OBJECTIVE: To study the prognostic implications of baseline levels and dynamic changes of the vibration-controlled transient elastography (VCTE)-based scores developed for the diagnosis of advanced fibrosis (Agile 3+) and cirrhosis (Agile 4) in patients with MASLD.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study included data from a natural history cohort of patients with MASLD who underwent VCTE examination at 16 tertiary referral centers in the US, Europe, and Asia from February 2004 to January 2023, of which the data were collected prospectively at 14 centers. Eligible patients were adults aged at least 18 years with hepatic steatosis diagnosed by histologic methods (steatosis in ≥5% of hepatocytes) or imaging studies (ultrasonography, computed tomography or magnetic resonance imaging, or controlled attenuation parameter ≥248 dB/m by VCTE).
MAIN OUTCOMES AND MEASURES: The primary outcome was liver-related events (LREs), defined as hepatocellular carcinoma or hepatic decompensation (ascites, variceal hemorrhage, hepatic encephalopathy, or hepatorenal syndrome), liver transplant, and liver-related deaths. The Agile scores were compared with histologic and 8 other noninvasive tests.
RESULTS: A total of 16 603 patients underwent VCTE examination at baseline (mean [SD] age, 52.5 [13.7] years; 9600 [57.8%] were male). At a median follow-up of 51.7 (IQR, 25.2-85.2) months, 316 patients (1.9%) developed LREs. Both Agile 3+ and Agile 4 scores classified fewer patients between the low and high cutoffs than most fibrosis scores and achieved the highest discriminatory power in predicting LREs (integrated area under the time-dependent receiver-operating characteristic curve, 0.89). A total of 10 920 patients (65.8%) had repeated VCTE examination at a median interval of 15 (IQR, 11.3-27.7) months and were included in the serial analysis. A total of 81.9% of patients (7208 of 8810) had stable Agile 3+ scores and 92.6% of patients (8163 of 8810) had stable Agile 4 scores (same risk categories at both assessments). The incidence of LREs was 0.6 per 1000 person-years in patients with persistently low Agile 3+ scores and 30.1 per 1000 person-years in patients with persistently high Agile 3+ scores. In patients with high Agile 3+ score at baseline, a decrease in the score by more than 20% was associated with substantial reduction in the risk of LREs. A similar trend was observed for the Agile 4 score, although it missed more LREs in the low-risk group.
CONCLUSIONS AND RELEVANCE: Findings of this study suggest that single or serial Agile scores are highly accurate in predicting LREs in patients with MASLD, making them suitable alternatives to liver biopsy in routine clinical practice and in phase 2b and 3 clinical trials for steatohepatitis.
OBJECTIVE: To describe the demographic characteristics, treatment duration, and survival of patients with GIST in LMICs treated with imatinib and sunitinib through The Max Foundation programs.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective database cohort analysis included patients in 2 access programs administered by The Max Foundation: the Glivec International Patient Assistance Program (GIPAP), from January 1, 2001, to December 31, 2016, and the Max Access Solutions (MAS) program, January 1, 2017, to October 12, 2020. Sixty-six countries in which The Max Foundation facilitates access to imatinib and sunitinib were included. Participants consisted of patients with approved indications for imatinib, including adjuvant therapy in high-risk GIST by pathologic evaluation of resected tumor or biopsy-proven unresectable or metastatic GIST. All patients were reported to have tumors positive for CD117(c-kit) by treating physicians. A total of 9866 patients received treatment for metastatic and/or unresectable disease; 2100 received adjuvant imatinib; 49 received imatinib from another source and were only included in the sunitinib analysis; and 53 received both imatinib and sunitinib through The Max Foundation programs. Data were analyzed from October 13, 2020, to January 30, 2024.
MAIN OUTCOMES AND MEASURES: Demographic and clinical information was reported by treating physicians. Kaplan-Meier analysis was used to estimate time to treatment discontinuation (TTD) and overall survival (OS). An imputation-based informed censoring model estimated events for patients lost to follow-up after treatment with adjuvant imatinib. Patients who were lost to follow-up with metastatic or unresectable disease were presumed deceased.
RESULTS: A total of 12 015 unique patients were included in the analysis (6890 male [57.6%]; median age, 54 [range, 0-100] years). Of these, 2100 patients were treated with imatinib in the adjuvant setting (median age, 54 [range 8-88] years) and 9866 were treated with imatinib for metastatic or unresectable disease (median age, 55 [range, 0-100] years). Male patients comprised 5867 of 9866 patients (59.5%) with metastatic or unresectable disease and 1023 of 2100 patients (48.7%) receiving adjuvant therapy. The median OS with imatinib for unresectable or metastatic disease was 5.8 (95% CI, 5.6-6.1) years, and the median TTD was 4.2 (95% CI, 4.1-4.4) years. The median OS with sunitinib for patients with metastatic or unresectable GIST was 2.0 (95% CI, 1.5-2.5) years; the median TTD was 1.5 (95% CI, 1.0-2.1) years. The 10-year OS rate in the adjuvant setting was 73.8% (95% CI, 67.2%-81.1%).
CONCLUSIONS AND RELEVANCE: In this cohort study of patients with GIST who were predominantly from LMICs and received orally administered therapy through the GIPAP or MAS programs, outcomes were similar to those observed in high-resource countries. These findings underscore the feasibility and relevance of administering oral anticancer therapy to a molecularly defined population in LMICs, addressing a critical gap in cancer care.
METHODS: Retrospective single-centre cohort study using the 2007-2019 database of the Head and Neck Cancer and Oral Medicine units of University College London Hospital. The exposure of interest was the presence of OLP, and the prognostic outcomes included the development of new primary episodes of OED, progression to malignancy and mortality. Cox proportional hazard and Poisson regression models were performed.
RESULTS: A total of 299 patients, of whom 144 had OED arising on the background of OLP (OLP/OED) and 155 had OED without underlying OLP (non-OLP/OED), were included. A pre-existing diagnosis of OLP was significantly associated with a twofold increased risk of subsequent primary OED events (HR = 2.02, p = 0.04), which also developed faster (1.46 vs. 2.96 years, p = 0.04) and with more involvement of non-cancer-prone sites (p = 0.001) than in the non-OLP/OED group. There was no difference between groups in the progression to malignancy or mortality.
CONCLUSIONS: Oral lichen planus/OED patients are at higher risk of multiple episodes of primary OED, which can develop faster and at non-cancer-prone sites as compared to non-OLP/OED individuals. Further research is needed to clarify the effects of OLP upon progression to OSCC and mortality.
METHODS: We performed an observational cohort study in tertiary care hospitals from 14 countries across Asia and Ibero-America. We included patients <5 years old who were admitted to participating pediatric intensive care units (PICUs) with moderate to severe traumatic brain injury (TBI). We performed descriptive analysis and multivariable logistic regression for risk factors of AHT.
RESULTS: 47 (12%) out of 392 patients were diagnosed with AHT. Compared to those with accidental injuries, children with AHT were more frequently < 2 years old (42, 89.4% vs 133, 38.6%, p cohort. Overall, children with AHT required more neurosurgical interventions and the use of anti-epileptic medications. Children younger than 2 years and with SDH were independently associated with a diagnosis of AHT.
TYPE OF STUDY: Observational cohort study.
LEVEL OF EVIDENCE: III.
METHODOLOGY: A single-center cohort study was performed at Indus Hospital and Health Network, Karachi, Pakistan, between April 1, 2021, and October 31, 2021. This study included 333 hospitalized hypertensive COVID-19 patients and evaluated their clinical characteristics and survival outcomes. A multivariate logistic regression model was applied in IBM SPSS 27.0 to determine the predictors of mortality.
RESULTS: The majority of patients were females (54.7%), the median age was 62 [55-70] years, with co-existing diabetes (56.5%) and severely ill (52.6%). The independent predictors of mortality identified were age ≥ 65 years (aOR 20.89, 95% CI, 5.81-75.15; p < 0.001), pulse rate (aOR 1.03, 95% CI 1.01-1.63; p = 0.006), serum creatinine (aOR 1.34, 95% CI 1.11-1.63; p = 0.002), use of antibiotics (aOR 3.40, 95% CI 1.29-8.98; p = 0.014)), corticosteroid (aOR 49.68, 95% CI 1.83-1350.31; p = 0.020), and who needed high flow oxygen supply (aOR 13.08, 95% CI 1.70-100.54; p < 0.001), non-invasive mechanical ventilation (aOR 229.01, 95% CI 29.30-1789.71; p < 0.001) and invasive mechanical ventilation (aOR 379.54, 95% CI 36.60-3935.87; p < 0.001).
CONCLUSIONS: Our study suggests that older age, elevated pulse rate, serum creatinine, use of antibiotics and corticosteroids, and the need for mechanical ventilation predict mortality among hypertensive COVID-19.
METHODS: This was an observational cohort study of incident ASCVD patients. MACE counts and incidence rates (IRs) per 100-person-years were reported for patients with normal (<65 nmol/L) and elevated (>150 nmol/L) Lp(a) within the first year after incident ASCVD diagnosis and overall follow-up. Cox proportional hazard models quantified the risk of MACE associated with a 100 nmol/L increase in Lp(a).
RESULTS: The study cohort included 32,537 incident ASCVD patients; 5204 with elevated and 22,257 with normal Lp(a). Of those with elevated Lp(a), 41.2% had a subsequent MACE, versus 35.61% with normal Lp(a). Within the first year of follow-up, the IRs of composite MACE and coronary revascularisation were significantly higher (p < 0.001) in patients with elevated versus normal Lp(a) (IR difference 6.79 and 4.66). This trend was also observed in the overall follow-up (median 4.7 years). Using time to first subsequent MACE, a 100 nmol/L increase in Lp(a) was associated with an 8.0% increased risk of composite MACE, and 18.6% increased risk of coronary revascularisation during the overall follow-up period.
CONCLUSIONS: The association of elevated Lp(a) with increased risk of subsequent MACE and coronary revascularisation highlights a population who may benefit from earlier and more targeted intervention for cardiovascular risk including Lp(a), particularly within the first year after ASCVD diagnosis. Proactive Lp(a) testing as part of routine clinical practice can help identify and better manage these higher-risk individuals.
METHOD: Based on a preregistered protocol (PROSPERO: CRD42021239635), PubMed, Web of Knowledge/Science, Ovid MEDLINE, Embase, and APA PsycInfo databases were searched until April 21, 2021, to identify empirical studies reporting indices of autonomic nervous system (ANS) functioning in youths meeting DSM (version III, IV, IV-TR, 5 or 5-TR) or International Classification of Diseases (ICD) (version 9 or 10) criteria for any psychopathological/neurodevelopmental condition and assessed for ED with a validated scale. Eligible outcomes included correlation coefficients between ED and ANS measures or differences in ANS measures between youths with and without ED. Study quality was assessed with the Appraisal tool for Cross-Sectional Studies (AXIS) and the Newcastle-Ottawa Scale (NOS) for cohort studies. Random-effects meta-analyses were used for data synthesis.
RESULTS: There were 12 studies (1,016 participants) included in the descriptive review and 9 studies (567 participants) included in the meta-analyses. No evidence of a significant association between ED and altered cardiac or electrodermal functioning was found. However, exploratory meta-regressions suggested a possible association between reduced resting-state cardiac vagal control and increased ED.
CONCLUSION: This study did not find evidence of an association between ED and autonomic dysfunction. However, preliminary evidence that reduced vagal control at rest might be a transdiagnostic marker of ED in young people was found. Additional studies comparing autonomic measures in youths with and without ED are needed and should also assess the effects of interventions for ED on ANS functioning.
STUDY PREREGISTRATION INFORMATION: Systematic Review and Meta-Analysis: Is Autonomic Nervous System Functioning Atypical in Children and Adolescents With Emotional Dysregulation? https://www.crd.york.ac.uk/prospero/; CRD42021239635.
METHODS: We analysed the cancerous and adjacent non-cancerous formalin-fixed paraffin embedded (FFPE) tissue of 83 CRC patients from a single medical centre in Malaysia. TaqMan probe-based qPCR targeting the 16S rRNA gene was used to detect the presence of FN in the extracted FFPE DNA. The differences in FN expression between cancer and non-cancer tissues were evaluated. Association studies between FN infection in the tumour and relative FN abundance with available clinical data were conducted.
RESULTS: FN was more abundant in the cancerous tissue compared to non-cancerous tissue (p = 0.0025). FN infection in the tumour was significantly associated with lymph node metastasis (p = 0.047) and cancer staging (p = 0.032), but not with other clinicopathologic variables. In double-positive patients where FN was detected in both cancerous and non-cancerous tissue, the expression fold-change of FN, calculated using 2-ΔΔCT formula, was significantly higher in patients with tumour size equal to or greater than 5 cm (p = 0.033) and in KRAS-mutated patients (p = 0.046).
CONCLUSIONS: FN is enriched in CRC tumour tissue and is associated with tumour size, lymph node metastasis, cancer staging, and KRAS mutation in this single-centre small cohort study.
METHODS: We developed a prediction model using the classical cross-validation method from the Pan-Asia Trauma Outcomes Study (PATOS) database from 1 January 2015 to 31 December 2020. Eligible patients aged ≥18 years were transported to the hospital by the EMS. The primary outcome (EMS-witnessed TCA) was defined based on changes in vital signs measured on the scene or en route. We included variables that were immediately measurable as potential predictors when EMTs arrived. An integer point value system was built using multivariable logistic regression. The area under the receiver operating characteristic (AUROC) curve and Hosmer-Lemeshow (HL) test were used to examine discrimination and calibration in the derivation and validation cohorts.
RESULTS: In total, 74,844 patients were eligible for database review. The model comprised five prehospital predictors: age <40 years, systolic blood pressure <100 mmHg, respiration rate >20/minute, pulse oximetry <94%, and levels of consciousness to pain or unresponsiveness. The AUROC in the derivation and validation cohorts was 0.767 and 0.782, respectively. The HL test revealed good calibration of the model (p = 0.906).
CONCLUSION: We established a prediction model using variables from the PATOS database and measured them immediately after EMS personnel arrived to predict EMS-witnessed TCA. The model allows prehospital medical personnel to focus on high-risk patients and promptly administer optimal treatment.
METHODS: We surveyed HFrEF patients from two hospitals in Malaysia, using Malay, English or Chinese versions of EQ-5D-5L. EQ-5D-5L dimensional scores were converted to utility scores using the Malaysian value set. A confirmatory factor analysis longitudinal model was constructed. The utility and visual analog scale (VAS) scores were evaluated for validity (convergent, known-group, responsiveness), and measurement equivalence of the three language versions.
RESULTS: 200 HFrEF patients (mean age = 61 years), predominantly male (74%) of Malay ethnicity (55%), completed the admission and discharge EQ-5D-5L questionnaire in Malay (49%), English (26%) or Chinese (25%) languages. 173 patients (86.5%) were followed up at 1-month post-discharge (1MPD). The standardized factor loadings and average variance extracted were ≥ 0.5 while composite reliability was ≥ 0.7, suggesting convergent validity. Patients with older age and higher New York Heart Association (NYHA) class reported significantly lower utility and VAS scores. The change in utility and VAS scores between admission and discharge was large, while the change between discharge and 1MPD was minimal. The minimal clinically important difference for utility and VAS scores was ±0.19 and ±11.01, respectively. Malay and English questionnaire were equivalent while the equivalence of Malay and Chinese questionnaire was inconclusive.
LIMITATION: This study only sampled HFrEF patients from two teaching hospitals, thus limiting the generalizability of results to the entire heart failure population.
CONCLUSION: EQ-5D-5L is a valid questionnaire to measure health-related quality of life and estimate utility values among HFrEF patients in Malaysia. The Malay and English versions of EQ-5D-5L appear equivalent for clinical and economic assessments.
MATERIALS AND METHODS: Epidemiological data for selfreported bone fractures were obtained through direct interviews using a validated questionnaire from the Prospective Urban and Rural Epidemiology (PURE) study.
RESULTS: Of 15,378 respondents, 6.63% (n=1019) reported bone fractures, with a higher proportion of men (65.8%, n=671) than women (34.2%, n=348). Higher odds of selfreporting bone fractures were seen in males (aOR, 2.12; 95%CI: 1.69, 2.65), those with a history of injury (aOR 5.01; 95%CI: 3.10, 6.32) and those who were obese (aOR: 1.46; 95% CI: 1.13, 1.89), highly active (aOR 1.25; 95%CI: 1.02, 1.53), smokers (aOR 1.35; 95%CI: 1.11, 1.65) and alcohol consumers (aOR 1.67; 95%CI: 1.20,2.32).
CONCLUSION: Adopting a healthier lifestyle that includes a balanced diet and moderate physical activity is critical for weight loss, increased muscle and bone mass and better stability, which reduces the likelihood of fractures following a fall.
METHODS: We used individual participant data (N = 39271, Mage = 70.67 (40-102), 58.86% female, Meducation = 8.43 years, Mfollow-up = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes.
RESULTS: We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality.
DISCUSSION: Different aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally.
HIGHLIGHTS: Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality.