A prospective observational study of preoperative natriuretic peptide testing in adult non-cardiac surgical patients in hospitals in Western Cape Province, South Africa.

BACKGROUND: International guidelines recommend risk stratification to identify high-risk non-cardiac surgical patients. It is also recommended that all patients aged ≥45 years with significant cardiovascular disease should have preoperative natriuretic peptide (NP) testing. Abnormal preoperative B-type NPs have a strong association with postoperative cardiac complications. In South African hospitals, it is not known how many patients with significant cardiovascular disease scheduled for intermediate- to high-risk surgery will have raised NPs. OBJECTIVES: To determine the prevalence of abnormal (raised) NPs in non-cardiac surgical patients with cardiac clinical risk factors. A secondary objective was to develop a model to identify surgical patients who may benefit from preoperative NP screening. METHODS: The inclusion criteria were patients aged ≥45 years presenting for elective, non-obstetric, intermediate- to high-risk non-cardiac surgery with at least one of the following cardiovascular risk factors: a history of ischaemic heart disease or peripheral vascular disease (coronary equivalent); a history of stroke or transient ischaemic attack; a history of congestive cardiac failure; diabetes mellitus currently on an oral hypoglycaemic agent or insulin; and serum creatinine level >175 µmol/L (>2.0 mg/dL). Blood samples for N-terminal-prohormone B-type NP (NT-proBNP) were collected before induction of anaesthesia. The preoperative prognostic threshold for abnormal (raised) NT-proBNP was ≥300 pg/mL. A generalised linear mixed model was used to determine the association between the risk factors and an abnormal NT-proBNP level. RESULTS: Of 172 patients, 63 (37%) had an elevated preoperative NT-proBNP level. The comorbidities independently associated with elevated preoperative NT-proBNP were coronary artery disease or peripheral vascular disease, congestive cardiac failure, and a creatinine level >175 µmol/L CONCLUSIONS: We strongly recommend that non-cardiac surgical patients aged ≥45 years undergoing intermediate- or high-risk noncardiac surgery with a history of coronary artery disease/peripheral vascular disease, congestive cardiac failure or elevated creatinine have preoperative NP testing as part of risk stratification.

Weight-adjusted tinzaparin for venous thromboembolism prophylaxis in bariatric surgery patients weighing 160 kg or more.

INTRODUCTION: Bariatric surgery patients experience an increased risk of venous thromboembolism (VTE), however, the optimal dose of low-molecular-weight heparin for VTE prophylaxis remains uncertain. Currently, St. Joseph's Healthcare Hamilton utilizes a weight-adjusted tinzaparin dosage (50 to 75 units/kg rounded to nearest pre-filled syringe) for postoperative VTE prophylaxis. OBJECTIVES: This study analyzed the safety of weight-adjusted tinzaparin for VTE prophylaxis in bariatric surgery patients weighing ≥160 kg. METHODS: This was a retrospective study involving patients weighing ≥160 kg that underwent bariatric surgery from September 2015 to September 2019. Patients received a single dose of weight-adjusted subcutaneous unfractionated heparin (UFH) [5000 or 7500 IU] immediately prior to surgery, subcutaneous UFH [5000 IU, 7500 IU, or unspecified] immediately postoperatively, and either 10,000 or 14,000 IU of tinzaparin, beginning on the day after surgery, for 10 days. Intra-operative sequential compression devices could be used at the attending surgeon's discretion. Occurrence of VTE and major bleeding within 30 days of surgery were assessed. RESULTS: A total of 389 patients were included for analysis, all patients received in-hospital follow-up while 349 patients had also 30-day follow-up. For the primary safety and efficacy analysis of in-hospital events, VTE and major bleeding rates were 0.26% [95% CI 0.01%-1.44%] (1/389) and 0.77% [95% CI 0.21%-2.24%] (3/389) respectively. For patients with 30-day follow-up VTE and major bleeding rates were 0.57% [95% CI 0.1%-2.07%] (2/349) and 1.43% [95% CI 0.61%-3.3%] (5/349) respectively. CONCLUSIONS: Weight-adjusted tinzaparin was associated with a low risk of bleeding and VTE events, supporting its use for VTE prophylaxis for patients weighing ≥160 kg.

Predictors of mortality following shoulder arthroplasty.

INTRODUCTION: This study aims to determine 30-day, 90-day and 1 year mortality following shoulder arthroplasty and identify predictors of mortality. MATERIALS AND METHODS: All shoulder arthroplasty cases performed at the host institution, between 2012 and 2018 were included. A review of patient records was completed to identify demographic data, Charlson comorbidity index, date of death and factors associated with mortality.Mortality analysis was undertaken using 1-Kaplan Meier estimates with 95% confidence intervals. Comparative analysis was performed for mortality following shoulder arthroplasty for elective vs. trauma and for primary vs. revision surgery. A multiple regression analysis was conducted to determine which factors were associated with increased mortality risk. RESULTS: 640 shoulder arthroplasty cases were performed in 566 patients. There were 44 deaths, 1 occurred within 90 days and 13 within 1 year. Trauma procedures had a hazard ratio of 5.3 (95% CI 1.9 to 15.0) for mortality compared to elective procedures (5 year survival trauma 78.6% (95% CI 60.7 to 89.0); elective 91.8% (95% CI 88.1 to 94.4). 1-year mortality was predicted by presence of malignancy, liver failure, cardiac failure, peptic ulcer, trauma surgery, revision surgery, intra-operative complication, transfusion and increased length of stay. DISCUSSION: 30-day, 90-day and 1-year mortality following shoulder arthroplasty were 0%, 0.16% and 2%; trauma procedures had a hazard ratio of 5.3 for 1-year mortality when compared to elective surgery. Malignancy, cardiac failure, liver failure, peptic ulcer and trauma surgery are associated with an increased risk of 1-year mortality.

Extended venous thromboembolism prophylaxis after abdominopelvic cancer surgery: a retrospective review.

Objective: Extended prophylaxis against venous thromboembolism (vte) after abdominal or pelvic cancer surgery with low molecular weight heparin (lmwh) is recommended by multiple guidelines. The primary objective of the present study was to assess adherence to that guideline recommendation at tertiary care centres within Hamilton Health Sciences (hhs). Methods: Given that an estimated 70% of the study population would be expected to receive extended prophylaxis, a sample size of 105 patients was calculated. Patients who had undergone abdominal or pelvic surgery for cancer from March 2012 to December 2015 were identified, and data were collected from electronic health records. The primary outcome was prescription of extended vte prophylaxis. Results: Of 105 patients, only 3 received extended vte prophylaxis. Those 3 patients had serous carcinoma of the uterus, transitional cell carcinoma of the bladder, and cecal cancer. Of the 3 patients, 2 were followed by the thrombosis service while in hospital; none of the other 102 patients received any form of extended vte prophylaxis. Conclusions: Based on multiple randomized controlled trials, guidelines suggest lmwh prophylaxis for up to 4 weeks after major abdominal or pelvic cancer surgery. Despite those recommendations, postoperative extended vte prophylaxis is not commonly prescribed at hhs facilities. Next steps will include identification of barriers and an examination of how those barriers could be addressed. Failure to use prophylaxis is not consistent with evidence-based guidelines and is placing patients at risk of vte.

Treatment algorithm in cancer-associated thrombosis: Canadian expert consensus.

Management of anticoagulant therapy for the treatment of venous thromboembolism (vte) in cancer patients is complex because of an increased risk of recurrent vte and major bleeding complications in those patients relative to the general population. Subgroups of patients with cancer also show variation in their risk for recurrent vte and adverse bleeding events. Accordingly, a committee of 10 Canadian clinical experts developed the consensus risk- stratification treatment algorithm presented here to provide guidance on tailoring anticoagulant treatment choices for the acute and extended treatment of symptomatic and incidental vte, to prevent recurrent vte, and to minimize the bleeding risk in patients with cancer. During a 1-day live meeting, a systematic review of the literature was performed, and a draft treatment algorithm was developed. The treatment algorithm was refined through the use of a Web-based platform and a series of online teleconferences. Clinicians using this treatment algorithm should consider the bleeding risk, the type of cancer, and the potential for drug-drug interactions in addition to informed patient preference in determining the most appropriate treatment for patients with cancer-associated thrombosis. Anticoagulant therapy should be regularly reassessed as the patient's cancer status and management change over time.

Weight-adjusted tinzaparin for the prevention of venous thromboembolism after bariatric surgery.

Essentials The optimal dose and duration of thromboprophylaxis after bariatric surgery are unclear. We evaluated the safety of weight-adjusted tinzaparin prophylaxis in 1212 patients. In-hospital rates of venous thromboembolism and major bleeding were 0.2% and 1.8% respectively. In a sub-set of patients, trough anti-Xa levels did not show excessive anticoagulant activity. SUMMARY: Background Patients undergoing bariatric surgery are at moderate to high risk of venous thromboembolism (VTE). The optimal dose and duration of anticoagulant prophylaxis is uncertain. Objective To evaluate the safety of extended-duration weight-adjusted tinzaparin after bariatric surgery. Patients/methods We conducted a single-center retrospective cohort study of consecutive patients undergoing bariatric surgery who received weight-adjusted tinzaparin 4500-14 000 IU daily (75 IU kg-1 rounded to the nearest prefilled syringe) for 10 days after surgery (7-9 days post-hospital discharge). Primary safety outcomes were the frequency of VTE and major bleeding within 30 days of surgery in patients receiving at least one dose of tinzaparin. Results A total of 1279 patients undergoing bariatric surgery between July 2009 and December 2012 were reviewed, of whom 1212 received weight-adjusted tinzaparin. Safety outcomes were collected for 819 patients at 30 days, and for 1212 patients in-hospital only. The median age was 45.0 years, median weight was 130.0 kg and 98.8% of patients underwent gastric bypass or sleeve gastrectomy. In patients completing 30 days of follow-up, VTE occurred in 4/819 (0.5%) and major bleeding occurred in 13/819 patients (1.6%). In-hospital rates of VTE and major bleeding during surgical admission were 3/1212 (0.2%) and 22/1212 (1.8%), respectively. Conclusions Extended thromboprophylaxis with weight-adjusted tinzaparin appears to be a safe strategy after bariatric surgery, with low rates of postoperative VTE and major bleeding.

A multicentre, cross-sectional study investigating the prevalence of hypertensive disease in patients presenting for elective surgery in the Western Cape Province, South Africa.

BACKGROUND: Hypertension is common, affecting over one billion people worldwide. In sub-Saharan Africa, hypertensive disease not only affects the older population but is becoming increasingly prevalent in younger individuals. In South Africa (SA), >30% of the adult population has hypertension, making it the single most common cardiovascular risk factor and the predominant contributor to cardiovascular disease and mortality. Elevated blood pressure is the most common perioperative comorbidity encountered in non-cardiac surgical patients, with an overall prevalence of 20 - 25%, and it remains poorly controlled in low- and middle-income countries. Hypertension in the perioperative setting may adversely affect patient outcome. It therefore not only flags possible perioperative challenges to anaesthesiologists, but also identifies patients at risk of long-term morbidity and mortality. OBJECTIVES: To determine the prevalence and severity of hypertension in elective adult surgical patients in the Western Cape Province, SA. RESULTS: The study population included all elective surgical patients from seven hospitals in the Western Cape during a 1-week period. Hypertension, defined as having had a previous diagnosis of hypertension or meeting the blood pressure criteria of >140/90 mmHg, was identified in 51.8% of patients during preoperative assessment. Significantly, newly diagnosed hypertension was present in 9.9% of all patients presenting for elective surgery. Although 98.1% of the known hypertensive patients were on antihypertensive therapy, 36.9% were inadequately controlled. There are numerous reasons for this, but notably 32.1% of patients admitted to forgetting to take their medication, making patient factors the most common reason for treatment non-compliance. CONCLUSIONS: The perioperative period may be an important opportunity to identify undiagnosed hypertensive patients. The perioperative encounter may have a significant public health implication in facilitating appropriate referral and treatment of patients with hypertension to decrease long-term cardiovascular complications in SA.

The relationship between pre-operative hypertension and intra-operative haemodynamic changes known to be associated with postoperative morbidity.

Hypertension is not consistently associated with postoperative cardiovascular morbidity and is therefore not considered a major peri-operative risk factor. However, hypertension may predispose to peri-operative haemodynamic changes known to be associated with peri-operative morbidity and mortality, such as intra-operative hypotension and tachycardia. The objective of this study was to determine whether pre-operative hypertension was independently associated with haemodynamic changes known to be associated with adverse peri-operative outcomes. We performed a five-day multicentre, prospective, observational cohort study which included all adult inpatients undergoing elective, non-cardiac, non-obstetric surgery. We recruited 343 patients of whom 164 (47.8%) were hypertensive. An intra-operative mean arterial pressure of < 55 mmHg occurred in 59 (18.2%) patients, of which 25 (42.4%) were hypertensive. Intra-operative tachycardia (heart rate> 100 beats.min-1 ) occurred in 126 (38.9%) patients, of whom 61 (48.4%) were hypertensive. Multivariable logistic regression did not show an independent association between the stage of hypertension and either clinically significant hypotension or tachycardia, when controlled for ASA physical status, functional status, major surgery, duration of surgery or blood transfusion. There was no association between pre-operative hypertension and peri-operative haemodynamic changes known to be associated with major morbidity and mortality. These data, therefore, support the recommendation of the Joint Guidelines of the Association of Anaesthetists of Great Britain and Ireland (AAGBI) and the British Hypertension Society to proceed with elective surgery if a patient's blood pressure is < 180/110 mmHg.

Adjusting for treatment switching in randomised controlled trials - A simulation study and a simplified two-stage method.

Estimates of the overall survival benefit of new cancer treatments are often confounded by treatment switching in randomised controlled trials (RCTs) - whereby patients randomised to the control group are permitted to switch onto the experimental treatment upon disease progression. In health technology assessment, estimates of the unconfounded overall survival benefit associated with the new treatment are needed. Several switching adjustment methods have been advocated in the literature, some of which have been used in health technology assessment. However, it is unclear which methods are likely to produce least bias in realistic RCT-based scenarios. We simulated RCTs in which switching, associated with patient prognosis, was permitted. Treatment effect size and time dependency, switching proportions and disease severity were varied across scenarios. We assessed the performance of alternative adjustment methods based upon bias, coverage and mean squared error, related to the estimation of true restricted mean survival in the absence of switching in the control group. We found that when the treatment effect was not time-dependent, rank preserving structural failure time models (RPSFTM) and iterative parameter estimation methods produced low levels of bias. However, in the presence of a time-dependent treatment effect, these methods produced higher levels of bias, similar to those produced by an inverse probability of censoring weights method. The inverse probability of censoring weights and structural nested models produced high levels of bias when switching proportions exceeded 85%. A simplified two-stage Weibull method produced low bias across all scenarios and provided the treatment switching mechanism is suitable, represents an appropriate adjustment method.

Clinical challenges in patients with cancer-associated thrombosis: Canadian expert consensus recommendations.

Venous thromboembolism is a common complication in cancer patients, and thromboembolism is the second most common cause of death after cancer progression. A number of clinical practice guidelines provide recommendations for the management of cancer-associated thrombosis. However, the guidelines lack recommendations covering commonly encountered clinical challenges (for example, thrombocytopenia, recurrent venous thromboembolism, etc.) for which little or no evidence exists. Accordingly, recommendations were developed to provide expert guidance to medical oncologists and other health care professionals caring for patients with cancer-associated thrombosis. The current expert consensus was developed by a team of 21 clinical experts. For each identified clinical challenge, the literature in medline, embase, and Evidence Based Medicine Reviews was systematically reviewed. The quality of the evidence was assessed, summarized, and graded. Consensus statements were generated, and the experts voted anonymously using a modified Delphi process on their level of agreement with the various statements. Statements were progressively revised through separate voting iterations and were then finalized. Clinicians using these recommendations and suggestions should tailor patient management according to the risks and benefits of the treatment options, patient values and preferences, and local cost and resource allocations.

Open reduction and plate fixation versus nonoperative treatment for displaced midshaft clavicular fractures: a multicenter, randomized, controlled trial.

BACKGROUND: There is a growing trend to treat displaced midshaft clavicular fractures with primary open reduction and plate fixation; whether such treatment results in improved patient outcomes is debatable. The aim of this multicenter, single-blinded, randomized controlled trial was to compare union rates, functional outcomes, and economic costs for displaced midshaft clavicular fractures that were treated with either primary open reduction and plate fixation or nonoperative treatment. METHODS: In a prospective, multicenter, stratified, randomized controlled trial, 200 patients between sixteen and sixty years of age who had an acute displaced midshaft clavicular fracture were randomized to receive either primary open reduction and plate fixation or nonoperative treatment. Functional assessment was conducted at six weeks, three months, six months, and one year with use of the Disabilities of the Arm, Shoulder and Hand (DASH) and Constant scores. Union was evaluated with use of three-dimensional computed tomography. Complications were recorded, and an economic evaluation was performed. RESULTS: The rate of nonunion was significantly reduced after open reduction and plate fixation (one nonunion) as compared with nonoperative treatment (sixteen nonunions) (relative risk = 0.07; p = 0.007). Group allocation to nonoperative treatment was independently predictive of the development of nonunion (p = 0.0001). Overall, DASH and Constant scores were significantly better after open reduction and plate fixation than after nonoperative treatment at the time of the one-year follow-up (DASH score, 3.4 versus 6.1 [p = 0.04]; Constant score, 92.0 versus 87.8 [p = 0.01]). However, when patients with nonunion were excluded from analysis, there were no significant differences in the Constant scores or DASH scores at any time point. Patients were less dissatisfied with symptoms of shoulder droop, local bump at the fracture site, and shoulder asymmetry in the open reduction and plate fixation group (p < 0.0001). The cost of treatment was significantly greater after open reduction and plate fixation (p < 0.0001). CONCLUSIONS: Open reduction and plate fixation reduces the rate of nonunion after acute displaced midshaft clavicular fracture compared with nonoperative treatment and is associated with better functional outcomes. However, the improved outcomes appear to result from the prevention of nonunion by open reduction and plate fixation. Open reduction and plate fixation is more expensive and is associated with implant-related complications that are not seen in association with nonoperative treatment. The results of the present study do not support routine primary open reduction and plate fixation for the treatment of displaced midshaft clavicular fractures.

FcγRIIa proteolysis as a diagnostic biomarker for heparin-induced thrombocytopenia.

BACKGROUND: A significant challenge in the management of heparin-induced thrombocytopenia (HIT) patients is making a timely and accurate diagnosis. The readily available enzyme immunoassays (EIAs) have low specificities. In contrast, platelet activation assays have higher specificities, but they are technically demanding and not widely available. In addition, ~ 10% of samples referred for HIT testing are initially classified as indeterminate by the serotonin release assay (SRA), which further delays accurate diagnosis. HIT is characterized by platelet activation, which leads to FcγRIIa proteolysis. This raises the possibility that identification of the proteolytic fragment of FcγRIIa could serve as a surrogate marker for HIT. OBJECTIVES: To determine the specificity of platelet FcγRIIa proteolysis induced by sera from patients with HIT, and to correlate the results with those of the SRA. METHODS/PATIENTS: Sera from HIT patients and control patients with other thrombocytopenic/prothrombotic disorders were tested for their ability to proteolyse FcγRIIa. The results were correlated with anti-platelet factor 4 (PF4)/heparin antibodies (EIA), and heparin-dependent platelet activation (SRA). RESULTS: Only HIT patient samples (20/20) caused heparin-dependent FcγRIIa proteolysis, similar to what was shown by the SRA. None of the samples from the other patient groups or hospital controls caused FcγRIIa proteolysis. Among nine additional samples that tested indeterminate in the SRA, FcγRIIa proteolysis resolved five samples that had a positive anti-PF4/heparin EIA result; three had no FcγRIIa proteolysis, and two were shown to have heparin-dependent FcγRIIa proteolysis CONCLUSIONS: This study suggests that heparin-dependent FcγRIIa proteolysis is at least as specific as the SRA for the diagnosis of HIT.

Should relative survival be used with lung cancer data?

BACKGROUND: Under certain assumptions, relative survival is a measure of net survival based on estimating the excess mortality in a study population when compared with the general population. Background mortality estimates are usually taken from national life tables that are broken down by age, sex and calendar year. A fundamental assumption of relative survival methods is that if a patient did not have the disease of interest then their probability of survival would be comparable to that of the general population. It is argued, as most lung cancer patients are smokers and therefore carry a higher risk of smoking-related mortalities, that they are not comparable to a population where the majority are likely to be non-smokers. METHODS: We use data from the Finnish Cancer Registry to assess the impact that the non-comparability assumption has on the estimates of relative survival through the use of a sensitivity analysis. RESULTS: Under realistic estimates of increased all-cause mortality for smokers compared with non-smokers, the bias in the estimates of relative survival caused by the non-comparability assumption is negligible. CONCLUSION: Although the assumption of comparability underlying the relative survival method may not be reasonable, it does not have a concerning impact on the estimates of relative survival, as most lung cancer patients die within the first 2 years following diagnosis. This should serve to reassure critics of the use of relative survival when applied to lung cancer data.

What is the clinical effectiveness and cost-effectiveness of using drugs in treating obese patients in primary care? A systematic review.

BACKGROUND: Obesity [defined as a body mass index (BMI) ≥ 30 kg/m(2)] represents a considerable public health problem and is associated with a significant range of comorbidities and an increased mortality risk. The primary aim of the management of obesity is to achieve weight reduction in the interests of health. For obese patients who cannot achieve or maintain a healthy weight by non-pharmacological means, drug therapy is recommended in combination with non-pharmacological interventions such as dietary modifications and exercise. OBJECTIVE: To evaluate the clinical effectiveness and cost-effectiveness of three pharmacological interventions in obese patients. DATA SOURCES: Clinical effectiveness data used in the meta-analysis were sourced from articles identified in a systematic review of the literature. Data used to inform transitions to obesity-related comorbidities were derived from the General Practice Research Database (GPRD). The results of the meta-analysis and GPRD analyses informed the economic model supplemented by data from the Health Survey for England and other UK-specific data sourced from the literature. REVIEW METHODS: A systematic literature review was conducted of the clinical effectiveness and cost-effectiveness of orlistat, sibutramine and rimonabant within their licensed indications for the treatment of obese patients. Electronic bibliographic databases including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases and Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched in January 2009, and the reference lists of relevant articles were checked. Studies were included if they compared orlistat, sibutramine or rimonabant with lifestyle and/or exercise advice (standard care), placebo or metformin. RESULTS: Overall, 94 studies involving 24,808 individuals were included in the clinical meta-analysis. Eighty-three trials included data on weight change, 41 included data on BMI change and 45 and 36 studies reported on 5% and 10% body weight loss, respectively. Overall, the results show that the active drug interventions are all effective at reducing weight and BMI compared with placebo. In the case of sibutramine, the higher dose (15 mg) resulted in a greater reduction than the lower dose (10 mg). Generally, the data quality of the trials included was low with poor reporting of standard errors and standard deviations. Results from the BMI risk models derived from the GPRD showed consistent increases in risk with increasing BMI. Adjustments for key confounders, such as age, sex and smoking status, were found to be statistically significant at the 5% level, in all risk models. Applying linear models to estimate BMI trajectories, for the diabetic cohort, an average increase in BMI of 0.040 per year for both men and women was observed. The non-diabetic cohort model showed an increase in BMI of 0.175 per year for women and 0.145 per year for men. The results of the cost-effectiveness analyses suggest that sibutramine 15 mg dominates the other three active interventions and the net benefit analyses show that sibutramine 15 mg is the most cost-effective alternative for thresholds > £2000 per quality-adjusted life-year (QALY). However, both sibutramine and rimonabant have been withdrawn because of safety concerns relating to potential treatment-induced fatal adverse events. If the proportion of patients who experienced a fatal adverse event was > 1.8% (1.5%, 1.0%) for sibutramine 15 mg (sibutramine 10 mg, rimonabant) the treatment would not be considered cost-effective when using a threshold of £20,000 per QALY. LIMITATIONS: The clinical review did not include all possible lifestyle comparators, with the inclusion limited to only those trials included one of the active drug interventions. We also excluded all studies not reported in English. Although the clinical review included data from 94 studies, the quality of data was generally low, particularly in terms of the reporting of standard deviation. There was also inconsistency between the results of the mixed-treatment comparison (MTC) and the pair-wise analyses. CONCLUSION: The MTC of anti-obesity treatments shows that all the active treatments are effective at reducing weight and BMI. The economic results show that, compared with placebo, the treatments are all cost-effective when using a threshold of £20,000 per QALY, and, within the limitations of the data available, sibutramine 15 mg dominates the other three interventions. This work has highlighted many areas of methodological research that could be explored, including assessing inconsistencies within a network to determine differences between the results of pair-wise and MTC analyses; the use of meta-regression methods to look for effect modifiers; exploring the effect of local publication bias; and the use of joint models to analyse the repeated measures of BMI and the time-to-event processes simultaneously. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Eltrombopag for the treatment of chronic idiopathic (immune) thrombocytopenic purpura (ITP).

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of eltrombopag for the treatment of adults with chronic idiopathic (immune) thrombocytopenic purpura (ITP), based on a review of the manufacturer's submission (MS) to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. ITP is an autoimmune disorder by which antibodies are formed against platelets with annual incidence rates in the UK/USA ranging from 1.13 to 6.62 cases per 100,000 adults. Eltrombopag increases the production of platelets at a rate that outpaces their destruction by the immune system, and has a UK marketing authorisation both for the treatment of adult ITP in splenectomised patients who are refractory to other treatments and as a second-line treatment for adult non-splenectomised patients for whom surgery is contraindicated. Both splenectomised and non-splenectomised patient groups were considered in the analysis. Two economic models were presented, one for a watch-and-rescue treatment scenario and the second for the long-term treatment of patients with more severe ITP. The submission's evidence was sourced from the relatively high-quality RAISE [RAndomized placebo-controlled Idiopathic thrombocytopenic purpura (ITP) Study with Eltrombopag] randomised controlled trial. The study indicated a statistically significant difference in favour of eltrombopag compared with placebo in the odds of achieving the primary outcome of a platelet count of between 50 and 400 × 109/l during the 6-month treatment period (odds ratio 8.2, 99% confidence interval 3.6 to 18.7). In the eltrombopag group, 50/83 (60%) non-splenectomised patients and 18/49 (37%) splenectomised patients achieved this outcome. Median duration of response for all patients was 10.9 weeks (splenectomised patients 6 weeks and non-splenectomised patients 13.4 weeks). Patients treated with eltrombopag required less rescue medication and had lower odds of bleeding events than placebo-treated subjects in both patient groups. In the watch-and-rescue economic model, the ERG found that substantial reductions in the cost of eltrombopag are needed for the incremental cost-effectiveness ratio (ICER) to fall below £ 30,000. Further analyses found that the ICER varied from £33,561 to £ 103,500 per quality-adjusted life-year (QALY) (splenectomised) and from £ 39,657 to £ 150,245 per QALY (non-splenectomised). Other than bleeding, no adverse events were modelled. In relation to the long-term treatment model, the ERG found that using non-randomised non-comparative data may result in biased estimates of unknown magnitude and direction. None of the treatment sequences resulted in an ICER approaching the recommended threshold of £ 30,000. The base-case results, using a 2-year time horizon and prescribing eltrombopag as second-line treatment post rituximab, were found to be favourable towards eltrombopag. In conclusion, based on the MS and additional ERG work, eltrombopag appears to be a safe treatment for ITP (although long-term follow-up studies are awaited) and has short-term efficacy. However, there is no robust evidence on long-term efficacy or cost-effectiveness of eltrombopag, and there is a lack of robust direct evidence on the effectiveness and cost-effectiveness of eltrombopag compared with other relevant comparators. NICE did not recommend eltrombopag for the treatment of chronic ITP within its marketing authorisation for splenectomised or non-splenectomised patients.

Inferior vena caval filter insertion prior to bariatric surgery: a systematic review of the literature.

Placement of inferior vena cava filters (IVCFs) is considered in many patients undergoing bariatric surgery. Their placement is driven by a high rate of pulmonary embolism (PE), uncertainty as to the effectiveness of pharmacologic prophylaxis, and a lack of alternate methods to prevent pulmonary embolism. We performed a systematic review of the literature to evaluate the evidence supporting placement of IVCFs in patients undergoing bariatric surgery. Eleven studies were identified; none were randomized trials. Descriptive analysis suggests that IVCFs reduced PE; however, the strength of this observation is tempered by the lack of use of effective forms of prophylaxis and the failure to account for complications of IVCF placement. We conclude, pending the results of controlled studies, that the use of IVCFs cannot be recommended for routine patients undergoing bariatric surgery.

Romiplostim for the treatment of chronic immune or idiopathic thrombocytopenic purpura: a single technology appraisal.

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of romiplostim for the treatment of adults with chronic immune or idiopathic thrombocytopenic purpura (ITP) based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from two relatively high-quality randomised controlled trials (RCTs). The ERG found no evidence that any important data were missed or that data extraction was inaccurate. In both RCTs more patients in the romiplostim than in the placebo group achieved a durable platelet response [non-splenectomised patients: romiplostim 25/41 (61%), placebo 1/21 (5%), odds ratio (OR) 24.45, 95% confidence interval (CI) 3.34 to 179.18; splenectomised patients: romiplostim 16/42 (38%), placebo 0/21 (0%), OR 8.5 (95% CI 1.15 to 372)] and an overall platelet response [non-splenectomised patients: romiplostim 36/41 (88%), placebo 3/21 (14%), OR 34.74, 95% CI 7.77 to 155.38; splenectomised patients: romiplostim 33/42 (79%), placebo 0/21 (0%), OR 16.6 (95% CI 2.37 to 706]. The difference in mean period with a platelet response was 13.9 weeks (95% CI 10.5 to 17.4) in favour of romiplostim in the RCT of non-splectomised patients and 12.1 weeks (95% CI 8.7 to 15.6) in favour of romiplostim in the RCT of splectomised patients. The manufacturer's economic model evaluated the cost-effectiveness of romiplostim compared with standard care. The ERG had concerns about the way the decision problem was addressed in the economic model and about the non-adjustment of findings for confounding factors. In non-splenectomised patients, using romiplostim as a first option treatment, the base-case incremental cost-effectiveness ratio (ICER) was 14,840 pounds per quality-adjusted life-year (QALY). In splenectomised patients the ICER was 14,655 pounds per QALY. Additional sensitivity analyses performed by the ERG identified two issues of importance: whether individuals entered the model on watch and rescue or on active therapy in the comparator arm (ICER 21,674 pounds per QALY for non-splenectomised patients, 29,771 pounds per QALY for splenectomised patients); whether it was assumed that any unused medicine would be wasted. Combining all of the separate sensitivity analyses, and assuming that watch and rescue was not the first-line treatment, increased the ICERs further (non-splenectomised 37,290 pounds per QALY; splenectomised 131,017 pounds per QALY). In conclusion, the manufacturer's submission and additional work conducted by the ERG suggest that romiplostim has short-term efficacy for the treatment of ITP, but there is no robust evidence on long-term effectiveness or cost-effectiveness of romiplostim compared with relevant comparators.

Incidence and predictors of bleeding or thrombosis after polypectomy in patients receiving and not receiving anticoagulation therapy.

BACKGROUND AND AIMS: To assess the effect of warfarin anticoagulation therapy (AC) on the incidence of colon bleeding after elective colonoscopy with polypectomy and to identify independent predictors of post-polypectomy colon bleeding. METHODS: This was a retrospective cohort analysis. Patients interrupting warfarin AC therapy for polypectomy (AC group) were matched on age (+/- 3 years) with up to two patients who underwent polypectomy but were not receiving AC (non-AC group). Data were extracted from electronic medical, pharmacy and laboratory claims and records and manual medical chart review. Incidence rates of colon bleeding requiring hospitalization, other gastrointestinal bleeding, thrombosis and death in the 30 days post-polypectomy were compared between groups. Multivariate regression techniques were used to identify independent predictors of post-polypectomy colon bleeding. RESULTS: A total of 425 AC group patients were matched to 800 non-AC group patients. Post-polypectomy colon bleeding occurred more often in AC group patients (2.6% vs. 0.2%, P = 0.005). There were no differences in the rates of other outcomes (P > 0.05). Independent predictors of colon bleeding included AC group status [adjusted odds ratio (AOR) = 11.6; 95% confidence interval (CI) = 2.3-57.3], number of polyps removed (AOR = 1.2; 95% CI = 1.1-1.4) and male gender (AOR = 9.2, 95% CI = 1.1-74.9). CONCLUSIONS: The incidence of post-polypectomy colon bleeding was higher in patients receiving AC even although warfarin was interrupted for the procedure. Independent predictors of colon bleeding were identified as: receiving AC, removal of multiple polyps and male gender. Our findings suggest that additional methods to reduce the likelihood of post-polypectomy colon bleeding in AC patients should be investigated.

Systematic review and meta-analyses of studies of glutamine supplementation in haematopoietic stem cell transplantation.

It is unclear whether supplemental glutamine is of benefit in haematopoietic stem cell transplantation (HSCT). We performed a systematic review and meta-analyses using Cochrane methodology. Seventeen randomized controlled trials (RCTs) were found. There was considerable heterogeneity between studies in terms of patient demographics and glutamine administration schedule. Many of the studies were small and scored poorly on methodological quality. Oral glutamine may reduce mucositis (average mucositis score: standard mean difference -0.38, 95% confidence interval (CI) -0.59 to -0.16) and days of opioids (mean difference -1.95 days, 95% CI -3.66 to -0.25) and GVHD (relative risk 0.42, 95% CI 0.21-0.85). Glutamine (i.v.) may reduce clinical infections (relative risk 0.75, 95% CI 0.58 to 0.97) and positive cultures (relative risk 0.72, 95% CI 0.57-0.91) but may also increase the risk of relapse (relative risk 2.91, 95% CI 1.34-6.29) but this is based on only two small studies. There was no effect of oral or i.v. glutamine on overall transplant-related mortality at day +100. In conclusion, there may be beneficial effects of glutamine in HSCT but larger, well-designed studies are required to confirm the beneficial effects and investigate possible adverse effects.