bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutral Polysaccharide from Panax notoginseng enhanced cyclophosphamide antitumor efficacy in hepatoma H22-bearing mice
Authors: Liu Yanhong , Qin Huayan , Zhong Yuanyuan , Li Shuang , Wang Huajing , Wang Hong , Chen Liling , Tang Xiang , Li Yalin , Qian Zhongyi , Li Huaiyu , Zhang Lei , Chen Tong
Published: January 2021

Background: Our previous studies demonstrated that the administration of crude Polysaccharide from Panax notoginseng (CPPN) can effectively prolong the lifespan of tumor-bearing mice via boosting the host immune system as well as weak cytotoxicity against hepatocellular carcinoma (HCC). In the present study, Neutral Polysaccharide (NPPN) were further purified from crude polysaccharide isolated from panax notoginseng. The effects of NPPN on the immune function and hematopoietic function of mice with low immunity and myelosuppression induced by cyclophosphamide (CTX) were investigated. The effect of NPPN combined with CTX on the tumor inhibition rate of the H22 tumor-bearing mice and the impact of NPPN on the proliferation of H22 liver cancer cells in vitro were investigated.Methods: CPPN was obtained by water extraction and alcohol precipitation method, and further purified by DEAE Sepharose Fast Flow ion exchange resin column. NPPN was added to the immunosuppressed with myelosuppression mice induced by CTX. Thymus index, spleen index, lymphocyte proliferation stimulation index by adding of concanavalin A, determination of serum hemolysin, NK cell activity assay, mice carbon clearance experiment, blood count tests were detected. The tumor inhibition rate of the H22 tumor-bearing mice treated with NPPN combined with CTX was recorded.Results: NPPN and 4 kinds of acid polysaccharide from Panax notoginseng (APPN) were successfully isolated from the CPPN by DEAE Sepharose Fast Flow ion exchange resin column. NPPN inhibited the growth of H22 cells and significantly increase the tumor inhibition rate of the H22 tumor-bearing mice combined with CTX. The elevation of the cellular and humoral immunity levels as well as a variety of blood count tests indicators of immunosuppressive with myelosuppression mice may contribute to the antitumor activity of NPPN.Conclusion: NPPN has a potential antitumor activity for the treatment of liver cancer combined with cyclophosphamide.
Short-term effectiveness of precise safety decompression via double percutaneous lumbar foraminoplasty and percutaneous endoscopic lumbar decompression for lateral lumbar spinal canal stenosis: a prospective cohort study
Authors: Wang Yu , Deng Mingyan , Wu Hao , Wu Ye , Guo Chuan , Zhang Dongfeng , Kong Qingquan
Published: January 2021

Purpose This prospective cohort study reports on a modified technique, namely precise safety decompression via double percutaneous lumbar foraminoplasty (DPLF) and percutaneous endoscopic lumbar decompression (PELD) for lateral lumbar spinal canal (LLSC) stenosis, and its short-term clinical outcomes.Methods The study analyzed 69 patients with single-level LLSC stenosis simultaneously occurring in both zones 1 and 2 (defined as retrodiscal space and upper bony lateral recess respectively by new LLSC classification) who underwent DPLF–PELD from November 2018 to April 2019. Clinical outcomes were evaluated according to preoperative, three months postoperatively, and last follow-up, via leg pain/low back pain (LBP) visual analog scale (VAS) scores, Oswestry disability index (ODI) scores, and the Macnab criteria. The postoperative MRI and CT were used to confirm the complete decompression, and flexion-extension x-rays at the last follow-up were used to observe lumbar stability.Results All patients successfully underwent DPLF–PELD, and the stenosis was completely decompressed, confirmed by postoperative MRI and CT. The mean follow-up duration was 13 months (range: 8–17 months). The mean preoperative leg pain VAS score is 7.05 ± 1.04 (range 5–9), which decreased to 1.03 ± 0.79(range: 0–3) at three months postoperatively and to 0.75 ± 0.63 (range: 0–2) by the last follow-up visit(p < 0.05). The mean preoperative ODI was 69.8 ± 9.05 (range: 52–85), which decreased to 20.3 ± 5.52 (range: 10–35) at the third month postoperatively and to 19.6 ± 5.21 (range: 10–34) by the final follow-up visit(p < 0.05). The satisfactory (excellent or good) results were 94.2%. There was one patient with aggravated symptoms, which were relieved after an open surgery. Two patients had a dural tear, and two patients suffered postoperative LBP. No recurrence or segmental instability was observed at the final follow-up.Conclusion DPLF–PELD could be a good alternative for the treatment of LLSC stenosis patients whose stenosis occurred in both zones 1 and 2.Trial registration Chinese Clinical Trial Registry (ChiCTR1800019551). Registered 18 November 2018.
Utilising Benefit-Risk Assessments within Clinical Trials – A Protocol for the BRAINS project
Authors: Totton Nikki , Julious Steven , Hughes Dyfrig , Cook Jonathan , Biggs Katie , Coates Lizzie , Cook Andrew , Hewitt Catherine , Day Simon
Published: January 2021

Background: Depending on the treatment to be investigated, a clinical trial could be designed to assess objectives of: superiority; equivalence or non-inferiority. The design of the study is affected by many different elements including: the control treatment, the primary outcome and associated relationships. In some studies, there could be more than one outcome of interest. In these situations, benefit-risk methodologies could be used to assess the outcomes simultaneously and consider the trade-off between the benefits against the risks of a treatment. Benefit-risk is used within the regulatory industry but seldom included within publicly funded clinical trials within the UK. This project aims to gain an expert consensus on how to select the appropriate trial design (e.g. superiority) and when to consider including benefit-risk methods.Methods: The project will consist of four work packages:1. A web-based survey to elicit current experiences and opinions,2. A rapid literature review to assess any current recommendations,3. A two-day consensus workshop to gain agreement on the recommendations,4. Production of a guidance document.Discussion: The aim of the project is to provide a guideline for clinical researchers, grant funding bodies and reviewers for grant bodies for how to select the most appropriate trial design and when it is appropriate to consider using benefit-risk methods. The focus of the guideline will be on publicly funded trials, however, the vision is that the work will be applicable across research settings and we will connect with other organisations and committees as appropriate.
Determining sample size for progression criteria for pragmatic pilot RCTs: The Hypothesis test Strikes Back!
Authors: Lewis Martyn , Bromley Kieran , Sutton Christopher J , McCray Gareth , Myers Helen Lucy , Lancaster Gillian A
Published: January 2021

Background The current CONSORT guidelines for reporting pilot trials do not recommend hypothesis testing of clinical outcomes on the basis that a pilot trial is under-powered to detect such differences and this is the aim of the main trial. It states that primary evaluation should focus on descriptive analysis of feasibility/process outcomes (e.g. recruitment, adherence, treatment fidelity). Whilst the argument for not testing clinical outcomes is justifiable, the same does not necessarily apply to feasibility/process outcomes, where differences may be large and detectable with small samples. Moreover, there remains much ambiguity around sample size for pilot trials. Methods Many pilot trials adopt a ‘traffic light’ system for evaluating progression to the main trial determined by a set of criteria set up a priori. We construct a hypothesis-testing approach for binary feasibility outcomes focused around this system that tests against being in the RED zone (unacceptable outcome) based on an expectation of being in the GREEN zone (acceptable outcome) and choose the sample size to give high power to reject being in the RED zone if the GREEN zone holds true. Pilot point estimates falling in the RED zone will be statistically non-significant and in the GREEN zone will be significant; the AMBER zone designates potentially acceptable outcome and statistical tests may be significant or non-significant.Results For example, in relation to treatment fidelity, if we assume the upper boundary of the RED zone is 50% and the lower boundary of the GREEN zone is 75% (designating unacceptable and acceptable treatment fidelity, respectively), the sample size required for analysis given 90% power and one-sided 5% alpha would be around n=34 (intervention group alone). Observed treatment fidelity in the range of 0-17 participants (0-50%) will fall into the RED zone and be statistically non-significant; 18-25 (51-74%) fall into AMBER and may or may not be significant; 26-34 (75-100%) fall into GREEN and will be significant indicating acceptable fidelity.Discussion In general, several key process outcomes are assessed for progression to a main trial; a composite approach would require appraising the rules of progression across all these outcomes. This methodology provides a formal framework for hypothesis-testing and sample size indication around process outcome evaluation for pilot RCTs.
Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - A multi-centric clinical study of GD-2008-ALL protocol
Authors: Li Xin-Yu , Li Jia-Qiang , Luo Xue-Qun , Wu Xue-Dong , Sun Xin , Xu Hong-Gui , Li Chang-Gang , Liu Ri-Yang , Sun Xiao-Fei , Chen Hui-Qin , Lin Yu-Deng , LI Chi-Kong , Fang Jian-Pei
Published: January 2021

Background The prognosis of childhood acute lymphoblastic leukemia (ALL) is optimistic with a 5-year event-free survival (EFS) rate of 70%-85%. However, the major causes of mortality are chemotherapy toxicity, infection and relapse. The Guangdong (GD)-2008-ALL collaborative protocol was carried out to study the effect of reduced intensity on treatment related mortality(TRM) based on Berlin-Frankfurt-Münster (BFM) 2002 backbone treatment. The study was designed to elucidate whether the reduced intensity is effective and safe for children with ALL. Methods The clinical data were obtained from February 28, 2008 to June 30, 2016. A total of 1,765 childhood ALL cases from 9 medical centers were collected and data were retrospectively analyzed. Patients were stratified into 3 groups according to bone marrow morphology, prednisone response, age, genotype, and karyotype information: standard risk (SR), intermediate risk (IR) and high risk (HR). For SR group, daunorubicin was decreased in induction IA while duration was reduced in Induction Ib (2 weeks in place of 4 weeks). Doses for CAM were same in all risk groups - SR patients received one CAM, others got two CAMs. Results The 5-year and 8-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 83.5±0.9% and 83.1±1.0%, 71.9±1.1% and 70.9±1.2%, and 19.5±1.0% and 20.5±1.1%, respectively. The 2-year treatment-related mortality (TRM) was 5.2±0.5%. The 5-year and 8-year OS were 90.7±1.4% and 89.6±1.6% in the SR group, while the 5-year and 8-year EFS were 81.5±1.8% and 80.0±2.0%. In the SR group, 74 (15.2 %) patients measured minimal residual disease (MRD) on Day 15 and Day 33 of induction therapy. Among them, 7 patients (9.46%) were MRD positive (≥ 0.01%) on Day 33. The incidence of relapse in the MRD Day33 positive group (n=7) was 28.6%, while in the MRD Day33 negative group (n=67) was 7.5% (p=0.129). Conclusions The results of GD-2008-ALL protocol are outstanding for reducing TRM in childhood ALL in China with excellent long term EFS. This protocol provided the evidence for further reducing intensity of induction therapy in the SR group according to the risk stratification. MRD levels on Day 15 and Day 33 are appropriate indexes for stratification.
Domestic Violence in Mozambique: From policy to practice
Authors: Jethá Eunice , Keygnaert Ines , Martins Emilia , Sidat Mohsin , Roelens Kristien
Published: January 2021

Background: To reduce the impact of domestic violence (DV), Mozambican governmental and non-governmental entities are making efforts to strengthen the legislative framework and improve the accessibility of care services for survivors of violence. Despite this remarkable commitment, the translation of policies and legislation into actions remains a huge challenge. Therefore, this paper aims to identify gaps in the implementation of existing national policies and laws for DV in the services providing care for survivors of DV.Methods: This study, using a qualitative approach had two components. The first was content analysis of guidelines and protocols for DV care provision. The second consisted of in-depth interviews with institutional gender focal points. The analysis of the document content was based on a framework developed according to key elements recommended by international agencies (PAHO and UN) for DV policies and strategies design. Data from the in-depth interviews, where analysed in accordance with study objectives.Results: Eleven (11) guidelines/protocols of care provision and innumerable brochures and pamphlets were identified and analysed. There is a standardised form highlighting the integrated approach incorporating fields for police and the health sector but excludes Civil Society Organisations. However, there is no national DV database specifically for DV. Although the focal points recognised the relevance of the reviewed documents, many identified gaps in implementation. This is related to the weaknesses of the offender’s penalisation and to the scarcity of care providers. And, many providers who do exist often lack appropriate training. They also recognised their performance is negatively influenced by socio-cultural factors.Conclusion: Within services providing care to survivors of DV, a scarcity of guidelines and protocols exist, compromising the quality and standardisation of care. Recognition of the relevance of care guidelines and protocols is a strength, there are challenges that governmental and non-governmental entities must address in order to ensure DV prevention and control strategies have the desired results.
Risk factors for recurrent wheezing after bronchiolitis in infants:2-year follow up in China
Authors: Chen Sainan , Gu Wenjing , Wu Min , Hao Chuangli , Zhu Canhong , Shao Xuejun , Wang Yuqing
Published: January 2021

Background: Infants with bronchiolitis have an increased risk of developing recurrent wheezing and asthma. However, the risk factors for the development of recurrent wheezing after bronchiolitis remains controversial.Objective: To investigate the incidence of post-bronchiolitis recurrent wheezing and associated risk factors.Methods: Infants with bronchiolitis were enrolled from November 2016 through March 2017. Nasopharyngeal aspirates were obtained for detection of respiratory viruses which were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and direct immunofluorescent assay. Serum cytokines including TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α were measured by flow cytometry. Patients were followed every 3 months for a duration of 2 years by telephone or at outpatient appointments.Results: We enrolled 89 infants, of which 81 patients were successfully followed up. In total, 22.2% of patients experienced recurrent wheezing episodes. The proportion of patients with history of eczema, systemic glucocorticoid use and patients with moderate-to-severe disease were significantly higher in the recurrent wheezing group than the non-recurrent wheezing group (83.3% vs 52.4%; 66.7% vs 36.5%; 61.1% vs 33.3%, respectively, all P<0.05); There were no significant differences between patients with and without recurrent wheezing episodes in the levels of TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α (P>0.05). Logistic regression analysis showed that history of eczema was an independent risk factor for post-bronchiolitis recurrent wheezing (odds ratio [OR]=5.622; 95% confidence interval [CI], 1.3–24.9; P=0.023).Conclusion: The incidence of recurrent wheezing among infants after contracting bronchiolitis was 22.2% during a 2-year follow-up. History of eczema was the only independent risk factor identified and no correlation was found between the specific virus and disease severity in children with post-bronchiolitis recurrent wheezing.
Changes in the characteristics of dental emergencies under the influence of SARS-CoV-2 pandemic: A retrospective study
Authors: Wu Kan , Li Chunjie , Yang Zheng , Yang Shangchun , Yang Wenbin , Hua Chengge
Published: January 2021

Background Further understanding of the distribution and changing characteristics of dental diseases is of great significance for all dental emergency centers for strengthening the medical staff’s treatment abilities and effective use of emergency resources in the face of public health emergencies involving highly infectious respiratory diseases.Methods The medical records of 4158 cases of dental emergency patients from 2019 to 2020 were retrospectively analyzed, with patients divided into the pre-SARS-COV-2 group and the SARS-COV-2 group, according to the date of their admission to the dental emergency center. The dental emergency patients’ demographic data, date and time, diagnoses, and treatment approaches were compared before and during the SARS-COV-2 pandemic.Results During the SARS-COV-2 pandemic, the number of dental emergency visits increased by 29.7%. The peak of the number of patients at weekends and at night is not obvious compared with the pre-SARS-COV-2 group. During the pandemic, males (n=286, 58.1%) were more likely to visit dental emergency centers for trauma than females (n=206, 41.9%) (P<0.05); females (n=242, 60.8%) were more likely to visit dental emergency centers for acute gingivitis and acute pericoronitis than males (n=156, 39.2%) (P<0.05). A major change in diagnosis was related to acute pulpitis (K04.0) and acute apical periodontitis (K04.4), which increased by 9.2%; acute gingivitis (K05.0) and acute pericoronitis (K05.2) increased by 3.5%; open wound of the lip and oral cavity (S01.5) decreased by 17.9%; other conditions (non-emergency diseases) increased by 6.8%, compared with the pre-SARS-COV-2 period. Among the treatment modalities, during the pre-SARS-COV-2 period, 304 patients (17.7%) received a prescription for antibiotics and analgesics, and 1485 (86.5%) received a prescription for local treatment. During the SARS-COV-2 period, 958 (39.2%) received a prescription for antibiotics and analgesics, and 1636 (67.0%) received a prescription for local treatment.Conclusion SARS-COV-2 pandemic led to changes in the characteristics of dental emergency patients. Trauma, acute pulpitis, and acute periodontitis are the leading reasons patients refer to dental emergency centers. Dental emergency centers should optimize treatment procedures, optimize the staff, and reasonably allocate materials according to the changes to improve the on-site treatment capacity and provide adequate dental emergency care.
Demographic Features of Identified PLWHA Infected through Commercial and Nonmarital Noncommercial Heterosexual Contact in China from 2015 – 2018: A Retrospective Cross-Sectional Study
Authors: Dong Zhilong , Ma Liying , Cai Chang , Gao George Fu , Lyu Fan
Published: January 2021

Background:Understanding the demographic characteristics of people living with HIV/AIDS (PLWHA) infected through commercial heterosexual contact (CHC) or nonmarital noncommercial heterosexual contact (NMNCHC) is important for HIV/AIDS prevention and control.Methods:Cases reported through the Chinese HIV/AIDS Case Reporting System (CRS) from 2015 to 2018 were analyzed. A descriptive and preliminary inferential analysis were performed for those demographic characteristics deemed of interest.Results:Overall, 523,121 identified PLWHA between 2015 and 2018 in the CRS were analyzed. The constituent ratio of heterosexual transmission increased from 66.25% in 2015 to 71.48% in 2018. The proportion of CHC heterosexual transmission decreased from 40.18% in 2015 to 37.99% in 2018, while that of NMNCHC increased from 46.33% in 2015 to 49.02% in 2018. PLWHA infected through NMNCHC were significantly younger than those who were infected through CHC (Student’s t test, P<0.0001), with an average age gap ranging from 5.63 (2015) to 7.46 (2018) years, and the average age of both groups increased annually. The frequency of newly identified PLWHA who were infected through CHC had a remarkable increase among the ages of 65 and above. Gender distribution was significantly different between CHC and NMNCHC (χ2 = 8909.00(2015), 9941.90(2016), 11004.00 (2017), 12836.00(2018), all P < 0.0001), and the ratio of men to women in the NMCHC group was 1.50:1 (2015), 1.51:1 (2016), 1.54:1 (2017), and 1.52:1 (2018), while in the commercial heterosexual contact (CHC) group, these ratios were 11.45:1 (2015), 12.08:1 (2016), 12.53:1 (2017), and 13.28:1 (2018). Marital status was significantly different between CHC and NMNCHC (χ2 = 94.67 (2015), 109.88(2016), 58.18(2017), 152.38(2018), all P < 0.0001). As the educational level improved, the proportion of NMNCHC also increased (Cochran - Armitage test, P<0.0001).Conclusions:We found that heterosexual transmission was the primary mode of HIV transmission in China from 2015 to 2018. PLWHA infected through CHC and NMNCHC had different characteristics in age, gender, marital status, and educational level. The frequency of PLWHA infected through CHC increased substantially in the age group of 65 and above. This study provides useful baseline data for future studies on the heterosexual transmission of HIV in China.
Early oral protein-containing diets following elective lower gastrointestinal tract surgery in adults: A meta-analysis of randomized clinical trials.
Authors: PU Hong , Heighes Philippa T. , Simpson Fiona , WANG Yaoli , LIANG Zeping , Wischmeyer Paul , Hugh Thomas J. , Doig Gordon S.
Published: January 2021

Background: Although current guidelines make consensus recommendations for the early resumption of oral intake after surgery, a recent comprehensive meta-analysis failed to identify any patient-centred benefits. We hypothesized this finding was attributable to pooling studies providing effective protein-containing diets with ineffective non-protein liquid diets. Therefore, the aim of this paper was to investigate the safety and efficacy of early oral protein-containing diets versus later (traditional) feeding after elective lower gastrointestinal tract surgery in adults.Methods: PubMed, Embase and the China National Knowledge Infrastructure databases were searched from inception until 1 August 2019. Reference lists of retrieved studies were hand searched to identify randomized clinical trials reporting mortality. No language restrictions were applied. Study selection, risk of bias appraisal and data abstraction were undertaken independently by two authors. Disagreements were settled by obtaining an opinion of a third author. Majority decisions prevailed. After assessment of underlying assumptions, a fixed-effects method was used for analysis. The primary outcome was mortality. Secondary outcomes included surgical site infections, postoperative nausea and vomiting, serious postoperative complications and other key measures of safety and efficacy.Results: Eight randomized clinical trials recruiting 657 patients were included. Compared with later (traditional) feeding, commencing an early oral protein-containing diet resulted in a statistically significant reduction in mortality (Odds Ratio [OR] 0.31, P=0.02, I2=0%). An early oral protein-containing diet also significantly reduced surgical site infections (OR 0.39, P=0.002, I2=32%), postoperative nausea and vomiting (OR 0.62, P=0.04, I2=37%), serious postoperative complications (OR 0.60, P=0.01, I2=25%) and significantly improved other major outcomes. No harms attributable to an early oral protein-containing diet were identified.Conclusions: The results of this systematic review can be used to upgrade current guideline statements to a Grade A recommendation supporting an oral protein-containing diet commenced before the end of postoperative day 1 after elective lower gastrointestinal surgery in adults.
Lateral lumbar interbody fusion after reduction using the percutaneous pedicle screw system in the lateral position for Meyerding grade II spondylolisthesis: a preliminary report of a new lumbar reconstruction strategy
Authors: Takami Masanari , Taiji Ryo , Okada Motohiro , Minamide Akihito , Hashizume Hiroshi , Yamada Hiroshi
Published: January 2021

Background: Utilization of a cage with a large footprint in lateral lumbar interbody fusion (LLIF) for the treatment of spondylolisthesis leads to a high fusion rate and neurological improvement owing to the indirect decompression effect and excellent alignment correction. However, if an interbody space is too narrow for insertion of an LLIF cage for cases of spondylolisthesis of Meyerding grade II or higher, LLIF cannot be used. Therefore, we developed a novel strategy, LLIF after reduction by the percutaneous pedicle screw (PPS) insertion system in the lateral position (LIFARL), for surgeons to perform accurate and safe LLIF with PPS in patients with such pathology. This study aimed to introduce the new surgical strategy and to present preliminary clinical and radiological results of patients with spondylolisthesis of Meyerding grade II.Methods: Six consecutive patients (four men and two women; mean age, 72.7 years-old; mean follow-up period, 15.3 months) with L4 spondylolisthesis of Meyerding grade II were included. Regarding the surgical procedure, first, PPSs were inserted into the L4 and L5 vertebrae fluoroscopically, and both rods were placed in the lateral position. The L5 set screws were fixed tightly, and the L4 side of the rod was floated. Second, the L4 vertebra was reduced by fastening the L4 set screws so that they expanded the anteroposterior width of the interbody space. At that time, the L4 set screws were not fully tightened to the rods to prevent the endplate injury. Finally, the LLIF procedure was started. After inserting the cage, a compression force was added to the PPSs, and the L4 set screws were completely fastened. Results: The mean operative time was 183 min, and the mean blood loss was 90.8 mL. All cages were positioned properly. Visual analog scale score and Oswestry disability index improved postoperatively. Bone union was observed using computed tomography 12 months after surgery.Conclusion: For cases with difficulty in LLIF cage insertion for Meyerding grade II spondylolisthesis due to the narrow anteroposterior width of interbody space, LIFARL is an option to achieve LLIF combined with posterior PPS accurately and safely.Trial registration: UMIN-Clinical Trials Registry, UMIN000040268, Registered 29 April 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000045938
Lung ultrasound score assessing the pulmonary edema in pediatric acute respiratory distress syndrome received continuous hemofiltration therapy: A prospective observational study
Authors: Wang Fei , Wang Chunxia , Shi Jingyi , Shan Yijun , Miao Huijie , Sun Ting , Zhou Yiping , Zhang Yucai
Published: January 2021

Background: Lung ultrasound score is a potential method for determining pulmonary edema in acute respiratory distress syndrome (ARDS). Continuous renal replacement therapy (CRRT) has become the preferred modality to manage fluid overload during ARDS. The aim of this study was to evaluate the value of lung ultrasound (LUS) score on assessing the effects of CRRT on pulmonary edema and pulmonary function in pediatric ARDS. Methods: We conducted a prospective cohort study in 70 children with moderate to severe ARDS in a tertiary university pediatric intensive care unit from January 2016 to December 2019. 37 patients received CRRT (CRRT group) and 33 patients treated by conventional therapy (Non-CRRT group). LUS score was measured within 2 hours identified ARDS as the value of 1st，and the following three days as the 2nd, 3rd, and 4th. We used Spearman correlation analysis to develop the relationship between LUS score and parameters related to respiratory dynamics, clinical outcomes as well as daily fluid balance during the first four days after ARDS diagnosed.Results: The 1st LUS score in CRRT group were significantly higher than Non-CRRT group (P < 0.001), but the LUS score decreased gradually following CRRT (P < 0.001). LUS score was significantly correlated with Cdyn (1st: r =-0.757, 2nd: r =-0.906, 3rd: r =-0.885, 4th: r =-0.834), OI (1st: r =0.678, 2nd: r =0.689, 3rd: r =0.486, 4th: r =0.324) based on 1st to 4th values (all P <0.05). Only values of the 3rd and 4th LUS score after ARDS diagnosed were correlated with duration of mechanical ventilation [1st: r = 0.167, P = 0.325; 2nd: r = 0.299, P = 0.072; 3rd: r = 0.579, P < 0.001; 4th: r = 0.483, P = 0.002]. LUS score decreased from 22 (18 - 25) to 15 (13 - 18) and OI decreased from 15.92 (14.07 -17.73) to 9.49 (8.70 -10.58) after CRRT for four days (both P < 0.001).Conclusions: LUS score is significantly correlated with lung function parameters in pediatric ARDS. The improvement of pulmonary edema in patient with ARDS received CRRT can be assessed by the LUS score.Trial registration: CCTR, ChiCTR-ONC-16009698. Registered 1 November 2016, prospectively registered, http://www.chictr.org.cn/edit.aspx?pid=16535&htm=4. This study adheres to CONSORT guidelines.
Increased acquired protease inhibitor drug resistance mutations in minor HIV-1 quasispecies from infected patients suspected of failing on national second-line therapy in South Africa
Authors: Obasa Adetayo Emmanuel , Ambikan Anoop T , Gupta Soham , Neogi Ujjwal , Jacobs Graeme Brendon
Published: January 2021

Background: HIV-1C has been shown to have a greater risk of virological failure and reduced susceptibility towards boosted protease inhibitors (bPIs), a component of second-line combination antiretroviral therapy (cART) in South Africa. This study entailed an evaluation of HIV-1 drug resistance-associated mutations (RAMs) among minor viral populations through high-throughput sequencing genotypic resistance testing (HTS-GRT) in patients on the South African national second-line cART regimen receiving bPIs.Methods: During 2017 and 2018, 67 patient samples were sequenced using high throughput sequencing (HTS), of which 56 samples were included in the analysis because the patient’s treatment regimen were available at the time of sampling. All patients were receiving bPIs as part of their cART. Viral RNA was extracted, and complete pol genes were amplified and sequenced using Illumina HiSeq2500, followed by bioinformatics analysis to quantify the RAMs according to the Stanford HIV Drug Resistance Database.Results: Statistically significantly higher PI RAMs were observed in minor viral quasispecies (25%; 14/56) compared to non-nucleoside reverse transcriptase inhibitors (9%; 5/56; p=0.042) and integrase inhibitor RAM (4%; 2/56; p=0.002). The majority of the drug resistance mutations in the minor viral quasispecies were observed in the V82A mutation (n=13) in protease and K65R (n=5), K103N (n=7) and M184V (n=5) in reverse transcriptase.Conclusions: HTS-GRT improved the identification of PI and reverse transcriptase inhibitor (RTI) RAMs in second-line cART patients from South Africa compared to the conventional GRT with ≥20% used in Sanger-based sequencing. Several RTI RAMs, such as K65R, M184V or K103N and PI RAM V82A, were identified in <20% of the population. Deep sequencing could be of greater value in detecting acquired resistance mutations early.
Qualitative views of Nigerian School Principals and Teachers on the barriers and opportunities for promoting students’ physical activity behaviour within the school settings
Authors: Oluwasanu Mojisola , Oladepo Oladimeji , Ibitoye Segun Emmanuel
Published: January 2021

Background: Insufficient physical activity is a growing public health challenge among Nigerian adolescents. Significant information gap exists on the school-related factors and its implication on the school-based physical activity participation of adolescents in Nigeria. This study was conducted to document the qualitative views of school principals and teachers on the barriers and opportunities for promoting the physical activity behaviours of adolescents within the school settings in light of the socio-ecological model.Methods: This was a qualitative study conducted in 12 public and private schools in two local government areas of Oyo state, Nigeria. Two key sources and data collection methods (i.e key informant interviews and focus group discussions) were used. Six key informant interviews were held with school principals and six focus group discussions with classroom teachers using pre-tested guides. Data was analysed using thematic analysis.Results: Fourteen sub-themes were identified as barriers to PA and linked to different levels of the socio-ecological model. Three themes were categorized as parental factors, three themes as socio-cultural and religious factors while the school-related factors had eight sub-themes. Specifically, the school related barriers were the declining number of trained physical health education teachers, limited opportunities for continuing education and low prioritisation of physical health education. Other school-related factors such as increasing demand for classroom academic time, negative attitudinal dispositions of other teachers and inadequate funding for schools which hampered the provision of facilities and equipment were identified as factors that limit the effective implementation of policies and programs for physical activity in schools. Opportunities to promote PA within the school settings during assemblies, breaktime, after-school and inter house sports competition exists. However; these opportunities are hampered by competing academic time, security threats, fear of causalities to students due to poor supervision after school, poor funding and brawling associated with competitive school-based sporting events. Conclusions: Factors that contribute to insufficient physical activity among in-school adolescents in the school settings are multifactorial. Implementation of holistic, multi-component interventions which address the social-cultural and school-level factors and enhance students’ opportunities for physical activity in schools are recommended.
The Effectiveness of Prolotherapy for Recalcitrant Medial Tibial Stress Syndrome: a Prospective Consecutive Case Series.
Authors: Padhiar Nat , Curtin Mark , Aweid Osama , Awied Bashaar , Morrissey Dylan , Chan Otto , Malliaras Peter , Crisp Tom
Published: January 2021

Background: Medial tibial stress syndrome (MTSS) is one of the most common lower leg injuries in sporting populations. It accounts for between 6%-16% of all running injuries, and up to 53% of lower leg injuries in military recruits. Various treatment modalities are available with varying degrees of success. In recalcitrant cases, surgery is often the only option.Objective: To evaluate whether ultrasound-guided injection of 15% dextrose for treatment of recalcitrant MTSS decreases pain and facilitates a return to desired activity levels for those who may otherwise be considering surgery or giving up the sport.Method: The study design was a prospective consecutive case series involving eighteen patients: fifteen male and three female; (mean age=31.2 years) with recalcitrant MTSS. They were referred from sports injury clinics across the UK, having failed all available conservative treatment.Intervention: An ultrasound-guided sub-periosteal injection of 15% dextrose was administered by the same clinician (NP) along the length of the symptomatic area. Typically, 1 mL of solution was injected per cm of the symptomatic area. Main Outcome Measures: Pain was assessed using a 10-cm visual analog scale (VAS) at baseline, short-term, medium-term (mean 18 weeks), and long-term (mean 52 weeks) follow-up. Symptom resolution and return to activity were measured using a Likert scale at medium and long-term follow-up. Statistical analyses were performed using SPSS for Mac version 19.0.0 (IBM, New York, NY, US). The Shapiro-Wilk test was used to evaluate the normality of the distribution of data. Friedman's non-parametric test was used to compare the within-patient treatment response over time. Post-hoc Wilcoxon signed-rank tests with Bonferroni corrections were performed to determine VAS average pain response to treatment over five paired periods.Results: Patients reported a significant (p<0.01) reduction in median VAS pain score at medium and long-term follow-up compared to baseline. Median improvement per patient was 4.5/10. Patients rated their condition as 'much improved' at medium-term follow-up and the median return to sports score was 'returned to desired but not pre-injury level' at medium-term and long-term follow-up. No adverse events were reported.Conclusions: Ultrasound-guided 15% dextrose prolotherapy injection has a significant medium-term effect on pain in MTSS. This benefit may be maintained long-term; however, more robust trials are required to validate these findings in the absence of controls.Clinical Relevance: Clinicians should consider the use of ultrasound-guided injection of 15% dextrose as a viable treatment option to reduce pain and aid return to activity for patients with recalcitrant MTSS.
Promoting the propensity for blood donation through the understanding of its determinants.
Authors: Mugion Roberta Guglielmetti , Giovina Pasca Maria , Laura Di Pietro , Renzi Maria Francesca
Published: January 2021

Background. The paper aims to understand the main antecedents related to the blood donation propensity related to both donors and non-donors. With our research, we will analyse the two perspectives to identify similarities and differences concentrating on the Italian context. Blood is a vital resource that strongly affects every national healthcare system's efficacy and sustainability and the system's ability to achieve the goal of universal coverage. Methods. The purpose of this paper is to understand the main antecedents of citizens' blood donation intention and the propensity to encourage communication about blood donation among both donors and non-donors. The Theory of Planned Behaviour is adopted as a theoretical lens. An empirical investigation was performed in Italy, adopting a mixed methods research design. First, a qualitative analysis was carried out through 30 in-depth interviews. Then, a survey was used to quantitatively investigate the intention to donate among both donors (N=173) and non-donors (N=87). A conceptual model was developed and tested through Structural Equation Modelling, developing a multi-group approach. Results. The present study confirms the relations proposed by the Theory of Planned Behaviour, even though some differences between the two groups are shown. The construct Information and Communication is crucial for donors, non-donors, whereas for non-donor inhibitors is vital. Service quality has an impact on the propensity to recommend and communicate the value of blood donation.Conclusion. This paper reveals the main differences between donor and non-donor perspectives. Fruitful insights for enhancing blood donation awareness are provided.
A comparative study on effect of different methods of recycling orthodontic brackets on shear bond strength
Authors: Khanal Purna Prasad , Shrestha Basanta Kumar , Yadav Rajiv , Gupta Sanjay Prasad
Published: January 2021

Aim: The aim of this study was to evaluate and compare the effect of different methods of recycling stainless steel orthodontic brackets on shear bond strength.Methods: One hundred twenty human premolars extracted for orthodontic purpose were randomly divided into four groups. Standard MBT (0.022”) brackets were bonded on buccal surface of all samples with light cured adhesive primer using LED curing unit for 10 seconds. Group-I was assigned as control and the brackets of Group-II, Group-III and Group-IV were subjected to recycling by flaming, flaming with sandblasting and flaming with ultrasonic cleaning respectively. The recycled brackets were rebonded and final debonding of all brackets was done with universal testing machine at a crosshead speed of 0.5mm/min and shear bond strength was determined. Data were analyzed with descriptive statistics, ANOVA and post hoc test. The adhesive remnant index was evaluated by stereomicroscope at 10X magnification.Results: The highest shear bond strength was obtained with Group I (10.35 ± 0.46 MPa), followed by Group III (9.36 ± 0.55 MPa), Group IV (5.97 ± 0.66 MPa) and the least value was obtained with Group II (4.30 ± 0.55 Mpa). Significant differences among the groups were detected by analysis of variance. Tukey post hoc multiple comparison test showed that the shear bond strength of each group was significantly different from one another (p < 0.001). Conclusions: Shear bond strength of new brackets was significantly higher than that of the recycled brackets. Among recycled brackets, flaming with sandblasting provided adequate shear bond strength, flaming with ultrasonic cleaning provided borderline value for clinical use while flaming alone led to significantly lower value.
Developing a complex intervention whilst considering implementation: the TANDEM (Tailored intervention for ANxiety and DEpression Management) intervention for patients with chronic obstructive pulmonary disease (COPD) 
Authors: Steed Liz , Heslop-Marshall Karen , Sohanpal Ratna , Saqi-Waseem Sarah , Kelly Moira , Pinnock Hilary , Taylor Stephanie
Published: January 2021

Background Guidelines now call for a thorough and comprehensive description of the development of healthcare interventions to aid evaluation and understanding of the processes of change. This was the primary aim of this study but we also recognized that effective interventions are commonly not implemented in clinical practice. It is suggested that insufficient attention is given to the implementation process at the development phase of interventions. This study outlines the 5 step iterative process we adopted for considering both implementation and effectiveness issues from the outset of intervention development. We use the development of a complex intervention Tailored intervention for ANxiety and DEpression Management (TANDEM) in patients with chronic obstructive pulmonary disease to illustrate this process. Methods Intervention development built upon the Medical Research Council framework for developing complex interventions and the Person Based Approach for development of behavioural interventions. Building an expert team, specifying theory, qualitative data collection and pre-piloting were all critical steps in our intervention development and are described here.Results Contact with experts in the field, and explicitly building on previous work, ensured efficiency of design. Qualitative work suggested guiding principles for the intervention such as introducing mood in relation to breathlessness, and providing flexible tailoring to patients’ needs, whilst implementation principles focused on training selected respiratory professionals and requiring supervision to ensure standards of care. Subsequent steps of intervention development, pre-piloting and intervention refinement led to an intervention that was deemed acceptable and if successful will be ready for implementation. Conclusions The TANDEM study was developed efficiently by building on previous work and considering implementation issues from the outset, with the aim that if shown to be effective it will have more rapid translation in to the health care system with accelerated patient benefits. Trial Registration ISRCTN, ID: ISRCTN59537391. Registered on 20 March 2017. Protocol version 6.0, 22 April 2018.
Growth and Elasticity of Output of MSMEs in India
Authors: PALAKA SETAKA , Das Sandhyarani
Published: January 2021

In the last few years, the phenomenon of a marked slowdown in the growth of employment has been noticed in many countries across the world including India. An important objective of development planning in India has been to provide for increasing employment opportunities not only to meet the backlog of the unemployed but also the new additions to the labour force. Micro, small and medium enterprises (MSMEs), including khadi and village industries generate the highest rates of employment growth and account for a significant share of industrial production and exports. The core objective of the present paper is to analyse the growth and elasticity output in the MSMEs sector. Extended Cobb Douglas Production Function has been utilized based on the secondary data. The study reveals that the output elasticity of employment during the study period is very low as compared to the output elasticity of export.
Musculo-skeletal phenotype of Costello syndrome and cardio-facio-cutaneous syndrome: insights on the functional assessment status
Authors: Leoni Chiara , Romeo Domenico M , Michele Pelliccioni , Mariangela Di Già , Roberta Onesimo , Valentina Giorgio , Elisabetta Flex , Tedesco Marta , Tartaglia Marco , Rigante Donato , Valassina Antonio , Zampino Giuseppe
Published: January 2021

BackgroundCostello syndrome (CS) and cardio-facio-cutaneous syndrome (CFCS) belong to the RASopathies, a group of neurodevelopmental disorders with skeletal anomalies. Due to their rarity, the characterization of the musculo-skeletal phenotype in both disorders has been poorly characterized.Patients and methodsHerein we reported data on orthopedic findings and functional status of a large sample of CS and CFCS patients. Thirty-four patients (CS=17 and CFCS=17) were recruited. Functional and disability evaluations were performed by assessing the 6-minute walking test (6MWT) and Pediatric Outcomes Data Collection Instrument (PODCI). Genotype/phenotype correlation was also provided.ResultsOrthopedic manifestations are highly prevalent in CS and CFCS and overlap in the two disorders. Overall, patients with CS harboring the recurrent HRAS Gly12Ser substitution show a more severe skeletal phenotype compared to patients carrying the Gly12Ala and Gly13Cys variants. Among CFCS patients, those with the MAP2K1/2 variant show different skeletal characteristics compared to BRAF variants, with a higher prevalence of orthopedic abnormalities. Functional assessment showed that patients with CS and CFCS reached lower values compared to the general population, with CFCS patients displaying the lowest scores.ConclusionsOrthopedic manifestations appear universal features of CS and CFCS and they can evolve across patients’ life. Longitudinal assessment of disability status by using 6MWT and PODCI could be useful to evaluate the functional impact of orthopedic manifestations on patients’ outcome and help planning a tailored treatment of these comorbidities.