bluuebunny/crossref_metadata_2025 huggingface dataset:
International medical students’ perspectives on factors affecting their academic success in China: a qualitative study
Authors: Jiang Qinxu , Horta Hugo , Yuen Mantak
Published: July 2022

Background

The number of international students who choose China as their destination for quality medical education is rising, particularly those from developing countries, but little is known about their adaptation and educational experiences at Chinese universities. This study explored the factors that these students perceived to have influenced their academic success.

Methods

Semi-structured interviews were conducted with international students (N = 40) from developing countries from September 2020 to January 2021. Participants were graduates or in their second, third, fourth, fifth, or sixth academic year in two university medical schools. Interviews were audio-recorded, transcribed, and analyzed using a thematic analysis approach.

Results

The participants chose China to study medicine based on cost, teaching resources, quality of medical education, recommendation, and safety factors. They considered an increase in medical knowledge, clinical skills and communication skills as an indicator of academic success. Positive factors affecting academic success were the support system (family, friends, seniors) and campus resources (library, laboratories, extra-curricular activities, scholarship). Negative factors were (i) issues affecting learning (English language barrier), adjusting to the medical education system in China, learning difficulties, failing exams, internship difficulties, problems with online learning during the pandemic, (ii) sociocultural issues (lacking knowledge of the Chinese language, challenges in daily life, perceived discrimination, interpersonal relationships), (iii) wellbeing issues (physical and mental health issues), and (iv) other challenges (climate, food, finance, scholarship). The influence of teachers, administrators and classmates was perceived as both positive and negative.

Conclusions

Factors affecting the academic success of international medical students at Chinese universities are multi-faceted. It is the collective responsibility of the host society, universities, teachers, administrators, classmates, families, and students themselves to address these factors in order to support and help students achieve academic success. Findings in our study support recommendations to improve teachers’ English language skills and pedagogy and to invest in administrators’ professional development. They also suggest that greater awareness of students’ sociocultural and mental challenges and optimizing the positive influence of classmates could strengthen student support and better address student academic difficulties. The English proficiency and prior academic performance of international students should be considered during recruitment. Given the rapid growth in international MBBS programs in China, further research on the experiences of international students in China’s medical programs is needed.
Rivalries for attention: insights from a realist evaluation of a postgraduate competency-based medical education implementation in Canada
Authors: Rachul Christen , Collins Benjamin , Chan Ming-Ka , Srinivasan Ganesh , Hamilton Joanne
Published: July 2022

Background

Implementing competency-based medical education (CBME) in post-graduate medical education (PGME) is a complex process that requires multiple systemic changes in a complex system that is simultaneously engaged in multiple initiatives. These initiatives often compete for attention during the implementation of CBME and produce unintended and unanticipated consequences. Understanding the impact of this context is necessary for evaluating the effectiveness of CBME. The purpose of the study was to identify factors, such as contexts and processes, that contribute to the implementation of CBME.

Methods

We conducted a realist evaluation using data collected from 15 programs through focus groups with residents (2 groups, n = 16) and faculty (one group, n = 8), and semi-structured interviews with program directors (n = 18), and program administrators (n = 12) from 2018 to 2021. Data were analyzed using a template analysis based on a coding framework that was developed from a sample of transcripts, the context-mechanism-outcomes framework for realist evaluations, and the core components of CBME.

Results

The findings demonstrate that simultaneous initiatives in the academic health sciences system creates a key context for CBME implementation – rivalries for attention – and specifically, the introduction of curricular management systems (CMS) concurrent to, but separate from, the implementation of CBME. This context influenced participants’ participation, communication, and adaptation during CBME implementation, which led to change fatigue and unmet expectations for the collection and use of assessment data.

Conclusions

Rival initiatives, such as the concurrent implementation of a new CMS, can have an impact on how programs implement CBME and greatly affect the outcomes of CBME. Mitigating the effects of rivals for attention with flexibility, clear communication, and training can facilitate effective implementation of CBME.
Adapting to CONNECT: modifying a nursing home-based team-building intervention to improve hospital care team interactions, functioning, and implementation readiness
Authors: Wang Virginia , D’Adolf Joshua , Decosimo Kasey , Robinson Katina , Choate Ashley , Bruening Rebecca , Sperber Nina , Mahanna Elizabeth , Van Houtven Courtney H. , Allen Kelli D. , Colón-Emeric Cathleen , Damush Teresa M. , Hastings Susan N.
Published: July 2022

Background

Clinical interventions often need to be adapted from their original design when they are applied to new settings. There is a growing literature describing frameworks and approaches to deploying and documenting adaptations of evidence-based practices in healthcare. Still, intervention modifications are often limited in detail and justification, which may prevent rigorous evaluation of interventions and intervention adaptation effectiveness in new contexts. We describe our approach in a case study, combining two complementary intervention adaptation frameworks to modify CONNECT for Quality, a provider-facing team building and communication intervention designed to facilitate implementation of a new clinical program.

Methods

This process of intervention adaptation involved the use of the Planned Adaptation Framework and the Framework for Reporting Adaptations and Modifications, for systematically identifying key drivers, core and non-core components of interventions for documenting planned and unplanned changes to intervention design.

Results

The CONNECT intervention’s original context and setting is first described and then compared with its new application. This lays the groundwork for the intentional modifications to intervention design, which are developed before intervention delivery to participating providers. The unpredictable nature of implementation in real-world practice required unplanned adaptations, which were also considered and documented. Attendance and participation rates were examined and qualitative assessment of reported participant experience supported the feasibility and acceptability of adaptations of the original CONNECT intervention in a new clinical context.

Conclusion

This approach may serve as a useful guide for intervention implementation efforts applied in diverse clinical contexts and subsequent evaluations of intervention effectiveness.

Trial registration

The study was registered at ClinicalTrials.gov (NCT03300336) on September 28, 2017.
Evaluating the medical direct costs associated with prematurity during the initial hospitalization in Rwanda: a prevalence based cost of illness study
Authors: Ngabonzima Anaclet , Asingizwe Domina , Cechetto David , Mukunde Gisele , Nyalihama Alain , Gakwerere Mathias , Epstein David Mark
Published: July 2022

Background

Prematurity is still the leading cause of global neonatal mortality, Rwanda included, even though advanced medical technology has improved survival. Initial hospitalization of premature babies (PBs) is associated with high costs which have an impact on Rwanda’s health budget. In Rwanda, these costs are not known, while knowing them would allow better planning, hence the purpose and motivation for this research.

Methods

This was a prospective cost of illness study using a prevalence approach conducted in 5 hospitals (University Teaching Hospital of Butare, Gisenyi, Masaka, Muhima, and Ruhengeri). It included PBs admitted from June to July 2021 followed up prospectively to determine the medical direct costs (MDC) by enumerating the cost of all inputs. Descriptive analyses and ordinary least squares regression were used to illustrate factors associated with and predictive of mean cost. The significance level was set at p < 0.05.

Results

A total of 123 PBs were included. Very preterm and moderate PBs were 36.6% and 23.6% respectively and the average birth weight (BW) was 1724 g (SD: 408.1 g). The overall mean MDC was $237.7 per PB (SD: $294.9) representing 28% of Gross Domestic Product (GDP) per capita per year. Costs per PB varied with weight category, prematurity degree, hospital level, and length of stay (LoS) among other variables. MDC was dominated by drugs and supplies (65%) with oxygen being an influential driver of MDC accounting for 38.4% of total MDC. Birth weight, oxygen therapy, and hospital level were significant MDC predictive factors.

Conclusion

This study provides an in-depth understanding of MDC of initial hospitalization of PBs in Rwanda. It also indicates predictive factors, including birth weight, which can be managed through measures to prevent or delay preterm birth.

Implication for prematurity prevention and management

The results suggest a need to revise the benefits and entitlements of insured people to include drugs and interventions not covered that are essential and where there are no alternatives. Having oxygen plants in hospitals may reduce oxygen-related costs. Furthermore, interventions to reduce prematurity should be evaluated using cost-effectiveness analysis since its overall burden is high.
Facility-based simulation as a programmatic tool for implementing a statewide contraceptive initiative
Authors: Cohen Susanna R. , Baayd Jami , García Gabriela , Quade Caitlin , Gero Alexandra , Ekey Madison , Poggio Catherine , Simmons Rebecca
Published: July 2022

Background

Assessing implementation fidelity is highly recommended, but successful approaches can be challenging. Family Planning Elevated (FPE) is a statewide contraceptive initiative which partnered with 28 health clinics across Utah. To assess implementation fidelity, we developed in-situ high-fidelity simulation training to both determine clinic adherence to FPE and offer education to implementing teams. This study aimed to develop, pilot, and assess the use of simulation as a tool for measuring implementation fidelity.

Methods

We developed two simulation scenarios to determine implementation fidelity: one scenario wherein a client is seeking a new method of contraception and another in which the same client has returned to discontinue the method. Both simulations contained multiple aspects of program implementation (e.g., determining program eligibility). We then offered simulations to all FPE partner organizations. To assess simulation training as a tool for determining implementation fidelity, we developed strategies aligned with each aspect of an adapted RE-AIM framework, including pre-post surveys, acceptability and self-efficacy testing, a checklist for programmatic adherence, field notes, action planning and analysis of monitoring data.

Results

Fifteen clinical sites and 71 team members participated in the in-situ simulations. Assessment of the checklist showed that 90% of the clinics successfully demonstrated key program components, including person-centered counseling techniques such as sitting at the patient’s level (95.8%); asking open-ended questions (100%); and explaining how to use the contraceptive method selected (91.7%). More than half of clinics fell short in programmatic areas including: confirmation that the FPE program covered same-day intrauterine device insertion (54.2%), and education on health risks associated with the selected contraceptive method (58.3%). After simulation, participants reported improved knowledge of how FPE works (p =  < 0.001), increased ability to identify FPE-eligible clients (p = 0.02) and heightened self-efficacy in helping clients select a method (p = 0.03). Participants were satisfied with the simulations, with most (84.1%) reporting that the simulation exceeded their expectations.

Conclusions

Highly-realistic in-situ family planning simulations are acceptable to participants, positively change knowledge and clinical team confidence, and can identify systems gaps in clinical care and program implementation. Simulation offers a reciprocal way of monitoring implementation fidelity of a family planning access initiative.

Trial registration

This project was determined to be exempt by the IRB of the University of Utah, the larger Family Planning Elevated program under which this pilot study was nested is registered at ClinicalTrials.gov Identifier: NCT03877757.
Attributes of primary health care in Mato Grosso do Sul state: PCAT-Brazil paired for users and health professionals, 2018
Authors: Bomfim Rafael Aiello , Leite Hazelelponi Querã Naumann Cerqueira , Zafalon Edilson José , De-Carli Alessandro Diogo , Santos Mara Lisiane de Moraes dos
Published: July 2022

Objective

The objective of the present study was to analyse the quality of adults and older adults health care in Primary Health Care (PHC) services in the State of Mato Grosso do Sul, 2018.

Methods

A quantitative survey was carried out in which the municipalities participating in the study included the four macro-regions following the Director Regional Plan (DRP). In this study, the quality of care was verified using the validated version of the PCAT-Br for adult and older adults users over 18 years of age and professionals. The professional’s and users’ views were compared between PHC attributes in the State of Mato Grosso do Sul. We performed the paired student t-test. STATA v.14.2 software (College Station, TX, USA) was used for the analyses. Sensitivity analysis was done to compare socio-demographic characteristics.

Results

Eight hundred twenty-five users and 424 professionals participated in the study. According to users, the Accessibility attribute had the worst performance in all macro-regions (mean score PCAT = 3.58). There were significant differences between the perception of users and professionals (PCAT = 5.32 for users and PCAT = 7.11 for professionals) in all attributes evaluated.

Conclusions

There was a difference in users’ and professionals’ perceptions between PHC attributes. Therefore, it is necessary to strengthen PHC care networks in the State, mainly considering the users’ perspectives.
Severe inflammation in new-borns induces long-term cognitive impairment by activation of IL-1β/KCC2 signaling during early development
Authors: Zhang Donghang , Yang Yujiao , Yang Yaoxin , Liu Jin , Zhu Tao , Huang Han , Zhou Cheng
Published: July 2022

Background

Neonatal sepsis can induce long-term cognitive impairment in adolescence or adulthood, but the underlying molecular mechanism is not fully understood. The expression of K+-Cl– co-transporter 2 (KCC2) plays a pivotal role in the GABAergic shift from depolarizing to hyperpolarizing during early postnatal development. In this study, we aimed to determine whether neonatal severe inflammation-induced cognitive impairment was associated with the expression of KCC2 during early development.

Methods

Neonatal severe inflammation was established by intraperitoneal injection of high dose lipopolysaccharide (LPS, 1 mg kg–1) in postnatal day 3 (P3) rats. The Morris water maze task and fear conditioning test were used to investigate long-term cognitive functions. ELISA, RT-PCR and Western blotting were used to examine the expression levels of proinflammatory cytokines and KCC2. Perforated patch-clamping recordings were used to determine the GABAergic shift.

Results

Neonatal severe inflammation led to long-term cognitive impairment in rats. Meanwhile, sustained elevation of interleukin-1 beta (IL-1β) levels was found in the hippocampus until P30 after LPS injection. Elevated expression of KCC2 and hyperpolarized GABA reversal potential (EGABA) were observed in CA1 hippocampal pyramidal neurons from the P7-P10 and P14-P16 rats after LPS injection. Specific knockdown of IL-1β mRNA expression rescued the elevated expression of KCC2 and the hyperpolarized EGABA at P7-P10 and P14-P16. Accordingly, specific knockdown of IL-1β or KCC2 expression improved the cognitive impairment induced by neonatal severe inflammation.

Conclusions

Sustained elevation of IL-1β in the hippocampus may induce cognitive impairment by upregulation of KCC2 during early development.
Increased blood-based intratumor heterogeneity (bITH) is associated with unfavorable outcomes of immune checkpoint inhibitors plus chemotherapy in non-small cell lung cancer
Authors: Zhou Juan , Bao Minwei , Gao Guanghui , Cai Yiran , Wu Lihong , Lei Lei , Zhao Jing , Ji Xianxiu , Huang Ying , Su Chunxia
Published: July 2022

Background

The combination of immune checkpoint inhibitors (ICIs) and chemotherapy has been the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) patients with driver-gene negative. However, efficacy biomarkers for ICIs-based combination therapy are lacking. We aimed to identify potential factors associated with outcomes of ICIs plus chemotherapy at baseline and dynamic changes in peripheral blood.

Methods

We collected plasma samples of 51 advanced NSCLC patients without EGFR/ALK/ROS1 alteration at baseline and/or after two treatment cycles of ICIs plus chemotherapy. A blood-based intratumor heterogeneity (bITH) score was calculated based on the allele frequencies of somatic mutations using a 520-gene panel. bITH-up was defined as a ≥ 10% increase in bITH score from baseline, with a second confirmatory measurement after treatment.

Results

At baseline, the number of metastatic organs and lung immune prognostic index (LIPI) were significantly associated with shorter progression-free survival (PFS) of ICIs plus chemotherapy, while bITH and other common molecular biomarkers, including ctDNA level, blood-based tumor mutational burden (bTMB), and PD-L1 expression, had no effect on PFS. LRP1B mutation at baseline was significantly associated with favorable outcomes to ICIs plus chemotherapy. There were 37 patients who had paired samples at baseline and after two cycles of treatment, with the median interval of 53 days. Intriguingly, patients with bITH-up had significant shorter PFS (HR, 4.92; 95% CI, 1.72–14.07; P = 0.001) and a lower durable clinical benefit rate (0 vs 41.38%, P = 0.036) than those with bITH-stable or down. Case studies indicated that bITH was promising to predict disease progression.

Conclusions

The present study is the first to report that increased bITH is associated with unfavorable outcomes of ICIs plus chemotherapy in advanced NSCLC patients.
Severe acute hepatitis of unknown aetiology in children—what is known?
Authors: Khader Susan , Foster Isabel , Dagens Andrew , Norton Alice , Sigfrid Louise
Published: July 2022

The ongoing investigations into clusters of children affected by severe acute hepatitis of unknown aetiology have put our global capacity for a coordinated, effective response to the test. The global health community have rapidly convened to share data and inform the response. In the UK, where most cases were initially identified, a coordinated public health and clinical research response was rapidly initiated. Since then, cases have been reported from other countries, predominantly from higher-income countries. While agencies are keeping an open mind to the cause, the working hypothesis and case notifications raise important questions about our capacity to detect emerging cases in lower-resourced settings with a recognised lack of access to diagnostics even for commonly circulating viruses such as hepatitis A. The limited capability to generate integrated global pathogen surveillance data is a challenge for the outbreak investigations, highlighting an urgent need to strengthen access to diagnostics, with a focus on lower-resourced settings, to improve the capacity to detect emerging diseases to inform care and to improve outcomes and outbreak control.
Mechanosensitive Piezo channels mediate the physiological and pathophysiological changes in the respiratory system
Authors: Xiong Huaiyu , Yang Jing , Guo Jun , Ma Aijia , Wang Bo , Kang Yan
Published: July 2022

Mechanosensitive Piezo ion channels were first reported in 2010 in a mouse neuroblastoma cell line, opening up a new field for studying the composition and function of eukaryotic mechanically activated channels. During the past decade, Piezo ion channels were identified in many species, such as bacteria, Drosophila, and mammals. In mammals, basic life activities, such as the sense of touch, proprioception, hearing, vascular development, and blood pressure regulation, depend on the activation of Piezo ion channels. Cumulative evidence suggests that Piezo ion channels play a major role in lung vascular development and function and diseases like pneumonia, pulmonary hypertension, apnea, and other lung-related diseases. In this review, we focused on studies that reported specific functions of Piezos in tissues and emphasized the physiological and pathological effects of their absence or functional mutations on the respiratory system.
Influence of diabetes on mortality and ICD therapies in ICD recipients: a systematic review and meta-analysis of 162,780 patients
Authors: Liu Hualong , Hu Jinzhu , Zhuo Wen , Wan Rong , Hong Kui
Published: July 2022

Background

The influence of diabetes on the mortality and risk of implantable cardioverter defibrillator (ICD) therapies is still controversial, and a comprehensive assessment is lacking. We performed this systematic review and meta-analysis to address this controversy.

Methods

We systematically searched the PubMed, Embase, Web of Science and Cochrane Library databases to collect relevant literature. Fixed and random effects models were used to estimate the hazard ratio (HR) with 95% CIs.

Results

Thirty-six articles reporting on 162,780 ICD recipients were included in this analysis. Compared with nondiabetic ICD recipients, diabetic ICD recipients had higher all-cause mortality (HR = 1.45, 95% CI 1.36–1.55). The subgroup analysis showed that secondary prevention patients with diabetes may suffer a higher risk of all-cause mortality (HR = 1.89, 95% CI 1.56–2.28) (for subgroup analysis, P = 0.03). Cardiac mortality was also higher in ICD recipients with diabetes (HR = 1.68, 95% CI 1.35–2.08). However, diabetes had no significant effect on the risks of ICD therapies, including appropriate or inappropriate therapy, appropriate or inappropriate shock and appropriate anti-tachycardia pacing (ATP). Diabetes was associated with a decreased risk of inappropriate ATP (HR = 0.56, 95% CI 0.39–0.79).

Conclusion

Diabetes is associated with an increased risk of mortality in ICD recipients, especially in the secondary prevention patients, but does not significantly influence the risks of ICD therapies, indicating that the increased mortality of ICD recipients with diabetes may not be caused by arrhythmias. The survival benefits of ICD treatment in diabetes patients are limited.
Toxic metals in the regulation of epithelial–mesenchymal plasticity: demons or angels?
Authors: Chen Xu-Li , Xu Yan-Ming , Lau Andy T. Y.
Published: July 2022

Epithelial cells can trans-differentiate into motile mesenchymal cells through a dynamic process known as epithelial–mesenchymal transition (EMT). EMT is crucial in embryonic development and wound healing but also contributes to human diseases such as organ fibrosis and cancer progression. Heavy metals are environmental pollutants that can affect human health in various ways, including causing cancers. The cytotoxicity and carcinogenicity of heavy metals are complex, and studies have demonstrated that some of these metals can affect the progress of EMT. Here, we focus on reviewing the roles of six environmentally common toxic metals concerning EMT: arsenic (AS), cadmium (Cd), cobalt (Co), chromium (Cr), nickel (Ni), and copper (Cu). Noteworthily, the effects of these elements on EMT may vary according to the form, dose, and exposure time; the dual role of heavy metals (e.g., AS, Cd, and Cu) on EMT is also observed, in which, sometimes they can promote while sometimes inhibit the EMT process. Given the vast number of toxicologically relevant metals that exist in nature, we believe a comprehensive understanding of their effects on EMT is required to dictate in what circumstances these metals act more likely as demons or angels.
Qualitative study on the use and maintenance of long-lasting insecticidal nets (LLINs) in Bouaké (Côte d’Ivoire), 17 months after the last mass distribution campaign
Authors: N’Guessan Gnagoran Kouakou Daniel , Coulibaly Fangala Hamidou , Barreaux Antoine Marc Gaby , Yapo Roseline Josée , Adou Kouassi Arsène , Tia Emmanuel , Fournet Florence
Published: July 2022

Background

The use of long-lasting insecticide-treated nets (LLINs) is one of the main malaria prevention method promoted by the World Health Organization (WHO) in Côte d'Ivoire. LLIN-coverage has reached 95% since 2015 and nearly 16 million LLINs were distributed in 2017. Despite these efforts, malaria incidence at the national level remains high (120‰ in 2012 to 164‰ in 2017) although this could be partly explained by increased screening efforts. This study aimed at determining what preventative measures were used against mosquito bites, as well as LLIN maintenance practices used by the inhabitants of the city of Bouaké, capital city of the Gbêkê region with a malaria incidence of 257‰ in 2017.

Methods

A descriptive qualitative investigation took place in Bouaké, in four neighbourhoods that were selected through purposive sampling based on their social composition. Data were collected using an interview guide based on convenience sampling.

Results

The results of the study reveal that LLINs are the most reported used malaria prevention measure (66.4%). Environmental health (28.8%) came second in their declarations, smoke coils (23.5%) third and aerosol cans (18.8%) last. The percentage of respondents who answered that they had slept under an LLIN the previous night was 53%. 57.7% reported that they wash their LLINs, 12.1% that they do not wash them, and 4% that they replace dirty LLINs with new ones. The LLINs washing methods described by the respondents did not comply with the WHO recommendations and there was no mention of LLINs repairs.

Conclusion

Despite mass distributions of LLINs in Côte d'Ivoire, this key malaria control tool remains under-used by the population. Regarding LLIN maintenance, more than half of the population reports that they wash their nets while not complying with recommended practices or repairing them.
Polarization disorder of decidual NK cells in unexplained recurrent spontaneous abortion revealed by single-cell transcriptome analysis
Authors: Pan Dingchen , Liu Qian , Du Le , Yang Yang , Jiang Guojing
Published: July 2022

Background

Unexplained recurrent spontaneous abortion (URSA) is one of the most common diseases in pregnancy and is mainly caused by immune disorders. The foetus is similar to semiallogeneic maternal tissue, so the balance of immune tolerance must be dynamically maintained during pregnancy. Decidual natural killer (dNK) cells primarily mediate the immune tolerance microenvironment at the maternal–fetal interface. By using single-cell RNA sequencing (scRNA-seq) and high-throughput transcriptome sequencing analysis, we explored the characteristic distribution of dNK cells in URSA patients.

Methods

Control maternal–fetal interface tissue (from normal pregnant women, n = 3) and case maternal–fetal interface tissue (from patients with URSA, n = 3) samples were analysed by scRNA-seq and high-throughput transcriptome sequencing.

Results

By scRNA-seq, we demonstrated the maturation process of the transition of dNK cells from cytotoxic characteristics to immune tolerance in transcriptome analysis. Moreover, compared with normal pregnant women, serious disturbances in the polarization process of dNK cells were found in URSA. Simultaneously, the transcriptional level of the extracellular matrix (ECM) in URSA patients showed a significant decrease. The dNK cells interacted with extravillous trophoblasts to achieve immune-tolerant polarization.

Conclusions

Insufficient expression of KIRs during dNK cell differentiation might be a key reason why polarized dNK cells still had high cytotoxic reactivity in URSA patients. Abnormal expression of ECM may affect the interaction of dNK cells with EVTs, making dNK cells immature. Both resulted in maternal immune intolerance to the foetus during pregnancy.
Financial risk protection from out-of-pocket health spending in low- and middle-income countries: a scoping review of the literature
Authors: Rahman Taslima , Gasbarro Dominic , Alam Khurshid
Published: July 2022

Background

Financial risk protection (FRP), defined as households’ access to needed healthcare services without experiencing undue financial hardship, is a critical health systems target, particularly in low- and middle-income countries (LMICs). Given the remarkable growth in FRP literature in recent times, we conducted a scoping review of the literature on FRP from out-of-pocket (OOP) health spending in LMICs. The objective was to review current knowledge, identify evidence gaps and propose future research directions.

Methods

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to conduct this scoping review. We systematically searched PubMed, Scopus, ProQuest and Web of Science in July 2021 for literature published since 1 January 2015. We included empirical studies that used nationally representative data from household surveys to measure the incidence of at least one of the following indicators: catastrophic health expenditure (CHE), impoverishment, adoption of strategies to cope with OOP expenses, and forgone care for financial reasons. Our review covered 155 studies and analysed the geographical focus, data sources, methods and analytical rigour of the studies. We also examined the level of FRP by disease categories (all diseases, chronic illnesses, communicable diseases) and the effect of health insurance on FRP.

Results

The extant literature primarily focused on India and China as research settings. Notably, no FRP study was available on chronic illness in any low-income country (LIC) or on communicable diseases in an upper-middle-income country (UMIC). Only one study comprehensively measured FRP by examining all four indicators. Most studies assessed (lack of) FRP as CHE incidence alone (37.4%) or as CHE and impoverishment incidence (39.4%). However, the LMIC literature did not incorporate the recent methodological advances to measure CHE and impoverishment that address the limitations of conventional methods. There were also gaps in utilizing available panel data to determine the length of the lack of FRP (e.g. duration of poverty caused by OOP expenses). The current estimates of FRP varied substantially among the LMICs, with some of the poorest countries in the world experiencing similar or even lower rates of CHE and impoverishment compared with the UMICs. Also, health insurance in LMICs did not consistently offer a higher degree of FRP.

Conclusion

The literature to date is unable to provide a reliable representation of the actual level of protection enjoyed by the LMIC population because of the lack of comprehensive measurement of FRP indicators coupled with the use of dated methodologies. Future research in LMICs should address the shortcomings identified in this review.
Reprogramming of glutamine metabolism and its impact on immune response in the tumor microenvironment
Authors: Ma Guofeng , Zhang Zhilei , Li Peng , Zhang Zhao , Zeng Manqin , Liang Zhijuan , Li Dan , Wang Liping , Chen Yuanbin , Liang Ye , Niu Haitao
Published: July 2022

Metabolic reprogramming and immune escape play a major role in tumorigenesis. Increasing number of studies have shown that reprogramming of glutamine metabolism is a putative determinant of the anti-tumor immune response in the tumor microenvironment (TME). Usually, the predatory uptake of glutamine by tumor cells in the TME results in the limited utilization of glutamine by immune cells and affects the anti-tumor immune response. The cell-programmed glutamine partitioning also affects the anti-tumor immune response. However, the reprogramming of glutamine metabolism in tumors modulates immune escape by regulating tumor PD-L1 expression. Likewise, the reprogramming of glutamine metabolism in the immune cells also affects their immune function. Additionally, different types of glutamine metabolism inhibitors extensively regulate the immune cells in the TME while suppressing tumor cell proliferation. Herein, we discuss how metabolic reprogramming of tumor and immune cells regulates anti-tumor immune responses, as well as functional changes in different immune cells in the context of targeting tumor glutamine metabolism, which can better explain the potential of targeting glutamine metabolism in combination with immunotherapy for cancer.
The health, cost and equity impacts of restrictions on the advertisement of high fat, salt and sugar products across the transport for London network: a health economic modelling study
Authors: Thomas Chloe , Breeze Penny , Cummins Steven , Cornelsen Laura , Yau Amy , Brennan Alan
Published: July 2022

Background

Policies aimed at restricting the marketing of high fat, salt and sugar products have been proposed as one way of improving population diet and reducing obesity. In 2019, Transport for London implemented advertising restrictions on high fat, salt and sugar products. A controlled interrupted time-series analysis comparing London with a north of England control, suggested that the advertising restrictions had resulted in a reduction in household energy purchases. The aim of the study presented here was to estimate the health benefits, cost savings and equity impacts of the Transport for London policy using a health economic modelling approach, from an English National Health Service and personal social services perspective.

Methods

A diabetes prevention microsimulation model was modified to incorporate the London population and Transport for London advertising intervention. Conversion of calorie to body mass index reduction was mediated through an approximation of a mathematical model estimating weight loss. Outcomes gathered included incremental obesity, long-term diabetes and cardiovascular disease events, quality-adjusted life years, healthcare costs saved and net monetary benefit. Slope index of inequality was calculated for proportion of people with obesity across socioeconomic groups to assess equity impacts.

Results

The results show that the Transport for London policy was estimated to have resulted in 94,867 (4.8%) fewer individuals with obesity, and to reduce incidence of diabetes and cardiovascular disease by 2,857 and 1,915 cases respectively within three years post intervention. The policy would produce an estimated 16,394 additional quality-adjusted life-years and save £218 m in NHS and social care costs over the lifetime of the current population. Greater benefits (e.g. a 37% higher gain in quality-adjusted life-years) were expected to accrue to individuals from the most socioeconomically deprived groups compared to the least deprived.

Conclusions

This analysis suggests that there are considerable potential health and economic gains from restricting the advertisement of high fat, salt and sugar products. The population health and economic impacts of the Transport for London advertising restrictions are likely to have reduced health inequalities in London.
Glucose metabolism in systemic juvenile idiopathic arthritis
Authors: Suppasit Papatsorn , Vilaiyuk Soamarat , Poomthavorn Preamrudee , Pongratanakul Sarunyu , Khlairit Patcharin , Mahachoklertwattana Pat
Published: July 2022

Background

Systemic juvenile idiopathic arthritis (SJIA) is a chronic systemic inflammatory disease in children. Overproduction of inflammatory cytokines in SJIA resembles that in adult onset Still disease. Chronic inflammation causes insulin resistance and consequently leading to abnormal glucose metabolism. Adults with rheumatoid arthritis (RA) have increased risks of abnormal glucose metabolism and diabetes. To date, glucose metabolism in patients with SJIA has not been elucidated.

Methods

Patients with SJIA aged 4–25 years were recruited. All patients underwent an oral glucose tolerance test (OGTT). Indices of insulin sensitivity [homeostasis model assessment for insulin resistance (HOMA-IR) and whole-body insulin sensitivity index (WBISI)] and β-cell function [insulinogenic index (IGI) and disposition index (DI)] were calculated. Obese children with normoglycemia who underwent the OGTT were served as a control group.

Results

A total of 39 patients with SJIA, aged 4–25 years, median (IQR) BMI SDS was 0.1 (-0.5 to 1.7). Patients were divided into 2 groups, overweight/obese (OW/OB) (n = 11) and lean (n = 28). Only one obese patient had prediabetes and none had diabetes. In comparison with sex- and age-matched OW/OB controls (n = 33), OW/OB patients with SJIA had higher insulin resistance [median (IQR) HOMA-IR: 2.6 (2.1–3.3) vs 1.5 (0.8–2.0), p = 0.001], lower insulin sensitivity [median (IQR) WBISI: 3.7 (2.7–5.9) vs 5.4 (4.5–8.7), p = 0.024], and higher insulin secretion [median (IQR) IGI: 2.5 (2.0–3.5) vs 1.0 (0.8–1.9), p = 0.001]. In lean patients with SJIA, insulin sensitivity indices seemed to be comparable with those of lean controls.

Conclusions

Overweight/obese children with SJIA seemed to have increased insulin resistance and thus may have an increased risk for developing diabetes.
The efficacy and safety of allogeneic stem cell transplantation in Mevalonate Kinase Deficiency
Authors: Jeyaratnam Jerold , Faraci Maura , Gennery Andrew R. , Drabko Katarzyna , Algeri Mattia , Morimoto Akira , Sirait Tiarlan , Lankester Arjan C. , Albert Michael , Neven Benedicte , Frenkel Joost ,   on behalf of the EBMT Inborn Errors Working Party
Published: July 2022

Objectives

Mevalonate kinase deficiency (MKD) is a rare autoinflammatory syndrome. Several reports have described allogeneic hematopoietic stem cell transplantation in severely affected patients, sometimes with promising results. In view of the scarcity of data, this study aims to analyse the efficacy and safety of allogeneic hematopoietic stem cell transplantation (HSCT) to give a more complete overview of this treatment.

Methods

This multicentre retrospective study on behalf of the European Society for Blood and Marrow Transplantation aimed to include all MKD patients who had undergone allogeneic HSCT. All centres related to EMBT and centres that have reported cases of allogeneic HSCT in the literature were contacted via the EBMT data office.

Results

We analyzed 9 patients (5 male). Treosulfan based conditioning was the most frequently used conditioning regimen. Engraftment occurred in all but one patient. Source of stem cells was cord blood (n = 2), peripheral blood stem cells (n = 4) and bone marrow (n = 5). Two patients needed a second transplantation due to an incomplete response or primary graft failure. Seven patients went into complete remission after stem cell transplantation. At final follow-up these patients reported no symptoms of MKD.

Four patients suffered from grade II-IV acute graft-versus-host disease (GvHD). During follow-up two patients died due to transplantation related complications.

Conclusion

In conclusion, allogeneic stem cell transplantation represents an effective treatment for the most severely affected MKD patients. However, treatment-related morbidity and mortality are significant. Transplantation may be justified in patients with a severe disease course on conservative therapy.
Bone remodeling serum markers in children with systemic lupus erythematosus
Authors: Hao Sheng , Zhang Jing , Huang Bingxue , Feng Dan , Niu Xiaoling , Huang Wenyan
Published: July 2022

Indroduction

SLE is an autoimmune multisystem disease. Glucocorticoid is an irreplaceable medication for SLE. Glucocorticoid and inflammatory mediators impact bone remodeling by OPG/RANKL/RANK signal system, which could lead to osteoporosis. Our aim is to detect the expression of RANKL/OPG in children with SLE, and to preliminarily explore the changes of bone remodeling serum markers in children with SLE.

Methods

Serum RANKL and OPG of 40 children with SLE and healthy children were detected by ELISA, while 25(OH)VitD3 was detected routinely. Clinical data of children with SLE were recorded, including gender, age, height, weight, BMI, SLEDAI, duration of the disease, cumulative dose of glucocorticoid, and correlation analysis was conducted with RANKL, OPG and 25(OH)VitD3.

Results

Serum RANKL concentrations in SLE group were significantly higher than health group (9.82 ± 7.20 vs. 6.80 ± 4.35 pg/ml and 0.081 ± 0.072 vs. 0.042 ± 0.034, P < 0.05) respectively, and the concentrations of OPG and 25(OH)VitD3 in serum were significantly lower than health group (156.34 ± 57.33 vs. 189.16 ± 68.70 pg/ml and 43.66 ± 31.27 vs. 59.04 ± 21.56 mmol/L, P < 0.05). Serum RANKL in children with SLE was positively correlated with the duration of SLE, cumulative dose of GC(r = 0.593, 0.727, P < 0.05). And it was negatively correlated with serum OPG and 25(OH)VitD3 (r = -0.601, -0.469, P < 0.05). In addition, serum OPG and 25(OH)VitD3 concentrations were inversely correlated with cumulative dose of GC (r = -0.66, -0.508, P < 0.05).

Conclusion

Low levels of vitamin D3 and bone metabolic abnormalities still persist in children with SLE even if the disease is in remission, while serum RANKL level was elevated, OPG expression was reduced. In the case of disease remission, GC is involved in the occurrence and development of abnormal bone remodeling through RANKL/OPG.
Activation of peripheral TRPM8 mitigates ischemic stroke by topically applied menthol
Authors: Huang Shiang-Suo , Su Hsing-Hui , Chien Szu-Yu , Chung Hsin-Yi , Luo Sih-Ting , Chu Yu-Ting , Wang Yi-Hsin , MacDonald Iona J. , Lee Hsun-Hua , Chen Yi-Hung
Published: July 2022

Background

No reports exist as to neuroprotective effects associated with topical activation of transient receptor potential melastatin 8 (TRPM8), a noted cold receptor. In the present study, we identified whether activating peripheral TRPM8 can be an adjuvant therapy for ischemic stroke.

Methods

Menthol, an agonist of TRPM8, was applied orally or topically to all paws or back of the mouse after middle cerebral artery occlusion (MCAO). We usedTrpm8gene knockout (Trpm8−/−) mice or TRPM8 antagonist and lidocaine to validate the roles of TRPM8 and peripheral nerve conduction in menthol against ischemic stroke.

Results

Application of menthol 16% to paw derma attenuated infarct volumes and ameliorated sensorimotor deficits in stroke mice induced by MCAO. The benefits of topically applied menthol were associated with reductions in oxidative stress, neuroinflammation and infiltration of monocytes and macrophages in ischemic brains. Antagonizing TRPM8 orTrpm8knockout dulls the neuroprotective effects of topically application of menthol against MCAO. Immunohistochemistry analyses revealed significantly higher TRPM8 expression in skin tissue samples obtained from the paws compared with skin from the backs, which was reflected by significantly smaller infarct lesion volumes and better sensorimotor function in mice treated with menthol on the paws compared with the back. Blocking conduction of peripheral nerve in the four paws reversed the neuroprotective effects of topical menthol administrated to paws. On the other hand, oral menthol dosing did not assist with recovery from MCAO in our study.

Conclusion

Our results suggested that activation of peripheral TRPM8 expressed in the derma tissue of limbs with sufficient concentration of menthol is beneficial to stroke recovery. Topical application of menthol on hands and feet could be a novel and simple-to-use therapeutic strategy for stroke patients.
Prevalence of preconception risk factors for adverse pregnancy outcome among women from tribal and non-tribal blocks in Nashik district, India: a cross-sectional study
Authors: Doke Prakash Prabhakarrao , Gothankar Jayashree Sachin , Chutke Amruta Paresh , Palkar Sonali Hemant , Patil Archana Vasantrao , Pore Prasad Dnyandeo , Bhuyan Khanindra Kumar , Karnataki Madhusudan Vamanrao , Deshpande Aniruddha Vinayakrao , Shrotri Aparna Nishikant , Narula Arvinder Pal Singh
Published: July 2022

Background

Although critical, the preconception phase in women’s lives is comparatively ignored. The presence of some risk factors during this phase adversely affects the wellbeing of the woman and the pregnancy outcome. The study objectives were to measure the prevalence of various known risk factors for adverse pregnancy outcome in the preconception period of women and their comparison between blocks.

Methods

This was a community-based cross-sectional study in two tribal and two non-tribal blocks each in Nasik district, Maharashtra, India. The study included married women desiring to conceive within 1 year. Trained Accredited Social Health Activists (field level health worker) collected information from women using a validated interview schedule through house-to-house visits and obtained women’s anthropometric measurements in a standard manner. The study assessed the presence of 12 documented risk factors.

Results

The study enlisted 7875 women desiring pregnancy soon. The mean age of women was 23.19 (± 3.71) years, and 16% of them were adolescents. Women’s illiteracy was higher in tribal areas than non-tribal (p < 0.001). About two-thirds of women have at least one risk factor, and 40.0% have a single risk factor. The most common risk factor observed was no formal education (44.35%). The prevalence of selected risk factors was significantly higher among women from tribal areas. The mean BMI of women was 19.73 (± 3.51), and a higher proportion (40.5%) of women from tribal areas had BMI < 18.5. Despite being of high parity status (≥ 4), about 7.7% of women from the tribal area and 3% from non-tribal desired pregnancy. Tobacco and alcohol consumption was higher among tribal women. The majority of women consumed meals with family members or husbands. Protein and calorie intake of about 1.4% of women was less than 50% of the recommended daily allowance; however, most of them perceived to have abundant food.

Conclusions

Health risks, namely younger age, illiteracy, high parity, consumption of tobacco, low protein, and calorie intake, were quite prevalent, and the risks were significantly more among women from tribal areas. “Continuum of care” must comprise preconception care inclusive of Behavioral Change Communication, particularly for easily modifiable risk factors and specially for tribal women.