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Ferumoxytol-Enhanced Cardiac Cine MRI Reconstruction Using a Variable-Splitting Spatiotemporal Network

J Magn Reson Imaging. 2024 Mar 4. doi: 10.1002/jmri.29295. Online ahead of print.

ABSTRACT

BACKGROUND: Balanced steady-state free precession (bSSFP) imaging is commonly used in cardiac cine MRI but prone to image artifacts. Ferumoxytol-enhanced (FE) gradient echo (GRE) has been proposed as an alternative. Utilizing the abundance of bSSFP images to develop a computationally efficient network that is applicable to FE GRE cine would benefit future network development.

PURPOSE: To develop a variable-splitting spatiotemporal network (VSNet) for image reconstruction, trained on bSSFP cine images and applicable to FE GRE cine images.

STUDY TYPE: Retrospective and prospective.

SUBJECTS: 41 patients (26 female, 53 ± 19 y/o) for network training, 31 patients (19 female, 49 ± 17 y/o) and 5 healthy subjects (5 female, 30 ± 7 y/o) for testing.

FIELD STRENGTH/SEQUENCE: 1.5T and 3T, bSSFP and GRE.

ASSESSMENT: VSNet was compared to VSNet with total variation loss, compressed sensing and low rank methods for 14× accelerated data. The GRAPPA×2/×3 images served as the reference. Peak signal-to-noise-ratio (PSNR), structural similarity index (SSIM), left ventricular (LV) and right ventricular (RV) end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) were measured. Qualitative image ranking and scoring were independently performed by three readers. Latent scores were calculated based on scores of each method relative to the reference.

STATISTICS: Linear mixed-effects regression, Tukey method, Fleiss’ Kappa, Bland-Altman analysis, and Bayesian categorical cumulative probit model. A P-value <0.05 was considered statistically significant.

RESULTS: VSNet achieved significantly higher PSNR (32.7 ± 0.2), SSIM (0.880 ± 0.004), rank (2.14 ± 0.06), and latent scores (-1.72 ± 0.22) compared to other methods (rank >2.90, latent score < -2.63). Fleiss’ Kappa was 0.52 for scoring and 0.61 for ranking. VSNet showed no significantly different LV and RV ESV (P = 0.938) and EF (P = 0.143) measurements, but statistically significant different (2.62 mL) EDV measurements compared to the reference.

CONCLUSION: VSNet produced the highest image quality and the most accurate functional measurements for FE GRE cine images among the tested 14× accelerated reconstruction methods.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

PMID:38436994 | DOI:10.1002/jmri.29295

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ADHD Rating Scale (ADHD-RS): Validation in Spanish in adult population according to the DSM-5

Span J Psychiatry Ment Health. 2024 Jan-Mar;17(1):46-50. doi: 10.1016/j.sjpmh.2023.06.002. Epub 2023 Sep 27.

ABSTRACT

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is the most common childhood neurodevelopmental disorder, with an estimated prevalence in adulthood of 2.5-3.4%. The Attention Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS) is an 18-item self-administered scale that assesses attention deficit and hyperactivity/impulsivity symptoms of ADHD in adults. This study aims to validate the ADHD-RS in Spanish according to the diagnostic criteria established by the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).

MATERIALS AND METHODS: A sample of 441 adult patients (mean age 33.34±11.37 years) was included, 396 subjects were diagnosed with ADHD (mean age 33.17±11.18 years), and 45 were controls (mean age 35.40±12.33 years). The clinical diagnosis of ADHD was established according to the DSM-5 criteria. The ADHD-RS was subsequently administered to all participants. A logistic regression study evaluated the model in terms of sensitivity, specificity, positive predictive value, and negative predictive value. The Kaiser-Meyer-Olkin (KMO) measure was performed to assess the adequacy of the data set, and to determine whether factor analysis was applicable, Bartlett’s sphericity test was performed. Principal component analysis was used, using the Varimax orthogonal rotation method, which minimizes the number of variables with high loads on each factor, obtaining two factors and thus, simplifying their interpretation.

RESULTS: The cut-off point that best discriminates the combined presentation of ADHD was 24 points, with a sensitivity of 94.78%, a specificity of 84.79%, a PPV (positive predictive value) of 93.74%, and an NPV (negative predictive value) of 78.33, with an area under the curve (AUC) of 0.85, and a kappa coefficient of 0.86. Regarding inattentive ADHD, the cut-off point that best discriminates was 21 points, with a sensitivity of 92.56%, a specificity of 76.26%, a PPV of 92.01%, an NPV of 78.33%, an AUC of 0.90, and a kappa coefficient of 0.87. Different cut-off values in the two subgroups suggests that a differentiated cut-off point for the inattentive and combined presentations may be an adequate assessment strategy for ADHD in adulthood.

CONCLUSIONS: The Spanish version of the ADHD-RS is a valid instrument to evaluate ADHD in adults according to the diagnostic criteria established by the DSM-5. Differentiated cut-off points for the inattentive and combined presentations discriminate more accurately than a single cut-off point.

PMID:38436988 | DOI:10.1016/j.sjpmh.2023.06.002

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Reidentification With Birth-Registered Sex in a Western Australian Pediatric Gender Clinic Cohort

JAMA Pediatr. 2024 Mar 4. doi: 10.1001/jamapediatrics.2024.0077. Online ahead of print.

ABSTRACT

IMPORTANCE: Some young people who identify as transgender and seek gender-affirming medical care subsequently reidentify with their sex registered at birth. Evidence regarding the frequency and characteristics of this experience is lacking.

OBJECTIVE: To determine the frequency of reidentification and explore associated characteristics in a pediatric gender clinic setting.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study examined all referrals to the Child and Adolescent Health Service Gender Diversity Service at Perth Children’s Hospital between January 1, 2014, and December 31, 2020. The Gender Diversity Service is the sole statewide specialist service in Western Australia that provides children and adolescents up to age 18 years with multidisciplinary assessment, information, support, and gender-affirming medical care. All closed referrals for this study were audited between May 1, 2021, and August 8, 2022.

EXPOSURE: Reidentification with birth-registered sex.

MAIN OUTCOMES AND MEASURES: The number of referrals closed due to reported reidentification with birth-registered sex was determined, as well as descriptives and frequencies of patient demographics (age, birth-registered sex), informant source, International Statistical Classification of Diseases, Tenth Revision gender-related diagnoses, pubertal status, any gender-affirming medical treatment received, and whether subsequent re-referrals were received.

RESULTS: Of 552 closed referrals during the study period, a reason for closure could be determined for 548 patients, including 211 birth-registered males (mean [SD] age, 13.88 [2.00] years) and 337 birth-registered females (mean [SD] age, 15.81 [2.22] years). Patients who reidentified with their birth-registered sex comprised 5.3% (29 of 548; 95% CI, 3.6%-7.5%) of all referral closures. Except for 2 patients, reidentification occurred before or during early stages of assessment (93.1%; 95% CI, 77.2%-99.2%). Two patients who reidentified with their birth-registered sex did so following initiation of puberty suppression or gender-affirming hormone treatment (1.0% of 196 patients who initiated any gender-affirming medical treatment; 95% CI, 0.1%-3.6%).

CONCLUSIONS AND RELEVANCE: These findings from a pediatric gender clinic audit indicate that a small proportion of patients, and a very small proportion of those who initiated medical gender-affirming treatment, reidentified with their birth-registered sex during the study period. Longitudinal follow-up studies, including qualitative self-report, are required to understand different pathways of gender identity experience.

PMID:38436975 | DOI:10.1001/jamapediatrics.2024.0077

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Associations of Medical Debt With Health Status, Premature Death, and Mortality in the US

JAMA Netw Open. 2024 Mar 4;7(3):e2354766. doi: 10.1001/jamanetworkopen.2023.54766.

ABSTRACT

IMPORTANCE: Medical debt is increasingly common in the US. Little is known regarding its association with population health.

OBJECTIVE: To examine the associations of medical debt with health status, premature death, and mortality at the county level in the US.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted at the US county level using 2018 medical debt data from the Urban Institute Debt in America project linked with 2018 data on self-reported health status and premature death from the County Health Rankings & Roadmaps and with 2015 to 2019 mortality data from the National Center for Health Statistics. Data analysis was performed from August 2022 to May 2023.

EXPOSURE: Share of population with any medical debt in collections and median amount of medical debt.

MAIN OUTCOMES AND MEASURES: Health status was measured as (1) the mean number of physically and mentally unhealthy days in the past 30 days per 1000 people, (2) the mean number of premature deaths measured as years of life lost before age 75 years per 1000 people, and (3) age-adjusted all-cause and 18 cause-specific mortality rates (eg, malignant cancers, heart disease, and suicide) per 100 000 person-years. Multivariable linear models were fitted to estimate the associations between medical debt and health outcomes.

RESULTS: A total of 2943 counties were included in this analysis. The median percentage of the county population aged 65 years or older was 18.3% (IQR, 15.8%-20.9%). Across counties, a median 3.0% (IQR, 1.2%-11.9%) of the population were Black residents, 4.3% (IQR, 2.3%-9.7%) were Hispanic residents, and 84.5% (IQR, 65.7%-93.3%) were White residents. On average, 19.8% (range, 0%-53.6%) of the population had medical debt. After adjusting for county-level sociodemographic characteristics, a 1-percentage point increase in the population with medical debt was associated with 18.3 (95% CI, 16.3-20.2) more physically unhealthy days and 17.9 (95% CI, 16.1-19.8) more mentally unhealthy days per 1000 people during the past month, 1.12 (95% CI, 1.03-1.21) years of life lost per 1000 people, and an increase of 7.51 (95% CI, 6.99-8.04) per 100 000 person-years in age-adjusted all-cause mortality rate. Associations of medical debt and elevated mortality rates were consistent for all leading causes of death, including cancer (1.12 [95% CI, 1.02-1.22]), heart disease (1.39 [95% CI, 1.21-1.57]), and suicide (0.09 [95% CI, 0.06-0.11]) per 100 000 person-years. Similar patterns were observed for associations between the median amount of medical debt and the aforementioned health outcomes.

CONCLUSIONS AND RELEVANCE: These findings suggest that medical debt is associated with worse health status, more premature deaths, and higher mortality rates at the county level in the US. Therefore, policies increasing access to affordable health care, such as expanding health insurance coverage, may improve population health.

PMID:38436960 | DOI:10.1001/jamanetworkopen.2023.54766

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Use of SGLT2 Inhibitors vs GLP-1 RAs and Anemia in Patients With Diabetes and CKD

JAMA Netw Open. 2024 Mar 4;7(3):e240946. doi: 10.1001/jamanetworkopen.2024.0946.

ABSTRACT

IMPORTANCE: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are associated with lower anemia risk, based on findings from post hoc analyses of the CREDENCE and DAPA-CKD trials; however, the effectiveness of SGLT2 inhibitors in a more generalizable type 2 diabetes (T2D) and chronic kidney disease (CKD) population, with active comparisons pertinent to current practice, is unknown.

OBJECTIVE: To evaluate and compare anemia incidence between SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) among patients with T2D and CKD stages 1 to 3.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used target trial emulation of an expanded CREDENCE and DAPA-CKD study framework. The study was conducted among adults with T2D and CKD initiating SGLT2 inhibitors or GLP-1 RAs between January 1, 2016, and December 31, 2021, with follow-up until December 31, 2022. The study was conducted at the Chang Gung Medical Foundation, the largest multi-institutional hospital system in Taiwan.

EXPOSURES: Initiation of SGLT2 inhibitors or GLP-1 RAs.

MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of anemia outcomes, including anemia event occurrence (hemoglobin level <12-13 g/dL or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes) or anemia treatment initiation. Changes in hematological parameters, including hemoglobin level, hematocrit level, and red blood cell count, were evaluated during the follow-up period for as long as 3 years.

RESULTS: The cohort included a total of 13 799 patients with T2D and CKD, initiating SGLT2 inhibitors (12 331 patients; mean [SD] age, 62.4 [12.3] years; 7548 [61.2%] male) or GLP-1 RAs (1468 patients; mean [SD] age, 61.5 [13.3] years; 900 [61.3%] male). After the median follow-up period of 2.5 years, patients receiving SGLT2 inhibitors had lower incidence of composite anemia outcomes (hazard ratio [HR], 0.81; 95% CI, 0.73-0.90) compared with those receiving GLP-1 RAs. SGLT2 inhibitors were associated with a lower incidence of anemia events (HR, 0.79; 95% CI, 0.71-0.87) but not with a lower rate of anemia treatment initiation (HR, 0.99; 95% CI, 0.83-1.19). Changes in hematological parameters for SGLT2 inhibitors and GLP-1 RAs throughout the 3-year follow-up period supported the primary analyses.

CONCLUSIONS AND RELEVANCE: In this multi-institutional cohort study with target trial emulation, SGLT2 inhibitors were associated with a decreased risk of composite anemia outcomes, especially anemia event occurrences. SGLT2 inhibitors may be considered as an adjunct therapy to reduce anemia incidence in patients with T2D and CKD.

PMID:38436955 | DOI:10.1001/jamanetworkopen.2024.0946

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Screen Time and Parent-Child Talk When Children Are Aged 12 to 36 Months

JAMA Pediatr. 2024 Mar 4. doi: 10.1001/jamapediatrics.2023.6790. Online ahead of print.

ABSTRACT

IMPORTANCE: Growing up in a language-rich home environment is important for children’s language development in the early years. The concept of “technoference” (technology-based interference) suggests that screen time may be interfering with opportunities for talk and interactions between parent and child; however, limited longitudinal evidence exists exploring this association.

OBJECTIVE: To investigate the longitudinal association between screen time and 3 measures of parent-child talk (adult words, child vocalizations, and conversational turns) when children are 12 to 36 months of age.

DESIGN, SETTING, AND PARTICIPANTS: This Australian prospective cohort study used advanced speech recognition technology to capture young children’s screen time and home language environment, on an average 16-hour day. Data were collected from 220 families once every 6 months in the family home when children were 12, 18, 24, 30, and 36 months of age, from January 1, 2018, to December 31, 2021. Statistical analysis took place from November 1, 2022, to July 31, 2023.

EXPOSURE: Language Environment Analysis (LENA) technology provided automated counts of children’s language environment and exposure to electronic noise. The exposure of interest was screen time, which was calculated based on manual coding of LENA electronic noise audio segments.

MAIN OUTCOMES AND MEASURES: Three measures of parent-child talk were outcomes of focus: adult words, child vocalizations, and conversational turns. Separate models were run for each of the 3 outcomes and included adjustment for child sex, child age, maternal educational level, number of children at home, number of home activities, and primary caregiver’s psychological distress.

RESULTS: The study included 220 families (120 girls [54.6%]; mean [SD] gestational age of children, 39.3 [1.5] weeks; mean [SD] age of mother at childbirth, 31.3 [4.8] years). Adjusted linear mixed-effect models demonstrated that increases in screen time were associated with decreases in measures of parent-child talk. The largest decreases were seen at 36 months, when an additional minute of screen time was associated with a reduction of 6.6 (95% CI, -11.7 to -1.5) adult words, 4.9 (95% CI, -6.1 to -3.7) child vocalizations, and 1.1 (95% CI, -1.4 to -0.8) conversational turns.

CONCLUSION AND RELEVANCE: Findings of this study support the notion of technoference for Australian families, whereby young children’s exposure to screen time is interfering with opportunities to talk and interact in their home environment. This finding has implications for interventions and supports aimed at promoting a language-rich home environment, with families needing support in understanding the potential association of screen time with opportunities for children and adults to talk and interact in their home environment.

PMID:38436942 | DOI:10.1001/jamapediatrics.2023.6790

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The human subthalamic nucleus transiently inhibits active attentional processes

Brain. 2024 Mar 4:awae068. doi: 10.1093/brain/awae068. Online ahead of print.

ABSTRACT

The subthalamic nucleus (STN) of the basal ganglia is key to the inhibitory control of movement. Consequently, it is a primary target for the neurosurgical treatment of movement disorders like Parkinson’s Disease, where modulating the STN via deep-brain stimulation (DBS) can release excess inhibition of thalamo-cortical motor circuits. However, the STN is also anatomically connected to other thalamo-cortical circuits, including those underlying cognitive processes like attention. Notably, STN-DBS can also affect these processes. This suggests that the STN may also contribute to the inhibition of non-motor activity, and that STN-DBS may cause changes to this inhibition. We here tested this hypothesis in humans. We used a novel, wireless outpatient method to record intracranial local field potentials (LFP) from STN DBS implants during a visual attention task (Experiment 1, N=12). These outpatient measurements allowed the simultaneous recording of high-density EEG, which we used to derive the steady-state visual evoked potential (SSVEP), a well-established neural index of visual attentional engagement. By relating STN activity to this neural marker of attention (instead of overt behavior), we avoided possible confounds resulting from STN’s motor role. We aimed to test whether the STN contributes to the momentary inhibition of the SSVEP caused by unexpected, distracting sounds. Furthermore, we causally tested this association in a second experiment, where we modulated STN via DBS across two sessions of the task, spaced at least one week apart (N=21, no sample overlap with Experiment 1). The LFP recordings in Experiment 1 showed that reductions of the SSVEP after distracting sounds were preceded by sound-related γ-frequency (>60Hz) activity in the STN. Trial-to-trial modeling further showed that this STN activity statistically mediated the sounds’ suppressive effect on the SSVEP. In Experiment 2, modulating STN activity via DBS significantly reduced these sound-related SSVEP reductions. This provides causal evidence for the role of the STN in the surprise-related inhibition of attention. These findings suggest that the human STN contributes to the inhibition of attention, a non-motor process. This supports a domain-general view of the inhibitory role of the STN. Furthermore, these findings also suggest a potential mechanism underlying some of the known cognitive side-effects of STN-DBS treatment, especially on attentional processes. Finally, our newly-established outpatient LFP recording technique facilitates the testing of the role of subcortical nuclei in complex cognitive tasks, alongside recordings from the rest of the brain, and in much shorter time than perisurgical recordings.

PMID:38436939 | DOI:10.1093/brain/awae068

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Anterior Segment Optical Coherence Tomography in Uveitis-Glaucoma-Hyphema Syndrome

Ocul Immunol Inflamm. 2024 Mar 4:1-7. doi: 10.1080/09273948.2024.2323094. Online ahead of print.

ABSTRACT

PURPOSE: Uveitis-Glaucoma-Hyphema (UGH) syndrome results from contact between the intraocular lens (IOL) and the iris or ciliary body, leading to uveal structure erosion and blood-aqueous barrier breakdown. Treatment involves various drugs, with IOL removal often being necessary. Diagnosis relies on clinical signs, but imaging techniques like ultrasound biomicroscopy (UBM) or anterior segment optical coherence tomography (AS-OCT) are crucial. AS-OCT accurately depicts IOL position and potential contact, emerging as a primary alternative to UBM in the diagnosis. Our study aimed to correlate AS-OCT findings with clinically detectable iris atrophy in pseudophakic patients with IOL-iris chafing and UGH syndrome.

METHODS: The study retrospectively analyzed patients diagnosed with UGH syndrome presenting at the Ocular Immunology Unit of Reggio Emilia, Italy, from January 2019 to August 2023. Patients’ data were collected. Ophthalmological exams and imaging were performed. The peephole sign in AS-OCT images was evaluated. Statistical analyses were conducted, with a significance level of p ≤ 0.05.

RESULTS: The study reviewed 22 eyes of 22 patients with UGH syndrome. Four eyes were excluded, leaving 18 patients (8 females, 10 males). Common misdiagnoses included idiopathic anterior uveitis (55.5%) and herpetic anterior uveitis (16.7%). All patients had iris transillumination defects, mostly focal (77.8%). AS-OCT revealed IOL chafing in all the eyes, with peephole sign correlation. More peephole signs occurred with IOL in the sulcus (p-value = 0.08).

CONCLUSION: The study recommends AS-OCT for UGH syndrome confirmation and UBM when IOL-iris chafing is not observed on AS-OCT scans.

PMID:38436932 | DOI:10.1080/09273948.2024.2323094

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Demonstrating Bioequivalence for Two Dose Strengths of Niraparib and Abiraterone Acetate Dual-Action Tablets Versus Single Agents: Utility of Clinical Study Data Supplemented with Modeling and Simulation

Clin Pharmacokinet. 2024 Mar 4. doi: 10.1007/s40262-023-01340-5. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: The combination of niraparib and abiraterone acetate (AA) plus prednisone is under investigation for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC). Regular-strength (RS) and lower-strength (LS) dual-action tablets (DATs), comprising niraparib 100 mg/AA 500 mg and niraparib 50 mg/AA 500 mg, respectively, were developed to reduce pill burden and improve patient experience. A bioequivalence (BE)/bioavailability (BA) study was conducted under modified fasting conditions in patients with mCRPC to support approval of the DATs.

METHODS: This open-label randomized BA/BE study (NCT04577833) was conducted at 14 sites in the USA and Europe. The study had a sequential design, including a 21-day screening phase, a pharmacokinetic (PK) assessment phase comprising three periods [namely (1) single-dose with up to 1-week run-in, (2) daily dose on days 1-11, and (3) daily dose on days 12-22], an extension where both niraparib and AA as single-agent combination (SAC; reference) or AA alone was continued from day 23 until discontinuation, and a 30-day follow-up phase. Patients were randomly assigned in a parallel-group design (four-sequence randomization) to receive a single oral dose of niraparib 100 mg/AA 1000 mg as a LS-DAT or SAC in period 1, and patients continued as randomized into a two-way crossover design during periods 2 and 3 where they received niraparib 200 mg/AA 1000 mg once daily as a RS-DAT or SAC. The design was powered on the basis of crossover assessment of RS-DAT versus SAC. During repeated dosing (periods 2 and 3, and extension phase), all patients also received prednisone/prednisolone 5 mg twice daily. Plasma samples were collected for measurement of niraparib and abiraterone plasma concentrations. Statistical assessment of the RS-DAT and LS-DAT versus SAC was performed on log-transformed pharmacokinetic parameters data from periods 2 and 3 (crossover) and from period 1 (parallel), respectively. Additional paired analyses and model-based bioequivalence assessments were conducted to evaluate the similarity between the LS-DAT and SAC.

RESULTS: For the RS-DAT versus SAC, the 90% confidence intervals (CI) of geometric mean ratios (GMR) for maximum concentration at a steady state (Cmax,ss) and area under the plasma concentration-time curve from 0-24 h at a steady state (AUC 0-24h,ss) were respectively 99.18-106.12% and 97.91-104.31% for niraparib and 87.59-106.69 and 86.91-100.23% for abiraterone. For the LS-DAT vs SAC, the 90% CI of GMR for AUC0-72h of niraparib was 80.31-101.12% in primary analysis, the 90% CI of GMR for Cmax,ss and AUC 0-24h,ss of abiraterone was 85.41-118.34% and 86.51-121.64% respectively, and 96.4% of simulated LS-DAT versus SAC BE trials met the BE criteria for both niraparib and abiraterone.

CONCLUSIONS: The RS-DAT met BE criteria (range 80%-125%) versus SAC based on 90% CI of GMR for Cmax,ss and AUC 0-24h,ss. The LS-DAT was considered BE to SAC on the basis of the niraparib component meeting the BE criteria in the primary analysis for AUC 0-72h; abiraterone meeting the BE criteria in additional paired analyses based on Cmax,ss and AUC 0-24h,ss; and the percentage of simulated LS-DAT versus SAC BE trials meeting the BE criteria for both.

GOV IDENTIFIER: NCT04577833.

PMID:38436924 | DOI:10.1007/s40262-023-01340-5

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Hepatitis C Virus-Related One-Year Hepatocellular Carcinoma Recurrence After Directly Acting Antivirals: A Randomized Controlled Trial

J Gastrointest Cancer. 2024 Mar 4. doi: 10.1007/s12029-024-01035-5. Online ahead of print.

ABSTRACT

PURPOSE: Available data on hepatocellular carcinoma (HCC) recurrence after direct-acting antivirals (DAAs) treatment for hepatitis C virus (HCV) are conflicting. No randomized trials were done. This study aims to compare the 1-year HCC recurrence rates in patients who received DAAs after tumor ablation versus those who postponed HCV treatment for 1 year.

METHODS: Included patients were randomized after complete HCC ablation into two groups: a postponed DAAs group for whom DAAs initiation was postponed for 12 months and a DAAs group who were given sofosbuvir/velpatasvir. Patients were followed for 1 year.

RESULTS: Eighty-four HCV patients with a mean age of 56.35 ± 8.12 years were included; 78.57% of them were males. The number of lesions per patient ranged from 1 to 3 lesions, and the size of the largest lesion ranged from 1.5 to 5 cm. There were no statistically significant differences between both groups regarding baseline characteristics. In the DAAs group (43 patients), 11 patients had HCC recurrence, while 25 patients in the postponed DAAs group (41 patients) had HCC recurrence. Using Kaplan-Meier analysis, the 1-year recurrence-free survival (RFS) was significantly higher in the DAAs group (72.2% vs. 38%, P = 0.001). On multivariate analysis, both higher albumin levels (HR 0.147, 95% CI 0.066-0.329) and receiving DAAs (HR 0.358, 95% CI 0.176-0.730) 1 year after ablation were associated with significantly lower recurrence.

CONCLUSION: Direct-acting antiviral usage after complete hepatocellular carcinoma ablation significantly decreases the 1-year HCC recurrence rates, but the risk of recurrence is still not eliminated. The study registration number on clinicaltrials.gov : NCT04653818 (initial release on 28/11/2020).

PMID:38436921 | DOI:10.1007/s12029-024-01035-5