GI Bleeding in the Elderly

Purpose: To determine the risk factors contributing to and etiologies of gastrointestinal bleeding in an elderly patient population seen by Southwest Gastroenterology (SWGA) providers. Methods: This study reviews charts of patients with GI bleeding from documented sources between 1/1999 and 3/2006. The cases are gathered retrospectively from the clinical records of SWGA, a 12-person private, single specialty gastroenterology group serving community hospitals. Etiology and risk factors for GI hemorrhages are recorded in an elderly population, defined as patients age 55 and older. Results: GI hemorrhages are identified in 105 patients. The majority (83, 79%) of hemorrhages are upper GI bleeds (UGIB) comparing to 22 (21%) lower GI bleeds (LGIB). In the UGIB group, the most common etiology of bleed is gastric ulcer (29%). We also found 72% of UGIB patients on prescribed anticoagulation medications, including anti-platelet agents or non-steroidal anti-inflammatory drugs (NSAIDs). 20% of these patients are also positive for H. Pylori. Thirty patients in the UGIB group smoke or consume alcohol heavily (consuming more than 3 drinks per day for men and two drinks per day for women) while 2 patients smoke or consume alcohol in the LGIB group. Previous bleeds are common in both groups with 39 (41%) in UGIB and 9 (47%) in LGIB. Co-morbidity is the most common risk factor with 20 (91%) in LGIB and 73 (88%) in UGIB. In the peptic ulcer disease (PUD) bleeds, the majority (77%) are taking NSAIDs, while in the non-PUD bleeds, only 38% are currently on NSAIDs. Overall, there are 2 mortalities resulting from cardiovascular complications of GI bleeding. Conclusion: The etiologies of GI bleeds in this population are comparable to other studies in the literature. The ratio of UGIB to LGIB in this elderly population is also similar to that reported in the literature. The risk factors shown to be most correlated to bleeding are co-morbidities, previous episodes of bleeding, anticoagulation, NSAID use, smoking and alcohol use. NSAID use is significant in PUD bleed patients. This study reinforces that increased knowledge of etiology, incidence and contributing factors of GI bleeding are necessary for physicians to efficiently treat GI bleeds in the elderly population

The Dominant Australian Community-Acquired Methicillin-Resistant Staphylococcus aureus Clone ST93-IV [2B] Is Highly Virulent and Genetically Distinct

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 has spread rapidly across North America, and CA-MRSA is also increasing in Australia. However, the dominant Australian CA-MRSA strain, ST93-IV [2B] appears distantly related to USA300 despite strikingly similar clinical and epidemiological profiles. Here, we compared the virulence of a recent Australian ST93 isolate (JKD6159) to other MRSA, including USA300, and found that JKD6159 was the most virulent in a mouse skin infection model. We fully sequenced the genome of JKD6159 and confirmed that JKD6159 is a distinct clone with 7616 single nucleotide polymorphisms (SNPs) distinguishing this strain from all other S. aureus genomes. Despite its high virulence there were surprisingly few virulence determinants. However, genes encoding α-hemolysin, Panton-Valentine leukocidin (PVL) and α-type phenol soluble modulins were present. Genome comparisons revealed 32 additional CDS in JKD6159 but none appeared to encode new virulence factors, suggesting that this clone's enhanced pathogenicity could lie within subtler genome changes, such as SNPs within regulatory genes. To investigate the role of accessory genome elements in CA-MRSA epidemiology, we next sequenced three additional Australian non-ST93 CA-MRSA strains and compared them with JKD6159, 19 completed S. aureus genomes and 59 additional S. aureus genomes for which unassembled genome sequence data was publicly available (82 genomes in total). These comparisons showed that despite its distinctive genotype, JKD6159 and other CA-MRSA clones (including USA300) share a conserved repertoire of three notable accessory elements (SSCmecIV, PVL prophage, and pMW2). This study demonstrates that the genetically distinct ST93 CA-MRSA from Australia is highly virulent. Our comparisons of geographically and genetically diverse CA-MRSA genomes suggest that apparent convergent evolution in CA-MRSA may be better explained by the rapid dissemination of a highly conserved accessory genome from a common source

Clinical practice: The bleeding child. Part II: Disorders of secondary hemostasis and fibrinolysis

Bleeding complications in children may be caused by disorders of secondary hemostasis or fibrinolysis. Characteristic features in medical history and physical examination, especially of hemophilia, are palpable deep hematomas, bleeding in joints and muscles, and recurrent bleedings. A detailed medical and family history combined with a thorough physical examination is essential to distinguish abnormal from normal bleeding and to decide whether it is necessary to perform diagnostic laboratory evaluation. Initial laboratory tests include prothrombin time and activated partial thromboplastin time. Knowledge of the classical coagulation cascade with its intrinsic, extrinsic, and common pathways, is useful to identify potential defects in the coagulation in order to decide which additional coagulation tests should be performed

Recent Advances in Childhood Arterial Ischemic Stroke

Although many underlying diseases have been reported in the setting of childhood arterial ischemic stroke, emerging research demonstrates that non-atherosclerotic intracerebral arteriopathies in otherwise healthy children are prevalent. Minor infections may play a role in arteriopathies that have no other apparent underlying cause. Although stroke in childhood differs in many aspects from adult stroke, few systematic studies specific to pediatrics are available to inform stroke management. Treatment trials of pediatric stroke are required to determine the best strategies for acute treatment and secondary stroke prevention. The high cost of pediatric stroke to children, families, and society demands further study of its risk factors, management, and outcomes. This review focuses on the recent findings in childhood arterial ischemic stroke

Pharmacogenetics of warfarin in a paediatric population: time in therapeutic range, initial and stable dosing and adverse effects

Warfarin is used in paediatric populations, but dosing algorithms incorporating pharmacogenetic data have not been developed for children. Previous studies have produced estimates of the effect of polymorphisms in Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) on stable warfarin dosing, but data on time in therapeutic range, initial dosing and adverse effects are limited. Participants (n=97) were recruited, and routine clinical data and salivary DNA samples were collected from all participants and analysed for CYP2C9*2, *3 and VKORC1-1639 polymorphisms.VKORC1 -1639 was associated with a greater proportion of the first 6 months’ treatment time spent within the target International Normalised Ratio (INR) range, accounting for an additional 9.5% of the variance in the proportion of time. CYP2C9*2 was associated with a greater likelihood of INR values exceeding the target range during the initiation of treatment (odds ratio (OR; per additional copy) 4.18, 95% confidence interval (CI) 1.42, 12.34). CYP2C9*2 and VKORC1-1639 were associated with a lower dose requirement, and accounted for almost 12% of the variance in stable dose. VKORC1-1639 was associated with an increased likelihood of mild bleeding complications (OR (heterozygotes vs homozygotes) 4.53, 95% CI 1.59, 12.93). These data show novel associations between VKORC1-1639 and CYP2C9*2 and INR values in children taking warfarin, as well as replicating previous findings with regard to stable dose requirements. The development of pharmacogenomic dosing algorithms for children using warfarin has the potential to improve clinical care in this population

Rivaroxaban Compared with Standard Anticoagulants for the Treatment of Acute Venous Thromboembolism in Children: a Randomised, Controlled, Phase 3 Trial

Background: Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism. Methods: In a multicentre, parallel-group, open-label, randomised study, children (aged 0–17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children <2 years of age with catheter-related venous thromboembolism). The primary efficacy outcome, symptomatic recurrent venous thromboembolism (assessed by intention-to-treat), and the principal safety outcome, major or clinically relevant non-major bleeding (assessed in participants who received ≥1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed. Findings: From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87–95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29–35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0·40, 95% CI 0·11–1·41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0·012). Major or clinically relevant non-major bleeding in participants who received ≥1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1·58, 95% CI 0·51–6·27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths. Interpretation: In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants. Funding: Bayer AG and Janssen Research & Development. © 2020 Elsevier Ltd