Heterogeneous Population Research Articles

The association between cancer literacy and cancer screening behaviours: a systematic review

Abstract Background This study aimed at investigating the association between cancer literacy (CL) and adherence to cancer screening programs. Methods PubMed, Scopus and Web of Science were searched. Any study, published until March 2024, that investigated the associations between CL and cancer screening intention or uptake in any target population were eligible. For CL measurement, both validated and ad hoc tools were considered. For each outcome, articles were grouped according to the type of cancer investigated and results were narratively synthesized. Results A total of 3426 records were retrieved. After deduplication and screening process, six studies were included. Population enrolled was heterogeneous as well as the tool used to measure CL. Four studies explored the relationship between CL and screening uptake, one focused solely on screening intention and another investigated both intention and uptake. Significant association was found between CL and screening intention in the two studies included, with higher literacy levels correlating to increased intent for screening. A significant association between higher CL and skin cancer screening uptake was reported, while the uptake of prostate cancer screening was not significantly associated with CL levels. By contrast, mixed results were obtained investigating breast, cervix and colorectal screening uptake. Conclusions Higher levels of cancer literacy appeared to be associated with screening intention, while its association with screening uptake was found barely significant for any screening type, suggesting that other factors influence the actual screening uptake. However, the scarce number of studies, along with the absence of validated tools and the heterogeneity of target populations, limits the generalizability of the results. Further research, differentiating screening types and timelines and using multivariate models, is needed to clarify the role of CL in screening behaviours. Key messages • Higher levels of cancer literacy appear to be associated with screening intention, suggesting its importance in promoting motivation for early cancer detection. • Association between cancer literacy and screening uptake was found barely significant for any screening type, suggesting that other factors influence actual screening uptake, urging further research.

National early warning score predicts 90 days all-cause mortality among patients with acute heart failure

Abstract Background Acute heart failure (AHF) is defined as new-onset or worsening of symptoms and signs of heart failure including symptoms or signs related to congestion and volume overload. Patients presenting with AHF are a heterogeneous group as AHF is not a specific disease but a shared clinical presentation of different cardiac abnormalities. Due to the heterogeneity of the patient population, a prognostic tool is needed to identify AHF patients with a high risk of death. The National Early Warning Score (NEWS) is a system for scoring the vital signs that are measured at the patient's bedside and is developed to predict acute mortality within 24 hours. The NEWS has previously been used to evaluate all cost mortality for patients admitted to the Emergency Department (ED). There is limited data regarding the role of the NEWS in predicting adverse outcomes in patients with acute heart failure. Purpose To evaluate NEWS measured at the ED and clinical outcomes in patients with AHF. Methods This prospective, observational cohort study included consecutive patients with AHF admitted through the emergency department (ED) at a large public hospital from 10 March 2020 to 31 March 2022 and had a follow-up period of 365 days. Trained cardiologists assessed all patients for the presence of AHF. According to the cut-off value for the NEWS, high-risk groups are defined by a NEWS score > 7. The patients were categorized into two groups, high-risk and low-risk, depending on the scores they received from the NEWS assessment. The primary outcome was all-cause mortality at 90 days. We used multivariable Cox regression (hazard ratios [HRs]) to compare survival, adjusting for age, sex, smoking, known heart failure (HF), and lactate levels at admission. Results In the study period from March 10, 2020, to March 31, 2022, 408 patients were identified with AHF. Upon arrival to the ED, the median first NEWS was 4 (IQR 2-6). 323 patients were categorized in the low-risk group and 69 patients in the high-risk group. 16 patients had missing values upon arrival at the ED. The high-risk group exhibited significantly faster heart rate, lower saturation, and higher oxygen demand compared. A Kaplan-Meier plot revealed a statistically significant difference in all-cause mortality over 90 days between low-risk and high-risk groups among AHF patients (log rank, p-value < 0.001). After multivariable adjustment, NEWS>7 (HR, 1.69; CI, 1.18 to 2.45) (p-value= 0.004) and higher age (HR, 1.04; CI 1.03 to 1.07) were statistically associated with higher all-cause mortality (p <0.001). Conclusion In this prospective, observational cohort study of AHF patients presenting at the ED an initial NEWS >7 was associated with a significant all-cause mortality after 90 days.GRAPHIC ABSTRACT

Biomarkers of cardiohepatic syndrome in the cardiac intensive care unit

Abstract Introduction Non-cardiovascular end-organ dysfunction is an important determinant of outcomes in cardiac intensive care unit (CICU) patients. We examined the association between in-hospital mortality with the severity and extent of admission liver function test (LFT) abnormalities in a heterogeneous CICU population. Purpose We hypothesized that a greater severity or extent of LFT abnormalities would be associated with higher in-hospital mortality. Methods We included consecutive unique adult CICU patients with available data for one or more of the admission LFT values of interest. Admission laboratory values were defined as those closest to CICU admission. We used the NIH Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 to categorize the severity of each LFT abnormality from Grade 0 (normal) to Grade 4 (life-threatening). We defined the extent of LFT abnormality as the number of individual LFTs meeting criteria for CTCAE Grade 1 or greater. The primary outcome of interest was all-cause in-hospital mortality. Odds ratio (OR) and 95% confidence interval (CI) values for in-hospital mortality were estimated using logistic regression, before and after multivariable adjustment. Results Of 12,428 unique CICU patients, 5,144 were excluded due to a lack of available data for any admission LFT values. The remaining 7,284 patients comprised the final study population. Among patients with available data for each individual LFT, abnormal values were present in: AST, 2,743/5,733 (47.8%); ALT 1,576/5,512 (28.6%); ALK 611/3,684 (16.6%); and TB 898/5,155 (17.4%). A total of 864 (11.9%) patients died during hospitalization. In-hospital mortality was higher for patients with one or more LFTs meeting criteria for CTCAE Grade 1 or greater (17.9% vs. 6.4%, adjusted OR 1.54 [1.27-1.86], p <0.001). A stepwise increase in in-hospital mortality was observed with increasing CTCAE grade, both overall (adjusted OR 1.25 per each higher CTCAE grade [1.16-1.34], p <0.001); (Figure 1A), and for each individual LFT (Figure 1B). Conclusion Cardiohepatic syndrome is an important predictor of prognosis in CICU patients, as the extent and severity of LFT abnormalities are strongly associated with in-hospital mortality. This is the first large-scale study to examine the association between the magnitude of hepatic biomarker derangement with in-hospital mortality in unselected CICU patients. Patients with markedly elevated LFT values exhibited the highest risk of in-hospital mortality. This analysis advocates for the inclusion of commonly obtained LFTs in future risk-prediction tools for enhanced prognostication.

Echocardiographic left atrial stiffness index predicts high left ventricular filling pressures in patients with acute heart failure: an observational study.

In acute heart failure (AHF) patients, non-invasive estimation of left ventricular filling pressures (LVFPs) appears crucial to guide management. Although poorly investigated, left atrial (LA) mechanics play a pivotal role in this setting. This report sought to assess the correlation of echocardiographic LA stiffness index with invasive LVFPs and its diagnostic accuracy as compared to other parameters used in clinical practice. In this observational, prospective study, 104 patients with suspected acute coronary syndrome and signs/symptoms of AHF were enrolled. Available invasive estimation of LVFPs was required. Comprehensive echocardiography was performed for all patients, including LA reservoir strain (LARS). LA stiffness index was derived by speckle-tracking analysis and Tissue Doppler imaging as early diastolic transmitral inflow velocity/mitral annulus early diastolic velocity [E/e']/LARS. Invasively measured LVFPs showed a strong correlation with LA stiffness index (Spearman ρ = 0.773, p < 0.0001), as well as with LARS and E/e'. Receiver operating characteristic (ROC) curve analysis was used to demonstrate better accuracy performed by LA stiffness index than average E/e', LA volume or LARS alone, in predicting high LVFPs. Guideline-recommended assessment of diastolic function was finally compared to LARS and LA stiffness index performances in an independent population group; we were hence able to obtain a LA stiffness threshold of 0.48 with a positive predictive value of 91.7% and a negative predictive value of 88.9% in identifying patients with high LVFPs. For the first time, diagnostic performance of LA stiffness index has been investigated in a heterogeneous AHF population, providing correlations with invasively measured LVFPs and comparisons with established diastolic function metrics.

Clinically Relevant and Precisely Printable Live Adipose Tissue-Based Bio-Ink for Volumetric Soft Tissue Reconstruction.

Autologous fat is widely used in soft tissue reconstruction; however, significant volume reduction owing to necrosis and degradation of the transplanted adipose tissue (AT) remains a major challenge. To address this issue, a novel live AT micro-fragment-based bio-ink (ATmf bio-ink) compatible with precision 3D printing, is developed. Live AT micro-fragments of ≈280µm in size are prepared using a custom tissue micronizer and they are incorporated into a fibrinogen/gelatin mixture to create the ATmf bio-ink. AT micro-fragments exhibit high viability and preserve the heterogeneous cell population and extracellular matrix of the native AT. The developed bio-ink enables precise micropatterning and provides an excellent adipo-inductive microenvironment. AT grafts produced by co-printing the bio-ink with polycaprolactone demonstrate a 500% improvement in volume retention and a 300% increase in blood vessel infiltration in vivo compared with conventional microfat grafts. In vivo engraftment of AT grafts is further enhanced by using a stem cell-laden ATmf bio-ink. Last, it is successfully demonstrated that the bio-ink is enabled for the creation of clinically relevant and patient-specific AT grafts for patients undergoing partial mastectomy. This novel ATmf bio-ink for volumetric soft tissue reconstruction offers a pioneering solution for addressing the limitations of existing clinical techniques.

Cultural Considerations in Intelligence Test Adaptations: a Critical Review of the WAIS-IV India and Its U.K. and U.S. Counterparts.

This study critically examined the adaptation and normative processes of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV)India. WAIS-IV U.K. Edition Administration and Scoring Manual, WAIS-IVIndia Administration and Scoring Manual, and WAIS-IV Administration and Scoring Manual and Technical and Interpretive Manuals were used to extract test development and adaptation process data. The analyses were descriptive and qualitative. A review of the manuals showed that the normative sample were fluent English speakers with high education levels, which is not representative of India's multilingual and educational diversity. The study identified minimal cultural and linguistic adaptations in subtests, which raised concern about potential biases in the test adaptation process across cultures. The lack of clarity in item selection, demographic data, sample selection, and psychometric properties raised questions about the test's reliability and validity. Issues related to education, age, gender, and regional distribution are discussed, emphasizing the test's limitations in capturing the diverse characteristics of the heterogeneous Indian population. WAIS-IV India may not adequately represent India's population. More careful consideration of socioecological and psychometric factors when adapting intelligence (IQ) tests and use of advanced data harmonization methods can provide robust cross-national statistical harmonization in the future along with more ecologically valid local test development efforts. This can allow consideration of social determinants of health and other factors that can inform a more nuanced approach to IQ test development in non-western contexts.

Clinical phenotypes in relation to outcomes in heart failure patients with cardiac resynchronization therapy and defibrillators (CRT-D): an unsupervised cluster analysis

Abstract Background Patients with heart failure undergoing CRT are an heterogenous and complex population. Selecting patients before implantation is essential to obtain a favorable response to CRT-D. Data-driven cluster analysis may be an approach to identify different patients’ phenotypic categories. Purpose To identify different clusters of patients with CRT-D who share similar clinical phenotypes, and to evaluate the associations between clusters and clinical outcomes, using cluster analysis. Methods Three agglomerative hierarchical cluster analysis were performed in CRT-D patients seen between 2010 and 2019 in French hospitals. Associations between clusters and death at one year and death during whole follow-up (FU) were evaluated using Cox regression analyses. Results The study included 23,029 CRT-D patients with no prior history of VT/VF/cardiac arrest (mean age 67.7 ± 9.9 years; 78.8 % male), who were analyzed in relation to 3 ways, as follows: the first group was a 50% random sample of all patients (n = 11,514), the second group included patients dead at 1 year (n = 1,604) and the third group included those alive at 3 years FU (n = 14,228). A cluster analysis was performed on each group. Four clusters were identified in the first group: Cluster 1 identified young patients with dilated cardiomyopathy and low prevalence of coronary artery disease (CAD), cardiovascular (CV) risk factors and comorbidities (chronic kidney disease, lung and liver disease) (low-risk phenotype); Cluster 2 was composed of male patients with CAD but low burden of CV risk factors and comorbidities (CAD phenotype); Cluster 3 included CRT recipients with several CV risk factors but low prevalence of comorbidities (CV risk factors phenotype); Cluster 4 identified old patients with high prevalence of CAD, atrial fibrillation, CV risk factors and comorbidities (clinical complex phenotype). These phenotypes were maintained in the other two groups (dead at 1 year and alive at 3 years FU), with the highest consistency for low-risk and high-risk phenotypes(Cluster 1 and 4 respectively). Compared with Cluster 1, Clusters 2, 3 and 4 were independently associated with an increased risk of all-cause death at 1-year FU and during the whole FU (Cluster 2: HR 1.21, 95% CI 1.08 - 1.36; Cluster 3: HR 1.15, 95%CI 1.04 - 1.26; and Cluster 4: HR 1.79, 95%CI 1.65 - 1.96). There were high prevalences of CAD, atrial fibrillation, mitral regurgitation, and comorbidities (which are all predictors of CRT-nonresponse) not only in Cluster 4 at baseline, but also among patients who died at 1-year FU in all 4 clusters. Conclusion Cluster analysis identified four statistically driven groups of CRT recipients, with specific clinical phenotypes and associated with different risks for all-cause death. Identifying those patients at higher risk of adverse events might help in the selection of patients with heart failure undergoing CRT-D implantation, especially in relation to CRT-nonresponse.Risk of all-cause death in 4 clusters

How to improve the inclusion of the elderly in the local community for better mental health?

Abstract Issue/problem Social exclusion, ageism and low health/digital literacy intertwine with growing trends in mental disorders, including abuse in Slovenian elderly. To cope with these issues, besides rising competencies, there is a need for stable and continuous partnerships of all relevant stakeholders in the local communities. Description of the problem Despite previous efforts of the Interdisciplinary Working Group (IWG) for mental health promotion in the elderly (established according to the Resolution of the National Mental Health Program, 2018-2028), there was a need for reconsidering approaches in the next Action plan (2024-2028). A national conference on decreasing social exclusion in the elderly contributed as a road map. Results Previous activities (events in the local communities, supported materials) were upgraded with a broad destigmatization campaign, (recruitment of the &amp;gt;&amp;gt;ambassadors &amp;lt;&amp;lt;) and collection of culturally adapted good practices. Better availability of information through &amp;gt;&amp;gt;info-spots &amp;lt;&amp;lt; and easier participation of the elderly in cultural events was enabled. Activities of the reinforced IWG were promoted. Lessons Empowerment of key actors and their continuous cooperation could improve information flow, competencies, the inclusion of the elderly in the local community, and decrease ageism and discrimination. Developing local strategies with the crucial involvement of elderly representatives is the opportunity for more intensive and better cooperation between local policy/stakeholders, public health experts, and the target population. Regular financial support will prevent additional inequities. Key messages • The empowered, connected, and proactive community is key to preventing the elderly’s exclusion. • Approaches should be fresh, accessible, and tailored to the heterogeneous population.

Stemness in solid malignancies: coping with immune attack.

Immunotherapy has become a key new pillar of cancer treatment, and this has sparked interest in understanding mechanisms of cancer immune evasion. It has long been appreciated that cancers are constituted by heterogeneous populations of tumour cells. This feature is often fuelled by specialized cells that have molecular programs resembling tissue stem cells. Although these cancer stem cells (CSCs) have capacity for unlimited self-renewal and differentiation, it is increasingly evident that some CSCs are capable of achieving remarkable immune resistance. Given that most immunotherapy regiments have overlooked CSC-specific immune-evasive mechanisms, many current treatment strategies often lead to cancer relapse. This Review focuses on advancements in understanding how CSCs in solid tumours achieve their unique immune-evasive properties, enabling them to drive tumour regrowth. Moreover, as cancers often arise from tissue stem cells that acquired oncogenic mutations, we discuss how tissue stem cells undergoing malignant transformation activate intrinsic immune-evasive mechanisms and establish close interactions with suppressive immune cells to escape immune surveillance. In addition, we summarize how in advanced disease stages, CSCs often hijack features of normal stem cells to resist antitumour immunity. Finally, we provide insights in how to design a new generation of cancer immunotherapies to ensure elimination of CSCs.

Proteogenomic characterization of highly enriched viable leukemic blasts in acute myeloid leukemia: A SWOG report

AbstractIntroductionAcute myeloid leukemia (AML) remains one of the deadliest hematopoietic malignancies. A better understanding of the molecular biology governing AML may lead to improved risk stratification and facilitate the development of novel therapies. Proteins are responsible for much of the biology of cells. Several studies have examined the global proteome in bulk mononuclear cells (MNCs) from AML specimens, which are comprised a heterogenous population of cells at various stages of differentiation.MethodsGiven the potential impact of the nonleukemic cells on protein expression profiles, we applied an integrative proteogenomic approach utilizing next‐generation sequencing and mass spectrometry‐based proteomics to identify novel protein biomarkers in unsorted MNCs and viable leukemic blasts (VLBs) isolated from blood and bone marrow specimens obtained at the time of AML diagnosis.ResultsWe identified significant differences in protein expression between VLBs and MNCs. Subsequent studies (N = 27) focused on proteomic profiling of VLBs that identified novel candidate biomarkers associated with mutational genotypes and clinical outcome, some of which were recapitulated in an independent cohort of patients. Using mass spectrometry, we also detected mutated protein products, some of which were predicted via in silico analyses to be potential neoantigens amenable to adoptive immunotherapy. As previously described, analyses comparing transcript and protein expression showed an overall modest correlation between mRNA and protein dataset, but enriching for genes associated with mutations significantly improved the protein–RNA correlation.ConclusionTogether, the results provide insight into the biology of VLBs and demonstrate the gains derived from examining the proteome in addition to genome and transcriptome.

Systematic review on resting-state fMRI in people with AUD and people who binge drink.

Resting-state functional magnetic resonance imaging (rsfMRI) has become ubiquitous in neuroimaging to study disorders, including alcohol use disorder (AUD), given its potential to serve as a biomarker of psychiatric symptoms. The number of techniques, sample heterogeneity, and findings demand the assessment of results to identify potential biomarkers for the development of treatment. This systematic review aimed to synthesize the alcohol rsfMRI literature by summarizing the results by analysis approach and groups to examine these findings in the context of the neurobiology of addiction model. Three databases were systematically searched, resulting in the inclusion of 17 studies with a total of 784 participants (387 were people with AUD, 38 engaged in binge drinking, and 359 were controls). Seed-based functional connectivity studies were the most prominent. Compared to controls, people who binge drink and people with AUD showed greater connectivity of the Middle Frontal Gyrus-a region associated with the preoccupation/anticipation stage of the theory. Regions of the prefrontal and limbic cortex were most consistently reported in studies. The different types of analyses, sample size, and variability in the sample may have contributed to differences reported across studies. This review synthesizes and examines the results of different studies using the neurobiology of addiction theory, which may inform future studies on potential regions of interest, recruitment approaches, and analysis methods. Standardizing the methods for such a heterogeneous population could lead to more rapid development of neurobiologically-informed treatments for AUD.

Treatment of lower-risk myelodysplastic syndromes.

Myelodysplastic neoplasms (MDS) involve clonal hematopoiesis and cellular dysplasia, driven by genetic and epigenetic alterations. Spliceosome mutations and epigenetic dysregulation underscore the intricate pathogenesis of MDS. The bone marrow microenvironment, stromal dysfunction, chronic inflammation, and immune dysregulation contribute to disease progression. This complex pathogenesis underscores the necessity for targeted therapies, offering a personalized medicine approach, particularly in lower-risk patients. The development of risk scores like the International Prognostic Scoring System (PISS), its revision IPSS-R, and the incorporation of molecular genetics in IPSS-M have refined the diagnostic and prognostic framework of MDS. These scoring systems facilitate tailored treatment strategies and better prognostication, especially for lower-risk MDS patients. The progression from IPSS to IPSS-R and now to IPSS-M epitomizes the shift towards personalized medicine in MDS management. In this review we discuss recent developments and positive phase III studies in lower-risk MDS. The review concludes by proposing a treatment algorithm for LR-MDS and highlighting ongoing trials in this heterogeneous patient population.

Decoding Infectious Disease Dynamics: A Stochastic Approach to Population Heterogeneity and Epidemic Outcomes

Decoding Infectious Disease Dynamics: A Stochastic Approach to Population Heterogeneity and Epidemic Outcomes

Characterization of Extracellular Vesicles by Sulfophosphovanillin Colorimetric Assay and Raman Spectroscopy.

Detailed characterization of extracellular vesicles (EVs) is crucial for their application in medical diagnostics. However, the complexity of their chemical composition and the heterogeneity of EV populations make their characterization challenging. Here we describe two analytical procedures that can help overcome this challenge. Small EVs were isolated from conditioned cell culture media using ultracentrifugation and characterized using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Raman spectroscopy was used to assess the overall composition of the isolated samples and lipids extracted from them. Sulfophosphovanillin (SPV) colorimetric assay was used to quantify the contents of lipid. Six samples of EVs were characterized. The lipid contents measured using SPV assay was in reasonable agreement with the quantitative estimates based on the particle size and concentration measured using NTA. The most peaks observed in the Raman spectra could be attributed to either proteins or lipids, and their origins was confirmed by lipid extraction. The protein-to-lipid ratio was estimated based on the Raman spectra. The experiential procedures described in this study will help to overcome the challenge of quick and highly informative characterization of the EVs.

Inbreeding accelerates reproductive senescence, but not survival senescence, in a precocial bird.

Inbreeding depression is predicted to increase with age, because natural selection is less efficient at purging deleterious alleles that are only expressed later in life. However, empirical results are scarce, and equivocal between studies. Here we performed controlled matings between related and unrelated individuals of domesticated Japanese quail (Coturnix japonica), and monitored the performance of their offspring for all fitness components over their complete life course. We found rapid senescence in adult survival and egg laying performance, and inbreeding depression at all life stages (reduced embryo viability, increased age at maturity, as well as reduced adult survival and reproduction). Inbreeding depression did not increase at later ages for survival, but did so for egg laying, thereby accelerating reproductive senescence. Moreover, the effect of inbreeding on egg laying persisted after correcting for lifespan, indicating that both survival and reproduction were independently affected by inbreeding. We suggest that in heterogeneous populations intra-generational purging may at earlier ages already select out the individuals that are homozygous for the specific alleles responsible for depressed survival, preventing the appearance of increased inbreeding depression in survival with age. Given that inbreeding affects reproduction independent of survival this should not apply to reproductive senescence or homogeneous populations, which may explain equivocal results between traits and studies.

Development and validation of a new anthropometric equation to predict fat mass percentage in a white Spanish population.

(1) To develop a new regression equation for estimating fat mass percentage (%FM) from anthropometric measurements in a heterogeneous Caucasian population and (2) to compare it with the Durnin and Womersley equation, which is one of the most used anthropometric equations for fat mass assessment. Body mass, stature, and four skinfolds (biceps, triceps, subscapular, and supracrestal) were assessed by an accredited anthropometrist, according to the International Society for Advancement in Kinanthropometry. Participants completed a dual-energy X-ray absorptiometry (DXA) whole-body scan to determine their %FM. A new anthropometric equation to estimate %FM was developed using multiple forward regression analyses with DXA as the reference method. Tests for the accuracy of the different equations included mean differences, coefficient of determination, standard error of the estimate (SEE), concordance correlation coefficient (CCC), and Bland-Altman plots. Spain. Two hundred and eighteen healthy Caucasian participants aged 18-65 years participated in this cross-sectional study. Our proposed equation explained 89.9% of the variance in the DXA-derived %FM, with a low random error (SEE = 3.00%), a very strong agreement (CCC = 0.93), no fixed or proportional bias, and a relatively low individual variability (5.84%). However, the Durnin and Womersley equations obtained a fixed bias of -3.65% when compared to DXA and a greater individual variability (6.74%). The proposed equation can accurately estimate %FM in a heterogeneous Caucasian population with a wide age range (18-65 years). Additionally, the Durnin and Womersley equation was inadequate when applied to our participants.

A longitudinal pre-post study: An evaluation of the Department of the Air Force bundled occupational fall prevention efforts.

Fall injuries are the second leading cause of traumatic injury and death for all US workers and are a leading injury concern for the Department of the Air Force (DAF). Bundled interventions can improve the likelihood of injury reduction, especially in large, heterogeneous working populations. In 2013, the DAF implemented the "Air Force Fall Prevention Focus," a bundled intervention of prevention efforts designed to reduce occupational fall injury events among DAF members. The purpose of this study is to describe the burden and risk factors associated with fall injuries and evaluate the effectiveness of the Fall Prevention Focus in reducing the burden of fall injuries. The National Institute for Occupational Safety and Health (NIOSH) partnered with the US Air Force Safety Center (AFSEC) to examine the impact of the Fall Prevention Focus as a bundled intervention. Injury events included a narrative description of the injury event, demographics, work environment, job tasks, and other structured details. Descriptive statistics and pre-post longitudinal modeling were used to evaluate changes in fall injury rates. The Fall Prevention Focus Implementation (2013-2018) resulted in an annual 10.4% (95% confidence interval [CI]: 8.5%, 12.2%) reduction, and a 6-year cumulative 48.3% (95% CI: 41.4%, 54.3%) reduction in fall injury event rates by 2018. Safety in the DAF involves a comprehensive approach. Documenting the impact of the Fall Prevention Focus may help translate these findings to improve fall prevention efforts in other sectors of the military and high fall-risk industries in the private sector, such as construction.

Seizure outcomes in patients with brain metastases and epilepsy: A systematic review on the efficacy of antitumor treatment and antiseizure medication

Abstract Background Epilepsy is a common symptom in patients with brain metastases (BMs), and because of the rising incidence of BMs, adequate seizure management is warranted. We conducted a systematic review on seizure outcomes after antitumor treatment and antiseizure medication (ASM) in patients with BMs from solid tumors and epilepsy. Methods A literature search was performed in six databases up to February 2024. Extracted outcomes were rates for (1) seizure freedom; (2) ≥50% seizure reduction; and (3) treatment failure (for ASM only). Weighted averages (WAs) were calculated for outcomes after surgery at 6 months follow-up. Quality assessment of the included studies was performed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. Results We retrieved 2244 references, of which 16 studies were eligible for inclusion. Eight studies were at critical, and 8 studies at serious risk of bias. The WA of seizure freedom rates at 6 months after surgical resection was 64% (based on 3 studies at serious risk of bias, n=151 patients). Results on ASM efficacy and tolerability were unreliable, as all eligible studies for these outcomes were at critical risk of bias. Conclusions Limited available evidence from heterogeneous study populations demonstrated that in the majority of patients with epilepsy due to BMs, seizure freedom 6 months after surgical resection may be reached. No substantial evidence on ASM efficacy and tolerability in patients with epilepsy due to BMs is available. High-quality cohort studies are warranted to expand the evidence on seizure outcomes after antitumor and ASM treatment.

A real-world study on the clinicopathological profile, treatment outcomes and health-related quality of life, anxiety and depression among patients with desmoid tumor at two tertiary care centers in India.

The medical management of DT comprises tyrosine kinase inhibitors (TKIs), hormonal agents, anti-inflammatory drugs with the recently approved gamma secretase inhibitor nirogacestat being the current standard of care. Real-world data on evolving treatment landscapes of DT remains scarce. This is a retrospective study of patients with DT registered between 1995 and 2020 at All India Institute of Medical Sciences, New Delhi and Tata Medical Center, Kolkata. Baseline characteristics were analyzed in form of median values and interquartile range. Categorical and continuous variables were compared by chi square and independent samples T- tests respectively. Anxiety, depression and QoL were prospectively measured among 30 patients using Hospital Anxiety and Depression (HADS) and Functional Assessment of Cancer Therapy-General (FACT-G) scales respectively between 2022 to 2023. 200 patients were included with a male-predominant (n=111, 55.5%) population and median age 26.5 (2.5-75) years. Extremity (n=100, 50%) and abdomen (n=65, 32.5%) were commonest primary sites and median of 2 (1-4) lines of treatment were received. First-line included surgery (n=116, 58%), systemic therapy (n=67, 33.5%), radiotherapy (10, n=5%) and active surveillance (n=7, 3.5%). First-line systemic agents included tamoxifen (n=55, 27.5%), imatinib (n=7, 3.5%), sorafenib (n=1, 0.5%) and chemotherapy (n=4, 2%). 2019 onward, 3% and 63% underwent active surveillance and surgery respectively. Best radiological response obtained with tamoxifen was stable disease (SD) (n=76, 59%) and partial response (PR) (n=31, 24.2%). Best radiological response obtained with sorafenib was PR (n=17, 60.7%) and SD (n=9, 32.1%). Thirty patients underwent HADS and FACT-G scale assessment. Mean HADS-Anxiety subscale score was 3.6 (+/-3.9 SD) and HADS-Depression sub-scale score was 2.6 (+/-3.5 SD) with clinically significant anxiety and depression in 2 (6.7%) patients each. The overall mean FACT-G score was 87.5 (+/-12.6 SD) and lower mean physical well-being (p=0.006) and emotional well-being (0.017) scores were significantly associated with higher HADS-anxiety (>/=8) scores. Assessment of anxiety, depression and QoL are paramount to gauge the psychological impact of DT. This study gives an overview of clinical and management profile of patients with DT in India, with limitations of selection bias, heterogeneous population and small sample size for QoL assessment.

Unveiling islet heterogeneity using an automated microfluidic imaging system

Islets of Langerhans are a therapeutic target for diabetes and prediabetes. Measurements of therapeutic inhibitory or excitatory concentrations are often performed using large groups of islets, however, the population heterogeneity cannot be observed when examining the ensemble response. Normal islet function and islet response to therapeutic treatment can be affected by islet heterogeneity, influencing the progression of diabetes mellitus. To identify heterogeneity in an islet population, we developed a simple microfluidic device capable of delivering a stimulant to four independent chambers, allowing measurements of individual responses from a population of 20–25 islets. The device enabled accurate delivery of the same stimulant concentration to all four chambers, with an error <1% between chambers. To demonstrate the capability of this system, ensemble and individual EC/IC\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$_{50}$$\\end{document} measurements of glucose and diazoxide were performed on murine islets. Results showed little heterogeneity of glucose EC\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$_{50}$$\\end{document} values with all 21 islets within ± 0.6 mM of the ensemble value of 7.4 mM. In contrast, application of diazoxide to 24 islets in the presence of 20 mM glucose resulted in 37% of islets having an IC\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$_{50}$$\\end{document} greater than 10% from the ensemble value of 10.2 μM. The simple system developed here is amenable to further studies on islet heterogeneity, and is applicable to investigate heterogeneity in other cell types.