Fasting increases serum bilirubin levels in clinically normal, healthy males but not females : a retrospective study from phase I clinical trial participants

Aim: To examine if fasting affects serum bilirubin levels in clinical healthy males and females. Methods: We utilised retrospective data from phase 1 clinical trials where blood was collected in either a fed or fasting state at screening and pre-dosing time points and analysed for total bilirubin levels as per standard clinical procedures. Participants were clinically healthy males (n = 105) or females (n = 30) aged 18 to 48 inclusive who participated in a phase 1 clinical trial in 2012 or 2013. Results: We found a statistically significant increase in total serum bilirubin levels in fasting males as compared to non-fasting males. The fasting time correlated positively with increased bilirubin levels. The age of the healthy males did not correlate with their fasting bilirubin level. We found no correlation between fasting and bilirubin levels in clinically normal females. Conclusions: The recruitment and screening of volunteers for a clinical trial is a time-consuming and expensive process. This study clearly demonstrates that testing for serum bilirubin should be conducted on non-fasting male subjects. If fasting is required, then participants should not be excluded from a trial based on an elevated serum bilirubin that is deemed non-clinically significant.

Web based surveillance systems could improve disease detection and the response to emerging disease events

The Chinese government should be commended for its open, concerted, and rapid response to the recent H7N9 influenza outbreak. However, the first known case was not reported until 48 days after disease onset.1 Although the difficulties in detecting the virus and the lack of suitable diagnostic methods have been the focus of discussion,2 systematic limitations that may have contributed to this delay have hardly been discussed. The detection speed of surveillance systems is limited by the highly structured nature of information flow and hierarchical organisation of these systems. Flu surveillance usually relies on notification to a central authority of laboratory confirmed cases or presentations to sentinel practices for flu-like illness. Each step in this pathway presents a bottleneck at which information and time can be lost; this limitation must be dealt with...

Extreme temperatures and paediatric emergency department admissions

Background Children are particularly vulnerable to the effects of extreme temperatures. Objective To examine the relationship between extreme temperatures and paediatric emergency department admissions (EDAs) in Brisbane, Australia, during 2003–2009. Methods A quasi-Poisson generalised linear model combined with a distributed lag non-linear model was used to examine the relationships between extreme temperatures and age-, gender- and cause-specific paediatric EDAs, while controlling for air pollution, relative humidity, day of the week, influenza epidemics, public holiday, season and long-term trends. The model residuals were checked to identify whether there was an added effect due to heat waves or cold spells. Results There were 131 249 EDAs among children during the study period. Both high (RR=1.27; 95% CI 1.12 to 1.44) and low (RR=1.81; 95% CI 1.66 to 1.97) temperatures were significantly associated with an increase in paediatric EDAs in Brisbane. Male children were more vulnerable to temperature effects. Children aged 0–4 years were more vulnerable to heat effects and children aged 10–14 years were more sensitive to both hot and cold effects. High temperatures had a significant impact on several paediatric diseases, including intestinal infectious diseases, respiratory diseases, endocrine, nutritional and metabolic diseases, nervous system diseases and chronic lower respiratory diseases. Low temperatures were significantly associated with intestinal infectious diseases, respiratory diseases and endocrine, nutritional and metabolic diseases. An added effect of heat waves on childhood chronic lower respiratory diseases was seen, but no added effect of cold spells was found. Conclusions As climate change continues, children are at particular risk of a variety of diseases which might be triggered by extremely high temperatures. This study suggests that preventing the effects of extreme temperature on children with respiratory diseases might reduce the number of EDAs.

Control strategies to prevent total hip replacement-related infections : a systematic review and mixed treatment comparison

OBJECTIVE: To synthesise the available evidence and estimate the comparative efficacy of control strategies to prevent total hip replacement (THR)-related surgical site infections (SSIs) using a mixed treatment comparison. DESIGN: Systematic review and mixed treatment comparison. SETTING: Hospital and other healthcare settings. PARTICIPANTS: Patients undergoing THR. PRIMARY AND SECONDARY OUTCOME MEASURES: The number of THR-related SSIs occurring following the surgical operation. RESULTS: 12 studies involving 123 788 THRs and 9 infection control strategies were identified. The strategy of 'systemic antibiotics+antibiotic-impregnated cement+conventional ventilation' significantly reduced the risk of THR-related SSI compared with the referent strategy (no systemic antibiotics+plain cement+conventional ventilation), OR 0.13 (95% credible interval (CrI) 0.03-0.35), and had the highest probability (47-64%) and highest median rank of being the most effective strategy. There was some evidence to suggest that 'systemic antibiotics+antibiotic-impregnated cement+laminar airflow' could potentially increase infection risk compared with 'systemic antibiotics+antibiotic-impregnated cement+conventional ventilation', 1.96 (95% CrI 0.52-5.37). There was no high-quality evidence that antibiotic-impregnated cement without systemic antibiotic prophylaxis was effective in reducing infection compared with plain cement with systemic antibiotics, 1.28 (95% CrI 0.38-3.38). CONCLUSIONS: We found no convincing evidence in favour of the use of laminar airflow over conventional ventilation for prevention of THR-related SSIs, yet laminar airflow is costly and widely used. Antibiotic-impregnated cement without systemic antibiotics may not be effective in reducing THR-related SSIs. The combination with the highest confidence for reducing SSIs was 'systemic antibiotics+antibiotic-impregnated cement+conventional ventilation'. Our evidence synthesis underscores the need to review current guidelines based on the available evidence, and to conduct further high-quality double-blind randomised controlled trials to better inform the current clinical guidelines and practice for prevention of THR-related SSIs.

Circles of care : should community development redefine the practice of palliative care?

Specialist palliative care, within hospices in particular, has historically led and set the standard for caring for patients at end of life. The focus of this care has been mostly for patients with cancer. More recently, health and social care services have been developing equality of care for all patients approaching end of life. This has mostly been done in the context of a service delivery approach to care whereby services have become increasingly expert in identifying health and social care need and meeting this need with professional services. This model of patient centred care, with the impeccable assessment and treatment of physical, social, psychological and spiritual need, predominantly worked very well for the latter part of the 20th century. Over the last 13 years, however, there have been several international examples of community development approaches to end of life care. The patient centred model of care has limitations when there is a fundamental lack of integrated community policy, development and resourcing. Within this article, we propose a model of care which identifies a person with an illness at the centre of a network which includes inner and outer networks, communities and service delivery organisations. All of these are underpinned by policy development, supporting the overall structure. Adoption of this model would allow individuals, communities, service delivery organisations and policy makers to work together to provide end of life care that enhances value and meaning for people at end of life, both patients and communities alike.

Psychological predictors of injury among elite athletes

Objectives: To establish injury rates among a population of elite athletes, to provide normative data for psychological variables hypothesised to be predictive of sport injuries, and to establish relations between measures of mood, perceived life stress, and injury characteristics as a precursor to introducing a psychological intervention to ameliorate the injury problem. Methods: As part of annual screening procedures, athletes at the Queensland Academy of Sport report medical and psychological status. Data from 845 screenings (433 female and 412 male athletes) were reviewed. Population specific tables of normative data were established for the Brunel mood scale and the perceived stress scale. Results: About 67% of athletes were injured each year, and about 18% were injured at the time of screening. Fifty percent of variance in stress scores could be predicted from mood scores, especially for vigour, depression, and tension. Mood and stress scores collectively had significant utility in predicting injury characteristics. Injury status (current, healed, no injury) was correctly classified with 39% accuracy, and back pain with 48% accuracy. Among a subset of 233 uninjured athletes (116 female and 117 male), five mood dimensions (anger, confusion, fatigue, tension, depression) were significantly related to orthopaedic incidents over the preceding 12 months, with each mood dimension explaining 6–7% of the variance. No sex differences in these relations were found. Conclusions: The findings support suggestions that psychological measures have utility in predicting athletic injury, although the relatively modest explained variance highlights the need to also include underlying physiological indicators of allostatic load, such as stress hormones, in predictive models.

The impact of funding deadlines on personal workloads, stress and family relationships : a qualitative study of Australian researchers

Objective To examine the impact of applying for funding on personal workloads, stress and family relationships. Design Qualitative study of researchers preparing grant proposals. Setting Web-based survey on applying for the annual National Health and Medical Research Council (NHMRC) Project Grant scheme. Participants Australian researchers (n=215). Results Almost all agreed that preparing their proposals always took top priority over other work (97%) and personal (87%) commitments. Almost all researchers agreed that they became stressed by the workload (93%) and restricted their holidays during the grant writing season (88%). Most researchers agreed that they submitted proposals because chance is involved in being successful (75%), due to performance requirements at their institution (60%) and pressure from their colleagues to submit proposals (53%). Almost all researchers supported changes to the current processes to submit proposals (95%) and peer review (90%). Most researchers (59%) provided extensive comments on the impact of writing proposals on their work life and home life. Six major work life themes were: (1) top priority; (2) career development; (3) stress at work; (4) benefits at work; (5) time spent at work and (6) pressure from colleagues. Six major home life themes were: (1) restricting family holidays; (2) time spent on work at home; (3) impact on children; (4) stress at home; (5) impact on family and friends and (6) impact on partner. Additional impacts on the mental health and well-being of researchers were identified. Conclusions The process of preparing grant proposals for a single annual deadline is stressful, time consuming and conflicts with family responsibilities. The timing of the funding cycle could be shifted to minimise applicant burden, give Australian researchers more time to work on actual research and to be with their families.

The comparative behaviour of two combat boots under impact

Background Improvised explosive devices have become the characteristic weapon of conflicts in Iraq and Afghanistan. While little can be done to mitigate against the effects of blast in free-field explosions, scaled blast simulations have shown that the combat boot can attenuate the effects on the vehicle occupants of anti-vehicular mine blasts. Although the combat boot offers some protection to the lower limb, its behaviour at the energies seen in anti-vehicular mine blast has not been documented previously. Methods The sole of eight same-size combat boots from two brands currently used by UK troops deployed to Iraq and Afghanistan were impacted at energies of up to 518 J, using a spring-assisted drop rig. Results The results showed that the Meindl Desert Fox combat boot consistently experienced a lower peak force at lower impact energies and a longer time-to-peak force at higher impact energies when compared with the Lowa Desert Fox combat boot. Discussion This reduction in the peak force and extended rise time, resulting in a lower energy transfer rate, is a potentially positive mitigating effect in terms of the trauma experienced by the lower limb. Conclusion Currently, combat boots are tested under impact at the energies seen during heel strike in running. Through the identification of significantly different behaviours at high loading, this study has shown that there is rationale in adding the performance of combat boots under impact at energies above those set out in international standards to the list of criteria for the selection of a combat boot.

Exposure to ambient heat and urolithiasis among outdoor workers in Guangzhou, China

Objectives: To assess the impact of exposure to ambient heat on urolithiasis among outdoor workers in a subtropical city of China. Methods: The 2003–2010 health check data of a shipbuilding company in Guangzhou, China were acquired. 190 cases and 760 matched controls were involved in this study. We assessed the relationship between exposure to ambient heat and urolithiasis for different occupations using conditional logistic regression. Results: Spray painters were most likely to develop urolithiasis (OR = 4.4; 95% CI: 1.7, 11.4), followed by smelter workers (OR = 4.0; 95% CI: 1.8, 9.2), welders (OR = 3.7; 95% CI: 1.9, 7.2), production security and quality inspectors (OR = 2.7; 95% CI: 1.4, 3.0), and assemblers (OR = 2.2; 95% CI: 1.1, 4.3). Overall, outdoor workers were more likely to present with urolithiasis compared with indoor employees (p b 0.05). In addition, workers with longer cumulative exposure time (OR = 1.5; 95% CI: 1.2, 1.8) and abnormal blood pressure (OR = 1.6; 95% CI: 1.0, 2.5) had higher risk for urolithiasis. Conclusions: Our findings demonstrate a significant association between exposure to ambient heat and urolithiasis among outdoor working populations. Public health intervention strategies should be developed to specifically target outdoor occupations.

An objective study of acid reflux and cough in children using an ambulatory pHmetry-cough logger

Objective There are no objective ambulatory studies on the temporal relationship between reflux and cough in children. Commercial pHmetry loggers have slow capture rates (0.25 Hz) that limit objective quantification of reflux and cough. The authors aimed to evaluate if there is a temporal association between cough and acid pH in ambulatory children with chronic cough. setting and patients The authors studied children (aged <14 years) with chronic cough, suspected of acid reflux and considered for pHmetry using a specifically built ambulatory pHmetry–cough logger that enabled the simultaneous ambulatory recording of cough and pH with a fast (10 Hz) capture rate. Main outcome measures Coughs within (before and after) 10, 30, 60 and 120 s of a reflux episode (pH<4 for >0.5 s). Results Analysis of 5628 coughs in 20 children. Most coughs (83.9%) were independent of a reflux event. Cough–reflux (median 19, IQR 3–45) and reflux–cough (24.5, 13–51) sequences were equally likely to occur within 120 s. Within the 10 and 30 s time frame, reflux–cough (10 s=median 2.5, IQR 0–7.25; 30 s=6.5, 1.25–22.25) sequences were significantly less frequent than reflux–no cough (10 s=27, IQR 15–65; 30 s=24.5, 14.5–55.5) sequences, (p=0.0001 and p=0.001, respectively). No differences were found for 60 and 120 s time frame. Cough–reflux sequence (median 1.0, IQR 0–8) within 10 s was significantly less (p=0.0001) than no cough–reflux sequences (median 29.5, 15–67), within 30 s (p=0.006) and 60 s (p=0.048) but not within 120 s (p=0.47). Conclusions In children with chronic cough and suspected of having gastro-oesophageal reflux disease, the temporal relationship between acid reflux and cough is unlikely causal.

Validation of a parent-proxy quality of life questionnaire for paediatric chronic cough (PC-QOL)

Background Quality of life (QOL) measures are an important patient-relevant outcome measure for clinical studies. Currently there is no fully validated cough-specific QOL measure for paediatrics. The objective of this study was to validate a cough-specific QOL questionnaire for paediatric use. Method 43 children (28 males, 15 females; median age 29 months, IQR 20–41 months) newly referred for chronic cough participated. One parent of each child completed the 27-item Parent Cough-Specific QOL questionnaire (PC-QOL), and the generic child (Pediatric QOL Inventory 4.0 (PedsQL)) and parent QOL questionnaires (SF-12) and two cough-related measures (visual analogue score and verbal category descriptive score) on two occasions separated by 2–3 weeks. Cough counts were also objectively measured on both occasions. Results Internal consistency for both the domains and total PC-QOL at both test times was excellent (Cronbach alpha range 0.70–0.97). Evidence for repeatability and criterion validity was established, with significant correlations over time and significant relationships with the cough measures. The PC-QOL was sensitive to change across the test times and these changes were significantly related to changes in cough measures (PC-QOL with: verbal category descriptive score, rs=−0.37, p=0.016; visual analogue score, rs=−0.47, p=0.003). Significant correlations of the difference scores for the social domain of the PC-QOL and the domain and total scores of the PedsQL were also noted (rs=0.46, p=0.034). Conclusion The PC-QOL is a reliable and valid outcome measure that assesses QOL related to childhood cough at a given time point and measures changes in cough-specific QOL over time.

A systematic review and meta-analysis : tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils)

Asthma severity and control can be measured both subjectively and objectively. Traditionally asthma treatments have been individualised using symptoms and spirometry/peak flow. Increasingly treatment tailored in accordance with inflammatory markers (sputum eosinophil counts or fractional exhaled nitric oxide (FeNO) data) is advocated as an alternative strategy. The objective of this review was to evaluate the efficacy of tailoring asthma interventions based on inflammatory markers (sputum analysis and FeNO) in comparison with clinical symptoms (with or without spirometry/peak flow) for asthma-related outcomes in children and adults. Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and reference lists of articles were searched. The last searches were in February 2009. All randomised controlled comparisons of adjustment of asthma treatment based on sputum analysis or FeNO compared with traditional methods (primarily clinical symptoms and spirometry/peak flow) were selected. Results of searches were reviewed against predetermined criteria for inclusion. Relevant studies were selected, assessed and data extracted independently by at least two people. The trial authors were contacted for further information. Data were analysed as 'intervention received' and sensitivity analyses performed. Six (2 adults and 4 children/adolescent) studies utilising FeNO and three adult studies utilising sputum eosinophils were included. These studies had a degree of clinical heterogeneity including definition of asthma exacerbations, duration of study and variations in cut-off levels for percentage of sputum eosinophils and FeNO to alter management in each study. Adults who had treatment adjusted according to sputum eosinophils had a reduced number of exacerbations compared with the control group (52 vs. 77 patients with >=1 exacerbation in the study period; p=0.0006). There was no significant difference in exacerbations between groups for FeNO compared with controls. The daily dose of inhaled corticosteroids at the end of the study was decreased in adults whose treatment was based on FeNO in comparison with the control group (mean difference -450.03 mug, 95% CI -676.73 to -223.34; p<0.0001). However, children who had treatment adjusted according to FeNO had an increase in their mean daily dose of inhaled corticosteroids (mean difference 140.18 mug, 95% CI 28.94 to 251.42; p=0.014). It was concluded that tailoring of asthma treatment based on sputum eosinophils is effective in decreasing asthma exacerbations. However, tailoring of asthma treatment based on FeNO levels has not been shown to be effective in improving asthma outcomes in children and adults. At present, there is insufficient justification to advocate the routine use of either sputum analysis (due to technical expertise required) or FeNO in everyday clinical practice.

Randomised controlled trial of amoxycillin clavulanate in children with chronic wet cough

Background Despite guideline recommendations, there are no published randomised controlled trial data on the efficacy of antibiotics for chronic wet cough in children. The majority of children with chronic wet cough have protracted bacterial bronchitis (PBB), a recognised condition in multiple national guidelines. The authors conducted a parallel 1:1 placebo randomised controlled trial to test the hypothesis that a 2-week course of amoxycillin clavulanate is efficacious in the treatment of children with chronic wet cough. Methods 50 children (median age 1.9 years, IQR 0.9–5.1) with chronic (>3 weeks) wet cough were randomised to 2 weeks of twice daily oral amoxycillin clavulanate (22.5 mg/kg/dose) or placebo. The primary outcome was ‘cough resolution’ defined as a >75% reduction in the validated verbal category descriptive cough score within 14 days of treatment compared with baseline scores, or cessation of cough for >3 days. In selected children, flexible bronchoscopy and bronchoalveolar lavage (BAL) were undertaken at baseline. Results Cough resolution rates (48%) were significantly higher in children who received amoxycillin clavulanate compared with those who received placebo (16%), p=0.016. The observed difference between proportions was 0.32 (95% CI 0.08 to 0.56). Post treatment, median verbal category descriptive score in the amoxycillin clavulanate group of 0.5 (IQR 0.0–2.0) was significantly lower than in the placebo group, 2.25 (IQR 1.15–2.9) (p=0.02). Pre-treatment BAL data were consistent with PBB in the majority of children, with no significant difference between groups. Conclusion A 2-week course of amoxycillin clavulanate will achieve cough resolution in a significant number of children with chronic wet cough. BAL data support the diagnosis of PBB in the majority of these children.

Clinical use of objective measures of physical activity

With measurement of physical activity becoming more common in clinical practice, it is imperative that healthcare professionals become more knowledgeable about the different methods available to objectively measure physical activity behaviour. Objective measures do not rely on information provided by the patient, but instead measure and record the biomechanical or physiological consequences of performing physical activity, often in real time. As such, objective measures are not subject to the reporting bias or recall problems associated with self-report methods. The purpose of this article was to provide an overview of the different methods used to objectively measure physical activity in clinical practice. The review was delimited to heart rate monitoring, accelerometers and pedometers since their small size, low participant burden and relatively low cost make these objective measures appropriate for use in clinical practice settings. For each measure, strengths and weakness were discussed; and whenever possible, literature-based examples of implementation were provided.

Intervening to reduce workplace sitting time : how and when do changes to sitting time occur?

Objective To investigate how and when changes in workplace sitting time occurred following a workplace intervention to inform evaluation of intervention success. Method The 4-week Stand Up Comcare study (June–September 2011) aimed to reduce workplace sitting time via regularly interrupting and replacing sitting time throughout the day. Activity monitor (activPAL3) workplace data from control (n=22) and intervention participants (n=21) were analysed. Differences in the number and usual duration of sitting bouts were used to evaluate how change occurred. To examine when change occurred, intervention effects were compared by hour since starting work and hour of the workday. Change in workplace activity (sitting, standing, stepping) was examined to further inform alignment with intervention messages. Individual variability was examined in how and when the change occurred. Results Overall, behavioural changes aligned with intervention aims. All intervention participants reduced total workplace sitting time, though there was wide individual variability observed (range −29 to −262 min per 8 h workday). On average, intervention participants reduced number of sitting bouts (−4.6 bouts (95% CI −10.1 to 1.0), p=0.106) and usual sitting bout duration (−5.6 min (95% CI −9.8 to −1.4, p=0.011)) relative to controls. Sitting time reductions were observed across the workday, though intervention effects varied by hour of the day (p=0.015). The intervention group successfully adopted the Stand Up and Sit Less intervention messages across the day. Conclusion These analyses confirmed that this workplace intervention successfully modified sitting behaviour as intended (ie, fewer and shorter sitting bouts, with changes occurring throughout the day).