Comparison of treatment effect sizes associated with surrogate and final patient relevant outcomes in randomised controlled trials: meta-epidemiological study

Objective To quantify and compare the treatment effect and risk of bias of trials reporting biomarkers or intermediate outcomes (surrogate outcomes) versus trials using final patient relevant primary outcomes. Design Meta-epidemiological study. Data sources All randomised clinical trials published in 2005 and 2006 in six high impact medical journals: Annals of Internal Medicine, BMJ, Journal of the American Medical Association, Lancet, New England Journal of Medicine, and PLoS Medicine. Study selection Two independent reviewers selected trials. Data extraction Trial characteristics, risk of bias, and outcomes were recorded according to a predefined form. Two reviewers independently checked data extraction. The ratio of odds ratios was used to quantify the degree of difference in treatment effects between the trials using surrogate outcomes and those using patient relevant outcomes, also adjusted for trial characteristics. A ratio of odds ratios >1.0 implies that trials with surrogate outcomes report larger intervention effects than trials with patient relevant outcomes. Results 84 trials using surrogate outcomes and 101 using patient relevant outcomes were considered for analyses. Study characteristics of trials using surrogate outcomes and those using patient relevant outcomes were well balanced, except for median sample size (371 v 741) and single centre status (23% v 9%). Their risk of bias did not differ. Primary analysis showed trials reporting surrogate endpoints to have larger treatment effects (odds ratio 0.51, 95% confidence interval 0.42 to 0.60) than trials reporting patient relevant outcomes (0.76, 0.70 to 0.82), with an unadjusted ratio of odds ratios of 1.47 (1.07 to 2.01) and adjusted ratio of odds ratios of 1.46 (1.05 to 2.04). This result was consistent across sensitivity and secondary analyses. Conclusions Trials reporting surrogate primary outcomes are more likely to report larger treatment effects than trials reporting final patient relevant primary outcomes. This finding was not explained by differences in the risk of bias or characteristics of the two groups of trials.

An incident database for improving metro safety: The case of shanghai

Large cities depend heavily on their metro systems to reduce traffic congestion, which is particularly the case with Shanghai, the largest and most developed city in China. For the purposes of enhancing the possibility in quantitative risk assessment and promoting the safety management level in Shanghai metro, an adaptable metro operation incident database (MOID) is therefore presented for containing details of all incidents that have occurred in metro operation. Taking compatibility and simplicity into consideration, Microsoft Access 2010 software is used for the comprehensive and thorough design of the MOID. Based on MOID, statistical characteristics of incident, such as types, causes, time, and severity, are discovered and 24 accident precursors are identified in Shanghai metro. The processes are demonstrated to show how the MOID can be used to identify trends in the incidents that have occurred and to anticipate and prevent future accidents. In order to promote the application of MOID, an organizational structure is proposed from the four aspects of supervision, research, implementation, and manufacturer. This research would be conducive to safety risk analysis in identifying relevant precursors in safety management and assessing safety level as a qualitative tool.

Impact of malnutrition on 12-month mortality following acute hip fracture

Background Studies investigating the relationship between malnutrition and post-discharge mortality following acute hip fracture yield conflicting results. This study aimed to determine whether malnutrition independently predicted 12-month post-fracture mortality after adjusting for clinically relevant covariates. Methods An ethics approved, prospective, consecutive audit was undertaken for all surgically treated hip fracture inpatients admitted to a dedicated orthogeriatric unit (November 2010–October 2011). The 12-month mortality data were obtained by a dual search of the mortality registry and Queensland Health database. Malnutrition was evaluated using the Subjective Global Assessment. Demographic (age, gender, admission residence) and clinical covariates included fracture type, time to surgery, anaesthesia type, type of surgery, post-surgery time to mobilize and post-operative complications (delirium, pulmonary and deep vein thrombosis, cardiac complications, infections). The Charlson Comorbidity Index was retrospectively applied. All diagnoses were confirmed by the treating orthogeriatrician. Results A total of 322 of 346 patients were available for audit. Increased age (P = 0.004), admission from residential care (P < 0.001), Charlson Comorbidity Index (P = 0.007), malnutrition (P < 0.001), time to mobilize >48 h (P < 0.001), delirium (P = 0.003), pulmonary embolism (P = 0.029) and cardiovascular complication (P = 0.04) were associated with 12-month mortality. Logistic regression analysis demonstrated that malnutrition (odds ratio (OR) 2.4 (95% confidence interval (CI) 1.3–4.7, P = 0.007)), in addition to admission from residential care (OR 2.6 (95% CI 1.3–5.3, P = 0.005)) and pulmonary embolism (OR 11.0 (95% CI 1.5–78.7, P = 0.017)), independently predicted 12-month mortality. Conclusions Findings substantiate malnutrition as an independent predictor of 12-month mortality in a representative sample of hip fracture inpatients. Effective strategies to identify and treat malnutrition in hip fracture should be prioritized.

Valence and spatial explanations for voting in the 2013 Australian election

This paper examines the 2013 Australian federal election to test two competing models of vote choice: spatial politics and valence issues. Using data from the 2013 Australian Election Study, the analysis finds that spatial politics (measured by party identification and self-placement on the left-right spectrum) and valence issues both have significant effects on vote choice. However, spatial measures are more important than valence issues in explaining vote choice, in contrast with recent studies from Britain, Canada and the United States. Explanations for these differences are speculative, but may relate to Australia’s stable party and electoral system, including compulsory voting and the frequency of elections. The consequently high information burden faced by Australian voters may lead to a greater reliance on spatial heuristics than is found elsewhere.

3D QSAR studies of N-4-arylacryloylpiperazin-1-yl-phenyl-oxazolidinones: A novel class of antibacterial agents

Three-dimensional QSAR studies for N-4-arylacryloylpiperazin-1-yl-phenyl-oxazolidinones were conducted using TSAR 3.3. The in vitro activities (MICs) of the compounds against Staphylococcus aureus ATCC 25923 exhibited a strong correlation with the prediction made by the model developed in the present study.

The influence of the elements of procedural justice and speed camera enforcement on young novice driver self-reported speeding

Road policing is an important tool used to modify road user behaviour. While other theories, such as deterrence theory, are significant in road policing, there may be a role for using procedural justice as a framework to improve outcomes in common police citizen interactions such as traffic law enforcement. This study, using a sample of 237 young novice drivers, considered how the four elements of procedural justice (voice, neutrality, respect and trustworthiness) were perceived in relation to two forms of speed enforcement: point-to-point (or average) speed and mobile speed cameras. Only neutrality was related to both speed camera types suggesting that it may be possible to influence behaviour by emphasising one or more elements, rather than using all components of procedural justice. This study is important as it indicates that including at least some elements of procedural justice in more automated policing encounters can encourage citizen compliance.

Genome-wide association study of prostate cancer-specific survival

BACKGROUND: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical. METHODS: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR). RESULTS: We observed no significant association between genetic variants and prostate cancer survival. CONCLUSIONS: Common genetic variants with large impact on prostate cancer survival were not observed in this study. IMPACT: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes.

Morbid obesity in total hip arthroplasty: Redefining outcomes for operative time, length of stay, and readmission

Background The incidence of obesity amongst patients presenting for elective Total Hip Arthroplasty (THA) has increased in the last decade and the relationship between obesity and the need for joint replacement has been demonstrated. This study evaluates the effects of morbid obesity on outcomes following primary THA by comparing short-term outcomes in THA between a morbidly obese (BMI ≥40) and a normal weight (BMI 18.5 - <25) cohort at our institution between January 2003 and December 2010. Methods Thirty-nine patients included in the morbidly obese group were compared with 186 in the normal weight group. Operative time, length of stay, complications, readmission and length of readmission were compared. Results Operative time was increased in the morbidly obese group at 122 minutes compared with 100 minutes (p=0.002). Post-operatively there was an increased 30-day readmission rate related to surgery of 12.8% associated with BMI ≥40 compared with 2.7% (p= 0.005) as well as a 5.1 fold increase in surgery related readmitted bed days - 0.32 bed days per patient for normal weight compared with 1.64 per patient for the morbidly obese (p=0.026). Conclusion Morbidly obese patients present a technical challenge and likely this and the resultant complications are underestimated. More work needs to be performed in order to enable suitable allocation of resources.