Burden Index Research Articles

A novel comorbidity index in Italy based on diseases detected by the surveillance system PASSI and the Global Burden of Diseases disability weights

BackgroundUnderstanding comorbidity and its burden characteristics is essential for policymakers and healthcare providers to allocate resources accordingly. However, several definitions of comorbidity burden can be found in the literature. The main reason for these differences lies in the available information about the analyzed diseases (i.e., the target population studied), how to define the burden of diseases, and how to aggregate the occurrence of the detected health conditions.MethodsIn this manuscript, we focus on data from the Italian surveillance system PASSI, proposing an index of comorbidity burden based on the disability weights from the Global Burden of Disease (GBD) project. We then analyzed the co-presence of ten non-communicable diseases, weighting their burden thanks to the GBD disability weights extracted by a multi-step procedure. The first step selects a set of GBD weights for each disease detected in PASSI using text mining. The second step utilizes an additional variable from PASSI (i.e., the perceived health variable) to associate a single disability weight for each disease detected in PASSI. Finally, the disability weights are combined to form the comorbidity burden index using three approaches common in the literature.ResultsThe comorbidity index (i.e., combined disability weights) proposed allows an exploration of the magnitude of the comorbidity burden in several Italian sub-populations characterized by different socioeconomic characteristics. Thanks to that, we noted that the level of comorbidity burden is greater in the sub-population characterized by low educational qualifications and economic difficulties than in the rich sub-population characterized by a high level of education. In addition, we found no substantial differences in terms of predictive values of comorbidity burden adopting different approaches in combining the disability weights (i.e., additive, maximum, and multiplicative approaches), making the Italian comorbidity index proposed quite robust and general.

Herpes simplex virus 2 serology is associated with thinner whole-brain cortex in community-dwelling older adults

Prior work in the Northern Manhattan Study (NOMAS) identified impaired cognition in cross-sectional analyses and more rapid memory decline in individuals with evidence of prior common infectious disease exposures. In this study, we sought to determine the cross-sectional relationship between prior exposure to cytomegalovirus, herpes simplex viruses 1 and 2, Chlamydia pneumoniae, and Helicobacter pylori and three magnetic resonance imaging (MRI) signatures (whole-brain cortical thickness, a previously validated AD signature, and hippocampal volume) in 455 NOMAS participants. We performed confounder-adjusted linear regression analyses between neuroimaging scores and both continuous serologies and categorical seropositivity of each pathogen, as well as a combined infectious burden index (IBI). We identified that increased serologic titers of herpes simplex virus 2 were associated with reduced whole-brain cortical thickness, and a combined score of HSV-2 and C. pneumoniae displayed an additive effect on reduced cortical thickness. Our findings suggest herpes simplex virus 2 seropositivity may contribute to accelerated brain aging, possibly resulting in an increased vulnerability to cognitive impairment and neurodegenerative disease in aging populations.

The global burden of traumatic amputation in 204 countries and territories.

Traumatic amputation leads to disability and imposes a heavy health burden. This study aims to explore the current status and temporal trends of the global burden of traumatic amputation according to sex, age, amputation site, cause, and reginal level of social development. The data were extracted from the Global Burden of Diseases (GBD) Study 2019. Prevalence, incidence, years lived with disability (YLDs) and corresponding age-standardized rate were compared. Estimated annual percentage change (EAPC) was applied to reflect trends in age-standardized rates over a specific period. Spearman rank test and curve fitting methods were used to analyze the relationship between disease burden and Socio-Demographic Index (SDI). Globally, the incidence and prevalence number of traumatic amputation increased from 11.37 million and 370.25 million in 1990, to 13.23 million and 552.45 million in 2019, with a raise of 16.4 and 49.2%, respectively. But the age-standardized incidence rate (ASIR) (EAPC = -0.56; 95%CI, -0.72 to -0.41) and age-standardize prevalence rate (ASPR) (EAPC = -0.63; 95%CI, -0.74 to -0.52) declined during this period. The YLDs count also increased by 39.2% globally (from 5.28 million to 7.35 million), while the age-standardize YLDs rate (ASYR) decreased by an average of 1.00% per year (95% CI, -1.10 to -0.90) from 1990 to 2019. The incidence, prevalence, and YLDs rate of traumatic amputation continue to increase with age. Traumatic amputations were most common in the fingers, while unilateral lower limb amputation caused the greatest burden of disability. ASIR and SDI were positively correlated (ρ = 0.442, p < 0.001), while ASYR and SDI were not significantly correlated (ρ = -0.030, p = 0.669), and EAPC in ASYR and SDI were negatively correlated (ρ = -0.275, p < 0.001). Exposure to mechanical forces and falls were the leading causes of traumatic amputation. Despite the declining trends in ASIR, ASPR, and ASYR, the incidence, prevalence, and YLDs counts of traumatic amputation have increased significantly worldwide, especially in the older adults population. With the population aging, targeted health policies are needed to address the increasing global burden of traumatic amputations in the future.

Associations of baseline obstructive sleep apnea and sleep macroarchitecture with cognitive function after 8 years in middle-aged and older men from a community-based cohort study.

Previous prospective studies examining associations of obstructive sleep apnea and sleep macroarchitecture with future cognitive function recruited older participants, many demonstrating baseline cognitive impairment. This study examined obstructive sleep apnea and sleep macroarchitecture predictors of visual attention, processing speed, and executive function after 8 years among younger community-dwelling men. Florey Adelaide Male Ageing Study participants (n = 477) underwent home-based polysomnography, with 157 completing Trail-Making Tests A and B and the Mini-Mental State Examination. Associations of obstructive sleep apnea (apnea-hypopnea index, oxygen desaturation index, and hypoxic burden index) and sleep macroarchitecture (sleep stage percentages and total sleep time) parameters with future cognitive function were examined using regression models adjusted for baseline demographic, biomedical, and behavioural factors, and cognitive task performance. The mean (standard deviation) age of the men at baseline was 58.9 (8.9) years, with severe obstructive sleep apnea (apnea-hypopnea index ≥30 events/h) in 9.6%. The median (interquartile range) follow-up was 8.3 (7.9-8.6) years. A minority of men (14.6%) were cognitively impaired at baseline (Mini-Mental State Examination score <28/30). A higher percentage of light sleep was associated with better Trail-Making Test A performance (B = -0.04, 95% confidence interval [CI] -0.06, -0.01; p = 0.003), whereas higher mean oxygen saturation was associated with worse performance (B = 0.11, 95% CI 0.02, 0.19; p = 0.012). While obstructive sleep apnea and sleep macroarchitecture might predict cognitive decline, future studies should consider arousal events and non-routine hypoxaemia measures, which may show associations with cognitive decline.

Association between inflammatory burden index and all-cause mortality in the general population aged over 45 years: Data from NHANES 2005–2017

Background and aimThe objective of this study was to investigate the association between inflammatory burden index (IBI) and all-cause mortality in the general population aged over 45 years. Methods and resultsThe study included 8827 participants from the National Health and Examination Nutrition Survey (NHANES) who were aged over 45 years. The IBI was calculated using three markers: C-reaction protein × neutrophil/lymphocyte, and all the participants were classified into four groups (Quartile 1: IBI ≤0.178, N = 2206; Quartile 2: 0.178 <IBI ≤0.440, N = 2219; Quartile 3: 0.440 <IBI ≤1.099, N = 2195; Quartile 4: IBI >1.099, 2207). Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95 % confidence interval (CI) for the association between IBI and all-cause mortality. During a median follow-up of 129 month, 2431 deaths occurred. The all-cause mortality rate in Quartile 1, Quartile 2, Quartile 3 and Quartile 4 was 14.76 %, 17.67 %, 23.18 % and 29.69 %, respectively (p < 0.001). After adjustment for demographic, and potential clinical factors, higher IBI was significantly associated with an increased risk of all-cause mortality (Quartile 3 vs. Quartile 1: HR = 1.26, 95 % CI: 1.08 to 1.46, p = 0.003; Quartile 4 vs. Quartile 1: HR = 1.59, 95 % CI: 1.40 to 1.80, p < 0.001). Furthermore, the results of the restricted cubic spline analysis suggested that the association between IBI and all-cause mortality was nonlinear and positive, without specific threshold value. ConclusionsThis study supports that higher IBI is associated with an increased risk of all-cause mortality in the general population aged over 45 years.

Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events in Atherosclerotic Patients and Lesions: A Systematic Review and Meta-Analysis

BackgroundThe clinical value of high-risk coronary plaque characteristics (CPCs) to inform intensified medical therapy or revascularization of non–flow-limiting lesions remains uncertain. ObjectivesThe authors performed a systematic review and meta-analysis to study the prognostic impact of CPCs on patient-level and lesion-level major cardiovascular adverse events (MACE). MethodsThirty studies (21 retrospective, 9 prospective) with 30,369 patients evaluating the association of CPCs with MACE were included. CPCs included high plaque burden, low minimal lumen area, thin cap fibroatheroma, high lipid core burden index, low-attenuation plaque, spotty calcification, napkin ring sign, and positive remodeling. ResultsCPCs were evaluated with the use of intracoronary modalities in 9 studies (optical coherence tomography in 4 studies, intravascular ultrasound imaging in 3 studies, and near-infrared spectroscopy intravascular ultrasound imaging in 2 studies) and by means of coronary computed tomographic angiography in 21 studies. CPCs significantly predicted patient-level and lesion-level MACE in both unadjusted and adjusted analyses. For most CPCs, accuracy for MACE was modest to good at the patient level and moderate to good at the lesion level. Plaques with more than 1 CPC had the highest accuracy for lesion-level MACE (AUC: 0.87). Because the MACE rate was low, estimated positive predictive values for lesion-level MACE were modest. Results were mostly consistent across imaging modalities and clinical presentations, and in studies with prevailing hard outcomes. ConclusionsCharacterization of CPCs identifies high-risk atherosclerotic plaques that place lesions and patients at risk for future MACE, albeit with modest sensitivity and positive predictive value (Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events Among Atherosclerotic Patients and Lesions; CRD42021251810)

Translation and psychometric testing of Indonesian Version of Chronic Kidney Disease– Symptom Burden Index

Introduction: Chronic Kidney Disease Symptom Burden Index (CKD-SBI) is an instrument measuring symptom burden developed by Almutary and colleagues in 2015 to refine the identification of symptom burden in chronic kidney disease population. This instrument has not been tested for Indonesian language, thus, the aim of study was to translate and psychometrically testing the Indonesian version of CKD-SBI. Methods: This study design was cross-sectional study. The study methods were divided into translation and psychometric testing. The translation was conducted by adapting Guillemin and Beaton's guidelines. The psychometric properties determined 320 hemodialysis patients with several inclusion criteria such as above 18 years old, regularly receiving hemodialysis for more than 3 months. Patients with cognitive impairment, psychiatric patients, and in critical condition were excluded. Results: The item content validity index of the Indonesian version was 0.92, and the subscale content validity was 0.78. The instrument demonstrated convergent validity with the Kidney Disease Quality of Life. Excellent internal consistency was demonstrated based on a Cronbach’s alpha coefficient of .91 and a subscale ranging from 0.86 to 0.92. The confirmatory factor analysis showed that the five factors of English Version did not fit the Indonesian version. Conclusions: Translated Indonesian versions of CKD-SBI can be used as instruments to assess symptom burden among patients with hemodialysis. By assessing symptom burden, we hope nurses in the hospital are able to decide effective symptom management to increase the health-related quality of life among these populations.

An instant inertia estimated and operation burden considered frequency regulation method for low inertia power systems

The application of virtual inertia (VI) has become a novel solution and new orientation for the frequency regulation of the high variable renewable energy (VRE) penetrated low inertia systems. How to provide a frequency regulation strategy for the system with VI is a key problem. Firstly, the power system is a multi inputs multi outputs (MIMO) system, in which the coupling characteristics of VI control and the primary and secondary frequency controls can’t be ignored. Secondly, the system inertia constant is time-varying and the estimation of it is crucial for gaining a satisfying regulation performance. This paper intends to provide a frequency regulation strategy for this problem. In this work, an Elman neural network (ENN) based inertia estimation with a deadband method is proposed for the identification of the system’s instant inertia. And the Laguerre function-based rate of change of frequency (ROCOF) constrained MIMO-MPC is constructed to provide the collaboration strategy. Then, the control parameters are tuned by the gravitational search algorithm (GSA) considering both the system performance indexes and the operation burden indexes. The proposed strategy is testified based on a three-area power system. The results prove not only the robustness of the controller but also the effectiveness of the ROCOF constraint, the operation burden index, and the instant inertia estimation method.

Comprehensive geriatric assessment and drug burden in elderly chronic kidney disease patients

Abstract Objectives Chronic kidney disease (CKD) is a condition characterized by atherosclerosis, cognitive impairment, physical limitations, biochemical abnormalities, and vascular aging. The proportion of those with a diagnosis of CKD in the older is increasing. With comprehensive geriatric assessment, it could be possible to detect the disorders that are related to biological aging. The aim is to evaluate geriatric syndromes like frailty, cognitive dysfunction, malnutrition, and polypharmacy in an aged population with pre-dialytic CKD (stages 3a–5), and to investigate possible relations with biochemical features and anticholinergic drug burden (ADB). Methods One hundred and fifty-six CKD patients aged 60 and older and 164 healthy controls were included in the study. Geriatric parameters that were used for the evaluation of the groups were, Clinical Frailty Index; Charlson Comorbidity Index; Montreal Cognitive Assessment and Mini Nutritional Assessment Short-Form. Besides, biochemical parameters and ADB defined with 3 scales Anticholinergic Burden Classification (ABC), Chew’s scale, and Drug Burden Index were recorded. Results Despite being younger, CKD patients had higher comorbidity and frailty scores than the controls. Patients and controls had similar nutritional status, and cognitive function test results. Frailty was an important predictor for geriatric parameters and eGFR. ABC score was higher in the CKD group in ADB scale. Conclusions Frailty and polypharmacy are more prevalent than expected in older with CKD. In addition, anticholinergic burden and polypharmacy may form causal links with one and other and lead to increased mortality rates especially with frailty. Therefore, geriatric assessment and appropriate ADB evaluation may be recommended in CKD patients.

Prognostic and predictive impact of molecular tumor burden index in non-small cell lung cancer patients.

The biomarkers of immune checkpoint inhibitors in the treatment of non-small cell lung cancer (NSCLC) patients have limited predictive performance. In this study we aimed to investigate the feasibility of molecular tumor burden index (mTBI) in circulating tumor DNA (ctDNA) as a predictor for immunotherapy in patients with NSCLC. From February 2017 to November 2020, pretreatment and on-treatment (3~6 weeks after first cycle of immunotherapy) dynamic plasma ctDNA samples from NSCLC patients receiving immune monotherapy or combination therapy were analyzed by targeted capture sequencing of 1021 genes. PyClone was used to infer the mTBI. The impact of pretreatment mTBI on survival outcomes was verified in the POPLAR/OAK trials. We found that patients without detectable baseline ctDNA had better survival outcomes (median overall survival [OS]: not reached vs. 12.8 months; hazard ratio [HR], 0.15; p = 0.035]). RB1 and SMARCA4 mutations were remarkably associated with worse survival outcomes. Furthermore, lower pretreatment mTBI was associated with superior OS (median: not reached vs. 8.1 months; HR, 0.22; p = 0.024) and PFS (median: 32.9 vs. 5.4 months; HR, 0.35; p = 0.045), but not objective response, which was validated in the POPLAR/OAK cohort, suggesting that baseline mTBI was a prognostic factor for NSCLC immunotherapy. Early dynamic changes of mTBI (ΔmTBI) significantly distinguished responsive patients, and patients with mTBI decrease to more than 68% at the final tumor evaluation had longer OS (median: 38.2 vs. 4.0 months; HR, 0.18; p = 0.017) and PFS (median: not reached vs. 2.3 months; HR, 0.24; p = 0.030). ΔmTBI had a good sensitivity to identify potential beneficial patients based on the best effect CT scans, demonstrating that mTBI dynamics were predictive of benefit from immune checkpoint blockade.

Deep dissection of stemness-related hierarchies in hepatocellular carcinoma

BackgroundIncreasing evidence suggests that hepatocellular carcinoma (HCC) stem cells (LCSCs) play an essential part in HCC recurrence, metastasis, and chemotherapy and radiotherapy resistance. Multiple studies have demonstrated that stemness-related genes facilitate the progression of tumors. However, the mechanism by which stemness-related genes contribute to HCC is not well understood. Here, we aim to construct a stemness-related score (SRscores) model for deeper analysis of stemness-related genes, assisting with the prognosis and individualized treatment of HCC patients.Further, we found that the gene LPCAT1 was highly expressed in tumor tissues by immunohistochemistry, and sphere-forming assay revealed that knockdown of LPCAT1 inhibited the sphere-forming ability of hepatocellular carcinoma cells.MethodsWe used the TCGA-LIHC dataset to screen stemness-related genes of HCC from the MSigDB database. Prognosis, tumor microenvironment, immunological checkpoints, tumor immune dysfunction, rejection, treatment sensitivity, and putative biological pathways were examined. Random forest created the SRscores model. The anti-PD-1/anti-CTLA4 immunotherapy, tumor mutational burden, medication sensitivity, and cancer stem cell index were compared between the high- and low-risk score groups. We also examined risk scores for different cell types using single-cell RNA sequencing data and correlated transcription factor activity in cancer stem cells with SRscores genes. Finally, we tested core marker expression and biological functions.ResultsPatients can be divided into two subtypes (Cluster1 and Cluster2) based on the TCGA-LIHC dataset's identification of 11 stemness-related genes. Additionally, a SRscores was developed based on subtypes. Cluster2 and the group with the lowest SRscores had superior survival and immunotherapy response than Cluster1 and the group with the highest SRscores. The group with a high SRscores was significantly more enriched in classical tumor pathways than the group with a low SRscores. Multiple transcription factors and SRscores genes are correlated. The core gene LPCAT1 is highly expressed in rat liver cancer tissues and promotes tumor cell sphere formation.ConclusionA SRscores model can be utilized to predict the prognosis of HCC patients as well as their response to immunotherapy.

Improving the assessment of malnutrition in cancer: Using systemic inflammation markers as a supplement to the inflammation items of the GLIM criteria

Systemic inflammation is a key pathogenic criterion for diagnosing malnutrition using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Although cancer is commonly considered as a chronic inflammation-related disease, the inflammatory burden may vary depending on the type and stage of cancer. Therefore, a more precise definition of inflammation criteria could facilitate the identification of malnutrition in cancer. This prospective multicenter study included 1683 cancer patients screened via NRS2002 for malnutrition risk. The inflammatory burden index (IBI), C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), and albumin (ALB) level were used to assess the inflammatory burden. Kaplan-Meier and Cox regression analyses were used to determine the relationship between the GLIM criteria and overall survival. Harrell's concordance index (C-index) was used to compare the discriminative performance of the original, IBI-based, CRP-based, NLR-based, and ALB-based GLIM criteria for survival. Logistic regression models were used to assess the association between GLIM criteria and short-term outcomes, length of hospital stay, and hospitalization costs. Compared to the original GLIM criteria, the IBI/CRP/NLR/ALB-based GLIM criteria better predicted the long-term outcomes of patients with cancer (chi-square: 1.316 vs. 78.321 vs. 74.740 vs. 88.719 vs. 100.921). The C-index revealed that the inflammation marker-based GLIM criteria showed significantly better prognostic accuracy than the original GLIM criteria. The ALB-based GLIM criteria exhibited the best prognostic accuracy. The inflammation marker-based GLIM criteria were independent predictive factors for the long-term prognosis of cancer. Patients with malnutrition had a 45% higher risk of adverse long-term prognoses than those without malnutrition. The inflammation marker-based GLIM criteria had good prognostic ability to predict outcomes at 3, 6, and 12 months. The stepwise effect of the grading of severity via the IBI-based GLIM criteria and CRP-based GLIM criteria was notable. The inflammation marker-based GLIM criteria are useful for predicting short-term outcomes, length of hospitalization, and hospitalization costs. The inflammation marker-based GLIM criteria have a stronger predictive value than the original GLIM criteria in evaluating both the short- and long-term prognoses of cancer patients. It is recommended to use the inflammation marker-based GLIM criteria for nutritional evaluation of cancer patients.

Inflammatory Burden Index: Association Between Novel Systemic Inflammatory Biomarkers and Prognosis as Well as in-Hospital Complications of Patients with Aneurysmal Subarachnoid Hemorrhage.

Systemic inflammation plays an important role in the pathophysiology and progression of aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to investigate the association between a new biomarker, the inflammatory burden index (IBI) and the prognosis as well as in-hospital complications of aSAH patients. We analyzed data from patients with aSAH between January 2019 and September 2022 who were included in the LongTEAM (Long-term Prognosis of Emergency Aneurysmal Subarachnoid Hemorrhage) registry study. The IBI was formulated as C-reactive protein × neutrophils/lymphocytes. The unfavorable functional prognosis was assessed by the modified Rankin Scale (mRS). Receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cut-off values for IBI to distinguish the unfavorable functional prognosis. Multivariate logistic regression was applied to investigate the association between IBI and in-hospital complications. Propensity score matching was adjusted for imbalances in baseline characteristics to assess the effect of IBI on prognosis. A total of 408 consecutive patients with aSAH enrolled in the study, of which 235 (57.6%) were female patients and the mean age was 55.28 years old. An IBI equal to 138.03 was identified as the best cut-off threshold to distinguish the unfavorable prognosis at 3 months (area under the curve [AUC] [95% CI] 0.637 [0.568-0.706]). ln IBI was independently associated with 3-month functional prognosis (OR [95% CI] 1.362 [1.148-1.615]; P<0.001), pneumonia (OR [95% CI] 1.427 [1.227-1.659]; P<0.001) and deep venous thrombosis (DVT). (OR [95% CI] 1.326 [1.124-1.564]; P=0.001). After propensity score matching (57:57), an increased proportion of patients with IBI ≥138.03 had a poor functional prognosis at 3 months and in-hospital complications including developed pneumonia and DVT. In patients with aSAH, high IBI level at admission was associated with unfavorable functional prognosis as well as pneumonia and deep vein thrombosis.

Nurses' Awareness of and Current Approaches to Oral Care in a Community Hospital in Japan: A Longitudinal Study of Dental Specialists' Interventions.

Objective: This study aimed to increase nurses' interest and priority in oral care by implementing educational interventions, such as teaching oral care methods suitable for each patient in clinical settings, over a period of one year. Materials and Methods: This study included all 150 nurses working in Unnan City Hospital in Japan who answered a questionnaire comprising 19 questions regarding awareness, actual implementation status of oral care provided, burden, and involvement with oral and maxillofacial surgery department of the hospital, along with participants' characteristics. The rate of interest in learning, need for oral care, time spent in oral care, and oral health-related caregiver burden index (OHBI) score were compared between pre- and post-intervention groups. Results: The number and rate of valid questionnaires were 136 and 90.7%, respectively. The mean years of clinical experience were 19.3 ± 12.5 years; 93.4% of the nurses were women. After the interventions by dental specialists, the nurses' level of interest in and priority to oral care were significantly higher than those before the interventions (p < 0.001), regardless of nurses' background, such as age, gender, or years of experience. However, the "burden" did not statistically decrease. Conclusions: This study shows that dental specialists succeeded in significantly increasing nurses' interest in and priority to oral care by intervening in clinical practice but failed in decreasing nurses' burden of oral care. In the future, we would like to investigate the problems that hinder the reduction of the sense of burden, reduce the burden of nurses' oral care, and improve oral care.

Concomitant Coronary Atheroma Regression and Stabilization in Response to Lipid-Lowering Therapy

BackgroundThe frequency, characteristics, and outcomes of patients treated with high-intensity lipid-lowering therapy and showing concomitant atheroma volume reduction, lipid content reduction, and increase in fibrous cap thickness (ie, triple regression) are unknown. ObjectivesThis study was designed to investigate rates, determinants, and prognostic implications of triple regression in patients presenting with acute myocardial infarction and treated with high-intensity lipid-lowering therapy. MethodsThe PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients with Acute Myocardial Infarction) trial used serial intravascular ultrasound, near-infrared spectroscopy, and optical coherence tomography to compare the effects of alirocumab vs placebo in patients receiving high-intensity statin therapy. Triple regression was defined by the combined presence of percentage of atheroma volume reduction, maximum lipid core burden index within 4 mm reduction, and minimal fibrous cap thickness increase. Clinical outcomes at 1-year follow-up were assessed. ResultsOverall, 84 patients (31.7%) showed triple regression (40.8% in the alirocumab group vs 23.0% in the placebo group; P = 0.002). On-treatment low-density lipoprotein cholesterol levels were lower in patients with vs without triple regression (between-group difference: −27.1 mg/dL; 95% CI: −37.7 to −16.6 mg/dL; P < 0.001). Triple regression was independently predicted by alirocumab treatment (OR: 2.83; 95% CI: 1.57-5.16; P = 0.001) and a higher baseline maximum lipid core burden index within 4 mm (OR: 1.03; 95% CI: 1.01-1.06; P = 0.013). The composite clinical endpoint of death, myocardial infarction, and ischemia-driven revascularization occurred less frequently in patients with vs without triple regression (8.3% vs 18.2%; P = 0.04). ConclusionsTriple regression occurred in one-third of patients with acute myocardial infarction who were receiving high-intensity lipid-lowering therapy and was associated with alirocumab treatment, higher baseline lipid content, and reduced cardiovascular events. (Vascular Effects of Alirocumab in Acute MI-Patients [PACMAN-AMI]; NCT03067844)

Optimizing Pharmacist Team-Integration for ICU Patient Management: Rationale, Study Design, and Methods for a Multicentered Exploration of Pharmacist-to-Patient Ratio.

The workload of healthcare professionals including physicians and nurses in the ICU has an established relationship to patient outcomes, including mortality, length of stay, and other quality indicators; however, the relationship of critical care pharmacist workload to outcomes has not been rigorously evaluated and determined. The objective of our study is to characterize the relationship of critical care pharmacist workload in the ICU as it relates to patient-centered outcomes of critically ill patients. Optimizing Pharmacist Team-Integration for ICU patient Management is a multicenter, observational cohort study with a target enrollment of 20,000 critically ill patients. Participating critical care pharmacists will enroll patients managed in the ICU. Data collection will consist of two observational phases: prospective and retrospective. During the prospective phase, critical care pharmacists will record daily workload data (e.g., census, number of rounding teams). During the retrospective phase, patient demographics, severity of illness, medication regimen complexity, and outcomes will be recorded. The primary outcome is mortality. Multiple methods will be used to explore the primary outcome including multilevel multiple logistic regression with stepwise variable selection to exclude nonsignificant covariates from the final model, supervised and unsupervised machine learning techniques, and Bayesian analysis. Our protocol describes the processes and methods for an observational study in the ICU. This study seeks to determine the relationship between pharmacist workload, as measured by pharmacist-to-patient ratio and the pharmacist clinical burden index, and patient-centered outcomes, including mortality and length of stay.

Expression and Prognostic Value of Cytokines in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma

To investigate the expression and prognostic value of cytokines in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Clinical data of 62 patients diagnosed with DLBCL in the First People's Hospital of Yunnan Province from June 2017 to November 2018 were collected. The differences in expression levels of 14 serum cytokines [interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL-22, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, TNF-β] in patients with different survival outcomes, and the impact of the cytokines on 3-year progression-free survival (PFS) and 3-year overall survival (OS) of patients with DLBCL were analyzed retrospectively. Among the 14 cytokines, only the expression of IL-10 was significantly different in patients with different survival outcomes (P =0.007). According to the receiver operating characteristic (ROC) curve, the optimal cut-off value for IL-10 was 11.74 pg/ml. Serum IL-10 was positively correlated with infection markers procalcitonin (PCT) (r =0.321, P =0.029), C-reactive protein (CRP) (r =0.320, P =0.013) and tumor burden index lactate dehydrogenase (LDH) (r =0.439, P <0.001) in newly diagnosed DLBCL patients. The level of IL-10 in patients with pulmonary infection was significantly higher than that in patients without pulmonary infection (P =0.012). However, there was no statistically significant difference on the 3-year survival outcomes between patients with or without pulmonary infection. There was no significant difference in IL-10 level in patients with different Ann Arbor stages (P >0.05). Patients with high IL-10 level (IL-10>11.74 pg/ml) had significantly higher LDH level than those with low IL-10 level (IL-10≤11.74 pg/ml) (P <0.001). The 3-year PFS rate and 3-year OS rate of DLBCL patients with high IL-10 level were significantly lower than those of low IL-10 level group [(44.4±11.7)% vs (81.8±5.8)%, P <0.001; (61.6±11.5)% vs (93.2±3.8)%, P =0.001]. Serum IL-10 level in newly diagnosed DLBCL patients can reflect the inflammatory state of the body, which may be related to tumor load. Newly diagnosed DLBCL patients with serum IL-10>11.74 pg/ml have higher early mortality and worse prognosis.

Safer medicines To reduce falls and refractures for OsteoPorosis (#STOP): a study protocol for a randomised controlled trial of medical specialist-initiated pharmacist-led medication management reviews in primary care

IntroductionMinimal trauma fractures (MTFs) often occur in older patients with osteoporosis and may be precipitated by falls risk-increasing drugs. One category of falls risk-increasing drugs of concern are those with...

Post Hoc Analyses of a Randomized Controlled Trial for the Effect of Pharmacist Deprescribing Intervention on the Anticholinergic Burden in Frail Community-Dwelling Older Adults.

Anticholinergic burden is detrimental to cognitive health. Multiple studies found that a high anticholinergic burden is associated with an increased risk for dementia, changes to the brain structure, function, and cognitive decline. We performed a post hoc analysis of a randomized controlled deprescribing trial. We compared the effect of the intervention on baseline anticholinergic burden across the treatment and control groups and the time of recruitment before and after a lockdown due to the COVID pandemic with subgroup analyses by baseline frailty index. Randomized controlled trial. We analyzed data from a de-prescribing trial of older adults (>65years) previously conducted in New Zealand that was focused on reducing the Drug Burden Index (DBI). We used the anticholinergic cognitive burden (ACB) to quantify the impact of the intervention on reducing the anticholinergic burden. Participants not taking anticholinergics at the start of the trial were excluded. The primary outcome for this subgroup analysis was a change in ACB, measured with the ĝHedges statistic describing the difference in standard deviation units of this change between intervention and control. For this analysis, the trial participants were stratified into low, medium, and high frailty and timing into prior- and post-lockdown (public health measures for COVID-19). Among the 295 participants in this analysis, the median (IQR) age was 79 (74, 85), and 67% were women. For the primary outcome ĝHedges=-0.04 (95% CI-0.26 to 0.19) with a-0.23 mean reduction in ACB in the intervention arm and-0.19 in the control arm. Before lockdown ĝHedges=-0.38 (95% CI-0.84 to 0.04) and post-lockdown ĝHedges= 0.07 (95% CI-0.19 to 0.33). The mean change in ACB for each of the frailty strata was as follows: low frailty (-0.02; 95% CI-0.65 to 0.18); medium frailty (0.05; 95% CI-0.28 to 0.38); high frailty (0.08; 95% CI-0.40 to 0.56). The study did not provide evidence for the effect of pharmacist deprescribing intervention on reducing the anticholinergic burden. However, this post hoc analysis examined the impact of COVID on the effectiveness of the intervention, and further research in this area may be warranted.

Value of ultrasound in assessing response to neoadjuvant chemotherapy in breast cancer

To analyse the utility of ultrasound in assessing response to neoadjuvant chemotherapy (NAC) and predicting residual cancer burden (RCB) index and pathological complete response (pCR) MATERIALS AND METHODS: This was a retrospective study with 417 patients over 7 years. The difference in longest diameter (LD) of the index lesion from baseline to end, baseline to mid, and mid to end was evaluated with respect to RCB class using logistic regression and ordered logistic regression. Change in LD measurements from baseline to end, baseline to mid, and mid to end of chemotherapy as a predictor of RCB class show a negative relationship with a statistically significant association. This would suggest that a smaller change in LD measurements would be associated with an eventual higher RCB class. Change in LD measurements from baseline to end and baseline to mid chemotherapy as a predictor of pCR class show a negative relationship with a statistically significant association (p<0.05). This similarly indicates an inversely proportional relationship between changes in LD measurements and RCB class 0 for baseline to end and baseline to mid. This study has shown significance in reducing LD measurements on ultrasound as a predictor of PCR and RCB class. This adds weight to the current practice of using ultrasound at the start, mid and end of chemotherapy cycles to monitor NACT responses.