Collaborative model of care between orthopaedics and allied healthcare professionals (CONNACT) in knee osteoarthritis: Effectiveness-implementation hybrid randomized controlled trial of a community-based, multidisciplinary, stratified intervention.

OBJECTIVE: To compare the clinical and cost effectiveness of the Collaborative Model of Care between Orthopaedics and Allied Healthcare Professionals (CONNACT), a community-based, stratified, multidisciplinary intervention consisting of exercise, education, psychological and nutrition delivered through a chronic care model to usual hospital care in adults with knee osteoarthritis (OA). METHODS: Pragmatic, parallel-arm, single-blinded superiority RCT trial. Community-dwelling, ambulant adults with knee OA (Kellgren-Lawrence grade > 1; Knee Injury and OA Outcome Score (KOOS4) ≤75) were enrolled. Primary outcome was KOOS4 at 12-months; secondary outcomes included: quality of life, physical performance measures, symptom satisfaction, psychological outcomes, dietary habits, and global perceived effect. Intention-to-treat analysis using generalized linear model (GLM) and regression modeling were conducted. Economic evaluation through a societal approach was embedded. RESULTS: 110 participants (55 control, 55 intervention) were randomized. No between-group difference found for the primary outcome (MD [95%CI]: -1.86 [-9.11. 5.38]), although both groups demonstrated within-group improvement over 12-months. Among the secondary outcomes, the CONNACT group demonstrated superior dietary change (12 months) and physical performance measures (3 months), and global perceived effect (6 months). While there was no between-group difference in total cost, significant productivity gains (reduced indirect cost) were seen in the CONNACT group. CONCLUSION: CONNACT was not superior to usual care at 1 year. Further efforts are needed to understand the underlying contextual and implementation factors in order to further improve and refine such community-based, stratified care models moving forward. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03809975. Registered January 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03809975.

Study on proximal humerus evaluation of effective treatment (SPHEER) - what is the effect of rehabilitation compliance on clinical outcomes of proximal humerus fractures.

INTRODUCTION: Proximal humeral fractures (PHFs) are 3rd commonest fragility fractures and cause significant functional impairment. This paper sought to determine impact of rehabilitation compliance on the clinical outcomes for non-surgically managed PHFs, while ascertaining reasons for non-compliance which can be addressed to improve compliance. METHODS: Prospective cohort study of patients undergoing non-surgical treatment for PHFs from August 2017 to April 2020 in a tertiary trauma centre was performed. Data was collected via questionnaire: patient demographic data, PHF injury details, clinical outcome measures, therapist-reported (Sport Injury Rehabilitation Adherence Scale [SIRAS]) and patient-reported (subjective compliance, frequency of exercise) rehabilitation compliance measures. Data was analysed using multiple linear regression model to account for confounding variables. RESULTS: 107 participants attended physical therapy follow-up for mean 137.8 days. 6-week SIRAS strongly predicted 3-month Constant score (p = 0.023; 95%CI = 0.265,3.423), OSS (p = 0.038; 95%CI = 0.049,1.634), flexion ROM (p < 0.001; 95%CI = 2.872,8.982), extension ROM (p = 0.035; 95%CI = 0.097,2.614), abduction ROM (p = 0.002;95%CI = 1.995,8.466) and achievement of functional active ROM at 3-months (p = 0.049; 95%CI = 1.001,1.638). Pain was the top reason impairing rehabilitation compliance from therapist (43.9% at 6-weeks and 20.6% at 3-months) and patient-perspective (33.6% at 6-weeks, 24.3% at 3-months). Author-developed patient-reported compliance measures had good correlation with validated SIRAS score (subjective compliance: p < 0.001 frequency of exercise: p = 0.001). CONCLUSION: Rehabilitation compliance predicts short-term clinical outcomes up to 3-months and potentially 1-year outcomes. Pain control should be optimised to maximise rehabilitation compliance and improve PHF outcomes. There is lack of consensus definition for rehabilitation compliance measures; patient-reported measures used have good correlation to existing validated measures and could serve as a steppingstone for further research. LEVEL OF EVIDENCE: II, cohort study.

Singapore KneE osTeoarthritis CoHort (SKETCH): protocol for a multi-centre prospective cohort study.

BACKGROUND: Knee osteoarthritis (OA) is a leading cause of global disability. The understanding of the role of psychosocial factors in knee OA outcomes is still evolving particularly in an Asian context. The primary aim of this study is to explore psychosocial factors that prognosticate short and long-term clinical outcomes, productivity, and healthcare utilization in patients with knee OA. Secondary aims are to explore the mediation and directional relationships and the role it plays in predicting the discordance between self-reported measures (SRM), physical-performance measures (PPMs) and objective clinical parameters. METHODS: A multi-centre prospective cohort study of community ambulant knee OA patients seeking treatment in the tertiary healthcare institutions in Singapore will be conducted. Patients with secondary arthritis, significant cognitive impairment, severe medical comorbidities or previous knee arthroplasty will be excluded. Primary clinical outcome measure is the Knee injury and OA Outcome Score-12 (KOOS-12). Baseline characteristics include sociodemographic status, arthritis status including symptom duration and radiographic severity, comorbidities and functional status through Charlson Comorbidities Index (CCI), Barthel Index (BI) and Parker Mobility Score (PMS). Psychosocial variables include social support, kinesiophobia, negative affect, self-efficacy, injustice, chronic illness shame and the built environment. Clinical outcomes include quality of life, physical performance, global assessment, satisfaction and physical activity levels. Productivity and healthcare utilization will be assessed by a modified OA Cost and Consequences Questionnaire (OCC-Q) and the Work Productivity and Activity Impairment Questionnaire (WPAI). Variables will be collected at baseline, 4, 12 months and yearly thereafter. Regression, mediation and structural equation modelling will be used for analysis. DISCUSSION: Results will allow contextualization, identification, and phenotyping of the critical (and potentially modifiable) psychosocial parameters that predict positive clinical outcomes in the OA population to guide optimization and refinement of healthcare and community. This will facilitate: 1. identification of high-risk knee OA subpopulations that will likely experience poor outcomes and 2. formulation of targeted multidisciplinary comprehensive approaches to address these psychosocial factors to optimize non-surgical treatment care, maximize functional outcomes and create more value-based care model for knee OA. ETHICS AND DISSEMINATION: The study has been registered under clinicaltrials.gov registry (Identifier: NCT04942236).

Discordance Between Self-Reported and Performance-Based Physical Function in Patients Who Have Knee Osteoarthritis: Associations With Pain Intensity and Negative Affect.

BACKGROUND: Although self-reported measures of physical disability are strong indication criterion for total knee arthroplasty (TKA) in painful knee osteoarthritis (OA), some patients may report greater-than-observed disability. Contributing factors to this discordance are relatively unexplored. We aimed to examine whether pain and negative affect, including anxiety and depression, were associated with the discordance of self-reported measures with performance-based measures (PPM) of physical function. METHODS: We used cross-sectional data (n = 212) from two randomized rehabilitation trials in knee OA. All patients were assessed for knee pain intensity and symptoms of anxiety and depression. Self-reported function was assessed by the Western Ontario and McMaster Universities Arthritis Index (WOMAC) physical-function subscale. Objective performance-based measures (PPMs) of physical function were assessed by timed gait and stair tests. Continuous discordance scores were quantified by the difference in percentiles between WOMAC and PPMs (WOMAC-PPM), where a positive discordance, WOMAC-PPM >0, implied greater perceived than observed disability. RESULTS: Around 1 in 4 patients had >20 percentile units in WOMAC-PPM discordance. In Bayesian regression analyses, knee pain intensity had >99% posterior probability of positive associations with WOMAC-PPM discordance. Among patients awaiting TKA, anxiety intensity had approximately 99% probability of positive associations with discordance, and these associations had >65% probability of exceeding 10 percentile units. In contrast, depression had low (79% to 88%) probability of any association with discordance. CONCLUSION: In patients who have knee OA, a sizable proportion reported substantially greater physical disability than actually observed. Pain and anxiety intensity, but not depression, were meaningful predictors of this discordance. If validated, our findings may help in refining patient selection criteria for TKA.

Detection of clinical progression through plasma ctDNA in metastatic melanoma patients: a comparison to radiological progression.

BACKGROUND: The validity of circulating tumour DNA (ctDNA) as an indicator of disease progression compared to medical imaging in patients with metastatic melanoma requires detailed evaluation. METHODS: Here, we carried out a retrospective ctDNA analysis of 108 plasma samples collected at the time of disease progression. We also analysed a validation cohort of 66 metastatic melanoma patients monitored prospectively after response to systemic therapy. RESULTS: ctDNA was detected in 62% of patients at the time of disease progression. For 67 patients that responded to treatment, the mean ctDNA level at progressive disease was significantly higher than at the time of response (P < 0.0001). However, only 30 of these 67 (45%) patients had a statistically significant increase in ctDNA by Poisson test. A validation cohort of 66 metastatic melanoma patients monitored prospectively indicated a 56% detection rate of ctDNA at progression, with only two cases showing increased ctDNA prior to radiological progression. Finally, a correlation between ctDNA levels and metabolic tumour burden was only observed in treatment naïve patients but not at the time of progression in a subgroup of patients failing BRAF inhibition (N = 15). CONCLUSIONS: These results highlight the low efficacy of ctDNA to detect disease progression in melanoma when compared mainly to standard positron emission tomography imaging.

Emergency department interventions for frailty (EDIFY): improving functional outcomes in older persons at the emergency department through a multicomponent frailty intervention.

OBJECTIVES: emergency department interventions for frailty (EDIFY) delivers frailty-centric interventions at the emergency department (ED). We evaluated the effectiveness of a multicomponent frailty intervention (MFI) in improving functional outcomes among older persons. DESIGN: a quasi-experimental study. SETTING: a 30-bed ED observation unit within a 1,700-bed acute tertiary hospital. PARTICIPANTS: patients aged ≥65 years, categorised as Clinical Frailty Scale 4-6, and planned for discharge from the unit. METHODS: we compared patients receiving the MFI versus usual-care. Data on demographics, function, frailty, sarcopenia, comorbidities and medications were gathered. Our primary outcome was functional status-Modified Barthel Index (MBI) and Lawton's iADL. Secondary outcomes include hospitalisation, ED re-attendance, mortality, frailty, sarcopenia, polypharmacy and falls. Follow-up assessments were at 3, 6 and 12 months. RESULTS: we recruited 140 participants (mean age 79.7 ± 7.6 years; 47% frail and 73.6% completed the study). Baseline characteristics between groups were comparable (each n = 70). For the intervention group, MBI scores were significantly higher at 6 months (mean: 94.5 ± 11.2 versus 88.5 ± 19.5, P = 0.04), whereas Lawton's iADL scores experienced less decline (change-in-score: 0.0 ± 1.7 versus -1.1 ± 1.8, P = 0.001). Model-based analyses revealed greater odds of maintaining/improving MBI in the intervention group at 6 months [odds ratio (OR) 2.51, 95% confidence interval (CI) 1.04-6.03, P = 0.04] and 12 months (OR 2.98, 95% CI 1.18-7.54, P = 0.02). This was similar for Lawton's iADL at 12 months (OR 4.01, 95% CI 1.70-9.48, P = 0.002). ED re-attendances (rate ratio 0.35, 95% CI 0.13-0.90, P = 0.03) and progression to sarcopenia (OR 0.19, 95% CI 0.04-0.94, P = 0.04) were also lower at 6 months. CONCLUSIONS: the MFI delivered to older persons at the ED can possibly improve functional outcomes and reduce ED re-attendances while attenuating sarcopenia progression.

A cluster-randomized trial of workplace ergonomics and neck-specific exercise versus ergonomics and health promotion for office workers to manage neck pain - a secondary outcome analysis.

BACKGROUND: Neck pain is prevalent among office workers. This study evaluated the impact of an ergonomic and exercise training (EET) intervention and an ergonomic and health promotion (EHP) intervention on neck pain intensity among the All Workers and a subgroup of Neck Pain cases at baseline. METHODS: A 12-month cluster-randomized trial was conducted in 14 public and private organisations. Office workers aged ≥18 years working ≥30 h per week (n = 740) received an individualised workstation ergonomic intervention, followed by 1:1 allocation to the EET group (neck-specific exercise training), or the EHP group (health promotion) for 12 weeks. Neck pain intensity (scale: 0-9) was recorded at baseline, 12 weeks, and 12 months. Participants with data at these three time points were included for analysis (n = 367). Intervention group differences were analysed using generalized estimating equation models on an intention-to-treat basis and adjusted for potential confounders. Subgroup analysis was performed on neck cases reporting pain ≥3 at baseline (n = 96). RESULTS: The EET group demonstrated significantly greater reductions in neck pain intensity at 12 weeks compared to the EHP group for All Workers (EET: ß = - 0.53 points 95% CI: - 0.84- - 0.22 [36%] and EHP: ß = - 0.17 points 95% CI: - 0.47-0.13 [10.5%], p-value = 0.02) and the Neck Cases (EET: ß = - 2.32 points 95% CI: - 3.09- - 1.56 [53%] and EHP: ß = - 1.75 points 95% CI: - 2.35- - 1.16 [36%], p = 0.04). Reductions in pain intensity were not maintained at 12 months with no between-group differences observed in All Workers (EET: ß = - 0.18, 95% CI: - 0.53-0.16 and EHP: ß = - 0.14 points 95% CI: - 0.49-0.21, p = 0.53) or Neck Cases, although in both groups an overall reduction was found (EET: ß = - 1.61 points 95% CI: - 2.36- - 0.89 and EHP: ß = - 1.9 points 95% CI: - 2.59- - 1.20, p = 0.26). CONCLUSION: EET was more effective than EHP in reducing neck pain intensity in All Workers and Neck Cases immediately following the intervention period (12 weeks) but not at 12 months, with changes at 12 weeks reaching clinically meaningful thresholds for the Neck Cases. Findings suggest the need for continuation of exercise to maintain benefits in the longer term. CLINICAL TRIAL REGISTRATION: hACTRN12612001154897 Date of Registration: 31/10/2012.

PD-L1 Expression on Circulating Tumor Cells May Be Predictive of Response to Pembrolizumab in Advanced Melanoma: Results from a Pilot Study.

BACKGROUND: PD-1 inhibitors are routinely used for the treatment of advanced melanoma. This study sought to determine whether PD-L1 expression on circulating tumor cells (CTCs) can serve as a predictive biomarker of clinical benefit and response to treatment with the PD-1 inhibitor pembrolizumab. METHODS: Blood samples were collected from patients with metastatic melanoma receiving pembrolizumab, prior to treatment and 6-12 weeks after initiation of therapy. Multiparametric flow cytometry was used to identify CTCs and evaluate the expression of PD-L1. RESULTS: CTCs were detected in 25 of 40 patients (63%). Patients with detectable PD-L1+ CTCs (14/25, 64%) had significantly longer progression-free survival (PFS) compared with patients with PD-L1- CTCs (26.6 months vs. 5.5 months; p = .018). The 12-month PFS rates were 76% versus 22% in the PD-L1+ versus PD-L1- CTCs groups (p = .012), respectively. A multivariate linear regression analysis confirmed that PD-L1+ CTC is an independent predictive biomarker of PFS (hazard ratio, 0.229; 95% confidence interval, 0.052-1.012; p = .026). CONCLUSION: Our results reveal the potential of CTCs as a noninvasive real-time biopsy to evaluate PD-L1 expression in patients with melanoma. PD-L1 expression on CTCs may be predictive of response to pembrolizumab and longer PFS. IMPLICATIONS FOR PRACTICE: The present data suggest that PD-L1 expression on circulating tumor cells may predict response to pembrolizumab in advanced melanoma. This needs further validation in a larger trial and, if proven, might be a useful liquid biopsy tool that could be used to stratify patients into groups more likely to respond to immunotherapy, hence leading to health cost savings.

Process evaluation of a workplace-based health promotion and exercise cluster-randomised trial to increase productivity and reduce neck pain in office workers: a RE-AIM approach.

BACKGROUND: This study uses the RE-AIM framework to provide a process evaluation of a workplace-based cluster randomised trial comparing an ergonomic plus exercise intervention to an ergonomic plus health promotion intervention; and to highlight variations across organisations; and consider the implications of the findings for intervention translation. METHOD: This study applied the RE-AIM (reach, effectiveness, adoption, implementation, maintenance) methodology to examine the interventions' implementation and to explore the extent to which differences between participating organisations contributed to the variations in findings. Qualitative and quantitative data collected from individual participants, research team observations and organisations were interrogated to report on the five RE-AIM domains. RESULTS: Overall reach was 22.7% but varied across organisations (range 9 to 83%). Participants were generally representative of the recruitment pool though more females (n = 452 or 59%) were recruited than were in the pool (49%). Effectiveness measures (health-related productivity loss and neck pain) varied across all organisations, with no clear pattern emerging to indicate the source of the variation. Organisation-level adoption (66%) and staffing level adoption (91%) were high. The interventions were implemented with minimal protocol variations and high staffing consistency, but organisations varied in their provision of resources (e.g. training space, seniority of liaisons). Mean adherence of participants to the EET intervention was 56% during the intervention period, but varied from 41 to 71% across organisations. At 12 months, 15% of participants reported regular EET adherence. Overall mean (SD) adherence to EHP was 56% (29%) across organisations during the intervention period (range 28 to 77%), with 62% of participants reporting regular adherence at 12 months. No organisations continued the interventions after the follow-up period. CONCLUSION: Although the study protocol was implemented with high consistency and fidelity, variations in four domains (reach, effectiveness, adoption and implementation) arose between the 14 participating organisations. These variations may be the source of mixed effectiveness across organisations. Factors known to increase the success of workplace interventions, such as strong management support, a visible commitment to employee wellbeing and participant engagement in intervention design should be considered and adequately measured for future interventions. TRIAL REGISTRATION: ACTRN12612001154897; 29 October 2012.

Collaborative model of care between Orthopaedics and allied healthcare professionals in knee osteoarthritis (CONNACT): study protocol for an effectiveness-implementation hybrid randomized control trial.

BACKGROUND: Knee Osteoarthritis (OA) is a leading cause of global disability. The Collaborative Model of Care between Orthopaedics and Allied Healthcare Professionals (CONNACT) Model of Care (MoC) was developed by optimizing evidence-based non-surgical treatments to deliver value-based care for people with knee OA. The primary aim of this study is to determine the clinical effectiveness of the CONNACT MoC (3 months) compared to usual care. The secondary aims are: a) To determine the cost-effectiveness and b) To develop an evaluation and implementation framework to inform large scale implementation for this MoC. METHODOLOGY: Type 1 Effectiveness-Implementation Hybrid Trial using an explanatory sequential mixed-method approach. The study consists of 3 components. The first component is the pragmatic, parallel-arm, single-blinded randomized control trial. Inclusion criteria are patients with knee OA based on the National Institute of Health and Care Excellence (NICE) criteria with radiographic severity of greater than Kellgren-Lawrence 1, and Knee Injury and OA Outcome Score (KOOS4) of equal or less than 75. Exclusion criteria include other forms of arthritis, history of previous knee arthroplasty or wheelchair-bound patient. KOOS4 is the primary outcome measure at 3 months, 6 months and 1 year. Secondary outcomes include KOOS individual subscales, quality of life scoring, functional performance, global, diet and psychological related outcomes. The second component is an economic evaluation of the cost-effectiveness of the CONNACT MoC using a societal perspective. The third component is an implementation and evaluation framework using process evaluation under the RE-AIM framework using a mixed-method approach. Sample size of 100 patients has been calculated. DISCUSSION: CONNACT MoC is a complex intervention. In line with the MRC guidance for developing and evaluating complex interventions, a pilot feasibility study was completed and a comprehensive approach including an RCT, economic evaluation and process evaluation is described in this study protocol. Results from this study will help clinicians, healthcare administrators and policymakers guide the sustainable and effective implementation of the CONNACT MoC for knee OA and serve as a basis for similar multidisciplinary MoC for chronic degenerative musculoskeletal conditions to be developed. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03809975 . Registered January 182,019.

Collaborative model of care between Orthopaedics and allied healthcare professionals trial (CONNACT) - a feasibility study in patients with knee osteoarthritis using a mixed method approach.

BACKGROUND: Osteoarthritis is a leading cause of global disability resulting in significant morbidity and cost to the healthcare system. Current guidelines recommend lifestyle changes such exercises and weight loss as first line treatment prior to surgical consideration. Our current model of care is inefficient with suboptimal allied health intervention for effective behaviour changes. A 12-week community based, individualized, multidisciplinary new model of care for knee osteoarthritis was developed in light of current deficiencies. METHODS: The primary aim of this study was to determine the feasibility of a full randomized controlled trial evaluating this new model of care using pre-defined progression criteria. The secondary aim was to optimize the intervention and study design through a process evaluation. A pilot exploratory, parallel arm, single blinded randomized trial design using a mixed method approach was utilized. Progression criteria for a full trial including key domains of patient recruitment and retention, outcome measure acceptability and improvement, adverse events were developed. The primary outcome measure was the Knee Injury and Osteoarthritis Outcome Score (KOOS) at baseline and 12-weeks. Secondary outcomes included quality of life, functional and psychological assessments. Semi-structured interviews were conducted with the patients at 12-weeks. RESULTS: 20 patients (3 males, 17 females) were randomized (10 intervention, 10 control). Intervention arm patients reported better improvements in their knee function, quality of life, psychological outcome, dietary improvement and weight loss compared to the control arm at 12-weeks. Semi-structured interviews revealed several themes pertaining to feasibility and intervention optimization. 5 out of the 6 progression criteria's domains were met (recruitment criteria not met). CONCLUSION: This pilot has demonstrated the feasibility of a full randomized control trial investigating the potential effectiveness of the new proposed model of care for knee osteoarthritis using pre-defined progression criteria and process evaluation. Results from the qualitative study were used to modify and improve the intervention content, delivery model and study design for a large effectiveness-implementation hybrid randomized control trial that is currently underway. TRIAL REGISTRATION: Retrospectively registered on 18 January 2019 at http://clinicaltrial.gov ID: NCT03809975 .

The ideal implant for Mayo 2A olecranon fractures? An economic evaluation.

BACKGROUND: The ideal implant for stable, noncomminuted olecranon fractures is controversial. Tension band wiring (TBW) is associated with lower cost but higher implant removal rates.On the other hand, plate fixation (PF) is purported to be biomechanically superior, with lower failure and implant removal rates, although associated with higher cost. The primary aim of this study is to look at the clinical outcomes for all Mayo 2A olecranon between PF and TBW. The secondary aim is to perform an economic evaluation of PF vs. TBW. MATERIALS AND METHODS: This is a retrospective study of all surgically treated Mayo 2A olecranon fractures in a tertiary hospital from 2005-2016. Demographic data, medical history, range of motion, and complications were collected. All inpatient and outpatient costs in a 1-year period postsurgery including the index surgical procedure were collected via the hospital administrative cost database (normalized to 2014). RESULTS: A total of 147 cases were identified (94 TBW, 53 PF). PF was associated with higher mean age (P < .01), higher American Society of Anesthesiologists score (P < .01), and higher proportion of hypertensives (P = .04). There was no difference in the range of motion achieved at 1 year for both groups. In terms of complications, TBW was associated with more symptomatic hardware (21.6% vs. 13.7%, P = .24) and implant failures (16.5% vs. none, P < .01), whereas the plate group had a higher wound complication (5.9% vs. none, P = .02) and infection rate (9.8% vs. 3.1%, P = .09). TBW had a higher implant removal rate of 30.9% compared with 22.7% for PF (P = .36). PF had a higher cost at all time points, from the index surgery ($10,313.64 vs. $5896.36, P < .01), 1-year cost excluding index surgery ($5069.61 vs. $3850.46, P = .46), and outpatient cost ($1667.80 vs. $1613.49, P = .27). DISCUSSION AND CONCLUSION: Based on our study results, we have demonstrated that TBW is the ideal implant for Mayo 2A olecranon fractures from both a clinical and economic standpoint, with comparable clinical results, potentially similar implant removal rates as PF's, and a lower cost over a 1-year period. In choosing the ideal implant, the surgeon must take into account, first, the local TBW and PF removal rate, which can vary significantly because of the patient's profile and beliefs, and second, the PF implant cost.

Correlation between circulating tumour DNA and metabolic tumour burden in metastatic melanoma patients.

BACKGROUND: Circulating tumour DNA (ctDNA) may serve as a measure of tumour burden and a useful tool for non-invasive monitoring of cancer. However, ctDNA is not always detectable in patients at time of diagnosis of metastatic disease. Therefore, there is a need to understand the correlation between ctDNA levels and the patients' overall metabolic tumour burden (MTB). METHODS: Thirty-two treatment naïve metastatic melanoma patients were included in the study. MTB and metabolic tumour volume (MTV) was measured by 18F-fluoro-D-glucose positron emission tomography/computed tomography (FDG PET/CT). Plasma ctDNA was quantified using droplet digital PCR (ddPCR). RESULTS: CtDNA was detected in 23 of 32 patients. Overall, a significant correlation was observed between ctDNA levels and MTB (p < 0.001). CtDNA was not detectable in patients with an MTB of ≤10, defining this value as the lower limit of tumour burden that can be detected through ctDNA analysis by ddPCR. CONCLUSIONS: We showed that ctDNA levels measured by ddPCR correlate with MTB in treatment naïve metastatic melanoma patients and observed a limit in tumour size for which ctDNA cannot be detected in blood. Nevertheless, our findings support the use of ctDNA as a non-invasive complementary modality to functional imaging for monitoring tumour burden.

Inter-rater reliability of an observation-based ergonomics assessment checklist for office workers.

OBJECTIVES: To establish the inter-rater reliability of an observation-based ergonomics assessment checklist for computer workers. METHODS: A 37-item (38-item if a laptop was part of the workstation) comprehensive observational ergonomics assessment checklist comparable to government guidelines and up to date with empirical evidence was developed. Two trained practitioners assessed full-time office workers performing their usual computer-based work and evaluated the suitability of workstations used. Practitioners assessed each participant consecutively. The order of assessors was randomised, and the second assessor was blinded to the findings of the first. Unadjusted kappa coefficients between the raters were obtained for the overall checklist and subsections that were formed from question-items relevant to specific workstation equipment. RESULTS: Twenty-seven office workers were recruited. The inter-rater reliability between two trained practitioners achieved moderate to good reliability for all except one checklist component. CONCLUSIONS: This checklist has mostly moderate to good reliability between two trained practitioners. Practitioner Summary: This reliable ergonomics assessment checklist for computer workers was designed using accessible government guidelines and supplemented with up-to-date evidence. Employers in Queensland (Australia) can fulfil legislative requirements by using this reliable checklist to identify and subsequently address potential risk factors for work-related injury to provide a safe working environment.

The impact of onsite workplace health-enhancing physical activity interventions on worker productivity: a systematic review.

The aim of this study is to investigate the effects of onsite workplace health-enhancing physical activity (HEPA) programmes on worker productivity. The PROSPERO registration number is CRD42014008750. A search for controlled trials or randomised controlled trials (RCTs) that investigated the effects of onsite workplace HEPA programmes on productivity levels of working adults was performed. Risk of bias of included studies was assessed, and the inter-rater reliability of the quality assessment was analysed. Qualitative synthesis of available evidence is presented. Eight studies were included in the review. There is consistent evidence that onsite workplace HEPA programmes do not reduce levels of sick leave. There appears to be inconsistent evidence of the impact of onsite workplace HEPA programmes on worker productivity. A high-quality study of an onsite combination (aerobic, strengthening and flexibility) HEPA regime and a moderate-quality study of a Tai Chi programme improved worker productivity measured with questionnaires in female laundry workers and older female nurses, respectively. Two high-quality studies and four moderate-quality studies did not show benefit. Studies that showed benefit were mainly those designed with productivity measures as primary outcomes, delivered to occupations involved with higher physical loads, and had higher compliance and programme intensity. The small number of studies and the lack of consistency among studies limited further analyses. There is inconsistent evidence that onsite workplace HEPA programmes improve self-reported worker productivity. Future high-quality RCTs of onsite workplace HEPA programmes should be designed around productivity outcomes, target at-risk groups and investigate interventions of sufficient intensity. High attendance with improved recording is needed to achieve significant results in augmenting worker productivity.

[Discourses on the nursing and psychiatric nurse models, published in the Annals of Nursing (1933-1951)]. / Discursos sobre os modelos de enfermagem e de enfermeira psiquiátrica nos Annaes de Enfermagem (1933-1951).

Social-historical study aimed at discussing the nursing and psychiatric nurse models, from the discourses published in the Annals of Nursing.The historical sources were articles published in the Annals of Nursing journal, from 1933 to 1951. An analysis of the discourse was subsidized by the genealogy of power by Michel Foucault.The analysis showed that the discourse on nursing and the psychiatric nurse, in the first half of the 20th century, is set, on one side, by the propositions used by psychiatrists, who sought to reiterate stereotypes and vocations to practice nursing, and, on the other side, by the active participation of nurses seeking to legitimize expertise for psychiatric nursing. It was concluded that the discourses analyzed defined a psychiatric care focused on the nurse and not the rest of the nursing staff, at that time.

Achieving satisfactory functional outcomes in conservatively treated proximal humerus fractures: relationship between shoulder range of motion and patient-reported clinical outcome scores.

Background: Proximal humerus fractures are common osteoporotic fractures. Postinjury outcome measures include objective clinician-measured range of motion (ROM) and subjective patient-reported outcome measures (PROMs), but the relationship between both has not been established. This study aimed to determine the relationship between shoulder ROM and PROMs and establish which ROMs correlated most with PROMs. Methods: A prospective cohort study was conducted on patients with acute proximal humerus fractures. Surgical intervention, open or pathological fractures, neurovascular compromise, polytrauma, or delayed presentations were excluded. Correlation and regression analyses between active ROM and PROMs (Quick Disabilities of Arm, Shoulder and Hand [QuickDASH] and Oxford Shoulder Score [OSS]) at 1-year postinjury were explored. ROM cutoffs predicting satisfactory PROM scores were established. Results: Fifty-five patients were recruited. Moderate correlations were observed between PROMs and flexion, extension, and abduction, but not internal and external rotation. Multivariate analysis showed significant relationships between PROMs and flexion [QuickDASH: adjusted coefficient (AC): -0.135, P = .013, OSS: AC: 0.072, P = .002], abduction [QuickDASH: AC: -0.115, P = .021, OSS: AC: 0.059, P = .005], and extension [QuickDASH: AC: -0.304, P = .020] adjusting for age, gender, Neer classification, injury on dominant side, and employment. Achieving 130° flexion, 59° extension, and 124° abduction were correlated with satisfactory OSS/QuickDASH scores, respectively. Conclusion: Overall, holistic assessment of outcomes with both subjective and objective outcomes are necessary, as shoulder flexion, extension, and abduction are only moderately correlated with PROMs. Attaining 130° flexion, 59° extension, and 124° abduction corresponded with satisfactory functional outcomes measured by OSS/QuickDASH and can guide rehabilitation.

Association of Apolipoprotein E (APOE) Polymorphisms With Serological Lipid and Inflammatory Markers.

Background  The study aims to assess the association of apolipoprotein E (APOE) gene polymorphisms with serological lipid and inflammatory markers to determine their potential role in predicting the risk of cardiovascular diseases (CVDs) and Alzheimer's disease (AD).  Methodology  A total of 915 individuals underwent testing for lipid and inflammatory biomarkers at Vibrant America Clinical Laboratory. Clinical data, blood lipid and inflammatory profiles, and APOE genotyping were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).  Results Compared to the E3/E3 genotype, individuals with E2/E3 genotypes showed higher levels of high-density lipoprotein (HDL), triglycerides, apolipoprotein A (APOA), high-sensitivity C-reactive protein (hs-CRP), and myeloperoxidase (MPO). E2/E4 genotype carriers had higher levels of HDL, triglycerides, Lp(a), and N-terminal pro b-type natriuretic peptide (BNPNT). E3/E4 genotypes were associated with elevated levels of total cholesterol, LDL, Lp(a), hs-CRP, small-density low-density lipoprotein (SDLDL), oxidized LDL (OXLDL), MPO, LDL-CAL, PLAC, and APOB. The E4/E4 group displayed higher concentrations of total cholesterol, LDL, APOB, Lp(a), hs-CRP, SDLDL, OXLDL, MPO, LDLCAL, and PLAC compared to E3/E3 carriers. These findings highlight the potential atherogenic effect of the ε4 allele and the protective effect of the ε2 allele based on lipid and inflammatory marker profiles.  Conclusions This study provides strong evidence linking APOE gene polymorphism to abnormal serum lipid and inflammatory profiles. Individuals carrying the ε4 alleles exhibited dysregulated lipid metabolism and abnormal inflammatory markers, increasing their risk of CVD and AD. Early detection and prompt diagnosis are crucial for implementing therapeutic, dietary, and lifestyle interventions to mitigate risks and prevent or delay lipid and inflammation-related disorders.

Heat and Acupuncture to Manage Osteoarthritis of the Knee (HARMOKnee): Protocol for an Effectiveness-Implementation Hybrid Randomized Controlled Trial.

BACKGROUND: Knee osteoarthritis (KOA) is one of most prevalent and fastest-growing causes of pain, impaired mobility, and poor quality of life in the rapidly aging population worldwide. There is a lack of high-quality evidence on the efficacy of traditional Chinese medicine (TCM), particularly acupuncture, and a lack of KOA practice guidelines that are tailored to unique population demographics and tropical climates. OBJECTIVE: Our HARMOKnee (Heat and Acupuncture to Manage Osteoarthritis of the Knee) trial aims to address these gaps by evaluating the short- and medium-term clinical and cost-effectiveness of acupuncture with heat therapy in addition to standard care, compared to standard care alone. Through a robust process and economic evaluation, we aim to inform evidence-based practice for patients with KOA to facilitate the large-scale implementation of a comprehensive and holistic model of care that harmonizes elements of Western medicine and TCM. We hypothesize that acupuncture with heat therapy as an adjunct to standard care is clinically more effective than standard care alone. METHODS: A multicenter, pragmatic, parallel-arm, single-blinded, effectiveness-implementation hybrid randomized controlled trial will be conducted. We intend to recruit 100 patients with KOA randomized to either the control arm (standard care only) or intervention arm (acupuncture with heat therapy, in addition to standard care). The inclusion criteria are being a community ambulator and having primary KOA, excluding patients with secondary arthritis or previous knee replacements. The primary outcome measure is the Knee Osteoarthritis Outcome Score at 6 weeks. Secondary outcome measures include psychological, physical, quality of life, satisfaction, and global outcome measures at 6, 12, and 26 weeks. A mixed method approach through an embedded process evaluation will facilitate large-scale implementation. An economic evaluation will be performed to assess financial sustainability. RESULTS: Patient enrollment has been ongoing since August 2022. The recruitment process is anticipated to conclude by July 2024, and the findings will be analyzed and publicized as they are obtained. As of November 6, 2023, our patient enrollment stands at 65 individuals. CONCLUSIONS: The findings of our HARMOKnee study will contribute substantial evidence to the current body of literature regarding the effectiveness of acupuncture treatment for KOA. Additionally, we aim to facilitate the creation of standardized national guidelines for evidence-based practice that are specifically tailored to our unique population demographics. Furthermore, we seek to promote the adoption and integration of acupuncture and heat therapy into existing treatment models. TRIAL REGISTRATION: ClinicalTrials.gov NCT05507619; https://clinicaltrials.gov/study/NCT05507619. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54352.

FERM domain interaction with myosin negatively regulates FAK in cardiomyocyte hypertrophy.

Focal adhesion kinase (FAK) regulates cellular processes that affect several aspects of development and disease. The FAK N-terminal FERM (4.1 protein-ezrin-radixin-moesin homology) domain, a compact clover-leaf structure, binds partner proteins and mediates intramolecular regulatory interactions. Combined chemical cross-linking coupled to MS, small-angle X-ray scattering, computational docking and mutational analyses showed that the FAK FERM domain has a molecular cleft (~998 Å(2)) that interacts with sarcomeric myosin, resulting in FAK inhibition. Accordingly, mutations in a unique short amino acid sequence of the FERM myosin cleft, FP-1, impaired the interaction with myosin and enhanced FAK activity in cardiomyocytes. An FP-1 decoy peptide selectively inhibited myosin interaction and increased FAK activity, promoting cardiomyocyte hypertrophy through activation of the AKT-mammalian target of rapamycin pathway. Our findings uncover an inhibitory interaction between the FAK FERM domain and sarcomeric myosin that presents potential opportunities to modulate the cardiac hypertrophic response through changes in FAK activity.