bluuebunny/crossref_metadata_2025 huggingface dataset:
Continuous Dosing of Apohemoglobin-Haptoglobin in Beta Thalassemic Mice to Establish Safety and Efficacy
Authors: Munoz Carlos J , Lucas Daniela , Muller Cynthia R , Martinez Jacinda , Govender Krianthan , Gopal Srila , Cabrales Pedro
Published: December 2023

Thalassemia is a blood disorder that affects the production of hemoglobin (Hb), the crucial protein responsible for carrying and delivering oxygen to tissues. It is caused by mutations in the genes that control the production of hemoglobin, leading to decreased or absent production of one of the globin chains (alpha or beta) that make up hemoglobin. Individuals with thalassemia often need regular blood transfusions to maintain adequate Hb levels. However, frequent transfusions can cause iron overload in the body, necessitating chelation therapy to remove excess iron and prevent organ damage. The iron overload also results in higher levels of hemolysis, leading to the release of free acellular Hb and heme, which the body's natural scavenging proteins (hemopexin and haptoglobin) cannot effectively handle.

To address this problem, our research group has recently explored a promising solution using a bioengineered Hb and heme scavenger called apohemoglobin-haptoglobin (apoHb-Hp) complex. This complex works as a scavenger for heme and hemoglobin from the circulation, helping to eliminate vasoconstriction, enhance perfusion, and reduce inflammation. We conducted a study to test the safety and effectiveness of apoHb-Hp in beta-thalassemic mice, and the results were quite encouraging.

Initially, we treated twenty beta-thalassemic mice with different dosing regimens of apoHb-Hp, ranging from 25 to 100 mg/kg. The mice received the complex every other day for a total of three doses. After the final dose, we measured various parameters, including total bilirubin concentration, plasma LDH, and plasma iron. As the dosing amount increased, there was a progressive decrease in all three measurements, reaching a therapeutic plateau at 75 mg/kg.

In he second part of the study, we treated eight beta-thalassemic mice with a dose of 80 mg/kg of apoHb-Hp for six weeks, every other day. Again, we measured total bilirubin concentration, plasma LDH, and plasma iron, and observed a significant drop compared to baseline levels at the start of the study.

These promising results suggest that apoHb-Hp could be a safe and effective treatment option for beta-thalassemia. Its ability to scavenge heme and Hb, along with its positive effects on various markers, makes it a potential game-changer in the management of this genetic blood disorder. Further research and testing will be necessary to fully explore the potential of apoHb-Hp as a therapeutic option for individuals with beta-thalassemia.
Flu Induced Acute Chest Syndrome in Sickle Cell Disease Mice
Authors: Kaminski Tomasz Waldemar , Katoch Omika , Sundd Prithu
Published: December 2023

Background: Sickle cell disease (SCD) affects over ~8 million people world-wide. Acute chest syndrome, a type of acute lung injury (ALI) is a major cause of mortality among SCD patients. Flu is an acute respiratory disease primarily caused by the influenza A virus (IAV), which is typically a self-resolving upper airway inflammation. However, epidemiological evidence suggests that flu can result in severe ACS in SCD patients. Although flu associates with a 50-fold higher risk of ICU admission among SCD than non-SCD humans, the etiological mechanism underlying the flu severity in SCD remains unknown.

Aim: To determine whether a mild dose of IAV promotes severe lung injury in SCD mice.

Methods: We have developed a model of A/PR/8/34 (H1N1) IAV induced respiratory infection in knock-in, humanized SCD mice. Mice were intranasally inoculated with a mild dose of IAV. The body weight was measured every day for three weeks after intranasal IAV administration followed by assessment of lung injury at day 10 and 14 post infection. Severity of lung injury was evaluated using histological scoring and oxygen saturation measurements. Real-time intravital ( in vivo) multi-photon-excitation fluorescence microscopy (MPE) was used to assess thrombo-inflammation and vascular leakage in the lung of mice at 10 and 14 days post IAV-infection.

Results: Over the first 8 days post-IAV infection, both SCD and control mice manifested comparable levels of mild lung injury and a mild drop in body weight (15%). Unlike the control mice that started to recover, the lung injury and drop in body weight continued to worsen in SCD mice at 8-10 days post IAV infection. By day 14 post IAV infection, the lung injury was resolved and body weight was recovered in control mice, while SCD mice still manifested severe lung injury and ~20% drop in body weight. Intravital lung microscopy revealed large areas with vascular occlusion, ischemia, neutrophil infiltration and vascular leakage in the lung of SCD mice 10 days post infection, however, such pathophysiology was rarely present in the lung of control mice at 10 days post infection.

Conclusions: Our current findings are the first to suggest that the inflammatory milieu in SCD mice promotes a severe non-resolving ALI following an IAV infection, which otherwise leads to a mild self-resolving lung inflammation in control mice.
Neurocognitive Improvement with Hydroxyurea Therapy in Children with Sickle Cell Anemia in Uganda: Interim Analysis at Month 18
Authors: Naggayi Shubaya Kasule , Kalibala Dennis , Opoka Robert , Rosano Caterina , Munube Deogratias , Kasirye Phillip , Mupere Ezekiel , Mboizi Vincent , Ssenkusu John , Green Nancy S. , Idro Richard , Bangirana Paul
Published: December 2023

Introduction: Cerebrovascular injury can lead to neurocognitive impairment in children with sickle cell anemia (SCA). The prospective impact of hydroxyurea therapy on neurocognitive function has not been previously reported in a large sample of children with SCA in sub-Saharan Africa. We assessed the impact of hydroxyurea therapy at the trial's18-month midpoint on neurocognitive function compared to baseline assessments and to non-SCA controls.

Methods: A sample of267 children with SCA, ages 3 to 9 years, were randomly selected for screening and enrollment from eligible patients who attended the Mulago Hospital Sickle Cell Clinic (MHSCC). BRAIN SAFE II is an open label hydroxyurea treatment trial with escalation to maximal tolerated dose. Primary outcomes are stroke, stroke risk and neurocognitive assessment. Controls were aged 3 to 12 years and siblings/relatives of participants with SCA.Attention, cognition and executive function were assessed for all participants by age-appropriate neurocognitive testing. Controlsestablished test z-scores for each age. Baseline (month 0) SCA group z-scores were compared to the controls and to the SCA sample at trial month 18.

Results: At trial baseline, SCA trial participants (n=267) were younger than the control group (mean age 5.1±1.7 vs. 7.1± 3.9 years, p<0.001), had lower weight-for-age ( p=0.03) and had similar socio-economic score and caregiver age and educational attainment. Participants had lower z-scores in attention (p<0.001) and neurocognitive ability (p<0.001), and in executive function ( p=0.001) in a total of 15 of 17 subtests. After 18 months of hydroxyurea therapy (mean dose 25.4mg/kg) for all active SCA participants (95.1%) (n=254), significant improvements in z-scores were seen at 18 months in attention ( p<0.001), all 4 subtests for cognitive ability ( p<0.001) and in 3 of 6 subtests of executive function ( p=0.003 to <0.001).

Conclusion: After 18 months of hydroxyurea therapy reaching MTD dosing, children showed significant improvements in attention and cognition, with more modest improvements in executive function. Their scores moved closer to those from non-SCA controls in most subtests. These findings suggest that hydroxyurea therapy may play an important role in enhancing overall neurocognitive function in children with SCA. Trial procedures are ongoing to assess the effects from longer-term therapy.
Racial Disparities in Hospital Outcomes of Autologous Stem Cell Transplantation for Multiple Myeloma: A Comparative NIS 2016 to 2020 Database Study
Authors: Neupane Niraj , Srivastava Arnav , Sanjeevi Aditya , Agrawal Shubham , Mahmoud Amir , Shah Anish , Budhathoki Pravash , Kharel Himal , Joshi Utsav , Dhakal Binod
Published: December 2023

Objective:

Due to the paucity of data and the difference in-hospital outcomes in the two most common races in America remains controversial. This study aims to compare hospital outcomes in multiple myeloma patients undergoing autologous stem cell transplantation (ASCT) between White and Black patients using data from the National Inpatient Sample (NIS) from 2016 to 2020.

Methods:

A retrospective analysis of the NIS database was conducted using International Classification of Diseases (ICD-10) codes to identify patients who underwent ASCT for multiple myeloma. STATA version MP14.2 was used for analysis. We used Fischer's exact test to compare proportions, the student's t-test to compare continuous variables, and multivariate regression analysis to calculate the adjusted odds ratio after controlling age, gender, primary payer, and CCI. Following are included in transplant complications (transplant rejection, failure, transplant infection).

Results:

Among 31,389 hospitalizations, 19,065 (60.74%) were whites, and 6,110 (19.47%) were blacks. The mean age was 62 in whites and 59 in blacks (P < 0.001). Most patients were male, constituting 59.46% among Whites and 71.11% among Blacks. A significantly higher proportion of blacks had comorbidities compared to whites, including CKD (18.9% vs. 14.98%), diabetes mellitus (25.94% vs. 14.29%), obesity (16.35% vs. 11.6%), and mean Charlson Comorbidity Index (2.51 vs. 2.42, P < 0.001). On multivariate analysis compared to whites, blacks had a non-significant difference in the risk of acute kidney injury (adjusted odds ratio [AOR]: 0.94, 95% confidence interval [CI]: 0.76-1.17, P =0.58), cardiac arrest (AOR: 0.71, 95% CI: 0.16-3.20, P = 0.71), and blood transfusion (AOR: 1.11, 95% CI: 0.89-1.37, P = 0.36). Additionally, there was no significant difference in the average length (16.53 vs. 16.52, P = 0.85) and total cost ($195,971 vs. $196,300, P = 0.76) of hospital stay between blacks and whites. However, blacks had significantly lower transplant complications (AOR: 0.56, 95% CI: 0.37-0.87, P = 0.01), ICU admission (AOR: 0.58, 95% CI: 0.35-0.97, P = 0.04) and in-hospital mortality (AOR: 0.28, 95% CI: 0.09-0.91, P = 0.03) compared to whites.

Conclusion:

According to our study, blacks who underwent ASCT for multiple myeloma had better outcomes than Whites. Despite having a higher mean age and more comorbidities, this finding emphasizes the importance of conducting additional research and providing personalized interventions to enhance patient outcomes. It also suggests the potential for more black Americans to undergo ASTCT and benefit from it while avoiding delays and improving overall survival rates.
Efficacy and Safety of Isavuconazole in the Treatment of Invasive Fungal Disease in Patients with Hematological Disorders
Authors: Pan Pan , Pang Aiming , Jiang Erlie
Published: December 2023

Objective: Invasive fungal disease (IFD) poses a significant threat to patients suffering from hematological disorders with high morbidity and mortality. isavuconazole has shown promising efficacy and safety in treating IFD caused by various pathogens including but not limited to Aspergillus and Mucor species in the previous studies. Thus, this retrospective single-arm case analysis study was conducted to evaluate the efficacy and safety of isavuconazole in patients with hematological disorders.

Method: This study included 12 patients diagnosed with IFD (including proven/probable/possible IFD) between August 2022 and March 2023 who underwent isavuconazole treatment for a minimum duration of 7 days. Only patients who received itraconazole monotherapy were involved, with 4 of whom taking initial treatment while 8 receiving isavuconazole as salvage therapy.

Results: Among the 12 patients included in this study, 7 were diagnosed with invasive aspergillosis and 5 were diagnosed with invasive mucormycosis. The median duration of isavuconazole treatment was 43.5 (11-86) days. At the conclusion of the treatment, the overall response (OR) rate for all patients was 67% (8/12), with a complete response rate of 42% (5/12) and a partial response rate of 25% (3/12). Among patients receiving initial treatment, 75% (3/4) patients achieved OR, while 62.5% (5/8) patients approached OR among those receiving salvage therapy. Importantly, only 1 patient experienced an increase in transaminases without demand to discontinuing isavuconazole treatment. Besides, no patients withdraw isavuconazole therapy due to other adverse reactions.

Conclusions: The study results demonstrate that isavuconazole exhibits both effect and safety in the treatment of invasive fungal disease in patients with hematological disorders. Furthermore, there are indications that initial antifungal treatment with itraconazole may yield higher response rates.
Macrophage Immune Checkpoint for Immunotherapy of Osteosarcoma
Authors: Suh Jin Kyung , Lee Jun Ah , Ko Yunmi , Park Meerim , Park Hyeon Jin
Published: December 2023

Purpose: Macrophages account for the majority of immune cells infiltrated in sarcoma tissues. CD47 is a “don't eat me” signal expressed on the cell surface. We tested a feasibility of CD47, a macrophage immune checkpoint, for immunotherapy of osteosarcoma.

Methods: Twenty-four biopsy samples of osteosarcoma patients younger than 20 years were retrospectively analyzed for CD47 protein expression by immunohistochemistry. Relationships between CD47 expression and clinicopathologic characteristics were evaluated. Two osteosarcoma cell lines, KHOS/NP and MG63, were analyzed for CD47 expression by western blotting and flowcytometry. Efficacies of CD47 antibody (B6-H12) on the phagocytic activity of M1-type macrophages, differentiated from peripheral blood monocytes, were evaluated.

Results: CD47 protein was expressed in 5 (20.8%) samples and in three osteosarcoma cell lines. Positive staining for CD47 was related to the presence of metastasis at diagnosis ( P=0.04). Patients with tumors stained positive for CD47 tended to be older than those with tumors stained negative (16.5±6.2 years vs. 15.7±3.0 years, P=0.07). However, sex, tumor size, histologic response to preoperative chemotherapy were not associated with CD47 protein expression.

Influence of CD47 antibody (B6-H12) on cell viability varied between KHOS/NP and MG63 cells. Phagocytic activity of M1-type macrophage on osteosarcoma cells was higher in cells pretreated with CD47 antibody, compared to cells not treated (4.52% vs. 2.02%). However, CD47 antibody pretreatment did not influence the viability of osteosarcoma cells.

Conclusion: The association between CD47 protein expression on biopsy tissues and clinical characteristics suggest a possibility of CD47 as a new target for immunotherapy of osteosarcoma. As we observed a discrepancy between phagocytic activity and cell viability, future studies needs to focus on coupling the macrophage phagocytosis and effector T cell function.
Headaches during pregnancy and the risk of subsequent stroke
Authors: Nam Ki-Woong , Ha Sungyeon , Oh Min-Jeong , Oh Kyungmi , Kim Chi Kyung , Cho Geum Joon , Kim Young Seo , Bushnell Cheryl D.
Published: December 2023

Background

Primary headache disorder is a known risk factor for stroke in women and usually improves during the first trimester of pregnancy. However, despite this, some women develop headaches during pregnancy (G-HA), and the effect of this headache on subsequent stroke is unknown. In this study, we evaluated the association between G-HA and stroke after delivery in women.

Methods

Based on the Korean National Health Insurance Service database, we included women hospitalized for delivery between 2012 and 2013. G-HA was defined as a headache diagnosed during pregnancy. Primary outcome was any stroke that occurred during the observational periods from delivery to December 31, 2020. All diseases were identified based on data registered in the database using the International Classification of Disease-10th Revision-Clinical Modification codes.

Results

Of 906,187 pregnant women, G-HA was found in 56,813 (6.3%). During the observational periods, the G-HA ( +) group had a significantly higher risk of any stroke [adjusted hazard ratio (aHR) = 1.59, 95% confidence interval (CI): 1.30–1.95], ischemic stroke (aHR = 1.50, 95% CI: 1.12–2.01), hemorrhagic stroke (aHR = 1.63, 95% CI: 1.23–2.15), and intracerebral hemorrhage (aHR = 1.63, 95% CI: 1.19–2.23) than the G-HA (-) group. When analyzed considering the interaction with history of headache disorder, G-HA showed a significant association with hemorrhagic stroke, but lost its effect on ischemic stroke.

Conclusions

We demonstrated that G-HA was associated with subsequent stroke occurrence after delivery. However, the relationship between G-HA and ischemic stroke is mitigated by a history of pre-pregnancy headache disorder.
How to improve public transport usage in a medium-sized city: key factors for a successful bus system
Authors: Al Suleiman Shireen , Cortez Adriana , Monzón Andrés , Lara Antonio
Published: December 2023

In recent years, the promotion and use of public transport (PT) has become key to overcoming the negative impacts of mobility, such as traffic congestion, high pollution (GHG), and traffic accidents. Improving users’ satisfaction and increasing the attractiveness of buses play an essential role in increasing PT patronage. Whilst most of the literature concentrates on large and complex bus systems, less attention has been paid to European medium-sized cities, the region’s most common urban configuration, where public transport mainly depends on bus services. To this end, a survey campaign was conducted on passengers of urban buses in Oviedo, Spain, a representative medium-sized city. An Exploratory Factor Analysis (EFA) was used to identify key user satisfaction factors. In this case, three factors were the most important: comfort and information, service performance, and integration. That was complemented by the overall satisfaction (OS) with services, which was used for ranking the importance of the factors using an ordinal logistic regression model; comfort and information appear as the most important. These findings can serve bus operators to identify service-related attributes that need more attention or investment to increase users’ satisfaction and to make the service attractive to potential users.
GC heterogeneity reveals sequence-structures evolution of angiosperm ITS2
Authors: Liu Yubo , Liang Nan , Xian Qing , Zhang Wei
Published: December 2023

Background

Despite GC variation constitutes a fundamental element of genome and species diversity, the precise mechanisms driving it remain unclear. The abundant sequence data available for the ITS2, a commonly employed phylogenetic marker in plants, offers an exceptional resource for exploring the GC variation across angiosperms.

Results

A comprehensive selection of 8666 species, comprising 165 genera, 63 families, and 30 orders were used for the analyses. The alignment of ITS2 sequence-structures and partitioning of secondary structures into paired and unpaired regions were performed using 4SALE. Substitution rates and frequencies among GC base-pairs in the paired regions of ITS2 were calculated using RNA-specific models in the PHASE package. The results showed that the distribution of ITS2 GC contents on the angiosperm phylogeny was heterogeneous, but their increase was generally associated with ITS2 sequence homogenization, thereby supporting the occurrence of GC-biased gene conversion (gBGC) during the concerted evolution of ITS2. Additionally, the GC content in the paired regions of the ITS2 secondary structure was significantly higher than that of the unpaired regions, indicating the selection of GC for thermodynamic stability. Furthermore, the RNA substitution models demonstrated that base-pair transformations favored both the elevation and fixation of GC in the paired regions, providing further support for gBGC.

Conclusions

Our findings highlight the significance of secondary structure in GC investigation, which demonstrate that both gBGC and structure-based selection are influential factors driving angiosperm ITS2 GC content.
Association between living arrangements and health risk behaviors among the Hakka older adults in Fujian, China
Authors: Liu Xiaojun , Zhang Lingling , Chang Huajing , Chen Mengshi , Huang Yimin
Published: December 2023

Background

Behavioral lifestyles are important social determinants of health. The impact of changes in living arrangements on behavioral lifestyles is currently under-explored. This study aims to examine the association between living arrangements and health risk behaviors among the Hakka older adults.

Methods

Data were extracted from China’s Health-Related Quality of Life Survey for Older Adults 2018. Living arrangements were divided into five categories: living alone, living with spouse only, living with child, mixed habitation, and others. Five health risk behaviors, including unhealthy dietary patterns, drinking, smoking, irregular sleep practices, and physical inactivity were measured. Logistic regression analysis was used to assess the association between living arrangements and specific health risk behaviors, and generalized linear models were established to test the association between living arrangements and the number of health risk behaviors.

Results

A total of 1,262 Hakka older adults were included in this study. Compared to those living alone, those living with spouse only were less likely to have unhealthy dietary patterns (OR = 0.45, P < 0.05) and drinking (OR = 0.50, P < 0.05), those living with the child were less likely to experience unhealthy dietary patterns (OR = 0.35, P < 0.001), drinking (OR = 0.32, P < 0.001), smoking (OR = 0.49, P < 0.05), and physical inactivity (OR = 0.13, P < 0.01). Moreover, those who were living with child (β = -0.78, P < 0.001) or mixed habitation (β = -0.33, P < 0.05) tended to engage in fewer health risk behaviors than those living alone.

Conclusions

This study suggests significant differences in health risk behaviors among the Hakka older adults with different living arrangements. Living with the child could reduce the occurrence of health risk behaviors in the Hakka older adults and thus maintain their health status.
Effects of inappropriate cause-of-death certification on mortality from cardiovascular disease and diabetes mellitus in Tonga
Authors: Figueroa Carah A. , Linhart Christine L. , Dearie Catherine , Fusimalohi Latu E. , Kupu Sioape , Morrell Stephen L. , Taylor Richard J.
Published: December 2023

Background

Cardiovascular disease (CVD) and diabetes mellitus are major health issues in Tonga and other Pacific countries, although mortality levels and trends are unclear. We assess the impacts of cause-of-death certification on coding of CVD and diabetes as underlying causes of death (UCoD).

Methods

Tongan records containing cause-of-death data (2001–2018), including medical certificates of cause-of-death (MCCD), had UCoD assigned according to International Classification of Diseases 10th revision (ICD-10) coding rules. Deaths without recorded cause were included to ascertain total mortality. Diabetes and hypertension causes were reallocated from Part 1 of the MCCD (direct cause) to Part 2 (contributory cause) if potentially fatal complications were not recorded, and an alternative UCoD was assigned. Proportional mortality by cause based on the alternative UCoD were applied to total deaths then mortality rates calculated by age and sex using census/intercensal population estimates. CVD and diabetes mortality rates for unaltered and alternative UCoD were compared using Poisson regression.

Results

Over 2001–18, in ages 35–59 years, alternative CVD mortality was higher than unaltered CVD mortality in men (p = 0.043) and women (p = 0.15); for 2010–18, alternative versus unaltered measures in men were 3.3/103 (95%CI: 3.0–3.7/103) versus 2.9/103 (95%CI: 2.6–3.2/103), and in women were 1.1/103 (95%CI: 0.9–1.3/103) versus 0.9/103 (95%CI: 0.8–1.1/103). Conversely, alternative diabetes mortality rates were significantly lower than the unaltered rates over 2001–18 in men (p < 0.0001) and women (p = 0.013); for 2010–18, these measures in men were 1.3/103 (95%CI: 1.1–1.5/103) versus 1.9/103 (95%CI: 1.6–2.2/103), and in women were 1.4/103 (95%CI: 1.2–1.7/103) versus 1.7/103 (95%CI: 1.5–2.0/103). Diabetes mortality rates increased significantly over 2001–18 in men (unaltered: p < 0.0001; alternative: p = 0.0007) and increased overall in women (unaltered: p = 0.0015; alternative: p = 0.014).

Conclusions

Diabetes reporting in Part 1 of the MCCD, without potentially fatal diabetes complications, has led to over-estimation of diabetes, and under-estimation of CVD, as UCoD in Tonga. This indicates the importance of controlling various modifiable risks for atherosclerotic CVD (including stroke) including hypertension, tobacco use, and saturated fat intake, besides obesity and diabetes. Accurate certification of diabetes as a direct cause of death (Part 1) or contributory factor (Part 2) is needed to ensure that valid UCoD are assigned. Examination of multiple cause-of-death data can improve understanding of the underlying causes of premature mortality to better inform health planning.
Muscle quality index and cardiovascular disease among US population-findings from NHANES 2011–2014
Authors: Chen Yanlin , Lin Weidong , Fu Lu , Liu Huiyi , Jin Shuyu , Ye Xingdong , Pu Sijia , Xue Yumei
Published: December 2023

Background and objective

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. However, current evidence on the association between muscle quality and CVD is limited. This study investigates the potential association between the muscle quality index (MQI) and the prevalence of CVD and CVD-related mortality.

Methods

Participants were selected from the National Health and Nutrition Examination Survey (NHANES) 2011–2014. Data on mortality and causes of death were obtained from the National Death Index (NDI) records through December 31, 2019. Statistical analysis used in this study, including weighted multivariable linear and logistic regression, cox regression and Kaplan-Meier (K-M) analysis, to estimate the association between MQI and all-cause mortality as well as CVD mortality. In addition, subgroup analysis was used to estimate the association between MQI and CVD subtypes, such as heart attack, coronary heart disease, angina, congestive heart failure, and stroke.

Results

A total of 5,053 participants were included in the final analysis. Weighted multivariable linear regression models revealed that a lower MQI.total level was independently associated with an increased risk of CVD development in model 3, with t value =-3.48, 95%CI: (-0.24, -0.06), P = 0.002. During 5,053 person-years of 6.92 years of follow-up, there were 29 deaths from CVD. Still, the association between MQI.total and CVD mortality, as well as all-cause mortality did not reach statistical significance in the fully adjusted model (HR = 0.58, 95% CI: 0.21–1.62, P = 0.30; HR = 0.91, 95% CI:0.65,1.28, P = 0.59, respectively). Subgroup analysis confirmed that MQI.total was negatively associated with congestive heart failure (OR = 0.35, 95% CI = 0.18,0.68, P = 0.01).

Conclusion

This study highlights the potential of MQI as a measure of muscle quality, its negative correlation with congestive heart failure (CHF). However, MQI was not very useful for predicting the health outcomes such as CVD and mortality. Therefore, more attention should be paid to the early recognition of muscle weakness progression in CHF. Further studies are needed to explore more effective indicator to evaluate the association between muscle quality and health outcomes.
Feasibility and acceptability of using biometric fingerprinting to track migrations and support retention in HIV prevention research in fishing population in East Africa
Authors: Abaasa Andrew , Mee Paul , Nanyonjo Agnes , Easton Sue , Tanser Frank , Asiki Gershim
Published: December 2023

Introduction

Fishing populations constitute a suitable key population amongst which to conduct HIV prevention trials due to very high HIV prevalence and incidence, however, these are highly mobile populations. We determined the feasibility and acceptability of using fingerprinting and geographical positioning systems to describe mobility patterns and retention among fisherfolks on the shoreline of Lake Victoria in South-western Uganda.

Methods

Between August 2015 and January 2017, two serial cross-sectional surveys were conducted during which fingerprinting of all residents aged 18–30 years on the shoreline of Lake Victoria was done. A mapper moving ahead of the survey team, produced village maps and took coordinates of every household. These were accessed by the survey team that assigned household and individual unique identifiers (ID) and collected demographic data. Using the assigned IDs, individuals were enrolled and their fingerprints scanned. The fingerprinting was repeated 6 months later in order to determine the participant’s current household. If it was different from that at baseline, a new household ID was assigned which was used to map migrations both within and between villages.

Results

At both rounds, over 99% accepted to be fingerprinted. No fingerprinting faults were recorded at baseline and the level was under 1% at round two. Over 80% of the participants were seen at round two and of these, 16.3%, had moved to a new location whilst the majority, 85%, stayed within the same village. Movements between villages were mainly observed for those resident in large villages. Those who did not consider a fishing village to be their permanent home were less likely to be migrants than permanent residents (adjusted odds ratio = 0.37, 95%CI:0.15–0.94).

Conclusion

Use of fingerprinting in fishing populations is feasible and acceptable. It is possible to track this mobile population for clinical trials or health services using this technology since most movements could be traced within and between villages.
Effect of a Patient Engagement, Education, and Restructuring of Cognitions (PEERC) approach on conservative care in rotator cuff related shoulder pain treatment: a randomized control trial
Authors: Myers Heather , Keefe Francis J. , George Steven Z. , Kennedy June , Lake Ashley Davis , Martinez Corina , Cook Chad E.
Published: December 2023

Background

Despite similar outcomes for surgery and physical therapy (PT), the number of surgeries to treat rotator cuff related shoulder pain (RCRSP) is increasing. Interventions designed to enhance treatment expectations for PT have been shown to improve patient expectations, but no studies have explored whether such interventions influence patient reports of having had surgery, or being scheduled for surgery. The purpose of this randomized clinical trial was to examine the effect of a cognitive behavioral intervention aimed at changing expectations for PT on patient-report of having had or being scheduled for surgery and on the outcomes of PT.

Methods

The Patient Engagement, Education, and Restructuring of Cognitions (PEERC) intervention, was designed to change expectations regarding PT. PEERC was evaluated in a randomized, pragmatic “add-on” trial in by randomizing patients with RCRSP to receive either PT intervention alone (PT) or PT + PEERC. Fifty-four (54) individuals, recruited from an outpatient hospital-based orthopedic clinic, were enrolled in the trial (25 randomized to PT, 29 randomized to PT + PEERC). Outcomes assessed at enrollment, 6 weeks, discharge, and six months after discharge included the patient report of having had surgery, or being scheduled for surgery (primary) and satisfaction with PT outcome, pain, and function (secondary outcomes).

Results

The average age of the 54 participants was 51.81; SD = 12.54, and 63% were female. Chronicity of shoulder pain averaged 174.61 days; SD = 179.58. Study results showed that at the time of six months follow up, three (12%) of the participants in the PT alone group and one (3.4%) in the PT + PEERC group reported have had surgery or being scheduled for surgery (p = .32). There were no significant differences between groups on measures of satisfaction with the outcome of PT (p = .08), pain (p = .58) or function (p = .82).

Conclusions

In patients with RCRSP, PT plus the cognitive behavioral intervention aimed at changing expectations for PT provided no additional benefit compared to PT alone with regard to patient report of having had surgery, or being scheduled to have surgery, patient reported treatment satisfaction with the outcome of PT, or improvements in pain, or function.

Trial registration

The trial is registered on ClinicalTrials.gov: NCT 03353272 (27/11/2017).
Identifying facilitators of and barriers to the adoption of dynamic consent in digital health ecosystems: a scoping review
Authors: Lee Ah Ra , Koo Dongjun , Kim Il Kon , Lee Eunjoo , Kim Hyun Ho , Yoo Sooyoung , Kim Jeong-Hyun , Choi Eun Kyung , Lee Ho-Young
Published: December 2023

Background

Conventional consent practices face ethical challenges in continuously evolving digital health environments due to their static, one-time nature. Dynamic consent offers a promising solution, providing adaptability and flexibility to address these ethical concerns. However, due to the immaturity of the concept and accompanying technology, dynamic consent has not yet been widely used in practice. This study aims to identify the facilitators of and barriers to adopting dynamic consent in real-world scenarios.

Methods

This scoping review, conducted in December 2022, adhered to the PRISMA Extension for Scoping Reviews guidelines, focusing on dynamic consent within the health domain. A comprehensive search across Web of Science, PubMed, and Scopus yielded 22 selected articles based on predefined inclusion and exclusion criteria.

Results

The facilitators for the adoption of dynamic consent in digital health ecosystems were the provision of multiple consent modalities, personalized alternatives, continuous communication, and the dissemination of up-to-date information. Nevertheless, several barriers, such as consent fatigue, the digital divide, complexities in system implementation, and privacy and security concerns, needed to be addressed. This study also investigated current technological advancements and suggested considerations for further research aimed at resolving the remaining challenges surrounding dynamic consent.

Conclusions

Dynamic consent emerges as an ethically advantageous method for digital health ecosystems, driven by its adaptability and support for continuous, two-way communication between data subjects and consumers. Ethical implementation in real-world settings requires the development of a robust technical framework capable of accommodating the diverse needs of stakeholders, thereby ensuring ethical integrity and data privacy in the evolving digital health landscape.
Compassion fatigue in healthcare providers: a scoping review
Authors: Garnett Anna , Hui Lucy , Oleynikov Christina , Boamah Sheila
Published: December 2023

The detrimental impacts of COVID-19 on healthcare providers’ psychological health and well-being continue to affect their professional roles and activities, leading to compassion fatigue. The purpose of this review was to identify and summarize published literature on compassion fatigue among healthcare providers and its impact on patient care. Six databases were searched: MEDLINE (Ovid), PsycINFO (Ovid), Embase (Ovid), CINAHL, Scopus, Web of Science, for studies on compassion fatigue in healthcare providers, published in English from the peak of the pandemic in 2020 to 2023. To expand the search, reference lists of included studies were hand searched to locate additional relevant studies. The studies primarily focused on nurses, physicians, and other allied health professionals. This scoping review was registered on Open Science Framework (OSF), using the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) extension to scoping review. From 11,715 search results, 24 met the inclusion criteria. Findings are presented using four themes: prevalence of compassion fatigue; antecedents of compassion fatigue; consequences of compassion fatigue; and interventions to address compassion fatigue. The potential antecedents of compassion fatigue are grouped under individual-, organization-, and systems-level factors. Our findings suggest that healthcare providers differ in risk for developing compassion fatigue in a country-dependent manner. Interventions such as increasing available personnel helped to minimize the occurrence of compassion fatigue. This scoping review offers important insight on the common causes and potential risks for compassion fatigue among healthcare providers and identifies potential strategies to support healthcare providers’ psychological health and well-being.
Gravity models for potential spatial healthcare access measurement: a systematic methodological review
Authors: Stacherl Barbara , Sauzet Odile
Published: December 2023

Background

Quantifying spatial access to care—the interplay of accessibility and availability—is vital for healthcare planning and understanding implications of services (mal-)distribution. A plethora of methods aims to measure potential spatial access to healthcare services. The current study conducts a systematic review to identify and assess gravity model-type methods for spatial healthcare access measurement and to summarize the use of these measures in empirical research.

Methods

A two-step approach was used to identify (1) methodological studies that presented a novel gravity model for measuring spatial access to healthcare and (2) empirical studies that applied one of these methods in a healthcare context. The review was conducted according to the PRISMA guidelines. EMBASE, CINAHL, Web of Science, and Scopus were searched in the first step. Forward citation search was used in the second step.

Results

We identified 43 studies presenting a methodological development and 346 empirical application cases of those methods in 309 studies. Two major conceptual developments emerged: The Two-Step Floating Catchment Area (2SFCA) method and the Kernel Density (KD) method. Virtually all other methodological developments evolved from the 2SFCA method, forming the 2SFCA method family. Novel methodologies within the 2SFCA family introduced developments regarding distance decay within the catchment area, variable catchment area sizes, outcome unit, provider competition, local and global distance decay, subgroup-specific access, multiple transportation modes, and time-dependent access. Methodological developments aimed to either approximate reality, fit a specific context, or correct methodology. Empirical studies almost exclusively applied methods from the 2SFCA family while other gravity model types were applied rarely. Distance decay within catchment areas was frequently implemented in application studies, however, the initial 2SFCA method remains common in empirical research. Most empirical studies used the spatial access measure for descriptive purposes. Increasingly, gravity model measures also served as potential explanatory factor for health outcomes.

Conclusions

Gravity models for measuring potential spatial healthcare access are almost exclusively dominated by the family of 2SFCA methods—both for methodological developments and applications in empirical research. While methodological developments incorporate increasing methodological complexity, research practice largely applies gravity models with straightforward intuition and moderate data and computational requirements.
Efficacy of transarterial chemoembolization with drug-eluting beads combined with systemic chemotherapy and targeted therapy in colorectal cancer liver metastasis
Authors: Chen Yen-Cheng , Huang Ching-Wen , Li Ching-Chun , Chang Tsung-Kun , Su Wei-Chih , Chen Po-Jung , Yeh Yung-Sung , Chang Yu-Tang , Tsai Hsiang-Lin , Shih Ming-Chen Paul , Wang Jaw-Yuan
Published: December 2023

Background

Systemic therapy is the standard treatment for unresectable colorectal cancer with liver metastasis (CRCLM). Transarterial chemoembolization with drug-eluting beads (DEB-TACE) is considered an effective treatment option for CRCLM. Few studies have investigated the combination of DEB-TACE, chemotherapy, and targeted therapy for CRCLM. In the present study, we evaluated the disease control rate (DCR), adverse events, and survival among patients with CRCLM who underwent the combination of DEB-TACE and chemotherapy/targeted therapy.

Materials

We retrospectively reviewed 35 patients with CRCLM who were treated between January 2015 and January 2021. Standard systemic chemotherapy, targeted therapy, and 66 DEB-TACE procedures were administered. Data were collected on each DEB-TACE procedure, including chemotherapy agents, tumor burden of liver metastasis, number of DEB-TACE courses, and adverse events. Patients who received DEB-TACE after failure of first-line systemic therapy were categorized into the first-line failure group. Patients who received DEB-TACE after the failure of second-line, third-line, or fourth-line therapy were categorized into the other group. Subgroup analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between the two groups.

Results

In total, 35 patients with CRCLM (34 patients with adenocarcinoma and 1 patient with neuroendocrine carcinoma) were enrolled. In total, 13 patients (37.1%) had extrahepatic metastases at initial diagnosis. In this study, 66 DEB-TACE procedures were performed. The DCR was 54.3%. The median OS period was 47.4 months, and the estimated 3-year OS rate was 59.5%. The median PFS period was 6.3 months, and the estimated 1-year PFS rate was 20.6%. The PFS period was longer in the first-line failure group than in the other group (7.2 vs. 6.3 months). No significant difference was observed in OS between the two groups. Four episodes (6.1%) of grade 3 intra-abdominal infection were observed.

Conclusion

The combination of chemotherapy, targeted therapy, and DEB-TACE can lead to a favorable DCR and survival outcomes in patients with CRCLM. Early intervention with DEB-TACE (i.e., after the failure of first-line therapy) has the potential to extend the PFS period in patients with CRCLM. Severe adverse events were rare and manageable. Further prospective, randomized controlled studies are warranted to obtain more conclusive findings.
Low-dose PLX5622 treatment prevents neuroinflammatory and neurocognitive sequelae after sepsis
Authors: Mein Nils , von Stackelberg Nikolai , Wickel Jonathan , Geis Christian , Chung Ha-Yeun
Published: December 2023

Background

Sepsis-associated encephalopathy (SAE) is characterized by symptoms of delirium including hallucinations, impaired concentration, agitation, or coma and is associated with poor outcome in the early phase of sepsis. In addition, sepsis survivors often suffer from persisting memory deficits and impaired executive functions. Recent studies provide evidence that microglia are involved in the pathophysiology of SAE.

Methods

Here, we investigated whether pharmacological depletion of microglia using PLX5622 (1200 ppm or 300 ppm) in the acute phase of sepsis is able to prevent long-term neurocognitive decline in a male mouse model of polymicrobial sepsis or lipopolysaccharide-induced sterile neuroinflammation. Therefore, we performed the novel object recognition test at different time points after sepsis to address hippocampus-dependent learning. To further assess synapse engulfment in microglia, colocalization analysis was performed using high-resolution 3D Airyscan imaging of Iba1 and Homer1. We also investigated the effect of PLX5622 on acute astrocyte and chronic microglia proliferation in the hippocampus after sepsis induction using immunofluorescence staining.

Results

High-dose application of the colony stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 (1200 ppm) seven days prior to sepsis induction lead to 70–80% microglia reduction but resulted in fatal outcome of bacterial sepsis or LPS induced inflammation. This is likely caused by severely compromised host immune response upon PLX5622-induced depletion of peripheral monocytes and macrophages. We therefore tested partial microglia depletion using a low-dose of PLX5622 (300 ppm) for seven days prior to sepsis which resulted in an increased survival in comparison to littermates subjected to high-dose CSF1R inhibiton and to a stable microglia reduction of ~ 40%. This partial microglia depletion in the acute stage of sepsis largely prevented the engulfment and microglia-induced stripping of postsynaptic terminals. In addition, PLX5622 low-dose microglia depletion attenuated acute astrogliosis as well as long-term microgliosis and prevented long-term neurocognitive decline after experimental sepsis.

Conclusions

We conclude that partial microglia depletion before the induction of sepsis may be sufficient to attenuate long-term neurocognitive dysfunction. Application of PLX5622 (300 ppm) acts by reducing microglia-induced synaptic attachement/engulfment and preventing chronic microgliosis.
Spatial mapping of posture-dependent resistance to passive displacement of the hypertonic arm post-stroke
Authors: Kanade-Mehta Priyanka , Bengtson Maria , Stoeckmann Tina , McGuire John , Ghez Claude , Scheidt Robert A.
Published: December 2023

Background

Muscles in the post-stroke arm commonly demonstrate abnormal reflexes that result in increased position- and velocity-dependent resistance to movement. We sought to develop a reliable way to quantify mechanical consequences of abnormal neuromuscular mechanisms throughout the reachable workspace in the hemiparetic arm post-stroke.

Methods

Survivors of hemiparetic stroke (HS) and neurologically intact (NI) control subjects were instructed to relax as a robotic device repositioned the hand of their hemiparetic arm between several testing locations that sampled the arm's passive range of motion. During transitions, the robot induced motions at either the shoulder or elbow joint at three speeds: very slow (6°/s), medium (30°/s), and fast (90°/s). The robot held the hand at the testing location for at least 20 s after each transition. We recorded and analyzed hand force and electromyographic activations from selected muscles spanning the shoulder and elbow joints during and after transitions.

Results

Hand forces and electromyographic activations were invariantly small at all speeds and all sample times in NI control subjects but varied systematically by transport speed during and shortly after movement in the HS subjects. Velocity-dependent resistance to stretch diminished within 2 s after movement ceased in the hemiparetic arms. Hand forces and EMGs changed very little from 2 s after the movement ended onward, exhibiting dependence on limb posture but no systematic dependence on movement speed or direction. Although each HS subject displayed a unique field of hand forces and EMG responses across the workspace after movement ceased, the magnitude of steady-state hand forces was generally greater near the outer boundaries of the workspace than in the center of the workspace for the HS group but not the NI group.

Conclusions

In the HS group, electromyographic activations exhibited abnormalities consistent with stroke-related decreases in the stretch reflex thresholds. These observations were consistent across repeated testing days. We expect that the approach described here will enable future studies to elucidate stroke's impact on the interaction between the neural mechanisms mediating control of upper extremity posture and movement during goal-directed actions such as reaching and pointing with the arm and hand.