Elham Sabri

Age of Transfused Blood in Critically Ill Adults

BACKGROUND Fresh red cells may improve outcomes in critically ill patients by enhancing oxygen delivery while minimizing the risks of toxic effects from cellular changes and the accumulation of bioactive materials in blood components during prolonged storage. METHODS In this multicenter, randomized, blinded trial, we assigned critically ill adults to receive either red cells that had been stored for less than 8 days or standard-issue red cells (the oldest compatible units available in the blood bank). The primary outcome measure was 90-day mortality. RESULTS Between March 2009 and May 2014, at 64 centers in Canada and Europe, 1211 patients were assigned to receive fresh red cells (fresh-blood group) and 1219 patients were assigned to receive standard-issue red cells (standard-blood group). Red cells were stored a mean (±SD) of 6.1±4.9 days in the fresh-blood group as compared with 22.0±8.4 days in the standard-blood group (P<0.001). At 90 days, 448 patients (37.0%) in the fresh-blood group and 430 patients (35.3%) in the standard-blood group had died (absolute risk difference, 1.7 percentage points; 95% confidence interval [CI], -2.1 to 5.5). In the survival analysis, the hazard ratio for death in the fresh-blood group, as compared with the standard-blood group, was 1.1 (95% CI, 0.9 to 1.2; P=0.38). There were no significant between-group differences in any of the secondary outcomes (major illnesses; duration of respiratory, hemodynamic, or renal support; length of stay in the hospital; and transfusion reactions) or in the subgroup analyses. CONCLUSIONS Transfusion of fresh red cells, as compared with standard-issue red cells, did not decrease the 90-day mortality among critically ill adults. (Funded by the Canadian Institutes of Health Research and others; Current Controlled Trials number, ISRCTN44878718.).

A Multicenter Randomized Controlled Trial Comparing Single-Row with Double-Row Fixation in Arthroscopic Rotator Cuff Repair

BACKGROUND Controversy exists regarding the optimal technique for arthroscopic rotator cuff repair. The purpose of this multicenter, randomized, double-blind controlled study was to compare the functional outcomes and healing rates after use of single-row and double-row suture techniques for repair of the rotator cuff. METHODS Ninety patients undergoing arthroscopic rotator cuff repair were randomized to receive either a single-row or a double-row repair. The primary objective was to compare the Western Ontario rotator cuff index (WORC) score at twenty-four months. Secondary objectives included comparison of the constant and american shoulder and elbow surgeons (ASES) scores and strength between groups. Anatomical outcomes were assessed with magnetic resonance imaging (MRI) or ultrasonography to determine the postoperative healing rates. RESULTS Baseline demographic data including age (p = 0.29), sex (p = 0.68), affected side (p = 0.39), and rotator cuff tear size (p = 0.28) did not differ between groups. The WORC score did not differ significantly between groups at any time point (p = 0.48 at baseline, p = 0.089 at three months, p = 0.52 at six months, p = 0.83 at twelve months, and p = 0.60 at twenty-four months). The WORC score at each postoperative time point was significantly better than the baseline value. The Constant score, ASES score, and strength did not differ significantly between groups at any time point. Logistic regression analysis demonstrated that a smaller initial tear size and double-row fixation were associated with higher healing rates. CONCLUSIONS No significant differences in functional or quality-of-life outcomes were identified between single-row and double-row fixation techniques. A smaller initial tear size and a double-row fixation technique were associated with higher healing rates as assessed with ultrasonography or MRI. LEVEL OF EVIDENCE Therapeutic level I. See Instructions for Authors for a complete description of levels of evidence.

Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review

Background Soy and red clover isoflavones are controversial due to purported estrogenic activity and possible effects on breast cancer. We conducted a systematic review of soy and red clover for efficacy in improving menopausal symptoms in women with breast cancer, and for potential impact on risk of breast cancer incidence or recurrence. Methods We searched MEDLINE, Embase, the Cochrane Library, and AMED from inception to March 2013 for human interventional or observational data pertaining to the safety and efficacy of soy and red clover isoflavones in patients with or at risk of breast cancer. Results Of 4179 records, we included a total of 131 articles: 40 RCTs, 11 uncontrolled trials, and 80 observational studies. Five RCTs reported on the efficacy of soy for hot flashes, showing no significant reductions in hot flashes compared to placebo. There is lack of evidence showing harm from use of soy with respect to risk of breast cancer or recurrence, based on long term observational data. Soy intake consistent with that of a traditional Japanese diet (2-3 servings daily, containing 25-50mg isoflavones) may be protective against breast cancer and recurrence. Human trials show that soy does not increase circulating estradiol or affect estrogen-responsive target tissues. Prospective data of soy use in women taking tamoxifen does not indicate increased risk of recurrence. Evidence on red clover is limited, however existing studies suggest that it may not possess breast cancer-promoting effects. Conclusion Soy consumption may be associated with reduced risk of breast cancer incidence, recurrence, and mortality. Soy does not have estrogenic effects in humans. Soy intake consistent with a traditional Japanese diet appears safe for breast cancer survivors. While there is no clear evidence of harm, better evidence confirming safety is required before use of high dose (≥100mg) isoflavones can be recommended for breast cancer patients.

Laparoscopic colon surgery: does operative time matter?

PURPOSE: The purpose was to determine if the perioperative benefits associated with laparoscopic colectomies are maintained as operative time increases. METHODS: A retrospective review was performed of a database that was prospectively collected from April 1991 to May 2005. Since operative time distributions were different, patients were divided into three groups: laparoscopic right colectomy or ileocecal resection, sigmoid resection, and total abdominal colectomy. The following outcomes were assessed: intraoperative and postoperative complications, days to surgical diet, length of stay, 30-day mortality, and the presence of a learning curve. RESULTS: Following exclusions, there were 231 right colon and ileocecal resections, 210 sigmoid colectomies, and 46 total abdominal colectomies. With increasing operative time in both right/ileocecal and sigmoid resections, logistic regression demonstrated no significant association between intraoperative and postoperative complications, days to surgical diet, or length of stay. Weight was significantly correlated with increasing operative time in the right/ileocecal and sigmoid resection groups. In the total abdominal colectomy group, significant relationships between increased operative time and postoperative complications (P = 0.04), days to surgical diet (P = 0.02), and hospital stay (P = 0.03) were found. An operative time cut-point was determined in the total abdominal colectomy group. Patients with operative times >270 minutes were more likely to have postoperative complications (P = 0.024), longer ileus (five vs. three median days to surgical diet, P = 0.003), and longer length of stay (seven vs. five days, P = 0.04). This increased risk remained significant after adjusting for weight and diagnosis. No significant learning curve was identified. CONCLUSION: Increasing operative time does not appear to adversely affect perioperative outcomes in segmental colectomies. Total abdominal colectomies lasting more than 270 minutes were associated with increased postoperative complications, days to surgical diet, and length of stay.

Evaluation of the incidence, risk factors, and impact on patient outcomes of postintubation hemodynamic instability

OBJECTIVES Postintubation hemodynamic instability (PIHI) is a potentially life-threatening adverse event of emergent endotracheal intubation. The objectives of this study were to determine the incidence, risk factors, and impact on patient outcomes associated with PIHI in intubations performed in emergency medicine. METHODS A structured chart audit was performed of all consecutive adult patients requiring emergent endotracheal intubations over a 16-month period at a tertiary care emergency department (ED). Data collection included medications, comorbidities, vital signs in the 30 minutes before and after intubation, hospital length of stay, and in-hospital mortality. PIHI was defined as a decrease in systolic blood pressure (SBP) to ≤ 90 mm Hg, a decrease in SBP of ≥ 20% from baseline, a decrease in mean arterial pressure to ≤ 65 mm Hg, or the initiation of any vasopressor medication at any time in the 30 minutes following intubation. RESULTS Overall, 218 patients intubated in the ED were identified, and 44% (96 of 218) developed PIHI. On multivariate analysis, increasing age (OR 1.03, 95% CI 1.01-1.05), chronic obstructive pulmonary disease (OR 3.00, CI 1.19-7.57), and pre-emergent endotracheal intubation hemodynamic instability (OR 2.52, 95% CI 1.27-4.99) were associated with the development of PIHI. The use of a neuromuscular blocking medication was associated with a decreased incidence of PIHI (OR 0.34, 95% CI 0.16-0.75). CONCLUSIONS Based on our data, postintubation hypotension occurs in a significant proportion of ED patients requiring emergent airway control. Further investigation is needed to confirm the factors we found to be associated with PIHI and to determine if PIHI is associated with increased morbidity and mortality.

The incidence and clinical impact of bone metastases in non-small cell lung cancer

INTRODUCTION Non-small cell lung cancer (NSCLC) is the leading global cause of cancer death. While bone metastases (BM) commonly cause morbidity, bone-targeted agent (BTA) use is variable. We investigated the incidence and impact of BM among unselected NSCLC patients. METHODS A retrospective chart review of all NSCLC patients seen at a single institution from January 2007 to January 2008 was performed. Various clinical and pathology data were collected. In BM patients, skeletal related events (SRE), interventions and outcomes were recorded. RESULTS We identified 383 patients; median age 68 (IQR 60-76); 54% female. Initially 156 patients (41%) were treated with curative intent of whom 91 subsequently relapsed; 227 (59%) were considered palliative from time of diagnosis, including 22 with early stage disease not amenable to radical therapy. Of 296 patients with advanced NSCLC, common metastatic sites were: lung/pleura (80%), mediastinal nodes (69%), bone (39%), brain (30%), and liver (24%). Of 118 patients with BM, 69 (59%) had ≥1 SREs (range 1-18). Common SREs were radiotherapy (63%), pathologic fractures (22%), spinal cord compression (6%) or surgery to bone (5%). Opioid analgesia was required in 69% of BM patients, only 6% of patients with BM received BTA. Overall survival (OS) in pts with mNSCLC was 7.3 months (IQR 3.1-20.5). Pts with BM had significantly shorter OS compared to those without BM (5.8 versus 10.2 months, p=0.03). CONCLUSIONS BM are common in patients with advanced NSCLC and associated with shorter survival. In this cohort, despite SREs occurred in many patients, BTA were rarely used.

Effects of Oxygen on Exercise Duration in Chronic Obstructive Pulmonary Disease Patients before and after Pulmonary Rehabilitation

BACKGROUND Supplemental oxygen therapy has been shown to improve exercise performance in patients with chronic obstructive pulmonary disease (COPD). It is unknown whether the magnitude of this benefit would be affected by participation in a pulmonary rehabilitation program. OBJECTIVE To compare the effects of supplemental oxygen on exercise capacity in nonhypoxemic COPD patients before and after participation in a pulmonary rehabilitation program. METHODS Sixteen patients with COPD underwent two pairs of constant-load exercise tests before and after participation in a three-month outpatient pulmonary rehabilitation program. Each pair of exercise tests consisted of a test performed with room air and a second test performed with 50% supplemental oxygen, in random order. The primary outcome was the difference in exercise duration between tests performed with supplemental oxygen and with room air. This difference was compared before and after participation in a pulmonary rehabilitation program. RESULTS Supplemental oxygen therapy improved exercise duration by 75 s before participation in a pulmonary rehabilitation program and by 153 s following pulmonary rehabilitation. Rehabilitation alone improved exercise duration by 28 s, but rehabilitation appeared to augment the exercise benefits of supplemental oxygen therapy by a mean of 78 s (95% CI 11 s to 145 s; P = 0.03). CONCLUSION The effects of supplemental oxygen therapy were augmented after pulmonary rehabilitation. The improvement in exercise duration with supplemental oxygen following rehabilitation was greater than either supplemental oxygen or pulmonary rehabilitation alone.

Effect of theophylline on exercise capacity in COPD patients treated with combination long-acting bronchodilator therapy: a pilot study

Background Many patients with chronic obstructive pulmonary disease continue to experience significant functional limitation despite the use of both long-acting anticholinergic and beta-agonist inhalers. Theophylline is a widely available medication which may further improve lung function and exercise performance. Previous studies evaluating the effects of theophylline on exercise capacity in chronic obstructive pulmonary disease (COPD) have demonstrated heterogeneous results. Methods We performed a randomized placebo-controlled double-blind pilot study assessing the effects of theophylline on constant load exercise duration and lung function, involving 24 COPD patients already treated with long-acting inhaled beta-agonist and long-acting anti-cholinergic bronchodilator therapy. Results Analyzable data was available in 10 of 12 subjects in the treatment arm and 11 of 12 subjects in the control arm. Theophylline was associated with a 26.1% (95% confidence interval [CI]: −17.3–69.5) improvement in exercise duration compared to placebo. Four of 10 treated patients demonstrated an improvement in exercise duration exceeding the minimum clinically important difference of 33%, compared to 1 of 11 controls (P = 0.15). Furthermore, peak ventilation was reduced by 11.1%, (95% CI: 0.77–21.5) which may suggest improvements in gas exchange. There were no significant observed differences in resting lung function nor measures of dyspnea between the two treatment groups. Conclusions Our study demonstrated a trend, but not a statistically significant improvement in exercise duration and a reduction in peak ventilation with theophylline. Based on the observed mean differences and standard deviations in this pilot study, a randomized controlled trial would require 45 subjects in each arm to detect a significant change in exercise duration.

Factors influencing a specific pathologic diagnosis of non-small-cell lung carcinoma.

INTRODUCTION Historically, a non-small-cell lung carcinoma diagnosis, without pathologic subclassification, provided sufficient information to guide therapy. Evidence now demonstrates that pathologic subtype classification is central in selecting optimal treatment. This review aimed to identify factors associated with a specific pathologic diagnosis. METHODS All nonoperative cases of non-small-cell lung carcinoma (NSCLC) referred to the medical oncology divisions of the Ottawa Hospital Cancer Centre (2008) and Princess Margaret Hospital, Toronto (2007-2010) were identified. The charts were reviewed for demographics, diagnostic methods, and final diagnosis. Logistic regression was performed to identify variables associated with a specific diagnosis. RESULTS Of 739 patient records analyzed, 377 (51%) were men, 299 (40%) were aged over 70 years, and 510 (69%) had an Eastern Cooperative Oncology Group performance status of 0-2. Three hundred and eighty five (52%) of patients were diagnosed in a tertiary academic center. The lung primary was sampled in 503 (68%) of patients. Computed tomography-guided biopsy (n = 370, 50%) and bronchoscopy (n = 179, 24%) were the most common techniques. Four hundred and seventy seven (65%) of biopsies were cytologic specimens alone, and immunohistochemistry was performed in 337 (46%) of cases. The most common diagnoses were adenocarcinoma (n = 338, 46%), NSCLC not otherwise specified (n = 254, 34%), and squamous cell carcinoma (n = 115, 16%). Overall, 456 (62%) of patients received a specific pathologic diagnosis. Factors significantly associated with attaining a specific pathologic diagnosis were diagnosis outside an academic center (adjusted odds ratios [OR] 2.1 [95% CI, 1.41-3.14]; P = .0003), histologic laboratory samples (adjusted OR 1.58 [95% CI, 1.003-2.49]; P = .049), and immunohistochemical testing (adjusted OR 1.82 [95% CI, 1.25-2.70], P = .0021). CONCLUSIONS A significant minority of patients with NSCLC do not receive a specific pathologic diagnosis. In an era of individualized medicine, this may potentially impact optimal clinical management.

Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial

Abstract Objective To determine the efficacy of high dose folic acid supplementation for prevention of pre-eclampsia in women with at least one risk factor: pre-existing hypertension, prepregnancy diabetes (type 1 or 2), twin pregnancy, pre-eclampsia in a previous pregnancy, or body mass index ≥35. Design Randomised, phase III, double blinded international, multicentre clinical trial. Setting 70 obstetrical centres in five countries (Argentina, Australia, Canada, Jamaica, and UK). Participants 2464 pregnant women with at least one high risk factor for pre-eclampsia were randomised between 2011 and 2015 (1144 to the folic acid group and 1157 to the placebo group); 2301 were included in the intention to treat analyses. Intervention Eligible women were randomised to receive either daily high dose folic acid (four 1.0 mg oral tablets) or placebo from eight weeks of gestation to the end of week 16 of gestation until delivery. Clinicians, participants, adjudicators, and study staff were masked to study treatment allocation. Main outcome measure The primary outcome was pre-eclampsia, defined as hypertension presenting after 20 weeks’ gestation with major proteinuria or HELLP syndrome (haemolysis, elevated liver enzymes, low platelets). Results Pre-eclampsia occurred in 169/1144 (14.8%) women in the folic acid group and 156/1157 (13.5%) in the placebo group (relative risk 1.10, 95% confidence interval 0.90 to 1.34; P=0.37). There was no evidence of differences between the groups for any other adverse maternal or neonatal outcomes. Conclusion Supplementation with 4.0 mg/day folic acid beyond the first trimester does not prevent pre-eclampsia in women at high risk for this condition. Trial registration Current Controlled Trials ISRCTN23781770 and ClinicalTrials.gov NCT01355159.