bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing trends in the prevalence of prior cancer in newly diagnosed lung, stomach, colorectal, breast, cervical, and corpus uterine cancer patients: a population-based study
Authors: Sato Akira , Matsubayashi Keisuke , Morishima Toshitaka , Nakata Kayo , Kawakami Koji , Miyashiro Isao
Published: March 2021

Background

Cancer survivors are frequently excluded from clinical research, resulting in their omission from the development of many cancer treatment strategies. Quantifying the prevalence of prior cancer in newly diagnosed cancer patients can inform research and clinical practice. This study aimed to describe the prevalence, characteristics, and trends of prior cancer in newly diagnosed cancer patients in Japan.

Methods

Using Osaka Cancer Registry data, we examined the prevalence, characteristics, and temporal trends of prior cancer in patients who received new diagnoses of lung, stomach, colorectal, female breast, cervical, and corpus uterine cancer between 2004 and 2015. Site-specific prior cancers were examined for a maximum of 15 years before the new cancer was diagnosed. Temporal trends were evaluated using the Cochran-Armitage trend test.

Results

Among 275,720 newly diagnosed cancer patients, 21,784 (7.9%) had prior cancer. The prevalence of prior cancer ranged from 3.3% (breast cancer) to 11.1% (lung cancer). In both sexes, the age-adjusted prevalence of prior cancer had increased in recent years (P values for trend < 0.001), especially in newly diagnosed lung cancer patients. The proportion of smoking-related prior cancers exceeded 50% in patients with newly diagnosed lung, stomach, colorectal, breast, and cervical cancer.

Conclusions

The prevalence of prior cancer in newly diagnosed cancer patients is relatively high, and has increased in recent years. Our findings suggest that a deeper understanding of the prevalence and characteristics of prior cancer in cancer patients is needed to promote more inclusive clinical research and support the expansion of treatment options.
Analysis of structural injury patterns in peripapillary retinal nerve fibre layer and retinal ganglion cell layer in ethambutol-induced optic neuropathy
Authors: Sheng Wen-Yan , Su Ling-Ya , Ge Wei , Wu Shuang-Qing , Zhu Li-Wei
Published: March 2021

Background

We investigated structural injury patterns in the peripapillary retinal nerve fibre layer (p-RNFL) and ganglion cell inner plexiform layer (GCIPL) caused by ethambutol treatment.

Methods

Sixty-four patients undergoing ethambutol treatment at Zhejiang Chinese Medicine and Western Medicine Integrated Hospital were recruited. Fourteen (14) exhibited visual dysfunction (abnormal group), and the remaining 50 had no visual dysfunction (subclinical group). The thickness of the p-RNFL, total macular retina layer and GCIPL were measured using Cirrus-HD Optical coherence tomography (Cirrus-HD OCT, Cirrus high-definition optical coherence tomography), and compared with 60 healthy, age-matched controls.

Results

The p-RNFL thickness was similar in both subclinical and control groups. When compared with the control group, p-RNFL thickness in the abnormal group was significantly increased in the inferior and superior quadrants (GEE, P = 0.040, P = 0.010 respectively). In contrast with the subclinical group, p-RNFL thickness in the inferior quadrant was increased in the abnormal group (GEE, P = 0.047). The GCIPL thickness in the inferonasal and inferior sectors was significantly deceased in the subclinical group when compared with controls (GEE, P = 0.028, P = 0.047, respectively). The average and minimum value of GCIPL thickness, and thickness in the superonasal, inferior, inferotemporal, superotemporal and superior sectors were significantly decreased in the abnormal group when compared with controls (GEE, P = 0.016, P = 0.001, P = 0.028, P = 0.010, P = 0.012, P = 0.015, P = 0.010, respectively). The cube average macular thickness (CAMT) in the abnormal group was significantly thinner than controls (GEE, P = 0.027).

Conclusions

GCIPL measurements using Cirrus-HD OCT detected retinal ganglion cell layer loss following ethambutol treatment, before visual dysfunction occurred.
Common mental disorders and HIV status in the context of DREAMS among adolescent girls and young women in rural KwaZulu-Natal, South Africa
Authors: Mthiyane Nondumiso , Harling Guy , Chimbindi Natsayi , Baisley Kathy , Seeley Janet , Dreyer Jaco , Zuma Thembelihle , Birdthistle Isolde , Floyd Sian , McGrath Nuala , Tanser Frank , Shahmanesh Maryam , Sherr Lorraine
Published: March 2021

Background

HIV affects many adolescent girls and young women (AGYW) in South Africa. Given the bi-directional HIV and mental health relationship, mental health services may help prevent and treat HIV in this population. We therefore examined the association between common mental disorders (CMD) and HIV-related behaviours and service utilisation, in the context of implementation of the combination DREAMS (Determined, Resilient, Empowered, AIDS-free, Mentored and Safe) HIV prevention programme in rural uMkhanyakude district, KwaZulu-Natal. DREAMS involved delivering a package of multiple interventions in a single area to address multiple sources of HIV risk for AGYW.

Methods

We analysed baseline data from an age-stratified, representative cohort of 13–22 year-old AGYW. We measured DREAMS uptake as a count of the number of individual-level or community-based interventions each participant received in the last 12 months. CMD was measured using the validated Shona Symptom Questionnaire, with a cut off score ≥ 9 indicating probable CMD. HIV status was ascertained through home-based serotesting. We used logistic regression to estimate the association between CMD and HIV status adjusting for socio-demographics and behaviours.

Results

Probable CMD prevalence among the 2184 respondents was 22.2%, increasing steadily from 10.1% among 13 year-old girls to 33.1% among 22 year-old women. AGYW were more likely to report probable CMD if they tested positive for HIV (odds ratio vs. test negative: 1.88, 95% confidence interval: 1.40–2.53). After adjusting for socio-demographics and behaviours, there was evidence that probable CMD was more prevalent among respondents who reported using multiple healthcare-related DREAMS interventions.

Conclusion

We found high prevalence of probable CMD among AGYW in rural South Africa, but it was only associated with HIV serostatus when not controlling for HIV acquisition risk factors. Our findings highlight that improving mental health service access for AGYW at high risk for HIV acquisition might protect them. Interventions already reaching AGYW with CMD, such as DREAMS, can be used to deliver mental health services to reduce both CMD and HIV risks. There is a need to integrate mental health education into existing HIV prevention programmes in school and communities.
Longitudinal study of MRI and functional outcome measures in facioscapulohumeral muscular dystrophy
Authors: Wang Leo H. , Shaw Dennis W. W. , Faino Anna , Budech Christopher B. , Lewis Leann M. , Statland Jeffrey , Eichinger Katy , Tapscott Stephen J. , Tawil Rabi N. , Friedman Seth D.
Published: March 2021

Background

Facioscapulohumeral muscular dystrophy (FSHD) is a patchy and slowly progressive disease of skeletal muscle. For MRI to be a useful biomarker in an FSHD clinical trial, it should reliably detect changes over relatively short time-intervals (~ 1 year). We hypothesized that fatty change over the study course would be most likely in muscles already demonstrating disease progression, and that the degree of MRI burden would be correlated with function.

Methods

We studied 36 patients with FSHD and lower-extremity weakness at baseline. Thirty-two patients returned in our 12-month longitudinal observational study. We analyzed DIXON MRI images of 16 lower-extremity muscles in each patient and compared them to quantitative strength measurement and ambulatory functional outcome measures.

Results

There was a small shift to higher fat fractions in the summed muscle data for each patient, however individual muscles demonstrated much larger magnitudes of change. The greatest increase in fat fraction was observed in muscles having an intermediate fat replacement at baseline, with minimally (baseline fat fraction < 0.10) or severely (> 0.70) affected muscles less likely to progress. Functional outcome measures did not demonstrate marked change over the interval; however, overall MRI disease burden was correlated with functional outcome measures. Direct comparison of the tibialis anterior (TA) fat fraction and quantitative strength measurement showed a sigmoidal relationship, with steepest drop being when the muscle gets more than ~ 20% fatty replaced.

Conclusions

Assessing MRI changes in 16 lower-extremity muscles across 1 year demonstrated that those muscles having an intermediate baseline fat fraction were more likely to progress. Ambulatory functional outcome measures are generally related to overall muscle MRI burden but remain unchanged in the short term. Quantitative strength measurement of the TA showed a steep loss of strength when more fatty infiltration is present suggesting that MRI may be preferable for following incremental change or modulation with drug therapy.
Effects of mouth breathing on facial skeletal development in children: a systematic review and meta-analysis
Authors: Zhao Ziyi , Zheng Leilei , Huang Xiaoya , Li Caiyu , Liu Jing , Hu Yun
Published: March 2021

Background

Mouth breathing is closely related to the facial skeletal development and malocclusion. The purpose of this systematic review and meta-analysis was to assess the effect of mouth breathing on facial skeletal development and malocclusion in children.

Methods

An electronic search in PubMed, the Cochrane Library, Medline, Web of Science, EMBASE and Sigle through February 23rd, 2020, was conducted. Inclusion criteria were children under 18 years of age with maxillofacial deformities due to mouth breathing. The risk of bias in nonrandomized studies of interventions (ROBINS-I) tool for controlled clinical trials. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach was used for the quality assessment. The included indicators were SNA, SNB, ANB, SN-OP, SN-PP, PP-MP, SNGoGn, MP-H, 1-NA, 1. NA, 1. NB, 1-NB, Overjet, Overbite, SPAS, PAS, and C3-H. Data concerning the mean difference in mesial molar movement and extent of canine retraction were extracted for statistical analysis. The mean differences and 95% confidence intervals were analyzed for continuous data. Review Manager 5.3, was used to synthesize various parameters associated with the impact of mouth breathing on facial skeletal development and malocclusion.

Results

Following full-text evaluations for eligibility, 10 studies were included in the final quantitative synthesis. In Sagittal direction, SNA (MD: − 1.63, P < 0.0001), SNB (MD: − 1.96, P < 0.0001) in mouth-breathing children was lower than that in nasal-breathing children. ANB (MD: 0.90, P < 0.0001), 1. NA (MD: 1.96, P = 0.009), 1-NA (MD: 0.66, P = 0.004), and 1-NB (MD: 1.03, P < 0.0001) showed higher values in children with mouth breathing. In vertical direction, SN-PP (MD: 0.68, P = 0.0050), SN-OP (MD: 3.05, P < 0.0001), PP-MP (MD: 4.92, P < 0.0001) and SNGoGn (MD: 4.10, P < 0.0001) were higher in mouth-breathing individuals. In airway, SPAS (MD: − 3.48, P = 0.0009), PAS (MD: − 2.11, P < 0.0001), and C3-H (MD: − 1.34, P < 0.0001) were lower in mouth breathing group.

Conclusions

The results showed that the mandible and maxilla rotated backward and downward, and the occlusal plane was steep. In addition, mouth breathing presented a tendency of labial inclination of the upper anterior teeth. Airway stenosis was common in mouth-breathing children.

Trial registration crd-register@york.ac.uk, registration number CRD42019129198.
Commercial sex work among university students: a case study of four public universities in Ghana
Authors: Gbagbo Fred Yao , Gbagbo Josephine Akosua
Published: March 2021

Background

Despite its criminalization in Ghana, commercial sex work dates back to ancient societies and occurs in various forms within communities. The authors examined commercial sex work in selected public Universities in Ghana to inform policy and program decisions for safer sex at the universities in Ghana.

Methods

The study was an exploratory-mixed-method design. Respondents were identified using purposive and snowballing techniques while semi-structured questionnaires and in-depth interviews were used for data collection between 2017and 2019. Quantitative data were analyzed using Statistical Package for Social Sciences version 23 and qualitative data analyzed thematically.

Results

Findings show that there is a proliferation of commercial sex work on university campuses in Ghana for financial, material, and emotional gains. Student sex workers have devised various strategies to combine academic work and sex work. Prospective customers are solicited by hanging out in drinking bars and nightclubs in and around university campuses at night and/or leaving contact details with pimps to be contacted for services. Brothels are also springing up in and around the university campuses in the form of movie houses and student sex workers convert their hostel rooms into brothels. Price negotiation is based on the environment, duration, the sex workers' perceived safety of the sexual act, customer's preferences for styles, and positions adopted for sex.

Conclusion

There is a need for further studies in this area and a multi-sectoral approach for appropriate policy and program interventions to regulate the practice on campus.
Assessment of the Adjusted Clinical Groups system in Dutch primary care using electronic health records: a retrospective cross-sectional study
Authors: Girwar Shelley-Ann M. , Fiocco Marta , Sutch Stephen P. , Numans Mattijs E. , Bruijnzeels Marc A.
Published: March 2021

Background

Within the Dutch health care system the focus is shifting from a disease oriented approach to a more population based approach. Since every inhabitant in the Netherlands is registered with one general practice, this offers a unique possibility to perform Population Health Management analyses based on general practitioners’ (GP) registries. The Johns Hopkins Adjusted Clinical Groups (ACG) System is an internationally used method for predictive population analyses. The model categorizes individuals based on their complete health profile, taking into account age, gender, diagnoses and medication. However, the ACG system was developed with non-Dutch data. Consequently, for wider implementation in Dutch general practice, the system needs to be validated in the Dutch healthcare setting. In this paper we show the results of the first use of the ACG system on Dutch GP data. The aim of this study is to explore how well the ACG system can distinguish between different levels of GP healthcare utilization.

Methods

To reach our aim, two variables of the ACG System, the Aggregated Diagnosis Groups (ADG) and the mutually exclusive ACG categories were explored. The population for this pilot analysis consisted of 23,618 persons listed with five participating general practices within one region in the Netherlands. ACG analyses were performed based on historical Electronic Health Records data from 2014 consisting of primary care diagnoses and pharmaceutical data. Logistic regression models were estimated and AUC’s were calculated to explore the diagnostic value of the models including ACGs and ADGs separately with GP healthcare utilization as the dependent variable. The dependent variable was categorized using four different cut-off points: zero, one, two and three visits per year.

Results

The ACG and ADG models performed as well as models using International Classification of Primary Care chapters, regarding the association with GP utilization. AUC values were between 0.79 and 0.85. These models performed better than the base model (age and gender only) which showed AUC values between 0.64 and 0.71.

Conclusion

The results of this study show that the ACG system is a useful tool to stratify Dutch primary care populations with GP healthcare utilization as the outcome variable.
Expression of a recombinant FLT3 ligand and its emtansine conjugate as a therapeutic candidate against acute myeloid leukemia cells with FLT3 expression
Authors: Zhang Dengyang , Guo Yao , Zhao Yuming , Yu Liuting , Chang Zhiguang , Pei Hanzhong , Huang Junbin , Chen Chun , Xue Hongman , Xu Xiaojun , Pan Yihang , Li Ningning , Zhu Chengming , Zhao Zhizhuang Joe , Yu Jian , Chen Yun
Published: March 2021

Background

Most patients with acute myeloid leukemia (AML) remain uncurable and require novel therapeutic methods. Gain-of-function FMS-like tyrosine kinase 3 (FLT3) mutations are present in 30–40% of AML patients and serve as an attractive therapeutic target. In addition, FLT3 is aberrantly expressed on blasts in > 90% of patients with AML, making the FLT3 ligand-based drug conjugate a promising therapeutic strategy for the treatment of patients with AML. Here,E. coliwas used as a host to express recombinant human FLT3 ligand (rhFL), which was used as a specific vehicle to deliver cytotoxic drugs to FLT3 + AML cells.

Methods

Recombinant hFL was expressed and purified from induced recombinant BL21 (DE3)E. coli. Purified rhFL and emtansine (DM1) were conjugated by anN-succinimidyl 3-(2-pyridyldithio)propionate (SPDP) linker. We evaluated the potency of the conjugation product FL-DM1 against FLT3-expressing AML cells by examining viability, apoptosis and the cell cycle. The activation of proteins related to the activation of FLT3 signaling and apoptosis pathways was detected by immunoblotting. The selectivity of FL-DM1 was assessed in our unique HCD-57 cell line, which was transformed with the FLT3 internal tandem duplication mutant (FLT3-ITD).

Results

Soluble rhFL was successfully expressed in the periplasm of recombinantE. coli. The purified rhFL was bioactive in stimulating FLT3 signaling in AML cells, and the drug conjugate FL-DM1 showed activity in cell signaling and internalization. FL-DM1 was effective in inhibiting the survival of FLT3-expressing THP-1 and MV-4-11 AML cells, with half maximal inhibitory concentration (IC50) of 12.9 nM and 1.1 nM. Additionally, FL-DM1 induced caspase-3-dependent apoptosis and arrested the cell cycle at the G2/M phase. Moreover, FL-DM1 selectively targeted HCD-57 cells transformed by FLT3-ITD but not parental HCD-57 cells without FLT3 expression. FL-DM1 can also induce obvious apoptosis in primary FLT3-positive AML cells ex vivo.

Conclusions

Our data demonstrated that soluble rhFL can be produced in a bioactive form in the periplasm of recombinantE. coli. FL can be used as a specific vehicle to deliver DM1 into FLT3-expressing AML cells. FL-DM1 exhibited cytotoxicity in FLT3-expressing AML cell lines and primary AML cells. FL-DM1 may have potential clinical applications in treating patients with FLT3-positive AML.
Absence of EpCAM in cervical cancer cells is involved in slug induced epithelial-mesenchymal transition
Authors: Liu Xian , Feng Qian , Zhang Yanru , Zheng PengSheng , Cui Nan
Published: March 2021

Background

Slug (Snai2) is a pivotal player in initiating epithelial-mesenchymal transition (EMT) through its trans-suppression effect on E-cadherin in various normal and malignant cells. In this study, the positive effect of Slug on promoting cell motility and metastasis in cervical cancer was further confirmed in this study.

Methods

RNA-Seq was performed to explore the potential molecules that participate in Slug-mediated EMT in cervical cancer cells. The negative correlation between Slug and EpCAM expression in cervical cancer cells was detected in this study, and linked them with in vitro migration and invasion assay, in vivo metastasis experiments, luciferase reporter assay and Chromatin immunoprecipitation.

Results

Transcriptome sequencing analysis revealed that epithelial cell adhesion molecule (EpCAM) was significantly decreased in Slug-overexpressing SiHa cells. Simultaneously, an absence of EpCAM expression was observed in Slug-overexpressing cells. Further studies revealed the trans-suppression effect of Slug on EpCAM through its binding to the E-boxes in the proximal promoter region of EpCAM in cervical cancer cells. Restoring EpCAM in Slug-overexpressing cells by transiently transfecting an EpCAM recombinant plasmid attenuated cell motility and promoted cell growth. Moreover, the negative correlation between Slug and EpCAM expression in human squamous cervical carcinoma (SCC) samples was verified by using Pearson correlation analysis.

Conclusions

These results demonstrated that the absence of EpCAM under Slug expression in cervical cancer cells probably participated in Slug-regulated EMT and further promoted tumor metastasis. Additionally, this study supports a potential way for Slug to initiate EMT progression in cervical cancer cells in addition to inhibiting E-cadherin.
Trends in access to anti‐malarial treatment in the formal private sector in Uganda: an assessment of availability and affordability of first‐line anti‐malarials and diagnostics between 2007 and 2018
Authors: Kibira Denis , Ssebagereka Anthony , van den Ham Hendrika A. , Opigo Jimmy , Katamba Henry , Seru Morries , Reed Tim , Leufkens Hubert G. , Mantel-Teeuwisse Aukje K.
Published: March 2021

Background

Malaria is the single largest cause of illness in Uganda. Since the year 2008, the Global Fund has rolled out several funding streams for malaria control in Uganda. Among these are mechanisms aimed at increasing the availability and affordability of artemisinin-based combination therapy (ACT). This paper examines the availability and affordability of first-line malaria treatment and diagnostics in the private sector, which is the preferred first point of contact for 61% of households in Uganda between 2007 and 2018.

Methods

Cross-sectional surveys were conducted between 2007 and 2018, based on a standardized World Health Organization/Health Action International (WHO/HAI) methodology adapted to assess availability, patient prices, and affordability of ACT medicines in private retail outlets. A minimum of 30 outlets were surveyed per year as prescribed by the standardized methodology co-developed by the WHO and Health Action International. Availability, patient prices, and affordability of malaria rapid diagnostic tests (RDTs) was also tracked from 2012 following the rollout of the test and treat policy in 2010. The median patient prices for the artemisinin-based combinations and RDTs was calculated in US dollars (USD). Affordability was assessed by computing the number of days’ wages the lowest-paid government worker (LPGW) had to pay to purchase a treatment course for acute malaria.

Results

Availability of artemether/lumefantrine (A/L), the first-line ACT medicine, increased from 85 to100% in the private sector facilities during the study period. However, there was low availability of diagnostic tests in private sector facilities ranging between 13% (2012) and 37% (2018). There was a large reduction in patient prices for an adult treatment course of A/L from USD 8.8 in 2007 to USD 1.1 in 2018, while the price of diagnostics remained mostly stagnant at USD 0.5. The affordability of ACT medicines and RDTs was below one day’s wages for LPGW.

Conclusions

Availability of ACT medicines in the private sector medicines retail outlets increased to 100% while the availability of diagnostics remained low. Although malaria treatment was affordable, the price of diagnostics remained stagnant and increased the cumulative cost of malaria management. Malaria stakeholders should consolidate the gains made and consider the inclusion of diagnostic kits in the subsidy programme.
Measuring health inequalities: a systematic review of widely used indicators and topics
Authors: Albert-Ballestar Sergi , García-Altés Anna
Published: March 2021

Background

According to many conceptual frameworks, the first step in the monitoring cycle of health inequalities is the selection of relevant topics and indicators. However, some difficulties may arise during this selection process due to a high variety of contextual factors that may influence this step. In order to help accomplish this task successfully, a comprehensive review of the most common topics and indicators for measuring and monitoring health inequalities in countries/regions with similar socioeconomic and political status as Catalonia was performed.

Methods

We describe the processes and criteria used for selecting health indicators from reports, studies, and databases focusing on health inequalities. We also describe how they were grouped into well-known health topics. The topics were filtered and ranked by the number of indicators they accounted for.

Results

We found 691 indicators used in the study of health inequalities. The indicators were grouped into 120 topics, 34 of which were selected for having five indicators or more. Most commonly found topics in the list include “Life expectancy”, “Infant mortality”, “Obesity and overweight (BMI)”, “Mortality rate”, “Regular smokers/tobacco consumption”, “Self-perceived health”, “Unemployment”, “Mental well-being”, “Cardiovascular disease/hypertension”, “Socioeconomic status (SES)/material deprivation”.

Conclusions

A wide variety of indicators and topics for the study of health inequalities exist across different countries and organisations, although there are some clear commonalities. Reviewing the use of health indicators is a key step to know the current state of the study of health inequalities and may show how to lead the way in understanding how to overcome them.
Health-related quality of life among patients with bipolar disorder in rural southwestern Uganda: a hospital based cross sectional study
Authors: Anyayo Lucas , Ashaba Scholastic , Kaggwa Mark Mohan , Maling Samuel , Nakimuli-Mpungu Etheldreda
Published: March 2021

Background

Bipolar disorder is a psychiatric disorder that alters mood and affects over 55 million people globally with an estimated lifetime prevalence of approximately 0.8–1.1%. In Africa, the lifetime prevalence of the bipolar spectrum disorders is slightly lower at 0.1–0.6%. Bipolar disorder is ranked the sixth leading cause of disability with high rates of morbidity and mortality and negatively impacts quality of life of those affected.

Methods

The aim of the study was to determine the health-related quality of life of patients with bipolar disorder attending a mental health clinic in south western Uganda. We enrolled a consecutive sample of 169 participants and evaluated their health-related quality of life using the medical outcomes health survey short form-36 (SF-36) scale. We used bivariate and multivariable logistic regression to determine associations between quality of life, sociodemographic and clinical factors setting the physical and mental component categories of quality life scale as the main outcome variables.

Results

The mean age of the participants was 37.23 (12.83) and slightly over half (54.4%) were females. More than half (66.86%) of the participants had poor physical component summary (mean = 45.06, SD = 8.44) while 81% of the participants had poor mental component summary (mean = 41.95, SD = 8.45). Poor physical quality of life had a statistically significant association with history of suicidal thoughts (OR = 2.75, 95% CI = 1.14–6.63, P = 0.02), while poor mental quality of life had a statistically significant association with history of suicidal thoughts (OR = 3.94, CI = 1.22–12.71, P = 0.02) and history of psychotic symptoms (OR = 2.46, CI = 1.07–5.64, P = 0.03).

Conclusion

The mental and physical quality of life of our participants was poor and history of suicidal thoughts and psychotic symptoms were associated with poor quality of life. There is need to address psychotic symptoms and suicidal thoughts in the management of patients with bipolar disorder to improve health related outcomes and quality of life.
System dynamics modelling of health workforce planning to address future challenges of Thailand’s Universal Health Coverage
Authors: Leerapan Borwornsom , Teekasap Pard , Urwannachotima Nipaporn , Jaichuen Wararat , Chiangchaisakulthai Kwanpracha , Udomaksorn Khunjira , Meeyai Aronrag , Noree Thinakorn , Sawaengdee Krisada
Published: March 2021

Background

System dynamics (SD) modelling can inform policy decisions under Thailand's Universal Health Coverage. We report on this thinking approach to Thailand's strategic health workforce planning for the next 20 years (2018–2037).

Methods

A series of group model building (GMB) sessions involving 110 participants from multi-sectors of Thailand's health systems was conducted in 2017 and 2018. We facilitated policymakers, administrators, practitioners and other stakeholders to co-create a causal loop diagram (CLD) representing a shared understanding of why the health workforce's demands and supplies in Thailand were mismatched. A stock and flow diagram (SFD) was also co-created for testing the consequences of policy options by simulation modelling.

Results

The simulation modelling found hospital utilisation created a vicious cycle of constantly increasing demands for hospital care and a constant shortage of healthcare providers. Moreover, hospital care was not designed for effectively dealing with the future demands of ageing populations and prevalent chronic illness. Hence, shifting emphasis to professions that can provide primary care, intermediate care, long-term care, palliative care, and end-of-life care can be more effective.

Conclusions

Our SD modelling confirmed that shifting the care models to address the changing health demands can be a high-leverage policy of health workforce planning, although very difficult to implement in the short term.
EVITA 2.0, an updated framework for understanding evidence-based mental health policy agenda-setting: tested and informed by key informant interviews in a multilevel comparative case study
Authors: Votruba Nicole , Grant Jonathan , Thornicroft Graham
Published: March 2021

Background

Mental health remains a neglected issue on the global health policy agenda, particularly in low- and middle-income countries (LMIC), and the translation of research evidence into policy and practice is slow. The new EVITA framework was developed to improve mental health evidence uptake and policy agenda-setting in LMICs. In addition, behavioural science methods may be able to support knowledge translation to policy.

Methods

Using a mixed-methods study design, we applied and tested the newly developed EVITA 1.1 framework against three case studies related to South Africa at the district, national and international levels. In-depth interviews with 26 experts were conducted between August and November 2019, transcribed, coded and analysed in NVivo, using iterative categorization. The data were analysed against both the EVITA framework and the MINDSPACE framework for behavioural insights.

Results

In our case study comparison, we found that (1) research translation to the policy agenda occurs in a complex, fluid system which includes multiple “research clouds”, “policy spheres” and other networks; (2) mental health research policy agenda-setting is based on key individuals and intermediaries and their interrelationships; and (3) key challenges and strategies for successful research to policy agenda impact are known, but are frequently not strategically implemented, such as including all stakeholders to overcome the policy implementation gap. Our data also suggest that behavioural science methods can be strategically applied to support knowledge translation to policy agenda-setting.

Conclusion

We found that the EVITA framework is useful for understanding and improving mental health research policy interrelationships to support evidence uptake to the policy agenda, and that behavioural science methods are effective support mechanisms. The revised EVITA 2.0 framework therefore includes behavioural insights, for improved mental health policy agenda-setting in LMICs. More research is needed to understand whether EVITA can be applied to other LMICs and to high-income contexts.
The how and why of producing policy relevant research: perspectives of Australian childhood obesity prevention researchers and policy makers
Authors: Newson Robyn , Rychetnik Lucie , King Lesley , Milat Andrew J. , Bauman Adrian E.
Published: March 2021

Background

Understanding why research is conducted may help address the under-utilisation of research. This study examined the reasons for childhood obesity prevention knowledge production in New South Wales (NSW), Australia, and the factors influencing research choices from the perspective of the researchers and health policy agencies contributing to the research.

Methods

A literature search of SCOPUS and ISI Web of Knowledge (affiliation and key word searches) was conducted to compile a database of NSW childhood obesity research outputs, published between 2000 and 2015 (n = 543). Descriptive statistics were used to quantify outputs by research type, differentiating measurement, descriptive, and intervention research, systematic reviews and other publications. Interviews were conducted with a sample of researchers drawn from the database (n = 13) and decision makers from health policy agencies who funded and contributed to childhood obesity research in NSW (n = 15). Researcher interviews examined views about societal impacts, why and under what circumstances the research was conducted. Decision-maker interviews examined policy agency research investment and how research was used in decision making. Content analysis and a thematic approach was used to analyse the interview transcripts.

Results

The research in this case was conducted for mix of reasons including those traditionally associated with academic inquiry, as well as intentions to influence policy and practice. Differences in funding mechanisms, administrative and employment arrangements, and ‘who’ initiated the research, created differing incentives and perspectives for knowledge production. Factors associated with the characteristics and experience of the individuals involved also influenced goals, as did the type of research conducted. Policy agencies played a role in directing research to address policy needs.

Conclusions

The findings of this study confirm that researchers are strongly influenced by their working environment. Funding schemes and other incentives to support policy relevant knowledge production are important. Contextual factors such as policy priorities, policy-driven research funding and the embedded nature or strong connections between some researchers and the policy agencies involved, are likely to have influenced the extent to which policy goals were reported in this study.
The epithelial-mesenchymal transition and the cytoskeleton in bioengineered systems
Authors: Leggett Susan E. , Hruska Alex M. , Guo Ming , Wong Ian Y.
Published: March 2021

The epithelial-mesenchymal transition (EMT) is intrinsically linked to alterations of the intracellular cytoskeleton and the extracellular matrix. After EMT, cells acquire an elongated morphology with front/back polarity, which can be attributed to actin-driven protrusion formation as well as the gain of vimentin expression. Consequently, cells can deform and remodel the surrounding matrix in order to facilitate local invasion. In this review, we highlight recent bioengineering approaches to elucidate EMT and functional changes in the cytoskeleton. First, we review transitions between multicellular clusters and dispersed individuals on planar surfaces, which often exhibit coordinated behaviors driven by leader cells and EMT. Second, we consider the functional role of vimentin, which can be probed at subcellular length scales and within confined spaces. Third, we discuss the role of topographical patterning and EMT via a contact guidance like mechanism. Finally, we address how multicellular clusters disorganize and disseminate in 3D matrix. These new technologies enable controlled physical microenvironments and higher-resolution spatiotemporal measurements of EMT at the single cell level. In closing, we consider future directions for the field and outstanding questions regarding EMT and the cytoskeleton for human cancer progression.
Optimal preparation of SARS-CoV-2 viral transport medium for culture
Authors: McAuley Julie , Fraser Claire , Paraskeva Elena , Trajcevska Elizabeth , Sait Michelle , Wang Nancy , Bert Eric , Purcell Damian , Strugnell Richard
Published: March 2021

Introduction

The sudden arrival of the COVID-19 pandemic placed significant stresses on supply chains including viral transport medium (VTM). The VTM that was urgently required needed to support viral replication, as well as other routine diagnostic approaches. We describe the preparation and validation testing of VTM for rapidly expanding diagnostic testing, where the capacity of the VTM to preserve viral integrity, for culture, isolation and full sequence analysis, was maintained.

Methods

VTM was prepared using different methods of sterilization then ‘spiked’ with virus. The VTM was investigated using viral culture in Vero cells, and for nucleic acid detection by quantitative PCR.

Results

The best results were obtained by filter and autoclave-based sterilization. The VTM proved robust for culture-based analyses provided the inoculated VTM was stored at 4 °C, and tested within 48 h. The filtered VTM also supported PCR-based diagnosis for at least 5 days when the mock inoculated VTM was held at room temperature.

Discussion

The manual handling of VTM production, including filling and sterilization, was optimized. SARS-CoV-2 was spiked into VTM to assess different sterilization methods and measure the effects of storage time and temperature upon VTM performance. While most diagnostic protocols will not require replication competent virus, the use of high quality VTM will allow for the next phase of laboratory analysis in the COVID-19 pandemic, including drug and antibody susceptibility analysis of re-isolated SARS-CoV-2, and for the testing of vaccine escape mutants.
The long noncoding RNA MALAT1 modulates adipose loss in cancer-associated cachexia by suppressing adipogenesis through PPAR-γ
Authors: Han Jun , Shen Lei , Zhan Zheng , Liu Yuguo , Zhang Chang , Guo Ruochen , Luo Yangjun , Xie Zhiqin , Feng Ying , Wu Guohao
Published: March 2021

Background

Cancer-associated cachexia is a multifactorial syndrome defined by progressive weight loss with ongoing loss of adipose tissue and skeletal muscle. Adipose loss occurs in the early stage of cachexia and is associated with reduced quality of life and survival time. Although numerous lncRNAs are regarded as novel regulators in adipose metabolism, the role of lncRNAs that selectively modulate the development of adipose loss in cachexia remains limited.

Methods

In this study, we analyzed microarray data of lncRNAs in adipose loss and further explored the function and mechanism of MALAT1 in adipose loss. First, we explored the expression and function of MALAT1 in adipose cell by quantitative PCR and RNA knockdown. Subsequently, the mechanism of MALAT1 involvement in adipose loss was analyzed via RNA-seq, bioinformatics analysis and reporter gene assay. Finally, we explored the clinical significance of MALAT1 through correlation analysis.

Results

Cellular experiments revealed that knocking down MALAT1 significantly inhibited the process of adipogenesis. RNA-seq data showed that numerous adipogenic genes were downregulated upon MALAT1 knockdown. A protein–protein interaction network analysis identified PPAR-γ as the central node transcription factor, the inhibition of which explains the downregulation of numerous adipogenic genes. A reporter gene assay suggested that MALAT1 can regulate the gene expression of PPAR-γ at the transcriptional level. Moreover, MALAT1 was weakly expressed in the subcutaneous white adipose tissue of cancer-associated cachexia patients and was related to low fat mass index and poor prognosis in cancer patients.

Conclusions

This study indicated that MALAT1 is associated with adipose loss in cancer-associated cachexia by regulating adipogenesis through PPAR-γ, which may potentially be a novel target for the diagnosis and treatment of cancer-associated cachexia in the clinic.
Retraction Note: Effect of sagittal femoral component alignment on biomechanics after mobile-bearing total knee arthroplasty
Authors: Koh Yong-Gon , Lee Jin-Ah , Lee Hwa-Yong , Suh Dong-Suk , Kim Hyo-Jeong , Kang Kyoung-Tak
Published: March 2021

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13018-019-1458-5.
Effect of childhood overweight on distal metaphyseal radius fractures treated by closed reduction
Authors: Liu Yu , Liu Chunjie , Guo Dongmei , Wang Ning , Zhao Ying , Li Dan
Published: March 2021

Background

The medical community has recognized overweight as an epidemic negatively affecting a large proportion of the pediatric population, but few studies have been performed to investigate the relationship between overweight and failure of conservative treatment for distal radius fractures (DRFs). This study was performed to investigate the effect of overweight on the outcome of conservative treatment for DRFs in children.

Methods

We performed a retrospective study of children with closed displaced distal metaphyseal radius fractures in our hospital from January 2015 to May 2020. Closed reduction was initially performed; if closed reduction failed, surgical treatment was performed. Patients were followed up regularly after treatment, and redisplacement was diagnosed on the basis of imaging findings. Potential risk factors for redisplacement were collected and analyzed.

Results

In total, 142 children were included in this study. The final reduction procedure failed in 21 patients, all of whom finally underwent surgical treatment. The incidences of failed final reduction and fair reduction were significantly higher in the overweight/obesity group than in the normal-weight group (P = 0.046 and P = 0.041, respectively). During follow-up, 32 (26.4%) patients developed redisplacement after closed reduction and cast immobilization. The three risk factors associated with the incidence of redisplacement were overweight/obesity [odds ratio (OR), 2.149; 95% confidence interval (CI), 1.320–3.498], an associated ulnar fracture (OR, 2.127; 95% CI, 1.169–3.870), and a three-point index of ≥ 0.40 (OR, 3.272; 95% CI, 1.975–5.421).

Conclusions

Overweight increases the risk of reduction failure and decreases the reduction effect. Overweight children were two times more likely to develop redisplacement than normal-weight children in the present study. Thus, overweight children may benefit from stricter clinical follow-up and perhaps a lower threshold for surgical intervention.
Risk factors of postoperative bone cement leakage on osteoporotic vertebral compression fracture: a retrospective study
Authors: Zhang Kui , She Jiang , Zhu Yandong , Wang Wenji , Li Erliang , Ma Ding
Published: March 2021

Purpose

To investigate risk factors of bone cement leakage in percutaneous vertebroplasty(PVP)for osteoporotic vertebral compression fracture (OVCF).

Methods

A total of 236 patients (344 vertebrae) who underwent PVP between November 2016 and June 2020 were enrolled in the study. Clinical and radiological characteristics, including age, gender, course of disease, trauma, type of vertebral fracture, cortical continuity of vertebral body, intervertebral vacuum cleft (IVC), fracture severity, fracture level, basivertebral foramen, bone cement dispersion types, the cement injection volume, the type of cement leakage, puncture approach, and intrusion of the posterior wall, were considered as potential risk factors. Three types of leakage (type-B, type-C, and type-S) were defined and risk factors for each type were analyzed. Logistic analysis was used to study the relationship between each factor and the type of cement leakage.

Results

The incidences of the three types of leakage were 28.5%, 24.4%, and 34.3%. The multinomial logistic analysis revealed that the factors of type-B leakage were the shape of cement and basivertebral foramen. One significant factor related to type-C leakage was cortical disruption, and the factors of type-S leakage were bone cement dispersion types, basivertebral foramen, cleft, fracture severity, an intrusion of the posterior wall, and gender.

Conclusion

Different types of cement leakage have their own risk factors, and the analysis of risk factors of these might be helpful in reducing the rate of cement leakage.
Value of amniotic fluid homocysteine assay in prenatal diagnosis of combined methylmalonic acidemia and homocystinuria, cobalamin C type
Authors: Chen Ting , Liang Lili , Zhang Huiwen , Ye Jun , Qiu Wenjuan , Xiao Bing , Zhu Hong , Wang Lei , Xu Feng , Gong Zhuwen , Gu Xuefan , Han Lianshu
Published: March 2021

Background

Combined methylmalonic acidemia and homocystinuria, cobalamin C type (cblC defect) is the most common inborn error of cobalamin metabolism, and different approaches have been applied to its prenatal diagnosis. To evaluate the reliability of biochemical method for the prenatal diagnosis of cblC defect, we conducted a retrospective study of our 10-year experience at a single center.

Methods

248 pregnancies whose probands were diagnosed as cblC defect were referred to our center for prenatal diagnosis from January 2010 to December 2019. Prenatal data of Hcy levels determined by enzymatic cycling assay, acylcarnitine analysis using liquid chromatography tandem mass spectrometry, organic acid analysis using gas chromatography mass spectrometry, and genetic analysis by direct sequencing of 248 at-risk fetuses were retrospectively reviewed.

Results

For 2.0 and 16.0 μmol/L levels of Hcy AF samples, the relative errors were − 2.5% and 2.8%, respectively. The respective measurement uncertainties were 13.07% and 14.20%. For the 248 at-risk fetuses, 63 fetuses were affected and 185 fetuses were unaffected. Hcy level of 13.20 (6.62–43.30) μmol/L in 63 affected fetuses was significantly higher than that in 185 unaffected fetuses of 2.70 (0.00–5.80) μmol/L, and there was no overlap between the affected and unaffected groups. The diagnostic sensitivity and specificity of Hcy were 100% and 92.05%, respectively. The positive and negative predictive values of the combination of Hcy, propionylcarnitine (C3), ratio of C3 to acetylcarnitine (C2; C3/C2), methylmalonic acid (MMA), and methylcitric acid (MCA) were both 100%. Sixteen fetuses displayed inconclusive genetic results of MMACHC variants, in which seven fetuses were determined to be affected with elevated levels of Hcy, C3, C3/C2 and MMA, and their levels were 18.50 (6.70–43.30) μmol/L, 8.53(5.02–11.91) μmol/L, 0.77 (0.52–0.97), 8.96 (6.55–40.32) mmol/mol Cr, respectively. The remaining nine fetuses were considered unaffected based on a normal amniotic fluid metabolite profile.

Conclusions

Hcy appears to be another characteristic biomarker for the prenatal diagnosis of cblC defect. The combination of Hcy assay with acylcarnitine and organic acid analysis is a fast, sensitive, and reliable prenatal diagnostic biochemical approach. This approach could overcome the challenge of the lack of genetic analysis for families with at-risk cblC defect fetuses.