of schooling and higher BMI independently predicted preference of electronic questionnaires in THR patients. Younger age and higher completed level of schooling independently predicted preference of electronic questionnaires in TKR patients. CONCLUSIONS: The majority of THR and TKR patients prefer pen-and-paper questionnaires. Patients who preferred electronic questionnaires differed from patients who preferred pen-and-paper questionnaires. Restricting the mode of patient-reported outcome measures to electronic questionnaires might introduce selection bias. Cite this article: Bone Joint Res 2013;2:238-44.

A randomized comparison of transfusion triggers in elective orthopaedic surgery using leucocyte-depleted red blood cells.

OBJECTIVE: In elective orthopaedic hip- and knee replacement surgery patients, we studied the effect of implementation of a uniform transfusion policy on RBC usage. STUDY DESIGN AND METHODS: A randomized, controlled study. A new uniform, restrictive transfusion policy was compared with standard care, which varied among the three participating hospitals. Only prestorage leucocyte-depleted RBC(s) were used. Primary end-point was RBC usage, related to length of hospital stay. Secondary end-points were Hb levels, mobilization delay and postoperative complications. RESULTS: Six hundred and three patients were evaluated. Adherence to the protocol was over 95%. Overall mean RBC usage was 0.78 U/patient in the new policy group and 0.86 U/patient in the standard care policy group (mean difference 0.08;95% CI [-0.3; 0.2]; P = 0.53). In two hospitals, the new transfusion policy resulted in a RBC reduction of 30% (0.58U RBC/patient) (P = 0.17) and 41% (0.29 U RBC/patient) (P = 0.05) respectively. In the third hospital, however, RBC usage increased by 39% (0.31 U RBC/patient) (P = 0.02) with the new policy, due to a more restrictive standard care policy in that hospital. Length of hospital stay was not influenced by either policy. CONCLUSIONS: Implementation of a uniform transfusion protocol for elective lower joint arthroplasty patients is feasible, but does not always lead to a RBC reduction. Length of hospital stay was not affected.

Triggers and appropriateness of red blood cell transfusions in the postpartum patient--a retrospective audit.

BACKGROUND AND OBJECTIVE: Despite published guidelines, a proportion of red blood cell (RBC) transfusions seem unnecessary. To evaluate the indications for and the appropriateness of RBC transfusions in the postpartum patient, we performed a retrospective audit over a 1-year period in two Dutch hospitals. STUDY DESIGN AND METHODS: Observational study of transfused obstetric patients, admitted in 2006 to the Departments of Obstetrics of a university and a general hospital, was carried out. Relevant clinical and laboratory data were recorded. The appropriateness of RBC transfusions was assessed using the national and age-based transfusion guidelines for the general population; for the studied group the transfusion threshold haemoglobin (Hb) value was 6.4 g/dl for non-massive and 8.1 g/dl for massive blood loss. From these we derived target Hb levels. RESULTS: Ninety patients received one or more RBC units within 48 h of delivery. Mean pretransfusion Hb level was 6.9 [SD 1.2] g/dl. Median number of transfusions was 2. Mean Hb level at discharge was 9.7 [SD 1.1] g/dl. Taking threshold Hb and the derived target Hb level into account, 68% (n = 61) of the patients may have received one or more RBC units inappropriately. Of 311 RBC units transfused, 143 units (46%) were possibly inappropriate, partly due to over-transfusion. CONCLUSION: A significant proportion of postpartum RBC transfusions are possibly inappropriate, partly due to over-transfusion. If current guidelines would be more specific, in particular, with respect to the target Hb levels, the total amount of RBC transfusions may be considerably decreased.

Efficacy, safety and user-friendliness of two devices for postoperative autologous shed red blood cell re-infusion in elective orthopaedic surgery patients: A randomized pilot study.

To determine the safety, efficacy and user-friendliness of two different postoperative autologous blood re-infusion systems, an open, randomized, controlled study was performed. Eligible consecutive primary and revision total hip and knee replacement patients were randomized for one of the two systems or for a control group in which shed blood was not re-infused. The nursing staff scored user-friendliness. Patients were monitored after re-infusion. In all three patient groups, a restrictive transfusion trigger was used. Sixty-nine of 70 randomized patients were evaluated. Ease of use, efficacy and safety of both re-infusion systems were comparable. There was no difference in allogeneic blood use between the groups. Thirty per cent of the patients re-infused with autologous blood developed a mainly mild, febrile transfusion reaction. No other adverse reactions were seen. Signs of coagulopathy after re-infusion were not found. In multivariate analysis, autologous re-infusion was an independent factor associated with a shorter hospital stay. Both postoperative autologous blood re-infusion systems were of equal efficacy and safety. The contribution of autologous wound blood re-infusion to reduce allogeneic transfusions must be investigated in a larger study.