METHODS: Patients chose to continue treatment with nonacog beta pegol in either one of two once-weekly prophylaxis arms (10IU/kg or 40IU/kg), or an on-demand arm (40IU/kg for mild/moderate bleeds; 80IU/kg for severe bleeds). The primary objective was to evaluate immunogenicity; key secondary objectives included assessing safety and haemostatic efficacy in the treatment and prevention of bleeds.
RESULTS: Seventy-one patients received prophylaxis or on-demand treatment. No patient developed an inhibitor and no safety concerns were identified. The success rate for the treatment of reported bleeds was 94.6%; most (87.9%) resolved with one injection. The median annualised bleeding rate for patients on prophylaxis was 1.36 (interquartile range [IQR] 0.00-2.23) and 1.00 (IQR 0.00-2.03) for the 10 and 40IU/kg treatment arms, respectively. The mean FIX activity trough achieved for 10 and 40IU once weekly was 9.8% and 21.3%, respectively. Fourteen patients on prophylaxis underwent 23 minor surgical procedures; haemostatic perioperative outcomes for all of those evaluated were 'excellent' or 'good'.
CONCLUSIONS: Nonacog beta pegol showed a favourable tolerability profile (with no safety issues identified) with good prophylactic protection and control of bleeding in previously treated adult and adolescent haemophilia B patients.
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.
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.).
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.
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.
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: 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 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.
METHODS: This retrospective cohort study includes adult patients of two tertiary hospitals in Malaysia. Potential study subjects were identified using pharmacy supply database or novel oral anticoagulant (NOAC) registry. Demographics, clinical data and laboratory test results were extracted from the medical records of the patients or electronic databases. The main outcome measure is the occurrence of a bleeding event. Bleeding events were classified into major bleeding, clinically relevant non-major bleeding, or minor bleeding, according to the International Society on Thrombosis and Haemostasis criteria. We consider clinically relevant non-major bleeding events or major bleeding events as clinically relevant bleeding events. An occurrence of any bleeding event was recorded from the initiation of NOAC therapy until the death of a patient, or the date of permanent discontinuation of NOAC use, or the last day of data collection. The predicted rate of dabigatran-induced bleeding events per 100 patient-years was estimated.
RESULTS: During a median follow-up period of 18 months, 73 patients experienced 90 bleeding events. Among these patients, 25 including 4 fatal cases, experienced major bleeding events. The predicted rate per 100 patient-years of follow-up of any bleeding events was 9.0 [95% CI 6.9 to 11.1]; clinically relevant bleeding events 6.0 [95% CI 4.8 to 8.3], and major bleeding events 3.0 [95% CI 1.9 to 4.2]. The independent risk factor for clinically relevant bleeding events is prior bleeding. While prior bleeding or congestive heart failure is linked with major bleeding events.
CONCLUSIONS: The predicted rate for dabigatran-induced major bleeding episodes is low but these adverse events carry a high fatality risk. Preventive measures should target older patients who have prior bleeding or congestive heart failure. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
METHODS: The rats were divided into seven groups according to their pretreatment: an untreated control group, an ulcer control group, a reference control group (20 mg/kg omeprazole), and four experimental groups (50, 100, 200, or 400 mg/kg of extract). Carboxymethyl cellulose was the vehicle for the agents. Prior to the induction of gastric ulcers with absolute ethanol, the rats in each group were pretreated orally. An hour later, the rats were sacrificed, and gastric tissues were collected to evaluate the ulcers and to measure enzymatic activity. The tissues were subjected to histological and immunohistochemical evaluations.
RESULTS: Compared with the extensive mucosal damage in the ulcer control group, gross evaluation revealed a marked protection of the gastric mucosa in the experimental groups, with significantly preserved gastric wall mucus. In these groups, superoxide dismutase and malondialdehyde levels were significantly increased (P < 0.05) and reduced (P < 0.05), respectively. In addition to the histologic analyses (HE and periodic acid-Schiff staining), immunohistochemistry confirmed the protection through the upregulation of Hsp70 and the downregulation of Bax proteins. The gastroprotection of the experimental groups was comparable to that of the reference control medicine omeprazole.
CONCLUSIONS: Our study reports the gastroprotective property of an ethanolic extract of C. olitorius against ethanol-induced gastric mucosal hemorrhagic lesions in rats.