Nevin Manimala

Health Aff (Millwood). 2025 Aug;44(8):963-969. doi: 10.1377/hlthaff.2025.00019.

ABSTRACT

In 2016, in response to two federal court decisions, the Centers for Medicare and Medicaid Services began allowing geographically urban hospitals to be dually classified as both rural and urban simultaneously. This dual classification enables hospitals to use urban wage indexes for calculating Medicare reimbursements, while also benefiting from Medicare policies solely intended to support rural health. Using Medicare cost reports and impact files, we documented a substantial increase in administratively rural hospitals in the US, driven by the dual classification of existing hospitals located in urban areas, which rose from 3 in 2017 to 425 in 2023, with prevalence varying by state. More than three-quarters of dually classified hospitals were nonprofit, including many large academic medical centers in metropolitan areas. Congress should ensure that federal programs supporting rural health are directed solely to geographically rural hospitals.

PMID:40758922 | DOI:10.1377/hlthaff.2025.00019

Health Aff (Millwood). 2025 Aug;44(8):1011-1017. doi: 10.1377/hlthaff.2024.01224.

ABSTRACT

Adopted children are likely to have health needs that exceed those of other children. Health insurance is critical for access to care in the US. We studied health insurance coverage of adopted children in the US and found variation across adoption statuses and, among adoptees, variation by the immigration status of adoptees and adoptive parents.

PMID:40758921 | DOI:10.1377/hlthaff.2024.01224

Phytopathology. 2025 Aug 4. doi: 10.1094/PHYTO-05-25-0187-R. Online ahead of print.

ABSTRACT

Measuring individual components of pathogen reproduction is key to understanding mechanisms underlying rate-reducing quantitative resistance (QR). Simulation models predict that lesion expansion plays a key role in seasonal epidemics of foliar diseases, but measuring lesion growth with sufficient precision and scale to test these predictions under field conditions has remained impractical. We used deep learning-based image analysis to track 6889 individual lesions caused by Zymoseptoria tritici on 14 wheat cultivars across two field seasons, enabling 27,218 precise and objective measurements of lesion growth in the field. Lesion appearance traits reflecting specific interactions between particular host and pathogen genotypes were consistently associated with lesion growth, whereas overall effects of host genotype and environment were modest. Both host cultivar and cultivar-by-environment interaction effects on lesion growth were highly significant and moderately heritable (h2 ≥ 0.40). After excluding a single outlier cultivar, a strong and statistically significant association between lesion growth and overall QR was found. Lesion expansion appears to be an important component of QR to STB in most-but not all-wheat cultivars, underscoring its potential as a selection target. By facilitating the dissection of individual resistance components, our approach can support more targeted, knowledge-based breeding for durable QR.

PMID:40758903 | DOI:10.1094/PHYTO-05-25-0187-R

J Magn Reson Imaging. 2025 Aug 4. doi: 10.1002/jmri.70056. Online ahead of print.

ABSTRACT

BACKGROUND: The effect of the positron emission tomography (PET) modality in hybrid PET/MR scanners on MR spectral quality is unclear.

PURPOSE: To evaluate spectral quality, quantification, and repeatability of brain MR spectroscopy (MRS) acquired on PET/MR and standalone MR scanners.

STUDY TYPE: Prospective.

SUBJECTS: 23 healthy adults (male/female = 11/12, age = 27 ± 11 years).

FIELD STRENGTH/SEQUENCE: 3T, semi-localized by adiabatic selective refocusing.

ASSESSMENT: Single voxel MR spectra were acquired with GE Signa PET/MR and Siemens Prisma Fit MR scanners in healthy volunteers, and additionally with a GE Premier MR scanner in vitro. Spectral quality, metabolite concentrations, and repeatability were evaluated.

STATISTICAL TESTS: Linear mixed models assessed signal-to-noise ratio (SNR), full width at half maximum (FWHM), and metabolites/total creatine (tCr). Intraclass correlation coefficients (ICCs) determined repeatability; mean squared error (MSE) evaluated accuracy of quantification. Values are reported as mean ± standard deviation. Significance was determined by p ≤ 0.05.

RESULTS: In vivo spectra acquired using the Siemens standalone MR showed significantly higher SNR (PET/MR: 118.8 ± 19.1, MR: 132.2 ± 24.4) but significantly broader FWHM (PET/MR: 7.2 ± 1.8 Hz, MR: 8.4 ± 2.5 Hz) compared to PET/MR. All metabolite ratios were significantly higher in spectra acquired on the standalone MR. Within-session repeatability was good (ICC > 0.75), and between-session repeatability was moderate to excellent (ICC 0.5 to > 0.90) for all metabolites in vivo. In vitro spectra acquired with the PET/MR had significantly higher SNR (329.1 ± 46.1) than the Siemens standalone MR (150.8 ± 49.3) but significantly lower than the GE standalone MR (395.9 ± 33.7). The PET/MR produced narrower FWHM (2.1 ± 0.4 Hz) than the Siemens standalone MR (4.1 ± 1.7 Hz) but broader than the GE standalone MR (1.6 ± 0.1 Hz) and lower MSE for some metabolites.

DATA CONCLUSION: MR spectral quality appears uncompromised when acquired with hybrid PET/MR compared to standalone MR.

PMID:40758419 | DOI:10.1002/jmri.70056

Eur J Public Health. 2025 Aug 4:ckaf137. doi: 10.1093/eurpub/ckaf137. Online ahead of print.

ABSTRACT

Retrospective studies identified SARS-CoV-2 worldwide circulation as early as late 2019. In Italy, the first autochthonous COVID-19 case was diagnosed in a Northern Region on 20 February 2020, raising the question whether high numbers of COVID-19 pneumonia cases were previously undetected. We explored whether unusual increases in hospitalizations for pneumonia occurred from October 2019 to February 2020 in Italy, particularly in Northern Regions. We analysed the Italian National Hospital Discharge Records with pneumonia ICD-9-CM codes from 2014 to 2020. Trend analysis and generalized linear models with negative binomial distribution were applied to compare observed pneumonia trends in the study period with previous years. Analyses were stratified by major regions (NUTS1) and provinces. During the study period, 2 501 074 hospitalizations were coded as pneumonia. No unusual increases of all hospitalizations associated to pneumonia were observed until mid-February 2020. Hospitalizations with viral pneumonia ICD9-CM codes were negligible until the end of January 2020, with a significant increase in two provinces of Lombardy Region 1-2 weeks before the first autochthonous COVID-19 case. Our analysis showed that a small increase in viral pneumonia hospitalizations in Northern Italy only in the weeks immediately preceding the first locally acquired SARS-CoV-2 case in two provinces of Lombardy. This excludes large-scale circulation in the last months of 2019 and in January 2020. Given the mild 2019-2020 influenza season and lower pneumonia hospitalization burden, the initial increase could have been interpreted as a fluctuation as it did not determine an overall excess case-load of pneumonia hospitalizations.

PMID:40758405 | DOI:10.1093/eurpub/ckaf137

Biom J. 2025 Aug;67(4):e70069. doi: 10.1002/bimj.70069.

ABSTRACT

In recent years, basket trials, which allow the evaluation of an experimental therapy across multiple tumor types within a single protocol, have gained prominence in early-phase oncology development. Unlike traditional trials, which evaluate each tumor type separately and often face challenges with limited sample sizes, basket trials offer the advantage of borrowing information across various tumor types to enhance statistical power. However, a key challenge in designing basket trials is determining the appropriate extent of information borrowing while maintaining an acceptable type I error rate control. In this paper, we propose a novel three-component local power prior (local-PP) framework that introduces a dynamic and flexible approach to information borrowing. The framework consists of three components: global borrowing control, pairwise similarity assessments, and a borrowing threshold, allowing for tailored and interpretable borrowing across heterogeneous tumor types. Unlike many existing Bayesian methods that rely on computationally intensive Markov chain Monte Carlo (MCMC) sampling, the proposed approach provides a closed-form solution, significantly reducing computation time in large-scale simulations for evaluating operating characteristics. Extensive simulations demonstrate that the proposed local-PP framework performs comparably to more complex methods while significantly shortening computation time.

PMID:40758396 | DOI:10.1002/bimj.70069

Crit Care Med. 2025 Aug 4. doi: 10.1097/CCM.0000000000006797. Online ahead of print.

ABSTRACT

OBJECTIVES: Invasive mechanical ventilation (IMV) is crucial for acute respiratory distress syndrome (ARDS) management, but mortality remains high. While spontaneous breathing is key to weaning, excessive respiratory effort may injure the lung and diaphragm. Most existing data on respiratory effort during IMV are based on brief periods of observation, potentially underestimating the burden of inappropriate efforts. This study aims to characterize the evolution of respiratory effort over time in ARDS patients and its relation to survival. We hypothesized that nonsurvivors would spend a greater proportion of time in the high-effort range during the active breathing phase compared with survivors.

DESIGN, SETTING, AND PATIENTS: In this prospective cohort study, we continuously recorded airway pressure, flow, esophageal, and gastric pressures in ARDS patients on mechanical ventilation during 7 days after the onset of spontaneous breathing. We analyzed physiologic respiratory effort variables, focusing on the proportion of time spent within defined effort ranges, and compared these data between ICU survivors and nonsurvivors. Statistical analysis was conducted using variance weighted methods to account for variability in the number of respiratory cycles analyzed per patient. This study is registered at ClinicalTrials.gov under identifier NCT06490523.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: A total of 1,485,405 respiratory cycles were analyzed from 26 ARDS patients (19 survivors, seven nonsurvivors). Nonsurvivors spent significantly more time in high effort (12% vs. 3%; p = 0.006). In contrast, survivors spent more time in the moderate-effort range (50% vs. 5%; p < 0.001). The time spend with high dynamic transpulmonary driving pressure (> 25 cm H2O) was also significantly different between groups (32% survivors vs. 74% nonsurvivors; p = 0.001).

CONCLUSIONS: Patients who die of ARDS are more likely to be exposed to high respiratory effort for prolonged periods of time compared with survivors.

PMID:40758388 | DOI:10.1097/CCM.0000000000006797

Health Technol Assess. 2025 Jul;29(33):1-16. doi: 10.3310/GJDM0320.

ABSTRACT

BACKGROUND: In patients who require mechanical ventilation for acute hypoxaemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes.

OBJECTIVE: To determine whether using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxaemic respiratory failure and is cost-effective.

DESIGN: A multicentre, randomised, allocation-concealed, open-label, pragmatic clinical trial.

SETTING: Fifty-one intensive care units across the United Kingdom.

PARTICIPANTS: Four hundred and twelve adult patients receiving mechanical ventilation for acute hypoxaemic respiratory failure, of a planned sample size of 1120.

INTERVENTIONS: Lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210).

MAIN OUTCOME MEASURES: All-cause mortality 90 days. Secondary outcomes included ventilator-free days; adverse events; extracorporeal membrane oxygenation use; long-term mortality; health-related quality of life; health service costs; long-term respiratory morbidity.

RESULTS: The trial was stopped early because of futility and feasibility. The 90-day mortality rate was 41.5% in the extracorporeal carbon dioxide removal group versus 39.5% in the standard care group (risk ratio 1.05, 95% confidence interval 0.83 to 1.33; difference 2.0%, 95% confidence interval – 7.6% to 11.5%; p = 0.68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1, 95% confidence interval 5.9 to 8.3) versus (9.2, 95% confidence interval 7.9 to 10.4) days; mean difference, -2.1 (95% confidence interval -3.8 to -0.3; p = 0.02). Serious adverse events were reported for 62 patients (31%) in extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial haemorrhage in 9 patients (4.5%) versus 0 (0%) and bleeding at other sites in 6 (3.0%) versus 1 (0.5%) in the extracorporeal carbon dioxide removal group versus the control group. Two-year mortality data were available for 95% of patients. There was no difference in the time to death between groups (hazard ratio 1.08, 95% confidence interval 0.81 to 1.44; log-rank test p = 0.61). There was no difference in long-term outcomes between groups. There was no difference in quality-adjusted life-years at 12 months (mean difference -0.01, 95% confidence interval -0.06 to 0.05). Total 12-month costs were statistically significantly higher in the extracorporeal carbon dioxide removal group (mean difference £7668.76, 95% confidence interval £159.75 to £15,177.77). Secondary analyses indicated there may be heterogeneity of treatment effect based on physiological characteristics of the patients. A systematic review supported these findings.

LIMITATIONS: Only 6% of screened patients were included in the study; most sites were naive to the intervention before the study commenced; other aspects of care were not standardised in each group, because this was a pragmatic trial; the trial may have been underpowered to detect a clinically important difference, because the trial was stopped early; blinding to the clinicians or patients was not possible.

CONCLUSIONS: There were no short- or long-term benefits found, and the device was associated with higher cost and potentially significant complications. We would advise against using this device in addition to standard care for the treatment of patients with hypoxaemic respiratory failure, outside of future clinical trials.

FUTURE WORK: Future studies could further explore whether different patient populations receiving a larger ‘dose’ of from extracorporeal carbon dioxide removal might benefit, use core outcome sets and collect broader long-term outcomes and consider measuring patients’ health-related quality of life at the soonest opportunity after regaining capacity.

FUNDING: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 13/143/02.

PMID:40758387 | DOI:10.3310/GJDM0320

Crit Care Med. 2025 Aug 4. doi: 10.1097/CCM.0000000000006809. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine whether low-density lipoprotein cholesterol (LDL-C) levels, set by the balance of clearance and production, causally contribute to septic shock 28-day mortality.

DESIGN: We measured LDL-C levels and genotypes in patients with septic shock. Using Genotyping and Genome-Wide Association Study summary statistics from over 150,000 Japanese participants, we genetically predicted pre-infection LDL-C levels. Two-sample Mendelian randomization was used to assess the causal relationship between predicted pre-infection LDL-C levels and 28-day mortality. We analyzed PCSK9 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) genotypes to determine if LDL-C clearance or production was the underlying mechanism.

SETTING: Multicenter ICUs in Japan.

PATIENTS: Genotyped septic shock patients (n = 614).

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Predicted pre-infection LDL-C levels were much higher than directly measured LDL-C levels at the onset of septic shock (141 mg/dL vs. 40 mg/dL, p < 0.001). Two-sample Mendelian randomization revealed that high predicted pre-infection LDL-C levels were causally associated with increased septic shock 28-day mortality (hazard ratio, 2.78; p = 0.039). PCSK9 genetic variants that increase LDL-C clearance via the LDL receptor (genetically proxied PCSK9 inhibitor treatment) were associated with decreased mortality (p = 0.003) while HMGCR genetic variants that decrease LDL-C production (genetically proxied statin treatment) were not associated with decreased septic shock mortality (indeed the opposite effect was observed, p = 0.039). The two main genetic variants driving the association between high predicted pre-infection LDL-C levels and increased mortality were in apolipoprotein genes (ApoB100-rs13306206 and ApoE-rs7412), apolipoproteins involved in LDL-C binding to the LDL receptor.

CONCLUSIONS: Low LDL-C clearance explains the causal association between high genetically predicted pre-infection LDL-C levels and increased septic shock mortality. PCSK9, ApoB, and ApoE variants were identified as causal, all related to the LDL receptor or its interaction with LDL-C. Enhancing LDL receptor-mediated clearance of pathogen lipid toxins may improve septic shock outcomes.

PMID:40758386 | DOI:10.1097/CCM.0000000000006809

Int Endod J. 2025 Aug 4. doi: 10.1111/iej.70009. Online ahead of print.

ABSTRACT

AIM: To evaluate the effect of electropolishing on the mechanical properties of One RECI and One Curve mini nickel-titanium (NiTi) instruments by comparing electropolished and non-electropolished versions of each instrument type.

METHODOLOGY: Electropolished and non-electropolished One RECI (reciprocating) and One Curve mini (rotary) NiTi instruments, all manufactured with identical geometry and heat treatment, were evaluated. Instrument design was analysed by light microscopy and scanning electron microscopy, while metallurgical characterisation was performed using energy-dispersive X-ray spectroscopy (EDS) and differential scanning calorimetry (DSC). Mechanical performance was assessed through torsional resistance, bending and buckling load, surface microhardness, and cutting efficiency. Statistical comparisons were performed using the independent samples t-test or the Mann-Whitney U-test, with significance set at p < 0.05.

RESULTS: Design and metallurgical analyses confirmed that electropolished and non-electropolished instruments within each group were equivalent in terms of geometry, cross-sectional design, tip configuration, elemental composition, and phase transformation temperatures. Electropolishing significantly enhanced flexibility in both instrument types, as indicated by reduced bending loads and lower buckling resistance (p < 0.05). However, torsional strength was significantly reduced in the electropolished One RECI instruments, reflected by lower maximum torque and angle of rotation prior to fracture (p < 0.05). No significant torsional differences were observed in the One Curve mini group (p > 0.05). Surface microhardness and cutting efficiency remained unaffected by electropolishing in both systems (p > 0.05).

CONCLUSIONS: Electropolishing improved the flexibility of both One RECI and One Curve mini NiTi instruments without compromising their surface microhardness or cutting efficiency. However, its impact on torsional resistance was system-dependent, resulting in reduced strength only in the reciprocating One RECI instruments.

PMID:40758383 | DOI:10.1111/iej.70009