Creating a therapeutic environment : a non-randomised controlled trial of a quiet time intervention for patients in acute care

Background: Noise is a significant barrier to sleep for acute care hospital patients, and sleep has been shown to be therapeutic for health, healing and recovery. Scheduled quiet time interventions to promote inpatient rest and sleep have been successfully trialled in critical care but not in acute care settings. Objectives: The study aim was to evaluate as cheduled quiet time intervention in an acute care setting. The study measured the effect of a scheduled quiet time on noise levels, inpatients’ rest and sleep behaviour, and wellbeing. The study also examined the impact of the intervention on patients’, visitors’ and health professionals’ satisfaction, and organisational functioning. Design: The study was a multi-centred non-randomised parallel group trial. Settings: The research was conducted in the acute orthopaedic wards of two major urban public hospitals in Brisbane, Australia. Participants: All patientsadmitted to the two wards in the5-month period of the study were invited to participate, withafinalsample of 299 participants recruited. This sample produced an effect size of 0.89 for an increase in the number of patients asleep during the quiet time. Methods: Demographic data were collected to enable comparison between groups. Data for noise level, sleep status, sleepiness and well being were collected using previously validated instruments: a Castle Model 824 digital sound level indicator; a three point sleep status scale; the Epworth Sleepiness Scale; and the SF12 V2 questionnaire. The staff, patient and visitor surveys on the experimental ward were adapted from published instruments. Results: Significant differences were found between the two groups in mean decibel level and numbers of patients awake and asleep. The difference in mean measured noise levels between the two environments corresponded to a ‘perceived’ difference of 2 to 1. There were significant correlations between average decibel level and number of patients awake and asleep in the experimental group, and between average decibel level and number of patients awake in the control group. Overall, patients, visitors and health professionals were satisfied with the quiet time intervention. Conclusions: The findings show that a quiet time intervention on an acute care hospital ward can affect noise level and patient sleep/wake patterns during the intervention period. The overall strongly positive response from surveys suggests that scheduled quiet time would be a positively perceived intervention with therapeutic benefit.

Measuring the effect of patient comfort rounds on practice environment and patient satisfaction : A pilot study

Hourly rounding in the acute hospital setting has been proposed as an intervention to increase patient satisfaction and safety, and improve the nursing practice environment, but the innovation has not been adequately tested. A quasiexperimental pretest post-test non-randomized parallel group trial design was used to test the effect of hourly patient comfort rounds on patient satisfaction and nursing perceptions of the practice environment, and to evaluate research processes and instruments for a proposed larger study. A Patient Satisfaction Survey instrument was developed and used in conjunction with the Practice Environment Scale of the Nursing Work Index. Results on patient satisfaction showed no significant changes. Significant changes were found for three of the five practice environment subscales. Consistent with the aim of a pilot study, this research has provided important information related to design, instruments and process that will inform a larger sufficiently powered study.

Antibiotics for bronchiectasis exacerbations in children: rationale and study protocol for a randomised placebo-controlled trial

Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. Methods We are conducting a bronchiectasis exacerbation study (BEST), which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland). In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed) to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily) with placebo-azithromycin; azithromycin (5 mg/kg daily) with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. Discussion Effective, evidence-based management of exacerbations in people with bronchiectasis is clinically important. Yet, there are few randomised controlled trials (RCTs) in the neglected area of non-cystic fibrosis bronchiectasis. Indeed, no published RCTs addressing the treatment of bronchiectasis exacerbations in children exist. Our multicentre, double-blind RCT is designed to determine if azithromycin and amoxicillin-clavulanic acid, compared with placebo, improve symptom resolution on day 14 in children with acute respiratory exacerbations. Our planned assessment of the predictors of antibiotic response, the role of antibiotic-resistant respiratory pathogens, and whether early treatment with antibiotics affects duration and time to the next exacerbation, are also all novel.

Bronchiectasis exacerbation study on azithromycin and amoxycillin-clavulanate for respiratory exacerbations in children (BEST-2) : study protocol for a randomized controlled trial

Background Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. Methods This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood inflammatory markers will be reported where available. Discussion Currently, there are no published randomized controlled trials (RCT) to underpin effective, evidence-based management of acute respiratory exacerbations in children with non-CF bronchiectasis. To help address this information gap, we are conducting two RCTs. The first (bronchiectasis exacerbation study; BEST-1) evaluates the efficacy of azithromycin and amoxycillin-clavulanate compared with placebo, and the second RCT (BEST-2), described here, is designed to determine if azithromycin is non-inferior to amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in children with acute respiratory exacerbations. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12612000010897. http://www.anzctr.org.au/trial_view.aspx?id=347879

Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis : protocol for a randomised controlled trial

Background Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. Methods A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW(135)) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and >= 6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged >= 6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine-related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged >= 6 years; and vaccine safety. Discussion As H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis.

Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study) : a multicentre, double-blind, randomised controlled trial

Background Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. Methods Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori, and Pacific Island children aged 1—8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. Eligible children had had at least one pulmonary exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by computer-generated sequence with permuted block design, stratified by study site and exacerbation frequency [1—2 vs ≥3 episodes in the preceding 12 months]) to receive either azithromycin (30 mg/kg) or placebo once a week for up to 24 months. Allocation concealment was achieved by double-sealed, opaque envelopes; participants, caregivers, and study personnel were masked to assignment until after data analysis. The primary outcome was exacerbation (respiratory episodes treated with antibiotics) rate. Analysis of the primary endpoint was by intention to treat. At enrolment and at their final clinic visits, children had deep nasal swabs collected, which we analysed for antibiotic-resistant bacteria. This study is registered with the Australian New Zealand Clinical Trials Registry; ACTRN12610000383066. Findings 45 children were assigned to azithromycin and 44 to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011, thus children received the intervention for 12—24 months. The mean treatment duration was 20·7 months (SD 5·7), with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group. Compared with the placebo group, children receiving azithromycin had significantly lower exacerbation rates (incidence rate ratio 0·50; 95% CI 0·35—0·71; p<0·0001). However, children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving placebo (four of 37, 11%; p=0·002). The most common adverse events were non-pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group) and bronchiectasis-related events (episodes or investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group); however, study drugs were well tolerated with no serious adverse events being attributed to the intervention. Interpretation Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. However, this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria, the clinical consequences of which are uncertain, and will need careful monitoring and further study.

Telephone-delivered health coaching improves anxiety outcomes after myocardial infarction: The 'ProActive Heart' trial

Background: Recently, we found a telephone-delivered secondary prevention programme using health coaching (‘ProActive Heart’) to be effective in improving a range of key behavioural outcomes for myocardial infarction (MI) patients. What remains unclear, however, is the extent to which these treatment effects translate to important psychological outcomes such as depression and anxiety outcomes, an issue of clinical significance due to the substantial proportion of MI patients who experience depression and anxiety. The objective of the study was to investigate, as a secondary hypothesis of a larger trial, the effects of a telephone-delivered health coaching programme on depression and anxiety outcomes of MI patients. Design: Two-arm, parallel-group, randomized, controlled design with six-months outcomes. Methods: Patients admitted to one of two tertiary hospitals in Brisbane, Australia following MI were assessed for eligibility. Four hundred and thirty patients were recruited and randomly assigned to usual care or an intervention group comprising up to 10 telephone-delivered ‘health coaching’ sessions (ProActive Heart). Regression analysis compared Hospital Anxiety and Depression Scale scores of completing participants at six months (intervention: n = 141 versus usual care: n = 156). Results: The intervention yielded reductions in anxiety at follow-up (mean difference = −0.7, 95% confidence interval=−1.4,−0.02) compared with usual care. A similar pattern was observed in mean depression scores but was not statistically significant. Conclusions: The ProActive Heart programme effectively improves anxiety outcomes of patients following myocardial infarction. If combined with psychological-specific treatment, this programme could impact anxiety of greater intensity in a clinically meaningful way.

Effects of resistance training on measures of muscular strength in people with Parkinson’s disease: A systematic review and meta-analysis

Objective The aim of this systematic review and meta-analysis was to determine the overall effect of resistance training (RT) on measures of muscular strength in people with Parkinson’s disease (PD). Methods Controlled trials with parallel-group-design were identified from computerized literature searching and citation tracking performed until August 2014. Two reviewers independently screened for eligibility and assessed the quality of the studies using the Cochrane risk-of-bias-tool. For each study, mean differences (MD) or standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for continuous outcomes based on between-group comparisons using post-intervention data. Subgroup analysis was conducted based on differences in study design. Results Nine studies met the inclusion criteria; all had a moderate to high risk of bias. Pooled data showed that knee extension, knee flexion and leg press strength were significantly greater in PD patients who undertook RT compared to control groups with or without interventions. Subgroups were: RT vs. control-without-intervention, RT vs. control-with-intervention, RT-with-other-form-of-exercise vs. control-without-intervention, RT-with-other-form-of-exercise vs. control-with-intervention. Pooled subgroup analysis showed that RT combined with aerobic/balance/stretching exercise resulted in significantly greater knee extension, knee flexion and leg press strength compared with no-intervention. Compared to treadmill or balance exercise it resulted in greater knee flexion, but not knee extension or leg press strength. RT alone resulted in greater knee extension and flexion strength compared to stretching, but not in greater leg press strength compared to no-intervention. Discussion Overall, the current evidence suggests that exercise interventions that contain RT may be effective in improving muscular strength in people with PD compared with no exercise. However, depending on muscle group and/or training dose, RT may not be superior to other exercise types. Interventions which combine RT with other exercise may be most effective. Findings should be interpreted with caution due to the relatively high risk of bias of most studies.

Whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults

Background Recovery strategies are often usedwith the intention of preventing orminimisingmuscle soreness after exercise. Whole-body cryotherapy, which involves a single or repeated exposure(s) to extremely cold dry air (below -100 °C) in a specialised chamber or cabin for two to four minutes per exposure, is currently being advocated as an effective intervention to reduce muscle soreness after exercise. Objectives To assess the effects (benefits and harms) of whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, the British Nursing Index and the Physiotherapy Evidence Database. We also searched the reference lists of articles, trial registers and conference proceedings, handsearched journals and contacted experts. The searches were run in August 2015. Selection criteria We aimed to include randomised and quasi-randomised trials that compared the use of whole-body cryotherapy (WBC) versus a passive or control intervention (rest, no treatment or placebo treatment) or active interventions including cold or contrast water immersion, active recovery and infrared therapy for preventing or treating muscle soreness after exercise in adults. We also aimed to include randomised trials that compared different durations or dosages of WBC. Our prespecified primary outcomes were muscle soreness, subjective recovery (e.g. tiredness, well-being) and adverse effects. Data collection and analysis Two review authors independently screened search results, selected studies, assessed risk of bias and extracted and cross-checked data. Where appropriate, we pooled results of comparable trials. The random-effects model was used for pooling where there was substantial heterogeneity.We assessed the quality of the evidence using GRADE. Main results Four laboratory-based randomised controlled trials were included. These reported results for 64 physically active predominantly young adults (mean age 23 years). All but four participants were male. Two trials were parallel group trials (44 participants) and two were cross-over trials (20 participants). The trials were heterogeneous, including the type, temperature, duration and frequency of WBC, and the type of preceding exercise. None of the trials reported active surveillance of predefined adverse events. All four trials had design features that carried a high risk of bias, potentially limiting the reliability of their findings. The evidence for all outcomes was classified as ’very low’ quality based on the GRADE criteria. Two comparisons were tested: WBC versus control (rest or no WBC), tested in four studies; and WBC versus far-infrared therapy, also tested in one study. No studies compared WBC with other active interventions, such as cold water immersion, or different types and applications of WBC. All four trials compared WBC with rest or no WBC. There was very low quality evidence for lower self-reported muscle soreness (pain at rest) scores after WBC at 1 hour (standardised mean difference (SMD) -0.77, 95% confidence interval (CI) -1.42 to -0.12; 20 participants, 2 cross-over trials); 24 hours (SMD -0.57, 95%CI -1.48 to 0.33) and 48 hours (SMD -0.58, 95% CI -1.37 to 0.21), both with 38 participants, 2 cross-over studies, 1 parallel group study; and 72 hours (SMD -0.65, 95% CI -2.54 to 1.24; 29 participants, 1 cross-over study, 1 parallel group study). Of note is that the 95% CIs also included either no between-group differences or a benefit in favour of the control group. One small cross-over trial (9 participants) found no difference in tiredness but better well-being after WBC at 24 hours post exercise. There was no report of adverse events. One small cross-over trial involving nine well-trained runners provided very low quality evidence of lower levels of muscle soreness after WBC, when compared with infrared therapy, at 1 hour follow-up, but not at 24 or 48 hours. The same trial found no difference in well-being but less tiredness after WBC at 24 hours post exercise. There was no report of adverse events. Authors’ conclusions There is insufficient evidence to determine whether whole-body cryotherapy (WBC) reduces self-reportedmuscle soreness, or improves subjective recovery, after exercise compared with passive rest or no WBC in physically active young adult males. There is no evidence on the use of this intervention in females or elite athletes. The lack of evidence on adverse events is important given that the exposure to extreme temperature presents a potential hazard. Further high-quality, well-reported research in this area is required and must provide detailed reporting of adverse events.

Clinical pathways for chronic cough in children

Background Chronic cough (a cough lasting longer than four weeks) is a common problem internationally. Chronic cough has associated economic costs and is distressing to the child and to parents; ignoring cough may lead to delayed diagnosis and progression of serious underlying respiratory disease. Clinical guidelines have been shown to lead to efficient and effective patient care and can facilitate clinical decision making. Cough guidelines have been designed to facilitate the management of chronic cough. However, treatment recommendations vary, and specific clinical pathways for the treatment of chronic cough in children are important, as causes of and treatments for cough vary significantly from those in adults. Therefore, systematic evaluation of the use of evidence-based clinical pathways for the management of chronic cough in children would be beneficial for clinical practice and for patient care. Use of a management algorithm can improve clinical outcomes; such management guidelines can be found in the guidelines for cough provided by the American College of Chest Physicians (ACCP) and the British Thoracic Society (BTS). Objectives To evaluate the effectiveness of using a clinical pathway in the management of children with chronic cough. Search methods The Cochrane Register of Controlled Trials (CENTRAL), the Cochrane Airways Group Specialised Register, MEDLINE, EMBASE, review articles and reference lists of re levant articles were searched. The latest search was conducted in January 2014. Selection criteria All randomised controlled trials of parallel-group design comparing use versus non-use of a clinical pathway for treatment of chronic cough in children (< 18 years of age). Data collection and analysis Results of searches were reviewed against predetermined cr iteria for inclusion. Two review authors independently selected studies and performed data extraction in duplicate. Main results One study was included in the review. This multi-centre trial was based in five Australian hospitals and recruited 272 children with chronic cough. Children were randomly assigned to early (two weeks) or delayed (six weeks) referral to respiratory specialists who used a cough management pathway. When an intention-to-treat analysis was performed, clinical failure at six wee ks post randomisation (defined as < 75% improvement in cough score, or total resolution for fewer than three consecutive days) was significantly less in the early pathway arm compared with the control arm (odds ratio (OR) 0.35, 95% confidence interval (CI) 0.21 to 0.58). These results indicate that one additional child will be cured for e very five children treated via th e cough pathway (number needed to treat for an additional beneficial outcome (NNTB) = 5, 95% CI 3 to 9) at six weeks. Cough-specific parent-reported quality of life scores were significantly better in th e early-pathway group; the mean difference (MD) between groups was 0.60 (95% CI 0.19 to 1.01). Duration of cough post randomisation was significantly shorter in the intervention group (early-pathway arm) compared with the control group (delayed-pathway arm) (MD -2.70 weeks, 95% CI -4.26 to -1.14). Authors’ conclusions. Current evidence suggests that using a clinical algorithm for the management of children with ch r onic cough in h ospital outpatient settings is more effective than providing wait-list care. Futher high-quality randomised controlled trials are needed to perform ongoing evaluation of cough management pathways in general practitioner and other primary care settings.

A 2-hour diagnostic protocol for possible cardiac chest pain in the emergency department: A randomized clinical trial

IMPORTANCE Patients with chest pain represent a high health care burden, but it may be possible to identify a patient group with a low short-term risk of adverse cardiac events who are suitable for early discharge. OBJECTIVE To compare the effectiveness of a rapid diagnostic pathway with a standard-care diagnostic pathway for the assessment of patients with possible cardiac chest pain in a usual clinical practice setting. DESIGN, SETTING, AND PARTICIPANTS A single-center, randomized parallel-group trial with blinded outcome assessments was conducted in an academic general and tertiary hospital. Participants included adults with acute chest pain consistent with acute coronary syndrome for whom the attending physician planned further observation and troponin testing. Patient recruitment occurred from October 11, 2010, to July 4, 2012, with a 30-day follow-up. INTERVENTIONS An experimental pathway using an accelerated diagnostic protocol (Thrombolysis in Myocardial Infarction score, 0; electrocardiography; and 0- and 2-hour troponin tests) or a standard-care pathway (troponin test on arrival at hospital, prolonged observation, and a second troponin test 6-12 hours after onset of pain) serving as the control. MAIN OUTCOMES AND MEASURES Discharge from the hospital within 6 hours without a major adverse cardiac event occurring within 30 days. RESULTS Fifty-two of 270 patients in the experimental group were successfully discharged within 6 hours compared with 30 of 272 patients in the control group (19.3% vs 11.0%; odds ratio, 1.92; 95% CI, 1.18-3.13; P = .008). It required 20 hours to discharge the same proportion of patients from the control group as achieved in the experimental group within 6 hours. In the experimental group, 35 additional patients (12.9%) were classified as low risk but admitted to an inpatient ward for cardiac investigation. None of the 35 patients received a diagnosis of acute coronary syndrome after inpatient evaluation. CONCLUSIONS AND RELEVANCE Using the accelerated diagnostic protocol in the experimental pathway almost doubled the proportion of patients with chest pain discharged early. Clinicians could discharge approximately 1 of 5 patients with chest pain to outpatient follow-up monitoring in less than 6 hours. This diagnostic strategy could be easily replicated in other centers because no extra resources are required.

Cognitive assessment in closed head injury : stability, validity and parallel forms for two neuropsychological measures of recovery

Investigated the psychometric properties of the original and alternate sets of the Trail Making Test (TMT) and the Controlled Oral Word Association Test (COWAT; A. L. Benton and D. Hamsher, 1978) in 50 orthopedic and 15 closed head injured (1 yr after trauma) patients (aged 15–59 yrs). Although the alternate forms of both measures proved to be stable and consistent with each other in both groups, only the parallel sets of TMT reliably discriminated the clinical group from controls. Practice effects in the head injured were significant only for Trail B of TMT. Factor analysis of the control group's results identified Verbal Knowledge as a major contributor to performance on COWAT, whereas TMT was more dependent on Rapid Visual Search and Visuomotor Sequencing.

Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes

Endometrial carcinoma is the most common gynecological malignancy in the United States. Although most women present with early disease confined to the uterus, the majority of persistent or recurrent tumors are refractory to current chemotherapies. We have identified a total of 11 different FGFR2 mutations in 3/10 (30%) of endometrial cell lines and 19/187 (10%) of primary uterine tumors. Mutations were seen primarily in tumors of the endometrioid histologic subtype (18/115 cases investigated, 16%). The majority of the somatic mutations identified were identical to germline activating mutations in FGFR2 and FGFR3 that cause Apert Syndrome, Beare-Stevenson Syndrome, hypochondroplasia, achondroplasia and SADDAN syndrome. The two most common somatic mutations identified were S252W (in eight tumors) and N550K (in five samples). Four novel mutations were identified, three of which are also likely to result in receptor gain-of-function. Extensive functional analyses have already been performed on many of these mutations, demonstrating they result in receptor activation through a variety of mechanisms. The discovery of activating FGFR2 mutations in endometrial carcinoma raises the possibility of employing anti-FGFR molecularly targeted therapies in patients with advanced or recurrent endometrial carcinoma.

Validity and use of the UV index : Report from the UVI working group, Schloss Hohenkammer, Germany, 5-7 December 2011

The adequacy of the UV Index (UVI), a simple measure of ambient solar ultraviolet (UV) radiation, has been questioned on the basis of recent scientific data on the importance of vitamin D for human health, the mutagenic capacity of radiation in the UVA wavelength, and limitations in the behavioral impact of the UVI as a public awareness tool. A working group convened by ICNIRP and WHO met to assess whether modifications of the UVI were warranted and to discuss ways of improving its effectiveness as a guide to healthy sun-protective behavior. A UV Index greater than 3 was confirmed as indicating ambient UV levels at which harmful sun exposure and sunburns could occur and hence as the threshold for promoting preventive messages. There is currently insufficient evidence about the quantitative relationship of sun exposure, vitamin D, and human health to include vitamin D considerations in sun protection recommendations. The role of UVA in sunlight-induced dermal immunosuppression and DNA damage was acknowledged, but the contribution of UVA to skin carcinogenesis could not be quantified precisely. As ambient UVA and UVB levels mostly vary in parallel in real life situations, any minor modification of the UVI weighting function with respect to UVA-induced skin cancer would not be expected to have a significant impact on the UV Index. Though it has been shown that the UV Index can raise awareness of the risk of UV radiation to some extent, the UVI does not appear to change attitudes to sun protection or behavior in the way it is presently used. Changes in the UVI itself were not warranted based on these findings, but rather research testing health behavior models, including the roles of self-efficacy and self-affirmation in relation to intention to use sun protection among different susceptible groups, should be carried out to develop more successful strategies toward improving sun protection behavior. Health Phys. 103(3):301-306; 2012

Amino group position dependent orientation of self-assembled monomolecular films of tetraaminophthalocyanatocobalt(II) on Au surfaces

Self-assembled monomolecular films of 1,8,15,22-tetraaminophthalocyanatocobalt(II) (4α-CoIITAPc) and 2,9,16,23-tetraaminophthalocyanatocobalt(II) (4β-CoIITAPc) on Au surfaces were prepared by spontaneous adsorption from solution. These films were characterized by cyclic voltammetry and Raman spectroscopy. Both the surface coverage (Γ) and intensity of the in-plane stretching bands obtained from Raman studies vary for these monomolecular films, indicating different orientations adopted by them on Au surfaces. The 4α-CoIITAPc-modified electrode exhibits an E1/2 of 0.35 V, while the 4β-CoIITAPc-modified electrode exhibits an E1/2 of 0.19 V, corresponding to the CoII/CoIII redox couple in 0.1 M H2SO4. The Γ estimated from the charge associated with the oxidation of Co(II) gives (2.62 ± 0.10) × 10-11 mol cm-2 for 4α-CoIITAPc and (3.43 ± 0.14) × 10-10 mol cm-2 for 4β-CoIITAPc. In Raman spectral studies, the intensity ratio between in-plane phthalocyanine (Pc) stretching and the Au−N stretching was found to be 6.6 for 4β-CoIITAPc, while it was 1.6 for 4α-CoIITAPc. The obtained lower Γ and intensity ratio values suggest that 4α-CoIITAPc adopts nearly a parallel orientation on the Au surface, while the higher Γ and intensity ratio values suggest that 4β-CoIITAPc adopts a perpendicular orientation. The electrochemical reduction of dioxygen was carried out using these differently oriented Pc's in phosphate buffer solution (pH 7.2). Both the Pc's catalyze the reduction of dioxygen; however, the 4α-CoIITAPc-modified electrode greatly reduces the dioxygen reduction overpotential compared to 4β-CoIITAPc-modified and bare Au electrodes.