Associations between static foot posture, dynamic in-shoe plantar foot forces and knee pain in people with medial knee osteoarthritis: a cross-sectional exploratory study.

OBJECTIVE: To investigate relationships between static foot posture, dynamic plantar foot forces and knee pain in people with medial knee osteoarthritis (OA). DESIGN: Data from 164 participants with symptomatic, moderate to severe radiographic medial knee OA were analysed. Knee pain was self-reported using a numerical rating scale (NRS; scores 0-10; higher scores worse) and the Knee Injury and Osteoarthritis Outcome Score pain subscale (KOOS; scores 0-100; lower scores worse). Static foot posture was assessed using clinical tests (foot posture index, foot mobility magnitude, navicular drop). Dynamic plantar foot forces (lateral, medial, whole foot, medial-lateral ratio, arch index) were measured using an in-shoe plantar pressure system while walking. Relationships between foot posture and plantar forces (independent variables) and pain (dependent variables) were evaluated using linear regression models, unadjusted and adjusted for sex, walking speed, KL grade, shoe category, and body mass (for dynamic plantar foot forces). RESULTS: No measure of static foot posture was associated with any knee pain measure. Higher medial-lateral foot force ratio at midstance, and a higher arch index during overall stance, were weakly associated with higher knee pain on the NRS (regression coefficient=0.69, 95% confidence interval (CI) 0.09 to 1.28) and KOOS (coefficient=3.03, 95% CI 0.71 to 5.35) pain scales, respectively. CONCLUSION: Dynamic plantar foot forces, but not static foot posture, were associated with knee pain in people with medial knee OA. However, the amount of pain explained by increases in plantar foot force was small, thus these associations are unlikely to be clinically meaningful.

Application of the Estimand Framework to Anesthesia Trials.

SUMMARY: Events occurring after randomization, such as use of rescue medication, treatment discontinuation, or death, are common in randomized trials. These events can change either the existence or interpretation of the outcome of interest. However, appropriate handling of these intercurrent events is often unclear. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E9(R1) addendum introduced the estimand framework, which aligns trial objectives with the design, conduct, statistical analysis, and interpretation of results. This article describes how the estimand framework can be used in anesthesia trials to precisely define the treatment effect to be estimated, key attributes of an estimand, common intercurrent events in anesthesia trials with strategies for handling them, and use of the estimand framework in a hypothetical anesthesia trial on postoperative delirium. When planning anesthesia trials, clearly defining the estimand is vital to ensure that what is being estimated is clearly understood, is clinically relevant, and helps answer the clinical questions of interest.

Personalising genetic counselling (POETIC) trial: Protocol for a hybrid type II effectiveness-implementation randomised clinical trial of a patient screening tool to improve patient empowerment after cancer genetic counselling.

BACKGROUND: Genetic counselling aims to identify, and address, patient needs while facilitating informed decision-making about genetic testing and promoting empowerment and adaptation to genetic information. Increasing demand for cancer genetic testing and genetic counsellor workforce capacity limitations may impact the quality of genetic counselling provided. The use of a validated genetic-specific screening tool, the Genetic Psychosocial Risk Instrument (GPRI), may facilitate patient-centred genetic counselling. The aim of this study is to assess the effectiveness and implementation of using the GPRI in improving patient outcomes after genetic counselling and testing for an inherited cancer predisposition. METHODS: The PersOnalising gEneTIc Counselling (POETIC) trial is a hybrid type 2 effectiveness-implementation trial using a randomised control trial to assess the effectiveness of the GPRI in improving patient empowerment (primary outcome), while also assessing implementation from the perspective of clinicians and the healthcare service. Patients referred for a cancer risk assessment to the conjoint clinical genetics service of two metropolitan hospitals in Victoria, Australia, who meet the eligibility criteria and consent to POETIC will be randomised to the usual care or intervention group. Those in the intervention group will complete the GPRI prior to their appointment with the screening results available for the clinicians' use during the appointment. Appointment audio recordings, clinician-reported information about the appointment, patient-reported outcome measures, and clinical data will be used to examine the effectiveness of using the GPRI. Appointment audio recordings, health economic information, and structured interviews will be used to examine the implementation of the GPRI. DISCUSSION: The POETIC trial takes a pragmatic approach by deploying the GPRI as an intervention in the routine clinical practice of a cancer-specific clinical genetics service that is staffed by a multidisciplinary team of genetics and oncology clinicians. Therefore, the effectiveness and implementation evidence generated from this real-world health service setting aims to optimise the relevance of the outcomes of this trial to the practice of genetic counselling while enhancing the operationalisation of the screening tool in routine practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry registration number 12621001582842p. Date of registration: 19th November 2021.

FEEDBACK trial - A randomised control trial to investigate the effect of personalised feedback and financial incentives on reducing the incidence of road crashes.

BACKGROUND: Road crashes continue to pose a significant threat to global health. Young drivers aged between 18 and 25 are over-represented in road injury and fatality statistics, especially the first six months after obtaining their license. This study is the first multi-centre two-arm parallel-group individually randomised controlled trial (the FEEDBACK Trial) that will examine whether the delivery of personalised driver feedback plus financial incentives is superior to no feedback and no financial incentives in reducing motor vehicle crashes among young drivers (18 to 20 years) during the first year of provisional licensing. METHODS: A total of 3,610 young drivers on their provisional licence (P1, the first-year provisional licensing) will participate in the trial over 28 weeks, including a 4-week baseline, 20-week intervention and 4-week post-intervention period. The primary outcome of the study will be police-reported crashes over the 20-week intervention period and the 4-week post-intervention period. Secondary outcomes include driving behaviours such as speeding and harsh braking that contribute to road crashes, which will be attained weekly from mobile telematics delivered to a smartphone app. DISCUSSION: Assuming a positive finding associated with personalised driver feedback and financial incentives in reducing road crashes among young drivers, the study will provide important evidence to support policymakers in introducing the intervention(s) as a key strategy to mitigate the risks associated with the burden of road injury among this vulnerable population. TRIAL REGISTRATION: Registered under the Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12623000387628p on April 17, 2023.

Anaesthetist prediction of postoperative opioid use: a multicentre prospective cohort study.

Background: The Apfel simplified risk score includes four risk factors: female sex, non-smoking status, postoperative nausea and vomiting or motion sickness history, and postoperative opioid use. The score is calculated preoperatively, so postoperative opioid use must be predicted. We aimed to determine whether anaesthetists can predict patients' postoperative opioid use and dose. Methods: Specialist anaesthetists from eight hospitals preoperatively predicted opioid use and dose in the post-anaesthesia care unit (PACU) and for the first 24 h postoperatively, which was compared with actual opioid use and dose. Opioid doses were converted to oral morphine equivalents (MEQ). Correlations between predicted and actual opioid use and dose were analysed with Spearman's rho and linear regression. Results: A total of 487 anaesthetist-patient pairs were included. Anaesthetists overpredicted opioid use (398 [82%] predicted vs 251 [52%] actual patients requiring opioids in the PACU; 396 [81%] predicted vs 291 [60%] actual in the first 24 h) (Spearman's rho [95% confidence interval] 0.24 [0.16-0.33], P<0.001 in the PACU; 0.36 [0.28-0.44], P<0.001 in the first 24 h). Anaesthetists also overpredicted opioid dose (median [inter-quartile range] 12 [8-20] mg predicted MEQ vs 4 [0-18] mg actual MEQ in the PACU; 32 [18-60] mg vs 24 [0-65] mg MEQ in the first 24 h) (Spearman's rho 0.21 [0.13-0.29], P<0.001 in the PACU; 0.53 [0.40-0.60], P<0.001 in the first 24 h). Conclusions: Specialist anaesthetists cannot accurately predict opioid use or dose in the PACU or the first 24 postoperative hours. The Apfel risk criterion for postoperative opioid use may be inaccurate in clinical practice.

Effects of a Massive Open Online Course on osteoarthritis knowledge and pain self-efficacy in people with hip and/or knee osteoarthritis: protocol for the MOOC-OA randomised controlled trial.

BACKGROUND: Osteoarthritis (OA) is a prevalent, chronic joint condition that commonly affects the knee and hip causing pain, impaired function, and reduced quality of life. As there is no cure, the main goal of treatment is to alleviate symptoms via ongoing self-management predominantly consisting of exercise and weight loss (if indicated). However, many people with OA do not feel adequately informed about their condition and management options to self-manage effectively. Patient education is recommended by all OA Clinical Practice Guidelines to support appropriate self-management, but little is known about the optimal delivery method and content. Massive Open Online Courses (MOOCs) are free, interactive, e-learning courses. They have been used to deliver patient education in other chronic health conditions but have not been used in OA. METHODS: A two-arm parallel-design, assessor- and participant-blinded superiority randomised controlled trial. People with persistent knee/hip pain consistent with a clinical diagnosis of knee/hip OA (n = 120) are being recruited from the Australia-wide community. Participants are randomly allocated into one of two groups i) electronic information pamphlet (control group) or ii) MOOC (experimental group). Those allocated to the control group receive access to an electronic pamphlet about OA and its recommended management, currently available from a reputable consumer organisation. Those allocated to the MOOC receive access to a 4-week 4-module interactive consumer-facing e-Learning course about OA and its recommended management. Course design was informed by behaviour theory and learning science, and consumer preferences. The two primary outcomes are OA knowledge and pain self-efficacy with a primary endpoint of 5 weeks and a secondary endpoint of 13 weeks. Secondary outcomes include measures of fear of movement, exercise self-efficacy, illness perceptions, OA management and health professional care seeking intentions, physical activity levels, and actual use of physical activity/exercise and weight loss, pain medication, and health professional care seeking to manage joint symptoms. Clinical outcomes and process measures are also collected. DISCUSSION: Findings will determine whether a comprehensive consumer-facing MOOC improves OA knowledge and confidence to self-manage joint pain compared to a currently available electronic OA information pamphlet. TRIAL REGISTRATION: Prospectively registered (Australian New Zealand Clinical Trials Registry ID: ACTRN12622001490763).

Multiple imputation approaches for handling incomplete three-level data with time-varying cluster-memberships.

Three-level data arising from repeated measures on individuals clustered within higher-level units are common in medical research. A complexity arises when individuals change clusters over time, resulting in a cross-classified data structure. Missing values in these studies are commonly handled via multiple imputation (MI). If the three-level, cross-classified structure is modeled in the analysis, it also needs to be accommodated in the imputation model to ensure valid results. While incomplete three-level data can be handled using various approaches within MI, the performance of these in the cross-classified data setting remains unclear. We conducted simulations under a range of scenarios to compare these approaches in the context of an acute-effects cross-classified random effects substantive model, which models the time-varying cluster membership via simple additive random effects. The simulation study was based on a case study in a longitudinal cohort of students clustered within schools. We evaluated methods that ignore the time-varying cluster memberships by taking the first or most common cluster for each individual; pragmatic extensions of single- and two-level MI approaches within the joint modeling (JM) and the fully conditional specification (FCS) frameworks, using dummy indicators (DI) and/or imputing repeated measures in wide format to account for the cross-classified structure; and a three-level FCS MI approach developed specifically for cross-classified data. Results indicated that the FCS implementations performed well in terms of bias and precision while JM approaches performed poorly. Under both frameworks approaches using the DI extension should be used with caution in the presence of sparse data.

Video-interpreting for cognitive assessments: An intervention study and micro-costing analysis.

INTRODUCTION: Evidence in the literature demonstrates the reliability of cognitive screening assessments using video technology in English-speaking older populations. However, this has not been tested in older culturally and linguistically diverse (CALD) populations who require an interpreter, and what the associated costs would be. The aim was to determine if the Rowland Universal Dementia Assessment Scale (RUDAS) and the Geriatric Depression Scale (GDS) could be reliably administered over video-interpreting methods compared with face-to-face interpreting. In addition, the study aims to compare the costs of video-interpreting with the costs of face-to-face interpreting. METHODS: We compared similarity of the RUDAS and GDS scores when administered face-to-face and via video-interpreting. The similarity of scores between methods was analysed using paired t-tests and Bland-Altman plots. A costing analysis was done using a micro-costing approach to estimate the costs of video-interpreting compared with face-to-face, extrapolated to a national level. RESULTS: Analysis found no significant differences in the mean assessment scores between video-interpreting and face-to-face (RUDAS mean difference: -0.36; 95% confidence interval (CI): -1.09, 0.38, GDS mean difference: 0.22; 95% CI: -0.38, 0.83). Bland-Altman plots demonstrated that 71% of RUDAS scores and 82% of GDS scores were within the maximum allowed difference of ±2 units. Costing analysis showed a A$7 saving per assessment when using video-interpreting compared with face-to-face, with a total national saving of A$247,350. DISCUSSION: Video-interpreting was found to be as reliable as face-to-face interpreting for both RUDAS and GDS assessments. Cost analysis indicates that video-interpreting is cheaper than face-to-face interpreting.

Alcohol availability and prevalent Chlamydia trachomatis in young Australians: a multi-level analysis.

Background Prevalence of sexually transmissible infections (STIs) has been associated with availability of alcohol. This paper investigates potential associations between prevalent cases of chlamydia in young people in Australia and the availability of alcohol within their local area, defined as postcode of residence. Methods Alcohol availability was determined at the postcode level using liquor licensing data, classified as total number of licences, number of 'take-away' licences and number of licenses by population. Participant data were drawn from a survey targeting Australians aged 16-29years in rural and regional Australia, capturing demographic details including postcode of residence, indicators of sexual behaviour including condom use and chlamydia test results. Mixed-effects logistic regression was used to examine potential associations between first, alcohol availability and chlamydia, and second, between condom use and chlamydia. Results We found little evidence of associations between alcohol availability and chlamydia in either unadjusted or adjusted models. After adjusting for alcohol availability, we observed significant associations between inconsistent condom use and chlamydia prevalence, whether alcohol availability was measured as total number (adjusted odds ratio (AOR) 2.20; 95% confidence interval (CI) 1.20, 3.70), number of take-away licenses (AOR 2.19; 95% CI1.30, 3.69) or licenses per 1000 population (AOR 2.19; 95% CI 1.30, 3.68). Conclusion Little evidence of association between alcohol availability and chlamydia at the postcode level was found. Further research is required to determine appropriate measures of 'local area' and how characteristics thereof may impact on sexual health.

Evaluation of approaches for accommodating interactions and non-linear terms in multiple imputation of incomplete three-level data.

Three-level data structures arising from repeated measures on individuals clustered within larger units are common in health research studies. Missing data are prominent in such studies and are often handled via multiple imputation (MI). Although several MI approaches can be used to account for the three-level structure, including adaptations to single- and two-level approaches, when the substantive analysis model includes interactions or quadratic effects, these too need to be accommodated in the imputation model. In such analyses, substantive model compatible (SMC) MI has shown great promise in the context of single-level data. Although there have been recent developments in multilevel SMC MI, to date only one approach that explicitly handles incomplete three-level data is available. Alternatively, researchers can use pragmatic adaptations to single- and two-level MI approaches, or two-level SMC-MI approaches. We describe the available approaches and evaluate them via simulations in the context of three three-level random effects analysis models involving an interaction between the incomplete time-varying exposure and time, an interaction between the time-varying exposure and an incomplete time-fixed confounder, or a quadratic effect of the exposure. Results showed that all approaches considered performed well in terms of bias and precision when the target analysis involved an interaction with time, but the three-level SMC MI approach performed best when the target analysis involved an interaction between the time-varying exposure and an incomplete time-fixed confounder, or a quadratic effect of the exposure. We illustrate the methods using data from the Childhood to Adolescence Transition Study.

Sugammadex, neostigmine and postoperative pulmonary complications: an international randomised feasibility and pilot trial.

BACKGROUND: Sugammadex reduces residual neuromuscular blockade after anaesthesia, potentially preventing postoperative pulmonary complications. However, definitive evidence is lacking. We therefore conducted a feasibility and pilot trial for a large randomised controlled trial of sugammadex, neostigmine, and postoperative pulmonary complications. METHODS: Patients aged ≥40 years having elective or expedited abdominal or intrathoracic surgery were recruited in Australia and Hong Kong. Perioperative care was at the discretion of clinicians, except for the use of rocuronium and/or vecuronium for neuromuscular blockade and the randomised intervention (sugammadex or neostigmine) for reversal. Feasibility measurements included recruitment, crossover, acceptability, completeness, and workload. Trial coordinator feedback was systematically sought. Patient-reported quality of life was measured using the EQ-5D-5L score. The primary pilot outcome was the incidence of new pulmonary complications up to hospital discharge (or postoperative day 7 if still in hospital). RESULTS: Among 150 eligible patients, 120 consented to participate (recruitment rate 80%, 95% confidence interval [CI] 73 to 86%). The randomised intervention was administered without crossover to 115 of 117 patients who received reversal (98%, 95% CI 94 to 100%). The protocol was acceptable or highly acceptable to the anaesthetist in 108 of 116 cases (93%, 95% CI 87 to 97%; missing = 4). Four patients of the 120 patients were lost to follow-up at 3 months (3.3%, 95% CI 0.9 to 8.3%). Case report forms were complete at 3 months for all remaining patients. The median time to complete trial processes was 3.5 h (range 2.5-4.5 h). Trial coordinators reported no barriers to trial processes. Patients were aged 64 (standard deviation 11) years, 70 (58%) were male and 50 (42%) were female, and planned surgeries were thoracic (23 [19%]), upper abdominal (41 [34%]), and lower abdominal (56 [47%]). The primary outcome was observed in 5 (8.5%) of the 59 sugammadex patients and 5 (8.2%) of the 61 neostigmine patients (odds ratio 1.02, 95% CI 0.28 to 3.67). CONCLUSIONS: A large international randomised controlled trial of sugammadex, neostigmine and postoperative pulmonary complications in adult patients having abdominal and intrathoracic surgery, including collection of cost-effectiveness evidence for Health Technology Appraisal, is feasible. TRIAL REGISTRATION: Prospectively registered at the Australian and New Zealand Clinical Trials Registry ( ACTRN12620001313921 ) on December 7, 2020. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380645&isReview=true .

Multiple imputation methods for handling missing values in longitudinal studies with sampling weights: Comparison of methods implemented in Stata.

Many analyses of longitudinal cohorts require incorporating sampling weights to account for unequal sampling probabilities of participants, as well as the use of multiple imputation (MI) for dealing with missing data. However, there is no guidance on how MI and sampling weights should be implemented together. We simulated a target population based on the Australian Bureau of Statistics Estimated Resident Population and drew 1000 random samples dependent on three design variables to mimic the Longitudinal Study of Australian Children. The target analysis was the weighted prevalence of overweight/obesity over childhood. We evaluated the performance of several MI approaches available in Stata, based on multivariate normal imputation (MVNI), fully conditional specification (FCS) and twofold FCS: a weighted imputation model, imputing missing data separately for each quintile sampling weight grouping, including the design stratum indicator in the imputation model, and using sampling weights as a covariate in the imputation model. Approaches based on available cases and inverse probability weighting (IPW), with time-varying weights, were also compared. We observed severe issues of convergence with FCS and twofold FCS. All MVNI-based approaches performed similarly, producing minimal bias and nominal coverage, except for when imputation was conducted separately for each quintile sampling weight group. IPW performed equally as well as MVNI-based approaches in terms of bias, however, was less precise. In similar longitudinal studies, we recommend using MVNI with the design stratum as a covariate in the imputation model. If this is unknown, including the sampling weight as a covariate is an appropriate alternative.

Development of a Frailty Index from Routine Hospital Data in Perioperative and Critical Care.

BACKGROUND/OBJECTIVES: Frailty is common in surgical and intensive care unit (ICU) populations, yet it is not routinely measured. Frailty indices are able to quantify this condition across a range of health deficits. We aimed to develop a frailty index (FI) from routinely collected hospital data in a surgical and ICU population. DESIGN: Prospective observational single-center cohort study. SETTING: Tertiary referral metropolitan Australian hospital. PARTICIPANTS: A total of 336 individuals aged 65 and older undergoing surgery or aged 50 and older admitted to the ICU. MEASUREMENTS: Routine admission health data were used to derive an FI comprising 36 health deficits. We examined the FI correlation with existing frailty tools (Clinical Frailty Scale [CFS] and Edmonton Frail Scale [EFS]) and assessed its predictive ability for negative outcomes including 30-day mortality. RESULTS: Median FI was .17 (interquartile range [IQR]) = .10-.24) for ICU patients and .17 (IQR = .11-.25) for surgical patients; maximum FI was .58, and 25% (95% confidence interval [CI] = 10.4-29.6) of patients overall were diagnosed with frailty (FI score ≥.25). Correlation was strong between the FI and the EFS: ρ = .76 (95% CI = .70-.83) for ICU patients and .71 (95% CI = .64-.78) for surgical patients, and the CFS was .77 (95% CI = .70-.84) for ICU patients and .72 (95% CI = .65-.79) for surgical patients. The FI had good discriminative ability for prediction of 30-day mortality in ICU patients (multivariate odds ratio for each increase in FI of .1 = 2.04 [95% CI = 1.19-3.48]), comparable with the performance of the Acute Physiology and Chronic Health Evaluation III score (ICU patients) and the Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity score (surgical patients). CONCLUSION: It is feasible to construct an FI from hospital admission data in a cohort of critically ill and surgical patients.

Accuracy of the Clinical Frailty Scale for perioperative frailty screening: a prospective observational study.

PURPOSE: Perioperative frailty increases postoperative complications, mortality, and new functional dependence. Despite this, routine perioperative frailty screening is not widespread. We aimed to assess the accuracy of the Clinical Frailty Scale (CFS) as a screening tool prior to anesthesia, and to determine which health domains are affected by frailty. METHODS: In a prospective, single-centre observational study, we enrolled 218 patients aged ≥ 65 yr undergoing elective and emergency surgery. The screening performance of the CFS was compared with the Edmonton Frail Scale, including the effect in individual frailty domains, and outcomes including discharge location and mortality. RESULTS: The median [interquartile range] age of the enrolled subjects was 74 [69-80] yr and 24% of the patients were frail. The CFS and Edmonton scales were highly correlated (Spearman correlation coefficient, 0.81; 95% confidence interval [CI], 0.77 to 0.86), and in substantial agreement (kappa coefficient, 0.76; 95% CI, 0.70 to 0.81), with an area under the receiver operating characteristic curve of 0.91 (95% CI, 0.86 to 0.94) indicating excellent discrimination for the CFS in predicting frailty status based on the Edmonton scale. Frail patients had higher 30-day mortality (odds ratio, 5.26; 95% CI, 1.28 to 21.62), and were less likely to be discharged home. Frail patients had poorer health throughout frailty domains, including functional dependence (42% of frail vs 4% of non-frail patients; P < 0.001), malnutrition (48% vs 19%, P < 0.001), and poor physical performance (47% vs 7%, P < 0.001). CONCLUSION: The CFS is a valid and accurate tool to screen for perioperative frailty, which encompasses the spectrum of health-related domains.

RéSUMé: OBJECTIF: La fragilité périopératoire augmente les complications postopératoires, la mortalité et une nouvelle dépendance fonctionnelle. Le dépistage de routine de la fragilité périopératoire n'est cependant pas une pratique répandue. Nous avions pour objectif d'évaluer la précision de l'échelle de mesure de fragilité CFS (pour Clinical Frailty Scale) comme outil de dépistage préanesthésique et de déterminer quels domaines de la santé étaient affectés par la fragilité. MéTHODE: Nous avons recruté 218 patients âgés de plus de 65 ans et subissant une chirurgie non urgente ou urgente dans notre étude observationnelle prospective et monocentrique. Les résultats du dépistage de la CFS ont été comparés à l'échelle de fragilité d'Edmonton (Edmonton Frail Scale), y compris en ce qui a trait à l'effet de la fragilité sur les domaines individuels de fragilité et aux résultats tels que la destination au congé et la mortalité. RéSULTATS: L'âge médian [écart interquartile] des patients recrutés était de 74 [69­80] ans et 24 % des patients étaient fragiles. Les échelles CFS et d'Edmonton avaient une forte corrélation (coefficient de corrélation de Spearman, 0,81; intervalle de confiance [IC] 95 %, 0,77 à 0,86) et étaient en accord substantiel (coefficient kappa, 0,76; IC 95 %, 0,70 à 0,81), avec une surface sous la courbe de fonction d'efficacité de l'observateur de 0,91 (IC 95 %, 0,86 à 0,94), indiquant une discrimination excellente de la CFS pour prédire l'état de fragilité fondé sur l'échelle d'Edmonton. Les patients fragiles souffraient d'une mortalité à 30 jours plus élevée (rapport de cotes, 5,26; IC 95 %, 1,28 à 21,62) et il était moins probable qu'ils reçoivent leur congé de l'hôpital à la maison. Les patients fragiles étaient en moins bonne santé dans tous les domaines de fragilité, notamment en dépendance fonctionnelle (42 % des patients fragiles vs 4 % des patients non fragiles; P < 0,001), en malnutrition (48 % vs 19 %, P < 0,001) et en mauvaise performance physique (47 % vs 7 %, P < 0,001). CONCLUSION: L'échelle CFS constitue un outil valable et précis pour dépister la fragilité périopératoire, qui englobe l'éventail des domaines liés à la santé.

Alcohol Abstinence in Drinkers with Atrial Fibrillation.

BACKGROUND: Excessive alcohol consumption is associated with incident atrial fibrillation and adverse atrial remodeling; however, the effect of abstinence from alcohol on secondary prevention of atrial fibrillation is unclear. METHODS: We conducted a multicenter, prospective, open-label, randomized, controlled trial at six hospitals in Australia. Adults who consumed 10 or more standard drinks (with 1 standard drink containing approximately 12 g of pure alcohol) per week and who had paroxysmal or persistent atrial fibrillation in sinus rhythm at baseline were randomly assigned in a 1:1 ratio to either abstain from alcohol or continue their usual alcohol consumption. The two primary end points were freedom from recurrence of atrial fibrillation (after a 2-week "blanking period") and total atrial fibrillation burden (proportion of time in atrial fibrillation) during 6 months of follow-up. RESULTS: Of 140 patients who underwent randomization (85% men; mean [±SD] age, 62±9 years), 70 were assigned to the abstinence group and 70 to the control group. Patients in the abstinence group reduced their alcohol intake from 16.8±7.7 to 2.1±3.7 standard drinks per week (a reduction of 87.5%), and patients in the control group reduced their alcohol intake from 16.4±6.9 to 13.2±6.5 drinks per week (a reduction of 19.5%). After a 2-week blanking period, atrial fibrillation recurred in 37 of 70 patients (53%) in the abstinence group and in 51 of 70 patients (73%) in the control group. The abstinence group had a longer period before recurrence of atrial fibrillation than the control group (hazard ratio, 0.55; 95% confidence interval, 0.36 to 0.84; P = 0.005). The atrial fibrillation burden over 6 months of follow-up was significantly lower in the abstinence group than in the control group (median percentage of time in atrial fibrillation, 0.5% [interquartile range, 0.0 to 3.0] vs. 1.2% [interquartile range, 0.0 to 10.3]; P = 0.01). CONCLUSIONS: Abstinence from alcohol reduced arrhythmia recurrences in regular drinkers with atrial fibrillation. (Funded by the Government of Victoria Operational Infrastructure Support Program and others; Australian New Zealand Clinical Trials Registry number, ACTRN12616000256471.).

Effectiveness of a Bundled Intervention Including Adjunctive Corticosteroids on Outcomes of Hospitalized Patients With Community-Acquired Pneumonia: A Stepped-Wedge Randomized Clinical Trial.

IMPORTANCE: Community-acquired pneumonia remains a leading cause of hospitalization, mortality, and health care costs worldwide. Randomized clinical trials support the use of adjunctive corticosteroids, early progressive mobilization, antibiotic switching rules, and dietary interventions in improving outcomes. However, it is uncertain whether implementing these interventions will translate into effectiveness under routine health care conditions. OBJECTIVE: To evaluate the effectiveness of a bundle of evidence-supported treatments under conditions of routine care in a representative population hospitalized for community-acquired pneumonia. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, stepped-wedge, cluster-randomized clinical trial with 90-day follow-up was conducted between August 1, 2016, and October 29, 2017, in the general internal medicine service at 2 tertiary hospitals in Melbourne, Australia, among a consecutive sample of patients with community-acquired pneumonia. The primary analysis and preparation of results took place between May 14 and November 25, 2018. INTERVENTIONS: Treating clinical teams were advised to prescribe prednisolone acetate, 50 mg/d, for 7 days (in the absence of any contraindication) and de-escalate from parenteral to oral antibiotics according to standardized criteria. Algorithm-guided early mobilization and malnutrition screening and treatment were also implemented. MAIN OUTCOMES AND MEASURES: Hospital length of stay, mortality, readmission, and intervention-associated adverse events (eg, gastrointestinal bleeding and hyperglycemia). RESULTS: A total of 917 patients were screened, and 816 (351 women and 465 men; mean [SD] age, 76 [13] years) were included in the intention-to-treat analysis, with 401 patients receiving the intervention and 415 patients in the control group. An unadjusted geometric mean ratio of 0.95 (95% CI, 0.78-1.16) was observed for the difference in length of stay (days) between the intervention and control groups. Similarly, no significant differences were observed for the secondary outcomes of mortality and readmission, and the results remained unchanged after further adjustment for sex and age. The study reported higher proportions of gastrointestinal bleeding in the intervention group (9 [2.2%]) compared with the controls (3 [0.7%]), with an unadjusted estimated difference in mean proportions of 0.008 (95% CI, 0.005-0.010). CONCLUSIONS AND RELEVANCE: This bundled intervention including adjunctive corticosteroids demonstrated no evidence of effectiveness and resulted in a higher incidence of gastrointestinal bleeding. Efficacy of individual interventions demonstrated in clinical trials may not necessarily translate into effectiveness when implemented in combination and may even result in net harm. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02835040.

Severe acute pain and persistent post-surgical pain in orthopaedic trauma patients: a cohort study.

BACKGROUND: We conducted a cohort study of adult patients presenting for orthopaedic trauma surgery at a statewide trauma centre, with the aims of determining (i) the incidence and risk factors for severe acute pain in the PACU, and (ii) the incidence and risk factors for persistent post-surgical pain at 3 months. METHODS: Data were collected before operation, in the PACU, 72 h after surgery and 3 months after surgery, and included numerical rating scale (NRS) scores for pain, and modified Brief Pain Inventory-Short Form, Kessler Psychological Distress Scale, World Health Organization Disability Assessment Schedule, and Pain Catastrophizing Scale scores. RESULTS: Severe acute pain in the PACU was reported by 171 (56%; 95% confidence interval [CI]: 51%, 62%) of the 303 included patients. Female sex (odds ratio [OR]: 1.86; 95% CI: 1.06, 3.26) and prior post-injury surgery (OR: 2.21; 95% CI: 1.11, 4.41) remained associated with severe acute pain after multivariable adjustment. Persistent post-surgical pain at 3 months was reported by 149 (65%; 95% CI: 59%, 71%) of the 229 included patients. The preoperative NRS score (OR: 1.17; 95% CI: 1.03, 1.32) remained associated with persistent pain after multivariable adjustment. CONCLUSIONS: We identified three easy-to-measure risk factors: female sex, prior post-injury surgery for severe acute pain, and preoperative NRS scores for persistent pain. Further research is required to identify pain management strategies and psychosocial interventions to reduce the burden of pain, disability, and distress in these patients.

Multiple imputation methods for handling missing values in a longitudinal categorical variable with restrictions on transitions over time: a simulation study.

BACKGROUND: Longitudinal categorical variables are sometimes restricted in terms of how individuals transition between categories over time. For example, with a time-dependent measure of smoking categorised as never-smoker, ex-smoker, and current-smoker, current-smokers or ex-smokers cannot transition to a never-smoker at a subsequent wave. These longitudinal variables often contain missing values, however, there is little guidance on whether these restrictions need to be accommodated when using multiple imputation methods. Multiply imputing such missing values, ignoring the restrictions, could lead to implausible transitions. METHODS: We designed a simulation study based on the Longitudinal Study of Australian Children, where the target analysis was the association between (incomplete) maternal smoking and childhood obesity. We set varying proportions of data on maternal smoking to missing completely at random or missing at random. We compared the performance of fully conditional specification with multinomial and ordinal logistic imputation, and predictive mean matching, two-fold fully conditional specification, indicator based imputation under multivariate normal imputation with projected distance-based rounding, and continuous imputation under multivariate normal imputation with calibration, where each of these multiple imputation methods were applied, accounting for the restrictions using a semi-deterministic imputation procedure. RESULTS: Overall, we observed reduced bias when applying multiple imputation methods with restrictions, and fully conditional specification with predictive mean matching performed the best. Applying fully conditional specification and two-fold fully conditional specification for imputing nominal variables based on multinomial logistic regression had severe convergence issues. Both imputation methods under multivariate normal imputation produced biased estimates when restrictions were not accommodated, however, we observed substantial reductions in bias when restrictions were applied with continuous imputation under multivariate normal imputation with calibration. CONCLUSION: In a similar longitudinal setting we recommend the use of fully conditional specification with predictive mean matching, with restrictions applied during the imputation stage.

A comparison of multiple imputation methods for handling missing values in longitudinal data in the presence of a time-varying covariate with a non-linear association with time: a simulation study.

BACKGROUND: Missing data is a common problem in epidemiological studies, and is particularly prominent in longitudinal data, which involve multiple waves of data collection. Traditional multiple imputation (MI) methods (fully conditional specification (FCS) and multivariate normal imputation (MVNI)) treat repeated measurements of the same time-dependent variable as just another 'distinct' variable for imputation and therefore do not make the most of the longitudinal structure of the data. Only a few studies have explored extensions to the standard approaches to account for the temporal structure of longitudinal data. One suggestion is the two-fold fully conditional specification (two-fold FCS) algorithm, which restricts the imputation of a time-dependent variable to time blocks where the imputation model includes measurements taken at the specified and adjacent times. To date, no study has investigated the performance of two-fold FCS and standard MI methods for handling missing data in a time-varying covariate with a non-linear trajectory over time - a commonly encountered scenario in epidemiological studies. METHODS: We simulated 1000 datasets of 5000 individuals based on the Longitudinal Study of Australian Children (LSAC). Three missing data mechanisms: missing completely at random (MCAR), and a weak and a strong missing at random (MAR) scenarios were used to impose missingness on body mass index (BMI) for age z-scores; a continuous time-varying exposure variable with a non-linear trajectory over time. We evaluated the performance of FCS, MVNI, and two-fold FCS for handling up to 50% of missing data when assessing the association between childhood obesity and sleep problems. RESULTS: The standard two-fold FCS produced slightly more biased and less precise estimates than FCS and MVNI. We observed slight improvements in bias and precision when using a time window width of two for the two-fold FCS algorithm compared to the standard width of one. CONCLUSION: We recommend the use of FCS or MVNI in a similar longitudinal setting, and when encountering convergence issues due to a large number of time points or variables with missing values, the two-fold FCS with exploration of a suitable time window.