The development and acceptability of an educational and training intervention for recruiters to neonatal trials: the TRAIN project.

BACKGROUND: Suboptimal or slow recruitment affects 30-50% of trials. Education and training of trial recruiters has been identified as one strategy for potentially boosting recruitment to randomised controlled trials (hereafter referred to as trials). The Training tRial recruiters, An educational INtervention (TRAIN) project was established to develop and assess the acceptability of an education and training intervention for recruiters to neonatal trials. In this paper, we report the development and acceptability of TRAIN. METHODS: TRAIN involved three sequential phases, with each phase contributing information to the subsequent phase(s). These phases were 1) evidence synthesis (systematic review of the effectiveness of training interventions and a content analysis of the format, content, and delivery of identified interventions), 2) intervention development using a Partnership (co-design/co-creation) approach, and 3) intervention acceptability assessments with recruiters to neonatal trials. RESULTS: TRAIN, accompanied by a comprehensive intervention manual, has been designed for online or in-person delivery. TRAIN can be offered to recruiters before trial recruitment begins or as refresher sessions during a trial. The intervention consists of five core learning outcomes which are addressed across three core training units. These units are the trial protocol (Unit 1, 50 min, trial-specific), understanding randomisation (Unit 2, 5 min, trial-generic) and approaching and engaging with parents (Unit 3, 70 min, trial-generic). Eleven recruiters to neonatal trials registered to attend the acceptability assessment training workshops, although only four took part. All four positively valued the training Units and resources for increasing recruiter preparedness, knowledge, and confidence. More flexibility in how the training is facilitated, however, was noted (e.g., training divided across two workshops of shorter duration). Units 2 and 3 were considered beneficial to incorporate into Good Clinical Practice Training or as part of induction training for new staff joining neonatal units. CONCLUSION: TRAIN offers a comprehensive co-produced training and education intervention for recruiters to neonatal trials. TRAIN was deemed acceptable, with minor modification, to neonatal trial recruiters. The small number of recruiters taking part in the acceptability assessment is a limitation. Scale-up of TRAIN with formal piloting and testing for effectiveness in a large cluster randomised trial is required.

Consent for routine neonatal procedures: A study of practices in Irish neonatal units. How do we compare with the gold standard BAPM guidelines?

The Irish National Consent Policy (NCP) proposes that the legal requirement for consent extends to all forms of interventions, investigations and treatment, carried out on or behalf of the Health Service Executive (HSE). This study employs a quantitative descriptive approach to investigate the practices for obtaining consent for an identified group of routine neonatal procedures in neonatal facilities throughout Ireland. The BAPM (British Association of Perinatal Medicine) guidelines were identified as 'gold standard' for the purposes of this study. The results indicated a lack of consistency between participating units pertaining to the modes of consent utilised and notable variances from 'gold standard' guidelines. Unanimity was evident for 3 procedures only (administering BCG, 6-in-1, and donor breast milk to infant). Significant findings related to EEG with video recordings, MRI/CT and gastro intestinal imaging, screening of an infant with suspected substance abuse or retinopathy of prematurity screening (ROP), administration of Vitamin K, and the carrying out of a lumbar puncture.

Sniffing out cancer using the JPL electronic nose: a pilot study of a novel approach to detection and differentiation of brain cancer.

UNLABELLED: A proof-of-concept study was done to determine whether an electronic nose developed for air quality monitoring at the Jet Propulsion Laboratory (JPL) could be used to distinguish between the odors of organ and tumor tissues, with an eye to using such a device as one of several modes in multi-modal imaging and tumor differentiation during surgery. HYPOTHESIS: We hypothesized that the JPL electronic nose (ENose) would be able to distinguish between the odors of various organ and tumor tissues. MATERIALS AND METHODS: The odor signatures, or array response, of two organs, chicken heart and chicken liver, and cultured glioblastoma and melanoma tumor cell lines were recorded using the JPL Electronic Nose. The overall array responses were compared to determine whether they were sufficiently different to allow the organs and cell lines to be identified by their array responses. RESULTS: The ENose was able to distinguish between the two types of organ tissue and between the two types of tumor cell lines. The variation in array response for the organ tissues was 19% and between the two types of cultured cell lines was 22%. CONCLUSION: This study shows that it is possible to use an electronic nose to distinguish between two types of tumor cells and between two types of organ tissue. As we conducted the experiment with a sensor array built for air quality monitoring rather than for medical purposes, it may be possible to select an array that is optimized to distinguish between different types of cells and organ tissues. Further focused studies are needed to investigate the odor signatures of different cells as well as cellular proliferation, growth, differentiation and infiltration.

Randomized trial of a chlorhexidine mouthwash for alleviation of radiation-induced mucositis.

PURPOSE: To determine whether a chlorhexidine mouthwash could alleviate radiation-induced oral mucositis. PATIENTS AND METHODS: Patients scheduled to receive radiation therapy to include greater than one third of the oral cavity mucosa were selected for study. Following stratification, they were randomized in a double-blind manner to receive a chlorhexidine mouthwash or a placebo mouthwash. Both groups were then similarly evaluated for mucositis and mouthwash toxicity. RESULTS: Twenty-five patients were randomized to receive the chlorhexidine mouthwash, while 27 received the placebo mouthwash. Treatment arms were well balanced. There was a trend for more mucositis and there was substantially more toxicity (eg, mouthwash-induced discomfort, taste alteration, and teeth staining) on the chlorhexidine arm. CONCLUSION: In contrast to the prestudy hypothesis that a chlorhexidine mouthwash might provide benefit for patients receiving radiation therapy to the oral mucosa, this study provides strong evidence suggesting that a chlorhexidine mouthwash is detrimental in this clinical situation.

Heat shock activates the I-kappaBalpha promoter and increases I-kappaBalpha mRNA expression.

Recent data indicate that the heat shock response inhibits nuclear translocation of the proinflammatory transcription factor NF-kappaB. Under basal conditions NF-kappaB is retained in the cytoplasm by an inhibitory protein called I-kappaB which exists as two major isoforms: I-kappaBalpha and I-kappaBbeta. Induction of the heat shock response in BEAS-2B cells, a human cell line representative of bronchial epithelium, increased expression of I-kappaBalpha mRNA in a time-dependent manner. Coincubation with actinomycin-D inhibited heat shock-mediated expression of I-kappaBalpha mRNA. Transient transfection assays with a plasmid containing the reporter gene firefly luciferase, under the control of the human I-kappaBalpha promoter, demonstrated that heat shock activated the I-kappaBalpha promoter. Heat shock-mediated induction of I-kappaBalpha was associated with inhibition of NF-kappaB activation. We conclude that heat shock increases I-kappaBalpha mRNA expression in BEAS-2B cells by activating the I-kappaBalpha promoter, and propose that heat shock-mediated up-regulation of I-kappaBalpha is a potential mechanism by which the heat shock response inhibits proinflammatory responses in lung cells.

Heat shock inhibits phosphorylation of I-kappaBalpha.

Previous studies demonstrated that induction of the heat shock response is associated with inhibition of the proinflammatory transcription factor NF-kappaB by a mechanism involving inhibition of I-kappaBalpha degradation. To provide further insight regarding the interactions of these fundamental cellular responses, the present experiments were designed to elucidate the mechanism(s) by which heat shock inhibits degradation of I-kappaBalpha. In an in vitro model of inflammatory cell signaling, treatment of RAW 264.7 murine macrophages with LPS (100 ng/mL) caused rapid degradation of I-kappaBalpha. Heat shock, 1 h before treatment with LPS, completely inhibited LPS-mediated degradation of I-kappaBalpha. Immunoprecipitation studies demonstrated that heat shock inhibited LPS-mediated ubiquitination of I-kappaBalpha. Western-blot analyses using a phosphorylated I-kappaBalpha-specific antibody demonstrated that heat shock inhibited LPS-mediated phosphorylation of I-kappaBalpha. In contrast, heat shock induced phosphorylation of c-jun. In murine fibroblasts having genetic ablation of the heat shock factor-1 gene, heat shock inhibited tumor necrosis factor-alpha mediated degradation of I-kappaBalpha. We conclude that the mechanism by which heat shock inhibits LPS-mediated degradation of I-kappaBalpha involves specific inhibition of I-kappaBalpha phosphorylation and subsequent I-kappaBalpha ubiquitination. In addition, this mechanism does not involve activation of heat shock factor-1 or the heat shock proteins regulated by heat shock factor-1.

Tuberculosis in the workplace: OSHA's compliance experience.

OBJECTIVE: Inspections of 272 facilities were performed between May 1992 and October 1994 to determine compliance with applicable Occupational Safety and Health Administration (OSHA) requirements for prevention of tuberculosis (TB) transmission. DESIGN: Retrospective record review of two data sources: (1) OSHA's Computerized Integrated Management Information System and (2) an inspector-completed questionnaire on inspection results. SETTING/PARTICIPANTS: Inspections of five types of facilities: healthcare institutions, correctional facilities, homeless shelters, long-term-care facilities for the elderly, and others, including drug treatment centers that the Centers for Disease Control and Prevention (CDC) identified as having a higher than expected rate of TB. METHODS: The OSHA Compliance Memorandum, based on the 1990 CDC Guidelines, which outlined elements of a TB prevention program, was used in performing 272 inspections of facilities between May 1992 and October 1994. Elements of compliance were recorded and reviewed from the IMIS database and inspectors' questionnaires. RESULTS: Regulated facilities were not fully compliant with OSHA guidance. Generally, healthcare facilities performed better than other facilities. Most facilities (79%) were compliant with administrative elements of a comprehensive TB control program, such as early identification of known or suspected infectious TB patients and skin testing of workers. Only 29% of inspected facilities were found to have acceptable respiratory protection programs for the prevention of occupational TB. CONCLUSION: Facilities have not been fully compliant with the OSHA memorandum describing protection of workers from TB. Facility compliance was better with some traditionally recognized TB infection control elements, but was weaker in the area of respiratory protection programs. This may reflect a lack of familiarity with the latter type of hazard protection.

The effect on serum lipids and oxidized low-density lipoprotein of supplementing self-selected low-fat diets with soluble-fiber, soy, and vegetable protein foods.

An increased intake of soluble fiber and soy protein may improve the blood lipid profile. To assess any additional benefit on serum lipids of providing soy protein and soluble-fiber foods to hyperlipidemic subjects already consuming low-fat, low-cholesterol therapeutic diets, 20 hyperlipidemic men and postmenopausal women completed 8-week test and control dietary treatments in a randomized crossover design as part of an ad libitum National Cholesterol Education Program (NCEP) step 2 therapeutic diet (<7% saturated fat and <200 mg/d cholesterol). During the test phase, foods high in soy, other vegetable proteins, and soluble fiber were provided. During the control phase, low-fat dairy and low-soluble-fiber foods were provided. Fasting blood lipid and apolipoprotein levels were measured at 4 and 8 weeks of each phase. On the test diet, 12 +/- 2 g/d soy protein was selected from the foods chosen. Direct comparison of test and control treatments indicated an elevated high-density lipoprotein (HDL) cholesterol concentration on the test diet (6.4% +/- 2.4%, P = .013) and a significantly reduced total to HDL cholesterol ratio (-5.9% +/- 2.3%, P = .020). The proportion of conjugated dienes in the low-density lipoprotein (LDL) cholesterol fraction was significantly reduced (8.5% +/- 3.3%, P = .020) as a marker of oxidized LDL. A combination of acceptable amounts of soy, vegetable protein, and soluble-fiber foods as part of a conventional low-fat, low-cholesterol therapeutic diet is effective in further reducing serum lipid risk factors for cardiovascular disease.

Combined effect of vegetable protein (soy) and soluble fiber added to a standard cholesterol-lowering diet.

Dietary treatment of hyperlipidemia focuses on reducing saturated fat and dietary cholesterol. Other aspects of diet are not emphasized at present, despite growing evidence that a number of plant components decrease serum cholesterol. We therefore determined whether a combination of two plant components, vegetable protein and soluble fiber, further reduce serum lipids when incorporated into the currently advocated low-saturated-fat diet. Thirty-one hyperlipidemic men and women ate two 1-month low-fat (<7% of total energy from saturated fat), low-cholesterol (<80 mg cholesterol/d) metabolic diets in a randomized crossover study. The major differences between test and control diets were an increased amount of vegetable protein (93% v 23% of total protein), of which 33 g/d was soy, and a doubling of soluble fiber. Fasting blood samples were obtained at the start and end of each phase. On the last 3 days of each phase, fecal collections were obtained. Compared with the low-fat control diet, the test diet decreased total cholesterol (6.2% +/- 1.2%, P < .001), low-density lipoprotein (LDL) cholesterol (6.7% +/- 1.7%, P < .001), apolipoprotein B (8.2% +/- 1.2%, P < .001), and the ratios of LDL to high-density lipoprotein (HDL) cholesterol (6.3% +/- 2.0%, P = .004) and apolipoprotein B to A-I (5.4% +/- 1.5%, P = .001). A combination of vegetable protein and soluble fiber significantly improved the lipid-lowering effect of a low-saturated-fat diet. The results support expanding the current dietary advice to include increased vegetable protein and soluble fiber intake so that the gap in effectiveness between a good diet and drug therapy is reduced.

Polymer-carbon black composite sensors in an electronic nose for air-quality monitoring.

An electronic nose that uses an array of 32 polymer-carbon black composite sensors has been developed, trained, and tested. By selecting a variety of chemical functionalities in the polymers used to make sensors, it is possible to construct an array capable of identifying and quantifying a broad range of target compounds, such as alcohols and aromatics, and distinguishing isomers and enantiomers (mirror-image isomers). A model of the interaction between target molecules and the polymer-carbon black composite sensors is under development to aid in selecting the array members and to enable identification of compounds with responses not stored in the analysis library.

Cost-effectiveness analysis of reacquiring and using adenovirus types 4 and 7 vaccines in naval recruits.

Adenovirus vaccines have controlled acute respiratory disease (ARD) in military recruits since 1971. Vaccine production, however, ceased and new facilities are required. We assessed whether reacquiring and using vaccines in naval recruits is cost-effective. Three policy options were evaluated: no vaccination, seasonal vaccination, and year-round vaccination. Morbidity (outpatient and inpatient), illness costs (medical and lost training), and vaccine program costs (start-up, acquisition, and distribution) were modeled using a decision-analytic method. Results were based on a cohort of 49,079 annual trainees, a winter vaccine-preventable ARD rate of 2.6 cases per 100 person-weeks, a summer incidence rate at 10% of the winter rate, a hospitalization rate of 7.6%, and a production facility costing US$12 million. Compared to no vaccination, seasonal vaccination prevented 4,015 cases and saved $2.8 million per year. Year-round vaccination prevented 4,555 cases and saved $2.6 million. Reacquiring and using adenovirus vaccines seasonally or year-round saves money and averts suffering.

Potential role of polyunsaturates in seizure protection achieved with the ketogenic diet.

Epilepsy is a serious neurological disease that responds to two very different treatments involving lipids. Clinically, it responds to a state of ketosis induced by a very high-fat 'ketogenic' diet. Experimentally, in vitro and in vivo models demonstrate that injection or infusion of free (non-esterified) polyunsaturates such as arachidonate and docosahexaenoate also reduces seizure susceptibility. In our experience, rats on a very high-fat ketogenic diet not only have mild-to-moderate ketosis, but also have raised serum free fatty acids. Some polyunsaturates, particularly linoleate and alpha-linolenate, are relatively easily beta-oxidized and are therefore ketogenic. We conclude that raised levels of free plasma polyunsaturates could contribute to the beneficial effect of the ketogenic diet in refractory epilepsy not only by helping sustain ketosis, but also by their own direct (though poorly defined) antiseizure effects.

Handwashing and respiratory illness among young adults in military training.

OBJECTIVES: In response to increasing concerns about respiratory illness in military recruits, a simple handwashing program was developed and evaluated at a large Navy training center. METHODS: Clinical records from 1996 through 1998 were reviewed to determine weekly rates of respiratory illness before and after program implementation (1,089,800 person-weeks reviewed). A supplemental survey was given to a sample of recruits to assess self-reported respiratory illness and compliance with the handwashing program. RESULTS: A 45% reduction in total outpatient visits for respiratory illness was observed after implementation of the handwashing program. No change was noted in hospitalization rates for respiratory illness, which remained low during the observation period. Survey data supported clinical observations, as frequent handwashers self-reported fewer respiratory illness episodes when compared to infrequent handwashers. Surveys also revealed challenges with handwashing compliance. CONCLUSIONS: Implementation of a handwashing program in this population of healthy young adults was associated with a marked reduction in outpatient visits for respiratory illness. Despite its success, maintenance of the handwashing program has been challenging in the time-constrained setting of military training.

Assessment of pain in advanced cancer patients.

This study tested the feasibility of standardized pain assessment instruments in a population of patients with far advanced cancer at the time of admission to a specialty hospital. As pain is a symptom, pain control must be based on patients' self-report. Cognitive impairment and severe physical illness, however, limited the ability to use these tools. Almost one-half (44.8%) of the patients were unable to use the McGill-Melzack Pain Questionnaire, the Memorial Pain Assessment Card, or the Faces Pain Rating Scale. Patients with far advanced cancer fall into three groups: those who report pain, those who report no pain, and those who are unable to state whether or not they have pain. This study demonstrates the need to undertake pain assessment while the patient is able to respond and to monitor behaviors that could be indicative of changes in pain.

Hospitalized advanced cancer patients: a profile.

More than half of all individuals diagnosed with cancer will not be cured and will require supportive care for some period. Nonetheless, few large scale studies have documented the prevalence and complexity of the problems of advanced disease. This study examined the demographic treatment and outcome variables for 1,103 admissions to a specialty acute care hospital devoted to the care of patients with advanced cancer. The population is profiled, and significant relationships among these variables are identified. The prevalence of major symptoms is documented. This data base study provides a foundation for further research.

Molecular modeling of polymer composite-analyte interactions in electronic nose sensors.

We report a molecular modeling study to investigate the polymer-carbon black (CB) composite-analyte interactions in resistive sensors. These sensors comprise the JPL electronic nose (ENose) sensing array developed for monitoring breathing air in human habitats. The polymer in the composite is modeled based on its stereoisomerism and sequence isomerism, while the CB is modeled as uncharged naphthalene rings with no hydrogens. The Dreiding 2.21 force field is used for the polymer, solvent molecules and graphite parameters are assigned to the carbon black atoms. A combination of molecular mechanics (MM) and molecular dynamics (NPT-MD and NVT-MD) techniques are used to obtain the equilibrium composite structure by inserting naphthalene rings in the polymer matrix. Polymers considered for this work include poly(4-vinylphenol), polyethylene oxide, and ethyl cellulose. Analytes studied are representative of both inorganic and organic compounds. The results are analyzed for the composite microstructure by calculating the radial distribution profiles as well as for the sensor response by predicting the interaction energies of the analytes with the composites.

Application of an intensified diode array system to diagnosis of matrix effects and the rapid sequential determination of thiamine and riboflavin with fluorescence detection.

The unique capabilities of a multiple wavelength spectrofluorometer based on an intensified diode array detector are used for diagnosis of matrix effects and for rapid sequential determination of two analytes. This system is used to investigate problems due to background fluorescence, blank reactions, and scattering for the determination of thiamine in cereal and urine samples by a fluorometric kinetic procedure. A novel determination of thiamine and riboflavin in vitamin pills is based on monitoring the native fluorescence of riboflavin over one wavelength region, and the rate of formation of fluorescent thiochrome from thiamine over another wavelength region, after a computer-controlled change in the pH of the reaction mixture.

Construction of a microcumputer-based reaction-rate ratemeter.

The design and construction of a ratemeter based on a KIM-1 single-board microcomputer are discussed. The reaction monitor signal is digitized with a voltage-frequency converter and the resulting data points are stored in computer memory. Through software, the reaction-rate is calculated by the fixed-time computation method. A unique software-hardware combination is used for conversion from binary to binary-coded decimal format so that the results are printed in decimal notation. The characteristics of the ratemeter are compared with those of earlier ratemeters.

Tissue phospholipid fatty acid composition in the diabetic rat.

Tissue phospholipid fatty acid compositions in streptozotocin-induced diabetic rats were studied. The major changes in liver, plasma, erythrocyte and heart were increased proportions of linoleic and dihomo-gamma-linolenic acids and a decreased proportion of arachidonic acid. The latter was not significantly changed in phospholipids of kidney, adrenal gland and testis. Skin fatty acids in diabetic rats showed an increase in the proportion of arachidonic acid and a reduction in the proportion of linoleic acid. The fatty acid desaturating activity in diabetes may be regulated differently in different tissues.

Synthesis of linoleate and alpha-linolenate by chain elongation in the rat.

The objective was to determine whether rats could synthesize longer chain polyunsaturates from hexadecadienoate (16:2n-6) and hexadecatrienoate (16:3n-3). Rats were gavaged with uniformly 13C-labelled hexadecadienoate or hexadecatrienoate, euthanized 24 h later, and total lipids were extracted from liver and carcass. Gas chromatography/combustion/isotope ratio mass spectrometry was used to measure 13C levels in individual liver, carcass, and whole body fatty acids. 13C Enrichment was present in desaturated and chain-elongated polyunsaturates, including linoleate, arachidonate, alpha-linolenate, and docosahexaenoate at 12-13% of the dose of tracer given. 13C Enrichment from hexadecatrienoate was highest in carcass and liver alpha-linolenate, representing 3.5 and 17.9% of the total alpha-linolenate pool, respectively. For linoleate, arachidonate, or docosahexaenoate, the contribution of 13C did not exceed 0.2% of the total body pool. Green leafy vegetables common in the human diet were shown to contain up to 1.2% of total fatty acids as hexadecadienoate and 11.6% as hexadecatrienoate. Hence, humans consuming green vegetables probably synthesize a small proportion of their total body content of linoleate and alpha-linolenate.