A systematic review and meta-analysis of the clinimetric properties of the core outcome measurement instruments for clinical effectiveness trials of nutritional and metabolic interventions in critical illness (CONCISE).

BACKGROUND: CONCISE is an internationally agreed minimum set of outcomes for use in nutritional and metabolic clinical research in critically ill adults. Clinicians and researchers need to be aware of the clinimetric properties of these instruments and understand any limitations to ensure valid and reliable research. This systematic review and meta-analysis were undertaken to evaluate the clinimetric properties of the measurement instruments identified in CONCISE. METHODS: Four electronic databases were searched from inception to December 2022 (MEDLINE via Ovid, EMBASE via Ovid, CINAHL via Healthcare Databases Advanced Search, CENTRAL via Cochrane). Studies were included if they examined at least one clinimetric property of a CONCISE measurement instrument or recognised variation in adults ≥ 18 years with critical illness or recovering from critical illness in any language. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist for systematic reviews of Patient-Reported Outcome Measures was used. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were used in line with COSMIN guidance. The COSMIN checklist was used to evaluate the risk of bias and the quality of clinimetric properties. Overall certainty of the evidence was rated using a modified Grading of Recommendations, Assessment, Development and Evaluation approach. Narrative synthesis was performed and where possible, meta-analysis was conducted. RESULTS: A total of 4316 studies were screened. Forty-seven were included in the review, reporting data for 12308 participants. The Short Form-36 Questionnaire (Physical Component Score and Physical Functioning), sit-to-stand test, 6-m walk test and Barthel Index had the strongest clinimetric properties and certainty of evidence. The Short Physical Performance Battery, Katz Index and handgrip strength had less favourable results. There was limited data for Lawson Instrumental Activities of Daily Living and the Global Leadership Initiative on Malnutrition criteria. The risk of bias ranged from inadequate to very good. The certainty of the evidence ranged from very low to high. CONCLUSIONS: Variable evidence exists to support the clinimetric properties of the CONCISE measurement instruments. We suggest using this review alongside CONCISE to guide outcome selection for future trials of nutrition and metabolic interventions in critical illness. TRIAL REGISTRATION: PROSPERO (CRD42023438187). Registered 21/06/2023.

Potential role for extracorporeal membrane oxygenation cardiopulmonary resuscitation (E-CPR) during in-hospital cardiac arrest in Australia: A nested cohort study.

Objective: This study aims to evaluate the characteristics and outcomes of patients who fulfilled extracorporeal membrane oxygenation cardiopulmonary resuscitation (E-CPR) selection criteria during in-hospital cardiac arrest (IHCA). Design: This is a nested cohort study. Setting: Code blue data were collected across seven hospitals in Australia between July 2017 and August 2018. Participants: Participants who fulfilled E-CPR selection criteria during IHCA were included. Main outcome measures: Return of spontaneous circulation and survival and functional outcome at hospital discharge. Functional outcome was measured using the modified Rankin scale, with scores dichotomised into good and poor functional outcome. Results: Twenty-three (23/144; 16%) patients fulfilled E-CPR selection criteria during IHCA, and 11/23 (47.8%) had a poor outcome. Patients with a poor outcome were more likely to have a non-shockable rhythm (81.8% vs. 16.7%; p = 0.002), and a longer duration of CPR (median 12.5 [5.5, 39.5] vs. 1.5 [0.3, 2.5] minutes; p < 0.001) compared to those with a good outcome. The majority of patients (18/19 [94.7%]) achieved sustained return of spontaneous circulation within 15 minutes of CPR. All five patients who had CPR >15 minutes had a poor outcome. Conclusion: Approximately one in six IHCA patients fulfilled E-CPR selection criteria during IHCA, half of whom had a poor outcome. Non-shockable rhythm and longer duration of CPR were associated with poor outcome. Patients who had CPR for >15 minutes and a poor outcome may have benefited from E-CPR. The feasibility, effectiveness and risks of commencing E-CPR earlier in IHCA and among those with non-shockable rhythms requires further investigation.

Core outcome measures for clinical effectiveness trials of nutritional and metabolic interventions in critical illness: an international modified Delphi consensus study evaluation (CONCISE).

BACKGROUND: Clinical research on nutritional and metabolic interventions in critically ill patients is heterogenous regarding time points, outcomes and measurement instruments used, impeding intervention development and data syntheses, and ultimately worsening clinical outcomes. We aimed to identify and develop a set of core outcome domains and associated measurement instruments to include in all research in critically ill patients. METHODS: An updated systematic review informed a two-stage modified Delphi consensus process (domains followed by instruments). Measurement instruments for domains considered 'essential' were taken through the second stage of the Delphi and a subsequent consensus meeting. RESULTS: In total, 213 participants (41 patients/caregivers, 50 clinical researchers and 122 healthcare professionals) from 24 countries contributed. Consensus was reached on time points (30 and 90 days post-randomisation). Three domains were considered 'essential' at 30 days (survival, physical function and Infection) and five at 90 days (survival, physical function, activities of daily living, nutritional status and muscle/nerve function). Core 'essential' measurement instruments reached consensus for survival and activities of daily living, and 'recommended' measurement instruments for physical function, nutritional status and muscle/nerve function. No consensus was reached for a measurement instrument for Infection. Four further domains met criteria for 'recommended,' but not 'essential,' to measure at 30 days post-randomisation (organ dysfunction, muscle/nerve function, nutritional status and wound healing) and three at 90 days (frailty, body composition and organ dysfunction). CONCLUSION: The CONCISE core outcome set is an internationally agreed minimum set of outcomes for use at 30 and 90 days post-randomisation, in nutritional and metabolic clinical research in critically ill adults.

Predictors of death and new disability after critical illness: a multicentre prospective cohort study.

PURPOSE: This study aimed to determine the prevalence and predictors of death or new disability following critical illness. METHODS: Prospective, multicentre cohort study conducted in six metropolitan intensive care units (ICU). Participants were adults admitted to the ICU who received more than 24 h of mechanical ventilation. The primary outcome was death or new disability at 6 months, with new disability defined by a 10% increase in the WHODAS 2.0. RESULTS: Of 628 patients with the primary outcome available (median age of 62 [49-71] years, 379 [61.0%] had a medical admission and 370 (58.9%) died or developed new disability by 6 months. Independent predictors of death or new disability included age [OR 1.02 (1.01-1.03), P = 0.001], higher severity of illness (APACHE III) [OR 1.02 (1.01-1.03), P < 0.001] and admission diagnosis. Compared to patients with a surgical admission diagnosis, patients with a cardiac arrest [OR (95% CI) 4.06 (1.89-8.68), P < 0.001], sepsis [OR (95% CI) 2.43 (1.32-4.47), P = 0.004], or trauma [OR (95% CI) 6.24 (3.07-12.71), P < 0.001] diagnosis had higher odds of death or new disability, while patients with a lung transplant [OR (95% CI) 0.21 (0.07-0.58), P = 0.003] diagnosis had lower odds. A model including these three variables had good calibration (Brier score 0.20) and acceptable discriminative power with an area under the receiver operating characteristic curve of 0.76 (95% CI 0.72-0.80). CONCLUSION: Less than half of all patients mechanically ventilated for more than 24 h were alive and free of new disability at 6 months after admission to ICU. A model including age, illness severity and admission diagnosis has acceptable discriminative ability to predict death or new disability at 6 months.

Early rehabilitation during extracorporeal membrane oxygenation has minimal impact on physiological parameters: A pilot randomised controlled trial.

BACKGROUND: Patients on extracorporeal membrane oxygenation (ECMO) often require prolonged periods of bed rest owing to their severity of illness along with the care required to maintain the position and integrity of the ECMO cannula. Many patients on ECMO receive passive exercises, and rehabilitation is often delayed owing to medical instability, with a high proportion of patients demonstrating severe muscle weakness. The physiological effects of an intensive rehabilitation program started early after ECMO commencement remain unknown. OBJECTIVES: The primary objective of this study was to describe the respiratory and haemodynamic effects of early intensive rehabilitation compared with standard care physiotherapy over a 7-d period in patients requiring ECMO. METHODS: This was a physiological substudy of a multicentre randomised controlled trial conducted in one tertiary referral hospital. Consecutive adult patients undergoing ECMO were recruited. Respiratory and haemodynamic parameters, along with ECMO settings, were recorded 30 min before and after each session and continuously during the session. In addition, the minimum and maximum values for these parameters were recorded outside of the rehabilitation or standard care sessions for each 24-h period over the 7 d. The number of minutes of exercise per session was recorded. RESULTS: Fifteen patients (mean age = 51.5 ± standard deviation of 14.3 y, 80% men) received ECMO. There was no difference between the groups for any of the respiratory, haemodynamic, or ECMO parameters. The minimum and maximum values for each parameter were recorded outside of the rehabilitation or standard care sessions. The intensive rehabilitation group (n = 7) spent more time exercising per session than the standard care group (n = 8) (mean = 28.7 versus 4.2 min, p < 0.0001). Three patients (43%) in the intensive rehabilitation group versus none in the standard care group mobilised out of bed during ECMO. CONCLUSIONS: In summary, early intensive rehabilitation of patients on ECMO had minimal effect on physiological parameters.

Survival and functional outcome at hospital discharge following in-hospital cardiac arrest (IHCA): A prospective multicentre observational study.

AIM: To evaluate the functional outcome of patients after in-hospital cardiac arrest (IHCA) and to identify associations with good functional outcome at hospital discharge. METHOD: Emergency calls were prospectively screened and data collected for IHCAs in seven Australian hospitals. Patients were included if aged > 18 years, admitted as an acute care hospital in-patient and experienced IHCA; defined by a period of unresponsiveness with no observed respiratory effort and commencement of external cardiac compressions. Data collected included patient demographics, clinical and cardiac arrest characteristics, survival and functional outcome at hospital discharge using the modified Rankin Scale (mRS) and Katz Index of Independence in ADLs (Katz-ADL). RESULTS: 152 patients suffered 159 IHCAs (male 66.4%; mean age 70.2 (± 13.9) years). Sixty patients (39.5%) survived, of whom 43 (71.7%) had a good functional outcome (mRS ≤ 3) and 38 (63.3%) were independent with activities of daily living (ADLs) at hospital discharge (Katz-ADL = 6). Younger age (OR 0.95; 95% CI 0.91-0.98; p = 0.003), shorter duration of CPR (OR 0.84; 95% CI 0.77-0.91; p < 0.0001) and shorter duration of hospital admission prior to IHCA (OR 0.96; 95% CI 0.93-0.998; p = 0.04) were independently associated with a good functional outcome at hospital discharge. CONCLUSION: The majority of survivors had a good functional outcome and were independent with their ADLs at hospital discharge. Factors associated with good functional outcome at hospital discharge were identified.

Adaptation and validation of the ICU Mobility Scale in Spain. / Adaptación y validación de la ICU Mobility Scale en España.

OBJECTIVE: To adapt the ICU Mobility Scale (IMS) to the area of intensive care units (ICU) in Spain and to evaluate the metric properties of the Spanish version of the IMS (IMS-Es). METHOD: Descriptive metric study developed in two phases. Phase 1, adaptation to Spanish of the IMS by a team of nurses and physiotherapists (translation, pilot, backtranslation and agreement). Phase 2, analysis of metric properties (convergent, divergent and predictive validity, interobserver reliability, sensitivity and minimum important difference) of the IMS-Es. Patient characteristics (Barthel, Charlson, BMI, sex), sedation/agitation level (RASS), ICU and hospital stays, survival, quality of life (SF-12), muscle weakness (MRC-SS) and mobility (IMS-Es) were recorded in the patients of the MOviPre national multicentre study. RESULTS: After obtaining the IMS-Es, it was implemented in 645 patients from 80 Spanish ICUs between April and June 2017. Convergent validity: moderate correlation between IMS-Es and MRC-SS (r=.389; P<.001) and significant comparison between groups with and without ICU-acquired weakness (P<.001). Divergent validity: no correlation between IMS-Es and BMI [r (95%CI): -.112 (-.232 to .011)], weight [r (95%CI): -.098 (-.219 to .026)], Charlson [r (95%CI): -.122 (-.242 to .001)] and Barthel [r(95%CI): -.037 (-.160 to .087)] and no differences between sexes (P=.587) or BMI categories (P=.412). Predictive validity: moderate and significant correlations with post-ICU hospital stay [r (95%CI): -.442 (-.502 to -.377)] and physical component of SF-12 (PCS) [r (95%CI): .318 (.063 to .534)]; patients without active mobilisation in ICU increased risk of hospital mortality [OR (95%CI): 3.769 (1.428 to 9.947)]. Interobserver reliability: very good concordance between nurses [CCI (95%CI): .987 (.983 to .990)] and nurse-physiotherapist [CCI (95%CI): .963 (.948 to .974)]. Sensitivity to change: small effect on discharge from ICU (d=.273) and moderate effect at 3months after hospital discharge (d=.709). Minimal important difference: 2-point difference cut-off point, 91.1% sensitivity and 100.0% specificity. CONCLUSIONS: The IMS-Es is useful, valid and reliable for implementation by ICU nurses and physiotherapists in assessing the mobility of critical patients.

Correction to: Effects of New Zealand blackcurrant extract on sport climbing performance.

The authors would like to correct the following errors in the online publication of the article. Incorrect values for % changes for climb duration were provided in the abstract, results and discussion session. The  % changes in climb duration was 15% with intake of New Zealand blackcurrant extract and -15% for the placebo condition. This correction does not change the conclusions derived from the study.

Effects of New Zealand blackcurrant extract on sport climbing performance.

PURPOSE: Blood flow to skeletal muscles and removal of metabolic by-products during a sport climb are essential to optimise performance and recovery. New Zealand blackcurrant (NZBC) extract has enhanced blood flow and performance in other exercise modalities. We examined the effect of NZBC extract on sport climbing performance and recovery. METHODS: The study employed a double-blind, randomised, crossover design. Male sport climbers (n = 18, age 24 ± 6 years, height 179 ± 6 cm, mass 71.4 ± 7.8 kg, French grade 6a-8b) undertook 7 days supplementation of NZBC extract (600 mg day-1 CurraNZ™ containing 210 mg anthocyanins) or a placebo (PL). Climbing ability was assessed through hang time (HT), pull-ups and total climbing time (TCT) in 3 intermittent climbing bouts on a Treadwall M6 rotating climbing wall to exhaustion with 20 min recovery between climbs. Heart rate (HR), blood lactate (BL), forearm girth (FG) and hand grip strength (HGS) were recorded. RESULTS: NZBC extract had no effect on pull-ups but provided a trend for higher HT and significantly improved TCT (+23%) compared to PL (-11%) over three climbs. HR, BL, FG and HGS all indicated that 20 min was insufficient for physiological recovery between the three climbing bouts indicating accumulative fatigue regardless of supplement condition. CONCLUSION: Despite indices of progressive fatigue across three bouts of climbing, NZBC extract facilitated not only a maintenance of TCT but an improved climbing endurance as compared with the PL condition. Blackcurrant anthocyanin-derived metabolites seem to affect physiological responses that facilitate sport climbing performance.

A prospective multicentre survey of complications associated with equine castration to facilitate clinical audit.

BACKGROUND: Despite the regularity with which castration is performed, the types of complications and current best practice are unknown. OBJECTIVES: The objective of this study was to perform a prospective audit of routine equine castrations performed in general practice to determine complication rates and factors associated with them. STUDY DESIGN: Multicentre, prospective audit of castrations. METHODS: Data on castrations were collected on the day of surgery from 18 veterinary practices; 30-days post-operatively follow-up was obtained and complications recorded. Frequency of complications was reported, and multilevel, multivariable logistic regression models used to investigate factors associated with the most common complications of bleeding in the first 24 h, stiffness of gait and/or swelling and discharge and/or infection. RESULTS: Data were collected on 495 castrations performed by 53 participating veterinary surgeons. Over two thirds of surgeries were performed outside, 21% were performed under standing sedation and 79% with the horse recumbent. Almost all (98 and 97%) patients received preoperative nonsteroidal anti-inflammatories (NSAIDs) and antimicrobials, respectively. One or more intraoperative complications were reported in 14.5% of procedures; most common were bleeding and excessive movement. Follow-up to 30 days was available for 392 equids. One or more complications were reported in 44 castrations (11.2%). Swelling was the most common, then infection and stiffness of gait. Serious complications were rare. MAIN LIMITATIONS: It is possible that there was bias towards submission of data for procedures where complications occurred. The low complication rates reduced the power to determine factors associated with complications. Minor complications may go unreported by owners and may be underrepresented. CONCLUSIONS: Overall complications associated with castration are low and mortality rare. Findings from this study can be used as guidelines for practices to perform regular audit to determine if their negative outcomes are comparable or warrant further investigation.

The rapid and accurate categorisation of critically ill patients (RACE) to identify outcomes of interest for longitudinal studies: a feasibility study.

The capacity to measure the impact of an intervention on long-term functional outcomes might be improved if research methodology reflected our clinical approach, which is to individualise goals of care to what is achievable for each patient. The objective of this multicentre inception cohort study was to evaluate the feasibility of rapidly and accurately categorising patients, who were eligible for simulated enrolment into a clinical trial, into unique categories based on premorbid function. Once a patient met eligibility criteria a rapid 'baseline assessment' was conducted to categorise patients into one of eight specified groups. A subsequent 'gold standard' assessment was made by an independent blinded assessor once patients had recovered sufficiently to allow such an assessment to occur. Accuracy was predefined as agreement in >80% of assessments. One hundred and twenty-two patients received a baseline assessment and 104 (85%) were categorised to a unique category. One hundred and six patients survived to have a gold standard assessment performed, with 100 (94%) assigned to a unique category. Ninety-two patients had both a baseline and gold standard assessment, and these agreed in 65 (71%) patients. It was not feasible to rapidly and accurately categorise patients according to premorbid function.

Effect of the application of cattle urine with or without the nitrification inhibitor DCD, and dung on greenhouse gas emissions from a UK grassland soil.

Emissions of nitrous oxide (N2O) from soils from grazed grasslands have large uncertainty due to the great spatial variability of excreta deposition, resulting in heterogeneous distribution of nutrients. The contribution of urine to the labile N pool, much larger than that from dung, is likely to be a major source of emissions so efforts to determine N2O emission factors (EFs) from urine and dung deposition are required to improve the inventory of greenhouse gases from agriculture. We investigated the effect of the application of cattle urine and dung at different times of the grazing season on N2O emissions from a grassland clay loam soil. Methane emissions were also quantified. We assessed the effect of a nitrification inhibitor, dicyandiamide (DCD), on N2O emissions from urine application and also included an artificial urine treatment. There were significant differences in N2O EFs between treatments in the spring (largest from urine and lowest from dung) but not in the summer and autumn applications. We also found that there was a significant effect of season (largest in spring) but not of treatment on the N2O EFs. The resulting EF values were 2.96, 0.56 and 0.11% of applied N for urine for spring, summer and autumn applications, respectively. The N2O EF values for dung were 0.14, 0.39 and 0.10% for spring, summer and autumn applications, respectively. The inhibitor was effective in reducing N2O emissions for the spring application only. Methane emissions were larger from the dung application but there were no significant differences between treatments across season of application.

Development of a technical external quality assurance scheme in non-gynaecological cytology in UK.

Technical external quality assurance (EQA) schemes are well established for histopathology and cervical cytology but, to date, sadly lacking for diagnostic cytology (DC). This timely review redresses the balance by describing the development and evaluation of a technical EQA scheme for DC available to the UK, Europe and beyond.

Non-invasive assessment of lung elastance in patients with acute respiratory distress syndrome.

BACKGROUND: Chest wall mechanics can be abnormal in patients with acute respiratory disease syndrome (ARDS). Therefore, partitioning respiratory system between lungs and chest wall at the bedside is useful to optimize ventilator settings. A non-invasive method for assessing lung elastance (EL), called lung barometry, was previously described on an animal model. METHODS: This prospective study was designed to compare EL assessed by lung barometry (ELLB) versus esophageal pressure (ELPeso). In sedated, paralyzed patients, PEEP was progressively increased from 5 to 40cmH2O then decreased from 40 to 5cmH2O by step of 5cmH2O every two minutes. ELLB was assessed for each step as the ratio between the change in PEEP and the induced end-expiratory lung volume change measured by direct spirometry. ELPeso was calculated from esophageal pressure measurement at each PEEP. EL and the ratio between EL and respiratory system elastance (ERS) calculated with the two methods were compared. RESULTS: Twenty six adult patients with early onset moderate or severe ARDS were included. There was a linear correlation between ELLB and ELPeso during the increase and decrease of PEEP (R²=0.26 and 0.42, respectively). Concordance using Bland and Altman method demonstrated bias and large limits of agreement during the increase (-0.5 cmH2O/L; -25 to 24 cmH2O/L) and during the decrease in PEEP (-0.3 cmH2O/L; -21 to 20 cmH2O/L). There were no linear correlation between ELLB/ERS and ELPeso/ERS during the increase and the decrease of PEEP (R²=0.00; R²=0.00, respectively). CONCLUSION: In ARDS patients, lung barometry method cannot be used instead of the esophageal pressure measurement to assess EL.

Colo-vesical fistula: Complete healing without surgical intervention.

INTRODUCTION: Colo-vesical (CV) fistulae are the most common type of fistulae associated with diverticular disease. Surgery remains the mainstay of treatment, without which, CV fistulae rarely achieve complete healing. PRESENTATION OF CASE: Herein, we report the case of a 62-year-old man who developed a CV fistula after reversal of Hartmann's procedure (initially for management of diverticular abscess), which healed with conservative management alone. DISCUSSION: We discuss possibilities of the aetiology of this fistula. The CV fistula may have been initially present, which came to light only after his reversal. Or an iatrogenic fistula that developed at the time of reversal of Hartmann's. CONCLUSION: This is the first time that such a fistula has been demonstrated clinically and radiologically to have healed spontaneously without surgery. We recommend that conservative management of CV fistulae should be considered.

The recovery of semen from bathwater using the Evidence Recovery System (ERS).

Sexual offences are under-reported and ascertaining accurate offence numbers is difficult. Any methods which could increase the ability to obtain biological evidence or reduce the additional distress associated with reporting a sexual offence may result in an increase in reporting this crime type. The Evidence Recovery System (ERS) is designed to collect trace evidence, including hairs, fibres and biological evidence, from bath or shower water in a non-invasive manner. Initially, samples of semen were placed in baths filled with water, and washing was simulated using a range of body wash products. The water was then drained through the ERS before its filters were subjected to acid phosphatase testing and haematoxylin and eosin staining of spermatozoa. Recovered spermatozoa were then graded accordingly. Following this, the experiment was repeated with the addition of dirt/dust particulates during the washing stage, to simulate recovery of biological evidence in a more realistic environment. The results showed that spermatozoa considered 'easy to find' could regularly be obtained from bathwater using the ERS. It appeared that this recovery was not affected by the presence of different body wash products. When dust/dirt particles were added, the number of spermatozoa recovered increased at two of the evidence collection stages. The difference in recovery was considered to be statistically significant. This study provides evidence to suggest the feasibility of use of the ERS as a method to collect semen evidence from individuals subjected to sexual offences. The recovery of spermatozoa does not appear to be affected by the presence of a body wash, but does appear to be improved when skin cells, hair and other debris are transferred into the water, as would be likely during a bath/shower. Further to this, the possibility of obtaining spermatozoa from the home bath or shower of a victim following a post-offence bathing experience is implied.

A Third Species of Hemilecanium Newstead (Hemiptera: Coccoidea: Coccidae) from the New World, with Keys to Species in the Genus.

A new species of Hemilecanium Newstead, Hemilecanium guanabana Kondo & Hodgson n. sp., is described and illustrated based on the adult female, adult male and first instar. The specimens were collected in the municipality of Palmira, state of Valle del Cauca, Colombia, on soursop, Annona muricata (Annonaceae). Updated identification keys are provided for the adult females of all 28 species of the genus Hemilecanium, and for known adult males and first instars. An updated list of the 23 species of soft scales (Coccidae) known from soursop worldwide is included.

Improved antibiotic-free plasmid vector design by incorporation of transient expression enhancers.

Methods to improve plasmid-mediated transgene expression are needed for gene medicine and gene vaccination applications. To maintain a low risk of insertional mutagenesis-mediated gene activation, expression-augmenting sequences would ideally function to improve transgene expression from transiently transfected intact plasmid, but not from spurious genomically integrated vectors. We report herein the development of potent minimal, antibiotic-free, high-manufacturing-yield mammalian expression vectors incorporating rationally designed additive combinations of expression enhancers. The SV40 72 bp enhancer incorporated upstream of the cytomegalovirus (CMV) enhancer selectively improved extrachromosomal transgene expression. The human T-lymphotropic virus type I (HTLV-I) R region, incorporated downstream of the CMV promoter, dramatically increased mRNA translation efficiency, but not overall mRNA levels, after transient transfection. A similar mRNA translation efficiency increase was observed with plasmid vectors incorporating and expressing the protein kinase R-inhibiting adenoviral viral associated (VA)1 RNA. Strikingly, HTLV-I R and VA1 did not increase transgene expression or mRNA translation efficiency from plasmid DNA after genomic integration. The vector platform, when combined with electroporation delivery, further increased transgene expression and improved HIV-1 gp120 DNA vaccine-induced neutralizing antibody titers in rabbits. These antibiotic-free vectors incorporating transient expression enhancers are safer, more potent alternatives to improve transgene expression for DNA therapy or vaccination.