Nutritional knowledge in British Army recruits during basic training.

BACKGROUND: Appropriate nutritional intake is essential to optimise both general health and performance in military recruits. General nutritional knowledge is a significant and modifiable determinant of dietary behaviour; however, the level of nutritional knowledge in British Army recruits undertaking basic training is poorly understood. METHODS: The Nutritional Knowledge Questionnaire for Athletes was completed by 29 male (age: 22.3±3.8 years) and 26 female (age: 22.0±3.0 years) standard-entry recruits at the end of basic training, and 15 male (age: 20.7±3.2 years) infantry recruits both at the start and end of basic training for the British Army. Between-group and within-group differences in total and subcomponent (ie, carbohydrate, protein, fat, vitamins and minerals, general nutrition, fluid intake, and sporting performance) scores were analysed. RESULTS: Standard-entry male recruits had more correct answers (52%) than standard-entry female recruits (38%) and male infantry recruits (40%) at the end of training. Infantry recruits had similar levels of nutritional knowledge at the start (39% correct) and end (40% correct) of training. Nutritional knowledge related to protein (range: 53%-75% correct answers) and vitamins and minerals (range: 42%-63% correct answers) were the two highest scoring subcomponents within each group. CONCLUSION: British Army recruits, in particular standard-entry female and infantry recruits, have poor nutritional knowledge, which did not improve throughout basic training. Better nutritional intervention, especially surrounding carbohydrate and fluid education, is required during British Army basic training to optimise career-long dietary behaviour.

The effects of a one-to-one nurse-to-patient ratio on the mortality rate in neonatal intensive care: a retrospective, longitudinal, population-based study.

OBJECTIVE: To estimate the effect of the provision of a one-to-one nurse-to-patient ratio on mortality rates in neonatal intensive care units. DESIGN: A population-based analysis of operational clinical data using an instrumental variable method. SETTING: National Health Service neonatal units in England contributing data to the National Neonatal Research Database at the Neonatal Data Analysis Unit and participating in the Neonatal Economic, Staffing, and Clinical Outcomes Project. PARTICIPANTS: 43 tertiary-level neonatal units observed monthly over the period January 2008 to December 2012. INTERVENTION: Proportion of neonatal intensive care days or proportion of intensive care admissions for which one-to-one nursing was provided. OUTCOMES: Monthly in-hospital intensive care mortality rate. RESULTS: Over the study period, the provision of one-to-one nursing in tertiary neonatal units declined from a median of 9.1% of intensive care days in 2008 to 5.9% in 2012. A 10 percentage point decrease in the proportion of intensive care days on which one-to-one nursing was provided was associated with an increase in the in-hospital mortality rate of 0.6 (95% CI 1.2 to 0.0) deaths per 100 infants receiving neonatal intensive care per month compared with a median monthly mortality rate of 4.5 deaths per 100 infants per month. The results remained robust to sensitivity analyses that varied the estimation sample of units, the choice of instrumental variables, unit classification and the selection of control variables. CONCLUSIONS: Our study suggests that decreases in the provision of one-to-one nursing in tertiary-level neonatal intensive care units increase the in-hospital mortality rate.

The effects of designation and volume of neonatal care on mortality and morbidity outcomes of very preterm infants in England: retrospective population-based cohort study.

OBJECTIVE: To examine the effects of designation and volume of neonatal care at the hospital of birth on mortality and morbidity outcomes in very preterm infants in a managed clinical network setting. DESIGN: A retrospective, population-based analysis of operational clinical data using adjusted logistic regression and instrumental variables (IV) analyses. SETTING: 165 National Health Service neonatal units in England contributing data to the National Neonatal Research Database at the Neonatal Data Analysis Unit and participating in the Neonatal Economic, Staffing and Clinical Outcomes Project. PARTICIPANTS: 20 554 infants born at <33 weeks completed gestation (17 995 born at 27-32 weeks; 2559 born at <27 weeks), admitted to neonatal care and either discharged or died, over the period 1 January 2009-31 December 2011. INTERVENTION: Tertiary designation or high-volume neonatal care at the hospital of birth. OUTCOMES: Neonatal mortality, any in-hospital mortality, surgery for necrotising enterocolitis, surgery for retinopathy of prematurity, bronchopulmonary dysplasia and postmenstrual age at discharge. RESULTS: Infants born at <33 weeks gestation and admitted to a high-volume neonatal unit at the hospital of birth were at reduced odds of neonatal mortality (IV regression odds ratio (OR) 0.70, 95% CI 0.53 to 0.92) and any in-hospital mortality (IV regression OR 0.68, 95% CI 0.54 to 0.85). The effect of volume on any in-hospital mortality was most acute among infants born at <27 weeks gestation (IV regression OR 0.51, 95% CI 0.33 to 0.79). A negative association between tertiary-level unit designation and mortality was also observed with adjusted logistic regression for infants born at <27 weeks gestation. CONCLUSIONS: High-volume neonatal care provided at the hospital of birth may protect against in-hospital mortality in very preterm infants. Future developments of neonatal services should promote delivery of very preterm infants at hospitals with high-volume neonatal units.

Perinatal outcomes for extremely preterm babies in relation to place of birth in England: the EPICure 2 study.

BACKGROUND: Expertise and resources may be important determinants of outcome for extremely preterm babies. We evaluated the effect of place of birth and perinatal transfer on survival and neonatal morbidity within a prospective cohort of births between 22 and 26 weeks of gestation in England during 2006. METHODS: We studied the whole population of 2460 births where the fetus was alive at the admission of the mother to hospital for delivery. Outcomes to discharge were compared between level 3 (most intensive) and level 2 maternity services, with and without transfers, and by activity level of level 3 neonatal unit; ORs were adjusted for gestation at birth and birthweight for gestation (adjusted ORs (aOR)). FINDINGS: Of this national birth cohort, 56% were born in maternity services with level 3 and 34% with level 2 neonatal units; 10% were born in a setting without ongoing intensive care facilities (level 1). When compared with level 2 settings, risk of death in level 3 services was reduced (aOR 0.73 (95% CI 0.59 to 0.90)), but the proportion surviving without neonatal morbidity was similar (aOR 1.27 (0.93 to 1.74)). Analysis by intended hospital of birth confirmed reduced mortality in level 3 services. Following antenatal transfer into a level 3 setting, there were fewer intrapartum or labour ward deaths, and overall mortality was higher for those remaining in level 2 services (aOR 1.44 (1.09 to 1.90)). Among level 3 services, those with higher activity had fewer deaths overall (aOR 0.68 (0.52 to 0.89)). INTERPRETATION: Despite national policy, only 56% of births between 22 and 26 weeks of gestation occurred in maternity services with a level 3 neonatal facility. Survival was significantly enhanced following birth in level 3 services, particularly those with high activity; this was not at the cost of increased neonatal morbidity.

A new cervical spine clearance protocol using computed tomography.

OBJECTIVE: The purpose of this study was to assess a cervical spine clearance protocol for blunt trauma patients using helical computed tomographic (CT) scan of the cervical spine (C-spine). METHODS: A protocol using CT scan of the C-spine was implemented and the first 6 months of use reviewed. Patients requiring a CT scan of the head had the C-spine evaluated by lateral C-spine radiography and a helical CT scan. Patients without indication for CT scan of the head had the C-spine evaluated by three-view radiography (anteroposterior, lateral, and odontoid) with selective CT scan of the C-spine for imaging areas not well visualized or those with abnormalities identified by radiography or by clinical examination alone. RESULTS: Three hundred twenty-four patients were admitted to the trauma center after blunt trauma during the first 6 months of protocol implementation. Head CT scans were obtained in 158 patients and lateral cervical spine radiography in conjunction with helical CT scanning evaluated the C-spine. The other 166 patients had the cervical spine cleared by three-view radiography series or by clinical examination alone. For patients in whom a head CT scan was not indicated, CT scanning was used only when plain radiographs failed to adequately visualize the entire C-spine. A total of 15 injuries (4.6% of the group) were detected. Seven injuries were suspected or detected by lateral plain radiographs and confirmed by CT scan. Six patients had an injury not detected by radiography but diagnosed by CT scan, and one patient had a false-positive radiograph. Of the remaining two injuries, one was diagnosed by magnetic resonance imaging and the other by CT scan outside of the protocol. Lateral plain radiographs alone failed to detect 46% (n = 6) of all injuries. CONCLUSION: In our series, the selective use of helical CT scanning with plain radiography increased the accuracy with which cervical spine injury was detected from 54% to 100%. The protocol allowed for more rapid evaluation in many patients as well. We recommend that practice guidelines include the use of helical CT scan of the entire C-spine as the diagnostic procedure for those blunt trauma patients undergoing CT scanning of the head.

Impact of a hospital-based antimicrobial management program on clinical and economic outcomes.

Inappropriate use of antimicrobial agents results in unnecessary exposure to medication, persistent or progressive infection, emergence of resistance, and increased costs. We implemented a program to control use of restricted agents while improving care. This study compared 2 major mechanisms for improving use of antimicrobial agents: (1) recommendations made by the Antimicrobial Management Team (AMT), which included a clinical pharmacist backed up by a physician from the Division of Infectious Diseases (ID), and (2) recommendations made by ID fellows. Outcome measures included appropriateness of recommendations, cure rate, number of treatment failures, and cost of care, which were assessed for 180 patients. The AMT outperformed the ID fellows in all outcomes examined by the study (including appropriateness [87% vs. 47%; P<.001], cure rate [64% vs. 42%; P=.007], and treatment failures [15% vs. 28%; P=.03]), although the differences in economic outcomes between cases managed by the AMT and those managed by the ID fellows were not statistically significant. In an academic setting with a restricted formulary, the AMT demonstrated better antimicrobial prescribing than ID fellows.

Toward an understanding of violence: neurobehavioral aspects of unwarranted physical aggression: Aspen Neurobehavioral Conference consensus statement.

OBJECTIVE: Violence is a global problem that poses a major challenge to individuals and society. This document is a consensus statement on neurobehavioral aspects of violence as one approach to its understanding and control. BACKGROUND: This consensus group was convened under the auspices of the Aspen Neurobehavioral Conference, an annual consensus conference devoted to the understanding of issues related to mind and brain. The conference is supported by the Brain Injury Association and by individual philanthropic contributions. Participants were selected by conference organizers to represent leading opinion in neurology, neuropsychology, psychiatry, trauma surgery, nursing, evolutionary psychology, medical ethics, and law. METHODS: A literature review of the role of the brain in violent behavior was conducted and combined with expert opinion from the group. The major goal was to survey this field so as to identify major areas of interest that could be targeted for further research. Additional review was secured from the other attendees at the Aspen Neurobehavioral Conference. RESULTS: The group met in the spring of 1998 and 1999 for two 5-day sessions, between which individual assignments were carried out. The consensus statement was prepared after the second meeting, and agreement on the statement was reached by participants after final review of the document. CONCLUSIONS: Violence can result from brain dysfunction, although social and evolutionary factors also contribute. Study of the neurobehavioral aspects of violence, particularly frontal lobe dysfunction, altered serotonin metabolism, and the influence of heredity, promises to lead to a deeper understanding of the causes and solution of this urgent problem.

Nosocomial blood stream infection in Auckland Healthcare hospitals.

AIM: To report the epidemiology of nosocomial bloodstream infections in Auckland Healthcare Hospitals. METHODS: From January 1995 to December 1997 every positive blood culture result was followed up by an infection control nurse who recorded relevant clinical, laboratory and treatment information on a data collection sheet. The clinical significance of each isolate was determined and the most likely source recorded. RESULTS: During the three year study period, there were 1,046 nosocomial blood stream infections yielding 1,147 isolates. The most common isolates/groups were: coagulase negative staphylococci 19%, S. aureus 18%, E. coli 12%, streptococci 10%, other Enterobacteriaceae 10%, Enterobacter spp. 7%, Pseudomonas spp. 5%, anaerobes 2%, and yeasts 4%. The most common sources were: intravascular lines 40%, urinary tract 8%, skin/soft tissue 8%, gastrointestinal 7%, and unknown 25%. The overall results were strongly influenced by the neonatal intensive care unit at National Women's Hospital where 58% of blood stream infections had intravascular-lines as the source and 53% of the isolates were coagulase negative staphylococci. The overall blood stream infection rate was approximately 6/1,000 admissions. Rates per 1,000 inpatient days for haematology, intensive care, oncology, neonatal and all other patients were 13, 11, 3, 3 and 1 respectively. CONCLUSIONS: Surveillance data that are clinically relevant are useful in identifying areas where infection prevention strategies can be implemented. Because of the importance of lines as a source of nosocomial blood stream infections all aspects of line care are being reviewed with the aim of reducing these devices as a source of blood stream infection.

Swallowing disorders in severe brain injury: risk factors affecting return to oral intake.

OBJECTIVE: To determine the incidence and type of swallowing disorders that accompany severe brain injury and to identify factors that affect oral intake. DESIGN: Inception cohort study. SETTING: Level I trauma center. PATIENTS: Consecutively admitted patients with severe brain injury who achieved cognitive levels during admission to assess swallowing and who did not sustain injuries preventing swallowing assessment (n = 54). MAIN OUTCOME MEASURES: Type of swallowing abnormalities and presence of aspiration evident on videofluoroscopic swallow studies (VFSS), days to initiation and achievement of oral feeding, ventilation days, presence of a tracheostomy, and cognitive levels at initiation and achievement of oral feeding. RESULTS: Sixty-one percent of subjects exhibited abnormal swallowing. Loss of bolus control and reduced lingual control occurred most commonly. Aspiration rate was 41%. Normal swallowers achieved oral feeding in 19 days versus 57 days for abnormal swallowers. Rancho Los Amigos (RLA) Level IV was needed for initiation of oral feeding; Level VI was needed for total oral feeding. Risk factors for abnormal swallowing included: lower admission Glasgow Coma Scale (GCS) and RLA scores, presence of a tracheostomy, and ventilation time longer than 2 weeks. Risk factors for aspiration were lower admission GCS and RLA scores. CONCLUSIONS: Swallowing disorders and behavioral/cognitive skills are frequently present in patients with severe brain injury and significantly affect oral intake of food. Persons who swallow abnormally take significantly longer to start eating and to achieve total oral feeding, and they require nonoral supplementation three to four times longer than those who swallow normally.

Factors affecting oral feeding with severe traumatic brain injury.

Safe and adequate nutrition, vital to the recovery from a traumatic brain injury, can be severely compromised by the presence of dysphagia. This study identified injury severity and swallowing factors that were associated with impaired oral intake in patients with severe brain injury. An admitting Glasgow Coma Scale (GSC) 3-5; a Rancho Los Amigos Scale of Cognitive Functioning (RLA) Level II; a computed tomography (CT) scan exhibiting midline shift, brainstem involvement, or brain pathology requiring emergent operative procedures; or ventilation time >/=15 days identified patients at highest risk for abnormal swallowing, aspiration, and delay in initiation of oral feeding and achievement of total oral feeding. When combined in multivariate models, RLA Level, CT scan, ventilation time and aspiration emerged as significant independent predictors of impaired oral intake.

Causes and complications associated with swallowing disorders in traumatic brain injury.

A major complication commonly seen in persons with severe brain injury is swallowing dysfunction. The neuropathology leading to impaired swallowing is discussed. In addition, Other risk factors associated with dysfunctional swallowing, such as tracheostomy and the need for prolonged ventilatory support, are discussed. Within the intensive care environment, the consequences of impaired swallowing leading to aspiration-a major cause of pneumonia-are discussed.

Round window administration of gentamicin: a new method for the study of ototoxicity of cochlear hair cells.

Damage to inner ear sensory hair cells after systemic administration of ototoxic drugs has been documented in humans and animals. Birds have the ability to regenerate new hair cells to replace those damaged by drugs or noise. Unfortunately, the systemic administration of gentamicin damages both ears in a variable fashion with potentially confounding systemic drug effects. We developed a method of direct application of gentamicin to one cochlea of hatchling chickens, allowing the other ear to serve as a within-animal control. We tested variables including the vehicle for application, location of application, dosage, and duration of gentamicin exposure. After 5 or 28 days survival, the percent length damage to the cochlea and regeneration of hair cells was evaluated using scanning electron microscopy. Controls consisted of the opposite unexposed cochlea and additional animals which received saline instead of gentamicin. Excellent damage was achieved using gentamicin-soaked Gelfoam pledgets applied to the round window membrane. The percent length damage could be varied from 15 to 100% by changing the dosage of gentamicin, with exposures as short as 30 min. No damage was observed in control animals. Regeneration of hair cells was observed in both the base and apex by 28 days survival.

Glutathione based approaches to improving cancer treatment.

The use of cytotoxic chemotherapy for cancer therapy has been very successful in the treatment and often cure of patients with particular neoplasms, such as testicular carcinomas and some lymphomas. In addition, the use of adjuvant chemotherapy in patients whose primary tumor has been surgically removed contributes significantly to cure rates in some of the more common malignancies such as breast carcinoma and colon cancer. Nonetheless, for most patients with metastatic malignancies, current antineoplastic drugs provide only brief remissions with few or no long term cures. In addition, the side effects of therapy lead to substantial morbidity in nearly all patients. Insights derived from model system studies on two glutathione based lead compounds, TER286 and TER199, suggest new clinical strategies and raise interesting basic research questions regarding the cell biology foundations of cancer chemotherapy.

Tumor efficacy and bone marrow-sparing properties of TER286, a cytotoxin activated by glutathione S-transferase.

TER286 is a latent drug activated by human glutathione S-transferase (GST) isoforms P1-1 and A1-1 to produce a nitrogen mustard alkylating agent. M7609 human colon carcinoma, selected for resistance to doxorubicin, and MCF-7 human breast carcinoma, selected for resistance to cyclophosphamide, both showed increased sensitivity to TER286 over their parental lines in parallel with increased expression of GST P1-1. In primary human tumor clonogenic assays, the spectrum of cytotoxic activity observed for TER286 was both broad and unusual when compared to a variety of current drugs. In murine xenografts of M7609 engineered to have high, medium, or low GST P1-1, responses to TER286 were positively correlated with the level of P1-1. Cytotoxicity was also observed in several other cell culture and xenograft models. In xenografts of the MX-1 human breast carcinoma, tumor growth inhibition or regression was observed in nearly all of the animals treated with an aggressive regimen of five daily doses. This schedule resulted in a 24-h posttreatment decline in bone marrow progenitors to 60% of control and was no worse than for a single dose of TER286. These studies have motivated election of TER286 as a clinical candidate.

Impact of a vancomycin restriction policy on use and cost of vancomycin and incidence of vancomycin-resistant Enterococcus.

OBJECTIVE: To review the appropriateness of vancomycin therapy, changes in vancomycin use, and the incidence of vancomycin-resistant Enterococcus (VRE) after implementation of a limited restriction policy requiring approval from the Infectious Diseases Approval service to continue vancomycin therapy beyond 72 hours. DESIGN: A prospective chart review was conducted in April 1995. Pharmacy billing data and infection control data were compared before and after policy implementation. SETTING: A 725-bed university teaching institution. PATIENTS: All patients receiving vancomycin during April 1995. MAIN OUTCOME MEASURES: Appropriateness of use was based on the Centers for Disease Control and Prevention (CDC) recommendations for prudent vancomycin use. RESULTS: A total of 333 courses of vancomycin therapy were reviewed. Vancomycin use was appropriate in 219 (66%) courses. Of the 114 courses that did not meet the CDC guidelines, 76 (67%) were for empiric use, 35 (31%) were for prophylactic use, and 3 (3%) were for therapeutic use. Overall, the total number of grams used decreased 9%, grams per 1000 patient-days decreased by 10, and the total number of patients exposed to vancomycin decreased 0.5%. Several services had large decreases in vancomycin use. Vancomycin expenditures decreased by $15788 for the 7-month time period. The incidence of VRE remained unchanged, at 30% of all enterococcal isolates 2 years after policy implementation. CONCLUSIONS: The limited restriction policy was effective in decreasing the total grams of vancomycin used. However, one-third of vancomycin therapy was inappropriate and the incidence of VRE was unchanged. A more stringent restriction policy could potentially increase appropriate use, further decrease the amount of vancomycin used, and decrease the incidence of VRE.

Design, synthesis, and evaluation of latent alkylating agents activated by glutathione S-transferase.

In search of compounds with improved specificity for targeting the important cancer-associated P1-1 glutathione S-transferase (GST) isozyme, new analogs 4 and 5 of the previously reported glutathione S-transferase (GST)-activated latent alkylating agent gamma-glutamyl-alpha-amino-beta-[[[2-[[bis[bis(2-chloroethyl)amino]ph osp horyl]oxy]ethyl]sulfonyl]propionyl]-(R)-(-)-phenylglycine (3) have been designed, synthesized, and evaluated. One of the diastereomers of 4 exhibited good selectivity for GST P1-1. The tetrabromo analog 5 of the tetrachloro compound 3 maintained its specificity and was found to be more readily activated by GSTs than 3. The GST activation concept was further broadened through design, synthesis, and evaluation of a novel latent urethane mustard 8 and its diethyl ester 9. Interestingly, 8 showed very good specificity for P1-1 GST. Cell culture studies were carried out on 4, 5, 8, and 9 using cell lines engineered to have varying levels of GST P1-1 isozyme. New analogs 4 and 5 exhibited increased toxicity to cell lines with overexpressed GST P1-1 isozyme. The urethane mustard 8 and its diethyl ester 9 were found to be not as toxic. However, they too exhibited more toxicity to a cell line engineered to have elevated P1-1 levels, which was in agreement with the observed in vitro specificity of 8 for P1-1 GST isozyme. Mechanistic studies on alkaline as well as enzyme-catalyzed decomposition of latent mustard 3 provided experimental proof for the hypothesis that 3 breaks down into an active phosphoramidate mustard and a reactive vinyl sulfone. The alkylating nature of the decomposition products was further demonstrated by trapping those transient species as relatively stable diethyldithiocarbamic acid adducts. These results substantially extend previous efforts to develop drugs targeting GST and provide a paradigm for development of other latent drugs.

Isozyme-specific glutathione S-transferase inhibitors potentiate drug sensitivity in cultured human tumor cell lines.

Novel glutathione (GSH) analogs, previously shown to inhibit glutathione S-transferase (GST) activity at about 1 microM in vitro, were tested for their ability to potentiate the killing of cultured tumor cells by chemotherapeutic drugs. When tested at doses up to 200 microM, the analogs were neither toxic nor capable of potentiating drug toxicity unless the diethyl ester (DEE) form was used for treatment of the cells. HPLC analysis revealed rapid internalization of the DEE and intracellular conversion to a monoethyl ester form that accumulated in the cell, followed by a more gradual loss of the second ester to generate the active parent form. For the four GSH analogs tested, the ability of the DEE forms to potentiate chlorambucil (CMB) toxicity in HT-29 human colon adenocarcinoma cells strongly correlated with the in vitro ability of the parent form to inhibit recombinant human P1-1. This isozyme is the dominant form of GST present in HT-29 cells. Of the four analog DEEs tested, gamma-glutamyl-S-(benzyl)cysteinyl-R(-)-phenyl glycine (TER 117) DEE was the most effective in potentiating CMB toxicity in several cell lines: HT-29, HT4-1 (HT-29 subclone), SKOV-3 ovarian carcinoma, and SK VLB (vinblastine-resistant variant of SKOV-3) cells. gamma-Glutamyl-S-(octyl)cysteinyl-glycine (TER 143) DEE potentiated mitomycin C (MTC) toxicity in HT4-1 and SK VLB cells while TER 117 DEE did not. TER 117 DEE enhanced melphalan effects on xenografts of HT4-1 in mice to a similar extent as that achieved with the previously described nonspecific GST inhibitor, ethacrynic acid. Taken together, our results indicate that cell-permeable analogs of GSH can potentiate cytotoxicity of common chemotherapeutic drugs and this effect has a strong positive correlation with the ability of the analogs to inhibit specific GST isozymes.