RESULTS: When 20% of OD patients were switched to prophylaxis, projected reduction in bleeds was estimated between 3% (Taiwan) through 14% (Algeria and India); projected reductions in hospitalisations ranged from 3% (Taiwan) through 15% (India). Projected HCRU-related annual cost savings were estimated at USD 0.45 m (Algeria), 0.77 m (Argentina), 0.28 m (Chile), 0.13 m (India), 0.29 m (Malaysia), 2.79 m (Mexico), 0.15 m (Taiwan) and 0.78 m (Thailand). Net change in annual CFC consumption ranged from a 0.05% reduction (Thailand) to an overall 5.4% increase (Algeria). Our model provides a flexible framework to estimate the clinical and cost offsets of improved prophylaxis. Modest increase in CFC consumption may be an acceptable offset for improvements in health and healthcare capacity in resource constrained economies.
METHODS: This is a double-blind randomized clinical trial, involving 26 patients with CRSwNP, who underwent FESS for failed medical therapy. The intervention nostril was packed with ribbon gauze soaked in 500 mg/5 ml TXA. The control nostril was packed with ribbon gauze soaked in Moffett's solution, containing 2 ml 10% cocaine, 1 ml adrenaline 1:1000, and 4 ml 0.9% sodium bicarbonate. Both nostrils were packed for 15 min before FESS. Intraoperative bleeding was recorded in the initial 30 min after commencing the surgery. The recordings were reviewed by two surgeons using Boezaart's scoring system. The scores were taken at 15 and 30 min of surgery. The mean score was then calculated. At the end of the surgery, the intervention nostril was packed with Merocel® soaked in 500 mg/5 ml TXA and the control nostril was packed with Merocel® soaked in normal saline. The amount of bleeding within 24 h post-surgery was evaluated using a bolster gauze.
RESULTS: There was no significant difference in intraoperative bleeding between the intervention (1.54 ± 0.71) and control nostrils (1.69 ± 0.55) with p = 0.172. The amount of bleeding in the postoperative period was significantly reduced in the intervention nostril (1.33 ± 0.55) compared to the control nostril saline (1.81 ± 0.48) with p = 0.001.
CONCLUSIONS: We found that the nasal packing soaked in TXA reduced intraoperative and immediate postoperative bleeding. It is a safe, efficacious and cost-effective alternative to Moffett's solution during FESS and also an alternative to normal saline post-surgery among patients with CRSwNP.
TRIAL REGISTRATION NUMBER: FF-2015-232, 2015.
METHODS: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025.
RESULTS: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority).
CONCLUSIONS: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.).
METHODS: We reviewed all children with gastroesophageal varices seen in our unit from 2000 to 2019. Primary prophylaxis was defined as endoscopic procedure without a preceding spontaneous bleeding and secondary prophylaxis as preceded by spontaneous bleeding. High-risk varices were defined as presence of grade III esophageal varices, cardia gastric varices or cherry red spots on the varices. Outcome measures (spontaneous rebleeding within 3 months after endoscopic procedure, number of additional procedures to eradicate varices, liver transplant [LT], death) were ascertained.
RESULTS: Sixteen of 62 (26%) patients (median [± S.D.] age at diagnosis = 5.0 ± 4.3 years) with varices had primary prophylaxis, 38 (61%) had secondary prophylaxis while 8 (13%) had no prophylaxis. No difference in the proportion of patients with high-risk varices was observed between primary (88%) and secondary (92%; P = 0.62) prophylaxis. As compared to secondary prophylaxis, children who had primary prophylaxis were significantly less likely to have spontaneous rebleeding (6% vs. 38%; P = 0.022) and needed significantly fewer repeated endoscopic procedures (0.9 ± 1.0 vs. 3.1 ± 2.5; P = 0.021). After 8.9 ± 5.5 years of follow-up, overall survival was 85%; survival with native liver was 73%. No statistical difference was observed in the eventual outcome (alive with native liver) between primary and secondary (71% vs. 78%, P = 0.78).
CONCLUSION: Children with PHT who had primary prophylaxis had less subsequent spontaneous rebleeding and needed fewer additional endoscopic procedures as compared to secondary prophylaxis but did not have an improved eventual outcome. Screening endoscopy in all children who have signs of PHT and primary prophylaxis in high-risk esophageal varices should be considered before eventual LT.
DATA SOURCES: EMBASE, MEDLINE, CENTRAL, and ISI Web of Science were systematically searched from their inception until May 31, 2019.
REVIEW METHODS: Parallel-arm randomized controlled trials were included.
RESULTS: Seventy-one trials (7539 participants: orthopedics 5450 vs nonorthopedics 1909) were included for quantitative meta-analysis. In comparison to placebo, topical TXA significantly reduced intraoperative blood loss [mean difference (MD) -36.83 mL, 95% confidence interval (CI) -54.77 to -18.88, P < 0.001], total blood loss (MD -319.55 mL, 95% CI -387.42 to -251.69, P < 0.001), and incidence of blood transfusion [odds ratio (OR) 0.30, 95% CI 0.26-0.34, P < 0.001]. Patients who received topical TXA were associated with a shorter length of hospital stay (MD -0.28 days, 95% CI -0.47 to -0.08, P = 0.006). No adverse events associated with the use of topical TXA were observed, namely mortality (OR 0.78, 95% CI 0.45-1.36, P = 0.39), pulmonary embolism (OR 0.73, 95% CI 0.27-1.93, P = 0.52), deep vein thrombosis (OR 1.07, 95% CI 0.65-1.77, P = 0.79), myocardial infarction (OR 0.79, 95% CI 0.21-2.99, P = 0.73), and stroke (OR 0.85, 95% CI 0.28-2.57, P = 0.77). Of all included studies, the risk of bias assessment was "low" for 20 studies, "unclear" for 26 studies and "high" for 25 studies.
CONCLUSIONS: In the meta-analysis of 71 trials (7539 patients), topical TXA reduced the incidence of blood transfusion without any notable adverse events associated with TXA in adults undergoing surgery.
PROSPERO: CRD 42018111762.
OBJECTIVES: The primary aim of this review was to investigate the effect of fibrinogen concentrate in postoperative blood loss in adult surgical patients.
DESIGN: Systematic review and meta-analysis.
DATA SOURCES: Databases of MEDLINE, EMBASE and CENTRAL were searched from their start date until July 2019.
ELIGIBILITY CRITERIA: All randomized clinical trials comparing intravenous fibrinogen concentrate and placebo in adult surgical patients were included, regardless of type of surgery. Observational studies, case reports, case series and non-systematic reviews were excluded.
RESULTS: Thirteen trials (n = 900) were included in this review. In comparison to placebo, fibrinogen concentrate significantly reduced the first 12-hour postoperative blood loss, with a mean difference of -134.6 ml (95% CI -181.9 to -87.4). It also significantly increased clot firmness in thromboelastometry (FIBTEM) with a mean difference of 2.5 mm (95%CI 1.1 to 3.8). No significant differences were demonstrated in the adverse events associated with fibrinogen concentrate use, namely incidence of thromboembolism, myocardial infarction and acute kidney injury.
CONCLUSIONS: In this meta-analysis of 13 randomized trials, low level of evidence and substantial heterogeneity with small sample size limit strong recommendation on the use of fibrinogen concentrate in adult surgical patients. However, its use is tolerable without any notable adverse events.
TRIAL REGISTRATION: CRD42019149164.
OBJECTIVES: To review and assess the efficacy of currently available treatment options for preventing and managing advanced liver disease in children and adults with cystic fibrosis.
SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 19 November 2019. We also searched the reference lists of relevant articles and reviews and online trials registries. Date of last search: 01 January 2020.
SELECTION CRITERIA: Any published and unpublished randomised controlled trials and quasi-randomised controlled trials of advanced liver disease in cystic fibrosis with cirrhosis or liver failure, portal hypertension or variceal bleeding (or both).
DATA COLLECTION AND ANALYSIS: Authors independently examined titles and abstracts to identify potentially relevant trials, but none were eligible for inclusion in this review.
MAIN RESULTS: A comprehensive search of the literature did not identify any published eligible randomised controlled trials.
AUTHORS' CONCLUSIONS: In order to develop the best source of evidence, there is a need to undertake randomised controlled trials of interventions for preventing and managing advanced liver disease in adults and children with cystic fibrosis.
METHODS: The selected patients were divided into three groups, Group I (PDT + SRP), Group II (SP + SRP) and group III (SRP alone). Clinical inflammatory periodontal parameters including plaque index (PI), bleeding on probing (BOP), probing depth (PD) and clinical attachment level (CAL) gain were assessed. Assessment of crevicular fluid interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α) was performed using enzyme-linked immunosorbent assay technique. All measurements were recorded at baseline, 3 months and 6 months follow-up periods, respectively.
RESULTS: A total of 73 patients completed the study. A significant improvement in the BOP was seen in Group II at both follow up visits when compared with other groups (p < 0.05). Only in Group-I that showed statistically significant reduction in moderate periodontal pockets at 3 months (p = 0.021), and significant reductions in deep pockets at 3-months (p = 0.003) and 6-months (p = 0.002), respectively. CAL gain also was reported to be seen in group-I at both visits (p < 0.05). Group- I and II significantly reduced the levels of IL-6 at 3-month period compared to Group-III. This reduction was further maintained by group-II and group-III at 6 months, respectively. TNF-α showed statistically significant decrease in Group II as compared to Group I and Group-III and this reduction was maintained by the end of 6-month visit (p = 0.045).
CONCLUSION: Both the treatment modalities PDT and SP helped in reducing periodontal inflammation. PDT reported significant gain in clinical attachment level, whereas the SP significantly reduced the bleeding levels.
METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up.
RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant.
CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.
METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation.
RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528).
CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.
METHOD: This is a retrospective study of all the patients that had undergone endoscopic variceal surveillance at the Gastroenterology endoscopy unit, Serdang Hospital from 1st January 2015 to 31st March 2017. Patients' demography, aetiologies of liver cirrhosis, platelet level and international normalised ratio (INR) prior banding procedure, and the post EVL complications were recorded and further analysed with SPSS version 16.
RESULTS: In this study, 105 patients were screened for varices. Fifty-five of them had undergone EVL, with a quarter of the patients requiring repeated ligation. There was a male preponderance with 76.4%. 56.4% of patients were in age from 40-59 years. The majority of our patients were of the Malay ethnicity. The major aetiology for liver cirrhosis in our patients was viral hepatitis with Hepatitis C (31.0%), and Hepatitis B (20.0%). Most of our patients had platelet count >50,000 and INR <1.5 prior to EVL. There was no major complication in all of our subjects.
CONCLUSION: EVL is relatively safe and feasible treatment for prevention of oesophageal variceal bleeds with a low complication rate.
MATERIALS AND METHODS: Major electronic databases were searched for randomized-controlled trials comparing carbetocin with oxytocin. Only trials involving cesarean deliveries were included. Non-randomized trials, non-cesarean deliveries, studies which did not directly compare carbetocin to oxytocin and studies which did not analyze the intended outcomes were excluded. Outcomes analysed were postpartum hemorrhage, additional use of uterotonic and transfusion requirement.
RESULTS: Seven studies involving 2012 patients were included in the meta-analysis. There was a significant reduction in the rates of postpartum hemorrhage (RR 0.79; 95% CI 0.66 to 0.94; p = 0.009), use of additional uterotonics (RR 0.57; 95% CI 0.49 to 0.65; p
METHODS: A systematic review of the literature was performed to identify randomized controlled trials that compared the use of carbetocin to oxytocin in the context of cesarean deliveries. Cost effectiveness analysis was then performed using secondary data from the perspective of a maternity unit within the Malaysian Ministry of Health, over a 24 h time period.
RESULTS: Seven randomized controlled trials with over 2000 patients comparing carbetocin with oxytocin during cesarean section were identified. The use of carbetocin in our center, which has an average of 3000 cesarean deliveries annually, would have prevented 108 episodes of PPH, 104 episodes of transfusion and reduced the need for additional uterotonics in 455 patients. The incremental cost effectiveness ratio of carbetocin for averting an episode of PPH was US$278.70.
CONCLUSION: Reduction in retreatment, staffing requirements, transfusion and potential medication errors mitigates the higher index cost of carbetocin. From a pharmacoeconomic perspective, in the context of cesarean section, carbetocin was cost effective as prophylaxis against PPH. Ultimately, the relative value placed on the outcomes above and the individual unit's resources would influence the choice of uterotonic.
AIM: This is a planned interim analysis of pathfinder™3, an international, open-label, Phase 3 trial evaluating the efficacy and safety (including immunogenicity) of N8-GP administered before, during and after major surgery in severe haemophilia A patients aged ≥12 years.
METHODS: Sixteen patients who underwent 18 major surgical procedures (including synovectomy, joint replacement and ankle arthrodesis) were included here. Postoperative assessments were conducted daily for days 1-6, and once for days 7-14. Primary endpoint was N8-GP haemostatic efficacy, assessed after completion of surgery using a four-point scale ('excellent', 'good', 'moderate', 'none').
RESULTS: Haemostasis was successful (rated 'excellent' or 'good') on completion of surgery in 17 (94.4%) procedures and rated as 'moderate' (5.6%) for one surgery in a patient with multiple comorbidities who needed an intraoperative N8-GP dose (20.7 IU kg-1 ). In the postoperative period, three bleeds occurred (one during days 1-6; two during days 7-14); all were successfully treated with N8-GP. Mean N8-GP consumption on day of surgery was 80.0 IU kg-1 ; patients received a mean of 1.7 doses (median: 2, range: 1-3). No safety concerns were identified.
CONCLUSION: The data showed that N8-GP was effective and well tolerated for the prevention and treatment of bleeds during major surgery; such FVIII products with extended half-lives may modify current treatment schedules, enabling fewer infusions and earlier patient discharge.