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Nevin Manimala Statistics

The Cytotoxicity Profile of Silver Carboxylate in a TiO2/Polydimethylsiloxane Matrix in Osteoblasts, Keratinocytes, Endothelial Cells, and Skeletal Muscle Cells

Surg Infect (Larchmt). 2025 Dec 19. doi: 10.1177/10962964251409563. Online ahead of print.

ABSTRACT

Introduction: Surgical site infections continue to pose a major challenge in healthcare, contributing to prolonged hospitalizations and increased morbidity and mortality. Despite advancements in antimicrobial agent treatments, bacterial resistance remains an important obstacle. Among various antimicrobial agents, silver compounds have been re-evaluated for their broad-spectrum efficacy. Previous studies, have demonstrated the potential of silver carboxylate embedded in a titanium dioxide/polydimethylsiloxane (TiO2/PDMS) matrix as a material of biomedical relevance. This study aims to expand upon these findings by examining the cytotoxicity profile of silver carboxylate in four human cell lines that play a crucial role in wound healing. Hypothesis: Controlled silver elution from the TiO2/PDMS matrix produces a cytotoxicity profile comparable with commonly used antibiotic agents at clinically relevant exposures. Methods: In this study, silver carboxylate beads were prepared using a modified method, whereby silver neodecanoate was incorporated into a TiO2/PDMS matrix. The modification involved adjusting the concentration ratios to optimize the release profile for controlled silver elution. Primary human osteoblasts (OBs), keratinocytes (KTs), skeletal muscle cells (SkMs), and endothelial cells (ETs) were cultured under standard conditions and, after 24 h, were exposed to specific silver carboxylate concentrations (1×, 10×, and 100%) without additional washing steps before exposure. In addition, we included a comparative analysis with newly developed silver formulations (silver nanoparticles at 10 and 30 nM, and colloidal silver at 100 and 300 nM) and a panel of conventional antibiotic agents, including vancomycin (5 and 50 µg/mL), tobramycin (5 and 50 µg/mL), linezolid (2 and 20 µg/mL), and polymyxin E (2 µg/mL). Cell viability following exposure was measured using the MTT assay, and the results were analyzed statistically using analysis of variance followed by post hoc Tukey tests. Results: OBs exhibited marked cytotoxicity at higher silver carboxylate concentrations, particularly at the 10× condition, with viability comparable with that observed with higher dose antibiotic agents such as vancomycin 50 µg/mL and tobramycin 50 µg/mL. SkMs and ETs demonstrated limited sensitivity at 1× exposure but showed substantial loss of viability at 10×, consistent with dose-dependent toxicity. KTs were the most sensitive cell type, displaying decreased viability even at 1× exposure. The modified TiO2/PDMS matrix demonstrated an enhanced controlled release mechanism, resulting in lower cytotoxicity compared with both early silver formulations and conventional antibiotic agents. Conclusion: This study builds upon previous investigations on silver carboxylate and provides new insights into its cytotoxic effects across additional human cell lines, including ETs and SkMs. The enhanced controlled release from the modified TiO2/PDMS matrix reduces cytotoxicity compared with previous formulations and commonly used antibiotic agents. These results highlight the importance of concentration-dependent toxicity and support further evaluation of this material in future in vivo and translational studies. The cytotoxicity profile of silver carboxylate embedded in a modified TiO2/PDMS matrix shows variability across different human cell types, but may be relevant for future evaluation in models that require a detailed assessment of biocompatibility. This study expands on previous research by introducing additional cell lines and optimizing the release mechanism of silver carboxylate to enhance its cytotoxicity profile and safety. Addressing current limitations, including lactate dehydrogenase (LDH) interference, will be essential for a comprehensive evaluation and for establishing safe concentration thresholds for future in vivo applications. Future research should focus on validating these findings in animal models and evaluating the systemic effects of prolonged silver exposure.

PMID:41468057 | DOI:10.1177/10962964251409563

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Nevin Manimala Statistics

Dam break modelling and flood inundation mapping using GIS and HEC-RAS: a case study of the Tiga Earth dam, Kano State, Nigeria

Water Sci Technol. 2025 Dec;92(12):1687-1708. doi: 10.2166/wst.2025.172. Epub 2025 Dec 3.

ABSTRACT

A dam is constructed across a river, which stores and supplies water for various purposes. Though the dams have many benefits, there is always a threat of a break. The research is aimed at developing a dam break simulation model for the Tiga dam and producing an inundation map of affected areas. The study conducted a dam break analysis for the Tiga dam in Kano State, Nigeria, using HEC-RAS and HEC-HMS. The analysis simulated dam failure scenarios to predict breach parameters and flood hydrograph downstream. The results showed that 213 communities would be affected, with 122 in Jigawa State and 91 in Kano, covering an area of 4,397.06 km2. Breach peak flow was estimated as 117,000 m3/s, arriving in 31.3 min. Validation of the hydrodynamic breach model performance was done using the observed annual outflow and simulated results, employing the Nash -Sutcliffe efficiency (NSE) statistical analysis. The NSE score of 0.71 indicates a decent fit of the HEC-RAS model to the data. The study recommends that the Hadejia Jama’are River Basin Development Authority implement the findings to develop emergency response plans and flood mitigation strategies to safeguard lives and property downstream. Future studies should conduct socio-economic impacts on affected areas.

PMID:41468046 | DOI:10.2166/wst.2025.172

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Nevin Manimala Statistics

Residential Neighborhood Disadvantage and Access to Kidney Transplantation

JAMA Netw Open. 2025 Dec 1;8(12):e2549679. doi: 10.1001/jamanetworkopen.2025.49679.

ABSTRACT

IMPORTANCE: Residence in a disadvantaged neighborhood is a key driver of racial and ethnic disparities in the diagnosis and management of chronic diseases; however, its impact on disparities in access to waitlisting and kidney transplantation (KT) is unclear.

OBJECTIVE: To examine the association between neighborhood disadvantage and access to waitlisting and KT.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study (January 1, 2015, to December 31, 2021) used a US national registry to assess adults (aged ≥18 years) with end-stage kidney disease (ESKD) and adult KT candidates. Statistical analysis was performed in March 2025.

EXPOSURE: Residential neighborhood disadvantage score (built environment disadvantage, criminal injustice, education disadvantage, unemployment, housing instability, poverty, social fragmentation, transportation barrier, and wealth inequality) ascertained by American Community Survey and other public data sources.

MAIN OUTCOMES AND MEASURES: The adjusted hazard ratios (AHRs) of waitlisting and KT (any KT, live-donor KT [LDKT], and preemptive KT) were assessed across tertiles of the neighborhood disadvantage score using cause-specific hazard models. Interaction terms were used to quantify these aforementioned associations by race and ethnicity.

RESULTS: The study included 501 444 adults with ESKD initiating dialysis (mean [SD] age, 63.9 [14.6] years; 293 937 [58.6%] male; 25 790 [5.1%] Asian [Asian American, Native Hawaiian, and Pacific Islander], 133 923 [26.7%] Black, 66 323 [13.2%] Hispanic, and 275 408 [54.9%] White) and 95 068 KT candidates on the waitlist (mean [SD] age, 53.7 [13.0] years; 60 328 [63.5%] male; 6956 [7.3%] Asian, 25 215 [26.5%] Black, 15 685 [16.5%] Hispanic, and 47 212 [49.7%] White). A total of 173 880 adults with ESKD (34.7%) and 26 718 KT candidates (28.1%) resided in high-disadvantage neighborhoods. After adjustment, adults residing in high-disadvantage neighborhoods were less likely to be waitlisted (AHR, 0.71; 95% CI, 0.69-0.72) compared with those in low-disadvantage neighborhoods. Specifically, Asian (AHR, 0.87; 95% CI, 0.80-0.95), Black (AHR, 0.68; 95% CI, 0.66-0.70), Hispanic (AHR, 0.89; 95% CI, 0.86-0.92), and White (AHR, 0.68; 95% CI, 0.66-0.71) adults in high-disadvantage neighborhoods were less likely to be waitlisted compared with White adults in low-disadvantage neighborhoods. Overall, candidates residing in high-disadvantage neighborhoods were less likely to receive any KT (AHR, 0.89; 95% CI, 0.87-0.92), LDKT (AHR, 0.65; 95% CI, 0.62-0.69), and preemptive KT (AHR, 0.62; 95% CI, 0.58-0.67). Notably, Black candidates residing in high-disadvantage neighborhoods were less likely to receive KT (AHR, 0.60; 95% CI, 0.58-0.62), LDKT (AHR, 0.23; 95% CI, 0.21-0.25), and preemptive KT (AHR, 0.22; 95% CI, 0.20-0.25) compared with White candidates in low-disadvantage neighborhoods.

CONCLUSIONS AND RELEVANCE: In this cohort study of adults with ESKD and KT candidates, residence in high-disadvantage neighborhoods was associated with reduced access to waitlisting and KT; it also was associated with persistent racial and ethnic disparities in LDKT and preemptive KT. These results suggest that to support equitable access, clinicians and transplant programs should work with social workers and community advocates to implement initiatives (eg, outreach and financial support) that address structural barriers and direct resources to affected neighborhoods.

PMID:41468017 | DOI:10.1001/jamanetworkopen.2025.49679

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Foster Care and Child Maltreatment Mortality Rates in the US

JAMA Netw Open. 2025 Dec 1;8(12):e2551677. doi: 10.1001/jamanetworkopen.2025.51677.

ABSTRACT

IMPORTANCE: Approximately 2000 children die each year of child abuse and/or neglect. Foster care is designed as a targeted intervention to reduce harm to children, but its association with child maltreatment mortality is not well understood.

OBJECTIVE: To examine whether foster care entry rates are negatively associated with rates of child mortality due to child abuse and/or neglect.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study assessed associations between child maltreatment mortality rates and foster care entry rates at the state level using administrative data from all US states from January 1, 2010, to December 31, 2023 (N = 700 state-years). Administrative records on all children in state-supervised foster care and all children whose death was attributed by child welfare agencies to child maltreatment were assessed.

EXPOSURES: Number of children entering foster care per 1000 child population.

MAIN OUTCOMES AND MEASURES: Number of child fatalities due to child abuse and/or neglect per 100 000 child population.

RESULTS: The study analyzed 3.4 million records of children in state-supervised foster care from 2010 to 2023 and 24 108 child fatalities that states attributed to child abuse and/or neglect. In 2023, states reported a mean (SD) of 2.62 (1.85) deaths per 100 000 child population and reported a mean (SD) of 3.21 (1.75) entries into foster care per 1000 child population. No evidence was found of a negative association between state-year level foster care entry rates and state-year-level child maltreatment mortality rates (β = 0.17; 95% CI, 0.01-0.34).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, child maltreatment mortality rates did not appear to decrease with higher foster care entry rates or increase with decreasing foster care entry rates. This evidence suggests that there is not a negative association between child maltreatment mortality rates and foster care entry rates.

PMID:41468015 | DOI:10.1001/jamanetworkopen.2025.51677

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Oral Medications for Treating Agitation in a Safety Net Emergency Department

JAMA Netw Open. 2025 Dec 1;8(12):e2551683. doi: 10.1001/jamanetworkopen.2025.51683.

ABSTRACT

IMPORTANCE: Best-practice guidelines recommend oral medications for treating agitation in the emergency department (ED). However, there is limited study of their use in the ED, especially in the setting of drug and alcohol intoxication.

OBJECTIVE: To evaluate the implementation of oral medications to treat agitation in an ED in which intramuscular medications were standard and to increase the use of oral medications to treat agitation.

DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study analyzed 2 populations. First, all ED patients in an urban level 1 adult and pediatric trauma center from January 1, 2018, to May 31, 2024, were studied to compare the preintervention and postintervention periods. Second, during the 12-month implementation period from September 16, 2020, to August 31, 2021, patients were prospectively observed in an area of the ED dedicated to caring for patients with drug and alcohol intoxication.

EXPOSURE: Oral medications to treat agitation, including olanzapine and lorazepam, were encouraged via education and real-time feedback for ED staff.

MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients receiving their first sedating medication via the oral route. Secondary outcomes included data on time to adequate sedation and adverse drug events.

RESULTS: Of 460 600 ED encounters (median patient age, 38 years [IQR, 27-55 years]; 57.8% men; 184 050 [40.0%] before the intervention, 276 550 [60.0%] after), the proportion of patients receiving any sedating medication was similar between time periods (11.8% before intervention vs 11.5% after). The proportion of patients receiving their first sedating medication via the oral route increased after the intervention (7.2% vs 31.4%; difference, 24.2 percentage points [pp] [95% CI, 23.6-24.8 pp]). Among 1178 patients receiving sedating medications during implementation (860 [73.0%] with alcohol intoxication; median breath or blood concentration, 0.22% [IQR, 0.16%-0.28%]), 630 (53.5%) were offered oral medication, of whom 446 (70.8%) accepted it. Time to adequate sedation was 15 minutes (IQR, 7-33 minutes) for oral and 15 minutes (IQR, 9-26 minutes) for intramuscular medications (median difference, 1 minute [95% CI, -0.6 to 2.6 minutes]). There were no significant differences between routes in rates of additional rescue medications (oral, 31.8%; intramuscular, 28.4%; difference, 3.4 pp [95% CI, -2.0 to 8.8 pp]) or adverse drug reactions (oral, 2.7%; intramuscular, 1.1%; difference, 1.6 pp [95% CI, -0.1 to 3.3 pp]).

CONCLUSIONS AND RELEVANCE: In this quality improvement study, emergency physicians successfully adopted oral medications for treating agitation, primarily from intoxication. No difference was found in time to adequate sedation when oral or intramuscular medications were used as primary therapy. These data support best-practice guidelines that suggest oral medications should be first-line treatment for agitation in the ED.

PMID:41468014 | DOI:10.1001/jamanetworkopen.2025.51683

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Atopic Disease Development in Offspring Conceived via Assisted Reproductive Technology

JAMA Netw Open. 2025 Dec 1;8(12):e2551690. doi: 10.1001/jamanetworkopen.2025.51690.

ABSTRACT

IMPORTANCE: As assisted reproductive technology (ART) becomes increasingly prevalent, concerns regarding the potential short-term and long-term health outcomes of children conceived through these methods have emerged.

OBJECTIVE: To investigate whether conception via ART is associated with a risk of atopic disease development in offspring.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, population-based cohort study was conducted using data obtained from Taiwan’s National Health Insurance Research Database, Assisted Reproduction Database, and Maternal and Child Health Database. Children conceived via ART and born between January 1, 2004, and December 31, 2014, were identified as the exposure group. A control group of children conceived naturally was selected using 1:4 matching based on maternal age, neonatal sex, and birth month. Data analysis was performed from December 1, 2023, to November 1, 2025.

EXPOSURE: Conception via ART or naturally.

MAIN OUTCOMES AND MEASURES: The primary outcome was development of atopic disease. Both groups were followed up until December 31, 2020. Cox proportional hazards regression models were used to adjust potential confounders.

RESULTS: A total of 69 785 children (13 957 in the ART group and 55 828 in the control group) were included in this study, with follow-up beginning at birth. The study population was 47.5% female and 52.5% male. For the ART and control groups, the mean (SD) follow-up duration was 7.99 (4.22) and 8.41 (4.18) years for asthma, 5.79 (4.12) and 6.34 (4.28) years for allergic rhinitis, and 7.34 (5.13) and 7.62 (5.14) years for atopic dermatitis, respectively. After adjusting for potential confounders, the ART group exhibited a higher likelihood of developing asthma (adjusted hazard ratio [AHR], 1.13 [95% CI, 1.09-1.18]), allergic rhinitis (AHR, 1.15 [95% CI, 1.12-1.18]), or atopic dermatitis (AHR, 1.08 [95% CI, 1.05-1.12]) (all P < .001) compared with the control group. Subgroup analysis revealed that children conceived with fresh embryos faced a greater risk of developing allergic rhinitis compared with those conceived with frozen embryos (AHR, 1.12 [95% CI, 1.06-1.19]; P < .001).

CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that children conceived via ART had a higher risk of developing asthma, allergic rhinitis, or atopic dermatitis. These findings underscore the importance of long-term follow-up for offspring conceived via ART and further investigation into the underlying biological mechanisms by which ART may contribute to atopic disease development.

PMID:41468013 | DOI:10.1001/jamanetworkopen.2025.51690

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Accelerated Brain Aging, Atherogenicity, and Neurocognition in Adult Survivors of Childhood Cancer

JAMA Netw Open. 2025 Dec 1;8(12):e2551865. doi: 10.1001/jamanetworkopen.2025.51865.

ABSTRACT

IMPORTANCE: Long-term survivors of childhood cancer may be at elevated risk for accelerated brain aging.

OBJECTIVES: To determine the brain age gap estimation (BrainAGE), defined as the difference between estimated brain age and chronological age; the association between BrainAGE scores and poor neurocognitive outcomes; and the correlations of plasma biomarkers of oxidative stress, neuroinflammation, and cardiovascular health with older BrainAGE scores and previous exposure to central nervous system-directed therapy in adult survivors of childhood cancer.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study analyzed participants in the St. Jude Lifetime Cohort Study. Included participants were survivors of childhood cancer (brain tumor, acute lymphoblastic leukemia, and Hodgkin lymphoma) and community controls (no history of childhood cancer) aged 18 years or older with a whole brain scan following a neurocognitive assessment. BrainAGE was calculated from January 2016 to February 2021 and analyzed from February 2022 to March 2025. Treatment information, plasma biomarkers, and neurocognitive outcomes were collected.

MAIN OUTCOMES AND MEASURES: The primary outcome was estimated brain age (using previously trained machine learning pipelines) and associations of brain age with neurocognitive outcomes. Associations among BrainAGE scores, plasma biomarkers, and neurocognitive outcomes were examined using multivariable linear regression models and Spearman correlations.

RESULTS: A total of 253 survivors of childhood cancer (127 males [50.2%]; mean [SD] age, 31.7 [8.6] years; mean [SD] time since diagnosis, 21.2 [9.8] years) and 43 community controls (24 females [55.8%]; mean [SD] age at evaluation, 31.4 [9.6] years) were included in analyses. Survivors had significantly higher mean BrainAGE scores than controls (6.6 [95% CI, -12.5 to 41.1] years vs 0.7 [95% CI, -1.0 to 2.4] years older than chronological age; P < .001). A 10-year increase in BrainAGE score was associated with lower cognitive flexibility (β = -0.63; 95% CI, -0.82 to -0.45), processing speed (β = -0.49; 95% CI, -0.67 to -0.31), working memory (β = -0.28; 95% CI, -0.53 to -0.03) and visual memory (β = -0.40; 95% CI, -0.58 to -0.22), vocabulary (β = -0.33; 95% CI, -0.48 to -0.18), and reading (β = -0.31; 95% CI, -0.45 to -0.18) z scores after adjusting for age at diagnosis and sex. Neurofilament light was correlated with BrainAGE score in female survivors (Spearman ρ = 0.24 [P = .04]) and controls (Spearman ρ = -0.47 [P = .03]). Female survivors who were younger than 10 years at cancer diagnosis and treated with 40 Gy or higher cranial radiation had mean BrainAGE scores higher than 30 years (37.34 [95% CI, 17.4-41.0] years) older than chronological age (P = .004) and had lower sex hormone precursor correlated with higher BrainAGE score (Spearman ρ = -0.44 [P = .01]) and higher cranial radiation dose (Spearman ρ = -0.48 [P = .01]). Among male survivors, correlations of BrainAGE score and cranial radiation dose with malondialdehyde (Spearman ρ = -0.25 [P = .04] and -0.26 [P = .04]) and oxidized low-density lipoprotein (Spearman ρ = 0.24 [P = .049] and 0.40 [P = .001]) were identified.

CONCLUSION AND RELEVANCE: This cross-sectional study found that accelerated brain aging was associated with poorer neurocognitive outcomes and correlated with cranial radiation, biomarkers of atherogenesis, neuronal damage, and sex hormone precursors. These findings can guide future research efforts to reduce the risk of vascular disease in this at-risk population.

PMID:41468012 | DOI:10.1001/jamanetworkopen.2025.51865

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Recent Advances in the Biosensors for the Detection of Lung Cancer Biomarkers: A Review

Crit Rev Anal Chem. 2025 Dec 30:1-13. doi: 10.1080/10408347.2025.2606194. Online ahead of print.

ABSTRACT

Nearly 10 million deaths from cancer occurred in 2020, making it a major cause of death globally, according to the WHO and other important statistics. Given that lung cancer is one of the most prevalent types of cancer, it accounts for around 25% of all deaths from cancer-related causes. The two forms of lung cancer that are treated and characterized differently are small-cell and non-small-cell lung cancer. To identify malignant cells, several techniques have been used in recent decades, including MRI (magnetic resonance imaging), CT (computed tomography scans), and PET (positron emission tomography). The standard detection threshold of conventional assays is insufficient for early-stage detection. As a result, numerous detection techniques have been used to identify lung cancer early. The stages of lung cancer are indicated by the amounts of these biomarkers. As a result, lung cancer screening and clinical diagnosis can be accomplished by the identification of biomarkers. EGFR, CEA, CYFRA 21-1, ENO1, NSE, CA 19-9, CA 125, and VEGF are among the many biomarkers for lung cancer. To identify lung cancer disease biomarkers, an organized summary of several biosensing platforms is given in this article. In particular, it addresses the most recent advancements in optical and electrochemical biosensors, the analytical capabilities of various biosensors, the challenges, and potential directions for future study in regular clinical analysis. Therefore, this study reviews the latest developments and enhancements (2011-2025) in biosensors for the identification of biomarkers for lung cancer.

PMID:41467998 | DOI:10.1080/10408347.2025.2606194

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Robotic-Assisted Versus Laparoscopic Adrenalectomy: Outcome Comparison from a Single-Center Experience

J Laparoendosc Adv Surg Tech A. 2025 Dec 18. doi: 10.1177/10926429251408415. Online ahead of print.

ABSTRACT

Background: Robotic-assisted laparoscopic adrenalectomy (RALA) became a useful tool for the treatment of adrenal lesions. This study aims to identify areas where RALA may offer better outcomes than laparoscopic techniques. Methods: We conducted a retrospective study between August 2014 and November 2024. We involved 321 patients who underwent adrenalectomy during this time. Among these patients, 170 had laparoscopic adrenalectomy (LA), and 151 underwent RALA. We grouped these patients according to the surgical approach, collected, and analyzed preoperative data, and compared their perioperative and postoperative outcomes. Results: In this study, we compared two groups, showing the robotic approach was associated with a significantly shorter operative time compared with the laparoscopic group, 100.5 (±51.7) minutes versus 117.9 (±67.4) minutes, P = .02. There were no significant differences in estimated blood loss (P = .97) or conversion to open (P = .6) between the two groups. But robotic patients did exhibit a shorter duration of hospital stay, a median of 1 versus 2 days in the case of the laparoscopic approach, P value <0.01, and statistically lower 30-day complication rates in the robotic approach, 7.3% versus 14.7%, P = .035. Other short- and long-term complications were comparable between the two groups. Subanalysis of large tumor mass (>5 cm) showed comparable outcomes, with robotic cases showing statistically lower early complication rates (P = .05). Conclusion: The study shows that RALA offers some advantages compared to the traditional LA, particularly with shorter operative time, lesser hospital stay, and fewer early complications. More randomized trials will help to confirm the findings and reach a more definitive conclusion.

PMID:41467988 | DOI:10.1177/10926429251408415

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Efficacy and Safety of Adjunctive Bile Acid Sequestrant Therapy for Thyrotoxicosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Thyroid. 2025 Dec 18. doi: 10.1177/10507256251409074. Online ahead of print.

ABSTRACT

Background: Bile acid sequestrants have been reported to reduce serum thyroid hormone levels by binding T4 and T3 excreted into the intestinal lumen, preventing their reabsorption into the systemic circulation and interrupting the enterohepatic circulation of these hormones. This meta-analysis evaluates whether adjunctive bile acid sequestrants accelerate reductions in serum iodothyronine when added to standard hyperthyroidism therapy. Methods: A systematic review and meta-analysis were conducted and registered in PROSPERO (CRD42025643217). MEDLINE, Embase, Web of Science, and Cochrane databases were searched from March 1971 to September 2025 for randomized controlled trials (RCTs) assessing adult non-critically ill patients with hyperthyroidism treated with standard therapy (thionamides and beta-blocker) plus adjunctive bile acid sequestrants (cholestyramine or colestipol) versus standard therapy alone. Primary outcomes included a reduction in serum-free T4 and total T3. The secondary outcome was adverse effect frequency. Results: Initial search yielded 705 results. After removal of duplicates and title/abstract screening, 17 full-text articles were reviewed, and five RCTs met the inclusion criteria, totaling 173 adult patients: 93 (53.75%) received adjunctive therapy, and 80 (46.25%) were controls. Causes for thyrotoxicosis included Graves’ disease, toxic adenoma, and multinodular goiter. Doses ranged from cholestyramine 1 g twice a day to 4 g four times a day, and colestipol 20 g daily. At 2 weeks of treatment, bile acid sequestrants showed a non-significant reduction in serum total T3 (mean difference [MD] -0.44 nmol/L, 95% confidence interval [CI]: -1.2 to +0.32) and free T4 level (MD -0.55 ng/dL, CI: -1.15 to +0.04). At 4 weeks, there was a statistically significant reduction in total T3 (MD -1.59 nmol/L, CI: -2.90 to -0.27) and free T4 level (MD -1 ng/dL, CI: -1.74 to -0.25). Conclusions: Adjunctive bile acid sequestrants with standard hyperthyroidism therapy appear to enhance reductions in serum total T3 and free T4 at the mark of four weeks and were well tolerated. However, due to considerable heterogeneity and low quality of evidence, our results should be interpreted with caution. Larger, high-quality RCTs are needed to strengthen the evidence regarding the efficacy of adjunctive bile acid sequestrant therapy.

PMID:41467975 | DOI:10.1177/10507256251409074