A Fibreoptic Endoscopic Study of Upper Gastrointestinal Bleeding at Bugando Medical Centre in Northwestern Tanzania: a Retrospective Review of 240 Cases.

Upper gastrointestinal (GI) bleeding is recognized as a common and potentially life-threatening abdominal emergency that needs a prompt assessment and aggressive emergency treatment. A retrospective study was undertaken at Bugando Medical Centre in northwestern Tanzania between March 2010 and September 2011 to describe our own experiences with fibreoptic upper GI endoscopy in the management of patients with upper gastrointestinal bleeding in our setting and compare our results with those from other centers in the world. A total of 240 patients representing 18.7% of all patients (i.e. 1292) who had fibreoptic upper GI endoscopy during the study period were studied. Males outnumbered female by a ratio of 2.1:1. Their median age was 37 years and most of patients (60.0%) were aged 40 years and below. The vast majority of the patients (80.4%) presented with haematemesis alone followed by malaena alone in 9.2% of cases. The use of non-steroidal anti-inflammatory drugs, alcohol and smoking prior to the onset of bleeding was recorded in 7.9%, 51.7% and 38.3% of cases respectively. Previous history of peptic ulcer disease was reported in 22(9.2%) patients. Nine (3.8%) patients were HIV positive. The source of bleeding was accurately identified in 97.7% of patients. Diagnostic accuracy was greater within the first 24 h of the bleeding onset, and in the presence of haematemesis. Oesophageal varices were the most frequent cause of upper GI bleeding (51.3%) followed by peptic ulcers in 25.0% of cases. The majority of patients (60.8%) were treated conservatively. Endoscopic and surgical treatments were performed in 30.8% and 5.8% of cases respectively. 140 (58.3%) patients received blood transfusion. The median length of hospitalization was 8 days and it was significantly longer in patients who underwent surgical treatment and those with higher Rockall scores (P < 0.001). Rebleeding was reported in 3.3% of the patients. The overall mortality rate of 11.7% was significantly higher in patients with variceal bleeding, shock, hepatic decompensation, HIV infection, comorbidities, malignancy, age > 60 years and in patients with higher Rockall scores and those who underwent surgery (P < 0.001). Oesophageal varices are the commonest cause of upper gastrointestinal bleeding in our environment and it is associated with high morbidity and mortality. The diagnostic accuracy of fibreoptic endoscopy was related to the time interval between the onset of bleeding and endoscopy. Therefore, it is recommended that early endoscopy should be performed within 24 h of the onset of bleeding

Tissue plasminogen activator dose and pulmonary artery pressure reduction in catheter directed thrombolysis of submassive pulmonary embolism.

PURPOSE:The purpose of this study is to assess the incremental effect of tissue plasminogen activator (t-PA) dose on pulmonary artery pressure (PAP) and bleeding during catheter directed thrombolysis (CDT) of submassive pulmonary embolism (PE). MATERIALS AND METHODS:Records of 46 consecutive patients (25 men, 21 women, mean age 55±14 y) who underwent CDT for submassive PE between September 2009 and February 2017 were retrospectively reviewed. Mean t-PA rate was 0.7±0.3 mg/h. PAP was measured at baseline and daily until CDT termination. Mixed-effects regression modeling was performed of repeated PAP measures in individual patients. Bleeding events were classified by Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) and t-PA dose at onset. RESULTS:Mean t-PA dose was 43.0±30.0 mg over 61.9± 28.8 h. Mean systolic PAP decreased from 51.7±15.5 mmHg at baseline to 35.6±12.7 mmHg at CDT termination (p&lt;0.001). Mixed-effects regression revealed a linear decrease in systolic PAP over time (β = -0.37 (SE = 0.05), p&lt;0.001) with reduction in mean systolic PAP to 44.8±1.9 mmHg at 12 mg t-PA/20 h, 39.5±2.0 mmHg at 24 mg t-PA/40 h, and 34.9±2.1 mmHg at 36 mg/60 h. No severe, one moderate, and 8 mild bleeding events occurred; bleeding onset was more frequent at ≤24 mg t-PA (p &lt;0.001). One patient expired from cardiopulmonary arrest after 16 h of CDT (15.4 mg t-PA); no additional intra-procedural fatalities occurred. CONCLUSION:Increased total t-PA dose and CDT duration were associated with greater PAP reduction without increased bleeding events

Timing and volume of fluid administration for patients with bleeding

Original article can be found at: http://www3.interscience.wiley.com Copyright John Wiley &amp; Sons. ‘This review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 2003, Issue 3. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.’ Kwan, I. , Bunn, F. and Roberts, I. 'Timing and volume of fluid administration for patients with bleeding.' Cochrane Database Systematic Reviews 2003, (3) CD002245. DOI: 10.1002/14651858.CD002245 http://dx.doi.org/10.1002/14651858.CD002245Background: Treatment of haemorrhagic shock involves maintaining blood pressure and tissue perfusion until bleeding is controlled. Different resuscitation strategies have been used to maintain the blood pressure in trauma patients until bleeding is controlled. However, while maintaining blood pressure may prevent shock, it may worsen bleeding. Objectives: To assess the effects of early versus delayed, and larger versus smaller volume of fluid administration in trauma patients with bleeding. Search strategy: We searched the CENTRAL (The Cochrane Library 2008, Issue 4), the Cochrane Injuries Group's Specialised Register (searched October 2008), MEDLINE (to October 2008), EMBASE (to October 2008), the National Research Register (in Current controlled trials.gov; searched October 2008) and the Science Citation Index (to October 2008). We checked reference lists of identified articles and contacted authors and experts in the field. Selection criteria: Randomised trials of the timing and volume of intravenous fluid administration in trauma patients with bleeding. Trials in which different types of intravenous fluid were compared were excluded. Data collection and analysis: Two authors independently extracted data and assessed trial quality. Main results: We did not combine the results quantitatively because the interventions and patient populations were so diverse. Early versus delayed fluid administration Three trials reported mortality and two coagulation data. In the first trial (n=598) relative risk (RR) for death with early fluid administration was 1.26 (95% confidence interval of 1.00−1.58). The weighted mean differences (WMD) for prothrombin time and partial thromboplastin time were 2.7 (95% CI 0.9−4.5) and 4.3 (95% CI 1.74−6.9) seconds respectively. In the second trial (n=50) RR for death with early blood transfusion was 5.4 (95% CI 0.3−107.1). The WMD for partial thromboplastin time was 7.0 (95% CI 6.0−8.0) seconds. In the third trial (n=1309) RR for death with early fluid administration was 1.06 (95% CI 0.77−1.47). Larger versus smaller volume of fluid administration Three trials reported mortality and one coagulation data. In the first trial (n=36) RR for death with a larger volume of fluid resuscitation was 0.80 (95% CI 0.28−22.29). Prothrombin time and partial thromboplastin time were 14.8 and 47.3 seconds in those who received a larger volume of fluid, as compared to 13.9 and 35.1 seconds in the comparison group. In the second trial (n=110) RR for death with a high systolic blood pressure resuscitation target (100mmHg) maintained with a larger volume of fluid, as compared to low systolic blood pressure resuscitation target (70mmHg) maintained with a smaller volume of fluid was 1.00 (95% CI 0.26−3.81). In the third trial (n=25) there were no deaths. Authors' conclusions: We found no evidence from randomised controlled trials for or against early or larger volume of intravenous fluid administration in uncontrolled haemorrhage. There is continuing uncertainty about the best fluid administration strategy in bleeding trauma patients. Further randomised controlled trials are needed to establish the most effective fluid resuscitation strategy.Peer reviewe

Uji Ekstrak Enatol 70% Daun Sirih (Piper Betle L.) Terhadap Bleeding Time Pada Mencit Jantan Galur Swiss Webster

Background:Betel plant (Piper betle L.) contains tannins and flavonoids,it was considered to have an effect as a hemostatic agent/cessation of bleeding. Objective: To determine the effect of the 70% ethanol extract of betel leaf (Piper betle L.) on bleeding time and to determine the concentration of extract which can give maximum decrease effect of bleeding time. Methods: This study was experimental laboratory method with Post Test Only With Control Group Design. The animals that used were 25 male Swiss Webster mice 2-3 months old, weight 20-30 grams, and were divided into 5 groups: negative control group was given sterile distilled water, Positive Control group was given epinephrine 1:1000, the first, second and third treatment group was given ethanol extract of betel leaf with concentration of 10%, 20%, and 40% respectively. Each group was calculated of the bleeding time using the Duke method. The data was analyzed with one-way ANOVA test and LSD (Least Significant Difference) test. Results: Ethanol extract of betel leaf with concentration of 10%, 20%, and 40% can decrease bleeding time with mean value of bleeding time in a row was 124.60 seconds, 104.80 seconds and 92.60 seconds. One-way ANOVA test showed that there were significantly difference mean of bleeding time in the five groups after given treatment, p = 0.000 (p <0.05). Conclusion: The ethanol extract 70% of betel leaf (Piper betle L.) concentration of 10%, 20%, and 40% could decrease bleeding time in male Swiss Webster mice. While the concentration of 20% and 40% had maximum decrease effect of bleeding time. Keywords: ethanol extract of betel leaf (Piper betle L.), bleeding time 1The Student of Medical Faculty, Muhammadiyah Surakarta University 2The Lecturer of Medical Faculty, Muhammadiyah Surakarta Universit

Autonomous Systems as Legal Agents: Directly by the Recognition of Personhood or Indirectly by the Alchemy of Algorithmic Entities

The clinical manifestations of platelet dense (δ) granule defects are easy bruising, as well as epistaxis and bleeding after delivery, tooth extractions and surgical procedures. The observed symptoms may be explained either by a decreased number of granules or by a defect in the uptake/release of granule contents. We have developed a method to study platelet dense granule storage and release. The uptake of the fluorescent marker, mepacrine, into the platelet dense granule was measured using flow cytometry. The platelet population was identified by the size and binding of a phycoerythrin-conjugated antibody against GPIb. Cells within the discrimination frame were analysed for green (mepacrine) fluorescence. Both resting platelets and platelets previously stimulated with collagen and the thrombin receptor agonist peptide SFLLRN was analysed for mepacrine uptake. By subtracting the value for mepacrine uptake after stimulation from the value for uptake without stimulation for each individual, the platelet dense granule release capacity could be estimated. Whole blood samples from 22 healthy individuals were analysed. Mepacrine incubation without previous stimulation gave mean fluorescence intensity (MFI) values of 83±6 (mean ± 1 SD, range 69–91). The difference in MFI between resting and stimulated platelets was 28±7 (range 17–40). Six members of a family, of whom one had a known δ-storage pool disease, were analysed. The two members (mother and son) who had prolonged bleeding times also had MFI values disparate from the normal population in this analysis. The values of one daughter with mild bleeding problems but a normal bleeding time were in the lower part of the reference interval

Effect of Vorapaxar Alone and in Combination with Aspirin on Bleeding Time and Platelet Aggregation in Healthy Adult Subjects.

The effect of the protease-activated receptor-1 (PAR-1) antagonist vorapaxar on human bleeding time is not known. This was a randomized, two-period, open-label trial in healthy men (n = 31) and women (n = 5). In period 1, subjects received 81 mg aspirin q.d. or a vorapaxar regimen achieving steady-state plasma concentrations equivalent to chronic 2.5 mg q.d. doses, for 7 days. In period 2, each group added 7 days of the therapy alternate to that of period 1 without washout. Bleeding time and platelet aggregation using arachidonic acid, ADP, and TRAP agonists were assessed. Bleeding time geometric mean ratio (90% CI) for vorapaxar/baseline was 1.01 (0.88-1.15), aspirin/baseline was 1.32 (1.15-1.51), vorapaxar + aspirin/vorapaxar was 1.47 (1.26-1.70), and vorapaxar + aspirin/aspirin was 1.12 (0.96-1.30). Unlike aspirin, vorapaxar did not prolong bleeding time compared with baseline. Bleeding time following administration of vorapaxar with aspirin was similar to that following aspirin alone

Predicting Bleeding and Thrombosis Complications in Patients with Continuous Flow Left Ventricular Assist Devices

Background: Left ventricular assist device (LVAD) therapy has been proven to relieve heart failure symptoms and improve survival, but is not devoid of bleeding and/or thrombotic complications. Risk stratification tools have been utilized in other cardiovascular disease populations to estimate the risk of bleeding and thrombosis with and without anticoagulation, including the HAS-BLED, HEMORR2HAGES, CHADS2 and CHA2DS2-VASc models. The study objective was to evaluate the predictive value of available risk models for bleeding and thrombotic complications in patients with an LVAD within one year of implantation. Methods: This was a retrospective, single-center analysis of patients implanted with the HeartMate II continuous-flow LVAD from July 2011 to June 2016. All patients who received an LVAD within the study period were eligible for inclusion. The primary endpoint was the first occurrence of bleeding or thrombosis within one year from implantation. Baseline risk model scores were calculated at the time of LVAD implantation. Chi-square and student’s t-test were used to measure baseline differences and compare mean risk model scores between patients who had an event. A receiver operator characteristic (ROC) curve analysis was performed to evaluate the accuracy of the risk models to predict an event. Results: A total of 129 patients underwent LVAD implantation within the study time period. Mean CHADS2, CHA2DS2-VASc, and HAS-BLED scores were not significantly different in patients with and without an event. The mean HEMORR2HAGES score was 3.09 and 2.51 in those with and without a bleeding event, respectively (p = 0.008). The ROC curve area for the HEMORR2HAGES model was the highest at 0.620. Conclusion: The HAS-BLED, HEMORR2HAGES, CHADS2and CHA2DS2-VASc risk stratification models did not accurately predict bleeding or thrombosis events in our population. The mean HEMORR2HAGES model score was higher in patients who experienced a bleeding event. However, this model did not have strong positive predictive value. Better risk models are needed to predict bleeding and thrombotic events in this patient population

Idarucizumab for Dabigatran Reversal - Full Cohort Analysis.

BACKGROUND: Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran. METHODS: We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time. Secondary end points included the restoration of hemostasis and safety measures. RESULTS: A total of 503 patients were enrolled: 301 in group A, and 202 in group B. The median maximum percentage reversal of dabigatran was 100% (95% confidence interval, 100 to 100), on the basis of either the diluted thrombin time or the ecarin clotting time. In group A, 137 patients (45.5%) presented with gastrointestinal bleeding and 98 (32.6%) presented with intracranial hemorrhage; among the patients who could be assessed, the median time to the cessation of bleeding was 2.5 hours. In group B, the median time to the initiation of the intended procedure was 1.6 hours; periprocedural hemostasis was assessed as normal in 93.4% of the patients, mildly abnormal in 5.1%, and moderately abnormal in 1.5%. At 90 days, thrombotic events had occurred in 6.3% of the patients in group A and in 7.4% in group B, and the mortality rate was 18.8% and 18.9%, respectively. There were no serious adverse safety signals. CONCLUSIONS: In emergency situations, idarucizumab rapidly, durably, and safely reversed the anticoagulant effect of dabigatran. (Funded by Boehringer Ingelheim; RE-VERSE AD ClinicalTrials.gov number, NCT02104947 .)

Analyse zeitveraenderlicher Kovariablen und rekurrenter Ereignisse am Beispiel einer Studie zur prophylaktischen Behandlung von Oesophagusvarizen

To assess the effect of prophylactic sclerotherapy on variceal hemorrhage and survival of patients with liver cirrhosis and esophageal varices, a randomized study had been carried out. We analysed the data from different points of view. The time-dependent Cox model and the linear counting process of Aalen are applied allowing for the time-dependent covariate ``variceal bleeding`` -- that switches up to three times -- in a multivariate analysis of the remaining life time. A model for the times to and between the recurrent events of bleeding including unobserved heterogeneity is estimated by a distribution-free and by a parametric method where the latter also admits time-dependent covariates such as repeated measurements of laboratory data. We find that high age, high Child-Pugh score and especially the first occurence of variceal bleeding have a statistically significant negative effect on survival whereas patients with fundic varices and/or alcoholic cirrhosis have a significant higher risk of bleeding. In both analyses, inclusion of time-dependent covariates does not change the estimation substantially. In particular, prophylactic sclerotherapy is not shown to reduce the risk of bleeding nor dying significantly