Capturing the ghost in the machine: a process for development and validation of measures of phenomenal consciousness in delirium.

BACKGROUND: Delirium has conventionally been considered a disorder of consciousness. Alertness and arousal are used as surrogates in clinical practice but are insufficient for the purposes of a more dimensional assessment of consciousness. We present a process of development and validation of candidate measures of phenomenal consciousness that could be applied to the diagnosis of delirium. METHODS: First, a narrative review of available instruments in the fields of phenomenal consciousness, including prereflective consciousness, the phenomenal-sensed experience and reflective thought, was undertaken. Eligibility of tools in the context of applicability to delirium was based upon objectivity in test interpretation and the requirement for tester administration. Second, where there was a gap in suitable cognitive tools, new items were derived using the silent generation technique. A process of face and construct validity using a diverse panel of experts was performed, and readability was evaluated. RESULTS: 814 articles were screened from the literature review. Fourteen candidate tools were reported from the three domains of phenomenal consciousness. One of these met the eligibility criteria for a delirium assessment. Fifty-seven new tests of phenomenal consciousness were identified. After a process of item reduction, a total of 26 individual tests were identified. After content validity, 22 of the 26 items were retained. The scale average content validity index was 0.89. The agreement between raters was between 80% and 97%. 100% of responses for face validity were rated as positive. Flesch Reading Ease Score was 91.6 (very easy to read). CONCLUSIONS: Candidate measures of phenomenal consciousness are described, and early validity studies are promising.

Ascertainment of Aboriginal and Torres Strait Islander status for assessment of perinatal health outcomes: Reported versus derived maternal ethnicity in Western Australian pregnancy data.

BACKGROUND: Under-identification of Aboriginal and Torres Strait Islander (hereafter referred to as Aboriginal) people can result in inaccurate estimation of health outcomes. Data linkage has improved identification of Aboriginal people in administrative datasets. AIM: To compare three methods of ascertainment of Aboriginal status using only pregnancy data from the Western Australian Midwives Notification System (MNS), to the linked Indigenous Status Flag (ISF) derived by the Department of Health. MATERIALS AND METHODS: This retrospective population-based cohort study utilised logistic regression to determine which demographic characteristics were associated with under-identification, and the effect of ascertainment method on perinatal adverse outcomes. RESULTS: All methods identified a core group of 19 017 (83.0%) Aboriginal women and the ISF identified 2298 (10.0%) women who were not identified using any other method. Under-ascertainment was lowest when a woman's Aboriginal status was determined by ever being recorded as Aboriginal in the MNS data, and highest when taken as it had been recorded for the birth in question. Maternal age <20 years, smoking during pregnancy, pre-existing diabetes, a history of singleton preterm birth and being in the lowest 20% of Socio-Economic Indexes for Areas score were all associated with a higher chance of being identified by the methods using only the MNS. These methods were less likely to identify nulliparous women, and those with maternal age ≥35 years. The method of ascertainment of Aboriginality did not make a significant difference to the adjusted predicted marginal probabilities of adverse perinatal outcomes. CONCLUSION: Unlinked pregnancy data can be used for epidemiological research in Aboriginal obstetric populations.

Maturation and biomechanical risk factors associated with anterior cruciate ligament injury: Is there a link? A systematic review.

OBJECTIVE: To establish the potential link between sex-specific maturation and biomechanical factors associated with ACL injury during dynamic tasks. DESIGN: Systematic review. LITERATURE SEARCH: Five databases (CINHAL®, Cochrane Library, PubMed®, Scopus®, and SPORTDiscus) were searched and monitored until 27 May 2024. STUDY SELECTION CRITERIA: Cross-sectional, cohort, case-control, or interventional studies reporting one or more biomechanical variable linked with ACL injury and which assessed participants across two or more maturation phases were considered eligible. DATA SYNTHESIS: Studies were assessed for risk of bias using a modified version of the Newcastle Ottawa Scale and overall quality of evidence was rated using GRADE. Metrics and effect sizes were presented where available. RESULTS: Eighteen included studies examined 400 males, 1377 females, and 315 participants of undefined sex across various maturation phases. The methodological quality of most studies (n = 16) was considered good, and satisfactory for two. Knee abduction angle, knee abduction moment, knee flexion angle, and ground reaction forces were most commonly reported. Knee abduction angles and moments and knee flexion angles were greater in late and post-pubertal females than males and pre-pubertal females during both landing and cutting tasks. When normalised for body mass, ground reaction forces were generally greater in males compared to females overall and for less mature participants for both sexes. Overall quality of evidence was low or medium across the four biomechanical measures. CONCLUSION: Sex-specific maturation considerations are important in the targeted development and implementation of ACL injury risk identification and prevention strategies.

Aggregation of melanoma tumour site within Western Australian families.

BACKGROUND: Evidence is emerging that melanoma has distinct aetiologic pathways and subtypes, characterized by factors like anatomic site of the tumour. To explore genetic influences on anatomic subtypes, we examined the extent to which melanomas in first-degree relatives shared the same body site of occurrence. METHODS: Population-level linked data was used to identify the study population of over 1.5 million individuals born in Western Australia between 1945 and 2014, and their first-degree relatives. There were 1009 pairs of invasive tumours from 677 family pairs, each categorised by anatomic site. Greater than expected representation of site-concordant pairs would suggest the presence of genetic factors that predispose individuals to site-specific melanoma. RESULTS: Comparing observed versus expected totals, we observed a modest increase in site concordance for invasive head/neck and truncal tumours (P=0.02). A corresponding analysis including in situ tumours showed a similar concordance (P=0.05). No further evidence of concordance was observed when stratified by sex. CONCLUSION: In conclusion, modest evidence of aggregation was observed but with inconsistent patterns between sites. Results suggest that further investigation into the familial aggregation of melanoma by tumour site is warranted, with the inclusion of genetic data in order to disentangle the relative contributions of genetic and environmental factors.

Toward Personalized Orthopedic Care: Validation of a Smart Knee Brace.

Introduction: Wearable technology offers a promising solution to advance current rehabilitation strategies for post-operative orthopedic care. The aim of this study was to determine the level of agreement and concurrent validity of a smart knee brace compared to the gold standard measurement system GAITRite® for assessing lower limb gait parameters. Methods: Thirty-four healthy participants were fitted with the smart knee brace (Digital Knee®) on their dominant limb. Gait parameters (stride length, stride time, and gait velocity) were measured simultaneously using the Digital Knee® and the GAITRite® electronic walkway. Two walks were performed at a comfortable speed and two at a fast-walking speed. Results: At a comfortable walking speed, stride time was moderately valid (ICC2,1 = 0.66 s), and stride length and gait velocity demonstrated poor validity (ICC2,1 = 0.29; ICC2,1 = 0.41). All gait parameters demonstrated poor validity at a fast-walking speed (ICC2,1 = -0.16 to -0.01). Bias ranged from -0.08 to 0.28, with more clinically acceptable percentage errors at a comfortable walking speed (14.1-30%) versus at a fast-walking speed (26.4-42.6%). Gait velocity and stride length had substantially higher biases in the fast-walking speed compared to the comfortable walking speed (0.28 ± 0.39 m s-1 vs. 0.02 ± 0.21 m s-1; 0.15 ± 0.23 m vs. -0.04 ± 0.17 m). Limits of agreement were considered narrower for stride time compared to stride length and gait velocity. Conclusion: The Digital Knee® is a promising approach to improving post-operative rehabilitation outcomes in patients with osteoarthritis. The Digital Knee® demonstrated good agreement and moderate concurrent validity for measuring gait metrics at a comfortable walking speed. These findings highlight the opportunity of the wearable sensor as an intervention for post-operative orthopedic care. This was a laboratory-based study; thus, further research is required to validate the wearable sensor in real-world contexts and in patients with knee pathologies. Further, refinement of the algorithm for measuring gait metrics at slow- and fast-walking speed with the Digital Knee® is warranted.

Does-dual mobility still offer improved stability in smaller cup sizes? A computer modelling comparison of stability with 22-mm versus 28-mm inner heads in dual-mobility versus single-bearing constructs.

PURPOSE: Dislocation remains 1 of the leading causes of revision after primary total hip arthroplasty (THA) and there is clear evidence the dual-mobility (DM) is used more frequently to minimise this. But in smaller cups, whether the use of DM with smaller 22-mm heads imparts any increased stability compared to standard bearing is unknown; especially when those smaller cups now allow for large single-bearing (SB) heads. METHODS: 3 primary cup sizes (48 mm, 50 mm, 52 mm) were chosen a priori for modelling. Head sizes trialled for the standard bearing (SB) constructs group were 28-0 mm, 32-0 mm and 36-0 mm against neutral polyethylene liners. In the modular sub-hemispheric DM constructs the inner head sizes for the DM constructs were altered where appropriate (22-0 mm vs. 28-0 mm). Cup position, stem offset, and stem size were standardised. RESULTS: Both DM constructs outperformed all SB constructs because of a statistically significant jump distance increase (p < 0.001). However, there was no difference in range of motion (ROM) or jump distances between the 22-mm and 28-mm DM inner heads.The ROM angle before impingement between the DM (with 22-mm or 28-mm heads) and SB (with different head sizes where appropriate) showed no statistically significant difference. However, DM constructs presented significantly larger jump distances than SB constructs for both provocative dislocation tests across all 3 cup sizes.Of interest, for 50-mm and 52-mm cup sizes (for which this particular DM construct design can accommodate both 22-mm and 28-mm inner heads), there were no differences in ROM or jump distance between 22-mm versus 28-mm inner heads. CONCLUSIONS: In this computer-modelling study, DM constructs are advantageous over SB constructs for improving jump distances in clinically provocative positions, but not range of motion angles. Inner head diameter of DM has no effect on stability.

30-Day Mortality among Very Old Patients Admitted to European Intensive Care Units for Major Trauma.

INTRODUCTION: Cases of major trauma in the very old (over 80 years) are increasingly common in the intensive care unit (ICU). Predicting outcome is challenging in this group of patients as chronological age is a poor marker of health and poor predictor of outcome. Increasingly, decisions are guided by the use of organ dysfunction scores of both acute conditions (e.g., sequential organ failure assessment [SOFA] score) and chronic health issues (e.g., clinical frailty scale [CFS]). Recent work suggests that increased CFS is associated with a worse outcome in elderly major trauma patients. We aimed to test whether this association held true in the very old (over 80) or whether SOFA had a stronger association with 30-day outcome. METHODS: Data from the very elderly intensive care patient (VIP)-1 and VIP-2 studies for patients over 80 years old with major trauma admissions were merged. These participants were recruited from 20 countries across Europe. Baseline characteristics, level of care provided, and outcome (ICU and 30-day mortality) were summarised. Uni- and multivariable regression analyses were undertaken to determine associations between CFS and SOFA score in the first 24 h, type of major trauma, and outcomes. RESULTS: Of the 8,062 acute patients recruited to the two VIP studies, 498 patients were admitted to intensive care because of major trauma. Median age was 84 years, median SOFA score was 6 (IQR 3, 9), and median CFS was 3 (IQR 2, 5). Survival for 30 days was 54%. Median and interquartile range of CFS were the same for survivors and non-survivors. In the logistic regression analysis, CFS was not associated with increased mortality. SOFA score (p < 0.001) and trauma with head injury (p < 0.01) were associated with increased mortality. CONCLUSIONS: Major trauma admissions in the very old are not uncommon, and 30-day mortality is high. We found that CFS was not a helpful predictor of mortality. SOFA and trauma with head injury were associated with worse outcomes in this patient group.

Evaluation of the awareness of Western Australian SunSmart campaigns between 2008 and 2022.

ISSUE ADDRESSED: It is unknown whether SunSmart health promotion campaigns in Western Australia are still effectively reaching their target audience of young people (under 45 years). This study examined trends over time in awareness, relevancy and believability of SunSmart advertisements and identified socio-demographic characteristics and risk factors associated with campaign awareness. METHOD: Linear regression and log-binomial modelling were undertaken using data from the annual SunSmart post-campaign evaluation surveys between 2008/2009 and 2021/2022. SunSmart campaigns were analysed and categorised into the following themes: (1) personal real-life stories; (2) daily activities/sun exposure leads to skin cancer; or (3) cartoon/animated. RESULTS: Between 2008 and 2022, there were declines in total awareness (74.2% to 20.4%), unprompted awareness (33.7% to 4.9%) and relevancy (89.5% to 54.8%) of SunSmart advertisements (representing annual percent decreases of 3.6%, 3.1% and 1.8%, respectively). However, believability remained high over time (>94% in each annual survey). Trends were inconsistent between the awareness of campaign themes and socio-demographic characteristics and risk factors. Several campaigns had greater awareness in their subsequent years, compared with the first campaign year. CONCLUSION: In more recent years, SunSmart advertisements and campaigns may not have reached their target audience. In addition to socio-demographic characteristics, particularly age, advertisement factors may also affect the awareness of specific campaigns. SO WHAT?: Given the changing advertising landscape and its rising costs, ongoing funding is pertinent to increase the reach of future SunSmart campaigns. Increasing advertisements on alternative platforms and designing campaigns which separately target adolescents and adults need to be considered.

The impact of operative approach and intraoperative imaging on leg length discrepancy and acetabular component angle in total hip arthroplasty: a retrospective cohort study.

PURPOSE: Operative approach in total hip arthroplasty (THA) has long been a topic of debate with each approach having unique benefits and disadvantages. One purported benefit of an anterior approach to THA is that it allows for intraoperative positioning using fluoroscopy rather than manual positioning. Proper positioning allows for improved outcomes including leg length discrepancy and acetabular component angle. This study aims to examine if operative approach and use of imaging in intraoperative positioning impact LLD and cup angle post-operatively. METHODS: A total of 300 hips were enrolled in the study with 100 hips per approach (anterior with fluoroscopy, lateral, and posterior). Retrospective chart review was conducted to assess patient demographics and radiographic analysis used to determine LLD and acetabular cup angle. RESULTS: Of the three groups, those receiving anterior approach THAs were on average older than those in the posterior group. Analysis comparing the LLD and acetabular angle across the three groups showed no statistically significant difference in LLD (p=0.091); this was also reflected when comparing hips that received fluoroscopy with those that did not (p=0.91). For acetabular angle, while no difference existed when comparing hips that received imaging versus those that did not, statistically significant differences were observed when comparing the three intraoperative approaches (p<0.0001). CONCLUSIONS: Neither intraoperative approach nor the use of intraoperative imaging in THA has a statistically significant effect on LLD post-operatively. However, approach did impact the acetabular cup angle across all three distinct approaches.

Education in Female Sexual Function and Dysfunction among American Urogynecologic Society Members: An Unmet Need.

OBJECTIVES: Sexual function is an important component of women's health that has not been traditionally emphasized during medical training, suggesting that further education is needed to provide comprehensive patient care. The purpose of this study was to describe education and interest in female sexual function among urogynecology providers. METHODS: Conducted in 2020, this was a cross-sectional survey of American Urogynecologic Society members assessing educational and clinical experience with female sexual function. RESULTS: Of 642 members who opened the survey, 123 (19%) completed it. Most of the respondents were fellowship trained (70%), and 74% reported ≥10% of their patients had sexual function questions or concerns unrelated to prolapse or incontinence. Most (71%) of the members strongly agreed/agreed that they were comfortable evaluating and managing these patients. This was more common in providers who saw more patients (≥25%) with sexual function concerns (83%) compared with those who saw <25% (65%; P = 0.04). Most of the respondents reported receiving ≤1 lecture on normal sexual function (82%) or sexual dysfunction (85%) during medical training. Most (67%) would expand their practice if they received additional education. The most requested topics were disorders of desire (72%), orgasm (71%), and arousal (67%). The most common reasons for not expanding practice even with additional education were female sexual function not being of significant interest (30%) and time and interruption of practice flow (28%). CONCLUSIONS: Most of the respondents felt comfortable caring for patients with sexual function concerns, but reported that they would expand their practice with additional education. The majority reported having received ≤1 female sexual function/dysfunction lecture during their medical training. This highlights a critical need and desire for more female sexual function education among the urogynecologic provider population.

Using implementation science to promote the use of the fascia iliaca blocks in hip fracture care.

PURPOSE: There is variable and suboptimal use of fascia iliaca compartment nerve blocks (FICBs) in hip fracture care. Our objective was to use an evidence-based and theory-informed implementation science approach to analyze barriers and facilitators to timely administration of FICB and select evidence-based interventions to enhance uptake. METHODS: We conducted a qualitative study at a single centre using semistructured interviews and site observations. We interviewed 35 stakeholders including health care providers, managers, patients, and caregivers. We mapped barriers and facilitators to the Theoretical Domains Framework (TDF) and Consolidated Framework for Implementation Research (CFIR). We compared the rate and timeliness of FICB administration before and after evidence-based implementation strategies were applied. RESULTS: The study identified 18 barriers and 11 facilitators within seven themes of influences of FICB use: interpersonal relationships between health care professionals; clinician knowledge and skills related to FICB; roles, responsibilities, and processes for delivering FICB; perceptions on using FICB for pain; patient and caregiver perceptions on using FICB for pain; communication of hip fracture care between departments; and resources for delivering FICBs. We mapped the behaviour change domains to eight implementation strategies: restructure the environment, create and distribute educational materials, prepare patients to be active participants, perform audits and give feedback, use local opinion leaders, use champions, train staff on FICB procedures, and mandate change. We observed an increase in the rates of FICBs administered (48% vs 65%) and a decrease in the median time to administration (1.63 vs 0.81 days). CONCLUSION: Our study explains why FICBs are underused and shows that the TDF and CFIR provide a framework to identify barriers and facilitators to FICB implementation. The mapped implementation strategies can guide institutions to improve use of FICB in hip fracture care.

RéSUMé: OBJECTIF: Il existe une utilisation variable et sous-optimale des blocs nerveux du compartiment fascia iliaca (FICB) dans les soins des fractures de la hanche. Notre objectif était d'utiliser une approche scientifique de la mise en œuvre fondée sur des données probantes et sur la théorie pour analyser les obstacles et les facilitateurs à l'administration opportune d'un FICB et pour sélectionner des interventions fondées sur des données probantes pour améliorer l'adoption de cette technique. MéTHODE: Nous avons mené une étude qualitative dans un seul centre à l'aide d'entrevues semi-structurées et d'observations sur place. Nous avons interviewé 35 intervenant·es, y compris des prestataires de soins de santé, des gestionnaires, des patient·es et des soignant·es. Nous avons cartographié les obstacles et les facilitateurs du cadre des domaines théoriques (Theoretical Domains Framework, TDF) et du cadre consolidé pour la recherche sur la mise en œuvre (Consolidated Framework for Implementation Research, CFIR). Nous avons comparé le taux et la rapidité d'administration d'un FICB avant et après l'application des stratégies de mise en œuvre fondées sur des données probantes. RéSULTATS: L'étude a identifié 18 obstacles et 11 facilitateurs dans sept thèmes d'influence de l'utilisation du FICB : les relations interpersonnelles entre les professionnel·les de la santé; les connaissances et les compétences des clinicien·nes liées au FICB; les rôles, responsabilités et processus d'exécution des FICB; les perceptions de l'utilisation des FICB pour soulager la douleur; les perceptions des patient·es et des soignant·es concernant l'utilisation de FICB pour soulager la douleur; la communication des soins des fractures de la hanche entre les services; et les ressources nécessaires à l'exécution des FICB. Nous avons mis en correspondance les domaines de changement de comportement avec huit stratégies de mise en œuvre : restructurer l'environnement, créer et distribuer du matériel éducatif, préparer les patient·es à participer activement, effectuer des audits et donner de la rétroaction, faire appel à des leaders d'opinion locales et locaux, utiliser des champion·nes, former le personnel sur les interventions de FICB et forcer au changement. Nous avons observé une augmentation des taux de FICB administrés (48% vs 65%) et une diminution du délai médian d'administration (1,63 vs 0,81 jour). CONCLUSION: Notre étude explique pourquoi les FICB sont sous-utilisés et montre que le TDF et le CFIR fournissent un cadre pour identifier les obstacles et les facilitateurs à la mise en œuvre des FICB. Les stratégies de mise en œuvre cartographiées peuvent aider les établissements à améliorer l'utilisation des FICB dans le traitement des fractures de la hanche.

Successful implementation of a quality improvement bundle to reduce opioid overprescribing following total hip and knee arthroplasty.

BACKGROUND: Opioid overprescribing is commonplace after total hip (THA) and total knee arthroplasty (TKA). Preliminary data demonstrated that approximately 32% of the opioids prescribed at discharge from our hospital following THA and TKA remain unused. This is a concern given that unused prescribed opioids are available for diversion and may result in misuse and abuse. METHODS: Pre-intervention data were collected between 1 November 2018 and 10 December 2018. An intervention bundle was then introduced, including education of patients and providers, a standardised pain management algorithm and an autopopulated discharge prescription. The aim of this quality improvement initiative was to reduce the amount of opioid (average oral morphine equivalents (OME)) dispensed (based on the discharge prescription provided) following THA and TKA at our institution by 15% by 1 April 2019. DESIGN: Using an interrupted time series design, the outcome measure was the amount of opioid (OME) dispensed from the discharge prescription provided. Process measures included the percentage of autopopulated discharge prescriptions, the percentage of patients receiving education at discharge and the percentage of nurses and residents receiving standardised education. Balancing measures included patient satisfaction with postoperative pain management, and the percentage of patients filling the second half of the part-fill or requiring a subsequent opioid prescription. RESULTS: With 600 patients identified, mean OME dispensed at discharge was reduced by 26.3% (from 522.2 to 384.9 mg) after our interventions started. Utilisation of autopopulated part-fill prescriptions was 95.8%. There was no change in patient satisfaction nor in the proportion of patients requiring an additional opioid prescription post-intervention. Only 39% of patients filled the second half of the part-fill prescription post-intervention. CONCLUSIONS: Mean OME dispensed at discharge per patient was reduced with no change in patient satisfaction after introduction of the intervention bundle.

Association of functional, inherited vitamin D-binding protein variants with melanoma-specific death.

BACKGROUND: It is unclear whether genetic variants affecting vitamin D metabolism are associated with melanoma prognosis. Two functional missense variants in the vitamin D-binding protein gene (GC), rs7041 and rs4588, determine 3 common haplotypes, Gc1s, Gc1f, and Gc2, of which Gc1f may be associated with decreased all-cause death among melanoma patients based on results of a prior study, but the association of Gc1f with melanoma-specific death is unclear. METHODS: We investigated the association of the Gc1s, Gc1f, and Gc2 haplotypes with melanoma-specific and all-cause death among 4490 individuals with incident, invasive primary melanoma in 2 population-based studies using multivariable Cox-proportional hazards regression. RESULTS: In the pooled analysis of both datasets, the patients with the Gc1f haplotype had a 37% lower risk of melanoma-specific death than the patients without Gc1f (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.47 to 0.83, P = .001), with adjustments for age, sex, study center, first- or higher-order primary melanoma, tumor site, pigmentary phenotypes, and Breslow thickness. Associations were similar in both studies. In pooled analyses stratified by Breslow thickness, the corresponding melanoma-specific death HRs for those patients with the Gc1f haplotype compared with those without Gc1f were 0.89 (95% CI = 0.63 to 1.27) among participants with tumor Breslow thickness equal to or less than 2.0 mm and 0.40 (95% CI = 0.25 to 0.63) among participants with tumor Breslow thickness greater than 2.0 mm (Pinteraction = .003). CONCLUSIONS: Our findings suggest that individuals with the GC haplotype Gc1f may have a lower risk of dying from melanoma-specifically from thicker, higher-risk melanoma-than individuals without this Gc1f haplotype.

Sex-Specific Associations of MDM2 and MDM4 Variants with Risk of Multiple Primary Melanomas and Melanoma Survival in Non-Hispanic Whites.

MDM2-SNP309 (rs2279744), a common genetic modifier of cancer incidence in Li-Fraumeni syndrome, modifies risk, age of onset, or prognosis in a variety of cancers. Melanoma incidence and outcomes vary by sex, and although SNP309 exerts an effect on the estrogen receptor, no consensus exists on its effect on melanoma. MDM2 and MDM4 restrain p53-mediated tumor suppression, independently or together. We investigated SNP309, an a priori MDM4-rs4245739, and two coinherited variants, in a population-based cohort of 3663 primary incident melanomas. Per-allele and per-haplotype (MDM2_SNP309-SNP285; MDM4_rs4245739-rs1563828) odds ratios (OR) for multiple-melanoma were estimated with logistic regression models. Hazard ratios (HR) for melanoma death were estimated with Cox proportional hazards models. In analyses adjusted for covariates, females carrying MDM4-rs4245739*C were more likely to develop multiple melanomas (ORper-allele = 1.25, 95% CI 1.03-1.51, and Ptrend = 0.03), while MDM2-rs2279744*G was inversely associated with melanoma-death (HRper-allele = 0.63, 95% CI 0.42-0.95, and Ptrend = 0.03). We identified 16 coinherited expression quantitative loci that control the expression of MDM2, MDM4, and other genes in the skin, brain, and lungs. Our results suggest that MDM4/MDM2 variants are associated with the development of subsequent primaries and with the death of melanoma in a sex-dependent manner. Further investigations of the complex MDM2/MDM4 motif, and its contribution to the tumor microenvironment and observed associations, are warranted.

The clinical frailty scale - does it predict outcome of the very-old in UK ICUs?

Introduction: The age of patients admitted into critical care in the UK is increasing. Clinical decisions for very-old patients, usually defined as over 80, can be challenging. Clinicians are frequently asked to predict outcomes as part of discussions around the pros and cons of an intensive care unit (ICU) admission. Measures of overall health in old age, such as the clinical frailty scale (CFS), are increasingly used to help guide these discussions. We aimed to understand the characteristics of the very-old critically unwell population in the UK and the associations between frailty and outcome of an ICU admission in our healthcare system (National Health Service, NHS). Methods: Baseline characteristics, ICU interventions and outcomes (ICU- and 30-day mortality) were recorded for sequential admissions of very old patients to UK ICUs as part of the European VIP 1 and 2 studies. Patient characteristics, interventions and outcome measures were compared by frailty group using standard statistical tests. Multivariable logistic regression modelling was undertaken to test association between baseline characteristics, admission type and outcome. Results: 1858 participants were enrolled from 95 ICUs in the UK. The median age was 83. The median CFS was 4 (IQR 3-5). 30-day survival was significantly lower in the frail group (CFS > 4, 58%) compared to vulnerable (CFS = 4, 65%) and fit (CFS < 4 68%, p = .004). Sequential organ failure assessment (SOFA) score, reason for admission and CFS were all independently associated with increased 30-day mortality (p < .01). Conclusion: In the UK, frailty is associated with an increase in mortality at 30-days following an ICU admission. At moderate frailty (CFS 5-6), three out of every five patients admitted survived to 30-days. This is a similar mortality to septic shock.

Choosing Money Over Meaningful Work: Examining Relative Job Preferences for High Compensation Versus Meaningful Work.

People sometimes must choose between prioritizing meaningful work or high compensation. Eight studies (N = 4,177; 7 preregistered) examined the relative importance of meaningful work and salary in evaluations of actual and hypothetical jobs. Although meaningful work and high salaries are both perceived as highly important job attributes when evaluated independently, when presented with tradeoffs between these job attributes, participants consistently preferred high-salary jobs with low meaningfulness over low-salary jobs with high meaningfulness (Studies 1-5). Forecasts of happiness and meaning outside of work helped explain condition differences in job interest (Studies 4 and 5). Extending the investigation toward actual jobs, Studies 6a and 6b showed that people express stronger preferences for higher pay (vs. more meaningful work) in their current jobs. Although meaningful work is a strongly valued job attribute, it may be less influential than salary to evaluations of hypothetical and current jobs.

The MC1R r allele does not increase melanoma risk in MITF E318K carriers.

BACKGROUND: Population-wide screening for melanoma is not cost-effective, but genetic characterization could facilitate risk stratification and targeted screening. Common Melanocortin-1 receptor (MC1R) red hair colour (RHC) variants and Microphthalmia-associated transcription factor (MITF) E318K separately confer moderate melanoma susceptibility, but their interactive effects are relatively unexplored. OBJECTIVES: To evaluate whether MC1R genotypes differentially affect melanoma risk in MITF E318K+ vs. E318K- individuals. MATERIALS AND METHODS: Melanoma status (affected or unaffected) and genotype data (MC1R and MITF E318K) were collated from research cohorts (five Australian and two European). In addition, RHC genotypes from E318K+ individuals with and without melanoma were extracted from databases (The Cancer Genome Atlas and Medical Genome Research Bank, respectively). χ2 and logistic regression were used to evaluate RHC allele and genotype frequencies within E318K+/- cohorts depending on melanoma status. Replication analysis was conducted on 200 000 general-population exomes (UK Biobank). RESULTS: The cohort comprised 1165 MITF E318K- and 322 E318K+ individuals. In E318K- cases MC1R R and r alleles increased melanoma risk relative to wild type (wt), P < 0.001 for both. Similarly, each MC1R RHC genotype (R/R, R/r, R/wt, r/r and r/wt) increased melanoma risk relative to wt/wt (P < 0.001 for all). In E318K+ cases, R alleles increased melanoma risk relative to the wt allele [odds ratio (OR) 2.04 (95% confidence interval 1.67-2.49); P = 0.01], while the r allele risk was comparable with the wt allele [OR 0.78 (0.54-1.14) vs. 1.00, respectively]. E318K+ cases with the r/r genotype had a lower but not significant melanoma risk relative to wt/wt [OR 0.52 (0.20-1.38)]. Within the E318K+ cohort, R genotypes (R/R, R/r and R/wt) conferred a significantly higher risk compared with non-R genotypes (r/r, r/wt and wt/wt) (P < 0.001). UK Biobank data supported our findings that r did not increase melanoma risk in E318K+ individuals. CONCLUSIONS: RHC alleles/genotypes modify melanoma risk differently in MITF E318K- and E318K+ individuals. Specifically, although all RHC alleles increase risk relative to wt in E318K- individuals, only MC1R R increases melanoma risk in E318K+ individuals. Importantly, in the E318K+ cohort the MC1R r allele risk is comparable with wt. These findings could inform counselling and management for MITF E318K+ individuals.

Virtual Fracture Care in Long-Term Care Homes Avoiding Emergency Department Visits.

Long-term care residents with suspected fractures as a result of a fall typically transfer to the emergency department (ED) for diagnostic imaging and care. During the COVID-19 pandemic, transfer to the hospital increased the risk of COVID-19 exposure and resulted in extended isolation days for the resident. A fracture care pathway was developed and implemented to provide rapid diagnostic imaging results and stabilization in the care home, reducing transportation and exposure risk to COVID-19. Eligible residents with a stable fracture would receive a referral to a designated fracture clinic for consultation; fracture care is provided in the care home by long-term care staff. Evaluation of the pathway was completed and demonstrated that 100% of residents did not transfer to the ED and 47% of the residents did not transfer to a fracture clinic for additional care.

Quality indicators in primary elective total hip and knee arthroplasty.

PURPOSE: Total hip arthroplasty (THA) and total knee arthroplasty (TKA) represent a significant portion of healthcare spending and are high-priority for quality improvement initiatives. This study aims to develop quality indicators (QIs) in the care of primary elective THA and TKA patients. These QIs serve a number of purposes including documentation of the quality of care, objective comparisons of institutions/providers, facilitating pay-for-performance initiatives, and supporting accountability, regulation, and accreditation. METHODS: A guideline-based approach, initially described by Kötter et al., was utilized. Eight clinical practice guidelines (CPGs) were evaluated for candidate indicators (CIs). CIs with high-quality evidence and consensus statements were extracted. Eighteen additional CIs were included from previous work that evaluated quality improvement databases. Each CI and supporting evidence was submitted for independent review by an expert panel. The RAND Corporation-University of California, Los Angeles (RAND/UCLA) appropriateness methodology was utilized and items were rated based on validity, reliability, and feasibility of measurement. After two rounds of ratings and ranking, a final ranked list of QIs was obtained. RESULTS: Fifty-six CIs were identified from the literature and CPGs or proposed by the expert panel. Two rounds of voting resulted in 12 total QIs that were deemed appropriate measures of high-quality care. The final 12 QIs were ranked by order of importance: use of peri-operative tranexamic acid, infusion of prophylactic antibiotics prior to inflation of tourniquet, appropriate post-operative venous thromboembolic prophylaxis, complication rate, rate of secondary procedure, readmission rate, early mobilization, average change of pre- to one year post-operative functional status, use of multimodal analgesia, use of neuraxial anesthesia, use of peri-articular injection in TKA, and use of pre-operative PO analgesia. CONCLUSION: This study is an expert opinion based on parameters observed in modern and high-quality academic settings. Twelve QIs are proposed to assess the quality of care in the peri-operative management of primary elective THA and TKA patients.

Capacity building at points of entry during COVID-19 pandemic: harmonising training curriculum for Economic Community of West African States.

This paper describes the process for developing, validating and disseminating through a train-the-trainer (TOT) event a standardised curriculum for public health capacity building for points of entry (POE) staff across the 15-member state Economic Community of West African States (ECOWAS) that reflects both international standards and national guidelines.A five-phase process was used in developing the curriculum: phase (1) assessment of existing materials developed by the US Centers for Disease Control and Prevention (CDC), Africa CDC and the West African Economic and Monetary Union, (2) design of retained and new, harmonised content, (3) validation by the national leadership to produce final content, (4) implementation of the harmonised curriculum during a regional TOT, and (5) evaluation of the curriculum.Of the nine modules assessed in English and French, the technical team agreed to retain six harmonised modules providing materials for 10 days of intensive training. Following the TOT, most participants (n=28/30, 93.3%) indicated that the International Health Regulations and emergency management modules were relevant to their work and 96.7% (n=29/30) reported that the training should be cascaded to POE staff in their countries.The ECOWAS harmonised POE curriculum provides a set of training materials and expectations for national port health and POE staff to use across the region. This initiative contributes to reducing the effort required by countries to identify emergency preparedness and response capacity-building tools for border health systems in the Member States in a highly connected region.