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Abstract Next-generation humanised mouse models and single-cell RNA sequencing (scRNAseq) approaches enable in-depth studies into human immune cell biology. Here we used NSG-SGM3 mice engrafted with human umbilical cord haematopoietic stem cells to investigate how human immune cells respond to and/or are changed by traumatic spinal cord injury (SCI). We hypothesised that the use of such mice could help advance our understanding of spinal cord injury-induced immune depression syndrome (SCI-IDS), and also how human leukocytes change as they migrate from the circulation into the lesion site. Our scRNAseq experiments, supplemented by flow cytometry, demonstrate the existence of up to 11 human immune cell (sub-) types and/or states across the blood and injured spinal cord (7 days post-SCI) of humanised NSG-SGM3 mice. Further comparisons of human immune cell transcriptomes between naïve, sham-operated and SCI mice identified a total of 579 differentially expressed genes, 190 of which were ‘SCI-specific’ (that is, genes regulated only in response to SCI but not sham surgery). Gene ontology analysis showed a prominent downregulation of immune cell function under SCI conditions, including for T cell receptor signalling and antigen presentation, confirming the presence of SCI-IDS and the transcriptional signature of human leukocytes in association with this phenomenon. We also highlight the activating influence of the local spinal cord lesion microenvironment by comparing the transcriptomes of circulating versus infiltrated human immune cells; those isolated from the lesion site were enriched for genes relating to both immune cell activity and function (e.g., oxidative phosphorylation, T cell proliferation and antigen presentation). We lastly applied an integrated bioinformatics approach to determine where immune responses in humanised NSG-SGM3 mice appear congruent to the native responses of human SCI patients, and where they diverge. Collectively, our study provides a valuable resource and methodological framework for the use of these mice in translational research.

Abstract Background Although mesenchymal stem cells (MSCs) have been proven to be appropriate candidates for the treatment of AKI-CKD, their efficacy is limited and variable. Astilbin (AST) had a protective effect on MSCs from oxidative stress via ROS-scavenging, however, whether it can improve MSCs’ renoprotection and the underlying mechanism need to be elucidated. Methods AST-pretreated MSCs were administered intravenously into the ischemia–reperfusion injury mice models and the renal function, pathological changes and inflammation. Were evaluated. In addition, DARTS, molecular docking, surface plasma resonance(SPR), dual-luciferase reporter gene assay and the ChIP-PCR were utilized to explore the potential signaling pathways through which AST exert renal protective effects on MSCs. Results AST-pretreated MSCs markedly improved kidney function, reduced kidney pathological injury and inflammation in AKI and AKI-CKD mice. RNA-seq results showed that PTGS2 related pathway was significantly up-regulated in MSCs after AST pretreatment. DARTS assay, molecular docking and SPR assay revealed that AST could bind with the transcriptional factor of Kruppel-Like Factor 4(KLF4) protein. The promoter of PTGS2 had the binding and transcriptional activation by KLF4. Furthermore, AST pretreatment promoted the secretion of PGE2 in MSCs. And then the westren blot results showed that the protein levels of CD163 and CD206 were upregulated after coculture in AST-pretreated MSCs, indicating that the polarization of RAW264.7 cells towards M2-like macrophages was induced. Knockdown of PTGS2 reversed the ability of AST-pretreated MSCs in converting macrophages to M2 phenotype and reducing their therapeutic effects on AKI-CKD mice. Conclusion AST pretreatment enhances the efficacy of MSCs on AKI and AKI-CKD mice by inducing of M2-like phenotype polarization in macrophages through the PTGS2-mediated pathway. This approach not only provides a novel strategy to strengthen the capability of MSCs but also helps elucidate the beneficial effects of the Chinese herbal medicine AST.

Abstract Background Although electronic alerts are being increasingly implemented in patients with acute kidney injury (AKI), their effect remains unclear. Therefore, we conducted this meta-analysis aiming at investigating their impact on the care and outcomes of AKI patients. Methods PubMed, Embase, Cochrane Library, and Clinical Trial Registries databases were systematically searched for relevant studies from inception to March 2024. Randomized controlled trials comparing electronic alerts with usual care in patients with AKI were selected. Results Six studies including 40,146 patients met the inclusion criteria. The pooled results showed that electronic alerts did not improve mortality rates (relative risk (RR) = 1.02, 95% confidence interval (CI) = 0.97–1.08, P = 0.44) or reduce creatinine levels (mean difference (MD) = − 0.21, 95% CI = − 1.60–1.18, P = 0.77) and AKI progression (RR = 0.97, 95% CI = 0.90–1.04, P = 0.40). Instead, electronic alerts increased the odds of dialysis and AKI documentation (RR = 1.14, 95% CI = 1.05–1.25, P = 0.002; RR = 1.21, 95% CI = 1.01–1.44, P = 0.04, respectively), but the trial sequential analysis (TSA) could not confirm these results. No differences were observed in other care-centered outcomes including renal consults and investigations between the alert and usual care groups. Conclusions Electronic alerts increased the incidence of AKI and dialysis in AKI patients, which likely reflected improved recognition and early intervention. However, these changes did not improve the survival or kidney function of AKI patients. The findings warrant further research to comprehensively evaluate the impact of electronic alerts.

Abstract Background High-density lipoprotein cholesterol (HDL-C) is widely recognized for its protective effects against cognitive decline. However, recent studies have presented conflicting results, with some suggesting no significant cognitive benefits or even an increased risk of dementia associated with high HDL-C levels. For those who suffer from depression, the cognitive benefits of HDL-C may be diminished or reversed. The purpose of this study is to investigate the associations between HDL-C, cognitive ability, and depressive symptoms in middle-aged and older Chinese adults. Methods The datasets utilized were sourced from the China Health and Retirement Longitudinal Study (CHARLS) for the years 2011 and 2015, comprising 4,302 participants. Cross-lagged models were employed to explore the temporal sequence between cognitive performance and HDL-C levels, and to examine the interplay among depression, cognition, and HDL-C. Confounding factors such as sociodemographic characteristics, sleep conditions, and history of chronic diseases were controlled for. Results The analysis revealed unidirectional effects of baseline impaired cognition and greater severity of depression on increased HDL-C levels at follow-up (β = − 0.036 and β = 0.028, respectively, P 0.05). Depressive symptoms and cognition were found to have a significant bidirectional association (β = − 0.026 and β = − 0.053, respectively, P

Abstract Objective To evaluate the efficacy and safety of hydroxychloroquine sulfate (HCQ) in the treatment of low risk phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN). Methods A total of 110 patients with low risk PLA2R-associated MN were included in the study. Patients who met the inclusion and exclusion criteria were assigned randomly to two groups: the HCQ treatment group and the control group. The control group received standard supportive treatment according to the guidelines, while the HCQ treatment group received HCQ in addition to the supportive treatment. The clinical data of the patients were analyzed, with comparisons made at baseline and during the six-month follow-up period. Any adverse reactions were recorded. Results The baseline data were comparable between the HCQ treatment group and the control group. At the end of the six-month follow-up period, the reductions in urine protein excretion and serum PLA2R antibody titer were more notable in the HCQ treatment group than those in the control group, with these differences being statistically significant (p

Abstract The whole-cell inorganic-biohybrid systems show special functions and wide potential in biomedical application owing to the exceptional interactions between microbes and inorganic materials. However, the hybrid systems are still in stage of proof of concept. Here, we report a whole-cell inorganic-biohybrid system composed of Spirulina platensis and gold nanoclusters (SP-Au), which can enhance the cancer radiotherapy through multiple pathways, including cascade photocatalysis. Such systems can first produce oxygen under light irradiation, then convert some of the oxygen to superoxide anion (•O2 −), and further oxidize the glutathione (GSH) in tumor cells. With the combination of hypoxic regulation, •O2 − production, GSH oxidation, and the radiotherapy sensitization of gold nanoclusters, the final radiation is effectively enhanced, which show the best antitumor efficacy than other groups in both 4T1 and A549 tumor models. Moreover, in vivo distribution experiments show that the SP-Au can accumulate in the tumor and be rapidly metabolized through biodegradation, further indicating its application potential as a new multiway enhanced radiotherapy sensitizer.

Abstract A promising new therapy option for acute kidney injury (AKI) is mesenchymal stem cells (MSCs). However, there are several limitations to the use of MSCs, such as low rates of survival, limited homing capacity, and unclear differentiation. In search of better therapeutic strategies, we explored all-trans retinoic acid (ATRA) pretreatment of MSCs to observe whether it could improve the therapeutic efficacy of AKI. We established a renal ischemia/reperfusion injury model and treated mice with ATRA-pretreated MSCs via tail vein injection. We found that AKI mice treated with ATRA-MSCs significantly improved renal function compared with DMSO-MSCs treatment. RNA sequencing screened that hyaluronic acid (HA) production from MSCs promoted by ATRA. Further validation by chromatin immunoprecipitation experiments verified that retinoic acid receptor RARα/RXRγ was a potential transcription factor for hyaluronic acid synthase 2. Additionally, an in vitro hypoxia/reoxygenation model was established using human proximal tubular epithelial cells (HK-2). After co-culturing HK-2 cells with ATRA-pretreated MSCs, we observed that HA binds to cluster determinant 44 (CD44) and activates the PI3K/AKT pathway, which enhances the anti-inflammatory, anti-apoptotic, and proliferative repair effects of MSCs in AKI. Inhibition of the HA/CD44 axis effectively reverses the renal repair effect of ATRA-pretreated MSCs. Taken together, our study suggests that ATRA pretreatment promotes HA production by MSCs and activates the PI3K/AKT pathway in renal tubular epithelial cells, thereby enhancing the efficacy of MSCs against AKI.

Abstract The 5′-HOXD genes are important for chondrogenesis in vertebrates, but their roles in osteoarthritis (OA) are still ambiguous. In our study, 5′-HOXD genes involvement contributing to cartilage degradation and OA was investigated. In bioinformatics analysis of 5′-HOXD genes, we obtained the GSE169077 data set related to OA in the GEO and analyzed DEGs using the GEO2R tool attached to the GEO. Then, we screened the mRNA levels of 5′-HOXD genes by quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR). We discovered that OA chondrocyte proliferation was inhibited, and apoptosis was increased. Moreover, it was discovered that SOX9 and COL2A1 were downregulated at mRNA and protein levels, while matrix metalloproteinases (MMPs) and a disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTSs) were upregulated. According to the results of differentially expressed genes (DEGs) and qRT-PCR, we evaluated the protein level of HOXD11 and found that the expression of HOXD11 was downregulated, reversed to MMPs and ADAMTSs but consistent with the cartilage-specific factors, SOX9 and COL2A1. In the lentivirus transfection experiments, HOXD11 overexpression reversed the effects in OA chondrocytes. In human OA articular cartilage, aberrant subchondral bone was formed in hematoxylin–eosin (H&E) and Safranin O and fast green (SOFG) staining results. Furthermore, according to immunohistochemistry findings, SOX9 and HOXD11 expression was inhibited. The results of this study established that HOXD11 was downregulated in OA cartilage and that overexpression of HOXD11 could prevent cartilage degradation in OA.

Abstract Background Pericyte-myofibroblast transition (PMT) has been confirmed to contribute to renal fibrosis in several kidney diseases, and transforming growth factor-β1 (TGF-β1) is a well-known cytokine that drives PMT. However, the underlying mechanism has not been fully established, and little is known about the associated metabolic changes. Methods Bioinformatics analysis was used to identify transcriptomic changes during PMT. PDGFRβ + pericytes were isolated using MACS, and an in vitro model of PMT was induced by 5 ng/ml TGF-β1. Metabolites were analyzed by ultraperformance liquid chromatography (UPLC) and tandem mass spectrometry (MS). 2-Deoxyglucose (2-DG) was used to inhibit glycolysis via its actions on hexokinase (HK). The hexokinase II (HKII) plasmid was transfected into pericytes for HKII overexpression. LY294002 or rapamycin was used to inhibit the PI3K-Akt-mTOR pathway for mechanistic exploration. Results An increase in carbon metabolism during PMT was detected through bioinformatics and metabolomics analysis. We first detected increased levels of glycolysis and HKII expression in pericytes after stimulation with TGF-β1 for 48 h, accompanied by increased expression of α-SMA, vimentin and desmin. Transdifferentiation was blunted when pericytes were pretreated with 2-DG, an inhibitor of glycolysis. The phosphorylation levels of PI3K, Akt and mTOR were elevated during PMT, and after inhibition of the PI3K-Akt-mTOR pathway with LY294002 or rapamycin, glycolysis in the TGF-β1-treated pericytes was decreased. Moreover, PMT and HKII transcription and activity were blunted, but the plasmid-mediated overexpression of HKII rescued PMT inhibition. Conclusions The expression and activity of HKII as well as the level of glycolysis were increased during PMT. Moreover, the PI3K-Akt-mTOR pathway regulates PMT by increasing glycolysis through HKII regulation.

Abstract Considering the high prevalence and the lack of targeted pharmacological management of acute kidney injury (AKI), the search for new therapeutic approaches for it is in urgent demand. Mesenchymal stem cells (MSCs) have been increasingly recognized as a promising candidate for the treatment of AKI. However, clinical translation of MSCs-based therapies is hindered due to the poor retention and survival rates as well as the impaired paracrine ability of MSCs post-delivery. To address these issues, a series of strategies including local administration, three-dimensional culture, and preconditioning have been applied. Owing to the emergence and development of these novel biotechnologies, the effectiveness of MSCs in experimental AKI models is greatly improved. Here, we summarize the different approaches suggested to optimize the efficacy of MSCs therapy, aiming at promoting the therapeutic effects of MSCs on AKI patients.

Abstract We sought to apply a simple cardiovascular health tool not requiring laboratory tests (the Fuster-BEWAT score, FBS) to predict subclinical atherosclerosis. This study included 2657 young adults (

Abstract Background Pediatric meningioma with YAP1 fusion is a rare subset of meningiomas. Currently, there are lack of integrated clinical, radiological, and pathological features on this subset. Here, we reported a case of pediatric meningioma with a novel MAML2-YAP1 fusion variant and reviewed the relevant literature. Case presentation We presented a case of 12-year-old boy with meningioma adjacent to the superior sagittal sinus and falx. Simpson grade II gross total resection was performed after diagnosis. Pathologically, he was diagnosed as WHO grade I meningothelial meningioma with rhabdoid features. A next-generation sequencing-based gene panel was performed to determine the molecular features for potential treatment, and a novel MAML2 - YAP1 fusion break point was identified. Conclusion Pediatric meningioma with the fusion of YAP1 and MAML2 genes is more likely to have pathological features of rhabdiod cells, which needs to be validated in large-scale studies for exploring better treatment under the integrated diagnosis.

Abstract Background Chemoresistance is one of the major obstacles that lead to poor prognosis in cervical cancer. linc00958 was reported to be an oncogene in cervical cancer. However, its role in mediating chemoresistance remains to be revealed. Purpose To explore the regulatory mechanisms of linc00958 in cisplatin-resistant cervical cancer cells and further validate in xenograft mice. Methods Online bioinformatic tools were used to conduct the pre-investigation of linc00958/miR-185-5p/RSF-1 and predict the associations between RSF-1 and AKT1/GSK3β/VEGFA in cervical cancer. RT-qPCR measured the RNA expression levels of linc00958/miR-185-5p/RSF-1 in SiHa and SiHa/DDP. Cell survival rates were evaluated by CCK8 methods after cells were exposed to differential concentrations of DDP. Dual-luciferase reporter methods were used to measure luciferase activity. Western blot measured RSF-1 protein and phosphorylated changes of AKT1/GSK3β. Immunofluorescence was employed to observe VEGFA secretion in vitro. Tube formation was applied to evaluate the in-vitro changes of angiogenesis. The SiHa/DDP cells stably transfected with pLKO-sh-NC or pLKO-sh-linc00958 plasmids, were injected into mice, establishing xenograft models. The changes in mice weight and tumor volumes were recorded. H&E staining and Immunohistochemistry (IHC) method was further performed. Results linc00958 expression was higher in SiHa/DDP cells. High linc00958 expression was associated with low overall survival. In SiHa/DDP cells linc00958/miR-185-5p/RSF-1 axis inhibited the cellular resistance to cisplatin and suppressed VEGFA and the tube formation through AKT1/GSK3β/VEGFA pathway. The knockdown of linc00958 inhibited RSF-1 and Ki67, curbing tumor growth; it also inhibited VEGFA and CD34, decreasing angiogenesis in mice. Conclusion linc00958/miR-185-5p/RSF-1 modulates cisplatin resistance and angiogenesis through AKT1/GSK3β/VEGFA pathway in cervical cancer.

Abstract Background Established prediction models of Diabetic kidney disease (DKD) are limited to the analysis of clinical research data or general population data and do not consider hospital visits. Construct a 3-year diabetic kidney disease risk prediction model in patients with type 2 diabetes mellitus (T2DM) using machine learning, based on electronic medical records (EMR). Methods Data from 816 patients (585 males) with T2DM and 3 years of follow-up at the PLA General Hospital. 46 medical characteristics that are readily available from EMR were used to develop prediction models based on seven machine learning algorithms (light gradient boosting machine [LightGBM], eXtreme gradient boosting, adaptive boosting, artificial neural network, decision tree, support vector machine, logistic regression). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was used to interpret the results of the best performing model. Results The LightGBM model had the highest AUC (0.815, 95% CI 0.747–0.882). Recursive feature elimination with random forest and SHAP plot based on LightGBM showed that older patients with T2DM with high homocysteine (Hcy), poor glycemic control, low serum albumin (ALB), low estimated glomerular filtration rate (eGFR), and high bicarbonate had an increased risk of developing DKD over the next 3 years. Conclusions This study constructed a 3-year DKD risk prediction model in patients with T2DM and normo-albuminuria using machine learning and EMR. The LightGBM model is a tool with potential to facilitate population management strategies for T2DM care in the EMR era.

Abstract Background Sarcopenia is one of the most frequent syndromes in older adults and one of its main characteristics is low muscle mass. Gastrointestinal tumor is a malignant disease with high incidence. This study aimed to investigate the risk factors of low muscle mass in older adults with gastrointestinal tumor, the prognostic indicators of and short-term outcomes after resection for gastrointestinal tumor, and to explore the relationship between low muscle mass and short-term postoperative prognosis. Method A total of 247 older patients with gastrointestinal tumors who underwent radical resection in 2019 were included in this study. Relevant indexes were calculated using L3 slice image of computed tomography (CT) to evaluate low muscle mass. Short-term postoperative complications and length of stay were considered as short-term outcomes of this study. Results Advanced age, lower higher body mass index (BMI), lower hemoglobin, having history of abdominal surgery and higher visceral fat index (VFI) were risk factors of low muscle mass, while higher BMI and lower subcutaneous fat index (SFI) were protective factors of low muscle mass. Further multivariate logistic regression analysis showed that having history of abdominal surgery, advanced age and lower BMI were independent risk factors. Low muscle mass and higher Charlson comorbidity index were independent risk factors of short-term postoperative complications in older adults with gastrointestinal tumor. Higher Charlson comorbidity index gave rise to longer length of stay. Conclusions Low muscle mass and higher Charlson comorbidity index predict poor short-term prognosis of older patients undergoing gastrointestinal tumor resection.

Abstract Background Pre-hospital services are not well developed in Vietnam, especially the lack of a trauma system of care. Thus, the prognosis of traumatic out-of-hospital cardiac arrest (OHCA) might differ from that of other countries. Although the outcome in cardiac arrest following trauma is dismal, pre-hospital resuscitation efforts are not futile and seem worthwhile. Understanding the country-specific causes, risk, and prognosis of traumatic OHCA is important to reduce mortality in Vietnam. Therefore, this study aimed to investigate the survival rate from traumatic OHCA and to measure the critical components of the chain of survival following a traumatic OHCA in the country. Methods We performed a multicenter prospective observational study of patients (> 16 years) presenting with traumatic OHCA to three central hospitals throughout Vietnam from February 2014 to December 2018. We collected data on characteristics, management, and outcomes of patients, and compared these data between patients who died before hospital discharge and patients who survived to discharge from the hospital. Results Of 111 eligible patients with traumatic OHCA, 92 (82.9%) were male and the mean age was 39.27 years (standard deviation: 16.38). Only 5.4% (6/111) survived to discharge from the hospital. Most cardiac arrests (62.2%; 69/111) occurred on the street or highway, 31.2% (29/93) were witnessed by bystanders, and 33.7% (32/95) were given cardiopulmonary resuscitation (CPR) by a bystander. Only 29 of 111 patients (26.1%) were taken by the emergency medical services (EMS), 27 of 30 patients (90%) received pre-hospital advanced airway management, and 29 of 53 patients (54.7%) were given resuscitation attempts by EMS or private ambulance. No significant difference between patients who died before hospital discharge and patients who survived to discharge from the hospital was found for bystander CPR (33.7%, 30/89 and 33.3%, 2/6, P > 0.999; respectively) and resuscitation attempts (56.3%, 27/48, and 40.0%, 2/5, P = 0.649; respectively). Conclusion In this study, patients with traumatic OHCA presented to the ED with a low rate of EMS utilization and low survival rates. The poor outcomes emphasize the need for increasing bystander first-aid, developing an organized trauma system of care, and developing a standard emergency first-aid program for both healthcare personnel and the community.

Abstract Background Mesenchymal stem cells (MSCs) have been reported to promote regeneration in both subjects with acute kidney injury (AKI) and chronic kidney disease (CKD), but their efficacy remains limited, probably because most of the cells accumulate in the lungs, liver, and spleen after an intravenous infusion. Therefore, ultrasound-guided administration of MSCs represents a possible approach to solve this problem. The greater omentum is used to promote cell survival due to its rich vasculature. We hypothesized that ultrasound-guided administration of MSCs combined with greater omentum might be more curative than currently available approaches. Methods In this study, we established an aristolochic acid nephropathy (AAN) model by intraperitoneally administering aristolochic acid I sodium salt (AA-I) at a dose of 5 mg/kg body weight on alternate days for 4 weeks. Subsequently, a laparotomy was performed, and the left kidney from which the capsule had been removed was wrapped with the greater omentum. A dose of 2 × 107 MSCs was injected into the space between the greater omentum and the left kidney. Equal amounts of MSCs were administered under ultrasound guidance every second week for a total of 4 treatments. Mice were sacrificed 4 weeks after surgery. Serum creatinine and blood urea levels were measured to assess renal function. qPCR, Western blot, and histological analyses were conducted to further investigate the therapeutic mechanism of MSCs. Results Ultrasound-guided injection of MSCs into the greater omentum that surrounds the kidney enriched cells in the kidney region for up to 5 days. Renal function tests indicated that MSCs improved renal function to a great extent, as reflected by decreased blood urea nitrogen and serum creatinine levels. In addition, histological analyses showed that MSCs noticeably attenuated kidney injury, as evidenced by the amelioration of tubular necrosis and peritubular interstitial fibrosis. Mitigation of renal interstitial fibrosis was further confirmed by immunohistochemistry, qPCR, and western blotting after MSC treatment. Moreover, immunofluorescence staining revealed that MSCs alleviated inflammatory responses by increasing the counts of CD206+ cells and decreasing the counts of CD68+ cells. MSC migration was initiated in response to AA-I-treated renal epithelial cells in an in vitro migration assay. Conclusions These findings suggested that administration of MSCs into the cavity formed by the injured kidney and the greater omentum under ultrasound guidance improved renal function, attenuated kidney injury, and mitigated renal interstitial fibrosis and inflammatory responses. Thus, this approach might be a safe and effective therapy for CKD.

Abstract Background Observational series suggest a mortality benefit from metformin in the heart failure (HF) population. However, the benefit of metformin in HF with preserved ejection fraction (HFpEF) has yet to be explored. We performed a systematic review and meta-analysis to identify whether variation in EF impacts mortality outcomes in HF patients treated with metformin. Methods MEDLINE and EMBASE were searched up to October 2019. Observational studies and randomised trials reporting mortality in HF patients and the proportion of patients with an EF > 50% at baseline were included. Other baseline variables were used to assess for heterogeneity in treatment outcomes between groups. Regression models were used to determine the interaction between metformin and subgroups on mortality. Results Four studies reported the proportion of patients with a preserved EF and were analysed. Metformin reduced mortality in both preserved or reduced EF after adjustment with HF therapies such as angiotensin converting enzyme inhibitors (ACEi) and beta-blockers (β = − 0.2 [95% CI − 0.3 to − 0.1], p = 0.02). Significantly greater protective effects were seen with EF > 50% (p = 0.003). Metformin treatment with insulin, ACEi and beta-blocker therapy were also shown to have a reduction in mortality (insulin p = 0.002; ACEi p

Abstract Background A COVID-19 outbreak started in Wuhan, China, last December and now has become a global pandemic. The clinical information in caring of critically ill patients with COVID-19 needs to be shared timely, especially under the situations that there is still a largely ongoing spread of COVID-19 in many countries. Methods A multicenter prospective observational study investigated all the COVID-19 patients received in 19 ICUs of 16 hospitals in Wuhan, China, over 24 h between 8 AM February 2h and 8 AM February 27, 2020. The demographic information, clinical characteristics, vital signs, complications, laboratory values, and clinical managements of the patients were studied. Results A total of 226 patients were included. Their median (interquartile range, IQR) age was 64 (57–70) years, and 139 (61.5%) patients were male. The duration from the date of ICU admission to the study date was 11 (5–17) days, and the duration from onset of symptoms to the study date was 31 (24–36) days. Among all the patients, 155 (68.6%) had at least one coexisting disease, and their sequential organ failure assessment score was 4 (2–8). Organ function damages were found in most of the patients: ARDS in 161 (71.2%) patients, septic shock in 34 (15.0%) patients, acute kidney injury occurred in 57 (25.2%) patients, cardiac injury in 61 (27.0%) patients, and lymphocytopenia in 160 (70.8%) patients. Of all the studied patients, 85 (37.6%) received invasive mechanical ventilation, including 14 (6.2%) treated with extracorporeal membrane oxygenation (ECMO) at the same time, 20 (8.8%) received noninvasive mechanical ventilation, and 24 (10.6%) received continuous renal replacement therapy. By April 9, 2020, 87 (38.5%) patients were deceased and 15 (6.7%) were still in the hospital. Conclusions Critically ill patients with COVID-19 are associated with a higher risk of severe complications and need to receive an intensive level of treatments. COVID-19 poses a great strain on critical care resources in hospitals. Trial registration Chinese Clinical Trial Registry, ChiCTR2000030164. Registered on February 24, 2020, http://www.chictr.org.cn/edit.aspx?pid=49983&htm=4

Abstract Background Diabetic ketoacidosis (DKA) is an acute, major, life-threatening complication of diabetes that requires immediate treatment. Allergic reaction to insulin is rare, especially when using recombinant human insulin. The clinical presentation of insulin allergy can range from minor local symptoms to a severe generalized allergic reaction such as anaphylaxis. A limited number of cases have been reported on the treatment of severe DKA in patients with type 2 diabetes with insulin allergy. Here, we describe a patient with type 2 diabetes with insulin allergy in which severe DKA resolved after the initiation of continuous intravenous (IV) recombinant human insulin infusion. Case presentation A 58-year-old man with type 2 diabetes initiated subcutaneous insulin administration (SIA) after failure of oral antidiabetic treatment. Symptoms of an allergic reaction developed, including pruritic wheals appearing within 10 min of injection and lasting over 24 h. Both skin prick and intradermal tests were positive with different types of insulin. Two days before admission, he stopped SIA because of allergic symptoms and then experienced weakness and upper abdominal pain. On admission, he was in severe metabolic acidosis with a pH of 6.984 and bicarbonate of 2.5 mmol/litre. The blood glucose level was 20.79 mmol/litre, BUN 4.01 mmol/litre, creatinine 128 μmol/litre, and urinary ketone 11.44 mmol/litre. Over 24 h, metabolic acidosis was refractory to IV fluids, bicarbonate and potassium replacement, as well as haemodialysis. Ultimately, he received continuous IV recombinant human insulin infusion at a rate of 0.1 units/kg/hour, in combination with haemodiafiltration, and no further allergic reactions were observed. On day 5, ketonaemia and metabolic acidosis completely resolved. He had transitioned from IV insulin infusion to SIA on day 14. He was discharged on day 21 with SIA treatment. Three months later, he had good glycaemic control but still had allergic symptoms at the insulin injection sites. Conclusions In this patient, SIA caused an allergic reaction, in contrast to continuous IV insulin infusion for which allergic symptoms did not appear. Continuous IV recombinant human insulin infusion in combination with haemodiafiltration could be an option for the treatment of severe DKA in patients with diabetes with insulin allergy.

Abstract Stem cell therapy has been applied in many fields. Basic and clinical studies on stem cell therapy for acute kidney injury (AKI) have been conducted. Stem cells have been found to exert renal protection through a variety of mechanisms, such as regulating the immune system and secreting growth factors, cytokines, and extracellular vesicles (EVs). Among them, EVs are considered to be important mediators for stem cell protection because they contain various biological components, including microRNAs (miRNAs). miRNAs are a class of small RNAs that function in posttranscriptional gene regulation. A number of studies have confirmed that miRNAs in stem cell-derived EVs can protect from AKI. miRNAs can enter the injured renal tissue through EVs released from stem cells, thereby exerting anti-inflammatory, anti-apoptotic, anti-fibrotic, and pro-angiogenesis effects on AKI. However, the stem cell sources and AKI models used in these studies have differed. This article will summarize the miRNAs that play a role in kidney protection in stem cell EVs and clarifies the treatment characteristics and mechanisms of different miRNAs. This may provide a reference for clinical practice for acute and chronic kidney diseases.

Abstract Background In Vietnam, few studies have determined the epidemiological status of toxoplasmosis in pregnant women and no routine prenatal screening is in place. This study was conducted to evaluate the seroprevalence of this zoonotic parasitic infection in pregnant women in Northern Vietnam and to assess the association with awareness, risk factors and congenital toxoplasmosis. Methods Approximately 800 pregnant women were included in the study from two hospitals, one in Hanoi and one in Thai Binh province, which is known to have a dense cat population. Serological immunoglobulin G (IgG) and immunoglobulin M (IgM) detection was performed to estimate the seroprevalence of toxoplasmosis and sero-incidence of maternal and congenital toxoplasmosis. In addition, a survey was conducted about awareness, clinical history, presentation of signs and symptoms relating to toxoplasmosis and to detect biologically plausible and socio-demographic risk factors associated with toxoplasmosis. Associations with seroprevalence were assessed using univariable and multivariable analysis. Results The mean IgG seroprevalence after the full diagnostic process was 4.5% (95% confidence interval(CI): 2.7–7.0) and 5.8% (95% CI: 3.7–8.6) in Hanoi and Thai Binh hospital, respectively, and included one seroconversion diagnosed in Thai Binh hospital. Only 2.0% of the pregnant women in Hanoi hospital and 3.3% in Thai Binh hospital had heard about toxoplasmosis before this study. Conclusion Since the percentage of seronegative, and thus susceptible, pregnant women was high and the awareness was low, we suggest to distribute information about toxoplasmosis and its prevention among women of child bearing age. Furthermore, future studies are recommended to investigate why such a low seroprevalence was seen in pregnant women in Northern Vietnam compared to other countries in South East Asia and globally.

Abstract Background Residents in border areas are vulnerable to HIV/AIDS due to high rates of risk behaviors such as unprotected sexual practices or illicit drug use. Improving knowledge and attitude toward HIV/AIDS prevention and treatment are vital to diminish the burden of the HIV epidemic in this setting. However, evidence about this issue in Vietnam has been limited. This study aims to explore the knowledge and attitude toward HIV/AIDS among people in Vietnam border zones. Methods We conducted a cross-sectional study in three border communes in Thanh Hoa province with 600 HIV(−) residents. Data about socio-demographic characteristics, general HIV knowledge, knowledge about prevention of mother-to-child transmission, treatment and care, HIV testing services, and attitude toward HIV/AIDS were collected. Multivariate Tobit regression was used to determine related factors with the knowledge and attitude. Results The highest percentage of people having correct statements was for “HIV could be transmitted from mother to child” (98.2%), while the lowest percentage was for item “Know health facilities where HIV-positive people could register for care and check-up” (28.2%). People had the highest score in “Knowledge about HIV transmission routes” and the lowest score in “Knowledge about HIV/AIDS prevention measures”. Most of the people were not afraid of being exposed to HIV-positive individuals (66.0%), willing to buy goods from HIV-positive sellers (78.9%), and willing to take care of people living with HIV in their family (90.1%). Education, ethnic, marital status, occupations, and HIV/AIDS information sources were found to be associated with knowledge and attitude toward HIV/AIDS. Conclusions The general knowledge and attitude on HIV/AIDS of residents were relatively good. Educational campaigns to improve knowledge and attitude toward PLWH, involving peer educators and local associations, are potential strategies for sustaining HIV intervention in this remote setting.

Abstract Background Globally, people who inject drugs are highly vulnerable to HIV transmission. Methadone maintenance treatment (MMT) programs are one of the most cost-effective mechanisms to substitute opioid use and improve the quality of life of patients. Since the coverage of MMT is still limited and even for those patients who are treated, improving their knowledge on HIV and maintaining healthy behaviors are key to maximizing the outcomes of HIV harm reduction programs. This study examined the knowledge on HIV, perceived risk and HIV testing among drug users accessing methadone maintenance services in three Vietnamese mountainous areas. Methods A cross-sectional study of 300 people enrolling for MMT services in three provinces in Vietnam was conducted. The factors associated with the knowledge, attitudes, and practices of respondents about HIV/AIDS were exploited using multivariable logistic model. Results Of the 300-people surveyed, 99% knew of HIV and 60.6% were identified as having good knowledge. While 75.2% identified that injecting drugs was a risk factor for HIV, 52.2% thought they were not at risk of HIV mainly as they did not share needles. 92.6% had undergone HIV testing with 17.4% being positive, a number which was significantly lower than Vietnam’s national average for people who inject drugs. Age, ethnicity and education were associated with knowledge of HIV while ART treatment was linked to self-assessed HIV status. Conclusions This study sheds new light on the knowledge attitudes and practices of people who inject drugs, particularly males in mountainous areas of Vietnam regarding HIV prevention. Overall, knowledge was good with most conducting safe practices towards transmission. Enhanced education and targeting of minority groups could help in increasing the numbers receiving MMT and HIV services.

Abstract Background Induced pluripotent stem cells (iPS) represent an innovative source for the standardized in vitro generation of macrophages (Mφ). Mφ show great promise in disease pathogenesis, particularly tuberculosis. However, there is no information about human iPS-derived (hiPS) macrophages (hiPS-Mφ) in response to tuberculosis infection. Methods In the present study, macrophages derived from hiPS were established via embryoid body (EB) formation by using feeder-free culture conditions, and the human monocyte cell line THP-1 (THP-1-Mφ) was used as control. iPS-Mφ were characterized by using morphology, Giemsa staining, nonspecific esterase staining (α-NAE), phagocytosis, and surface phenotype. Additionally, after treatment with Bacillus Calmette-Guérin (BCG) for 24 h, cell apoptosis was detected by using an Annexin V-FITC Apoptosis Detection assay. The production of nitric oxide (NO), expression of tumor necrosis factor alpha (TNF-α), activity of apoptosis-related protein cysteine-3 (Caspase-3) and expression of B-cell lymphoma-2 (Bcl-2) were analyzed. Results With respect to morphology, surface phenotype, and function, the iPS-Mφ closely resembled their counterparts generated in vitro from a human monocyte cell line. iPS-Mφ exhibited the typically morphological characteristics of macrophages, such as round, oval, fusiform and irregular characteristics. The cells were Giemsa-stained-positive, α-NAE-positive, and possessed phagocytic ability. iPS-Mφ express high levels of CD14, CD11b, CD40, CD68, and major histocompatibility complex II (MHC-II). Moreover, with regard to the apoptotic rate, the production of NO, expression of TNF-α, and activity of Caspase-3 and Bcl-2, iPS-Mφ closely resemble that of their counterparts generated in vitro from human monocyte cell line in response to BCG infection. The rate of apoptosis of BCG-treated iPS-Mφ was 37.77 ± 7.94% compared to that of the untreated group at 4.97 ± 1.60% (P < 0.01) by using Annexin V-FITC Apoptosis Detection. Additionally, the rate of apoptosis of BCG-treated THP-1-Mφ was 37.1 ± 2.84% compared to that of the untreated group at 6.19 ± 1.68% (P < 0.001). The expression of TNF-α and the production of NO were significantly increased (P < 0.001), and the activity of Caspase-3 was increased. However, the expression of Bcl-2 was inhibited (P < 0.001). Conclusions Our results demonstrate that Mφ derived from hiPS perform the immunological function in response to Bacillus Calmette-Guérin infection by undergoing apoptosis, increasing the production of NO and expression of TNF-α. Thus, our study may help to overcome the limitations of research into certain rare diseases due to the lack of adequate supply of disease-specific primary cells.

Abstract Background The Asian population is one of the fastest growing ethnic minority groups in western countries. However, cancer screening uptake is consistently lower in this group than in the native-born populations. As a first step towards developing an effective cancer screening intervention program targeting Asian women, we conducted a comprehensive systematic review, without geographic, language or date limitations, to update current knowledge on the effectiveness of existing intervention strategies to enhance breast and cervical screening uptake in Asian women. Methods This study systematically reviewed studies published as of January 2010 to synthesize knowledge about effectiveness of cancer screening interventions targeting Asian women. Fifteen multidisciplinary peer-reviewed and grey literature databases were searched to identify relevant studies. Results The results of our systematic review were reported in accordance with the PRISMA Statement. Of 37 selected intervention studies, only 18 studies included valid outcome measures (i.e. self-reported or recorded receipt of mammograms or Pap smear). 11 of the 18 intervention studies with valid outcome measures used multiple intervention strategies to target individuals in a specific Asian ethnic group. This observed pattern of intervention design supports the hypothesis that employing a combination of multiple strategies is more likely to be successful than single interventions. The effectiveness of community-based or workplace-based group education programs increases when additional supports, such as assistance in scheduling/attending screening and mobile screening services are provided. Combining cultural awareness training for health care professionals with outreach workers who can help healthcare professionals overcome language and cultural barriers is likely to improve cancer screening uptake. Media campaigns and mailed culturally sensitive print materials alone may be ineffective in increasing screening uptake. Intervention effectiveness appears to vary with ethnic population, methods of program delivery, and study setting. Conclusions Despite some limitations, our review has demonstrated that the effectiveness of existing interventions to promote breast and cervical cancer screening uptake in Asian women may hinge on a variety of factors, such as type of intervention and study population characteristics. While some studies demonstrated the effectiveness of certain intervention programs, the cost effectiveness and long-term sustainability of these programs remain questionable. When adopting an intervention program, it is important to consider the impacts of social-and cultural factors specific to the Asian population on cancer screening uptake. Future research is needed to develop new interventions and tools, and adopt vigorous study design and evaluation methodologies to increase cancer screening among Asian women to promote population health and health equity.

Abstract Background The purpose of this study was to assess whether or not the change in coding classification had an impact on diagnosis and comorbidity coding in hospital discharge data across Canadian provinces. Methods This study examined eight years (fiscal years 1998 to 2005) of hospital records from the Hospital Person-Oriented Information database (HPOI) derived from the Canadian national Discharge Abstract Database. The average number of coded diagnoses per hospital visit was examined from 1998 to 2005 for provinces that switched from International Classifications of Disease 9th version (ICD-9-CM) to ICD-10-CA during this period. The average numbers of type 2 and 3 diagnoses were also described. The prevalence of the Charlson comorbidities and distribution of the Charlson score one year before and one year after ICD-10 implementation for each of the 9 provinces was examined. The prevalence of at least one of the seventeen Charlson comorbidities one year before and one year after ICD-10 implementation were described by hospital characteristics (teaching/non-teaching, urban/rural, volume of patients). Results Nine Canadian provinces switched from ICD-9-CM to ICD-I0-CA over a 6 year period starting in 2001. The average number of diagnoses coded per hospital visit for all code types over the study period was 2.58. After implementation of ICD-10-CA a decrease in the number of diagnoses coded was found in four provinces whereas the number of diagnoses coded in the other five provinces remained similar. The prevalence of at least one of the seventeen Charlson conditions remained relatively stable after ICD-10 was implemented, as did the distribution of the Charlson score. When stratified by hospital characteristics, the prevalence of at least one Charlson condition decreased after ICD-10-CA implementation, particularly for low volume hospitals. Conclusion In conclusion, implementation of ICD-10-CA in Canadian provinces did not substantially change coding practices, but there was some coding variation in the average number of diagnoses per hospital visit across provinces.

Abstract Background Ulcerative colitis (UC) patients failing medical management require colectomy. This study compares risk estimates for predictors of postoperative complication derived from administrative data against that of chart review and evaluates the accuracy of administrative coding for this population. Methods Hospital administrative databases were used to identify adults with UC undergoing colectomy from 1996–2007. Medical charts were reviewed and regression analyses comparing chart versus administrative data were performed to assess the effect of age, emergent operation, and Charlson comorbidities on the occurrence of postoperative complications. Sensitivity, specificity, and positive/negative predictive values of administrative coding for identifying the study population, Charlson comorbidities, and postoperative complications were assessed. Results Compared to chart review, administrative data estimated a higher magnitude of effect for emergent admission (OR 2.52 [95% CI: 1.80–3.52] versus 1.49 [1.06–2.09]) and Charlson comorbidities (OR 2.91 [1.86–4.56] versus 1.50 [1.05–2.15]) as predictors of postoperative complications. Administrative data correctly identified UC and colectomy in 85.9% of cases. The administrative database was 37% sensitive in identifying patients with ≥ 1Charlson comorbidity. Restricting analysis to active comorbidities increased the sensitivity to 63%. The sensitivity of identifying patients with at least one postoperative complication was 68%; restricting analysis to more severe complications improved the sensitivity to 84%. Conclusions Administrative data identified the same risk factors for postoperative complications as chart review, but overestimated the magnitude of risk. This discrepancy may be explained by coding inaccuracies that selectively identifying the most serious complications and comorbidities.

Abstract Background Failure to adhere to cardiac medications after acute myocardial infarction (AMI) is associated with increased mortality. Language barriers and preference for traditional medications may predispose certain ethnic groups at high risk for non-adherence. We compared prescribing and adherence to ACE-inhibitors (ACEI), beta-blockers (BB), and statins following AMI among elderly Chinese, South Asian, and Non-Asian patients. Methods Retrospective-cohort study of elderly AMI survivors (1995-2002) using administrative data from British Columbia. AMI cases and ethnicity were identified using validated ICD-9/10 coding and surname algorithms, respectively. Medication adherence was assessed using the 'proportion of days covered' (PDC) metric with a PDC ≥ 0.80 indicating optimal adherence. The independent effect of ethnicity on adherence was assessed using multivariable modeling, adjusting for socio-demographic and clinical characteristics. Results There were 9926 elderly AMI survivors (258 Chinese, 511 South Asian patients). More Chinese patients were prescribed BBs (79.7% vs. 73.1%, p = 0.04) and more South Asian patients were prescribed statins (73.5% vs. 65.2%, p = 0.001). Both Chinese (Odds Ratio [OR] 0.53; 95%CI, 0.39-0.73; p < 0.0001) and South Asian (OR 0.78; 95%CI, 0.61-0.99; p = 0.04) patients were less adherent to ACEI compared to Non-Asian patients. South Asian patients were more adherent to BBs (OR 1.3; 95%CI, 1.04-1.62; p = 0.02). There was no difference in prescribing of ACEI, nor adherence to statins among the ethnicities. Conclusion Despite a higher likelihood of being prescribed evidence-based therapies following AMI, Chinese and South Asian patients were less likely to adhere to ACEI compared to their Non-Asian counterparts.

Abstract Background Co-morbidity information derived from administrative data needs to be validated to allow its regular use. We assessed evolution in the accuracy of coding for Charlson and Elixhauser co-morbidities at three time points over a 5-year period, following the introduction of the International Classification of Diseases, 10th Revision (ICD-10), coding of hospital discharges. Methods Cross-sectional time trend evaluation study of coding accuracy using hospital chart data of 3'499 randomly selected patients who were discharged in 1999, 2001 and 2003, from two teaching and one non-teaching hospital in Switzerland. We measured sensitivity, positive predictive and Kappa values for agreement between administrative data coded with ICD-10 and chart data as the 'reference standard' for recording 36 co-morbidities. Results For the 17 the Charlson co-morbidities, the sensitivity - median (min-max) - was 36.5% (17.4-64.1) in 1999, 42.5% (22.2-64.6) in 2001 and 42.8% (8.4-75.6) in 2003. For the 29 Elixhauser co-morbidities, the sensitivity was 34.2% (1.9-64.1) in 1999, 38.6% (10.5-66.5) in 2001 and 41.6% (5.1-76.5) in 2003. Between 1999 and 2003, sensitivity estimates increased for 30 co-morbidities and decreased for 6 co-morbidities. The increase in sensitivities was statistically significant for six conditions and the decrease significant for one. Kappa values were increased for 29 co-morbidities and decreased for seven. Conclusions Accuracy of administrative data in recording clinical conditions improved slightly between 1999 and 2003. These findings are of relevance to all jurisdictions introducing new coding systems, because they demonstrate a phenomenon of improved administrative data accuracy that may relate to a coding 'learning curve' with the new coding system.

Abstract Background Over the past decade there has been a growing body of literature on how the Systematised Nomenclature of Medicine Clinical Terms (SNOMED CT) can be implemented and used in different clinical settings. Yet, for those charged with incorporating SNOMED CT into their organisation's clinical applications and vocabulary systems, there are few detailed encoding instructions and examples available to show how this can be done and the issues involved. This paper describes a heuristic method that can be used to encode clinical terms in SNOMED CT and an illustration of how it was applied to encode an existing palliative care dataset. Methods The encoding process involves: identifying input data items; cleaning the data items; encoding the cleaned data items; and exporting the encoded terms as output term sets. Four outputs are produced: the SNOMED CT reference set; interface terminology set; SNOMED CT extension set and unencodeable term set. Results The original palliative care database contained 211 data elements, 145 coded values and 37,248 free text values. We were able to encode ~84% of the terms, another ~8% require further encoding and verification while terms that had a frequency of fewer than five were not encoded (~7%). Conclusions From the pilot, it would seem our SNOMED CT encoding method has the potential to become a general purpose terminology encoding approach that can be used in different clinical systems.

Abstract Background As populations in Western countries continue to change in their ethnic composition, there is a need for regular surveillance of diseases that have previously shown some health disparities. Earlier data have already demonstrated high rates of cardiovascular mortality among South Asians and relatively lower rates among people of Chinese descent. The aim of this study was to describe the differences in the incidence of hospitalized acute myocardial infarction (AMI) among the three largest ethnic groups in British Columbia (BC), Canada. Methods Using hospital administrative data, we identified all patients with incident AMI in BC between April 1, 1995, and March 31, 2002. Census data from 2001 provided the denominator for the entire BC population. Ethnicity was determined using validated surname analysis and applied to the census and hospital administrative datasets. Direct age standardization was used to compare incidence rates. Results A total of 34,848 AMI cases were identified. Among men, South Asians had the highest age standardized rate of AMI hospitalization at 4.97/1000 population/year, followed by Whites at 3.29, and then Chinese at 0.98. Young South Asian men, in particular, showed incidence rates that were double that of young Whites and ten times that of young Chinese men. South Asian women also had the highest age-standardized rate of AMI hospitalization at 2.35/1000 population/year, followed by White women (1.53) and Chinese women (0.49). Conclusions South Asians continue to have a higher incidence of hospitalized AMI while incidence rates among Chinese remain low. Ethnic differences are most notable among younger men.

Abstract Background Administrative data are widely used to study health systems and make important health policy decisions. Yet little is known about the influence of coder characteristics on administrative data validity in these studies. Our goal was to describe the relationship between several measures of validity in coded hospital discharge data and 1) coders' volume of coding (≥13,000 vs. Methods This descriptive study examined 6 indicators of face validity in ICD-10 coded discharge records from 4 hospitals in Calgary, Canada between April 2002 and March 2007. Specifically, mean number of coded diagnoses, procedures, complications, Z-codes, and codes ending in 8 or 9 were compared by coding volume and employment status, as well as hospital type. The mean number of diagnoses was also compared across coder characteristics for 6 major conditions of varying complexity. Next, kappa statistics were computed to assess agreement between discharge data and linked chart data reabstracted by nursing chart reviewers. Kappas were compared across coder characteristics. Results 422,618 discharge records were coded by 59 coders during the study period. The mean number of diagnoses per record decreased from 5.2 in 2002/2003 to 3.9 in 2006/2007, while the number of records coded annually increased from 69,613 to 102,842. Coders at the tertiary hospital coded the most diagnoses (5.0 compared with 3.9 and 3.8 at other sites). There was no variation by coder or site characteristics for any other face validity indicator. The mean number of diagnoses increased from 1.5 to 7.9 with increasing complexity of the major diagnosis, but did not vary with coder characteristics. Agreement (kappa) between coded data and chart review did not show any consistent pattern with respect to coder characteristics. Conclusions This large study suggests that coder characteristics do not influence the validity of hospital discharge data. Other jurisdictions might benefit from implementing similar employment programs to ours, e.g.: a requirement for a 2-year college training program, a single management structure across sites, and rotation of coders between sites. Limitations include few coder characteristics available for study due to privacy concerns.

Abstract Background The literature comparing private not-for-profit, for-profit, and government providers mostly relies on empirical evidence from high-income and established market economies. Studies from developing and transitional economies remain scarce, especially regarding patient case-mix and quality of care in public and private hospitals, even though countries such as China have expanded a mixed-ownership approach to service delivery. The purpose of this study is to compare the operations and performance of public and private hospitals in Guangdong Province, China, focusing on differences in patient case-mix and quality of care. Methods We analyze survey data collected from 362 government-owned and private hospitals in Guangdong Province in 2005, combining mandatorily reported administrative data with a survey instrument designed for this study. We use univariate and multi-variate regression analyses to compare hospital characteristics and to identify factors associated with simple measures of structural quality and patient outcomes. Results Compared to private hospitals, government hospitals have a higher average value of total assets, more pieces of expensive medical equipment, more employees, and more physicians (controlling for hospital beds, urban location, insurance network, and university affiliation). Government and for-profit private hospitals do not statistically differ in total staffing, although for-profits have proportionally more support staff and fewer medical professionals. Mortality rates for non-government non-profit and for-profit hospitals do not statistically differ from those of government hospitals of similar size, accreditation level, and patient mix. Conclusions In combination with other evidence on health service delivery in China, our results suggest that changes in ownership type alone are unlikely to dramatically improve or harm overall quality. System incentives need to be designed to reward desired hospital performance and protect vulnerable patients, regardless of hospital ownership type.

Abstract Background Heart failure (HF) is a major cause of hospitalization and death in the aging population around the world. Home care utilization is associated with improved survival for the patients with HF, and varies by ethno-culture. The purpose of this study was to investigate the difference in hospital readmission rate and mortality between Asian and other Canadian HF patients. Methods HF patients were identified using hospital discharge abstracts from March 31, 2000 to April 1, 2006 in Calgary Health Region. Readmission and one-year mortality for HF were determined by linking hospital discharge and vital statistics data. Stratified by home care services use, readmission and mortality rates were compared between the Asians and other Canadians while controlling for age, sex, comorbidities, and household income. Results Of 26,171 HF patients discharged from hospital, 56.6% of Asians and 58.0% of other Canadians used home care services [adjusted odds ratio (OR) for Asian: 0.84, 95% confidence interval (CI): 0.74-0.89]. The hospital readmission rate was similar between Asians and other Canadians regardless of home care services use. Mortality was similar between those who used home care services (adjusted OR for Asian: 0.96, 95% CI: 0.81-1.13). For patients who did not use home care services, Asians had significantly lower mortality than other Canadians (adjusted OR for Asian: 0.76, 95% CI: 0.60-0.86). Conclusion Mortality was similar between Asian and other Canadian patients when home care services were utilized. However, among those without home care, Asian patients had a significantly lower mortality than other Canadian patients.

Abstract Background Screening and early diagnosis has been shown to reduce the morbidity and mortality associated with certain conditions such as cervical cancer. The role of general practitioners in promoting primary prevention of diseases is particularly important given that they have frequent contact with a large proportion of the population. This study assessed the extent to which general practitioners documented recommended preventive screening interventions among eligible patients. Methods We used a retrospective chart audit to assess patient visits to primary care clinics in Calgary, Canada from 2002-2004. We included fee for service physicians who practiced ≥ 2 days per week at their current location and excluded those whose primary practice was at walk-in clinics, community health centers, hospitals or emergency rooms. We included charts of patients who during the study period were age 35 years or older and had at least 2 visits to a clinic. We randomly selected and reviewed charts (N = 600) from 12 primary care clinics and abstracted information on 6 conditions recommended for preventive screening. Opportunities for preventive screening were determined based on recommendations of the Canadian Task Force on Preventive Health Care, the American College of Physicians, and the Canadian Cancer Society. Our main outcome measures included cancer screening (mammography and pap smears), immunization (influenza and pneumococcal), and risk factor assessment (cholesterol measurement and smoking cessation consultation). Results Patient visits to GP clinics present opportunities for preventive screening. However, we found that documentation of interventions was low, ranging from 40.3% (cholesterol measurement) to 0.9% (pneumococcal vaccination) within 1 year, and from 67.4% to 1.8% within the prior 3 years. Conclusions Documentation of preventive screening interventions by general practitioners was relatively low compared to the number of patients eligible for preventive screening. Some physicians opt to screen for PSA and DRE which is not recommended by the Canadian Task Force on Preventive HealthCare.

Abstract Background In the past 50 years there has been a substantial increase in the volume of published research and in the number of authors per scientific publication. There is also significant pressure exerted on researchers to produce publications. Thus, the purpose of this study was to survey corresponding authors in published medical journals to determine their opinion on publication impact in relation to performance review and promotion. Methods Cross-sectional survey of corresponding authors of original research articles published in June 2007 among 72 medical journals. Measurement outcomes included the number of publications, number of authors, authorship order and journal impact factor in relation to performance review and promotion. Results Of 687 surveys, 478 were analyzed (response rate 69.6%). Corresponding authors self-reported that number of publications (78.7%), journal impact factor (67.8%) and being the first author (75.9%) were most influential for their annual performance review and assessment. Only 17.6% of authors reported that the number of authors on a manuscript was important criteria for performance review and assessment. A higher percentage of Asian authors reported that the number of authors was key to performance review and promotion (41.4% versus 7.8 to 22.2%). compared to authors from other countries. Conclusions The number of publications, authorship order and journal impact factor were important factors for performance reviews and promotion at academic and non-academic institutes. The number of authors was not identified as important criteria. These factors may be contributing to the increase in the number of authors per publication.

Abstract Background The aim of this study was to determine whether South Asian patients with diabetes have a worse prognosis following hospitalization for acute myocardial infarction (AMI) compared with their White counterparts. We measured the risk of developing a composite cardiovascular outcome of recurrent AMI, congestive heart failure (CHF) requiring hospitalization, or death, in these two groups. Methods Using hospital administrative data, we performed a retrospective cohort study of 41,615 patients with an incident AMI in British Columbia and the Calgary Health Region between April 1, 1995, and March 31, 2002. South Asian ethnicity was determined using validated surname analysis. Baseline demographic characteristics and co-morbidities were included in Cox proportional hazard models to compare time to reaching the composite outcome and its individual components. Results Among the AMI cohort, 29.7% of South Asian patients and 17.6% of White patients were identified as having diabetes (n = 7416). There was no significant difference in risk of developing the composite cardiovascular outcome (Hazard Ratio = 0.90, 95% CI = 0.80-1.01). However, South Asian patients had significantly lower mortality at long term follow-up (HR = 0.62, 95% CI = 0.51-0.74) compared to their White counterparts. Conclusions Following hospitalization for AMI, South Asian patients with diabetes do not have a significantly different long term risk of a composite cardiovascular outcome compared to White patients with diabetes. While previous research has suggested worse cardiovascular outcomes in the South Asian population, we found lower long-term mortality among South Asians with diabetes following AMI.

Abstract Background Observational outcome studies of patients with obstructive sleep apnea (OSA) require adjustment for co-morbidity to produce valid results. The aim of this study was to evaluate whether the combination of administrative data and self-reported data provided a more complete estimate of co-morbidity among patients referred for sleep diagnostic testing. Methods A retrospective observational study of 2149 patients referred for sleep diagnostic testing in Calgary, Canada. Self-reported co-morbidity was obtained with a questionnaire; administrative data and validated algorithms (when available) were also used to define the presence of these co-morbid conditions within a two-year period prior to sleep testing. Results Patient self-report of co-morbid conditions had varying levels of agreement with those derived from administrative data, ranging from substantial agreement for diabetes (κ = 0.79) to poor agreement for cardiac arrhythmia (κ = 0.14). The enhanced measure of co-morbidity using either self-report or administrative data had face validity, and provided clinically meaningful trends in the prevalence of co-morbidity among this population. Conclusion An enhanced measure of co-morbidity using self-report and administrative data can provide a more complete measure of the co-morbidity among patients with OSA when agreement between the two sources is poor. This methodology will aid in the adjustment of these coexisting conditions in observational studies in this area.

Abstract Background Risk adjustment and mortality prediction in studies of critical care are usually performed using acuity of illness scores, such as Acute Physiology and Chronic Health Evaluation II (APACHE II), which emphasize physiological derangement. Common risk adjustment systems used in administrative datasets, like the Charlson index, are entirely based on the presence of co-morbid illnesses. The purpose of this study was to compare the discriminative ability of the Charlson index to the APACHE II in predicting hospital mortality in adult multisystem ICU patients. Methods This was a population-based cohort design. The study sample consisted of adult (>17 years of age) residents of the Calgary Health Region admitted to a multisystem ICU between April 2002 and March 2004. Clinical data were collected prospectively and linked to hospital outcome data. Multiple regression analyses were used to compare the performance of APACHE II and the Charlson index. Results The Charlson index was a poor predictor of mortality (C = 0.626). There was minimal difference between a baseline model containing age, sex and acute physiology score (C = 0.74) and models containing either chronic health points (C = 0.76) or Charlson index variations (C = 0.75, 0.76, 0.77). No important improvement in prediction occurred when the Charlson index was added to the full APACHE II model (C = 0.808 to C = 0.813). Conclusion The Charlson index does not perform as well as the APACHE II in predicting hospital mortality in ICU patients. However, when acuity of illness scores are unavailable or are not recorded in a standard way, the Charlson index might be considered as an alternative method of risk adjustment and therefore facilitate comparisons between intensive care units.

Abstract Background Kappa is commonly used when assessing the agreement of conditions with reference standard, but has been criticized for being highly dependent on the prevalence. To overcome this limitation, a prevalence-adjusted and bias-adjusted kappa (PABAK) has been developed. The purpose of this study is to demonstrate the performance of Kappa and PABAK, and assess the agreement between hospital discharge administrative data and chart review data conditions. Methods The agreement was compared for random sampling, restricted sampling by conditions, and case-control sampling from the four teaching hospitals in Alberta, Canada from ICD10 administrative data during January 1, 2003 and June 30, 2003. A total of 4,008 hospital discharge records and chart view, linked for personal unique identifier and admission date, for 32 conditions of random sampling were analyzed. The restricted sample for hypertension, myocardial infarction and congestive heart failure, and case-control sample for those three conditions were extracted from random sample. The prevalence, kappa, PABAK, positive agreement, negative agreement for the condition was compared for each of three samples. Results The prevalence of each condition was highly dependent on the sampling method, and this variation in prevalence had a significant effect on both kappa and PABAK. PABAK values were obviously high for certain conditions with low kappa values. The gap between these two statistical values for the same condition narrowed as the prevalence of the condition approached 50%. Conclusion Kappa values varied more widely than PABAK values across the 32 conditions. PABAK values should usually not be interpreted as measuring the same agreement as kappa in administrative data, particular for the condition with low prevalence. There is no single statistic measuring agreement that captures the desired information for validity of administrative data. Researchers should report kappa, the prevalence, positive agreement, negative agreement, and the relative frequency in each cell (i.e. a, b, c and d) to enable the reader to judge the validity of administrative data from multiple aspects.

Abstract Background Under the current healthcare system in China, there is no government-sponsored health insurance program for children. Children from families who move from rural and interior regions to large urban centres without a valid residency permit might be at higher risk of being uninsured due to their low socioeconomic status. We conducted a survey in Shanghai to describe children's health insurance coverage according to their migration status. Method Between 2005 and 2006, we conducted an in-person health survey of the adult care-givers of children aged 7 and under, residing in five districts of Shanghai. We compared uninsurance rates between temporary and permanent child residents, and investigated factors associated with child health uninsurance. Results Even though cooperative insurance eligibility has been extended to temporary residents of Shanghai, the uninsurance rate was significantly higher among temporary (65.6%) than permanent child residents (21.1%, adjusted odds ratio (OR): 5.85, 95% confidence interval (95% CI): 4.62–7.41). For both groups, family income was associated with having child health insurance; children in lower income families were more likely to be uninsured (OR: 1.96, 95% CI: 1.40–2.96). Conclusion Children must rely on their parents to make the insurance purchase decision, which is constrained by their income and the perceived benefits of the insurance program. Children from migrant families are at even higher risk for uninsurance due to their lower socioeconomic status. Government initiatives specifically targeting temporary residents and providing health insurance benefits for their children are urgently needed.

Abstract Background With rapid economic growth and globalization, lifestyle in China has been changing dramatically. This study aimed to describe the male and female adult Chinese population health status. Methods The Chinese Third National Health Services Survey was conducted in 2003 to collect information about health status and quality of life from randomly selected residents. Of the 193,689 respondents to the survey (response rate 77.8%), 139,831 (69,748 male and 70,083 female) respondents who were 18 years of age or older were analyzed. Results Among the respondents, fewer males than females rated their overall wellbeing as being poor or very poor (4.8% versus 6.2%), reported illness in the last 2 weeks (14.1% versus 17.4%), presence of physician diagnosed chronic disease (15.0% versus 17.7%) and at least one functional problem in seven items of the quality of life (26.9% versus 32.8%). More males than females were currently smoking (52.4% versus 3.4%) and drank alcohol more than three times per week (16.5% versus 1.1%). Physically inactive rate was similar between males and females (85.8% versus 87.0%). Fewer rural respondents reported chronic disease than urban respondents (13.0% versus 19.9% for males and 15.5% versus 22.8% for females). In all seven items of the quality of life measured, rural respondents reported less problems than urban respondents (26.2% versus 28.7% for males and 32.0% versus 34.7% for females). Conclusion Males had better health status than females in terms of self-perceived wellbeing, presence of illness, chronic disease, and quality of life. However, smoking and frequent alcohol drinking was more prevalent among males than that among females. In contrast with the social-economic gradient in health commonly found in the literature, the wealthier urban population in China was not found to be healthier than the rural population in terms of physician diagnosed chronic disease.

Abstract Background The lycophyte Selaginella moellendorffii is a vascular plant that diverged from the fern/seed plant lineage at least 400 million years ago. Although genomic information for S. moellendorffii is starting to be produced, little is known about basic aspects of its molecular biology. In order to provide the first glimpse to the epigenetic landscape of this early divergent vascular plant, we used the methylation filtration technique. Methylation filtration genomic libraries select unmethylated DNA clones due to the presence of the methylation-dependent restriction endonuclease McrBC in the bacterial host. Results We conducted a characterization of the DNA methylation patterns of the S. moellendorffii genome by sequencing a set of S. moellendorffii shotgun genomic clones, along with a set of methylation filtered clones. Chloroplast DNA, which is typically unmethylated, was enriched in the filtered library relative to the shotgun library, showing that there is DNA methylation in the extremely small S. moellendorffii genome. The filtered library also showed enrichment in expressed and gene-like sequences, while the highest-copy repeats were largely under-represented in this library. These results show that genes and repeats are differentially methylated in the S. moellendorffii genome, as occurs in other plants studied. Conclusion Our results shed light on the genome methylation pattern in a member of a relatively unexplored plant lineage. The DNA methylation data reported here will help understanding the involvement of this epigenetic mark in fundamental biological processes, as well as the evolutionary aspects of epigenetics in land plants.

Abstract Background Symptoms tend to occur in what have been called symptom clusters. Early symptom cluster research was imprecise regarding the causal foundations of the coordinations between specific symptoms, and was silent on whether the relationships between symptoms remained stable over time. This study develops a causal model of the relationships between symptoms in cancer palliative care patients as they approach death, and investigates the changing associations among the symptoms and between those symptoms and well-being. Methods Complete symptom assessment scores were obtained for 82 individuals from an existing palliative care database. The data included assessments of pain, anxiety, nausea, shortness of breath, drowsiness, loss of appetite, tiredness, depression and well-being, all collected using the Edmonton Symptom Assessment System (ESAS). Relationships between the symptoms and well-being were investigated using a structural equation model. Results The model fit acceptably and explained between 26% and 83% of the variation in appetite, tiredness, depression, and well-being. Drowsiness displayed consistent effects on appetite, tiredness and well-being. In contrast, anxiety's effect on well-being shifted importantly, with a direct effect and an indirect effect through tiredness at one month, being replaced by an effect working exclusively through depression at one week. Conclusion Some of the causal forces explaining the variations in, and relationships among, palliative care patients' symptoms changed over the final month of life. This illustrates how investigating the causal foundations of symptom correlation or clustering can provide more detailed understandings that may contribute to improved control of patient comfort, quality of life, and quality of death.

Abstract Background We have previously described a method for dealing with missing data in a prospective cardiac registry initiative. The method involves merging registry data to corresponding ICD-9-CM administrative data to fill in missing data 'holes'. Here, we describe the process of translating our data merging solution to ICD-10, and then validating its performance. Methods A multi-step translation process was undertaken to produce an ICD-10 algorithm, and merging was then implemented to produce complete datasets for 1995–2001 based on the ICD-9-CM coding algorithm, and for 2002–2005 based on the ICD-10 algorithm. We used cardiac registry data for patients undergoing cardiac catheterization in fiscal years 1995–2005. The corresponding administrative data records were coded in ICD-9-CM for 1995–2001 and in ICD-10 for 2002–2005. The resulting datasets were then evaluated for their ability to predict death at one year. Results The prevalence of the individual clinical risk factors increased gradually across years. There was, however, no evidence of either an abrupt drop or rise in prevalence of any of the risk factors. The performance of the new data merging model was comparable to that of our previously reported methodology: c-statistic = 0.788 (95% CI 0.775, 0.802) for the ICD-10 model versus c-statistic = 0.784 (95% CI 0.780, 0.790) for the ICD-9-CM model. The two models also exhibited similar goodness-of-fit. Conclusion The ICD-10 implementation of our data merging method performs as well as the previously-validated ICD-9-CM method. Such methodological research is an essential prerequisite for research with administrative data now that most health systems are transitioning to ICD-10.

Abstract Background The performance of the Charlson and Elixhauser comorbidity measures in predicting patient outcomes have been well validated with ICD-9 data but not with ICD-10 data, especially in disease specific patient cohorts. The objective of this study was to assess the performance of these two comorbidity measures in the prediction of in-hospital and 1 year mortality among patients with congestive heart failure (CHF), diabetes, chronic renal failure (CRF), stroke and patients undergoing coronary artery bypass grafting (CABG). Methods A Canadian provincial hospital discharge administrative database was used to define 17 Charlson comorbidities and 30 Elixhauser comorbidities. C-statistic values were calculated to evaluate the performance of two measures. One year mortality information was obtained from the provincial Vital Statistics Department. Results The absolute difference between ICD-9 and ICD-10 data in C-statistics ranged from 0 to 0.04 across five cohorts for the Charlson and Elixhauser comorbidity measures predicting in-hospital or 1 year mortality. In the models predicting in-hospital mortality using ICD-10 data, the C-statistics ranged from 0.62 (for stroke) – 0.82 (for diabetes) for Charlson measure and 0.62 (for stroke) to 0.83 (for CABG) for Elixhauser measure. Conclusion The change in coding algorithms did not influence the performance of either the Charlson or Elixhauser comorbidity measures in the prediction of outcome. Both comorbidity measures were still valid prognostic indicators in the ICD-10 data and had a similar performance in predicting short and long term mortality in the ICD-9 and ICD-10 data.

Abstract Background Acetaminophen overdose (AO) is the most common cause of acute liver failure. We examined temporal trends and sociodemographic risk factors for AO in a large Canadian health region. Methods 1,543 patients hospitalized for AO in the Calgary Health Region (population ~1.1 million) between 1995 and 2004 were identified using administrative data. Results The age/sex-adjusted hospitalization rate decreased by 41% from 19.6 per 100,000 population in 1995 to 12.1 per 100,000 in 2004 (P < 0.0005). This decline was greater in females than males (46% vs. 29%). Whereas rates fell 46% in individuals under 50 years, a 50% increase was seen in those ≥ 50 years. Hospitalization rates for intentional overdoses fell from 16.6 per 100,000 in 1995 to 8.6 per 100,000 in 2004 (2004 vs. 1995: rate ratio [RR] 0.49; P < 0.0005). Accidental overdoses decreased between 1995 and 2002, but increased to above baseline levels by 2004 (2004 vs. 1995: RR 1.24;P < 0.0005). Risk factors for AO included female sex (RR 2.19; P < 0.0005), Aboriginal status (RR 4.04; P < 0.0005), and receipt of social assistance (RR 5.15; P < 0.0005). Conclusion Hospitalization rates for AO, particularly intentional ingestions, have fallen in our Canadian health region between 1995 and 2004. Young patients, especially females, Aboriginals, and recipients of social assistance, are at highest risk.