SIMULASI PENDISTRIBUSIAN AIR MINUM PADA SUMBER AIR GUA SEROPAN KABUPATEN GUNUNG KIDUL

Kabupaten Gunung Kidul adalah salah satu wilayah yang mempunyai potensi air berlimpah tapi penduduk kekurangan air. Karena sebagian besar kondisi alamnya merupakan pegunungan kapur, maka digunakan teknologi untuk memperoleh air. Tujuan dari penulisan ini adalah adalah membuat simulasi jam pendistribusian air yang efektif khusus untuk kecamatan Ngawen dengan bantuan program Epanet 2.0, sehingga diperoleh waktu pendistribusian sesuai dengan kebutuhan pelanggan dengan waktu distribusi dilihat dari kebiasaan masyarakat mengkonsumsi atau menggunakan air dalam aktifitas sehari-harinya. Metode yang digunakan pada penulisan ini yaitu deskripsi komperatif yaitu mejelaskan pengaturan pendistribusian air yang terdapat di Kecamatan Ngawen dibandingkan dengan pengaturan simulasi dengan bantuan program Epanet 2.0, sehingga diperoleh simulasi pendistribusian yang efektif. Berdasarkan hasil analisa jaringan air minum kecamatan Ngawen untuk waktu pelayanan kondisi eksisting 12 jam selalu terjadi kekurangan. Sedangkan hasil simulasi jam pendistribusian kecamatan Ngawen untuk waktu distribusi 24 jam masih terjadik kekurangan. Dari hal tersebut diatas perlu adanya penelitian lebih lanjut tentang masalah yang menyebabkan jaringan air minum di kecamatan Ngawen sering terjadi kekurangan

Fixed Versus Variable Dosing of Prothrombin Complex Concentrate for Bleeding Complications of Vitamin K Antagonists:The PROPER3 Randomized Clinical Trial

STUDY OBJECTIVE: To determine if a fixed dose of 1000 IU of 4-factor prothrombin complex concentrate (4F-PCC) is as effective as traditional variable dosing based on body weight and international normalized ratio (INR) for reversal of vitamin K antagonist (VKA) anticoagulation. METHODS: In this open-label, multicenter, randomized clinical trial, patients with nonintracranial bleeds requiring VKA reversal with 4F-PCC were allocated to either a 1,000-IU fixed dose of 4F-PCC or the variable dose. The primary outcome was the proportion of patients with effective hemostasis according to the International Society of Thrombosis and Haemostasis definition. The design was noninferiority with a lower 95% confidence interval of no more than -6%. When estimating sample size, we assumed that fixed dosing would be 4% superior. RESULTS: From October 2015 until January 2020, 199 of 310 intended patients were included before study termination due to decreasing enrollment rates. Of the 199 patients, 159 were allowed in the per-protocol analysis. Effective hemostasis was achieved in 87.3% (n=69 of 79) in fixed compared to 89.9% (n=71 of 79) in the variable dosing cohort (risk difference 2.5%, 95% confidence interval -13.3 to 7.9%, P=.27). Median door-to-needle times were 109 minutes (range 16 to 796) in fixed and 142 (17 to 1076) for the variable dose (P=.027). INR less than 2.0 at 60 minutes after 4F-PCC infusion was reached in 91.2% versus 91.7% (P=1.0). CONCLUSION: The large majority of patients had good clinical outcome after 4F-PCC use; however, noninferiority of the fixed dose could not be demonstrated because the design assumed the fixed dose would be 4% superior. Door-to-needle time was shortened with the fixed dose, and INR reduction was similar in both dosing regimens

Outcome of intracranial bleeding managed with prothrombin complex concentrate in patients on direct factor Xa inhibitors or vitamin K antagonists

Intracranial hemorrhage (ICH) is the most feared complication of anticoagulation with a high mortality and morbidity. Before registration of a specific reversal agent for factor Xa inhibitors (FXa-I), international guidelines recommended prothrombin complex concentrate (PCC), which also is the specific reversal agent for vitamin K antagonists (VKA). In two contemporary cohorts, we compared clinical outcomes between patients with FXa-I and VKA related ICH treated with PCC between 2014 and 2018. Primary outcome was effective hemostasis after 24 h, according to the International Society of Thrombosis and Hemostasis definition. Safety outcomes were defined as venous and arterial thromboembolic complications and death within 30 days. Thirty-six patients with FXa-I-ICH and 39 patients with VKA-ICH were available for analysis. Baseline characteristics were comparable between both groups, except for time from start of symptoms to presentation at the hospital. In the FXa-I-ICH cohort, 24 (73%) patients achieved effective hemostasis compared to 23 (62%) patients in the VKA-ICH cohort (crude odds ratio [OR] 1.62 [95%CI 0.59–4.48], adjusted OR 1.45 [95%CI 0.44–4.83]). Eight (24%) patients with FXa-I-ICH deceased compared to 17 (45%) patients with VKA-ICH (crude OR 0.38 [95%CI 0.14–1.24], adjusted OR 0.41 [95%CI 0.12–1.24]). In this observational cohort study, the outcome of ICH managed with PCC was similar in patients with FXa-I-ICH and in patients with VKA-ICH

Clinical outcome of patients with a vitamin K antagonist-associated bleeding treated with prothrombin complex concentrate

Background: Vitamin K antagonists (VKA) are used for the treatment of thromboembolism. Patients with severe VKA-associated bleeding require immediate restoration of haemostasis. Clinical studies on the effect of prothrombin complex concentrate (PCC) are heterogeneous with respect to outcome of bleeding. Objective: To evaluate the clinical outcome of patients treated with PCC for VKA-associated bleeding. Methods: We performed a cohort study of consecutive patients who received PCC for VKA-related bleeding in five Dutch hospitals. Data were collected by chart review on the bleeding event, international normalized ratio (INR), haemostatic efficacy, thromboembolic (TE) complications, and mortality. The primary outcome was effective haemostasis, assessed by an adaptation of the Sarode criteria with a surrogate outcome for patients with ICH without repeat CT. Results: One hundred patients were included. Mean age was 74 years, 54% were male and 79% received VKA for atrial fibrillation. Most patients presented with ICH (41%) or GI bleeding (36%). Effective haemostasis was achieved in 67/98 (68%) patients using the adapted classification. Surrogate outcomes were applied for 32 patients and data for two patients was missing. Median pre-treatment INR was 3.9 (IQR 2.9-5.8). One hour after PCC infusion, the INR was available for 50 patients and of these, 35 (70%) had an INR s1.4. TE complications occurred in five patients and 22 died (60% bleeding-related) within 30 days. Conclusion: PCC achieved effective haemostasis in 68% of evaluable patients with VKA-associated bleeding. TE complication rates were low, but mortality rates were high, due to the large number of patients with ICH

Method agreement analysis and interobserver reliability of the ISTH proposed definitions for effective hemostasis in management of major bleeding

Introduction In 2016 the Scientific and Standardization Subcommittee (SSC) on Control of Anticoagulation of the International Society on Thrombosis and Haemostasis (ISTH) proposed criteria to evaluate the effectiveness of anticoagulant reversal in major bleeding management. Testing and validation of these criteria are required. Objective To investigate the method agreement, interobserver reliability and applicability of the ISTH proposed definitions for hemostatic effectiveness. Methods Patient data from three anticoagulant-antidote studies were used for hemostatic effectiveness assessment using the ISTH-proposed definitions and clinical opinion. For every patient a case document was produced. For each cohort, four adjudicators were asked to assess the hemostatic effectiveness independently on a case-by-case basis. Agreement between the two methods of hemostatic effectiveness assessment was calculated using Cohen's kappa (), with a calculated sample size of at least 73 cases. Results The full dataset consisted of 116 cases, resulting in 464 assessments. Method agreement in outcome was observed in 364 of 464 assessments (78.5%), resulting in of 0.634 (95% CI: 0.575-0.694), or substantial agreement. Interobserver reliability analysis of the proposed definitions computed an overall agreement of 54.2% with of 0.312 (fair agreement). Discussion Method agreement analysis shows that the conclusions drawn using the ISTH definitions have substantial agreement with clinical opinion. Interobserver reliability analysis demonstrated acceptable agreement. In-depth analysis provided minor opportunities for further improvement and correct application of the definition. The definition is recommended to be used in all future studies evaluating hemostatic effectiveness, taking the suggested recommendations into account

Emergencies on direct oral anticoagulants: Management, outcomes, and laboratory effects of prothrombin complex concentrate

Background In the initial absence of specific reversal agents for factor Xa inhibitors (FXa-Is), prothrombin complex concentrate (PCC) as a hemostatic agent has been recommended by guidelines. Since 2017, idarucizumab has been registered for dabigatran reversal. Still, data on the clinical outcome of direct oral anticoagulant (DOAC)-related emergencies (major bleeding or urgent interventions) is scarce. In addition, it is unknown to what extent PCC restores thrombin generation in FXa-I-related emergencies. Our aim was to describe management and clinical outcomes of DOAC-related emergencies and to assess the laboratory effect of PCC in patients with FXa-I emergencies. Methods In this prospective cohort study in 5 Dutch hospitals, patients presenting with DOAC-related emergencies were eligible. The primary outcome was effective hemostasis according to the ISTH definition. Safety outcomes were 30-day mortality and thromboembolic rate. In patients treated with PCC, additional blood samples were taken to assess the effect on thrombin generation. Results We included 101 patients with major bleeding (FXa-I, 76; dabigatran, 25) and 21 patients requiring an urgent intervention (FXa-I, 16; dabigatran, 5). Of patients with major bleeding, 67% were treated with PCC or idarucizumab. Effective hemostasis, 30-day mortality, and thromboembolism rate were 67%, 22%, and 1%, respectively. In a subset of bleeding patients on FXa-I managed with PCC, thrombin generation increased, with 96% immediately after PCC administration. In patients requiring an urgent intervention, effective hemostasis, 30-day mortality, and thromboembolic rate were 95%, 14%, and 5%. Conclusions Effective hemostasis was achieved in the majority of patients presenting with DOAC-related emergencies;, thromboembolic complications were rare, and mortality was quite high