Soreness Research Articles

Patient-reported outcomes in physical, cognitive, and sexual health in early-onset gastrointestinal cancers (EOGIC).

72 Background: Incidence of early-onset (ages 18-49) gastrointestinal cancers is alarmingly increasing. To assess unmet needs in health-related quality of life (HRQoL), we conducted this pilot study using PRO measures in patients with EOGIC. Methods: Patients ages 18-49 with any GI cancer seen at our center during a clinic visit were invited to participate in this cross-sectional study. Validated PRO tools PROMIS 29+2, GP5 from FACT-G, AYA Sexual Health PRO Battery and Adult Neuro-QOL Cognitive Function short form were administered. Participants’ PROMIS 29+2 responses were scored to generate a T score, and two-tailed t-tests were used to compare T scores with the average score from a large general US population. The electronic medical record was reviewed to collect demographic, diagnosis and treatment information. Results: 39 (85% response rate) patients were enrolled from 03-08/24. Table 1 describes demographics, diagnoses, and treatment. In the PROMIS 29+2, EOGIC patients reported significantly lower physical function and higher anxiety, depression, fatigue and pain interference compared to the general US population: t-score (T-test p-value) 40.4 (p 0.0003), 57.7 (p 0.005), 55.7 (p 0.017), 55.1 (p 0.033) and 58.5 (p 0.0001), respectively. 56% reported being at least somewhat “bothered by side effects of treatment,” and this measure has a known correlation with clinician reported adverse events. Regarding sexual health (SH) in prior 30 days, 79% of participants felt less whole or “damaged” due to their disease, 64% were sexually active, 56% had some distress due to change in SH, and 50% were worried about their romantic relationship(s). Patients identified discussing safe sex with low counts, body image, contraception and addressing sexual problems as areas of unmet need during their care. They reported not receiving counseling from their care teams: only 15% discussed safe sex with low counts, 28% contraception, 13% STI prevention, and 18% discussed effect of cancer on body image. No significant change in cognitive functioning over the preceding 7 days was reported in this study. Conclusions: PROs are an important tool in clinical and survivorship care of young patients with GI cancers. We discovered that decreased physical function, increased anxiety, depression, fatigue and pain significantly effect HRQoL patients with EOGIC. We also found high unmet need to address sexual health in patients with EOGIC. Our ongoing work aims to better understand and address these needs for our patients. Demographic, diagnostic, and therapeutic characteristics of participants. Age At study participation 24-49 median 43 Gender Female 26 66.7% Primary cancer Colorectal 19 48.7% Pancreatic 5 12.8% Biliary tract cancers 5 12.8% Esophageal/Gastric 3 7.7% Other (including anal, NET, GIST, appendiceal) 7 17.9% Stage Metastatic 22 56.4% Treatment On any active treatment 24 61.5% On chemotherapy 20 51.2%

Worse Pain and Disability at Presentation Predicts Greater Improvement in Pain, Disability, and Mental Health in Patients Undergoing Minimally Invasive Transforaminal Lumbar Interbody Fusion for Degenerative Spondylolisthesis.

Retrospective Review. To assess the impact of preoperative pain and disability on patient-reported outcome measures (PROMs) following minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) for degenerative spondylolisthesis. Varying preoperative symptom severity in lumbar fusion patients alters perceptions of surgical success. Degenerative spondylolisthesis patients undergoing elective, primary, single-level MI-TLIF were stratified by preoperative symptom severity: Mild (VAS-B<7/ODI<50), Moderate (VAS-B≥7/ODI<50 or VAS-B<7/ODI≥50), and Severe (VAS-B≥7/ODI≥50). PROMs, Patient-reported Outcomes Measurement Information System-Physical Function (PROMIS-PF), ODI, VAS-B, VAS-Leg (VAS-L), and 9-item Patient Health Questionnaire (PHQ-9) were compared at baseline, 6 weeks, and final follow-up (μ=16.3±8.8mo). Postoperative PROMs, magnitudes of improvement, and minimal clinically important difference (MCID) achievement rates were compared between cohorts through multivariable regression. A total of 177 patients were included. Acute postoperative pain and narcotic consumption were highest in the severe cohort ( P ≤0.003). All preoperative PROMs worsened from mild to severe cohorts ( P <0.001). All PROMs continued to be significantly different between cohorts at 6 weeks and final follow-up, with the worst scores in the Severe cohort ( P ≤0.003). At 6 weeks, all cohorts improved in ODI, VAS-B, VAS-L, and PHQ-9 (P≤0.003), with the Moderate cohort also improving in PROMIS-PF (P=0.017). All Cohorts improved across PROMs at the final follow-up ( P ≤0.044). Magnitudes of improvement in ODI, VAS-B, and PHQ-9 increased with worsening preoperative symptom severity ( P ≤0.042). The Moderate and Severe cohorts demonstrated higher MCID achievement in ODI, VAS-B, and PHQ-9 rates than the Mild cohort. Despite preoperative pain and disability severity, patients undergoing MI-TLIF for degenerative spondylolisthesis report significant improvement in physical function, pain, disability, and mental health postoperatively. Patients with increasing symptom severity continued to report worse severity postoperatively compared with those with milder symptoms preoperatively but were more likely to report larger improvements and achieve clinically meaningful improvement in disability, pain, and mental health.

Hardware Removal After Lisfranc Open Reduction and Internal Fixation Results in Improved Physical Function.

The purpose of this study was to investigate whether hardware removal (HWR) after Lisfranc open reduction and internal fixation (ORIF) resulted in significant impact through PROMIS physical function (PF) and pain intensity (PI) scores. Retrospective cohort. Level-1 trauma center. Adult patients with isolated Lisfranc injuries who were treated through ORIF between 2002 and 2023 who had PROMIS PF and PI scores through 6 months follow-up were included. Patients were excluded if they received index treatment other than ORIF or underwent secondary surgical intervention before HWR. A subanalysis was performed at 1-year follow-up. Primary outcomes were PROMIS PF and PI scores. The Wilcoxon signed-rank test compared differences between PROMIS scores within the HWR group. The Wilcoxon ranked-sum test compared differences between HWR versus no HWR. Distributive MCID was calculated using the 0.5 SD method. There were 482 patients (489 feet) identified with isolated Lisfranc injuries. Seventy-seven feet underwent ORIF followed by HWR. Thirty feet underwent ORIF without HWR. The average age of the no HWR group was 45.8 (18.0-81.3) years versus the HWR group that was 38.7 (18.3-74.1) years ( P = 0.053). Nineteen (63.3%) were women in the no HWR group compared with 33 (42.9%) in the HWR group ( P = 0.084). HWR occurred an average of 4.43 months after ORIF. Patients who underwent HWR had a statistically significant increase in average PF scores (39.7-45.9, P < 0.001) at their standard 6 weeks (1.5 months) postoperative visit. HWR patients had a nonsignificant decrease in average PI scores (56.5-53.9, P = 0.24). Compared with those with retained hardware, the HWR group demonstrated a statistically significant net improvement in PF and PI scores from surgery, with an average improvement of 5.6 and 1.7, respectively ( P = 0.002, 0.008). Patients experienced significant improvement in PROMIS PF scores for Lisfranc ORIF at 6 weeks after HWR. Compared with patients with retained hardware, they also experienced significant improvement in PROMIS PF and PI scores. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Impact of tislelizumab + chemotherapy versus placebo + chemotherapy on patient-reported symptoms and overall survival (OS) by programmed death-ligand 1 (PD-L1) expression in advanced or metastatic esophageal squamous cell carcinoma (ESCC): A post hoc analysis of the RATIONALE-306 trial.

366 Background: While improved survival has been previously demonstrated, the impact of immunotherapy on HRQoL in ESCC has not been well examined. Traditional PRO-based analyses in oncology trials, such as time to deterioration (TTD) and mixed models for repeated measures (MMRMs), are limited by discounting recurrent PRO events. Thus, we applied a 3-component joint model (JM) framework to define more clinically interpretable associations between patient-reported symptoms, treatment effects, and OS among subgroups of patients with ESCC from RATIONALE-306, which met its primary endpoint, with PD-L1 expression of ≥1%, ≥5%, and ≥10%. Methods: The final analytic sample included 226 patients in the tislelizumab + chemotherapy arm (T+C), 242 in the placebo + chemotherapy arm (P+C) for PD-L1 ≥1%, 113 in the T+C arm and 103 in the P+C arm for PD-L1 ≥5%, and 168 in the T+C arm and 178 in the P+C arm for PD-L1 ≥10%.From EORTC QLQ-C30 and OES18, 7 keysymptom domains were modeled (GHS, physical functioning, fatigue, dysphagia, pain, reflux, dietary restrictions). PRO data were collected at baseline and at every treatment cycle (up to 6 cycles), then every other cycle, and at safety follow-up, and change from baseline (CFBL) was analyzed. The joint model comprised three components: 1) linear mixed model predicting CFBL symptom scores; 2) Cox proportional hazard model (CPH) for time to OS; and 3) frailty (random effects for recurrent deterioration events [RDEs]) CPH model for time to PRO-based RDEs. Osoba (1998) 10-point threshold was used to define RDEs. Results: Adjusted completion rates were &gt;90% in the ITT population for both arms. Significant T+C treatment effects wereobserved for physical functioning in PD-L1 ≥5% ( P =0.0476), and pain in PD-L1 ≥1% ( P =0.0028) and PD-L1 ≥5% ( P =0.0149) subgroups, but not in PD-L1 ≥10%. For other 5 symptoms (ie, GHS, fatigue, reflux, dysphagia, dietary restrictions), there were no statistically significant differences between treatment arms. However, T+C was associated with significant reductions in the risk of death across all 7 key symptoms and PD-L1 subgroups. As one example, with respect to interaction between pain and OS, T+C was associated with a 22% (HR, 0.78 [95% CI, 0.652-0.931]), 33% (HR, 0.67 [95% CI, 0.515-0.860]), and 47% (HR, 0.50 [95% CI, 0.344-0.720]) reduction in the risk of death in PD-L1 ≥1%, ≥5%, and ≥10%, respectively compared with P+C. Conclusions: In this analysis, the addition of tislelizumab to chemotherapy was associated with significantly less deterioration in multiple PRO symptoms including physical functioning and pain, alongside a lower risk of death, after adjusting for recurring deterioration events using a frailty model across multiple PD-L1 expression subgroups.

Retinoid-impregnated nanoparticles enable control of bone growth by site-specific modulation of endochondral ossification in mice.

Growth-plate (GP) injures in limbs and other sites can impair GP function and cause deceleration of bone growth, leading to progressive bone lengthening imbalance, deformities and/or physical discomfort, decreased motion and pain. At present, surgical interventions are the only means available to correct these conditions by suppressing the GP activity in the unaffected limb and/or other bones in the ipsilateral region. Here, we aimed to develop a pharmacologic treatment of GP growth imbalance that involves local application of nanoparticles-based controlled release of a selective retinoic acid nuclear receptor gamma (RARγ) agonist drug. When RARγ agonist-loaded nanoparticles were implanted near the medial and lateral sides of proximal tibial growth plate in juvenile C57BL/6j mice, the GP underwent involution and closure. Overall tibia length was shortened compared to the contralateral element implanted with drug-free control nanoparticles. Importantly, when the RARγ agonist nanoparticles were implanted on the lateral side only, the adjacent epiphysis tilted toward the lateral site, leading to apical angulation of the tibia. In contrast to the local selectivity of these responses, systemic administration of RARγ agonists led to GP closure at many sites, inhibiting skeletal growth over time. Agonists for RARα and RARβ elicited no obvious responses over parallel regimens. Our findings provide novel evidence that RARγ agonist-loaded nanoparticles can control activity, function and directionality of a targeted GP, offering a potential and clinically-relevant alternative or supplementation to surgical correction of limb length discrepancy and angular deformities.

Defining Substantial Clinical Benefits of PROMIS Pain Interference and Physical Function in Patients Undergoing Lumbar and Thoracolumbar Spine Surgery.

Prospective cohort study. This study aims to define Substantial Clinical Benefit (SCB) thresholds for PROMIS physical function (PF) and pain interference (PI) in lumbar or thoracolumbar spine surgery population. Patient-reported outcome measures (PROMs) are widely used in spine surgery to assess treatment efficacy. SCB is a relatively new concept that represents a substantial improvement perceived by the patient. This is a prospective study that included adults aged 21-85 years, undergoing lumbar/ thoracolumbar surgery for degenerative spine disease, and reporting at least 3/10 back or leg pain on a numeric rating scale. PROMs including Oswestry Disability Index, PROMIS PF, and PROMIS PI were collected preoperatively and at one year postoperatively. The North American Spine Surgery Patient Satisfaction (NASS) Index was collected one year postoperatively. SCB thresholds of absolute and percentage changes were calculated using anchor-based methods with ODI and NASS index as anchors. ROC analysis was used to determine optimal SCB cutoffs. We included 137 patients. Using a fixed 19-point reduction in ODI as an anchor yielded SCB thresholds of 6.8 and 11.3 points for PROMIS PF and PI respectively. When using a dynamic anchor based on preoperative disability (50% ODI improvement), SCB thresholds were defined as achieving 18 and 27% of maximum possible improvement for PROMIS PF and PI respectively. Using NASS index, thresholds were 11 points or 24% for PROMIS PF, and 11.2 points or 21% for PROMIS PI. ROC values ranged from 0.81 to 0.9, with the dynamic ODI anchor cutoffs demonstrating the best discrimination. Our study is the first to define SCB thresholds for PROMIS PF and PROMIS PI using both fixed and dynamic cutoffs based on preoperative disability in lumbar and thoracolumbar patients. These thresholds will help in patient counseling and outcome evaluation for spine surgery research.

Changes in physical activity since cancer diagnosis and associations with health-related quality of life: a study of adults living with advanced cancer.

Physical activity (PA) is associated with better quality of life for cancer survivors; however, less is known about this association among individuals with advanced cancer. This study assesses whether changes in PA following an advanced cancer diagnosis are associated with health-related quality of life (HRQoL) outcomes. Data were collected from 247 participants in a survey of adults with advanced cancer who visited the University of Wisconsin Carbone Cancer Center (January 2021-2023). PA since cancer diagnosis was assessed using a validated, self-reported tool. HRQoL was assessed using the Functional Assessment of Cancer Therapy - General and Patient-Reported Outcomes Measurement Information System measures of physical function, fatigue, and pain interference. We used generalized linear models to assess relationships between PA and HRQoL. Most adults with advanced cancer were insufficiently active (53%), and reported a lot less activity (41%) after diagnosis, followed by a little less activity (33%), and the same/more activity (26%). Compared to the other activity groups, those who reported a lot less activity had the worst HRQoL scores, including lower HRQoL (x̄ = 70.3 vs. x̄ = 82.6, 90.7) and physical function (x̄ = 40.3 vs. x̄ = 47.3, 52.5), and higher fatigue (x̄ = 59.3 vs. x̄ = 51.4, 42.3) and pain interference (x̄ = 55.5 vs. x̄ = 48.8, 45.6). Adults with advanced cancer who report PA reductions have worse HRQoL, higher pain and fatigue, and lower physical function than those engaging in the same/more PA since their diagnosis. Future interventions focused on improving HRQoL among adults with advanced cancer should incorporate light-intensity PA to reduce declines following diagnosis.

The Relationship Between Trait Mindfulness and Depression Severity Among People With Schizophrenia: The Role of Perceived Public Stigma Toward Mental Illness.

Studies have found that trait mindfulness is associated with lower levels of depressive symptoms among people diagnosed with schizophrenia. Still, the role of the perceived public stigma in this association has yet to be established. The purpose of this study was to assess the association between mindfulness and depressive symptoms experienced by people diagnosed with schizophrenia, controlling for the impact of their demographics and their perceived public stigma against mental illness. A quantitative descriptive correlational design was used. The sample included 184 Jordanian outpatients diagnosed with schizophrenia who completed self-administered measures of mindfulness, depressive symptoms, public stigma against mental illness, and demographic information. Multiple hierarchical regression analysis was performed to identify the unique variance in perceived depression explained by participants' demographic and clinical variables, public stigma, and mindfulness. Participants had moderate perceived discrimination and moderate to severe depression. Age, gender, perceived physical pain, perceived public stigma, and mindfulness were significantly correlated with depression among the study participants. After controlling for demographic and clinical variables, public stigma was significantly associated with depression and accounted for 14% additional variance above and beyond the 37% accounted for by demographic and clinical variables. Mindfulness accounted for a 15% additional variance above and beyond the variance accounted for by all other predictors. Anti-stigma programs could be combined with mindfulness-based interventions to reduce depression in people diagnosed with schizophrenia.

Know the Score: Empowering Sport Choices With a Straightforward Solution.

Risk factors associated with depression in athletes include biological sex, physical pain, and history of sport-related concussion (SRC). However, although there are well-documented benefits of sport and physical activity on mental health, many sportspeople still take the risk of competing in contact sports. Therefore, this infographic, supported by scientific evidence, aims to provide sportspeople with an informed decision on their participation. This infographic can be used by sports clubs or governing bodies to illustrate the risk that SRC has on the mental health of sportspeople. Likewise, it highlights the elevated risk of being in physical pain and being a female sportsperson. Therefore, this infographic provides a simple message to enhance the decision-making process of sportspeople, ensuring they are making a better-informed choice of their sporting participation and making their own cost/reward judgment.

Musculoskeletal adverse events associated with CDK4/6 inhibitors: a real-world study using FDA Adverse Event Reporting System (FAERS) database

ObjectiveCyclin-dependent kinase (CDK)-4/6 inhibitors have significantly improved outcomes in several cancers but can also induce various organ system toxicities, including musculoskeletal disorders. This study aimed to comprehensively characterize the musculoskeletal adverse events (MSAEs) associated with CDK4/6 inhibitors based on real-world data.MethodsReports of MSAEs linked to CDK4/6 inhibitors from the first quarter (Q1) of 2015 and 2023 Q4 were extracted from the FAERS. Descriptive analyses evaluated report frequencies over time and patient characteristics. Disproportionality analyses using reporting odds ratios (RORs) identified signals for specific musculoskeletal preferred terms (PTs). Time-to-onset analyses examined the temporal patterns of MSAEs.ResultsA total of 10,095 MSAE reports associated with CDK4/6 inhibitors were identified, most involving Palbociclib (n = 7819). The median age of patients was 64 years (IQR: 55–72), predominantly female (97.73%). Most reports were submitted by consumers (47.62%) and the majority of reports were from the United States (71.53%). Disproportionality analyses revealed distinct signals, with Ribociclib showing prominent signals for bone pain and bone lesions, and Abemaciclib for osteonecrosis of the jaw and pathological fractures. Palbociclib demonstrated a consistent but less pronounced signal across musculoskeletal PTs. Time-to-onset analyses demonstrated a significantly longer onset of MSAEs for Palbociclib (median 82 days, IQR[14–311]) compared to Abemaciclib (32.5 days, IQR[12–119]) and Ribociclib (34 days, IQR[8-177]) using the nonparametric Kruskal-Wallis test (P-value = 3.048e-11).ConclusionMusculoskeletal toxicities is a significant adverse event that affects drug safety. Early identification and proper management of these events are crucial for patients receiving CDK4/6 inhibitors. Further research is warranted to elucidate the underlying mechanisms and improve risk mitigation strategies.

P-1905. Quality of Life 6 Months After SARS-CoV-2 Infection in Ambulatory and Hospitalized Patients from Lima, Peru: FUNCTION Cohort Study

Abstract Background COVID-19 survivors overcome long-lasting symptoms that affect their quality of life (QoL). We assessed the impact on QoL and the factors associated with the persistence and reversibility of poor QoL 6 months after acute COVID 19. Methods We enrolled symptomatic patients who tested positive for SARS-COV-2 with an antigenic or RT-PCR test between August 2021 and October 2022. We classified subjects according to disease severity: B1 (mild: outpatient), B2 (moderate: outpatient with pneumonia), B3 (severe: inpatient with oxygen supply) and B4 (critical: inpatient admitted to intensive care unit). Measurements were taken at baseline (BL), month 1 (M1), 3 (M3), and 6 (M6) after acute infection. We evaluated QoL with the RAND-36 questionnaire which provides a score for the Physical Component Score (PCS) and the Mental Component Score (MCS). The PCS comprises scales for physical functioning, role limitations due to physical health, pain and general health. MCS includes scales of role limitations due to mental health, energy/fatigue, emotional wellbeing, and social functioning. PCS and MCS scores were standardized on a 0-100 scale and poor QoL was considered &amp;lt; 40 in each scale. Results We enrolled 147 participants: 46 in B1 (31%), 39 in B2 (27%), 22 in B3 (15%), and 40 in B4 (27%). We lost to follow-up 33 participants (22.5%) from BL to M6. Significant improvements in PCS were observed between BL and M6 within B3 [35.77 (95%CI 29.7-41.8) vs 51.63 (95%CI 47.1-56.2), p=0.0002] and B4 [28.8 (95%CI 24.5-33.2) vs 43.3 (95%CI 39.4-47.2), p&amp;lt; 0.0001]. In the MCS, significant improvement occurred within B3 between BL and M6 [44.0 (95%CI 36.9-51.0) vs 54.4 (95%CI 49.89-58.86) p=0.0229]. Low MCS and PCS at M6 after COVID-19 was associated with both pulmonary and cardiac clinical abnormalities at M1, M3 and M6. Additionally, only low PCS at M6 was associated with diabetes, age older than 60 years and cardiac clinical abnormalities at BL. Patients who reversed their poor QoL at M6 to a normal value were 122 (83%) for MCS and 93 (63.27%) for PCS. Factors associated with increased reversibility in both scales were severity group B3 and male sex. Conclusion Our findings, the first cohort study on post COVID-19 from Peru, underscore the need for ongoing physical and mental patient monitoring beyond the acute phase of COVID-19. Disclosures All Authors: No reported disclosures

Health Care Costs After Lumbar Fusion and Disk Replacement for Diskogenic Pain.

Lumbar fusion is the most common surgical intervention for chronic or severe low back pain. However, lumbar disk replacement (LDR) may be appropriate for certain patients. The objective of this study was to describe the postoperative management costs associated with both lumbar fusion and LDR in the 2-year period after surgery. An observational cohort study was conducted using the Merative MarketScan databases. Patients who underwent lumbar fusion or LDR between January 1, 2017, and December 31, 2017, were identified and included in the study. The primary outcome was the cost of payments for physical therapy, pain medication, injections, and bladder management in the 2-year period after surgery. A total of 1660 patients (mean age, 50.1±10.6 years; lumbar fusion, 99%; LDR, 1%) were included in the study. The mean total cost of postoperative interventions identified was $2832±$5461 per patient, with no differences found between patients for identified interventions. The mean 30-day episode-of-care cost was $65,777±$40,869 and was similar (P=.894) between the two groups of patients. The main driver of cost was physical therapy for both groups of patients (lumbar fusion, 53.7%; LDR, 64.9%). Patients who underwent lumbar fusion and LDR had similar postoperative management costs. The shorter recovery periods associated with LDR may not necessarily translate into reduced long-term health care expenditure. [Orthopedics. 202x;4x(x):xx-xx.].

Efficacy and Safety of Boswellia serrata and Apium graveolens L. Extract Against Knee Osteoarthritis and Cartilage Degeneration: A Randomized, Double-blind, Multicenter, Placebo-Controlled Clinical Trial.

Osteoarthritis is the prevailing form of inflammatory condition in joints of adults and the aging population, leading to long-term disability and chronic pain. Current therapeutic options have variable therapeutic efficacy and/or several side effects. A randomized, placebo-controlled, double-blind clinical trial was conducted in 62 participants using a nutraceutical [standardized Boswellia serrata Roxb. gum resin (300 mg) and Apium graveolens L. seed extract (250 mg)], to determine its safety and efficacy forsupporting cartilage health and reduction in knee osteoarthritis symptoms. All participants were assessed for physical function and pain with the help of WOMAC, VAS, Physicians' Global Assessment for the six-minute walk test/pain. Knee X-ray, KOOS questionnaire score, and FACIT-F score were assessed. Additionally, inflammatory, cartilage degeneration and regeneration biomarkers in serum and urine were evaluated at baseline and after 90 days of treatment. Oral administration of the nutraceutical resulted in prolonged symptomatic relief with reduced pain, stiffness, and swelling. Inflammatory (serum IL-7, IL-1, IL-6, hs-CRP, TNF-α, ESR) and cartilage degeneration biomarkers (serum CTX-II, COMP, MMP-3 and urinary CTX-II) were decreased in the nutraceutical group compared to baseline and placebo. Furthermore, serum N-propeptide of collagen IIA (PIIANP) and procollagen-type-C propeptide (PIICP) levels were increased in the nutraceutical group, suggesting collagen synthesis contributing to cartilage regeneration. At given doses for 90 days, there were no adverse effects based on the clinical examination, biochemical, hematological, and ECG analysis. Taken together, the combination of Boswellia and celery could be a safe and promising herbal nutraceutical option for managing osteoarthritis and cartilage health effectively.

Innocent Addictions: Discourse Analysis of Media Coverage of Pharmaceutical Dependence in Australia

Media coverage of non-medical pharmaceutical use has consistently presented it to be a “different” kind of drug problem, one that involves substances not typically thought of as drugs of abuse or addiction and among people not normally associated with illicit drugs and the “criminal addict.” Though differential media treatment of dependence on criminalized drugs versus pharmaceutical products is well documented in the North American context, less is known about how the Australian media covers the issue of pharmaceutical dependence. In this study, we conducted a discourse analysis of Australian media articles between 2018 and 2023 that covered dependence on pharmaceuticals. We found that media accounts use discursive frameworks to speak about pharmaceutical dependence that differentiate it from “drug addiction,” or from the way dependence on criminalized substances are typically constructed as a social issue. Media stories present pharmaceutical dependence as a “hidden problem,” made up of those unlikely to become addicted to drugs, people who are suffering genuine physical pain and for whom medical systems of care have failed. These emphasized differences are notable in part because they contradict the claims made by the now popularized bio-medical model of addiction, that addiction does not discriminate, that it is a disease that can impact anyone, and that its effects on individuals are universal. This paper draws on critical addiction studies and the sociological concept of iatrogenesis in order to highlight the power relations and political judgments involved in media representations of pharmaceutical dependence, especially that which arises in the context of medical treatment. Despite seemingly progressive attempts to destigmatize addiction in this media reporting, we demonstrate how the examples used to illustrate the issue draw on long discursive histories which associate whiteness with innocence and reinforce the unquestioned benefit of contact with the medical establishment.

Effects of Physical Exercise on Chemotherapy-Induced Peripheral Neuropathy: A Systematic Review and Meta-Analysis.

The aim of this systematic review and meta-analysis is to systematically collect, evaluate, and critically synthesize research findings on the effects of physical exercise on chemotherapy-induced peripheral neuropathy (CIPN). The Joanna Briggs Institute (JBI) methodology for systematic reviews was adopted for this study. We searched the Medline®, CINAHL, SportDiscus, and Scopus databases to identify relevant articles published from inception to March 2024. This review was reported in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Twelve studies met the inclusion criteria, totaling 928 participants. Interventions ranged from aerobic and resistance exercises to balance and strength training. A range of physical exercise interventions was explored, including brisk walking, endurance training, weight exercises, and resistance bands, as well as combined programs of aerobics, resistance, and balance training, all tailored to improve symptoms and quality of life in patients with chemotherapy-induced peripheral neuropathy. The meta-analysis focused on five studies that used the FACT/GOG-Ntx scale indicated a standardized mean difference of 0.50 (95% CI: 0.26, 0.74), favoring exercise, reflecting significant improvements in neuropathy symptoms. The heterogeneity among the studies was low (I² = 2%), suggesting consistency in the beneficial effects of exercise. From the results analyzed, the descriptive analysis of the 12 included studies shows promising outcomes not only related to individuals' perceptions of CIPN severity but also in terms of physical functioning, balance, ADL (Activities of Daily Living) performance, pain, and quality of life. The findings support the integration of structured exercise programs into oncological treatment plans.

Qualitative analysis of pain impact in adult patients with X-linked hypophosphatemia

Abstract We previously reported pain as a predominant finding in adult patients with XLH. This study explored health-related quality-of-life using the 36-item Short Form survey instrument (SF-36v1) and pain experiences of adults with X-linked hypophosphatemia (XLH) through qualitative analysis of interviews with 15 patients (11 females, 4 males). Age-adjusted differences using SF-36 were lower than the general population in all domains of health-related quality of life, with significant differences notably related to physical function and pain. Ten themes emerged from semi-structured interviews: 1) Chronic and Variable Pain: Patients reported persistent pain of varying intensity and location; 2) Impact on Mobility and Daily Life: Pain severely restricted daily activities, affecting lifestyle, employment, and independence; 3) Pain Management: Patients used medications, physical therapy, lifestyle changes, alternative therapies, and assistive devices; 4) Healthcare and Accessibility Challenges: Access to appropriate care and treatments was limited by insurance issues and healthcare providers’ lack of XLH knowledge; 5) Emotional and Psychological Impact: Chronic pain and limitations led to social isolation, depression, and emotional burden; 6) Desire for Improved Information and Support: Patients sought better information, treatment, and community support; 7) Challenges with Physical Inactivity: Staying active was essential but difficult, as inactivity worsened pain; 8) Navigating Healthcare Services: Accessing therapy and insurance was often challenging; 9) Long-term Outlook and Concerns: Patients worried about disease progression and future health; and 10) Advocacy and Awareness: Increased public and medical awareness was needed to improve care. Although pain is not a universal experience within this population, it is a significant issue for many individuals with XLH. These data illustrate the profound impact of XLH on multiple life aspects underscoring the need for effective pain management strategies, better healthcare accessibility, supportive tools, and a more knowledgeable medical community to improve quality of life. Insights from this study will guide the development of a digital pain self-management intervention tailored to XLH patients to address these needs.

The Cutaneous Pathology of Erythromelalgia and Its Role in Establishing Critical Clues Regarding Pathogenesis.

Erythromelalgia, a rare cutaneous pain syndrome, is characterized by acral burning pain and flushing, often alleviated by cold and rest. Primary erythromelalgia is caused by gain-of-function mutations of genes encoding for sodium channels, resulting in hyperexcitability of pain signaling neurons. Autoimmunity and hematologic dyscrasias such as thrombocythemia have been implicated in secondary erythromelalgia. The pathology of this rare disease remains poorly defined. The Weill Cornell dermatopathology database was analyzed for acral biopsies procured from patients here there was a clinical concern for erythromelalgia. We identified 9 patients with clinical diagnoses of erythromelalgia who had a skin biopsy from an affected area. The female-to-male ratio was 2:1. Three of 9 individuals had concurrent diagnoses of autoimmune disease including vitiligo, lupus erythematosus, and psoriatic arthritis. Biopsies showed superficial vascular ectasia in association with microvascular C5b-9 and variable upregulation of type I interferon expression in endothelial cells. CD56 stain revealed diminished autonomic innervation of the eccrine coil and arteries, mirroring similar autonomic denervation seen in small fiber neuropathy. This study suggests that erythromelalgia is a dysautonomia syndrome with reproducible findings on biopsy, hallmarked by vascular ectasia and denervation of the eccrine coil and arteries. In addition, there is a potential link to immune and nonimmune-based microvascular compromise.

Association of GLP1R locus with mental ill-health endophenotypes and cardiometabolic traits: A trans-ancestry study in UK Biobank.

Glucagon-like peptide 1 receptor agonists (GLP1RA), used to treat type 2 diabetes and obesity, have been associated with off-target behavioural effects. We systematically assessed genetic variation in the GLP1R locus for impact on mental ill-health (MIH) and cardiometabolic phenotypes across diverse populations within UK Biobank. All genetic variants with minor allele frequency >1% in the GLP1R locus were investigated for associations with MIH phenotypes and cardiometabolic phenotypes. Linear or Logistic regression analyses (adjusted for age, sex, population structure and genotyping chip) were conducted separately in unrelated individuals of self-reported white British (N = 408 774), white European (N = 50 314), South Asian (N = 7667), multiple-ancestry groups (N = 10 437) or African-Caribbean (N = 7641) subsets. All ancestries were subsequently combined in an inverse variance-weighted fixed effects meta-analysis. Bonferroni correction for multiple testing was applied (for number of independent genetic variants). Associations were identified between GLP1R variants and body mass index (BMI), blood pressure and type 2 diabetes in all ancestries. All ancestries except South Asian had significant MIH associations (mood instability: rs111265626-G, odds ratio [OR] 0.851 [confidence interval, CI 0.79-0.92], risk-taking behaviour: rs75408972-T, OR 1.05 [CI 1.03-1.08] or chronic pain: rs9296280-C, OR 0.645 [CI 0.54-0.78]). The trans-ancestry meta-analysis showed mainly consistent effect sizes and directions for metabolic traits, but discordant directions MIH associations. Only signals for chronic pain, stroke and BMI influenced expression of GLP1R. GLP1R variants have consistent cardiometabolic effects across ancestries, but effects on MIH phenotypes are more varied. Any observed behavioural changes with GLP1RA are likely not acting directly through GLP1R.

Association Between Oral Health Status and DMFT Index with Cognitive Dysfunction in Community-Dwelling Older Adults with Type 2 Diabetes: A Cross-Sectional Study

ABSTRACT Objective Cognitive dysfunction is a significant issue in old age and can cause many problems in older adults, especially those with diabetes. This study aimed to investigate the association between oral health status and DMFT index with cognitive dysfunction in community-dwelling older adults with T2D (type 2 diabetes). Methods This was a cross-sectional study that included 245 older people aged 60 years and older with T2D, visiting healthcare centers in north of Iran, using the cluster sampling method. Data collection tools included clinical-demographic questionnaire, the Geriatric Oral Health Assessment Index (GOHAI) and the Mini-Mental State Examination (MMSE) questionnaire. A P-value <.05 was considered significant. Results The mean age of older adults in this study was 64.86 ± 3.99 years. The mean and standard deviation for the DMFT index, GOHAI index and MMSE scale were 9.39 ± 3.83, 34.29 ± 17.93 and 15.18 ± 10.04 respectively. The results showed statistically significant relationship between poor oral health status and the cognitive status of older adults with T2D (p < .001). Additionally, the relationship between oral health index domains (physical function, psychosocial function and pain) and cognitive status in older adults was significant (p < .001). Another finding indicated an inverse and significant relationship between the DMFT index and cognitive dysfunction in older adults (p < .001). Conclusion Poor oral health was associated with cognitive dysfunction among the community-dwelling older adults with T2D. Given the high prevalence of T2D in older adults and the critical importance of oral and dental health for cognition, it is necessary to develop interventions to improve oral health in older adults with T2D.

Population pharmacokinetic modeling and exposure-response analysis of anrikefon: insights and implications in clinical analgesia

ABSTRACT Background Anrikefon (HSK21542), a potent and selective peripheral kappa opioid receptor (KOR) agonist developed by Haisco, effectively blocks pain and itch signals. Aim To develop a population pharmacokinetic (PK) model for anrikefon and conduct exposure-response (E-R) analysis for safety and efficacy in postoperative pain patients. Method The Population PK analysis uses NONMEM software with data from six trials. E-R relationships were assessed using safety and efficacy data from three trials. Covariate screening and Bayesian post-hoc simulations identified relevant factors and compared exposure metrics. The fixed dosing regimen was evaluated by simulation. Safety and efficacy endpoints were evaluated using logistic regression and Emax models. Results A three-compartment model with linear elimination accurately described anrikefon’s PK, incorporating weight through allometric scaling. Significant covariates affecting clearance included creatinine clearance, total bilirubin, albumin, aspartate transaminase, and age. Fixed and weight-based dosing showed similar exposures. No apparent E-R trend was observed for safety endpoints. The Emax model indicated that most of subjects achieved over 90% of the maximum effect for SPID0–24 h at 1.0 μg/kg. Safety analysis confirmed this dose was well tolerated with no safety issues. Conclusion This study provides valuable insights into dose selection, PK variability, and safety and efficacy endpoints.