Safety concerns about CCR5 as an antiviral target.

PURPOSE OF REVIEW: Clinical trials of CCR5 antagonists attest to their efficacy and tolerance in HIV treatment. However, there has been debate on their long-term safety because of the role of CCR5 in innate immunity. This review highlights gaps in our understanding of epidemiology of infections that are modulated by CCR5, in particular, in HIV-infected individuals. RECENT FINDINGS: In the mouse model, CCR5 has a role in the response against pathogens as diverse as Toxoplama gondii, West Nile virus, Mycobacterium tuberculosis, herpes simplex virus, Trypanosoma cruzi, Cryptococcus neoformans, Chlamydia trachomatis, Listeria, and plasmodia. In human cohorts, individuals carrying the defective CCR5Delta32 allele present an increased susceptibility to flavivirus (West Nile virus and tickborne encephalitis virus). The selective pressures that led to the spread of loss-of-function CCR5 mutations in humans (CCR5Delta32), and in mangabeys (CCR5Delta24) are not understood. SUMMARY: The recent availability of CCR5 antagonists has raised concern that genetic, biological, or chemical CCR5 knockout, although beneficial against some pathogens (i.e. HIV), could be deleterious for other processes implicated in pathogen response. The consequences of long-term pharmaceutical intervention on CCR5 should be carefully assessed through rigorous postmarketing surveillance.

Safety of a new algorithm for the management of childhood illness (Almanach) to improve quality of care and rational use of drugs

Introduction New evidence from randomized controlled and etiology of fever studies, the availability of reliable RDT for malaria, and novel technologies call for revision of the IMCI strategy. We developed a new algorithm based on (i) a systematic review of published studies assessing the safety and appropriateness of RDT and antibiotic prescription, (ii) results from a clinical and microbiological investigation of febrile children aged <5 years, (iii) international expert IMCI opinions. The aim of this study was to assess the safety of the new algorithm among patients in urban and rural areas of Tanzania.Materials and Methods The design was a controlled noninferiority study. Enrolled children aged 2-59 months with any illness were managed either by a study clinician using the new Almanach algorithm (two intervention health facilities), or clinicians using standard practice, including RDT (two control HF). At day 7 and day 14, all patients were reassessed. Patients who were ill in between or not cured at day 14 were followed until recovery or death. Primary outcome was rate of complications, secondary outcome rate of antibiotic prescriptions.Results 1062 children were recruited. Main diagnoses were URTI 26%, pneumonia 19% and gastroenteritis (9.4%). 98% (531/541) were cured at D14 in the Almanach arm and 99.6% (519/521) in controls. Rate of secondary hospitalization was 0.2% in each. One death occurred in controls. None of the complications was due to withdrawal of antibiotics or antimalarials at day 0. Rate of antibiotic use was 19% in the Almanach arm and 84% in controls.Conclusion Evidence suggests that the new algorithm, primarily aimed at the rational use of drugs, is as safe as standard practice and leads to a drastic reduction of antibiotic use. The Almanach is currently being tested for clinician adherence to proposed procedures when used on paper or a mobile phone

Social Media in health. What are the safety concerns for healthcare consumers?

Recent literature has discussed the unintended consequences of clinical information technologies (IT) on patient safety, yet there has been little discussion about the safety concerns in the area of consumer health IT. This paper presents a range of safety concerns for consumers in social media, with a case study on YouTube. We conducted a scan of abstracts on 'quality criteria' related to YouTube. Five areas regarding the safety of YouTube for consumers were identifi ed: (a) harmful health material targeted at consumers (such as inappropriate marketing of tobaccoor direct-to-consumer drug advertising); (b) public display of unhealthy behaviour (such as people displaying self-injury behaviours or hurting others); (c) tainted public health messages (i.e. the rise of negative voices againstpublic health messages); (d) psychological impact from accessing inappropriate, offensive or biased social media content; and (e) using social media to distort policy and research funding agendas. The examples presented should contribute to a better understanding about how to promote a safe consumption and production of social media for consumers, and an evidence-based approach to designing social media interventions for health. The potential harm associated with the use of unsafe social media content on the Internet is a major concern. More empirical and theoretical studies are needed to examine how social media infl uences consumer health decisions, behaviours and outcomes, and devise ways to deter the dissemination of harmful infl uences in social media.

Experimental thermal hydraulic studies on the enhancement of safety of LWRs

The safe use of nuclear power plants (NPPs) requires a deep understanding of the functioning of physical processes and systems involved. Studies on thermal hydraulics have been carried out in various separate effects and integral test facilities at Lappeenranta University of Technology (LUT) either to ensure the functioning of safety systems of light water reactors (LWR) or to produce validation data for the computer codes used in safety analyses of NPPs. Several examples of safety studies on thermal hydraulics of the nuclear power plants are discussed. Studies are related to the physical phenomena existing in different processes in NPPs, such as rewetting of the fuel rods, emergency core cooling (ECC), natural circulation, small break loss-of-coolant accidents (SBLOCA), non-condensable gas release and transport, and passive safety systems. Studies on both VVER and advanced light water reactor (ALWR) systems are included. The set of cases include separate effects tests for understanding and modeling a single physical phenomenon, separate effects tests to study the behavior of a NPP component or a single system, and integral tests to study the behavior of the whole system. In the studies following steps can be found, not necessarily in the same study. Experimental studies as such have provided solutions to existing design problems. Experimental data have been created to validate a single model in a computer code. Validated models are used in various transient analyses of scaled facilities or NPPs. Integral test data are used to validate the computer codes as whole, to see how the implemented models work together in a code. In the final stage test results from the facilities are transferred to the NPP scale using computer codes. Some of the experiments have confirmed the expected behavior of the system or procedure to be studied; in some experiments there have been certain unexpected phenomena that have caused changes to the original design to avoid the recognized problems. This is the main motivation for experimental studies on thermal hydraulics of the NPP safety systems. Naturally the behavior of the new system designs have to be checked with experiments, but also the existing designs, if they are applied in the conditions that differ from what they were originally designed for. New procedures for existing reactors and new safety related systems have been developed for new nuclear power plant concepts. New experiments have been continuously needed.

Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: systematic review and meta-analysis.

Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on efficacy, safety and tolerability of linezolid-containing regimes based on individual data analysis. 12 studies (11 countries from three continents) reporting complete information on safety, tolerability, efficacy of linezolid-containing regimes in treating MDR-TB cases were identified based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analysis was performed using the individual data of 121 patients with a definite treatment outcome (cure, completion, death or failure). Most MDR-TB cases achieved sputum smear (86 (92.5%) out of 93) and culture (100 (93.5%) out of 107) conversion after treatment with individualised regimens containing linezolid (median (inter-quartile range) times for smear and culture conversions were 43.5 (21-90) and 61 (29-119) days, respectively) and 99 (81.8%) out of 121 patients were successfully treated. No significant differences were detected in the subgroup efficacy analysis (daily linezolid dosage ≤600 mg versus >600 mg). Adverse events were observed in 63 (58.9%) out of 107 patients, of which 54 (68.4%) out of 79 were major adverse events that included anaemia (38.1%), peripheral neuropathy (47.1%), gastro-intestinal disorders (16.7%), optic neuritis (13.2%) and thrombocytopenia (11.8%). The proportion of adverse events was significantly higher when the linezolid daily dosage exceeded 600 mg. The study results suggest an excellent efficacy but also the necessity of caution in the prescription of linezolid.

Drift and ownership toward a distant virtual body.

In body ownership illusions participants feel that a mannequin or virtual body (VB) is their own. Earlier results suggest that body ownership over a body seen from behind in extra personal space is possible when the surrogate body is visually stroked and tapped on its back, while spatially and temporal synchronous tactile stimulation is applied to the participant's back. This result has been disputed with the claim that the results can be explained by self-recognition rather than somatic body ownership. We carried out an experiment with 30 participants in a between-groups design. They all saw the back of a VB 1.2 m in front, that moved in real-time determined by upper body motion capture. All felt tactile stimulation on their back, and for 15 of them this was spatially and temporally synchronous with stimulation that they saw on the back of the VB, but asynchronous for the other 15. After 3 min a revolving fan above the VB descended and stopped at the position of the VB neck. A questionnaire assessed referral of touch to the VB, body ownership, the illusion of drifting forwards toward the VB, and the VB drifting backwards. Heart rate deceleration (HRD) and the amount of head movement during the threat period were used to assess the response to the threat from the fan. Results showed that although referral of touch was significantly greater in the synchronous condition than the asynchronous, there were no other differences between the conditions. However, a further multivariate analysis revealed that in the visuotactile synchronous condition HRD and head movement increased with the illusion of forward drift and decreased with backwards drift. Body ownership contributed positively to these drift sensations. Our conclusion is that the setup results in a contradiction-somatic feelings associated with a distant body-that the brain attempts to resolve by generating drift illusions that would make the two bodies coincide.

The building blocks of the full body ownership illusion

Previous work has reported that it is not difficult to give people the illusion of ownership over an artificial body, providing a powerful tool for the investigation of the neural and cognitive mechanisms underlying body perception and self consciousness. We present an experimental study that uses immersive virtual reality (IVR) focused on identifying the perceptual building blocks of this illusion. We systematically manipulated visuotactile and visual sensorimotor contingencies, visual perspective, and the appearance of the virtual body in order to assess their relative role and mutual interaction. Consistent results from subjective reports and physiological measures showed that a first person perspective over a fake humanoid body is essential for eliciting a body ownership illusion. We found that the illusion of ownership can be generated when the virtual body has a realistic skin tone and spatially substitutes the real body seen from a first person perspective. In this case there is no need for an additional contribution of congruent visuotactile or sensorimotor cues. Additionally, we found that the processing of incongruent perceptual cues can be modulated by the level of the illusion: when the illusion is strong, incongruent cues are not experienced as incorrect. Participants exposed to asynchronous visuotactile stimulation can experience the ownership illusion and perceive touch as originating from an object seen to contact the virtual body. Analogously, when the level of realism of the virtual body is not high enough and/or when there is no spatial overlap between the two bodies, then the contribution of congruent multisensory and/or sensorimotor cues is required for evoking the illusion. On the basis of these results and inspired by findings from neurophysiological recordings in the monkey, we propose a model that accounts for many of the results reported in the literature.

Measuring the effects through time of the influence of visuomotor and visuotactile synchronous stimulation on a virtual body ownership illusion

Previous studies have examined the experience of owning a virtual surrogate body or body part through specific combinations of cross-modal multisensory stimulation. Both visuomotor (VM) and visuotactile (VT) synchronous stimulation have been shown to be important for inducing a body ownership illusion, each tested separately or both in combination. In this study we compared the relative importance of these two cross-modal correlations, when both are provided in the same immersive virtual reality setup and the same experiment. We systematically manipulated VT and VM contingencies in order to assess their relative role and mutual interaction. Moreover, we present a new method for measuring the induced body ownership illusion through time, by recording reports of breaks in the illusion of ownership ("breaks") throughout the experimental phase. The balance of the evidence, from both questionnaires and analysis of the breaks, suggests that while VM synchronous stimulation contributes the greatest to the attainment of the illusion, a disruption of either (through asynchronous stimulation) contributes equally to the probability of a break in the illusion.

Efficacy and safety of tigecycline versus levofloxacin for community-acquired pneumonia.

Abstract Background: Tigecycline, an expanded broad-spectrum glycylcycline, exhibits in vitro activity against many common pathogens associated with community-acqui red pneumonia (CAP), as well as penetration into lung tissues that suggests effectiveness in ho spitalized CAP patients. The aim of the present study was to compare the efficacy and safety of intravenous (IV) tigecycline with IV levofloxacin in hospitalized adults with CAP. Methods: In this prospective, double-blin d, non-inferiority phase 3 trial, eligible patients with a clinical diagnosis of CAP supported by radiographic evidence were stratified by Fine Pneumonia Severity Index and randomized to tigecycline or levofloxacin for 7-14 days of therapy. Co-primary efficacy endpoints were clinical response in the clinically evaluable (CE) and clinical modified intent- to-treat (c-mITT) populations at te st-of-cure (Day 10-21 post-therapy). Results: Of the 428 patients who received at least on e dose of study drug, 79% had CAP of mild-moderate severity according to their Fine score. Clinical cure rates for the CE population were 88.9% for tigecycline and 85.3% for levofloxac in. Corresponding c-mITT population rates were 83.7% and 81.5%, respectively. Eradication rates for Streptococcus pneumoniae were 92% for tigecycline and 89% for levofloxac in. Nausea, vomiting, and diarrhoea were the most frequently reported adverse events. Rates of premature disc continuation of study drug or study withdrawal because of any adverse event were similar for both study drugs. Conclusion: These findings suggest that IV tigecycline is non-inferior to IV levofloxacin and is generally well-tolerated in the treatment of hospitalized adults with CAP.

Vaccines safety; effect of supervision or SMS on reporting rates of adverse events following immunization (AEFI) with meningitis vaccine (MenAfriVac?): a randomized controlled trial.

BACKGROUND: To ensure vaccines safety, given the weaknesses of the national pharmacovigilance system in Cameroon, there is a need to identify effective interventions that can contribute to improving AEFI reporting. OBJECTIVE: To assess the effect of: (i) sending weekly SMS, or (ii) weekly supervisory visits on AEFI reporting rate during a meningitis immunization campaign conducted in Cameroon in 2012 using the meningitis A conjugate vaccine (MenAfriVac?). METHODS: Health facilities that met the inclusion criteria were randomly assigned to receive: (i) a weekly standardized SMS, (ii) a weekly standardized supervisory visits or (iii) no intervention. The primary outcome was the reported AEFI incidence rate from week 5 to 8 after the immunization campaign. Poisson regression model was used to estimate the effect of interventions after adjusting for health region, type of health facility, type and position of health workers as well as the cumulative number of AEFI reported from weeks 1 to 4. RESULTS: A total of 348 (77.2%) of 451 health facility were included, and 116 assigned to each of three groups. The incidence rate of reported AEFI per 100 health facility per week was 20.0 (15.9-24.1) in the SMS group, 40.2 (34.4-46.0) in supervision group and 13.6 (10.1-16.9) in the control group. Supervision led to a significant increase of AEFI reporting rate compared to SMS [adjusted RR=2.1 (1.6-2.7); p<0.001] and control [RR=2.8(2.1-3.7); p<0.001)] groups. The effect of SMS led to some increase in AEFI reporting rate compared to the control group, but the difference was not statistically significant [RR=1.4(0.8-1.6); p=0.07)]. CONCLUSION: Supervision was more effective than SMS or routine surveillance in improving AEFI reporting rate. It should be part of any AEFI surveillance system. SMS could be useful in improving AEFI reporting rates but strategies need to be found to improve its effectiveness, and thus maximize its benefits.

Safety of intramuscular influenza vaccine in patients receiving oral anticoagulation therapy: a single blinded multi-centre randomized controlled clinical trial

Influenza vaccines are recommended for administration by the intramuscular route. However, many physicians use the subcutaneous route for patients receiving an oral anticoagulant because this route is thought to induce fewer hemorrhagic side effects. Our aim is to assess the safety of intramuscular administration of influenza vaccine in patients on oral anticoagulation therapy. Methods: Design: Randomised, controlled, single blinded, multi-centre clinical trial. Setting: 4 primary care practices in Barcelona, Spain. Participants: 229 patients on oral anticoagulation therapy eligible for influenza vaccine during the 20032004 season. Interventions: intramuscular administration of influença vaccine in the experimental group (129 patients) compared to subcutaneous administration in the control group (100 patients). Primary outcome: change in the circumference of the arm at the site of injection at 24 hours. Secondary outcomes: appearance of local reactions and pain at 24 hours and at 10 days; change in INR (International Normalized Ratio) at 24 hours and at 10 days. Analysis was by intention to treat using the 95% confidence intervals of the proportions or mean differences. Results: Baseline variables in the two groups were similar. No major side effects or major haemorrhage during the follow-up period were reported. No significant differences were observed in the primary outcome between the two groups. The appearance of local adverse reactions was more frequent in the subcutaneous administration group (37,4% vs. 17,4%, 95% confidence interval of the difference 8,2% to 31,8%). Conclusion: This study shows that the intramuscular administration route of influenza vaccine in patients on anticoagulant therapy does not have more side effects than the subcutaneous administration route

The Effect of Family Ownership on Firm Performance: Empirical Evidence from Norway

Tutkimuksen tavoitteena on selvittää, onko perheomistajuus, eli yksityisomistus, kannattavampi omistusmuoto kuin institutionaalinen omistajuus ja, onko yrityksen iällä ja koolla vaikutusta perheyritysten menestymiseen. Aikaisempaan tutkimustietoon tukeutuen, tutkimuksen aluksi käydään myös läpi perheomistajuuteen yleisesti liitettyjä ominaispiirteitä sekä perheyritysten menestymistä verrattuna ei-perheyrityksiin. Empiirinen analyysi perheomistajuuden vaikutuksista yrityksen kannattavuuteen sekä yrityksen iän ja koon vaikutuksista perheyritysten menestymiseen toteutetaan kahden otoksen avulla, jotka koostuvat listaamattomista norjalaisista pienistä ja keskisuurista yrityksistä (pk-yrityksistä). Näin ollen satunnaisotos ja päätoimialaotos, johon listaamattomat pk-yritykset on valittu satunnaisesti Norjan tärkeimmiltä toimialoilta, analysoidaan erikseen. Analyysi toteutetaan käyttäen lineaarista regressioanalyysia. Vaikka satunnaisotoksen perusteella perheyritykset eivät näytä olevan ei-perheyrityksiä kannattavampia, päätoimialaotos osoittaa, että listaamattomissa pk-yrityksissä perhe- eli yksityisomistajuus on merkittävästi institutionaalista omistajuutta kannattavampi omistusmuoto. Eritoten nuoret ja pienet yritykset vastaavat perheyritysten paremmasta kannattavuudesta.

Henkilöstön suhde osuuspankkiin

Tämän tutkimuksen tarkoituksena on kuvata ja ymmärtää henkilöstön suhdetta suomalaiseen osuustoiminnalliseen organisaatioon. Suhdetta pyritään ymmärtämään organisaatioon identifioitumisen, psykologisen omistajuuden, organisaatioon sitoutumisen ja psykologisen sopimuksen kautta. Tavoitteena on tulkita mikä näistä henkilöstön ja organisaation suhdetta kuvaavista käsitteistä auttaa parhaiten ymmärtämään kyseistä suhdetta. Lisäksi pyritään ymmärtämään osuustoiminnallisuuden merkitystä henkilöstön ja organisaation suhteessa. Tutkimus on luonteeltaan laadullinen tutkimus, jossa tutkimusmetodina on käytetty teemahaastattelua. Tutkimuksen aineisto on kerätty kahdellatoistayksilöhaastattelulla tutkimuksen kohteena olevan organisaation henkilöstöstä. Haastateltavien valinnalla pyrittiin saamaan mahdollisimman laaja ja monipuolinenkuva organisaatiosta mm. henkilöstön työtehtävien, aseman ja työssäolovuosien avulla. Tutkimustulosten perusteella voidaan todeta, että henkilöstön suhdetta organisaatioon määrittävät parhaiten organisaatioon sitoutuminen ja identifioituminen, joihin osuustoiminnallisuus luo pohjaa arvomaailmallaan ja turvallisuuden tunteen avulla.