Fall-related traumatic brain injury deaths and hospitalizations among older adults--United States, 2005.

PROBLEM: Among older adults, both unintentional falls and traumatic brain injuries (TBI) result in significant morbidity and mortality; however, only limited national data on fall-related TBI are available. METHOD: To examine the relationship between older adult falls and TBI deaths and hospitalizations, CDC analyzed 2005 data from the National Center for Health Statistics' National Vital Statistics System and the Agency for Healthcare Research and Quality's Nationwide Inpatient Sample. RESULTS: In 2005, among adults>or=65 years, there were 7946 fall-related TBI deaths and an estimated 56,423 hospitalizations for nonfatal fall-related TBI in the United States. Fall-related TBI accounted for 50.3% of unintentional fall deaths and 8.0% of nonfatal fall-related hospitalizations. SUMMARY: These findings underscore the need for greater dissemination and implementation of evidence-based fall prevention interventions.

Severe paediatric ulcerative colitis: incidence, outcomes and optimal timing for second-line therapy.

BACKGROUND: Despite the predominance of extensive disease in children with ulcerative colitis, data concerning severe paediatric ulcerative colitis are sparse. We reviewed rates and predictors of response to intravenous-corticosteroid therapy in a single-centre cohort with long-term follow-up. METHODS: 99 children (49% males; age 2-17 years) were hospitalised (1991-2000) for treatment of severe ulcerative colitis (90% extensive; 49% new onset ulcerative colitis). Clinical, laboratory and radiographic data were reviewed. A population-based subset was used to assess incidence. Predictors of corticosteroid response were analysed using univariate and multivariate analyses at days 3 and 5 of therapy. Colectomy rates were calculated using Kaplan-Meier survival analyses. RESULTS: 28% (95% CI, 23 to 34%) of children with ulcerative colitis resident in the Greater Toronto Area required admission for intravenous corticosteroid therapy, of whom 53 (53%; 95% CI, 44 to 63%) responded. Several predictors were associated with corticosteroid failure, but in multivariable modelling only C-reactive protein [OR = 3.5 (1.4 to 8.4)] and number of nocturnal stools [OR = 3.2 (1.6 to 6.6)] remained significant at both days 3 and 5. The Pediatric Ulcerative Colitis Activity Index (PUCAI), Travis and Lindgren's indices strongly predicted non-response. Radiographically, the upper range of colonic luminal width was 40 mm in children younger than 11 years versus 60 mm in older patients. Cumulative colectomy rates at discharge, 1 year and 6 years were 42%, 58% and 61%, respectively. CONCLUSIONS: Children with ulcerative colitis commonly experience at least one severe exacerbation. Response to intravenous corticosteroids is poor. The PUCAI, determined at day 3 (>45 points) should be used to screen for patients likely to fail corticosteroids and at day 5 (>70 points) to dictate the introduction of second-line therapies.

Non-fatal horse related injuries treated in emergency departments in the United States, 2001-2003.

OBJECTIVE: To characterise and provide nationally representative estimates of persons with non-fatal horse related injuries treated in American emergency departments. METHODS: The National Electronic Injury Surveillance System All Injury Program (NEISS-AIP) is a stratified probability sample comprising 66 hospitals. Data on injuries treated in these emergency departments are collected and reported. NEISS-AIP data on all types (horseback riding and otherwise) of non-fatal horse related injuries from 2001 to 2003 were analysed. RESULTS: An estimated 102,904 persons with non-fatal horse related injuries (35.7 per 100,000 population) were treated in American emergency departments each year from 2001 to 2003 inclusive. Non-fatal injury rates were higher for females (41.5 per 100,000) than for males (29.8 per 100,000). Most patients were injured while mounted on a horse (66.1%), commonly from falling or being thrown by the horse; while not mounted, injuries most often resulted from being kicked by the horse. The body parts most often injured were the head/neck region (23.2%), lower extremity (22.2%), and upper extremity (21.5%). The most common principal diagnoses were contusions/abrasions (31.4%) and fractures (25.2%). For each year that was studied, an estimated 11 502 people sustained traumatic brain injuries from horse related incidents. Overall, more than 11% of those injured were admitted to hospital. CONCLUSIONS: Horse related injuries are a public health concern not just for riders but for anyone in close contact with horses. Prevention programmes should target horseback riders and horse caregivers to promote helmet use and educate participants about horse behaviour, proper handling of horses, and safe riding practices.

Impaired IFN-gamma production in IFN regulatory factor-1 knockout mice during endotoxemia is secondary to a loss of both IL-12 and IL-12 receptor expression.

Mice with a targeted mutation in the gene that encodes the transcription factor IFN regulatory factor-1 (IRF-1) were used to assess the contribution of IRF-1 to IL-12-dependent and IL-12-independent pathways of IFN-gamma production. In response to LPS, IRF. 1-/- mice produced less IL-12 p40, IL-12 p35, and IFN-gamma mRNA in the liver than IRF-1+/+ mice. While pulmonary IFN-gamma mRNA levels were also mitigated in IRF-1-/- mice, pulmonary IL-12 p40 and IL-12 p35 mRNA were not dysregulated. Circulating IL-12 p70 and IFN-gamma levels were profoundly attenuated in LPS-challenged IRF-1-/- mice. Further analysis revealed a major deficiency in hepatic IL-12Rbeta1 and IL-12Rbeta2 mRNA expression as well as pulmonary IL-12Rbeta1 mRNA expression in LPS-challenged IRF-1-/- mice. In vitro, IFN-gamma up-regulated IL-12Rbeta1 mRNA in macrophages from IRF-1+/+, but not IRF-1-/-, mice. IFN-gamma-induced IL-12Rbeta2 mRNA expression was also diminished in macrophages from IRF-1-/- mice. In contrast to IRF-1+/+ mice, administration of exogenous IL-12 to IRF-1-/- mice resulted in reduced serum IFN-gamma and hepatic and pulmonary IFN-gamma mRNA, demonstrating that loss of IL-12R results in diminished IL-12 responsiveness. While LPS-challenged IRF-1-/- mice also had reduced IL-15 mRNA levels, serum IL-18 responses were intact. Finally, induction of IRF-1 mRNA by LPS in livers of IFN-gamma knockout mice were markedly attenuated, suggesting a feedback amplification loop. These studies indicate that IRF-1 deficiency disrupts both IL-12-dependent and -independent pathways of IFN-gamma production and that IRF-1 is a critical transcription factor involved in the regulation of not only IL-12, but also IL-12R.

Efficacy of chest CT in a pediatric ICU: a prospective study.

STUDY OBJECTIVES: (1) To determine whether chest CT provides additional information compared with chest radiography regarding the nature of intrathoracic disease in critically ill children, (2) to determine whether such information alters clinical management, (3) to assess the role of a low-dose high-resolution CT (HRCT) protocol in pediatric ICU (PICU) patients. DESIGN: Prospective study. SETTING: Specialized PICU in a teaching hospital serving London and the south of England. PATIENTS: Twenty children (age range, 3 weeks to 12 years; median, 11 months) underwent chest CT during a 33-month period. Inclusion criteria were (1) inconclusive diagnosis from chest radiograph (CXR) or (2) CXR appearances inconsistent with high oxygenation or ventilatory requirements (PaO(2) to fraction of inspired oxygen ratio < 30 or mean airway pressure > 15 cm H(2)O). INTERVENTIONS: Low-dose HRCT scans (50 mA, 2-mm slice thickness at intervals of 10 or 15 mm) were performed on 12 patients, and helical CT (50 to 250 mA; pitch, 1 to 1.5) performed on 8 patients. MEASUREMENTS AND RESULTS: CT provided additional information regarding the nature of intrathoracic disease in 17 of 20 patients (85%) and resulted in changes to subsequent clinical management in 12 of 20 patients (60%). CONCLUSIONS: Chest CT can add to the accuracy of intrathoracic diagnosis provided by the CXR and may directly influence the acute management of critically ill children. The CT protocol should be tailored to the clinical and radiologic question posed for each individual patient. Noncontiguous HRCT can often provide accurate assessment of pulmonary parenchymal and pleural disease at a reduced radiation dose compared with helical CT.

The relationship among demographic variables, professionalism, and level of involvement in a state occupational therapy association.

Research on professional occupations has defined varying criteria that an occupation must meet to be considered a profession. Involvement by the members in their professional organization is a recurrent theme. A questionnaire consisting of Hall's Occupational Inventory, an involvement scale, and a demographic survey was used to determine the relationship among three factors of the Indiana Occupational Therapy Association members: (a) demographics, (b) professional attributes, and (c) involvement in a state occupational therapy organization. Determining these relationships is significant for understanding membership and involvement in a state occupational therapy association. Findings indicated significant differences in terms of hourly involvement in a state occupational therapy association between respondents with entry-level and post-professional degrees and respondents who were married and those who were not married.

Reproductive toxicity testing of pharmaceutical compounds to support the inclusion of women in clinical trials.

1. The potential for toxicity to reproduction and the developing fetus is an important concern requiring attention during the development of new medicines. However, there are differences in the opinions of the regulatory authorities in Europe, Japan and the USA regarding the nature and amount of data from reproductive toxicity tests that should be available at the various stages of clinical development. 2. Forty-one companies or their subsidiaries from Europe, Japan and the USA provided data for a questionnaire-based study, carried out in 1994, to ascertain the practices of pharmaceutical companies and their views on an ideal approach to the timing of reproduction and development toxicity studies in relation to clinical investigation. 3. Differences were identified in the stage of drug development at which animal studies were completed, the sequence of completion of specific studies, and the extent of reproduction testing completed to support the inclusion of women in clinical trials. 4. A harmonised, but flexible, guidelines, encompassing the timing of reproductive toxicity studies in relation to clinical trials, would permit better integration between clinical and non-clinical studies in an international drug development programme.

Isolation and structure of leukotriene-A4 hydrolase inhibitor: 8(S)-amino-2(R)-methyl-7-oxononanoic acid produced by Streptomyces diastaticus.

The novel amino acid 8(S)-amino-2(R)-methyl-7-oxononanoic acid (1) was isolated from the soil-borne microorganism Streptomyces diastaticus during our screening for inhibitors of leukotriene-A4 hydrolase (LTA4H), a requisite enzyme in the biosynthesis of the potent inflammatory mediator leukotriene-B4 (LTB4). The structure of 1 was determined by detailed spectroscopic analyses and is related to 7-keto-8-aminopelargonic acid (2), a biosynthetic precursor of biotin. The relative potency of 1 (LTA4H IC50 = 0.6 microM) warranted further biological studies.

A three centre audit of IVU referrals in patients with asymptomatic microscopic haematuria.

There is considerable debate concerning the investigation of patients with asymptomatic microscopic haematuria. Urine dipstick testing is a sensitive screening test but may be positive in some normal individuals. The present consensus is that urine microscopy should be performed to confirm haematuria prior to further investigation. We have performed a retrospective study to establish whether urine microscopy was used in addition to dipstick testing before a request for intravenous urography (IVU) in three centres. IVU request forms from a District General, a Teaching Hospital and a Uroradiological Referral Centre were audited over a 9-month-period. Patients referred with asymptomatic microscopic haematuria were selected. The case notes and urine microscopy results were reviewed. The date of microscopy and its result and the interval between the result and the IVU request were established. One hundred and two cases have been examined, 17 (16.7%) of which were under the age of 40. Only 37 in total had significant haematuria on microscopy and of these, 32 results (31.4% of all cases) were available before the IVU request. In eight patients there was no evidence that urine microscopy had been performed. Fourteen patients had a urinary tract infection. Our findings show that IVUs are often requested on the basis of dipstick testing alone. Only one third of patients had confirmed significant haematuria at the time of IVU request and in some patients infection had not yet been excluded. Although prompt investigation of microscopic haematuria is important, it is essential that the diagnosis is established by microscopy before an IVU is requested.

The timing of preclinical toxicological studies: pharmaceutical company approaches to toxicity testing in support of initial clinical investigations.

The completion of preclinical toxicity studies to support the first administration to humans is a time-critical step in the clinical development of medicines, and is complicated by differences in national regulatory requirements. A questionnaire-based study was carried out in 1994 to ascertain pharmaceutical companies' actual practices and views on an ideal approach to the timing of different types of nonclinical safety studies in relation to clinical investigation. Forty-one companies or their subsidiaries from Europe, Japan, and the United States responded by providing data. A range of preclinical packages were indicated as being used by companies prior to initiating Phase I clinical trials. The selection of studies tended to be based on the recommendations of the regulatory authority of the region in which the respondents were located. Differences were evident regarding the extent of genetic toxicity testing, the duration of repeat-dose toxicity studies, and the need for male fertility testing to support the first single administration of a compound to humans. In an ideal situation, the respondents would have preferred to conduct shorter duration repeat-dose toxicity studies prior to the first single administration to humans than was their actual practice in 1994. A harmonized guideline on the timing of toxicity studies in relation to clinical trials will allow better integration between clinical and nonclinical studies in an international development program. However, the diversity in the responses has demonstrated the need for flexibility in any future guideline.

Chicken lacks the testis specific isozyme of angiotensin converting enzyme found in mammals.

Chicken angiotensin converting enzyme (ACE) cDNA was cloned based on homology to the mouse ACE sequence. The chicken ACE protein is highly homologous to the somatic isozyme of ACE found in human, mouse, bovine, and rabbit. Like the mammalian somatic forms, the chicken enzyme consists of two putative zinc binding sites at the center of two homologous domains. All known functional residues are absolutely conserved. Unlike the mammals, no evidence for a single domain, testis specific form of ACE was found in the chicken testis by either Northern blot or enzyme assay. This result is unexpected since the adult mammalian testis expresses one of the highest tissue levels of ACE.

The quality of student-tutor interactions in the clinical learning environment.

We surveyed 403 students in their clinical years for their perceptions of the quality of clinical clerkships. Between 42.6 and 67.0% of tutorials were said to contain positive factors such as a relaxed teaching atmosphere, enthusiasm, a good selection of patients and adequate preparation. Negative features in 18.2-37.2% of tutorials included unreasonable expectations, conflicting information, late arrival, early departure, failure to show up and the display of anger, a patronizing attitude, favouritism or ridicule. While two-thirds of tutors were regarded as friendly and helpful, the remaining one-third were perceived as unconcerned, discouraging, derogatory or hostile. Overall, only half the clinical tutors were rated as effective teachers; more specifically in medicine and psychiatry, less than one-third of consultants were regarded as effective teachers, as compared with some two-thirds of consultants in obstetrics and gynaecology and paediatrics who were so regarded. Almost two-thirds of the students had predominantly positive reactions to interactions with their tutors, in terms of being motivated to learn, enthused about the subject and having their self-confidence increased. Some one-quarter had negative reactions such as indifference, depression, anger, embarrassment and fearfulness. However, the impact of student-tutor interactions was mainly confined to the students' academic well-being, with little effect on their personal-social lives. Finally, one-third of students had experienced at least some form of mistreatment by their tutors, including gender, appearance, religious and racial discrimination, unfair grading and public humiliation. These findings suggest that the clinical clerkship may not be providing an optimal learning environment for medical students.

The effect of intranasal azelastine, Rhinolast, on nasal airways obstruction and sneezing following provocation testing with histamine and allergen.

The effect of single dose topical nasal therapy with azelastine hydrochloride (azelastine) on the response of nasal airways resistance (NAR) to provocation testing was studied in 36 patients with seasonal allergic rhinitis. Nasal provocation testing (NPT) with histamine or grass pollen was performed after a single dose of azelastine, 0.28 mg to each nostril, or placebo. NAR was assessed by rhinomanometry for 10 hr following NPT. Compared to placebo the NAR response to histamine was inhibited at both 1 and 2 hr following azelastine administration, significant at 1 hr (P less than 0.02) and 2 hr (P less than 0.0001). No such effect was observed in relation to allergen-induced changes in NAR. Azelastine also inhibited numbers of sneezes for up to 10 hr following both histamine NPT (P less than 0.02) and allergen NPT (P less than 0.05), when compared to placebo. Forty-seven per cent of participants experienced bitter or unpleasant taste sensations after azelastine administration but no other unwanted effects were clearly related to azelastine therapy.

Factors relating to the development of respiratory symptoms in coffee process workers.

After several cases of occupational asthma had been reported in a coffee processing factory in England, 197 coffee workers representing 80% of the production workforce were studied to determine the factors affecting the development of work related respiratory symptoms of wheeze, cough, and dyspnoea. Two computer administered questionnaires concerning the presence of respiratory symptoms and the occurrence of work related respiratory symptoms were used. Workers underwent skin prick testing to green coffee bean extract (GCB) and 11 common inhalant allergen extracts and bronchial provocation testing with methacholine. The presence of specific immunoglobulin E (IgE) antibodies to GCB and castor bean extract (CAB) were determined by a radioallergosorbent test (RAST). The prevalence of work related respiratory symptoms was 12.7%, bronchial hyperresponsiveness 30%, atopy 54%, positive GCB skin prick test 14.7%, positive GCB RAST 14%, and positive CAB RAST 14.7%. None of the workers was sensitised to fungi present in the factory and the numbers of certain species of fungi, despite being greater than may be found out of doors or in an uncontaminated indoor environment, were fewer than are generally associated with the presence of work related respiratory symptoms among agricultural workers. Storage mites were not isolated. Green coffee bean extract and CAB RAST were significantly correlated using the McNemar test but there was limited allergenic cross reactivity in RAST inhibition studies of the two extracts. The only factors that were significantly and independently associated with work related symptoms were CAB RAST and duration of employment. Bronchial hyperresponsiveness was not independently associated with work related respiratory symptoms. The significant independent associations of bronchial hyperresponsiveness included GCB RAST, duration of employment, and resting forced expiratory volume in one second. Exposure to CAB, a highly potent antigen, may be overriding the effects of other factors such a GCB, atopy, bronchial hyperresponsiveness, and smoking. This study suggests that CAB contamination remains a potential problem in the coffee processing industry and all efforts to eliminate it from the working environment should continue.

The effects of topical fluticasone propionate on allergen-induced immediate nasal airways response and eosinophil activation: preliminary results.

Nasal application of grass pollen allergen in atopic individuals with seasonal rhinitis leads to an early rise in nasal airways resistance. The effects of fluticasone propionate, a powerful, topically active glucocorticosteroid, on nasal airways resistance and cellular infiltration of the nasal mucous membrane were investigated. Fluticasone propionate blunted the rise in nasal airway resistance following allergen challenge (P = 0.089). Although this glucocorticosteroid did not affect the total number of eosinophils in biopsies of nasal mucous membrane, the number of activated eosinophils was significantly reduced (P less than 0.05).

Bronchial provocation testing of sodium iso-nonanoyl oxybenzene sulphonate.

1. Asthmatic symptoms have been reported in workers following occupational exposure to certain low molecular ratio chemicals. 2. A small number of workers involved in the initial manufacture of a new low temperature bleach activating chemical, sodium iso-nonanoyl oxybenzene sulphonate (SINOS) developed rashes, rhinitis and conjunctivitis following exposure to the compound. One worker also developed asthma. An investigative study was undertaken to examine the possible asthmatic effects of inhaling SINOS in naive non-asthmatic and asthmatic subjects handling the material in the laboratory setting. 3. Since SINOS has a similar chemical structure to aspirin, it was hypothesized that SINOS-associated asthma might be elicited by a mechanism similar to the mechanism associated with aspirin asthma. Therefore aspirin-sensitive asthmatics were also included in the study. 4. No adverse respiratory reactions were observed in the non-asthmatic subjects or in the aspirin and non-aspirin-sensitive patient volunteers following exposure to SINOS dust at atmospheric concentrations of up to 36.3 micrograms m-3. 5. Skin prick tests to increasing concentrations of SINOS were carried out in all subjects. No positive reactions were observed on any occasion. 6. This study indicates that SINOS does not elicit asthma via a mechanism similar to aspirin. Additionally, the study suggests that the addition of SINOS to washing powder will not cause significant respiratory reactions in consumers even if they are asthmatic or intolerant to aspirin.

Examining the needs of youth in secure custody: why we need to "recreate the wheel" in Canadian juvenile justice.

The current study reviews the personal characteristics of 32 consecutive admissions to a secure custody centre in one southwest Ontario jurisdiction under the Young Offenders Act. Results indicated that there was considerable variability amongst the group regarding court history and the seriousness of the charge on which committal was made. Background history data suggested that the problems of youths committed to secure custody reflect considerable difficulties within families and school. The discussion questions whether the youths in this group are better served through the dispositions emphasizing custody-deterrence or rehabilitation-treatment. Implications for young offender policy are also presented.