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Nevin Manimala Statistics

Cardiac manifestations of Fabry disease in G3Stg/GlaKO and GlaKO mouse models-Translation to Fabry disease patients

PLoS One. 2024 May 31;19(5):e0304415. doi: 10.1371/journal.pone.0304415. eCollection 2024.

ABSTRACT

Fabry disease (FD) is an X-linked disorder of glycosphingolipid metabolism caused by mutations in the GLA gene encoding alpha-galactosidase A (α-Gal). Loss of α-Gal activity leads to progressive lysosomal accumulation of α-Gal substrate, predominately globotriaosylceramide (Gb3) and its deacylated derivative globotriaosylsphingosine (lyso-Gb3). FD manifestations include early onset neuropathic pain, gastrointestinal symptoms, and later onset life-threatening renal, cardiovascular and cerebrovascular disorders. Current treatments can preserve kidney function but are not very effective in preventing progression of cardiovascular pathology which remains the most common cause of premature death in FD patients. There is a significant need for a translational model that could be used for testing cardiac efficacy of new drugs. Two mouse models of FD have been developed. The α-Gal A-knockout (GlaKO) model is characterized by progressive tissue accumulation of Gb3 and lyso-Gb3 but does not develop any Fabry pathology besides mild peripheral neuropathy. Reports of minor cardiac function abnormalities in GlaKO model are inconsistent between different studies. Recently, G3Stg/GlaKO was generated by crossbreeding GlaKO with transgenic mice expressing human Gb3 synthase. G3Stg/GlaKO demonstrate higher tissue substrate accumulation and develop cellular and tissue pathologies. Functional renal pathology analogous to that found in early stages of FD has also been described in this model. The objective of this study is to characterize cardiac phenotype in GlaKO and G3Stg/GlaKO mice using echocardiography. Longitudinal assessments of cardiac wall thickness, mass and function were performed in GlaKO and wild-type (WT) littermate controls from 5-13 months of age. G3Stg/GlaKO and WT mice were assessed between 27-28 weeks of age due to their shortened lifespan. Several cardiomyopathy characteristics of early Fabry pathology were found in GlaKO mice, including mild cardiomegaly [up-to-25% increase in left ventricular (LV mass)] with no significant LV wall thickening. The LV internal diameter was significantly wider (up-to-24% increase at 9-months), when compared to the age-matched WT. In addition, there were significant increases in the end-systolic, end-diastolic volumes and stroke volume, suggesting volume overload. Significant reduction in Global longitudinal strain (GLS) measuring local myofiber contractility of the LV was also detected at 13-months. Similar GLS reduction was also reported in FD patients. Parameters such as ejection fraction, fractional shortening and cardiac output were either only slightly affected or were not different from controls. On the other hand, some of the cardiac findings in G3Stg/GlaKO mice were inconsistent with Fabry cardiomyopathy seen in FD patients. This could be potentially an artifact of the Gb3 synthase overexpression under a strong ubiquitous promoter. In conclusion, GlaKO mouse model presents mild cardiomegaly, mild cardiac dysfunction, but significant cardiac volume overload and functional changes in GLS that can be used as translational biomarkers to determine cardiac efficacy of novel treatment modalities. The level of tissue Gb3 accumulation in G3Stg/GlaKO mouse more closely recapitulates the level of substrate accumulation in FD patients and may provide better translatability of the efficacy of new therapeutics in clearing pathological substrates from cardiac tissues. But interpretation of the effect of treatment on cardiac structure and function in this model should be approached with caution.

PMID:38820517 | DOI:10.1371/journal.pone.0304415

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Nevin Manimala Statistics

Temporal trends in peripartum hysterectomy among individuals with a previous cesarean delivery by race/ethnicity in the United States: A population-based cohort study

PLoS One. 2024 May 31;19(5):e0304777. doi: 10.1371/journal.pone.0304777. eCollection 2024.

ABSTRACT

OBJECTIVES: Rates of severe maternal morbidity have highlighted persistent and growing racial disparities in the United States (US). We aimed to contrast temporal trends in peripartum hysterectomy by race/ethnicity and quantify the contribution of changes in maternal and obstetric factors to temporal variations in hysterectomy rates.

METHODS: We conducted a population-based, retrospective study of 5,739,569 US residents with a previous cesarean delivery, using National Vital Statistics System’s Natality Files (2011-2021). Individuals were stratified by self-identified race/ethnicity and classified into four periods based on year of delivery. Temporal changes in hysterectomy rates were estimated using odds ratios (ORs) and 95% confidence intervals (CIs). We used sequential logistic regression models to quantify the contribution of maternal and obstetric factors to temporal variations in hysterectomy rates.

RESULTS: Over the study period, the peripartum hysterectomy rate increased from 1.23 (2011-2013) to 1.44 (2019-2021) per 1,000 deliveries (OR 2019-2021 vs. 2011-2013 = 1.17, 95% CI 1.10 to 1.25). Hysterectomy rates varied by race/ethnicity with the highest rates among Native Hawaiian and Other Pacific Islander (NHOPI; 2.73 per 1,000 deliveries) and American Indian or Alaskan Native (AIAN; 2.67 per 1,000 deliveries) populations in 2019-2021. Unadjusted models showed a temporal increase in hysterectomy rates among AIAN (2011-2013 rate = 1.43 per 1,000 deliveries; OR 2019-2021 vs. 2011-2013 = 1.87, 95% CI 1.02 to 3.45) and White (2011-2013 rate = 1.13 per 1,000 deliveries; OR 2019-2021 vs. 2011-2013 = 1.21, 95% CI 1.11 to 1.33) populations. Adjustment ranged from having no effect among NHOPI individuals to explaining 14.0% of the observed 21.0% increase in hysterectomy rates among White individuals.

CONCLUSION: Nationally, racial disparities in peripartum hysterectomy are evident. Between 2011-2021, the rate of hysterectomy increased; however, this increase was confined to AIAN and White individuals.

PMID:38820511 | DOI:10.1371/journal.pone.0304777

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Nevin Manimala Statistics

High groundwater depletion risk in South Korea in 2080s

Team utilizes advanced statistical techniques to project the future groundwater depletion risk.
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Nevin Manimala Statistics

Current khat (Catha edulis F.) use among Ethiopian women and its association with anemia and underweight: A cross-sectional analysis from Ethiopian Demographic and Health Survey

PLoS One. 2024 May 31;19(5):e0297831. doi: 10.1371/journal.pone.0297831. eCollection 2024.

ABSTRACT

BACKGROUND: Chewing fresh leaves of Catha edulis (khat) is a popular pastime activity among Ethiopians where 12% women chew it. Reports show that khat use has been associated with poor nutritional status. This study aimed to determine whether khat chewing is linked to underweight and anemia.

METHOD: We analyzed data from the 2016 Ethiopian Demographic and Health Survey (EDHS). The EDHS used two stage stratified cluster sampling to collected data from 16,650 households. We used data from a total of 15,683 respondents and 1904 respondents who chewed ever chewed khat in their lives. We used Pearson’s chi-square, and logistic regression while stratifying by residence (urban vs rural) to control for confounders.

RESULT: Our results indicated 10.7% (95%CI: 10.92,11.26) of women chewed khat for an average of 16.5 days in the previous month. A woman’s current khat chewing status was significantly associated with age, educational level, region, religion, wealth group, and marital status. Women aged 40-44 were significantly more likely to chew (AOR = 2.89,) compared to those aged 15-19. Compared with Protestant women, Muslim women were 210 times more likely (AOR = 210, 95% CI 102,435.7) to chew and women in the poorest wealth quintile had 73% higher odds (AOR = 1.73, 95% CI 1.22,2.44) of chewing khat when compared with the richest. Anemia was not associated with a woman’s chewing status, whereas rural women who chewed khat for more than 26 days in a month had a 78% increased risk (OR = 1.78) of being underweight when compared to non-chewers.

CONCLUSION: Khat chewing is associated with sociodemographic factors and current khat use is associated with a higher risk of underweight among women living in rural areas. Implementing targeted awareness campaigns for women about the risks of khat chewing is recommended.

PMID:38820499 | DOI:10.1371/journal.pone.0297831

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Nevin Manimala Statistics

Exposure to mass media chronic health campaign messages and the uptake of non-communicable disease screening in Ghana

PLoS One. 2024 May 31;19(5):e0302942. doi: 10.1371/journal.pone.0302942. eCollection 2024.

ABSTRACT

The main goal of this study was to examine the relationship between exposure to mass media health campaign massages and the uptake of non-communicable diseases (NCDs) screening services in Ghana and whether this relationship differs by place of residence. Available evidence suggests a general low uptake of NCDs screening in developing country settings. Unfortunately, many NCDs evolve very slowly and are consequently difficult to detect early especially in situations where people do not screen regularly and in settings where awareness is low. In this study, we contribute to understanding the potential role of the media in scaling up NCDs screening in developing countries. We fitted multivariate logistic regression models to a sample of 1337 individual surveys which were collected at the neighborhood level in three Ghanaian cities. Overall, the results show that exposure to mass media chronic NCD health campaign messages was significantly associated with increased likelihood of screening for NCDs. The results further highlight neighborhood-level disparities in the uptake of NCDs screening services as residents of low-income and deprived neighborhoods were significantly less likely to report being screened for NCDs. Other factors including social capital, knowledge about the causes of NCDs and self-rated health predicted the likelihood of chronic NCDs screening. The results demonstrate mass media can be an important tool for scaling up NCDs screening services in Ghana and similar contexts where awareness might be low. However, place-based disparities need to be addressed.

PMID:38820497 | DOI:10.1371/journal.pone.0302942

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Nevin Manimala Statistics

Venovenous bypass in adult liver transplant recipients: A single-center observational case series

PLoS One. 2024 May 31;19(5):e0303631. doi: 10.1371/journal.pone.0303631. eCollection 2024.

ABSTRACT

BACKGROUND: Very little information is currently available on the use and outcomes of venovenous bypass (VVB) in liver transplantation (LT) in adults in Australia. In this study, we explored the indications, intraoperative course, and postoperative outcomes of patients who underwent VVB in a high-volume LT unit.

METHODS: The study was a single-center, retrospective observational case series of adult patients who underwent VVB during LT at Austin Health in Melbourne, Australia between March 2008 and March 2022. Information on baseline preoperative status and intraoperative variables, including specific VVB characteristics as well as postoperative and VVB-related complications was collected. The lengths of intensive care unit and hospital stays as well as intraoperative and in-hospital mortality were recorded.

RESULTS: Of the 900 LTs performed at this center during the aforementioned 14-year period, 27 (3%) included a VVB procedure. VVB was performed electively in 16 of these 27 patients (59.3%) and as a rescue technique to control massive bleeding in the other 11 (40.1%). The median (interquartile range [IQR]) age of those who underwent VVB procedures was 48 (39-55) years; the median age was 56 (47-62) years in the non-VVB group (p<0.0001). The median model for end-stage liver disease (MELD) scores were similar between the two patient groups. Complete blood data was available for 622 non-VVB patients. Twenty-six VVB (96.3%) and 603 non-VVB (96.9%) patients required intraoperative blood transfusions. The median (IQR) number of units of packed red blood cells transfused was 7 (4.8-12.5) units in the VVB group compared to 3.0 units (1.0-6.0) in the non-VVB group (p<0.0001). Inpatient mortality was 18.5% and 1.1% for the VVB and non-VVB groups, respectively (p<0.0001). There were no significant differences in length of hospital stay or incidence of acute kidney injury, primary graft dysfunction, or long-term graft failure between the two groups. Patients in the VVB group experienced a higher rate of postoperative non-anastomotic biliary stricture compared to patients in the non-VVB group (33% and 7.9%, respectively; p = 0.0003).

CONCLUSIONS: VVB continues to play a vital role in LT. This case series highlights the heightened risk of major complications linked to VVB. However, the global transition to selective use of VVB underscores the urgent need for collaborative multi-center studies designed to address outstanding questions and parameters related to the safe implementation of this procedure.

PMID:38820491 | DOI:10.1371/journal.pone.0303631

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Nevin Manimala Statistics

MCE: Medical Cognition Embedded in 3D MRI feature extraction for advancing glioma staging

PLoS One. 2024 May 31;19(5):e0304419. doi: 10.1371/journal.pone.0304419. eCollection 2024.

ABSTRACT

In recent years, various data-driven algorithms have been applied to the classification and staging of brain glioma MRI detection. However, the restricted availability of brain glioma MRI data in purely data-driven deep learning algorithms has presented challenges in extracting high-quality features and capturing their complex patterns. Moreover, the analysis methods designed for 2D data necessitate the selection of ideal tumor image slices, which does not align with practical clinical scenarios. Our research proposes an novel brain glioma staging model, Medical Cognition Embedded (MCE) model for 3D data. This model embeds knowledge characteristics into data-driven approaches to enhance the quality of feature extraction. Approach includes the following key components: (1) Deep feature extraction, drawing upon the imaging technical characteristics of different MRI sequences, has led to the design of two methods at both the algorithmic and strategic levels to mimic the learning process of real image interpretation by medical professionals during film reading; (2) We conduct an extensive Radiomics feature extraction, capturing relevant features such as texture, morphology, and grayscale distribution; (3) By referencing key points in radiological diagnosis, Radiomics feature experimental results, and the imaging characteristics of various MRI sequences, we manually create diagnostic features (Diag-Features). The efficacy of proposed methodology is rigorously evaluated on the publicly available BraTS2018 and BraTS2020 datasets. Comparing it to most well-known purely data-driven models, our method achieved higher accuracy, recall, and precision, reaching 96.14%, 93.4%, 97.06%, and 97.57%, 92.80%, 95.96%, respectively.

PMID:38820482 | DOI:10.1371/journal.pone.0304419

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Nevin Manimala Statistics

Predicting Lung Cancer Survival to the Future: Population-Based Cancer Survival Modeling Study

JMIR Public Health Surveill. 2024 May 31;10:e46737. doi: 10.2196/46737.

ABSTRACT

BACKGROUND: Lung cancer remains the leading cause of cancer-related mortality globally, with late diagnoses often resulting in poor prognosis. In response, the Lung Ambition Alliance aims to double the 5-year survival rate by 2025.

OBJECTIVE: Using the Taiwan Cancer Registry, this study uses the survivorship-period-cohort model to assess the feasibility of achieving this goal by predicting future survival rates of patients with lung cancer in Taiwan.

METHODS: This retrospective study analyzed data from 205,104 patients with lung cancer registered between 1997 and 2018. Survival rates were calculated using the survivorship-period-cohort model, focusing on 1-year interval survival rates and extrapolating to predict 5-year outcomes for diagnoses up to 2020, as viewed from 2025. Model validation involved comparing predicted rates with actual data using symmetric mean absolute percentage error.

RESULTS: The study identified notable improvements in survival rates beginning in 2004, with the predicted 5-year survival rate for 2020 reaching 38.7%, marking a considerable increase from the most recent available data of 23.8% for patients diagnosed in 2013. Subgroup analysis revealed varied survival improvements across different demographics and histological types. Predictions based on current trends indicate that achieving the Lung Ambition Alliance’s goal could be within reach.

CONCLUSIONS: The analysis demonstrates notable improvements in lung cancer survival rates in Taiwan, driven by the adoption of low-dose computed tomography screening, alongside advances in diagnostic technologies and treatment strategies. While the ambitious target set by the Lung Ambition Alliance appears achievable, ongoing advancements in medical technology and health policies will be crucial. The study underscores the potential impact of continued enhancements in lung cancer management and the importance of strategic health interventions to further improve survival outcomes.

PMID:38819904 | DOI:10.2196/46737

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Comparison of the Working Alliance in Blended Cognitive Behavioral Therapy and Treatment as Usual for Depression in Europe: Secondary Data Analysis of the E-COMPARED Randomized Controlled Trial

J Med Internet Res. 2024 May 31;26:e47515. doi: 10.2196/47515.

ABSTRACT

BACKGROUND: Increasing interest has centered on the psychotherapeutic working alliance as a means of understanding clinical change in digital mental health interventions in recent years. However, little is understood about how and to what extent a digital mental health program can have an impact on the working alliance and clinical outcomes in a blended (therapist plus digital program) cognitive behavioral therapy (bCBT) intervention for depression.

OBJECTIVE: This study aimed to test the difference in working alliance scores between bCBT and treatment as usual (TAU), examine the association between working alliance and depression severity scores in both arms, and test for an interaction between system usability and working alliance with regard to the association between working alliance and depression scores in bCBT at 3-month assessments.

METHODS: We conducted a secondary data analysis of the E-COMPARED (European Comparative Effectiveness Research on Blended Depression Treatment versus Treatment-as-usual) trial, which compared bCBT with TAU across 9 European countries. Data were collected in primary care and specialized services between April 2015 and December 2017. Eligible participants aged 18 years or older and diagnosed with major depressive disorder were randomized to either bCBT (n=476) or TAU (n=467). bCBT consisted of 6-20 sessions of bCBT (involving face-to-face sessions with a therapist and an internet-based program). TAU consisted of usual care for depression. The main outcomes were scores of the working alliance (Working Alliance Inventory-Short Revised-Client [WAI-SR-C]) and depressive symptoms (Patient Health Questionnaire-9 [PHQ-9]) at 3 months after randomization. Other variables included system usability scores (System Usability Scale-Client [SUS-C]) at 3 months and baseline demographic information. Data from baseline and 3-month assessments were analyzed using linear regression models that adjusted for a set of baseline variables.

RESULTS: Of the 945 included participants, 644 (68.2%) were female, and the mean age was 38.96 years (IQR 38). bCBT was associated with higher composite WAI-SR-C scores compared to TAU (B=5.67, 95% CI 4.48-6.86). There was an inverse association between WAI-SR-C and PHQ-9 in bCBT (B=-0.12, 95% CI -0.17 to -0.06) and TAU (B=-0.06, 95% CI -0.11 to -0.02), in which as WAI-SR-C scores increased, PHQ-9 scores decreased. Finally, there was a significant interaction between SUS-C and WAI-SR-C with regard to an inverse association between higher WAI-SR-C scores and lower PHQ-9 scores in bCBT (b=-0.030, 95% CI -0.05 to -0.01; P=.005).

CONCLUSIONS: To our knowledge, this is the first study to show that bCBT may enhance the client working alliance when compared to evidence-based routine care for depression that services reported offering. The working alliance in bCBT was also associated with clinical improvements that appear to be enhanced by good program usability. Our findings add further weight to the view that the addition of internet-delivered CBT to face-to-face CBT may positively augment experiences of the working alliance.

TRIAL REGISTRATION: ClinicalTrials.gov NCT02542891, https://clinicaltrials.gov/study/NCT02542891; German Clinical Trials Register DRKS00006866, https://drks.de/search/en/trial/DRKS00006866; Netherlands Trials Register NTR4962, https://www.onderzoekmetmensen.nl/en/trial/25452; ClinicalTrials.Gov NCT02389660, https://clinicaltrials.gov/study/NCT02389660; ClinicalTrials.gov NCT02361684, https://clinicaltrials.gov/study/NCT02361684; ClinicalTrials.gov NCT02449447, https://clinicaltrials.gov/study/NCT02449447; ClinicalTrials.gov NCT02410616, https://clinicaltrials.gov/study/NCT02410616; ISRCTN Registry ISRCTN12388725, https://www.isrctn.com/ISRCTN12388725?q=ISRCTN12388725&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10; ClinicalTrials.gov NCT02796573, https://classic.clinicaltrials.gov/ct2/show/NCT02796573.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-016-1511-1.

PMID:38819882 | DOI:10.2196/47515

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Shifting the Lens on Lung Cancer Screening Inequities

JAMA Netw Open. 2024 May 1;7(5):e2412782. doi: 10.1001/jamanetworkopen.2024.12782.

NO ABSTRACT

PMID:38819829 | DOI:10.1001/jamanetworkopen.2024.12782