Increasing the reliability of fully automated surveillance for central line–associated bloodstream infections

OBJECTIVETo increase reliability of the algorithm used in our fully automated electronic surveillance system by adding rules to better identify bloodstream infections secondary to other hospital-acquired infections.METHODSIntensive care unit (ICU) patients with positive blood cultures were reviewed. Central line–associated bloodstream infection (CLABSI) determinations were based on 2 sources: routine surveillance by infection preventionists, and fully automated surveillance. Discrepancies between the 2 sources were evaluated to determine root causes. Secondary infection sites were identified in most discrepant cases. New rules to identify secondary sites were added to the algorithm and applied to this ICU population and a non-ICU population. Sensitivity, specificity, predictive values, and kappa were calculated for the new models.RESULTSOf 643 positive ICU blood cultures reviewed, 68 (10.6%) were identified as central line–associated bloodstream infections by fully automated electronic surveillance, whereas 38 (5.9%) were confirmed by routine surveillance. New rules were tested to identify organisms as central line–associated bloodstream infections if they did not meet one, or a combination of, the following: (I) matching organisms (by genus and species) cultured from any other site; (II) any organisms cultured from sterile site; (III) any organisms cultured from skin/wound; (IV) any organisms cultured from respiratory tract. The best-fit model included new rules I and II when applied to positive blood cultures in an ICU population. However, they didn’t improve performance of the algorithm when applied to positive blood cultures in a non-ICU population.CONCLUSIONElectronic surveillance system algorithms may need adjustment for specific populations.Infect. Control Hosp. Epidemiol. 2015;36(12):1396–1400</jats:sec

The consent process: enabling or disabling patients’ active participation?

Standards expected by doctors’ regulatory bodies in respect of the process of consent to treatment have arguably sought to restructure the nature of the doctor-patient relationship from one of paternalism to that of shared decision-making. Yet, few studies have explored empirically, from patients’ perspectives, the extent to which the process of consent to treatment enables or disables patients’ participation in medical decision-making. Our paper examines patients’ attitudes towards the consent process, exploring how and why these attitudes influence patients’ active participation in decision-making and considering possible consequent medico-legal issues. Data were collected longitudinally using semi-structured interviews and field observations involving 35 patients and 19 of their caregivers, in an English hospital between February and November 2014. These indicate that generally patients defer to the doctor in respect of treatment decision-making. Although most patients and their caregivers wanted detailed information and discussion, they did not necessarily expect that this would be provided. Further, patients perceived that signing the consent form was an obligatory routine principally to protect doctors from legal action should something go wrong. Our study suggests that patients’ predominantly paternalistic perceptions of the consent process can not only undermine attempts by doctors to involve them in decision-making but, as patients are now considered in law as informed actors, their perceptions of the consent form as not being in their interests could be a self-fulfilling prophecy if signing is undertaken without due consideration to the content

Protective efficacy of cross-reactive CD8⁺ T cells recognising mutant viral epitopes depends on peptide-MHC-I structural interactions and T cell activation threshold

Emergence of a new influenza strain leads to a rapid global spread of the virus due to minimal antibody immunity. Pre- existing CD8+ T-cell immunity directed towards conserved internal viral regions can greatly ameliorate the disease. However, mutational escape within the T cell epitopes is a substantial issue for virus control and vaccine design. Although mutations can result in a loss of T cell recognition, some variants generate cross-reactive T cell responses. In this study, we used reverse genetics to modify the influenza NP336-374 peptide at a partially-solvent exposed residue (N->A, NPN3A mutation) to assess the availability, effectiveness and mechanism underlying influenza-specific cross-reactive T cell responses. The engineered virus induced a diminished CD8+ T cell response and selected a narrowed T cell receptor (TCR) repertoire within two Vb regions (Vβ8.3 and Vβ9). This can be partially explained by the H-2DbNPN3A structure that showed a loss of several contacts between the NPN3A peptide and H-2Db, including a contact with His155, a position known to play an important role in mediating TCR-pMHC-I interactions. Despite these differences, common cross-reactive TCRs were detected in both the naïve and immune NPN3A-specific TCR repertoires. However, while the NPN3A epitope primes memory T-cells that give an equivalent recall response to the mutant or wild-type (wt) virus, both are markedly lower than wt->wt challenge. Such decreased CD8+ responses elicited after heterologous challenge resulted in delayed viral clearance from the infected lung. Furthermore, mice first exposed to the wt virus give a poor, low avidity response following secondary infection with the mutant. Thus, the protective efficacy of cross-reactive CD8+ T cells recognising mutant viral epitopes depend on peptide- MHC-I structural interactions and functional avidity. Our study does not support vaccine strategies that include immunization against commonly selected cross-reactive variants with mutations at partially-solvent exposed residues that have characteristics comparable to NPN3A. © 2010 Valkenburg et al.Link_to_subscribed_fulltex

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Patients' willingness and ability to participate actively in the reduction of clinical errors: a systematic literature review

This systematic review identifies the factors that both support and deter patients from being willing and able to participate actively in reducing clinical errors. Specifically, we add to our understanding of the safety culture in healthcare by engaging with the call for more focus on the relational and subjective factors which enable patients' participation (Iedema, Jorm, & Lum, 2009; Ovretveit, 2009). A systematic search of six databases, ten journals and seven healthcare organisations' web sites resulted in the identification of 2714 studies of which 68 were included in the review. These studies investigated initiatives involving patients in safety or studies of patients' perspectives of being actively involved in the safety of their care. The factors explored varied considerably depending on the scope, setting and context of the study. Using thematic analysis we synthesized the data to build an explanation of why, when and how patients are likely to engage actively in helping to reduce clinical errors. The findings show that the main factors for engaging patients in their own safety can be summarised in four categories: illness; individual cognitive characteristics; the clinician-patient relationship; and organisational factors. We conclude that illness and patients' perceptions of their role and status as subordinate to that of clinicians are the most important barriers to their involvement in error reduction. In sum, patients' fear of being labelled "difficult" and a consequent desire for clinicians' approbation may cause them to assume a passive role as a means of actively protecting their personal safety

Impact of a Plasmodium falciparum AMA1 Vaccine on Antibody Responses in Adult Malians

Apical Membrane Antigen 1 (AMA1) of Plasmodium falciparum merozoites is a leading blood-stage malaria vaccine candidate. Protection of Aotus monkeys after vaccination with AMA1 correlates with antibody responses.A randomized, controlled, double-blind phase 1 clinical trial was conducted in 54 healthy Malian adults living in an area of intense seasonal malaria transmission to assess the safety and immunogenicity of the AMA1-C1 malaria vaccine. AMA1-C1 contains an equal mixture of yeast-expressed recombinant proteins based on sequences from the FVO and 3D7 clones of P. falciparum, adsorbed on Alhydrogel. The control vaccine was the hepatitis B vaccine (Recombivax). Participants were enrolled into 1 of 3 dose cohorts (n = 18 per cohort) and randomized 2:1 to receive either AMA1-C1 or Recombivax. Participants in the first, second, and third cohorts randomized to receive AMA1-C1 were vaccinated with 5, 20 and 80 microg of AMA1-C1, respectively. Vaccinations were administered on days 0, 28, and 360, and participants were followed until 6 months after the final vaccination. AMA1-C1 was well tolerated; no vaccine-related severe or serious adverse events were observed. AMA1 antibody responses to the 80 microg dose increased rapidly from baseline levels by days 14 and 28 after the first vaccination and continued to increase after the second vaccination. After a peak 14 days following the second vaccination, antibody levels decreased to baseline levels one year later at the time of the third vaccination that induced little or no increase in antibody levels.Although the AMA1-C1 vaccine candidate was well-tolerated and induced antibody responses to both vaccine and non-vaccine alleles, the antibody response after a third dose given at one year was lower than the response to the initial vaccinations. Additionally, post-vaccination increases in anti-AMA1 antibody levels were not associated with significant changes in in vitro growth inhibition of P. falciparum.ClinicalTrials.gov NCT00343005

Phase Ia Clinical Evaluation of the Safety and Immunogenicity of the Plasmodium falciparum Blood-Stage Antigen AMA1 in ChAd63 and MVA Vaccine Vectors

Traditionally, vaccine development against the blood-stage of Plasmodium falciparum infection has focused on recombinant protein-adjuvant formulations in order to induce high-titer growth-inhibitory antibody responses. However, to date no such vaccine encoding a blood-stage antigen(s) alone has induced significant protective efficacy against erythrocytic-stage infection in a pre-specified primary endpoint of a Phase IIa/b clinical trial designed to assess vaccine efficacy. Cell-mediated responses, acting in conjunction with functional antibodies, may be necessary for immunity against blood-stage P. falciparum. The development of a vaccine that could induce both cell-mediated and humoral immune responses would enable important proof-of-concept efficacy studies to be undertaken to address this question