Version Of Criterion Research Articles

Relationship between self-rated health, physical frailty, and incidence of disability among Japanese community-dwelling older adults: A longitudinal prospective cohort study.

Poor self-rated health (SRH) and physical frailty are both significant predictors of disability in older adults, but their joint association on health outcomes remain unclear. This study aimed to examine the relationship between SRH, physical frailty, and incidence of disability among community-dwelling older adults. This longitudinal cohort study included 2838 older adults aged 65 years or older (mean age, 73.1 ± 5.9 years) living in Takahama, Japan, who participated in the baseline assessment from September 2015 to February 2017. Participants were followed prospectively until June 2021. SRH was assessed on a four-point scale, and frailty was evaluated using the Japanese version of the Cardiovascular Health Study criteria. Participants were categorized into four groups based on SRH (Good or Poor) and frailty status (Robust or Frail). Cox proportional hazard models were used to assess the association between these categories and the incidence of disability over a 5-year follow-up. During the median follow-up of 60 months, 349 of the 2838 participants developed a disability. The risk of disability was significantly higher in the Poor/Robust (HR 1.64, 95 % CI 1.20-2.25), Good/Frail (HR 2.58, 95 % CI 1.91-3.49), and Poor/Frail (HR 2.03, 95 % CI 1.37-3.01) groups than in the Good/Robust reference group. Frail older adults who report good health were associated with the risk of disability, suggesting that discrepancies between subjective and objective health assessments may lead to adverse outcomes. Recognizing and addressing these discrepancies is crucial to promote successful aging.

PEARL: A multicenter phase 2 study of lorlatinib in patients with ALK-rearranged NSCLC and central nervous system disease

BackgroundPatients with ALK-rearranged non-small cell lung cancer (ALK+ NSCLC) with symptomatic brain (BM) and leptomeningeal (LM) metastases are underrepresented in clinical trials due to poor performance status. Additionally, the need for improved and validated assessment criteria for evaluating central nervous system (CNS) response remains critical. Lorlatinib has demonstrated systemic activity in patients with ALK+ NSCLC. This ongoing phase II study aims to evaluate the efficacy and safety of lorlatinib in ALK+ NSCLC patients with progressive CNS metastases. Patients and MethodsThis study is a multicenter, open-label, single-arm, prospective trial. Fifty eligible subjects will be divided into two cohorts: BM (progressive or new brain parenchymal; n=30) and LM (positive cerebrospinal fluid cytology and/or MRI ± brain parenchymal metastasis; n=20). Key inclusion criteria include ALK status confirmed using FDA-approved tests, at least one CNS lesion, with or without CNS-related symptoms, and an ECOG performance status of 0-2 for the BM cohort and 0-3 for the LM cohort. Primary endpoint is intracranial objective response rate based on the modified version of response evaluation criteria in solid tumors v1.1 for BM and modified RANO-LM criteria for LM. Key secondary endpoints include intracranial progression-free survival, overall progression-free survival, objective response rate, overall survival, safety and quality of life. Biomarker analysis of paired pre-treatment tumor, blood and optional cerebrospinal fluid will be performed as preplanned exploratory analyses. ConclusionsThe PEARL study (CTONG2303) will evaluate efficacy of lorlatinib in CNS metastases in ALK+ NSCLC using refined CNS response evaluation criteria, with biomarker analyses providing insights into response and resistance mechanisms.

Development, Validation, and Clinical Utility of Electronic Patient-Reported Outcome Measure-Enhanced Prediction Models for Overall Survival in Patients With Advanced Non-Small Cell Lung Cancer Receiving Immunotherapy.

Electronic patient-reported outcome measures (ePROMs) are increasingly collected routinely in clinical practice and may be prognostic for survival in adults with advanced non-small cell lung cancer (NSCLC) in addition to clinical data. This study developed ePROM-enhanced models for predicting 1-year overall survival in patients with advanced NSCLC at the start of immunotherapy. This is a single-center study using consecutive patients from a tertiary cancer hospital in England. Using Cox proportional hazards models, we developed one clinical factor-only model and three ePROM-enhanced models, each including one of the following factors: quality of life (as measured by EuroQoL five-dimension five-level utility score) and overall symptom burden and number of moderate-to-severe symptoms (as measured by patient-reported version of Common Terminology Criteria for Adverse Events). Predictive performance was evaluated and compared through bootstrapping internal validation, and clinical utility was determined via decision curve analysis. The clinical factor-only model contained age, histology, performance status, and neutrophile-to-lymphocyte ratio. While calibration was similar between the clinical factor-only and ePROM-enhanced models, the latter showed improved discrimination by 0.020 (95% CI, 0.011 to 0.024), 0.024 (95% CI, 0.016 to 0.031), and 0.024 (95% CI, 0.014 to 0.029) when enhanced with ePROMs on quality of life, overall symptom burden, and number of moderate-to-severe symptoms, respectively. If care decisions are to be made at risk thresholds between 25% and 75%, the ePROM-enhanced models led to higher net benefit than the clinical factor-only model and the default strategies of intervention for all and intervention for none. The ePROM-enhanced models outperformed the clinical factor-only model in predicting 1-year overall survival for patients with advanced NSCLC receiving immunotherapy and showed potential clinical utility for informing decisions in this population. Future studies should focus on validating the models in external data sets.

Bayesian information criteria for multiple regression models: A study of robustness and comparisons

It is recommended to employ robust versions of selection criteria for variables in linear regression when extreme outliers and high leverage points present. This article investigates the robust version of the Bayesian information criterion based on the MM-estimation scale BICMM . Furthermore, the robustness properties of the proposed BICMM criterion are examined via its breakdown point, influence function, and gross-error sensitivity. Performance of the proposed criterion is compared to existing non-robust and robust Bayesian information criterion, robust Akaike’s information criterion, robust Mallows’ C p , and robust Schwarz information criterion, based on the least-trimmed squares estimator. Simulation studies and applications on real data reveal that BICMM selects more suitable models in situations where there are outliers or leverage points. Consequently, when multicollinearity exists, the proposed robust BICMM can be used to select the tuning parameter in shrinkage regression methods such as ridge and lasso regression.

Optimizing medication therapy in elderly patients: The impact of medication review using STOPP and START criteria version 2.

Background: Higher prevalence of inappropriate medication use among cancer patients increases risk of drug-related problems(DRP) like drug-drug interactions, ADR, and non-adherence. Potentially inappropriate medication (PIM) and Potential Prescription Omission (PPO) were identified using Screening Tool of Older Person's Prescriptions (STOPP) and Screening Tool to Alert Doctors to the Right Treatment (START) criteria. Objectives: The study objective was to optimize prescriptions for the elderly by analyzing the impact of medication review. Methods: An observational study in which PIM and/or PPO were identified and the prescriptions were optimized by a physician. Results: Out of 150 patients, a total of 35 drugs were stopped and 12 drugs were started. Medication omissions were identified in 12 patients (8%). There were no DRPs associated with medication adjustments. Conclusion: Based on a pharmacist-led comprehensive medication review of the elderly, the STOPP and START criteria allow the optimization of prescriptions.

Translation and Adaptation of the STOPP/START Criteria Version 3 for Potentially Inappropriate Prescribing in Older People to European Portuguese: A Study Protocol.

As the global population ages, managing medication use in older adults becomes increasingly complex due to polypharmacy and the associated risks of adverse drug events. To improve the safety and appropriateness of medication use in the older population, tools like the Screening Tool of Older Persons' Prescriptions (STOPP) and Screening Tool to Alert doctors to Right Treatment (START) criteria have been developed. The availability of updated criteria is crucial to better support healthcare professionals in Portuguese-speaking regions. The aim of this study is to translate and validate the STOPP/START version 3 criteria for Portuguese, providing an updated and useful tool for healthcare professionals. This study will be conducted through four phases: I) translation of the STOPP/START version 3 criteria to European Portuguese; II) collection of sociodemographic, clinical, and medication data; III) intrarater reliability study; and IV) interrater agreement study. This study obtained ethics approval by the Ethics Committee of the Administração Regional de Saúde do Centro, Portugal. The availability of the translated criteria will enable the integration of STOPP/START version 3 into clinical practice in Portugal, facilitating improved medication safety and appropriateness. This integration is expected to lead to better management of polypharmacy and a reduction in adverse drug events, ultimately enhancing patient outcomes and supporting evidence-based prescribing practices.

Rohdea maoershanensis, a new species of Asparagaceae from Guangxi, South China

A new species, Rohdea maoershanensis, endemic to the Mao’er Mountain National Nature Reserve in northern Guangxi, is described herein. It is morphologically similar to R. chinensis, R. jinshanensis, and R. chlorantha, but it is easy to distinguish from the latter three because of leaves 9–13, linear, length of peduncle about 22 cm, length of bract about 3 mm, triangular lanceolate, filament base enlarged and connected to form a rough annular appendage, ovary is flattened spherical shape. Following the IUCN Red List Categories and Criteria (Version 3.1) [C2(a)(ii)], the species is preliminarily classified as Endangered (EN).

Identification of meaningful individual-level change thresholds for worsening on the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE®).

We derived meaningful individual-level change thresholds for worsening in selected patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE®) items and their composite scores. We used two data sources, the PRO-TECT trial (Alliance AFT-39) that collected PRO-CTCAE data from adults with advanced cancer at 26 United States (U.S.) community oncology practices and the PRO-CTCAE validation study that collected PRO-CTCAE data from adults undergoing chemotherapy or radiation therapy at nine U.S. cancer centers or community oncology practices. Both studies administered selected PRO-CTCAE items and EORTC QLQ-C30 scales. Conceptually, relevant QLQ-C30 domains were used as anchors to estimate meaningful change thresholds for deterioration in corresponding PRO-CTCAE items and their composite scores. Items or composites with ǀρǀ ≥ 0.30 correlation with QLQ-C30 scales were included. Changes in PRO-CTCAE scores and composites were estimated for patients who met or exceeded a 10-point deterioration on the corresponding QLQ-C30 scale. Change scores were computed between baseline and the 3-month timepoint in PRO-TECT, and in the PRO-CTCAE validation study between baseline and a single follow-up visit that occurred between 1 and 7weeks later. For each PRO-CTCAE item, change scores could range from - 4 to 4; for a composite, change scores could range from - 3 to 3. Change scores in QLQ-C30 and PRO-CTCAE were available in 406 and 792 patients in PRO-TECT and the validation study, respectively. Across QLQ-C30 scales, the proportion of patients with a 10-point or greater worsening on QLQ-C30 ranged from 15 to 30% in the PRO-TECT data and 13% to 34% in the validation data. Across PRO-CTCAE items, anchor-based meaningful change estimates for deterioration ranged from 0.05 to 0.30 (mean 0.19) in the PRO-TECT data and from 0.19 to 0.53 (mean 0.36) in the validation data. For composites, they ranged from 0.06 to 0.27 (mean 0.17) in the PRO-TECT data and 0.22 to 0.51 (mean 0.37) in the validation data. In both datasets, the minimal meaningful individual-level change threshold for worsening was one point for all items and composite scores. gov: NCT03249090 (AFT-39), NCT02158637 (MC1091).

[Artículo traducido] Adherencia al tratamiento con quimioterapia oral en pacientes con cáncer de pulmón no microcítico localmente avanzado o metastásico: protocolo para un estudio de vida real realizado en farmacia hospitalaria

ObjectiveThis article describes a study protocol for evaluating adherence to oral chemotherapy (OCT) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) in Spain. MethodsThis multicenter, observational, prospective study will be conducted by six hospital pharmacists from six Spanish hospitals. The study will include men and women aged 18 years or older with a diagnosis of locally advanced or metastatic NSCLC who are being treated or have been prescribed OCT. Once included, the patient will be active and prospectively followed up for 3 months, including four study visits to record information on sociodemographic variables, antineoplastic treatment and adherence, pharmaceutical care, clinical variables, and patient-reported outcomes (PRO) (the 3-level version of EQ-5D, the EORTC Core Quality of Life Questionnaire, the Brief Illness Perception Questionnaire, the Treatment Satisfaction with Medicines Questionnaire, and the PRO version of Common Terminology Criteria for Adverse Events). Twelve months after patient inclusion, we will record information on the disease progression status and dispensed prescriptions. The primary outcome is the percentage of treatment adherence that will be calculated based on the pill count as follows: the difference between the number of pills dispensed minus the number of unused pills will be divided by the number of days of treatment multiplied by the number of pills/day prescribed by the oncologist; this quotient will be multiplied by 100 to obtain the percentage of adherence. Based on the that pill count reconciliation, those with a percentage adherence greater than80% will be primarily categorized as adherent. Secondarily, treatment adherence will be also calculated based on the proportion of days covered and the 4-items Morisky Green Levine Medication Adherence Scale. To analyze the impact of patients' and treatment characteristics on adherence, bivariate analyses will be performed using different adherence cut-off points. To evaluate the impact of adherence on treatment efficacy as evaluated by progression-free survival, we will be using the Kaplan–Meier method and compare it with the log-rank test and univariate Cox regression analysis. ConclusionsWe expect that our study will provide initial information on key aspects of adherence to OCT (measurement, facilitators, and barriers) and its relationship with patients' and clinically relevant outcomes in the setting of NSCLC, and that this information will help in designing pharmaceutical interventions to improve adherence.

Efficacy and safety of long-term edoxaban treatment for low body weight cancer patients with isolated distal deep vein thrombosis: a post-hoc subgroup analysis of the ONCO DVT study

Abstract Background Low body weight is known to be a bleeding risk in the anticoagulation treatment. ONCO DVT study revealed that 12-month edoxaban treatment for cancer patients with isolated distal deep vein thrombosis (DVT) reduced a composite outcome of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death compared with 3-month edoxaban treatment. However, the efficacy and safety of long-term edoxaban treatment for cancer patients with low body weight is unclear. Purpose In this subgroup analysis, we assessed the efficacy and safety of 12-month edoxaban treatment for low body weight cancer patients with isolated distal DVT. Methods We conducted a post-hoc subgroup analysis of the ONCO DVT study in the low body weight patients. ONCO DVT study was a multicenter, open-label, adjudicator-blinded, randomized clinical trial. Cancer patients with isolated distal DVT were assigned to 12-month or 3-month edoxaban treatment. The primary endpoint was a composite outcome of a symptomatic recurrent VTE or VTE-related death at 12 months. The major secondary endpoint was major bleeding at 12 months. We enrolled patients who met low body weight defined in Japanese Version of High Bleeding Risk criteria (<55 kg for men, <50 kg for women) and evaluated the efficacy and safety of 12-month edoxaban treatment using logistic regression models and log-rank test. Results Among 601 patients in the intention-to-treat population of ONCO DVT study, 322 patients (53.6%) met low body weight: 151 patients were in 12-month edoxaban group and 171 patients were in 3-month edoxaban group. The body weight was similar between two group (47.1±5.2 kg in 12-month edoxaban group vs. 46.9±5.4 kg in 3-month edoxaban group; P=0.77). All of them used a lower dose edoxaban (30 mg once daily) following the dose reduction criteria. 12-month edoxaban group had lower rates of the primary endpoint compared with 3-month edoxaban group (2 patients (1.3%) vs. 10 patients (5.8%); Odds ratio 0.22 [95% CI, 0.05–1.00]; Log-rank P=0.036). There was no significant difference in the major secondary endpoint of major bleeding (12 patients (7.9%) in 12-month edoxaban group vs. 16 patients (9.4%) in 3-month edoxaban group; Odds ratio 0.83 [95% CI, 0.38–1.83]; Log-rank P=0.65). All clinically relevant bleeding events occurred in 22 patients (14.6%) in 12-month edoxaban group and in 27 patients (15.8%) in 3-month edoxaban group (Odds ratio 1.40 [0.90–2.19]; Log rank P=0.13), resulting in the comparable risk of bleeding in the 12-month edoxaban group. Conclusions Our study suggests that 12-month edoxaban treatment for low body weight cancer patients with isolated distal DVT prevents recurrent VTE or VTE-related death without increasing the risk of bleeding compared to 3-month edoxaban treatment.primary endpointsecondary endpoint

The utility of cardiac rehabilitation in improving endothelium-dependent vascular function in very elderly patients

Abstract Background Endothelial function is crucial for cardiovascular health and diseases. Cardiac rehabilitation has been reported to be useful in enhancing physical performance, quality of life, and endothelial function. The aging of patients with cardiovascular diseases is further progressing, and it is unclear whether cardiac rehabilitation improves physical function and endothelial function in very elderly patients with cardiovascular diseases. Purpose The purpose of this study is to investigate whether outpatient cardiac rehabilitation for individuals aged 80 and above improves physical function, quality of life (QOL), and vascular endothelial function. Methods Forty nine patients aged over 80 years with cardiovascular diseases participated in an outpatient cardiac rehabilitation program. Cardiac rehabilitation was conducted for 1 hour per session, 1-2 times per week for 3-4 months. Cardiopulmonary exercise testing (CPX) was conducted for the evaluation of physical function. QOL was assessed with Kansas City Cardiomyopathy Questionnaire (KCCQ) scores. The reactive hyperemia index (RHI) was measured using EndoPAT2000 in each patient to assess endothelial function. An RHI ≤ 1.67 was defined as endothelial dysfunction. Results The mean ± standard deviation of age was 84 ± 4 years, with 16 (33%) being male. Peak oxygen uptake improved significantly (from 14.1 ± 4.0 to 15.4 ± 3.9 mL/kg/min, P=0.002), as did short physical performance battery scores (from 10.1 ± 2.7 to 10.7 ± 2.0, P=0.004), mini-mental state examination scores (from 27.7 ± 2.2 to 28.2 ± 2.0, P=0.004), Japanese version of the Cardiovascular Health Study criteria (from 2.3 ± 1.3 to 1.5 ± 1.2, P<0.0001), and KCCQ scores (from 76.8 ± 18.4 to 81.4 ± 20.4, P=0.02) after the cardiac rehabilitation program. Endothelial function also improved (LogRHI 0.48 ± 0.39 to 0.57 ± 0.30, P=0.027), and the prevalence of endothelial dysfunction decreased from 54% to 36% after the cardiac rehabilitation program. Conclusion Even in the very elderly patients, outpatient cardiac rehabilitation is beneficial for improving physical function, quality of life, and endothelial function.

Association between self-care behaviour and multiple frailty domains in older patients with heart failure

Abstract Background/Introduction Heart failure (HF) self-care is important for the effective management of HF, reducing clinical events such as all-cause mortality and hospitalizations. HF self-care behaviours encompass comply with a regimen involving medication, diet, and exercise, symptom monitoring, and seeking assistance when symptoms occur. Frailty, prevalent among older patients with HF, involves physical, social, and cognitive domains. Identified factors influencing self-care behaviours in patients with HF include age, social support, and knowledge of the condition. Despite research on the association between self-care behaviours and frailty, there is a notable gap in studies that explore the relationship between self-care behaviour and multiple domains of frailty, particularly with adjustments for clinical characteristics. Purpose The aim of this study was to assess the association between self-care behaviour and multiple domains of frailty in older patients with HF. Methods The study included 182 patients with HF who were aged 65 years or older. Self-care behaviour was assessed 5 months after their discharge using the European Heart Failure Self-Care Behaviour Scale (EHFScBS), a self-report questionnaire. Frailty was assessed using the revised Japanese version of the Cardiovascular Health Study criteria (J-CHS) for physical frailty, and using Makizako’s five items for social frailty, and using Mini-Cog for cognitive decline. We used multiple regression analysis to assess the association between self-care score and multiple frailty domains and the number of frailty domains. The adjusted model was constructed based on age, gender, body mass index, New York Heart Association Classification, left ventricular ejection fraction, log-transformed B-type natriuretic peptide, estimated glomerular filtration rate and history of HF. In addition, we used multiple regression analysis to assess the association between the EHFScBS subitems score complying with regimen, asking for help, and adapting activities and multiple frailty domains and the number of frailty domains. Results According to the results of a multiple regression analysis, poor self-care behaviour was significantly associated with physical and social frailty and the number of frailty domains (all p < 0.05), even after adjusting for clinical characteristics. Poor complying with regimen was also significantly associated with physical and social frailty and the number of frailty domains (all p < 0.05). Poor asking for help was significantly associated with social frailty and the number of frailty domains (all p < 0.05). Conclusion The study indicates that poor self-care behaviour is linked to physical and social frailty, in addition to the cumulative number of frailty domains in older patients with HF, even when clinical characteristics are taken into consideration. This underscores the importance of factoring in the frailty status when guiding patients with HF in disease management.

Statistical properties of items and summary scores from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) in a diverse cancer sample.

The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE®) was developed to capture symptomatic adverse events from the patient perspective. We aim to describe statistical properties of PRO-CTCAE items and summary scores and to provide evidence for recommendations regarding PRO-CTCAE administration and reporting. Using data from the PRO-CTCAE validation study (NCT02158637), prevalence, means, and standard deviations of PRO-CTCAE items, composite scores, and mean and maximum scores across attributes (frequency, severity, and/or interference) of symptomatic adverse events were calculated. For each adverse event, correlations and agreement between attributes, correlations between attributes and composite scores, and correlations between composite, mean, and maximum scores were estimated. PRO-CTCAE items were completed by 899 patients with various cancer types. Most patients reported experiencing one or more adverse events, with the most prevalent being fatigue (87.7%), sad/unhappy feelings (66.0%), anxiety (63.6%), pain (63.2%), insomnia (61.8%), and dry mouth (60.0%). Attributes were moderately to strongly correlated within an adverse event (r = 0.53 to 0.77, all p < 0.001) but not fully concordant (κweighted = 0.26 to 0.60, all p < 0.001), with interference demonstrating lowest mean scores and prevalence among attributes of the same adverse event. Attributes were moderately to strongly correlated with composite scores (r = 0.67 to 0.97, all p < 0.001). Composite scores were moderately to strongly correlated with mean and maximum scores for the same adverse event (r = 0.69 to 0.94, all p < 0.001). Correlations between composite scores of different adverse events varied widely (r = 0.04 to 0.68) but were moderate to strong for conceptually related adverse events. Results provide evidence for PRO-CTCAE administration and reporting recommendations that the full complement of attributes be administered for each adverse event, and that attributes as well as summary scores be reported.

Pathological response following neoadjuvant immune checkpoint inhibitors in patients with hepatocellular carcinoma: a cross-trial, patient-level analysis

Neoadjuvant use of immune checkpoint inhibitors (ICIs) before liver resection results in pathological tumour regression in patients with hepatocellular carcinoma. We aimed to describe the characteristics of pathological responses after preoperative ICI therapy for hepatocellular carcinoma and to evaluate the association between the depth of tumour regression and relapse-free survival. In this cross-trial, patient-level analysis, we performed a pooled analysis of data from patients with hepatocellular carcinoma receiving ICI therapy before liver resection as part of a global collaborative consortium (NeoHCC) of five phase 1 and 2 clinical trials and standardised observational protocols conducted in 12 tertiary referral centres across the USA, UK, and Taiwan. Eligible patients were adults (aged ≥18 years) diagnosed with hepatocellular carcinoma by tissue core biopsy before treatment initiation, a Liver Imaging Reporting and Data System score of 5 on imaging, or both, with an Eastern Cooperative Oncology Group performance status score of 0-1, and no extrahepatic spread or previous ICI treatment. Pathological response was measured as the percentage of non-viable tumour in the resected surgical specimen, with major pathological response corresponding to at least 70% tumour regression and pathological complete response corresponding to 100% tumour regression. We correlated pathological response with radiological overall response using RECIST criteria (version 1.1) and relapse-free survival, and evaluated the threshold of tumour regression that could be optimally associated with relapse-free survival. At data cutoff on Jan 31, 2024, 111 patients were included in the study, of whom data on pathological response were available for 104 (94%) patients. Patients received treatment from Oct 5, 2017, to Nov 15, 2023, mostly ICI combinations (76 [69%]), for a median of 1·4 months (IQR 0·7-2·9). 87 (78%) patients were men and 24 (22%) were women. Most patients had underlying viral chronic liver disease (73 [66%]) and Barcelona Clinic Liver Cancer stage A hepatocellular carcinoma (61 [55%]), without portal vein thrombosis (87 [78%]). We observed major pathological response in 33 (32%) patients and pathological complete response in 19 (18%) patients. Radiological overall response was associated with major pathological response, with 23 (74%) of 31 patients with radiological response showing major pathological response compared with ten (14%) of 73 patients without radiological response (p<0·0001). However, ten (30%) of 33 major pathological responses were not predicted by radiological response. After a median follow-up of 27·2 months (95% CI 22·3-32·1), median relapse-free survival for the whole cohort was 43·6 months (95% CI 28·3-not evaluable). Relapse-free survival was significantly longer in patients with major pathological response than in those who did not have a major pathological response (not reached [95% CI not evaluable-not evaluable] vs 28·3 months [12·8-43·8]; hazard ratio 0·26 [0·10-0·66]; p=0·0024) and in patients with pathological complete response than in those who did not have a pathological complete response (NR [95% CI not evaluable-not evaluable] vs 32·8 months [15·0-50·5]; 0·19 [0·05-0·78]; p=0·010). Unbiased recursive partitioning of the cohort for the risk of relapse, death, or both identified a threshold of 90% as the optimal cutoff of pathological tumour regression to predict improved relapse-free survival. The extent of tumour regression following neoadjuvant ICI therapy could identify patients with improved relapse-free survival following liver resection. The threshold of at least 90% tumour regression should be validated for its surrogate role for relapse-free survival in phase 3 randomised controlled trials. None.

Investigating the Association between Catechol-O-Methyltransferase Gene Activity and Pain Perception in South African Patients with Different Temporomandibular Disorders Diagnoses.

Background: Temporomandibular disorders (TMD) affect a significant portion of the population, with profound psychological, behavioral, and social repercussions. Recent investigations have explored the genetic basis underlying pain perception in individuals with TMD, aiming to elucidate the role of specific genetic factors in modulating the condition. Notably, genetic variations have been implicated in the pathogenesis of TMD, particularly genes involved in pain perception pathways. One of the primary candidates is the Catechol-O-Methyltransferase (COMT) gene, which plays a crucial role in the catecholaminergic system and has been associated with the regulation of nociceptive processes. This study seeks to investigate the correlation between COMT gene activity and pain perception among South African patients diagnosed with varying forms of TMD. Methodology: In this study, a total of 196 participants were enrolled, comprising 97 patients diagnosed with TMD and 99 control participants. The control group was meticulously matched with the TMD group for age, gender, and ethnicity. Data collection involved clinical and radiological investigations, and saliva sampling. The English version of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) Axis I was utilized to evaluate all TMD participants, focusing on standard diagnostic measures based on clinical signs and symptoms of TMD, which primarily describe common physical manifestations of the disorder. Genomic DNA was extracted from saliva samples, enabling the analysis of single-nucleotide polymorphisms (SNPs) in the COMT gene, specifically targeting polymorphisms rs165774, rs9332377, rs6269, rs4646310, rs165656, and rs4680. Results: The current study demonstrated a pronounced gender disparity, with 80.41% of the participants being female and 19.59% male, suggesting that women in South Africa either exhibit a higher susceptibility to TMD or are more likely to seek treatment for the condition compared to men. The highest prevalence of TMD was observed in the white population (58.76%). Additionally, over 65% of TMD patients were diagnosed with at least two Axis I diagnoses, a figure that increased to 89% for those diagnosed with three Axis I diagnoses. The findings further indicated significant associations between several single-nucleotide polymorphisms (SNPs) in the Catechol-O-Methyltransferase (COMT) gene-specifically rs165656, rs9332377, rs4646310, rs6269, and rs165774-and both TMD and TMD-related pain. Myofascial pain with referral and myalgia showed a strong association with the COMT SNPs rs9332377 and rs4646310. Furthermore, COMT SNP rs4646310 was also associated with disability related to TMD. Conclusions: This study substantiates the hypothesis that pain is prevalent in a considerable proportion of patients affected by TMD. Furthermore, the findings reveal a significant association between COMT gene activity and pain perception in South African patients diagnosed with TMD.

Oral Frailty as a Risk Factor for Malnutrition and Sarcopenia in Patients on Hemodialysis: A Prospective Cohort Study.

Oral frailty is a concept that encompasses various aspects of impaired oral function in elderly people, leading to reduced food intake and less dietary diversity, which can result in sarcopenia and physical frailty. However, there have been no studies on the relationship between oral frailty and malnutrition, sarcopenia, and physical frailty in patients on hemodialysis (HD). This prospective observational cohort study assessed the oral status of patients on HD. The patients were divided into an oral frailty group and non-oral frailty group using the Oral Frailty Index-8. Malnutrition was assessed using the Geriatric Nutritional Risk Index (GNRI), the Nutritional Risk Index for Japanese Hemodialysis Patients (NRI-JH), and the Short-Form Mini-Nutritional Assessment (MNA-SF). Sarcopenia was assessed using the Asian Working Group for Sarcopenia 2019's criteria. Physical frailty was assessed using the Japanese version of the Cardiovascular Health Study criteria. One year later, the changes in nutritional status, sarcopenia, and physical frailty risk categories were compared between the oral frailty and non-oral frailty groups. The study enrolled 201 patients (non-oral frailty group, 123; oral frailty group, 78). After 1 year, the oral frailty group had a significantly higher proportion of patients with worsening nutrition status (GNRI, p = 0.0011; NRI-JH, p = 0.0019; MNA-SF, p < 0.001) and sarcopenia (p = 0.0024). There was no significant between-group difference in the proportion of patients in a worse risk category for physical frailty after 1 year. Oral frailty predicts future malnutrition and the progression of sarcopenia in HD patients. In particular, our results strongly suggested that oral frailty was a strong determinant of worsening malnutrition and sarcopenia in HD patients aged ≥65 years.

Amenability of quadratic automaton groups

We give lower bounds for the electrical resistance between vertices in the Schreier graphs of the action of the linear (degree 1) and quadratic (degree 2) mother groups on the orbit of the 0-ray. These bounds, combined with results of Juschenko et al. (2016), show that every quadratic activity automaton group is amenable. The resistance bounds use an apparently new “weighted” version of the Nash-Williams criterion which may be of independent interest.

Dietary quality and chemotherapy-induced peripheral neuropathy in colon cancer.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dose-limiting chemotoxicity caused by oxaliplatin. This study investigated the relationship between dietary quality and the development of moderate and/or severe CIPN in colon cancer survivors using data from the Focus on Reducing Dose-Limiting Toxicities in Colon Cancer with Resistance Exercise trial (ClinicalTrials.gov identifier NCT03291951). Diet quality was collected using a 127-item food-frequency questionnaire and was scored using the Alternative Healthy Eating Index-2010 (AHEI-2010). CIPN was assessed with the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events at each chemotherapy cycle. The association of dietary quality with time to the first moderate-to-severe (moderate-severe) or severe event of CIPN was estimated using Cox proportional hazards models. Only participants who received oxaliplatin were included in this analysis (n=132). Seventy-four participants (56.1%) reported moderate-severe CIPN. Higher dietary quality was associated with a significantly decreased risk of moderate-severe CIPN (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.93-0.99) and severe CIPN (HR, 0.91; 95% CI, 0.85-0.98). Consumption of red and processed meat (HR, 1.78; 95% CI, 1.07-2.83) and sugar-sweetened beverages (HR, 1.33; 95% CI, 1.10-1.59) was associated with an increased risk of moderate-severe CIPN. Consumption of sugar-sweetened beverages also was associated with an increased risk of severe CIPN (HR, 1.57; 95% CI, 1.14-2.18), whereas vegetable consumption was associated with a reduced risk of severe CIPN (HR, 0.29; 95% CI, 0.09-0.73). Among patients with colon cancer who received oxaliplatin-based chemotherapy, higher baseline dietary quality was associated with a reduced risk of moderate-severe CIPN.

Conjugate points along spherical harmonics

Utilizing structure constants, we present a version of the Misiolek criterion for identifying conjugate points. We propose an approach that enables us to locate these points along solutions of the quasi-geostrophic equations on the sphere S2. We demonstrate that for any spherical harmonics Ylm with 1≤|m|≤l, except for Y1±1 and Y2±1, conjugate points can be determined along the solution generated by the velocity field elm=∇⊥Ylm. Subsequently, we investigate the impact of the Coriolis force on the occurrence of conjugate points. Moreover, for any zonal flow generated by the velocity field ∇⊥Yl10, we demonstrate that proper rotation rate can lead to the appearance of conjugate points along the corresponding solution, where l1=2k+1.∈N Additionally, we prove the existence of conjugate points along (complex) Rossby-Haurwitz waves and explore the effect of the Coriolis force on their stability.

Comparison of symptom clusters between Black and White patients with cancer within an electronic patient-reported outcome remote symptom monitoring program.

328 Background: Disparities in pain management for Black patients with cancer are well-documented, but less is known about other symptom clusters like gastrointestinal (GI), respiratory, and urinary symptoms. This study assessed racial disparities in electronically reported symptom clusters among Black and White patients with cancer enrolled in a Remote Symptom Monitoring (RSM) program. Methods: Patients with cancer at the University of Alabama at Birmingham (UAB) and the Mitchell Cancer Institute (MCI) reported symptoms weekly using the Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAEs). The GI symptom cluster included decreased appetite, nausea, vomiting, constipation, and diarrhea; the respiratory cluster included cough and shortness of breath; the urinary cluster included frequent urinary problems. We assessed the presence of any moderate/severe symptoms or any severe symptoms (triggering a nurse alert) in the clusters. The study evaluated surveys submitted within the first six months after RSM enrollment. Generalized linear mixed effects modeling with random effects adjusting for cancer type, sex, and age were used to calculate the odds of reporting any moderate/severe pain between Black and White patients. Results: Among 1454 patients (31% Black, 69% White), 17,937 surveys were analyzed. The median age for Black patients was 59 (IQR 47-66) and 63 (IQR 54-71) for White patients. Breast cancer was most common in both groups (36% Black, 23% White), followed by gynecological (20% Black, 17% White) and gastrointestinal cancers (19% Black, 18% White). At baseline, both races reported similar proportions of moderate/severe or severe symptom for all clusters (Table). During the first six months in the RSM program, symptom proportions remained similar (Table). These findings were consistent in adjusted analysis for the GI (OR 0.85; 95% CI 0.68-1.07), respiratory (OR 1.18; 95% CI 0.87-1.61), and urinary clusters (OR 0.92; 95% CI 0.61-1.39). Conclusions: Our findings suggest no significant racial disparities in reporting moderate/severe or severe symptoms among Black and White patients with cancer at baseline or within their initial six months in the RSM program across GI, respiratory, and urinary symptom clusters. Survey characteristics. Total Surveys(N=17,937) Baseline Surveys 6 Months Surveys White (n=999) Black(n=455) White(n=11,344) Black(n=5139) Gastrointestinal Symptoms, No. (%) Severe 1376 (8) 121 (12) 59 (13) 783 (7) 413 (8) Moderate/Severe 4701 (26) 300 (30) 130 (29) 2971 (26) 1300 (25) Respiratory Symptoms, No. (%) Severe 438 (2) 28 (3) 29 (6) 241 (2) 140 (3) Moderate/Severe 1612 (9) 90 (9) 62 (14) 996 (8) 464 (9) Urinary Symptoms, No. (%) Severe 333 (2) 31 (3) 13 (3) 184 (2) 105 (2) Moderate/Severe 620 (3) 44 (4) 21 (5) 372 (3) 183 (4)