Regularized parametric survival modeling to improve risk prediction models.

We propose to combine the benefits of flexible parametric survival modeling and regularization to improve risk prediction modeling in the context of time-to-event data. Thereto, we introduce ridge, lasso, elastic net, and group lasso penalties for both log hazard and log cumulative hazard models. The log (cumulative) hazard in these models is represented by a flexible function of time that may depend on the covariates (i.e., covariate effects may be time-varying). We show that the optimization problem for the proposed models can be formulated as a convex optimization problem and provide a user-friendly R implementation for model fitting and penalty parameter selection based on cross-validation. Simulation study results show the advantage of regularization in terms of increased out-of-sample prediction accuracy and improved calibration and discrimination of predicted survival probabilities, especially when sample size was relatively small with respect to model complexity. An applied example illustrates the proposed methods. In summary, our work provides both a foundation for and an easily accessible implementation of regularized parametric survival modeling and suggests that it improves out-of-sample prediction performance.

Developing a Natural History Model for Duchenne Muscular Dystrophy.

BACKGROUND: The aim of this study was to pool multiple data sets to build a patient-centric, data-informed, natural history model (NHM) for Duchenne muscular dystrophy (DMD) to estimate disease trajectory across patient lifetime under current standard of care in future economic evaluations. The study was conducted as part of Project HERCULES, a multi-stakeholder collaboration to develop tools to support health technology assessments of new treatments for DMD. METHODS: Health states were informed by a review of NHMs for DMD and input from clinicians, patients and caregivers, and defined using common outcomes in clinical trials and real-world practice. The primary source informing the NHM was the Critical Path Institute Duchenne Regulatory Science Consortium (D-RSC) database. This was supplemented with expert input obtained via an elicitation exercise, and a systematic literature review and meta-analysis of mortality data. RESULTS: The NHM includes ambulatory, transfer and non-ambulatory phases, which capture loss of ambulation, ability to weight bear and upper body and respiratory function, respectively. The NHM estimates patients spend approximately 9.5 years in ambulatory states, 1.5 years in the transfer state and the remainder of their lives in non-ambulatory states. Median predicted survival is 34.8 years (95% CI 34.1-35.8). CONCLUSION: The model includes a detailed disease pathway for DMD, including the clinically and economically important transfer state. The NHM may be used to estimate the current trajectory of DMD in economic evaluations of new treatments, facilitating inclusion of a lifetime time horizon, and will help identify areas for further research.

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.

Quality of early evidence on the pathogenesis, diagnosis, prognosis and treatment of COVID-19.

Since the initial description of the SARS-CoV-2 outbreak and its declaration as a worldwide pandemic, the number of publications on the novel virus has increased rapidly. We studied the trends and quality of evidence in early SARS-CoV-2 publications. A comprehensive search of MEDLINE and EMBASE was performed for papers published between 1 January 2020 and 21 April 2020. Two reviewers independently screened titles and abstracts and subsequently full texts for eligibility in this systematic review. The search yielded 2504 citations published between January and February 2020 or an unspecified date, 109 of which remained for extraction after screening. Data extracted included study design, year of publication, country of basis, journal of publication, impact factor of publishing journal, study sample size, number of citations and topic of investigation. Study design-specific critical appraisal tools were used to evaluate the scientific rigour of all included papers: the Joanna Briggs Institute checklist was used for case series, Scale for the Assessment of Narrative Review Articles scale for narrative reviews, Newcastle-Ottawa scale for cohort studies and AMSTAR 2 for systematic reviews. The overall quality of the literature was low-moderate. Of 541 papers that reported clinical characteristics, 295 were commentaries/expert opinions and 36 were case reports. There were no randomised clinical trials, 45 case series studies, 58 narrative reviews, 1 cohort study and 5 systematic reviews. We encourage clinicians to be attentive to these findings when utilising early SARS-CoV-2 evidence in their practices.

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.

Predictors of length of stay following shoulder arthroplasty in a high-volume UK centre.

INTRODUCTION: Shoulder arthroplasty rates are increasing in the UK. No data have been published from a UK centre on predictors of length of inpatient stay following shoulder arthroplasty. This study analyses the length of inpatient stay following shoulder arthroplasty in a high-volume UK centre and identifies predictors of prolonged inpatient stay. MATERIALS AND METHODS: All shoulder arthroplasty cases performed between 2012 and 2018 were identified. A review of case notes and electronic patient records was completed to identify demographic data, Charlson comorbidity score, length of inpatient stay and factors associated with length of stay. Multiple linear regression analysis was conducted to determine which factors were independently associated with length of inpatient stay. RESULTS: A total of 640 shoulder arthroplasty cases were performed in 566 patients. Median length of stay was two days. Length of stay was predicted by age, sex, chronic kidney disease, congestive cardiac failure, previous myocardial infarction, intraoperative complication and postoperative transfusion. DISCUSSION: Increasing age, female sex, chronic kidney disease, congestive cardiac failure, previous myocardial infarction, intraoperative complication and transfusion were independent predictors of increased length of stay. Strategies to reduce perioperative complication and transfusion, and to optimise renal and cardiac comorbidities may reduce overall length of stay for shoulder arthroplasty patients.

Jointly modelling longitudinally measured urinary human chorionic gonadotrophin and early pregnancy outcomes.

Human chorionic gonadotrophin (hCG) is largely used to confirm pregnancy. Yet evidence shows that longitudinal hCG profiles are distinguishable between healthy and failing pregnancies. We retrospectively fitted a joint longitudinal-survival model to data from 127 (85 healthy and 42 failing pregnancies) US women, aged 18-45, who were attempting to conceive, to quantify the association between longitudinally measured urinary hCG and early miscarriage. Using subject-specific predictions, obtained uniquely from the joint model, we investigated the plausibility of adaptively monitoring early pregnancy outcomes based on updating hCG measurements. Volunteers collected daily early morning urine samples for their menstrual cycle and up to 28 days post day of missed period. The longitudinal submodel for log hCG included a random intercept and slope and fixed linear and quadratic time terms. The survival submodel included maternal age and cycle length covariates. Unit increases in log hCG corresponded to a 63.9% (HR 0.36, 95% CI 0.16, 0.47) decrease in the risk of miscarriage, confirming a strong association between hCG and miscarriage. Outputted conditional survival probabilities gave individualised risk estimates for the early pregnancy outcomes in the short term. However, longer term monitoring would require a larger sample size and prospectively followed up data, focusing on emerging extensions to the joint model, which allow assessment of the specificity and sensitivity.

Blood transfusion rates following shoulder arthroplasty in a high volume UK centre and analysis of risk factors associated with transfusion.

AIMS: To determine the blood transfusion rates following shoulder arthroplasty and to establish risk factors associated with increased risk of transfusion. MATERIALS AND METHODS: All shoulder arthroplasty cases performed between January 2012 and March 2017 in a tertiary upper limb unit were identified. Patients who received perioperative tranexamic acid were excluded. Retrospective review of case notes was completed to identify transfusion rate and risk factors. Univariate and multivariate analysis were performed to analyse the association between risk factors and transfusion rate. RESULTS: Five hundred and thirty-seven shoulder arthroplasties performed in 474 patients were included. Peri- or post-operative transfusion was required in 21 cases (3.9%). Univariate analysis suggested significant association with age (p = 0.005), female sex (0.015), preoperative haemoglobin/haematocrit (p < 0.001), perioperative drop in haemoglobin (p < 0.001), ASA grade (p < 0.001) and transfusion rate. Only perioperative drop in haemoglobin (p < 0.001) and American Society of Anaesthesiologist score (ASA) grade (p = 0.039) retained significance on multivariable analysis. CONCLUSIONS: The blood transfusion rate following shoulder arthroplasty was 3.9%. Greater perioperative drop in haemoglobin and higher ASA grade were associated with increased risk of transfusion on multivariate analysis.

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.

Resumption of anticoagulant therapy after anticoagulant-related gastrointestinal bleeding: A systematic review and meta-analysis.

INTRODUCTION: Oral anticoagulation (OAC) is permanently discontinued in up to 50% of patients following a gastrointestinal (GI) bleed. A previous meta-analysis showed a reduced risk of thromboembolism and death, and a non-statistically significant increased risk of re-bleeding associated with resumption. We conducted an updated meta-analysis to determine the risks of recurrent GI bleeding, thromboembolism, and death in patients who resumed OAC compared to those who did not. MATERIALS AND METHODS: We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials for new references from January 2014 to September 2017. Randomized controlled trials and observational studies involving adults with OAC-related GI bleeding were included. Risk of bias was assessed using the Cochrane Collaboration's ROBINS-I tool. Pooled relative risk (RR) ratios were calculated using a random-effects model. RESULTS: We identified 12 observational studies involving 3098 patients. There was an increased risk of recurrent GI bleeding (RR 1.91, 95% CI 1.47-2.48, I2 = 0%, 11 studies), and a reduced risk of thromboembolism (RR 0.30, 95% CI 0.13-0.68, I2 = 59.8%, 9 studies) and death (RR 0.51, 95% CI 0.38-0.70, I2 = 71.8%, 8 studies) in patients who resumed OAC compared to those who did not. Eleven studies were judged to be at serious risk of bias due to confounding. CONCLUSIONS: Resuming OAC after OAC-related GI bleeding appears to be associated with an increase in recurrent GI bleeding, but a reduction in thromboembolism and death. Further prospective data are needed to identify patients for whom the net clinical benefit favours OAC resumption and the optimal timing of resumption.

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.

McMaster RARE-Bestpractices clinical practice guideline on diagnosis and management of the catastrophic antiphospholipid syndrome.

Background The McMaster RARE-Bestpractices project group selected the catastrophic antiphospholipid syndrome (CAPS) for a pilot exercise in guideline development for a rare disease. Objectives The objectives of this exercise were to provide a proof of principle that guidelines can be developed for rare diseases and assist in clinical decision making for CAPS. Patients/Methods The GIN-McMaster Guideline Development checklist and GRADE methodology were followed throughout the guideline process. The CAPS guideline was coordinated by a steering committee, and the guideline panel was formed with representation from all relevant stakeholder groups. Systematic reviews were performed for the key questions. To supplement the published evidence, we piloted novel methods, including use of an expert-based evidence elicitation process and ad hoc analysis of registry data. Results This paper describes the CAPS guideline recommendations, including evidence appraisal and discussion of special circumstances and implementation barriers identified by the panel. Many of these recommendations are conditional, because of subgroup considerations in this heterogeneous disease, as well as variability in patient values and preferences. Conclusions The CAPS clinical practice guideline initiative met the objective of the successful development of a clinical practice guideline in a rare disease using GRADE methodology. We expect that clinicians caring for patients with suspected CAPS will find the guideline useful in assisting with diagnosis and management of this rare disease.

Reduced-dose direct oral anticoagulants in the extended treatment of venous thromboembolism: a systematic review and meta-analysis.

Essentials In venous thromboembolism (VTE), benefits of extended treatment are balanced by bleeding risks. This is a meta-analysis of reduced-dose direct oral anticoagulants (DOACs) in extended treatment. Reduced-dose DOACs are as effective as full anticoagulation with bleeding risks similar to placebo. Reduced-dose DOACs are an attractive option for patients in the extended phase of VTE treatment. SUMMARY: Background Extended-duration anticoagulation is beneficial for preventing recurrent venous thromboembolism (VTE). Reduced-dose direct oral anticoagulants (DOACs) may be preferable if they preserve efficacy and cause less bleeding. We conducted a systematic review and meta-analysis of trials comparing reduced-dose DOACs with full-dose DOACs and aspirin or placebo in the extended phase of VTE treatment. Methods A literature search was conducted by use of the MEDLINE, EMBASE and CINAHL databases, supplemented by hand-searching. One thousand three hundred and ninety-nine titles were screened, with data from accepted studies being extracted by two independent reviewers. Major outcomes analyzed included recurrent VTE and major and clinically relevant non-major bleeding events, presented as risk ratios (RRs) and 95% confidence intervals (CI). Results Two trials met the prespecified inclusion criteria. Data from 5847 patients were analyzed for efficacy outcomes, and from 5842 patients for safety outcomes. Reduced-dose DOACs were as effective as full-dose treatment in preventing recurrent VTE at 1 year (RR 1.12 [95% CI 0.67-1.87]), and more effective than aspirin or placebo (RR 0.26 [95% CI 0.14-0.46]). Rates of major or clinically relevant non-major bleeding events were similar between patients receiving reduced-dose DOACs and and those receiving aspirin or placebo (RR 1.19 [95% CI 0.81-1.77]). There was a trend towards less bleeding when reduced-dose and full-dose DOACs were compared (RR 0.74 [95% CI 0.52-1.05]). Conclusions Extended-duration treatment of VTE with reduced-dose DOACs may be as efficacious as full-dose treatment, with rates of major bleeding being similar to those in patients receiving treatment with aspirin or placebo, but further long-term studies are needed.

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.

McMaster RARE-Bestpractices clinical practice guideline on diagnosis and management of the catastrophic antiphospholipid syndrome

Background The McMaster RARE-Bestpractices project group selected the catastrophic antiphospholipid syndrome (CAPS) for a pilot exercise in guideline development for a rare disease. Objectives The objectives of this exercise were to provide a proof of principle that guidelines can be developed for rare diseases and assist in clinical decision making for CAPS. Patients/Methods The GIN-McMaster Guideline Development checklist and GRADE methodology were followed throughout the guideline process. The CAPS guideline was coordinated by a steering committee, and the guideline panel was formed with representation from all relevant stakeholder groups. Systematic reviews were performed for the key questions. To supplement the published evidence, we piloted novel methods, including use of an expert-based evidence elicitation process and ad hoc analysis of registry data. Results This paper describes the CAPS guideline recommendations, including evidence appraisal and discussion of special circumstances and implementation barriers identified by the panel. Many of these recommendations are conditional, because of subgroup considerations in this heterogeneous disease, as well as variability in patient values and preferences. Conclusions The CAPS clinical practice guideline initiative met the objective of the successful development of a clinical practice guideline in a rare disease using GRADE methodology. We expect that clinicians caring for patients with suspected CAPS will find the guideline useful in assisting with diagnosis and management of this rare disease.