Nevin Manimala

PLoS One. 2025 Jan 14;20(1):e0317315. doi: 10.1371/journal.pone.0317315. eCollection 2025.

ABSTRACT

OBJECTIVE: Blood urea nitrogen (BUN) is a commonly used biomarker for assessing kidney function and neuroendocrine activity. Previous studies have indicated that elevated BUN levels are associated with increased mortality in various critically ill patient populations. The focus of this study was to investigate the relationship between BUN and 28-day mortality in intensive care patients.

METHODS: This was a multi-centre retrospective cohort study that made use of data from the eICU Collaborative Research Database. The primary exposure variable was BUN, and the outcome was 28-day mortality. The following variables were included as covariates: age, gender, BMI, white blood cell count, creatinine, GCS score, APACHE IV score, and diabetes. The statistical analyses included univariate and multivariate logistic regression, as well as generalized additive modelling, which was employed to assess the non-linear relationship between BUN and mortality.

RESULTS: A total of 63,757 elderly patients were included in the study, with a 28-day mortality of 6.5%. The univariate analysis indicated that elevated BUN quartiles were associated with an increased risk of mortality. The results of the multivariate analysis further confirmed the non-linear relationship between BUN and mortality. When BUN was less than 32 mg/dL, there was a significant positive association, with an adjusted odds ratio of 1.230 (95% CI: 1.154-1.311, p<0.0001) for every 10 mg/dL increase in BUN. However, when BUN was greater than or equal to 32 mg/dL, BUN level had no significant effect on mortality.

CONCLUSION: BUN showed a nonlinear, threshold correlation with 28-day mortality in critically ill patients. The higher the BUN, the greater the risk of death if the BUN is below the threshold.

PMID:39808678 | DOI:10.1371/journal.pone.0317315

PLoS Comput Biol. 2025 Jan 14;21(1):e1012234. doi: 10.1371/journal.pcbi.1012234. Online ahead of print.

ABSTRACT

Chronic pain is a wide-spread condition that is debilitating and expensive to manage, costing the United States alone around $600 billion in 2010. In a common symptom of chronic pain called allodynia, non-painful stimuli produce painful responses with highly variable presentations across individuals. While the specific mechanisms remain unclear, allodynia is hypothesized to be caused by the dysregulation of excitatory-inhibitory (E-I) balance in pain-processing neural circuitry in the dorsal horn of the spinal cord. In this work, we analyze biophysically-motivated subcircuit structures that represent common motifs in neural circuits in laminae I-II of the dorsal horn. These circuits are hypothesized to be part of the neural pathways that mediate two different types of allodynia: static and dynamic. We use neural firing rate models to describe the activity of populations of excitatory and inhibitory interneurons within each subcircuit. By accounting for experimentally-observed responses under healthy conditions, we specify model parameters defining populations of subcircuits that yield typical behavior under normal conditions. Then, we implement a sensitivity analysis approach to identify the mechanisms most likely to cause allodynia-producing dysregulation of the subcircuit’s E-I signaling. We find that disruption of E-I balance generally occurs either due to downregulation of inhibitory signaling so that excitatory neurons are “released” from inhibitory control, or due to upregulation of excitatory neuron responses so that excitatory neurons “escape” their inhibitory control. Which of these mechanisms is most likely to occur, the subcircuit components involved in the mechanism, and the proportion of subcircuits exhibiting the mechanism can vary depending on the subcircuit structure. These results suggest specific hypotheses about diverse mechanisms that may be most likely responsible for allodynia, thus offering predictions for the high interindividual variability observed in allodynia and identifying targets for further experimental studies on the underlying mechanisms of this chronic pain symptom.

PMID:39808669 | DOI:10.1371/journal.pcbi.1012234

J Psychosoc Nurs Ment Health Serv. 2025 Jan 15:1-10. doi: 10.3928/02793695-20250107-03. Online ahead of print.

ABSTRACT

PURPOSE: To describe relationships among grit, spirituality, and hope in women Veterans (N = 80).

METHOD: A descriptive, correlational design was used. Study variables were measured with the Short Grit Scale, Daily Spiritual Experience Scale, and Hope Scale.

RESULTS: Mean scores for spirituality, grit, and hope were 4.37 (SD = 1.04), 3.47 (SD = 0.68), and 51.24 (SD = 7.17), respectively. Spirituality was positively associated with grit but was not statistically significant (r = 0.17, p = 0.14). Spirituality was positively associated with total hope (r = 0.241, p = 0.04). Total hope was positively correlated with grit (r = 0.378, p < 0.001). The coefficient measuring the total effect of spirituality on grit was 0.12 (p = 0.11). When hope was introduced, the coefficient was reduced to 0.05, indicating that hope mediated the relationship between spirituality and grit.

CONCLUSION: Strong levels of spirituality, grit, and hope were evident in women Veterans. Positive relationships were found between variables, with hope influencing the relationship between spirituality and grit. Spirituality, hope, and grit are sources of strength in women Veterans that provide opportunities for support by the health care team. [Journal of Psychosocial Nursing and Mental Health Services, xx(xx), xx-xx.].

PMID:39808489 | DOI:10.3928/02793695-20250107-03

JAMA. 2025 Jan 14. doi: 10.1001/jama.2024.21653. Online ahead of print.

ABSTRACT

IMPORTANCE: Fragility fractures result in significant morbidity.

OBJECTIVE: To review evidence on osteoporosis screening to inform the US Preventive Services Task Force.

DATA SOURCES: PubMed, Embase, Cochrane Library, and trial registries through January 9, 2024; references, experts, and literature surveillance through July 31, 2024.

STUDY SELECTION: Randomized clinical trials (RCTs) and systematic reviews of screening; pharmacotherapy studies for primary osteoporosis; predictive and diagnostic accuracy studies.

DATA EXTRACTION AND SYNTHESIS: Two reviewers assessed titles/abstracts, full-text articles, study quality, and extracted data; when at least 2 similar studies were available, meta-analyses were conducted.

MAIN OUTCOMES AND MEASURES: Hip, clinical vertebral, major osteoporotic, and total fractures; mortality; harms; accuracy.

RESULTS: Three RCTs and 3 systematic reviews reported benefits of screening in older, higher-risk women. Two RCTs used 2-stage screening: Fracture Risk Assessment Tool estimate with bone mineral density (BMD) testing if risk threshold exceeded. One RCT used BMD plus additional tests. Screening was associated with reduced hip (pooled relative risk [RR], 0.83 [95% CI, 0.73-0.93]; 3 RCTs; 42 009 participants) and major osteoporotic fracture (pooled RR, 0.94 [95% CI, 0.88-0.99]; 3 RCTs; 42 009 participants) compared with usual care. Corresponding absolute risk differences were 5 to 6 fewer fractures per 1000 participants screened. The discriminative accuracy of risk assessment instruments to predict fracture or identify osteoporosis varied by instrument and fracture type; most had an area under the curve between 0.60 and 0.80 to predict major osteoporotic fracture, hip fracture, or both. Calibration outcomes were limited. Compared with placebo, bisphosphonates (pooled RR, 0.67 [95% CI, 0.45-1.00]; 6 RCTs; 12 055 participants) and denosumab (RR, 0.60 [95% CI, 0.37-0.97] from the largest RCT [7808 participants]) were associated with reduced hip fractures. Compared with placebo, no statistically significant associations were observed for adverse events.

CONCLUSIONS AND RELEVANCE: Screening in higher-risk women 65 years or older was associated with a small absolute risk reduction in hip and major fractures compared with usual care. No evidence evaluated screening with BMD alone or screening in men or younger women. Risk assessment instruments, BMD alone, or both have poor to modest discrimination for predicting fracture. Osteoporosis treatment with bisphosphonates or denosumab over several years was associated with fracture reductions and no meaningful increase in adverse events.

PMID:39808441 | DOI:10.1001/jama.2024.21653

JAMA Netw Open. 2025 Jan 2;8(1):e2454000. doi: 10.1001/jamanetworkopen.2024.54000.

ABSTRACT

IMPORTANCE: Adolescent and young adult (AYA) patients with advanced cancer often die in hospital settings. Data characterizing the degree to which this pattern of care is concordant with patient goals are sparse.

OBJECTIVE: To evaluate the extent of concordance between the preferred and actual location of death among AYA patients with cancer.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective cohort study included AYA patients (aged 12-39 years) with cancer who died between January 1, 2003, and December 31, 2019, after receiving care at Dana-Farber Cancer Institute and Kaiser Permanente Northern California or who died between January 1, 2009, and December 31, 2019, after receiving care at Kaiser Permanente Southern California. Data were analyzed from January 12 to July 1, 2024.

EXPOSURE: Death due to cancer.

MAIN OUTCOMES AND MEASURES: Medical record documentation of discussions about preferred location of death, actual location of death, and concordance between preferred and actual location of death.

RESULTS: The analytic population included 1929 AYA decedents, of whom 1049 (54.4%) were female; 227 (11.8%), Asian; 157 (8.1%), Black; 514 (26.6%), Hispanic; and 1184 (61.4%), White. Median age at death was 32 (IQR, 25-37) years. A total of 1226 AYA patients (63.6%) had a documented discussion about preferred location of death. Among those with a documented discussion, 594 (48.5%) did not have a documented preference, 402 (32.8%) wanted to die at home, 177 (14.4%) preferred a hospital death, and 48 (3.9%) desired inpatient hospice. Eight hundred and thirty patients (43.0%) died in acute care settings (256 [13.3%] intensive care unit [ICU], 548 [28.4%] hospital [non-ICU], and 26 [1.3%] emergency department), while 643 (33.3%) died at home and 47 (2.4%) in an inpatient hospice. Among the 528 patients with both a documented preferred death location of home, hospital, or inpatient hospice and documented death in one of these locations, the concordance between preferred and actual location of death was 401 (75.9%). One hundred and sixty-four of 172 patients (95.3%) who preferred a hospital death died there; 224 of 317 (70.7%) who preferred a home death died at home, and 13 of 39 (33.3%) who desired to die in inpatient hospice did so.

CONCLUSIONS AND RELEVANCE: Although many AYA patients with cancer died in their preferred location, over one-quarter of those who desired to die at home did not realize this goal. These findings highlight the need for effective solutions to enable goal-concordant care for this population.

PMID:39808433 | DOI:10.1001/jamanetworkopen.2024.54000

JAMA Netw Open. 2025 Jan 2;8(1):e2454084. doi: 10.1001/jamanetworkopen.2024.54084.

ABSTRACT

IMPORTANCE: The integration of patient-reported outcome (PRO) assessments in cardiovascular care has encountered considerable obstacles despite their established clinical relevance.

OBJECTIVE: To assess the impact of a physician- and patient-friendly electronic PRO (ePRO) monitoring system on the quality of cardiovascular care in clinical practice.

DESIGN, SETTING, AND PARTICIPANTS: This open-label, multicenter, pilot randomized clinical trial was phase 2 of a multiphase study that was conducted from October 2022 to October 2023 and focused on the implementation and evaluation of an ePRO monitoring system in outpatient clinics in Japan. During phase 1 (conducted from December 2021 to March 2022), this ePRO monitoring system was developed at a single outpatient center using feedback from patients and physicians. Eligible patients were older than 18 years with a clinical diagnosis of heart failure (HF), atrial fibrillation (AF), or coronary artery disease (CAD). Participants were randomly assigned 1:1 to either the ePRO or control group. Statistical analysis was based on the intention-to-treat approach.

INTERVENTION: Patients in the ePRO group were asked to complete the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), Atrial Fibrillation Effect on Quality-of-Life Questionnaire (AFEQT), or Seattle Angina Questionnaire (SAQ) on smart tablets before their clinical examination. Results were reviewed by physicians at each outpatient visit. The control group received usual care consisting of medication management, lifestyle modification, and invasive procedures in accordance with clinical guidelines. Both groups had 5 monthly outpatient visits.

MAIN OUTCOMES AND MEASURES: Patient satisfaction, quality of information (QOI) provided by physicians, and disease knowledge were assessed using questionnaires (eg, Patient Satisfaction Questionnaire [PSQ]; score range: 5-25, with higher scores indicating greater patient satisfaction) at baseline and the fifth visit, over approximately 4 months.

RESULTS: Of the 50 patients included, 48 (median [SD] age, 71.0 [62.3-75.0] years; 28 males [58.3%]) completed follow-up. The prevalence was 56.2% (n = 27) for HF, 75.0% (n = 36) for AF, and 10.4% (n = 5) for CAD. The distribution of PRO measures used was 21 patients (43.8%) for KCCQ-12, 24 (50.0%) for AFEQT, and 3 (6.2%) for SAQ. Compared with the control group, the ePRO group showed significant improvements in mean (SD) PSQ score (0.16 [2.06] vs 1.61 [1.75]; P = .01) and QOI score regarding treatment (-0.12 [0.53] vs 0.35 [0.71]; P = .01). The ePRO group exhibited a greater increase in the PSQ score regarding communication (-0.12 [0.53] vs 0.43 [0.90]; P = .01).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, implementation of the ePRO monitoring system significantly enhanced patient-physician communication and the clarity of physicians’ explanations about treatment. These findings suggest that the ePRO monitoring system is capable of supporting patient-centered cardiovascular care.

TRIAL REGISTRATION: University Hospital Medical Information Network Identifier: UMIN000049251.

PMID:39808432 | DOI:10.1001/jamanetworkopen.2024.54084

JAMA Netw Open. 2025 Jan 2;8(1):e2454608. doi: 10.1001/jamanetworkopen.2024.54608.

ABSTRACT

IMPORTANCE: Cigarette companies have been introducing synthetic cooling agent menthol-mimicking cigarettes into the US marketplace as menthol cigarette bans are implemented. These cigarettes may reduce the public health benefits of menthol cigarette bans.

OBJECTIVE: To examine the epidemiology of the use of synthetic cooling agent menthol-mimicking cigarettes among adults in the US.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cross-sectional survey study of adults in the US (≥21 years) with oversampling of Asian, American Indian or Alaska Native, Black or African American, and Hispanic or Latino peoples was conducted from March to May 2024. Participants were recruited from an online panel using a sample-matching approach to achieve national representation. Data were weighted to be nationally representative. Descriptive statistics were used to summarize the population characteristics. Weighted prevalence of awareness of, ever use (among those aware), current use (among ever used), susceptibility (among noncurrent use), and likely to switch to synthetic cooling agent menthol-mimicking cigarettes were estimated overall and by covariate. Sequential weighted logistic regression models were used to estimate the associations between covariates and synthetic cooling agent menthol-mimicking-related outcomes (awareness, ever use, current use, susceptibility). Statistical analysis was performed from July to September 2024.

EXPOSURES: Demographics, state menthol cigarette ban, cigarette smoking, and disclosure of synthetic cooling agent.

MAIN OUTCOMES AND MEASURES: Awareness of, susceptibility to, ever and currently using synthetic cooling agent menthol-mimicking cigarettes and intention to switch to these cigarettes if a nationwide menthol cigarette ban were enacted.

RESULTS: The study population included 3200 US adults (47.4% men; 0.8% American Indian or Alaska Native, 5.9% Asian, 12.0% Black or African American, 16.0% Hispanic or Latino, 63.6% White, and 1.9% other race; 34.8% with a college degree; and 36.7% with annual household income of ≥$75 000). Overall, 29.1% (95% CI, 27.0%-31.1%) of US adults were aware of synthetic cooling agent menthol-mimicking cigarettes, 36.9% (95% CI, 33.1%-40.8%) of those aware ever used these cigarettes, 24.7% (95% CI, 20.1%-29.3%) of those who ever used reported currently using these cigarettes, and 37.5% (95% CI, 33.4%-41.6%) of those not currently using were susceptible to using them. Black or African American (vs White), men (vs women), adults aged 60 years or younger (vs adults aged ≥61 years), adults who used menthol and nonmenthol cigarettes (vs adults who did not smoke cigarettes), and those who lived in states with a menthol cigarette ban (vs those who lived in states with no ban) had higher odds of awareness, ever use, current use, and/or susceptibility to these cigarettes. Considering a national menthol cigarette ban, 50.8% (95% CI, 42.8%-58.7%) of adults who smoked menthol cigarettes and were aware of menthol-mimicking cigarettes with a synthetic cooling agent reported likely to switch to these cigarettes. Ever using these cigarettes was associated with the likelihood of switching (adjusted odds ratio, 2.61 [95% CI, 1.20-5.68]).

CONCLUSIONS AND RELEVANCE: In this survey study of US adults, a substantial proportion were aware of and had already experimented with synthetic cooling agent menthol-mimicking cigarettes. These products may serve as a substitute for menthol cigarettes and reduce the public health benefits of a menthol cigarette ban in promoting smoking cessation.

PMID:39808430 | DOI:10.1001/jamanetworkopen.2024.54608

JAMA Netw Open. 2025 Jan 2;8(1):e2454699. doi: 10.1001/jamanetworkopen.2024.54699.

ABSTRACT

IMPORTANCE: Nearly all Medicare Advantage (MA) plans offer dental, vision, and hearing benefits not covered by traditional Medicare (TM). However, little is known about MA enrollees’ use of those benefits or how much they cost MA insurers or enrollees.

OBJECTIVE: To estimate use, out-of-pocket (OOP) spending, and insurer payments for dental, hearing, and vision services among Medicare beneficiaries.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional analysis used pooled 2017-2021 Medical Expenditure Panel Survey (MEPS) and Medicare Current Beneficiary Survey (MCBS) data for MA and TM beneficiaries (excluding those also covered by Medicaid). The analysis was performed from September 10, 2023, to June 30, 2024.

EXPOSURES: MA compared with TM coverage.

MAIN OUTCOMES AND MEASURES: The main outcome was receipt of eye examinations, corrective lenses, hearing aids, optometry and dental visits, and MA and TM enrollees’ and insurers’ spending for such services. MEPS and MCBS data were weighted to be nationally representative.

RESULTS: We included 76 557 non-dually eligible Medicare beneficiaries, including 23 404 from the MEPS and 53 153 from the MCBS. Weighted demographic characteristics of MA and TM beneficiaries were similar (54.7% and 51.9% female; 39.8% and 35.2% older than 75 years, respectively). Only 54.2% (95% CI, 52.4%-55.9%) and 54.3% (95% CI 52.2%-56.3%) of MA beneficiaries were aware of having MA dental and vision coverage, respectively. MA enrollees were no more likely to receive eye examinations, hearing aids, or eyeglasses than TM enrollees. After adjustment for demographic differences, MA and TM enrollees paid OOP $205.86 (95% CI, $192.44-$219.27) and $226.12 (95% CI, $212.02-$240.23), respectively, for eyeglasses (MA – TM difference, -$20.27 [95% CI, -$33.77 to -$6.77] or -9.0% [95% CI, -14.9% to -3.0%]); $226.82 (95% CI, $202.24-$251.40) and $249.98 (95% CI, $226.22-$273.74) for dental visits, respectively (MA – TM difference, -$23.16 [95% CI, -$43.15 to -$3.17] or -9.3% [95% CI, -17.3% to -1.3%]); and no less for optometry visits or durable medical equipment (a proxy for hearing aids). Nationwide, MA plans’ annual spending on vision, dental services, and durable medical equipment totaled $3.9 billion (95% CI, $3.3-$4.4 billion), while enrollees spent OOP $9.2 billion (95% CI, $8.2-$10.2 billion) annually for these services and other private insurers covered $2.8 billion (95% CI, $2.7-$3.0 billion).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of 2 nationally representative surveys, MA beneficiaries did not receive more supplemental services than TM beneficiaries, possibly because of cost-sharing and limited awareness of benefit coverage.

PMID:39808428 | DOI:10.1001/jamanetworkopen.2024.54699

Biometrics. 2025 Jan 7;81(1):ujae164. doi: 10.1093/biomtc/ujae164.

ABSTRACT

As a commonly employed method for analyzing time-to-event data involving functional predictors, the functional Cox model assumes a linear relationship between the functional principal component (FPC) scores of the functional predictors and the hazard rates. However, in practical scenarios, such as our study on the survival time of kidney transplant recipients, this assumption often fails to hold. To address this limitation, we introduce a class of high-dimensional partially linear functional Cox models, which accommodates the non-linear effects of functional predictors on the response and allows for diverging numbers of scalar predictors and FPCs as the sample size increases. We employ the group smoothly clipped absolute deviation method to select relevant scalar predictors and FPCs, and use B-splines to obtain a smoothed estimate of the non-linear effect. The finite sample performance of the estimates is evaluated through simulation studies. The model is also applied to a kidney transplant dataset, allowing us to make inferences about the non-linear effects of functional predictors on patients’ hazard rates, as well as to identify significant scalar predictors for long-term survival time.

PMID:39808421 | DOI:10.1093/biomtc/ujae164

J Med Syst. 2025 Jan 14;49(1):7. doi: 10.1007/s10916-025-02143-w.

ABSTRACT

The “no-show” problem in healthcare refers to the prevalent phenomenon where patients schedule appointments with healthcare providers but fail to attend them without prior cancellation or rescheduling. In addressing this issue, our study delves into a multivariate analysis over a five-year period involving 21,969 patients. Our study introduces a predictive model framework that offers a holistic approach to managing the no-show problem in healthcare, incorporating elements into the objective function that address not only the accurate prediction of no-shows but also the management of service capacity, overbooking, and idle resource allocation resulting from mispredictions. Our approach simplifies preprocessing and eliminates the need for expert judgment in variable selection, thereby enhancing the model’s usability in routine healthcare operations. Our research revealed that key predictors of no-shows are consistent across various studies. We employed semi-automatic feature selection techniques, achieving results comparable to state-of-the-art approaches but with significantly reduced complexity in their selection. This method not only streamlines the feature selection process but also enhances the overall efficiency and scalability of our predictive models, making them more adaptable to diverse healthcare settings. This comprehensive strategy enables healthcare providers to optimize resource allocation and improve service delivery, making our findings relevant for healthcare systems globally facing similar challenges. Future work aims to expand the analysis by incorporating additional third-party data sources, such as weather and commuting activities, to explore the broader impacts of external factors on patient no-show behavior. To the best of our knowledge, this innovative approach is expected to provide deeper insights and further enhance the predictability and effectiveness of no-show mitigation strategies in healthcare systems.

PMID:39808378 | DOI:10.1007/s10916-025-02143-w