bluuebunny/crossref_metadata_2025 huggingface dataset:
Addressing low-value pharmacological prescribing in primary prevention of CVD through a structured evidence-based and theory-informed process for the design and testing of de-implementation strategies: the DE-imFAR study
Authors: Sanchez Alvaro , Pijoan Jose Ignacio , Pablo Susana , Mediavilla Marta Maialen , Sainz Rita , Lekue Itxasne , Gonzalez-Larragan Susana , Lantaron Gaspar , Argote Jon Imanol , García-Álvarez Arturo , Latorre Pedro Maria , Helfrich Christian D. , Grandes Gonzalo
Published: December 2019

Background: De-implementation or abandonment of ineffective or low-value healthcare is becoming a priority research field globally due to the growing empirical evidence of the high prevalence of such care and its impact in terms of patient safety and social inefficiency. Little is known, however, about the factors, barriers and facilitators involved or about interventions that are effective in promoting and accelerating the de-implementation of low-value healthcare. The De-imFAR study seeks to carry out a structured, evidence-based and theory-informed process involving the main stakeholders (clinicians, managers, patients and researchers) for the design, deployment and assessment of de-implementation strategies for reducing low-value pharmacological prescribing.Methods: A Phase I formative study using a systematic and comprehensive framework based on theory and evidence for the design of implementation strategies – specifically, the Behavior Change Wheel (BCW) - will be conducted to design and model de-implementation strategies to favour reductions in low-value pharmacological prescribing of statins in primary prevention of cardiovascular disease (CVD) by main stakeholders (clinicians, managers, patients and researchers) in a collegiate way. Subsequently, a Phase II comparative hybrid trial will be conducted to assess the feasibility and potential effectiveness of at least one active de-implementation strategy to reduce low-value pharmacological prescribing of statins in primary prevention of CVD compared to the usual procedures for dissemination of clinical practice guidelines ("what-not-to-do" recommendations). A mixed methods evaluation will be used: quantitative for the results of the implementation at the professional level (e.g., adoption, reach and implementation or execution of the recommended clinical practice); and qualitative to determine the feasibility and perceived impact of the de-implementation strategies from the clinicians’ perspective, and patients’ experiences related to the clinical care received.Discussion: The DE-imFAR study aims to generate valid scientific knowledge about the design and development of de-implementation strategies using theory- and evidence-based methodologies suggested by implementation science. It will explore the effectiveness of these strategies and their acceptability among clinicians, policy makers and patients. Its ultimate goal is to maximize the quality and efficiency of our health system by abandoning low-value pharmacological prescribing.
Developing a behavioural intervention package to identify and amend incorrect penicillin allergy records in UK general practice
Authors: Santillo Marta , Wanat Marta , Davoudianfar Mina , Bongard Emily , Savic Sinisa , Savic Luoise , Porter Catherine , Fielding Joanne , Butler Chris , Pavitt Sue , Sandoe Jonathan , Tonkin-Crine Sarah
Published: December 2019

Background: To develop a behavioural intervention package to support clinicians and patients to identify and amend incorrect penicillin allergy records in English general practice. The intervention aimed to: 1) support general practice clinicians to refer patients for penicillin allergy testing (PAT), 2) support patients to attend for PAT and 3) support clinicians and patients to prescribe or consume penicillin, when indicated, following a negative PAT result.Methods: Theory-based, evidence-based and person-based approaches were utilised in the intervention development. We used evidence from a rapid review, two qualitative studies, one with patients and one with general practice clinicians, and expert consultation with the clinical research team in order to identify the intervention guiding principles and develop an intervention plan. Barriers and facilitators to the target behaviours were mapped to behaviour change theory in order to describe the proposed mechanisms of change. In the final stage, think-aloud interviews and consultations with the clinical research team were conducted to optimise intervention materials.Results: The collated evidence showed that the key barriers to referral of patients by clinicians were limited experience of referral and limited knowledge of referral criteria and PAT. Barriers for patients attending PAT were lack of knowledge of the benefits of testing and lack of motivation to get tested. Intervention materials were designed and developed to address these barriers. Conclusions: We present a novel behavioural intervention package designed to address the multiple barriers to uptake of PAT in general practice by clinicians and patients. The intervention development details how behaviour change techniques have been incorporated to hypothesise how the intervention is likely to work to help amend incorrect penicillin allergy records. The intervention will go on to be tested in a feasibility trial and randomised controlled trial in England.
Scaling-up an evidence-based intervention for osteoarthritis in real world settings: A pragmatic evaluation using the RE-AIM framework
Authors: Walker Andrew , Boaz Annette , Gibney Amber , Zambelli Zoe , Hurley Michael V
Published: December 2019

Background: Scaling-up and sustaining effective healthcare interventions is essential for improving healthcare; however, relatively little is known about these processes. In addition to quantitative experimental designs we need approaches that use embedded, observational studies on practice-led, naturally-occurring scale-up processes. There are also tensions between having adequately rigorous systems to monitor and evaluate scale-up well that are proportionate and pragmatic in practice. The study investigated the scale-up of an evidence-based complex intervention for knee and hip osteoarthritis (ESCAPE-pain) within ‘real-world’ settings by England’s 15 Academic Health Science Networks (AHSNs).Methods: A pragmatic evaluation of the scale-up of ESCAPE-pain using the RE-AIM framework to measure reach, effectiveness, adoption, implementation and maintenance. The evaluation used routine monitoring data collected from April 2014 to December 2019 as part of a national scale-up programme.Results: Between 2014-2018 ESCAPE-pain was adopted by over 110 clinical and non-clinical sites reaching over 9,000 people with osteoarthritis. The programme showed sustained clinical effectiveness (pain, function and quality of life) and high levels of adherence (78.5% completing 75% of the programme) within a range of real world settings. 770 people (physiotherapists and exercise professionals) have been trained to deliver ESCAPE-pain and 84.1% of sites have continued to deliver the programme post-implementation.Conclusions: ESCAPE-pain successfully moved from being an efficacious “research intervention” into an effective intervention within ‘real world’ clinical and non-clinical community settings. However, scale-up has been a gradual process requiring on-going, dedicated resources over 5 years by a national network of Academic Health Science Networks (AHSNs). Whilst the collection of monitoring and evaluation data is critical in understanding implementation and scale-up, there remain significant challenges in developing systems sufficiently rigorous, proportionate and locally acceptable.
Influence of China’s 2009 healthcare reform on the utilisation of continuum of care for maternal health services: Evidence from two cross-sectional household surveys in Shaanxi Province
Authors: Fan Xiaojing , Kumar Meghan Bruce , Zhou Zhongliang , Lee Ching-Hung , Wang Duolao , Liu Haixia , Dang Shaonong , Gao Jianmin
Published: December 2019

Background: Continuum of care for maternal health services (CMHS) is a proven approach to improve health and safety for mothers and newborns. This study aims to explore the influence of China’s 2009 healthcare reform on improving the CMHS utilisation. Methods: This population-based cross-sectional quantitative study included 2332 women drawn from the fourth and fifth National Health Service Surveys of Shaanxi Province, conducted in 2008 and 2013 respectively, before and after China’s 2009 healthcare reform. A generalised linear mixed model (GLMM) was applied to analyse the influence of this healthcare reform on utilisation of CMHS. Concentration curves, concentration indexes and its decomposition method were used to analyse the equity of changes in utilisation. Results: According to China’s policy defining CMHS, post-reform CMHS utilisation was higher in both rural and urban women. The rate of CMHS utilisation increased from 24.66% to 41.55% for urban women and from 18.31% to 50.49% for rural women (urban: χ2=20.64, P<0.001; rural: χ2=131.38, P<0.001). This finding is consistent when the WHO’s level of CMHS is applied for rural women after reform (12.13% vs 19.26%; χ2=10.99, P=0.001); for urban women, CMHS utilisation increased from 15.70% to 20.56% (χ2=2.57, P=0.109). The GLMM showed the rate of CMHS utilisation for urban women post-reform was five times higher than pre-reform rates (OR=5.02, 95%CL: 1.90, 13.31); it was close to 15 times higher for rural women (OR=14.70, 95%CL: 5.43, 39.76). The concentration index decreased from 0.130 pre-reform (95%CI: -0.026, 0.411) to -0.041 post-reform (95%CI: -0.096, 0.007) for urban women; it decreased from 0.104 (95%CI: -0.012, 0.222) to 0.019 (95%CI: -0.014, 0.060) for rural women. The horizontal inequity index for both groups of women also decreased (0.136 to -0.047 urban and 0.111 to 0.019 for rural). Conclusions: China’s 2009 healthcare reform has positively influenced utilisation rates and equity of utilisation of the CMHS among both urban and rural women in Shaanxi Province. We expect that similar impacts might be observed in other settings in China and, if so, may provide lessons in policy design to other countries looking to reduce maternal and newborn mortality.
Red cell distribution width to platelet ratio (RPR) predicts liver fibrosis in patients with autoimmune hepatitis
Authors: Wang Huali , Wang Jian , Xia Juan , Yan Xiaomin , Feng Yanhong , Li Lin , Chen Jun , Liu Duxian , Ding Weimao , Yang Yongfeng , Wu Chao , Huang Rui
Published: December 2019

Background Accurately evaluate the stages of liver fibrosis are critical for the management of patients with autoimmune hepatitis (AIH). We evaluated the accuracy of red cell distribution width (RDW) to platelet (PLT) ratio (RPR) in predicting liver fibrosis in AIH patients.Methods One hundred and nineteen AIH patients with liver biopsy was retrospectively enrolled. Scheuer scoring system was used to stage liver fibrosis. Receiver operating characteristic curve (AUROC) was performed to evaluate the diagnostic accuracy of RPR.Results The median RPR values were 0.10, 0.10 and 0.14 for AIH patients with S2-S4, S3-S4 and S4, which were significantly higher than patients with S0-S1 (0.07, P<0.001), S0-S2 (0.08, P=0.025) and S0-S3 (0.09, P=0.014), respectively. The RPR levels were positively associated with the fibrosis stages (r=0.412, P<0.001), whereas there were no associations between liver fibrosis stages and aspartate transaminase to platelet ratio index (APRI) and fibrosis-4 score (FIB-4). The AUROCs of RPR were 0.780 (95%CI 0.696 to 0.865), 0.639 (95%CI 0.530 to 0.748) and 0.724 (95%CI 0.570 to 0.878) in diagnosing significant fibrosis (S2-S4), advanced fibrosis (S3-S4) and cirrhosis (S4) for AIH patients, respectively. The AUROCs of RPR were significantly higher than those of APRI and FIB-4 in staging liver fibrosis for AIH patients.Conclusion RPR is a simple predictor of liver fibrosis and is superior to APRI and FIB-4 in identifying liver fibrosis in AIH patients.
Beyond invasion: land use influencing bovine tuberculosis (bTB) infection as a function of ecosystem services
Authors: Dejene Sintayehu , Elbur E. van , Heitkönig Ignas M.A. , Prins Herbert H.T. , Bartholomeus H. , Boer Willem F. de
Published: December 2019

Background: Changes in land use and associated ecosystem change have been described as one of the causal drivers in emerging and re-emerging of infectious diseases, but there is a notable scarcity of scientific knowledge to show whether, and how, land use change plays this role. Land use change may include the invasion of non-native woody species. We studied how and to what extent Prosopis juliflora, a most powerful invasive woody species, influences the prevalence of bovine tuberculosis (bTB) in cattle in the Afar Region, Ethiopia between November 2013 and April 2016. We examined the potential underlying mechanisms by which ecological consequences of land use, such as an invading woody species, alters the risk of bTB transmission. Methods: A total of 2550 cattle from 102 herds were investigated for the presence of bTB using the comparative intradermal tuberculin test (CITT). Landsat images from 2014 were used to quantify the proportion of different land use types by applying a k-means unsupervised classification, and analyzing this within a buffer of 16km from the location of each cattle herd. A generalized linear model was used to quantify the relationship between bTB prevalence and the proportion of land use types. Then, multiple regression tree analyses were used to identify the most important land use predictor accounting for the variation in bTB prevalence. Results: A model averaging analyses identified the proportion of P. juliflora as a significant risk factor for increasing bTB prevalence in cattle (b=12.2, 95%CI=8.9-15.5, p<0.001), and multiple regression tree analysis identified the proportion of Prosopis as the most important land use predictor of bTB in cattle. Conclusions: The loss in host species evenness and the increase in cattle movement as a consequence of the loss of palatable grasses in Prosopis areas could be potential mechanisms accounting for the observed higher bTB prevalence in these areas. Given the projected spread of Prosopis, land use changes and associated changes in host community composition could affect the risk of infectious diseases, which is important for decision makers when formulating disease control strategies.
Urinary tract infection caused by enterococcus spp: risk factors and mortality.
Authors: Artero Elisa Alvarez , Campo Amaia , Garcia Inmaculada Garcia , Bravo Moises Garcia , Cores Olaia , Galindo Inmaculada , Pendones Josue , Bernus Amparo Lopez , Belhassen-Garcia Moncef , Lledias Javier Pardo
Published: December 2019

Purpose: Complicated urinary tract infections (UTIs) are frequently caused by Enterococcus spp. We aim to define the risk factors involved in UTIs caused by Enterococcus. Determine the overall mortality and predictive risk factors.Methods: A retrospective study was conducted. We compared the results with those of a random sample of patients with complicated UTIs infection caused by Escherichia coli.Results: We found 106 in-patients with UTIs caused by Enterococcus spp., 56 of whom had positive blood cultures. Distribution by species: 83% E. faecalis and 17% E. faecium, with a Charlson comorbidity index of 5.9±2.9. Only male sex with an OR of 2.8 (95%CI 1.2-6.4), nosocomial infection with an OR of 2.8 (95%CI 1.1-7), urinary catheter with an OR of 4.5 (95%CI 1.8-11.3), urinary cancer with an OR of 6.4 (2.1-19.4), and previous antimicrobial treatment with an OR of 4.3 (1.8-10.2) were independent predictors of Enterococcus infection. Overall, in-patient mortality was 16.5%, which was associated with a higher Sequential Organ Failure Assessment (SOFA) score (>4), severe comorbidity such as immunosuppression, malignant hemopathy and nephrostomy, or Enterococcus faecium species and its pattern or resistance to ampicillin or vancomycin (p<0.05). Appropriate empiric antibiotic therapy was not associated with a better prognosis (p >0.05).Conclusions: Enterococcus spp. is a frequent cause of complicated UTI by a profile of risk factors. High mortality secondary to a severe clinical setting and high comorbidity may be sufficient reasons for implementing empiric treatment of patients at risk, although we did not show a higher survival rate in patients with this treatment strategy.
A cross-sectional research conducted in Malatya province, Turkey: Knowledge levels and awareness about rational antibiotic use and antimicrobial resistance before and after graduation
Authors: KOSE ADEM
Published: December 2019

Background Irrational antibiotic use can adversely affect treatment outcomes or even lead to increased antimicrobial resistance. We aimed to determine antimicrobial prescribing habits and to evaluate the level of theoretical knowledge of rational antibiotic use and awareness about antimicrobial resistance among the senior students of medical faculty and the family physicians in Malatya province in Turkey. Methods This study was cross-sectional research and was carried out between dates of 01 February-30 April 2019, in Malatya province. Power analysis was calculated as minimum 240 participants when considering a proportion difference of 0.18 between the groups, a type I error of 0.05 and a type II error of 0.20. A total 225 senior students in Inonu University Medical Faculty (Group 1) and 230 actively-working family physicians in Malatya primary healthcare services who were found eligible (Group 2) were included in to this study. A questionnaire form was prepared including seven sections and thirty questions. All of the participants were interviewed face to face. Before the questions, the purpose of the study and the contents of the questions were explained to participants. Qualitative data were analyzed by Pearson chi-square test. A p<0.05 value was considered to be statistically significant. Results The group 1 had a tendency to apply to specialist physician when starting to themselves antibiotic treatment, they were more cautious when making antibiotic decision, and their theoretical knowledge level was better. They argued that penal sanctions could be more effective by developing strict use policies to raise awareness of resistance to antibiotics. The group 2 had higher self-confidence and it was also concluded that forgot their theoretical antibiotic knowledge over time and could not follow the novel information because of the intensity of working life. Both groups stated that post-graduation trainings could be used effectively for reducing the antibiotic resistance. Conclusion This study highlighted the need for immediate action of training and corrective actions and might create awareness to determine the difference in theoretical knowledge levels and behavior models of physicians before and after graduation and to reduce higher use rates to lower levels. Key words: Antimicrobial resistance, antibiotic, awareness, rational use
Psychosocial barriers and enablers of exclusive breastfeeding: lived experiences of mothers in low-income townships, North West Province, South Africa
Authors: Witten Chantell Beverley , Claasen Nicole , Kruger Herculina S , Coutsoudis Anna , Grobler Herman
Published: December 2019

Background Despite national efforts to promote exclusive breastfeeding (EBF), South Africa’s EBF rate is only 32%. The aim of this study was to examine the rate of EBF discontinuation and the lived experiences of breastfeeding mothers at postnatal time points 3-14 days, 4-8 weeks, 10-14 weeks and 20-24 weeks.Methods This community-based mixed-methods study collected data within a prospective cohort study on socio-demographics, the Edinburgh Postnatal Depression Scale (EPDS) and the Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF) at 6-8 weeks with infant feeding data collected at 4-8, 10-14 and 20-24 weeks from 159 mothers living in low income areas. Six focus groups with 32 mothers with infants aged 6-24 weeks were conducted. Descriptive statistics was used for the quantitative data and thematic analysis for qualitative data.Results The majority of mothers were unmarried (84.9%), living with family (69.2%) and unemployed (74.2%). EBF decreased from 34% at 4-8 weeks to 9.7% at 20-24 weeks. Mixed feeding with infant formula increased from 17.0% to 50.1% and food feeding from 3.1% to 54.2%. While there were no statistically significant associations between EBF and any of the quantitative socio-demographic variables, in the qualitative data, codes associated with barriers were more than enablers. The themes were Mothers’ attributes (wellbeing, experiences and relationships) with the code mother’s stress the strongest barrier, Mother’s knowledge, attitudes and practices of breastfeeding with the code conventional medicines the strongest barrier , Family environment with the code home setting the strongest barrier, Social environment with public spaces and places a barrier and in Baby cues the code baby stomach ailments the barrier. Within these same themes mother’s positive emotions , benefits of breastfeeding , support in the home , access to information and services from health professionals and baby’s health were strong enabling factors.Conclusions Low EBF, high mixed feeding and a high EPDS score were explained by the barriers identified in the qualitative data. The data suggests that mothers from low-income households would be better supported through interventions that address food insecurity; family relationships and those that build confidence in mothers and resilience in confronting difficult and hostile breastfeeding environments.
Allo-HSCT compared with immunosuppressive therapy for acquired aplastic anemia: Is superiority a one-sided understanding?
Authors: Zhu Yangmin , Gao Qingyan , Hu Jing , Guan Dongrui , Liu Xu , Zhang Fengkui
Published: December 2019

Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) and immunosuppressive therapy (IST) are two major competing treatment strategies for acquired aplastic anemia (AA). Whether allo-HSCT is superior to IST as a front-line treatment for patients with AA has been a subject of debate. To comprehensively compare the efﬁcacy and safety of allo-HSCT with IST as a front-line treatment for patients with AA. Methods: We searched the Medline, Embase, and Cochrane Registry of Controlled Trials databases from January 2000 to March 2019. Studies comparing allo-HSCT with IST as a first-line therapy for patients with AA were included. Results: Fifteen studies including a total of 5336 patients were included in the meta-analysis. The pooled hazard ratio (HR) for overall survival (OS) was 0.4 (95% CI 0.074–0.733, P = 0.016, I2 = 58.8%) and the pooled HR for failure-free survival (FFS) was 1.962 (95% CI 1.43–2.493, P = 0.000, I2 = 0%). The pooled relative risk (RR) for overall response rate (ORR) was 1.691 (95% CI 1.433–1.996, P = 0.000, I2 = 11.6%). Conclusion: Although survival was significantly longer among AA patients undergoing first-line allo-HSCT compared to those undergoing first-line IST, the selection of initial treatment for patients with newly diagnosed AA still requires comprehensive evaluation of donor availability, patient age, expected quality of life, risk of disease relapse or clonal evolution after IST, and potential use of adjunctive eltrombopag.
Medical Costs of Alpha-1 Antitrypsin Deficiency-Associated COPD in the United States
Authors: Sieluk Jan , Slejko Julia F , Silverman Henry , Perfetto Eleanor , Mullins C. Daniel
Published: December 2019

Background There are limited data on economic aspects of the genetic variant of chronic obstructive pulmonary disease (COPD) in the context of the more prevalent form of COPD. The objective of this study was to isolate the healthcare resource utilization and economic burden attributable to the presence of a genetic factor among COPD patients with and without Alpha-1 Antitrypsin Deficiency (AATD), twelve months before and after their initial COPD diagnosis.Results The study population consisted of 8,881 patients (953 cases matched with 7,928 controls). The AATD-associated COPD cohort had higher expenditures and use of OV and OTH services, as well as OV, OP, ER, RX, and OTH before and after the index date, respectively. Adjusted total cost ratios for AATD-associated COPD patients as compared to controls were 2.04 [95% CI: 1.60 – 2.59] and 1.98 [95% CI: 1.55 – 2.52] while the incremental cost difference totaled $6,861 [95% CI: $3,025 - $10,698] and $5,772 [95% CI: $1,940 - $9,604] per patient before and after the index date, respectively.Conclusions Twelve months before and after their initial COPD diagnosis, patients with AATD incur higher healthcare utilization costs that are double the cost of similar COPD patients without AATD. This study also suggests that increased costs of AATD-associated COPD are not solely attributable to augmentation therapy use. Future studies should further explore the relationship between augmentation therapy, healthcare resource use, and other AATD-associated COPD expenditures.
An Investigation of the Prevalence of Giardia agilis in Anuran Amphibians Reveals Special Parasitic Adaptations of this Giardia Species
Authors: Lyu Zhangxia , Cheng Jiaoni , Shao Jingru , Ye Qingqing , Bai Huixian , Wang Jiangxin , Wen Jianfan
Published: December 2019

Background: Giardia agilis is a Giardia species with a very narrow and elongated body distinct from others. It was first reported in 1882, and was detected in several species of anuran amphibians. Although there were some studies about its morphology, no investigations about its prevalence have ever been reported to date.Methods: We detected G. agilis in frogs and tadpoles from some areas of China based on its distinct morphology. Statistical analysis was performed using mid-P exact probability tests and differences were considered significant when p-values ≤0.05 were obtained.Results: We investigated the prevalence of G. agilis in 25 anuran amphibian species and found that 195 of the 463 (42.1%) samples were detected to be positive. Our molecular phylogenetic analysis indicated all the detected G. agilis were from the same species. The 195 positive frog samples were from 9 frog species, which are distributed scatteredly in four families that are not closely related rather than just restricted to a narrow lineage. The statistical prevalence among adults of different frog species showed no significant difference, and so did among tadpoles, but the prevalence in the tadpoles is significantly higher than in their adults. More interestingly, although the prevalence in Kaloula verrucosa from the same area showed no significant differences between its tadpoles without legs and the ones with two legs, but is significantly higher in these two developmental stages than in the four-legged stage, which is still much higher than in the adults. Moreover, all the positive samples were found to be from the areas with relatively high altitude (more than 870 meters).Conclusions: G. agilis is probably able to infect all anuran amphibians without species-bias. The turning point of prevalence in the period of front leg development might be related with the development of immune system of the hosts. That G. agilis tends to infect easily the frogs living in high altitude areas means that it has adapted to the dramatic temperature change in the poikilothermal animal hosts. Therefore, G. agilis has evolved some special successful parasitism strategies for parastizing the poikilothermal hosts with metamorphosis development -- anuran amphibians.
The first report on the occurrence of Dirofilaria species in stray dogs in Siddharthnagar, Lumbini, Nepal
Authors: Rimal Subash , Adhikari Anil , Acharya Rabin , Singh Dinesh Kumar , Joshi Naresh Prasad , Shrestha Birendra , Kaphle Krishna , El-Dakhly Khaled Mohamed
Published: December 2019

Backround: Dirofilaria species are important zoonotic filarioid nematodes transmitted by mosquitoes causing a heartworm disease in canines worldwide. Map of the distribution pattern of dirofilariois in Nepalese context is lacking. Methodology: A study was done to access the occurrence of dirofilarioids among stray dogs population in Siddharthanagar, sub-metropolitan city of Lumbini, Nepal. A total of 150 blood specimens were examined using direct microscopy, buffy coat centrifugation and modified Knott's method. Haematobiochemical parameters including packed cell volume (PCV), alanine aminotransferase (SGPT), aspartate aminotransferase (SGOT), alkaline phosphate (ALP), creatinine, blood urea nitrogen (BUN), urea and total protein were evaluated. Furhter, the clinical performance, comprising the body temperature and respiratory rate, were also assessed. Results: The dirofilariod is recognized as Dirofilaria immitis . Overall prevalence of dirofilariosis was reported to be 19.33% (29/150). Meanwhile, microfilariae were noticed to be 16.0, 16.0 and 19.33 % using the direct blood smear microscopy, buffy coat and modified Knott technique, respectively. The infection rate was significantly ( P <0.05) higher in aged dogs with high respiratory rates. The response of sex was non-significant. Among haematobiochemical parameters, only SGPT and SGOT were significantly ( P <0.05) elevated. The body temperature was not altered.Conclusion: Coinciding with the existence of stray dog communities and the recent zoonotic appearance of such filarioids, further investigations including molecular approaches, are urgently needed to accurately differentiate both dirofilarioids and other filarioid nematodes in both pets and humans.
Histone demethylase KDM4C is required for ovarian cancer stem cell maintenance
Authors: Chen Guoqing , Ye Ping , Zeng Fa , Zhu Xiongshan , Chen Lu , Huang Yan , Xu Ling , Xie Xiaoying
Published: December 2019

Ovarian cancer is a highly deadly disease, which is often diagnosed at a late stage with metastases. However, most ovarian cancers relapse after surgery combined with platinum based chemotherapy. Cancer stem cells (CSCs) are stem-like cells that possess high tumorigenic capability and display higher resistant capability against current therapies. However, our knowledge of ovarian CSCs and their molecular mechanism remain sparse. In current study, we found that KDM4C, a histone demethylase, was required for ovarian cancer stem cells (CSCs) maintenance. Depletion of KDM4C significantly reduced the CSCs population and sphere formation in vitro. Moreover, we found that KDM4C can regulate the expression of stem cell factor OCT-4 via binding to its promoter. These data indicate that KDM4C is relevant for ovarian CSCs maintenance and underscore its importance as a potential therapeutic target.
Patient-reported outcomes following primary total hip arthroplasty in Crowe type Ⅲ or Ⅳ developmental dysplasia are comparable to those in Crowe type Ⅰ: a case-control study of 96 hips
Authors: Ueoka Ken , Kabata Tamon , Kajino Yoshitomo , Inoue Daisuke , Ohmori Takaaki , Ueno Takuro , Yoshitani Junya , Yamamuro Yuki , Tsuchiya Hiroyuki
Published: December 2019

Background: A few previous studies have investigated patient satisfaction following total hip arthroplasty (THA) according to the degree of pelvic deformity. This study compared patient-reported outcomes following primary THA for Crowe types Ⅲ, Ⅳ, and I dysplasia.Methods: Questionnaires were sent to patients who underwent primary THA for Crowe type III and IV dysplasia to evaluate postoperative satisfaction. Twenty-three patients were enrolled in the high hip dislocation group (H group), while the control group had 46 patients with Crowe type I dysplasia. To investigate the influence of femoral shortening osteotomy, the H group was divided according to whether or not femoral shortening osteotomy was performed. Ten patients underwent THA with femoral shortening osteotomy (FO group), while 12 patients underwent THA without femoral shortening osteotomy (N-FO group). Clinical evaluations were performed using the Japanese Orthopaedic Association (JOA) scores, 36-item short-form survey (SF-36), visual analogue scale (VAS), and questionnaires. Results: Postoperative leg length discrepancy (LLD) was significantly greater in the H group than in the control group. The H and control groups were not significantly different in terms of the pre- and postoperative JOA scores and SF-36. In the H group, VAS score at the final follow-up was significantly higher, and significantly more patients felt that postoperative rehabilitation was serious, expressing that they underwent THA for LLD correction. In addition, VAS scores in the FO group were higher than those in the N-FO group.Conclusion: The postoperative VAS score was higher in Crowe type Ⅲ and Ⅳ dysplasia than in Crowe type I dysplasia, but there were no significant differences in the postoperative satisfaction, JOA score, and SF-36. These findings can help determine the need for THA in patients with Crowe type Ⅲ and Ⅳ dysplasia and can preoperatively predict the THA outcomes.
Proteasome Inhibitors Reduce Thrombospondin-1 Release in Human Dysferlin-Deficient Myotubes
Authors: Fernández-Simón Esther , Lleixà Cinta , Suarez-Calvet Xavier , Diaz-Manera Jordi , Illa Isabel , Gallardo Eduard , de Luna Noemí
Published: December 2019

Background: Dysferlin is a type-II transmembrane protein and the causative gene of dysferlinopathies, which are characterized by absence or marked reduction in dysferlin protein and muscle weakness. Dysferlin is implicated in vesicle fusion, trafficking, and membrane repair. The muscle biopsy of patients with dysferlinopathy is characterized by the presence of inflammatory infiltrates. Release of thrombospondin-1 (TSP-1) by dysferlin deficient muscle has been reported as a possible factor of the inflammation observed in the muscle of both human and mouse models of dysferlinopathy. It has also been reported that treatment with vitamin D3 enhances dysferlin expression. The ubiquitin-proteasome system recognizes and removes proteins that fail to fold or assemble properly and previous studies suggest that its inhibition could have a therapeutic implication in muscle dystrophies. Here we assessed whether inhibition of the ubiquitin proteasome system prevented degradation of dysferlin in immortalized myoblasts from a patient carrying two missense mutationsMethods: Dysferlin deficient myotubes were treated with EB1089, a vitamin D3 analog, oprozomib and ixazomib to assess proteasome inhibition. Western blot was performed to analyze the effect of the different treatments on the recovery of dysferlin and myogenin expression. TSP-1 was quantified using Enzyme Linked Immunosorbent Assay to analyze the effect of these drugs on its release.A membrane repair assay was designed to assess the ability of treated myotubes to recover after membrane injury. Data were analyzed using a one-way ANOVA test followed by by Tukey post hoc test and analysis of variance. Ap≤0.05 was considered statistically significant. Results : Treatment with proteasome inhibitors and EB1089 resulted in a slight increase of dysferlin expression which was accompanied by a low increase of myogenin expression. Also, EB1089 and proteasome inhibitors reduced the release of TSP-1 in myotubes from a dysferlinopathy patient. However, the increase of dysferlin had no effect on the repair of muscle membrane after injury. Conclusions: Our findings indicate that the ubiquitin-proteasome system might not be the main mechanism of mutant dysferlin degradation. However, its inhibition could help to improve muscle inflammation by reducing TSP-1 release.
Noise after total knee arthroplasty has limited effect on joint awareness and patient reported clinical outcomes
Authors: Taniguchi Hiroto , Itoh Masafumi , Yoshimoto Nobuyuki , Itou Junya , Kuwashima Umito , Okazaki Ken
Published: December 2019

BackgroundSome patients complain of noise after total knee arthroplasty (TKA). Controversy still exists how the noise affect the clinical outcomes including joint awareness after TKA. Forgotten Joint Score-12 (FJS-12) measures the clinical outcomes focusing on joint awareness after surgery. The Knee Society Scoring System-2011 (KSS-2011) includes questionnaires for satisfaction, expectation, and functional activities. The aim of this study is to clarify the relationship among FJS-12, KSS-2011 and the noise. Furthermore, the relationship between FJS-12 and KSS-2011 was validated. MethodsUsing the FJS-12 and KSS-2011, 295 knees from 225 patients who underwent TKA was retrospectively evaluated. Noise perception was evaluated by a questionnaire with five grades which is a method that follows the questionnaire form of FJS-12 [“Are you aware of the noise of your artificial joint?” ; never, almost never, seldom, sometimes, mostly]. The correlations among FJS-12, KSS-2011, and noise were analyzed. In addition, patients were divided into four groups based on the mechanism of their implant [cruciate retaining, posterior stabilized, cruciate sacrificed, and bicruciate stabilized (BCS)]. FJS-12, KSS-2011, and noise were compared among the groups. ResultsA strong correlation was observed between FJS-12 and the total score of KSS-2011 (0.70; P < 0.001). FJS-12 also was correlated with KSS-2011 subcategories for “symptoms,” “satisfaction,” and “standard activities” that these correlation coefficients were approximately 0.60. Noise was limited to have weak correlations with FJS-12 (0.28; P < 0.001) and KSS-2011 (0.20 P < 0.001). With comparison among the TKA mechanisms, BCS showed significantly better KSS-2011 and greater range of movement but worse noise scores.ConclusionsNoise perception after TKA had limited effect on joint awareness and clinical outcomes. FJS-12 was correlated strongly with KSS-2011 and associated with satisfaction, residual symptoms, and daily activities as assessed by KSS-2011 subscores.
Comparisons among three approaches—two minimally invasive and one conventional—for total knee arthroplasty: a retrospective cohort study with minimum follow-up of 10 years
Authors: Yuan Fuzhen , Sun Zewen , Fan Baoshi , Jiang Dong , Zhang Jiying , Yu Jiakuo
Published: December 2019

BackgroundFew studies have investigated whether the mini-medial parapatellar (MMP) and quadriceps-sparing (QS) approaches have good long-term results compared to the conventional medial parapatellar (MP) approach in terms of clinical evaluations and radiographic assessments for total knee arthroplasty (TKA). The purpose of this study was to perform comparisons among the MMP, QS and MP approaches with a follow-up at 10 to 17 years.MethodsThis is a retrospective comparative study of 93 patients who underwent MMP TKA (32 TKAs), QS TKA (47 TKAs) or MP TKA (31 TKAs) with the same arthroplasty system. The clinical evaluations were performed according to the new American Knee Society score (KSS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the visual analogue scale (VAS), range of motion (ROM), incidence of anterior knee pain (AKP), the Feller patellofemoral score (PFS), the reoperation rate and the complication rates. Radiographic assessments included observation of the mechanical axis of the lower limb and calculations of the lateral distal femoral angle (LDFA), femoral flexion angle (FFA), medial proximal tibial angle (MPTA), tibial slope angle (TSA), lateral patella displacement (LPD), and lateral patella tilt (LPT).ResultsThere were no differences in the long-term follow-up results of the new KSS, WOMAC score, ROM, VAS, patellofemoral functions, reoperation rate or complication rates among the groups. In addition, no radiographic differences in terms of lower limb mechanical axis or femoral, tibial or patellar position were observed.ConclusionThese results provide conclusive evidence that equivalent, long-term clinical results can be obtained using any one of these three approaches.
Coexisting sonographic features of “tumor neovascularization-like pattern” and “echogenic areas” in thyroid nodules: Diagnostic performance in prediction of papillary carcinoma
Authors: Tong Mengying , Qiu Meng , Li Shuang , Feng Xiao , Guo Liying , Xie Wenlong , Jia Juanjuan , Che Ying
Published: December 2019

Purpose To determine the diagnostic performance of the sonographic finding of tumor neovascularization-like patterns and echogenic areas in differentiating papillary carcinomas from benign nodules.Materials and methods We prospectively analyzed ultrasound-guided fine-needle aspiration (FNA) of thyroid nodules for the two features. In total, 299 nodules (evenly distributed benign vs papillary carcinoma) were evaluated by two blinded readers for intense small penetrating vessels and homogenous mild hyper-echoic areas within the nodules and correlated with FNA-confirmed pathologic diagnosis. A set of nodules with and without the features was selected for further pathologic review and comparison to establish a pathologic basis for the finding.Results The specificity of the “tumor neovascularization-like pattern” and “echogenic areas” in papillary thyroid cancers (PTCs) was 90.6% and 91.3%, respectively. There was a significant correlation, with P < 0.0001, between the “tumor neovascularization-like pattern” and “echogenic areas” in PTCs on both sonographic and pathologic levels. Additionally, the newly identified features as a single variable were more predictive of malignancy than the well-studied features. Inclusion of these new features markedly improved the predictive ability of PTC (AUROC = 0.873 versus 0.801, P < 0.0001).Conclusion Despite their relatively low sensitivity, the “tumor neovascularization-like pattern” and “echogenic areas” are highly specific for PTC and can be a useful sonographic finding in decisions regarding FNA.
The DLC-1 tumor suppressor is involved in regulating immunomodulation of human mesenchymal stem cells through interacting with the Notch1 protein
Authors: Na Tao , Zhang Kehua , Yuan Bao-Zhu
Published: December 2019

Immunomodulatory activities of human mesenchymal stem cells (hMSCs) have been widely accepted as the most critical function of the cells for exerting its therapeutic effects. The activities include the inhibition by hMSCs on pro-inflammatory CD4 + -T lymphocytes, and the release of immunomodulatory molecules, like IDO1. However, the detailed mechanisms responsible for regulating the immunomodulation of hMSCs still remain largely unknown. Previously, the Notch1 protein has been demonstrated to be able to promote the immunomodulation of hMSCs through inhibiting CD4 + -Th1 lymphocyte proliferation and enhancing IDO1 expression. The present study further revealed that it was the Notch1-Hey1 axis, rather than the Notch1-Hes1 axis, that was likely responsible for mediating the immunomodulation of the Notch1 signaling. Meanwhile, following a previously proposed hypothesis to identify proteasome-regulated protein(s) for limiting the activity of the Notch1 signaling in hMSCS, the DLC-1 tumor suppressor was identified to be such a candidate protein, which was subjected to protein degradation mediated by the DDB1 and FBXW5 E3 ligases . It was further shown that the DLC-1 signaling composing of DLC-1, Rock1 and FBXW5 proteins was involved in inhibiting the immunomodulation of hMSCs. More importantly, the immunomodulation was achieved through an interaction between the DLC-1-FBXW5-Rock1 signaling and the Notch1-Hey1 signaling . In fact, the present study a novel function of DLC-1 tumor suppressor as well as proposed a new mutual exclusion mechanism likely responsible for fine-tuning the immunomodulation of hMSCs.
LRIG1 gene copy number analysis by ddPCR and correlations to clinical factors in breast cancer
Authors: Faraz Mahmood , Tellström Andreas , Ardnor Christina Edwinsdotter , Grankvist Kjell , Huminiecki Lukasz , Tavelin Björn , Henriksson Roger , Hedman Håkan , Ljuslinder Ingrid
Published: December 2019

Background Leucine-rich repeats and immunoglobulin-like domains 1 ( LRIG1 ) copy number alterations and unbalanced gene recombination events have been reported to occur in breast cancer. Importantly, LRIG1 loss was recently shown to predict early and late relapse in stage I-II breast cancer.Methods We developed droplet digital PCR (ddPCR) assays for the determination of relative LRIG1 copy numbers and used these assays to analyze LRIG1 in twelve healthy individuals, 34 breast tumor samples previously analyzed by fluorescence in situ hybridization (FISH), and 423 breast tumor cytosols.Results Four of the LRIG1 /reference gene assays were found to be precise and robust, showing copy number ratios close to 1 (mean, 0.984; standard deviation, +/-0.031) among the healthy control population. The correlation between the ddPCR assays and previous FISH results was low, possibly because of the different normalization strategies used. One in 34 breast tumors (2.9%) showed an unbalanced LRIG1 recombination event. LRIG1 copy number ratios were associated with the breast cancer subtype, steroid receptor status, ERBB2 status, tumor grade, and nodal status. Both LRIG1 loss and gain were associated with unfavorable metastasis-free survival; however, they did not remain significant prognostic factors after adjustment for common risk factors in the Cox regression analysis. Furthermore, LRIG1 loss was not significantly associated with survival in stage I and II cases.Conclusions Although LRIG1 gene aberrations may be important determinants of breast cancer biology, and prognostic markers, the results of this study do not verify an important role for LRIG1 copy number analyses in predicting the risk of relapse in early-stage breast cancer.
Barriers and facilitators of community based health insurance membership in rural Amhara region, northwest Ethiopia: A qualitative study
Authors: Demissie Getu Debalkie , Atnafu Asmamaw
Published: December 2019

Background: More than 150 million people encounter huge cost of health expenses every year, and most of these treatment seekers face poverty owing to out of pocket payments. Community-based health insurance won popularity as a makeshift health financing mechanism for out of pocket payments in poor communities. The aim of this study was to identify the facilitators and impediments of enrollment to community based health insurance in rural parts of the Amhara region, Ethiopia.Method: Focus group discussions (FGD) were the main research methodology supplemented by key informant interviews (KII). The FGD participants were selected by purposive sampling techniques based on the membership status of CBHI (members or non-members). Six FGDs and four key informant interviewees were conducted in March 2018 in three districts. Before analyzing the data, all FGDs and KIIs were transcribed and transferred into Atlasti version 7.1 software. Thematic analysis was done according to key themes arising from the data. Results: Low level of awareness, perception of high amount of premium, poor perception of quality of services and lack of trust in community based health insurance are the barriers to membership in community based health insurance.Conclusion: There has been a low level of awareness and misconception about community based health insurance. The major reason for not joining CBHI was incapacity to pay the premium.