Citations

Abstract Background/Aims The aim of this prospective cohort study was to evaluate the extent that kinesiophobia at baseline contributed to pain intensity at follow-up after starting first line treatments in patients with a range of musculoskeletal conditions, including rheumatoid arthritis (RA), fibromyalgia (FM) and knee osteoarthritis (OA). Methods 469 patients (RA n = 156, FM n = 149, OA n = 164) recruited from the Nuffield Orthopaedic Centre, Oxford University Hospitals, participated in this study. Pain was assessed with the pain detect questionnaire, with the item average pain severity over the last 4 weeks used for the primary analysis. The Tampa Scale for Kinesiophobia (TSK) was administered to assess fear of movement. The association between TSK and pain at baseline was investigated by analysing their correlation using Pearson’s Product-Moment Correlation. RA, FM and OA groups were treated with standard care, which consisted of DMARDs, pain rehabilitation therapy, and total knee arthroplasty, respectively. The correlation between baseline TSK and change from baseline in 4-week average pain severity was calculated at 3-, 6- and 12-month follow-up using Pearson’s Product-Moment Correlation. A simple linear regression model was used for each cohort to evaluate the extent TSK contributed to change in pain from baseline. Results At baseline, mean TSK was 38.8±7.0 and mean 4-week average pain severity was 6.6±2.0 (all conditions pooled), with a Pearson’s Product-Moment Correlation of 0.28 [95% CI: 0.18-0.37], representing a small positive correlation (p < 0.01) between baseline TSK and baseline pain. The results were similar for all 3 conditions independently (RA correlation 0.30 [95% CI: 0.14-0.44], FM correlation 0.31 [95% CI: 0.15-0.46], OA correlation 0.25 [95% CI: 0.06-0.41], all ps < 0.01). No correlation was found between TSK and change from baseline in pain severity for the RA or FM cohorts at any follow-up. A weak negative correlation between TSK and change in pain severity was found in the knee OA group at 3 months (correlation: -0.18 [95% CI: -0.39-0.04]) and 12 months (correlation: -0.16 [95% CI: -0.39-0.08]); however, these results were not statistically significant (p = 0.12 and 0.19 respectively). The linear regression analysis showed that TSK was not associated with change in pain from baseline for any condition at any timepoint. Mean pain decreased in the RA and OA groups irrespective of TSK, with no improvement in pain seen in the FM group (RA mean pain at baseline: 6.5±2.1, at 12 months: 4.3±2.6; FM mean pain at baseline: 6.6±1.6, at 12 months: 6.6±1.8; OA mean pain at baseline: 6.5±2.2, at 12 months: 1.9±2.6). Conclusion Whilst kinesiophobia and pain severity were correlated at baseline, kinesiophobia did not negatively influence change in pain with treatment in any of the cohorts studied. Disclosure R.C. Murphy: None. A. Irani: None. E. Kelleher: None. A.J. Wall: None.

PURPOSE Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The higher incidence and earlier onset of HCC in sub-Saharan Africa suggest a potential role for a genetic predisposition. This study evaluated the association of TERT -rs2242652-(A), a variant linked to lower HCC risk, with HCC in populations from Ghana, Nigeria, and Cameroon, compared with a population from the United States. METHODS The study included 537 patients with HCC: United States (n = 348), Ghana (n = 79), Nigeria (n = 43), and Cameroon (n = 67). The control group had 2,872 cancer-free individuals: United States (n = 2,399), Ghana (n = 323), Nigeria (n = 85), and Cameroon (n = 65). Whole-exome sequencing was conducted using germline DNA, and data for TERT -rs2242652 were analyzed. Odds ratios (ORs) and 95% CIs were calculated using unconditional logistic regression. Chi-square tests assessed protective allele frequencies. RESULTS In the US cohort, TERT -rs2242652 was significantly associated with lower HCC risk (OR, 0.75 [95% CI, 0.58 to 0.96]; P = .02), with an allele frequency of 18.8% (15.4% in HCC cases v 19.3% in controls). In the combined sub-Saharan African population, no significant association was observed, but there was a trend toward decreased HCC risk (OR, 0.80 [95% CI, 0.53 to 1.22]; P = .29), with an allele frequency of 12.2% (10.6% in HCC cases v 12.9% in controls). Separate analyses of Ghanaian, Nigerian, and Cameroonian populations showed similar nonsignificant trends. The protective allele frequency in the combined African populations was significantly lower than in the US cohort ( P < .0001). CONCLUSION In sub-Saharan African populations, there was a lower frequency of the HCC protective allele TERT -rs2242652 compared with European Americans. These findings underscore the importance of multiethnic genetic studies in understanding population differences in HCC risk and developing prevention strategies.

Abstract Despite effective control of inflammation in rheumatoid arthritis (RA), persistent and severe pain remains a challenge. Dysregulated pain processing in the central nervous system may underlie this disconnect. The PainDETECT questionnaire, originally developed to identify neuropathic pain, may capture features of central sensitization. We hypothesized that neuropathic-like pain at diagnosis predicts worse pain prognosis in early RA, independent of baseline pain severity and inflammation. We also explored brain activation patterns using neuroimaging. In this prospective cohort study, adults with newly diagnosed RA completed the PainDETECT questionnaire at baseline. Bodily pain was measured using the SF-36 Bodily Pain Subscale at baseline, 3, 6, and 12 months. C-reactive protein (CRP) was monitored. Linear mixed-effects models examined associations between PainDETECT, as a continuous measure, and bodily pain and CRP over time, adjusting for baseline outcome values. A neuroimaging substudy (n = 27) used task-based functional MRI to assess brain responses to evoked pressure pain. Among 158 participants (mean age 58.4 years; 35% male), 24.7% had likely neuropathic-like pain (PainDETECT ≥19) at baseline. Higher baseline PainDETECT scores were associated with worse bodily pain throughout follow-up in fully adjusted models (β = −0.43; 95% CI: −0.84 to −0.02; P = 0.043), independent of socio-demographics and comorbidities. No association was found between PainDETECT and CRP. On neuroimaging, higher PainDETECT scores correlated with increased activation in the left insula, dorsal anterior cingulate cortex, and left amygdala during evoked wrist pain. Neuropathic-like pain at diagnosis predicts a worse pain prognosis in early RA, independently of inflammation. Early identification may support more targeted and effective pain management.

Abstract Background: As with most Sub-Saharan African countries, Nigeria has a rising incidence of cancer, with disproportionate mortality rates. The financial burden of cancer care often results in catastrophic healthcare spending, leading to treatment refusal, disruption, and discontinuation. This is particularly significant in Nigeria, where nearly all patients are uninsured, and out-of-pocket costs often exceed households’ ability to pay. Financial Navigation Programs (FNPs) have been shown to mitigate treatment-related financial toxicity in cancer care and reduce treatment abandonment, but there is a paucity of high-quality data on this intervention in resource-constrained settings. Here, we present a randomized controlled trial to evaluate the impact of a novel FNP in Nigeria. Methods: We designed the COST-FIN trial, a multi-site pragmatic single-blinded randomized controlled trial of newly diagnosed (<6 weeks from diagnosis) adults (≥18 years) with breast, colorectal, or prostate cancer at two tertiary cancer centers in Nigeria. Participants (n=200) will be randomized (1:1) to either the intervention (FNP) or the control arm and followed for 12 months. Data on key individual, treatment, and financial parameters will be collected via structured interviews and chart abstraction at baseline, 3, 6, and 12-month follow-up. In addition, participants randomized to the FNP will receive a tailored financial literacy assessment, financial planning support, and enhanced access to resources by trained financial navigators. Primary and secondary outcomes are Financial Catastrophe (FC) and Financial Distress (FD), respectively. Exploratory outcomes will include cost-related non-adherence and cost-effectiveness of the program. An interim analysis will be conducted when 50% of the estimated accruals reach 6 months of follow-up, with crossover if compelling evidence of benefit is demonstrated at that time point. All participants will be followed for 12 months from recruitment. Discussion: This first-of-its-kind study will provide evidence on the role of FNP in potentially eliminating financial barriers to cancer care in Nigeria. Given the country’s renewed interest in cancer control through the passage of the National Cancer Control Plan, findings from this study have the potential to influence policy reform and set the stage for further studies to evaluate the scalability and implementation of similar interventions in resource-limited settings. Trial registration : ClinicalTrials.gov NCT06630962. Oct 8, 2024 (https://clinicaltrials.gov/study/NCT06630962)

Abstract Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality globally, with particularly high burdens among people living with HIV (PLWH) in low‐resource settings like Nigeria. Effective early detection remains a major challenge due to limited access to imaging‐based surveillance and the low sensitivity of current biomarkers such as alpha‐fetoprotein (AFP). We conducted an epigenome‐wide association study (EWAS) of circulating cell‐free DNA (ccfDNA) methylation in a Nigerian cohort of HIV‐positive individuals ( n = 245), spanning HCC, cirrhosis (FibroScan ≥12.3 kPa), fibrosis (FibroScan ≥7.6 and <12.3 kPa), and HCC‐free without fibrosis (FibroScan <7.6 kPa) groups. Using random forest modeling, we developed and evaluated a ccfDNA methylation classifier (ccfDNAmRF) for HCC risk prediction. We identified 73 CpG sites significantly associated with HCC (false discovery rate <0.01). The ccfDNAmRF model demonstrated strong discriminatory power, achieving 100% sensitivity and 80%–91% specificity for distinguishing HCC from cirrhosis, fibrosis, and HCC‐free groups (area under the curve [AUC]: 92%–97%). Combining ccfDNA methylation risk scores with AFP further improved classification accuracy (AUC up to 98.5%). Notably, ccfDNA methylation patterns displayed clear dose–response relationships across the disease spectrum, supporting their utility for early‐stage detection and risk stratification. Our findings highlight the promise of ccfDNA methylation biomarkers as a non‐invasive, blood‐based screening tool for improving early identification of HCC cases among PLWH.

Abstract Objectives Sleep disturbance is a key symptom of fibromyalgia and a risk factor for chronic widespread pain. This systematic review and meta-analysis aims to assess the effectiveness of pharmacological treatments and cognitive behavioural therapy (CBT) in improving sleep quality in fibromyalgia patients. Methods A systematic search of PubMed, MEDLINE, Embase, Cochrane CENTRAL and CINAHL was conducted for randomized controlled trials (RCTs) published up to April 2023. Studies assessing pharmacological or CBT interventions with sleep-related outcomes were included. Data were extracted, and meta-analyses were performed where applicable. Study quality and bias were evaluated using the Cochrane Risk of Bias tool. Results Forty-seven RCTs, including 11 094 participants, were reviewed. CBT for insomnia (CBT-I) showed a significant improvement in sleep quality (SMD −0.63, 95% CI −0.98 to −0.27), while CBT for pain (CBT-P) had no significant impact. Pharmacological agents such as pregabalin and sodium oxybate moderately improved sleep, but there was uncertainty around this evidence. Amitriptyline, milnacipran and duloxetine showed no significant benefit for sleep. Study heterogeneity was moderate, and no publication bias was detected. Conclusion CBT-I is a promising treatment for enhancing sleep quality in fibromyalgia. Pharmacological treatments like pregabalin may be beneficial but should be used cautiously due to potential risks. Future research should prioritize trials focusing on sleep as a primary outcome and explore the comparative effectiveness of pharmacological treatments and CBT-I in fibromyalgia. Understanding the mechanisms linking sleep and fibromyalgia will also help guide future therapies.

Abstract Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. In countries with high human immunodeficiency virus (HIV) prevalence, such as Nigeria, HIV-associated HCC causes a great health burden due to its early onset, late diagnosis, and poorer prognosis. HIV infection is involved in inflammation of the liver, which may determine an increased risk of hepatocyte neoplastic transformation. Inflammation-related DNA methylation signatures obtained in liquid biopsy, such as circulating cell-free DNA (ccfDNA) extracted from serum/plasma are promising minimally-invasive biomarkers that may inform HCC among people living with HIV. Methods: A total of 289 Nigerian participants with information on ccfDNA and other covariates were included. Participants were classified into three groups by their HCC/HIV status: 1) HCC+/HIV+ (n=28); 2) HCC-/HIV+ (n=185); and 3) HCC+/HIV- (n=76). We constructed ccfDNA methylation inflammation scores using 49 CpGs previously linked to circulating C-reactive protein (CRP) concentrations, and higher scores represented elevated CRP concentrations with lower methylation levels. To compare the ccfDNA methylation inflammation score across the groups, we performed multivariable logistic regression analyses adjusting for age, sex, alcohol consumption, smoking status, body mass index, study sites, and technical variables. Results: Participants with HCC+/HIV+ presented the highest ccfDNA methylation inflammation scores (mean=-0.03, standard deviation [SD] =0.01). Participants with HCC-/HIV+ presented the lowest scores (mean=-0.05, SD=0.01). In the multivariable logistic regressions, one SD increase of inflammation score was associated with 2.5 times higher odds of having HCC among HIV-infected participants (HCC+/HIV+ vs. HCC+/HIV-; OR=2.56, 95% CI=1.39-4.73, P=0.002). No evidence was found for the association between the inflammation score and HIV status among HCC patients (HCC+/HIV+ vs. HCC+/HIV-; OR=1.00, 95% CI=0.59-1.70, P=0.991). In the secondary analysis comparing HCC+ vs. HCC- adjusting for HIV status, one SD increase of inflammation score was associated with 3.2 times higher odds of having HCC (OR=3.22, 95% CI=1.39-7.46, P=0.006). Conclusions: We observed that ccfDNA methylation inflammation score is associated with HCC status among people with HIV. Our findings suggest that ccfDNA methylation-based inflammatory profiles may serve as a potential biomarker for early detection and risk stratification of HCC in resource-constrained countries with a high prevalence of HIV. Citation Format: Kyeezu Kim, Yinan Zheng, Claudia Hawkins, Edith Okeke, Olufunmilayo Lesi, Yishu Qu, Lewis R. Roberts, Demirkan Gursel, Fatimah B. Abdulkareem, Alani Akanmu, Godwin Imade, Jian-Jun Wei, Masha Kocherginsky, Kwang-Youn Kim, Wasiu L. Adeyemo, Firas Wehbe, Chad J. Achenbach, Atiene Sagay, Folasade T. Ogunsola, Robert L. Murphy, Lifang Hou. DNA methylation-based inflammation score is associated with hepatocellular carcinoma among people living with HIV. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6013.

Objective The objective of this study was to determine whether a triple therapy regimen incorporating twice-daily saquinavir is as effective as a three-times daily regimen. Methods This was an open-label, Phase III, multicentre, 48-week study involving 837 HIV-1-infected patients randomised to one of the following: saquinavir soft gel capsule (SGC) 1200 mg three-times daily, plus two nucleoside reverse transcriptase inhibitors (NRTIs) (arm A); saquinavir SGC 1600 mg twice-daily, plus two NRTIs (arm B); saquinavir SGC 1200 mg twice-daily and nelfinavir 1250 mg twice-daily, plus a single NRTI (arm C). The primary outcome measure was the virological response in arm A versus B and in arm A versus C with respect to the percentage of patients whose plasma HIV-1 RNA levels fell below the level of quantification for the Amplicor assay (<400 copies/ml) at weeks 24 and 48. Results At 48 weeks, the percentage of patients with plasma HIV-1 RNA levels <400 copies/ml was 47.1% (arm A), 45.3% (arm B) and 42.7% (arm C) in the intention-to-treat analysis. The treatment difference between arm B–arm A was -1.8% (95% confidence intervals -10.1, 6.5) and for arm C–arm A was -4.5% (95% confidence intervals -12.7, 3.7) in the intention-to-treat analysis. These differences fell within the maximum allowable difference (±12%) for arm B compared with arm A. At week 24, the percentage of patients with HIV-1 RNA levels <400 copies/ml was 59.6% (arm A), 57.6% (arm B) and 51.3% (arm C). Conclusions A twice-daily triple therapy regimen incorporating saquinavir SGC plus two NRTIs was of equivalent efficacy to the three-times daily regimen studied. All regimens were generally well tolerated.

Abstract Purpose: Hepatocellular Carcinoma (HCC) is the leading cause of cancer-related mortality in Nigeria. HIV and viral hepatitis B (HBV) and C (HCV) co-infection are common in Nigeria that significantly accelerates liver disease progression including HCC. Aging-related DNA methylation signatures obtained in liquid biopsy, such as circulating cell-free DNA (ccfDNA) extracted from serum/plasma are promising minimally-invasive biomarkers that may inform HIV-associated HCC. We examined the epigenetic age acceleration (EpiAgeAccel) in ccfDNA in HCC patients with HIV. Methods: The study included three groups of participants: a) HIV positive with HCC (n=7); b) HIV positive and cancer-free (n=45); and c) HIV negative with HCC (n=33). Epigenetic age was estimated by Horvath's calculator using genome-wide ccfDNA methylation data profiled by Illumina EPIC array. EpiAgeAccel was computed as the residuals of a linear model of epigenetic age on chronological age, namely the unexplained portion of epigenetic age by chronological age. We used multiple linear regression to compare EpiAgeAccel between HIV/HCC groups, adjusting for sex, age, education, alcohol intake, and HBV/HCV infection. Results: Among HIV positive participants, there was a higher percentage of men (57% vs. 22%, p&lt;0.001), HBV infection (29% vs. 11%, p=0.004), and HCV infection (57% vs. 2%, p&lt;0.001) in the HCC group compared to the cancer-free group. EpiAgeAccel was 4.8 years higher in HIV positive patients with HCC compared to cancer-free HIV positives (p=0.02). Among HCC patients, EpiAgeAccel was 2.1 years higher in HIV positives compared to HIV negative but not statistically significant. Conclusion: Epigenetic age in ccfDNA is accelerated in HIV-positive HCC patients. EpiAgeAccel measured in ccfDNA may be developed into a surrogate biomarker for minimally invasive HCC detection among HIV-infected patients in low- and middle-income countries. Citation Format: Yinan Zheng, Claudia Hawkins, Edith Okeke, Mary Duguru, Emuobor Odeghe, Olufunmilayo Lesi, Yishu Qu, Kyeezu Kim, Brian Joyce, Jun Wang, Lewis Roberts, Demirkan Gursel, Abdulkareem Fatimah, Alani Akanmu, Godwin Imade, Jian-Jun Wei, Masha Kocherginsky, Kwang-Youn Kim, Oluwakemi Odukoya, Wasiu Adeyemo, Firas Wehbe, Chad Achenbach, Atiene Sagay, Folasade Ogunsola, Robert Murphy, Lifang Hou. Blood-Based Circulating Cell-Free DNA Epigenetic Age Is Accelerated Among HIV-Infected Patients with Hepatocellular Carcinoma in Nigeria [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 83.

e16137 Background: Hepatocellular Carcinoma (HCC) is the leading cause of cancer-related mortality in Nigeria. HIV and viral hepatitis B (HBV) and C (HCV) co-infection are common in Nigeria that significantly accelerates liver disease progression including HCC. Aging-related DNA methylation signatures obtained in liquid biopsy, such as circulating cell-free DNA (ccfDNA) extracted from serum/plasma are promising minimally-invasive biomarkers that may inform HIV-associated HCC. We examined the epigenetic age acceleration (EpiAgeAccel) in ccfDNA in HCC patients with HIV. Methods: The study included three groups of participants: a) HIV positive with HCC (n=7); b) HIV positive and cancer-free (n=45); and c) HIV negative with HCC (n=33). Epigenetic age was estimated by Horvath’s calculator using genome-wide ccfDNA methylation data profiled by Illumina EPIC array. EpiAgeAccel was computed as the residuals of a linear model of epigenetic age on chronological age, namely the unexplained portion of epigenetic age by chronological age. We used multiple linear regression to compare EpiAgeAccel between HIV/HCC groups, adjusting for sex, age, education, alcohol intake, and HBV/HCV infection. Results: Among HIV positive participants, there was a higher percentage of men (57% vs. 22%, p<0.001), HBV infection (29% vs. 11%, p=0.004), and HCV infection (57% vs. 2%, p<0.001) in the HCC group compared to the cancer-free group. EpiAgeAccel was 4.8 years higher in HIV positive patients with HCC compared to cancer-free HIV positives (p=0.02). Among HCC patients, EpiAgeAccel was 2.1 years higher in HIV positives compared to HIV negative but not statistically significant. Conclusions: Epigenetic age in ccfDNA is accelerated in HIV-positive HCC patients. EpiAgeAccel measured in ccfDNA may be developed into a surrogate biomarker for minimally invasive HCC detection among HIV-infected patients in low- and middle-income countries.