Background Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0•9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0•9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.

A nosocomial outbreak of Crimean-Congo hemorrhagic fever occurred in Rawalpindi, Pakistan in February 2002. The identified index case died shortly after admission to a hospital. Two of the health care workers became secondary cases; one of them died on day 13 after coming in contact with the index case. The other secondary case was successfully treated with oral ribavirin.

A 25-year-old woman, later identified as index case of Crimean-Congo hemorrhagic fever (CCHF), presented to Holy Family Hospital in Rawalpindi, Pakistan with fever and generalized coagulopathy. A retrospective contact tracing was conducted to explore the modes of exposure possibly associated with transmission of CCHF infection among contacts. We traced 32 contacts of the index case and 158 contacts of secondary cases and tested them for IgG and IgM antibodies against CCHF virus by an enzyme-linked immunosorbent assay technique. According to the type of exposure, contacts were divided into five subsets: percutaneous contact with blood, blood contact to unbroken skin, cutaneous contact to non-sanguineous body fluids, physical contact with patients without body fluids contact, and close proximity without touching. Two out of four contacts who reported percutaneous exposure tested positive for antibodies to CCHF virus. We conclude that simple barrier methods and care in provision of CCHF cases may prevent transmission of this infection.

Homocysteine and its modulating genes have strongly emerged as novel biomarkers for coronary artery disease (CAD). In the present study, we investigated whether polymorphisms in homocysteine pathway genes and the plasma levels of homocysteine, folate, and vitamin B, independently or in combination, are associated with CAD risk. A total of 504 participants were recruited (cases, n = 254; controls, n = 250, respectively). Tetra primer allele refractory mutation system polymerase chain reaction (PCR) was used for resolving the genotypes of 5'10' methylenetetrahydrofolate reductase 'MTHFR' polymorphisms (rs1801133, rs1801131), 5' methyl tetrahydrofolate homocysteine methyltransferase 'MTR' polymorphism (rs1805087), paroxanse1 'PON1' polymorphism (rs662), and cystathionine beta synthase 'CBS' polymorphism (rs5742905). Conventional PCR amplification was carried out for resolving angiotensin converting enzyme 'ACE' insertion/deletion (I/D) polymorphism (rs4646994). ANOVA analysis, adjusted for the covariates, revealed that rs1801133, rs1805087 polymorphisms and homocysteine levels were associated with CAD. Logistic regression analysis (adjusted) revealed similar findings. Logistic regression analysis after applying factorial design to the studied single nucleotide polymorphisms (SNPs) revealed that homocysteine levels and heterozygous and mutant alleles at rs1801133, rs1805087, along with mutant alleles at rs1801131, rs4646994, conferred higher risk for CAD. Our results provide insight into the multifactorial nature of coronary artery disease. We highlight that SNPs in folate pathway genes and homocysteine have role in disease causation and can be used in disease prediction strategies.

Cerebrovascular accidents (CVAs) are vascular multifactorial, multigenic ailments with intricate genetic, environmental risk influences. The present study aimed to establish affiliation of CVAs/stroke with blood parameters, differences in prescribed drugs consumption, and with differences in homocysteine pathway genes polymorphisms. The participants in study included controls n = 251, transient ischemic attack (TIA) patients n = 16, and stroke cases n = 122, respectively, (total participants, n = 389). The analyzed single nucleotide polymorphisms (SNPs) included C677T(rs1801133), A1298C(rs1801131) of methylene tetrahydrofolate reductase (MTHFR), A2756G(rs1805087) of methyl tetrahydrofolate homocysteine methyltransferase/methionine synthase (MS), and the A192G(rs662) of paraoxonase 1(PON1) genes, all validated by tetra-primer allele refractory mutation system polymerase chain reaction (T-ARMS-PCR). The insertion deletion (I/D; rs4646994) polymorphism in angiotensin converting enzyme (ACE) gene was analyzed using routine PCR. All studied traits were scrutinized through analysis of variance (ANOVA), and later through regression analysis. Through ANOVA and multiple comparison, there was association of CVA with serum homocysteine, cholesterol, and with diastolic blood pressure readings. When data was subjected to regression, serum homocysteine and diastolic blood pressure (significant through ANOVA), as well as two additional traits, high-density lipoproteins (HDL), and rs1801133 MTHFR SNP sustained statistical significance and noteworthy odds in relation to CVA and stroke. The ailments affecting cerebral vasculature are mutifactorial, whereby genes, proteins, and environmental cues all exert cumulative effects enhancing CVA risk. The current study emphasizes that SNPs and variation in circulating biomarkers can be used for screening purposes and for reviewing their effects in stroke/CVA-linked risk progression.