Nevin Manimala

Science. 2025 Mar 28;387(6741):1397-1401. doi: 10.1126/science.adp5357. Epub 2025 Mar 27.

ABSTRACT

Prior research on racial profiling has found that in encounters with law enforcement, minorities are punished more severely than white civilians. Less is known about the causes of these encounters and their implications for our understanding of racial profiling. Using high-frequency location data of rideshare drivers in Florida (N = 222,838 individuals), we estimate the effect of driver race on citations and fines for speeding using 19.3 million location pings. Compared with a white driver traveling the same speed, we find that racial or ethnic minority drivers are 24 to 33% more likely to be cited for speeding and pay 23 to 34% more money in fines. We find no evidence that accident and reoffense rates explain these estimates, which suggests that an animus against minorities underlies our results.

PMID:40146819 | DOI:10.1126/science.adp5357

PLoS Med. 2025 Mar 27;22(3):e1004565. doi: 10.1371/journal.pmed.1004565. eCollection 2025 Mar.

ABSTRACT

BACKGROUND: Adverse drug reactions (ADRs) harm patients and are costly for healthcare systems. Genetic variation contributes to variability in medication response and prospective knowledge of these variants can decrease risk of ADRs, as shown in the PREPARE trial. Reduction in ADRs would affect only those reactions to drugs contained in well-validated pharmacogene-drug pairs. The scope of ADRs represented by these drugs on a population scale is unclear. The objective of this study was to characterize the pharmacogene-drug-associated ADR reporting landscape from a national regulatory pharmacovigilance dataset to elucidate the scale of potential ADR mitigation by pharmacogenomics (PGx) implementation.

METHODS AND FINDINGS: All publicly available Yellow Card ADR reports to the United Kingdom Medicines and Healthcare Products Regulatory Agency, from 1963 to 2024, were compiled using programmatic data extraction. The ADRs were analysed with descriptive statistics, stratified by PGx status and by associated genes. Prescribing prevalence from the literature was compared with age range matched ADR reports for PGx-associated drugs. There were 1,345,712 ADR reports, attributed to 2,499 different substances. 115,789 adverse drug reports (9%) were associated with drugs for which ADR risk can be modified based on pharmacogenomic prescribing guidance. Seventy-five percent of these (n = 87,339) were due to medicines which interact with only three pharmacokinetic pharmacogenes (CYP2C19, CYP2D6, SLCO1B1). Forty-seven percent of all the PGx mitigatable ADRs identified were attributed to psychiatric medications (n = 54,846), followed by 24% attributed to cardiovascular medications (n = 28,279). Those experiencing PGx mitigatable ADRs, as compared with non-PGx mitigatable ADRs, were older and the ADRs more often consisted of severe non-fatal reactions. Many PGx-associated psychiatric drug ADRs were overrepresented as compared with prescribing prevalence, but fatal cardiac arrhythmias were uncommon consequences, comprising only 0.4% of these ADRs (n = 172 of n = 48,315 total ADRs). Limitations of this data source include under reporting of ADRs and reporting bias. These findings are based on analysis of the Yellow Card dataset described and may not represent all ADRs from a generalised patient population.

CONCLUSIONS: Nine percent of all reported ADRs are associated with drugs where a genetic variant can cause heightened risk of an ADR and inform prescribing. A panel of only three pharmacogenes could potentially mitigate three in every four PGx modifiable ADRs. Based on our findings, Psychiatry may be the single highest impact specialty to pilot PGx to reduce ADRs and associated morbidity, mortality and costs.

PMID:40146782 | DOI:10.1371/journal.pmed.1004565

Int J Surg. 2025 Mar 28. doi: 10.1097/JS9.0000000000002363. Online ahead of print.

ABSTRACT

BACKGROUND: Percutaneous nephrolithotomy (PCNL) is widely regarded as the first-line treatment for upper urinary tract stones larger than 2 cm, as recommended by major urological associations. However, a growing body of research highlights the safety and effectiveness of retrograde intrarenal surgery (RIRS) for managing stones of this size in the upper urinary tract, especially with the advent of suction-assisted techniques in RIRS. This study aims to systematically evaluate the safety and efficacy of negative pressure aspiration-assisted retrograde intrarenal surgery (NPAA-RIRS) in comparison to traditional PCNL.

METHOD: Eligible studies were found by searching the PubMed, Embase, Web of Science and the CNKI databases for relevant reports published until July 2024. Outcome measures included initial and final stone-free rate (SFR), secondary operation, operation time, hemoglobin level reduction, blood transfusion, interventional embolization, postoperative hospital stay, complications. The assessment of publication bias was conducted using a funnel plot. Ten studies from nine articles were included, involving 1,259 patients.

RESULTS: NPAA-RIRS group showed lower hemoglobin level reduction (WMD = – 1.31, 95% CI [-1.64, – 0.99], P < 0.001), less blood transfusion (RR = 0.15, 95% CI [0.05, 0.50], P = 0.002), shorter postoperative hospital stay (WMD: – 1.93, 95% CI [-2.54, – 1.32], P < 0.001), lower Clavien-Dindo I-II complication rate (RR: 0.51, 95% CI [0.38, 0.67], P < 0.001), and lower overall complication rate (RR = 0.52, 95% CI [0.40, 0.68], P < 0.001) compared to the PCNL group. The PCNL group had shorter operation time (WMD = 0.68, 95% CI [0.22, 1.13], P = 0.003), higher initial SFR (RR = 0.87, 95% CI [0.83, 0.92], P < 0.001), and lower rate of secondary operation (RR = 2.51, 95% CI [1.52, 4.12], P < 0.001) compared to the NPAA-RIRS group. There were no statistically significant differences between the two groups in interventional embolization (RR = 0.28, 95% CI [0.06, 1.33], P = 0.11), final SFR (RR = 0.98, 95% CI [0.94, 1.01], P = 0.740), and Clavien-Dindo III-IV complication rate (RR: 0.65, 95% CI [0.28, 1.51], P = 0.316).

CONCLUSION: For upper urinary tract stones larger than 2 cm, both NPAA-RIRS and PCNL are equally safe and effective, achieving comparable final SFR. NPAA-RIRS offers advantages in terms of reduced complications, whereas PCNL shows benefits in shorter operation times and a lower likelihood of requiring secondary procedures. Clinicians can therefore select the most suitable approach based on individual patient circumstances.

PMID:40146778 | DOI:10.1097/JS9.0000000000002363

PLoS One. 2025 Mar 27;20(3):e0320689. doi: 10.1371/journal.pone.0320689. eCollection 2025.

ABSTRACT

Elder mistreatment (EM) of older persons with cognitive impairment is thought to be grossly underestimated in part due to communication barriers experienced by victims and a lack of consistent screening and reporting, which can skew current understandings of this problem. To improve EM risk and prevalence screening in relation to cognitive impairment, it is important to understand specific approaches for implementing assessment tools and interventions for members of this population. Accordingly, this scoping review (OSF registration osf.io/759k3) will identify, summarize, and compare methodological considerations adopted in studies assessing EM risk and occurrence among older persons with varying degrees of cognitive impairment. Through mapping out existing strategies and approaches used to develop, test, and implement EM screening tools or interventions, this review will outline previously identified recommendations and challenges pertinent to future EM assessment, reduction, and prevention efforts. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines and apply the Arksey and O’Malley (2005) scoping review framework. We will identify relevant studies by comprehensively searching electronic databases, including Ovid (Medline), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Cochrane Trials (CENTRAL), and Elsevier’s Scopus. Reference lists of included studies will also be examined. For article selection, we will use Covidence software to guide a two-step process of title/abstract and full article screening, which will allow us to identify eligible studies based on our inclusion and exclusion criteria that follows the Study Design, Data, Methods, Outcomes (SDMO) framework. A standardized data extraction tool will be used to collect information related to authors, year of publication, research objectives, sample and study design characteristics, measures, analysis, outcomes, limitations, and study conclusions and implications related to cognition. Data will be analyzed using a thematic approach and presented through the reporting of descriptive statistics and summaries.

PMID:40146770 | DOI:10.1371/journal.pone.0320689

Ophthalmol Ther. 2025 Mar 27. doi: 10.1007/s40123-025-01128-9. Online ahead of print.

ABSTRACT

INTRODUCTION: Amblyopia is a neurodevelopmental disorder characterized by a reduction in best-corrected visual acuity (BCVA). This meta-analysis aimed to analyze the effectiveness of perceptual learning and video game training for adults with amblyopia.

METHODS: Following Cochrane guidelines (PROSPERO CRD42024504502), we conducted a systematic search across multiple databases. Randomized controlled trials (RCTs) on adults with amblyopia receiving behavioral therapies were included. Data on interventions, sample size, and logMAR visual acuity were extracted and analyzed using Review Manager 5.4 and Stata 17.0.

RESULTS: A total of 6439 studies were identified, with 22 meeting the inclusion criteria after screening. The meta-analysis included 422 adult patients with amblyopia across these studies. Quality assessment revealed that 78% of studies had a low risk of bias. The analysis showed a statistically significant standardized mean difference (SMD) of -0.68 in the experimental group compared with controls, indicating an improvement in visual acuity (P < 0.05). Subgroup analyses indicated that perceptual learning and video game training also resulted in visual improvement (P < 0.05). In addition, the results indicated a significant improvement in visual acuity with dichoptic training or monocular training, reaching visual acuity improvement (P < 0.05).

CONCLUSIONS: These findings indicate that targeted visual training facilitates neural plasticity, reduces interocular suppression, and reinforces neural pathways associated with visual processing. While video game-based interventions represent a viable and engaging rehabilitation strategy, a combined approach may be most effective in enhancing monocular and binocular functions. Future research should focus on refining training protocols to enhance both monocular and binocular visual function more effectively.

PMID:40146483 | DOI:10.1007/s40123-025-01128-9

Clin Oral Investig. 2025 Mar 27;29(4):209. doi: 10.1007/s00784-025-06264-x.

ABSTRACT

OBJECTIVES: The existing literature indicates insufficient conclusive evidence regarding the efficacy of root canal therapy (RCT) in conjunction with third molar autologous tooth transplantation (ATT). This systematic review aims to evaluate the long-term survival rates and complications associated with this method.

MATERIALS AND METHODS: A comprehensive search was conducted across multiple databases, including PubMed, EMBASE (OVID), Web of Science (WOS), EBSCO, SpringerLink, Oxford, and ScienceDirect. This systematic review adhered to the guidelines set forth by the PRISMA and was registered in PROSPERO (CRD42024585817). This study calculated pooled survival rates, root resorption rates, and overall survival metrics. Subgroup analyses were performed to investigate the influence of follow-up duration, sample size, timing of endodontic treatment, and endodontic treatment on outcomes. Statistical significance was determined using an alpha value of 0.05, with 95% confidence intervals (CI) reported for pooled estimates. Heterogeneity was assessed using the I² statistic and Cochran’s Q test.

RESULTS: Among the 17 included studies, the follow-up period ranged from 1 to 29 years. After excluding two studies with 100% survival rates, the overall 1-year survival rate was 96% (P < .0001). Studies with mixed samples showed a higher 20-year survival rate compared to those exclusively involving third molars (46.2% vs. 41.3%; P = 0.029). RCT significantly improved survival and success rates in third molar autotransplantation, though heterogeneity varies across studies. The success rate reflects the completeness of treatment and indicates the restoration of tooth function, whereas the survival rate focuses more on the long-term retention of the tooth. The higher risk difference (RD) observed in the RCT group suggests that RCT enhances both survival and success rates. This finding highlights the potential role of RCT in enhancing the success of ATT. However, significant heterogeneity was observed across studies (I² = 73%), and the difference between the two groups were not statistically significant (P = 0.37, I² = 0%). These results may be influenced by follow-up duration, timing of endodontic treatment, and sample size. Therefore, the conclusions should be read with caution.

CONCLUSION: ATT of third molars with intact root formation represents a reliable approach for the replacement of missing teeth, demonstrating a high survival rate. Furthermore, RCT is associated with reduced complication rates and enhanced long-term survival.

PMID:40146481 | DOI:10.1007/s00784-025-06264-x

Clin Pharmacokinet. 2025 Mar 27. doi: 10.1007/s40262-025-01484-6. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Navitoclax, an orally bioavailable B-cell lymphoma-2 (Bcl-2) family protein inhibitor, inhibits antiapoptotic Bcl-2 family proteins (with high affinity to Bcl-XL, Bcl-2, and Bcl-W). Navitoclax in combination with ruxolitinib has been investigated to treat patients with myelofibrosis (MF).

METHODS: Since navitoclax undergoes hepatic metabolism, we evaluated the pharmacokinetics (PK) and safety of single-dose navitoclax 50 mg in a phase 1 study in participants with mild (N = 6), moderate (N = 6), or severe (N = 1) hepatic impairment and matched participants with normal hepatic function (N = 7). All participants in this study were enrolled per Child-Pugh classification, with demographics matched per age, weight, and race.

RESULTS: Navitoclax maximum plasma concentration (C_max), area under the plasma concentration-time curve for time zero to infinity (AUC_0-∞), and terminal elimination half-life (t_1/2) in participants with mild or moderate hepatic impairment were comparable to participants with normal hepatic function. The change in C_max and AUC_0-∞ values in participants with mild and moderate hepatic impairment were within 25% of normal hepatic function. Overall, 2/20 (10%) participants receiving a 50 mg single dose reported grade 1 treatment-emergent adverse events of nausea (N = 1) and diarrhea (N = 1).

CONCLUSIONS: In summary, no new safety issues were identified. On the basis of the pharmacokinetic results, no dose adjustment is required for patients with MF with mild or moderate hepatic impairment.

PMID:40146460 | DOI:10.1007/s40262-025-01484-6

Discov Oncol. 2025 Mar 27;16(1):411. doi: 10.1007/s12672-025-02126-w.

ABSTRACT

PURPOSE: To investigate the value of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging in interim therapeutic and prognostic evaluation of patients with diffuse large B-cell lymphoma (DLBCL).

MATERIALS AND METHODS: Data of 86 patients with pathologically confirmed DLBCL who underwent ¹⁸F-FDG PET/CT imaging before chemotherapy, radiotherapy, and after interim chemotherapy, were retrospectively analyzed. Receive operating characteristic (ROC) curve analysis was performed to assess the predictive capacity of changes and change rates in PET/CT imaging parameters [maximum standardized uptake value (SUV_max), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum tumor dissemination (D_max)] for progression-free survival (PFS) and to identify optimal cutoff values. Kaplan-Meier survival curves were constructed, and the log-rank test was used to assess intergroup differences. Cox regression analysis was used to explore potential factors influencing PFS.

RESULTS: Among 86 patients [(45 men, 41 women, age: 57.8 ± 12.2 years)], the median PFS was 22.5 (14.5, 46) months. Until the last follow-up date, progression or recurrence occurred in 14 patients, while 9 patients died. The ROC curves indicated that the optimal cutoff values for predicting PFS were 99.10%, 99.72%, and 96.47% for ΔMTV%, ΔTLG%, and ΔD_max%, respectively (area under the curve = 0.786-0.849, all P < 0.05). Cox univariate analysis demonstrated that the alteration rates in metabolic and diffusion parameters before and after treatment, including SUV_max%, MTV%, TLG%, and D_max%, were predictive of PFS (hazard ratio [HR] = 6.213-13.430, all P < 0.05). The Cox multivariate analysis demonstrated that ΔMTV% and ΔD_max% independently predicted PFS, with HRs of 10.727 (95% confidence interval [CI] = 1.928-56.672, P = 0.007) and 7.178 (95%CI = 1.514-34.041, P = 0.013), respectively. We established a new prediction model by combining the ΔMTV% and ΔD_max% parameters, and the results of the model showed statistically significant differences in PFS between the high, intermediate, and low-risk groups. The model predicted higher effects than individual indicators.

CONCLUSION: The rate of change in metabolic and diffusion parameters on interim PET/CT can predict the prognosis of patients with DLBCL.

PMID:40146454 | DOI:10.1007/s12672-025-02126-w

Neurosurg Rev. 2025 Mar 27;48(1):333. doi: 10.1007/s10143-025-03479-0.

ABSTRACT

Deep brain stimulation in the subthalamic nucleus (STN-DBS) is a therapeutic intervention for patients with Parkinson’s disease (PD) primarily aimed at improving motor symptoms. However, the effects of STN-DBS on non-motor symptoms (NMS), such as olfactory dysfunction (OD), remain poorly understood. We performed a systematic review and single-arm meta-analysis to evaluate the effects of STN-DBS on OD in PD patients. We searched Medline, Scopus, and Web of Science databases. Eligible studies included observational studies with ≥ 4 patients reporting the effects of STN-DBS on OD in PD patients. Mean differences (MD) between pre- and post-operative, along with the final mean pooled analysis, olfactory scores values with 95% confidence intervals (CI) with a random effects model were used. The statistical analysis was performed using the software R Studio. The heterogeneity was assessed with I² statistics, and leave-one-out sensitivity analysis was used to address high heterogeneity. A total of seven studies, encompassing 188 PD patients, with a mean age of 60.8 years, were included in our analysis. There was a statistically significant difference between pre- and post-operative value in Odor discrimination (ODI) (MD 2.16; 95% CI 1.37 to 2.96; p < 0.01; I² = 0%) and Unified Parkinson’s Disease Rating Scale part III OFF medication (UPDRS III OFF_MED) (MD -11.96; 95% CI -22.57 to -1.35; p = 0.03; I² = 88%), showing improvement in OD and motor function after DBS, compared to baseline. In contrast, there was no statistically significant difference between the initial and final value in Odor thresholds (OT) (MD 1.54; 95% CI -0.22 to 3.30; p = 0.09; I² = 90%), and the University of Pennsylvania Smell Identification Test (UPSIT) (MD -0.37; 95% CI -3.40 to 2.66; p = 0.81; I² = 0%). Additionally, the pooled analysis for Odor identification (OI) showed a final mean of 7.06 (95% CI 4.39 to 9.72; I² = 100%), and for the TDI score (composite score derived from the sum of OD, OI, and OT results), a final mean of 25.96 (95% CI 17.31 to 34.62; I² = 94%). Despite the prior indication of STN-DBS for motor symptoms, it may improve OD in PD patients. Clinical trial number Not applicable.

PMID:40146437 | DOI:10.1007/s10143-025-03479-0

Breast Cancer Res Treat. 2025 Mar 27. doi: 10.1007/s10549-025-07671-0. Online ahead of print.

ABSTRACT

PURPOSE: Racial disparities exist regarding cardiovascular (CV) toxicities following breast cancer treatment; however, studies on racial differences in cardiac arrhythmias are lacking. This study examined associations between demographic and clinical factors and arrhythmia diagnosis in Black and White breast cancer survivors.

METHODS: This study included a retrospective cohort of Black and White women who were diagnosed with breast cancer and who received potentially cardiotoxic treatment. Cardiac arrhythmia data were captured via International Classification of Diseases, Tenth and Ninth Versions (ICD-10 and ICD-9). Experiences with cardiac arrhythmias were compared across racial groups. The associations of demographic and clinical factors with cardiac arrhythmias were evaluated using logistic regression for all women and in race-stratified models.

RESULTS: Thirty-three percent of the total 860 women in our study sample (mean (standard deviation) age 50.3 (10.7) years) old) experienced cardiac arrhythmias. In bivariate analyses, we observed a statistically discernible association between race and arrhythmia status following a breast cancer diagnosis (p = 0.004); however, this association was no longer significant in the multivariable model. In race-stratified multivariable analysis, the odds of experiencing arrhythmias in Black women over 50 years old are 51% lower than in Black women aged 50 years old or younger (adjusted odds ratio (OR): 0.49; 95% confidence interval (CI): 0.28, 0.86). All else being equal, Black women with hypertension had 2.68 times (95% CI: 1.51, 4.81) higher odds of experiencing arrhythmias than those without hypertension. White women with obesity had higher odds of experiencing arrhythmias than those with normal weight or underweight status. (adjusted OR 1.93: [1.17, 3.20]).

CONCLUSION: Survivors with chronic conditions like hypertension and obesity may require enhanced cardiac surveillance. Further investigation into hypertension management in Black survivors may shed light on its impact on CV toxicities in this group.

PMID:40146434 | DOI:10.1007/s10549-025-07671-0