An investigation of the clinical impact and therapeutic relevance of a DNA damage immune response (DDIR) signature in patients with advanced gastroesophageal adenocarcinoma.

BACKGROUND: An improved understanding of which gastroesophageal adenocarcinoma (GOA) patients respond to both chemotherapy and immune checkpoint inhibitors (ICI) is needed. We investigated the predictive role and underlying biology of a 44-gene DNA damage immune response (DDIR) signature in patients with advanced GOA. MATERIALS AND METHODS: Transcriptional profiling was carried out on pretreatment tissue from 252 GOA patients treated with platinum-based chemotherapy (three dose levels) within the randomized phase III GO2 trial. Cross-validation was carried out in two independent GOA cohorts with transcriptional profiling, immune cell immunohistochemistry and epidermal growth factor receptor (EGFR) fluorescent in situ hybridization (FISH) (n = 430). RESULTS: In the GO2 trial, DDIR-positive tumours had a greater radiological response (51.7% versus 28.5%, P = 0.022) and improved overall survival in a dose-dependent manner (P = 0.028). DDIR positivity was associated with a pretreatment inflamed tumour microenvironment (TME) and increased expression of biomarkers associated with ICI response such as CD274 (programmed death-ligand 1, PD-L1) and a microsatellite instability RNA signature. Consensus pathway analysis identified EGFR as a potential key determinant of the DDIR signature. EGFR amplification was associated with DDIR negativity and an immune cold TME. CONCLUSIONS: Our results indicate the importance of the GOA TME in chemotherapy response, its relationship to DNA damage repair and EGFR as a targetable driver of an immune cold TME. Chemotherapy-sensitive inflamed GOAs could benefit from ICI delivered in combination with standard chemotherapy. Combining EGFR inhibitors and ICIs warrants further investigation in patients with EGFR-amplified tumours.

Fatigue in children who have recently completed treatment for acute lymphoblastic leukemia: a longitudinal study.

BACKGROUND: This study examined fatigue in patients treated for childhood acute lymphoblastic leukemia (ALL) over a 2-year period (3- to 27-months post-treatment completion), from the perspective of children and parent caregivers, compared to a healthy comparison group. METHODS: Eighty-three patients (4-16 years at enrolment) and their parents, reported on the child's fatigue using the Pediatric Quality of Life Inventory- Multidimensional Fatigue Scale (PedsQL-MFS), at 3- 15- and 27-months post-treatment completion, and 53 healthy children and their parents reported on fatigue across the same timepoints. RESULTS: Parent proxy-reporting showed that parents of ALL patients reported more total fatigue than parents of the comparison group at all time points, with all subscales elevated (general, cognitive, and sleep/rest fatigue). In contrast, patient self-report of fatigue over this period differed from the comparison children for the general fatigue subscale only. Self-reported total fatigue was worse than the comparison group at the 27-month timepoint, with cognitive and sleep/rest fatigue symptoms contributing to this difference. Expected improvements in fatigue over time were not evident in either patient or parent report and no demographic risk factors were identified. Parents and children from both groups reported significantly more fatigue at all time points compared to commonly utilised normative population data. CONCLUSIONS: Patients treated for childhood ALL are impacted by fatigue symptoms in the post-treatment and early survivorship period. These findings highlight that patients in the 2-years following treatment require increased symptom surveillance and may benefit particularly from interventions that target cognitive and sleep/rest fatigue.

Vascular access device type for systemic anti-cancer therapies in cancer patients: A scoping review.

BACKGROUND: Patients with cancer can expect to receive numerous invasive vascular access procedures for intravenous therapy and clinical diagnostics. Due to the increased incidence and prevalence of cancer globally there will be significantly more people who require first-line intravenous chemotherapy over the next ten years. METHODS: Our objective was to determine the types of evidence that exist for the vascular access device (VAD) type for the delivery of systemic anti-cancer therapy (SACT) in cancer patients. We used JBI scoping review methodology to identify the types of VADs used for SACT and with a specific search strategy included articles from 2012-2022 published in the English language. We identify (i) type of VADs used for SACT delivery (ii) the type of insertion and post-insertion complications (iii) the geographical location and clinical environment (iv) and whether VAD choice impacts on quality of life (QOL). Findings were presented using the PAGER framework. MAIN FINDINGS: Our search strategy identified 10,390 titles, of these, 5318 duplicates were removed. The remaining 5072 sources were screened for eligibility, 240 articles met the inclusion criteria. The most common design include retrospective study designs (n = 91) followed by prospective study designs (n = 31). We found 28 interventional studies with 21 registered in a clinical trial registry and identified no core outcome sets papers specific to VAD for SACT. The most prevalent publications were those that featured two or more VAD types (n = 70), followed by tunnelled intravenous VADs (n = 67). Of 38 unique complications identified, the most frequent catheter related complication was catheter related thrombosis (n = 178, 74%), followed by infection (n = 170, 71%). The county where the most publications originated from was China (n = 62) with one randomized controlled multicenter study from a comprehensive cancer centre. Of the thirty three studies that included QOL we found 4 which reported on body image. No QOL measurement tools specific to the process of SACT administration via VAD are available INTERPRETATION: Our findings suggest a systematic review and meta-analysis of VAD use for intravenous SACT can be considered. However, the development of a core outcome set for SACT should be prioritised. Funding for high quality programs of research for VAD in cancer are needed. Comprehensive cancer centres should lead this research agenda.

Are Population-Level Approaches to Dementia Risk Reduction Under-Researched? A Rapid Review of the Dementia Prevention Literature.

Dementia is forecast to become increasingly prevalent, particularly in low- and middle-income countries, and is associated with high human and economic costs. Primary prevention of dementia -preventing risk factors leading to disease development - is an emerging global public health priority. Primary prevention can be achieved in two ways: individual-level or population-level. In this rapid review, we quantify the proportion of contributing interventional evidence to the dementia primary prevention literature that is concerned with either approach. We searched Medline, the National Institute for Health and Care Excellence, Cochrane, the World Health Organization, and Google to identify systematic reviews that described primary prevention interventions for dementia. We used search terms related to dementia risk reduction, intervention/policy, and review. We analysed reference lists of included dementia prevention reviews to identify contributing primary prevention evidence, and categorised these as either individual-level or population-level. Additionally, we examined search strategies to investigate the likelihood of reviews identifying available population-level interventions. We included twelve of the 527 articles retrieved. Population-level evidence was summarised by only two reviews. In these two reviews, <2.5% of the interventions described where population-level interventions. Most search strategies were weighted towards identifying individual-level evidence. Existing systematic reviews of dementia primary prevention interventions include almost no population-level evidence. Correction of this imbalance is needed to ensure that dementia prevention policies can achieve meaningful reductions in the prevalence of, and inequalities in, dementia.

Reduction in re-rupture rates following implementation of return-to-sport testing after anterior cruciate ligament reconstruction in 313 patients with a mean follow-up of 50 months.

OBJECTIVES: The objective of this study was to assess the mid-term effectiveness of a return to sport (RTS) test in relation to preventing anterior cruciate ligament (ACL) re-rupture and contralateral ACL injury following ACL reconstruction (ACLR). Furthermore, this study aimed to assess the timing of passing a, RTS-test after surgery, and the effect age has on RTS outcomes. METHODS: Patients undergoing ACLR between August 2014 and December 2018 took an RTS-test following rehabilitation. The RTS-test consisted of the Anterior Cruciate Ligament Return to Sport After Injury Scale, a single-leg hop, a single-leg triple hop, a single-leg triple cross-over hop, a box-drop vertical jump down, a single-leg 4-rep max-incline leg press, and a modified agility T test. RTS-passing criteria were ≥90% limb symmetry index in addition to defined takeoff and landing parameters. Mid-term review assessed sporting level, ACL re-injury, and contralateral ACL injury. RESULTS: A total of 352 patients underwent RTS-testing, following ACLR with 313 (89%) contactable at follow-up, a mean of 50 months (standard deviation: 11.41, range: 28-76) after surgery. The re-rupture rate was 6.6% after passing the RTS-test and 10.3% following failure (p â€‹= â€‹0.24), representing a 36% reduction. Contralateral ACL injury rate after surgery was 6% and was 19% lower in those passing the RTS test. The mean age of patients passing their first RTS-test was significantly higher than that of those who failed (p â€‹= â€‹0.0027). Re-ruptures in those who passed the RTS test first time occurred late (>34 months), compared to those who failed first time, which all occurred early (<33 months) (p â€‹= â€‹0.0015). The mean age of re-rupture was significantly less than those who did not sustain a re-rupture (p â€‹= â€‹0.025). CONCLUSION: Passing a RTS-test following ACLR reduces ACL re-rupture by 36.21% and contralateral ACL injury by 19.15% at mid-term follow-up. Younger patients are more likely to fail a RTS-test and are at higher risk of contralateral ACL rupture.

What is a population-level approach to prevention, and how could we apply it to dementia risk reduction?

The World Health Organisation's 2022 'blueprint for dementia research' highlights the need for more research into population-level risk reduction. However, definitions of population-level prevention vary, and application to dementia is challenging because of its multi-factorial aetiology and a maturing prevention evidence base. This paper compares and contrasts key concepts of 'population-level prevention' from the literature, explores related theoretical models and policy frameworks, and applies this to dementia risk reduction. We reach a proposed definition of population-level risk reduction of dementia, which focusses on the need to change societal conditions such that the population is less likely to develop modifiable risk factors known to be associated with dementia, without the need for high-agency behaviour change by individuals. This definition, alongside identified policy frameworks, can inform synthesis of existing evidence and help to co-ordinate the generation of new evidence.

A novel approach using electroacupuncture for erectile dysfunction after radical prostatectomy: A case report.

INTRODUCTION: Research shows that electrical stimulation to damaged peripheral nerves has promising effects on nerve regeneration and recovery of function. DESCRIPTION: A 71 yr. old male, who was 12 months post left intrafacial and right incremental nerve sparing robotic radical prostatectomy received 6 sessions of sacral electroacupuncture/acupuncture at weekly intervals, commencing 12 months post operatively. METHODS: CARE guidelines informed the case study report. Positive changes in erectile function after electroacupuncture was recorded using validated scores (IIEF-5 and EHS). Qualitative information was collected via a feedback box. DISCUSSION: Given that current treatments for post radical prostatectomy erectile dysfunction are invasive and largely unsuccessful, further investigation into electroacupuncture for this population should be pursued.

Food Assistance Programs and Reduced Hospitalizations for Older Adults with Diabetes.

Diabetes is an increasingly common and costly condition for older adults. Each year, as many as 1 in 3 Medicare dollars is spent to treat and manage diabetes and associated comorbidities for people with diabetes. To control health care spending in the US, it is imperative that we identify factors for reducing hospitalizations for these individuals. The purpose of this cross-sectional study was to identify predictors of hospitalization in the past 12 months for community-dwelling older adults with diabetes. Data from round five of the National Health and Aging Trends Study were analyzed to assess the impact of food assistance programs on the risk of hospitalization in the past 12 months for 1094 Medicare recipients ages 65 and older with diabetes. Previous research on the social determinants of health has demonstrated that social stressors like poverty and exposure to racism are associated with poorer health outcomes overall, but we did not find a statistically-significant association between race, gender, age or Medicare/ Medicaid dual-eligibility and hospitalization for our study population. Notably, receipt of Supplemental Nutrition Assistance Program (SNAP) benefits, Meals on Wheels services or other food assistance was associated with a 43% reduction in the risk of hospitalization in the past 12 months. Food assistance programs appear to be a promising strategy for reducing hospitalizations associated with diabetes and its comorbidities. Primary care providers, diabetes educators and other health professionals should be more proactive in their referrals to food assistance programs and other community supports.

Axial ablation versus terminal interruption of the reflux source (AAVTIRS): a randomised controlled trial.

BACKGROUND: Treatment of superficial venous reflux has been shown to improve ulcer healing time and reduce the risk of ulcer recurrence. Terminal ablation of the reflux source (TIRS) is an alternative to formal endovenous ablation or surgery which can be performed by injecting sclerosant foam into the peri-ulcer plexus of the veins. TIRS has been shown to be successful and in our experience is the option preferred by many patients, when offered as an alternative to axial ablation (AA). AIM: To determine if the proportion of ulcers healed within 6 months of endovenous treatment differs between patients undergoing AA of varicose veins or TIRS by peri-ulcer foam sclerotherapy. METHODS: AAVTIRS is an assessor-blinded randomised controlled trial. Patients will be recruited from a dedicated ulcer clinic in Roscommon University Hospital and from the vascular surgical clinics in University Hospital Galway. All patients attending the ulcer clinic will be screened for eligibility. RANDOMISATION: Random computer-generated sequence is stratified by ulcer size. Allocation will be concealed using sealed opaque envelopes. BLINDING: Assessors reviewing wounds at follow -p visits will be blinded to patient allocation. PRIMARY ENDPOINT: The proportion of ulcers healed within 6 months of enrolment. DISCUSSION: This will be the first time that TIRS has been evaluated with a properly powered randomised trial in the setting of venous ulcer management. Streamlining the management of venous ulcers has broad health economic benefits. If it is found that TIRS is superior or non-inferior to AA, then a less expensive, less invasive injection can be offered as an alternative to AA in an attempt to encourage the healing of venous ulcers. If AA is found to be superior to TIRS, then this would suggest that all patients undergoing ablation in the management of venous ulcers should have their superficial reflux fully treated, building on the evidence of the EVRA trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT04484168. Registered on 23 July 2020.

Risk factors for local atypical fibroxanthoma recurrence and progression to pleomorphic dermal sarcoma: A meta-analysis of individualized participant data.

BACKGROUND: Risk factors for local atypical fibroxanthoma (AFX) recurrence and progression to pleomorphic dermal sarcoma (PDS) have not previously been identified. OBJECTIVE: To identify risk factors and provide follow-up suggestions for local AFX recurrence and progression to PDS. METHODS AND MATERIALS: A literature search was performed in the PubMed, EMBASE, and Cochrane databases. The PRISMA and MOOSE guidelines were followed. The risks of local AFX recurrence and progression to PDS were presented as Kaplan-Meier plots and risk factors were presented as hazard ratios (HRs) calculated with univariate and multivariate Cox regression. RESULTS: Five hundred and ninety-eight patients with AFX from 14 studies were included. Age >74 years and male sex significantly increased the risk of local recurrence (HR: 7.31 [95% confidence interval [CI]: 1.78-30.0], p < 0.01 and HR: 2.89 [95% CI: 1.04-8.01], p < 0.05, respectively). There was no difference when comparing wide local excision and Mohs' micrographic surgery (p = 0.89). The risks of local AFX recurrence and progression to PDS after 2 years were <1%. CONCLUSION: A more intensive follow-up regimen could be considered in patients >74 years old and males due to the higher risk of local AFX recurrence.

A cross-sectional analysis of psychological distress among higher education students in Ireland.

OBJECTIVES: To examine levels of psychological distress among higher education students in Ireland overall and across a range of personal, higher education, and socioeconomic characteristics, prior to the COVID-19 pandemic. METHODS: A cross-sectional online survey of college students in Ireland was undertaken in 2018. Data on 5201 students from 13 higher education institutions (HEIs) were analyzed. Stress, anxiety, and depression symptom scores based on the Depression, Anxiety and Stress Scale (DASS-21) were calculated and reported, with statistical testing used to compare across groups. RESULTS: Overall, 29.6% and 19.1% of respondents were classified in the mild to moderate and severe to extremely severe range for depression respectively. The corresponding proportions were 25.9% and 20.7% for anxiety, and 24.5% and 14.8% for stress. Differences across groups included higher levels of psychological distress for transgender and female students compared to males (p < 0.01), for gay/lesbian/bisexual students compared to heterosexuals (p < 0.01), for undergraduates compared to postgraduates (p < 0.01), for students from intermediate/technical/service/unskilled social classes compared to professional/self-employed social classes (p < 0.01), and for those with financial difficulties compared to those without financial difficulties (p < 0.01). CONCLUSIONS: Rates of psychological distress were high amongst college students in Ireland prior to the COVID-19 pandemic, with substantial differences across groups. Due to study limitations, such as possible selection bias, the findings need replication. Further research is needed to determine the impact of the pandemic on the prevalence of mental illness in this population.

Review of the prevalence, pathogenesis and management of OSA-COPD overlap.

PURPOSE: OSA-COPD overlap is an important and prevalent condition yet remains under-recognised among the vast majority of respiratory health professionals. Patients with OSA-COPD overlap experience more severe respiratory symptoms and worse quality of life, and the relative risk of exacerbations, hospitalisations, and mortality is higher than in either disease state alone. METHODS: Electronic databases PUBMED and Google Scholar were searched for studies and academic papers that discussed OSA-COPD overlap. Relevant papers that discussed prevalence, pathophysiology, microbiome studies, treatment regimens and outcomes were included in this paper. RESULTS: High-risk patients with either COPD or OSA should be screened for overlap syndrome as part of routine clinical practice. Screening questionnaires can identify high-risk patients with COPD who may benefit from formal polysomnography. Patients with OSA who are aged over 40 with a significant smoking history or environmental exposures have an increased pre-test probability of obstructive airway disease. The potential roles of gastro-oesophageal reflux disease and lung-gut microbiome are evolving and merit further investigation. A tailored approach to reach a timely diagnosis and thus optimisation of both conditions are key to management. CPAP is the primary therapy for OSA; however, patients with more advanced COPD, with daytime hypercapnia or severe nocturnal desaturations, may benefit from bilevel positive airway pressure. CONCLUSION: Increased awareness, access to timely investigations and initiation of therapy will improve overall outcomes in OSA-COPD overlap by reducing hospitalisations for exacerbations of COPD and improve mortality rates.

Ultrasound-guided foam sclerotherapy as a therapeutic modality in venous ulceration.

OBJECTIVES: The objective of this systematic review and meta-analysis was to evaluate rates of ulcer healing following ultrasound-guided foam sclerotherapy (UGFS). METHODS: The MEDLINE, CENTRAL and Embase databases were used to search for relevant studies using the terms ' (sclerotherapy AND ulcer) OR (vein AND ulcer) OR (sclerotherapy AND vein)'. Heterogeneity between studies was quantified using the I2 statistic. A random effects model was used to calculate risk ratios where substantial heterogeneity was found. RESULTS: The initial search yielded 8266 articles. 8 studies were included in the qualitative synthesis and 3 in the meta-analysis. Superior complete ulcer healing rates were noted in patients treated with foam sclerotherapy versus compression therapy alone (pooled OR 6.41, 95% CI = 0.3-148.2, p = 0.246, random effects method). A marked degree of heterogeneity was observed between studies (I2 = 81%). CONCLUSION: A prospective, trial is warranted in order to determine the true merits of UGFS in the setting of venous ulceration.

Total neoadjuvant chemotherapy: a silver lining during the COVID pandemic for a patient with locally advanced diffuse distal gastric adenocarcinoma.

Perioperative oncological therapies resulting in pathological complete response (pCR) in diffuse-type distal gastric adenocarcinoma are extremely rare. We report a case of locally advanced (cT3 N2 M0) diffuse-type distal gastric adenocarcinoma treated with 'total neoadjuvant' FLOT (eight cycles), due to the COVID-19 pandemic, and laparoscopic radical subtotal gastrectomy with D2 lymphadenectomy. The patient demonstrated a progressive radiological response on positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-d-glucose integrated with computed tomography (18F-FDG PET-CT) and pCR in the resected specimen (ypT0 N0). As far as we are aware, this is the first case of pCR in locally advanced T3 N2 diffuse distal gastric cancer to be reported in the literature. It introduces a novel approach of total neoadjuvant chemotherapy with 18F-FDG PET-CT to assess response, combined with radical minimally invasive surgical management to provide optimal care for patients with gastric cancer.

Demonstrating the processes and outcomes of a rural Community Mental Health Rehabilitation Service: A realist evaluation.

BACKGROUND: As part of significant mental health reform, the Community Mental Health Rehabilitation Service (CMHRS) was implemented in rural South Australia. The CMHRS is a 10-bed mental health residential program offering rehabilitative mental health support to rural residents. AIM: To analyse the CMHRS service delivery model and its impact on recovery outcomes for consumers. METHODS: A mixed method, realist evaluation approach was utilised. A purposive sample of CMHRS staff (n = 6) and consumers (n = 8) were recruited. Consumer recovery was measured using the RAS-DS (on admission and discharge). Participants' perspectives of the service were gained via one staff focus group (n = 6) and individual semi-structured interviews (consumers n = 6; staff n = 2). Pre-post RAS-DS scores were analysed using paired t-tests/Wilcoxon paired-signed rank test, with qualitative data analysed thematically. RESULTS: Significant positive increases in RAS-DS total scores were observed at discharge, supported by the qualitative themes of (re)building relationships and social connections and recovering health and wellbeing. Contextual factors (e.g. staffing) and program mechanisms (e.g. scheduling) impacting on service implementation were identified. CONCLUSION: Maintaining a rehabilitation recovery-focused approach, balanced with an appropriately trained multi-disciplinary team, are vital for maximising positive consumer outcomes. SIGNIFICANCE: This realist evaluation identifies critical factors impacting rural mental health rehabilitation service delivery.