Incidence and outcome of in-hospital cardiac arrest in the United Kingdom National Cardiac Arrest Audit

Objective To report the incidence, characteristics and outcome of adult in-hospital cardiac arrest in the United Kingdom (UK) National Cardiac Arrest Audit database. Methods A prospectively defined analysis of the UK National Cardiac Arrest Audit (NCAA) database. 144 acute hospitals contributed data relating to 22,628 patients aged 16 years or over receiving chest compressions and/or defibrillation and attended by a hospital-based resuscitation team in response to a 2222 call. The main outcome measures were incidence of adult in-hospital cardiac arrest and survival to hospital discharge. Results The overall incidence of adult in-hospital cardiac arrest was 1.6 per 1000 hospital admissions with a median across hospitals of 1.5 (interquartile range 1.2–2.2). Incidence varied seasonally, peaking in winter. Overall unadjusted survival to hospital discharge was 18.4%. The presenting rhythm was shockable (ventricular fibrillation or pulseless ventricular tachycardia) in 16.9% and non-shockable (asystole or pulseless electrical activity) in 72.3%; rates of survival to hospital discharge associated with these rhythms were 49.0% and 10.5%, respectively, but varied substantially across hospitals. Conclusions These first results from the NCAA database describing the current incidence and outcome of adult in-hospital cardiac arrest in UK hospitals will serve as a benchmark from which to assess the future impact of changes in service delivery, organisation and treatment for in-hospital cardiac arrest

Evaluating the effectiveness of e-cigarettes compared with usual care for smoking cessation when offered to smokers at homeless centres: Protocol for a multi-centre cluster-randomized controlled trial in Great Britain

Background and aims Smoking is extremely common among adults experiencing homelessness, but there is lack of evidence for treatment efficacy. E-cigarettes are an effective quitting aid, but they have not been widely tested in smokers with complex health and social needs. Here we build upon our cluster feasibility trial and evaluate the offer of an e-cigarette or usual care to smokers accessing a homeless centre. Design, Setting and Participants Multi-centre two-arm cluster-randomized controlled trial with mixed-method embedded process and economic evaluation in homeless centres in England, Scotland and Wales. Adult smokers (18+ years; n = 480) accessing homeless centres and who are known to centre staff and willing to consent. Intervention and Comparator Clusters (n = 32) will be randomized to either an e-cigarette starter pack with weekly allocations of nicotine containing e-liquid for 4 weeks [choice of flavours (menthol, fruit and tobacco) and strengths 12 mg/ml and 18 mg/ml] or the usual care intervention, which comprises very brief advice and a leaflet signposting to the local stop smoking service. Measurements The primary outcome is 24-week sustained carbon monoxide-validated smoking cessation (Russell Standard defined, intention-to-treat analysis). Secondary outcomes: (i) 50% smoking reduction (cigarettes per day) from baseline to 24 weeks; (ii) 7-day point prevalence quit rates at 4-, 12- and 24-week follow-up; (iii) changes in risky smoking practices (e.g. sharing cigarettes, smoking discarded cigarettes) from baseline to 4, 12 and 24 weeks; (iv) cost-effectiveness of the intervention; and (v) fidelity of intervention implementation; mechanisms of change; contextual influences and sustainability. Conclusions This is the first study, to our knowledge, to randomly assign smokers experiencing homelessness to an e-cigarette and usual care intervention to measure smoking abstinence with embedded process and economic evaluations. If effective, its results will be used to inform the larger-scale implementation of offering e-cigarettes throughout homeless centres to aid smoking cessation

Temperature correction of spectra to improve solute concentration monitoring by in situ ultraviolet and mid-infrared spectrometries towards isothermal local model performance

Changes in temperature can significantly affect spectroscopic-based methods for in situ monitoring of processes. As varying temperature is inherent to many processes, associated temperature effects on spectra are unavoidable, which can hinder solute concentration determination. Ultraviolet (UV) and mid-infrared (IR) data were acquired for l-ascorbic acid (LAA) in MeCN/H2O (80:20 w/w) at different concentrations and temperatures. For both techniques, global partial least squares (PLS) models for prediction of LAA concentration constructed without preprocessing of the spectra required a high number of latent variables to account for the effects of temperature on the spectra (root mean square error of cross validation (RMSECV) of 0.18 and 0.16 g/100 g solvent, for UV and IR datasets, respectively). The PLS models constructed on the first derivative spectra required fewer latent variables, yielding variable results in accuracy (RMSECV of 0.23 and 0.06 g/100 g solvent, respectively). Corresponding isothermal local models constructed indicated improved model performance that required fewer latent variables in the absence of temperature effects (RMSECV of 0.01 and 0.04 g/100 g solvent, respectively). Temperature correction of the spectral data via loading space standardization (LSS) enabled the construction of global models using the same number of latent variables as the corresponding local model, which exhibited comparable model performance (RMSECV of 0.06 and 0.04 g/100 g solvent, respectively). The additional chemometric effort required for LSS is justified if prediction of solute concentration is required for in situ monitoring and control of cooling crystallization with an accuracy and precision approaching that attainable using an isothermal local model. However, the model performance with minimal preprocessing may be sufficient, for example, in the early phase development of a cooling crystallization process, where high accuracy is not always required. UV and IR spectrometries were used to determine solubility diagrams for LAA in MeCN/H2O (80:20 w/w), which were found to be accurate compared to those obtained using the traditional techniques of transmittance and gravimetric measurement. For both UV and IR spectrometries, solubility values obtained from models with LSS temperature correction were in better agreement with those determined gravimetrically. In this first example of the application of LSS to UV spectra, significant improvement in the predicted solute concentration is achieved with the additional chemometric effort. There is no extra experimental burden associated with the use of LSS if a structured approach is employed to acquire calibration data that account for both temperature and concentration

Cognitive Function in Young Persons With and Without Perinatal HIV in the AALPHI Cohort in England: Role of Non–HIV-Related Factors

Background. There is limited evidence about the cognitive performance of older adolescents with perinatally acquired human immunodeficiency virus (HIV) compared with HIV-negative (HIV−) adolescents. Methods. A total of 296 perinatally HIV-infected (PHIV+) and 97 HIV− adolescents (aged 12–21 and 13–23 years, respectively) completed 12 tests covering 6 cognitive domains. The HIV− participants had PHIV+ siblings and/or an HIV-infected mother. Domain-specific and overall (NPZ-6) z scores were calculated for PHIV+ participants, with or without Centers for Disease Control and Prevention (CDC) stage C disease, and HIV− participants. Linear regression was performed to explore predictors of NPZ-6. Results. One hundred twenty-five (42%) of the PHIV+ and 31 (32%) of the HIV− participants were male; 251 (85%) and 69 (71%), respectively, were black African; and their median ages (interquartile range) were 16 (15–18) and 16 (14–18) years, respectively. In PHIV+ participants, 247 (86%) were receiving antiretroviral therapy, and 76 (26%) had a previous CDC C diagnosis. The mean (standard deviation) NPZ-6 score was −0.81 (0.99) in PHIV+ participants with a CDC C diagnosis (PHIV+/C), −0.45 (0.80) in those without a CDC C diagnosis (PHIV+/no C), and −0.32 (0.76) in HIV− participants (P < .001). After adjustment, there was no difference in NPZ-6 scores between PHIV+/no C and HIV− participants (adjusted coefficient, −0.01; 95% confidence interval, −.22 to .20). PHIV+/C participants scored below the HIV− group (adjusted coefficient, −0.44; −.70 to −.19). Older age predicted higher NPZ-6 scores, and black African ethnicity and worse depression predicted lower NPZ-6 scores. In a sensitivity analysis including PHIV+ participants only, no HIV-related factors apart from a CDC C diagnosis were associated with NPZ-6 scores. Conclusions. Cognitive performance was similar between PHIV+/no C and HIV− participants and indicated relatively mild impairment compared with normative data. The true impact on day-to-day functioning needs further investigation

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

The CALORIES trial: statistical analysis plan.

BACKGROUND: The CALORIES trial is a pragmatic, open, multicentre, randomised controlled trial (RCT) of the clinical effectiveness and cost-effectiveness of early nutritional support via the parenteral route compared with early nutritional support via the enteral route in unplanned admissions to adult general critical care units (CCUs) in the United Kingdom. The trial derives from the need for a large, pragmatic RCT to determine the optimal route of delivery for early nutritional support in the critically ill. OBJECTIVE: To describe the proposed statistical analyses for the evaluation of the clinical effectiveness in the CALORIES trial. METHODS: With the primary and secondary outcomes defined precisely and the approach to safety monitoring and data collection summarised, the planned statistical analyses, including prespecified subgroups and secondary analyses, were developed and are described. RESULTS: The primary outcome is all-cause mortality at 30 days. The primary analysis will be reported as a relative risk and absolute risk reduction and tested with the Fisher exact test. Prespecified subgroup analyses will be based on age, degree of malnutrition, acute severity of illness, mechanical ventilation at admission to the CCU, presence of cancer and time from CCU admission to commencement of early nutritional support. Secondary analyses include adjustment for baseline covariates. CONCLUSION: In keeping with best trial practice, we have developed, described and published a statistical analysis plan for the CALORIES trial and are placing it in the public domain before inspecting data from the trial

Trial of the route of early nutritional support in critically ill adults

Uncertainty exists about the most effective route for delivery of early nutritional support in critically ill adults. We hypothesized that delivery through the parenteral route is superior to that through the enteral route

Evaluating the effectiveness of e‐cigarettes compared with usual care for smoking cessation when offered to smokers at homeless centres: Protocol for a multi‐centre cluster randomised controlled trial in Great Britain

Background and aims: Smoking is extremely common among adults experiencing homelessness but there is lack of evidence for treatment efficacy. E-cigarettes are an effective quit aid, but they have not been widely tested in smokers with complex health and social needs. Here we build on our cluster feasibility trial and evaluate the offer of an e-cigarette or usual care to smokers accessing a homeless centre. Design: Multi-centre two-arm cluster randomised controlled trial with mixed-method embedded process and economic evaluation. Setting: Homeless centres in England, Scotland and Wales. Participants: Adult smokers (18+ years; n= 480) accessing homeless centres and who are known to centre staff and willing to consent. Intervention and comparator: Clusters (n=32) will be randomised to either an e-cigarette starter pack with weekly allocations of nicotine containing e-liquid for 4-weeks (choice of flavours (menthol, fruit and tobacco) and strengths 12 mg/mL and 18mg/mL), or the usual care intervention which comprises very brief advice and a leaflet signposting to the local stop smoking service. Measurements: The primary outcome is 24-week sustained CO validated smoking cessation (Russell Standard defined, intention-to-treat analysis). Secondary outcomes: i) Fifty percent smoking reduction (cigarettes per day) from baseline to 24 weeks; ii) 7-day point prevalence quit rates at 4-, 12- and 24-week follow-up; iii) changes in risky smoking practices (e.g. sharing cigarettes, smoking discarded cigarettes) from baseline to 4-, 12- and 24-weeks; iv) cost-effectiveness of the intervention; v) fidelity of intervention implementation; mechanisms of change; contextual influences and sustainability. Comments: This is the first study to randomly assign smokers experiencing homelessness to an e-cigarette and usual care intervention to measure smoking abstinence with embedded process and economic evaluations. If effective, the results will be used to inform the larger scale implementation of offering e-cigarettes across homeless centres to aid smoking cessation

Growing up with perinatal HIV: changes in clinical outcomes before and after transfer to adult care in the UK

Introduction: With improved survival, adolescents with perinatal HIV (PHIV) are transitioning from paediatric to adult care, but there are few published data on clinical outcomes post-transfer. Using linked data from patients in the national UK/Ireland paediatric cohort (CHIPS) and an adult UK cohort of outpatient clinics (UK CHIC), we describe mortality and changes in immunological status post-transfer. Methods: Participants in CHIPS aged ≥13 years by the end of 2013 were linked to the UK CHIC database. Mixed effects models explored changes in CD4 count before and after transfer, including interactions between time and variables where interaction p < 0.05. Results: Of 1,215 paediatric participants aged ≥13 years, 271 (22%) had linked data in UK CHIC. One hundred and forty-six (53%) were female, median age at last visit in paediatric care was 17 [interquartile range, IQR 16,18] years, median duration in paediatric care was 11.8 [6.6,15.5] years, and in adult care was 2.9 [1.5,5.9] years. At last visit in paediatric care, 74% (n = 200) were on ART, increasing to 84% (n = 228, p = 0.001) at last visit in adult care. In the 12 months before leaving paediatric care, 92 (47%) had two consecutive viral loads >400 copies/mL or one viral load >10,000 copies/mL, and likewise 102 (52%) in the 12 months post-transfer (p = 0.79). Seven (3%) people died in adult care. In multivariable analysis, CD4 declined as patients approached transition with a greater decline in those with higher nadir CD4 count (mean rates of decline of 3, 13, 15, 30 cells/mm3 per year for those with nadir CD4 < 100, 100–199, 200–299 and ≥300 cells/mm3, respectively). Post-transition, CD4 continued to decline in some groups (e.g. black males, −20 (−34, −5) cells/mm3 per year post transition, p = 0.007)) while it improved in others. Overall CD4 was higher with later year of birth (14 (7, 21) cells/mm3 per later year). There was no effect of age at transfer or changing hospital at transfer on CD4. Conclusions: Our findings suggest that CD4 in adolescents with perinatal HIV in the UK was declining in the period before transition to adult care, and there was some reversal in this trend post-transfer in some groups. Across the transition period, CD4 was higher in those with later birth years, suggesting improvements in clinical care and/or transition planning over time