Implementation of a national system for best practice delivery of paediatric infusions.

BACKGROUND: Standard concentration infusions and 'smart-pumps' are recognised as best practice in the paediatric setting. Implementation rates in European hospitals remain low. Children's Health Ireland (CHI) developed a paediatric 'smart-pump' drug library using standardised concentrations. At time of development, other Irish hospitals continued to use traditional pumps and weight-based paediatric infusions. AIM: To expand best paediatric infusion practices by nationalising use of the CHI drug library. SETTING: Tertiary paediatric, maternity and general acute hospitals, and associated transport services in Ireland. DEVELOPMENT: The CHI drug library was first developed for paediatric intensive care and then adapted over a 10-year period for use in emergency departments, general paediatric wards, neonatal units, adult intensive care and transport services. The original library (42 drug lines, 1 'care-unit') was substantially expanded (223 drug lines, 6 'care-units'). A neonatal sub-library was created. IMPLEMENTATION: Executive support, dedicated resources and governance structures were secured. Implementation and training packages were developed. Implementation has occurred across CHI, in paediatric and neonatal transport services, 58% (n = 11) of neonatal units, and 23% (n = 6) of paediatric sites. EVALUATION: A before and after study demonstrated significant reductions in infusion prescribing errors (29.0% versus 8.4%, p < 0.001). Direct observation of infusions (n = 1023) found high compliance rates (98.9%) and low programming errors (1.6%). 100% of nurses (n = 132) surveyed 9 months after general ward implementation considered the drug library had enhanced patient safety. CONCLUSION: Strategic planning and collaboration can standardise infusion practices. The CHI drug library has been approved as a National Standard of Care, with implementation continuing.

Single-Dose Anti-Thymocyte Globulin Compared With Divided-Dose for Induction Therapy in Kidney Transplantation in a Predominantly Black Population.

BACKGROUND: The aim of this study was to compare single-dose rabbit anti-thymocyte globulin (rATG) with a divided dose in kidney transplant recipients within a majority Black patient population. METHODS: We analyzed the outcomes before and after a change in protocol from divided-dose (1.5 mg/kg/day over 4 days) to single-dose (6 mg/kg over 24 hours) rATG in a retrospective cohort study. All patients who received rATG for kidney transplant induction between December 2015 and July 2018 were included. RESULTS: A total of 197 patients (n = 98 in the divided-dose group, n = 99 in the single-dose group) received rATG. There was no difference in time to rejection at 1 year (P = .82) or incidence of rejection (P = .80). There was also no difference in delayed graft function, serum creatinine, or survival at 1 year. Patients in the single-dose group were more likely to leave the hospital by postoperative day 3 (12% vs 2%, P = .006). The cytomegalovirus infection rate was higher in the single-dose group (P = .031). CONCLUSIONS: Use of a single-dose rATG regimen is an acceptable accelerated induction compared with the standard divided dose for induction therapy in kidney transplant in a predominantly Black population.

Successful Treatment of UL97 Mutation Ganciclovir-Resistant Cytomegalovirus Viremia in a Renal Transplant Recipient With Letermovir and Adjunct Hyperimmune Cytomegalovirus Immunoglobulin: A Case Report.

Letermovir is an antiviral agent indicated for primary prophylaxis of cytomegalovirus (CMV) infection and disease in adult allogeneic hematopoietic stem cell transplant recipients. In this case, UL97 mutation that conferred resistance to ganciclovir was seen in a patient 8 months after renal transplant. We report the off-label use of letermovir with adjunct hyperimmune CMV immunoglobulin in the successful treatment of CMV disease. This report is the first to use this combination for treatment of CMV infection with a high viral load. It contributes to the limited available literature supporting the use of letermovir in the treatment of resistant CMV, where current therapeutic options can be suboptimal due to adverse effects and the risk of cross-resistance.

Safety, immunogenicity, and efficacy of the candidate tuberculosis vaccine MVA85A in healthy adults infected with HIV-1: a randomised, placebo-controlled, phase 2 trial.

BACKGROUND: HIV-1 infection is associated with increased risk of tuberculosis and a safe and effective vaccine would assist control measures. We assessed the safety, immunogenicity, and efficacy of a candidate tuberculosis vaccine, modified vaccinia virus Ankara expressing antigen 85A (MVA85A), in adults infected with HIV-1. METHODS: We did a randomised, double-blind, placebo-controlled, phase 2 trial of MVA85A in adults infected with HIV-1, at two clinical sites, in Cape Town, South Africa and Dakar, Senegal. Eligible participants were aged 18-50 years, had no evidence of active tuberculosis, and had baseline CD4 counts greater than 350 cells per µL if they had never received antiretroviral therapy or greater than 300 cells per µL (and with undetectable viral load before randomisation) if they were receiving antiretroviral therapy; participants with latent tuberculosis infection were eligible if they had completed at least 5 months of isoniazid preventive therapy, unless they had completed treatment for tuberculosis disease within 3 years before randomisation. Participants were randomly assigned (1:1) in blocks of four by randomly generated sequence to receive two intradermal injections of either MVA85A or placebo. Randomisation was stratified by antiretroviral therapy status and study site. Participants, nurses, investigators, and laboratory staff were masked to group allocation. The second (booster) injection of MVA85A or placebo was given 6-12 months after the first vaccination. The primary study outcome was safety in all vaccinated participants (the safety analysis population). Safety was assessed throughout the trial as defined in the protocol. Secondary outcomes were immunogenicity and vaccine efficacy against Mycobacterium tuberculosis infection and disease, assessed in the per-protocol population. Immunogenicity was assessed in a subset of participants at day 7 and day 28 after the first and second vaccination, and M tuberculosis infection and disease were assessed at the end of the study. The trial is registered with ClinicalTrials.gov, number NCT01151189. FINDINGS: Between Aug 4, 2011, and April 24, 2013, 650 participants were enrolled and randomly assigned; 649 were included in the safety analysis (324 in the MVA85A group and 325 in the placebo group) and 645 in the per-protocol analysis (320 and 325). 513 (71%) participants had CD4 counts greater than 300 cells per µL and were receiving antiretroviral therapy; 136 (21%) had CD4 counts above 350 cells per µL and had never received antiretroviral therapy. 277 (43%) had received isoniazid prophylaxis before enrolment. Solicited adverse events were more frequent in participants who received MVA85A (288 [89%]) than in those given placebo (235 [72%]). 34 serious adverse events were reported, 17 (5%) in each group. MVA85A induced a significant increase in antigen 85A-specific T-cell response, which peaked 7 days after both vaccinations and was primarily monofunctional. The number of participants with negative QuantiFERON-TB Gold In-Tube findings at baseline who converted to positive by the end of the study was 38 (20%) of 186 in the MVA85A group and 40 (23%) of 173 in the placebo group, for a vaccine efficacy of 11·7% (95% CI -41·3 to 44·9). In the per-protocol population, six (2%) cases of tuberculosis disease occurred in the MVA85A group and nine (3%) occurred in the placebo group, for a vaccine efficacy of 32·8% (95% CI -111·5 to 80·3). INTERPRETATION: MVA85A was well tolerated and immunogenic in adults infected with HIV-1. However, we detected no efficacy against M tuberculosis infection or disease, although the study was underpowered to detect an effect against disease. Potential reasons for the absence of detectable efficacy in this trial include insufficient induction of a vaccine-induced immune response or the wrong type of vaccine-induced immune response, or both. FUNDING: European & Developing Countries Clinical Trials Partnership (IP.2007.32080.002), Aeras, Bill & Melinda Gates Foundation, Wellcome Trust, and Oxford-Emergent Tuberculosis Consortium.

Integrating social science and design inquiry through interdisciplinary design charrettes: an approach to participatory community problem solving.

Interdisciplinary collaborations that aim to facilitate meaningful community outcomes require both the right mix of disciplinary knowledge and effective community participation, which together can deepen collective knowledge and the capacity to take action. This article explores three interdisciplinary design charrettes, intensive participatory workshops that addressed specific community problems and provided a context for integrating design and social science inquiry with local community knowledge. Evaluation data from the charrettes shed light on how students from the design and social science disciplines experienced the charrettes, and on their interactions with community members. Key advantages to this interdisciplinary, community-based collaboration included expanded knowledge derived from the use of multiple modes of inquiry, particularly the resulting visualization tools that helped community members understand local issues and envision novel solutions. Key drawbacks included difficulties in balancing the two disciplines, the tendency for social scientists to feel out of place on designers' turf, and the increased disciplinary and interpersonal conflicts arising from a more diverse pool of participants.