Evidence-based appraisal of two guidelines for the diagnosis of suspected, uncomplicated urinary tract infections in primary care: a diagnostic accuracy validation study

Objectives: Given the lack of accurate rapid diagnostics for Urinary Tract Infection (UTI) in women, many countries have developed guidelines aiming to support appropriate antibiotic prescribing, but some guidelines have not been validated. We performed a diagnostic accuracy validation study of two guidelines: Public Health England (GW-1263) and Scottish Intercollegiate Guidelines Network (SIGN160). Methods: We used data from women with symptoms suggestive of uncomplicated UTI from a randomised controlled trial comparing urine collection devices. Symptom information was recorded via baseline questionnaire and primary care assessment. Women provided urine samples for dipstick testing and culture. We calculated the number within each risk category of diagnostic flowcharts who had positive/mixed growth/no significant growth urine culture. Results were presented as positive/negative predictive values, with 95% confidence intervals. Results: Of women under-65 years, 311/509 (61.1%, 95% CI 56.7-65.3%) classified to the highest risk category (recommended to consider immediate antibiotic prescribing) and 80/199 (40.2%, 95% CI 33.4-47.4%) classified to the lowest risk category (recommended to reassure that UTI is less likely) by GW-1263 guideline (n=810) had positive culture. For the SIGN160 guideline (n=814), the proportion with positive culture ranged from 60/82 (73.2%, 95% CI 62.1-82.1%) in those for whom immediate treatment was indicated to 33/76 (43.4%, 95% CI 32.3-55.3%) in those recommended a self19 care/waiting strategy. Conclusions: Clinicians should be aware of the potential for diagnostic error when using diagnostic guidelines for managing uncomplicated UTI and making antimicrobial prescribing decisions. Infection cannot be excluded on the basis of symptoms and dipstick testing alone

What effect have NHS commissioners’ policies for body mass index had on access to knee replacement surgery in England?:An interrupted time series analysis from the National Joint Registry

ObjectiveTo assess the impact of local commissioners' policies for body mass index on access to knee replacement surgery in England.MethodsA Natural Experimental Study using interrupted time series and difference-in-differences analysis. We used National Joint Registry for England data linked to the 2015 Index of Multiple Deprivation for 481,555 patients who had primary knee replacement surgery in England between January 2009 and December 2019. Clinical Commissioning Group policies introduced before June 2018 to alter access to knee replacement for patients who were overweight or obese were considered the intervention. The main outcome measures were rate per 100,000 of primary knee replacement surgery and patient demographics (body mass index, Index of Multiple Deprivation, independently-funded surgery) over time.ResultsRates of surgery had a sustained fall after the introduction of a policy (trend change of -0.98 operations per 100,000 population aged 40+, 95% confidence interval -1.22 to -0.74, PConclusionsBody mass index policy introduction was associated with decreases in the rates of knee replacement surgery across localities that introduced policies. This affected all patient groups, not just obese patients at whom the policies were targeted. Changes in patient demographics seen after policy introduction suggest these policies may increase health inequalities and further qualitative research is needed to understand their implementation and impact

The intrinsic aqueous solubility of indomethacin

A value of 8.8 μg/mL was measured for the intrinsic solubility of indomethacin. Evidence of a form with a solubility of about 77 μg/mL was also obtained. Solubility measurements were conducted using the CheqSol and Curve Fitting methods using a maximum pH of 9. It is also demonstrated that a published intrinsic solubility of 410 μg/mL was in error due to decomposition of indomethacin at pH 12. The decomposition of indomethacin at pH 12 was investigated. Decomposition products comprising p-chlorobenzoic acid and 5-Methoxy-2-methyl-3-indoleacetic acid were isolated and characterised

Higher Height, Higher Ability: Judgment Confidence as a Function of Spatial Height Perception

Based on grounded cognition theories, the current study showed that judgments about ability were regulated by the subjects' perceptions of their spatial height. In Experiment 1, we found that after seeing the ground from a higher rather than lower floor, people had higher expectations about their performance on a knowledge test and assigned themselves higher rank positions in a peer comparison evaluation. In Experiment 2, we examined the boundary conditions of the spatial height effects and showed that it could still occur even if we employed photos rather than actual building floors to manipulate the perceptions of spatial heights. In addition, Experiment 2 excluded processing style as an explanation for these observations. In Experiment 3, we investigated a potential mechanism for the spatial height effect by manipulating the scale direction in the questionnaire. Consequently, consistent with our representational dependence account, the effect of spatial heights on ability judgments was eliminated when the mental representation of ability was disturbed by a reverse physical representation. These results suggest that people's judgments about their ability are correlated with their spatial perception

Sport versus climate: Introducing the climate vulnerability of sport organizations framework

© 2018 Sport Management Association of Australia and New Zealand Climate change presents a significant and growing challenge to the sport industry, especially outdoor and winter sports. The authors present a conceptual framework that elucidates the varying states of climate vulnerability a sport organization may face, so practitioners may better understand the risks of climate change. The authors developed the Climate Vulnerability of Sport Organizations (CVSO) framework by building on—and linking—concepts of climate vulnerability, exposure, sensitivity, and adaptive capacity in the context of sport organizations. By placing potential impact on one axis and organizational climate capacity on the other, the authors present four quadrants representing four types of climate vulnerability: the Problem State, the Redundant State, the Responsive State, and the Fortified State. Positioning organizations within the CVSO framework facilitates a better understanding of the effort and resources needed to address climate-related risks. Though not all sport organizations will be equally impacted by climate change, all must be prepared to identify the risks to their organizations

Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection

The potential for ischemic preconditioning to reduce infarct size was first recognized more than 30 years ago. Despite extension of the concept to ischemic postconditioning and remote ischemic conditioning and literally thousands of experimental studies in various species and models which identified a multitude of signaling steps, so far there is only a single and very recent study, which has unequivocally translated cardioprotection to improved clinical outcome as the primary endpoint in patients. Many potential reasons for this disappointing lack of clinical translation of cardioprotection have been proposed, including lack of rigor and reproducibility in preclinical studies, and poor design and conduct of clinical trials. There is, however, universal agreement that robust preclinical data are a mandatory prerequisite to initiate a meaningful clinical trial. In this context, it is disconcerting that the CAESAR consortium (Consortium for preclinicAl assESsment of cARdioprotective therapies) in a highly standardized multi-center approach of preclinical studies identified only ischemic preconditioning, but not nitrite or sildenafil, when given as adjunct to reperfusion, to reduce infarct size. However, ischemic preconditioning—due to its very nature—can only be used in elective interventions, and not in acute myocardial infarction. Therefore, better strategies to identify robust and reproducible strategies of cardioprotection, which can subsequently be tested in clinical trials must be developed. We refer to the recent guidelines for experimental models of myocardial ischemia and infarction, and aim to provide now practical guidelines to ensure rigor and reproducibility in preclinical and clinical studies on cardioprotection. In line with the above guideline, we define rigor as standardized state-of-the-art design, conduct and reporting of a study, which is then a prerequisite for reproducibility, i.e. replication of results by another laboratory when performing exactly the same experiment

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome