Incidence of intracranial bleeds in new users of low-dose aspirin: a cohort study using The Health Improvement Network.

Essentials Intracranial bleeds (ICB) are serious clinical events that have been associated with aspirin use. Incidence rates of ICB were calculated among new-users of low-dose aspirin in the UK (2000-2012). Over a median follow-up of 5.58 years, the incidence of ICB was 0.08 per 100 person-years. Our estimates are valuable for inclusion in risk-benefit assessments of low-dose aspirin use. SUMMARY: Background Low-dose aspirin protects against both ischemic cardiovascular (CV) events and colorectal cancer (CRC). However, low-dose aspirin may be associated with a slightly increased risk of intracranial bleeds (ICBs). Objectives To obtain the incidence rates of ICBs overall and by patient subgroups among new users of low-dose aspirin. Patients/Methods Using The Health Improvement Network (THIN) UK primary-care database (2000-2012), we identified a cohort of new users of low-dose aspirin aged 40-84 years (N = 199 079; mean age at start of follow-up, 63.9 years) and followed them for up to 14 years (median 5.58 years). Incident ICB cases were identified and validated through linkage to hospitalization data and/or review of THIN records with free-text comments. Incidence rates with 95% confidence intervals (CIs) were calculated. Results Eight hundred and eighty-one incident ICBs cases were identified: 407 cases of intracerebral hemorrhage (ICH), 283 cases of subdural hematoma (SDH), and 191 cases of subarachnoid hemorrhage (SAH). Incidence rates per 100 person-years were 0.08 (95% CI 0.07-0.08) for all ICBs, 0.04 (95% CI 0.03-0.04) for ICH, 0.03 (95% CI 0.02-0.03) for SDH, and 0.02 (95% CI 0.01-0.02) for SAH. The ICB incidence rates per 100 person-years for individuals with an indication of primary CV disease prevention were 0.07 (95% CI 0.06-0.07) and 0.09 (95% CI 0.08-0.10) for secondary CV disease prevention. Incidence rates were higher in men for SDH, and higher in women for ICH and SAH. Conclusions Our results provide valuable estimates of the absolute ICB risk for incorporation into risk-benefit assessments of low-dose aspirin use.

Higher proportion of G2P[4] rotaviruses in vaccinated hospitalized cases compared with unvaccinated hospitalized cases, despite high vaccine effectiveness against heterotypic G2P[4] rotaviruses.

The overall vaccine effectiveness of the monovalent rotavirus vaccine in an observational, prospective, multicentre, hospital-based case-control study in Belgium (RotaBel) was 90%. However, rotavirus genotype and co-infecting pathogens are important parameters to take into account when assessing vaccine effectiveness. In this study we specifically investigated the effect of rotavirus genotypes and co-infecting pathogens on vaccine effectiveness of the monovalent vaccine. In addition, we also investigated the effect of co-infecting pathogens on disease severity. From February 2008 to June 2010 stool samples of rotavirus gastroenteritis cases of a random sample of 39 Belgian hospitals were collected and subsequently genotyped. Fisher's exact tests were performed to investigate the relationships between rotavirus genotype, co-infecting pathogens and disease severity. The vaccine effectiveness of a full series of the monovalent rotavirus vaccine against hospitalized rotavirus gastroenteritis caused by G1P[8] rotavirus strains was 95% (95% CI 77.5-98.7). Against G2P[4], the vaccine effectiveness was 85% (95% CI: 63.7-93.8). G4P[8]- and G3P[8]-specific vaccine effectiveness was 90% (95% CI 19.2-98.7) and 87% (95% CI -5.2 to 98.4), respectively. A post-hoc analysis showed that the genotype distribution was significantly related to the vaccination status (p <0.001), whereby G2P[4] strains were proportionally more prevalent in vaccinated cases than in unvaccinated cases. No statistical associations were found between co-infection status and vaccination status, Vesikari severity score or rotavirus genotype. The high vaccine effectiveness against the individual genotypes implies robust protection of the monovalent rotavirus vaccine against hospitalized rotavirus gastroenteritis caused by the major human rotavirus genotypes. The prevalence of G2P[4] requires continued monitoring.

Meningococcal disease in Asia: an under-recognized public health burden.

A literature search traced existing information on meningococcal disease in Asia. Reviewed data describing the epidemiology of meningococcal disease in Asia are incomplete, due in part to absence of surveillance in many countries, poor bacterial detection methods and social and healthcare barriers to disease reporting. This suggests that meningococcal disease in some Asian countries may be under-recognized, with a need to introduce/improve existing surveillance and case identification systems. Nevertheless, in some developing Asian countries, the disease burden may be significant. Serogroup A meningococcal epidemics are responsible for high morbidity and mortality in some countries and continue to be an ongoing threat, particularly in developing countries. There is an increasing role played by serogroups C, Y, and W-135 in invasive disease, indicating evolving meningococcal disease epidemiology in some countries. Multivalent meningococcal conjugate vaccines offer new opportunities in the region for reducing the meningococcal disease burden.

Estimating the vaccine-preventable burden of hospitalized pneumonia among young Mozambican children.

Polysaccharide-protein conjugate vaccines against Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae have proven efficacy against radiologically confirmed pneumonia. Measurement of pneumonia incidence provides a platform to estimate of the vaccine-preventable burden. Over 24 months, we conducted surveillance for radiologically confirmed severe pneumonia episodes among children <2 years of age admitted to a rural hospital in Manhiça, southern Mozambique. Study children were tested for HIV during the second year of surveillance. Severe pneumonia accounted for 15% of 5132 hospital admissions and 32% of in-hospital mortality among children <2 years of age. Also, 43% of chest radiographs were interpreted as radiologically confirmed pneumonia. HIV-infection was associated with 81% of fatal pneumonia episodes among children tested for HIV. The minimum incidence rate of radiologically confirmed pneumonia requiring hospitalization was 19 episodes/1000 child-years. Incidence rates among HIV-infected children were 9.3-19.0-fold higher than HIV-uninfected. Introduction of Hib and pneumococcal conjugate vaccines would have a substantial impact on pneumonia hospitalizations among African children if vaccine effects are similar to those observed in clinical trials.

A mathematical model of the indirect effects of rotavirus vaccination.

Rotavirus (RV) infections progressively confer natural immunity against subsequent infection. Similarly to natural infection, vaccination with a live attenuated vaccine potentially reduces RV transmission and induces herd protection. A mathematical transmission model was developed to project the impact of a vaccination programme on the incidence of RV infection and disease for five countries in the European Union. With vaccination coverage rates of 70%, 90% and 95% the model predicted that, in addition to the direct effect of vaccination, herd protection induced a reduction in RV-related gastroenteritis (GE) incidence of 25%, 22% and 20%, respectively, for RV-GE of any severity, and of 19%, 15%, and 13%, respectively, for moderate-to-severe RV-GE, 5 years after implementation of a vaccination programme.

Aetiologies and risk factors for neonatal sepsis and pneumonia mortality among Alaskan infants.

We evaluated all fatal neonatal sepsis and pneumonia cases occurring in Alaska during 1992-2000. Risk factors were evaluated using a database of all births occurring during the study period. Of 32 cases, group B streptococcus (GBS) was isolated from 21% (all 7 days of age), non-GBS Gram-positive bacteria from 50% (53% <7 days of age), and Gram-negative infections from 38% (58% <7 days of age). Infants born at <37 weeks gestation accounted for 72% of cases and had an increased risk of GBS [rate ratio (RR) 9.1, 95% confidence interval (CI) 2.0-41] and non-GBS (RR 40, 95% CI 16-101) disease. Neonatal sepsis mortality has become an outcome concentrated among pre-term infants. Aetiologies include GBS during the early neonatal period, Candida spp. during the late neonatal period, and other bacteria during both periods.

Vaccines for the prevention of meningococcal disease in children.

Neisseria meningitidis is one of the most feared infections in pediatrics as the result of its rapid progression, high fatality rate, and frequent occurrence of sequelae. The 5 major meningococcal serogroups associated with disease are A, B, C, Y, and W-135. Currently available polysaccharide vaccines are effective in preventing disease caused by serogroups A, C, Y, and W-135 in older children and adults but do not elicit good long-term protection in young children. Vaccines that protect against serogroup B disease are still in development. As with the Haemophilus influenzae type b and pneumococcal polysaccharide vaccines, conjugation of the polysaccharide vaccine to a protein carrier dramatically changes vaccine characteristics, with resulting efficacy in infants. New meningococcal conjugate vaccines against serogroups A, C, Y, and W-135 are being developed. A serogroup C conjugate vaccine has been introduced successfully into the routine childhood schedule in the United Kingdom. New meningococcal conjugate vaccines are likely to have a dramatic effect on the burden of meningococcal disease within the next decade.

Direct immunomagnetic method for CD34+ cell selection from cryopreserved cord blood grafts for ex vivo expansion protocols.

BACKGROUND: Cord blood is a useful source of HPCs for allogeneic transplantation. HPC ex vivo expansion of a cord blood graft has been proposed as a way to increase the speed of engraftment and thus to reduce the occurrence of transplantation-related complications. OBJECTIVE: The purpose of this study was to optimize a method for CD34+ cell selection of thawed cord blood grafts under clinical grade conditions, intended for application in a static, serum-free expansion culture. MATERIAL AND METHODS: Twelve samples were thawed and washed with dextran, albumin, and rHu-deoxyribo-nuclease I (RHu-DNase) to avoid clumping. CD34+ cells were selected by using a sensitized immunomagnetic bead and 9C5 MoAb complex. A buffer containing rHu-DNase, citrate, albumin, and immunoglobulin in PBS was used during the procedure. CD34+ cells were eluted and detached by using an immunomagnetic cell selection device. Cells from the enriched fraction were cultured for 6 days in serum-free medium supplemented with rHu-SCF, rHu-IL-3, rHu fetal liver tyrosine kinase 3 ligand, and rHu thrombopoietin (50 ng/mL each). Cells were expanded in well plates and in two semipermeable bags. RESULTS: A mean of 1.94 x 10(6) (+/- 1.55) CD34+ cells was obtained, yielding a CD34+ cell recovery of 52 +/- 12 percent. Nonspecific loss of CD34+ cells was 32 +/- 10 percent. CFU-GM and BFU-E/CFU-Mixed recoveries were 33 +/- 15 percent and 27 +/- 12 percent, respectively. CD34+ cells obtained were functionally comparable with fresh CD34+ cells selected for clonogenic potential. The capacity for expansion was not significantly different in the two types of bags studied. HPCs in wells were expanded 33 +/- 14-fold for CD34+ cells and 42 +/- 19-fold for overall colonies. The expansion rates observed in wells were significantly superior to those obtained in bags. CONCLUSION: The feasibility of a clinical-scale cord blood selection procedure based on a direct immunomagnetic method after thawing, followed by an ex vivo expansion culture using semipermeable bags, is shown. After 6 days of expansion, it was possible to generate a 9-fold increase in CD34+ cells, a 6-fold increase in CFU-GM and a 13-fold increase in BFU-E/CFU-Mixed colonies.

The placental blood program of the Barcelona Cord Blood Bank.

Cord blood has recently become an alternative to bone marrow transplantation, generating the need for cord blood banks where large numbers of frozen cord blood units can be stored. The Barcelona Cord Blood Bank (bcB) was created in October 1995. Initially, several methods for volume reduction were tested, including Ficoll, Percoll, Gelatin and HES sedimentation. Of these, HES sedimentation (88% +/- 11 CD34+ cells recovery) was the one chosen for routine banking. Up to November 1997, the bank has processed 754 units with a median of 1.05 x 10(9) nucleated cells and 2.5 x 10(6) CD34+ cells stored per unit. Nine of these units have been shipped for transplantation.