Timothy M. Rawson

A systematic review of clinical decision support systems for antimicrobial management: are we failing to investigate these interventions appropriately?

OBJECTIVES Clinical decision support systems (CDSS) for antimicrobial management can support clinicians to optimize antimicrobial therapy. We reviewed all original literature (qualitative and quantitative) to understand the current scope of CDSS for antimicrobial management and analyse existing methods used to evaluate and report such systems. METHOD PRISMA guidelines were followed. Medline, EMBASE, HMIC Health and Management and Global Health databases were searched from 1 January 1980 to 31 October 2015. All primary research studies describing CDSS for antimicrobial management in adults in primary or secondary care were included. For qualitative studies, thematic synthesis was performed. Quality was assessed using Integrated quality Criteria for the Review Of Multiple Study designs (ICROMS) criteria. CDSS reporting was assessed against a reporting framework for behaviour change intervention implementation. RESULTS Fifty-eight original articles were included describing 38 independent CDSS. The majority of systems target antimicrobial prescribing (29/38;76%), are platforms integrated with electronic medical records (28/38;74%), and have a rules-based infrastructure providing decision support (29/38;76%). On evaluation against the intervention reporting framework, CDSS studies fail to report consideration of the non-expert, end-user workflow. They have narrow focus, such as antimicrobial selection, and use proxy outcome measures. Engagement with CDSS by clinicians was poor. CONCLUSION Greater consideration of the factors that drive non-expert decision making must be considered when designing CDSS interventions. Future work must aim to expand CDSS beyond simply selecting appropriate antimicrobials with clear and systematic reporting frameworks for CDSS interventions developed to address current gaps identified in the reporting of evidence.

Mapping the decision pathways of acute infection management in secondary care among UK medical physicians: a qualitative study

BackgroundThe inappropriate use of antimicrobials drives antimicrobial resistance. We conducted a study to map physician decision-making processes for acute infection management in secondary care to identify potential targets for quality improvement interventions.MethodsPhysicians newly qualified to consultant level participated in semi-structured interviews. Interviews were audio recorded and transcribed verbatim for analysis using NVIVO11.0 software. Grounded theory methodology was applied. Analytical categories were created using constant comparison approach to the data and participants were recruited to the study until thematic saturation was reached.ResultsTwenty physicians were interviewed. The decision pathway for the management of acute infections follows a Bayesian-like step-wise approach, with information processed and systematically added to prior assumptions to guide management. The main emerging themes identified as determinants of the decision-making of individual physicians were (1) perceptions of providing ‘optimal’ care for the patient with infection by providing rapid and often intravenous therapy; (2) perceptions that stopping/de-escalating therapy was a senior doctor decision with junior trainees not expected to contribute; and (3) expectation of interactions with local guidelines and microbiology service advice. Feedback on review of junior doctor prescribing decisions was often lacking, causing frustration and confusion on appropriate practice within this cohort.ConclusionInterventions to improve infection management must incorporate mechanisms to promote distribution of responsibility for decisions made. The disparity between expectations of prescribers to start but not review/stop therapy must be urgently addressed with mechanisms to improve communication and feedback to junior prescribers to facilitate their continued development as prudent antimicrobial prescribers.

Antimicrobial stewardship: are we failing in cross-specialty clinical engagement?

BACKGROUND Antimicrobial resistance (AMR) is a public health priority and leading patient safety issue. Globally, antimicrobial stewardship (AMS) has been integral in promoting therapeutic optimization whilst minimizing harmful antimicrobial use. A cross-sectional, observational study was undertaken to investigate the coverage of AMS and antibacterial resistance across clinical scientific conferences in 2014, as a surrogate marker for current awareness and attributed importance. METHODS Clinical specialties were identified, and the largest corresponding clinical scientific/research conferences in 2014 determined (i) within the UK and (ii) internationally. Conference characteristics and abstracts were interrogated and analysed to determine those related to AMS and AMR. Inter-specialty variation was assessed using χ(2) or Fishers exact statistical analysis. RESULTS In total, 45 conferences from 23 specialties were analysed representing 59,682 accepted abstracts. The UK had a significantly greater proportion of AMS-AMR-related abstracts compared with international conferences [2.8% (n = 221/7843) compared with 1.8% (n = 942/51,839); P < 0.001]. Infection conferences contained the greatest proportion of AMS-AMR abstracts, representing 20% (732/3669) of all abstracts [UK 66% (80/121) and international 18% (652/3548); P < 0.0001]. AMS-AMR coverage across all general specialties was poor [intensive care 9% (116/1287), surgical 1% (8/757) and medical specialties 0.64% (332/51,497)] despite high usage of antimicrobials across all. CONCLUSIONS Despite current AMS-AMR strategies being advocated by infection specialists and discussed by national and international policy makers, AMS-AMR coverage remained limited across clinical specialty scientific conferences in 2014. We call for further intervention to ensure specialty engagement with AMS programmes and promote the AMR agenda across clinical practice.

Outcomes from treating tuberculosis with rifampicin or rifabutin in HIV-infected persons also receiving antiretroviral therapy.

To the Editors: Treatment of tuberculosis (TB) and HIV co-infection poses a number of important challenges for clinicians, including drug–drug interactions between components of antiretroviral therapy (ART) and anti-TB treatment. This is especially important between ritonavirboosted protease inhibitor (PI) therapy and rifampicin, a key component of quadruple short-course TB treatment. The current United Kingdom and United States guidelines recommend that HIV–TB co-infected patients should be treated for both TB and HIV contemporaneously, to achieve optimal outcomes. Where the use of first-line ART with a non-nucleoside reverse transcriptase inhibitor (NNRTI) is contraindicated, for example, acquired or transmitted resistance, intolerance, or toxicity of NNRTI, a ritonavir-boosted PI ART regimen is recommended. However, there are significant interactions between ritonavir-boosted PIs and rifampicin. Rifampicin is a potent inducer of several cytochrome P450 isoenzymes, including CYP3A4, as well as P-glycoprotein, and phase-2 enzyme activity, which have important actions on the metabolism of PIs and NNRTI. These effects may lead to subtherapeutic PI levels even when PI pharmacokinetics are boosted by ritonavir and, as a result ritonavir-boosted PI regimes are contraindicated in coadministration with rifampicin. Rifabutin, a rifamycin family member, is effective in treatment of TB in HIV-negative subjects. Based on pharmacokinetic studies, rifabutin has less of an effect than rifampicin on inducing hepatic enzymes and can be used in combination with PI-based ART regimens. Several studies have reported good outcomes from rifabutinbased regimens for treatment of TB in HIV-infected individuals, but there is a paucity of data describing outcomes in HIV-infected patients with TB treated with rifabutin, while also receiving ART. We undertook a retrospective observational study of outcomes among HIV/TB co-infected patients, who received either rifampicin or rifabutin for the treatment of TB and ART, to identify if outcomes differed according to the type of rifamycin used. Adult HIV-infected individuals treated for TB with either rifampicin or rifabutin, and who received ART (containing either a ritonavir-boosted PI or an NNRTI) at 2 inner city HIV treatment centers (Chelsea and Westminster Hospital and University College London Hospitals, London, United Kingdom), between April 1999 and August 2011 were identified. Data were extracted from case note and electronic patient records, including patient demographics (age, gender, ethnicity, risk factor for HIV acquisition), previous history of TB, site of TB (pulmonary, lymph node, or disseminated), interval between diagnosis of TB and HIV, details of anti-TB and ART regimens, occurrence of adverse drug reactions (ADRs) (grade 3/4) requiring TB treatment interruption, occurrence of immune reconstitution inflammatory syndrome (IRIS), and outcomes (completed treatment, died). End of treatment plasma HIV viral load, and change in CD4 count between the start and end of TB treatment were noted. Each patient was followed up for 24 months: outcomes during follow-up, including death or recurrence, were recorded. Patients with known rifamycin and/or isoniazid resistance were excluded. Patients were categorized as having either definite or presumptive TB, as previously described. ART was defined as the use of at least 3 antiretroviral drugs including either a ritonavirboosted PI (lopinavir or darunavir) or an NNRTI. Prescription of anti-TB medication and ART was based on the British HIV Association Guidelines, and was at the discretion of individual physicians: treatment was self-administered in the majority of patients. All patients started standard 4-drug TB therapy with isoniazid, pyrazinamide, ethambutol, and either rifabutin or rifampicin, except for 2 rifabutin-treated patients who started a quinolone in place of pyrazinamide (both had indeterminate pyrazinamide sensitivities and were fully sensitive to the other first-line medications). Rifampicin dosing was weight-based (450 or 600 mg once daily) and was given with a gvfNNRTI. Rifabutin 450 mg once daily was used with efavirenz, 300 mg once daily with nevirapine, and 150 mg 3 times weekly was given with a ritonavir-boosted PI. All other anti-TB drugs were taken daily. Data were analyzed using STATA SE12 (Statacorp LP, College Station, TX). The x2, Mann–Whitney U test, and Fisher exact tests were used to compare rifabutinand rifampicintreated groups. A P , 0.05 was considered significant. Ethics committee approval was not required because this R.F.M. has received honoraria from Gilead, Janssen, Merck, and ViiV, for giving nonpromotional lectures on clinical aspects of HIV and tuberculosis, is a member of the British HIV Association TB/HIV Guidelines Committee, and is a panel member for Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-infected Adults and Adolescents. A.L.P. has received honoraria from AbbVie, BMS, Gilead, Janssen, Merck, Tobira, and ViiV, for giving nonpromotional lectures on clinical aspects of HIV and tuberculosis, has received payment from Janssen for expert testimony relating to an HIV drug submission to the European Medicines Agency, is Chair of the British HIV Association TB/HIV Guidelines Committee and a member of the British HIV Association, European Aids Clinical Society, and WHO HIV Treatment Guidelines Committees. The remaining authors have no conflicts of interest to disclose. T.M.R. and R.F.M. acquired data, analyzed, and interpreted the data, wrote the first and final drafts of the article. A.L.P. was responsible for the study concept and design, analyzed and interpreted the data, critically reviewed drafts of the article for important intellectual content. N.B.,S.M., and A.J.C. analyzed and interpreted the data, critically reviewed drafts of the article for important intellectual content. F.A.,A.J.,S.B., and L.K. acquired data, analyzed and interpreted the data, critically reviewed drafts of the article for important intellectual content.

Assessing the role of peripheral CD8 T cells in neurocognitive impairment in HIV-infected men who have sex with men: data from the MSM Neurocog Study

Studies have suggested CD8 lymphocytes may be a possible marker for inflammation, which is believed to be a contributing factor to neurocognitive impairment. Individuals enrolled in the MSM Neurocog Study were analysed. Those with depression, anxiety or mood disorders were excluded. Individuals with neurocognitive impairment were identified using the Brief NeuroCognitive Screen and compared to those with normal scores. CD4 and CD8 T cell values and CD4:CD8 ratios were compared between groups. In all, 144 men, aged 18–50 years, were included in the analysis. Twenty were diagnosed with neurocognitive impairment. We were unable to identify any significant difference between current, nadir or peak CD4 and CD8 counts. CD4:CD8 ratios and CD4:CD8 ratio inversion (<1) were also found to be similar between both groups. However, neurocognitive impairment subjects were 8% more likely to have inversion of CD4:CD8 ratio and higher median peak CD8 cell counts reported compared to non-impaired subjects. Analysis of data from the MSM Neurocog Study, demonstrated trends in peripheral CD8 counts and CD4:CD8 ratios. However, we are unable to demonstrate any significant benefit. Plasma biomarkers of neurocognitive impairment in HIV-infected subjects would be of great benefit over current methods of invasive CSF analysis and technical neuroimaging used in the diagnosis of neurocognitive impairment. Future, prospective, longitudinal work with large numbers of neurocognitive impairment subjects is required to further investigate the role of peripheral CD8 T cells as markers of neurocognitive impairment.

Supervised learning for infection risk inference using pathology data

BackgroundAntimicrobial Resistance is threatening our ability to treat common infectious diseases and overuse of antimicrobials to treat human infections in hospitals is accelerating this process. Clinical Decision Support Systems (CDSSs) have been proven to enhance quality of care by promoting change in prescription practices through antimicrobial selection advice. However, bypassing an initial assessment to determine the existence of an underlying disease that justifies the need of antimicrobial therapy might lead to indiscriminate and often unnecessary prescriptions.MethodsFrom pathology laboratory tests, six biochemical markers were selected and combined with microbiology outcomes from susceptibility tests to create a unique dataset with over one and a half million daily profiles to perform infection risk inference. Outliers were discarded using the inter-quartile range rule and several sampling techniques were studied to tackle the class imbalance problem. The first phase selects the most effective and robust model during training using ten-fold stratified cross-validation. The second phase evaluates the final model after isotonic calibration in scenarios with missing inputs and imbalanced class distributions.ResultsMore than 50% of infected profiles have daily requested laboratory tests for the six biochemical markers with very promising infection inference results: area under the receiver operating characteristic curve (0.80-0.83), sensitivity (0.64-0.75) and specificity (0.92-0.97). Standardization consistently outperforms normalization and sensitivity is enhanced by using the SMOTE sampling technique. Furthermore, models operated without noticeable loss in performance if at least four biomarkers were available.ConclusionThe selected biomarkers comprise enough information to perform infection risk inference with a high degree of confidence even in the presence of incomplete and imbalanced data. Since they are commonly available in hospitals, Clinical Decision Support Systems could benefit from these findings to assist clinicians in deciding whether or not to initiate antimicrobial therapy to improve prescription practices.

Patient engagement with infection management in secondary care: a qualitative investigation of current experiences

Objective To understand patient engagement with decision-making for infection management in secondary care and the consequences associated with current practices. Design A qualitative investigation using in-depth focus groups. Participants Fourteen members of the public who had received antimicrobials from secondary care in the preceding 12 months in the UK were identified for recruitment. Ten agreed to participate. All participants had experience of infection management in secondary care pathways across a variety of South-East England healthcare institutes. Study findings were subsequently tested through follow-up focus groups with 20 newly recruited citizens. Results Participants reported feelings of disempowerment during episodes of infection in secondary care. Information is communicated in a unilateral manner with individuals ‘told’ that they have an infection and will receive an antimicrobial (often unnamed), leading to loss of ownership, frustration, anxiety and ultimately distancing them from engaging with decision-making. This poor communication drives individuals to seek information from alternative sources, including online, which is associated with concerns over reliability and individualisation. Failures in communication and information provision by clinicians in secondary care influence individuals’ future ideas about infections and their management. This alters their future actions towards antimicrobials and can drive prescription non-adherence and loss to follow-up. Conclusions Current infection management and antimicrobial prescribing practices in secondary care fail to engage patients with the decision-making process. Secondary care physicians must not view infection management episodes as discrete events, but as cumulative experiences which have the potential to shape future patient behaviour and understanding of antimicrobial use.

Serious electronic games as behavioural change interventions in healthcare-associated infections and infection prevention and control: a scoping review of the literature and future directions

BackgroundThe uptake of improvement initiatives in infection prevention and control (IPC) has often proven challenging. Innovative interventions such as ‘serious games’ have been proposed in other areas to educate and help clinicians adopt optimal behaviours. There is limited evidence about the application and evaluation of serious games in IPC. The purposes of the study were: a) to synthesise research evidence on the use of serious games in IPC to support healthcare workers’ behaviour change and best practice learning; and b) to identify gaps across the formulation and evaluation of serious games in IPC.MethodsA scoping study was conducted using the methodological framework developed by Arksey and O’Malley. We interrogated electronic databases (Ovid MEDLINE, Embase Classic + Embase, PsycINFO, Scopus, Cochrane, Google Scholar) in December 2015. Evidence from these studies was assessed against an analytic framework of intervention formulation and evaluation.ResultsNine hundred sixty five unique papers were initially identified, 23 included for full-text review, and four finally selected. Studies focused on intervention inception and development rather than implementation. Expert involvement in game design was reported in 2/4 studies. Potential game users were not included in needs assessment and game development. Outcome variables such as fidelity or sustainability were scarcely reported.ConclusionsThe growing interest in serious games for health has not been coupled with adequate evaluation of processes, outcomes and contexts involved. Explanations about the mechanisms by which game components may facilitate behaviour change are lacking, further hindering adoption.

The role of the multidisciplinary team in decision making for vascular graft infection

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Microbiological characterisation of prosthetic vascular graft infection

• In the general ward setting, we observe high rates of both gram positive and gram negative organisms causing vascular graft infections (VGI).