Post-prostatectomy adjuvant androgen deprivation therapy- Current opinions and practices of Canadian urologists.

INTRODUCTION: Despite the proven benefit of adjuvant androgen deprivation therapy (ADT) for patients receiving primary radiation, there are few studies evaluating adjuvant ADT after prostatectomy. In the absence of evidence, opinions and practice patterns vary. We surveyed Canadian prostate cancer surgeons about their use of adjuvant ADT and their opinions on the design of a potential adjuvant ADT trial. METHODS: An electronic survey was devised and distributed using a modified Dillman approach. The survey was sent to 38 Canadian urologists that perform radical prostatectomy and representing all 17 major academic institutions in Canada and all 10 Canadian provinces. Reminders were sent three and four weeks following the original request. In addition to demographic information, we asked surgeons about their current use of postoperative adjuvant ADT and their opinion about the need for a clinical trial. To inform trial design, we asked respondents their opinions about which patients should be eligible, what duration of ADT was most appropriate, and which outcomes are clinically meaningful. The survey was sent in February 2020 and all responses were received by March 2020. RESULTS: All 38 (100%) invited urologists completed the survey. Only 3 (7%) respondents currently offer postoperative adjuvant ADT as an option for patients without metastases. 35 (92%) urologists believed that a trial is needed before short-term adjuvant treatment should be offered to prevent recurrence. 15 (45%) urologists believed an adjuvant ADT trial was most appropriate for patients with an estimated PSA recurrence risk of >25% and 16 (42%) believed a recurrence risk of >50% was most appropriate. 25 (66%) respondents believed 12-month was the optimal duration of treatment with adjuvant ADT for a randomized trial. 37 (97%) respondents felt that prolonging the time to PSA recurrence and/or pelvic radiation was a clinically important outcome. The majority (20; 53%) of respondents would recommend 12 months of adjuvant ADT in their practice if a randomized trial showed a 50% relative risk reduction in PSA recurrence at 5-year postoperative. CONCLUSION: The vast majority of Canadian prostate cancer surgeons do not offer adjuvant ADT following prostatectomy in patients without metastases. Based on the results from this survey, a randomized trial was considered warranted and feasible, and would influence patient care.

Lysine analogue use during cancer surgery: a survey from a Canadian tertiary care centre.

Background: When used during surgery, antifibrinolytic hemostatic agents such as lysine analogues are effective at reducing blood loss and the need for transfusions. Despite proven efficacy, use of hemostatic agents remains low during some surgeries. Our objective was to explore surgeon opinions about, and use of lysine analogues in, oncologic surgeries at a large tertiary care academic institution. Methods: We administered a survey to surgeons who perform high-transfusion-risk oncologic surgeries at a large academic hospital in Ottawa, Ontario. Design and distribution of the survey followed a modified Dillman method. To ensure that the survey questionnaire was relevant, clear, and concise, we performed informant interviews, cognitive interviews, and pilot-testing. The final survey consisted of 19 questions divided into 3 sections: respondent demographics, use of hemostatic agents, and potential clinical trial opinions. Results: Of 28 surgeons, 24 (86%) participated. When asked to indicate the frequency of lysine analogue use, "never" accounted for 46% of the responses, and "rarely" (<10% of the time) accounted for 23% of the responses. Reasons for never using included "unfamiliar with benefits" and "prefer alternatives." Fifteen surgeons (63%) felt that a trial was needed to demonstrate the efficacy and safety of lysine analogues in their cancer field. Conclusions: Our survey found that lysine analogues are infrequently used during oncologic surgeries at our institution. Many surgeons are unfamiliar with the benefits and side effects of lysine analogues and, alternatively, use topical hemostatic agents. Our results demonstrate that future trials exploring the efficacy and safety of lysine analogues in oncologic surgery are needed.

A randomized trial of individualized versus standard of care antiemetic therapy for breast cancer patients at high risk for chemotherapy-induced nausea and vomiting.

PURPOSE: Despite triple antiemetic therapy use for breast cancer patients receiving emetogenic chemotherapy, nausea remains a clinical challenge. We evaluated adding olanzapine (5 mg) to triple therapy on nausea control in patients at high personal risk of chemotherapy-induced nausea and vomiting (CINV). METHODS: This multi-centre, placebo-controlled, double-blind trial randomized breast cancer patients scheduled to receive neo/adjuvant chemotherapy with anthracycline-cyclophosphamide or platinum-based chemotherapy to olanzapine (5 mg, days 1-4) or placebo. Primary endpoint was frequency of self-reported significant nausea, repeated for all cycles of chemotherapy. Secondary endpoints included: duration of nausea, overall total control of CINV, Health Related Quality of Life (HRQoL) using FLIE questionnaire, use of rescue mediation and treatment-related adverse events. RESULTS: 218 eligible patients were randomised to placebo (105) or olanzapine (113). From days 0-5 following each cycle of chemotherapy, 41.3% (95%CI: 36.1-46.7%) of patients in the placebo group reported significant nausea compared to 27.7% (95%CI: 23.2-32.4%) in the olanzapine group (p = 0.001). Across all cycles of chemotherapy, patients receiving olanzapine experienced a statistically significant improvement in HRQoL (p < 0.001). Grade 1/2 sedation was the most commonly side effect reported at 40.8% in the placebo group vs. 54.1% with olanzapine (p < 0.001). CONCLUSION: In patients at high personal risk of CINV, the addition of olanzapine 5 mg daily to standard antiemetic therapy significantly improves the control of nausea, HRQoL, with no unexpected toxicities.

A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer.

BACKGROUND: The optimal duration of filgrastim as primary febrile neutropenia (FN) prophylaxis in early breast cancer patients is unknown, with 5, 7 or 10 days being commonly prescribed. This trial evaluates whether 5 days of filgrastim was non-inferior to 7/10 days. PATIENTS AND METHODS: In this randomised, open-label trial, early breast cancer patients who were to receive filgrastim as primary FN prophylaxis were randomly allocated to 5 versus 7 versus 10 days of filgrastim for all chemotherapy cycles. A protocol amendment in November 2017 allowed subsequent patients (N = 324) to be randomised to either 5 or 7/10 days. The primary outcome was a composite of either FN or treatment-related hospitalisations. Secondary outcomes included chemotherapy dose reductions, delays and discontinuations. Analyses were carried out by per protocol (primary) and intention-to-treat, and the non-inferiority margin was set at 3% for the risk of having FN and/or hospitalisation per cycle of chemotherapy. RESULTS: Patients (N = 466) were randomised to receive 5 (184, 39.5%), or 7/10 (282, 60.5%) days of filgrastim. In our primary analysis, the difference in risk of either FN or treatment-related hospitalisation per cycle was -1.52% [95% confidence interval (CI): -3.22% to 0.19%] suggesting non-inferiority of a 5-day filgrastim schedule compared with 7/10-days. The difference in events per cycle for FN was 0.11% (95% CI: -1.05 to 1.27) while for treatment-related hospitalisations it was -1.68% (95% CI: -2.73% to -0.63%). The overall proportions of patients having at least one occurrence of either FN or treatment-related hospitalisation were 11.8% and 14.96% for the 5- and 7/10-day groups, respectively (risk difference: -3.17%, 95% CI: -9.51% to 3.18%). CONCLUSION: Five days of filgrastim was non-inferior to 7/10 days. Given the cost and toxicity of this agent, 5 days should be considered standard of care. CLINICALTRIALS. GOV REGISTRATION: NCT02428114 and NCT02816164.

Phlebotomy resulting in controlled hypovolaemia to prevent blood loss in major hepatic resections (PRICE-1): a pilot randomized clinical trial for feasibility.

BACKGROUND: Major liver resection is associated with blood loss and transfusion. Observational data suggest that hypovolaemic phlebotomy can reduce these risks. This feasibility RCT compared hypovolaemic phlebotomy with the standard of care, to inform a future multicentre trial. METHODS: Patients undergoing major liver resections were enrolled between June 2016 and January 2018. Randomization was done during surgery and the surgeons were blinded to the group allocation. For hypovolaemic phlebotomy, 7-10 ml per kg whole blood was removed, without intravenous fluid replacement. Co-primary outcomes were feasibility and estimated blood loss (EBL). RESULTS: A total of 62 patients were randomized to hypovolaemic phlebotomy (31) or standard care (31), at a rate of 3·1 patients per month, thus meeting the co-primary feasibility endpoint. The median EBL difference was -111 ml (P = 0·456). Among patients at high risk of transfusion, the median EBL difference was -448 ml (P = 0·069). Secondary feasibility endpoints were met: enrolment, blinding and target phlebotomy (mean(s.d.) 7·6(1·9) ml per kg). Blinded surgeons perceived that parenchymal resection was easier with hypovolaemic phlebotomy than standard care (16 of 31 versus 10 of 31 respectively), and guessed that hypovolaemic phlebotomy was being used with an accuracy of 65 per cent (20 of 31). There was no significant difference in overall complications (10 of 31 versus 15 of 31 patients), major complications or transfusion. Among those at high risk, transfusion was required in two of 15 versus three of nine patients (P = 0·326). CONCLUSION: Endpoints were met successfully, but no difference in EBL was found in this feasibility study. A multicentre trial (PRICE-2) powered to identify a difference in perioperative blood transfusion is justified. Registration number: NCT02548910 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La resección hepática mayor se asocia con pérdida de sangre y necesidad de transfusión. Datos observacionales sugieren que la flebotomía hipovolémica (hypovolaemic phlebotomy, HP) puede reducir estos riesgos. Este ensayo clínico aleatorizado (randomised clinical trial, RCT) de factibilidad comparó HP con el tratamiento estándar con el fin de proporcionar información para un futuro ensayo multicéntrico. MÉTODOS: Se reclutaron pacientes sometidos a resecciones hepáticas mayores entre junio 2016 y enero 2018. La aleatorización se realizó durante el intraoperatorio y los cirujanos eran ciegos al resultado de la asignación. Para la HP, se extrajeron 7-10 mL/kg de sangre total, sin reposición de líquidos intravenosos. Los resultados primarios fueron la factibilidad y la pérdida de sangre estimada (estimated blood loss, EBL). RESULTADOS: Un total de 62 pacientes se aleatorizaron a HP (n = 31) y a tratamiento estándar (n = 31), a un ritmo de 3,1 pacientes/mes, cumpliendo el co-objetivo primario de la factibilidad. La mediana de la diferencia de EBL fue 11 mL (P = 0,46). Entre los pacientes con alto riesgo de transfusión, la mediana de la diferencia de EBL fue 448 mL (P = 0,069). Los objetivos secundarios de factibilidad se consiguieron: reclutamiento (89%), cegamiento (98%), y objetivo de la flebotomía (7,6 ± 1,9 mL/kg). Los cirujanos que fueron cegados percibieron que la resección fue más fácil con la HP (52% versus 32%) y acertaron el uso de HP con una exactitud del 65%. No hubo diferencia significativa en las complicaciones globales (32% versus 48%), complicaciones mayores y transfusión. Entre aquellos pacientes de alto riesgo, la trasfusión se realizó en un 13% versus 33% (P = 0,33). CONCLUSIÓN: Se cumplieron los objetivos, pero no se identificó diferencia en EBL en este estudio de factibilidad. Ello justifica un ensayo multicéntrico (PRICE-2) con poder estadístico para identificar una diferencia en la transfusión de sangre perioperatoria.

The epidemiology of multicomponent blood transfusion: a systematic review.

We performed a systematic review to describe the prevalence of multicomponent blood transfusion and, as a secondary objective, to determine patient characteristics and outcomes associated with multicomponent transfusion. There is a lack of literature on the epidemiology of multicomponent transfusion as most studies concentrate on a single blood product and its utilisation. Patient care and blood management can be optimised by better understanding the patients who receive multicomponent transfusions. The databases Medline, EMBASE and the Cochrane Library of Systematic Reviews were searched. Observational cohort and cross-sectional studies of hospital patients reporting on multicomponent transfusion prevalence or on patient characteristics and outcomes associated with multicomponent transfusion were included. A descriptive synthesis of studies was performed. A total of 37 eligible studies were included. It was found that multicomponent transfusion prevalence varied greatly by patient population and by the combination of blood products given in the multicomponent transfusion. Multicomponent-transfused patients included burn, cardiac surgery, liver surgery and transplant, cancer, infectious diseases, trauma and intensive care unit patients. Five studies found associations between multicomponent transfusion and adverse health outcomes; however, these findings are likely confounded by indication. The overall quality of evidence was low given a fair-to-poor individual study quality, inconsistent multicomponent transfusion prevalence estimates and confounding by indication. Further research is needed to better understand the epidemiology of multicomponent transfusion, including studies on multicomponent transfusion in haematological cancer patients and studies looking for patient characteristics that can better predict multicomponent transfusion need.

The effect of surgery report cards on improving radical prostatectomy quality: the SuRep study protocol.

BACKGROUND: The goal of radical prostatectomy is to achieve the optimal balance between complete cancer removal and preserving a patient's urinary and sexual function. Performing a wider excision of peri-prostatic tissue helps achieve negative surgical margins, but can compromise urinary and sexual function. Alternatively, sparing peri-prostatic tissue to maintain functional outcomes may result in an increased risk of cancer recurrence. The objective of this study is to determine the effect of providing surgeons with detailed information about their patient outcomes through a surgical report card. METHODS: We propose a prospective cohort quasi-experimental study. The intervention is the provision of feedback to prostate cancer surgeons via surgical report cards. These report cards will be distributed every 3 months by email and will present surgeons with detailed information, including urinary function, erectile function, and surgical margin outcomes of their patients compared to patients treated by other de-identified surgeons in the study. For the first 12 months of the study, pre-operative, 6-month, and 12-month patient data will be collected but there will be no report cards distributed to surgeons. This will form the pre-feedback cohort. After the pre-feedback cohort has completed accrual, surgeons will receive quarterly report cards. Patients treated after the provision of report cards will comprise the post-feedback cohort. The primary comparison will be post-operative function of the pre-feedback cohort vs. post-feedback cohort. The secondary comparison will be the proportion of patients with positive surgical margins in the two cohorts. Outcomes will be stratified or case-mix adjusted, as appropriate. Assuming a baseline potency of 20% and a baseline continence of 70%, 292 patients will be required for 80% power at an alpha of 5% to detect a 10% improvement in functional outcomes. Assuming 30% of patients may be lost to follow-up, a minimum sample size of 210 patients is required in the pre-feedback cohort and 210 patients in the post-feedback cohort. DISCUSSION: The findings from this study will have an immediate impact on surgeon self-evaluation and we hypothesize surgical report cards will result in improved overall outcomes of men treated with radical prostatectomy.

Optimizing vascular access for patients receiving intravenous systemic therapy for early-stage breast cancer-a survey of oncology nurses and physicians.

Background: Despite advances in systemic therapy choices for patients with early-stage breast cancer, optimal practices for intravenous (IV) access remain unknown. That lack of knowledge holds particularly true for the use of central venous access devices (cvads) such as peripherally inserted central catheters (piccs) and implanted vascular access devices (ports). Methods: Using a survey of Canadian oncologists and oncology nurses responsible for the care of breast cancer patients, we evaluated current access practices, perceptions of complications, and perceptions of risk, and we estimated complication rates and evaluated perceived risk factors for lymphedema. Results: Survey responses were received from 25 physicians and 57 oncology nurses. Administration of trastuzumab or an anthracycline was associated with a higher likelihood of a cvad being recommended. Other factors associated with recommendation of a cvad included prior difficult IV access and a recommendation from the chemotherapy nurse. Although the complication rates perceived to be associated with the use of piccs and ports remained high, respondents felt that cvads might improve patient quality of life. Risk factors perceived to be associated with the risk of lymphedema were axillary lymph node dissection, radiation to the axilla, and line-associated infection. Factors known to be unrelated to lymphedema risk (specifically, blood draws and blood pressure measurement) continue to be perceived as posing a higher risk. Conclusions: Despite widespread use of chemotherapy for patients with breast cancer, the type of venous access used for treatment varies significantly, as do perceptions about the risks of cvad use and the risk for lymphedema development. Further prospective studies are needed to identify best-practice strategies.

Perceptions of vascular access for intravenous systemic therapy and risk factors for lymphedema in early-stage breast cancer-a patient survey.

Background: The choice of vascular access for systemic therapy administration in breast cancer remains an area of clinical equipoise, and patient preference is not consistently acknowledged. Using a patient survey, we evaluated the patient experience with vascular access during treatment for early-stage breast cancer and explored perceived risk factors for lymphedema. Methods: Patients who had received systemic therapy for early-stage breast cancer were surveyed at 2 Canadian cancer centres. Results: Responses were received from 187 patients (94%). The route of vascular access was peripheral intravenous line (IV) in 24%, a peripherally inserted central catheter (picc) in 42%, and a surgically inserted central catheter (port) in 34%. Anthracycline-based regimens were associated with a greater use of central vascular access devices (cvads- that is, a picc or port; 86/97, 89%). Trastuzumab use was associated with greater use of ports (49/64, 77%). Although few patients (7%) reported being involved in the decisions about vascular access, most were satisfied or very satisfied (88%) with their access type. Patient preference centred mainly on avoiding delays in the initiation of chemotherapy. Self-reported rates of complications (183 evaluable responses) were infiltration with peripheral IVs (9/44, 20%), local skin infections with piccs (7/77, 9%), and thrombosis with ports (4/62, 6%). Perceived risk factors for lymphedema included use of the surgical arm for blood draws (117/156, 75%) and blood pressure measurement (115/156, 74%). Conclusions: Most patients reported being satisfied with the vascular access used for their treatment. Improved education and understanding about the evidence-based requirements for vascular access are needed. Perceived risk factors for lymphedema remain variable and are not evidence-based.

Optimal sequence of adjuvant endocrine and radiation therapy in early-stage breast cancer - A systematic review.

IMPORTANCE: Clinical equipoise exists around the optimal time to start adjuvant endocrine therapy in patients who will receive post-operative radiotherapy for breast cancer. Concerns continue to exist regarding potential reduced efficacy, or increased toxicity, when radiation, and endocrine therapy are administered concurrently. OBJECTIVE: To perform a systematic review of studies comparing outcomes between sequential and concurrent adjuvant radiation and endocrine therapy in early-stage breast cancer. All modalities of radiation therapy were considered, and endocrine therapy could be either tamoxifen or an aromatase inhibitor. Outcomes of interest included; local, regional or distant recurrence, overall survival and treatment-related toxicities. EVIDENCE REVIEWED: PubMed, Ovid Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from 1946 to December 2017. Two reviewers independently assessed each citation using the criteria outlined above. Study quality was assessed using the Cochrane Collaboration's tool for prospective studies, and the Newcastle-Ottawa scale for retrospective studies. FINDINGS: Of 2137 unique citations identified, 13 met eligibility criteria. Eleven were unique studies (7569 patients), while 2 of the studies were updated analyses of previous studies. Studies evaluated the timing of adjuvant radiation, and tamoxifen (5 studies, 1550 patients), or aromatase inhibitors (6 studies, 6019 patients). We identified 1 complete randomized clinical trial (150 patients), and 5 retrospective studies (1580 patients), in addition to conference abstracts (5 studies, 5839 patients). Overall, none of the studies showed a significant difference in efficacy, or toxicity, with concurrent versus sequential treatment. However, given the significant heterogeneity of the study populations, it was not possible to conduct a meta-analysis. CONCLUSIONS AND RELEVANCE: In the absence of high quality data, adequately powered randomized trials are required to answer this important clinical question.

Cost implications of unwarranted imaging for distant metastasis in women with early-stage breast cancer in Ontario.

INTRODUCTION: Despite the publication of multiple evidence-based guidelines recommending against routine imaging for distant metastasis in patients with early-stage (i/ii) breast cancer, such imaging is frequently performed. The present retrospective cohort study was conducted to estimate the cost of unnecessary imaging tests in women with stage i and ii breast cancer diagnosed between 1 January 2007 and 31 December 2012 in Ontario. METHODS: We obtained patient-level demographic and tumour data from a large provincial dataset. The total cost of unwarranted imaging tests (in 2015 Canadian dollars) was considered to be equal to the sum of imaging costs incurred between 2007 and 2012 and was stratified by disease stage, imaging modality, and body site. RESULTS: Of the 26,547 identified patients with early-stage breast cancer, 22,811 (85.9%) underwent at least 1 imaging test, with an average of 3.7 tests per patient (3.2 for stage i patients and 4.0 for stage ii patients) over 5 years. At least 1 imaging test was performed in 79.6% of stage i and 92.7% of stage ii patients. During a 5-year period, the cost of unwarranted imaging in patients with early-stage breast cancer ranged from CA$4,418,139 to CA$6,865,856, depending on guideline recommendations. CONCLUSIONS: Our study highlights the substantial cost of excess imaging that could be saved and re-allocated to patient care if evidence-based guidelines are followed. Future studies should assess strategies to ensure that evidence-based guidelines are followed and to increase awareness of the cost implications of nonadherence to guidelines.

Persistency of Pseudomonas aeruginosa in sputum cultures and clinical outcomes in adult patients with cystic fibrosis.

Our objective was to describe the natural history of infection with transmissible and unique strains of P. aeruginosa (PA) in adult CF patients and to determine if clearance of PA from sputum was associated with an improvement in clinical status. This was a 3-year prospective cohort study of adult patients with CF. Sputum was collected at baseline and annually. Rate of decline of FEV1, BMI, exacerbation rate, and time to death or transplant were compared between patients who cleared PA versus those in whom PA was persistent. A total of 373 patients were included in the study, 75% were infected with PA at baseline; 24% were infected with transmissible strains and 51% with unique strains. Patients infected with unique strains were more likely to clear PA from their sputum over 3 years compared to those infected with transmissible strains (19% vs 10%, P=0.05). Declines in FEV1 and rates of pulmonary exacerbations, deaths, or lung transplants were not different between patients who cleared PA compared to those who remained persistently infected. No clinical benefit was identified in patients who cleared PA from sputum compared to those who remained persistently infected.

Detection, evaluation, and management of preoperative anaemia in the elective orthopaedic surgical patient: NATA guidelines.

Previously undiagnosed anaemia is common in elective orthopaedic surgical patients and is associated with increased likelihood of blood transfusion and increased perioperative morbidity and mortality. A standardized approach for the detection, evaluation, and management of anaemia in this setting has been identified as an unmet medical need. A multidisciplinary panel of physicians was convened by the Network for Advancement of Transfusion Alternatives (NATA) with the aim of developing practice guidelines for the detection, evaluation, and management of preoperative anaemia in elective orthopaedic surgery. A systematic literature review and critical evaluation of the evidence was performed, and recommendations were formulated according to the method proposed by the Grades of Recommendation Assessment, Development and Evaluation (GRADE) Working Group. We recommend that elective orthopaedic surgical patients have a haemoglobin (Hb) level determination 28 days before the scheduled surgical procedure if possible (Grade 1C). We suggest that the patient's target Hb before elective surgery be within the normal range, according to the World Health Organization criteria (Grade 2C). We recommend further laboratory testing to evaluate anaemia for nutritional deficiencies, chronic renal insufficiency, and/or chronic inflammatory disease (Grade 1C). We recommend that nutritional deficiencies be treated (Grade 1C). We suggest that erythropoiesis-stimulating agents be used for anaemic patients in whom nutritional deficiencies have been ruled out, corrected, or both (Grade 2A). Anaemia should be viewed as a serious and treatable medical condition, rather than simply an abnormal laboratory value. Implementation of anaemia management in the elective orthopaedic surgery setting will improve patient outcomes.

Cigarette smoking and suicidal behaviour: results from a 25-year longitudinal study.

BACKGROUND: This study examined the associations between cigarette smoking and suicidal ideation and suicide attempts, both before and after control for potentially confounding using fixed effects regression models. METHOD: Data were gathered during the Christchurch Health and Development Study, a 25-year longitudinal study of a birth cohort of New Zealand children (635 males, 630 females). The analysis was based on a sample of 1041 participants with available data on cigarette smoking and suicidal behaviour from ages 16 to 25 years. The main outcome measures were suicidal ideation and suicide attempts, ages 16-18, 18-21, and 21-25. RESULTS: There were significant bivariate associations between the frequency of cigarette smoking and both suicidal ideation and suicide attempts. Cohort members who smoked 20 or more cigarettes per day had odds of suicidal ideation that were 3.39 times (95% CI 2.06-5.59) those of non-smokers, and odds of suicide attempt that were 4.39 (95% CI 2.18-8.85) times those of non-smokers. Control for non-observed fixed confounding factors reduced the association between cigarette smoking and suicidal ideation and suicide attempts to statistical non-significance. After adjustment, those smoking more than 20 cigarettes per day had odds of suicidal ideation that were 1.00 times (95% CI 0.46-2.18) those of non-smokers, and odds of suicide attempt that were 1.84 (95% CI 0.81-4.18) times those of non-smokers. CONCLUSIONS: The findings suggest that the associations between frequency of cigarette smoking and suicidal behaviour may largely be explained by the non-observed background factors and life circumstances that are associated with both cigarette smoking and suicidal behaviour.

Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion.

BACKGROUND: Concerns regarding the safety of transfused blood have led to the development of a range of interventions to minimise blood loss during major surgery. Anti-fibrinolytic drugs are widely used, particularly in cardiac surgery and previous reviews have found them to be effective in reducing blood loss and the need for transfusion. Recently, questions have been raised regarding the comparative performance of the drugs and the safety of the most popular agent, aprotinin. OBJECTIVES: To assess the comparative effects of the anti-fibrinolytic drugs aprotinin, tranexamic acid (TXA), and epsilon aminocaproic acid (EACA) on blood loss during surgery, the need for red blood (RBC) transfusion, and adverse events, particularly vascular occlusion, renal dysfunction, and death. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE, and the internet. References in identified trials and review articles were checked and trial authors were contacted to identify any additional studies. The searches were last updated in July 2006. SELECTION CRITERIA: Randomised controlled trials (RCTs) of anti-fibrinolytic drugs in adults scheduled for non-urgent surgery. Eligible trials compared anti-fibrinolytic drugs with placebo (or no treatment), or with each other. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: This review summarises data from 211 RCTs that recruited 20,781 participants. Data from placebo/inactive controlled trials, and from head-to-head trials suggest an advantage of aprotinin over the lysine analogues TXA and EACA in terms of operative blood loss, but the differences were small. Aprotinin reduced the probability of requiring RBC transfusion by a relative 34% (relative risk [RR] 0.66, 95% confidence interval [CI] 0.61 to 0.71). The RR for RBC transfusion with TXA was 0.61 (95% CI 0.54 to 0.69) and it was 0.75 (95% CI 0.58 to 0.96) with EACA. When the pooled estimates from the head-to-head trials of the two lysine analogues were combined and compared to aprotinin alone, aprotinin appeared superior in reducing the need for RBC transfusion: RR 0.83 (95% CI 0.69 to 0.99). Aprotinin reduced the need for re-operation due to bleeding: RR 0.48 (95% CI 0.35 to 0.68). This translates into an absolute risk reduction of just under 3% and a number needed-to-treat (NNT) of 37 (95% CI 27 to 56). Similar trends were seen with TXA and EACA, but the data were sparse and the differences failed to reach statistical significance. The blood transfusion data were heterogeneous and funnel plots indicate that trials of aprotinin and the lysine analogues may be subject to publication bias. Evidence of publication bias was not observed in trials reporting re-operation rates. Adjustment for these effects reduced the magnitude of estimated benefits but did not negate treatment effects. However, the apparent advantage of aprotinin over the lysine analogues was small and may be explained by publication bias and non-equivalent drug doses. Aprotinin did not increase the risk of myocardial infarction (RR 0.92, 95% CI 0.72 to 1.18), stroke (RR 0.76, 95% CI 0.35 to 1.64) renal dysfunction (RR 1.16, 95% CI 0.79 to 1.70) or overall mortality (RR 0.90, 95% CI 0.67 to 1.20). The analyses of myocardial infarction and death included data from the majority of subjects recruited into the clinical trials of aprotinin. However, under-reporting of renal events could explain the lack of effect seen with aprotinin. Similar trends were seen with the lysine analogues but data were sparse. These results conflict with the results of recently published non-randomised studies. AUTHORS' CONCLUSIONS: Anti-fibrinolytic drugs provide worthwhile reductions in blood loss and the need for allogeneic red cell transfusion. Based on the results of randomised trials their efficacy does not appear to be offset by serious adverse effects. In most circumstances the lysine analogues are probably as effective as aprotinin and are cheaper; the evidence is stronger for tranexamic acid than for aminocaproic acid. In high risk cardiac surgery, where there is a substantial probability of serious blood loss, aprotinin may be preferred over tranexamic acid. Aprotinin does not appear to be associated with an increased risk of vascular occlusion and death, but the data do not exclude an increased risk of renal failure. There is no need for further placebo-controlled trials of aprotinin or lysine analogues in cardiac surgery. The principal need is for large comparative trials to assess the relative efficacy, safety and cost-effectiveness of anti-fibrinolytic drugs in different surgical procedures.

Cell salvage for minimising perioperative allogeneic blood transfusion.

BACKGROUND: Concerns regarding the safety of transfused blood, have prompted reconsideration of the use of allogeneic (blood from an unrelated donor) red blood cell (RBC) transfusion, and a range of techniques to minimise transfusion requirements. OBJECTIVES: To examine the evidence for the efficacy of cell salvage in reducing allogeneic blood transfusion and the evidence for any effect on clinical outcomes. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Current Contents and the websites of international health technology assessment agencies. The reference lists in identified trials and review articles were also searched, and study authors were contacted to identify additional studies. The searches were updated in January 2004. SELECTION CRITERIA: Controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to cell salvage, or to a control group, who did not receive the intervention. DATA COLLECTION AND ANALYSIS: Two authors independently screened search results, extracted data and assessed methodological quality. The main outcomes measures were the number of patients exposed to allogeneic red cell transfusion, and the amount of blood transfused. Other outcomes measured were re-operation for bleeding, blood loss, post-operative complications (thrombosis, infection, non-fatal myocardial infarction, renal failure), mortality, and length of hospital stay (LOS). MAIN RESULTS: Overall, the use of cell salvage reduced the rate of exposure to allogeneic RBC transfusion by a relative 39% (relative risk [RR] = 0.61: 95% confidence interval [CI] 0.52 to 0.71). The absolute reduction in risk (ARR) of receiving an allogeneic RBC transfusion was 23% (95% CI 16% to 30%). In orthopaedic procedures the RR of exposure to RBC transfusion was 0.42 (95% CI 0.32 to 0.54) compared to 0.77 (95% CI 0.68 to 0.87) for cardiac procedures. The use of cell salvage resulted in an average saving of 0.67 units of allogeneic RBC per patient (weighted mean difference was -0.64; 95% CI -0.89 to -0.45). Cell salvage did not appear to impact adversely on clinical outcomes. AUTHORS' CONCLUSIONS: The results suggest cell salvage is efficacious in reducing the need for allogeneic red cell transfusion in adult elective surgery. However, the methodological quality of trials was poor. As the trials were unblinded and lacked adequate concealment of treatment allocation, transfusion practices may have been influenced by knowledge of the patients' treatment status biasing the results in favour of cell salvage.