Marc Afilalo

Efficacy and Safety of Tapentadol Extended Release Compared with Oxycodone Controlled Release for the Management of Moderate to Severe Chronic Pain Related to Osteoarthritis of the Knee: A Randomized, Double-Blind, Placebo- and Active-Controlled Phase III Study

AbstractBackground: Tapentadol is a novel, centrally acting analgesic with μ-opioid receptor agonist and norepinephrine reuptake inhibitor activity. Objective: To evaluate the efficacy and safety of tapentadol extended release (ER) compared with oxycodone controlled release (CR) for management of moderate to severe chronic osteoarthritis-related knee pain. Methods: This was a randomized, double-blind, active- and placebo-controlled, parallel-arm, multicentre, phase III study during which patients received tapentadol ER, oxycodone CR or placebo for a 3-week titration period followed by a 12-week maintenance period. The study was carried out at sites in Australia, Canada, New Zealand and the US. A total of 1030 patients with chronic osteoarthritis-related knee pain were randomized to receive tapentadol ER 100–250 mg twice daily, oxycodone HCl CR 20–50 mg twice daily or placebo. Primary endpoints (as determined prior to initiation of the study) were the changes from baseline in average daily pain intensity (rated by patients on an 11-point numerical rating scale) over the last week of maintenance and over the entire 12-week maintenance period; last observation carried forward was used to impute missing values after early treatment discontinuation. Results: Efficacy and safety were evaluated for 1023 patients. Tapentadol ER significantly reduced average pain intensity from baseline to week 12 of the maintenance period versus placebo (least squares mean [LSM] difference [95% CI], −0.7 [−1.04, −0.33]), and throughout the maintenance period (−0.7 [−1.00, −0.33]). Oxycodone CR significantly reduced average pain intensity from baseline throughout the maintenance period versus placebo (LSM difference [95% CI], −0.3 [−0.67, −0.00]) but not at week 12 (−0.3 [−0.68, 0.02]). A significantly higher percentage of patients achieved ≥50% improvement in pain intensity in the tapentadol ER group (32.0% [110/344]) compared with the placebo group (24.3% [82/337]; p = 0.027), indicating a clinically significant improvement in pain intensity, while a significantly lower percentage of patients achieved ≥50% improvement in pain intensity in the oxycodone CR group (17.3% [59/342]; p = 0.023 vs placebo). In the placebo, tapentadol ER and oxycodone CR groups, respectively, 61.1% (206/337), 75.9% (261/344) and 87.4% (299/342) of patients reported at least one treatment-emergent adverse event (TEAE); incidences of gastrointestinal-related TEAEs were 26.1% (88/337), 43.0% (148/344) and 67.3% (230/342). Conclusion: Treatment with tapentadol ER 100–250 mg twice daily or oxycodone HCl CR 20–50 mg twice daily was effective for the management of moderate to severe chronic osteoarthritis-related knee pain, with substantially lower incidences of gastrointestinal-related TEAEs associated with treatment with tapentadol ER than with oxycodone CR. [Trial registration number: NCT00421928 (ClinicalTrials.gov Identifier)]

Canada Acute Coronary Syndrome Risk Score: A new risk score for early prognostication in acute coronary syndromes

BACKGROUND Despite the availability of several acute coronary syndrome (ACS) prognostic risk scores, there is no appropriate score for early-risk stratification at the time of the first medical contact with patients with ACS. The primary objective of this study is to develop a simple risk score that can be used for early-risk stratification of patients with ACS. METHODS We derived the risk score from the Acute Myocardial Infarction in Quebec and Canada ACS-1 registries and validated the risk score in 4 other large data sets of patients with ACS (Canada ACS-2 registry, Canada-GRACE, EFFECT-1, and the FAST-MI registries). The final risk score is named the Canada Acute Coronary Syndrome Risk Score (C-ACS) and ranged from 0 to 4, with 1 point assigned for the presence of each of these variables: age ≥75 years, Killip >1, systolic blood pressure <100 mm Hg, and heart rate >100 beats/min. The primary end points were short-term (inhospital or 30-day) and long-term (1- or 5-year) all-cause mortality. RESULTS The C-ACS has good predictive values for short- and long-term mortality of patients with ST-segment elevation myocardial infarction and non-ST-segment elevation ACS. The negative predictive value of a C-ACS score ≥1 is excellent at ≥98% (95% CI 0.97-0.99) for short-term mortality and ≥93% (95% CI 0.91-0.96) for long-term mortality. In other words, a C-ACS score of 0 can potentially identify correctly ≥97% short-term survivors and ≥91% long-term survivors. CONCLUSION The C-ACS risk score permits rapid stratification of patients with ACS. Because this risk score is simple and easy to memorize and calculate, it can be rapidly applied by health care professionals without advanced medical training.

Evidence of viremia in 2 cases of severe pandemic influenza A H1N1/09

The recent pandemic of the 2009 pandemic influenza A (H1N1) infrequently caused severe disease. We describe 2 cases of 2009 H1N1 influenza with rapid progression resulting in respiratory failure and need for prolonged intensive care support. Real-time polymerase chain reaction amplification for influenza A (using a Centers for Disease Control and Prevention protocol) and the 2009 H1N1 influenza (using an in-house protocol) was performed on serial respiratory and serum specimens from both patients collected over 3 weeks. Both patients repeatedly demonstrated 2009 H1N1 influenza in respiratory specimens. Evidence of influenza A viremia was also detected in both cases, although it was confirmed as 2009 H1N1 influenza in only one. The presence of viremia in cases of severe 2009 H1N1 influenza has potential prognostic and therapeutic implications. Detection of viremia may be useful as a predictive marker for severe disease. Antiviral agents with low serum levels may be ineffective if administered to patients with influenza viremia.

Effectiveness and safety of glycoprotein IIb/IIIa inhibitors in patients with myocardial infarction undergoing primary percutaneous coronary intervention: A meta-analysis of observational studies

INTRODUCTION Meta-analyses of randomized controlled trials (RCT) showed that glycoprotein IIb/IIIa inhibitors (GPI) are associated with reduced adverse events following primary percutaneous coronary revascularization (PCI). However, the external validity of RCTs is generally limited due to their restricted inclusion of patients. The objective of this study is to evaluate the effectiveness and safety of GPI, as adjuvant therapy for primary PCI in real-life patients with myocardial infarction with ST segment elevation (STEMI) from the general population. METHODS We identified all published peer-reviewed observational studies enrolling STEMI patients who underwent primary PCI. We performed random-effect meta-analyses to determine the association of GPI with major adverse events. RESULTS A total of 11 studies, enrolling 12,253 patients, were retained for this meta-analysis. GPI was associated with approximately 53% reduction in short-term mortality (odds ratio (OR): 0.47, 95% confidence intervals (CI): 0.32-0.68). There was a 62% reduction in long-term mortality associated with GPI (OR: 0.38, 95% CI: 0.30-0.50). GPI was associated with a 62% reduction in 30-day re-infarction (OR: 0.38, 95% CI: 0.24-0.60) and 42% reduction in 30-day repeat PCI (OR: 0.58, 95% CI: 0.36-0.94). A non-significant increase in major bleeding with GPI was observed with an OR of 1.55 (95% CI: 0.92-2.62). CONCLUSIONS GPI is associated with significant reductions in short-term mortality, re-infarction and repeat PCI, long-term mortality and an inconclusive increase in major bleeding. These results provide evidence for the safety and effectiveness of GPI as adjuvant therapy for primary PCI in real-life STEMI patients.

Clarithromycin vs Combined Cefuroxime and Erythromycin in the Treatment of Hospitalised Community-Acquired Pneumonia Patients — Intravenous Followed by Oral Therapy

SummaryThis study compared intravenous followed by oral clarithromycin (500mg twice daily; manufactured by Abbott Laboratories) with intravenous followed by oral erythromycin and cefuroxime (1g erythromycin three times daily, 1.5g cefuroxime three times daily intravenously, 500mg erythromycin, 500mg cefuroxime axetil orally) in the treatment of patients admitted to hospital with community-acquired pneumonia in 21 centres in Europe and Canada. 235 patients were enrolled for the study, of whom 169 (88 clarithromycin and 81 erythromycin/cefuroxime) were clinically evaluable and 47 (24 clarithromycin and 23 erythromycin/cefuroxime) were bacteriologically evaluable. All clinically evaluable patients received intravenous therapy for between 2 and 5 days. No significant differences between the treatment groups were seen regarding age, underlying disease, extent of chest x-ray shadowing and other indices of severity of pneumonia. A satisfactory clinical response was observed in 91 and 88% of clinically evaluable patients and 71 and 66% of all patients (intent-to-treat analysis) in the clarithromycin and erythromycin/cefuroxime groups, respectively, and similar bacterial cure rates were obtained (67 and 70%, respectively). There were no significant differences in the clinical and bacterial response rates between the two treatment groups. There was a significantly greater number of patients experiencing drug-related adverse events in the erythromycin/cefuroxime group (65%) than in the clarithromycin group (49%; p = 0.018), with significantly less nausea, vomiting, diarrhoea and abdominal pain occurring in the clarithromycin group. We concluded that clarithromycin is a suitable monotherapy for patients with community-acquired pneumonia who require intravenous treatment, and is associated with significantly fewer adverse effects than the combination of erythromycin and cefuroxime.

Evaluation and Management of Seasonal Influenza in the Emergency Department

Seasonal influenza causes significant morbidity and mortality, primarily due to increased complication rates among the elderly population and patients with chronic diseases. Timely diagnosis of influenza and early recognition of an influenza outbreak or epidemic are key components in preventing influenza-related complications, hospitalizations, and deaths. Emergency departments are the most frequent points of entry for most influenza cases and are well positioned to identify and manage influenza community outbreaks and epidemics. Emergency departments need specific infection control measures to curb the spread of influenza in the Emergency Department and hospital during the influenza season.

A Young Man Presenting with Acute Encephalopathy, Hemiparesis, and Headache

BACKGROUND Familial hemiplegic migraine (FHM) is a rare type of migraine. Correct diagnosis is challenging for emergency physicians (EPs) due to its variable clinical picture, as well as its lack of diagnostic biological markers. OBJECTIVES To raise awareness among EPs regarding FHMs diverse clinical picture, and to highlight FHMs diagnostic criteria to facilitate an accurate and timely diagnosis of FHM in patients presenting to the emergency department (ED) with indicative symptomatology. CASE REPORT A 24-year-old male student presented to the ED complaining of dizziness, general weakness, and blurred vision that had developed the previous night. The initial physical examination revealed drowsiness, slow speech production, and slight weakness with paresthesia in all limbs. Detailed communication with the patients aunt revealed that he had experienced several similar attacks since the age of 12 years, and that there was also an extensive family history of the same symptoms. In addition, 2 h after arrival, the patient experienced severe throbbing headache, vomiting, severe dysphasia, and the weakness shifted to the right side. A computed tomography scan of the brain showed no anomalies. He was admitted with a tentative diagnosis of FHM. CONCLUSION A diagnosis of FHM should be considered if the patients clinical features include headache and weakness, with a family history of similar symptomatology. However, atypical symptoms of FHM may present as recurrent episodes of unexplained encephalopathy. Crucial elements for making an accurate and timely diagnosis of FHM include a detailed knowledge of weakness-related diseases and an ability to consider FHM in the differential diagnosis, as well as obtaining a thorough family history with repeated neurologic assessments.

Changes in emergency department concordance with guidelines for the management of stinging insect-induced anaphylaxis: 1999–2001 vs 2013–2015

BACKGROUND Changes in emergency department (ED) concordance with guidelines for the management of stinging insect-induced anaphylaxis (SIIA) are not known. OBJECTIVE To describe temporal changes in ED concordance with guidelines for the management of SIIAs. METHODS We analyzed data from 2 multicenter retrospective studies of patients with stinging insect-related acute allergic reactions seen in 1 of 14 North American EDs during 2 periods: 1999 through 2001 and 2013 through 2015. Visits were identified similarly across studies (eg, using International Classification of Diseases, Ninth Revision, Clinical Modification codes 989.5, 995.0, and 995.3). Anaphylaxis was defined as an acute allergic reaction with involvement of at least 2 organ systems or hypotension. We compared concordance between periods with 4 guideline recommendations: (1) treatment with epinephrine, (2) discharge prescription for epinephrine auto-injector, (3) referral to an allergist/immunologist, and (4) instructions to avoid the offending allergen. RESULTS We compared 182 patients with SIIA during 1999 to 2001 with 204 during 2013 to 2015. Any treatment with epinephrine (before arrival to the ED or in the ED) increased over time (30% vs 49%; P < .001). Prescriptions for epinephrine auto-injector at discharge increased significantly (34% vs 57%; P < .001), whereas documentation of referral to an allergist/immunologist decreased (28% vs 12%; P = .002), and instructions to avoid the offending allergen did not change (23% vs 24%; P = .94). Receipt of at least 3 guideline recommendations increased over time; however, the comparison was not statistically significant (10% vs 16%; P = .15). CONCLUSION During the nearly 15-year study interval, we observed increased ED concordance with epinephrine-related guideline recommendations for the management of SIIA. Reasons for the decrease in allergy/immunology referrals merit further study.

Recurrent Cardiovascular Events in Survivors of Myocardial Infarction With ST-Segment Elevation (from the AMI-QUEBEC Study)

The characteristics and predictors of long-term recurrent ischemic cardiovascular events (RICEs) after myocardial infarction with ST-segment elevation (STEMI) have not yet been clarified. We aimed to characterize the 10-year incidence, types, and predictors of RICE. We obtained 10-year follow-up of STEMI survivors at 17 Quebec hospitals in Canada (the AMI-QUEBEC Study) in 2003. There were 858 patients; mean age was 60 years and 73% were male. The majority of patients receive reperfusion therapy; 53.3% and 39.2% of patients received primary percutaneous coronary intervention (PCI) and fibrinolytic therapy, respectively. Seventy-five percent of patients underwent in-hospital PCI (elective, rescue, and primary). At 10 years, 42% of patients suffered a RICE, with most RICEs (88%) caused by recurrent cardiac ischemia. The risk of RICE was the highest during the first year (23.5 per patient-year). At 10 years, the all-cause mortality was 19.3%, with 1/3 of deaths being RICE-related. Previous cardiovascular event, heart failure during the index STEMI hospitalization, discharge prescription of calcium blocker increased the risk of RICE by almost twofold. Each point increase in TIMI (Thrombolysis In Myocardial Infarction) score augmented the risk of RICE by 6%, whereas discharge prescription of dual antiplatelets reduced the risk of RICE by 23%. Our findings suggested that survivors of STEMI remain at high long-term risk of RICE despite high rate of reperfusion therapy and in-hospital PCI. Patients with previous cardiovascular event, in-hospital heart failure, and high TIMI score were particularly susceptible to RICE. Future studies are needed to confirm the impacts of calcium blocker and dual antiplatelets on long-term risk of RICE.

LONGTERM RECURRENT ISCHEMIC CARDIOVASCULAR EVENTS AMONG PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION: INSIGHTS FROM THE AMI-QUÉBEC REGISTRY

RESULTS: Results showed that 5608 obese patients underwent CABG during the study period. After propensity scoring, 494 patients receiving BIMA revascularization were matched to 5089 patients receiving single internal mammary artery (SIMA) revascularization. All pre-operative characteristics were comparable except for a higher prevalence of heart failure in the SIMA group. In-hospital post-operative mortality in the two groups was comparable (1.0% BIMA vs 1.8% SIMA, p1⁄40.86). In-hospital DSWI was also comparable (1.2% BIMA vs 1.0% SIMA, p1⁄40.63). However total DSWI (including post-discharge DSWI, median time 19 days) was significantly higher in the BIMA group compared to the SIMA group (3.6% vs 2.2%; p<0.0001). Over a median follow-up of 7.2 years (mean follow-up 7.7 4.2 years), there was no observed longterm survival advantage in the BIMA vs the SIMA group (p1⁄40.22). CONCLUSION: Using BIMA instead of SIMA increases the risk of DSWI in obese patients. The use of BIMA is not associated with better survival compared to the use of SIMA in this population. These results suggest that the increased short-term risk of post-operative infection associated with BIMA revascularization is not offset by a long-term survival benefit. Given the increased risk of DSWI and absence of midto long-term survival benefit, caution should be exerted when selecting the use of BIMA grafting in the obese population.