bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosomal Loop Editing Reveals New Epigenomic Landscape in the β-Globin Locus with Implications for Hemoglobinopathy Therapies
Authors: Himadewi Pamela , Zhang Xiaotian , Gore Haley , Wang Xue Qing David
Published: February 2020

Human β-globin locus consists of at least six genes encoding components of the oxygen transport protein hemoglobin and an upstream locus control region (LCR) containing five DNase I hypersensitive sites. In addition, there are at least four conserved CTCF insulator elements surrounding the locus, which form dynamic chromatin interaction patterns across different cell types in the course of hematopoietic stem and progenitor cells (HSPCs) development. Chromatin conformation of the β-globin locus in normal adult CD34+ HSPCs reveals the formation of three topological associated domains (TADs), in which individual TAD boundaries are demarcated by CTCF sites (Figure 1). By comparing chromatin loop interactions between CD34+ HSPCs and its differentiated erythroid progenitors, we identify a chromatin loop that forms in erythroid progenitors and is not evident in the CD34+ HSPCs. Detailed examination of this loop shows that a DNase I hypersensitivity site, also called 3'HS1, overlaps with a CTCF site that forms a loop with another CTCF site adjacent to OR52A5 gene (Figure 2). To investigate the role of this specific chromatin loop in the regulation of hemoglobin gene expression, we knock out the 3'HS1 CTCF motif in adult CD34+ HSPCs under erythroid differentiation medium by CRISPR/Cas9-mediated gene editing. We find that deletion of 3'HS1 CTCF results in a 2-fold decrease of β-globin (HBB) and a 4-fold increase of the fetal hemoglobin gene encoded by γ-globin (HBG1/2) in erythroid colonies of edited CD34+ cells (Figure 3). Elevation of fetal hemoglobin upon 3'HS1 CTCF deletion was also confirmed in human umbilical cord blood-derived erythroid progenitor-2 cells (HUDEP-2), which results in a 12-fold increase of γ-globin expression (Figure 4). These results suggest that the 3'HS1 CTCF plays a crucial role in regulating the expression of fetal hemoglobin gene, however it remains unclear whether changes in chromatin structure is responsible for these changes.

CTCF looping interactions have been described to form under convergent directionality. To validate the role of 3'HS1 CTCF in establishing chromatin interactions at the β-globin locus, we aim to invert this binding motif and evaluate how it disrupts chromatin organization and gene expression at this locus. Deciphering the underlying mechanisms will shed light on how three-dimensional chromatin structure is reorganized in differentiating erythroid cells as it undergoes nuclear condensation. Furthermore, elevation of fetal hemoglobin expression can potentially be a new therapeutic gene editing strategy to treat sickle cell disease and some cases of β-hemoglobinopathies.

Disclosures

No relevant conflicts of interest to declare.
Sensing of Liver Iron Content Requires Cell-Cell Communication between Hepatocytes and Liver Sinusoidal Endothelial Cells
Authors: Colucci Silvia , Altamura Sandro , Hentze Matthias , Muckenthaler Martina U.
Published: February 2020

The liver stores iron and senses systemic and tissue iron availability. Hepatocytes control iron homeostasis by producing the peptide hormone hepcidin that controls dietary iron absorption and iron release from intracellular stores. Recent data challenged the exclusive role of hepatocytes in controlling iron levels. Indeed, liver sinusoidal endothelial cells (LSECs) increase BMP2 and BMP6 levels in response to iron, which control hepcidin expression in a paracrine manner. However the molecular mechanism(s) of how BMPs respond to iron levels remain unknown. We established primary murine LSEC cultures and exposed these to iron sources. Unexpectedly, BMP2 mRNA expression is strongly reduced by iron treatment, while BMP6 levels are only mildly increased. This finding suggests that intracellular iron content cannot directly activate BMP2 transcription and only slightly contribute to BMP6 upregulation in LSEC cultures. However, if LSECs are co-cultured with iron-loaded primary hepatocytes the expression of BMP2 and BMP6 is increased and the fold induction of BMP6 is greater compared to LSECs cultured alone, suggesting that the iron status of hepatocytes instructs the LSEC BMP response. These data are supported by findings in a genetic mouse model of iron overload (Slc40a1C326S/C326S). Hepatocytes isolated from Slc40a1C326S/C326S mice display an iron-loaded molecular signature and the expected low mRNA expression of Transferrin Receptor 1 (Tfr1). By contrast, LSECs show high expression of Tfr1, indicating intracellular iron deficiency. Despite this, hepatic BMP levels are increased, suggesting that BMP2 and BMP6 expression are directly related to the intracellular iron content of hepatocytes but not LSECs. RNA-sequencing of isolated hepatic cell populations is ongoing to identify putative hepatocyte regulators involved in the iron-mediated BMP2 and BMP6 regulation.

Disclosures

Muckenthaler: Silence Therapeutics: Consultancy; Novartis: Research Funding.
Clonal Hematopoiesis in Donor-Recipient Pairs after Allogeneic Hematopoietic Cell Transplantation
Authors: Ueda Masumi , Beppu Lan , Campbell Judy , Flowers Mary E. D. , Radich Jerald P. , Storb Rainer
Published: February 2020

After allogeneic hematopoietic cell transplantation (HCT), a relatively small number of donor hematopoietic cells must reconstitute the entire recipient hematopoietic system, while the donor is left with a near normal pool of hematopoietic cells. We hypothesized that the increased replicative demand on donor cells in the recipient after allogeneic HCT will accelerate telomere shortening and magnify the genetic alterations that are associated with normal aging, including clonal hematopoiesis. We aimed to compare mutation frequency in genes associated with clonal hematopoiesis of indeterminant potential (CHIP) and myeloid diseases between donors and recipients, with a focus on transplant pairs with older donors.

We obtained contemporary blood samples from 10 related donor-recipient pairs surviving a median of 36.6 years (range 6.6-45.7 years) after HCT. Information on donor-recipient pairs is summarized in Table 1. Variant libraries were prepared from bulk peripheral blood mononuclear cells (PBMCs) using Archer Dx VariantPlex Myeloid panel of 75 myeloid disease-associated genes (ArcherDx, Boulder, CO). Sequencing was completed on the Illumina HiSeq system.

Variants with allelic frequency (AF) ≥2% were detected in donors (median number of variants 50.5, range 35-107) and recipients (median number of variants 50, range 32-109). In all pairs, there was significant overlap in the variants detected, although some were unique to donors or recipients (Figure 1). Two of the 3 donor-recipient pairs with >25 years difference in donor age (84 and 71 years) and recipient age (47 and 42 years) showed an increase in the shared variant AF in the recipient in DNMT3A (nonsense and frameshift mutations) of 5 to 18% and 5 to 16%, respectively. All other shared variants in CHIP-associated genes (DNMT3A, ASXL1, TET2) detected in 6 pairs did not show significant difference in AF (Table 2). Among other shared variants of non-CHIP genes, 7 pairs showed mutations with ≥5% difference in AF, but the difference was small (mean difference 5.3%, range 4.5-7.4%) (Table 3).

In conclusion, our results suggest that even decades after transplantation and high replicative demand, most donor variants, at the level of detection of this assay, do not preferentially expand in the recipient. Donor-recipient pairs with older donors and ~30-year difference in age with the recipient showed a modest expansion in DNMT3A clones. Future studies will compare contemporary samples to historical samples from the time of transplant.

Disclosures

Radich: Novartis: Other: RNA Sequencing; TwinStrand Biosciences: Research Funding.
Sickle Cell Disease Promotes Dysregulation of Hepatic Iron Homeostasis By Regulating Hepcidin Expression
Authors: Pradhan Tirthadipa , Sundd Prithu , Monga Satdarshan Pal , Gladwin Mark T , Kato Gregory J
Published: February 2020

Sickle cell disease (SCD) is an autosomal-recessive-genetic disorder that affects millions of people worldwide. Although hepatic crisis affects 10-40% of hospitalized SCD patients and can progress to fatal liver failure, the current treatment is primarily supportive and the molecular pathophysiology remains largely unknown. We found that transgenic, humanized SCD mice developed liver injury with age, manifested by increased inflammation, necrosis and hepatic iron accumulation. The presence of iron particles in SCD liver was confirmed by transmission electron micrograph (TEM) analysis and prussian blue staining which revealed increased iron accumulation in the central and midzonal region of the SCD liver tissue. An increase in aggregates of iron pigment reminiscent of hemosiderin-laden macrophages was also observed in SCD liver tissue. Interestingly, the SCD mice also showed significant enrichment of both hepatic (p=0.02) and serum iron (p=0.04) compared to control AS mice. We determined the expression level of genes commonly involved in iron homeostasis by RT-PCR. Interestingly, a significantly lower expression level of hepcidin transcripts was observed in the liver of SCD mice compared to control mice (AS) (p=0.01).

In order to define the pathways controlling hepcidin transcription in SCD, we performed an RNA-seq analysis in the liver of SCD mice. Remarkably, our data showed significant misexpression of hypoxia signaling pathways. Further analysis revealed a significant increase in hypoxia-inducible factor (HIF)-2α levels in the liver of SCD mice by western blot. Reduced levels of Hepcidin were also confirmed in serum samples from SCD patients compared to controls. Work is currently underway to understand how HIF2α might hypothetically regulate hepcidin expression in the liver. This is particularly relevant because HIF2a translation is known to be regulated by iron through an iron response element at the 5' end of its transcript.

In summary, our results reveal a significant defect in iron homeostasis in the liver of SCD mice, suggesting that impaired iron homeostasis may contribute to hepatobiliary injury in SCD independent of blood transfusions. Our study also highlights the importance of hepcidin as potential therapeutic target in regulation of hepatic injury in SCD.

Disclosures

Gladwin: Bayer Pharmaceuticals: Other: Co-investigator; United Therapeutics: Patents & Royalties: Co-inventor on an NIH government patent for the use of nitrite salts in cardiovascular diseases ; Globin Solutions, Inc: Patents & Royalties: Provisional patents for the use of recombinant neuroglobin and heme-based molecules as antidotes for CO poisoning. Kato:Novartis, Global Blood Therapeutics: Consultancy, Research Funding; Bayer: Research Funding.
A Highly Sensitive and Room Temperature CNTs/SnO2/CuO Sensor for H2S Gas Sensing Applications
Authors: Zhao Yang , Zhang Jijun , Wang Yan , Chen Zexiang
Published: February 2020

Gas sensors based on tin dioxide-carbon nanotube composite films were fabricated by a simple inexpensive sol-gel spin-coating method using PEG400 as a solvent. Nanostructured copper was coated on CNTs/SnO2 film, and then copper was transformed into copper oxide at 250 °C. Resistivity of the final composite films is highly sensitive to the presence of H2S, which became easily attached or detached at room temperature. The response and recovery time of the sensor are 4 min and 10 min, and the value of sensitivity is 4.41, respectively. Meanwhile, the CNTs/SnO2/CuO sensor also has low detection limit, high selectivity toward H2S, and stable performance with different concentrations of H2S.
Comparative milk proteome analysis of Kashmiri and Jersey cattle identifies differential expression of key proteins involved in immune system regulation and milk quality
Authors: Bhat Shakil A. , Ahmad Syed M. , Ibeagha-Awemu Eveline M. , Mobashir Mohammad , Dar Mashooq A. , Mumtaz Peerzada T. , Shah Riaz A. , Dar Tanveer A. , Shabir Nadeem , Bhat Hina F. , Ganai Nazir A.
Published: February 2020

Background

Exploration of the bioactive components of bovine milk has gained global interest due to their potential applications in human nutrition and health promotion. Despite advances in proteomics profiling, limited studies have been carried out to fully characterize the bovine milk proteome. This study explored the milk proteome of Jersey and Kashmiri cattle at day 90 of lactation using high-resolution mass spectrometry based quantitative proteomics nano-scale LC-MS/Q-TOF technique. Data are available via ProteomeXchange with identifier PXD017412.

Results

Proteins from whey were fractionated by precipitation into high and low abundant proteins. A total of 81 high-abundant and 99 low-abundant proteins were significantly differentially expressed between Kashmiri and Jersey cattle, clearly differentiating the two breeds at the proteome level. Among the top differentiating proteins, the Kashmiri cattle milk proteome was characterised by increased concentrations of immune-related proteins (apelin, acid glycoprotein, CD14 antigen), neonatal developmental protein (probetacellulin), xenobiotic metabolising enzyme (flavin monooxygenase 3 (FMO3), GLYCAM1 and HSP90AA1 (chaperone) while the Jersey milk proteome presented higher concentrations of enzyme modulators (SERPINA1, RAC1, serine peptidase inhibitor) and hydrolases (LTF, LPL, CYM, PNLIPRP2). Pathway analysis in Kashmiri cattle revealed enrichment of key pathways involved in the regulation of mammary gland development like Wnt signalling pathway, EGF receptor signalling pathway and FGF signalling pathway while a pathway (T-cell activation pathway) associated with immune system regulation was significantly enriched in Jersey cattle. Most importantly, the high-abundant FMO3 enzyme with an observed 17-fold higher expression in Kashmiri cattle milk seems to be a characteristic feature of the breed. The presence of this (FMO3) bioactive peptide/enzyme in Kashmiri cattle could be economically advantageous for milk products from Kashmiri cattle.

Conclusion

In conclusion, this is the first study to provide insights not only into the milk proteome differences between Kashmiri and Jersey cattle but also provides potential directions for application of specific milk proteins from Kashmiri cattle in special milk preparations like infant formula.
Tanshinone IIA prevents platelet activation and down-regulates CD36 and MKK4/JNK2 signaling pathway
Authors: Wang Hua , Zhong Lin , Mi Shaohua , Song Nianpeng , Zhang Wei , Zhong Ming
Published: February 2020

Background

Tanshinone IIA (TS IIA), a multi-pharmaceutical compound from traditional Chinese herb, is effective for treatment of atherothrombosis. However, the underlying mechanisms of TS IIA-mediated anti-platelet activation effect are still poorly understood. As shown in our previous study, platelet-derived microvesicles (PMVs) generated in response to oxidant insult could activate CD36/mitogen-activated protein kinase kinase 4/Jun N-terminal kinase 2 (CD36/MKK4/JNK2) signals and lead to platelet activation. The present study aims to investigate the effect of TS IIA on platelet activation and the possible mechanisms.

Methods

The production of PMVs induced by Interleukin 6 (IL-6) was detected by flow cytometry. We performed activating studies of platelets with PMVs derived from IL-6–treated platelets (IL-6–PMVs) in vitro. Sometimes, platelet suspensions were incubated with serial concentrations of TS IIA for 15 min before being stimulated with IL-6–PMVs. Expression of platelet integrin αIIbβ3 and CD36 was detected by flow cytometry. Phosphorylation of MKK4 and JNK were detected by immunoblotting.

Results

Here we demonstrated firstly that TS IIA could prevent platelet activation induced by PMVs and down-regulates CD36 and MKK4/JNK2 signaling pathway. CD36 may be the target of atherosclerosis (AS)-related thrombosis.

Conclusions

This study showed the possible mechanisms of TS IIA-mediated anti-platelet activation and may provide a new strategy for the treatment of AS-related thrombosis by targeting platelet CD36.
Severe pulmonary radiological manifestations are associated with a distinct biochemical profile in blood of tuberculosis patients with dysglycemia
Authors: Barreda Nadia Nilda , Arriaga Maria B. , Aliaga Juan Gonzalo , Lopez Kattya , Sanabria Oswaldo Martin , Carmo Thomas A. , Fróes Neto José F. , Lecca Leonid , Andrade Bruno B. , Calderon Roger I.
Published: February 2020

Background

Diabetes mellitus (DM) is thought to affect tuberculosis (TB) clinical presentation and treatment response. Whether DM impacts radiological manifestations of pulmonary TB is still not clear. This study investigated the impact of glycemic status on radiological manifestations of pulmonary TB cases and its relationship with concentration of biochemical parameters in peripheral blood.

Methods

A retrospective cross-sectional study used data from 132 microbiologically confirmed pulmonary TB patients from Lima, Peru, evaluated in a previous investigation performed between February and December 2017. Chest radiographs were analyzed by a radiologist and a pulmonologist. Radiographic lesions were identified as cavities, alveolar infiltrates and fibrous tracts. Hyperglycemia in TB patients was identified by use of fasting plasma glucose, HbA1c and oral glucose tolerance test. Clinical, biochemical and hematological parameters were also analyzed.

Results

TB patients with hyperglycemia presented more frequently with cavities, alveolar infiltrates and fibrous tracts than those with normoglycemia. Hierarchical clustering analysis indicated that patients with more diverse and higher number of lung lesions exhibited a distinct laboratorial profile characterized by heightened white blood cell counts and circulating levels of total cholesterol, triglycerides and transaminases and simultaneously low levels of albumin and hemoglobin. Multivariable regression analyses adjusted for age, sex, prior TB, hemoglobin levels and acid-fast bacilli ≥2+ in sputum smears, demonstrated that presence of prediabetes or diabetes in TB patients was associated with increased odds of having 3 pulmonary lesion types (p = 0.003 and p < 0.01 respectively) or ≥ 4 lesions (p = 0.001 and p = 0.01 respectively).

Conclusion

Hyperglycemia (both DM and prediabetes) significantly affected the presentation of radiographic manifestations and the number of lesions in pulmonary TB patients as well as the biochemical profile in peripheral blood.
Utility of anaerobic bottles for the diagnosis of bloodstream infections
Authors: Lafaurie M. , d’Anglejan E. , Donay J. L. , Glotz D. , Sarfati E. , Mimoun M. , Legrand M. , Oksenhendler E. , Bagot M. , Valade S. , Bercot B. , Molina J. M.
Published: February 2020

Background

Obligate anaerobes usually account for less than 10% of bacteria recovered from blood cultures (BC). The relevance of routine use of the anaerobic bottle is under debate. The aim of this study was to evaluate the utility of anaerobic bottles for the diagnosis of bloodstream infections (BSI).

Methods

We conducted a 6-month, retrospective, monocentric study in a tertiary hospital. All positive BC were grouped into a single episode of bacteremia when drawn within 7 consecutive days. Bacteremia were classified into contaminants and BSI. Charts of patients with BSI due to obligate anaerobes were studied.

Results

A total of 19,739 blood cultures were collected, 2341 of which (11.9%) were positive. Anaerobic bottles were positive in 1528 (65.3%) of all positive BC but were positive alone (aerobic bottles negative) in 369 (15.8%). Overall 1081 episodes of bacteremia were identified, of which 209 (19.3%) had positive anaerobic bottles alone. The majority 126/209 (60.3%) were contaminants and 83 (39.7%) were BSI. BSI due to facultative anaerobes, obligate aerobes and obligate anaerobes were identified in 67 (80.7%), 3 (3.6%) and 13 (15.7%) of these 83 episodes, respectively. BSI due to obligate anaerobic bacteria were reported in 9 patients with gastro-intestinal disease, in 3 with febrile neutropenia and in 1 burned patient.

Conclusions

Anaerobic bottles contributed to the diagnosis of a significant number of episodes of bacteremia. Isolated bacteria were mostly contaminants and non-obligate anaerobic pathogens. Rare BSI due to obligate anaerobes were reported mainly in patients with gastro-intestinal disorders and during febrile neutropenia.
Albumin-globulin ratio and mortality in patients on peritoneal dialysis: a retrospective study
Authors: Peng Fenfen , Sun Lingzhi , Chen Ting , Zhu Yan , Zhou Weidong , Li Peilin , Chen Yihua , Zhuang Yiyi , Huang Qianyin , Long Haibo
Published: February 2020

Background

Albumin-globulin ratio (AGR), a variable based on serum albumin and non-albumin proteins, has been demonstrated as a predictor of mortality in patients with malignant neoplasm. The aim of this study was to evaluate the prognostic value of AGR on peritoneal dialysis (PD) patients.

Methods

We retrospectively analyzed 602 incident PD patients from January 1st, 2008, to December 31st, 2017, at our center and followed them until December 31st, 2018. Kaplan-Meier curves and multivariate Cox regression models were applied to analyze the association between AGR and all-cause of mortality and cardiovascular mortality.

Results

The median follow-up time was 32.17 (interquartile range = 32.80) months. During follow-up, 131 (21.8%) patients died, including 57 patients (43.5%) who died due to cardiovascular diseases. Kaplan-Meier curves showed that patients with AGR > 1.26 had better rates of survival than those with AGR ≤ 1.25 (p < 0.001). After adjusting for potential confounders, the lower AGR level was significantly associated with an increased all-cause and cardiovascular mortality [hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.07–2.32,p = 0.022 and HR: 2.01, 95% CI: 1.10–3.69,p = 0.023 respectively].

Conclusions

Patients with a low AGR level had an increased all-cause and cardiovascular mortality. AGR may be a useful index in identifying patients on PD at risk for CVD and all-cause of mortality.
Study design of a stepped wedge cluster randomized controlled trial to evaluate the effect of a locally tailored approach for preconception care – the APROPOS-II study
Authors: Maas Veronique Y. F. , Koster Maria P. H. , Ista Erwin , Vanden Auweele Kim L. H. , de Bie Renate W. A. , de Smit Denhard J. , Visser Bianca C. , van Vliet-Lachotzki Elsbeth H. , Franx Arie , Poels Marjolein
Published: February 2020

Background

In a previous feasibility study (APROPOS) in a single municipality of the Netherlands, we showed that a locally tailored preconception care (PCC) approach has the potential to positively affect preconceptional lifestyle behaviours. Therefore, we designed a second study (APROPOS-II) to obtain a more robust body of evidence: a larger group of respondents, more municipalities, randomization, and a more comprehensive set of (clinical) outcomes. The aim of this study is to assess the effectiveness and the implementation process of a local PCC-approach on preconceptional lifestyle behaviours, health outcomes and the reach of PCC among prospective parents and healthcare providers.

Methods

This study is an effectiveness-implementation hybrid type 2 trial. This involves a stepped-wedge cluster randomized controlled trial design aiming to include over 2000 future parents from six municipalities in the Netherlands. The intervention has a dual-track approach, focusing on both the uptake of PCC among future parents and the provision of PCC by healthcare providers. The PCC-approach consists of 1) a social marketing strategy directed towards prospective parent(s) and 2) a local care pathway to improve interdisciplinary collaboration. Data will be collected before and after the introduction of the intervention through questionnaires and medical records in each of the participating municipalities. The primary outcome of this study is change in lifestyle behaviours (e.g. folic acid use, smoking and alcohol use). Secondary outcomes are pregnancy outcomes (e.g. miscarriage, preterm birth, gestational diabetes) and the uptake of PCC. Moreover, a process evaluation will be performed, providing information on the efficacy, feasibility, barriers and facilitators regarding the implementation of the intervention.

Discussion

The APROPOS-II study introduces a locally tailored PCC-approach in six municipalities in the Netherlands that will contribute to the body of evidence regarding the effectiveness of PCC and its implementation. If this intervention has a positive effect on lifestyle behaviour changes, leading to improved pregnancy outcomes and the future health of prospective parents and their offspring, it could subsequently be upscaled to (inter)national implementation.

Trial registration

Dutch Trial register: NL7784 (Registered June 6th, 2019).
Debate: Why should gender-affirming health care be included in health science curricula?
Authors: de Vries Elma , Kathard Harsha , Müller Alex
Published: February 2020

Background

Every person who seeks health care should be affirmed, respected, understood, and not judged. However, trans and gender diverse people have experienced significant marginalization and discrimination in health care settings. Health professionals are generally not adequately prepared by current curricula to provide appropriate healthcare to trans and gender diverse people. This strongly implies that health care students would benefit from curricula which facilitate learning about gender-affirming health care.

Main body

Trans and gender diverse people have been pathologized by the medical profession, through classifications of mental illness in the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Classification of Disease (ICD). Although this is changing in the new ICD-11, tension remains between depathologization discourses and access to gender-affirming health care.

Trans and gender diverse people experience significant health disparities and an increased burden of disease, specifically in the areas of mental health, Human Immunodeficiency Virus, violence and victimisation. Many of these health disparities originate from discrimination and systemic biases that decrease access to care, as well as from health professional ignorance.

This paper will outline gaps in health science curricula that have been described in different contexts, and specific educational interventions that have attempted to improve awareness, knowledge and skills related to gender-affirming health care. The education of primary care providers is critical, as in much of the world, specialist services for gender-affirming health care are not widely available. The ethics of the gatekeeping model, where service providers decide who can access care, will be discussed and contrasted with the informed-consent model that ﻿upholds autonomy by empowering patients to make their own health care decisions.

Conclusion

There is an ethical imperative for health professionals to reduce health care disparities of trans and gender diverse people and practice within the health care values of social justice and cultural humility. As health science educators, we have an ethical duty to include gender-affirming health in health science curricula in order to prevent harm to the trans and gender diverse patients that our students will provide care for in the future.
Direct medical costs of end-stage kidney disease and renal replacement therapy: a cohort study in Guangzhou City, southern China
Authors: Zhang Hui , Zhang Chao , Zhu Sufen , Ye Hongjian , Zhang Donglan
Published: February 2020

Background

Renal replacement therapy was a lifesaving yet high-cost treatment for people with end-stage kidney disease (ESKD). This study aimed to estimate the direct medical costs per capita of ESKD by different treatment strategies: haemodialysis (HD); peritoneal dialysis (PD); kidney transplantation (KT) (in the first year); KT (in the second year), and by two urban health insurance schemes.

Methods

This was a retrospective observational cohort study. Data were obtained from outpatient and inpatient claims database of two urban health insurance from Guangzhou City, Southern China. Adult patients with HD (n = 3765; mean age 58 years), PD (n = 1237; 51 years), KT (first year) (n = 117; 37 years) and KT (second year) (n = 41; 39 years) were identified between 2010 and 2012. The primary outcome was the annual per patient medical costs in 2013 Chinese Yuan (CNY) incurred in the outpatient and inpatient sectors. Secondary outcomes were annual outpatient visits and inpatient admissions, length of stay per admission. Generalized linear regression and bootstrapping statistical methods were used for analysis.

Results

The estimated average annual medical costs for patients on HD were CNY 94,760.5 (US$15,066.0), 95% Confidence Interval (CI): CNY85,166.6–106,972.2, which was higher than those for patients on PD [CNY80,762.9 (US$12,840.5), 95% CI: CNY 76,249.8-85,498.9]. The estimated annual cost ratio of HD versus PD was 1.17 (95% CI: 1.12–1.25). Among the transplanted patients, the estimated average annual medical costs in the first year were CNY132,253.0 (US$21,026.9), 95%CI: CNY114,009.9–153,858.6, and in the second year were CNY93,155.3 (US$14,810.8), 95%CI: CNY61,120.6–101,989.1. The mean annual medical costs for dialysis patients under Urban Employee-based Basic Medical Insurance scheme were significantly higher than those for patients under Urban Resident-based Basic Medical Insurance scheme (P < 0.001).

Conclusions

The direct medical costs of ESKD patients were high and different by types of renal replacement therapy and insurance. The findings can be used to conduct cost-effectiveness research on different types of RRT for ESKD patients that provides economic evidence for health policy design in China.
Improving medicines management for people with dementia in primary care: a qualitative study of healthcare professionals to develop a theory-informed intervention
Authors: Barry Heather E. , Bedford Laura E. , McGrattan Máiréad , Ryan Cristín , Passmore A. Peter , Robinson A. Louise , Molloy Gerard J. , Darcy Carmel M. , Buchanan Hilary , Hughes Carmel M.
Published: February 2020

Background

People with dementia (PwD) face unique challenges with medicines management, yet little is known about these challenges from the perspectives of primary healthcare professionals, particularly general practitioners (GPs) and community pharmacists. Few medicines management interventions have been developed which are aimed at community-dwelling PwD. This study sought to develop an intervention to improve medicines management for PwD in primary care using a theory-informed approach.

Methods

Semi-structured interviews were conducted with GPs (n = 15) and community pharmacists (n = 15) to explore participants’ views and experiences of medicines management for PwD, and their perceptions of barriers and facilitators to successful medicines management for PwD. The 14-domain Theoretical Domains Framework was the underpinning theoretical guide, allowing key theoretical domains to be identified and mapped to behaviour change techniques (BCTs) which are considered the ‘active ingredients’ of an intervention. Draft interventions were developed to operationalise selected BCTs and were presented to GPs and community pharmacists during task groups. Final selection of an intervention for feasibility testing was guided by feedback provided during these task groups and through application of the APEASE (Affordability, Practicability, Effectiveness/cost-effectiveness, Acceptability, Side-effects/safety, Equity) criteria.

Results

Participants expressed a number of concerns about medicines management for PwD, particularly monitoring adherence to medication regimens and conducting medication review. Two draft interventions comprising selected BCTs (‘Modelling or demonstration of behaviour’; ‘Salience of consequences’; ‘Health consequences’; ‘Social and environmental consequences’; ‘Action planning’; Social support or encouragement’, ‘Self-monitoring of behaviour’) were developed, each targeting GPs and community pharmacists. Following the task groups and discussions within the research team, the community pharmacy-based intervention was selected for future feasibility testing. The intervention will target community pharmacists to conduct a medication review (incorporating an adherence check) with a PwD, delivered as an online video demonstrating key behaviours. The video will include feedback emphasising positive outcomes of performing the behaviours. Action planning and a quick reference guide will be used as complementary intervention components.

Conclusions

A community pharmacist-based intervention has been developed targeting medicines management for PwD in primary care using a systematic, theory-informed approach. Future work will determine the usability and acceptability of implementing this intervention in clinical practice.
A cluster-randomized field trial to reduce cesarean section rates with a multifaceted intervention in Shanghai, China
Authors: Zhang Lulu , Zhang Lin , Li Meng , Xi Jie , Zhang Xiaohua , Meng Zhenni , Wang Ying , Li Huaping , Liu Xiaohua , Ju Feihua , Lu Yuping , Tang Huijun , Qin Xianju , Ming Yanhong , Huang Rong , Li Guohong , Dai Hongying , Zhang Rong , Qin Min , Zhu Liping , Zhang Jun
Published: February 2020

Background

Cesarean section (CS) rate has risen dramatically and stayed at a very high level in China over the past two to three decades. Given the short- and long-term adverse effects of CS, effective strategies are needed to reduce unnecessary CS. We aimed to evaluate whether a multifaceted intervention would decrease the CS rate in China.

Methods

We carried out a cluster-randomized field trial with a multifaceted intervention in Shanghai, China, from 2015 to 2017. A total of 20 hospitals were randomly allocated into an intervention or a control group. The intervention consisted of more targeted health education to pregnant women, improved hospital CS policy, and training of midwives/doulas for 8 months. The study included a baseline survey, the intervention, and an evaluation survey. The primary outcome was the changes of overall CS rate from the pre-intervention to the post-intervention period. A subgroup analysis stratified by the Robson classification was also conducted to examine the CS change among women with various obstetric characteristics.

Results

A total of 10,752 deliveries were randomly selected from the pre-intervention period and 10,521 from the post-intervention period. The baseline CS rates were 42.5% and 41.5% in the intervention and control groups, respectively, while the post-intervention CS rates were 43.4% and 42.4%, respectively. Compared with the control group, the intervention did not significantly reduce the CS rate (adjusted OR = 0.92; 95% CI 0.73, 1.15). Similar results were obtained in subgroup analyses stratified by the risk level of pregnancy, maternal age, number of previous CS, or parity. Scarred uterus and maternal request remained the primary reasons for CS after the interventions in both groups. The intervention did not alter the perinatal outcomes (adjusted change of risk score = − 0.06; 95%CI − 0.43, 0.31).

Conclusions

A multifaceted intervention including more targeted prenatal health education, improved hospital CS policy, and training of midwives/doulas, did not significantly reduce the CS rate in Shanghai, China. However, our experience in implementing a multifaceted intervention may provide useful information to other similar areas with high CS use.

Trial registration

This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) (ChiCTR-IOR-16009041) on 17 August 2016.
Health-related quality of life and extent of self-care practice among heart failure patients in Ethiopia
Authors: Seid Mohammed Assen
Published: February 2020

Background

Heart Failure (HF) results in an immense impact on the patients’ Health-related quality of life (HRQOL). Heart failure patients HRQOL is dependent on the patients’ level of engagement in self-care behaviors. Therefore this study aimed to determine HF patients’ health-related quality of life and its relationship with self-care behaviors.

Methods

An institutional-based study was conducted on 284 heart failure patients at the University of Gondar referral hospital. The data were collected using a structured questionnaire-based interview. The data were analyzed using SPSS version 20. Both descriptive and analytical statistical tests were utilized. A multinomial logistic regression analysis was done to determine the association between HRQOL and different independent variables. Variables with a p-value< 0.05 were considered as a significant predictor of the outcome variable.

Results

The finding of this study showed that more than sixty-six percent of the study population were females. The overall mean score of HF patients’ quality of life was 46.4 ± 22.4 and the physical and emotional subscale mean score was 20.2 ± 9.8 and 10.5 ± 6.8 respectively. The majority of the study participants 147(51.8%) had poor quality of life. The multinomial logistic regression analysis result showed that rural residence (odds ratio 2.41, 95% CI, 1.23 to 4.71) and inadequate level of self-care practice (odds ratio 2.61, 95% CI, 1.43 to 4.78) were independent predictors of poor HRQOL. The correlation analysis also showed that there was a significant negative relationship between HF patients’ HRQOL score and Self-care practice score (r = − 0.127, P = 0.032).

Conclusion

Overall, the majority of HF patients had poor HRQOL. Heart failure patients’ HRQOL was significantly associated with place of residence and patients’ level of self-care practice. Therefore, patients with HF are required to learn the benefit of self-care behaviors to improve their quality of life and to decrease the disease progression. Furthermore, HF patients who come from rural areas need special emphasis in each follow-up evaluation.
Patterns and predictors of exercise behavior during 24 months of follow-up after a supervised exercise program during breast cancer chemotherapy
Authors: An Ki-Yong , Kang Dong-Woo , Morielli Andria R. , Friedenreich Christine M. , Reid Robert D. , McKenzie Donald C. , Gelmon Karen , Mackey John R. , Courneya Kerry S.
Published: February 2020

Background

Understanding the longer-term exercise behavior of patients with breast cancer after chemotherapy is important to promote sustained exercise. The purpose of the current study was to report the longer-term patterns and predictors of exercise behavior in patients with breast cancer who exercised during chemotherapy.

Methods

In the Combined Aerobic and Resistance Exercise (CARE) Trial, 301 patients with breast cancer were randomized to three different exercise prescriptions during chemotherapy. Exercise behaviors after chemotherapy were self-reported at 6-, 12-, and 24-month follow-up. Exercise patterns were identified by categorizing patients according to which exercise guideline they were meeting (neither, aerobic only, resistance only, or combined) at each of the three follow-up timepoints (64 possible patterns). Predictors of longer-term exercise behavior included physical fitness, patient-reported outcomes, and motivational variables from the theory of planned behavior assessed at postintervention (postchemotherapy). Univariate and multivariate stepwise multinomial logistic regression and linear regression were used for statistical analyses.

Results

A total of 264 (88%) participants completed all three follow-up exercise behavior assessments and exhibited 50 different exercise patterns. Postintervention aerobic fitness was the most consistent predictor of longer-term exercise behavior at all three timepoints. For example, higher aerobic fitness (per 1 ml/kg/min) predicted better adherence to the “aerobic only” (OR = 1.09; p = 0.005) and “combined” (OR = 1.12; p < 0.001) guidelines compared to “neither” guideline at 6-month follow-up. Additionally, higher postintervention muscular strength (per 1 kg) was associated with better adherence to the “resistance only” (OR = 1.07; p = 0.025) and “combined” (OR = 1.08; p < 0.001) guidelines compared to “neither” guideline at 24-month follow-up. Finally, lower perceived difficulty (per 1 scale point) was associated with better adherence to the “combined” (OR = 0.62; p = 0.010) and “aerobic only” (OR = 0.58; p = 0.002) guideline compared to the “neither” guideline at the 24-month follow-up.

Conclusions

Our study is the first to show that the longer-term exercise patterns of patients with breast cancer who exercised during chemotherapy are diverse and predicted by physical fitness and motivational variables after chemotherapy. Our novel implications are that improving physical fitness during chemotherapy and applying motivational counseling after chemotherapy may improve longer-term exercise behavior in patients with breast cancer.

Trial registration

(NCT00249015).
Concerns and educational needs of Iranian parents regarding the sexual health of their male adolescents: a qualitative study
Authors: Babayanzad Ahari Shahnaz , Behboodi Moghadam Zahra , Azin Seyed Ali , Maasoumi Raziyeh
Published: February 2020

Background

Parents play an important role in promoting the sexual health of their adolescents. However, many parents experience several challenges. The purpose of this study was to explore the concerns and educational needs of Iranian parents regarding the sexual health of their male adolescents.

Methods

This qualitative study was designed based on the conventional content analysis approach. Semi-structured and in-depth interviews were conducted with 16 parents of male adolescents aged 12–18 years. All interviews were audio recorded and transcribed verbatim. The data were collected through purposeful sampling and continued until data saturation. Finally, the Graneheim and Landman strategies were used to analyze data.

Results

According to the participants’ comments, four main categories were extracted as follows: fear of emotional and sexual harms, quality of parent-child relationships, effect of media and cyberspace, and necessity of sexuality health education.

Conclusions

The findings highlighted the need for sexuality health education through cooperation with schools for offering appropriate education to the students, parents, and school staffs.

The results showed that parents required training to enhance their knowledge and skills to improve their communication with their adolescents about sexuality issues. Therefore, it is necessary to design, implement, and evaluate culture-appropriate educational programs to address the parents’ concerns regarding adolescents’ sexual health.
Should compression bandage be performed after total knee arthroplasty? A meta-analysis of randomized controlled trials
Authors: Liu Pei , Mu Xiaohong , Zhang Qidong , Liu Zhaohui , Wang Weiguo , Guo Wanshou
Published: February 2020

Background

Compression bandage often is used after total knee arthroplasty (TKA) to alleviate pain, ameliorate swelling, and reduce bleeding. However, there is controversy about its application due to conflicting clinical outcomes and potential compression-related complications. This meta-analysis aimed to answer the question of if compression bandage should be implemented routinely after TKA.

Methods

Relevant randomized controlled trials (RCTs) on compression bandage were comprehensively retrieved utilizing search engines such as PubMed, EMBASE, Web of Science, and the Cochrane Library, up to September 2019. Studies included in the meta-analysis were those that compared post-operative pain score, swelling, total blood loss, pre- and post-operative hematocrit levels differences, range of motion (ROM), and complications, using Review Manager 5.3.0.

Results

Included were seven RCTs, which reported on 511 knees. The pooled results showed the compression bandage group was associated with a greater post-operative pain score during ambulation at 48 h (WMD = 0.70, 95% CI 0.07 to 1.34, P = 0.03), compared with the non-compression bandage group. No statistically significant differences were found between the groups in post-operative pain scores at the other times, swelling, blood loss, ROM, or other complications (P > 0.05).

Conclusions

The current evidence is unable to conclude that compression bandage is necessary after primary TKA. Surgeons routinely undertaking compression bandage should deliberate whether there is enough clinical evidence.
Efficacy of the treatment with dapagliflozin and metformin compared to metformin monotherapy for weight loss in patients with class III obesity: a randomized controlled trial
Authors: Ferreira-Hermosillo Aldo , Molina-Ayala Mario Antonio , Molina-Guerrero Diana , Garrido-Mendoza Ana Pamela , Ramírez-Rentería Claudia , Mendoza-Zubieta Victoria , Espinosa Etual , Mercado Moisés
Published: February 2020

Background

Mexico has one of the highest prevalence rates of obesity worldwide. New pharmacological strategies that focus on people with class III obesity are required. Metformin and dapagliflozin are two drugs approved for the treatment of diabetes. Beyond its effects on glucose, metformin has been suggested by some studies to result in weight loss. Therapy with dapagliflozin is associated with a mild but sustained weight loss in patients with diabetes.

The primary outcome of the study is to determine if the combined treatment with dapagliflozin and metformin is more effective than monotherapy with metformin for weight loss in patients with class III obesity and prediabetes or diabetes who are awaiting bariatric surgery (including those patients who do have surgery). We also aimed to assess the effect of this combined treatment on waist circumference, triglycerides, blood pressure, and inflammatory cytokines.

Methods

This randomized phase IV clinical trial will include patients with diabetes or prediabetes who are between the ages of 18 and 60 years and exhibit grade III obesity (defined as body mass index ≥ 40 kg/m2). Patients using insulin will be excluded. Subjects will be randomized to one of two groups as follows: 1) metformin tablets 850 mg PO bid or 2) metformin tablets 850 mg PO bid plus dapagliflozin tablets 10 mg PO qd. The sample size required is 108 patients, which allows for a 20% dropout rate: 54 patients in the metformin group and 54 in the metformin/dapagliflozin group. All participants will receive personalized nutritional advice during the study. A run-in period of one month will be used to assess tolerance and adherence to treatment regimens. Anthropometric and biochemical variables will be recorded at baseline and at 1, 3, 6, and 12 months. A serum sample to determine glucagon, ghrelin, adiponectin, resistin, interleukin 6, and interleukin 10 will be collected at baseline and before surgery, or at 12 months (whatever happens first).

Adherence to treatment and adverse and secondary events will be recorded throughout the study. An intention-to-treat analysis will be used.

Discussion

Forty-six percent of the patients in our Obesity Clinic have been diagnosed with prediabetes (32%) or diabetes (14%). The use of dapagliflozin in this population could improve weight loss and other cardiovascular factors. This effect could be translated into less time before undergoing bariatric surgery and better control of associated comorbidities.

Trial registration

Clinicaltrials.gov, ID: NCT03968224. Retrospectively registered on May 29, 2019.