Nevin Manimala

Harm Reduct J. 2025 Jul 14;22(1):119. doi: 10.1186/s12954-025-01268-y.

ABSTRACT

BACKGROUND: Naloxone, a life-saving medication that reverses opioid overdoses, was available in the United States only by prescription until March 2023, when the federal government approved nasal-spray formulations for over the counter sales to expand access. We assessed the availability of naloxone in a sample of pharmacies across the state of Connecticut.

METHODS: Between September 15 and November 24, 2024, trained community-based volunteers surveyed a convenience sample of pharmacies throughout the state, focusing on naloxone signage, availability, cost, and in-store location. Pharmacies were categorized into three groups: chain pharmacies, pharmacies within grocery stores, and independent pharmacies. Summary statistics for the full sample and the three subgroups were tabulated, and differences between groups were analyzed using Fisher’s exact tests.

RESULTS: A total of 162 pharmacies across all Connecticut counties were evaluated. While naloxone was available in most pharmacies, it was predominantly kept behind the pharmacy counter (n = 111, 73.5%) or the general checkout counter (n = 46, 30.5%). Fewer than 20% of pharmacies (n = 29) had naloxone easily accessible on an aisle shelf. Pricing was often high (≥ $60), particularly in independent pharmacies (n = 7, 22.6%; p < 0.001). Additionally, fewer than 20% of pharmacies (n = 31) displayed signage related to naloxone availability, and all signage was exclusively in English.

CONCLUSIONS: Despite widespread availability, naloxone access was restricted by its in-store location, high cost, and inadequate signage. This highlights a notable discrepancy between naloxone availability and accessibility, suggesting a lag in the effective implementation of policy in intended settings.

PMID:40660265 | DOI:10.1186/s12954-025-01268-y

J Med Internet Res. 2025 Jul 14;27:e71527. doi: 10.2196/71527.

ABSTRACT

BACKGROUND: Health care systems are increasingly facing challenges posed by the aging of populations. In particular, hospitalization, both initial and subsequent, is often observed among older adult patients. However, research suggests that nearly 23% of all hospitalizations could be avoided. In this perspective, remote patient monitoring (RPM) systems are emerging as a promising solution, enabling professionals to detect and manage patient complexities early within home-based care settings.

OBJECTIVE: This study aims to provide additional analyses regarding the impact of the EPOCA RPM system for polypathological older adult patients on the total number of unplanned hospitalization days and admissions, as well as emergency department (ED) visits. In a prior study, we evaluated the impact when the operator of the RPM system is a geriatrician. In this study, we assess the impact when the general practitioner is the operator.

METHODS: We used a retrospective, before-and-after cohort design. Polypathological older adult patients aged 70 and older, who benefited from the EPOCA RPM system for at least 1 year (between February 2022 and August 2024), were included in the analysis. We compared the outcomes between the previous year (Y-1) and the follow-up year (Y) by the EPOCA RPM system. Statistical analyses were significant at P value <.05.

RESULTS: In total, 80 patients were included in the analysis, with an average age of 87. The results showed a significant reduction (P<.001) between Y-1 and Y in the total number of unplanned hospital admissions (by 57%), hospitalization days (by 49%), and ED visits (by 62%). Our findings reflected a significant decrease per patient from 0.99 to 0.42 in hospital admissions, from 0.99 to 0.37 in ED visits, and a reduction of 9.7 hospitalization days per year (P<.001). Additional analyses stratifying by hospitalization history, disability level, and caregiver status showed that the greatest effect of the RPM system was on patients with high risk and severe disability. Finally, there was no observed increase in mortality or transfers to intensive care units.

CONCLUSIONS: Our findings are consistent with our previous results regarding the potential benefits of the EPOCA RPM system in managing care for polypathological older adult patients, this time with general practitioners as system operators. They also support existing evidence on the promise of RPM in improving care and health outcomes for older adult patients while alleviating hospital burdens by reducing unplanned hospitalizations and ED visits. It is, therefore, essential to incorporate reimbursement policies for these RPM initiatives so as to facilitate their adoption within health care systems and enhance their impact on health outcomes.

PMID:40658993 | DOI:10.2196/71527

J Bras Nefrol. 2025 Jul-Sep;47(3):e20240178. doi: 10.1590/2175-8239-JBN-2024-0178en.

ABSTRACT

INTRODUCTION: Graduate studies in Brazil have experienced significant growth since the 1990s. Over a 40-year period, the Graduate Program in Nephrology at Unifesp has qualified 261 master’s graduates, 111 doctors and 146 individuals who completed both a master’s and a doctoral degree. Of these, 278 hold a degree in Medicine. Medical postgraduates were responsible for 124 master’s dissertations and 243 doctoral theses completed.

OBJECTIVE: This study analyzed the profile and professional trajectories of graduate students from the Nephrology Graduate Program at Unifesp.

METHODS: The authors used the university’s database to establish the graduates’ profile and applied a questionnaire to identify their professional performance in academia and the job market. The graduates were divided into three groups: G1 – 1976 to 1997 (N = 127); G2 – 1998 to 2006 (N = 150); G3 – 2007 to 2015 (N = 241).

RESULTS: Regarding sex, male medical graduates were responsible for 53.6% of all completion papers; however, in the most recent period, women accounted for 61% of the works. Female participation was consistently higher among graduates from other areas, at 73.8% of the total. Among the physicians, 65.5% graduated from public universities, with the first group standing out with 73%. In the other groups, 59.5% and 59.8% came from public HEIs, respectively. The overall average income reported by master’s graduates responding to the questionnaire ranged from 5 to 10 minimum wages (MW), and for doctors, above 10 MW.

CONCLUSION: Doctoral graduates had a strong presence in academia, predominantly within the public sector.

PMID:40658958 | DOI:10.1590/2175-8239-JBN-2024-0178en

Ann Intern Med. 2025 Jul 15. doi: 10.7326/ANNALS-25-00997. Online ahead of print.

ABSTRACT

BACKGROUND: Aluminum is used as an adjuvant in nonlive vaccines administered in early childhood. Concerns persist about potential associations between vaccination with aluminum-adsorbed vaccines and increased risk for chronic autoimmunity, atopy or allergy, and neurodevelopmental disorders. Large-scale safety data remain limited.

OBJECTIVE: To assess the association between cumulative aluminum exposure from early childhood vaccination and risk for autoimmune, atopic or allergic, and neurodevelopmental disorders.

DESIGN: A cohort study linking nationwide registry data on childhood vaccinations, outcome diagnoses, and potential confounders, leveraging the variations in the aluminum content of childhood vaccines over time.

SETTING: Denmark, 1997 to 2020.

PARTICIPANTS: 1 224 176 children born in Denmark between 1997 and 2018 who were alive and residing in the country at age 2 years.

INTERVENTION: Cumulative aluminum amount received (per 1-mg increase) through vaccination during the first 2 years of life.

MEASUREMENTS: Incident events of 50 chronic disorders, including autoimmune (dermatologic, endocrinologic, hematologic, gastrointestinal, and rheumatic), atopic or allergic (asthma, atopic dermatitis, rhinoconjunctivitis, and allergy), and neurodevelopmental (autism spectrum disorder and attention deficit-hyperactivity disorder).

RESULTS: Cumulative aluminum exposure from vaccination during the first 2 years of life was not associated with increased rates of any of the 50 disorders assessed. For groups of combined outcomes, adjusted hazard ratios per 1-mg increase in aluminum exposure were 0.98 (95% CI, 0.94 to 1.02) for any autoimmune disorder, 0.99 (CI, 0.98 to 1.01) for any atopic or allergic disorder, and 0.93 (CI, 0.90 to 0.97) for any neurodevelopmental disorder. For most individually analyzed outcomes, the upper bounds of the 95% CIs were incompatible with relative increases greater than 10% or 30%.

LIMITATION: Individual medical records were not reviewed.

CONCLUSION: This nationwide cohort study did not find evidence supporting an increased risk for autoimmune, atopic or allergic, or neurodevelopmental disorders associated with early childhood exposure to aluminum-adsorbed vaccines. For most outcomes, the findings were inconsistent with moderate to large relative increases in risk, although small relative effects, particularly for some rarer disorders, could not be statistically excluded.

PRIMARY FUNDING SOURCE: None.

PMID:40658954 | DOI:10.7326/ANNALS-25-00997

Chaos. 2025 Jul 1;35(7):073125. doi: 10.1063/5.0273619.

ABSTRACT

In this study, we investigate the dynamic mechanisms of tumor progression in response to fluctuations and uncertainties within the tumor-immune microenvironment. Utilizing temporal single-cell data, we develop a novel stochastic reaction-convection model that captures the spatiotemporal dynamics of macrophage responses to tumor cells subjected to both multiplicative and additive noise generated by non-homologous microenvironmental fluctuations. We prove the existence and uniqueness of a global positive solution for the proposed stochastic model. Then, by combining the stochastic Lyapunov analysis and the comparison theorem, we explore the moment boundaries for cell populations, as well as the asymptotic behavior at the boundary equilibrium points; sufficient conditions for driving sustained tumor growth and clearance are derived by employing the ergodicity theorem and are interestingly found to be only related to multiplicative noise. Furthermore, we employ an upwind finite difference scheme to simulate the effects of different noise types on a cell population distribution and the persistence of tumor growth. Results show that while additive noise influences the multimodal distribution of early tumor cell phenotypes, it has minimal impact on the mean density of tumor cells, indicating that additive noise acts primarily as a diffusion factor. In contrast, increasing multiplication noise effectively inhibits the development without altering the number of peaks in a phenotypic distribution. Interestingly, when additive and multiplicative noises are correlated, stronger additive noise can have dual effects on the steady-state distribution of tumor cells, with increased correlation positively influencing tumor cell elimination. These results provide novel insight into the tumor-immune microenvironment dynamics.

PMID:40658932 | DOI:10.1063/5.0273619

Chaos. 2025 Jul 1;35(7):073124. doi: 10.1063/5.0274274.

ABSTRACT

We explore the behavior of statistical complexity as a possible indicator of the crossover between classical and quantum behaviors in thermodynamic systems. Using the López-Ruiz, Mancini, and Calbet statistical complexity measure C, along with the disequilibrium D, we analyze both the ideal and van der Waals gases as they approach regimes where quantum statistics become significant. We find that C reaches a well-defined maximum at a characteristic temperature Tc in all cases considered. Interestingly, the numerical value of C at this temperature is the same across these models. While the underlying reason for this behavior is not yet fully understood, it suggests that statistical complexity may capture structural changes in the system’s phase space that are associated with the emergence of quantum effects. The shift of Tc in the van der Waals case, depending on the excluded volume parameter b, reflects the influence of interactions on this crossover behavior. These results indicate that C might serve as a useful proxy for detecting the changes in the statistical structure of many-body systems as they transition from classical to quantum regimes.

PMID:40658929 | DOI:10.1063/5.0274274

Clin Orthop Relat Res. 2025 Jun 25. doi: 10.1097/CORR.0000000000003602. Online ahead of print.

ABSTRACT

BACKGROUND: In most patients, a soft tissue sarcoma is sporadic and not related to a specific known cause; however, demographic, environmental, and lifestyle factors may be linked to its development. Alcohol consumption, a major risk factor for oncogenesis, has increased, particularly among females, and it might be a risk factor for soft tissue sarcoma, with potential differences in the association based on the biological differences between males and females. Nevertheless, there is a lack of research data to determine the association between alcohol consumption and soft tissue sarcoma. Because soft tissue sarcoma often has poor oncologic and functional outcomes once it develops, identifying controllable factors for prevention would be beneficial.

QUESTIONS/PURPOSES: (1) Is there a dose-response association between overall alcohol consumption and the incidence of soft tissue sarcoma? (2) Are there associations between the amount of alcohol consumption per occasion and drinking frequency with the incidence of soft tissue sarcomas?

METHODS: This was a retrospective, population-based comparative study using the National Health Insurance Service database, which offers large-scale data from a relatively ethnically homogeneous Korean population, along with comprehensive health information. The database includes demographic, socioeconomic, health checkups, social behavior surveys, and claims data. We screened 4,234,415 people 20 years or older who underwent health checkups in 2009. Soft tissue sarcoma was defined as ICD-10 codes C47 or C49 and the registration code for cancer (V193), with at least two outpatient claims or more than one inpatient claim per year. Among the screened individuals, we excluded 7% (286,384) because of incomplete data, and we excluded 0.02% (198) with soft tissue sarcoma diagnosed before the index year. To better explore the association, we excluded 0.2% (10,088) of patients who died or developed soft tissue sarcoma in the index year. Finally, we included 3,937,745 participants (2,148,348 males and 1,789,397 females) and followed them until December 31, 2020 (mean follow-up 10 ± 1 years). The mean daily alcohol consumption was calculated using the drinking frequency (number of days per week) and the mean amount consumed on each occasion (the number of glasses [8 grams of ethanol per glass]), based on the concept of a standard drink in Korea. Based on the ethanol consumption, alcohol drinking levels were divided into three categories: individuals who did not drink, those who drank < 30 grams per day of ethanol, and those who drank ≥ 30 grams per day of ethanol. The soft tissue sarcoma incidence was calculated by dividing the number of events by the total person-years of follow-up. To address our primary study question, which was about the association of soft tissue sarcoma incidence and overall alcohol consumption, the analysis model was adjusted for age (years), smoking status (nonsmoker, past smoker, and current smoker), regular exercise (yes versus no), and metabolic syndrome (yes versus no). To address our secondary outcome, which was about associations between the amount of alcohol consumption per occasion and drinking frequency with the incidence of soft tissue sarcomas, alcohol consumption was divided into drinking frequency and amount of alcohol intake per occasion. Among the participants, 969 (males n = 550, females n = 419) were diagnosed with soft tissue sarcoma during the follow-up period, resulting in an incidence of 2.43 (males 2.55, females 2.30) per 100,000 person-years. To identify a monotonic dose-response association, we considered not only the statistical significance for individual exposure groups, but also the overall consistent directional trend in association across all groups.

RESULTS: Compared with the individuals who did not drink (reference), alcohol consumption was not associated with an increased incidence of soft tissue sarcoma in overall participants who drank < 30 grams per day and those who drank ≥ 30 grams per day of ethanol (adjusted HR 1.05 [95% confidence interval (CI) 0.9 to 1.22] and adjusted HR 0.92 [95% CI 0.70 to 1.21], respectively; p = 0.58 among three groups) or in males who drank < 30 grams per day and those who drank ≥ 30 grams per day of ethanol (adjusted HR 0.84 [95% CI 0.70 to 1.01] and adjusted HR 0.75 [95% CI 0.56 to 1.00], respectively; p = 0.17 among three groups). In females, compared with individuals who did not drink (reference), soft tissue sarcoma incidence increased in those who drank < 30 grams per day and those who drank ≥ 30 grams per day of ethanol (adjusted HR 1.51 [95% CI 1.20 to 1.9]; p = 0.01 and adjusted HR 2.48 [95% CI 1.17 to 5.27]; p = 0.06, respectively). Although a drinking frequency of 1 to 2 days per week was associated with increased risk of developing a soft tissue sarcoma (adjusted HR 1.61 [95% CI 1.27 to 2.04]; p = 0.003), the HR did not increase with higher drinking frequency across all four groups (adjusted HR 1.21 [95% CI 0.66 to 2.200; p = 0.88 for 3 to 5 days and adjusted HR 1.46 [95% CI 0.47 to 4.56]; p = 0.60 for 6 to 7 days, respectively). However, for females consuming 3 to 4, 5 to 7, and ≥ 14 glasses per occasion, the adjusted HRs were 1.51 (95% CI 1.07 to 2.13; p = 0.09), 1.73 (95% CI 1.16 to 2.58; p = 0.06), and 3.70 (95% CI 1.37 to 9.98; p = 0.03), respectively, and the HR tended to increase with higher consumption levels per occasion across all six groups (adjusted HR 1.30 [95% CI 0.94 to 1.81]; p = 0.09 for 1 to 2 glasses and adjusted HR 1.73 [95% CI 0.81 to 3.68]; p = 0.38 for 8 to 13 glasses).

CONCLUSION: This nationwide population-based study demonstrated a tendency toward a dose-response relationship between the level of alcohol consumption and the incidence of soft tissue sarcoma among females. These findings suggest that strategies for individuals vulnerable to alcohol-related complications could be considered. These strategies might include campaigns, education programs, and policy interventions; social guidelines to reduce alcohol consumption may be warranted, and alcohol consumption may be considered as a screening factor for soft tissue sarcoma. To clarify whether there is a causal relationship, further research is required on the mechanisms through which alcohol consumption and drinking patterns may contribute to the development of soft tissue sarcoma.

LEVEL OF EVIDENCE: Level III, prognostic study.

PMID:40658922 | DOI:10.1097/CORR.0000000000003602

J Nurs Care Qual. 2025 Jul 9. doi: 10.1097/NCQ.0000000000000891. Online ahead of print.

ABSTRACT

BACKGROUND: Postoperative surgical site infections (SSIs) are a significant concern in cardiac surgery.

PURPOSE: To characterize clinical and perioperative factors associated with the absence of deep SSIs in a cohort of patients who underwent coronary artery bypass grafting (CABG) surgery.

METHODS: A retrospective, single-center study was conducted, analyzing data from 214 patients between August 2023 and June 2024. Perioperative care measures included adherence to an established cardiothoracic SSI prevention bundle, consisting of preoperative chlorhexidine gluconate bathing, preoperative nasal decolonization, intraoperative antibiotics, and intraoperative and postoperative glycemic control.

RESULTS: Adherence to the prevention bundle varied (82.7-98.6%). A statistically significant difference in postoperative glycemic control was observed between elective and urgent surgery cases.

CONCLUSION: This study’s findings highlight the potential effect of rigorous protocol adherence and the critical role of standardized nursing care in SSI prevention. Future research to optimize patient care and outcomes during and after CABG surgery is recommended.

PMID:40658920 | DOI:10.1097/NCQ.0000000000000891

Crit Care Explor. 2025 Jul 14;7(7):e1290. doi: 10.1097/CCE.0000000000001290. eCollection 2025 Jul 1.

ABSTRACT

IMPORTANCE: While corticosteroid administration in septic shock has been shown to reduce vasopressor requirements and accelerate shock reversal, the optimal discontinuation strategy remains unexplored.

OBJECTIVES: The purpose of this study was to assess whether rates of hemodynamic instability differ among patients with septic shock undergoing abrupt hydrocortisone discontinuation compared with gradual tapering.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study conducted in five medical and surgical ICUs at a tertiary care hospital, involving adult patients (≥ 18 yr) with septic shock who received at least 48 hours of stress-dose hydrocortisone (≥ 200 mg/d).

MAIN OUTCOMES AND MEASURES: The primary outcome was hemodynamic instability, defined as vasopressor reinitiation during tapering or within 72 hours of hydrocortisone discontinuation. Secondary outcomes included dysglycemia, duration of mechanical ventilation, ICU and hospital length of stay, and mortality.

RESULTS: Patients were grouped based on their hydrocortisone discontinuation strategy into abrupt and gradual tapering groups. A total of 414 patients were included in this evaluation. Gradual tapering was associated with higher rates of hemodynamic instability (29.2% vs. 12.9%; p < 0.001), more frequent dysglycemia (59.4% vs. 43.1%; p < 0.001), longer hydrocortisone use (9.9 vs. 4.1 d; p < 0.001), and extended mechanical ventilation (20 vs. 15 d; p = 0.014) and ICU stay (23 vs. 17 d; p = 0.008). Total hydrocortisone duration was the strongest independent predictor of post-discontinuation hemodynamic instability, regardless of strategy (adjusted odds ratio, 1.083; 95% CI, 1.025-1.145; p = 0.004).

CONCLUSIONS AND RELEVANCE: While abrupt hydrocortisone discontinuation was associated with fewer ICU-related adverse events, hydrocortisone duration was the primary factor influencing hemodynamic instability post-discontinuation among patients with septic shock. Prospective studies are needed to determine the optimal discontinuation strategy in septic shock.

PMID:40658883 | DOI:10.1097/CCE.0000000000001290

J Chem Inf Model. 2025 Jul 14. doi: 10.1021/acs.jcim.4c01652. Online ahead of print.

ABSTRACT

Breast cancer (BC) is the second most common cause of cancer in women and the most common kind of cancer diagnosed with a high mortality rate. This heterogeneous disease is classified into multiple subtypes based on the expression of key biomarkers, including human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and progesterone receptor (PR). These biomarkers have significantly transformed breast cancer treatment and played a crucial role in improving the patient prognosis. Given the complexity of BC, there is a pressing need to develop additional therapeutic agents and pharmacological targets. To address this, network-based gene expression profiling has emerged as a valuable method for identifying potential therapeutic targets, as it considers various factors such as disease conditions, gene expression levels, and protein-protein interactions We began our analysis by employing statistical methods, including p-values and false discovery rates (FDR), to identify differentially expressed genes (DEGs) as potential biomarkers in breast cancer (BC). A total of 123 DEGs were identified, with 101 genes showing downregulation and 11 genes exhibiting upregulation. Survival and expression analyses indicated that each hub gene plays a crucial role in the initiation and progression of BC. An enrichment analysis revealed that most of these genes are integral components of various signaling networks. Additionally, we identified key kinases and transcription factors that regulate the proteins involved in protein-protein interactions (PPIs) associated with the DEGs. From this analysis, we also deduced potential pharmaceuticals that could interact with these hub genes. Notably, HMOX1 (Heme Oxygenase 1) emerged as a particularly promising hub gene based on our computational analysis. Promising novel compounds were investigated, resulting in high potency of binding affinities through docking and simulation investigation. The molecular dynamics simulation demonstrated significant stability of the anticipated compounds, especially the top2 complex system at the docked site. The significant binding affinity between the chemical and the binding pockets of HMOX1 complexes was confirmed by the calculation of binding free energies using MMPBSA and MMGBSA followed by hydrogen bond analysis. Hence, these findings significantly enhance our understanding of critical biomarkers in breast cancer.

PMID:40658875 | DOI:10.1021/acs.jcim.4c01652