Community-Acquired Bacterial Meningitis in Alcoholic Patients

BACKGROUND: Alcoholism is associated with susceptibility to infectious disease, particularly bacterial pneumonia. In the present study we described characteristics in alcoholic patients with bacterial meningitis and delineate the differences with findings in non-alcoholic adults with bacterial meningitis. METHODS/PRINCIPAL FINDINGS: This was a prospective nationwide observational cohort study including patients aged >16 years who had bacterial meningitis confirmed by culture of cerebrospinal fluid (696 episodes of bacterial meningitis occurring in 671 patients). Alcoholism was present in 27 of 686 recorded episodes of bacterial meningitis (4%) and alcoholics were more often male than non-alcoholics (82% vs 48%, P = 0.001). A higher proportion of alcoholics had underlying pneumonia (41% vs 11% P<0.001). Alcoholics were more likely to have meningitis due to infection with Streptococcus pneumoniae (70% vs 50%, P = 0.01) and Listeria monocytogenes (19% vs 4%, P = 0.005), whereas Neisseria meningitidis was more common in non-alcoholic patients (39% vs 4%, P = 0.01). A large proportion of alcoholics developed complications during clinical course (82% vs 62%, as compared with non-alcoholics; P = 0.04), often cardiorespiratory failure (52% vs 28%, as compared with non-alcoholics; P = 0.01). Alcoholic patients were at risk for unfavourable outcome (67% vs 33%, as compared with non-alcoholics; P<0.001). CONCLUSIONS/SIGNIFICANCE: Alcoholic patients are at high risk for complications resulting in high morbidity and mortality. They are especially at risk for cardiorespiratory failure due to underlying pneumonia, and therefore, aggressive supportive care may be crucial in the treatment of these patient

Українська культура як чинник української державності: історичний аспект

У статті подано особливості формування української національної культури кінця XIX - XX століть. Охарактеризовано розвиток культури за умови становлення української державності. Автор намагався простежити вплив національного суспільства на розвиток культури в конкретний історичний період.The article introduces the features of formation of the Ukrainian national culture of the 19th-20th centuries. Characterized by the development of culture during becoming of Ukrainian statehood. The author tried to trace the influence of the national society for the development of culture in a specific historical period

Genetic Variation in the β2-Adrenocepter Gene Is Associated with Susceptibility to Bacterial Meningitis in Adults

Recently, the biased β2-adrenoceptor/β-arrestin pathway was shown to play a pivotal role in crossing of the blood brain barrier by Neisseria meningitidis. We hypothesized that genetic variation in the β2-adrenoceptor gene (ADRB2) may influence susceptibility to bacterial meningitis. In a prospective genetic association study we genotyped 542 patients with CSF culture proven community acquired bacterial meningitis and 376 matched controls for 2 functional single nucleotide polymorphisms in the β2-adrenoceptor gene (ADRB2). Furthermore, we analyzed if the use of non-selective beta-blockers, which bind to the β2-adrenoceptor, influenced the risk of bacterial meningitis. We identified a functional polymorphism in ADRB2 (rs1042714) to be associated with an increased risk for bacterial meningitis (Odds ratio [OR] 1.35, 95% confidence interval [CI] 1.04–1.76; p = 0.026). The association remained significant after correction for age and was more prominent in patients with pneumococcal meningitis (OR 1.52, 95% CI 1.12–2.07; p = 0.007). For meningococcal meningitis the difference in genotype frequencies between patients and controls was similar to that in pneumococcal meningitis, but this was not statistically significant (OR 1.43, 95% CI 0.60–3.38; p = 0.72). Patients with bacterial meningitis had a lower frequency of non-selective beta-blockers use compared to the age matched population (0.9% vs. 1.8%), although this did not reach statistical significance (OR 1.96 [95% CI 0.88–4.39]; p = 0.09). In conclusion, we identified an association between a genetic variant in the β2-adrenoceptor and increased susceptibility to bacterial meningitis. The potential benefit of pharmacological treatment targeting the β2-adrenoceptor to prevent bacterial meningitis in the general population or patients with bacteraemia should be further studied in both experimental studies and observational cohorts

Population genomics of Group B Streptococcus reveals the genetics of neonatal disease onset and meningeal invasion

Group B Streptococcus (GBS), or Streptococcus agalactiae, is a pathogen that causes preterm births, stillbirths, and acute invasive neonatal disease burden and mortality. Here, we investigate bacterial genetic signatures associated with disease onset time and meningeal tissue infection in acute invasive neonatal GBS disease. We carry out a genome-wide association study (GWAS) of 1,338 GBS isolates from newborns with acute invasive disease; the isolates had been collected annually, for 30 years, through a national bacterial surveillance program in the Netherlands. After controlling for the population structure, we identify genetic variation within noncoding and coding regions, particularly the capsule biosynthesis locus, statistically associated with neonatal GBS disease onset time and meningeal invasion. Our findings highlight the impact of integrating microbial population genomics and clinical pathogen surveillance, and demonstrate the effect of GBS genetics on disease pathogenesis in neonates and infants

Temporal profile of pneumonia after stroke

The occurrence of pneumonia after stroke is associated with a higher risk of poor outcome or death. We assessed the temporal profile of pneumonia after stroke and its association with poor outcome at several time points to identify the most optimal period for testing pneumonia prevention strategies. METHODS: We analyzed individual patient data stored in the VISTA (Virtual International Stroke Trials Archive) from randomized acute stroke trials with an inclusion window up to 24 hours after stroke onset and assessed the occurrence of pneumonia in the first 90 days after stroke. Adjusted odds ratios and hazard ratios were calculated for the association between pneumonia and poor outcome and death by means of logistic and Cox proportional hazard regression, respectively, at different times of follow-up. RESULTS: Of 10 821 patients, 1017 (9.4%) had a total of 1076 pneumonias. Six hundred eighty-nine (64.0%) pneumonias occurred in the first week after stroke. The peak incidence was on the third day and the median time of onset was 4.0 days after stroke (interquartile range, 2–12). The presence of a pneumonia was associated with an increased risk of poor outcome (adjusted odds ratio, 4.8 [95% CI, 3.8–6.1]) or death (adjusted hazard ratio, 4.1 [95% CI, 3.7–4.6]). These associations were present throughout the 90 days of follow-up. CONCLUSIONS: Two out of 3 pneumonias in the first 3 months after stroke occur in the first week, with a peak incidence on the third day. The most optimal period to assess pneumonia prevention strategies is the first 4 days after stroke. However, pneumonia occurring later was also associated with poor functional outcome or death

Infection of zebrafish embryos with live fluorescent Streptococcus pneumoniae as a real-time pneumococcal meningitis model

Background: Streptococcus pneumoniae is one of the most important causes of bacterial meningitis, an infection where unfavourable outcome is driven by bacterial and host-derived toxins. In this study, we developed and characterized a pneumococcal meningitis model in zebrafish embryos that allows for real-time investigation of early host-microbe interaction. Methods: Zebrafish embryos were infected in the caudal vein or hindbrain ventricle with green fluorescent wild-type S. pneumoniae D39 or a pneumolysin-deficient mutant. The kdrl:mCherry transgenic zebrafish line was used to visualize the blood vessels, whereas phagocytic cells were visualized by staining with far red anti-L-plastin or in mpx:GFP/mpeg1:mCherry zebrafish, that have green fluorescent neutrophils and red fluorescent macrophages. Imaging was performed by fluorescence confocal and time-lapse microscopy. Results: After infection by caudal vein, we saw focal clogging of the pneumococci in the blood vessels and migration of bacteria through the blood-brain barrier into the subarachnoid space and brain tissue. Infection with pneumolysin-deficient S. pneumoniae in the hindbrain ventricle showed attenuated growth and migration through the brain as compared to the wild-type strain. Time-lapse and confocal imaging revealed that the initial innate immune response to S. pneumoniae in the subarachnoid space mainly consisted of neutrophils and that pneumolysin-mediated cytolytic activity caused a marked reduction of phagocytes. Conclusions: This new meningitis model permits detailed analysis and visualization of host-microbe interaction in pneumococcal meningitis in real time and is a very promising tool to further our insights in the pathogenesis of pneumococcal meningitis

V-akt murine thymoma viral oncogene homolog 3 (AKT3) contributes to poor disease outcome in humans and mice with pneumococcal meningitis

Pneumococcal meningitis is the most common and severe form of bacterial meningitis. Fatality rates are substantial, and long-term sequelae develop in about half of survivors. Here, we have performed a prospective nationwide genetic association study using the Human Exome BeadChip and identified gene variants in encoding dynactin 4 (DCTN4), retinoic acid early transcript 1E (RAET1E), and V-akt murine thymoma viral oncogene homolog 3 (AKT3) to be associated with unfavourable outcome in patients with pneumococcal meningitis. No clinical replication cohort is available, so we validated the role of one of these targets, AKT3, in a pneumococcal meningitis mouse model. Akt3 deficient mice had worse survival and increased histopathology scores for parenchymal damage (infiltration) and vascular infiltration (large meningeal artery inflammation) but similar bacterial loads, cytokine responses, compared to wild-type mice. We found no differences in cerebrospinal fluid cytokine levels between patients with risk or non-risk alleles. Patients with the risk genotype (rs10157763, AA) presented with low scores on the Glasgow Coma Scale and high rate of epileptic seizures. Thus, our results show that AKT3 influences outcome of pneumococcal meningiti

Update of the Preventive Antibiotics in Stroke Study (PASS): Statistical analysis plan

Background: Infections occur in 30% of stroke patients and are associated with unfavorable outcomes. Preventive antibiotic therapy lowers the infection rate after stroke, but the effect of preventive antibiotic treatment on functional outcome in patients with stroke is unknown. The PASS is a multicenter, prospective, phase three, randomized, open-label, blinded end-point (PROBE) trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to standard stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. The aim of this study is to assess whether preventive antibiotic treatment improves functional outcome at 3 months by preventing infections. This paper presents in detail the statistical analysis plan (SAP) of the Preventive Antibiotics in Stroke Study (PASS) and was submitted while the investigators were st

Viininmaistelun alkeet -tapahtuma Maria P:ssä

Tiivistelmä Tekijät: Paananen Riina ja Korkiakoski Merika Työn nimi: Viininmaistelun alkeet -tapahtuma Maria P:ssä Tutkintonimike: Restonomi (AMK), matkailun koulutus Asiasanat: tapahtuma, viini, viininmaistelu, Chile Opinnäytetyön tarkoituksena oli suunnitella ja järjestää Viininmaistelun alkeet -tapahtuma. Tapahtuman toimeksiantajana toimi kajaanilainen yritys Viinibaari Maria P. Tapahtuma haluttiin toteuttaa baarin imagoon sopivaksi. Opinnäytetyön tavoitteena oli saada Viini-baarille lisää asiakkaita tutustuttamalla kokemattomia viininmaistajia viineihin. Työ oli toiminnallinen opinnäytetyö, jonka tuotoksena oli Viininmaistelun alkeet -tapahtuma. Opinnäytetyöhön kerättiin teoriapohjaa viininmaistelusta sekä viinin ja ruoan yhdistämisestä, Chilestä viinimaana ja tapahtuman järjestämisestä. Näitä kaikkia käytettiin lopullisen tuotoksen valmistumiseen. Toteutuksen arviointina toimi tapahtumaan osallistuneilta saatu kirjallinen palaute. Palautteen mukaan kehittämistehtävän toteutuksessa onnistuttiin hyvin, sillä opinnäytetyön ennalta määritellyt tavoitteet saavutettiin. Opinnäytetyötä voidaan käyttää apuna jatkossa vastaavien tapahtumien suunnittelussa.Abstract Authors: Paananen Riina & Korkiakoski Merika Title of the Publication: Basics of wine tasting- event Degree title: Bachelor of Hospitality Management Keywords: event, wine, tasting, Chile The purpose for this thesis was to plan and arrange Basics of wine tasting –event. The commissioner for this thsesis was a local bar in Kajaani called Viinibaari Maria P. The event was planned to suit the imago of the bar. The objective of the thesis was to gain more customers to Viinibaari Maria P by introducing various wines to novice wine tasters. This research was a functional thesis which produced the Basics wine tasting event. The theory of this thesis focused on wine tasting, combining wine and food, Chile as a wine producer, and on planning and arranging an event. The feedback for the execution consists of the feedback forms that the customers of the event were asked to fill in. In addition observation method was used for evaluation. According to the feedback the event was successful because the objective of the thesis was reached. Our conclusion is that this thesis can be used as a guide in planning similar events

PRECIOUS: PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke: rationale and design of a randomised, open, phase III, clinical trial with blinded outcome assessment

Background: Elderly patients are at high risk of complications after stroke, such as infections and fever. The occurrence of these complications has been associated with an increased risk of death or dependency. Hypothesis: Prevention of aspiration, infections, or fever with metoclopramide, ceftriaxone, paracetamol, or any combination of these in the first four days after stroke onset will improve functional outcome at 90 days in elderly patients with acute stroke. Design: International, 3 × 2-factorial, randomised-controlled, open-label clinical trial with blinded outcome assessment (PROBE) in 3800 patients aged 66 years or older with acute ischaemic stroke or intracerebral haemorrhage and an NIHSS score ≥ 6. Patients will be randomly allocated to any combination of oral, rectal, or intravenous metoclopramide (10 mg thrice daily); intravenous ceftriaxone (2000 mg once daily); oral, rectal, or intravenous paracetamol (1000 mg four times daily); or usual care, started within 24 h after symptom onset and continued for four days or until complete recovery or discharge from hospital, if earlier. Outcome: The primary outcome measure is the score on the modified Rankin Scale at 90 days (± 14 days), as analysed with multiple regression. Summary: This trial will provide evidence for a simple, safe and generally available treatment strategy that may reduce the burden of death or disability in patients with stroke at very low costs. Planning: First patient included in May 2016; final follow-up of the last patient by April 202