Direct Oral Anticoagulants in Antiphospholipid Syndrome-Associated Venous Thromboembolism: Real World Evidence.

BACKGROUND: The efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin in patients with antiphospholipid syndrome-associated venous thromboembolism (APS-VTE) remain uncertain. We aimed to evaluate efficacy and safety of DOACs in patients with APS-VTE. METHODS: Using the Korean Health Insurance Review and Assessment Service database, we retrospectively identified all APS-VTE cases. We examined the VTE recurrence, arterial thrombosis, death and bleeding in patients who received DOACs compared with warfarin for therapeutic anticoagulation. RESULTS: Of all the VTE cases (n = 84,916) detected between 2014 and 2018, patients with APS-VTE (n = 410) accounted for 0.48%. Most patients with APS-VTE (73%) were aged < 60 years. The recurrent VTE occurred in 8 of 209 patients (3.8%) who received DOACs and in 7 of 201 (3.5%) who received warfarin (relative risk [RR], 1.099; 95% confidence interval [CI], 0.41-2.98; P = 1.000). The arterial thrombosis (ATE) occurred in 8 of 209 patients (3.8%) who received DOAC and in 20 of 201 (10%) who received warfarin (RR, 0.385; 95% CI, 0.17-0.85; P = 0.024). The composite outcomes of VTE recurrence, ATE, or mortality were significantly lower in patients (9.1%) on DOAC than in those (16.3%) on warfarin (RR, 0.537; 95% CI, 0.32-0.91; P = 0.028). The bleeding outcome occurred in 7 of 209 (3.4%) patients in the DOACs group and 7 of 201 (3.5%) patients in the warfarin group (RR, 0.96; 95% CI, 0.34-2.69; P = 0.840). CONCLUSION: In patients with APS-VTE, DOACs group showed comparable rates of recurrent VTE, bleeding, and deaths, but a significantly lower incidence of ATE and composite outcomes compared with the warfarin group in Korea.

Incidence of Venous Thromboembolism: The 3rd Korean Nationwide Study.

BACKGROUND: The incidence of venous thromboembolism (VTE) has gradually increased in the Korean population. This study aimed to evaluate the annual age- and sex-adjusted incidence rates (ASR) of VTE and anticoagulation trends between 2014 and 2018. METHODS: Using the Korean Health Insurance Review and Assessment Service database, we retrospectively identified VTE patients between 2014 and 2018 using both diagnostic and medication anticoagulant codes assigned within 6 months of the initial index event. Anticoagulant patterns were classified as follows: direct oral anticoagulants (DOAC), parenteral anticoagulants, warfarin, and mixed anticoagulation regimens. RESULTS: We identified 95,205 patients with VTE (female, 56.8%). The ASR for VTE per 100,000 person-years increased from 32.8 in 2014 to 53.7 cases in 2018 (relative risk of 1.63; 95% confidence interval, 1.6-1.67). The VTE incidence rates were 25 times higher in the ≥ 80 group than in the 30s group. VTE occurred 1.29 times more often in women than in men. The proportion of DOAC prescriptions increased from 40.5% to 72.8%, whereas warfarin prescriptions decreased from 27% to 5.6% in 2014 and 2018. CONCLUSION: In Korea, the ASRs of VTE continued to increase since 2014, but the rate of increase slowed in 2018. The VTE occurred more often in the elderly and in women. Five years after the introduction of DOACs in 2013, they accounted for 73% of all anticoagulants used to treat VTE.

Clinical profiles of early and tuberculosis-related mortality in South Korea between 2015 and 2017: a cross-sectional study.

BACKGROUND: Although the incidence of tuberculosis (TB) has decreased in South Korea, the mortality rate remains high. TB mortality is a key indicator for TB control interventions. The purpose of this study was to assess early and TB-related mortality during anti-TB treatment and describe the associated clinical characteristics. METHODS: A multicenter cross-sectional study was performed across South Korea. Patients with pulmonary TB who died during anti-TB treatment and whose records were submitted to the national TB surveillance system between 2015 and 2017 were enrolled. All TB deaths were categorized based on cause (TB-related or non-TB-related) and timing (early or late). We identified statistical associations using the frequency table, chi-square test, and binary logistic regression. RESULTS: Of 5595 notifiable mortality cases, 3735 patients with pulmonary TB were included in the analysis. There were 2541 (68.0%) male patients, and 2935 (78.6%) mortality cases were observed in patients older than 65 years. There were 944 (25.3%) cases of TB-related death and 2545 (68.1%) cases of early death. Of all cases, 187 (5.0%) patients were diagnosed post-mortem and 38 (1.0%) patients died on the first day of treatment. Low body mass index (adjusted odds ratio (aOR) = 1.26; 95% confidence interval (CI) = 1.08-1.48), no reported illness (aOR = 1.36; 95% CI = 1.10-1.68), bilateral disease on chest X-ray (aOR = 1.30; 95% CI = 1.11-1.52), and positive acid-fast bacilli smear result (aOR = 1.30; 95% CI = 1.11-1.52) were significantly associated with early death, as well as TB-related death. Acute respiratory failure was the most common mode of non-TB-related death. Malignancy was associated with both late (aOR = 0.71; 95% CI = 0.59-0.89) and non-TB-related (aOR = 0.35; 95% CI = 0.26-0.46) death. CONCLUSIONS: A high proportion of TB death was observed in elderly patients and attributed to non-TB-related causes. Many TB-related deaths occurred during the intensive phase, particularly within the first month. Further studies identifying risk factors for different causes of TB death at different phases of anti-TB treatment are warranted for early targeted intervention in order to reduce TB mortality.

Aggressive Contact Investigation of In-Hospital Exposure to Active Pulmonary Tuberculosis.

BACKGROUND: In-hospital detection of newly diagnosed active pulmonary tuberculosis (TB) is important for prevention of potential outbreaks. Here, we report our experience of the aggressive contact investigation strategy in a university hospital in the Republic of Korea after healthcare workers (HCWs), patients, and visitors experience an in-hospital exposure to active pulmonary TB. METHODS: A contact investigation after the unexpected detection of newly diagnosed active pulmonary TB (index patients) was performed in a university hospital from August 2016 to April 2017. Initial and 3-month-post-exposure chest radiographs were advised for all patients, visitors, and HCWs in close contact with the index patients. An additional tuberculous skin test or interferon gamma releasing assay was performed at the time of exposure and 3 months post-exposure in HCWs in close contact with the index patients. RESULTS: Twenty-four index patients were unexpectedly diagnosed with active pulmonary TB after admission to the hospital with unassociated diseases. The median time from admission to TB diagnosis was 5 days (range, 1-22 days). In total, 1,057 people were investigated because of contact with the index patients, 528 of which had close contact (206 events in 157 HCWs, 322 patients or visitors). Three months post exposure, 9 (9.2%) among 98 TB-naïve close contact HCWs developed latent tuberculosis infections (LTBIs). Among the 65 close contact patients or visitors, there was no radiological or clinical evidence of active pulmonary TB. CONCLUSION: An aggressive contact investigation after an unexpected in-hospital diagnosis of active pulmonary TB revealed a high incidence of LTBI among TB-naïve HCWs who had contact with the index patients.

The Perioperative Management of Antithrombotic Therapies Using Enoxaparin.

Oral anticoagulant therapy is frequently and increasingly prescribed for patients at risk of arterial or venous thromboembolism (VTE). Although elective surgical or invasive procedures have necessitated temporary interruption of anticoagulants, managing these patients has been performed empirically and been poorly investigated. This study was designed to evaluate the adequacy of perioperative anticoagulation using enoxaparin. This was a retrospective, single-center study that evaluated the efficacy and safety of therapeutic-dose enoxaparin for bridging therapy in patients on long-term warfarin at Soonchunhyang University Hospital in Korea between August 2009 and July 2011. Warfarin was discontinued 5 days before surgery, and enoxaparin was administered twice daily by subcutaneous injection at a dose of 1 mg per kg from 3 days before the procedure to the last dose 24 hours before the procedure. Anticoagulation was restarted if proper hemostasis had been confirmed. There were 49 patients, of whom 25 (51%) were men, and the mean age was 63 years. Thirty-four (69%) received warfarin therapy for VTE, and 9 (18%) for atrial fibrillation. Twenty-nine patients (59%) underwent major surgery and 20 (41%) minor surgery. The mean postoperative duration of enoxaparin was 4 days. No patients had thromboembolic complications through 30 days after the procedure. The overall 30-day mortality rate was 0%. In conclusion, our findings demonstrate that bridging therapy with therapeutic-dose enoxaparin is feasible and associated with a low incidence of major bleeding and no thromboembolic complications. However, the optimal approach to managing patients perioperatively is uncertain and requires further evaluation.

Early diagnosis based on clinical history and BALF for successful management of smoking-induced acute eosinophilic pneumonia without unnecessary antibiotic usage: a case report.

INTRODUCTION: Acute eosinophilic pneumonia (AEP) is a rapid onset and severe respiratory illness characterized by acute febrile respiratory insufficiency, eosinophilic infiltration in the lungs and unique findings on chest imaging. Difficulty in differentiating from other respiratory distress caused by community-acquired pneumonia may result in a delayed diagnosis or treatment with empirical antibiotics. CASE STUDY: Sixteen-year-old boy who developed AEP with marked eosinophilia in bronchoalveolar lavage fluid (BALF, 36.6%), decreased diffusion capacity of the lung for carbon monoxide (62%) and unique radiological findings. Although he initially denied tobacco use, on repeated thorough clinical history questioning, he eventually admitted beginning smoking 19 days before the onset of symptoms with gradually increasing frequency. RESULTS: His symptoms resolved quickly without use of antibiotics after cessation of tobacco and treatment with corticosteroids. CONCLUSION: Careful clinical history taking regarding tobacco use combined with early examination of BALF and recognition of unique radiological findings are critical for proper management of AEP.

Prevention of venous thromboembolism in medical intensive care unit: a multicenter observational study in Korea.

Patients admitted to medical intensive care unit (MICU) are at increased risk for venous thromboembolism (VTE); and prophylaxis is recommended. However, the actual range and frequency of VTE prophylaxis administered to MICU patients are not well defined. Patients over 40 yr of age and expected MICU stay of more than 48 hr were eligible for this observational cohort study of 23 MICUs in Korea. Patients already on anticoagulation therapy or those requiring anticoagulation for reasons other than VTE were excluded. Among 830 patients, VTE prophylaxis was given to 560 (67.5%) patients. Among 560 patients, 323 (38.9%) received pharmacoprophylaxis, 318 (38.4%) received mechanical prophylaxis and 81 (9.8%) received both forms of prophylaxis. About 74% of patients in the pharmacoprophylaxis group received low molecular weight heparin and 53% of the patients in the mechanical prophylaxis group used intermittent pneumatic compression. Most of the patients (90%) had more than one risk factor for VTE and the most common risk factor was old age, followed by heart and respiratory failure. In this observational cohort study of 23 MICUs in Korea, 67.5% of patients received thromboprophylaxis. Further studies are needed to clarify the role and efficacy of VTE prophylaxis in Korean critically ill patients.

Prevention of venous thromboembolism, 2nd edition: Korean Society of Thrombosis and Hemostasis Evidence-based Clinical Practice Guidelines.

In 2010, we proposed the first Korean Guidelines for the Prevention of Venous Thromboembolism (VTE). It was applicable to Korean patients, by modifying the contents of the second edition of the Japanese guidelines for the prevention of VTE and the 8th edition of the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines. From 2007 to 2011, we conducted a nationwide study regarding the incidence of VTE after major surgery using the Health Insurance Review and Assessment Service (HIRA) database. In addition, we have considered the 9th edition of the ACCP Evidenced-Based Clinical Practice Guidelines, published in 2012. It emphasized the importance of clinically relevant events as opposed to asymptomatic outcomes with preferences for both thrombotic and bleeding outcomes. Thus, in the development of the new Korean guidelines, three major points were addressed: 1) the new guidelines stratify patients into 4 risk groups (very low, low, moderate, and high) according to the actual incidence of symptomatic VTE from the HIRA databases; 2) the recommended optimal VTE prophylaxis for each group was modified according to condition-specific thrombotic and bleeding risks; 3) guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and/or physician advice.

Clinical Experiences of High-Risk Pulmonary Thromboembolism Receiving Extracorporeal Membrane Oxygenation in Single Institution.

BACKGROUND: The main cause of death in pulmonary embolism (PE) is right-heart failure due to acute pressure overload. In this sense, extracorporeal membrane oxygenation (ECMO) might be useful in maintaining hemodynamic stability and improving organ perfusion. Some previous studies have reported ECMO as a bridge to reperfusion therapy of PE. However, little is known about the patients that benefit from ECMO. METHODS: Patients who underwent ECMO due to pulmonary thromboembolism at a single university-affiliated hospital between January 2010 and December 2018 were retrospectively reviewed. RESULTS: During the study period, nine patients received ECMO in high-risk PE. The median age of the patients was 60 years (range, 22-76 years), and six (66.7%) were male. All nine patients had cardiac arrests, of which three occurred outside the hospital. All the patients received mechanical support with veno-arterial ECMO, and the median ECMO duration was 1.1 days (range, 0.2-14.0 days). ECMO with anticoagulation alone was performed in six (66.7%), and ECMO with reperfusion therapy was done in three (33.3%). The 30-day mortality rate was 77.8%. The median time taken from the first cardiac arrest to initiation of ECMO was 31 minutes (range, 30-32 minutes) in survivors (n=2) and 65 minutes (range, 33-482 minutes) in non-survivors (n=7). CONCLUSION: High-risk PE with cardiac arrest has a high mortality rate despite aggressive management with ECMO and reperfusion therapy. Early decision to start ECMO and its rapid initiation might help save those with cardiac arrest in high-risk PE.

Treatment and Bleeding Complications of Cancer-Associated Venous Thromboembolism: A Korean Population-Based Study.

OBJECTIVES: This study investigated the treatment pattern and the rate of bleeding complications in real-world practice in cancer-associated venous thromboembolism (CT) patients. METHODS: We used the Korean Health Insurance Review and Assessment Service database (2014-2018). Among patients with venous thromboembolism, patients with concomitant malignancy diagnostic codes were categorized as CT, while all others were categorized as non-CT. Treatments were categorized as direct oral anticoagulant (DOAC), parenteral anticoagulant (PAC), warfarin, and mixed anticoagulants. RESULTS: We identified 27,205 CT and 57,711 non-CT patients. DOACs were the most frequently used anticoagulants. The proportion of patients treated with PAC was higher in CT than in non-CT patients (35.7 vs. 19.5%; p < 0.01). In CT, the cumulative incidence of any/major bleeding was higher with DOAC (8.1%/3.9%) than with PAC (7.5%/3.2%; p = 0.04 and 0.01, respectively). However, there was no difference in major bleeding when compared with warfarin (p = 0.11) or mixed anticoagulants (p = 0.94). Overall, gastrointestinal (GI) cancer patients showed higher risks of bleeding. The cumulative incidence of major GI bleeding was higher with DOAC than with PAC (4.9 vs. 3.0%; p < 0.01), while there was no difference compared with warfarin (p = 0.59) or mixed anticoagulants (p = 0.80). Major bleeding with each DOAC showed no difference among entire CT (p = 0.94), GI cancer (p = 0.27), and genitourinary cancer (p = 0.88) patients. CONCLUSION: Five years after their introduction into clinical practice, DOACs have become the most prescribed anticoagulant in Korea. In our patient population, bleeding complications occurred more frequently in CT than in non-CT, especially in patients treated with DOACs.

A promoter SNP rs4073T>A in the common allele of the interleukin 8 gene is associated with the development of idiopathic pulmonary fibrosis via the IL-8 protein enhancing mode.

BACKGROUND: Interleukin-8 (IL-8) is a potent chemo-attractant cytokine responsible for neutrophil infiltration in lungs with idiopathic pulmonary fibrosis (IPF). The IL-8 protein and mRNA expression are increased in the lung with IPF. We evaluated the effect of single nucleotide polymorphisms (SNPs) of the IL-8 gene on the risk of IPF. METHODS: One promoter (rs4073T>A) and two intronic SNPs (rs2227307T>G and rs2227306C>T) of the IL-8 genes were genotyped in 237 subjects with IPF and 456 normal controls. Logistic regression analysis was applied to evaluate the association of these SNPs with IPF. IL-8 in BAL fluids was measured using a quantitative sandwich enzyme immunoassay, and promoter activity was assessed using the luciferase reporter assay. RESULTS: The minor allele frequencies of rs4073T>A and rs2227307T>G were significantly lower in the 162 subjects with surgical biopsy-proven IPF and 75 subjects with clinical IPF compared with normal controls in the recessive model (OR = 0.46 and 0.48, p = 0.006 and 0.007, respectively). The IL-8 protein concentration in BAL fluids significantly increased in 24 subjects with IPF compared with 14 controls (p = 0.009). Nine IPF subjects homozygous for the rs4073 T>A common allele exhibited higher levels of the IL-8 protein compared with six subjects homozygous for the minor allele (p = 0.024). The luciferase activity of the rs4073T>A common allele was significantly higher than that of the rs4073T>A minor allele (p = 0.002). CONCLUSION: The common allele of a promoter SNP, rs4073T>A, may increase susceptibility to the development of IPF via up-regulation of IL-8.

Venous thromboembolism associated with combined oral contraceptive use: a single-institution experience.

OBJECTIVE: Combined oral contraceptives (COCs) are used for various reasons. However, venous thromboembolism (VTE), a significant side effect, can be fatal. This study reports the first case series in Korea involving patients with COC-associated VTE registered at a university hospital. METHODS: This study recruited 13 patients diagnosed with COC-associated VTE between June 2006 and May 2018. Risk factors, including age, body mass index, smoking habits, estrogen dosage, type of progestin, and duration of COC use, were evaluated. RESULTS: Among patients with VTE, 9 showed pulmonary embolism (PE) concomitant with deep vein thrombosis (DVT). However, the remaining patients showed DVT (1 patient), PE (1 patient), and cerebral venous thrombosis (2 patients). The median duration between the onset of symptoms and a hospital visit was 3 days, and it sometimes took as long as 32 days. Among the 10 patients with PE, 1 high-risk group and 2 intermediate-high risk groups were treated with tissue plasminogen activators before anticoagulants. There were no cases of recurrence among patients who continued to take anticoagulants for 3 months. CONCLUSION: These findings emphasize that healthcare professionals who prescribe or dispense COCs to women must inform them of the risk of VTE, including the risk factors, differences in risk depending on the type of progestin present in the product, and pertinent signs and symptoms. Efforts should also be made to inform patients of VTE, even through information campaigns such as brochures. Most importantly, women should remain alert for signs and symptoms of VTE when using COCs.

Therapy-related myeloid leukemia during erlotinib treatment in a non-small cell lung cancer patient: A case report.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are tolerable drugs used for patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC). Serious adverse reactions are uncommon compared with cytotoxic drugs. CASE SUMMARY: A 52-year-old man presented with general weakness and cytopenia. He had been taking erlotinib for 11 mo to treat NSCLC. The pathological diagnosis from the right upper lobe mass was adenocarcinoma with an EGFR mutation in exon 21 (L858R). He had previously received paclitaxel/carboplatin, gemcitabin/ vinorelbine chemotherapy, stereotactic radiosurgery for brain metastasis, and whole-brain radiotherapy as treatment for NSCLC. We diagnosed the patient with acute myeloid leukemia (AML). During the induction and consolidation chemotherapy for AML, the erlotinib was discontinued. When complete remission of the AML was achieved, since the lung masses were increased, pemetrexed/ cisplatin for the NSCLC was initiated. After two cycles of chemotherapy, the cytopenia was prolonged. AML relapse occurred with the same karyotype. CONCLUSION: Therapy-related acute myeloid neoplasm (t-MN) is a rare but fatal late complication. Although a patient may be taking EGFR-TKIs, the possibility of t-MN should be considered. Further studies are needed to determine whether EGFR-TKI usage is a predisposing factor for t-MN.

Electronic Cigarette or Vaping Product Use-Associated Lung Injury: A Case Report.

Electronic cigarette (e-cigarette) or vaping product use-associated lung injury (EVALI) has emerged as a social issue as e-cigarette use is rapidly increasing worldwide and is related to many deaths in the United States. To our knowledge, this is the first case report of EVALI in South Korea of a 24-year-old man with acute respiratory symptoms and a history of e-cigarette use. Chest CT revealed diffuse bilateral ground-glass opacities with subpleural sparing, airspace consolidation, and centrilobular micronodules as typical patterns of EVALI with organizing pneumonia and diffuse alveolar damage. Infection was excluded with meticulous laboratory examinations, and the patients' illnesses were not attributed to other causes. EVALI was diagnosed by meeting the diagnostic criteria with consistent clinico-radiologic findings through a multidisciplinary approach. Radiologists should have good knowledge of EVALI radiologic findings and play a cardinal role in the proper diagnosis and management of EVALI.

Optimal timing of resumption of warfarin after intracranial hemorrhage.

BACKGROUND AND PURPOSE: The optimum timing of resumption of anticoagulation after warfarin-related intracranial hemorrhage in patients with indication for continued anticoagulation is uncertain. We performed a large retrospective cohort study to obtain more precise risk estimates. METHODS: We reviewed charts of 2869 consecutive patients with objectively verified intracranial hemorrhage over 6 years at 3 tertiary centers. We calculated the daily risk of intracranial hemorrhage or ischemic stroke with and without resumption of warfarin; we focused on patients who survived the first week and had cardiac indication for anticoagulation or previous stroke. Using a Cox model, we estimated rates for these 2 adverse events in relation to different time points of resumed anticoagulation. The combined risk of either a new intracranial hemorrhage or an ischemic stroke was calculated for a range of warfarin resumption times. RESULTS: We identified warfarin-associated intracranial hemorrhage in 234 patients (8.2%), of whom 177 patients (76%) survived the first week and had follow-up information available; the median follow-up time was 69 weeks (interquartile range [IQR] 19-144). Fifty-nine patients resumed warfarin after a median of 5.6 weeks (IQR 2.6-17). The hazard ratio for recurrent intracranial hemorrhage with resumption of warfarin was 5.6 (95% CI, 1.8-17.2), and for ischemic stroke it was 0.11 (95% CI, 0.014-0.89). The combined risk of recurrent intracranial hemorrhage or ischemic stroke reached a nadir if warfarin was resumed after approximately 10 to 30 weeks. CONCLUSIONS: The optimal timing for resumption of warfarin therapy appears to be between 10 and 30 weeks after warfarin-related intracranial hemorrhage.

Association between colony-stimulating factor 1 receptor gene polymorphisms and asthma risk.

Colony-stimulating factor 1 receptor (CSF1R) is expressed in monocytes/macrophages and dendritic cells. These cells play important roles in the innate immune response, which is regarded as an important aspect of asthma development. Genetic alterations in the CSF1R gene may contribute to the development of asthma. We investigated whether CSF1R gene polymorphisms were associated with the risk of asthma. Through direct DNA sequencing of the CSF1R gene, we identified 28 single nucleotide polymorphisms (SNPs) and genotyped them in 303 normal controls and 498 asthmatic patients. Expression of CSF1R protein and mRNA were measured on CD14-positive monocytes and neutrophils in peripheral blood of asthmatic patients using flow cytometry and real-time PCR. Among the 28 polymorphisms, two intronic polymorphism (+20511C>T and +22693T>C) were associated with the risk of asthma by logistic regression analysis. The frequencies of the minor allele at CSF1R +20511C>T and +22693T>C were higher in asthmatic subjects than in normal controls (4.6 vs. 7.7%, p = 0.001 in co-dominant and dominant models; 16.4 vs. 25.8%, p = 0.0006 in a recessive model). CSF1R mRNA levels in neutrophils of the asthmatic patients having the +22693CC allele were higher than in those having the +22693TT allele (p = 0.026). Asthmatic patients with the +22693CC allele also showed significantly higher CSF1R expression on CD14-positive monocytes and neutrophils than did those with the +22693TT allele (p = 0.045 and p = 0.044). The +20511C>T SNP had no association with CSF1R mRNA or protein expression. In conclusion, the minor allele at CSF1R +22693T>C may have a susceptibility effect in the development of asthma, via increased CSF1R protein and mRNA expression in inflammatory cells.

The increased risk of bleeding due to drug-drug interactions in patients administered direct oral anticoagulants.

INTRODUCTION: Direct oral anticoagulants (DOACs) have the potential to increase bleeding due to drug-drug interactions (DDIs). In the present study, the risk of bleeding was evaluated when drugs with potential DDIs were simultaneously prescribed with DOACs. MATERIALS AND METHODS: The present study included patients with non-valvular atrial fibrillation (AF) and venous thromboembolism (VTE) who were newly prescribed DOACs between January 2014 and December 2016. RESULTS: The study included 115,362 patients with AF or VTE who were newly administered DOACs (median age, 73 years, range, 19-108 years; males, 53.0%; AF, 81.9%). A total of 7001 any bleeding (6.1%) and 2283 major bleeding (2.0%) events occurred with DOAC prescriptions. Based on multiple logistic regression analysis, the number of DDIs was significantly associated with bleeding events independent of CHA2DS2-VASc score and Charlson Comorbidity Index (CCI). The rates of exposure to DDI drugs associated with any bleeding and major bleeding were 56.7% and 66.1%, respectively. The most common DDI drugs showed similar distributions in any or major bleeding; non-steroidal anti-inflammatory drugs (NSAIDs), antiplatelet agents, diltiazem, and amiodarone were frequently prescribed. CONCLUSIONS: Physicians prescribing DOACs for AF or VTE should be aware of the increasing risk of bleeding associated with drugs having potential DDIs regardless of comorbidities.

Cervical artery dissection: pathology, epidemiology and management.

BACKGROUND: Cervical artery dissection is often treated with anticoagulants to prevent ischemic stroke. The risk-benefit ratio of anticoagulation versus antiplatelet therapy is unclear. OBJECTIVES: To provide an educational review of current data on the disease to explain the rationale for the treatment options and to explore the results of management studies in order to determine if anticoagulation is justified. METHODS: We searched the databases MEDLINE and EMBASE as well as bibliographies for information on anticoagulants and antiplatelet agents in cervical, i.e. carotid and/or vertebral artery, dissection. RESULTS: There are no randomized controlled trials on the treatment. One systematic review from 2003 identified 20 case series or cohort studies. We identified 9 additional studies with a total of 1,033 patients. Of those, 731 received anticoagulation sometimes followed by platelet inhibition vs. 282 patients treated with antiplatelet agents alone. The rate of ischemic stroke was 2.3% vs. 6.9% and bleeding complications were reported in 0.7% vs. 0%. CONCLUSION: It cannot be excluded that there is a net benefit from anticoagulant therapy in cervical dissection, but the studies are flawed by considerable bias. Very ill patients at a high risk of ischemic stroke may have been given aspirin due to fear of hemorrhagic complications. A randomized controlled trial is planned and will be crucial to resolve this issue.

Screening and Treatment of Latent Tuberculosis Infection among Healthcare Workers at a Referral Hospital in Korea.

BACKGROUND: Healthcare workers (HCWs) have a high risk of tuberculosis (TB) infection. Since August 2017, Korea has mandated the testing of latent TB infection (LTBI) and recommended treatment from HCWs at medical institutions. However, the acceptance/completion rate and adverse events of LTBI treatment have not been analyzed. MATERIALS AND METHODS: From February to August 2017, we conducted a retrospective study at a referral university hospital in Korea, to screen the interferon-gamma release assay (IGRA) tests conducted for all HCWs for detecting and treating LTBI. HCWs diagnosed with LTBI were offered a 9-month isoniazid (9H), 3-month isoniazid/rifampin (3HR), or 4-month rifampin regimen. We investigated the acceptance/completion rate, adverse events, and causes of discontinuation or change in LTBI medication. A major adverse event was one wherein a patient had any adverse event ≥grade 3 causing LTBI treatment interruption. RESULTS: Of the 1,538 HCWs, 1,379 underwent IGRA testing for LTBI. Among them, 13.6% (187/1,379) tested positive and 73.3% (137/187) received treatment. The overall completion rate was 97.8% (134/137). HCWs were significantly more likely to complete first-line therapy with 3HR than with 9H (91.4% vs. 76.7%, P = 0.02). The most common major adverse event was hepatotoxicity (n = 7), followed by thrombocytopenia (n = 1) and anaphylactic shock (n = 1). Hepatotoxicity and hepatotoxicity (≥ grade 2) were more frequent in 9H than in 3HR (39.5% vs. 17.2%, P = 0.006 and 18.6% vs. 3.7%, P = 0.005, respectively). The median time to hepatotoxicity was 96 days (interquartile range, 20 - 103 days). CONCLUSION: Completion of first-line therapy for LTBI is more likely with 3HR than with 9H. This might be related to the development of hepatotoxicity after around 3 months of treatment. Anaphylactic shock and platelet count should be carefully monitored in those receiving rifampin-containing regimens.

Association of Genetic Variants of NLRP4 with Exacerbation of Asthma: The Effect of Smoking.

Asthma exacerbation is induced by the interaction of genes and environmental factors such as cigarette smoke. NLRP4 counteracts the activity of the inflammasome, which is responsible for asthma exacerbation. In this study, we analyzed the association of single-nucleotide polymorphisms of NLRP4 with the annual rate of exacerbation and evaluated the additive effect of smoking in 1454 asthmatics. Asthmatics possessing the minor allele of rs1696718G > A had more frequent exacerbation episodes than those homozygous for the common allele (0.59 vs. 0.36/year) and the association was present only in current and ex-smokers. There was a significant interaction between the amount smoked and rs16986718 genotypes (p = 0.014) and a positive correlation between the number of annual exacerbation episodes and amount smoked only in rs16986718G > A AA homozygotes. The prevalence of frequent exacerbators (≥2 exacerbation episodes/year) was 2.5 times higher in rs16986718G > A minor allele homozygotes than in common allele homozygotes (12.0% vs. 5.9%). Furthermore, the prevalence was 6 times higher in rs16986718G > A minor allele homozygotes who were current and ex-smokers than in nonsmokers (25.6% vs. 4.1%). The minor allele of rs16986718G > A in NLRP4 may be a genetic marker that predicts asthma exacerbation in adult asthmatics who smoke.