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Background: The Geriatric Assessment and Medical Preoperative Screening (GrAMPS) program was an initial attempt to understand and to define the prevalence of age-related risk factors in older patients undergoing elective ventral hernia repair (VHR) or inguinal hernia repair (IHR). Preliminary analysis found significant rates of previously unrecognized objective cognitive dysfunction, multimorbidity and polypharmacy. We now examine whether chronological age as a sole risk factor can predict a patient's perioperative outcomes, and if traditional risk calculators that rely heavily on chronological age can accurately capture a patient's true risk.Methods: This was a retrospective secondary analysis of the previously reported GrAMPS trial enrolling patients 60 years and older with a planned elective repair of a ventral or inguinal hernia. The rates of key postoperative outcomes were compared between various cohorts stratified by chronological age. Previously validated risk screening calculators [Charlson Comorbidity Index (CCI), National Surgical Quality Improvement Program (NSQIP)] were compared between cohorts.Results: In total, 55 (78.6%) of the 70 patients enrolled in GrAMPS underwent operative intervention by May 2021, including 26 VHR and 29 IHRs. Cohorts stratified by chronological age had similar rates of key perioperative wound and age-related outcomes including readmissions, postoperative complications, non-home discharges, and length of stay. Additionally, while the commonly used risk calculators, CCI and NSQIP, consistently predicted worse outcomes for older hernia patients (stratified by both median age and age-tertiles), screening positive on these risk assessments were not actually predictive of a greater incidence of postoperative complications.Conclusions: Chronological age does not accurately predict worse adverse postoperative complications in older hernia patients. Additionally, traditional risk screening calculators that rely heavily on age to risk stratify may not accurately capture a patient's true surgical risk. Surgeons should continue to explore nuanced patient risk assessments that more accurately capture age-related risk factors to better individualize perioperative risk. [ABSTRACT FROM AUTHOR]

Background: Transversus abdominis release (TAR) is an effective procedure for the repair of complex ventral hernias. However, TAR is not a low risk operation, particularly in older adults who are disproportionately affected by multiple age-related risk factors. While past studies have suggested that age alone inconsistently predicts patient outcomes, data regarding age's effect on postoperative outcomes and wound complications following a TAR are lacking.Methods: Patients who underwent either an open or robotic bilateral TAR from 1/2018 to 9/2020 were eligible for the study. Patients were stratified by age groups (≥ 60 years vs. < 60 years and < 60, 60-70, and ≥ 70) and by both age and operative approach. The rates of key postoperative outcomes and wound morbidity were compared between the various cohorts.Results: A total of 300 patients were included: 165 patients were ≥ 60 and 135 patients were < 60. Cohorts stratified by age were well-matched for important hernia factors: defect size (p = 0.31), BMI ≥ 30 (p = 0.46), OR time (p = 0.25), percent open TAR (p = 0.42), diabetes (p = 0.45) and history of prior surgical site infection (p = 0.40). The older cohort had significantly higher rates of coronary artery disease, hypertension, and COPD. On univariate analysis, cohorts stratified by age had similar rates of key postoperative and wound complications including in-hospital complications (p = 0.62), length of stay (p = 0.47), readmissions (p = 0.66), and surgical site occurrences (p = 0.68). Additionally, cohorts stratified by both age and operative approach also had similar outcomes. Multivariate analysis showed that chronological age was not independently associated with surgical site occurrences (p = 0.22), readmissions (p = 0.99), in-hospital complications (p = 0.15), or severe complications (p = 0.79).Conclusion: Open and robotic TARs can be safely performed in older adults and chronological age alone is a poor predictor of patient morbidity following TAR. Further investigation of alternative preoperative screening tools that do not rely solely on age are needed to better optimize surgical outcomes in older adults following TAR. [ABSTRACT FROM AUTHOR]

Background: Falls and fall-related injuries remain a global challenge and threat to the health of older adults. Specific strength and balance exercises are effective in preventing falls among community-dwelling older adults. Nevertheless, provision of evidence-based fall prevention interventions to a broad population represents a healthcare challenge, indicating that new models for promoting exercise among community-dwelling older adults need to be addressed. Here, we aimed to evaluate the effects of a peer-led group-based exercise intervention provided using the train-the-trainer approach and targeting physical performance, activity level, handgrip strength, quality of life, fall-related self-efficacy, fear of falling, and falling techniques compared with a control group at 8-week follow-up., Methods: This randomized controlled trial (RCT) included trainers and participants who were recruited from four collaborating regional organizations for retired persons. The intervention was planned to be provided in five municipalities in Sweden, depending on the location of the registered trainers. Eligible participants included adults aged ≥ 60 years who could walk independently and understand written and oral information in Swedish. The FallFitness multicomponent exercise program delivered weekly strength, balance, and falling techniques over eight weeks. It was evaluated using the train-the-trainer approach. Fourteen older adults were eligible for trainer education, and 101 participants were randomly allocated for the FallFitness exercise (n = 50) or a control group (n = 51)., Results: After 8 weeks of peer-led training, the short multicomponent exercise program significantly improved the physical activity levels (p = 0.036) and backward and sideways falling techniques (p < 0.001) compared to those in the control group. Fear of falling significantly decreased in the exercise group (p = 0.009). Other outcomes in this study showed to be non-significant., Conclusions: The multicomponent exercise program provided in eight sessions using the train-the-trainer approach may be effective in promoting physical activity and the learning of motor skills and safe landing strategies. Furthermore, the FallFitness exercise program may reduce the fear of falling and may be both time- and cost-effective., Trial Registration: ClinicalTrials.gov, NCT06265480 (20240208)., Competing Interests: Declarations. Ethics approval and consent to participate: The current study was approved by the Swedish Ethical Review Authority (approval no. 2023-04577-01) and was conducted in accordance with the principles embodied in the 1964 Declaration of Helsinki, which concerns human rights, informed consent, and correct procedures regarding treatment in research involving human participants. Verbal and written informed consent to participate was obtained from all of the participants in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Many FDA-approved cancer therapies, whether as a multiagent combination or as a single agent, have demonstrated only modest clinical benefit. To investigate the drug development landscape, this analysis focuses on whether newly approved drugs are added to existing standards as combination therapy or replace a former drug as monotherapy., Methods: A retrospective analysis of package inserts and corresponding trials for the treatment of nonhematology solid tumor malignancies from January 2011 to December 2023 was conducted to categorize an approval as monotherapy or combination therapy. Drug characteristics, treatment indications, study design, approval history, and efficacy results were compared between the 2 cohorts., Results: Among the 292 approval entries and 110 drugs, 193 (66.1%) were monotherapies and 99 (33.9%) were combinations. Combinations, when compared with monotherapies, were more frequently approved as regular than accelerated approval (85 [85.9%] vs 132 [68.4%], P <.01), in the first-line setting (66 [66.7%] vs 69 [35.8%], P <.01), and with overall survival as the criteria (49 [49.5%] vs 40 [20.7%], P <.01). Monotherapies were more likely to be novel drugs compared with combinations (80 [41.5%] vs 14 [14.1%] P <.01). Monotherapies were more likely to be small molecule targeted agents, while combinations were more likely to be immunotherapies (P <.02). There was no difference comparing the time-to-event endpoints and validated clinical benefit scale, but the median response rate of combinations (46%) was higher than monotherapies (34%, P <.01)., Discussion: Given that clinical benefit appears limited in combination therapy compared with monotherapy, drug development could focus on simplifying cancer therapies toward patient-centered paradigms., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: Acutely hospitalised older patients often live with frailty and have an increased risk of impaired physical function. Previous studies suggest that exercise might mitigate the risk of physical impairment; however, further research is needed to compare the effect of different types of exercise interventions. In this paper, we report a protocol for a trial that aims to examine (1) if multicomponent exercise interventions (interventions that include both mobility and strengthening exercises) have effects on physical function compared with usual care in older adults and (2) if a comprehensive multicomponent exercise programme is more effective than a simple multicomponent exercise programme that only include walking and sit-to-stand exercises., Methods and Analysis: This is a three-armed randomised controlled trial, with two intervention groups (comprehensive and simple exercise programme) and a control group receiving usual care. We will include 320 participants aged ≥75 years from geriatric medical departments of four hospitals in Stockholm, Sweden. Assessments will be conducted at hospital admission, discharge and 3 months thereafter concerning physical function (primary outcome), activities of daily living, health-related quality of life, sarcopenia and falls. The number of readmissions will be registered up to 1 year after discharge. Data will be analysed with linear mixed effects models, according to the intention-to-treat approach., Ethics and Dissemination: Ethical approval for this trial has been granted by the Swedish Ethical Review Authority (approval number 2022-03032-01). Data collection will consider the information requirement, the requirement of consent, confidentiality obligations and the utilisation requirement. Trial findings will be disseminated through multiple channels, including scientific publications and conferences, and workshops with healthcare professionals and the public., Trial Registration Number: NCT05366075., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Ventral hernias are common in older adults, and may be repaired via a transversus abdominus release (TAR). Older adults undergoing surgery have unique age-related risk factors, including polypharmacy. Polypharmacy is highly prevalent in older adults and is associated with adverse postoperative outcomes. Our aim was to examine the prevalence and association of polypharmacy with clinical outcomes in older adults undergoing a TAR., Methods: Patients 60 years and older who underwent elective open or robotic bilateral TAR were included in the study. Average daily medications taken preoperatively was collected and stratified by tertiles. Baseline demographic data, peri- and postoperative outcomes, and 30-day outcomes were collected., Results: There were 132 total patients with an average age of 67.8 years. The number of daily medications ranged from 0 to 28, with an overall mean of 11.2 medications. Patients in tertile 1 took an average of 5.3 medications, tertile 2 10.5 medications, and tertile 3 17.9 medications. Patients in tertile 3 had more than double the rate of in-hospital complications (0.7) compared to tertiles 1 and 2 (0.3 and 0.3, respectively; p = 0.03). A greater number of daily medications was independently associated with postoperative delirium [odds ratio (OR) 1.2, 95% confidence interval (CI) 1.0-1.3], cardiac events (OR 1.2, 95% CI 1.0-1.3), ICU stay (OR 1.2, 95% CI 1.0-1.3), and discharge to a skilled nursing facility (SNF) (OR 1.2, 95% CI 1.0-1.5)., Conclusions: Polypharmacy was very common in older adults undergoing a TAR, and was associated with in-hospital complications, postoperative delirium, cardiac events, ICU stay, length of stay, and discharge to a SNF. Additional study is needed to assess if preoperative interventions to limit polypharmacy will improve outcomes for older adults undergoing a TAR., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

How cognitive task behavior is generated by brain network interactions is a central question in neuroscience. Answering this question calls for the development of novel analysis tools that can firstly capture neural signatures of task information with high spatial and temporal precision (the "where and when") and then allow for empirical testing of alternative network models of brain function that link information to behavior (the "how"). We outline a novel network modeling approach suited to this purpose that is applied to noninvasive functional neuroimaging data in humans. We first dynamically decoded the spatiotemporal signatures of task information in the human brain by combining MRI-individualized source electroencephalography (EEG) with multivariate pattern analysis (MVPA). A newly developed network modeling approach-dynamic activity flow modeling-then simulated the flow of task-evoked activity over more causally interpretable (relative to standard functional connectivity [FC] approaches) resting-state functional connections (dynamic, lagged, direct, and directional). We demonstrate the utility of this modeling approach by applying it to elucidate network processes underlying sensory-motor information flow in the brain, revealing accurate predictions of empirical response information dynamics underlying behavior. Extending the model toward simulating network lesions suggested a role for the cognitive control networks (CCNs) as primary drivers of response information flow, transitioning from early dorsal attention network-dominated sensory-to-response transformation to later collaborative CCN engagement during response selection. These results demonstrate the utility of the dynamic activity flow modeling approach in identifying the generative network processes underlying neurocognitive phenomena., Competing Interests: The authors have declared that no competing interests exist.

Background: As the population ages, the incidence of ventral hernias in older adults is increasing. Ventral hernia repairs (VHR) should not be considered low risk operations, particularly in older adults who are disproportionately affected by multiple age-related factors that can complicate surgery and adversely affect outcomes. Although age-related risk factors have been well established in other surgical fields, there is currently little data describing their impact on VHR., Methods: We performed a systematic review of the literature to identify studies that examine the effects of age-related risk factors on VHR outcomes. This was conducted using Cochrane Library, Embase, PubMed (Medline), and Google Scholar databases, all updated through June 2020. We selected relevant studies using the keywords, multimorbidity, comorbidities, polypharmacy, functional dependence, functional status, frailty, cognitive impairment, dementia, sarcopenia, and malnutrition. Primary outcomes include mortality and overall complications following VHR., Results: We summarize the evidence basis for the significance of age-related risk factors in elective surgery and discuss how these factors increase the risk of adverse outcomes following VHR. In particular, we explore the impact of the following risk factors: multimorbidity, polypharmacy, functional dependence, frailty, cognitive impairment, sarcopenia, and malnutrition. As opposed to chronological age itself, age-related risk factors are more clinically relevant in determining VHR outcomes., Conclusions: Given the increasing complexity of VHR, addressing age-related risk factors pre-operatively has the potential to improve surgical outcomes in older adults. Preoperative risk assessment and individualized prehabilitation programs aimed at improving patient-centered outcomes may be particularly useful in this population., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: It is of utmost importance to investigate risk factors for falls and learning techniques for falling safely. Therefore, the aim of this study was to assess the feasibility of a novel judo-inspired exercise intervention for community-dwelling older adults., Methods: We included 28 participants, 60-88 years of age, in this study. In three different settings, the feasibility of carrying out a full-scale study was evaluated by the following: the study process, resource management and scientific aspects. The outcome measures evaluated were physical performance, fall related self-efficacy and fall techniques (backwards and forwards) among the older adults., Results: The intervention was judged to be feasible in the different settings used in this study. Some changes regarding duration of the intervention were suggested as being important. Significant improvements were seen in the selected outcome measures, physical performance (p=.030) and fall techniques (p=<.001). A corresponding difference was not found for fall related self- efficacy (p=.113)., Conclusions: This study confirms the judo inspired exercise programme, Judo4Balance, to be a feasible intervention for active older adults. This study will provide a safe and thoroughly planned protocol for the planned study and provides indication of appropriate setting depending on the target group., Competing Interests: The authors have no conflict of interest., (Copyright: © 2020 Hylonome Publications.)

Background: Ischemia-reperfusion is one of the unavoidable steps in lung transplantation; it is associated with acute inflammatory responses and cell death. The intracellular signal transduction mechanisms of these events are largely unknown. We hypothesize that activation of mitogen-activated protein kinases (MAPKs) is one of the important signaling events during human lung transplantation., Methods: Lung tissue biopsies were performed on 15 patients undergoing transplantation: after cold ischemic preservation; after warm ischemia (implantation); and after 1- or 2-hour reperfusion. The phosphorylation status of MAPK isoforms (ERK, p38-MAPK and JNK) was examined by Western blotting., Results: Phosphorylation of ERK was dramatically increased during the first 2 hours of reperfusion. Phosphorylation of JNK also significantly increased at lower levels. In contrast, phosphorylation of p38 showed no significant changes., Conclusions: We speculate that the rapid and sustained activation of ERK and JNK during the early reperfusion period may contribute to acute inflammatory responses and cell death of lung grafts.