Valproic Acid Protects Against Acute Kidney Injury in Hemorrhage and Trauma.

INTRODUCTION: Trauma is the leading cause of death among young people. These patients have a high incidence of kidney injury, which independently increases the risk of mortality. As valproic acid (VPA) treatment has been shown to improve survival in animal models of lethal trauma, we hypothesized that it would also attenuate the degree of acute kidney injury. METHODS: We analyzed data from two separate experiments where swine were subjected to lethal insults.  Model 1: hemorrhage (50% blood volume hemorrhage followed by 72-h damage control resuscitation). Model 2: polytrauma (traumatic brain injury, 40% blood volume hemorrhage, femur fracture, rectus crush and grade V liver laceration). Animals were resuscitated with normal saline (NS) +/- VPA 150 mg/kg after a 1-h shock phase in both models (n = 5-6/group). Serum samples were analyzed for creatinine (Cr) using colorimetry on a Liasys 330 chemistry analyzer. Proteomic analysis was performed on kidney tissue sampled at the time of necropsy. RESULTS: VPA treatment significantly (P < 0.05) improved survival in both models. (Model 1: 80% vs 20%; Model 2: 83% vs. 17%). Model 1 (Hemorrhage alone): Cr increased from a baseline of 1.2 to 3.0 in NS control animals (P < 0.0001) 8 h after hemorrhage, whereas it rose only to 2.1 in VPA treated animals (P = 0.004). Model 2 (Polytrauma): Cr levels increased from baseline of 1.3 to 2.5 mg/dL (P = 0.01) in NS control animals 4 h after injury but rose to only 1.8 in VPA treated animals (P = 0.02). Proteomic analysis of kidney tissue identified metabolic pathways were most affected by VPA treatment. CONCLUSIONS: A single dose of VPA (150 mg/kg) offers significant protection against acute kidney injury in swine models of polytrauma and hemorrhagic shock.

Rationale and design for the study of rivaroxaban to reduce thrombotic events, hospitalization and death in outpatients with COVID-19: The PREVENT-HD study.

BACKGROUND: COVID-19 is associated with both venous and arterial thrombotic complications. While prophylactic anticoagulation is now widely recommended for hospitalized patients with COVID-19, the effectiveness and safety of thromboprophylaxis in outpatients with COVID-19 has not been established. STUDY DESIGN: PREVENT-HD is a double-blind, placebo-controlled, pragmatic, event-driven phase 3 trial to evaluate the efficacy and safety of rivaroxaban in symptomatic outpatients with laboratory-confirmed COVID-19 at risk for thrombotic events, hospitalization, and death. Several challenges posed by the pandemic have necessitated innovative approaches to clinical trial design, start-up, and conduct. Participants are randomized in a 1:1 ratio, stratified by time from COVID-19 confirmation, to either rivaroxaban 10 mg once daily or placebo for 35 days. The primary efficacy end point is a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality. The primary safety end point is fatal and critical site bleeding according to the International Society on Thrombosis and Haemostasis definition. Enrollment began in August 2020 and is expected to enroll approximately 4,000 participants to yield the required number of end point events. CONCLUSIONS: PREVENT-HD is a pragmatic trial evaluating the efficacy and safety of the direct oral anticoagulant rivaroxaban in the outpatient setting to reduce major venous and arterial thrombotic events, hospitalization, and mortality associated with COVID-19.

Early and prehospital trauma deaths: Who might benefit from advanced resuscitative care?

BACKGROUND: Recent civilian and military data from the United States and the United Kingdom suggest that further reductions in mortality will require prehospital or preoperating room hemorrhage control and blood product resuscitation. The aims of this study were to examine the potential preventability of prehospital and early in-hospital fatalities, and to consider the geographical location of such incidents, to contextualize how the use of advanced resuscitative techniques could be operationalized. METHODS: Retrospective analysis of prehospital and early in-hospital trauma deaths from January to December 2017. Data were obtained from the Coroner/ME's Office. Each death was reviewed by a panel of two trauma surgeons and a forensic pathologist. Anatomical and physiological survivabilities were evaluated separately, and then combined, leading to a holistic assessment of preventability. Incident locations were mapped and analyzed using ArcGIS. RESULTS: Three hundred sixteen trauma deaths were identified. Two hundred thirty-one (73%) were deemed anatomically not survivable; 29 (9%) anatomically survivable, but only with hospital care; 43 (14%) anatomically survivable with advanced prehospital care; and 13 (4%) anatomically survivable with basic prehospital care. Physiologically, 114 (36%) of the patients had been dead for some time when found; 137 (43%) had no cardiorespiratory effort on arrival of Emergency Medical Services (EMS) at the scene; 24 (8%) had cardiorespiratory effort at the scene, but not on arrival at the emergency department; and 41 (13%) had cardiorespiratory effort on arrival at the emergency department, but died shortly after. Combining the assessments, 10 (3%) deaths were deemed probably not preventable, 38 (12%) possibly preventable, and the remaining 278 (85%) not preventable. CONCLUSION: Twelve percent of trauma deaths were potentially preventable and might be amenable to advanced resuscitative interventions. Operationalizing this type of care will be challenging and will require either prehospital doctors, or very highly trained paramedics, nurses, or physician assistants. LEVEL OF EVIDENCE: Epidemiological, level III.

Short-term dual antiplatelet therapy (DAPT) followed by P2Y12 monotherapy versus traditional DAPT in patients undergoing percutaneous coronary intervention: meta-analysis and viewpoint.

The optimal duration dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) is subject to debate. A short-duration DAPT (one month to three months) followed by P2Y12 monotherapy instead of standard 6 to 12 months DAPT followed by aspirin monotherapy after PCI has been suggested. We meta-analyzed studies comparing short-term (≤ 3 months) DAPT followed by P2Y12 monotherapy versus standard DAPT in patients after PCI. In total, 2304 studies were screened at title and abstract level. The primary endpoint was major bleeding. Secondary endpoints included myocardial infarction, stent thrombosis, stroke, and all-cause mortality. Study level data were analyzed. Heterogeneity was assessed using the I2 statistic. Risk rates (RR) were calculated using a random-effects model (DerSimonian and Laird) for clinical outcomes for each individual study and consecutive pooling. In total, 21970 patients from three studies were analyzed. Between P2Y12 inhibitor monotherapy versus DAPT, there were similar rates of major bleeding (RR 0.67 95%CI 0.34-1.32; p = 0.25; I2 75%), mortality (RR 0.92 95%CI 0.78-1.09; p = 0.33; I2 0%) and stroke (RR 0.97 95%CI 0.52 - 0.18; p = 0.92; I2 57%). Endpoints assessing thrombotic events showed no statistically significant difference including myocardial infarction (RR 0.99 95%CI 0.85-1.15; p = 0.86; I2 0%) and stent thrombosis (RR 1.03 95%CI 0.74-1.44; p = 0.87; I2 0%). The experimental treatment with P2Y12 monotherapy after very short-term DAPT was not superior to standard DAPT. Our meta-analysis adds insight that DAPT might be safely shortened in selected patient strategies. However, DAPT remains the gold standard for antithrombotic treatment after PCI.

Safety and effectiveness of a prothrombin complex concentrate in approved and off-label indications.

OBJECTIVE: To evaluate the effectiveness and safety of prothrombin complex concentrates (PCCs) in approved and off-label indications. BACKGROUND: PCCs are approved for the urgent reversal of vitamin K antagonists (VKAs). Data concerning the efficacy, safety and dosing for off-label indications are limited, but they are included in massive bleeding protocols. METHODS: This was a retrospective review of cases treated with four-factor PCCs (4F-PCCs) between January 2009 and 2016. Efficacy end-points include: (i) VKA reversal efficacy assessed by international normalised ratio (INR) normalisation (<1·5) and (ii) clinical efficacy as bleeding cessation and/or decreased number of transfused blood components and 24-h mortality in bleeding coagulopathy. The safety end-point is the incidence of thromboembolic events. RESULTS: A total of 328 patients were included (51·8% male, median age 78 years old). Indications were as follows: VKA reversal (66·6%), bleeding coagulopathy (30·5%) and direct anticoagulant (DOAC) reversal due to bleeding (2·5%). VKA reversal was effective in 97·1% of patients, and 76·5% demonstrated complete reversal (INR < 1·5); only 34·3% patients needed hemoderivatives. Prior to emergency procedures, PCCs achieved global responses in 83% of patients, with no bleeding complication during intervention. DOAC reversal was effective in 88·9% of patients. Bleeding cessation was associated with the dose administered (P = 0·002). In coagulopathy bleeding, haemorrhage cessation, established by the International Society of Thrombosis and Haemostais (ISTH) definition, occurred in 56·7% of massive bleeding events and in 42·5% of other coagulopathies; 24-h mortality was 30%, mainly related to active bleeding. Ten thrombotic episodes were observed (3·1%). CONCLUSION: 4F-PCC was effective as adjuvant treatment with an acceptable safety profile, not only for the emergent reversal of VKAs but also for refractory coagulopathy associated with major bleeding.

Sequel and therapeutic modalities of leptospirosis associated severe pulmonary haemorrhagic syndrome (SPHS); a Sri Lankan experience.

BACKGROUND: The emergence of leptospirosis-associated severe pulmonary hemorrhagic syndrome (SPHS) with high case fatality has been reported from many countries. Understanding of clinical disease and sequel of SPHS needs larger studies with adequate numbers. The purpose of this study was to describe the characteristics and sequel by different therapeutic approaches for SPHS in Leptospirosis in Sri Lanka. METHODS: This study was conducted at Teaching Hospital-Karapitiya (THK), Galle, Sri Lanka from June 2015 to December 2017. THK is the main tertiary care center for the Southern Province. All confirmed-cases of leptospirosis who presented during this period and were admitted to five medical units of THK were included in this study. SPHS was defined as a patient presenting; haemoptysis, arterial hypoxemia (Acute Lung Injury Score < 2.5), haemoglobin drop (10% from the previous value), or diffused alveolar shadows in the chest radiograph, without alternative explanation other than leptospirosis. RESULTS: Of the 128 MAT confirmed cases of leptospirosis, 111 (86.7%) had acute kidney injury (AKI) whilst SPHS was seen in 80 (62.5%). Patients typically developed SPHS within the first week of illness, mostly on days 4 and 5. The case fatality rate of this study sample was 28.1% (n = 36), while for patients with SPHS, it was 41.5%. Most of the deaths (n = 19) were within the first 3 days of admission (on the same day 8, and within next 48 h 11). Among SPHS patients, 59 received therapeutic plasma exchange (TPE). The survival rate was higher (n = 35, 74.5%) when the TPE was performed within the first 48 h of detecting SPHS compared to patients in whom the procedure was done after 48 h (n = 5, 54.5%). Of the 19 leptosprosis patients with SPHS who did not receive TPE, 17 died (89.5%). However, the group of patients who received TPE was primarily the patients survived beyond day 3. CONCLUSIONS: We observed that during the study period, SPHS was common and the mortality rate was higher in the study area. The treatment modalities tested need further evaluation and confirmation.

The use of ABC score in activation of massive transfusion: The yin and the yang.

BACKGROUND: Hemorrhage is the most common cause of early death in trauma patients. Massive transfusion protocols (MTPs) have been designed to accelerate the release of blood products but can result in waste if activated inappropriately. The Assessment of Blood Consumption (ABC) score has become a widely accepted score for MTP activation. In this study, we compared the use of ABC criteria to physician judgment in MTP activation. METHODS: Adult trauma patients treated at University of Louisville Trauma Center from January 2016 to December 2016 were studied. Activation via ABC score was assessed retrospectively from emergency department (ED) data. Location, timing of activation, percent of patients using more than 5 units of packed red blood cells, amount of product waste, factors associated with early activation by physicians, and mortality were analyzed. RESULTS: Three thousand four hundred twenty-one patients were included in this study. Only 33% of the patients who would have had MTP activation based on the ABC criteria used more than 5 units of blood products within 24 hours of admission compared with 65% of the patients in whom clinical judgment was used. Seventy-six percent of all MTP activations from clinical judgment would have been activated by the ABC criteria in the ED. Fifty-five percent of all MTP activations via clinical judgment were activated in the operating room and 41% in the ED. Eighty-one percent of activations that occurred in the operating room by physician judgment could have been activated earlier in the ED if the ABC criteria had been used. However, ABC score can lead to higher potential fresh frozen plasma waste (588 vs. 84 units) compared with physician judgment. CONCLUSIONS: The ABC criteria overestimate need for massive transfusion and can lead to increased product waste compared with physician judgment, but its use leads to earlier MTP activation. Criteria to trigger MT activation should rely on both clinical acumen and validated prediction tools. LEVEL OF EVIDENCE: Prognostic, level III.

Safety and effectiveness of rivaroxaban and apixaban in patients with venous thromboembolism: a nationwide study.

Aims: To investigate the risk of all-cause mortality, recurrent venous thromboembolism (VTE), and hospitalized bleeding in patients with VTE treated with either rivaroxaban or apixaban. Methods and results: Using Danish nationwide registries, patients with VTE treated with rivaroxaban or apixaban in the period from 1 January 2015 to 30 June 2017 were identified. Standardized absolute risks were estimated based on outcome-specific Cox regression models, adjusted for potential confounders. A total of 8187 patients were included in the study, of which 1504 (18%) were treated with apixaban [50% males, median age 70 years; interquartile range (IQR) 56-80] and 6683 (82%) were treated with rivaroxaban (55% males, median age 67 years; IQR 53-76). The 180 days risk of all-cause mortality was 5.08% [95% confidence interval (95% CI) 4.08% to 6.08%)] in the apixaban group and 4.60% (95% CI 4.13% to 5.18%) in the rivaroxaban group [absolute risk difference: -0.48% (95% CI -1.49% to 0.72%)]. The 180 days risk of recurrent VTE was 2.16% (95% CI 1.49% to 2.88%) in the apixaban group and 2.22% (95% CI 1.89% to 2.52%) in the rivaroxaban group [absolute risk difference of 0.06% (95% CI -0.72% to 0.79%)]. The 180 days risk of hospitalized bleeding was 1.73% (95% CI 1.22% to 2.35%) for patients in the apixaban group and 1.89% (95% CI 1.56% to 2.20%) in the rivaroxaban group [absolute risk difference: 0.16% (95% CI -0.59% to 0.81%)]. Conclusion: In a nationwide cohort of 8187 patients with VTE treated with rivaroxaban or apixaban, there were no significant differences in the risks of all-cause mortality, recurrent VTE, or hospitalized bleeding.

Length of hospitalization and mortality for bleeding during treatment with warfarin, dabigatran, or rivaroxaban.

BACKGROUND: Different outcomes among patients hospitalized for bleeding after starting anticoagulation could influence choice of anticoagulant. We compared length of hospitalization, proportion of Intensive Care Unit (ICU) admissions, ICU length of stay, and 30- and 90-day mortality for adults with atrial fibrillation hospitalized for bleeding after starting warfarin, dabigatran, or rivaroxaban. METHODS: An US commercial database of 38 million members from 1 November 2010 to 31 March 2014 was used to examine adults with atrial fibrillation hospitalized for bleeding after starting warfarin (2,446), dabigatran (442), or rivaroxaban (256). Outcomes included difference in mean total length of hospitalization, proportion of ICU admissions, mean length of ICU stay, and all-cause 30- and 90-day mortality. RESULTS: Warfarin users were older and had more comorbidities. Multivariable regression modeling with propensity score weighting showed warfarin users were hospitalized 2.0 days longer (95% CI 1.8-2.3; p < 0.001) than dabigatran users and 2.6 days longer (95% CI 2.4-2.9; p < 0.001) than rivaroxaban users. Dabigatran users were hospitalized 0.6 days longer (95% CI 0.2-1.0; p = 0.001) than rivaroxaban users. There were no differences in the proportion of ICU admissions. Among ICU admissions, warfarin users stayed 3.0 days (95% CI 1.9-3.9; p < 0.001) longer than dabigatran users and 2.4 days longer (95% CI 0.9-3.7; p = 0.003) than rivaroxaban users. There was no difference in ICU stay between dabigatran and rivaroxaban users. There were no differences in 30- and 90-day all-cause mortality. CONCLUSIONS: Rivaroxaban and dabigatran were associated with shorter hospitalizations; however, there were no differences in 30- and 90-day mortality. These findings suggest bleeding associated with the newer agents is not more dangerous than bleeding associated with warfarin.

Hypoprothrombinemia and severe perioperative haemorrhagic complications in cardiac surgery patients treated with high-dose cefazolin for infective endocarditis.

Endocarditis is a serious and common disease that requires prolonged antimicrobial therapy. The recent shortage of oxacillin has led to the use of other antimicrobial agents such as cefazolin to treat endocarditis due to methicillin-sensitive Staphylococcus aureus. We describe four cases of life-threatening haemorrhagic complications (fatal in two cases) in patients treated with high-dose cefazolin. All of these patients with major bleeding presented with hypoprothrombinemia secondary to hypovitaminosis K. This adverse event may be due to inhibition of vitamin K epoxide reductase and/or gamma-glutamyl-carboxylase by the 2-methyl-1,2,3-thiadiazol-5-thiol group of cefazolin. This inhibition may result in hypoprothrombinemia by altering the synthesis of vitamin K-dependent coagulation factors. The increasing use of cefazolin, especially at a high dose and for a prolonged period of time, should be accompanied by regular monitoring of coagulation, including prothrombin index, and vitamin K supplementation.

Safety and efficacy of transcatheter embolization with Glubran®2 cyanoacrylate glue for acute arterial bleeding: a single-center experience with 104 patients.

PURPOSE: To assess the efficacy and the safety of Glubran®2 n-butyl cyanoacrylate metacryloxysulfolane (NBCA-MS) transcatheter arterial embolization (TAE) for acute arterial bleeding from varied anatomic sites and to evaluate the predictive factors associated with clinical success and 30-day mortality. METHODS: A retrospective review of consecutive patients who underwent emergent NBCA-MS Glubran®2 TAE between July 2014 and August 2016 was conducted. Variables including age, sex, underlying malignancy, cardiovascular comorbidities, coagulation data, systolic blood pressure, and number of red blood cells units (RBC) transfused before TAE were collected. Clinical success, 30-day mortality, and complication rates were evaluated. Prognostic factors were evaluated by uni- and multivariate logistic regression analyses for clinical success, and by uni- and bivariate analyses after adjustment by bleeding sites for 30-day mortality. RESULTS: 104 patients underwent technically successful embolization with bleeding located in muscles (n = 34, 32.7%), digestive tract (n = 28, 26.9%), and viscera (n = 42, 40.4%). Clinical success rate was 76% (n = 79) and 30-day mortality rate was 21.2% (n = 22). Clinical failure was significantly associated with mortality (p < 0.0001). A number of RBC units transfused greater than or equal to 3 were associated with poorer clinical success (p = 0.025) and higher mortality (p = 0.03). Complications (n = 4, 3.8%) requiring surgery occurred only at puncture site. No ischemic complications requiring further invasive treatment occurred. Mean TAE treatment time was 4.55 min. CONCLUSIONS: NBCA-MS Glubran®2 TAE is a fast, effective, and safe treatment for acute arterial bleeding whatever the bleeding site.

Effects of Probiotics on Necrotizing Enterocolitis, Sepsis, Intraventricular Hemorrhage, Mortality, Length of Hospital Stay, and Weight Gain in Very Preterm Infants: A Meta-Analysis.

Probiotics are increasingly used as a supplement to prevent adverse health outcomes in preterm infants. We conducted a systematic review, meta-analysis, and subgroup analysis of findings from randomized controlled trials (RCTs) to assess the magnitude of the effect of the probiotics on health outcomes among very-low-birth-weight (VLBW) infants. Relevant articles from January 2003 to June 2017 were selected from a broad range of databases, including Medline, PubMed, Scopus, and Embase. Studies were included if they used an RCT design, involved a VLBW infant (birthweight <1500 g or gestational age <32 wk) population, included a probiotic intervention group, measured necrotizing enterocolitis (NEC) as a primary outcome, and measured sepsis, mortality, length of hospital stay, weight gain, and intraventricular hemorrhage (IVH) as additional outcomes. The initial database search yielded 132 potentially relevant articles and 32 (n = 8998 infants) RCTs were included in the final meta-analysis. Subgroup analysis was used to evaluate the effects of the moderators on the outcome variables. In the probiotics group, it was found that NEC was reduced by 37% (95% CI: 0.51%, 0.78%), sepsis by 37% (95% CI: 0.72%, 0.97%), mortality by 20% (95% CI: 0.67%, 0.95%), and length of hospital stay by 3.77 d (95% CI: -5.94, -1.60 d). These findings were all significant when compared with the control group. There was inconsistent use of strain types among some of the studies. The results indicate that probiotic consumption can significantly reduce the risk of developing medical complications associated with NEC and sepsis, reduce mortality and length of hospital stay, and promote weight gain in VLBW infants. Probiotics are more effective when taken in breast milk and formula form, consumed for <6 wk, administered with a dosage of <109 CFU/d, and include multiple strains. Probiotics are not effective in reducing the incidence of IVH in VLBW infants.

Management of rivaroxaban- or apixaban-associated major bleeding with prothrombin complex concentrates: a cohort study.

There is uncertainty regarding the effectiveness and occurrence of thromboembolic events in patients treated with prothrombin complex concentrates (PCCs) for the management of major bleeding events (MBEs) on rivaroxaban or apixaban. We investigated the effectiveness of PCCs given for the management of MBEs in patients on rivaroxaban or apixaban. Between 1 January 2014 and 1 October 2016, we prospectively included patients on rivaroxaban or apixaban treated with PCCs for the management of MBEs. The effectiveness of PCCs was assessed by using the International Society of Thrombosis and Hemostasis Scientific and Standardization Subcommittee criteria for the assessment of the effectiveness of major bleeding management. The safety outcomes were thromboembolic events and all-cause mortality within 30 days after treatment with PCCs. A total of 84 patients received PCCs for the reversal of rivaroxaban or apixaban due to a MBE. PCCs were given at a median (interquartile range) dose of 2000 IU (1500-2000 IU). Intracranial hemorrhage (ICH) was the most common site of bleeding requiring reversal (n = 59; 70.2%), followed by gastrointestinal bleeding in 13 (15.5%) patients. Management with PCCs was assessed as effective in 58 (69.1%) patients and ineffective in 26 (30.9%) patients. Most patients with ineffective hemostasis with PCCs had ICH (n = 16; 61.5%). Two patients developed an ischemic stroke, occurring 5 and 10 days after treatment with PCC. Twenty-seven (32%) patients died within 30 days after a MBE. The administration of PCCs for the management of MBEs associated with rivaroxaban or apixaban is effective in most cases and is associated with a low risk of thromboembolism. Our findings are limited by the absence of a control group in the study.

Application of Incident Command Structure to clinical trial management in the academic setting: principles and lessons learned.

BACKGROUND: Clinical trial success depends on appropriate management, but practical guidance to trial organisation and planning is lacking. The Incident Command System (ICS) is the 'gold standard' management system developed for managing diverse operations in major incident and public health arenas. It enables effective and flexible management through integration of personnel, procedures, resources, and communications within a common hierarchical organisational structure. Conventional ICS organisation consists of five function modules: Command, Planning, Operations, Logistics, and Finance/Administration. Large clinical trials will require a separate Regulatory Administrative arm, and an Information arm, consisting of dedicated data management and information technology staff. We applied ICS principles to organisation and management of the Prehospital Use of Plasma in Traumatic Haemorrhage (PUPTH) trial. This trial was a multidepartmental, multiagency, randomised clinical trial investigating prehospital administration of thawed plasma on mortality and coagulation response in severely injured trauma patients. We describe the ICS system as it would apply to large clinical trials in general, and the benefits, barriers, and lessons learned in utilising ICS principles to reorganise and coordinate the PUPTH trial. RESULTS: Without a formal trial management structure, early stages of the trial were characterised by inertia and organisational confusion. Implementing ICS improved organisation, coordination, and communication between multiple agencies and service groups, and greatly streamlined regulatory compliance administration. However, unfamiliarity of clinicians with ICS culture, conflicting resource allocation priorities, and communication bottlenecks were significant barriers. CONCLUSIONS: ICS is a flexible and powerful organisational tool for managing large complex clinical trials. However, for successful implementation the cultural, psychological, and social environment of trial participants must be accounted for, and personnel need to be educated in the basics of ICS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02303964 . Registered on 28 November 2014.

Bridge Therapy Outcomes in Patients With Mechanical Heart Valves.

BACKGROUND: Bridge therapy is associated with an increased risk of major bleeding in patients with atrial fibrillation and venous thromboembolism (TE) without a corresponding reduction in TE. The benefits of bridge therapy in patients with mechanical heart valve (MHV) prostheses interrupting warfarin for invasive procedures are not well described. METHODS AND RESULTS: A retrospective cohort study was conducted at an integrated health-care delivery system. Anticoagulated patients with MHV interrupting warfarin for invasive diagnostic or surgical procedures between January 1, 2006, and March 31, 2012, were identified. Patients were categorized according to exposure to bridge therapy during the periprocedural period and TE risk (low, medium, and high). Outcomes validated via manual chart review included clinically relevant bleeding, TE, and all-cause mortality in the 30 days following the procedure. There were 547 procedures in 355 patients meeting inclusion criteria. Mean cohort age was 65.2 years, and 38% were female. Bridge therapy was utilized in 466 (85.2%) procedures (95.2%, 77.3%, and 65.8% of high, medium, and low TE risk category procedures, respectively). The 30-day rate of clinically relevant bleeding was numerically higher in bridged (5.8%; 95% confidence interval [CI], 3.9%-8.3%) versus not bridged procedures (1.2%; 95% CI, <0.1%-6.7%; P = .102). No TEs or deaths were identified. CONCLUSION: The use of bridge therapy is common among patients with MHV and may be associated with increased bleeding risk. Further research is needed to determine whether bridge therapy reduces TE in patients with MHV interrupting warfarin for invasive procedures.

Efficacy and safety of aspirin combined with warfarin after acute coronary syndrome : A meta-analysis.

A comprehensive meta-analysis was performed to investigate whether the combination of high-/low-dose of aspirin and various intensities of warfarin (W) offer greater benefit than aspirin (ASA) alone. A total of 14 randomized clinical trials (RCTs) having 26,916 patients with acute coronary syndrome (ACS) met inclusion criteria. The efficacy and safety of all outcomes which included myocardial infarction (MI), all-cause death, stroke, and bleeding were calculated. The overall outcomes analysis showed there was no significant difference in the risk of MI (relative ratio [RR] 0.959, 95 % confidence interval [CI] 0.78-1.04, P = 0.308), stroke (RR 0.789, 95 % CI 0.57-1.09, P = 0.145), and all-cause death (RR 1.007, 95 % CI 0.93-1.09, P = 0.87) between the combination group and ASA group. The subgroup analysis suggested that ASA (≤100 mg/day) plus W (mean international normalized ratio [INR] 2.0-3.0) decreased the risk rate of stroke (RR 0.660, 95 % CI 0.50-0.87, P = 0.003). There was a lower risk of MI (RR 0.605, 95 % CI 0.47-0.77, P < 0.0001) as well as stroke (RR 0.594, 95 % CI 0.45-0.79, P < 0.0001) between W (INR 2.0-3.0) combined with ASA (mean dose ≥100 mg/day) and ASA. However, the risk of major bleeding (RR 1.738, 95 % CI 1.45-2.08, P < 0.0001) and minor bleeding (RR 2.767, 95 % CI 2.12-3.61, P < 0.0001) was almost doubled in the combined groups. Compared with ASA, high-dose aspirin with moderate-intensity warfarin (INR 2.0-3.0) may better reduce the risk of MI and stroke but confer an increased risk of bleeding.

Risk of thromboembolism, recurrent hemorrhage, and death after warfarin therapy interruption for intracranial hemorrhage.

BACKGROUND: Whether and when to resume oral anticoagulant therapy for patients who survive warfarin-related intracranial hemorrhage (ICH) remains a dilemma lacking consensus recommendations and high-quality evidence to guide clinical decision making. OBJECTIVE: To determine the incidences of recurrent ICH, thrombosis, and death in relation to resumption or non-resumption of warfarin therapy during the 365 days after incident ICH. METHODS: We conducted a retrospective cohort study of adult patients in an integrated healthcare delivery system who were receiving warfarin therapy at the time of incident (index) ICH between 1/1/2000 and 12/31/2007 and survived to hospital discharge. The primary outcomes were recurrent ICH, thrombosis (stroke, systemic embolism, and venous thromboembolism), and all-cause mortality during the 365 days following index ICH. Patients were assigned to one of two groups defined by warfarin therapy resumption after the index ICH. RESULTS: There were 160 patients discharged from the hospital following warfarin-related index ICH; of these 54 (33.8%) resumed warfarin therapy and 106 (66.2%) did not. Recurrent ICH occurred in a numerically greater, but statistically non-significant, proportion of patients who did not resume warfarin therapy (7.6% vs. 3.7%, p=0.497). Similarly, patients who did not resume warfarin had a three-fold higher (12.3% vs. 3.7%, p=0.092) and approximately two-fold higher (31.1% vs. 18.5%, p=0.089) rates of thrombosis and all-cause mortality, respectively, during follow up. CONCLUSION: Resumption of warfarin therapy following warfarin-associated ICH appeared not to be associated with increased risk of recurrent ICH but trended toward reduced thrombosis and all-cause mortality.

Medico-legal evaluation of firearm injuries--an original study from India with review of literature.

Firearm (FA) injuries pose great health burden and presents enormous challenge for health and national economies. This study was undertaken to analyze the characteristics of fatal gunshot injuries, their pattern, associated factors, and postmortem findings in central India, to provide data for such fatalities in this region, which has not been reported earlier. This is a descriptive, retrospective cross-sectional study carried out on the victims of FA injuries referred to the mortuary. Of the autopsies conducted during study, 2.09% were firearm-related deaths. Of the cases, males (92.42%) notably outnumbered females in a ratio of 12.2:1. Homicidal attacks were maximum, and unlicensed, illegal country-made weapons were the preferred choice. Suicides were least. Result signifies that illegal country-made weapons should be strictly limited to save the precious lives. A holistic approach encompassing public awareness, behavioral modification, and stringent management of law and order is the need of the hour.