Nevin Manimala

JAMA Netw Open. 2025 Apr 1;8(4):e254763. doi: 10.1001/jamanetworkopen.2025.4763.

ABSTRACT

IMPORTANCE: Older Medicare beneficiaries are susceptible to receiving potentially inappropriate medications (PIMs), where the risks outweigh the benefits. Racial and ethnic differences in PIM use may perpetuate health disparities and disproportionately lead to costly adverse drug events for some groups.

OBJECTIVE: To examine associations of race and ethnicity with PIM use among older Medicare beneficiaries.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used nationwide Medicare Part D Event files, fee-for-service claims, and Medicare Advantage (MA) encounter data among Medicare beneficiaries 65 years or older with Part D prescription drug coverage. The study population included random samples of 20% of traditional Medicare (TM) beneficiaries and 50% of MA enrollees from January 1, 2016, to December 31, 2019. Analysis was conducted from May 28 to September 16, 2024.

EXPOSURE: Race and ethnicity.

MAIN OUTCOMES AND MEASURES: Linear probability models were estimated for outcomes of (1) high-risk medication use among older adults, (2) potentially harmful drug-disease interactions in patients with dementia, and (3) potentially harmful drug-disease interactions in patients with a history of falls.

RESULTS: The study sample included 21 193 170 patients with 32 199 587 beneficiary-year observations (mean [SD] age, 75.5 [7.3] years; 18 936 697 [58.8%] female; 983 513 [3.1%] Asian or Pacific Islander, 3 190 515 [9.9%] Black, 2 710 930 [8.4%] Hispanic, and 25 314 629 [78.6%] White). Compared with White beneficiaries, the rates of high-risk medication use were 1.7 [95% CI, -1.8 to -1.6] percentage points lower for Asian or Pacific Islander beneficiaries, 3.4 [95% CI, -3.4 to -3.3] percentage points lower for Black beneficiaries, and 0.6 [95% CI, -0.6 to -0.5] percentage points lower for Hispanic beneficiaries. Similarly, White beneficiaries had the highest rates of potentially harmful drug-disease interactions among those with dementia as well as those with a history of falls. The pattern of racial and ethnic differences was similar in analyses stratified by enrollment in TM or MA plans. However, the differences between White individuals and other groups were smaller in MA than in TM plans for all comparisons.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of 32 199 587 Medicare beneficiary-years from 2016 to 2019, White Medicare beneficiaries had consistently higher rates of PIM use compared with other racial and ethnic groups. The observed differences may be partially explained by racial and ethnic differences in overall prescription drug use and suggest the need to reduce PIM use in all racial and ethnic groups.

PMID:40227682 | DOI:10.1001/jamanetworkopen.2025.4763

JAMA Netw Open. 2025 Apr 1;8(4):e254852. doi: 10.1001/jamanetworkopen.2025.4852.

ABSTRACT

IMPORTANCE: Housing instability may worsen control of type 2 diabetes outcomes.

OBJECTIVE: To estimate the association between stable vs unstable housing and type 2 diabetes outcomes.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed electronic health record data of adults with type 2 diabetes from US community-based health centers from June 2016 to April 2023. Targeted minimum loss estimation was used to examine the association between having vs not having housing instability and subsequent type 2 diabetes outcomes, adjusting for age, date of housing instability assessment, sex, race and ethnicity (social constructs that may indicate the experience of racism), language, comorbidities, health insurance, income, and census-tract level social vulnerability index. Analyses were conducted from July 2023 to September 2024.

EXPOSURE: Report of housing stability or instability.

MAIN OUTCOMES AND MEASURES: Mean hemoglobin A1c (HbA1c) level was the primary outcome; secondary outcomes included systolic and diastolic blood pressure (SBP and DBP) and low-density lipoprotein (LDL) cholesterol. The primary time point was 12 months after initial assessment, with secondary time points at 6, 18, 24, 30, and 36 months.

RESULTS: A total of 90 233 individuals were included (mean [SD] age, 55.4 [13.7] years; 50 772 female [56.3%]; 25 602 Black [28.4%], 27 277 Hispanic [31.4%], 51 720 White [57.3%]); 28 784 individuals (31.9%) had a primary language other than English, and 15 713 (17.4%) reported housing instability. Prior to first housing instability assessment, mean (SD) HbA1c was 7.64% (1.94%), mean (SD) SBP was 130.0 (13.5) mm Hg, mean (SD) DBP was 78.2 (7.8) mm Hg, and mean (SD) LDL cholesterol was 101.1 (35.2) mg/dL. We estimated had all individuals experienced stable housing, compared with unstable housing, mean HbA1c would have been 0.12% lower (95% CI, -0.16% to -0.07%; P < .001), SBP would have been 0.77 mm Hg lower (95% CI, -1.14 mm Hg to -0.39 mm Hg; P < .001), and DBP 0.27 mm Hg lower (95% CI, -0.49 mm Hg to -0.06 mm Hg; P = .01), but LDL cholesterol would not have been lower (estimated difference, -1.46 mg/dL, 95% CI, -2.96 mg/dL to 0.03 mg/dL; P = .05) at 12 months, with numerically similar results at other time points.

CONCLUSIONS AND RELEVANCE: In this cohort study, housing stability was associated with small differences in type 2 diabetes outcomes; combining housing stability interventions with other diabetes interventions may be needed to improve type 2 diabetes outcomes more substantially.

PMID:40227681 | DOI:10.1001/jamanetworkopen.2025.4852

BJU Int. 2025 Apr 14. doi: 10.1111/bju.16727. Online ahead of print.

ABSTRACT

OBJECTIVES: To present the long-term outcomes of men with Grade Group (GG) 1 prostate cancer (PCa), included in the Prostate Cancer Research International Active Surveillance (PRIAS) study, and to assess the effect of the inclusion of magnetic resonance imaging (MRI) within the active surveillance (AS) protocol.

PATIENTS AND METHODS: The PRIAS study is a multicentre, prospective, web-based cohort study monitoring patients on AS. In total, 8910 men with GG1 PCa were followed in 169 centres worldwide. The cumulative incidences of definitive treatment, metastasis and PCa-specific mortality (PCSM) were estimated using competing risk analyses. Additionally, multivariable analysis was performed to assess the risk of reclassification, stratified by MRI performed around the time of diagnosis.

RESULTS: The cumulative incidence of definitive treatment 15 years post-diagnosis was 55% (95% confidence interval [CI] 53-57). For metastasis, the 15-year cumulative incidence was 2.7% (95% CI 1.5-4.4). Eight men of died from PCa, resulting in a 15-year cumulative PCSM incidence of 0.23% (95% CI 0.09-0.54). Compared to men with no MRI around the time of diagnosis, those who underwent MRI during the first 18 months of AS were associated with a significantly higher risk of reclassification to ≥GG2, while men with a positive MRI before diagnosis were associated with a higher risk of reclassification to GG2, but not to ≥GG3. Men with GG2 PCa on MRI-targeted rebiopsy who underwent definitive treatment did not show a statistically significant higher risk of 5-year disease recurrence compared to those who had GG1 PCa on last biopsy during AS.

CONCLUSIONS: Our study confirms the safety of AS for GG1 PCa, with low metastasis and PCSM rates over 15 years. Furthermore, the inclusion of MRI in AS prompts increased detection of GG2, leading to increased treatment rates despite similar short-term risks. To minimise overtreatment, expanding eligibility for AS and the uptake of AS in men with favourable GG2 PCa is crucial to address the stage shift resulting from the increased accuracy of MRI.

PMID:40223578 | DOI:10.1111/bju.16727

J Gynecol Oncol. 2025 Apr 8. doi: 10.3802/jgo.2025.36.e65. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to investigate the impact of bladder volume on dosimetric outcomes of organs at risk (OARs) in postoperative volumetric-modulated arc therapy (VMAT) for patients with cervical cancer.

METHODS: The study included 71 cervical cancer patients who received radical hysterectomy and postoperative VMAT between January 2020 and January 2023. Patients were divided into 3 groups according to average bladder volume observed in computed tomography simulation positioning images: Group A (<300 mL), Group B (300-500 mL), and Group C (≥500 mL). The study compared dosimetric parameters(V₃₀, V₄₀, V₄₅, and D_2cc) for OARs like the bladder, rectum, small intestine, and sigmoid colon, as well as the incidence of radiation cystitis and proctitis among these groups.

RESULTS: The median follow-up of the cohort was 33 months, with a median patient age of 48 years. Group A demonstrated the highest V₄₀ and V₄₅ values for the bladder (p<0.05). Conversely, Group C displayed the highest values for the V₄₀ and V₄₅ of the rectum, as well as the V₄₅ and D_2cc of the sigmoid colon (p<0.05). No statistically significant differences were observed in the incidence of acute radiation cystitis and radiation cystitis among the 3 groups. Significant difference was observed in the incidence rates of late radiation cystitis (p<0.05) and radiation proctitis (p<0.05) among the 3 groups. Group A exhibited the highest prevalence of late radiation cystitis, whereas Group C demonstrated the highest prevalence of late radiation proctitis.

CONCLUSION: Bladder volume significantly affects dosimetry of the bladder, rectum, and sigmoid colon in postoperative VMAT for cervical cancer patients. A recommended bladder volume of 300-500 mL helps reduce radiation-induced cystitis and proctitis.

PMID:40223551 | DOI:10.3802/jgo.2025.36.e65

Ann Ig. 2025 Apr 10. doi: 10.7416/ai.2025.2699. Online ahead of print.

ABSTRACT

BACKGROUND: It has been observed that women vaccinated against coronavirus disease 2019 (COVID-19) may show axillary lymphadenopathy at screening mammogram, which may become suspicious for malignancy, leading to an increased recall rate for further diagnostic evaluations and a higher number of false-positive results, as well as considerable emotional distress for the women involved.

STUDY DESIGN: The study aimed to assess the incidence of doubt/positive results in the 1st level mammogram among women who received a COVID-19 vaccine within 4 weeks before mammogram, compared to unvaccinated women. Further aims included the analysis of the distribution of doubt/positive 1st level screening mammogram results according to different women-related and diagnostic work-up-related characteristics, and the evaluation of the incidence of false-positive results observed at the 2nd level.

METHODS: The cohort study was carried out by retrospectively reviewing electronic data records related to the breast screening program of the Local Health Authority of Bologna in 2021 concerning women between 45 and 74 years old. Excluded were the women outside the age range, with prior breast cancer history, or receiving COVID-19 vaccination more than 4 weeks before the mammogram.

RESULTS: A total of 43,856 (mean age 56.6 ± 8.7) women met the study’s inclusion criteria. Among all enrolled women, the recall rate was 5.5% (N=2,394). There were no statistically significant differences in doubt/positive results between vaccinated within 4 weeks before the mammogram and unvaccinated women (5.5% versus 5.4%, p=0.649). However, those who received the Pfizer vaccine showed a significantly higher rate of doubt/positive results.

CONCLUSIONS: Healthcare professionals’ awareness of vaccine records and educating patients about rare adverse effects can help prevent unnecessary biopsies, interventions, and changes in patient management. Further research is needed to confirm our findings.

PMID:40223494 | DOI:10.7416/ai.2025.2699

Iran Biomed J. 2025 Jan 1;29(1 & 2):68-81.

ABSTRACT

BACKGROUND: Metacyclogenesis is a critical developmental process in the life cycle of Leishmania parasites, particularly in their transition from non-infective procyclic to infective metacyclic promastigotes. This transformation is closely linked to the metabolic adaptation of the parasite, optimizing its survival and infectivity under varying environmental conditions. In this study, we integrated metabolomics and transcriptomics data to gain deeper insights into the underlying molecular mechanisms of L. major metacyclogenesis.

METHODS: The metabolic profiles of procyclic and metacyclic promastigotes were first identified using ¹H-NMR spectroscopy. Multivariate statistical analysis revealed 44 significantly different metabolites between the two forms. Metabolic pathway analysis for differentially expressed metabolites identified 10 significantly different pathways (p < 0.05 and impact > 0.05). Finally, the differential gene expression analysis was conducted on transcriptomic data retrieved from public repositories.

RESULT: Results indicated the upregulation of 238 genes and the downregulation of 49 genes during metacyclogenesis. These genes underwent GO and KEGG pathway analyses, revealing upregulated GO categories in the metacyclic phase, including protein phosphorylation, ion transport, signal transduction, and phosphorylation reactions, as well as several downregulated GO categories. Integrating metabolomic and transcriptomic data demonstrated seven significantly different KEGG pathways between procyclic and metacyclic forms, including fructose and mannose, galactose, ascorbate and aldarate, arginine and proline, histidine, inositol phosphate, and pyruvate metabolism.

CONCLUSION: Our findings suggest distinct metabolic profiles and changes in gene expression associated with the transition from procyclic to metacyclic promastigotes. By integrating diverse omics data, we could identify more reliable altered pathways and biomarkers.

PMID:40223480

Cancer. 2025 Apr 15;131(8):e35793. doi: 10.1002/cncr.35793.

ABSTRACT

BACKGROUND: Major events, such as Hurricanes Irma and Maria and the coronavirus disease 2019 (COVID-19) pandemic disrupted Puerto Rico’s health system. Lack of access to colorectal cancer (CRC) screening services may have impeded timely diagnosis. The authors examined the impact of these events on CRC incidence in Puerto Rico.

METHODS: The Puerto Rico Central Cancer Registry database allowed the authors to obtain CRC cases from 2012 to 2021. An interrupted time-series analysis was performed to examine changes in CRC incidence immediately after and during the periods after the hurricanes and the pandemic. Analysis periods included: pre-hurricanes, post-hurricanes, and post-COVID-19 lockdown restrictions.

RESULTS: We observed a level change of -8.3 CRC cases was observed in the month the hurricanes struck Puerto Rico, corresponding to an immediate decrease of 17.5%. After a slight upward trend, a second decline of 39.4 CRC cases was estimated after the COVID-19 lockdown restrictions, representing an immediate change of -24.2%. By the end of the study, the estimated numbers of patients with early stage CRC patients and those aged 50-75 years did not reach the expected numbers. In addition, CRC cases in patients with late-stage disease and in those aged younger than 50 years and aged 76 years and older exceeded the expected numbers.

CONCLUSIONS: Hurricanes Irma and Maria and the COVID-19 pandemic caused a decrease in CRC incidence in Puerto Rico. This analysis suggests that limited access to CRC screening services during these events likely hindered CRC diagnoses. To fully understand the long-term effects, monitoring of CRC trends will be necessary in the coming years.

PMID:40223414 | DOI:10.1002/cncr.35793

Hand (N Y). 2025 Apr 14:15589447251322916. doi: 10.1177/15589447251322916. Online ahead of print.

ABSTRACT

BACKGROUND: Thumb trapeziometacarpal joint (TMj) contact area, pressures, and stability were quantified during metacarpal osteotomy and distraction lengthening with and without TMj-spanning fixation in a cadaver model. Spanning fixation was hypothesized to decrease TMj contact pressure, contact area, joint space narrowing, and subluxation compared with metacarpal fixation alone.

METHODS: Twenty matched-paired cadaver specimens underwent ligament-sparing thumb TMj dissection. A metacarpal external fixator was applied with and without a TMj-spanning component in 2 groups: spanning and nonspanning. A diaphyseal osteotomy was performed. The TMj contact pressure and area were recorded with an intraarticular sensor at baseline and at distraction intervals of 10, 20, 30, and 35 mm. The number of overloaded sensor cells (sensels), (>2000 psi) were recorded. The TMj subluxation and joint space width were assessed at all intervals with lateral thumb radiographs. Statistical analysis used paired 2-tailed t tests to account for inherent specimen characteristics.

RESULTS: Group 1 (TMj-spanning) exhibited a nonstatistically significant reduction in contact area and demonstrated fewer overloaded sensels. There was significantly less joint space narrowing and joint subluxation from 10 to 30 mm of distraction compared with group 2 (nonspanning).

CONCLUSIONS: The TMj spanning fixation during metacarpal distraction decreased joint space narrowing and TMj subluxation. Despite finding reduced contact area and fewer overloaded sensels in group 1, these parameters did not reach statistical significance. Spanning TMj fixation may mitigate TMj instability during metacarpal distraction osteogenesis.

PMID:40223408 | DOI:10.1177/15589447251322916

Small. 2025 Apr 13:e2412312. doi: 10.1002/smll.202412312. Online ahead of print.

ABSTRACT

Gas separation is a critical industrial process that consumes a significant amount of energy due to the widely used techniques that are currently employed. Adsorptive materials-such as metal-organic frameworks (MOFs)-show promise as an energy-efficient alternative. Of particular current interest are novel, temperature-dependent separation processes in MOFs, such as the recently reported separation of ternary isomeric hydrocarbon mixtures within one and the same material. However, the mechanisms of these highly desirable separations remain poorly understood. Herein, through a combination of ab initio simulations and statistical mechanics, it is shown that the temperature dependence is the result of a constraint on the guest molecule’s entropic degrees of freedom when loaded into the MOF, caused by the fortuitous tight fitting of the guest inside the pore. While the framework applies to all molecular adsorption in porous media, it is essential for the description of large molecules in small pores, which is demonstrated here using the separation of C6 isomers in Ca(H₂tcpb) as a test case. The developed framework and analysis not only reveal the reason why separation occurs but also predict the temperatures at which it takes place, thus opening the door to newly designed MOFs with tailor-made precision.

PMID:40223407 | DOI:10.1002/smll.202412312

Physiol Rep. 2025 Apr;13(7):e70337. doi: 10.14814/phy2.70337.

ABSTRACT

Poor recovery pattern of oxygen consumption (V̇O₂) post-exercise is associated with adverse clinical outcomes. However, it remains unknown which component of the O₂ pathway (Fick principle) defines this prognostic risk, for example, peripheral extraction, stroke volume, heart rate. Retrospective cohort study included 120 participants (heart failure with preserved ejection fraction: HFpEF = 68, pre-capillary pulmonary hypertensio n = 31, non-cardiac dyspnea = 21). Percent recovery metrics were calculated as the percent reduction of each hemodynamic variable from peak exercise to recovery, for example, (exercise-recovery)/exercise ×100%. Overall, the mean age (standard deviation) was 62.6 (14.4) years and 54% were females. Among the three groups (HFpEF, pre-capillary pulmonary hypertension, non-cardiac dyspnea), recovery patterns of O₂ pathway components were statistically non-significant. Peripheral extraction recovery (r² = 0.43, p < 0.001) and heart rate recovery (r² = 0.25, p < 0.001) correlated with peak V̇O₂, but only peripheral extraction recovery remained significant in multivariate analysis (p = 0.01). Peripheral extraction recovery (<41%; median) demonstrated poor one-year survival from mortality and heart failure hospitalizations (HR 2.82; CI 95% 1.38-5.74, p = 0.003). Peripheral extraction recovery pattern is the most significant component of the O₂ pathway and defines adverse outcomes. Physiologically, it elucidates the importance of skeletal muscle and peripheral vascular function.

PMID:40223379 | DOI:10.14814/phy2.70337