Gastrointestinal safety of coxibs: systematic review and meta‐analysis of observational studies on selective inhibitors of cyclo‐oxygenase 2

Prior meta‐analyses have shown a higher gastrointestinal risk of nonselective NSAIDs versus placebo and a lower gastrointestinal risk of coxibs versus nonselective NSAIDs. However, the available data about gastrointestinal risk for coxibs versus placebo are scarce. The aim of this study was to review the current evidence on the use of coxibs and to evaluate the risk of gastrointestinal adverse outcomes (GAO) associated with coxibs versus nonexposed. Search was conducted on PubMed and Embase databases. We selected cohort observational, case‐control, nested case‐control and case‐crossover studies that reported the risk of GAO associated with coxibs versus nonexposed as relative risk (RR), odds ratio (OR), hazard ratio (HR) or incidence rate ratio (IRR). It was estimated the pooled RR and the 95% confidence interval (CI) for coxibs both individually and as a whole by the DerSimonian and Laird method. Twenty‐eight studies met inclusion criteria. Overall, coxibs were associated with a significant increment in the risk of GAO [RR 1.64 (95% CI 1.44–1.86)]. The analysis by individual drugs showed that etoricoxib [RR 4.85 (95% CI 2.64–8.93)] presented the highest gastrointestinal risk, followed by rofecoxib [RR 2.02 (95% CI 1.56–2.61)] and celecoxib [RR 1.53 (95% CI 1.19–1.97)]. Gastrointestinal risk was also high for the subgroups aged <65 years and low‐dose coxibs. The use of coxibs is associated with a statistically significant increased risk of GAO, which would be high even for low‐dose coxibs and <65‐year‐old subgroups. The risk would be higher for etoricoxib than for celecoxib and rofecoxib.     

Safety and efficacy of treatment with sitagliptin or glipizide in patients with type 2 diabetes inadequately controlled on metformin: a 2‐year study

Objectives: To evaluate the 2‐year safety and efficacy of adding sitagliptin or glipizide to ongoing metformin in patients with type 2 diabetes. Methods: Patients who were on a stable dose of metformin (≥ 1500 mg/day) for at least 8 weeks were randomised in a double‐blind manner to receive either sitagliptin 100 mg q.d. (N = 588) or glipizide 5 mg/day (up‐titrated up to 20 mg/day based upon prespecified glycaemic criteria) (N = 584). The efficacy analysis assessed the change in HbA_1c from baseline using the per‐protocol (PP) population. Results: For the PP cohort, mean baseline HbA_1c was 7.3% in both groups. After 2 years, the least squares (LS) mean change in HbA_1c from baseline [95% confidence interval (CI)] was ?0.54% (?0.64, ?0.45) with sitagliptin (n = 248) and ?0.51% (?0.60, ?0.42) with glipizide (n = 256). The rise in HbA_1c from week 24 to week 104 [i.e. coefficient of durability (COD)] was smaller with sitagliptin [COD (95% CI) 0.16%/year (0.10, 0.21)] compared with glipizide [0.26%/year (0.21, 0.31)]. The proportion of patients with an HbA_1c< 7% was 63% and 59% with sitagliptin and glipizide, respectively. The beta‐cell responsiveness to a meal challenge was maintained with sitagliptin and decreased with glipizide. The proportion of patients who reported hypoglycaemia was 5% with sitagliptin and 34% with glipizide [difference in proportions (95% CI) = ?29% (?33, ?25)]. Relative to baseline, sitagliptin was associated with weight loss (?1.6 kg) compared with weight gain (+0.7 kg) with glipizide. Conclusion: In patients with type 2 diabetes, adding sitagliptin to metformin monotherapy improved glycaemic control over 2 years, similar to the glucose‐lowering efficacy observed with adding glipizide, but with greater durability and generally better maintenance of beta‐cell function. Sitagliptin was generally well tolerated with a lower risk of hypoglycaemia and weight loss compared with weight gain observed with glipizide.     

Computer analysis of upper gastrointestinal endoscope images

Gastro‐oesophageal reflux disease (GORD) occurs in up to 40% of adults in the West. Oesophagitis is a major determinant in the treatment of GORD but its current classification systems are subjective. In order to help to provide objective interpretation of upper gastro‐intestinal (GI) endoscope examination and reduce inter‐observer variability, we developed a computer image analysis system. Digital video recordings were made on patients with clinical evidence of reflux oesophagitis. Cross‐sectional profiles of hue and saturation data were analysed on images from seven patients with grade B or C oesophagitis (LA grading). This analysis showed clear changes in hue (p?=?0.01) and saturation (p?=?0.001). These results suggest that quantification of upper GI endoscopic images is feasible and may help in objective assessment.     

Relation between D‐dimer level,venous valvular reflux and the development of post‐thrombotic syndrome after deep vein thrombosis

Summary. Background: The pathophysiology of post‐thrombotic syndrome (PTS) is postulated to involve persistent venous obstruction and venous valvular reflux. Objective: To study the association between D‐dimer level, valvular reflux and the PTS in a well‐defined cohort of deep vein thrombosis (DVT) patients. Methods: Consecutive patients with acute symptomatic DVT were recruited at eight centers and were followed for 24 months. D‐dimer was measured at 4 months. A standardized ultrasound assessment for popliteal valvular reflux was performed at 12 months. Using the Villalta scale, patients were assessed for PTS during follow‐up by evaluators who were unaware of D‐dimer or reflux results. Results: Three hundred and eighty‐seven patients were recruited; of these, 305 provided blood samples for D‐dimer and 233 had a 12‐month reflux assessment. PTS developed in 45.1% of subjects. Mean D‐dimer was significantly higher in patients with vs. without PTS (712.0 vs. 444.0 μg L^?1; P = 0.02). In logistic regression analyses adjusted for warfarin use at the time of D‐dimer determination and risk factors for PTS, D‐dimer level significantly predicted PTS (P = 0.03); when stratifying for warfarin use at the time of blood draw, adjusted odds ratio (OR) for developing PTS per unit difference in log D‐dimer was 2.33 (95% CI 0.89, 6.10) in those not on warfarin vs. 1.25 (95% CI 0.87, 1.79) in those on warfarin. Ipsilateral reflux was more frequent in patients with moderate‐to‐severe PTS than in patients with mild PTS (65% vs. 40%, respectively; P = 0.01) and was independently associated with moderate‐to‐severe PTS in logistic regression analyses (P = 0.01). Conclusion: D‐dimer levels, measured 4 months after DVT in patients not on warfarin, are associated with subsequent development of PTS. Venous valvular reflux is associated with moderate‐to‐severe PTS.     

Low‐molecular‐weight heparins vs. unfractionated heparin in the setting of percutaneous coronary intervention for ST‐elevation myocardial infarction: a meta‐analysis

Summary. Background: The aim of the current study was to perform two separate meta‐analyses of available studies comparing low‐molecular‐weight heparins (LMWHs) vs. unfractionated heparin (UFH) in ST‐elevation myocardial infarction (STEMI) patients treated (i) with primary percutaneous coronary intervention (pPCI) or (ii) with PCI after thrombolysis. Methods: All‐cause mortality was the pre‐specified primary endpoint and major bleeding complications were recorded as the secondary endpoints. Relative risk (RR) with a 95% confidence interval (CI) and absolute risk reduction (ARR) were chosen as the effect measure. Results: Ten studies comprising 16 286 patients were included. The median follow‐up was 2 months for the primary endpoint. Among LMWHs, enoxaparin was the compound most frequently used. In the pPCI group, LMWHs were associated with a reduction in mortality [RR (95% CI) = 0.51 (0.41–0.64), P < 0.001, ARR = 3%] and major bleeding [RR (95% CI) = 0.68 (0.49–0.94), P = 0.02, ARR = 2.0%] as compared with UFH. Conversely, no clear evidence of benefits with LWMHs was observed in the PCI group after thrombolysis. Meta‐regression showed that patients with a higher baseline risk had greater benefits from LMWHs (r = 0.72, P = 0.02). Conclusions: LMWHs were associated with greater efficacy and safety than UFH in STEMI patients treated with pPCI, with a significant relationship between risk profile and clinical benefits. Based on this meta‐analysis, LMWHs may be considered as a preferred anticoagulant among STEMI patients undergoing pPCI.     

Clinical implications of clopidogrel non‐response in cardiovascular patients: a systematic review and meta‐analysis

Summary. Background: Previous studies have shown an important risk of cardiovascular events in patients with clopidogrel biological non‐response, and data have shown considerable, unexplored heterogeneity. Objectives: To evaluate the magnitude of cardiovascular risk associated with clopidogrel non‐response and to explore heterogeneity. Methods: This was a systematic review and meta‐analysis of prospective studies of patients treated with clopidogrel for symptomatic atherothrombosis, evaluated by light transmission aggregometry with ADP and monitored prospectively for clinical ischemic events. Results: Fifteen studies were included, totaling 3960 patients, of whom 25% were considered to be clopidogrel non‐responders. The global relative risk (RR) for recurrent ischemic events in clopidogrel non‐responders was 3.5 [95% confidence interval (CI) 2.4–5.2, P < 0.0001]. The results of the different studies were heterogeneous (Cochran P = 0.01 and I² = 52%). The most recent studies yielded lower RRs [global RR = 2.9 (95% CI 2.3–3.8) after 2007, and global RR = 6.6 (95% CI 3.7–11.9) before 2007, P = 0.01]. Heterogeneity was present in the group of studies in which more than 10% of patients took glycoprotein (GP)IIb–IIIa inhibitors [Cochran P = 0.003 and I² = 70%; RR = 3.8 (95% CI 2.9–5.1)] and was absent in the other studies [Cochran P = 0.88 and I² = 0; RR = 2.5 (95% CI 1.7–3.6)]. The RR was significantly higher in studies using higher ADP maximal aggregation cut‐offs (> 65%) for clopidogrel non‐response than in studies using lower cut‐offs [RR = 5.8 (95% CI 3.2–10.3) and RR = 2.9 (95% CI 2.2–3.7), respectively, P = 0.03]. Conclusions: The risk of ischemic events associated with clopidogrel non‐response is now more precisely defined. The risk is heterogeneous across studies, possibly because of an interaction with GPIIb–IIIa inhibitors and the use of different cut‐offs to identify non‐responders.     

Upregulated N‐cadherin expression is associated with poor prognosis in epithelial‐derived solid tumours: A meta‐analysis

Background

N‐cadherin is an important molecular in epithelial‐mesenchymal transition (EMT) and has been reported to be associated with aggressive behaviours of tumours. However, prognostic value of N‐cadherin in solid malignancies remains controversially.

Materials and Methods

The Pubmed/MELINE and EMBASE databases were used for a comprehensive literature searching. Pooled risk ratio (RR) and hazard ratio (HR) with their corresponding 95% confidence intervals (CIs) were employed to quantify the prognostic role.

Results

Involving 36 studies with 5705 patients were performed to investigate relationships between N‐cadherin upregulation and clinicopathological features, survival. Results suggested upregulated N‐cadherin was associated with lymph node metastasis (RR = 1.16, 95% CI [1.00, 1.35]), higher histological grade (RR = 1.36, 95%CI [1.14, 1.62]), angiolymphatic invasion (RR = 1.19, 95% CI [1.06, 1.34]) and advanced clinical stage (RR = 1.32, 95% CI [1.06, 1.64]), while upregulated N‐cadherin was apt to be associated with distant metastasis (RR = 1.43, 95% CI [0.99, 2.05]). Moreover, N‐cadherin was correlated with poor prognosis of 3‐year survival (HR = 1.78, 95% CI [1.51, 2.10]), 5‐year survival (HR = 1.57, 95% CI [1.17, 2.10]) and overall survival (OS) (HR = 1.32, 95% CI [1.20, 1.44]). Subgroup analyses according to cancer types were also conducted for applying these conclusions to some tumours more properly. No publication bias was found except subgroup analysis of distant metastasis (P = .652 for Begg's test and 0.023 for Egger's test).

Conclusions

Taken together, upregulation of N‐cadherin is associated with more aggressive behaviours of epithelial‐derived solid malignancies and can be regarded as a predictor of poor survival.     

Relationship between pre‐discharge occupational therapy home assessment and prevalence of post‐discharge falls

Rationale, aims and objective Pre‐discharge occupational therapy home assessments are common practice, and considered important for falls prevention in older people. This prospective, observational cohort study describes the association between pre‐discharge home assessment and falls in the first month post‐discharge from a rehabilitation hospital. Methods 342 inpatients were recruited and followed up 1 month post‐discharge. Patients were classified into diagnostic groups (cardiac, orthopaedic trauma, spinal, peripheral joint surgery, neurological and deconditioned). Age, gender, falls risk [Falls Risk Assessment Scoring System (FRASS)], functional independence scores (FIM?) and receipt (or not) of a home assessment were recorded. Patients completed a diary to document post‐discharge falls. Logistic regression analysis tested the effect on falling of receiving a home assessment, age, gender, diagnostic group, FRASS and FIM?. Results Considering all subjects, not receiving a home assessment increased the risk of falling 1 month post‐discharge [odds ratio (OR) 2.6, 95% confidence interval (CI) 1.4–4.7, P = 0.003]. Neurological and orthopaedic trauma patients had significantly elevated risks of falling [OR (95% CI), respectively, 12.5 (4.7–33.2), 3.4 (1.4–8.4)] relative to the orthopaedic joint group. For all diagnostic groups except neurological, falls risk was mitigated by a home assessment. In non‐neurological patients, adjusting for the effect of diagnostic group, FRASS and FIM? scores indicated a significant association between not receiving a home assessment and falling (OR 4.2, 95% CI 2.1–8.2, P < 0.001). Conclusions Pre‐discharge occupational therapy home assessments are sound post‐discharge falls‐prevention strategies in non‐neurological patients. The decision to conduct a home assessment should consider diagnosis, falls risk and functional independence.     

Once or twice‐daily,algorithm‐based intravenous cephazolin for home‐based cellulitis treatment

Objective: Cellulitis is a common presentation to the ED and a significant cause of hospitalization that can be managed in hospital‐in‐the‐home programmes. Current clinical‐practice guidelines recommend once or twice‐daily i.v. antibiotics; however, there is an absence of data describing the impact of these guidelines in real‐world practice‐based settings. This study aims to describe the safety and effectiveness of home‐based cellulitis treatment according to an online treatment algorithm. Methods: Over 12 months, 301 patients with a diagnosis of uncomplicated cellulitis requiring i.v. antibiotics and eligible for home‐based therapy completed once‐daily (cephazolin plus probenecid) or twice‐daily (cephazolin alone) treatment, according to the treatment algorithm. Time (days) until non‐progression of cellulitis was the primary outcome measure. Length of stay and treatment‐related side‐effects were also recorded. Results: The mean time until non‐progression was 2.11 (95% confidence interval [CI] 1.98–2.23) days versus 2.13 (95% CI 1.81–2.45) days for the once‐daily (n = 213) and twice‐daily (n = 88) regimens, respectively (P = 0.92, difference in means 0.02 [95% CI ?0.36–0.33]). The corresponding mean length of stay was 6.55 (95% CI 5.96–7.15) days versus 7.67 (95% CI 6.69–8.65) days (P = 0.06, difference in means 1.12 [CI 0.03–1.23]). Treatment‐related side‐effects were reported in 15.5% (33/213 [95% CI 10.6–20.3]) of patients receiving the once‐daily regimen compared with 9.1% (8/88 [95% CI 3.1–15.1]) treated twice‐daily. Application of the once‐daily strategy increased hospital‐in‐the‐home cellulitis‐related treatment capacity by 52% (1396/2688 [95% CI 50–54]). Conclusions: An online decision support algorithm can support the effective use of a once or twice‐daily treatment regimen for uncomplicated cellulitis. This approach can increase the efficiency and capacity of home‐based therapy, resulting in better alignment of treatment options with clinicians and patients' preferences.     

PRODIGE: a randomized placebo‐controlled trial of dalteparin low‐molecular‐weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma

Summary. Background and objectives: Venous thromboembolism (VTE) occurs in 20–30% of patients with malignant glioma per year of survival. We tested the efficacy of long‐term dalteparin low‐molecular‐weight heparin (LMWH) for prevention of VTE in these patients. Patients/methods: Adults with newly diagnosed malignant glioma were randomized to receive dalteparin 5000 anti‐Xa units or placebo, both subcutaneously once daily for 6 months starting within 4 weeks of surgery. Treatment continued for up to 12 months. The primary outcome was the cumulative risk of VTE over 6 months. The target sample size was 512 patients. Events were adjudicated by a committee unaware of treatment. Results: The trial began in 2002 and closed in May 2006 because of expiration of study medication. Ninety‐nine patients were randomized to LMWH and 87 to placebo. Twenty‐two patients developed VTE in the first 6 months: nine in the LMWH group and 13 in the placebo group [hazard ratio (HR) = 0.51, 95% confidence interval (CI): 0.19–1.4, P = 0.29]. At 6 months, there were three major bleeds on LMWH and none on placebo; at 12 months, 5 (5.1%) major bleeds on LMWH and 1 (1.2%) on placebo occurred (HR = 4.2, 95% CI: 0.48–36, P = 0.22). All major bleeds were intracranial and occurred while on study medication. The 12‐month mortality rates were 47.8% for LMWH and 45.4% for placebo (HR = 1.2, 95% CI: 0.73–2.0, P = 0.48). Conclusions: Trends suggesting reduced VTE and increased intracranial bleeding were seen in the LMWH thromboprophylaxis group. The role of long‐term anticoagulant thromboprophylaxis in patients with brain tumors remains uncertain.     

Behavior of Hepatocellular Adenoma on Real‐time Low‐Mechanical Index Contrast‐Enhanced Ultrasonography With a Second‐Generation Contrast Agent

Objective. The purpose of this study was to describe the behavior of histologically proven hepatocellular adenoma (HCA) on low‐mechanical index (MI) contrast‐enhanced ultrasonography (CEUS). Methods. A review of the databases from 4 academic hospitals revealed 18 patients (15 female and 3 male; mean age, 40 years; range, 25–71 years) with 25 histologically proven HCA lesions who were studied with CEUS at a low MI (0.04–0.1). Results. Twenty‐four of 25 lesions (96%; 95% confidence interval [CI], 80.5%–99.3%) showed high‐intensity enhancement, scored as 3 on a scale of 0 to 3, whereas only 1 lesion (4%; 95% CI, 0.7%–19.5%) was scored as 2. The time of peak enhancement ranged between 10 and 19 seconds (average, 13 seconds). All but 1 of the 25 lesions (96%; 95% CI, 80.5%–99.3%) showed early homogeneous and centripetal enhancement during the hepatic arterial phase. No portal venous phase enhancement was observed in any lesion because all showed rapid wash‐out (100%; 95% CI, 86.7%–100%). Twenty lesions (80%; 95% CI, 60.9%–91.1%) were found to be isoechoic to slightly hypoechoic during the portal phase, and 19 (76%; 95% CI, 56.6%–88.5%) were isoechoic to mildly hypoechoic, whereas 7 (24%; 95% CI, 11.5%–43.4%) were hypoechoic during the late phase. Conclusions. Contrast‐enhanced ultrasonography is an effective technique for identifying the microvascular and macrovascular characteristics of HCA. Typically, HCA shows early (10–19 seconds) and centripetal enhancement during the arterial phase and isoechogenicity or mild hypoechogenicity during the portal phase, remaining slightly hypoechoic or isoechoic during the late phase in most cases.     

The efficacy and safety of vildagliptin in patients with type 2 diabetes: a meta-analysis of randomized clinical trials

What is known and Objective: Dipeptidyl peptidase‐4 (DPP‐4) inhibitors are a relatively new class of drugs for the management of type 2 diabetes (T2DM). Vildagliptin is an oral DPP‐4 inhibitor approved in more than 70 countries. The purpose of this meta‐analysis is to provide an update on the clinical efficacy and safety of vildagliptin in patients with T2DM. Methods: A literature search identified 30 randomized controlled trials comparing vildagliptin with comparators (placebo or other hypoglycaemic agents). Meta‐analyses were conducted for HbA1c, weight, fasting plasma glucose (FPG), hypoglycaemia and other adverse events. The outcomes of HbA1c, weight and FPG were analysed as weighted mean differences (WMD), and the number of ADRs events as relative risks (RR). Results: Compared with placebo, vildagliptin lowered HbA1c {WMD, ?0·77% [95% confidence interval (CI), ?0·96% to ?0·58%] for 100 mg/day of vildagliptin and ?0·58% [95% CI, ?0·72% to ?0·44%] for 50 mg/day of vildagliptin}. The effect was non‐inferior to thiazolidinediones, sulfonylureas and α‐glycosidase inhibitors, but inferior to metformin. Compared with placebo, treatment with 50 mg/day of vildagliptin caused neutral weight changes, while 100 mg/day of vildagliptin resulted in slight weight gain [0·95 kg (95% CI, 0·73–1·17 kg)]. In addition, compared to comparators, vildagliptin was not associated with an increase in overall risk for any adverse events [RR, 0·97 (95% CI, 0·94–0·99)]. The incidence of hypoglycaemia was low with vildagliptin, and the risk with vildagliptin was not significantly different from the comparators [0·85 (95% CI, 0·49–1·47)]. The use of vildagliptin did not display any increased risks of infection [1·03 (95% CI, 0·94–1·13) for nasopharyngitis and 1·07 (95% CI, 0·90–1·27) for upper respiratory tract infection]. What is new and Conclusion: Vildagliptin is effective in glycaemic control with a low risk of hypoglycaemia and other adverse reactions. This may have an important impact on patient adherence to this medication.     

The effectiveness of esomeprazole 40 mg in patients with persistent symptoms of gastro‐oesophageal reflux disease following treatment with a full dose proton pump inhibitor

Background: Some patients with gastro‐oesophageal reflux disease (GORD) remain symptomatic despite proton pump inhibitor (PPI) treatment. There is a need to determine the most appropriate management of these patients. Aims: To assess the effectiveness of esomeprazole 40 mg in GORD symptoms persisting in patients receiving a full daily dose PPI. Methods: In this multi‐centre open label study patients who had received full daily dose PPI for 8 weeks, but were still experiencing persistent GORD symptoms, were treated with esomeprazole 40 mg for 8 weeks (n = 99). The primary outcome variable was the change in the frequency of heartburn. Patient‐reported outcomes were also assessed using the Reflux Disease Questionnaire (RDQ) and the GORD Impact Scale (GIS). Results: The mean frequency of heartburn was reduced by 78% from 4.4 days a week to 1 day a week at the end of the 8‐week treatment period (p < 0.0001). Other GORD symptoms were also significantly reduced following of treatment with esomeprazole (all p < 0.0001). All RDQ dimensions and the level of symptom control as measured by the GIS also showed significant improvement at 8 weeks. Conclusions: In patients with persistent GORD symptoms despite full dose daily PPI therapy, esomeprazole 40 mg significantly improved the frequency and severity of all GORD symptoms.     

Comorbidity of headache and gastrointestinal complaints. The Head-HUNT Study

Associations between headache, including migraine, and gastrointestinal (GI) symptoms were studied in a large questionnaire-based cross-sectional study (the Head-HUNT Study). The headache questionnaire was completed by 43 782 individuals, who answered all the questions concerning nausea, reflux symptoms, diarrhoea and constipation. In the multivariate analyses, adjusting for age, sex, educational level, medication use, depression and anxiety, a higher prevalence of headache was found in individuals with much reflux [odds ratio (OR) 2.4, 95% confidence interval (CI) 2.2, 2.6], diarrhoea (OR 2.4, 95% CI 2.1, 2.8), constipation (OR 2.1, 95% CI 1.9, 2.4) and nausea (OR 3.2, 95% CI 2.6, 3.8) compared with those without such complaints. All the GI symptoms investigated seemed to be approximately as common among persons with non-migrainous headache as among migraine sufferers, but the association between headache and GI complaints increased markedly with increasing headache frequency. This may suggest that headache sufferers generally are predisposed to GI complaints.     

β‐Blocker in Post‐Myocardial Infarct Survivors with Preserved Left Ventricular Systolic Function

Background: Long‐term β‐blockade therapy is beneficial in post‐myocardial infarct (MI) patients with left ventricular (LV) dysfunction; nevertheless, its benefit in post‐MI patients with preserved LV function remains unclear. The objective of this study is to investigate the effects of long‐term β‐blockade therapy on the clinical outcomes in post‐MI patients with preserved LV function. Hypothesis: The beneficial effects of long‐term β‐blockade therapy in post‐MI patients with impaired LV function may extend to those with preserved LV function. Methods: Of 617 consecutive post‐MI patients referred for cardiac rehabilitation program, 208 patients (age: 62.7 ± 0.8 years; male: 76%) with preserved LV function (ejection fraction ≥ 50%), negative exercise stress test, and on angiotensin‐converting enzyme inhibition were studied. Results: Baseline characteristics were comparable between patients on β‐blocker (n = 154) and not on β‐blocker (n = 54). After a mean follow‐up of 58.5 ± 2.7 months, 14 patients not on β‐blocker (26%) and 14 patients on β‐blocker (9%) died with hazard ratio (HR) of 2.5 (95% confidence interval [CI]: 1.25–6.42, P = 0.01). Likewise, patients not on β‐blocker had a higher incidence of cardiac death (HR: 3.0, 95% CI: 1.07–12.10, P = 0.04), and non‐sudden cardiac death (HR: 10.1, 95% CI: 1.82–89.65, P = 0.01), but not sudden cardiac death compared with patients on β‐blocker (HR: 1.6, 95% CI: 0.34–7.61, P = 0.54). A Cox regression analysis revealed that only advanced age (≥75 years; HR: 2.55, 95% CI: 1.18–5.49, P = 0.02) and the absence of β‐blocker (HR: 2.41, 95% CI: 1.14–5.09, P = 0.02) were independent predictors for mortality. Conclusion: β‐blocker use was associated with a decrease in overall mortality and cardiac death in post‐MI patients with preserved LV function. (PACE 2010; 33:675–680)     

Predictors of the post‐thrombotic syndrome with non‐invasive venous examinations in patients 6 weeks after a first episode of deep vein thrombosis

Summary. Background: Post‐thrombotic syndrome (PTS) is a chronic complication of deep vein thrombosis (DVT) affecting a large number of patients. Because of its potential debilitating effects, identification of patients at high risk for the development of this syndrome is relevant, and only a few predictors are known. Objectives: To assess the incidence and potential predictors of PTS. Methods: We prospectively followed 111 consecutive patients for 2 years after a first episode of objectively documented DVT of the leg. With non‐invasive venous examinations, residual thrombosis, valvular reflux, calf muscle pump function and venous outflow resistance were assessed at 6 weeks, 3 months, 6 months, 1 year, and 2 years. The Clinical, Etiologic, Anatomic, and Pathophysiologi classification was used to record the occurrence and severity of PTS. Regression analysis with area under the receiver operating characteristic (ROC) curve was performed to identify potential predictors. Results: The cumulative incidence of PTS was 46% after 3 months, and the incidence and severity did not increase further. Men appeared to be at increased risk as compared with women (risk ratio [RR] 1.4, 95% confidence interval [CI] 0.9–2.2), as were patients over 50 years as compared with younger patients (RR 1.4%, 95% CI 0.9–2.1). Patients with thrombosis localized in the proximal veins at diagnosis had an increased risk of PTS as compared with patients with distal thrombosis (RR 2.3%, 95% CI 1.0–5.6). PTS developed in 32 of 52 patients (62%) with residual thrombosis in the proximal veins 6 weeks after diagnosis, as compared with 17 of 45 patients (38%) without residual proximal thrombosis, leading to a 1.6‐fold increased risk (95% CI 1.0–2.5). The presence of valvular reflux in the superficial veins was also a predictor at 6 weeks, with a 1.6‐fold increased risk as compared with patients without superficial reflux (95% CI 1.1–2.3). A multivariate analysis of these predictors yielded an area under the ROC curve of 0.72 (95% CI 0.62–0.82). Conclusions: PTS develops in half of all patients within 3 months, with no further increase being seen up to 2 years of follow‐up. Male sex, age over 50 years, proximal localization of the thrombus at entry, residual proximal thrombosis and superficial valvular reflux at 6 weeks seem to be the most important predictors of PTS in patients with a first episode of DVT. Duplex scanning 6 weeks after diagnosis appears to be clinically useful for the identification of patients at risk of PTS.     

Exploratory cross‐sectional study of factors associated with pre‐hospital management of pain

Rationale, aims and objectives Improving pain management is important in pre‐hospital settings. We aimed to investigate how pain was managed in pre‐hospital suspected acute myocardial infarction (AMI) or fracture and how this could be improved. Method We conducted a cross‐sectional study in Lincolnshire using recorded suspected AMI and fracture between April 2005 and March 2006. Outcomes included pain assessment, improvement in pain scores and administration of Entonox, opiates or GTN (in AMI). Results We accessed 3654 patients with suspected AMI or fracture. Pain was assessed in over three quarters of patients but analgesics administered in under two‐fifths. Assessment was more likely in patients with suspected AMI (OR 2.05, 95% CI [1.70, 2.47]), and who were alert (OR 3.55, 95% CI [2.32, 5.43]). Entonox was less likely to be administered for suspected AMI (OR 0.11, 95% CI [0.087, 0.15]) or by paramedic crews (OR 0.56, 95% CI [0.45, 0.68]) but more likely to be given when pain had been assessed (OR 3.54, 95% CI [2.77, 4.52]). Opiates were more likely to be prescribed for suspected AMI (OR 1.30, 95% CI [1.07, 1.57]), in alert patients (OR 1.35, 95% CI [0.71, 2.56]) assessed for pain (OR 2.20, 95% CI [1.73, 2.80]) by paramedic crews. Conclusions This exploratory study showed shortfalls in assessment and treatment of pain, but also demonstrated that assessment of pain was associated with more effective treatment. Further research is needed to understand barriers to pre‐hospital pain management and investigate mechanisms to overcome these.     

The utilization of CTA in management of gastrointestinal bleeding in a tertiary care center ED. Are we using it enough?

BackgroundGastrointestinal (GI) bleeding is a common patient presentation to the Emergency Department (ED) and the source can be difficult to diagnose.ProcedureComputed tomography angiography (CTA) is a new but validated modality with high sensitivity and specificity for diagnosis and treatment of GI bleeds, especially in differentiating arterial from venous bleeding. With high reported validity of CTA, some studies have suggested its ability to better triage patients in the ED and impact ED workflow and resource utilization. We evaluated the use of CTA use an academic tertiary care center ED for GI bleeding.FindingsRetrospective chart review of 1493 patient (2012–2015), one - way ANOVA, and one-tail t-test, found CTA is used significantly less (0.7%) compared to classical endoscopy (75.7%, p < .001), video capsule endoscopy (VCE)(4.8%, p < .001), tagged red blood cell scintigraphy(4.4%, p < .001), and traditional catheter-directed angiography(2.88%, p < .001). In our subset of 11 CTA cases, we found mean time (in hours) to CTA was faster than mean time to endoscopy, 31:47 [95% CI: −7:50–71:24] and 42:44 [95% CI: 18:27–67:01] respectively. The difference in means between time to CTA and time to endoscopy did not achieve statistical significance, 12:57 h [95% CI −18:51–44:45; p = .40].ConclusionWe concluded that in light of its validation against these other diagnostic modalities, CTA may be underutilized in the care of patients with GI bleeding and should be studied further to study its impact on early risk stratification, treatment, and resource utilization.     

Insulin resistance and risk of venous thromboembolism: results of a population‐based cohort study

Summary. Background: Obesity is an established risk factor for venous thromboembolism (VTE), but it is uncertain how this is mediated. Insulin resistance has a central role in the pathophysiology of the metabolic effects of obesity. Objective: We aimed to investigate whether insulin resistance is a risk factor for VTE. Methods: For this analysis we used the PREVEND prospective community‐based observational cohort study. Insulin resistance was measured as HOMA‐IR (homeostasis model assessment of insulin resistance) and fasting insulin. VTE was assessed using databases of the national registries of hospital discharge diagnoses, death certificates and the regional anticoagulation clinic. Results: Out of 7393 subjects, 114 developed VTE during a median follow‐up of 10.5 years. High HOMA‐IR was associated with increased risk of VTE after adjustment for traditional cardiovascular risk factors, CRP and markers of endothelial dysfunction (hazard ratio [HR], 1.38; 95% confidence interval [95% CI], 1.09–1.75; P = 0.007). When body mass index (BMI) was added to the model, BMI was a strong risk predictor for VTE (HR, 1.53; 95% CI, 1.24–1.88; P < 0.001) whereas HOMA‐IR no longer showed such an association (HR, 1.11; 95% CI, 0.85–1.43; P = 0.45). Results were similar for fasting insulin. Conclusion: Our population‐based cohort study shows an increased risk of VTE in subjects with increasing insulin resistance but not independently of BMI.     

Systematic review of megestrol acetate in the treatment of anorexia-cachexia syndrome

This study aimed to assess the efficacy and safety of megestrol acetate (MA) in anorexia-cachexia syndrome (ACS). Literature and relevant databases were searched for randomized controlled trials of MA to treat ACS in patients with cancer, AIDS, or other pathologies. Data were extracted by two independent reviewers, and meta-analyses were performed where possible. Twenty-six studies were included (n=3,887). Compared to placebo, MA increased appetite in oncology patients [RR=2.31 (95% CI 1.52-3.59)], led to weight gain [RR=1.88 (95% CI 1.43-2.47)] and improved HRQOL [RR=1.52 (95% CI 1.00-2.30)]. In AIDS patients, it increased weight [RR=2.16 (95% CI 1.45-3.21)]. MA showed significant benefits over dronabinol in improving appetite, but no statistically significant advantages over other drugs for treating ACS were observed. There were no appreciable differences between lower (<800 mg/day) and higher (>800 mg/day) doses of MA. Few serious adverse events were recorded. MA is an effective and safe treatment for ACS in cancer and AIDS patients, particularly in terms of improvement in appetite and weight gain.