bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between echinococcosis-specific health literacy and behavioural intention to prevent echinococcosis among herdsmen on the Tibet Plateau in China: a cross-sectional study
Authors: Zhao Jie , Dawa Yangzong , A Kezhong , Dejicuo  , Lengbao  , Li Zengyue , Chen Wanli , Wang Jingya , Zhang Yuxin , Dengbentai  , Wang Jiwei , Shi Lizheng , Jiang Qingwu
Published: January 2021

Background

Echinococcosis is considered a neglected zoonotic disease and has been a major worldwide public health problem. Although it is known that health literacy is closely related to health behaviours and health outcomes, few studies have paid attention to echinococcosis related health literacy. This study aims to examine the association between echinococcosis-specific health literacy (ES-HL) and behavioural intention to prevent echinococcosis (BIPE) among herdsmen on the Tibet Plateauin in China.

Methods

A cross-sectional study of 401 Tibetan herdsmen was conducted in Gande county of Qinghai Province, China. Participants were recruited from August to September 2018 and from February to March 2019. A self-developed questionnaire was used to measure demographic information, ES-HL and BIPE. Hierarchical regression analysis was done to identify the factors associated with BIPE.

Results

In the hierarchical regression analysis, we entered age, sex, education level, marital state and family monthly income per capita into model 1 which explained a significant amount of variance in BIPE (Adjusted R2change = 0.029,P = 0.006). Sex (β = − 0.125,P = 0.013) and family monthly income per capita (β = − 0.133,P = 0.009) were found to be associated with BIPE. Subsequently, the three factors of ES-HL were added to Model 1 to create Model 2. In Model 2, the two factors of ES-HL, perceived echinococcosis information support (β = 0.229,P < 0.001) and echinococcosis-specific self-management ability (β = 0.252, P < 0.001), were significantly associated with BIPE, while the information acquisition and evaluation ability factor (β =0.093,P = 0.089) was not found to be associated with BIPE. The model improved significantly when ES-HL was included (Model 2) explaining the 25.8% of variance of BIPE (Adjust R2change =0.229,P < 0.001).

Conclusions

ES-HL is an important predictor of whether individuals take preventive actions against echinococcosis. An ES-HL promotion action project should be developed targeting specific populations to enhance the prevention of echinococcosis.
Epidemiological survey and screening strategy for dengue virus in blood donors from Yunnan Province
Authors: Li Ling , Li Ying , Lu Shaofang , Dong Jing , Xu Haixia , Zhang Qian , Weng Rong , Yin Yundi , He Rui , Fang Peng , Shi Hua , Yu Yinghan , Wu Ji , Liu Zhong , Hess John R.
Published: January 2021

Background

Dengue virus (DENV) infection is increasingly common in southern China and can be transmitted through blood transfusion but is not currently part of donor screening throughout the region. We assessed DENV prevalence among donors at the Xishuangbanna Blood Center, Yunnan, to support development of DENV screening strategies.

Methods

Blood samples were collected randomly between June 2019 and August 2019. These were screened for anti-DENV IgG and IgM using enzyme-linked immunosorbent assay (ELISA). Then, all reactive samples and some randomly-chosen non-reactive samples were used to detect DENV RNAs using real-time polymerase-chain-reaction (RT-PCR) assays. After RT-PCR, samples were further tested for soluble nonstructural protein 1 (NS1) using the colloidal gold method. Donors demographics were also collected and assessed.

Results

Over the study period, 2254 donor samples were collected and tested for anti-DENV IgG and IgM by ELISA. This revealed 598 anti-DENV IgG and/or IgM reactive samples, a serological prevalence of 26.53%. Of these, 26 were RT-PCR positive and/or NS1 positive. Significant differences in DENV prevalence were noted by occupation (P = 0.001), education (P < 0.001), and ethnicity (P = 0.026).

Conclusion

The prevalence of DENV in Xishuangbanna Blood Center was higher than most other blood centers that have implemented DENV donor screening. Our study provides first-hand data about the prevalence of DENV and allows the development of a screening strategy for clinical use.
Use of the A2DS2 scale to predict morbidity in stroke-associated pneumonia: a systematic review and meta-analysis
Authors: Huang Jie , Liu Ming , He Weiliang , Liu Feifei , Cheng Jinming , Wang Hebo
Published: January 2021

Background

This review aims to evaluate the performance and clinical applicability of the A2DS2 scale via systematic review and meta-analysis.

Methods

The Medline, Embase, Cochrane Library, CBM, CNKI, and Wanfang databases were searched. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Funnel plots and Egger’s test were used to evaluate publication bias. The bivariate random-effect model was used for calculating the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve (AUC). A Fagan nomogram was applied to evaluate the clinical applicability of the A2DS2 scale.

Results

A total of 29 full-text articles met the inclusion criteria, including 19,056 patients. Bivariate mixed-effects regression models yielded a mean sensitivity of 0.78 (95 % CI: 0.73–0.83), a specificity of 0.79 (95 % CI: 0.73–0.84), a positive likelihood ratio of 3.7 (95 % CI: 2.9–4.6), and a negative likelihood ratio of 0.27 (95 % CI: 0.23–0.33). The area under the receiver operating characteristic curve was 0.85 (95 % CI: 0.82–0.88). If given a pre-test probability of 50 %, the Fagan nomogram showed that when A2DS2 was positive, the post-test probability improved to 79 %. In contrast, when A2DS2 was negative, it decreased to 22 %. The results of the subgroup analysis showed no effect on the diagnostic accuracy of the A2DS2 scale in predicting stroke-associated pneumonia, except for the optimal cut-off value.

Conclusions

The A2DS2 scale demonstrates high clinical applicability and could be a valid scale for the early prediction of stroke-associated pneumonia in stroke patients.
A case of hemichorea in RNF213-related vasculopathy
Authors: Hosoki Satoshi , Yoshimoto Takeshi , Ihara Masafumi
Published: January 2021

Background

Internal carotid artery (ICA) stenosis has been recently reported to cause hemichorea, mainly in East Asia. The East Asian-specific p.R4810K variant of RNF213, a susceptibility gene for moyamoya disease (MMD), accounts for up to 25% of sporadic ischemic stroke with ICA stenosis cases in East Asia. However, as RNF213-related vasculopathy does not meet the diagnostic criteria for MMD, the creation of a new disease category has been suggested. Here, we report the first case of hemichorea in RNF213-related vasculopathy.

Case presentation

An 81-year-old woman was admitted to our hospital with choreic movements in the periphery of the right extremities at rest. Though head magnetic resonance imaging showed no fresh or old cerebral infarction, 123I-iodoamphetamine-single photon emission computed tomography showed cerebral blood flow of < 80% in the anterior territory of the left middle cerebral artery (MCA) in a resting state and cerebrovascular reactivity of < 10% in the broader area supplied by the left MCA after acetazolamide challenge. Head magnetic resonance angiography and digital subtraction angiography revealed left ICA C1 portion stenosis with compromised collateral vessels. Involuntary movements resolved with haloperidol administration within 3 days, without apparent recurrence from continuation of the medication for a year. Genetic testing revealed the presence of the heterozygous RNF213 p.R4810K variant.

Conclusions

Chorea is thought to be caused by damage to circuitry connecting the basal ganglia with the cerebral cortex, as found in cases of MMD, which possess aberrant vessels in the basal ganglia. However, aberrant vessels and cerebral infarctions were not observed in the basal ganglia in the current case, decreasing the likelihood of a role in chorea. Alternatively, as RNF213 regulates vascular endothelial function and angiogenesis, dysregulation may impair the neurovascular unit and damage basal ganglia circuitry, contributing to the development of chorea. This case may renew interest in the concept of RNF213-related vasculopathy and the pathophysiological mechanisms behind chorea in ICA stenosis.
Maternal alcohol use, adverse neonatal outcomes and pregnancy complications in British Columbia, Canada: a population-based study
Authors: Popova Svetlana , Dozet Danijela , O’Hanlon Graham , Temple Valerie , Rehm Jürgen
Published: January 2021

Background

The current study aimed to estimate the prevalence of alcohol use identified as a risk factor during pregnancies by the antenatal care providers, resulting in live births in British Columbia (BC) and to examine associations between alcohol use, adverse neonatal outcomes, and pregnancy complications.

Methods

This population-based cross-sectional study utilized linked obstetrical and neonatal records within the BC Perinatal Data Registry (BCPDR), for deliveries that were discharged between January 1, 2015 and March 31, 2018. The main outcome measures were alcohol use identified as a risk factor during pregnancy, associated maternal characteristics, pregnancy complications, and adverse neonatal outcomes. Estimates for the period and fiscal year prevalence were calculated. Chi-square tests were used to compare adverse neonatal outcomes and pregnancy complications by alcohol use during pregnancy identified as a risk factor. Logistic regression was used to examine the association between alcohol use identified as a risk factor during pregnancy and adverse neonatal outcomes and pregnancy complications, after adjusting for identified risk factors.

Results

A total of 144,779 linked records within the BCPDR were examined. The period prevalence of alcohol use during pregnancy identified as a risk factor was estimated to be 1.1% and yearly prevalence was 1.1, 1.1, 1.3 and 0.9% from the 2014/2015 to 2017/2018 fiscal years, respectively.

Alcohol use identified as a risk factor was associated with younger maternal age, fewer antenatal visits, being primiparous, a history of mental illness, substance use and smoking.

Neonates with alcohol use during pregnancy identified as a risk factor had greater odds of being diagnosed with: “low birth weight (1000-2499g)” (ICD-10: P07.1; aOR = 1.25; 95% CI: 1.01, 1.53), “other respiration distress of newborn” (ICD-10: P22.8; aOR = 2.57; 95% CI: 1.52, 4.07), “neonatal difficulty in breastfeeding” (ICD-10: P92.5; aOR = 1.97; 95% CI: 1.27, 2.92) and “feeding problems, unspecified” (ICD-10: P92.9; aOR = 2.06; 95% CI: 1.31, 3.09).

Conclusions

The prevalence of alcohol use during pregnancy identified as a risk factor was comparable to previous estimates within the BCPDR. Identified prenatal alcohol exposure was associated with notable differences in maternal and neonatal characteristics and adverse neonatal outcomes. More consistent, thorough screening and prevention efforts targeting alcohol use in pregnancy are urgently needed in Canada.
Amniotic fluid disorders and the effects on prenatal outcome: a retrospective cohort study
Authors: Bakhsh H. , Alenizy H. , Alenazi S. , Alnasser S. , Alanazi N. , Alsowinea M. , Alharbi L. , Alfaifi B.
Published: January 2021

Background

The amniotic fluid is a protective liquid present in the amniotic sac. Two types of amniotic fluid disorders have been identified. First refers to polyhydramnios, which is an immoderate volume of amniotic fluid with an Amniotic Fluid Index (AFI) greater than 24 cm. Second includes oligohydramnios, which refers to decreased AFI i.e., less than 5 cm. This study aims to; a) identify the maternal risk factors associated with amniotic fluid disorders, b) assess the effect of amniotic fluid disorders on maternal and fetal outcome c) examine the mode of delivery in pregnancy complicated with amniotic fluid disorders.

Methods

A comparative retrospective cohort study design is followed. Sample of 497 pregnant women who received care at King Abdullah bin Abdul-Aziz University Hospital (KAAUH) between January 2017 to October 2019 was included. Data were collected from electronic medical reports, and was analyzed using descriptive statistics. Association of qualitative variables was conducted by Chi-square test, where p-value < 0.05 was considered statistically significant.

Results

Among the collected data, 2.8% of the cases had polyhydramnios and 11.7% patients had oligohydramnios. One case of still born was identified. A statically significant association was found between polyhydramnios and late term deliveries (P = 0.005) and cesarean section (CS) rates (P = 0.008). The rate of term deliveries was equal in normal AFI and oligohydramnios group (P = 0.005). Oligohydramnios was mostly associated with vaginal deliveries (P = 0.008). Oligohydramnios and polyhydramnios were found to be associated with diabetes mellitus patients (P = 0.005), and polyhydramnios with gestational diabetes patients (P = 0.052). Other maternal chronic diseases showed no effect on amniotic fluid index, although it might cause other risks on the fetus.

Conclusion

Diabetes mellitus and gestational diabetes are the most important maternal risk factors that can cause amniotic fluid disorders. Maternal and fetal outcome data showed that oligohydramnios associated with gestational age at term and low neonatal birth weight with high rates of vaginal deliveries, while polyhydramnios associated with gestational age at late term and high birth weight with higher rates of CS.
Implementing a modified World Health Organization safe childbirth checklist in health centers of Ethiopia: a pre and post intervention study
Authors: Abawollo Hailemariam Segni , Tsegaye Zergu Tafesse , Desta Binyam Fekadu , Mamo Tsega Teferi , Mamo Haregewoin Getachew , Mehari Zebyderu Tesfay , Gebremedhin Zenawork Kassa , Beshir Ismael Ali
Published: January 2021

Background

Childbirth is a complex process, and checklists are useful tools to remember steps of such complex processes. The World Health Organization safe childbirth checklist is a tool used to improve the quality of care provided to women giving birth. The checklist was modified by Ministry of Health and was introduced to health centers in Ethiopia by the USAID Transform: Primary Health Care Activity.

Methods

A pre and post intervention study design with prospective data collection was employed. The availability of essential childbirth supplies and adherence of health care providers to essential birth practices were compared for the pre and post intervention periods.

Results

The pre and post intervention assessments were conducted in 247 and 187 health centers respectively. A statistically significant improvement from 63.6% pre intervention to 83.5% post intervention was observed in the availability of essential childbirth supplies, t (389.7) = − 7.1, p = 0.000. Improvements in adherence of health care providers to essential birth practices were observed with the highest being at pause point three (26.2%, t (306.3) = − 10.6, p = 0.000) followed by pause point four (21.1%, t (282.5) = − 8.0, p = 0.000), and pause point two (18.2%, t (310.8) = − 9.7, p = 0.000). The least and statistically non-significant improvement was observed at pause point one (3.3%, t (432.0) = − 1.5, p = 0.131).

Conclusion

Improvement in availability of essential childbirth supplies and adherence of health care providers towards essential birth practices was observed after introduction of a modified World Health Organization safe childbirth checklist. Scale up of the use of the checklist is recommended.
The NeST (Neoadjuvant systemic therapy in breast cancer) study: National Practice Questionnaire of United Kingdom multi-disciplinary decision making
Authors:   on behalf of the NeST Study Research Collaborative, Whitehead I. , Irwin G. W. , Bannon F. , Coles C. E. , Copson E. , Cutress R. I. , Dave R. V. , Gardiner M. D. , Grayson M. , Holcombe C. , Irshad S. , O’Brien C. , O’Connell R. L. , Palmieri C. , Shaaban A. M. , Sharma N. , Singh J. K. , Potter S. , McIntosh S. A.
Published: January 2021

Background

Neoadjuvant systemic therapy (NST) is increasingly used in the treatment of breast cancer, yet it is clear that there is significant geographical variation in its use in the UK. This study aimed to examine stated practice across UK breast units, in terms of indications for use, radiological monitoring, pathological reporting of treatment response, and post-treatment surgical management.

Methods

Multidisciplinary teams (MDTs) from all UK breast units were invited to participate in the NeST study. A detailed questionnaire assessing current stated practice was distributed to all participating units in December 2017 and data collated securely usingREDCap. Descriptive statistics were calculated for each questionnaire item.

Results

Thirty-nine MDTs from a diverse range of hospitals responded. All MDTs routinely offered neoadjuvant chemotherapy (NACT) to a median of 10% (range 5–60%) of patients. Neoadjuvant endocrine therapy (NET) was offered to a median of 4% (range 0–25%) of patients by 66% of MDTs. The principal indication given for use of neoadjuvant therapy was for surgical downstaging. There was no consensus on methods of radiological monitoring of response, and a wide variety of pathological reporting systems were used to assess tumour response. Twenty-five percent of centres reported resecting the original tumour footprint, irrespective of clinical/radiological response. Radiologically negative axillae at diagnosis routinely had post-NACT or post-NET sentinel lymph node biopsy (SLNB) in 73.0 and 84% of centres respectively, whereas 16% performed SLNB pre-NACT. Positive axillae at diagnosis would receive axillary node clearance at 60% of centres, regardless of response to NACT.

Discussion

There is wide variation in the stated use of neoadjuvant systemic therapy across the UK, with general low usage of NET. Surgical downstaging remains the most common indication of the use of NAC, although not all centres leverage the benefits of NAC for de-escalating surgery to the breast and/or axilla. There is a need for agreed multidisciplinary guidance for optimising selection and management of patients for NST. These findings will be corroborated in phase II of the NeST study which is a national collaborative prospective audit of NST utilisation and clinical outcomes.
4’-O-Methylbroussochalcone B as a novel tubulin polymerization inhibitor suppressed the proliferation and migration of acute myeloid leukaemia cells
Authors: Liu Ziying , Wang Changshui , Wang Yali , Wang Lei , Zhang Yueyuan , Yan Genquan
Published: January 2021

Background

Recent years, survival rates of human with high-risk acute myeloid leukaemia (AML) have not raised substantially. This research aimed to investigate the role of 4′-O-Methylbroussochalcone B, for the treatment of human AML.

Methods

Firstly, we evaluated the effects of six chalcones on AML cells activity by MTT assay. Immunofluorescence staining, tubulin polymerization assay and N,N′-ethylenebis (iodoacetamide) (EBI) competition assay were performed on ML-2 cells. Transwell and apoptosis assay were also utilized in ML-2 cells and OCI-AML5 cells. The expressions of migration-related proteins, apoptosis-related proteins and Wnt/β-catenin pathway were detected by Western Blot.

Results

The results found six chalcones exhibited the anti-proliferative activity against different AML cell lines. Based on the results of immunofluorescence staining, tubulin polymerization assay and EBI competition assay, 4′-O-Methylbroussochalcone B was discovered to be a novel colchicine site tubulin polymerization inhibitor. 4′-O-Methylbroussochalcone B could induce apoptosis, inhibit proliferation and migration of ML-2 cells and OCI-AML5 cells. The cells were arrested in the G2-M phase by the treatment of 4′-O-Methylbroussochalcone B. In addition, 4′-O-Methylbroussochalcone B regulated MAPK and Wnt/β-catenin pathways in AML cells.

Conclusion

4′-O-Methylbroussochalcone B might inhibit proliferation and migration of the AML cells by MAPK and Wnt/β-catenin pathways as a tubulin polymerization inhibitor. It is promising for 4′-O-Methylbroussochalcone B to become a new drug to treat AML.
Conceptual causal models of socioeconomic status, family structure, family functioning and their role in public health
Authors: Booysen Frederik , Botha Ferdi , Wouters Edwin
Published: January 2021

Social determinants of health frameworks are standard tools in public health. These frameworks for the most part omit a crucial factor: the family. Socioeconomic status moreover is a prominent social determinant of health. Insofar as family functioning is poorer in poor families and family structure and functioning are linked to health, it is critical to consider the pathways between these four constructs. In this correspondence, we reflect on how empirical studies of this conceptual nexus mirror two causal models. We conclude by reflecting on future directions for research in this field.
Discrepancies in periodontitis classification among dental practitioners with different educational backgrounds
Authors: Oh Se-Lim , Yang Ji Seung , Kim Yoon Jeong
Published: January 2021

Background

The 2018 classification of periodontal disease characterizes the disease with a multidimensional staging and grading system.
The purpose of this multicenter study was to examine variations in periodontitis classification among dental practitioners with different postgraduate educational backgrounds at the University of Maryland School of Dentistry and the Loma Linda University School of Dentistry using the 2018 classification.

Methods

This cross-sectional observational study included two cohorts: dental practitioners with periodontal backgrounds (n1 = 31) and those with other educational backgrounds (n2 = 33). The survey instrument contained three periodontitis cases presented with the guideline of the 2018 classification and a questionnaire including closed and open-ended questions. The participants were asked to review each case and to fill out the questionnaire independently. Fisher’s exact test was conducted to examine the differences in responses between the two cohorts. Polychoric correlations were calculated to examine the relation between the level of familiarity with the 2018 classification and the accuracy of the classification.

Results

The distribution of item responses was significantly different between the two cohorts regarding only one item, grading for Case 1 (p = 0.01). No significant differences in accuracy between the two cohorts were observed except for two items, grading in Case 1 (p = 0.03) and staging in Case 3 (p = 0.04). There were no significant differences in risk factor identification for each case among the two cohorts (p = 1.00, Case 1; p = 0.22, Case 2). Staging in Case 3 ($$\widehat{\rho }$$

ρ
^

= 0.52) and risk factor identification in Case 2 ($$\widehat{\rho }$$

ρ
^

= 0.32) were significantly correlated with familiarity with the 2018 classification.

Conclusion

A fair level of agreement in periodontitis classification was observed among dental practitioners with different educational backgrounds when the 2018 classification was used. The periodontal cohort showed better agreement levels and partially better accuracy. Risk factor identification for periodontal disease was difficult regardless of the educational background.
Aesthetic evaluation of the labiolingual position of maxillary lateral incisors by orthodontists and laypersons
Authors: Jiang Xue , Cao Zhiwei , Yao Yang , Zhao Zhihe , Liao Wen
Published: January 2021

Background

The maxillary anterior teeth play a crucial role in smile aesthetics. Previous studies regarding the importance of maxillary lateral incisors for smile aesthetics concentrated on their size, incisor edge level, and inclination, etc. However, the aesthetic effect of lateral incisor movement in the spatial position has not been studied yet. Therefore, the purpose of this study was to explore the influence of the labiolingual position of maxillary lateral incisors on the aesthetic perception of smiles by orthodontists and laypersons, as well as analyze differences in this perception between male and female raters.

Methods

A three-dimensional (3D) dental model was generated from the photograph of a man’s smile using iOrtho7.0 software (Time Angel, Wuxi, China). Based on this model, seven images were generated with different labiolingual positions of the maxillary lateral incisors in 0.5 mm increments (+ indicating labial translation, and—indicating lingual translation). The images were evaluated by 86 orthodontists and 161 laypersons using a visual analog scale, with lower scores indicating less attractiveness. Data were analyzed using Student’sttest and one-way analysis of variance with post hoc test.

Results

There was no significant difference in smile ratings by males and females. Orthodontists assigned lower scores to all images than laypersons. The smile at + 1.5 mm was considered the least attractive by orthodontists, while smiles at + 1.5 mm and − 1.5 mm were regarded as the least attractive by laypersons. The smile at 0 mm was evaluated as the most attractive by all raters. Laypersons gave different scores to smiles at 0 or − 0.5 mm, but orthodontists did not.

Conclusions

The labiolingual position of maxillary lateral incisors does affect the perception of smile aesthetics. Orthodontists may rate smile aesthetics more critically than laypersons. Therefore, communication and discussion between orthodontists and patients is needed to achieve better therapeutic and aesthetic outcomes.
Continuous quality improvement as a tool to implement evidence-informed problem solving: experiences from the district and health facility level in Uganda
Authors: Tibeihaho Hector , Nkolo Charles , Onzima Robert Anguyo , Ayebare Florence , Henriksson Dorcus Kiwanuka
Published: January 2021

Background

Continuous quality improvement processes in health care were developed for use at health facility level, and that is where they have been used the most, often addressing defined care processes. However, in different settings different factors have been important to support institutionalization. This study explores how continuous quality improvement processes were institutionalized at the district level and at the health facility level in Uganda.

Methods

This qualitative study was carried out in seven districts in Uganda. Semi-structured interviews with key informants from the district health management teams and document review were conducted. Thematic analysis was used to analyze the data.

Results

All districts that participated in the study formed Continuous Quality Improvement (CQI) teams both at the district level and at the health facilities. The district CQI teams comprised of members from different departments within the district health office. District level CQI teams were mandated to take the lead in addressing management gaps and follow up CQI activities at the health facility level. Acceptability of quality improvement processes by the district leadership was identified across districts as supporting the successful implementation of CQI. However, high turnover of staff at health facility level was also reported as a detrimental to the successful implementation of quality improvement processes. Also the district health management teams did not engage much in addressing their own roles using continuous quality improvement.

Conclusion

The leadership and management provided by the district health management team was an important factor for the use of Continuous Quality Improvement principles within the district. The key roles of the district health team revolved around the institutionalisation of CQI at different levels of the health system, monitoring results of continuous quality improvement implementation, mobilising resources and health care delivery hence promoting the culture of quality, direct implementation of CQI, and creating an enabling environment for the lower-level health facilities to engage in CQI. High turnover of staff at health facility level was also reported as one of the challenges to the successful implementation of continuous quality improvement. The DHT did not engage much in addressing gaps in their own roles using continuous quality improvement.
An opportunistic evaluation of a routine service improvement project to reduce falls in hospital
Authors: Sheppard Diane , Clarke Elaine , Hemming Karla , Martin James , Lilford Richard
Published: January 2021

Background

Preventing falls in hospital is a perennial patient safety issue. The University Hospital Coventry and Warwickshire initiated a programme to train ward staff in accordance with guidelines. The National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care West Midlands was asked to expedite an independent evaluation of the initiative. We set out to describe the intervention to implement the guidelines and to evaluate it by means of a step-wedge cluster study using routinely collected data.

Methods

The evaluation was set up as a partially randomised, step-wedge cluster study, but roll-out across wards was more rapid than planned. The study was therefore analysed as a time-series. Primary outcome was rate of falls per 1000 Occupied Bed Days (OBDs) collected monthly using routine data. Data was analysed using a mixed-effects Poisson regression model, with a fixed effect for intervention, time and post-intervention time. We allowed for random variations across clusters in initial fall rate, pre-intervention slope and post-intervention slope.

Results

There was an average of 6.62 falls per 1000 OBDs in the control phase, decreasing to an average of 5.89 falls per 1000 OBDs in the period after implementation to the study end. Regression models showed no significant step change in fall rates (IRR: 1.02, 95% CI: 0.92–1.14). However, there was a gradual decrease, of approximately 3%, after the intervention was introduced (IRR: 0.97 per month, 95% CI: 0.95–0.99).

Conclusion

The intervention was associated with a small but statistically significantly improvement in falls rates. Expedited roll-out of an intervention may vitiate a step-wedge cluster design, but the intervention can still be studied using a time-series analysis. Assuming that there is some value in time series analyses, this is better than no evaluation at all. However, care is needed in making causal inferences given the non-experimental nature of the design.
Cost‐effectiveness of intensive care for hospitalized COVID-19 patients: experience from South Africa
Authors: Cleary S. M. , Wilkinson T. , Tamandjou Tchuem C. R. , Docrat S. , Solanki G. C.
Published: January 2021

Background

Given projected shortages of critical care capacity in public hospitals during the COVID-19 pandemic, the South African government embarked on an initiative to purchase this capacity from private hospitals. In order to inform purchasing decisions, we assessed the cost-effectiveness of intensive care management for admitted COVID-19 patients across the public and private health systems in South Africa.

Methods

Using a modelling framework and health system perspective, costs and health outcomes of inpatient management of severe and critical COVID-19 patients in (1) general ward and intensive care (GW + ICU) versus (2) general ward only (GW) were assessed. Disability adjusted life years (DALYs) were evaluated and the cost per admission in public and private sectors was determined. The model made use of four variables: mortality rates, utilisation of inpatient days for each management approach, disability weights associated with severity of disease, and the unit cost per general ward day and per ICU day in public and private hospitals. Unit costs were multiplied by utilisation estimates to determine the cost per admission. DALYs were calculated as the sum of years of life lost (YLL) and years lived with disability (YLD). An incremental cost-effectiveness ratio (ICER) - representing difference in costs and health outcomes of the two management strategies - was compared to a cost-effectiveness threshold to determine the value for money of expansion in ICU services during COVID-19 surges.

Results

A cost per admission of ZAR 75,127 was estimated for inpatient management of severe and critical COVID-19 patients in GW as opposed to ZAR 103,030 in GW + ICU. DALYs were 1.48 and 1.10 in GW versus GW + ICU, respectively. The ratio of difference in costs and health outcomes between the two management strategies produced an ICER of ZAR 73,091 per DALY averted, a value above the cost-effectiveness threshold of ZAR 38,465.

Conclusions

Results indicated that purchasing ICU capacity from the private sector during COVID-19 surges may not be a cost-effective investment. The ‘real time’, rapid, pragmatic, and transparent nature of this analysis demonstrates an approach for evidence generation for decision making relating to the COVID-19 pandemic response and South Africa’s wider priority setting agenda.
Factors associated with work-private life conflict and leadership qualities among line managers of health professionals in Swiss acute and rehabilitation hospitals – a cross-sectional study
Authors: Peter Karin A. , Halfens Ruud J. G. , Hahn Sabine , Schols Jos M. G. A.
Published: January 2021

Background

The workforce shortage of health professionals is a matter of global concern. Among possible causative factors in this shortage are the incompatibility of health professionals’ work with their private life, which may lead to increased stress and burnout symptoms, job dissatisfaction and a higher intention to leave the profession prematurely. Also, poor leadership qualities among direct line managers (e.g. clinic directors, leading physicians, ward managers, team leaders) have been associated with health professionals’ job dissatisfaction and intention to leave in previous studies. This study therefore aimed to identify key factors associated with health professionals’ work-private life conflicts and their managers’ leadership quality.

Methods

The study is based on a cross-sectional survey in 26 Swiss acute and rehabilitation hospitals, consisting of 3398 health professionals from various disciplines. For data analysis, multilevel models (with hospitals as the second level variable) were performed for ‘work-private life conflict’ and ‘quality of leadership’, considering significant main effects (using AIC) and significant interactions (using BIC) of potential explanatory variables.

Results

The main findings reveal that the compatibility of health professionals’ work and private life is associated with how much they can influence shift planning (possibility of exchanging shifts, B = -2.87, p < 0.01), the extent to which their individual preferences are considered (e.g. working on one specific shift only, B = 6.31, p < 0.01), number of work shifts per weekend (B = 1.38, p < 0.01) and working hours per week (B = 0.13, p < 0.01). In addition, the factors high quantitative demands (B = 0.25, p < 0.01), being required to hide their emotions (B = 0.16, p < 0.01) and poor social community support at work (B = -0.12, p < 0.01) were related to severe work-private life conflicts among health professionals. Regarding managerial leadership, health professionals perceived the leadership qualities of their direct line manager as being better if they received more social support (B = 0.61, p < 0.01) and rewards (B = 0.41, p < 0.01) at work.

Conclusions

The results show key components of improving the compatibility of work and private life for health professionals as well as managerial leadership qualities, and may help leaders working in acute or rehabilitation hospitals to develop appropriate interventions.
Single-cell resolution landscape of equine peripheral blood mononuclear cells reveals diverse cell types including T-bet+ B cells
Authors: Patel Roosheel S. , Tomlinson Joy E. , Divers Thomas J. , Van de Walle Gerlinde R. , Rosenberg Brad R.
Published: January 2021

Background

Traditional laboratory model organisms represent a small fraction of the diversity of multicellular life, and findings in any given experimental model often do not translate to other species. Immunology research in non-traditional model organisms can be advantageous or even necessary, such as when studying host-pathogen interactions. However, such research presents multiple challenges, many stemming from an incomplete understanding of potentially species-specific immune cell types, frequencies, and phenotypes. Identifying and characterizing immune cells in such organisms is frequently limited by the availability of species-reactive immunophenotyping reagents for flow cytometry, and insufficient prior knowledge of cell type-defining markers.

Results

Here, we demonstrate the utility of single-cell RNA sequencing (scRNA-Seq) to characterize immune cells for which traditional experimental tools are limited. Specifically, we used scRNA-Seq to comprehensively define the cellular diversity of equine peripheral blood mononuclear cells (PBMC) from healthy horses across different breeds, ages, and sexes. We identified 30 cell type clusters partitioned into five major populations: monocytes/dendritic cells, B cells, CD3+PRF1+ lymphocytes, CD3+PRF1− lymphocytes, and basophils. Comparative analyses revealed many cell populations analogous to human PBMC, including transcriptionally heterogeneous monocytes and distinct dendritic cell subsets (cDC1, cDC2, plasmacytoid DC). Remarkably, we found that a majority of the equine peripheral B cell compartment is comprised of T-bet+ B cells, an immune cell subpopulation typically associated with chronic infection and inflammation in human and mouse.

Conclusions

Taken together, our results demonstrate the potential of scRNA-Seq for cellular analyses in non-traditional model organisms and form the basis for an immune cell atlas of horse peripheral blood.
pH-responsive antibodies for therapeutic applications
Authors: Klaus Tomasz , Deshmukh Sameer
Published: January 2021

Therapeutic antibodies are instrumental in improving the treatment outcome for certain disease conditions. However, to enhance their efficacy and specificity, many efforts are continuously made. One of the approaches that are increasingly explored in this field are pH-responsive antibodies capable of binding target antigens in a pH-dependent manner. We reviewed suitability and examples of these antibodies that are functionally modulated by the tumor microenvironment. Provided in this review is an update about antigens targeted by pH-responsive, sweeping, and recycling antibodies. Applicability of the pH-responsive antibodies in the engineering of chimeric antigen receptor T-cells (CAR-T) and in improving drug delivery to the brain by the enhanced crossing of the blood–brain barrier is also discussed. The pH-responsive antibodies possess strong treatment potential. They emerge as next-generation programmable engineered biologic drugs that are active only within the targeted biological space. Thus, they are valuable in targeting acidified tumor microenvironment because of improved spatial persistence and reduced on-target off-tumor toxicities. We predict that the programmable pH-dependent antibodies become powerful tools in therapies of cancer.
Silenced lncRNA SNHG14 restrains the biological behaviors of bladder cancer cells via regulating microRNA-211-3p/ESM1 axis
Authors: Feng Rui , Li Zhongxing , Wang Xing , Ge Guangcheng , Jia Yuejun , Wu Dan , Ji Yali , Wang Chenghao
Published: January 2021

Background

Bladder cancer (BCa) is a malignant tumor that occurs on the mucosa of the bladder, in which dysregulated long non-coding RNAs (lncRNAs) are involved. This study investigated the effect of lncRNA small nucleolar RNA host gene 1 (SNHG14) on the biological characteristics of BCa cells from microRNA (miR)-211-3p/ESM1 signaling axis.

Methods

BCa tissues and the matched normal tissues were collected to test SNHG14, miR-211-3p and ESM1 levels. SNHG14, miR-211-3p and ESM1 levels in BCa cell lines (T24, 5637, UMUC-3 and EJ) and normal bladder epithelial cells SV-HVC-1 were detected for screening the cell lines for follow-up experiments. T24 and UMUC-3 cells were transfected with different plasmids of SNHG14, miR-211-3p or ESM1 to observe the biological characteristics of BCa cells by MTT, colony formation, Transwell assays and flow cytometry. Tumor xenograft was implemented to inspect tumor growth in vivo. The targeting relationships of SNHG14, miR-211-3p and ESM1 were verified by bioinformatics software, RNA pull down assay and luciferase reporter assay.

Results

Enhanced SNHG14, ESM1 and suppressed miR-211-3p were found in BCa tissues and cells. SNHG14 up-regulated ESM1 via competitive binding with miR-211-3p. Decreased SNHG14 or up-regulated miR-211-3p depressed cell cycle entry, colony formation, invasion, migration and proliferation abilities, and facilitated apoptosis of BCa cells. Decreased SNHG14 or up-regulated miR-211-3p reduced the tumor volume and weight of nude mice with BCa, as well as promoted apoptosis and restrained proliferation of tumor cells. miR-211-3p inhibition or ESM1 overexpression reversed the effects of down-regulation of SNHG14 on BCa, and miR-211-3p up-regulation or ESM1 downregulation reversed the effect of SNHG14 overexpression on BCa. SNHG14 targeted miR-211-3p to regulate ESM1 expression.

Conclusion

Our study highlights that silenced SNHG14 or elevated miR-211-3p represses the tumorigenic ability of BCa cells, which may be linked to ESM1 knockdown.
Cofilin-1, LIMK1 and SSH1 are differentially expressed in locally advanced colorectal cancer and according to consensus molecular subtypes
Authors: Sousa-Squiavinato Annie Cristhine Moraes , Vasconcelos Renata Ivo , Gehren Adriana Sartorio , Fernandes Priscila Valverde , de Oliveira Ivanir Martins , Boroni Mariana , Morgado-Díaz Jose Andrés
Published: January 2021

Background

Colorectal cancer (CRC) is among the deadliest cancers, wherein early dissemination of tumor cells, and consequently, metastasis formation, are the main causes of mortality and poor prognosis. Cofilin-1 (CFL-1) and its modulators, LIMK1/SSH1, play key roles in mediating the invasiveness by driving actin cytoskeleton reorganization in various cancer types. However, their clinical significance and prognostic value in CRC has not been fully explored. Here, we evaluated the clinical contribution of these actin regulators according to TNM and consensus molecular subtypes (CMSs) classification.

Methods

CFL-1, LIMK1 and SSH1 mRNA/protein levels were assessed by real-time PCR and immunohistochemical analyses using normal adjacent and tumor tissues obtained from a clinical cohort of CRC patients. The expression levels of these proteins were associated with clinicopathological features by using the chi square test. In addition, using RNA-Seq data of CRC patients from The Cancer Genome Atlas (TCGA) database, we determine how these actin regulators are expressed and distributed according to TNM and CMSs classification. Based on gene expression profiling, Kaplan–Meier survival analysis was used to evaluated overall survival.

Results

Bioinformatic analysis revealed that LIMK1 expression was upregulated in all tumor stages. Patients with high levels of LIMK1 demonstrated significantly lower overall survival rates and exhibited greater lymph node metastatic potential in a clinical cohort. In contrast, CFL-1 and SSH1 have expression downregulated in all tumor stages. However, immunohistochemical analyses showed that patients with high protein levels of CFL-1 and SSH1 exhibited greater lymph node metastatic potential and greater depth of local invasion. In addition, using the CMSs classification to evaluate different biological phenotypes of CRC, we observed that LIMK1 and SSH1 genes are upregulated in immune (CMS1) and mesenchymal (CMS4) subtypes. However, patients with high levels of LIMK1 also demonstrated significantly lower overall survival rates in canonical (CMS2), and metabolic (CMS3) subtypes.

Conclusions

We demonstrated that CFL-1 and its modulators, LIMK1/SSH1, are differentially expressed and associated with lymph node metastasis in CRC. Finally, this expression profile may be useful to predict patients with aggressive signatures, particularly, the immune and mesenchymal subtypes of CRC.
Protein liposomes-mediated targeted acetylcholinesterase gene delivery for effective liver cancer therapy
Authors: Wang Kai , Shang Fusheng , Chen Dagui , Cao Tieliu , Wang Xiaowei , Jiao Jianpeng , He Shengli , Liang Xiaofei
Published: January 2021

Background

Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. Proteolipid integrated with tumor-targeting potential of functional protein and excellent gene delivery performance has shown potential for targeted gene therapy.

Results

Herein, we prepared transferrin-modified liposomes (Tf-PL) for the targeted delivery of acetylcholinesterase (AChE) therapeutic gene to liver cancer. We found that the derived Tf-PL/AChE liposomes exhibited much higher transfection efficiency than the commercial product Lipo 2000 and shown premium targeting efficacy to liver cancer SMMC-7721 cells in vitro. In vivo, the Tf-PL/AChE could effectively target liver cancer, and significantly inhibit the growth of liver cancer xenografts grafted in nude mice by subcutaneous administration.

Conclusions

This study proposed a transferrin-modified proteolipid-mediated gene delivery strategy for targeted liver cancer treatment, which has a promising potential for precise personalized cancer therapy.
The state of health research governance in Africa: what do we know and how can we improve?
Authors: Nabyonga-Orem Juliet , Asamani James Avoka , Makanga Micheal
Published: January 2021

Background

The developments in global health, digital technology, and persistent health systems challenges, coupled with global commitments like attainment of universal health coverage, have elevated the role of health research in low- and middle-income countries. However, there is a need to strengthen health research governance and create a conducive environment that can promote ethics and research integrity and increase public trust in research.

Objective

To assess whether the necessary structures are in place to ensure health research governance.

Methods

Employing a cross-sectional survey, we collected data on research governance components from 35 Member States of the World Health Organization (WHO) African Region. Data were analysed using basic descriptive and comparative analysis.

Results

Eighteen out of 35 countries had legislation to regulate the conduct of health research, while this was lacking in 12 countries. Some legislation was either grossly outdated or too limiting in scope, while some countries had multiple laws. Health research policies and strategies were in place in 16 and 15 countries, respectively, while research priority lists were available in 25 countries. Overlapping mandates of institutions responsible for health research partly explained the lack of strategic documents in some countries. The majority of countries had ethical committees performing a dual role of ethical and scientific review. Research partnership frameworks were available to varying degrees to govern both in-country and north–south research collaboration. Twenty-five countries had a focal point and unit within the ministries of health (MoH) to coordinate research.

Conclusion

Governance structures must be adaptive to embrace new developments in science. Further, strong coordination is key to ensuring comprehensiveness and complementarity in both research development and generation of evidence. The majority of committees perform a dual role of ethics and scientific review, and these need to ensure representation of relevant expertise. Opportunities that accrue from collaborative research need to be seized through strong MoH leadership and clear partnership frameworks that guide negotiations.