Nevin Manimala

Environ Health Perspect. 2025 Jun 12. doi: 10.1289/EHP15725. Online ahead of print.

ABSTRACT

BACKGROUND: Diarrheal diseases remain a leading cause of mortality and morbidity among under-five children in South Asia. In rural Bangladesh, deep tubewells that tap into low-arsenic deep aquifers have been installed to provide microbially safe and arsenic-free drinking-water at source. However, unlike more widely used shallow tubewells, deep tubwells are sparsely distributed, and households often travel farther for drinking-water consumption from such wells. Hence, benefits from deep tubewells may be abated by higher levels of microbial contamination during water handling and storage that could increase the risk of diarrheal diseases.

OBJECTIVES: We examined the association between deep tubewell use and diarrheal disease risk in under-five children and investigated the role of social and environmental factors on modifying the association.

METHODS: We implemented community diarrheal disease surveillance across households with under-five children using deep and shallow tubewells in Matlab, Bangladesh from March 2018 to October 2019. We used Generalized Estimating Equations (GEE) to measure the association between deep tubewell use compared to shallow tubewell use on diarrheal disease prevalence.

RESULTS: Children in households using deep tubewells had diarrheal disease prevalence 0.83 times that of children in households using shallow tubewells (95% Confidence interval (CI): 0.71-0.96). Protective effects of deep tubewell use on diarrhea risk were observed among children in households that drank from wells within their household compound (Risk ratio (RR) =0.70, 95% CI: 0.54-0.91), were in flood-prone areas (RR=0.83, 95% CI: 0.75-0.92), and used unimproved latrines (RR=0.62, 95% CI: 0.43-0.89). Deep tubewell use was more protective against diarrhea than shallow tubewell use during the dry season (RR = 0.71, 95% CI: 0.52-0.97).

CONCLUSIONS: Despite concerns, using deep tubewells may not translate to higher diarrhea risk among under-five children, and may reduce diarrhea further especially in social and environmental contexts associated with higher groundwater microbial contamination. https://doi.org/10.1289/EHP15725.

PMID:40504602 | DOI:10.1289/EHP15725

Transl Vis Sci Technol. 2025 Jun 2;14(6):24. doi: 10.1167/tvst.14.6.24.

ABSTRACT

PURPOSE: To develop a methodology for analyzing dynamic corneal images using pixel intensity tracking and hue, saturation, and value (HSV) color space transformation, aiming to quantify and visually interpret corneal responsiveness to mechanical stimulation.

METHODS: This study utilized the OCULUS Corvis ST device to obtain dynamic corneal images from two subject groups (young and older individuals). To ensure accurate pixel tracking, segmentation and registration techniques were implemented. To counteract potential biases due to alterations in curvature and eye retraction caused by the air-puff mechanical stimulus, the last 30 frames available post-stimulus were used for analysis. Pixel intensity tracking calculations were then performed in the frequency domain to compute H, S, and V values for each pixel within the overall region of interest. Additionally, corneal biomechanical parameters from the Corvis ST were extracted to examine their relationship with HSV values.

RESULTS: The HSV transformation provided a quantitative visual interpretation of corneal dynamics, with reddish vibrant areas indicating higher responsiveness to mechanical stimulation and dull blue areas indicating lower responsiveness. Additionally, significant differences were found between the young and older groups in each of the three HSV channels (all P < 0.001). Four biomechanical parameters showed statistically significant differences between groups (P < 0.05), but no statistically significant correlation with HSV values was found.

CONCLUSIONS: The HSV methodology effectively visualizes and quantifies corneal responsiveness to mechanical stimulation, offering a new approach for assessing corneal dynamics.

TRANSLATIONAL RELEVANCE: HSV color space analysis has the potential to enhance the diagnosis and management of conditions in which corneal dynamics are affected.

PMID:40504568 | DOI:10.1167/tvst.14.6.24

Oncologist. 2025 Jun 4;30(6):oyaf123. doi: 10.1093/oncolo/oyaf123.

ABSTRACT

BACKGROUND: CDK4/6 inhibitors (CDK4/6i) are cornerstone therapies in Hormone Receptor Positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Breast Cancer (BC) and emerging evidence suggests that they may influence immune function, potentially enhancing antitumor immunity but also triggering autoimmune reactions. This study aims to investigate the prevalence of autoimmune diseases (AD) in patients with HR+/HER2- BC to identify potential predictive biomarkers and to assess the impact of AD on disease progression.

PATIENTS AND METHODS: This retrospective-prospective cohort study included consecutive HR+/HER2- BC patients treated with CDK4/6i at Humanitas Research Hospital. Clinical-pathological features, treatment data, AD occurrence, and blood test values were collected. Descriptive statistics were used to determine AD prevalence, Kaplan-Meier method to estimate progression-free survival (PFS), and log-rank test to compare survival curves.

RESULTS: 352 patients (median age: 54 years) were enrolled, of which 87.2% had metastatic disease and received palbociclib, abemaciclib, or ribociclib (45.2%, 31.0%, and 23.9%, respectively). 12.8% of patients had early BC and received abemaciclib. ADs were identified in 49 patients: most had pre-existing conditions (38 stable and 4 flaring during treatment) while 7 developed new-onset ADs. The most frequent AD were Hashimoto thyroiditis, vitiligo, and rheumatoid arthritis. In the metastatic setting, the median PFS was significantly longer in patients with AD compared to those without (P = .0013), with patients with flaring or new-onset AD showing a better PFS (P = .0015). No significant predictive biomarkers for AD evolution were found.

CONCLUSION: CDK4/6i therapy is feasible in patients with pre-existing AD. Interestingly, the onset or flaring of AD during treatment is associated with improved PFS, suggesting a potential immune activation induced by CDK4/6i. However, further robust and prospective studies are required to validate these findings and explore the underlying mechanisms.

PMID:40504547 | DOI:10.1093/oncolo/oyaf123

JAMA Oncol. 2025 Jun 12. doi: 10.1001/jamaoncol.2025.1433. Online ahead of print.

ABSTRACT

IMPORTANCE: The rising incidence of young-onset colorectal cancer (CRC) has prompted health policymakers to consider lowering the recommended starting age for screening. However, population-based evidence supporting the long-term effectiveness of early-age screening remains limited.

OBJECTIVE: To evaluate whether initiating fecal immunochemical test (FIT) screening at ages 40 to 49 years, rather than at the currently recommended age of 50 years, reduces CRC incidence and mortality.

DESIGN, SETTING, AND PARTICIPANTS: This study analyzed a community-based screening cohort of Taiwanese residents aged 40 to 49 years, categorized into 4 subcohorts based on participation in early screening (age 40 to 49 years) and continuation of nationwide regular screening (50 years and older). The cohort was followed up until 2019 to compare CRC incidence and mortality across subcohorts. To mitigate self-selection bias, a delayed screening design and efficient propensity score matching was used, restricting analyses to participants attending regular screening. To validate the findings, an extended nonadherence adjustment was applied to all 4 subcohorts. Data were collected from January 2001 to December 2019, and data were analyzed from January 2021 to December 2024.

EXPOSURES: Biennial FIT screening was initiated for the early screening group at ages 40 to 49 years and for the regular screening group at age 50 years, with follow-up continuing under Taiwan’s national screening program.

MAIN OUTCOMES AND MEASURES: Primary outcomes were CRC incidence and mortality rates, reported as cases per 100 000 person-years, with adjusted relative risks (aRRs) comparing early vs regular screening groups.

RESULTS: Of 263 125 included participants, 146 796 (55.8%) were female. A total of 39 315 participated in early and regular screening, and 223 810 participated in regular screening only. The early screening group exhibited lower CRC incidence (26.1 [95% CI, 22.3-29.9] vs 42.6 [95% CI, 40.5-44.7] per 100 000 person-years) and mortality (3.2 [95% CI, 1.9-4.6] vs 7.4 [95% CI, 6.5-8.2] per 100 000 person-years). In propensity score-matched analyses, early screening significantly reduced CRC incidence (aRR, 0.79; 95% CI, 0.67-0.94) and mortality (aRR, 0.61; 95% CI, 0.38-0.98). Findings were consistent in the extended nonadherence adjustment model, showing a 25% reduction in incidence (aRR, 0.75; 95% CI, 0.72-0.77) and a 34% reduction in mortality (aRR, 0.66; 95% CI, 0.62-0.71).

CONCLUSIONS AND RELEVANCE: This study found that initiating FIT screening at age 40 to 49 years was associated with further reduction in CRC mortality and incidence compared with starting screening at age 50 years. These results provide strong empirical support for lowering the CRC screening age, with substantial public health implications.

PMID:40504543 | DOI:10.1001/jamaoncol.2025.1433

JAMA Netw Open. 2025 Jun 2;8(6):e2514997. doi: 10.1001/jamanetworkopen.2025.14997.

ABSTRACT

IMPORTANCE: Drug overdose deaths (DODs) surged with the advent of fentanyl. Recent US reports indicated a decline, but standard surveillance systems do not account for monthly variability or seasonality and require monthly population data to calculate DOD rates.

OBJECTIVE: To identify when US DOD rates began to decelerate and to examine patterns by census region, drug type, and demographics.

DESIGN, SETTING, AND PARTICIPANTS: This repeated cross-sectional study of DOD rates was conducted from January 2015 to October 2024, using data from the National Center for Health Statistics and US Census Bureau. Decedents included those whose drug poisoning death was classified as unintentional, intentional (suicide or homicide), or undetermined intent, identified by International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes for external overdose causes and T codes for opioids, cocaine, and psychostimulants (eg, methamphetamine).

MAIN OUTCOMES AND MEASURES: The main outcome was change in monthly DOD rates nationally and by drug type (opioids, cocaine, or methamphetamine), census region, and demographics. Joinpoint regression evaluated significant shifts in DOD rates applying the weighted bayesian information criterion and 2-sided z tests (α = .05).

RESULTS: A total of 800 645 US residents (68.3% male; median age, 42 years [IQR, 33-54 years]) died of drug overdose between January 2015 and October 2024. The national DOD rate increased from 14.54 (95% CI, 14.52-14.55) per 100 000 population in January 2015 to 33.24 (95% CI, 33.15 to 33.33) per 100 000 population in August 2023. From August 2023 to February 2024, the monthly DOD rate declined by -0.36 (95% CI, -0.46 to -0.27) per 100 000 population, accelerating to -0.84 (95% CI, -0.77 to -0.92) per 100 000 population through October 2024 and reaching 24.29 (95% CI, 24.21-24.37) per 100 000 population. Opioid-related DOD rates declined faster than stimulant-related DOD rates (-0.80 [95% CI, -0.74 to -0.87] vs -0.25 [95% CI, -0.23 to -0.27] per 100 000 population). While the national DOD rate peaked in August 2023, rates peaked in the Northeast, Midwest, and South census regions in October 2022 and the West peaked a year later. By late 2023, death rates continued to accelerate among adults aged 55 years or older (0.07 per 100 000 population) and American Indian or Alaska Native (0.02 per 100 000 population), Black or African American (1.70 per 100 000 population), Hispanic or Latino (0.20 per 100 000 population), and multiracial (0.28 per 100 000 population) populations, though the pace of increase was slowing, suggesting a potential inflection point.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, US DOD rates entered a new wave of sustained deceleration in 2023 after 2 decades of increase. This shift may reflect changes in drug markets, treatment access, harm reduction efforts, and population-level risk. Although the decline is encouraging, persistent disparities highlight the need for targeted interventions and improved understanding of the underlying drivers.

PMID:40504530 | DOI:10.1001/jamanetworkopen.2025.14997

JAMA Netw Open. 2025 Jun 2;8(6):e2515205. doi: 10.1001/jamanetworkopen.2025.15205.

ABSTRACT

IMPORTANCE: Racial and ethnic disparities in breast cancer clinical trial participation pose a significant barrier to providing equitable care. Black and Hispanic patients are underrepresented in clinical trials, and an improved understanding of barriers to enrollment is needed.

OBJECTIVE: To examine patterns of clinical trial discussion and participation and patient attitudes toward clinical trial participation in a diverse cohort of patients with breast cancer.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used survey data from patients enrolled in the Chicago Multiethnic Epidemiologic Breast Cancer Cohort. Patients were queried about clinical trial discussion and subsequent enrollment in a therapeutic clinical trial. Barriers to trial enrollment were also assessed. Surveys were conducted from July to September 2022, and data were analyzed from February to October 2024.

EXPOSURE: Self-reported race and ethnicity, including Asian, Black, Hispanic, and White.

MAIN OUTCOMES AND MEASURES: Outcomes of interest were discussing participation in a breast cancer clinical trial with a health care practitioner, participating in a clinical trial, and barriers to trial enrollment.

RESULTS: Of 1150 respondents (mean [SD] age, 53.7 [11.9] years), 51 (4.4%) were Asian, 224 (19.5%) were Black, 35 (3.1%) were Hispanic, and 838 (73.0%) were White. A total of 447 respondents (38.9%) reported discussing trial participation with a health care practitioner. There were no differences in trial discussion between White patients and other racial groups (Asian: adjusted odds ratio [AOR], 0.75; 95% CI, 0.31-1.82; Black: AOR, 1.31; 95% CI, 0.78-2.21; Hispanic: AOR, 0.73; 95% CI, 0.26-2.08). Among 443 patients offered a trial, 285 (64.3%) participated. While there were differences in trial participation across racial and ethnic groups, these differences were not significant after adjusting for sociodemographic and clinical factors. Among 158 patients who did not enroll in the trial offered, 37 (23.4%) reported ineligibility, 17 (10.8%) were worried about the possibility of getting a placebo, 16 (10.1%) were worried about extra time required, and 14 (8.9%) were worried about possible adverse effects.

CONCLUSIONS AND RELEVANCE: This cross-sectional study demonstrated that when offered, patients across racial and ethnic groups were equally likely to participate in clinical trials. In addition to ineligibility, time toxicity was a significant barrier to enrollment. These data provide valuable insights that can serve as a roadmap for how to expand access to trials for all patients, regardless of racial, ethnic, and socioeconomic background.

PMID:40504527 | DOI:10.1001/jamanetworkopen.2025.15205

JAMA Netw Open. 2025 Jun 2;8(6):e2515376. doi: 10.1001/jamanetworkopen.2025.15376.

ABSTRACT

IMPORTANCE: During the COVID-19 pandemic, pediatric intensive care units (PICUs) reportedly relied more on temporary contract nurses hired through staffing agencies (agency nurses) to fill gaps related to increased nurse turnover. It is unknown whether these changes in nurse staffing were associated with patient outcomes.

OBJECTIVE: To determine whether the proportion of PICU agency staff or nurse turnover was associated with patient outcomes during the pandemic.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective, multicenter, linked database cross-sectional study was performed at PICUs in the US between January 1, 2019, and December 31, 2022. Participants included patients younger than 19 years admitted to a PICU with data in both the Children’s Hospital Association Pediatric Health Information Systems and PROSPECT Hospital Essentials databases. Data were analyzed from March 15, 2023, to August 1, 2024.

EXPOSURE: The yearly proportion of agency nurses and nurse turnover.

MAIN OUTCOMES AND MEASURES: Descriptive characteristics were examined for PICUs grouped by the median proportion of agency nurses or nursing turnover each year. A variable staffing metric was defined as greater than 10% change in the proportion of agency nurses from the intrahospital baseline in 2019. Multivariable negative binomial models controlling for illness severity and hospital effect with median yearly staffing metrics examined whether the proportion of agency nurses or nurse turnover was associated with mortality, PICU complications, central line-associated bloodstream infections, or ventilator-associated pneumonias.

RESULTS: There were 218 789 admissions across 20 PICUs, with a median patient age of 45 (IQR, 9-138) months (119 997 [54.8%] male). PICUs with a variable proportion of agency nurses had significantly more patients with PICU complications (9695 of 120 017 [8.1%] vs 7141 of 98 772 [7.2%]; P < .001). Multivariable analysis indicated an increase of 19 (95% CI, 7-39) ventilator-associated pneumonias per 10 000 ventilator-days in 2020. For a PICU with 10% higher nurse turnover than the median turnover, there were 10 (95% CI, 8-13) more PICU complications per 10 000 patient-days in 2022.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of nurse staffing measures and patient outcomes during COVID-19, complex associations existed throughout the study years. More data are needed to determine optimal staffing strategies during times of workforce strain.

PMID:40504525 | DOI:10.1001/jamanetworkopen.2025.15376

JAMA Otolaryngol Head Neck Surg. 2025 Jun 12. doi: 10.1001/jamaoto.2025.1304. Online ahead of print.

ABSTRACT

IMPORTANCE: Smell distortion (parosmia) is a symptom of post-COVID-19 condition that persists and has immeasurable detriments on quality of life. To date, a standard criterion for treatment of this bothersome condition has not been identified.

OBJECTIVE: To determine whether stellate ganglion block (SGB) is effective and safe in improving olfactory dysfunction in patients with persistent COVID-19-induced parosmia.

DESIGN, SETTING, AND PARTICIPANTS: This was a randomized, double-blinded, placebo-controlled clinical trial conducted from October 2023 to September 2024 at a single center study (the Washington University in St Louis/Barnes Jewish Hospital). A volunteer sample of 192 individuals were screened; 57 were enrolled after meeting eligibility criteria (age 18-70 years with self-reported parosmia of ≥6 months since COVID-19 infection, and a screening score of ≥40 on the Parosmia Olfactory Dysfunction Outcomes Rating [DisODOR] scale). Of 135 excluded, the most common reasons were prior SGB (n = 42) and parosmia resolution or non-COVID-19-induced parosmia (n = 28). Data were analyzed from September to October 2024.

INTERVENTION: Ultrasonography-guided injection of 6 to 8 mL of active mepivacaine, 1%, or saline, 0.9%, at the right or left (randomized 1:1) stellate ganglion was performed by a board-certified anesthesiologist and pain medicine specialist.

MAIN OUTCOME AND MEASURE: Between-subject difference of 25% in proportion of responders (defined by a 15-point decrease in DisODOR score) from baseline.

RESULTS: The study evaluated 48 participants, 32 randomized to SGB (median [range] age, 45 [19-64] y; 25 [81%] female), and 16 to placebo (median [SD] age, 45 [26-64] y; 13 [81%] female). Time since COVID-19 infection was similar between groups (SGB, 35.3 vs placebo, 30.6 months; MD = -3.1 months; 95% CI, -10.9 to 3.7). Three-month response rate was 43% (n = 13) for SGB and 38% (n = 6) for placebo (difference, -5%; 95% CI, -32% to 33%). There was no between-group difference in clinical global impression of improvement.

CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that SGB is not superior to placebo in treating COVID-19-induced parosmia, and thus, should not be recommended as treatment.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06253806.

PMID:40504522 | DOI:10.1001/jamaoto.2025.1304

FEMS Microbiol Lett. 2025 Jun 12:fnaf059. doi: 10.1093/femsle/fnaf059. Online ahead of print.

ABSTRACT

The emergence and rapid spread of multidrug-resistant pathogens have caused a need for alternative antimicrobials, and bacteriocins are considered promising alternatives due to their lower risk of resistance development. Regarding this, we aimed to investigate the long-term sub-inhibitory and semi-sub-inhibitory concentrations of a commonly used bacteriocin (nisin) in Staphylococcus aureus using an experimental evolution approach followed by genome sequencing. We then performed RT-qPCR to examine changes in the expression level of the biofilm-related icaA gene in evolved lines. We found that while nisin treatment did not significantly elevate the base-substitution rates, there was a significant decrease in the insertion/deletion rate in the lines exposed to the sub-inhibitory concentration of nisin. We also revealed an increase in nonsynonymous mutations in specific genes (e.g. sarS and cap8) associated with resistance and virulence mechanisms. Importantly, we observed a transition bias in the nisin-treated lines for the first time, and it may be related to the resistance development to nisin. RT-qPCR analysis of the icaA gene showed a reduced expression levels in nisin-treated groups, although the results were not statistically significant. These findings show the potential outcomes of nisin exposure in S. aureus and emphasize the need for careful consideration of bacteriocins in clinical practice.

PMID:40504520 | DOI:10.1093/femsle/fnaf059

Biomol Biomed. 2025 Jun 10. doi: 10.17305/bb.2025.12157. Online ahead of print.

ABSTRACT

As the most common form of peripheral arterial disease, lower extremity arterial disease-caused by atherosclerotic stenosis or occlusion-has led to widespread concern due to the high risk of postoperative restenosis. This study aimed to evaluate the effectiveness of drug-coated balloon (DCB) angioplasty in treating severe infrapopliteal artery (IPA) lesions. Plain old balloon (POB) angioplasty served as the control. Patients who underwent procedures at our center for Trans-Atlantic Inter-Society Consensus (TASC) C/D IPA lesions between June 2020 and June 2022 and met the inclusion criteria were enrolled in this retrospective cohort study, which used the propensity score matching (PSM) method. The primary outcomes were the 2-year cumulative rates and survival trends of primary patency (PP) and target lesion revascularization (TLR), based on the treated lesions. Secondary outcomes included limb-based major amputation (MA) and patient-based all-cause death (ACD). A total of 278 target lesions were initially included, with significant differences (p < 0.05) observed in some non-outcome variables. After PSM, analyses were conducted on 240 target lesions, 221 limbs, and 195 patients. The PSM models satisfied both the common support and parallel trend assumptions. In terms of PP, the 2-year cumulative rate in the DCB group was significantly higher than in the POB group (48.0% vs. 22.9%, p < 0.001). The log-rank test yielded a p-value of < 0.001, and the adjusted hazard ratio (HR) from Cox regression analysis was 2.303 [95% confidence interval (CI): 1.518-3.495]. However, there was no statistically significant difference in TLR between the two groups: the 2-year cumulative rates were 25.0% vs. 27.1% (p = 0.767), the log-rank test p-value was 0.563, and the adjusted HR was 0.956 (95% CI: 0.523-1.747). Similarly, no significant differences were found between groups in MA or ACD (p > 0.05). Based on these findings, the study concludes that for severe IPA lesions such as TASC C/D, DCB angioplasty is superior to POB angioplasty in maintaining primary patency over a 2-year period, without any inferiority in other clinical outcomes.

PMID:40504503 | DOI:10.17305/bb.2025.12157