bluuebunny/crossref_metadata_2025 huggingface dataset:
The radiographic, pulmonary, and clinical outcomes of patients with severe rigid spinal deformities treated via halo‐pelvic traction
Authors: Chen Jian , Sui Wen-yuan , Yang Jing-fan , Deng Yao-long , Xu Jing , Huang Zi-fang , Yang Jun-lin
Published: January 2021

Background

The severe rigid deformity patients with pulmonary dysfunction could not tolerate complicated corrective surgery. Preoperative traction are used to reduce the curve magnitude and improve the pulmonary function before surgery, including halo-gravity traction (HGT) and halo-pelvic traction (HPT). The present study aimed to retrospectively compare the radiographic, pulmonary and clinical outcomes of preoperative HGT and HPT in severe rigid spinal deformity with respiratory dysfunction.

Methods

81 cases of severe rigid kyphoscoliosis treated with preoperative traction prior to corrective surgery for spinal deformity between 2016 and 2019 were retrospectively reviewed. Two patient groups were compared, HPT group (N = 30) and HGT group (N = 51). Patient demographics, coronal and sagittal Cobb angles and correction rates, pulmonary function, traction time, osteotomy grade, and postoperative neurological complications were recorded for all cases.

Results

The coronal Cobb angle was corrected from 140.67 ± 2.63 to a mean of 120.17 ± 2.93° in the HGT group, and from 132.32 ± 4.96 to 87.59 ± 3.01° in the HPT group (mean corrections 15.33 ± 1.53 vs. 34.86 ± 3.11 %) (P = 0.001). The mean major sagittal curve decreased from 134.28 ± 3.77 to 113.03 ± 4.57° in the HGT group and from 129.60 ± 8.45 to 65.61 ± 7.86° in the HPT group (P < 0.001); the mean percentage corrections were 16.50 ± 2.13 and 44.09 ± 9.78 % (P < 0.001). A significant difference in the pulmonary function test results was apparent between the two groups; the mean improvements in the FVC% of the HGT and HPT groups were 6.76 ± 1.85 and 15.6 ± 3.47 % (P = 0.024). The HPT group tended to exhibit more FEV% improvement than the HGT group, but the difference was not significant (5.15 ± 2.27 vs. 11.76 ± 2.22 %, P = 0.91).

Conclusions

Patients with severe rigid kyphoscoliosis who underwent preoperative HPT exhibited better radiographic correction of the deformity, and pulmonary function, and required fewer osteotomies compared to the HGT group. Thus, HPT may be useful for severe rigid spinal deformity patients with pulmonary dysfunction.
Mortality in older adults following a fragility fracture: real-world retrospective matched-cohort study in Ontario
Authors: Brown Jacques P. , Adachi Jonathan D. , Schemitsch Emil , Tarride Jean-Eric , Brown Vivien , Bell Alan , Reiner Maureen , Oliveira Thiago , Motsepe-Ditshego Ponda , Burke Natasha , Slatkovska Lubomira
Published: January 2021

Background

Recent studies are lacking reports on mortality after non-hip fractures in adults aged > 65.

Methods

This retrospective, matched-cohort study used de-identified health services data from the publicly funded healthcare system in Ontario, Canada, contained in the ICES Data Repository. Patients aged 66 years and older with an index fragility fracture occurring at any osteoporotic site between 2011 and 2015 were identified from acute hospital admissions, emergency and ambulatory care using International Classification of Diseases (ICD)-10 codes and data were analyzed until 2017. Thus, follow-up ranged from 2 years to 6 years. Patients were excluded if they presented with an index fracture occurring at a non-osteoporotic fracture site, their index fracture was associated with a trauma code, or they experienced a previous fracture within 5 years prior to their index fracture. This fracture cohort was matched 1:1 to controls within a non-fracture cohort by date, sex, age, geography and comorbidities. All-cause mortality risk was assessed.

Results

The survival probability for up to 6 years post-fracture was significantly reduced for the fracture cohort vs matched non-fracture controls (p < 0.0001; n = 101,773 per cohort), with the sharpest decline occurring within the first-year post-fracture. Crude relative risk of mortality (95% confidence interval) within 1-year post-fracture was 2.47 (2.38–2.56) in women and 3.22 (3.06–3.40) in men. In the fracture vs non-fracture cohort, the absolute mortality risk within one year after a fragility fracture occurring at any site was 12.5% vs 5.1% in women and 19.5% vs 6.0% in men. The absolute mortality risk within one year after a fragility fracture occurring at a non-hip vs hip site was 9.4% vs 21.5% in women and 14.4% vs 32.3% in men.

Conclusions

In this real-world cohort aged > 65 years, a fragility fracture occurring at any site was associated with reduced survival for up to 6 years post-fracture. The greatest reduction in survival occurred within the first-year post-fracture, where mortality risk more than doubled and deaths were observed in 1 in 11 women and 1 in 7 men following a non-hip fracture and in 1 in 5 women and 1 in 3 men following a hip fracture.
Evaluation of the pediatric life support instructors courses
Authors:   y Grupo Madrileño de Cuidados Intensivos Pediátricos, López-Herce Jesús , Carrillo Angel , Urbano Javier , Manrique Gema , Mencía y Santiago
Published: January 2021

Objective

To evaluate the results and quality of pediatric cardiopulmonary resuscitation (CPR) instructor training courses.

Methods

A retrospective analysis was performed of the results of 24 pediatric CPR instructor courses held over 21 years (1999 to 2019). The results of participants’ evaluation of theory and practice sessions were analyzed. In addition, participants were asked to answer an anonymous survey to assess their opinion on the quality of theory and practice lessons, course organization and methodology, and instructor training. The results were compared by professional groups.

Results

A total of 560 participants completed the instructor course. Of them, 554 passed theory and practice tests (98.9 %). The mean score obtained in theory tests was 9.2 (0.8) out of 10. The mean score obtained in all practice tests was > 3.5 out of 5. Participants evaluated all the aspects of the course (theory and practice content, organization, teaching methodology, and instructors) with mean scores over 8 out of 10.

Conclusions

Specific pediatric and neonatal CPR instructor courses are a cornerstone in the process of CPR training and ensuring the homogeneity and quality of training. Most of the participants obtained the qualification of instructors and their evaluation of the course was very positive.
Experiences of psychiatrists and support staff providing telemental health services to Indigenous peoples of Northern Quebec
Authors: Shang Zhida , Arnaert Antonia , Hindle Yvonne , Debe Zoumanan , Côté-Leblanc Geneviève , Saadi Amine
Published: January 2021

Background

Due to regional, professional, and resource limitations, access to mental health care for Canada’s Indigenous peoples can be difficult. Telemental health (TMH) offers the opportunity to provide care across vast distances and has been proven to be as effective as face-to-face services. To our knowledge, there has been no qualitative study exploring the experiences of TMH staff serving the Indigenous peoples in Northern Quebec, Canada; which is the purpose of this study.

Methods

Using a qualitative descriptive design, the entire staff of a TMH clinic was recruited, comprising of four psychiatrists and four support staff. Individual semi-structured interviews were conducted through videoconferencing, and results were thematically analyzed.

Results

To address the mental health gap in Northern communities, all psychiatrists believe in the necessity of in-person care and note the synergistic effect of combining in-person care and TMH services. This approach to care allows psychiatrists to maintain both an insider and outsider identity. However, if a patient’s condition requires hospitalization, then the TMH staff face a new set of information sharing and communication challenges with the inpatient staff. TMH staff believe that the provision of culturally sensitive care to Northern patients at the inpatient unit is progressing; however, more work needs to be done. Despite the strong collegial atmosphere within the clinic and collective efforts to provide quality TMH services, all participants express a sense of frustration with the paper-based and scattered documentation system.

Conclusion

The TMH team works in cohesion to offer TMH services to Indigenous peoples; yet, automatization is needed to improve the workflow efficiency within the clinic and collaboration with the Northern clinics. More research is needed on the functioning of TMH teams and the separate but important roles of each team member.
A quantum dot fluorescent microsphere based immunochromatographic strip for detection of brucellosis
Authors: Kong Yufang , Wang Huiyu , Wu Shaoqiang , Lv Jizhou , Mei Lin , Zhou Huifang , Lin Xiangmei , Han Xueqing
Published: January 2021

Background

Brucellosis is a serious zoonosis disease that frequently causes significant economic loss in animal husbandry and threatens human health. Therefore, we established a rapid, accurate, simple and sensitive fluorescent immunochromatographic strip test (ICST) based on quantum dots (QDs) for detection the antibodies of Brucella infection animals serum.

Results

The test strips were successfully prepared by quantum dot fluorescent microspheres (QDFM) as tracers, which were covalently coupled to an outer membrane protein of Brucella OMP22. The outer membrane protein OMP28 and monoclonal antibodies of OMP22 were separately dispensed onto a nitrocellulose membrane as test and quality control lines, respectively. The critical threshold for determining negative or positive through the ratio of the fluorescent signal of the test line and the control line (HT / HC) is 0.0492. The repeatability was excellent with an overall average CV of 8.78%. Under optimum conditions, the limit of detection was 1.05 ng/mL (1:512 dilution). With regard to the detection of brucellosis in 150 clinical samples, the total coincidence rate of ICST and Rose Bengal plate test (RBPT) was 97.3%, the coincidence rate of positive samples was 98.8%, the coincidence rate of negative samples was 95.3%, the sensitivity of RBPT is 1:32, and no cross reaction with the sera of other related diseases was observed.

Conclusion

In our present study, the QDFM has promising application for on-site screening of brucellosis owing to its high detection speed, high sensitivity, high specificity and low cost.
Promoting the health of refugee women: a scoping literature review incorporating the social ecological model
Authors: Hawkins Maren M. , Schmitt Marin E. , Adebayo Comfort Tosin , Weitzel Jennifer , Olukotun Oluwatoyin , Christensen Anastassia M. , Ruiz Ashley M. , Gilman Kelsey , Quigley Kyla , Dressel Anne , Mkandawire-Valhmu Lucy
Published: January 2021

The health of refugee women after settlement in a new country, can be adversely or positively affected by individual, interpersonal, community, and organizational factors. While much of the previous literature highlights these factors individually, there is a lack of comprehensive synthesis regarding how the factors interact to influence the health of refugee women. We conducted a thematic analysis in our literature review to elucidate how providers can work with refugee women to prevent adverse health outcomes and intervene at multiple levels to improve their health outcomes after resettlement. We reviewed peer-reviewed literature from 2009 to 2019 from Google Scholar, JSTOR, Global Health, PubMed, CINAHL, Sociological Abstracts, and Social Service Abstracts, and also used citation chaining, to identify relevant information pertaining to refugee women’s health. The key terms used for our literature review were, health care, violence, social support, and mental health. In total, we included 52 articles, 3 books, and 8 other sources. We found that refugee women are vulnerable to violence during migration and typically have high rates of post-traumatic stress disorder. There were also concerns of secondary victimization by providers after resettlement. We also found that social support is an important factor for reducing isolation, and improving access to health care, as well as improving mental health outcomes. However, social support was often difficult to maintain, and was moderated by factors such as English language fluency. Health care was influenced by health literacy, cultural difference, communication concerns, and access issues. The findings suggest that at the individual and interpersonal levels there is a need to address language barriers, improve provider-patient communication, and provide appropriate medical and mental health screenings. At the organizational level, inter-organizational communication and awareness are vital. At the community level, providers can work with community leaders, to educate, create dialogue and collaboration, to help facilitate understanding and bolster community social support. Improved communication and knowledge about the unique needs and concerns of refugee women through an integrated, multi-system approach is necessary to improve their health outcomes.
Inequalities in stunting among under-five children in Tanzania: decomposing the concentration indexes using demographic health surveys from 2004/5 to 2015/6
Authors: Musheiguza Edwin , Mahande Michael J. , Malamala Elias , Msuya Sia E. , Charles Festo , Philemon Rune , Mgongo Melina
Published: January 2021

Background

Child stunting is a global health concern. Stunting leads to several consequences on child survival, growth, and development. The absolute level of stunting has been decreasing in Tanzania from from 50% in 1991/92 to 34% in 2016 although the prevalence is still high (34%)Stunting varyies across socioeconomic determinants with a larger burden among the socioeconomic disadvantaged group. The reduction of inequalities in stunting is very crucial as we aim to reduce stunting to 28% by 2021 and hence attain zero malnutrition by 2030 under Sustainable Development Goal 2.2.This study aimed at determining the trend, contributing factors and changes of inequalities in stunting among children aged 3–59 months from 2004 to 2016.

Methods

Data were drawn from the Tanzania Demographic and Health Surveys. The concentration index (CIX) was used to quantify the magnitude of inequalities in stunting. The pooled Poisson regression model was used to determine the factors for stunting, decision criterion for significant determinants was at 5% level of significance. The CIX was decomposed using the Wagstaff and Watanabe decomposition methods., the percentage contribution of each factor to the toal concentration index was used to rank the factors for socioeconomic inequalities in stutning.

Results

Inequalities in stunting were significantly concentrated among the poor; evidenced by CIX = − 0.019 (p < 0.001) in 2004, − 0.018 (p < 0.001) in 2010 and − 0.0096 (p < 0.001) in 2015. There was insignificant decline in inequalities in stunting; the difference in CIX from 2004 to 2010 was 0.0015 (p = 0.7658), from 2010 to 2015/6 was − 0.0081 (p = 0.1145). The overall change in CIX from 2004 to 2015/6 was 0.00965 (p = 0.0538). Disparities in the distribution of wealth index (mean contribution > 84.7%) and maternal years of schooling (mean contribution > 22.4%) had positive impacts on the levels of inequalities in stunting for all surveyed years. Rural-urban differences reduced inequalities in stunting although the contribution changed over time.

Conclusion

Inequalities in stunting declined, differentials in wealth index and maternal education had increased contribution to the levels of inequalities in stunting. Reducing stunting among the disadvantaged groups requires initiatives which should be embarked on the distribution of social services including maternal and reproductive education among women of reproductive age, water and health infrastructures in remote areas.
PARP inhibitor Olaparib overcomes Sorafenib resistance through reshaping the pluripotent transcriptome in hepatocellular carcinoma
Authors: Yang Xiao-Dong , Kong Fan-En , Qi Ling , Lin Jia-Xin , Yan Qian , Loong Jane Ho Chun , Xi Shao-Yan , Zhao Yue , Zhang Yan , Yuan Yun-Fei , Ma Ning-Fang , Ma Stephanie , Guan Xin-Yuan , Liu Ming
Published: January 2021

Hepatocellular carcinoma (HCC) is one of the most common human malignancies worldwide with very poor prognosis. Resistance to targeted therapeutic drugs such as sorafenib remains one of the major challenges in clinical treatment. In the present study, PARP1 was found to be highly expressed in human embryonic stem cells, but progressively decreased upon specified hepatic differentiation. Reactivation of PARP1 expression was also detected in HCC residual tumors after sorafenib treatment in xenograft mouse model, indicating the potential important roles of PARP1 in stem cell pluripotency and HCC sorafenib treatment resistance. Overexpression of PARP1 was frequently observed in HCC patients, and closely associated with poor clinical outcome. Treatment of Sorafenib induced activation of DNA damage repair signaling, which is highly active and essential for maintenance of stem cell pluripotency in HCC residual tumors. PARP inhibitor Olaparib extensively suppressed the DNA damage repair signaling, and significantly inhibited the global pluripotent transcriptional network. The repression of key pluripotent transcriptional factors and DNA damage repair signaling by Olaparib was mainly through CHD1L-mediated condensation of the chromatin structure at their promotor regions. The global reshaping of the pluripotent transcriptome by Olaparib might reinforce Sorafenib in eliminating HCC residual tumors and enhance therapeutic efficiency.
Preoperative Controlling Nutritional Status (CONUT) score predicts short-term outcomes of patients with gastric cancer after laparoscopy-assisted radical gastrectomy
Authors: Qian Yun , Liu Huaying , Pan Junhai , Yu Weihua , Lv Jiemin , Yan Jiafei , Gao Jiaqi , Wang Xianfa , Ge Xiaolong , Zhou Wei
Published: January 2021

Background

An emerging prediction tool, the Controlling Nutritional Status (CONUT) score, has shown good assessment ability of postoperative outcomes in cancer patients. This study evaluated the role of the preoperative CONUT score regarding the short-term outcomes of gastric cancer (GC) after laparoscopic gastrectomy.

Methods

Three hundred and nine GC patients undergoing laparoscopic gastrectomy from January 2016 to June 2019 were analysed, retrospectively. The patients were divided into two groups according to the CONUT optimal cut-off value. Clinical characteristics and postoperative complications in the two groups were analysed and evaluated. Risk factors for complications were identified by univariate and multivariate analyses.

Results

A total of 309 patients underwent laparoscopic gastrectomy; 91 (29.4%) patients experienced postoperative complications. The preoperative CONUT score showed a good predictive ability for postoperative complications (area under the curve (AUC) = 0.718, Youden index = 0.343) compared with other indices, with an optimal cut-off value of 2.5. Patients with high CONUT score had a significantly higher incidence of overall complications (P < 0.001). Age, haemoglobin, C-reactive protein, red blood cell levels, CONUT scores, surgical procedure type, T1, T4, N0 and N3 pathological TNM classification, and pathological stages of I and III were associated with postoperative complications (P < 0.05). Furthermore, the preoperative CONUT score was identified as an independent risk predictor of postoperative complications (P = 0.012; OR = 2.433; 95% CI, 1.218-4.862) after multivariate analysis.

Conclusions

The preoperative CONUT score is a practical nutritional assessment for predicting short-term outcomes in GC patients after laparoscopy-assisted gastrectomy.
The impact of school uniforms on primary school student’s physical activity at school: outcomes of a cluster randomized controlled trial
Authors: Nathan Nicole , McCarthy Nicole , Hope Kirsty , Sutherland Rachel , Lecathelinais Christophe , Hall Alix , Lane Cassandra , Trost Stewart , Yoong Sze Lin , Wolfenden Luke
Published: January 2021

Background

Many school-based physical activity (PA) interventions are complex and have modest effects when delivered in real world contexts. A commonly reported barrier to students’ PA, particularly among girls, are uniforms that are impractical (e.g. tunic/dress and black leather shoes). Modifying student uniforms may represent a simple intervention to enhance student PA. The primary aim of this trial was to assess the impact of a PA enabling uniform intervention (shorts, polo shirt and sports shoes) on girls’ moderate-to-vigorous physical activity (MVPA) and total PA i.e. counts per minute (cpm).

Methods

A cluster randomized controlled trial was undertaken in 42 primary schools in New South Wales, Australia. Schools were randomized on one school day to the intervention group, where students wore a PA enabling uniform (their sports uniform) or a control group, where students wore their usual traditional uniform. Student PA was measured using wrist-worn Actigraph GT3X and GT9X accelerometers. Linear mixed models controlling for student characteristics were used to examine the effects of the intervention..

Results

Of the 3351 eligible students, 2315 (69.1%) had parental consent and 2180 of these consenting students participated (94.2%) of which 1847 (84.7%) were included in the analysis. For the primary aim the study found no significant differences between girls at schools allocated to the intervention relative to the control on change in MVPA (0.76 min, 95% CI − 0.47 to 1.99, p = 0.22) or cpm (36.99, 95% CI − 13.88 to 87.86, p = 0.15). Exploratory analysis revealed small effects for a number of findings, including significant reduction in sedentary activity (− 1.77, 95% CI − 3.40 to − 0.14, p = 0.035) among all students at schools allocated to the intervention, and non-significant improvements in girls’ light intensity PA (1.47 min, 95% CI − 0.06 to 3.00, p = 0.059) and sedentary activity (− 2.23 min; 95% CI − 4.49 to 0.02, p = 0.052).

Conclusion

The findings suggests that the intervention may yield small improvements in some measure of PA and require substantiation in a larger RCT with longer-term follow-up. The inclusion of additional intervention components may be required to achieve more meaningful effects.

Trial registration

The trial was prospectively registered with Australian New Zealand Clinical Trials Register ACTRN12617001266358 1st September 2017.
School-based gardening, cooking and nutrition intervention increased vegetable intake but did not reduce BMI: Texas sprouts - a cluster randomized controlled trial
Authors: Davis Jaimie N. , Pérez Adriana , Asigbee Fiona M. , Landry Matthew J. , Vandyousefi Sarvenaz , Ghaddar Reem , Hoover Amy , Jeans Matthew , Nikah Katie , Fischer Brian , Pont Stephen J. , Richards Daphne , Hoelscher Deanna M. , Van Den Berg Alexandra E.
Published: January 2021

Background

Although school garden programs have been shown to improve dietary behaviors, there has not been a cluster-randomized controlled trial (RCT) conducted to examine the effects of school garden programs on obesity or other health outcomes. The goal of this study was to evaluate the effects of a one-year school-based gardening, nutrition, and cooking intervention (called Texas Sprouts) on dietary intake, obesity outcomes, and blood pressure in elementary school children.

Methods

This study was a school-based cluster RCT with 16 elementary schools that were randomly assigned to either the Texas Sprouts intervention (n = 8 schools) or to control (delayed intervention, n = 8 schools). The intervention was one school year long (9 months) and consisted of: a) Garden Leadership Committee formation; b) a 0.25-acre outdoor teaching garden; c) 18 student gardening, nutrition, and cooking lessons taught by trained educators throughout the school-year; and d) nine monthly parent lessons. The delayed intervention was implemented the following academic year and received the same protocol as the intervention arm. Child outcomes measured were anthropometrics (i.e., BMI parameters, waist circumference, and body fat percentage via bioelectrical impedance), blood pressure, and dietary intake (i.e., vegetable, fruit, and sugar sweetened beverages) via survey. Data were analyzed with complete cases and with imputations at random. Generalized weighted linear mixed models were used to test the intervention effects and to account for clustering effect of sampling by school.

Results

A total of 3135 children were enrolled in the study (interventionn = 1412, 45%). Average age was 9.2 years, 64% Hispanic, 47% male, and 69% eligible for free and reduced lunch. The intervention compared to control resulted in increased vegetable intake (+ 0.48 vs. + 0.04 frequency/day,p = 0.02). There were no effects of the intervention compared to control on fruit intake, sugar sweetened beverages, any of the obesity measures or blood pressure.

Conclusion

While this school-based gardening, nutrition, and cooking program did not reduce obesity markers or blood pressure, it did result in increased vegetable intake. It is possible that a longer and more sustained effect of increased vegetable intake is needed to lead to reductions in obesity markers and blood pressure.

Clinical trials number

NCT02668744.
Role of epidermal growth factor receptor inhibitor-induced interferon pathway signaling in the head and neck squamous cell carcinoma therapeutic response
Authors: Korpela Sean P. , Hinz Trista K. , Oweida Ayman , Kim Jihye , Calhoun Jacob , Ferris Robert , Nemenoff Raphael A. , Karam Sana D. , Clambey Eric T. , Heasley Lynn E.
Published: January 2021

Background

Epidermal growth factor receptor (EGFR) is frequently amplified or overexpressed in head and neck squamous cell carcinoma (HNSCC) and is a clinically validated target for the therapeutic antibody, cetuximab, in the management of this cancer. The degree of response to EGFR inhibitors measured by tumor shrinkage varies widely among HNSCC patients, and the biological mechanisms that underlie therapeutic heterogeneity amongst HNSCC patients remain ill-defined.

Methods

EGFR-dependent human and murine HNSCC cell lines were treated with the EGFR/ERBB inhibitors, gefitinib and AZD8931, and submitted to RNAseq, GSEA, and qRT-PCR. Conditioned media was analyzed by ELISA and Luminex assays. Murine HNSCC tumors were stained for T cell markers by immunofluorescence. Primary HSNCC patient specimens treated with single agent cetuximab were stained with Vectra multispectral immunofluorescence.

Results

The transcriptional reprogramming response to EGFR/ERBB-specific TKIs was measured in a panel of EGFR-dependent human HNSCC cell lines and interferon (IFN) α and γ responses identified as top-ranked TKI-induced pathways. Despite similar drug sensitivity, responses among 7 cell lines varied quantitatively and qualitatively, especially regarding the induced chemokine and cytokine profiles. Of note, the anti-tumorigenic chemokine, CXCL10, and the pro-tumorigenic factor, IL6, exhibited wide-ranging and non-overlapping induction. Similarly, AZD8931 exerted potent growth inhibition, IFNα/IFNγ pathway activation, and CXCL10 induction in murine B4B8 HNSCC cells. AZD8931 treatment of immune-competent mice bearing orthotopic B4B8 tumors increased CD8 + T cell content and the therapeutic response was abrogated in nu/nu mice relative to BALB/c mice. Finally, Vectra 3.0 analysis of HNSCC patient tumors prior to and after 3–4 weeks of single agent cetuximab treatment revealed increased CD8 + T cell content in specimens from patients exhibiting a therapeutic response relative to non-responders.

Conclusions

The findings reveal heterogeneous, tumor cell-intrinsic, EGFR/ERBB inhibitor-induced IFN pathway activation in HNSCC and suggest that individual tumor responses to oncogene-targeted agents are a sum of direct growth inhibitory effects and variably-induced participation of host immune cells.
Delivery of paediatric rheumatology care: a survey of current clinical practice in Southeast Asia and Asia-Pacific regions
Authors: Tangcheewinsirikul Sirikarn , Tang Swee-Ping , Smith Nicola , Sukharomana Maynart , Charuvanij Sirirat , Vilaiyuk Soamarat , Arkachaisri Thaschawee , Scott Christiaan , Foster Helen E.
Published: January 2021

Background

Paediatric rheumatic diseases are a leading cause of acquired disability in Southeast Asia and Asia-Pacific Countries (SE ASIA/ASIAPAC). The aims of this study were to identify and describe the challenges to the delivery of patient care and identify solutions to raise awareness about paediatric rheumatic diseases.

Methods

The anonymised online survey included 27 items about paediatric rheumatology (PR) clinical care and training programmes. The survey was piloted and then distributed via Survey-Monkey™ between March and July 2019. It was sent to existing group lists of physicians and allied health professionals (AHPs), who were involved in the care pathways and management of children with rheumatic diseases in SE ASIA/ASIAPAC.

Results

Of 340 participants from 14 countries, 261 participants had been involved in PR care. The majority of the participants were general paediatricians. The main reported barriers to providing specialised multidisciplinary service were the absence or inadequacy of the provision of specialists and AHPs in addition to financial issues. Access to medicines was variable and financial constraints cited as the major obstacle to accessing biological drugs within clinical settings. The lack of a critical mass of specialist paediatric rheumatologists was the main perceived barrier to PR training.

Conclusions

There are multiple challenges to PR services in SE ASIA/ASIAPAC countries. There is need for more specialist multidisciplinary services and greater access to medicines and biological therapies. The lack of specialist paediatric rheumatologists is the main barrier for greater access to PR training.
Towards achieving the family planning targets in the African region: a rapid review of task sharing policies
Authors: Ouedraogo Leopold , Habonimana Desire , Nkurunziza Triphonie , Chilanga Asmani , Hayfa Elamin , Fatim Tall , Kidula Nancy , Conombo Ghislaine , Muriithi Assumpta , Onyiah Pamela
Published: January 2021

Background

Expanding access and use of effective contraception is important in achieving universal access to reproductive healthcare services, especially in low- and middle-income countries (LMICs), such as those in sub-Saharan Africa (SSA). Shortage of trained healthcare providers is an important contributor to increased unmet need for contraception in SSA. The World Health Organization (WHO) recommends task sharing as an important strategy to improve access to sexual and reproductive healthcare services by addressing shortage of healthcare providers. This study explores the status, successes, challenges and impacts of the implementation of task sharing for family planning in five SSA countries. This evidence is aimed at promoting the implementation and scale-up of task sharing programmes in SSA countries by WHO.

Methodology and findings

We employed a rapid programme review (RPR) methodology to generate evidence on task sharing for family planning programmes from five SSA countries namely, Burkina Faso, Cote d’Ivoire, Ethiopia, Ghana, and Nigeria. This involved a desk review of country task sharing policy documents, implementation plans and guidelines, annual sexual and reproductive health programme reports, WHO regional meeting reports on task sharing for family planning; and information from key informants on country background, intervention packages, impact, enablers, challenges and ways forward on task sharing for family planning. The findings indicate mainly the involvement of community health workers, midwives and nurses in the task sharing programmes with training in provision of contraceptive pills and long-acting reversible contraceptives (LARC). Results indicate an increase in family planning indicators during the task shifting implementation period. For instance, injectable contraceptive use increased more than threefold within six months in Burkina Faso; contraceptive prevalence rate doubled with declines in total fertility and unmet need for contraception in Ethiopia; and uptake of LARC increased in Ghana and Nigeria. Some barriers to successful implementation include poor retention of lower cadre providers, inadequate documentation, and poor data systems.

Conclusions

Task sharing plays a role in increasing contraceptive uptake and holds promise in promoting universal access to family planning in the SSA region. Evidence from this RPR is helpful in elaborating country policies and scale-up of task sharing for family planning programmes.
Wearable vibrotactile stimulation for upper extremity rehabilitation in chronic stroke: clinical feasibility trial using the VTS Glove
Authors: Seim Caitlyn E. , Wolf Steven L. , Starner Thad E.
Published: January 2021

Objective

Evaluate the feasibility and potential impacts on hand function using a wearable stimulation device (the VTS Glove) which provides mechanical, vibratory input to the affected limb of chronic stroke survivors.

Methods

A double-blind, randomized, controlled feasibility study including sixteen chronic stroke survivors (mean age: 54; 1-13 years post-stroke) with diminished movement and tactile perception in their affected hand. Participants were given a wearable device to take home and asked to wear it for three hours daily over eight weeks. The device intervention was either (1) the VTS Glove, which provided vibrotactile stimulation to the hand, or (2) an identical glove with vibration disabled. Participants were randomly assigned to each condition. Hand and arm function were measured weekly at home and in local physical therapy clinics.

Results

Participants using the VTS Glove showed significantly improved Semmes-Weinstein monofilament exam results, reduction in Modified Ashworth measures in the fingers, and some increased voluntary finger flexion, elbow and shoulder range of motion.

Conclusions

Vibrotactile stimulation applied to the disabled limb may impact tactile perception, tone and spasticity, and voluntary range of motion. Wearable devices allow extended application and study of stimulation methods outside of a clinical setting.
Intimate partner violence and exclusive breastfeeding of infants: analysis of the 2013 Nigeria demographic and health survey
Authors: Ariyo Tolulope , Jiang Quanbao
Published: January 2021

Background

Existing knowledge on the relationship between intimate partner violence (IPV) and exclusive breastfeeding (EBF) in the context of Nigeria is minimal and limited to a lifelong measure of IPV experience. An abuse experienced a long time ago may not have as much negative effect as that encountered at a more proximal time to the breastfeeding phase. To this effect, we examined this relationship with maternal IPV experienced around the time of pregnancy and postpartum.

Method

We analyzed data from the 2013 Nigeria Demographic and Health Survey. The sample includes 2668 breastfeeding mothers having a child aged under 6 months. The outcome variable was EBF or mixed-feeding (24 h recall). The exposure variables were: the maternal experience of psychological, physical, and sexual intimate partner violence. Also, there was an experience of any form of IPV and frequency score of intimate partner violence. Analysis includes chi-square and t-test bivariates, complete case and imputed logistic regressions for binary outcome.

Results

In the imputed analysis, compared to mothers who experienced no IPV, those who experienced IPV had a 26% reduced likelihood of EBF practice (AOR 0.74; 95% CI 0.55, 1.00). Also, a unit dose of maternal IPV experience was associated with a 5% reduced likelihood of EBF practice (AOR 0.69; 95% CI 0.49, 0.98). Among the three forms of IPV, physical IPV had the highest effect size. Physical IPV was associated with a 37% reduced likelihood of EBF practice (AOR 0.63; 95% CI 0.44, 0.90), while psychological IPV was associated with a 34% reduced likelihood of EBF practice (AOR 0.66; 95% CI 0.47, 0.92), when compared to the respective reference groups. On the other hand, those who reported sexual IPV were just as likely to breastfeed as those who did not (AOR 0.94; 95% CI 0.62, 1.41).

Conclusions

In this study, maternal IPV is associated with EBF practice. Policies aimed at promoting EBF should also be framed to combat IPV against pregnant women and nursing mothers.
The congenital sternoclavicular sinus: a single-institution retrospective study of 88 patients
Authors: Yang Gang , He Taozhen
Published: January 2021

Background

Sinus near the sternoclavicular joint was considered as a rare congenital neck abnormality. Though it was reported as a dermoid sinus in some literatures, the embryological origin of the sinus was unclear. This study aimed at reviewing the clinical and histological characteristics and analyzing the possible embryological origin of this malformation in children.

Methods

The medical records of all patients with congenital sternoclavicular sinus who underwent surgical resection between March 2018 through June 2020 were reviewed retrospectively. The clinical presentations, complications, histological examination, and treatment were analyzed.

Results

Of the 88 patients with congenital sternoclavicular sinus included, the mean age of surgery was 2.73 ± 1.71 years old. The sinuses occurred on the left side in 73 (83.0%) cases. Sixty-three patients experienced sinus infection and 44 patients underwent incision and drainage before excision. All patients received surgical resection with one patient who recurred after surgery. Histopathological examination showed that the sinuses were lined by squamous epithelium in most patients. However, ciliated epithelium was observed in one patient and salivary glands were detected in two patients.

Conclusions

The congenital sternoclavicular sinus should be excised promptly to prevent recurrent infection. According to the ciliated epithelium and salivary gland were found in the wall of sinus, it should be viewed as the skin side remnant of the fourth branchial cleft rather than a dermoid cyst/sinus.
Systematic literature review of the economic burden of spinal muscular atrophy and economic evaluations of treatments
Authors: Dangouloff Tamara , Botty Camille , Beaudart Charlotte , Servais Laurent , Hiligsmann Mickaël
Published: January 2021

Background

Spinal muscular atrophy (SMA) is a rare and devastating condition for which new disease-modifying treatments have recently been approved. Given the increasing importance of economic considerations in healthcare decision-making, this review summarizes the studies assessing the cost of SMA and economic evaluations of treatments. A systematic review of the literature in PubMed and Scopus up to 15 September 2020 was conducted according to PRISMA guidelines.

Results

Nine studies reporting the annual cost of care of patients with SMA and six evaluations of the cost-effectiveness of SMA treatments were identified. The average annual cost of SMA1, the most frequent and severe form in which symptoms appear before the age of 6 months were similar according to the different studies, ranged from $75,047 to $196,429 per year. The yearly costs for the forms of the later-onset form, called SMA2, SMA3, and SMA4, which were usually pooled in estimates of healthcare costs, were more variable, ranging from $27,157 to $82,474. The evaluations of cost-effectiveness of treatment compared nusinersen treatment against standard of care (n = 3), two treatments (nusinersen and onasemnogene abeparvovec) against each other and no drug treatment (n = 1), nusinersen versus onasemnogene abeparvovec (n = 1), and standard of care versus nusinersen with and without newborn screening (n = 1). The incremental cost-effectiveness ratio (ICER) of nusinersen compared to standard of care in SMA1 ranged from $210,095 to $1,150,455 per quality-adjusted life years (QALY) gained and that for onasemnogene abeparvovec ranged from $32,464 to $251,403. For pre-symptomatic patients, the ICER value ranged from $206,409 to $735,519. The ICERs for later-onset forms of SMA (2, 3 and 4) were more diverse ranging from $275,943 to $8,438,049.

Conclusion

This review confirms the substantial cost burden of standard of care for SMA patients and the high cost-effectiveness ratios of the approved drugs at the current price when delivered in post-symptomatic patients. Since few studies have been conducted so far, there is a need for further prospective and independent economic studies in pre- and post-symptomatic patients.
NOX1 inhibition attenuates the development of a pro‐tumorigenic environment in experimental hepatocellular carcinoma
Authors: Vandierendonck Astrid , Degroote Helena , Vanderborght Bart , Verhelst Xavier , Geerts Anja , Devisscher Lindsey , Van Vlierberghe Hans
Published: January 2021

Background

The poor prognosis of advanced HCC and limited efficacy of current systemic treatments emphasize the need for new or combined targeted therapies. The development of HCC is a multistage process in which liver injury appears in a complex microenvironment associated with oxidative stress. NOX enzymes are the main source of ROS during hepatocarcinogenesis and NOX1 in particular has shown correlation with poor prognosis of HCC patients. This study evaluates the effect of pharmacological NOX1 inhibition on the development and progression of HCC and its effect on the tumor microenvironment.

Methods

The in vitro cytotoxic effects of the NOX1 inhibitor GKT771 (Genkyotex) on human Huh7 and Hep3B and murine Hepa1-6 HCC cell lines, the human THP1 monocyte cell line and mouse macrophages were evaluated via MTT, LDH activity and CaspGlo® assays. In order to induce in vivo HCC, male SV129 wild-type mice received weekly IP injections of diethylnitrosamine (DEN) (35 mg/kg) for 20–25 weeks. Mice were treated with vehicle or GKT771 (30 mg/kg) via oral gavage, daily or twice daily, in preventive and therapeutic studies. The liver damage was evaluated for inflammation, angiogenesis, fibrosis and HCC development via histology, RT-qPCR, multiplex analyses and ROS levels.

Results

A concentration-dependent reduction in cellular activity of the human HCC cell lines without cytotoxicity was observed. GKT771 treatment reduced LPS-induced pro-inflammatory bone-marrow derived macrophage polarization. DEN injections resulted in 100 % tumor formation and the induction of HCC markers which could be reduced by twice daily dosing of GKT771 at early onset of advanced HCC. DEN-induced HCC resulted in an upregulation of pro-inflammatory, angiogenic and fibrotic markers which was less pronounced in GKT771 treated mice in all treatment regimens. In line, liver fibrosis was induced in HCC mice and this to a lesser extend upon GKT771 treatment.

Conclusions

NOX1 inhibition showed to be safe and well tolerated and was able to attenuate the induction of a pro-inflammatory, angiogenic and pro-fibrotic microenvironment suggesting that this might be a promising adjuvant therapeutic strategy in the treatment of advanced HCC.
Intrabodies targeting human papillomavirus 16 E6 and E7 oncoproteins for therapy of established HPV-associated tumors
Authors: Paolini Francesca , Amici Carla , Carosi Mariantonia , Bonomo Claudia , Di Bonito Paola , Venuti Aldo , Accardi Luisa
Published: January 2021

Background

The oncogenic activity of the high risk human papillomavirus type 16 (HPV16) is fully dependent on the E6 and E7 viral oncoproteins produced during viral infection. The oncoproteins interfere with cellular homeostasis by promoting proliferation, inhibiting apoptosis and blocking epithelial differentiation, driving the infected cells towards neoplastic progression. The causal relationship between expression of E6/E7 and cellular transformation allows inhibiting the oncogenic process by hindering the activity of the two oncoproteins. We previously developed and characterized some antibodies in single-chain format (scFvs) against the HPV16 E6 and E7 proteins, and demonstrated both in vitro and in vivo their antitumor activity consisting of protective efficacy against tumor progression of HPV16-positive cells.

Methods

Envisioning clinical application of the best characterized anti-HPV16 E6 and –HPV16 E7 scFvs, we verified their activity in the therapeutic setting, on already implanted tumors. Recombinant plasmids expressing the anti-HPV16 E6 scFvI7 with nuclear targeting sequence, or the anti-HPV16 E7 scFv43M2 with endoplasmic reticulum targeting sequence were delivered by injection followed by electroporation to three different preclinical models using C57/BL6 mice, and their effect on tumor growth was investigated. In the first model, the HPV16+ TC-1 Luc cells were used to implant tumors in mice, and tumor growth was measured by luciferase activity; in the second model, a fourfold number of TC-1 cells was used to obtain more aggressively growing tumors; in the third model, the HPV16+ C3 cells where used to rise tumors in mice. To highlight the scFv possible mechanism of action, H&E and caspase-3 staining of tumor section were performed.

Results

We showed that both the anti-HPV16 E6 and HPV16 E7 scFvs tested were efficacious in delaying tumor progression in the three experimental models and that their antitumor activity seems to rely on driving tumor cells towards the apoptotic pathway.

Conclusion

Based on our study, two scFvs have been identified that could represent a safe and effective treatment for the therapy of HPV16-associated lesions. The mechanism underlying the scFv effectiveness appears to be leading cells towards death by apoptosis. Furthermore, the validity of electroporation, a methodology allowed for human treatment, to deliver scFvs to tumors was confirmed.
Association between morphologic grading and implantation rate of Euploid blastocyst
Authors: Lou Hua , Li Na , Guan Yichun , Zhang Yuchao , Hao Dayong , Cui Shihong
Published: January 2021

Background

Standard morphologic evaluation has been the most widely adopted approach to embryo selection, and remains the most common strategy.The objective of the study to determine the association between the morphologic grading and implantation rate of euploid blastocysts in single frozen-thawed embryo transfer (SET) cycles.

Methods

A total of 271 patients aged 20–40 years undergoing euploid SET from January 2017 to December 2019 were included in retrospective cohort study.The cycles were divided into three groups based on their morphologic grading before cryopreservation: good-quality (n = 58), average-quality (n = 88) and poor-quality blastocysts (n = 125). The pregnancy outcome of the three morphologic groups were analyzed and a logistic regression of implantation rate was conducted.

Results

Good-quality blastocysts yielded statistically significantly higher implantation rates than poor-quality (79.31% vs. 48%; P<0.001). Planned subgroup analyses by age and the day of TE biopsy were conducted. Logistic regression analyses that adjusted for these variables identified higher implantation rates (adjusted odds ratio(aOR) = 4.083, 95% confidence interval (CI):1.836–9.082, P<0.001) for the good-quality blastocysts than for those that underwent poor-quality cycles in women aged < 35 years, but not in women aged ≥35 years (aOR = 6.074, 95% CI: 0.456–80.919, P = 0.172). The implantation rates were higher among women with good-quality blastocysts on both Day 5 and Day 6 of TE biopsy than among those with poor-quality blastocysts (Day 5, aOR = 3.294, 95% CI:1.260–8.616, P = 0.015; Day 6, aOR = 4.179, 95% CI:1.004 ~ 17.399, P = 0.049). Day 5 euploid blastocysts had no significant difference in implantation potential and early spontaneous abortion rate compared with similarly graded Day 6 euploid blastocysts.

Conclusions

Blastocyst morphologic grading was associated with implantation rate for euploid embryo transfers after adjustment for potential confounders. These findings suggest that evaluating blastocyst morphology is critical when selecting the best euploid blastocyst.