Patient and hospital-level factors associated with time to surgery after hip fracture in Ireland: Analysis of national audit data 2016-2020.

INTRODUCTION: In hip fracture care, time to surgery (TTS) is a commonly used quality indicator associated with patient outcomes including mortality. This study aimed to identify patient and hospital-level characteristics associated with TTS in Ireland. METHODS: National data from the Irish Hip Fracture Database (IHFD) (2016-2020) were analysed along with hospital-level characteristics obtained from a 2020 organisational survey. Generalised linear model regression was used to explore the association of TTS with case-mix, surgical details, hospital-level staffing and specific protocols recommended to expedite surgery. RESULTS: A total of 14,951 patients with surgically treated hip fracture from 16 hospitals were included (Mean age= 80.6 years (SD=8.8), 70.4% female). Mean TTS was 40.9 h (SD=60.3 h). Case-mix factors associated with longer TTS were male sex and higher American Society of Anaesthesiologists (ASA) grade. Other factors found to be associated with longer TTS included low pre-morbid mobility, inter-hospital transfer, weekday presentation, pre-operative medical physician assessment, intracapsular fracture type, arthroplasty surgery, general anaesthesia, consultant grade of surgeon and lower hospital-level orthopaedic surgical capacity. The oldest age-group and pre-fracture nursing home residence were associated with shorter TTS when adjusted for other case-mix factors. None of four explored protocols for expediting surgery were associated with TTS. CONCLUSION: Patients with more comorbidity experience longer surgical delay after hip fracture in Ireland, in line with international research. Low availability of senior orthopaedic surgeons in Ireland may be delaying hip fracture surgery. Pathway of presentation, including via inter-hospital transfer or hospital bypass, is an important factor that requires further exploration. Further research is required to identify successful system-level protocols and interventions that may expedite hip fracture surgery within this setting.

Harms of off-label erythropoiesis-stimulating agents for critically ill people.

BACKGROUND: Anaemia is a common problem experienced by critically-ill people. Treatment with erythropoiesis-stimulating agents (ESAs) has been used as a pharmacologic strategy when the blunted response of endogenous erythropoietin has been reported in critically-ill people. The use of ESAs becomes more important where adverse clinical outcomes of transfusing blood products is a limitation. However, this indication for ESAs is not licensed by regulatory authorities and is called off-label use. Recent studies concern the harm of ESAs in a critical care setting. OBJECTIVES: To focus on harms in assessing the effects of erythropoiesis-stimulating agents (ESAs), alone or in combination, compared with placebo, no treatment or a different active treatment regimen when administered off-label to critically-ill people. SEARCH METHODS: We conducted a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO via OvidSP, CINAHL, all evidence-based medicine (EBM) reviews including IPA and SCI-Expanded, Conference Proceedings Citation Index- Science, BIOSIS Previews and TOXLINE up to February 2017. We also searched trials registries, checked reference lists of relevant studies and tracked their citations by using SciVerse Scopus. SELECTION CRITERIA: We considered randomized controlled trials (RCTs) and controlled observational studies, which compared scheduled systemic administration of ESAs versus other effective interventions, placebo or no treatment in critically-ill people. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and evaluated the eligibility of retrieved records, extracted data and assessed the risks of bias and quality of the included studies. We resolved differences in opinion by consensus or by involving a third review author. We assessed the evidence using GRADE and created a 'Summary of findings' table. We used fixed-effect or random-effects models, depending on the heterogeneity between studies. We fitted three-level hierarchical Bayesian models to calculate overall treatment effect estimates. MAIN RESULTS: Of the 27,865 records identified, 39 clinical trials and 14 observational studies, including a total of 945,240 participants, were eligible for inclusion. Five studies are awaiting classification. Overall, we found 114 adverse events in 33 studies (30 RCTs and three observational studies), and mortality was reported in 41 studies (32 RCTs and nine observational studies). Most studies were at low to moderate risk of bias for harms outcomes. However, overall harm assessment and reporting were of moderate to low quality in the RCTs, and of low quality in the observational studies. We downgraded the GRADE quality of evidence for venous thromboembolism and mortality to very low and low, respectively, because of risk of bias, high inconsistency, imprecision and limitations of study design.It is unclear whether there is an increase in the risk of any adverse events (Bayesian risk ratio (RR) 1.05, 95% confidence interval (CI) 0.93 to 1.21; 3099 participants; 9 studies; low-quality evidence) or venous thromboembolism (Bayesian RR 1.04, 95% CI 0.70 to 1.41; 18,917 participants; 18 studies; very low-quality evidence).There was a decreased risk of mortality with off-label use of ESAs in critically-ill people (Bayesian RR 0.76, 95% CI 0.61 to 0.92; 930,470 participants; 34 studies; low-quality evidence). AUTHORS' CONCLUSIONS: Low quality of evidence suggests that off-label use of ESAs may reduce mortality in a critical care setting. There was a lack of high-quality evidence about the harm of ESAs in critically-ill people. The information for biosimilar ESAs is less conclusive. Most studies neither evaluated ESAs' harm as a primary outcome nor predefined adverse events. Any further studies of ESA should address the quality of evaluating, recording and reporting of adverse events.

A mixed treatment comparison of the efficacy of anti-TNF agents in rheumatoid arthritis for methotrexate non-responders demonstrates differences between treatments: a Bayesian approach.

BACKGROUND: A number of tumour necrosis factor α (TNFα) antagonists (anti-TNFα) are available to treat rheumatoid arthritis. All of these have demonstrated considerable efficacy in placebo controlled trials, but few head-to-head comparisons exist to date. This work's objective is to estimate the relative efficacy among licensed anti-TNFs in patients who have had an inadequate response to methotrexate (MTX). Different outcome measures are used to highlight the advantages of continuous measures in such analyses. METHODS: A systematic review identified randomised controlled trials comparing the efficacy of licensed anti-TNFα agents with placebo at 24 weeks in patients who have had an inadequate response to MTX. Relative efficacy was estimated using Bayesian mixed treatment comparison (MTC) models. Three different outcome measures were used: RR of achieving an American College of Rheumatology (ACR) 20 and ACR50 response and the percentage improvement in Health Assessment Questionnaire (HAQ) score. RESULTS: 16 published trials were included in the analysis. All anti-TNFs show considerably improved efficacy over placebo. The MTC results also provide evidence of some differences in efficacy of the TNFα antagonists. Etanercept appears superior to infliximab and golimumab, and certolizumab to infliximab and adalimumab. ACR results indicate improved efficacy of certolizumab over golimumab. On HAQ analysis, adalimumab, certolizumab, etanercept and golimumab appear superior to infliximab, and etanercept shows improved efficacy compared with adalimumab. CONCLUSIONS: There are differences in efficacy among the TNFα antagonists. In a MTC, a continuous outcome measure has more strength to detect such differences than a binomial outcome measure because of its enhanced sensitivity to change.

The effect of the menstrual cycle on electrophysiological and behavioral measures of memory and mood.

Event-related potentials (ERPs) were compared between the menses and ovulatory phase of the menstrual cycle in response to visually presented words, some of which were repeated as part of direct and indirect memory tasks. Twelve spontaneously cycling women were tested during the menses and ovulatory phases. For the direct task, participants had to discriminate between new words and those repeated after a mean of six trials. In the indirect task, subjects were required to discriminate between target and nontarget words. Some of the nontarget words were repeated after a mean of six trials. The ERP repetition effect mean amplitude was significantly greater in response to repeated words at both cycle phases but did not differ across the cycle. P300 amplitude was significantly greater during menses than the ovulatory phase. We conclude that context updating mechanisms as indexed by the P300 are sensitive to cyclic hormonal fluctuations.