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Nevin Manimala Statistics

Cell Death Regulation by Smed-foxO in the Planarian Schmidtea mediterranea

Methods Mol Biol. 2025;2871:179-191. doi: 10.1007/978-1-0716-4217-7_17.

ABSTRACT

The planarian Schmidtea mediterranea shows nutrient-dependent whole-body plasticity. Starvation leads to body size reduction, while feeding triggers growth. The balance of cell proliferation and cell death controls cell number, driving organismal body size. Here, we uncovered the role of FoxO in controlling cell death through TUNEL and caspase-3 assays and bak qPCR detection in foxO RNAi planarians.

PMID:39565589 | DOI:10.1007/978-1-0716-4217-7_17

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Nevin Manimala Statistics

Quantification of normal bone and osseous metastases in castration-resistant prostate cancer using SPECT/CT with xSPECT Quant: prospective imaging sub-study of a phase 2 clinical trial investigating the combination of pembrolizumab plus radium-223 compared to radium-223 alone

Radiol Med. 2024 Nov 20. doi: 10.1007/s11547-024-01931-7. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study is to demonstrate the consistency and reproducibility of quantitative SPECT/CT by evaluating the maximum SUV (SUVmax) in normal bone, to provide the reference value of metastatic lesions, and to evaluate the clinical implication of SUVmax changes of osseous metastasis during treatment.

MATERIAL AND METHODS: This prospective imaging sub-study was performed as part of a phase 2 clinical trial of patients with metastatic castration-resistant prostate cancer (mCRPC) randomized to the combination of pembrolizumab plus radium-223 or to radium-223 alone (NCT03093428). The maximum standardized uptake value (SUVmax) and mean Hounsfield Unit (HUmean) of normal bone as well as metastases were measured using a 1.5 cm region of interest (ROI) on CT and xSPECT Quant reconstruction on the baseline study (S0) and restaging scans. The most tracer-avid metastatic lesion in each patient on S0 was selected as a target lesion, and changes of SUVmax and HUmean of the target lesion were compared on the first restaging scan (S1). Correlations between the percentage changes of SUVmax of the target lesion with alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were assessed.

RESULTS: Twenty-one patients were enrolled on the imaging sub-study of which 15 had paired baseline S0 and S1 data. On S0, the median SUVmax and HUmean of normal bone was 5.85 g/mL (0.42-14.98) and 133.03 (range, 28.47-461.91), respectively. The median SUVmax and HUmean of metastasis were 42.2 g/mL (range, 17.96-143.36) and 549.58 (177.87-1107.64), respectively. There was significant reduction in SUVmax (- 40.1%, range – 86.2 to + 23.5%), p < 0.001) and increase in HUmean (+ 8.3%, range – 11.3 to + 61.7%, p = 0.0479, Wilcoxon signed-rank test) of target lesions between S0 and S1. Spearman correlation between the percentage changes of SUVmax of a target lesion and both serum PSA (r = 0.33, p = 0.226) and ALP (r = 0.45, p = 0.094) were not statistically significant.

CONCLUSION: Quantitative SPECT/CT provides consistent and objective imaging parameters, which can help monitor tumor burden. The median SUVmax of metastasis at baseline was roughly 7.2-fold higher than normal bone. Quantitative SPECT/CT may help visualize the early osteoblastic treatment response in prostate cancer patients treated with radium-223 alone or combined with pembrolizumab.

PMID:39565570 | DOI:10.1007/s11547-024-01931-7

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Nevin Manimala Statistics

Evaluating the Effectiveness of Prophylactic Strategies for Hemophilia A Management: A Real-World, Longitudinal Observational Study

Drugs Real World Outcomes. 2024 Nov 20. doi: 10.1007/s40801-024-00452-z. Online ahead of print.

ABSTRACT

BACKGROUND: Hemophilia A (HA) treatment strategies aim to manage bleeding episodes and improve patients’ quality of life. This study investigates the effectiveness of a preventative approach using intermediate-dose prophylaxis with standard half-life FVIII products in reducing bleeding rates and enhancing the quality of life for patients with severe HA.

METHODS: A 4-year prospective longitudinal study followed 35 patients with severe HA (without FVIII inhibitors) who transitioned from a reactive treatment approach to intermediate-dose prophylaxis in Taiwan from 2014 until 2018. The study tracked annual bleeding rates (ABR) and annual joint bleeding rates (AjBR) alongside associated costs and patient-reported quality-of-life measures.

RESULTS: Prophylaxis significantly reduced both ABR and AjBR compared with the previous treatment. After one year, ABR and AjBR decreased by 76.9% and 72.5%, respectively, with further reductions to 91.0% and 90.8% after 4 years (p < 0.001). While the average annual cost of factor VIII concentrate increased by 41.0% in the first year, the incremental cost-effectiveness ratio demonstrated ongoing benefits from ABR avoidance over the 4 years. Additionally, patients reported significant improvements in quality-of-life measures following the switch to prophylaxis (p = 0.036).

CONCLUSION: Intermediate-dose prophylaxis effectively reduced bleeding rates and improved quality of life in patients with severe HA. Despite initial cost increases, the intervention became cost effective over time. This study provides valuable data for healthcare policymakers, highlighting the long-term benefits of prophylaxis as a preventative approach for managing bleeding and improving overall well-being in patients with severe HA.

PMID:39565566 | DOI:10.1007/s40801-024-00452-z

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Nevin Manimala Statistics

EQ-5D-5L value set for Norway: a hybrid model using cTTO and DCE data

Qual Life Res. 2024 Nov 20. doi: 10.1007/s11136-024-03837-3. Online ahead of print.

ABSTRACT

PURPOSE: To develop the Norwegian value set for the EQ-5D-5L based on interviews with a representative sample of the Norwegian adult population.

METHODS: Random and quota sampling were used to recruit the sample of adults (age> 18 years) representative of the Norwegian general population. Data collection followed EQ-VT 2.1 undertaken before and after the COVID-19 pandemic from November 2019 to December 2022, using PC-assisted and video conferencing interviews, respectively. Each respondent valued 10 health states using composite time trade-off (cTTO) and 7 health states using a discrete choice experiment (DCE). Different statistical models were assessed for logical consistency and predictive accuracy using cTTO and DCE data alone or in combination as hybrid models.

RESULTS: Of the 1,321 respondents, 1,237 met inclusion criteria. All statistical models demonstrated logical consistency. The weighted hybrid model combining both cTTOand DCE data was preferred and had the highest predictive accuracy. Predicted values ranged from -0.453 to 1, and the dimension of anxiety/depression was the most highly valued by respondents, followed by pain/discomfort, self-care, mobility, and usual activities. These findings are not dissimilar to those for most Western European countries, and regression coefficients are closest to those for other Scandinavian countries.

CONCLUSION: This study provides the Norwegian value set for the EQ-5D-5L based on health state values obtained from members of the adult general population in Norway. This is an important contribution to economic evaluation and the broader application ofthe EQ-5D-5L in Norway including clinical and health services research, and quality measurement.

PMID:39565555 | DOI:10.1007/s11136-024-03837-3

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Nevin Manimala Statistics

Health-related quality of life profiles of adults with arthritis and/or fibromyalgia: a cross-sectional study

Qual Life Res. 2024 Nov 20. doi: 10.1007/s11136-024-03831-9. Online ahead of print.

ABSTRACT

PURPOSE: Adults with arthritis experience poor health-related quality of life (HRQOL), though research often focuses on single HRQOL outcomes or summary scores. We aimed to identify HRQOL profiles in adults with different arthritis types and determine risk and protective factors.

METHODS: Data including PROMIS-29 Profile v2.1 and PROMIS Short Form v2.0 – Emotional Support 4a were collected through a national foundation’s online survey of adults with arthritis in the U.S. We used latent profile analysis (LPA) to characterize the heterogeneity in arthritis patients by clustering them into HRQOL profiles, based on statistical model fit and clinical interpretability. We fit a multinomial logistic regression model with HRQOL profile assignment as the outcome to determine associations with protective and risk factors.

RESULTS: We included 25,305 adults with arthritis. The LPA results favored a five-HRQOL profile solution (entropy = 0.83). While some profiles displayed better HRQOL in some domains, 93% of the sample displayed impacted pain and physical functioning. One profile (20%) displayed mean T-scores nearly 2 standard deviations below the population mean. Despite poor physical HRQOL outcomes, one profile (10%) displayed average mental health. All demographic and clinical factors contributed significantly to the model, including risk factors (arthritis types, work status) and protective factors (more emotional support, starting exercise).

CONCLUSION: We identified profiles with consistently impacted HRQOL in arthritis, though one displayed average mental health functioning despite poor physical functioning. These results highlight the value of considering the patient’s HRQOL experience alongside treatment options, and the potentially positive impact of non-pharmacological interventions.

PMID:39565554 | DOI:10.1007/s11136-024-03831-9

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Nevin Manimala Statistics

Health-related quality of life and its association with socioeconomic status and mental health in 5- to 7-year-old children: a cross-sectional study

Qual Life Res. 2024 Nov 20. doi: 10.1007/s11136-024-03834-6. Online ahead of print.

ABSTRACT

PURPOSE: Assessing socioeconomic status (SES), mental health, and health-related quality of life (HRQoL) in young children is crucial for making informed health care decisions and identifying areas of intervention. The present study aimed to investigate potential associations between SES, mental health, and HRQoL in 5-7-year-old children.

METHOD: The present study included mother-reported health assessments for 621 children aged 5-7 years in Grade 1 collected between 2019 and 2023 as part of the Starting Right™ project. Online questionnaires were used to support public health nurses in assessing children’s health status. HRQoL (KIDSCREEN-27, 5 subscales) and mental health [Strength and Difficulties Questionnaire (SDQ), 4 subscales] were assessed. Sociodemographic characteristics, sex, maternal education, and income were obtained from Statistics Norway. The data were analyzed using multiple robust regression.

RESULTS: Mother-reported mean scores for the KIDSCREEN-27 were within the normal range compared with European norms (8-11 years). However, for each KIDSCREEN-27 dimension, there were individuals whose mothers reported scores that were substantially lower than average. Having mental health problems, defined as being in the 80th and 90th percentiles of the SDQ Total problem score, was associated with 2.1-10.7-point lower KIDSCREEN-27 scores (p < 0.001-0.021), which was most noticeable in the KIDSCREEN-27 school environment subscale. Weak but significant positive associations were found between SES and HRQoL.

CONCLUSION: Our results provide important insights into the associations between SES, mental health, and HRQoL in young children. Given the strong association between mental health problems and HRQoL in Grade 1 children, the assessment of both is essential, so that early interventions, an improved caring environment, and nurturing support can be initiated.

PMID:39565553 | DOI:10.1007/s11136-024-03834-6

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Nevin Manimala Statistics

Multiple social factors are associated with wellbeing when accounting for shared genetic and environmental confounding

Qual Life Res. 2024 Nov 20. doi: 10.1007/s11136-024-03832-8. Online ahead of print.

ABSTRACT

PURPOSE: Social factors are associated with mental health and wellbeing. However, few studies have examined genetic and environmental influences on social factors themselves, limiting current understanding of influences on aspects of the social environment. Most studies which have identified links between social factors and mental health are also limited by the possible influence of unmeasured genetic and environmental confounding. In this study, we investigated the genetic and environmental underpinnings of multiple social factors (relationship satisfaction, loneliness, attachment, trust, relationship disruptions), and their associations with life satisfaction measured concurrently and six years later, after accounting for shared genetic and environmental confounding.

METHODS: Data from a population-based sample of adult twins (N = 1987) and two measurement timepoints were used for the primary analyses. We used multivariate Cholesky models to estimate genetic and environmental influences across five social factors. Subsequently, we conducted co-twin control analyses to examine associations between social factors and wellbeing after controlling for shared genetic and environmental confounding.

RESULTS: Heritability estimates for the social factors ranged from 24 to 42%. Genetic correlations across social factors were substantial, indicative of considerable genetic overlap. Associations between wellbeing and relationship satisfaction, loneliness, anxious and avoidant attachment, trust, and disruptions in relationships in the past year were attenuated in co-twin control analyses but remained statistically significant. Relationship satisfaction, loneliness, and attachment avoidance were also associated with wellbeing measured six years later in estimates which controlled for shared genetic and environmental confounding.

CONCLUSION: Our findings provide evidence that multiple social factors are associated with wellbeing after accounting for potential confounding by shared genetic and/or environmental factors. These findings highlight the importance of multiple aspects of the social environment for wellbeing in older adulthood. Future studies should examine the directionality in associations between social factors and mental health and assess these relationships beyond older adulthood.

PMID:39565552 | DOI:10.1007/s11136-024-03832-8

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Nevin Manimala Statistics

Development of a prediction model for recurrent parathyroid carcinoma lesions based on 3D-EnCT and ultrasound imaging features

Clin Transl Oncol. 2024 Nov 20. doi: 10.1007/s12094-024-03787-9. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to analyze the three-dimensional enhanced computed tomography (3D-EnCT) and ultrasound imaging features of recurrent parathyroid carcinoma lesions and develop a prediction model based on these features.

METHODS: The clinical data of 34 patients (48 cases) with recurrent parathyroid carcinoma who underwent surgical treatment at Beijing Chaoyang Hospital’s Thyroid and Neck Surgery Department between January 2017 and April 2024 were retrospectively analyzed. A total of 103 suspicious lesions were identified through a combination of preoperative 3D-EnCT and ultrasound examinations. Patients admitted prior to 1 January 2023 were included in the training set, and those admitted after 1 January 2023 were included in the validation set. In the training set, lesions were categorized as positive or negative based on pathological analysis. Statistically significant imaging features were identified via intergroup comparisons. An imaging prediction model was developed based on the 3D-EnCT and ultrasound features, and the predictive performance of the model was evaluated via receiver operating characteristic curves in the validation set.

RESULTS: Arterial- and venous-phase CT values, lesion boundaries, and blood flow signals were associated with pathological positivity. The 3D-EnCT prediction model based on these features achieved areas under the curve (AUCs) of 0.9 and 0.714 in the training and validation sets, respectively, whereas the ultrasound prediction model achieved AUCs of 0.601 and 0.621, respectively. The 3D-EnCT model demonstrated superior predictive performance.

CONCLUSION: The 3D-EnCT prediction model demonstrated superior predictive performance for recurrent parathyroid carcinoma lesions.

PMID:39565549 | DOI:10.1007/s12094-024-03787-9

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Nevin Manimala Statistics

Differential risk of healthcare workers versus the general population during outbreak, war and pandemic crises

Eur J Epidemiol. 2024 Nov 20. doi: 10.1007/s10654-024-01169-7. Online ahead of print.

ABSTRACT

Healthcare workers may have different risk for severe outcomes compared with the general population during diverse crises. This paper introduces the concept of healthcare worker versus population hazard (HPH), the risk of an outcome of interest in active healthcare workers compared with the general population they serve. HPH can be expressed with relative risk (HPH(r)) and absolute risk difference (HPH(a)) metrics. Illustrative examples are drawn from infectious outbreaks, war, and the COVID-19 pandemic on death outcomes. HPH can be extreme for lethal outbreaks (HPH(r) = 30 to 143, HPH(a) = 8 to 91 per 1000 for Ebola deaths in 3 Western African countries in 2013-5), and modestly high in relative terms and very high in absolute terms for protracted, major armed conflicts (HPH(r) = 1.38 and HPH(a) = 10.2 for Syria during 2011-2024). Conversely, healthcare workers had 8-12-fold lower risk than the population they served for pandemic excess deaths (physicians in USA) or COVID-19 deaths (physicians in Ontario, healthcare workers in Finland), while healthcare workers in Indonesia did not have this advantage for COVID-19 deaths versus the general population. HPH is susceptible to data inaccuracies in numbers of at-risk populations and of outcomes of interest. Importantly, inferences about healthcare worker risk can be misleading, if deaths of retired healthcare workers contaminate the risk calculations- as in the case of misleading early perceptions of exaggerated COVID-19 risk for healthcare professionals. HPH can offer useful insights for risk assessment to healthcare professionals, the general public, and policy makers and may be useful to monitor for planning and interventions during crises.

PMID:39565536 | DOI:10.1007/s10654-024-01169-7

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Nevin Manimala Statistics

The Jiangsu Biobank for the Prevention and Control of Diabetes (JBPCD) in China

Eur J Epidemiol. 2024 Nov 20. doi: 10.1007/s10654-024-01172-y. Online ahead of print.

ABSTRACT

The Jiangsu Biobank for the Prevention and Control of Diabetes (JBPCD) is a community-based prospective cohort study initiated in Jiangsu province, to examine the burden of complications associated with type 2 diabetes mellitus (T2DM). This study aims to better understand the incidence, risk factors, and long-term outcomes of T2DM complications to inform prevention and control strategies. From October 2013 to July 2014, 20,053 T2DM patients (7,862 males and 12,191 females) were recruited from Suzhou city and Huai’an city. Baseline data were collected through questionnaire survey, physical examination and biochemical testing, with blood samples stored in a biobank. The follow-up focused on the incidence and mortality related to T2DM complications, linked to national and local medical datasets. Between August 2019 and October 2020, the repeated assessments were completed for 13,973 participants, including questionnaire, physical examination and repeated blood collection. The study identified 1,479 new cancer cases and 3,324 cardiovascular disease cases, with an overall mortality rate of 25.66 per 1,000 person-years. JBPCD welcomes research collaborations and data access requests via email. Currently, there are no plans to provide cohort data for free public access, but specific proposals for further collaboration are welcome. For further information and collaboration, please email [[email protected]] and [[email protected]].

PMID:39565534 | DOI:10.1007/s10654-024-01172-y