Tag: pubmed

Pharmacoeconomics. 2025 Jan 3. doi: 10.1007/s40273-024-01462-z. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Approximately half of lung adenocarcinomas in East Asia harbor epidermal growth factor receptor (EGFR) mutations. EGFR testing followed by tissue-based next-generation sequencing (NGS), upfront tissue-based NGS, and complementary NGS approaches have emerged on the front line to guide personalized therapy. We study the cost effectiveness of exclusionary EGFR testing for Taiwanese patients newly diagnosed with advanced lung adenocarcinoma.

METHODS: This economic evaluation was conducted from the perspective of the healthcare sector with a lifetime horizon. Simulated patients were entered into a joint model combining decision trees and partitioned survival models upon diagnosis of advanced lung adenocarcinoma. We compared exclusionary EGFR testing with upfront tissue-based NGS and complementary NGS approaches. The model inputs were derived from regional estimates (prevalence of targetable gene alterations), trials (testing accuracy, survival outcomes, and adverse events), ACT Genomics (testing costs), National Health Insurance payments, retail prices (drug costs), and hospital cohorts (utility values). All costs were made equivalent to 2023 US dollars. An annual discount rate of 3% was applied. We adopted a willingness-to-pay threshold of US$70,000 per quality-adjusted life-year. One-way deterministic and probabilistic analyses were performed.

RESULTS: The incremental cost-effectiveness ratio of exclusionary EGFR testing versus upfront tissue-based NGS was US$15,521 per quality-adjusted life-year, whereas the incremental net monetary benefit was US$2530. The costs of osimertinib and pembrolizumab were the major determinants. The incremental net monetary benefit of exclusionary EGFR testing versus complementary NGS approach was US$2174, and its major determinants included the true-negative rate of EGFR testing and the prevalence rate of an EGFR mutation. Given the willingness-to-pay thresholds of US$35,000, US$70,000, and US$105,000 (1, 2, and 3 per capita gross domestic product) per quality-adjusted life-year, the probabilities that exclusionary EGFR testing would be cost effective were 79.1%, 95.6%, and 91.2%, respectively.

CONCLUSIONS: Our analysis suggests that exclusionary EGFR testing is a cost-effective strategy for Taiwanese patients newly diagnosed with advanced lung adenocarcinoma.

PMID:39752129 | DOI:10.1007/s40273-024-01462-z

Bull Math Biol. 2025 Jan 3;87(2):26. doi: 10.1007/s11538-024-01402-0.

ABSTRACT

Immune events such as infection, vaccination, and a combination of the two result in distinct time-dependent antibody responses in affected individuals. These responses and event prevalence combine non-trivially to govern antibody levels sampled from a population. Time-dependence and disease prevalence pose considerable modeling challenges that need to be addressed to provide a rigorous mathematical underpinning of the underlying biology. We propose a time-inhomogeneous Markov chain model for event-to-event transitions coupled with a probabilistic framework for antibody kinetics and demonstrate its use in a setting in which individuals can be infected or vaccinated but not both. We conduct prevalence estimation via transition probability matrices using synthetic data. This approach is ideal to model sequences of infections and vaccinations, or personal trajectories in a population, making it an important first step towards a mathematical characterization of reinfection, vaccination boosting, and cross-events of infection after vaccination or vice versa.

PMID:39752117 | DOI:10.1007/s11538-024-01402-0

CJEM. 2025 Jan 3. doi: 10.1007/s43678-024-00839-5. Online ahead of print.

ABSTRACT

OBJECTIVES: POCUS is a core emergency medicine skill and mainstay of early pregnancy assessment. The ultrasound competency assessment tool was developed as an entrustment-based assessment tool for use by content experts evaluating trainees performing multiple POCUS study types. The objective of this study was to evaluate the scoring and extrapolation inferences of the tool within Kane’s validity framework when used to assess trainees performing an early pregnancy POCUS.

METHODS: This was a multicentered study of emergency medicine residents participating in a POCUS assessment. After a background questionnaire, participants were read a case stem requesting a POCUS evaluation of an early pregnancy patient. Trainees were independently assessed by two fellowship-trained faculty. Descriptive statistics and two-way random, intraclass correlation coefficients, Cronbach’s alpha were calculated on the merged data and used to assess all domains. Domain scores and an entrustment score for each participant were used to create a composite score. A one-way analysis of variance was performed.

RESULTS: 36 trainees and 5 assessors completed the study. When used to assess trainee POCUS performance in early pregnancy, the tool demonstrated good to excellent interrater reliability for image acquisition, image generation, clinical integration, and entrustment (intraclass correlation coefficients 80-91 p < .001). The preparation domain had poor, but statistically significant interrater reliability (intraclass correlation coefficient 0.46 p = .04). An analysis of variance suggested the POCUS performance scores differed based on prior experience [F(2,32) = 3.74, p = .021).

CONCLUSION: This study adds further validity evidence relating to scoring and extrapolation of the ultrasound competency assessment tool when used to assess trainees performing a POCUS study in early pregnancy.

PMID:39752091 | DOI:10.1007/s43678-024-00839-5

World J Pediatr. 2025 Jan 3. doi: 10.1007/s12519-024-00861-8. Online ahead of print.

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus (T2DM) poses an escalating public health challenge among adolescents and young adults worldwide. Despite the rising incidence, comprehensive data on the burden and trends of T2DM in this demographic remain scarce. This study aims to evaluate the burden of T2DM among individuals aged 10-24 years globally, regionally, and nationally from 1990 to 2021.

METHODS: Utilizing data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, we assessed incidence rates, disability-adjusted life-years (DALYs), and average annual percentage changes (AAPCs) for T2DM in the specified age group. Analyses accounted for variations by age, sex, and socio-demographic index (SDI). Joinpoint regression analysis identified years of significant trend shifts.

RESULTS: The global incidence of T2DM among adolescents and young adults rose from 56.02 per 100,000 (95% UI 43.03-72.32) in 1990 to 123.86 per 100,000 (95% UI 100.43-149.79) in 2021, reflecting an AAPC of 3.01 (95% CI 2.78-3.23). Notable increases were recorded in 1995, 2002, and 2009, with joinpoints indicating significant trend stabilization post-2010 for prevalence and DALYs. The largest relative incidence increase was observed in the 15-19 age group [AAPC 2.97 (95% CI 2.71-3.24)]. Although T2DM mortality was 2.4 times higher in the 15-19 age group compared to the 20-24 age group, the latter exhibited a significantly higher overall mortality rate. Regionally, Oceania recorded the highest incidence rates in 2021, while North Africa and the Middle East showed the greatest AAPCs. High-SDI countries experienced the most substantial increase in T2DM burden, with males comprising 54.8% of cases.

CONCLUSIONS: From 1990 to 2021, the global burden of T2DM among adolescents and young adults has markedly increased, underscoring the necessity for targeted, region-specific interventions to address this issue. The observed demographic disparities in mortality rates necessitate the implementation of age-specific strategies. Furthermore, the emergent trends in T2DM indicators warrant urgent attention to mitigate the rising burden in this vulnerable population.

PMID:39752048 | DOI:10.1007/s12519-024-00861-8

Community Ment Health J. 2025 Jan 3. doi: 10.1007/s10597-024-01441-w. Online ahead of print.

ABSTRACT

Pharmacists are highly accessible healthcare professionals with presence in communities, hospitals, and clinics. They are well positioned to expand their roles in supporting individuals with mental health challenges. A cross-sectional study was conducted to identify trends in how pharmacists assess, monitor, identify, and care for patients with mental health challenges. The survey was distributed to licensed pharmacists in Washington State (n = 8,082) in 2023. Questions addressed the provision of mental health supports and services provided by pharmacists, respondents’ self-assessed preparedness in delivering services, and professional and personal demographics. Data were analyzed using descriptive statistics and logistic regression. A total of 856 responses were received (10.6%) and 810 were included in the final dataset. Most respondents held a PharmD degree (74%). Common practice environments included community (37%), hospital (27%), and clinic (21%) settings. Less than 1% were board-certified psychiatric pharmacists. The most common mental health services provided involved medication-related services, including talking to patients regarding psychiatric medication (51%), consulting with physicians (47%), and assessing side effects (45%). Over 60% of pharmacists reported being prepared to deliver these services. Less than 30% of pharmacists indicated they were prepared to conduct mental health screenings or make referrals, and provision of these services was low. A statistically significant association was found between preparedness and providing supports and services (p < 0.001). Overall, pharmacists indicated they were more prepared and frequently delivered services related to medication use for mental health indications, while preparedness and offerings for non-medication activities was low, highlighting opportunities for further professional development.

PMID:39752035 | DOI:10.1007/s10597-024-01441-w

Aging Clin Exp Res. 2025 Jan 3;37(1):18. doi: 10.1007/s40520-024-02911-7.

ABSTRACT

BACKGROUND: Many studies have developed or validated predictive models to estimate the risk of sarcopenia in dialysis patients, but the quality of model development and the applicability of the models remain unclear.

OBJECTIVE: To systematically review and critically evaluate currently available predictive models for sarcopenia in dialysis patients.

METHODS: We systematically searched five databases until March 2024. Observational studies that developed or validated predictive models or scoring systems for sarcopenia in dialysis patients were considered eligible. We included studies of adults (≥ 18 years of age) on dialysis and excluded studies that did not validate the predictive model. Data extraction was performed independently by two authors using a standardized data extraction table based on a checklist of key assessments and data extraction for systematic evaluation of predictive modeling research. The quality of the model was assessed using the Predictive Model Risk of Bias Assessment Tool.

RESULTS: Of the 104,454 studies screened, 13 studies described 13 predictive models. The incidence of sarcopenia in dialysis patients ranged from 6.6 to 34.4%. The most commonly used predictors were age and body mass index. In the derivation set, the reported area under the curve or C-statistic is between 0.81 and 0.95. The area under the curve reported by the external validation set is between 0.78 and 0.93. All studies had a high risk of bias, mainly due to poor reporting in the outcome and the analysis domains, and three studies had a high risk of bias in terms of applicability.

CONCLUSION: Future research should focus on validating and improving existing predictive models or developing new models using rigorous methods.

PMID:39752019 | DOI:10.1007/s40520-024-02911-7

Clin Exp Med. 2025 Jan 3;25(1):28. doi: 10.1007/s10238-024-01545-3.

ABSTRACT

Sepsis is a major cause of morbidity and mortality worldwide. Among the various types of end-organ damage associated with sepsis, hepatic injury is linked to significantly higher mortality rates compared to dysfunction in other organ systems. This study aimed to investigate potential biomarkers of hepatic injury in sepsis patients through a multi-center, case-control approach. We enrolled three matched cohorts: 37 sepsis patients with hepatic dysfunction (S-HD), 37 sepsis patients without hepatic dysfunction (S-CON), and 18 healthy controls (HC). We measured five proposed biomarkers of hepatic dysfunction-ARG1, MDH1, GSTα, 5-NT, and SDH-using multiplex immunoassays. These biomarkers were compared to traditional markers of hepatic dysfunction, including albumin, bilirubin, ALT, AST, and GGT, across the cohorts using both conventional statistical methods and machine learning techniques. The median age of participants was comparable across cohorts: S-HD (65.0 years, IQR 49.5-82.5), S-CON (65.0 years, IQR 48.0-81.5), and HC (62.5 years, IQR 53.0-65.0; P = 0.794). Patients with hepatic dysfunction (S-HD) exhibited higher illness severity scores compared to those without hepatic dysfunction (S-CON): MODS scores were median 7.0 (IQR 4.0-10.0) in S-HD versus median 4.0 (IQR 2.0-7.0) in S-CON (P = 0.005), and SOFA scores were median 7.0 (IQR 4.0-11.0) in S-HD versus median 3.0 (IQR 2.0-6.0) in S-CON (P < 0.001). Hemoglobin and platelet counts were lower, while creatinine levels were higher in S-HD compared to S-CON (P < 0.05). On ICU Day 1, bilirubin, ALT, AST, GGT, and INR were significantly elevated in S-HD relative to S-CON (P ≤ 0.001), and albumin levels were lower (P < 0.05). Additionally, ARG1, GSTα, 5-NT, and SDH were significantly higher in S-HD patients on ICU Day 1 compared to S-CON (P < 0.05). ARG1, MDH1, and SDH showed positive correlations with AST, ALT, and MODS (P < 0.01). From ICU Day 1 to Day 7, ARG1, GSTα, SDH, and AST levels significantly decreased in S-HD patients (P < 0.05), whereas MDH1 and 5-NT levels did not. Among the proposed biomarkers, GSTα and 5-NT did not correlate with traditional hepatic dysfunction markers but were significant in identifying S-HD patients (feature importance 0.131 and 0.097, respectively) in a random forest classification model. This comprehensive model demonstrated excellent performance in distinguishing sepsis patients with hepatic injury, with sensitivity 0.93, specificity 0.94, NPV 0.94, PPV 0.94, and AUC 0.94. The biomarkers ARG1, MDH1, GSTα, 5-NT, and SDH show promise as novel indicators of hepatic dysfunction associated with sepsis. This study provides a foundational basis for subsequent research aimed at characterizing and clinically validating these markers. Future investigations should focus on integrating these potential biomarkers into routine laboratory assessments for sepsis and related hepatic injury.

PMID:39751971 | DOI:10.1007/s10238-024-01545-3

Lasers Med Sci. 2025 Jan 3;40(1):6. doi: 10.1007/s10103-024-04275-w.

ABSTRACT

To assess and compare two techniques of low-level laser application-transgingival (TLLLT) and intrasulcular (ILLLT)-used in photobiomodulation as an adjunct to basic periodontal therapy (BPT) in patients with periodontitis. A randomized, split-mouth, double-blind clinical trial was conducted, selecting three diseased periodontal sites from different quadrants in each patient. These sites were assigned to one of three treatment groups: SRP (control), SRP + TLLLT (test 1), and SRP + ILLLT (test 2). Low-level laser therapy in the test groups was applied at 48 h, 7 days, and 14 days after full-mouth SRP. Clinical parameters such as probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) were assessed at baseline (T0), 3 months (T1), and 6 months (T2). Standardized periapical radiographs were used to assess radiographic bone density (RBD) 6 months post-treatment. Statistical analyses included repeated measures ANOVA for continuous variables and chi-square tests for categorical variables, with significance set at p < 0.05 and a 95% confidence interval. Significant reductions in PD (p < 0.001) and CAL (p < 0.001) were observed across all groups at 3 and 6 months, with no significant differences between groups. There were also no significant changes in BOP and RBD between groups at the follow-up intervals. Adjunctive photobiomodulation did not provide additional clinical or radiographic benefits over SRP alone, regardless of the laser application technique employed.

PMID:39751964 | DOI:10.1007/s10103-024-04275-w

Oral Maxillofac Surg. 2025 Jan 3;29(1):23. doi: 10.1007/s10006-024-01319-x.

ABSTRACT

PURPOSE: This study aimed to evaluate the dental and skeletal stability one year after Miniscrew-Assisted Rapid Palatal Expansion (MARPE) by using 3D image data.

METHODS: Patients with transverse maxillary deficiency from the age of 16 onwards were enrolled consecutively in this prospective longitudinal cohort study. The MARPE appliance was digitally and individually designed and fabricated. Cone-beam computed tomography (CBCT) scans and intra-oral scans (IOS) were acquired before the start of MARPE treatment (T0), immediately after active expansion (T1) and one-year post-expansion (T2). Nasal floor width (NFW), palatal alveolar width at the first molar (M1) and first premolar (P1) (PAW), nasal cavity width (NCW), intermolar width (IMW) and interpremolar width (IPW) were measured to assess the immediate (ΔT0-T1) and net (ΔT0-T2) skeletal and dentoalveolar expansion and relapse (ΔT1-T2). Potential correlations with age, sex and midpalatal suture maturation (MSM) stage were also investigated.

RESULTS: Thirty-one patients (6 men, 25 women, mean age: 26.2 years) were included. The mean follow-up time (T0-T2) was 12.2 months. The initial NFW increase demonstrated a relapse of 0.6 ± 1.2 mm, or 11.6% of the initial expansion (p < 0.01). Expansion at the alveolar level remained stable during the follow-up. IPW also remained stable during the follow-up (4.2 ± 1.3 mm at T1; 4.4 ± 2.6 mm at T2). IMW exhibited a relapse of 3.8 ± 2.1 mm, or 60.2% of the initial expansion (p < 0.001) during T1-T2. There was no statistically significant correlation between stability and age, sex and MSM stage.

CONCLUSIONS: MARPE is an effective therapy for the correction of transverse maxillary discrepancy in late adolescents and adults, achieving a clinically stable skeletal outcome one year after expansion.

PMID:39751963 | DOI:10.1007/s10006-024-01319-x

Mol Genet Genomics. 2025 Jan 3;300(1):12. doi: 10.1007/s00438-024-02221-7.

ABSTRACT

Precursors of microRNAs (pre-miRNAs) are less used in silico to mine miRNAs. This study developed PmiR-Select^® based on covariance models (CMs) to identify new pre-miRNAs, detecting conserved secondary structural features across RNA sequences and eliminating the redundancy. The pipeline preceded PmiR-Select^® filtered 20% plant pre-miRNAs (from 38589 to 8677) from miRBase. The second filter reduced pre-miRNAs by 7% (from 8677 to 8045) through length limit to pre-miRNAs (70-300 nt) and miRNAs (20-24 nt). The 80% redundancy threshold was statistically the best, eliminating 55% pre-miRNAs (from 8045 to 3608). Angiosperms retained the highest number of pre-miRNAs and their families (2981 and 2202), followed by gymnosperms (362 and 271), bryophytes (183 and 119), and algae (82 and 78). Thirty-seven conserved pre-miRNA families happened among plant land clades, but none with algae. The PmiR-Select^® was applied to the rice genome, producing 8536 pre-miRNAs from 36 families. The 80% redundancy threshold retained 3% pre-miRNAs (n = 264) from 36 families, valuable experimental and computational research resources. 14% (n = 1216) of 8536 were new pre-miRNAs from 19 new families in rice. Only 16 new sequences from six families overlapped (39 to 54% identities) with rice pre-miRNAs and five species on miRBase. The validation against mature miRNAs identified 8086 pre-miRNAs from 13 families. Eleven ones have already been recorded, but two new and abundant pre-miRNAs [miR437 (n = 296) and miR1435 (n = 725)] scattered in all 12-rice chromosomes. PmiR-Select^® identified pre-miRNAs, decreased the redundancy, and discovered new miRNAs. These findings pave the way to delineating benchtop and computational experiments.

PMID:39751956 | DOI:10.1007/s00438-024-02221-7