Background: Pediatric chronic pain affects up to one-third of youth and is associated with significant disruptions in social, emotional, and behavioral functioning. Although behavioral treatments are effective, access remains limited due to geographic, financial, and systemic barriers. Digital behavioral health interventions offer a promising solution, but many lack user-centered design, iterative refinement, and implementation-informed development strategies that support usability and scalability. Objective: This study aimed to develop and iteratively refine iGET Living, a digital graded exposure intervention for youth with chronic pain, using a combined user-centered and implementation-informed framework, and to evaluate its preliminary acceptability, feasibility, and user-perceived success. Methods: Guided by the Consolidated Framework for Implementation Research (CFIR) and the mHealth (mobile health) Agile Development and Lifecycle model, intervention development proceeded through 3 phases. Phase 0 translated an evidence-based in-person graded exposure treatment (GET Living) into an initial digital prototype. Phase 1 involved iterative user-centered refinement across 3 cycles of qualitative development sessions with youth with chronic pain (n=15), incorporating think-aloud usability testing, Likert-rated feedback, and rapid qualitative analysis mapped to CFIR constructs to guide real-time modifications to content, design, and functionality. Phase 2 piloted the refined intervention with a new sample of youth (n=38, n=30 completers) recruited from a tertiary pediatric pain clinic to evaluate feasibility, acceptability, treatment credibility and expectancy, and user-perceived functional improvements. Quantitative outcomes were summarized descriptively, and qualitative exit interview data were analyzed using rapid qualitative analysis. Results: Across development cycles, youth feedback informed substantive refinements to the intervention, including reducing text density, incorporating animated educational videos, enhancing interactive features, and improving navigation and layout. These changes resulted in progressive improvements in clarity, satisfaction, and acceptability across prototypes. In the Phase 2 pilot study, participants reported moderate-to-high treatment credibility (mean of 19.71 out of 30) and expectancy (mean of 17.96 out of 30), as well as high satisfaction (mean of 46.12 out of 60). Acceptability ratings across domains of the Theoretical Framework of Acceptability were favorable. Qualitative exit interviews highlighted the interventions’ perceived role in helping youth re-engage in valued activities. Conclusions: Using a combined CFIR and agile development approach, iGET Living emerged as a feasible, acceptable, engaging digital graded exposure intervention for youth with chronic pain. These findings highlight the value of integrating implementation frameworks and participatory design early in digital intervention development and support further evaluation in a preliminary efficacy trial. Trial Registration: ClinicalTrials.gov NCT05079984; https://clinicaltrials.gov/study/NCT05079984 International Registered Report Identifier (IRRID): RR2-10.1136/bmjopen-2022-065997
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Experiences From an Internet-Delivered Treatment Program for Individuals With Obesity: Pilot Study
Background: The prevalence of obesity is a global health challenge, as obesity is associated with various comorbidities, reduced quality of life, and increased mortality. Providing effective treatment to improve health and quality of life for people with obesity is a major health care concern. Internet-delivered treatment (IDT) is an alternative treatment that increases patient accessibility and reachability; however, pilot testing is required before such interventions are evaluated in full-scale studies or implemented. Objective: This study aims to investigate the feasibility and user-friendliness of an IDT program for obesity (IDT-O); to evaluate body weight, dietary habits, physical activity, psychosocial functioning, and experiences of treatment in those who completed the 6-month treatment; and to investigate the dropouts’ experiences of the treatment. Methods: A prospective 1-year observational approach, evaluated through a multimethod research design, was adopted. Inclusion criteria were age 18 years and older, BMI of ≥30 kg/m, or BMI of 28‐29.9 kg/m with obesity-related comorbidity. Participants were offered a 6-month therapist-assisted IDT-O program providing evidence-based obesity treatment, behavioral and lifestyle support, and strategies to address weight stigma. BMI, participants’ dietary habits, self-reported physical activity, psychosocial functioning, experiences of treatment effects, and treatment satisfaction were measured before treatment and after 6 and 12 months. Dropouts were followed up through qualitative interviews. Results: A total of 20 participants (17 females and 3 male; mean age 44.2, SD 16.4 years) started the IDT-O program, and 35% (7/20) completed all 12 modules. Ten (8 females) out of 13 dropouts were interviewed. Both quantitative and qualitative findings showed that participants were generally satisfied with the content and design of the intervention. Those who completed the IDT-O lost some weight (mean 2.0%, 95% CI −1.09 to 5.13), reported improved dietary habits (effect size [ES] 0.25, 95% CI −0.51 to 1.00), increased physical activity (ES 0.93, 95% CI −0.08 to 1.87), and improved psychosocial functioning (distress: ES 0.43, 95% CI 0.‐0.37 to 1.19; avoidance: ES 0.67, 95% CI −0.18 to 1.48), 6 months after completing the treatment. The qualitative analysis of the interviews revealed “The programme was OK, but it does not suit everyone” as the main theme. The main themes were based on the 3 subthemes: “It wasn’t for me,” “There were good things,” and “There are things to improve.” Conclusions: The findings indicate that the IDT-O holds potential as a treatment for people with obesity, although one limitation is that only 35% (7/20) of the participants completed the pilot program. Improvements in lifestyle habits and psychosocial functioning were observed in those who completed the IDT-O, but these findings are preliminary and need to be confirmed in a more comprehensive study. The issue of nonadherence underscores the importance of both thoroughly assessing patients before treatment and further development of IDT-O programs. Trial Registration: ClinicalTrials.gov NCT04150445; https://clinicaltrials.gov/study/NCT04150445
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STAT+: A pancreatic cancer expert on why Revolution Medicines’ study could ‘open up a new era’ of treatment
Revolution Medicines announced a stunning survival benefit for its experimental drug in a Phase 3 pancreatic cancer study this week.
Patients with advanced pancreatic adenocarcinoma who were treated with the company’s daily pill called daraxonrasib lived a median of 13.2 months compared to 6.7 months for patients who received standard chemotherapy.
Revolution said it plans to use the data to apply for Food and Drug Administration approval, although it did not say when. When it does submit the data, approval might come fast.
STAT spoke with Paul Oberstein of NYU Langone’s Perlmutter Cancer Center, an investigator in the trial, on its biotech podcast “The Readout Loud.”
This transcript has been lightly edited for length and clarity.
Let’s start by talking about pancreatic cancer generally. Why is it so challenging to treat it and what are the current survival rates?
Anemia May Be a Modifiable Risk Factor for Alzheimer’s Disease
Older adults with anemia have significantly higher levels of blood biomarkers for Alzheimer’s disease and a significantly increased risk for the disease itself, particularly when anemia is combined with the presence of the biomarkers, Swedish study data show.
The findings “suggest that anemia may interact with neuropathologic processes, potentially accelerating dementia development,” write Martina Valletta, MD, from Karolinska Institutet and Stockholm University in Sweden, and co-authors in JAMA Network Open.
Their analysis included data for 2282 dementia-free participants (median age, 72 years, 62% women) of the population-based Swedish National Study on Aging and Care in Kungsholmen. Of these, 8.7% had anemia at baseline.
The researchers report that participants with anemia had significantly higher baseline levels of the Alzheimer’s disease blood biomarkers phosphorylated tau 217 (p-tau217; 0.2 vs 0.1 pg/mL), neurofilament light chain (NfL; 36.6 vs 17.0 pg/mL), and glial fibrillary acidic protein (GFAP; 187.8 vs 117.4 pg/mL) relative to individuals with normal hemoglobin levels.
During a mean follow-up of 9.3 years, 362 (15.9%) participants developed dementia, with the incidence significantly higher among those with versus without anemia, at 4.4 and 1.7 cases per 100 person–years, respectively.
After adjustment for multiple potential confounding factors, like age, sex, education level, chronic kidney disease, heart disease, cerebrovascular disease, cancer, weight, iron and vitamin supplementation, and interleukin-6 level, the difference between the two groups corresponded to a significant 1.7-fold higher risk for developing dementia during follow-up among the participants with anemia relative to those with normal hemoglobin levels.
Valletta and colleagues note that the relationship between baseline hemoglobin levels and incident dementia was nonlinear. Specifically, below hemoglobin levels of approximately 14 g/dL dementia risk was inversely associated with hemoglobin level. Above this cutoff, the association plateaued.
In addition, the team found that co-occurrence of low hemoglobin and elevated Alzheimer’s disease blood biomarkers further amplified dementia risk.
For example, compared with participants without anemia and with low NfL, the risk for dementia was a non-significant 1.1-fold higher among those with anemia only, a significant 2.2-fold higher among those with high NfL only, and a significant 3.6-fold higher among participants with both anemia and high NfL.
Elevated dementia risk also occurred when anemia was combined with high p-tau217 or GFAP levels, but no additive interaction was detected for these biomarkers.
In general, the risk associations were stronger in men than women and among participants not carrying APOE ε4 compared with carriers.
The researchers say there are several potential interpretations for their findings, including the possibility that “anemia may reduce brain resilience, thereby lowering the threshold at which neuropathology manifests clinically as dementia.”
They conclude that the study data “suggest anemia is a clinically relevant factor in the context of dementia risk stratification and is possibly a modifiable target in dementia prevention strategies.”
“Future studies should further investigate this possibility and formally assess whether—and which—blood biomarkers mediate the relationship between anemia and dementia development.”
The post Anemia May Be a Modifiable Risk Factor for Alzheimer’s Disease appeared first on Inside Precision Medicine.
STAT+: FDA eyes expanding testosterone therapy for libido
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Hellooooo, friends. Psychedelics and testosterone are front and center today, but also we note that GLP-1’s dominance in obesity may not be as inevitable as it looks. Early animal data from GLP-1 pioneers suggest that pathways like GIP-glucagon offer effectiveness and better overall tolerability.
The need-to-know this morning
- Kailera Therapeutics raised $625 million in an initial public offering — the largest-ever Wall Street debut for a drug company. Kailera is developing obesity drugs licensed from China.
Do we even need GLP-1 anymore?
The scientists whose work helped spur the development of GLP-1-based obesity drugs are now questioning whether that target is necessary at all. Instead, they’re proposing that using GIP-glucagon as a dual target could deliver comparable — or even superior — weight loss, without the nausea and dosing limitations that come with current therapies.
The deadly consequences of ICE detention
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Earth Day is next week, meaning it’s time for one of my favorite traditions: listening to the annual 24-hour livestream of a marsh in unceded W̱SÁNEĆ territory in British Columbia.
TRACERx MRD Results Showcase ppmSeq’s Ultra-Sensitive ctDNA Detection at AACR
Minimal residual disease (MRD) continues to be a central focus at the AACR meeting. The small numbers of cancer cells that remain in the body after treatment helps gauge the effectiveness of a treatment and relapse risk. The ability to detect those cells, even in tiny amounts, is an ongoing goal of the cancer community.
At this year’s AACR, the sequencing company Ultima Genomics is announcing new findings in this area using its ppmSeq technology. The data will be presented across six abstracts, including a plenary session.
Highlighting the program will be initial TRACERx (TRAcking Cancer Evolution through therapy (Rx)) MRD data showcasing performance of ppmSeq relative to ultrasensitive bespoke panels.
TRACERx is a long-term study—one of the largest tumor evolution studies—funded by Cancer Research UK. The program analyzes how cancer evolves, spreads to other parts of the body, and develops resistance to treatments. Instead of taking just one biopsy, researchers sample different parts of the same tumor and metastases; the program involves sequencing multi-region and multi-time-point genetic data from over 3,200 tumor samples from over 800 lung cancer patients.
The data will be presented at a plenary session by Charles Swanton, FRCP, BSc, PhD, professor at The Francis Crick Institute in the U.K. He will present an early validation pilot of ppmSeq across 50 plasma samples—using tumor-specific variants identified from prior whole genome sequencing—achieved high analytical sensitivity for ctDNA detection at low single-digit parts-per-million.
“TRACERx has always followed the science of cancer evolution wherever it leads,” said Swanton. “Improving the sensitivity of ctDNA detection is central to the wider ambition for MRD monitoring, and expanding studies across a broader patient population will give us the statistical power and clinical context to determine how whole genome MRD monitoring can be deployed at NHS scale and beyond.”
Data from collaborators will also be presented at the conference. Labcorp will present data from an independent analytical study of an assay developed in coordination with ppmSeq technology, including the performance across multiple solid tumor types in pre-surgical, treatment-naive plasma samples. This analysis of 120 non-cancerous donor samples showed specificity exceeding 99.9%, underscoring the ability of ppmSeq whole genome sequencing to accurately differentiate between cancerous and non-cancerous samples, minimizing false positives. Additional analysis across three commercially available cancer cell lines spanning 13 concentration levels from 0.5 to 500 parts per million showed a 95% limit of detection below 3 ppm, demonstrating the assay’s capacity to detect ultra-low levels of circulating tumor DNA (ctDNA).
“For a long time, the question has been whether you can get truly ultra-sensitive MRD detection from a whole genome approach without all the complexity of bespoke assays,” notes Gilad Almogy, PhD, CEO of Ultima Genomics. “What these AACR data show is that the answer is yes. We’re seeing ppmSeq deliver the level of sensitivity needed to make whole genome MRD practical, scalable, and much easier to deploy globally.”
The post TRACERx MRD Results Showcase ppmSeq’s Ultra-Sensitive ctDNA Detection at AACR appeared first on GEN – Genetic Engineering and Biotechnology News.
Cerebral blood flow and functional connectivity immediate changes following intradermal acupuncture in major depressive disorder
BackgroundAcupuncture has been increasingly applied as an adjunctive treatment for major depressive disorder (MDD), yet its central neurobiological mechanisms remain insufficiently understood. Cerebral blood flow (CBF) and functional connectivity strength (FCS) provide complementary perspectives on regional metabolic activity and large-scale functional integration, and their coupling may reflect neurovascular coordination relevant to depression.MethodsTwenty patients with MDD and twenty matched healthy controls (HC) underwent resting-state MRI. Patients received intradermal acupuncture (IA) and were scanned before and immediately after stimulation, while healthy controls were scanned once. Voxel-wise analyses of CBF, FCS, and their ratio (CBF/FCS) were performed to characterize acupuncture-related changes in neurovascular coupling. Group comparisons and pre–post acupuncture effects were assessed at the whole gray matter level.ResultsAcupuncture induced significant alterations in CBF/FCS coupling across widespread brain regions, including the bilateral precuneus, postcentral gyrus, superior temporal pole, superior frontal gyrus, occipital cortex, and cerebellum. These regions are primarily involved in sensorimotor processing, cognitive control, and emotional regulation. Overall, IA was associated with an immediate increase in CBF/FCS coupling, suggesting enhanced coordination between cerebral perfusion and functional network integration.ConclusionThis study provides evidence that intradermal acupuncture modulates neurovascular coupling in patients with MDD, offering neuroimaging-based insights into its antidepressant mechanisms. The findings support the notion that acupuncture may facilitate more efficient brain function by optimizing the balance between neural activity and metabolic supply.
Effect of low-intensity focused ultrasound on hippocampus of alcohol addicted mice: a preliminary study
Alcohol addiction is a chronic relapsing brain disorder characterized by significant neurobiological changes, particularly within the hippocampus, which mediates emotional regulation and reward-seeking behavior. Previous studies have shown that alcohol-induced neuronal injury contributes to withdrawal-associated anxiety and persistent alcohol preference. This study investigated the therapeutic effects of low-intensity focused ultrasound (LIFU) on the hippocampus in a mouse model of alcohol addiction. Twenty-six male C57BL/6 mice were allocated to an alcohol-exposed group (n = 20) and a control group (n = 6). Following a 28-day modeling period, the alcohol group was randomly subdivided into a therapy group and a sham group. The therapy group received LIFU treatment, while the sham group underwent an identical procedure with the ultrasound transducer powered off. After seven days of treatment, the therapy group exhibited less severe anxiety symptoms upon alcohol withdrawal and a reduced preference for alcohol compared to the sham group. The brain-derived neurotrophic factor (BDNF) concentration was significantly lower in the therapy group than in the sham group, but did not differ significantly from the control group. Hippocampal HE staining revealed more pronounced degeneration and apoptosis of granule cells in the dentate gyrus (DG) region in the sham group relative to the therapy group. These preliminary findings suggest that LIFU may modulate alcohol addiction by mitigating hippocampal neuronal injury.
Psychometric validation of the revised Chinese version of the Dimensional Anhedonia Rating Scale in psychiatric outpatients
ObjectiveTo refine the Chinese version of the Dimensional Anhedonia Rating Scale (DARS) and evaluate the psychometric properties of the Revised Chinese DARS (RC-DARS) in a large sample of first-visit psychiatric outpatients.MethodsThe study was conducted in two sequential phases at a specialized psychiatric hospital. In Phase I (n = 277), the existing Chinese DARS underwent semantic and cultural refinement in accordance with ISPOR and TRAPD guidelines, incorporating cognitive interviews and back-translation procedures. In Phase II (n = 788), the RC-DARS was administered alongside the Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Pittsburgh Sleep Quality Index (PSQI), and the MMPI Suicide Ideation Subscale (MMPI-SI). Exploratory and confirmatory factor analyses were conducted using common-factor extraction and the WLSMV estimator for ordinal indicators. Internal consistency, gender-based measurement invariance, and convergent validity were evaluated.ResultsExploratory analyses supported a four-factor domain structure. Confirmatory factor analysis demonstrated good model fit for the domain-based model (χ²/df = 3.81, CFI = 0.98, TLI = 0.97, RMSEA = 0.08, SRMR = 0.05), with substantially superior fit relative to an alternative reward-processing model. Internal consistency was excellent (Cronbach’s α = 0.95; McDonald’s ω = 0.96). Multi-group analyses supported configural, metric, and scalar invariance across gender (ΔCFI < 0.01). RC-DARS total scores were significantly negatively correlated with depressive symptoms (r = −0.443), anxiety (r = −0.317), sleep disturbance (r = −0.494), and suicide risk (r = −0.312) (all p <.001). Individuals with severe depressive symptoms exhibited significantly lower RC-DARS scores than those below the clinical threshold.ConclusionsThe RC-DARS demonstrates robust psychometric properties in a first-visit outpatient sample. The revision primarily enhances semantic precision and structural differentiation without materially altering score distributions. The scale may serve as a refined instrument for dimensional assessment of anhedonia in similar clinical contexts, pending longitudinal and multi-site validation.