Does screening neonates in the neonatal intensive care unit for Pseudomonas aeruginosa colonization help prevent infection?

BACKGROUND: Pseudomonas aeruginosa (PA) is a Gram-negative environmental organism that can cause severe infection in immunosuppressed patients, including preterm neonates. In recent years, it has become common practice to screen neonates for PA colonization. AIM: To assess the value of screening neonates for PA in (1) predicting the risk of developing severe PA infection and (2) directing infection control practice. METHODS: Between August 2012 and September 2015, babies admitted to the neonatal intensive care unit (NICU) at North Bristol NHS Trust were screened routinely for PA colonization on admission and weekly thereafter. Data were also collected on babies who developed PA infection. Environmental samples from the NICU were tested for the presence of PA. Variable number tandem repeat (VNTR) typing was performed on all strains of PA from babies and the environment. FINDINGS: No babies with positive screens subsequently developed PA infection. There was no VNTR strain evidence supporting cross-infection from the environment or other babies. CONCLUSION: Screening neonates for PA did not identify babies who subsequently developed PA infection. Following cessation of screening in September 2015, there was no increase in the number of babies identified with PA infection.

Impact of moving to a new hospital build, with a high proportion of single rooms, on healthcare-associated infections and outbreaks.

Clostridium difficile infection, meticillin-sensitive Staphylococcus aureus (MSSA) and Escherichia coli bacteraemia rates, and bed-days lost during norovirus outbreaks at North Bristol NHS Trust were analysed over a five-year period to determine whether moving to a new-build hospital with 75% single rooms reduced healthcare-associated infection rates. C. difficile, MSSA bacteraemia and E. coli bacteraemia showed no change in the rate of decline after the move. Bed-days lost due to norovirus were significantly lower after the move. Increased availability of single rooms had an impact on the transmission of highly contagious norovirus infection, dispersed via the airborne route, in contrast to bacterial infections, which may originate from patient's own colonizing flora and are not widely dispersed through airborne spread.

Campylobacter infection associated with consumption of duck liver pâté: a retrospective cohort study in the setting of near universal exposure.

SUMMARY: A retrospective cohort study was performed following several reported cases of gastrointestinal illness after a catered event. The attack rate was 45/77 (58·4%) by clinical case definition, with four individuals confirmed to have Campylobacter. There was near universal exposure to most foodstuffs served; consumption of duck liver pâté [relative risk (RR) 2·53, 95% confidence interval (CI) 1·05-6·10], mixed leaf salad (RR 2·91, 95% CI 1·22-6·92) and table water (RR undefined, P < 0·01) were associated with illness in univariate analysis, with only the latter associated in the final multivariable model (P < 0·001). Samples of cooked duck liver pâté subsequently prepared using identical methods at the venue were contaminated with Campylobacter jejuni and C. coli; water sampling was negative. Making inferences about causation in the presence of near universal exposures in this study required consideration of the limitations of statistical analysis, with the most compelling evidence of the causal role of inadequately prepared duck liver pâté provided by environmental investigation.

An exploration of clinical dementia phenotypes among individuals with and without traumatic brain injury.

OBJECTIVE: To characterize the clinical profiles of individuals with dementia who do and do not report a history of TBI. INTRODUCTION: Some evidence suggests that a history of traumatic brain injury (TBI) is associated with an increased risk of dementia later in life. The clinical features of dementia associated with TBI have not been well investigated. While there is some evidence that TBI is associated with increased risk of Alzheimer's disease (AD), there are also indications that dementia associated with TBI has prominent behavioral, affective, and motor symptoms, making it distinct from AD. METHODS: The current study involves secondary analysis of baseline data from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS). RESULTS: Individuals with dementia who reported a history of TBI had higher fluency and verbal memory scores and later onset of decline, but they are on more medications, had worse cardiovascular and cerebrovascular health, were more likely to have received medical attention for depression, and were more likely to have a gait disorder, falls, and motor slowness. CONCLUSION: These findings suggest that dementia among individuals with a history of TBI may represent a unique clinical phenotype that is distinct from known dementia subtypes.

Utility of post-traumatic amnesia in predicting 1-year productivity following traumatic brain injury: comparison of the Russell and Mississippi PTA classification intervals.

BACKGROUND: Duration of post-traumatic amnesia (PTA) correlates with global outcomes and functional disability. Russell proposed the use of PTA duration intervals as an index for classification of traumatic brain injury (TBI) severity. Alternative duration-based schemata have been recently proposed as better predictors of outcome to the commonly cited Russell intervals. OBJECTIVE: Validate a TBI severity classification model (Mississippi intervals) of PTA duration anchored to late productivity outcome, and compare sensitivity against the Russell intervals. METHODS: Prospective observational data on TBI Model System participants (n=3846) with known or imputed PTA duration during acute hospitalisation. Productivity status at 1-year postinjury was used to compare predicted outcomes using the Mississippi and Russell classification intervals. Logistic regression model-generated curves were used to compare the performance of the classification intervals by assessing the area under the curve (AUC); the highest AUC represented the best-performing model. RESULTS: All severity variables evaluated were individually associated with return to productivity at 1 year (RTP1). Age was significantly associated with RTP1; however, younger patients had a different association than older patients. After adjustment for individually significant variables, the odds of RTP1 decrease by 14% with every additional week of PTA duration (95% CI 12% to 17%; p<0.0001). The AUC for the Russell intervals was significantly smaller than the Mississippi intervals. CONCLUSIONS: PTA duration is an important predictor of late productivity outcome after TBI. The Mississippi PTA interval classification model is a valid predictor of productivity at 1 year postinjury and provides a more sensitive categorisation of PTA values than the Russell intervals.

The Traumatic Brain Injury Model Systems: a longitudinal database, research, collaboration and knowledge translation.

In 1988, the National Institute on Disability and Rehabilitation Research (NIDRR) launched the Traumatic Brain Injury Model Systems (TBIMS) program, creating the longest and largest longitudinal database on individuals with moderate-to-severe traumatic brain injury (TBI) available today. In addition to sustaining the longitudinal database, centers that successfully compete to be part of the TBIMS centers are also expected to complete local and collaborative research projects to further scientific knowledge about TBI. The research has focused on areas of the NIDRR Long Range Plan which emphasizes employment, health and function, technology for access and function, independent living and community integration, and other associated disability research areas. Centers compete for funded participation in the TBIMS on a 5-year cycle. Dissemination of scientific knowledge gained through the TBIMS is the responsibility of both individual centers and the TBIMS as a whole. This is accomplished through multiple venues that target a broad audience of those who need to receive the information and learn how to best apply it to practice. The sites produce many useful websites, manuals, publications and other materials to accomplish this translation of knowledge to practice.

A multicentre study on the clinical utility of post-traumatic amnesia duration in predicting global outcome after moderate-severe traumatic brain injury.

BACKGROUND: Past research shows that post-traumatic amnesia (PTA) duration is a particularly robust traumatic brain injury (TBI) outcome predictor, but low specificity limits its clinical utility. OBJECTIVES: The current study assessed the relationship between PTA duration and probability thresholds for Glasgow Outcome Scale (GOS) levels. METHODS: Data were prospectively collected in this multicentre observational study. The cohort was a consecutive sample of rehabilitation patients enrolled in the National Institute on Disability and Rehabilitation Research funded TBI Model Systems (n = 1332) that had documented finite PTA duration greater than 24 h, and 1-year and 2-year GOS. RESULTS: The cohort had proportionally more Good Recovery (44% vs 39%) and less Severe Disability (19% vs 23%) at year 2 than at year 1. Longer PTA resulted in an incremental decline in probability of Good Recovery and a corresponding increase in probability of Severe Disability. When PTA ended within 4 weeks, Severe Disability was unlikely (<15% chance) at year 1, and Good Recovery was the most likely GOS at year 2. When PTA lasted beyond 8 weeks, Good Recovery was highly unlikely (<10% chance) at year 1, and Severe Disability was equal to or more likely than Moderate Disability at year 2. CONCLUSIONS: Two PTA durations, 4 weeks and 8 weeks, emerged as particularly salient GOS probability thresholds that may aid prognostication after TBI.

Long-term recovery course after traumatic brain injury: a comparison of the functional independence measure and disability rating scale.

OBJECTIVES: To study group changes over time after traumatic brain injury (TBI). DESIGN: Prospective cohort. SETTING AND PARTICIPANTS: TBI Model System Database with 1160 subjects using cohort with complete data. MAIN OUTCOME MEASURES: Functional Independence Measure (FIM) and Disability Rating Scale (DRS) at rehabilitation discharge and annually after injury. RESULTS: Statistically significant differences existed between FIM-total, FIM-Motor, FIM-Cognitive subscales, and DRS at rehabilitation discharge and year 1. Comparisons of year-to-year intervals, years 1 and 3, 1 and 5, and 3 and 5, revealed no statistically significant differences except between years 1 and 3 and 1 and 5 with DRS, and years 1 and 5 with FIM. Including only those more dependent at year 1 revealed statistically significant differences between years 1 and 2 and 1 and 5 on FIM-Cognitive and DRS, but not the FIM-Motor. The proportion of change for FIM and DRS items from year 1 to years 2 and 5 revealed DRS Level of Functioning and Employability items accounted for most DRS change, whereas FIM change was more spread across its components. CONCLUSIONS: DRS is more sensitive to changes during a shorter time period than FIM and seems to be more appropriate for detecting long-term deficits. However, research studies aimed at detecting meaningful changes year to year after TBI may need to use other tools or consider changes among individuals instead of group changes. DRS Level of Function and Employability Items represent complex functions expected to recover later than the more basic DRS items. Sole use of these two DRS items might provide an efficient means of measuring long-term recovery when resources are limited, whereas expansion of these two items might allow greater sensitivity and detail.

Isolation of antibodies which neutralise the activity of early pregnancy factor.

Early pregnancy factor (EPF) is a secreted protein with growth regulatory and immunomodulatory properties. It functions as an autocrine growth factor for tumour cells and as an autocrine or paracrine growth factor for regenerating normal cells. Anti-EPF antibodies have demonstrable anti-tumour activity and, as a result, hybridomas which produce such antibodies are unstable. In this study, the phage display antibody techniques have been investigated as a means of producing recombinant anti-EPF antibodies. Mice were immunised with synthetic peptides which correspond to the N or C terminal regions of EPF, and their splenic tissue was used to make combinatorial antibody libraries. The Fab repertoire was displayed on the surface of phage and panned over recombinant EPF. Reactive Fabs were identified by ELISA and their binding was characterised by BIAcore analysis and functional studies. Three libraries with a size of greater than 5x10(7)cfu were constructed and a total of 26 unique Fabs with specific reactivity against EPF were identified. Three Fabs were purified and of these one demonstrated strong EPF neutralising activity, one had intermediate activity and the other was not neutralising. Phage display has provided the means of circumventing the problems of anti-EPF hybridoma development and has resulted in the production of antibodies with potential applications in the diagnosis of pregnancy and the diagnosis and therapy of cancer.

Use of injury severity variables in determining disability and community integration after traumatic brain injury.

BACKGROUND: Long-term outcome is important in managing traumatic brain injury (TBI), an epidemic in the United States. Many injury severity variables have been shown to predict major morbidity and mortality. Less is known about their relationship with specific long-term outcomes. METHODS: Glasgow Coma Scale, Revised Trauma Score, Injury Severity Score, and Trauma and Injury Severity Score, along with other demographic and premorbid values, were obtained for 378 consecutive patients hospitalized after TBI at a Level I trauma center between September 1997 and May 1998. Of this cohort, 120 patients were contacted for 1-year follow-up assessment with the Disability Rating Scale, Community Integration Questionnaire, and employment data. RESULTS: Univariate analyses showed these to be significant single predictors of 1-year outcome. Multivariate analyses revealed that the Revised Trauma Score and Glasgow Coma Scale had significant additive value in predicting injury variables Disability Rating Scale scores when combined with other demographic and premorbid variables studied. Predictive models of 1-year outcome were developed. CONCLUSION: Injury severity variables are significant single outcome predictors and, in combination with premorbid and demographic variables, help predict long-term disability and community integration for individuals hospitalized with TBI.

Intentional traumatic brain injury: epidemiology, risk factors, and associations with injury severity and mortality.

BACKGROUND: Intentional injury is associated with significant morbidity and mortality and has been associated with certain demographic and socioeconomic groups. Less is known about the relationship of intentional traumatic brain injury (TBI) to injury severity, mortality, and demographic and socioeconomic profile. The objective of this study was to delineate demographic and event-related factors associated with intentional TBI and to evaluate the predictive value of intentional TBI on injury severity and mortality. METHODS: Prospective data were obtained for 2,637 adults sustaining TBIs between January 1994 and September 1998. Descriptive, univariate, and multivariate analyses were conducted to determine the predictive value of intentional TBI on injury severity and mortality. RESULTS: Gender, minority status, age, substance abuse, and residence in a zipcode with low average income were associated with intentional TBI. Multivariate analysis found minority status and substance abuse to be predictive of intentional injury after adjusting for other demographic variables studied. Intentional TBI was predictive of mortality and anatomic severity of injury to the head. Penetrating intentional TBI was predictive of injury severity with all injury severity markers studied. CONCLUSION: Many demographic variables are risk factors for intentional TBI, and such injury is a risk factor for both injury severity and mortality. Future studies are needed to definitively link intentional TBI to disability and functional outcome.

The value of trauma scores: predicting discharge after traumatic brain injury.

OBJECTIVE: To determine the association of acute variables with disposition after acute hospitalization. DESIGN: Revised Trauma Score (RTS), Injury Severity Score (ISS), and the Combined Trauma Score Injury Severity Score (TRISS(RTS)) were compared with discharge disposition after acute hospitalization of 378 consecutive patients who sustained a traumatic brain injury (TBI) and were treated at a level 1 trauma center between September 1997 and May 1998. RESULTS: Logistic regression modeling found TRISS(RTS) to predict discharge to home with or without home health assistance or inpatient rehabilitation vs. nursing home placement or death. Subsequent modeling, excluding patients who died or went to nursing homes, identified RTS and ISS as predictors of discharge to home with or without home health vs. inpatient rehabilitation. A sensitivity of 97.78% and 93.91% were achieved with these two models when tested on a population of 4,625 patients with TBI treated during the last 10 yr at the same facility. CONCLUSIONS: The results suggest that RTS, ISS, and TRISS(RTS) are predictors of discharge disposition after acute hospitalization with TBI and may be useful measures of rehabilitation services resource planning early in the course of TBI management.

Advanced life support: retention of registered nurses' knowledge 18 months after initial training.

In 1996, The Wesley Hospital introduced a 2 day Advanced Life Support (ALS) course, targeted at all critical care registered nurses and medical officers. The purpose of this study was to explore the retention of theoretical knowledge and clinical skills of registered nurses who had successfully completed the 2 day ALS course 18 months previously and to establish effective retesting timeframes. The study utilised a repeated post-test measure design. Forty registered nurses participated in the study. Data were collected during ALS retesting using scores from a theoretical examination and from the results of four practical skill assessments (basic life support, airway management, defibrillation and code management). Using Wilcoxon test, data were analysed with and compared to the participant's original scores from the training program 18 months previously. The findings demonstrate that the participant's theoretical knowledge remained at an equivalent level over the 18 month timeframe. However, 18 months after successfully completing an ALS course, only 75 per cent (n = 30) of participants passed the practical skill assessment components, with the 25 per cent (n = 10) requiring a second attempt to pass. The implications from this study focus on the model of assessment utilised and the dichotomy between theoretical and practical skill assessment results. Additional study is required to determine the optimal timeframe for ALS retesting and educational strategies to help retain skills over time.

Venous thromboembolism in the patient with acute traumatic brain injury: screening, diagnosis, prophylaxis, and treatment issues.

Venous thromboembolism is a life-threatening complication of traumatic brain injury. Consequently, knowledge of available screening, diagnostic, prophylactic, and treatment methods is critical to the management of the individual with traumatic brain injury. Venous thromboembolic risk varies among individuals, resulting in unique screening and prophylactic needs for each patient. In addition, anticoagulation, commonly employed for prophylaxis and treatment in other patient populations, may create an increased risk for intracranial hemorrhage when utilized following traumatic brain injury. The cost, sensitivity, specificity, efficacy, potential side effects, and alternatives for preventing, detecting, and treating venous thromboembolism are important considerations discussed in this article.

Regulation and expression of human Fabs under the control of the Escherichia coli arabinose promoter, PBAD.

BACKGROUND: The L-arabinose operon from E. coli contains an inducible promoter PBAD which has been extensively studied for the control of gene expression. PBAD has a number of potential advantages over Plac, and has been used successfully to promote high level expression of recombinant proteins. OBJECTIVES: The aim of this study was to investigate PBAD as an alternative system to Plac for the bacterial expression of recombinant Fabs. STUDY DESIGN: The promoter PBAD from the E. coli arabinose operon araBAD and the gene encoding the regulator of this promoter, were cloned into the phagemid expression vector MCO1. Expression of human recombinant tetanus toxoid (TT) and c-erbB2 Fabs under the control of PBAD was compared at two induction temperatures with the same Fabs produced under the control of Plac. RESULTS: Expression of TT and c-erbB2 Fabs under the control of PBAD was comparable to Fab expression from Plac. However, highly expressed TT Fab under the control of PBAD was localised to the soluble periplasmic fraction whereas under the control of Plac, there was greater leakage of Fab into the culture supernatant. In addition, Fab expression from PBAD could be more tightly repressed than from Plac. CONCLUSION: PBAD is a useful and cheaply inducible alternative to the more commonly used Plac for the rapid expression of soluble recombinant human antibody fragments.

Posttraumatic amnesia: its relation to functional outcome.

OBJECTIVE: To investigate the relation between duration of posttraumatic amnesia (PTA) and functional outcome in a traumatically brain injured population. PATIENTS: Two hundred seventy-six patients with traumatic brain injury (TBI) who were admitted to a Level I university trauma center and required inpatient rehabilitation. MEASURES: Duration of PTA was assessed by serial administrations of the Galveston Orientation Amnesia Test (GOAT). Functional Independence Measure (FIM) total scores, FIM cognitive and motor subscores, and Disability Rating Scale (DRS) scores were obtained at admission and discharge from inpatient rehabilitation. RESULTS: Duration of PTA was a significant predictor of all admission and discharge DRS and FIM scores. Duration of PTA and age at the time of injury, in combination, contributed significantly to the prediction of the DRS score and FIM total, cognitive, and motor scores at discharge. CONCLUSION: Duration of PTA appears to be a useful variable in predicting specific functional outcome in the TBI population receiving inpatient rehabilitation services. The use of age as a factor in addition to duration of PTA enhances the prediction of functional outcome.

Production of endometrial matrix metalloproteinases, but not their tissue inhibitors, is modulated by progesterone withdrawal in an in vitro model for menstruation.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are implicated in normal menstruation, but the mechanism of their regulation is not yet clear. Human endometrial stromal cell cultures were established to mimic the events of the late luteal phase of the menstrual cycle: after 6 days of culture with estradiol 17beta (10 nmol/L) and progestin (P, 100 nmol/L), half the cells were subjected to P withdrawal, and medium was harvested on day 10. Decidualization of the cells was verified by PRL immunohistochemistry. Latent MMP-1, -2, -3, and -9 were detected by zymography and quantitated by densitometry, and production of all enzymes was increased on withdrawal of P. This increase was confirmed by enzyme-linked immunosorbent assay for MMP-1. TIMP-1, -2, and -3 also were produced by the cells, with a mean ratio of 3.9:1:1.2, respectively. There was no effect of P withdrawal on either the amount of each TIMP or their relative concentrations. Expression of the messenger RNA for TIMP-1 or TIMP-2 also was not changed by P withdrawal. Thus, withdrawal of P alters the ratio of MMPs to TIMPs in this model in favor of MMPs and, hence, of tissue degradation. However, the focal nature of menstruation-associated MMP activity suggests that P withdrawal is unlikely to be the only factor responsible for in vivo induction of MMPs at menstruation.

Risk factors for acute care transfer among traumatic brain injury patients.

OBJECTIVE: Acute inpatient traumatic brain injury (TBI) rehabilitation has seen a jump in complexity of medical patient care over the past several years, often necessitating transfer back to an acute care facility. The purpose of this study was to determine the association between selected clinical variables and transfer from inpatient rehabilitation to an acute care facility. DESIGN: A retrospective review of cases from 1992 to 1994. SETTING: A TBI unit in a freestanding rehabilitation hospital. PATIENTS: Twenty-two patients were identified as having received acute care transfer. This group was compared with 78 patients, admitted in the same interval, who did not require acute care transfer. The variables evaluated included recent surgery, pneumonia, fracture, intracranial blood, tracheostomy use, percutaneous feeding tube use, deep venous thrombosis, focal neurological examination, following simple commands, serum sodium level of < 135 mmol/L, serum white blood cell count of > 11,000 cells/microL, and serum hemoglobin level of < 10.0 g/dl. ANALYSIS: Chi-square analysis was performed on the association between acute care transfer and the noted variables. RESULTS: History of pneumonia (p < .03) and history of recent surgery (p < .02) were both associated with acute care transfer, and serum hemoglobin of < 10.0 g/dL had a trend towards association (p < .10). CONCLUSION: Physiatrists caring for the TBI patient may warrant more acute observation of individuals with these parameters to prevent the problems necessitating acute care transfer.