bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporary ICUs during the COVID-19 pandemic first wave: description of the cohort at a French centre
Authors: Zappella Nathalie , Dirani Chadi , Lortat Jacob Brice , Tanaka Sébastien , Kantor Elie , El Kalai Adnan , Rkik Yassine , Gouel Cheron Aurélie , Tran Dinh Alexy , Montravers Philippe
Published: October 2022

Background

During the COVID-19 first wave in France, the capacity of intensive care unit (ICU) beds almost doubled, mainly because of the opening of temporary ICUs with staff and equipment from anaesthesia.

Objectives

We aim to investigate if the initial management in temporary ICU is associated with a change in ICU mortality and short-term prognosis.

Design

Retrospective single-centre cohort study.

Setting

Surgical ICU of the Bichat Claude Bernard University Hospital during the COVID-19 “first wave” (from 18 March to 10 April 2020).

Patients

All consecutive patients older than 18 years of age with laboratory-confirmed SARS-CoV-2 infection and/or typical radiological patterns were included during their first stay in the ICU for COVID-19.

Intervention

Patients were admitted to a temporary ICU if no room was available in the classical ICU and if they needed invasive mechanical ventilation but no renal replacement therapy or Extracorporeal Membrane Oxygenation (ECMO) in the short term. The temporary ICUs were managed by mixed teams (from the ICU and anaesthesiology departments) following a common protocol and staff meetings.

Main outcome measure

ICU mortality

Results

Among the 59 patients admitted, 37 (62.7%) patients had initial management in the temporary ICU. They had the same characteristics on admission and the same medical management as patients admitted to the classical ICU. ICU mortality was similar in the 2 groups (32.4% in temporary ICUs versus 40.9% in classical ICUs; p=0.58). SAPS-II and ECMO use were associated with mortality in multivariate analysis but not admission to the temporary ICU.

Conclusion

In an overload context of the ICU of a geographical area, our temporary ICU model allowed access to intensive care for all patients requiring it without endangering them.
Knowledge, safety, and teamwork: a qualitative study on the experiences of anaesthesiologists and nurse anaesthetists working in the preanaesthesia assessment clinic
Authors: Kristoffersen Eirunn Wallevik , Opsal Anne , Tveit Tor Oddbjørn , Fossum Mariann
Published: October 2022

Background

The preanaesthesia assessment clinic (PAC) has been shown to contribute to safe anaesthesia assessment in hospitals. In the PAC, patients are assessed with an interview and can also ask relevant questions about anaesthesia. The intention is to ensure that patients are comprehensively prepared for the surgery and hospital stay. Although earlier studies have assessed the effects of PAC, attitudes and satisfaction of the healthcare personnel working in PAC remain unknown. Thus, this study aimed to examine the experiences of anaesthesiologists and nurse anaesthetists working in PACs as well as to explore barriers and facilitators in this context.

Methods

A descriptive qualitative approach was used to explore the experiences of anaesthesiologists and nurse anaesthetists working in PACs. Thirteen semi-structured interviews were conducted using face-to-face, telephone, or digital platforms in five hospitals in west, south, and north Norway between 2020 and 2021. The interviews were transcribed and thematically analysed according to Braun and Clarke’s six-steps semantic reflexive analysis.

Results

Four themes and nine subthemes were identified through an active analysis process, including developing competence in clinical anaesthesia practice, identifying barriers and facilitators influencing collaboration and teamwork, improving patient safety and outcomes through structured assessment, and identifying other organisational factors affecting the delivery of healthcare to surgical patients.

Conclusions

Working in the PAC contributed to competence development among the personnel. Additionally, teamwork was considered important for the proper functioning of the PAC. Patient safety was perceived as improved owning to the structured assessment in PAC, with patients getting the opportunity to improve their knowledge and being more involved in the upcoming anaesthesia.
The influence of baseline characteristics, treatment and depression on health-related quality of life in patients with multiple myeloma: a prospective observational study
Authors: Fischer Julia , Knop Stefan , Danhof Sophia , Einsele Hermann , Keller Daniela , Löffler Claudia
Published: October 2022

Background

Multiple myeloma (MM) is the third most common hematologic malignancy with increasing importance due to improving treatment strategies and long-term outcomes in an aging population. This study aims to analyse influencing factors on health-related quality of life (HRQoL), such as treatment strategies, participation in a clinical trial and patient characteristics like anxiety, depression, gender, and age. A better understanding of the individual factors in context with HRQoL could provide a helpful instrument for clinical decisions.

Methods

In this prospective observational study, the HRQoL of MM patients with different therapies (first-line and relapse) was quantified by standardized questionnaires (EORTC QLQ-C30 and -MY20) in the context of sociodemographic data, individual anxiety and depressiveness (PHQ-4), and a selected number of clinical parameters and symptoms at defined time-points before, during, and after therapy.

Results

In total, 70 patients were included in the study. The median age of the study cohort was 62 years. 44% were female and 56% were male patients. More than half of the patients were fully active with an ECOG 0. Global health status was significantly higher in patients with first-line treatment and even increased after start of therapy, while the pain level decreased. In contrast, patients with relapsed MM reported a decreasing global health status and increasing pain. Additionally, there was a higher global health status in less anxious/depressive patients. HRQoL decreased significantly after start of chemotherapy in the parameters body image, side effects of treatment, and cognitive functioning. Tandem stem-cell transplantation was not found to be a risk factor for higher impairment of HRQoL. Participation in a clinical study led to an improvement of most aspects of HRQoL. Among others, increased anxiety and depression, female gender, older age, impaired performance status, and recurrent disease can be early indicators for a reduced HRQoL.

Conclusion

This study showed the importance of regular longitudinal assessments of patient reported outcomes (PROs) in routine clinical care. For the first time, to our knowledge, we were able to demonstrate a potential impact between participation in clinical trials and HRQoL. However, due to frequently restrictive inclusion criteria for clinical trials, these MM patients might not be directly comparable with patients treated within standard therapy concepts. Further studies are needed to clarify the relevance of this preliminary data in order to develop an individualized, patient-centred, therapy concept.
Time to appropriate antimicrobial therapy serves an independent prognostic indicator in children with nosocomial Klebsiella pneumoniae bloodstream infection
Authors: Cheng Jie , Li Qinyuan , Zhang Guangli , Xu Huiting , Li Yuanyuan , Tian Xiaoyin , Chen Dapeng , Luo Zhengxiu
Published: October 2022

We tend to investigate the connection between time to appropriate therapy (TTAT) and prognosis in pediatric patients with nosocomial Klebsiella pneumoniae (K. pneumoniae) bloodstream infection, and find the optimal cutoff point for the empirical administration of antimicrobials. This retrospective study was conducted in Children’s Hospital of Chongqing Medical University, and inpatients with nosocomial K. pneumoniae bloodstream infection were finally enrolled. We applied the Classification and Regression Tree (CART) analysis to find the TTAT cutoff point and the Logistic Regression analysis to evaluate prognostic indicators. The incidence of septic shock and mortality was 17.91% (12/67) and 13.43% (9/67), respectively. The CART-derived TTAT cutoff point was 10.7 h. The multivariate logistic regression analysis indicated delayed therapy (TTAT ≥ 10.7 h), pediatric risk of mortality (PRISM) III scores ≥ 10, time to positivity (TTP) ≤ 13 h, and requiring for invasive mechanical ventilation were independently associated with the incidence of septic shock (Odds ratio [OR] 9.87, 95% Confidence interval [CI] 1.46–66.59, P = 0.019; OR 9.69, 95% CI 1.15–81.39, P = 0.036; OR 8.28, 95% CI 1.37–50.10, P = 0.021; OR 6.52, 95% CI 1.08–39.51, P = 0.042; respectively) and in-hospital mortality (OR 22.19, 95% CI 1.25–393.94, P = 0.035; OR 40.06, 95% CI 2.32–691.35, P = 0.011; OR 22.60, 95% CI 1.78–287.27, P = 0.016; OR 12.21, 95% CI 1.06–140.67, P = 0.045; respectively).

Conclusions TTAT is an independent predictor of poor outcomes in children with nosocomial K. pneumoniae bloodstream infection. Initial appropriate antimicrobial therapy should be administrated timely and within 10.7 h from the onset of bloodstream infection is recommended.
The impact of an unemployment insurance reform on incidence rates of hospitalisation due to alcohol-related disorders: a quasi-experimental study of heterogeneous effects across ethnic background, educational level, employment status, and sex in Sweden
Authors: Almquist Ylva B. , Miething Alexander
Published: October 2022

Background

Many Western countries have scaled back social and health expenditure, including decreases in the generosity and coverage of unemployment insurance, resulting in negative effects on general health and well-being at the aggregate level. Yet, research has not sufficiently looked into heterogeneity of such effects across different subgroups of the population. In Sweden, the 2006 unemployment insurance reform, implemented on the 1st of January 2007, encompassed a drastic increase of insurance fund membership fees, reduced benefit levels, and stricter eligibility requirements. As this particularly affected already socioeconomically disadvantaged groups in society, such as foreign-born and low-educated individuals, the current study hypothesise that the reform would also have a greater impact on health outcomes in these groups.

Methods

Based on register data for the total population, we utilise a quasi-experimental approach to investigate heterogeneous health effects of the reform across ethnic background, educational level, employment status, and sex. Due to behaviourally caused diseases having a relatively shorter lag time from exposure, hospitalisation due to alcohol-related disorders serves as the health outcome. A series of regression discontinuity models are used to analyse monthly incidence rates of hospitalisation due to alcohol-related disorders among individuals aged 30–60 during the study period (2001–2012), with the threshold set to the 1st of January 2007.

Results

The results suggest that, in general, there was no adverse effect of the reform on incidence rates of hospitalisation due to alcohol-related disorders. A significant increase is nonetheless detected among the unemployed, largely driven by Swedish-born individuals with Swedish-born or foreign-born parents, low-educated individuals, and men.

Conclusions

We conclude that the Swedish 2006 unemployment insurance reform generally resulted in increasing incidence rates of hospitalisation due to alcohol-related disorders among unemployed population subgroups known to have higher levels of alcohol consumption.
Cholelithiasis increased prostate cancer risk: evidence from a case–control study and a meta-analysis
Authors: Li Ya-Dong , Ren Zheng-Ju , Gao Liang , Ma Jun-Hao , Gou Yuan-Qing , Tan Wei , Liu Chuan
Published: October 2022

Introduction

Cholelithiasis represents a known risk factor for digestive system neoplasm. Few studies reported the association between cholelithiasis and the risk of prostate cancer (PCa), and the results were controversial.

Methods

We reviewed the medical records of the Second Affiliated Hospital of Chongqing Medical University Hospital to perform a retrospective matched case–control study, which included newly diagnosed 221 PCa patients and 219 matched controls. Logistic regression was applied to compare cholelithiasis exposure and adjusted for confounding factors. Additionally, we conducted a meta-analysis pooling this and published studies further to evaluate the association between cholelithiasis and PCa risk. Related ratio (RR) and 95% confidence interval (95%CI) were used to assess the strength of associations.

Results

Our case–control study showed that cholelithiasis was associated with a higher incidence of PCa (OR = 1.87, 95% CI: 1.06–3.31) after multivariable adjustment for covariates. The incidence of PCa was increased in patients with gallstones but not cholecystectomy. 7 studies involving 80,403 individuals were included in the meta-analysis. Similarly, the results demonstrated that cholelithiasis was associated with an increased risk of PCa (RR = 1.35, 95%CI: 1.17–1.56) with moderate-quality evidence. Cholelithiasis patients with low BMI increased the PCa incidence. Moreover, Subgroup analysis based on region showed that cholelithiasis was associated with PCa in Europe (RR = 1.24, 95%CI 1.03–1.51) and Asia (RR = 1.32, 95%CI 1.24–1.41).

Conclusions

The results suggested an association between cholelithiasis and the risk of PCa. There was no significant relationship between cholecystectomy therapy and PCa risk. Further cohort studies should be conducted to demonstrate the results better.
Detection of soluble urokinase type plasminogen activator receptors in children with gingivitis and normal subjects
Authors: El‑Patal Mohamed Abd‑Ellatif , Khalil Mona A. , Shipl Walaa , Barakat Ibrahim , Youssef Eman M. I. , El Attar Shahinaz , Fathi Adel , Abdallah Alaa A.
Published: October 2022

Background

Gingivitis is a reversible condition; however, if left untreated, it progresses to periodontitis, which a serious infection that leads to bone destruction. Soluble urokinase-type plasminogen activator receptor (suPAR) measurement may be of value in the early assessment of gingivitis in children, thereby minimizing risk of tooth loss.

Objectives

In this observational study, we assessed salivary and serum concentrations of suPAR for the diagnosis of gingivitis and correlation of salivary suPAR with the periodontal clinical parameters.

Methods

Ninety children participated in the study, with 20 healthy subjects as controls and 70 patients with gingivitis. The gingivitis group was divided into mild, moderate, and severe cases. According to the gingival index (GI), salivary and serum samples were analyzed for the suPAR and C-reactive protein levels using an enzyme-linked immunosorbent assay.

Results

The salivary suPAR was significantly higher in patients with gingivitis (10.8 ± 2.9 ng/mL) than in the control group (7.0 ± 1.1 ng/mL) as P < 0.001. SuPAR was correlated with gingivitis severity. It was 7.7 ± 1.5 1 ng/mL in mild cases, 10.9 ± 1.2 ng/mL in moderate cases, and 14.4 ± 0.9 ng/mL in severe cases. The difference was significantly high (P < 0.001) between the groups; however, the difference between the mild cases and the control was nonsignificant as P < 0.066. The salivary suPAR was correlated with periodontal clinical parameters, which included GI and simple oral hygiene index (SOHI). Conversely the serum suPAR was not correlated with the salivary suPAR or the periodontal clinical parameters.

Conclusion

The results of the present study demonstrated that the salivary suPAR is increased in proportionate with the degree of severity of gingivitis in children. Moreover, salivary suPAR was correlated with the periodontal clinical parameters.
Effect of pelvic floor muscle training using mobile health applications for stress urinary incontinence in women: a systematic review
Authors: Hou Yuqing , Feng Suwen , Tong Baoqin , Lu Shuping , Jin Ying
Published: October 2022

Background

Pelvic floor muscle training (PFMT) is the first-line treatment for urinary incontinence, but adherence to PFMT is generally poor. Currently, a number of novel strategies exist to facilitate adherence of PFMT. We sought to determine effectiveness of mHealth app-based PFMT for treating stress urinary incontinence (SUI) or stress-predominant mixed urinary incontinence (MUI) in women. The primary objective was to assess the effects of mHealth app-based PFMT and usual treatment on severity of the symptom, the quality of life (QoL) of users and the patient’s global impression of improvement. The secondary objective was to assess how mHealth app use affects adherence of PFMT.

Methods

All randomized controlled trials and quasi-randomized controlled trials aimed at evaluating the effects of mHealth app-based PFMT in women with SUI or stress-predominant MUI were included. Twelve electronic databases, namely the Cochrane Library, PubMed, CINAHL, Embase, Web of science, OVID, SciELO, REHABDATA, PEDro database, Chinese CNKI and Wanfang and the Open Grey databases were used as search sources. The protocol was registered in PROSPERO (CRD 42020183515). This systematic review was developed following the PRISMA 2020 Checklist. The Cochrane Handbook for Systematic Reviews of Interventions for Randomized Controlled Trials was used to assess risk of bias in included studies. Two authors extracted the data into a standardized spreadsheet.

Results

Six studies that met the eligibility criteria were included. The full sample included 439 patients with treatment via mHealth app and 442 controls of usual treatment. ICIQ-UI SF, ICIQ-VS, and QUID scores decreased after follow-up in the mHealth app and control groups in six studies. ICIQ-LUTS QoL scores decreased after follow-up in the mHealth app and control groups in three studies. In only one study, ICIQ-VS QoL scores decreased after 1 month and 2 months of follow-up in the mHealth app group, but increased abruptly after 3 months of follow-up. EQ5D-VAS scores increased in both groups in one study. The percentage of PGI-I increased in the mHealth app group in three studies after follow-up. After follow-up in three studies, BPMSES scores and self-reported adherence scores increased in the mHealth app group relative to the initial time point, but in one study, at 6 months compared with 3 months of follow-up, adherence scores decreased slightly in the mHealth app group.

Conclusions

This systematic review determined that mHealth app-based PFMT showed promise from the perspective of improving both outcomes and exercise adherence.
Construction and validation of a revised satisfaction index model for the Chinese urban and rural resident-based basic medical insurance scheme
Authors: Cheng Wenwei , Wang Shiwen , Liu Xiaofang , Wu Yanyan , Cheng Jin , Sun Weichu , Yan Xiaofang , Wang Qi , Peng Liai , Liu Xiaoli , Sha Tingting , Shi Jingcheng , Yang Fang
Published: October 2022

Background

Quality is the most important factor in satisfaction. However, the existing satisfaction index model of urban and rural resident-based basic medical insurance scheme (SIM_URRBMI) lacks the segmentation of perceived quality elements, it couldn’t provide a reference for quality improvement and satisfaction promotion. This study aims to construct a revised SIM_URRBMI that can accurately and detailly measure perceived quality and provide feasible and scientific suggestions for improving the satisfaction of urban and rural residents' basic medical insurance scheme (URRBMI) in China.

Methods

Based on the theoretical framework of the American Customer Satisfaction Index, the elements of perceived quality were refined through literature review and expert consultation, and a pool of alternative measurement variables was formed. A three-stage randomized stratified cluster sampling was adopted. The main decision makers of URRBMI in the families of primary school students in 8 primary schools in Changsha were selected. Both the classic test theory and the item response theory were used for measurement variables selection. The reliability and validity of the model were tested by partial least squares (PLS)-related methods.

Results

A total of 1909 respondents who had URRBMI for their children were investigated. The SIM_URRBMI1.0 consists of 11 latent variables and 28 measurement variables with good reliability and validity. Among the three explanatory variables of public satisfaction, perceived quality had the largest total effect (path coefficient) (0.737). The variable with the greatest effect among the five first-order latent variables on perceived quality was the quality of the medical insurance policy (0.472).

Conclusions

The SIM_URRBMI1.0 consists of 28 measurement variables and 11 latent variables. It is a reliable, valid, and standard satisfaction measurement tool for URRBMI with good prediction ability for public satisfaction. In addition, the model provides an accurate evaluation of the perceived quality, which will greatly help with performance improvement diagnosis. The most critical aspects of satisfaction improvement are optimizing the scope and proportion of reimbursement as well as setting appropriate level of deductible and capitation of URRBMI.
Changes in health care utilization and financial protection after integration of the rural and urban social health insurance schemes in Beijing, China
Authors: Shi Zhenyu , He Ping , Zhu Dawei , Lu Feng , Meng Qingyue
Published: October 2022

Background

China expanded health coverage to residents in informal economic sectors by the rural new cooperative medical scheme (NCMS) for rural population and urban resident basic medical insurance scheme (URBMI) for non-working urban residents. Fragmentation of resident social health insurance schemes exacerbated the health inequity and China started the integration of urban and rural resident medical insurance schemes since 2016. Beijing finished the insurance integration in 2017 and has been implementing a unified urban and rural resident basic medical insurance scheme (URRBMI) since the beginning of 2018. This study aims to examine changes in health care utilization and financial protection after integration of the rural and urban social health insurance schemes.

Methods

We used household survey data from Beijing Health Services Survey in 2013 and 2018. Respondents who were 15 or older and covered by URBMI, NCMS or URRBMI were included in this study. Our study finally included 8,554 individuals in 2013 and 6,973 individuals in 2018, about 70% of which were rural residents in each year. Descriptive analysis was used to compare the healthcare utilization, healthcare expenditure and incidence of catastrophic health expenditure between different groups. A series of two-part regression models were used to analyze the changes of healthcare utilization, healthcare expenditure and incidence of catastrophic health expenditure.

Results

From 2013 to 2018, urban–rural disparity in outpatient care utilization seemed widened because urban residents’ utilization of outpatient care increased 131% while rural residents’ utilization only increased 72%; both rural and urban residents’ spending on outpatient care increased about 50%. Utilization of inpatient care changed little and poor residents still used significantly less inpatient care compared with the rich residents. Poor residents still suffered heavily catastrophic health expenditures.

Conclusion

From 2013 to 2018, residents’ utilization of healthcare, especially outpatient care, increased in Beijing. Health insurance reforms increased residents’ utilization of healthcare but failed to reduce their healthcare financial burden, especially for poor people. Our study advocates more pro-poor insurance policies and more efforts on the efficiency of health system.
Plasmodium pitheci malaria in Bornean orang-utans at a rehabilitation centre in West Kalimantan, Indonesia
Authors: Sanchez Karmele Llano , Greenwood Alex D. , Nielsen Aileen , Nugraha R. Taufiq P. , Prameswari Wendi , Nurillah Andini , Agustina Fitria , Campbell-Smith Gail , Dharmayanthi Anik Budhi , Pratama Rahadian , Exploitasia Indra , Baird J. Kevin
Published: October 2022

Background

Plasmodial species naturally infecting orang-utans, Plasmodium pitheci and Plasmodium silvaticum, have been rarely described and reportedly cause relatively benign infections. Orang-utans at Rescue Rehabilitation Centres (RRC) across the orang-utan natural range suffer from malaria illness. However, the species involved and clinical pathology of this illness have not been described in a systematic manner. The objective of the present study was to identify the Plasmodium species infecting orang-utans under our care, define the frequency and character of malaria illness among the infected, and establish criteria for successful diagnosis and treatment.

Methods

During the period 2017–2021, prospective active surveillance of malaria among 131 orang-utans resident in a forested RRC in West Kalimantan (Indonesia) was conducted. A total of 1783 blood samples were analysed by microscopy and 219 by nucleic acid based (PCR) diagnostic testing. Medical records of inpatient orang-utans at the centre from 2010 to 2016 were also retrospectively analysed for instances of symptomatic malaria.

Results

Active surveillance revealed 89 of 131 orang-utans were positive for malaria at least once between 2017 and 2021 (period prevalence = 68%). During that period, 14 cases (affecting 13 orang-utans) developed clinical malaria (0.027 attacks/orang-utan-year). Three other cases were found to have occurred from 2010–2016. Sick individuals presented predominantly with fever, anaemia, thrombocytopenia, and leukopenia. All had parasitaemias in excess of 4000/μL and as high as 105,000/μL, with severity of illness correlating with parasitaemia. Illness and parasitaemia quickly resolved following administration of artemisinin-combined therapies. High levels of parasitaemia also sometimes occurred in asymptomatic cases, in which case, parasitaemia cleared spontaneously.

Conclusions

This study demonstrated that P. pitheci very often infected orang-utans at this RRC. In about 14% of infected orang-utans, malaria illness occurred and ranged from moderate to severe in nature. The successful clinical management of acute pitheci malaria is described. Concerns are raised about this infection potentially posing a threat to this endangered species in the wild.
Sero-prevalence of malaria and the knowledge, attitudes and practices relating to the prevention of malaria among indigenous people living in the central forest spine in Peninsular Malaysia: a mixed-methods study
Authors: Kader Maideen Siti Fatimah , Rashid Abdul , Ahmad Nur Indah , Zahari Siti Nur Afiqah , Hamat Rukman Awang
Published: October 2022

Background

Malaria is still a major public health threat in some parts of the world. Many countries are targeting to achieve malaria free status country. This study aimed to determine the sero-prevalence of malaria and the knowledge, attitudes and practices relating to the prevention of malaria among the indigenous adults living in the central forest spine in Peninsular Malaysia.

Methods

A mixed method study was conducted in indigenous settlements in 2020. Blood film for malaria parasite (BFMP) was used to diagnose malaria in this study. A structured questionnaire was used to collect data from the participants. For the qualitative data, in-depth interviews were conducted and data was collected until data saturation was reached. Multiple linear regression was used to determine the predictors after adjusting for confounders. A p-value of < 0.05 is considered as statistically significant. Meaningful statements from the in-depth interviews were assigned to the relevant codes using NVivo version 12 software.

Results

A total of 284 indigenous people participated in the study. The prevalence of malaria in this study was 0%. Those in the middle age group between 25 and 41 years and tested positive for malaria previously were significantly more likely to have better knowledge and attitude scores. Significant correlations were also observed between knowledge-attitude and knowledge-practice. For the qualitative results, most of the respondents were unsure of monkey malaria, but all were aware of human malaria.

Conclusion

The present study highlighted the absence of malaria in the study population and relatively good knowledge, attitudes and practices relating to the prevention of malaria.
Cooking or heating with solid fuels increased the all-cause mortality risk among mid-aged and elderly People in China
Authors: Yang Yuxiang , Liu Yang , Peng Luolan , Zhang Shuai , Yuan Changzheng , Li Wenyuan , Liu Zuyun , Ma Yanan
Published: October 2022

Background

Our study aimed to explore the associations between solid fuels burning for either heating or cooking and all-cause mortality based on 2859 participants from the China Health and Retirement Longitudinal Study during 2011–2018.

Methods

Logistic regression models were performed to estimate the risk for all-cause mortality between different types of fuels in the current longitudinal study. Furthermore, the combined impacts of applying solid fuels for both cooking and heating and the effect among those who switched types of fuels in cooking or heating during follow-up were also analyzed. Interaction and stratification analysis by covariables was applied further to explore the relationship between fuel burning and all-cause mortality.

Results

After full-adjustment, usage of solid fuels was associated with higher all-cause mortality (for heating: OR = 1.93, 95% CI = 1.25, 3.00; for cooking: OR = 1.76, 95% CI = 1.10, 2.82). Using solid fuels for both cooking and heating (OR = 2.36; 95% CI, 1.38, 4.03) was associated with a higher risk of all-cause mortality, while using solid fuels with a single purpose was not (OR = 1.52; 95% CI, 0.90, 2.55). Protective tendencies were detected in switching solid to clean fuel for cooking (OR = 0.62; 95% CI, 0.32, 1.17) and heating (OR = 0.62; 95% CI, 0.35, 1.10).

Conclusion

Either cooking or heating with solid fuels increases the risk of all-cause mortality among Chinese mid-aged and aging people in the urban area of China.
Evidence of transgenerational effects on autism spectrum disorder using multigenerational space-time cluster detection
Authors: Richards Steed Rebecca , Bakian Amanda V. , Smith Ken Robert , Wan Neng , Brewer Simon , Medina Richard , VanDerslice James
Published: October 2022

Background

Transgenerational epigenetic risks associated with complex health outcomes, such as autism spectrum disorder (ASD), have attracted increasing attention. Transgenerational environmental risk exposures with potential for epigenetic effects can be effectively identified using space-time clustering. Specifically applied to ancestors of individuals with disease outcomes, space-time clustering characterized for vulnerable developmental stages of growth can provide a measure of relative risk for disease outcomes in descendants.

Objectives

(1) Identify space-time clusters of ancestors with a descendent with a clinical ASD diagnosis and matched controls. (2) Identify developmental windows of ancestors with the highest relative risk for ASD in descendants. (3) Identify how the relative risk may vary through the maternal or paternal line.

Methods

Family pedigrees linked to residential locations of ASD cases in Utah have been used to identify space-time clusters of ancestors. Control family pedigrees of none-cases based on age and sex have been matched to cases 2:1. The data have been categorized by maternal or paternal lineage at birth, childhood, and adolescence. A total of 3957 children, both parents, and maternal and paternal grandparents were identified. Bernoulli space-time binomial relative risk (RR) scan statistic was used to identify clusters. Monte Carlo simulation was used for statistical significance testing.

Results

Twenty statistically significant clusters were identified. Thirteen increased RR (> 1.0) space-time clusters were identified from the maternal and paternal lines at a p-value < 0.05. The paternal grandparents carry the greatest RR (2.86–2.96) during birth and childhood in the 1950’s–1960, which represent the smallest size clusters, and occur in urban areas. Additionally, seven statistically significant clusters with RR < 1 were relatively large in area, covering more rural areas of the state.

Conclusion

This study has identified statistically significant space-time clusters during critical developmental windows that are associated with ASD risk in descendants. The geographic space and time clusters family pedigrees with over 3 + generations, which we refer to as a person’sgeographic legacy, is a powerful tool for studying transgenerational effects that may be epigenetic in nature. Our novel use of space-time clustering can be applied to any disease where family pedigree data is available.
CREB3L1 promotes tumor growth and metastasis of anaplastic thyroid carcinoma by remodeling the tumor microenvironment
Authors: Pan Zongfu , Xu Tong , Bao Lisha , Hu Xiaoping , Jin Tiefeng , Chen Jinming , Chen Jianqiang , Qian Yangyang , Lu Xixuan , li Lu , Zheng Guowan , Zhang Yiwen , Zou Xiaozhou , Song Feifeng , Zheng Chuanming , Jiang Liehao , Wang Jiafeng , Tan Zhuo , Huang Ping , Ge Minghua
Published: October 2022

Anaplastic thyroid carcinoma (ATC) is an extremely malignant type of endocrine cancer frequently accompanied by extrathyroidal extension or metastasis through mechanisms that remain elusive. We screened for the CREB3 transcription-factor family in a large cohort, consisting of four microarray datasets. This revealed that CREB3L1 was specifically up regulated in ATC tissues and negatively associated with overall survival of patients with thyroid cancer. Consistently, high expression of CREB3L1 was negatively correlated with progression-free survival in an independent cohort. CREB3L1 knockdown dramatically attenuated invasion of ATC cells, whereas overexpression of CREB3L1 facilitated the invasion of papillary thyroid carcinoma (PTC) cells. Loss of CREB3L1 inhibited metastasis and tumor growth of ATC xenografts in zebrafish and nude mouse model. Single-cell RNA-sequencing analysis revealed that CREB3L1 expression gradually increased during the neoplastic progression of a thyroid follicular epithelial cell to an ATC cell, accompanied by the activation of the extracellular matrix (ECM) signaling. CREB3L1 knockdown significantly decreased the expression of collagen subtypes in ATC cells and the fibrillar collagen in xenografts. Due to the loss of CREB3L1, ATC cells were unable to activate alpha-smooth muscle actin (α-SMA)-positive cancer-associated fibroblasts (CAFs). After CREB3L1 knockdown, the presence of CAFs inhibited the growth of ATC spheroids and the metastasis of ATC cells. Further cytokine array screening showed that ATC cells activated α-SMA-positive CAFs through CREB3L1-mediated IL-1α production. Moreover, KPNA2 mediated the nuclear translocation of CREB3L1, thus allowing it to activate downstream ECM signaling. These results demonstrate that CREB3L1 maintains the CAF-like property of ATC cells by activating the ECM signaling, which remodels the tumor stromal microenvironment and drives the malignancy of ATC.

Graphical Abstract
Spontaneous rectus sheath hematoma associated with apixaban in an elderly gentleman with chronic obstructive airway disease – a case report
Authors: Wong Cheuk-Lik , So Clarence Hao-Yu
Published: October 2022

Background

Rectus sheath hematoma (RSH) is a relatively uncommon cause of acute abdominal pain and can be mistaken as other surgical causes of acute abdomen. A diagnosis requires high index of suspicion especially in susceptible patients, for example, in patients on anticoagulation. While anticoagulation is the commonest risk factor for RSH, direct-acting oral anticoagulants have only been very recently implicated as a potential cause with fewer than ten cases reported in the literature.

Case presentation.

An 82-year-old Chinese man with chronic obstructive airway disease, ischemic heart disease, heart failure and atrial fibrillation on apixaban presenting with acute onset of lower abdominal pain. Physical examination showed peritoneal signs with tenderness and guarding over the lower quadrants with hypotension. Computed tomography (CT) of the abdomen confirmed a large rectus sheath hematoma (RSH) without active extravasation. He was given fluid resuscitation and was managed successfully with supportive treatment and cessation of apixaban. A follow-up CT two months later showed resolving hematoma and aspirin was resumed primarily for ischemic heart disease. The patient tolerated anti-platelet therapy without recurrence of RSH. The risk factors, treatment options, prognosis and issue related to anticoagulation resumption after an episode of RSH are discussed. Reported cases of RSH associated with direct-acting oral anticoagulants are reviewed.

Conclusions

Direct-acting oral anticoagulant-associated rectus sheath hematoma is rare. With increasing use of direct-acting oral anticoagulants in multiple clinical settings, clinicians should remain vigilant of this potentially life-threatening bleeding complication when a patient presents with acute abdominal pain. Conservative treatment with cessation of anti-coagulant and supportive transfusion remains the mainstay of treatment.
Incidence and severity prediction score of COVID-19 in people living with HIV (SCOVHIV): experience from the first and second waves of the pandemic in Indonesia
Authors: Yunihastuti Evy , Karjadi Teguh Harjono , Widhani Alvina , Mahdi Haridana Indah Setiawati , Sundari Salma , Hapsari Aljira Fitya , Koesnoe Sukamto , Djauzi Samsuridjal
Published: October 2022

Background

People living with HIV (PLHIV) have higher risk of COVID-19 infection and mortality due to COVID-19. Health professionals should be able to assess PLHIV who are more likely to develop severe COVID-19 and provide appropriate medical treatment. This study aimed to assess clinical factors associated with COVID-19 severity and developed a scoring system to predict severe COVID-19 infection among PLHIV.

Methods

This retrospective cohort study evaluated PLHIV at four hospitals diagnosed with COVID-19 during the first and second wave COVID-19 pandemic in Indonesia. The independent risk factors related to the severity of COVID-19 were identified with multivariate logistic regression.

Results

342 PLHIV were diagnosed with COVID-19, including 23 with severe-critical diseases. The cumulative incidence up to December 2021 was 0.083 (95% CI 0.074–0.092). Twenty-three patients developed severe-critical COVID-19, and the mortality rate was 3.2% (95% CI 1.61%–5.76%). Having any comorbidity, CD4 count of < 200 cells/mm3, not being on ART, and active opportunistic infection were independent risk factors for developing severe COVID-19. SCOVHIV score was formulated to predict severity, with 1 point for each item. A minimum score of 3 indicated a 58.4% probability of progressing to severe COVID-19. This scoring system had a good discrimination ability with the area under the curve (AUC) of 0.856 (95% CI 0.775–0.936).

Conclusion

SCOVHIV score, a four-point scoring system, had good accuracy in predicting COVID-19 severity in PLHIV.
VHHs as tools for therapeutic protein delivery to the central nervous system
Authors: Wouters Yessica , Jaspers Tom , Rué Laura , Serneels Lutgarde , De Strooper Bart , Dewilde Maarten
Published: October 2022

Background

The blood brain barrier (BBB) limits the therapeutic perspective for central nervous system (CNS) disorders. Previously we found an anti-mouse transferrin receptor (TfR) VHH (Nb62) that was able to deliver a biologically active neuropeptide into the CNS in mice. Here, we aimed to test its potential to shuttle a therapeutic relevant cargo. Since this VHH could not recognize the human TfR and hence its translational potential is limited, we also aimed to find and validate an anti-human transferrin VHH to deliver a therapeutic cargo into the CNS.

Methods

Alpaca immunizations with human TfR, and subsequent phage selection and screening for human TfR binding VHHs was performed to find a human TfR specific VHH (Nb188). Its ability to cross the BBB was determined by fusing it to neurotensin, a neuropeptide that reduces body temperature when present in the CNS but is not able to cross the BBB on its own. Next, the anti–β-secretase 1 (BACE1) 1A11 Fab and Nb62 or Nb188 were fused to an Fc domain to generate heterodimeric antibodies (1A11AM-Nb62 and 1A11AM-Nb188). These were then administered intravenously in wild-type mice and in mice in which the murine apical domain of the TfR was replaced by the human apical domain (hAPI KI). Pharmacokinetic and pharmacodynamic (PK/PD) studies were performed to assess the concentration of the heterodimeric antibodies in the brain over time and the ability to inhibit brain-specific BACE1 by analysing the brain levels of Aβ1–40.

Results

Selections and screening of a phage library resulted in the discovery of an anti-human TfR VHH (Nb188). Fusion of Nb188 to neurotensin induced hypothermia after intravenous injections in hAPI KI mice. In addition, systemic administration 1A11AM-Nb62 and 1A11AM-Nb188 fusions were able to reduce Aβ1-40 levels in the brain whereas 1A11AM fused to an irrelevant VHH did not. A PK/PD experiment showed that this effect could last for 3 days.

Conclusion

We have discovered an anti-human TfR specific VHH that is able to reach the CNS when administered systemically. In addition, both the currently discovered anti-human TfR VHH and the previously identified mouse-specific anti-TfR VHH, are both able to shuttle a therapeutically relevant cargo into the CNS. We suggest the mouse-specific VHH as a valuable research tool in mice and the human-specific VHH as a moiety to enhance the delivery efficiency of therapeutics into the CNS in human patients.
One size does not fit all: Participants’ experiences of the selfBACK app to support self-management of low back pain—a qualitative interview study
Authors: Svendsen Malene J. , Nicholl Barbara I. , Mair Frances S. , Wood Karen , Rasmussen Charlotte D. N. , Stochkendahl Mette J.
Published: October 2022

Background

Low back pain (LBP) is one of the most common reasons for disability globally. Digital interventions are a promising means of supporting people to self-manage LBP, but implementation of digital interventions has been suboptimal. An artificial intelligence-driven app, selfBACK, was developed to support self-management of LBP as an adjunct to usual care. To better understand the process of implementation from a participant perspective, we qualitatively explored factors influencing embedding, integrating, and sustaining engagement with the selfBACK app, and the self-perceived effects, acceptability, and satisfaction with the selfBACK app.

Methods

Using a qualitative interview study and an analytic framework approach underpinned by Normalization Process Theory (NPT), we investigated the experiences of patients who participated in the selfBACK randomized controlled trial (RCT). Interviews focused on the motivation to participate in the RCT, experiences of using the selfBACK app, and views about future intended use and potential of using digital health interventions for self-management of LBP. Participants were purposively sampled to represent diversity in age, sex, and implementation reflected by a proxy measure of number of app-generated self-management plans during the first three months of RCT participation.

Results

Twenty-six participants aged 21–78, eleven females and fifteen men, with two to fourteen self-management plans, were interviewed between August 2019 and April 2020. A broad range of factors influencing implementation of selfBACK within all constructs of NPT were identified. Key facilitating factors were preferences and beliefs favoring self-management, a friendly, motivational, and reassuring supporter, tailoring and personalization, convenience and ease of use, trustworthiness, perceiving benefits, and tracking achievements. Key impeding factors were preferences and beliefs not favoring self-management, functionality issues, suboptimal tailoring and personalization, insufficient time or conflicting life circumstances, not perceiving benefits, and insufficient involvement of health care practitioners. Self-perceived effects on pain and health, behavior/attitude, and gaining useful knowledge varied by participant.

Conclusions

The high prevalence of LBP globally coupled with the advantages of providing help through an app offers opportunities to help countless people. A range of factors should be considered to facilitate implementation of self-management of LBP or similar pain conditions using digital health tools.
Non-infectious sternal dehiscence after coronary artery bypass surgery
Authors: Silverborn Martin , Heitmann Leon Arnar , Sveinsdottir Nanna , Rögnvaldsson Sigurjon , Kristjansson Tomas Thor , Gudbjartsson Tomas
Published: October 2022

Introduction

Non-infectious sternal dehiscence (NISD) is a known complication following coronary artery bypass grafting (CABG), with previous studies estimating an incidence of 0.4–1% of surgeries. We aimed to study the incidence of NISD together with short- and long-term outcomes in a whole-nation cohort of patients.

Materials and methods

A retrospective study on consecutive CABG patients diagnosed with NISD at Landspitali from 2001 to 2020. Patients diagnosed with infectious mediastinitis (n = 20) were excluded. NISD patients were compared to patients with an intact sternum regarding patient demographics, cardiovascular risk factors, intra- and postoperative data, and estimated overall survival. The median follow-up was 9.5 years.

Results

Twenty out of 2280 eligible patients (0.88%) developed NISD, and the incidence did not change over the study period (p = 0.98). The median time of diagnosis was 12 days postoperatively (range, 4–240). All patients were re-operated using a Robicsek-rewiring technique, with two cases requiring a titanium plate for fixation. Patients with NISD were older, had a higher BMI and EuroSCORE II, lower LVEF, and more often had a history of COPD, MI, and diabetes compared to those without NISD. Length of stay was extended by 15 days for NISD patients, but short and long-term survival was not statistically different between the groups.

Conclusions

The incidence of NISD was low and in line with previous studies. Although the length of hospital stay was extended, both short- and long-term survival of NISD patients was not significantly different from patients with an intact sternum.