The prognostic and potentially immunomodulatory role of cartilage oligomeric matrix protein in patients with gastric and esophageal adenocarcinoma.

BACKGROUND: Cartilage oligomeric matrix protein (COMP) is a novel regulator of the tumor microenvironment. Studies in colon cancer and pancreatobiliary adenocarcinoma have revealed COMP expression to be associated with decreased infiltration of immune cells in the tumor microenvironment. Herein, the expression of COMP was investigated in gastric and esophageal adenocarcinoma with particular reference to its the relationship with the immune microenvironment. METHODS: COMP expression was evaluated in tissue microarrays representing primary tumors from 159 patients with chemo- and radiotherapy naïve esophageal and gastric adenocarcinoma and 67 matched samples of lymph node metastases using immunohistochemistry. Additionally, collagen fibers were stained with Sirius Red and evaluated with the FIJI macro TWOMBLI algorithm. RESULTS: The expression of COMP in cancer cells in the entire cohort was associated with shorter overall survival (OS) (p = 0.013) and recurrence-free survival (RFS) (p = 0.029), while COMP expression in the stroma was correlated with shorter RFS (p = 0.042). Similar correlations were found for patients with gastric adenocarcinoma, whereas COMP expression was not prognostic in esophageal adenocarcinoma. Further, in the entire cohort, the expression of COMP in the stroma was correlated with exclusion of different populations of immune cells (CD8+, CD3+, FoxP3+, CD20+) from the tumor microenvironment. Finally, higher density and alignment of collagen fibers were correlated with the expression of COMP in the stroma. CONCLUSIONS: Expression of COMP in gastric and esophageal adenocarcinoma was correlated with shorter OS and RFS. A reduced number of immune cells infiltrated the tumor microenvironment when COMP expression was detected. This phenomenon could be attributed to the denser collagen deposits, a hallmark of tumor fibrosis observed in COMP-expressing tumors.

Meta-analysis prediction intervals are under reported in sport and exercise medicine.

AIM: Prediction intervals are a useful measure of uncertainty for meta-analyses that capture the likely effect size of a new (similar) study based on the included studies. In comparison, confidence intervals reflect the uncertainty around the point estimate but provide an incomplete summary of the underlying heterogeneity in the meta-analysis. This study aimed to estimate (i) the proportion of meta-analysis studies that report a prediction interval in sports medicine; and (ii) the proportion of studies with a discrepancy between the reported confidence interval and a calculated prediction interval. METHODS: We screened, at random, 1500 meta-analysis studies published between 2012 and 2022 in highly ranked sports medicine and medical journals. Articles that used a random effect meta-analysis model were included in the study. We randomly selected one meta-analysis from each article to extract data from, which included the number of estimates, the pooled effect, and the confidence and prediction interval. RESULTS: Of the 1500 articles screened, 866 (514 from sports medicine) used a random effect model. The probability of a prediction interval being reported in sports medicine was 1.7% (95% CI = 0.9%, 3.3%). In medicine the probability was 3.9% (95% CI = 2.4%, 6.6%). A prediction interval was able to be calculated for 220 sports medicine studies. For 60% of these studies, there was a discrepancy in study findings between the reported confidence interval and the calculated prediction interval. Prediction intervals were 3.4 times wider than confidence intervals. CONCLUSION: Very few meta-analyses report prediction intervals and hence are prone to missing the impact of between-study heterogeneity on the overall conclusions. The widespread misinterpretation of random effect meta-analyses could mean that potentially harmful treatments, or those lacking a sufficient evidence base, are being used in practice. Authors, reviewers, and editors should be aware of the importance of prediction intervals.

Unmet healthcare needs, access to services and experiences with health providers among persons with spinal cord injury in Australia.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: Appropriate and timely lifelong access to healthcare following a spinal cord injury (SCI) is critical, yet unmet healthcare needs in this population are common. Poor experiences with healthcare providers can be a barrier to health-seeking behaviour, and we hypothesised that there would be an association between unmet healthcare needs and care experiences. This study aimed to: (1) describe healthcare provider utilisation in the past year, unmet care needs and satisfaction with healthcare services; (2) explore the association between experiences with healthcare providers and unmet healthcare needs; and (3) explore the association between healthcare provider utilisation and participant characteristics, including unmet healthcare needs. SETTING: Community. METHODS: Analysis of data for 1579 Australians aged ≥ 18, who were ≥ 1-year post-SCI and living in the community. Bayesian penalised regression was used to model six binary outcomes: unmet healthcare needs; the use of general practitioners (GPs), allied health practitioners, rehabilitation specialists; medical specialists; and hospitalisations in the past 12-months. RESULTS: Unmet needs were reported by 17% of participants, with service cost the common deterrent. There was evidence of an effect for provider experiences on unmet healthcare needs, but no evidence that unmet healthcare needs was associated with the use of GPs, allied health practitioners, and rehabilitation or medical specialists. CONCLUSIONS: Unmet healthcare needs were reported in the context of high healthcare use and large proportions of secondary conditions in a cohort with long-term SCI. Improved health access for people with SCI include better primary-secondary care collaboration is needed.

Practical cooling interventions for preventing heat strain in indoor factory workers in Thailand.

BACKGROUND: Occupational heat stress, exacerbated by factors such as climate change and insufficient cooling solutions, endangers the health and productivity of workers, especially in low-resource workplaces. OBJECTIVE: To evaluate the effectiveness of two cooling strategies in reducing physiological strain and productivity of piece-rate workers over a 9-h work shift in a southern Thailand sawmill. METHODS: In a crossover randomized control trial design, 12 (33 ± 7 y; 1.58 ± 0.05 m; 51 ± 9 kg; n = 5 females) medically screened sawmill workers were randomly allocated into three groups comprising an established phase change material vest (VEST), an on-site combination cooling oasis (OASIS) (i.e., hydration, cold towels, fans, water dousing), and no cooling (CON) across 3 consecutive workdays. Physiological strain was measured via core temperature telemetry and heart rate monitoring. Productivity was determined by counting the number of pallets of wood sorted, stacked, and stowed each day. RESULTS: Relative to CON, OASIS lowered core temperature by 0.25°C [95% confidence interval = 0.24, 0.25] and heart rate by 7 bpm [6, 9] bpm, compared to 0.17°C [0.17, 0.18] and 10 [9,12] bpm reductions with VEST. It was inconclusive whether productivity was statistically lower in OASIS compared to CON (mean difference [MD] = 2.5 [-0.2, 5.2]), and was not statistically different between VEST and CON (MD = 1.4 [-1.3, 4.1]). CONCLUSIONS: Both OASIS and VEST were effective in reducing physiological strain compared to no cooling. Their effect on productivity requires further investigation, as even small differences between interventions could lead to meaningful disparities in piece-rate worker earnings over time.

Intrinsic motor neuron excitability is increased after resistance training in older adults.

This study investigated the effects of high-intensity resistance training on estimates of the motor neuron persistent inward current (PIC) in older adults. Seventeen participants (68.5 ± 2.8 yr) completed a 2-wk nonexercise control period followed by 6 wk of resistance training. Surface electromyographic signals were collected with two 32-channel electrodes placed over soleus to investigate motor unit discharge rates. Paired motor unit analysis was used to calculate delta frequency (ΔF) as an estimate of PIC amplitudes during 1) triangular-shaped contractions to 20% of maximum torque capacity and 2) trapezoidal- and triangular-shaped contractions to 20% and 40% of maximum torque capacity, respectively, to understand their ability to modulate PICs as contraction intensity increases. Maximal strength and functional capacity tests were also assessed. For the 20% triangular-shaped contractions, ΔF [0.58-0.87 peaks per second (pps); P ≤ 0.015] and peak discharge rates (0.78-0.99 pps; P ≤ 0.005) increased after training, indicating increased PIC amplitude. PIC modulation also improved after training. During the control period, mean ΔF differences between 20% trapezoidal-shaped and 40% triangular-shaped contractions were 0.09-0.18 pps (P = 0.448 and 0.109, respectively), which increased to 0.44 pps (P < 0.001) after training. Also, changes in ΔF showed moderate to very large correlations (r = 0.39-0.82) with changes in peak discharge rates and broad measures of motor function. Our findings indicate that increased motor neuron excitability is a potential mechanism underpinning training-induced improvements in motor neuron discharge rate, strength, and motor function in older adults. This increased excitability is likely mediated by enhanced PIC amplitudes, which are larger at higher contraction intensities.NEW & NOTEWORTHY Resistance training elicited important alterations in soleus intrinsic motor neuronal excitability, likely mediated by enhanced persistent inward current (PIC) amplitude, in older adults. Estimates of PICs increased after the training period, accompanied by an enhanced ability to increase PIC amplitudes at higher contraction intensities. Our data also suggest that changes in PIC contribution to self-sustained discharging may contribute to increases in motor neuron discharge rates, maximal strength, and functional capacity in older adults after resistance training.

Impact of Laparoscopic Gastrectomy on the Completion Rate of the Perioperative Chemotherapy Regimen in Gastric Cancer: A Swedish Nationwide Study.

BACKGROUND: Omission of prescheduled chemotherapy following surgery for gastric cancer is a frequent clinical problem. This study examined whether laparoscopic gastrectomy (LG) had a positive impact on compliance with adjuvant chemotherapy compared with open (OG). METHODS: Patients with cT2-4aN0-3M0 adenocarcinoma treated with gastrectomy and perioperative chemotherapy between 2015 and 2020 were identified in the Swedish national register. Additional information regarding chemotherapy was retrieved from medical records. Regression models were used to investigate the association between surgical approach and the following outcomes: initiation of adjuvant chemotherapy, modification, and time interval from surgery to start of treatment. RESULTS: A total of 247 patients were included (121 OG and 126 LG, conversion rate 11%), of which 71.3% had performance status ECOG 0 and 77.7% clinical stage II/III. In total, 86.2% of patients started adjuvant chemotherapy, with no significant difference between the groups (LG 88.1% vs OG 84.3%, p = 0.5). Reduction of chemotherapy occurred in 37.4% of patients and was similar between groups (LG 39.4% vs OG 35.1%, p = 0.6), as was the time interval from surgery. In multivariable analysis, LG was not associated with the probability of starting adjuvant chemotherapy (OR 1.36, p = 0.4) or the need for reduction (OR 1.29, p = 0.4). Conversely, major complications had a significant, negative impact on both outcomes. CONCLUSIONS: This nationwide study demonstrated a high rate of adjuvant chemotherapy initiation after curative intended surgery for gastric cancer. A beneficial effect of LG compared with OG on the completion rate was not evident.

Perceptions of fatigue and neuromuscular measures of performance fatigability during prolonged low-intensity elbow flexions.

NEW FINDINGS: What is the central question of this study? What is the predictive relationship between self-reported scales to quantify perceptions of fatigue during exercise and gold standard measures used to quantify the development of neuromuscular fatigue? What is the main finding and its importance? No scale was determined to be substantively more effective than another. However, the number of ongoing contractions performed was shown to be a better predictor of fatigue in the motor system than any of the subjective scales. ABSTRACT: The purpose of this study was to determine the relationship between transcranial magnetic stimulation (TMS) measures of performance fatigability and commonly used scales that quantify perceptions of fatigue during exercise. Twenty healthy participants (age 23 ± 3 years, 10 female) performed 10 submaximal isometric elbow flexions at 20% maximal voluntary contraction (MVC) for 2 min, separated by 45 s of rest. Biceps brachii muscle electromyography and elbow flexion torque responses to single-pulse TMS were obtained at the end of each contraction to assess central factors of performance fatigability. A rating of perceived exertion (RPE) scale, Omnibus Resistance scale, Likert scale, Rating of Fatigue scale and a visual analogue scale (VAS) were used to assess perceptions of fatigue at the end of each contraction. The RPE (root mean square error (RMSE) = 0.144) and Rating of Fatigue (RMSE = 0.145) scales were the best predictors of decline in MVC torque, whereas the Likert (RMSE= 0.266) and RPE (RMSE= 0.268) scales were the best predictors of electromyographic amplitude. Although the Likert (RMSE = 7.6) and Rating of Fatigue (RMSE = 7.6) scales were the best predictors of voluntary muscle activation of any scale, the number of contractions performed during the protocol was a better predictor (RMSE = 7.3). The ability of the scales to predict TMS measures of performance fatigability were in general similar. Interestingly, the number of contractions performed was a better predictor of TMS measures than the scales themselves.

Factors Related to Engagement in Employment After Spinal Cord Injury in Australia: A Cross-sectional Study.

OBJECTIVE: To explore the association between sociodemographic, health, functional independence, and environmental variables with engagement in paid work for people with spinal cord injury (SCI). DESIGN: Self-reported, cross-sectional Australian data from a large international SCI survey. SETTING: Community-based. PARTICIPANTS: 1189 working-age people with SCI (18-67 years) or aged >67 years and engaged in paid employment. Respondents were community based and at least 1 year after injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Employment and work integration variables. Bayesian penalized regression was used to determine associations between 23 predictor variables and engagement in paid work. RESULTS: Most participants (87%) were employed pre-injury, with 39% in paid employment at the time of the survey. Participants who attained a master's/doctoral degree (odds ratio [OR]=3.01; 95% credible interval [CrI], 1.63, 5.44) and those married (OR=1.68; 95% CrI, 1.13, 2.49) were more likely to be engaged in paid work. Women (OR=0.55; 95% CrI, 0.37, 0.81), people receiving a disability pension (OR=0.17; 95% CrI, 0.13, 0.24), and older participants (OR=0.75; 95% CrI, 0.63, 0.90) were less likely to be in paid work. Working participants identified hardships including problems completing their work (60%) and accessing the workplace (32%), as well as unmet needs relating to assistive devices required for completing their work (50%). CONCLUSIONS: Findings from the current study can assist in directing resources to subgroups within the SCI population who need greater assistance or intervention related to employment outcomes, including through vocational rehabilitation services/programs. Unmet needs and workplace issues expressed by employed individuals identify gaps in work integration and satisfaction that could affect employment sustainability that need to be addressed.

Blood oxidative stress biomarkers in women: influence of oral contraception, exercise, and N-acetylcysteine.

PURPOSE: To compare physiological responses to submaximal cycling and sprint cycling performance in women using oral contraceptives (WomenOC) and naturally cycling women (WomenNC) and to determine whether N-acetylcysteine (NAC) supplementation mediates these responses. METHODS: Twenty recreationally trained women completed five exercise trials (i.e., an incremental cycling test, a familiarisation trial, a baseline performance trial and two double-blind crossover intervention trials). During the intervention trials participants supplemented with NAC or a placebo 1 h before exercise. Cardiopulmonary parameters and blood biochemistry were assessed during 40 min of fixed-intensity cycling at 105% of gas-exchange threshold and after 1-km cycling time-trial. RESULTS: WomenOC had higher ventilation (ß [95% CI] = 0.07 L·min-1 [0.01, 0.14]), malondialdehydes (ß = 12.00 mmol·L-1 [6.82, 17.17]) and C-reactive protein (1.53 mg·L-1 [0.76, 2.30]), whereas glutathione peroxidase was lower (ß =  22.62 mU·mL-1 [- 41.32, - 3.91]) compared to WomenNC during fixed-intensity cycling. Plasma thiols were higher at all timepoints after NAC ingestion compared to placebo, irrespective of group (all p < 0.001; d = 1.45 to 2.34). For WomenNC but not WomenOC, the exercise-induced increase in malondialdehyde observed in the placebo trial was blunted after NAC ingestion, with lower values at 40 min (p = 0.018; d = 0.73). NAC did not affect cycling time-trial performance. CONCLUSIONS: Blood biomarkers relating to oxidative stress and inflammation are elevated in WomenOC during exercise. There may be an increased strain on the endogenous antioxidant system during exercise, since NAC supplementation in WomenOC did not dampen the exercise-induced increase in malondialdehyde. Future investigations should explore the impact of elevated oxidative stress on exercise adaptations or recovery from exercise in WomenOC.

The influence of personal factors, unmet need and service obstacles on the relationship between health service use and outcome after brain injury.

BACKGROUND: This exploratory study aimed to: (i) examine the relationship between health service use and quality of life, psychological wellbeing, global function and participation after discharge from brain injury inpatient rehabilitation, and (ii) determine the influence of personal factors, unmet need for services and service obstacles on the relationship between service use and these outcomes. METHODS: Using a prospective cohort design, 41 adults with acquired brain injury (median age = 46 years; 71% male; 61% severe traumatic injury) were followed for 6-months after discharge from specialist brain injury inpatient rehabilitation. Service use was continuously recorded and obtained through data linkage methods, focusing on the use of: outpatient medical services, outpatient nursing, outpatient allied health; medical acute services; incidents of re-hospitalization; and transitional rehabilitation service use. Outcome questionnaire measures were completed via telephone, at 6-months after discharge, and included: the EuroQol-5D; Depression Anxiety and Stress Scale, Mayo-Portland Adaptability Inventory and Sydney Psychosocial Reintegration Scale. Data were analyzed in a heterogeneous treatment effects framework, using Bayesian Additive Regression Trees. RESULTS: There was weak evidence that transitional rehabilitation service use was associated with better psychological wellbeing scores. The posterior probability of lower depression, anxiety and stress scores was .87, .81 and .86, respectively (average treatment effect). There was also weak evidence that re-hospitalization was associated with worse independent living skills scores. The posterior probability of worse scores was .87. However, most re-hospitalizations were due to unavoidable medical complications. We did not find that place of residence at discharge, marital status, unmet need, or service obstacles affected the relationship between service use and the studied outcomes. CONCLUSIONS: This study may highlight the importance of participation in transitional rehabilitation, in the 6-months after discharge from brain injury rehabilitation. Replication in a larger sample size is required to confirm these findings.

Longitudinal effects of time since injury and age at injury on outcomes of people with spinal cord injury in Queensland, Australia.

STUDY DESIGN: Longitudinal cohort study. OBJECTIVES: To investigate the longitudinal effects of time since injury and age at injury on outcomes of quality of life, physical function, secondary conditions and participation, in people with traumatic spinal cord injury (SCI). SETTING: Community resident people with spinal cord injury in Queensland, Australia. METHODS: A baseline sample of 270 people with SCI was recruited. Telephone surveys on measures of quality of life (WHOQOL-Bref), secondary conditions (Secondary Conditions Surveillance Instrument, subset), physical functioning (Functional Independence Measure motor subscale) and participation (Community Integration Measure) were conducted each year between 2004 and 2008, and again in 2018. Random-effect within-between models were used to determine the effect of time since injury and age at injury on each outcome variable. Inverse probability-of-censoring weights were used to correct for selection bias. RESULTS: There was an effect of time since injury on secondary conditions, with a one-year change associated with 9% higher odds of having worse Secondary Conditions Surveillance Instrument scores (odds ratio = 1.09, 95% confidence interval = 1.02, 1.17; p = 0.006). We did not find any evidence of a time since injury effect on quality of life, physical function, or participation. Similarly, we did not find any evidence of an age at injury effect on any outcome variable. CONCLUSIONS: Secondary conditions may increase with longer time since injury among people with SCI, suggesting appropriate formal and informal supports are required to minimise the impact of these emerging health problems as individuals age.

COVID-19 and vaccination induced changes in hospital activity in Malta, Q1 2020 to Q1 2021: a population-based study.

BACKGROUND: COVID-19 has severely impacted global healthcare services. Malta has only one acute state hospital, Mater Dei Hospital (MDH), and at the time of writing is the most vaccinated country in Europe. Malta thus provides an ideal setting to assess the impact of COVID-19 on healthcare services at population level, including the impact of vaccination on hospital admissions. METHODS: Hospital data was obtained as anonymised totals from MDH's Clinical Performance Unit and the European Centre for Disease Prevention and Control. COVID-19-related data was obtained from the Ministry of Health dashboard. Comparative assessments were performed to explore associations between the COVID-19 situation, vaccination, and hospital activity. Poisson regression was used to model the counts of monthly accident and emergency (A&E), outpatient clinics attendances and hospital admissions. RESULTS: A&E, hospital admissions, and outpatient clinics attendances declined (31.88%; 23.89%; 29.57%; p < 0.01 respectively) with onset of COVID-19 till April 2021 when compared to pre-COVID years (2017-2019). Admissions due to COVID-19 initially increased in parallel to the population's COVID positivity. Vaccination rollout led to a decline in COVID-19 admissions. CONCLUSIONS: The drastic drop in admissions and outpatient attendees was expected but not for A&E attendees as acutely ill patients should still have attended. This is of public health concern since delayed or deferred medical management increases population morbidity, mortality and increases the eventual burden on the healthcare system. Mass vaccination saw the return to normality with an increase in A&E burden.

Short-term heat acclimation preserves knee extensor torque but does not improve 20 km self-paced cycling performance in the heat.

PURPOSE: This study investigated the effect of 5 days of heat acclimation training on neuromuscular function, intestinal damage, and 20 km cycling (20TT) performance in the heat. METHODS: Eight recreationally trained males completed two 5-day training blocks (cycling 60 min day-1 at 50% peak power output) in a counter-balanced, cross-over design, with a 20TT completed before and after each block. Training was conducted in hot (HA: 34.9 ± 0.7 °C, 53 ± 4% relative humidity) or temperate (CON: 22.2 ± 2.6 °C, 65 ± 8% relative humidity) environment. All 20TTs were completed in the heat (35.1 ± 0.5 °C, 51 ± 4% relative humidity). Neuromuscular assessment of knee extensors (5 × 5 s maximum voluntary contraction; MVC) was completed before and after each 20TT and on the first and last days of each training block. RESULTS: MVC torque was statistically higher after 5 days of HA training compared to CON (mean difference = 14 N m [95% confidence interval; 6, 23]; p < 0.001; d = 0.77). However, 20TT performance after 5 days of HA training was not statistically different to CON, with a between-conditions mean difference in the completion time of 68 s [95% confidence interval; - 9, 145] (p = 0.076; d = 0.35). CONCLUSION: Short-term heat acclimation training may increase knee extensor strength without changes in central fatigue or intestinal damage. Nevertheless, it is insufficient to improve 20 km self-paced cycling performance in the heat compared to workload-matched training in a temperate environment. These data suggest that recreationally trained athletes gain no worthwhile performance advantage from short-term heat-training before competing in the heat.

Palliative short-course hypofractionated radiotherapy followed by chemotherapy in esophageal adenocarcinoma: the phase II PALAESTRA trial.

Background: The majority of patients with incurable esophageal adenocarcinoma suffer from dysphagia. We assessed a novel treatment strategy with initial short-course radiotherapy followed by chemotherapy with the primary aim to achieve long-term relief of dysphagia.Methods: This phase II trial included treatment-naîve patients with dysphagia due to esophageal adenocarcinoma not eligible for curative treatment. External beam radiotherapy with 20 Gy in five fractions to the primary tumor was followed by four cycles of chemotherapy (FOLFOX regimen). Dysphagia was assessed using a five-grade scale.Results: From October 2014 to May 2018 a total of 29 patients were enrolled. The rate of dysphagia improvement was 79%, median duration of improvement 6.7 months (12.2 months for responders) and median overall survival 9.9 months. In the pre-specified per protocol analysis (23 patients) the rate of dysphagia improvement was 91%, median duration of improvement 12.2 months (14.0 months for responders) and median overall survival 16.0 months. The most common grade 3-4 adverse events were neutropenia (29%), infection (25%), anorexia (11%), esophagitis (11%) and fatigue (11%).Conclusion: Initial palliative short-course radiotherapy followed by chemotherapy is a promising treatment strategy that can provide long-lasting relief of dysphagia in patients with esophageal adenocarcinoma.

The Effect of Health Service Use, Unmet Need, and Service Obstacles on Quality of Life and Psychological Well-Being in the First Year After Discharge From Spinal Cord Injury Rehabilitation.

OBJECTIVE: This study examined the effects of health and rehabilitation service use, unmet need for services, and service obstacles on health-related quality of life (HR QoL) and psychological well-being after discharge from spinal cord injury (SCI) rehabilitation. DESIGN: Prospective cohort study, with participants followed up at 6 and/or 12 months after discharge from SCI inpatient rehabilitation. SETTING: Community setting. PARTICIPANTS: People with SCI (N=55; mean age 51y; 76.4% men; 61.8% traumatic injury; mean length of stay 137d). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Service Usage Scale, Service Obstacles Scale, the EuroQol-5D, and the Depression Anxiety and Stress Scale short form. Eight predictors of outcome were considered: service use (ie, use of general practitioner, medical specialist, nursing, and allied health, and rehospitalization), unmet need, and service obstacles (ie, finances and transport). Possibly important predictors of each outcome were identified via penalized regression, and a final model was fit using Bayesian hierarchical regression with a Gaussian or zero-inflated Poisson response distribution. RESULTS: Financial obstacles were associated with a poorer HR QoL (ß [95% credible interval]= -0.095 [-0.166 to -0.027]) and higher anxiety (odds ratio, OR [95% credible interval]=1.63 [1.16-2.23]). Rehospitalization was associated with a lower EuroQol visual analog scale (ß= -11.2 [-19.7 to -2.5]) and, interestingly, lower anxiety (OR=1.63 [1.16-2.23]). Use of allied health was associated with higher anxiety (OR=2.48 [1.42-4.44]). CONCLUSION: The varying degrees of financial hardship experienced after injury with complex rehabilitation needs requires investigation, as does the interactive effects of service use, unmet need, and service obstacles on outcomes like QoL and psychological well-being.

The effect of access to a designated interdisciplinary post-acute rehabilitation service on participant outcomes after brain injury.

OBJECTIVE: This study aimed to determine the influence of participation in a designated acquired brain injury (ABI) transitional rehabilitation service (ABI TRS) on outcome, in the context of a historical comparison group (HIST). Design: A cohort study, with retrospective comparison. Participants: 187 persons with ABI. Measures: The Depression, Anxiety and Stress Scale (DASS-21), Mayo-Portland Adaptability Index (MPAI-4) and Sydney Psychosocial and Reintegration Scale (SPRS) were completed at discharge and 3 months after discharge. Participation in the ABI TRS involved interdisciplinary rehabilitation, 2-4 times per week, for 3 months after hospital discharge. Results: There was evidence that at 3 months, participants with ABI TRS showed stabilized psychological wellbeing, and improvements in MPAI-4 ability and participation scores; in addition to improvements in SPRS occupational activity and living skills scores. Conclusion: A designated ABI TRS may improve the transition from hospital to home, and could form an important part of the brain injury rehabilitation continuum, between the inpatient and community setting.

Thermal Infrared Imaging Can Differentiate Skin Temperature Changes Associated With Intense Single Leg Exercise, But Not With Delayed Onset of Muscle Soreness.

Muscle damage and soreness associated with increased exercise training loads or unaccustomed activity can be debilitating and impact the quality of subsequent activity/performance. Current techniques to assess muscle soreness are either time consuming, invasive or subjective. Infrared thermography has been identified as a quick, non-invasive, portable and athlete friendly method of assessing skin temperature. This study assessed the capability of thermal infrared imaging to detect skin temperature changes that may accompany the inflammatory response associated with delayed onset muscular soreness (DOMS). Eight recreationally trained participants (age 25 ± 3 years, mass 74.9 ± 13.6 kg, training minutes 296 ± 175 min·wk-1) completed 6 sets of 25 maximal concentric/eccentric contractions of the right knee flexors/extensors on a dynamometer to induce muscle damage and DOMS. The left knee extensors acted as a non-exercise control. Neuromuscular performance, subjective pain assessment and infrared thermography were undertaken at baseline, 24 and 48 hr post the DOMS-inducing exercise protocol. Data were analysed using Bayesian hierarchical regression and Cohen's d was also calculated. Maximal voluntary contraction torque was statistically lower at 24 hr (d = -0.70) and 48 hr (d = -0.52) compared to baseline, after the DOMS-inducing exercise protocol. These neuromuscular impairments coincided with statistically higher ratings of muscle soreness at 24 hr (d = 0.96) and 48 hr (d = 0.48). After adjusting for ambient temperature, anterior thigh skin temperature was statistically elevated at 24 hr, but not 48 hr, compared with baseline, in both the exercised and non-exercised leg. Thigh temperature was not different statistically between legs at these time points. Infrared imaging was able to detect elevations in skin temperature, at 24 hrs after the DOMS inducing exercise protocol, in both the exercised and non-exercised thigh. Elevations in the skin temperature of both thighs, potentially identifies a systemic inflammatory response occurring at 24 hr after the DOMS-inducing exercise protocol.

Acute glutamine supplementation does not improve 20-km self-paced cycling performance in the heat.

INTRODUCTION: The premise of this study was to investigate the effect of acute glutamine supplementation on 20 km time trial cycling performance in the heat, neuromuscular function, inflammation and endotoxemia. METHODS: Twelve cyclists completed two, 20-km time trials (20TT) in 35 °C (50% relative humidity). Participants ingested either glutamine (GLUT; 0.9 g kg-1 fat-free mass) or a placebo (CON) 60 min before each 20TT. Physiological and perceptual measures were recorded during each 20TT, and neuromuscular function assessed pre- and post-exercise. Venous blood was analysed for endotoxins, markers of gut damage (inflammatory fatty acid binding protein; I-FABP) and inflammatory cytokines (interleukin-6, IL-6; tumour necrosis factor-alpha, TNF-α). Data were analysed using linear mixed models in a Bayesian framework. RESULTS: 20TT in the heat increased I-FABP and elevated inflammatory cytokines (IL-6 and TNF-α) compared to pre-exercise values but did not result in endotoxemia. Completion time was not statistically different between conditions (mean difference [95% credible interval] = 11 s [- 23, 44]). Relative to CON, GLUT did not alter any physiological or perceptual measures during the 20TT. CONCLUSION: Glutamine supplementation does not improve 20TT performance in the heat or preserve neuromuscular function when compared to a placebo. These findings suggest that glutamine is not an ergogenic aid or prophylactic intervention for heat-induced gut damage during short-duration self-paced exercise in hot environments.

Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: The ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer. Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer. We aimed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer. METHODS: We did a phase 3, two-group, open-label, multicentre, randomised clinical trial at 92 hospitals in England, Scotland, Wales, Germany, France, and Sweden. Eligible patients were aged 18 years or older and had undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection). We randomly assigned patients (1:1) within 12 weeks of surgery to receive six cycles of either 1000 mg/m2 gemcitabine alone administered once a week for three of every 4 weeks (one cycle) or with 1660 mg/m2 oral capecitabine administered for 21 days followed by 7 days' rest (one cycle). Randomisation was based on a minimisation routine, and country was used as a stratification factor. The primary endpoint was overall survival, measured as the time from randomisation until death from any cause, and assessed in the intention-to-treat population. Toxicity was analysed in all patients who received trial treatment. This trial was registered with the EudraCT, number 2007-004299-38, and ISRCTN, number ISRCTN96397434. FINDINGS: Of 732 patients enrolled, 730 were included in the final analysis. Of these, 366 were randomly assigned to receive gemcitabine and 364 to gemcitabine plus capecitabine. The Independent Data and Safety Monitoring Committee requested reporting of the results after there were 458 (95%) of a target of 480 deaths. The median overall survival for patients in the gemcitabine plus capecitabine group was 28·0 months (95% CI 23·5-31·5) compared with 25·5 months (22·7-27·9) in the gemcitabine group (hazard ratio 0·82 [95% CI 0·68-0·98], p=0·032). 608 grade 3-4 adverse events were reported by 226 of 359 patients in the gemcitabine plus capecitabine group compared with 481 grade 3-4 adverse events in 196 of 366 patients in the gemcitabine group. INTERPRETATION: The adjuvant combination of gemcitabine and capecitabine should be the new standard of care following resection for pancreatic ductal adenocarcinoma. FUNDING: Cancer Research UK.

Podocalyxin-like protein as a predictive biomarker for benefit of neoadjuvant chemotherapy in resectable gastric and esophageal adenocarcinoma.

BACKGROUND: We have previously shown that podocalyxin-like protein (PODXL) is a prognostic biomarker for poor survival in gastric and esophageal adenocarcinoma treated with surgery up-front. The aim of the present study was to assess PODXL expression in tumors from patients treated with neoadjuvant ± adjuvant (i.e. preoperative with or without postoperative) chemotherapy, with regard to histopathologic response, time to recurrence (TTR) and overall survival (OS). METHODS: The neoadjuvant cohort encompasses 148 consecutive patients who received neoadjuvant ± adjuvant chemotherapy for resectable gastric or esophageal adenocarcinoma between 2008 and 2014. Immunohistochemical expression of PODXL was assessed in pre-neoadjuvant biopsies, resected primary tumors and lymph node metastases. Histopathologic response was evaluated using the Chirieac grading. TTR and OS were estimated using Kaplan-Meier and Cox regression analyses. To investigate a potential predictive role for PODXL, the neoadjuvant cohort was pooled with the previously reported surgery up-front cohort. RESULTS: The majority (> 95%) of the patients were treated with fluoropyrimidine- and oxaliplatin-based chemotherapy. Patients with high PODXL expression in their pre-neoadjuvant biopsies had a superior histopathologic response (notably 36% with no residual cancer cells) compared to those with negative or low PODXL expression, and were all recurrence-free at last follow-up. In the pooled cohort, no benefit of chemotherapy could be shown for PODXL negative cases, whereas PODXL positive (low or high) cases had a prolonged TTR and OS when treated with neoadjuvant ± adjuvant chemotherapy compared to surgery alone. The potential predictive role of PODXL was further strengthened for TTR in Cox regression analyses, especially for patients treated with neoadjuvant fluoropyrimidine and oxaliplatin for a minimum of 8 weeks, with a significant interaction term in both unadjusted (p = 0.006) and adjusted (p = 0.024) analyses. The interaction term was not statistically significant for overall survival. CONCLUSIONS: Patients with resectable gastric or esophageal adenocarcinoma with high PODXL expression in their diagnostic biopsies have an excellent prognosis when treated with neoadjuvant ± adjuvant fluoropyrimidine- and oxaliplatin-based chemotherapy. If the suggested predictive role of PODXL for benefit of chemotherapy can be confirmed, patients with PODXL negative tumors could be spared chemotherapy and treated with surgery alone.