bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Patron Saint Festivities on Cholera in Three Communes in Haiti
Authors: Moise Kenny , Achille Aude Mélody , Batumbo Doudou , Bourdeau Bertiny , Rebaudet Stanislas , Lerebours Gérald , Henrys Jean Hugues , Raccurt Christian
Published: September 2020

Introduction: Religious pilgrimages are among the anthropogenic factors known to be associated with the
transmission of diarrheal diseases, such as cholera. This ecological study aimed to describe the evolution of cholera and assess the relationship between the implementation of the ‘coup de poing’ strategy during the patron saint festivities and the incidence of cholera in the three communes of Cabaret, Carrefour, and Croix-des-Bouquets in Haiti in 2017.

Materials/Methods: An epidemiological curve was produced to illustrate the evolution of cholera at the communal level. Generalized linear models assuming a Poisson distribution were used to weight the annual
cholera incidence of communal sections against variables such as the number of patronal
festivities, population density and annual precipitation rates. The number of cases in the week of
the festivity as well as one and two weeks later was weighted against patronal festivities and
weekly precipitation rates.

Results: In total, 3 633 suspected cholera cases were continuously reported in three communes in Haiti
(Cabaret, Carrefour, Croix-des-bouquets) during the 52-epidemiological week period in 2017.
After controlling for rainfall and population density, the implementation of the ‘coup de poing’ strategy during the patron saint festivities was associated with a significant reduction in cholera incidence of 57.23% [PR=0.4277 (97.5% CI: 0.2798-0.6193), p=0.0000244]. The implementation of the strategy was associated with a reduction in cholera incidence of 25.41% one week following patronal festivities.

Conclusion: This study showed a continuous presence of cholera in three communes in Haiti in 2017 and an
association between the implementation of the ‘coup de poing’ strategy during patronal festivities and a reduction in cholera incidence. The findings imply that the multi-partner ‘coup de poing’ strategy may have contributed to the reduced cholera incidence following patron saint festivities and in Ouest department in Haiti in 2017.
The modules of mental health programs implemented in schools in low- and middle-income countries: Findings from a systematic literature review
Authors: Gimba Solomon Musa , Harris Paul , Saito Amornrat , Udah Hyacinth , Martin Averil , Wheeler Amanda J.
Published: September 2020

Background Secondary schools in low- and middle-income countries (LMICs) provide promotional, preventive, and early intervention services. Nevertheless, literature indicates that the modules of these services are either adapted or modified from existing mental health programs in developed countries. The aim of this review was to identify the modules of school-based mental health programs (SBMHP) that have been implemented in LMICs to guide the development of a culturally sensitive comprehensive mental health program for adolescents in a LMIC. Methods The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was used to guide this review. The following databases were searched in September 2018, to identify the relevant literature: PubMed, CINAHL, Scopus, Web of Science, PsycINFO, and ERIC. The search was conducted by the first author and reviewed by the authors.Results The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for rating the quality of evidence and strength of recommendations was used to assess the quality of the 11 studies. Most of the studies had adequate quality ratings. Following the screening process, a total of 11 papers were identified and reviewed for quality. The systematic review highlighted that the mental health programs provided in schools included: an introduction module, a communication and relationship module, a psychoeducation module, a cognitive skills module, a behavioral skills module, establishing social networks for recovery and help seeking behavioral activities and a summary/conclusion module. Two programs were found to be universal in nature. Five programs were directed at key risk factors or at-risk groups, and four were early intervention programs. The review also revealed that only one program out of the 11 programs included modules for parents. Five programs were significantly effective across all measured outcomes, and were measured after a period that ranged from three months to four years.Conclusion A total of 11 papers were identified and reviewed for quality. Most of the papers included in the review were of adequate quality. All the identified programs (two universal, five selective and four indicated) were adapted or modified from existing programs from high income countries (HICs). The characteristics of the programs in LMICs was also highlighted in this review. The dearth of comprehensive programs in LMICs was also revealed. The review revealed seven modules in total.
Nimodipine reduces delayed cerebral vasospasm after intracranial tumor surgery: a retrospective study
Authors: Yu Ying , Li Yunqian , Jin Zheng , Zhao Shuai , Chen Fan
Published: September 2020

Background：Cerebral vasospasm (CVS) is a serious neurosurgical complication. This retrospective study was performed to analyze if nimodipine can improve prognosis and reduces ischemia secondary to delayed CVS after intracranial tumor surgery.Methods：Retrospective analysis of 94 patients with an anterior cranial fossa tumor and underwent intracranial tumor surgery was performed, with 42 cases treated with normal saline and 52 cases treated with nimodipine solution. Transcranial Doppler ultrasonography was used to measure velocity in the middle cerebral artery (MCA) and the distal extracranial internal carotid artery (eICA). An examination was conducted 1 day before surgery and 1, 3, 5, 7, and 14 days after surgery. Follow-up was performed using the Glasgow Outcome Scale (GOS) 3 months after discharge.Results：We showed that in the nimodipine group, CVS occurred in 13 (25%) patients who did not have CVS in the first three days after operation; nine patients had CVS between 4 and 7 days, and 4 had CVS between 8 and 14 days. In the normal saline group, nineteen (45%) patients had CVS, 3 presented with CVS within 3 days, 11 between 4-7 days and 5 between 8-14 days. A significant difference in the occurrence of CVS was observed between the two groups. Preoperative and postoperative the MCA velocities were compared, revealing a significant change in the normal saline group (P < 0.05) but not in the nimodipine group. Furthermore, significant differences in the outcome were observed between the two groups at the 3-month follow-up (P < 0.05).Conclusions：Nimodipine markedly improves prognosis and significantly reduces ischemia secondary to delayed CVS after intracranial tumor surgery, as well as the risks of mortality and morbidity.
Predictors of Outpatients’ No-Show: Big Data Analytics using Apache Spark
Authors: Daghistani Tahani , AlGhamdi Huda , Alshammari Riyad , AlHazme Raed H.
Published: September 2020

Outpatients who fail to attend their appointments have a negative impact on the healthcare outcome. Thus, healthcare organizations facing new opportunities, one of them is to improve the quality of healthcare. The main challenges is predictive analysis using techniques capable of handle the huge data generated. We propose a big data framework for identifying subject outpatients’ no-show via feature engineering and machine learning (MLlib) in the Spark platform. This study evaluates the performance of five machine learning techniques, using the (2,011,813) outpatients’ visits data. Conducting several experiments and using different validation methods, the Gradient Boosting (GB) performed best, resulting in an increase of accuracy and ROC to 79% and 81%, respectively. In addition, we showed that exploring and evaluating the performance of the machine learning models using various evaluation methods is critical as the accuracy of prediction can significantly differ. The aim of this paper is exploring factors that affect no-show rate and can be used to formulate predictions using big data machine learning techniques.
Multiple Sclerosis incidence rate in southern Iran: A Bayesian epidemiological study
Authors: Asmarian Naeimehossadat , Sharafi Zahra , Mousavi Amin , Jacques Reis , Tamayo Ibon , Bind Marie-Abèle , abutorabi-zarchi Marzie , Moradian Mohammad Javad , Izadi Sadegh
Published: September 2020

Background: Multiple Sclerosis (MS) remains to be a public health challenge, due to its unknown biological mechanisms and clinical impacts on young people. The prevalence of this disease in Iran is reported to be 5.3 to 74.28 per 100,000-person. Because of high prevalence of this disease in Fars province, the purpose of this study was to assess the spatial pattern of MS incidence rate by modeling both the effects of spatial dependence between neighboring regions and risk factors in a Bayesian Poisson model, which can lead to the improvement of health resource allocation decisions.Method: Data from 5,468 patients diagnosed with MS were collected, according to the McDonald’s criteria. New cases of MS were reported by the MS Society of Fars province from 1991 until 2016. The effects of percentage of vitamin D intake, smoking, percentage of people with normal BMI and alcohol consumption in addition to spatial structure in a Bayesian spatio-temporal hierarchical model were used to determine the relative risk and trend of MS incidence rate in 29 counties of Fars province. Results: County-level crude incidence rates ranged from 0.22 to 11.31 cases per 100,000-person population. The highest relative risk was estimated at 1.8 in the county of Shiraz, the capital of Fars province, while the lowest relative risk was estimated at 0.11 in Zarindasht county in southern of Fars. The percentages of vitamin D3 intake and smoking were significantly associated with the incidence rate of MS. The results showed that 1% increase in Vitamin D3 intake is associated with 2% decrease in the risk of MS and 1% increase in smoking is associated with 16% increase in the risk of MS.Conclusion: Spatial analysis of MS revealed low incidence rate of this disease in the south and south east of Fars province, which is due to the effects of different covariates. As suggested by previous studies, vitamin D and smoking, among all covaiates, might be associated with high incidence of MS.
Just Say “No”: Can Dentists Refuse Care on the Basis of Finances? A Survey Using an Ethical Vignette in an Iranian Dental School
Authors: Kazemian Ali , Fayyazi Mahsa , Shafiee Shahrzad
Published: September 2020

Objective: The aim of this study was to evaluate how dental students and tutors think about their position for, or against fee reduction at dental offices. Method: It was a questionnaire-based survey, which examined the ethical attitudes of students and tutors of an Iranian Dental School. The questionnaire included a vignette about an ethical dilemma at a dental office. Different ethical approaches, i.e. duty-based, virtue-oriented and consequentialist arguments, for or against fee reduction at dental office were suggested. Respondents were asked to rank those ethical options. Data was entered and analyzed in SPSS 16.0. Result: 121 dental students and thirty-six faculty members (dental specialists) participated in this study. It revealed that a majority of dental students and tutors (68%) are in favor of charging patients less, when facing an imagined request at dental office, using either virtue-oriented (54%) or consequentialist (14%) argument for fee reduction. The difference between rankings of four options was statistically significant, while no statistically significant difference exists neither between male and female respondents, nor students and tutors. Conclusion: This case study provides a basis for fruitful discussions in ethics courses for dental students. Our study suggests that financial issues should be considered as a part of ethical training within the dental student's curriculum.
Vitamin C ameliorates tetrahydrocannabinol-induced spermatotoxicity in-vitro
Authors: Alagbonsi Abdullateef Isiaka , Olayaki Luqman Aribidesi
Published: September 2020

Background: We investigated the in-vitro effects of vitamin C on delta-9-tetrahydrocannabinol (THC)-induced reduction in spermatozoa motility and kinematics. Methods: Six rats were used for the study. Semen from each of the 6 rats was randomly divided into 6 groups such that each rat’s semen was in all of the groups. Groups I-III received placebo, THC (1 mM), and vitamin C (5 mM) respectively. Group IV was pretreated with cannabinoid receptors’ blockers (CBs-) 1 and 2, followed by THC. Groups V and VI received THC and vitamin C, but group VI was additionally pre-treated with CBs-. Results: The spermatozoa progressive motility, average path velocity (VAP), curvilinear velocity (VCL), straight-line velocity (VSL), amplitude of lateral head (ALH) and beat cross frequency (BCF) were reduced by THC (6.08±1.16%; 5.64±0.82 µm/s; 6.96±0.74 µm/s; 2.75±0.23 µm/s; 0.31±0.02 µm; and 0.78±0.08 Hz respectively) but increased by vitamin C (51.20±1.32 %; 17.90±0.21 µm/s; 25.11±0.96 µm/s; 8.80±0.27 µm/s; 0.75±0.01 µm; and 3.15±0.03 Hz respectively) when compared to control (39.72±0.38 %; 13.70±0.29 µm/s; 18.04±0.58 µm/s; 7.54±0.34 µm/s; 0.65±0.02 µm; and 2.79±0.01 Hz respectively). Vitamin C inhibited the THC-induced reduction in these parameters (37.36±0.73 %; 10.98±0.45 µm/s; 13.58±0.30 µm/s; 7.11±0.22 µm/s; 0.58±0.01 µm; and 2.60±0.01 Hz respectively) in the absence of CBs- 1 and 2, and even caused additional increases in progressive motility (49.54±1.01 %), VAP (15.70±0.38 µm/s) and VCL (22.53±0.29 µm/s) above the control levels with CBs-.Conclusion: Vitamin C ameliorates the THC-induced reduction in spermatozoa motility in-vitro by modulation of their kinematics.
Spie charts for quantifying treatment effectiveness and safety in multiple outcome network meta-analysis: A proof-of-concept study
Authors: Daly Caitlin , Mbuagbaw Lawrence , Thabane Lehana , Straus Sharon E , Hamid Jemila S
Published: September 2020

Background: Network meta-analysis (NMA) simultaneously synthesises direct and indirect evidence on the relative efficacy and safety of at least three treatments. A decision maker may use the coherent results of an NMA to determine which treatment is best for a given outcome. However, this evidence must be balanced across multiple outcomes. This study aims to provide a framework that permits the objective integration of the comparative effectiveness and safety of treatments across multiple outcomes.Methods: In the proposed framework, measures of each treatment’s performance are plotted on its own pie chart, superimposed on another pie chart representing the performance of a hypothetical treatment that is the best across all outcomes. This creates a spie chart for each treatment, where the coverage area represents the probability a treatment ranks best overall. The angles of each sector may be adjusted to reflect the importance of each outcome to a decision maker. The framework is illustrated using two published NMA datasets comparing dietary oils and fats and psoriasis treatments. Outcome measures are plotted in terms of the surface under the cumulative ranking curve. The use of the spie chart was contrasted with that of the radar plot.Results: In the NMA comparing the effects of dietary oils and fats on four lipid biomarkers, the ease of incorporating the lipids’ relative importance on spie charts was demonstrated using coefficients from a published risk prediction model on coronary heart disease. Radar plots produced two sets of areas based on the ordering of the lipids on the axes, while the spie chart only produced one set. In the NMA comparing psoriasis treatments, the areas inside spie charts containing both efficacy and safety outcomes masked critical information on the treatments’ comparative safety. Plotting the areas inside spie charts of the efficacy outcomes against measures of the safety outcome facilitated simultaneous comparisons of the treatments’ benefits and harms.Conclusions: The spie chart is more optimal than a radar plot for integrating the comparative effectiveness or safety of a treatment across multiple outcomes. Formal validation in the decision-making context, along with statistical comparisons with other recent approaches are required.
Cancer Associated Macrophage-Like Cells and Prognosis of Esophageal Cancer after Chemoradiation Therapy
Authors: Gironda Daniel Joseph , Adams Daniel Lee , He Jianzhong , Xu Ting , Gao Hui , Qiao Yawei , Komaki Ritsuko , Reuben James M. , Liao Zhongxing , Blum-Murphy Mariela , Hofstetter Wayne L. , Tang Cha-Mei , Lin Steven H.
Published: September 2020

Background:Cancer Associated Macrophage-Like cells (CAMLs) are polynucleated circulating stromal cells found in the bloodstream of numerous solid-tumor malignancies. Variations within CAML size have been associated with poorer progression free survival (PFS) and overall survival (OS) in a variety of cancers; however, no study has evaluated their clinical significance in esophageal cancer (EC). Methods:To examine this significance, we ran a two-year prospective pilot study consisting of newly diagnosed stage I-III EC patients (n=32) receiving chemoradiotherapy (CRT). CAML sizes were sequentially monitored prior to CRT (BL), ~2 weeks into treatment (T1), and at the first available sample after the completion of CRT (T2). Results:We found CAMLs in 88% (n=28/32) of all patient samples throughout the trial, with a sensitivity of 76% (n=22/29) in pre-treatment screening samples. Improved 2 year PFS and OS was found in patients with CAMLs <50μm by the completion of CRT over patients with CAMLs ≥50μm; PFS (HR=12.0, 95%CI=2.7-54.1, p=0.004) and OS (HR=9.0, 95%CI=1.9-43.5, p=0.019).Conclusions:Tracking CAML sizes throughout CRT as a minimally invasive biomarker may serve as a prognostic tool in mapping EC progression, and further studies are warranted to determine if presence of these cells prior to treatment suggest diagnostic value for at-risk populations.
Allogeneic Administration of Human Umbilical Cord-derived Mesenchymal Stem/Stromal Cells for Bronchopulmonary Dysplasia: Preliminary Outcomes in Four Vietnamese Infants.
Authors: Thanh Liem Nguyen , Hong Thai Trieu Thi , Hong Hue Bui Thi , Hoang Van T. , Tuyet Anh Nguyen Thi , Hong Nhung Trinh Thi , Nguyen Kien T. , Hoang Duc M.
Published: September 2020

Background: Bronchopulmonary dysplasia (BPD) is a severe condition in premature infants that compromises lung function and necessitates oxygen support. Despite major improvements in perinatal care minimizing the devastating effects, BPD remains the most frequent complication of extreme preterm birth. Our study reports the safety of the allogeneic administration of umbilical cord-derived mesenchymal stem/stromal cells (allo-UC-MSCs) and the preliminary improvements in four infants with established BPD.Methods: UC tissue was collected from a healthy donor, followed by propagation at the Stem Cell Core Facility at Vinmec Research Institute of Stem Cell and Gene Technology. UC-MSC culture was conducted under xeno- and serum-free conditions. Four patients with established BPD were enrolled in this study between May 25, 2018, and December 31, 2018. All four patients received two intravenous doses of allo-UC-MSCs (1 million cells/kg patient body weight (PBW) per dose) with an intervening interval of 7 days. Safety and patient conditions were evaluated during hospitalization and at 7 days and 1, 6 and 12 months postdischarge.Results: No intervention-associated severe adverse events or prespecified adverse events were observed in the four patients throughout the study period. At the time of this report, all patients had recovered from BPD and were weaned off of oxygen support. Chest X-rays and CT scans confirmed the potential reductions in fibrosis.Conclusions: Allo-UC-MSC administration is safe and might improve respiratory function and decrease lung fibrosis in preterm infants with established BPD.Trial registration: This preliminary study was approved by the Vinmec International Hospital Ethics Board (approval number: 88/2019/QĐ-VMEC; retrospectively registered March 12, 2019).
Clinical and genetic characteristics and prenatal diagnosis of patients presented GDD/ID with rare monogenic causes
Authors: Lin Liling , Zhang Ying , Pan Hong , Wang Jingmin , Qi Yu , Ma Yinan
Published: September 2020

Background: Global developmental delay/intellectual disability (GDD/ID), used to be named as mental retardation (MR), is one of the most common phenotypes in neurogenetic diseases. In this study, we described the diagnostic courses, clinical and genetic characteristics and prenatal diagnosis of a cohort with patients presented GDD/ID with monogenic causes, from the perspective of a tertiary genetic counseling and prenatal diagnostic center.Method:We retrospectively analyzed the diagnostic courses, clinical characteristics, and genetic spectrum of patients presented GDD/ID with rare monogenic causes. We also conducted a follow-up study on prenatal diagnosis in these families. Pathogenicity of variants was interpreted by molecular geneticists and clinicians according to the guidelines of the American College of Medical Genetics and Genomics (ACMG).Results:Among 81 [1] patients with GDD/ID caused by rare monogenic variants it often took 0.5-4.5 years and 2-8 referrals to obtain genetic diagnoses. Devlopmental delay typically occurred before 3 years of age, and patients usually presented severe to profound GDD/ID. The most common co-existing conditions were epilepsy (58%), microcephaly (21%) and facial anomalies (17%). In total, 111 pathogenic variants were found in 62 different genes among the 81 pedigrees, and 56 variants were novel. The most common inheritance patterns in this outbred Chinese population were autosomal dominant (AD; 47%), following autosomal recessive (AR; 37%), and X-linked (XL; 16%). SCN2A, SHANK3 and STXBP1 were important causal genes. Hot-spot variants were rarely found. By the follow-up, 33 affected families, including 15, 13 and 5 families inherited in AR, AD and XL modes respectively, had undergone prenatal diagnosis. And the recurrence rates are 26.7%, 15.4% and 20% for families inherited in AR, AD, and XL patterns.Conclusion:Patients presented with GDD/ID caused by rare single gene variants are characterized by early onset, relatively severe symptoms and great clinical variability and genetic heterogeneity. Timely referrals to genetic counseling and prenatal diagnostic laboratories are important for affected families planning to have additional children.
Assessment of irreducible aspects in developmental hip dysplasia by magnetic resonance imaging
Authors: Jia Huihui , Wang Liang , Chang Yan , Song Yongrui , Liu Yuqi , Zhang Fuyong , Feng Jie , Yang Xiaodong , Sheng Mao
Published: September 2020

Background: The developmental dysplasia of the hip (DDH) can cause a wide range of pathological changes, and often requires surgical treatment. Preoperative evaluation is very important for DDH. We aimed to assess the diagnostic capability of magnetic resonance imaging (MRI) for irreducible aspects preventing hip reduction in DDH. Methods: A total of 39 pediatric patients who received DDH evaluation in pediatric orthopedics from January 2015 to December 2019 were included. The samples included 4 cases of bilateral DDH and 35 cases of unilateral DDH, a total of 43 hip joint samples. All patients underwent surgical treatment, pathological examination and MRI of hip joint.Results: With pathological results or intraoperative findings as the gold standard, the sensitivity and specificity of MRI were 90.3% and 83.3% for the affected labrum, 92% and 83.3% for thickening of the round ligament, 90.0% and 91.3% for atrophy of the iliopsoas muscle, and 100% and 100% for fibrofatty pulvinar tissue and joint effusion, respectively. Conclutions: The MRI showed an extraordinary capability of detecting these irreducible factors and helped surgeon choose the appropriate treatment strategies.
Gravimetric geoid modeling from the combination of satellite gravity model, terrestrial and airborne gravity data: a case study in the mountainous area, Colorado
Authors: Jiang Tao , Dang Yamin , Zhang Chuanyin
Published: September 2020

Constructing a high precision and high resolution gravimetric geoid model in the mountainous area is a quite challenging task because of the the lack of terrestrial gravity observations, rough high, rough nature of topography and the geological complexity. One way out is to use as hight quality and well distributed satellite and airborne gravity data to fill the gravity data gapsmany gravity observations from different sources as possible such as satellite, terrestrial and airborne gravity data, thus the proper combination of heterogeneous gravity datasets is critical. In a rough topographic area in Colorado, we computed a set of gravimetric geoid models based on different combination modes of satellite gravity models, terrestrial and airborne gravity data using the spectral combination method. The gravimetric geoid model obtained from the combination of satellite gravity model GOCO06S and terrestrial gravity data agrees with the GPS leveling measured geoid heights at 194 benchmarks in 5.8 cm in terms of the standard deviation of discrepancies, and the standard deviation reduces to 5.3 cm after including the GRAV-D airborne gravity data collected at ~6.2 km altitude into the data combination. The contributions of airborne gravity data to the signal and accuracy improvements of the geoid models were quantified for different spatial distribution and density of terrestrial gravity data. The results demonstrate that, although the airborne gravity survey was flown at a high altitude, the additions of airborne gravity data improved the accuracies of geoid models by 13.4% - 19.8% in the mountainous area (elevations > 2000 m) and 12.7% - 21% (elevations < 2000 m) in the moderate area in the cases of terrestrial gravity data spacings are larger than 15 km.
Variation of mitochondrial minichromosome composition in Hoplopleura lice (Phthiraptera: Hoplopleuridae) from rats
Authors: Fu Yi-Tian , Nie Yu , Duan De-Yong , Liu Guo-Hua
Published: September 2020

Background: The family Hoplopleuridae contains at least 183 species of blood-sucking lice, which widely parasitize both mice and rats. Fragmented mitochondrial (mt) genomes have been reported in two rat lice (Hoplopleura kitti and H. akanezumi) from this family, but some minichromosomes were unidentified in their mt genomes.Methods: We sequenced the mt genome of the rat louse Hoplopleura sp. with an Illumina platform and compared its mt genome organization with H. kitti and H. akanezumi.Results: Fragmented mt genome of the rat louse Hoplopleura sp. contains 37 genes which are on 12 circular mt minichromosomes. Each mt minichromosome is 1.8–2.7 kb long and contains 1–5 genes and one large non-coding region. The gene content and arrangement of mt minichromosomes of Hoplopleura sp. (n = 3) and H. kitti (n = 3) are different from those in H. akanezumi (n = 3). Phylogenetic analyses based on the deduced amino acid sequences of the eight protein-coding genes showed that the Hoplopleura sp. was more closely related to H. akanezumi than to H. kitti, and then they formed a monophyletic group.Conclusions: Comparison among the three rat lice revealed variation in the composition of mt minichromosomes within the genus Hoplopleura. Hoplopleura sp. is the first species from the family Hoplopleuridae for which a complete fragmented mt genome has been sequenced. The new data provide useful genetic markers for studying the population genetics, molecular systematics and phylogenetics of blood-sucking lice.
Comparison of adherence between fixed and unfixed topical combination glaucoma therapies using Japanese healthcare/pharmacy claims database: A retrospective non-interventional cohort study
Authors: Shirai Chikako , Matsuoka Nobushige , Nakazawa Toru
Published: September 2020

Background: Adherence to chronic therapies is crucial to prevent the progression of disease, such as glaucoma. However, only a limited number of studies have investigated them using real-world data in Japan. This study aimed to evaluate Japanese patients’ adherence to fixed- and unfixed-combination eye drops as a second-line therapy for glaucoma in real-world practice.Methods: This retrospective, non-interventional cohort study utilized a commercially available Japanese healthcare database (MinaCare database). Medical/pharmacy claims data were collected from 2011 to 2016. The primary endpoint was adherence to medications, assessed by proportion of days covered (PDC) with medication during a 12-month post-index period. Meanwhile, the secondary endpoints included the persistence rate.Results: A total of 738 patients were included in this study: 309 and 329 in the fixed- and unfixed-combination cohorts, respectively. Prostaglandin analog (PG)/β-blocker (BB) was most commonly claimed in 241/309 (78.0%) patients in the fixed-combination cohort. In the unfixed-combination cohort, PG and BB were claimed in 130/329 (39.5%) patients, whereas PG and α2-agonist were claimed in 87/329 (26.4%) patients. Patients were more adherent to the fixed-combination than the unfixed-combinations (mean PDCs [SD], 79.1% [32.1] vs. 62.2% [38.0]; P < 0.0001). The proportion of patients with good adherence (PDC ≥ 80%) was also higher in the fixed-combination cohort (69.6%) than in the unfixed-combination cohort (48.6%) (P < 0.0001). During the 12-month post-index period, the persistence rate was higher in the fixed-combination cohort than in the unfixed-combination cohort (47.6% [95% confidence intervals (CI): 41.9–53.0] vs. 24.9% [95% CI: 20.4–29.7], P < 0.0001).Conclusions: Japanese patients with glaucoma preferred the fixed-combination therapies over the unfixed-combination therapies. Hence, fixed-combination therapies would contribute to the improvement of adherence.
­­­­The usage of Mate Select, a web-based selection tool for pedigree dogs for promoting sustainable breeding
Authors: Janes Mateja , Lewis Thomas W. , Ilska Joanna J. , Woolliams John A.
Published: September 2020

BackgroundInbreeding is a phenomenon that accumulates through the mating of relatives within closed populations, such as pedigree dog breeds, and results in reduced genetic variation within breeds, and may lead to poorer health and fertility from inbreeding depression. The impact of inbreeding is driven by the selection and mating of parents, but information on choices to reduce inbreeding is difficult to assess for individual breeders. Tools to inform dog breeders on the current state of the inbreeding and the relationships among possible parents are potentially useful for providing guidance towards choices that are more beneficial to the breed. However, their utility depends on their usage and this study examines the usage of Mate Select, a web-based tool offered by The Kennel Club, covering 222 breeds for a period of 7 years following its launch in 2011.ResultsThe average usage was 2830 searches/week in 2012 with a slight fall of 2.2% per year (P<0.001) to 2480 searches/week in 2018. Of these, 4% originated from outside the UK, across all continents except Antarctica, with the majority coming from English speaking countries. Searches/week showed a cyclical pattern with two cycles of 26.0 and 50.11 weeks. Sin­­­­ce Mate Select’s launch there has been a steady increase in searches from mobile devices, from 11% in 2012 to 43% in 2018. For the 197 breeds with more than 10 dams registered with the Kennel Club during the study period, there was a relationship between usage and registrations, with the average number of searches as a multiple of the number of dams increasing from 2 to 10 for breeds with up to 70 dams and declining towards 2 again for the largest breeds with approximately 20,000 registered dams. However, there remained substantial variation among breeds of similar size, and breeds for which EBVs had become available during the study period had a 2.46 fold greater frequency of searches per registered bitch (P<0.001), but this was not linked directly to the publication of EBVs.Conclusions Mate Select has sustained and substantial usage, although there is also substantial variation in usage among breeds, which offers an opportunity to develop further guidance.
A Hypocaloric High-Protein Diet Supplemented with β-Cryptoxanthin Improves Non-Alcoholic fatty liver disease: A randomized controlled trial
Authors: Haidari Fatemeh , Hojhabrimanesh Abdollah , Helli Bizhan , Seyedian Seyed-Saeed , Ahmadi-Angali Kambiz , Abiri Behnaz
Published: September 2020

Background: Despite promising animal data, there is no randomized controlled trial (RCT) on the effects of high protein (HP)-diet and/or β-cryptoxanthin in non-alcoholic fatty liver disease (NAFLD).Aims: Safety and efficacy assessment of a hypocaloric HP-diet supplemented with β-cryptoxanthin in NAFLD.Methods: Ninety-two Iranian NAFLD outpatients were recruited for this 12-week, single-center, parallel-group, double-blind RCT and randomized into 4 arms (n=23): HP-diet & β-cryptoxanthin (hypocaloric HP-diet + β-cryptoxanthin), HP-diet (hypocaloric HP-diet + placebo), β-cryptoxanthin (standard hypocaloric diet + β-cryptoxanthin), and control (standard hypocaloric diet + placebo). Serum levels of liver enzymes and grade of hepatic steatosis were assessed at baseline and study endpoint as outcome measures.Results: In the intention-to-treat population (N=92), HP-diet & β-cryptoxanthin group experienced greater 12-week reductions in serum levels of liver enzymes than control group (mean difference for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase: -27.2, -7.2, -39.2, and -16.3 IU/L, respectively; all p<0.010). Clinical remission rate (achieving grade 0 hepatic steatosis) in HP-diet & β-cryptoxanthin group (82.6%) was also higher than other groups (13.0%, 17.4%, and 0.0% in HP-diet, β-cryptoxanthin, and control groups, respectively; p<0.001). Sixteen patients reported minor adverse events.Conclusion: A hypocaloric HP-diet supplemented with β-cryptoxanthin safely and efficaciously improves NAFLD.Trial registration number: This trial was registered at http://www.irct.ir as IRCT2017060210181N10.
Construction of a new T7 promoter compatible Escherichia coli Nissle 1917 strain for recombinant production of heme-dependent proteins
Authors: Fiege Kerstin , Frankenberg-Dinkel Nicole
Published: September 2020

Background: Heme proteins and heme-derived molecules are essential in numerous cellular processes. Research into their in vitro functionality requires the production of large amounts of protein. Unfortunately, high yield expression is hampered by the lack of E. coli strains naturally capable of taking up heme from the medium. We recently reported the use of the probiotic E. coli strain Nissle 1917 (EcN) to sufficiently produce heme containing proteins, as it encodes the outer membrane heme receptor, ChuA, which allows for natural uptake of heme. The EcN strain however lacks the gene for T7 RNA polymerase, which is necessary for the expression of genes under the control of the T7-promotor, widely used in expression vectors like the pET or Duet series.Results: A new T7-promoter compatible EcN strain was constructed by integrating the gene for T7-RNA polymerase under the control of a lacUV5 promoter into the malEFG operon of EcN. Test expressions of genes via T7 promoter-based vectors in the new EcN(T7) strain were successful. Expression in EcN(T7) resulted in the efficient production of recombinant heme proteins in which the heme cofactor was incorporated during protein production. In addition, the new EcN(T7) strain can be used to co-express genes for the production of heme-derived molecules like biliverdin or other linear tetrapyrroles. We demonstrate the successful recombinant production of the phytochromes BphP, from Pseudomonas aeruginosa, and Cph1, from Synechocystis sp. PCC6803, loaded with their linear tetrapyrrole cofactors, biliverdin and phycocyanobilin, respectively. Conclusion: We present a new E. coli strain for efficient production of heme proteins and heme-derived molecules using T7-promoter based expression vectors. The new EcN(T7) strain enables the use of a broader spectrum of expression vectors, as well as the co-expression of genes using the Duet expression vectors, for expressing heme containing proteins. By utilizing E. coli strains EcN and EcN(T7), capable of being fed heme, the rate limiting step of heme biosynthesis in E. coli is eliminated, thereby permitting higher heme saturation of heme proteins and also higher yields of heme-derived molecules.
Pilot Trial of High-dose vitamin C in critically ill COVID-19 patients
Authors: Zhang Jing , Rao Xin , Li Yiming , Zhu Yuan , Liu Fang , Guo Guangling , Luo Guoshi , Meng Zhongji , Backer Daniel De , Xiang Hui , Peng Zhi-Yong
Published: September 2020

Background: No specific medication has been proven effective for the treatment of patients with severe coronavirus disease 2019 (COVID-19). Here, we tested whether high-dose vitamin C infusion was effective for severe COVID-19.Methods: This randomized, controlled, clinical trial was performed at 3 hospitals in Hubei, China. Patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the ICU were randomly assigned in as 1:1 ratio to either the high-dose intravenous vitamin C (HDIVC) or the placebo. HDIVC group received 12 g of vitamin C/50 ml every 12 hours for 7 days at a rate of 12 ml/hour, and the placebo group received bacteriostatic water for injection in the same way. The primary outcome was invasive mechanical ventilation-free days in 28 days(IMVFD28). Secondary outcomes were 28-day mortality, organ failure, and inflammation progression.Results: Only fifty-six critical COVID-19 patients were ultimately recruited due to the early control of the outbreak. There was no difference in IMVFD28 between two groups. During the 7-day treatment period, patients in the HDIVC group had a steady rise in the PaO2/FiO2 (day 7: 229 vs. 151 mmHg, 95% CI 33 to 122, P=0.01). Patients with SOFA scores ≥3 in the HDIVC group exhibited a trend of reduction in 28-day mortality (P=0.06) in univariate survival analysis. IL-6 in the HDIVC) group was lower than that in the placebo group (19.42 vs. 158.00; 95% CI -301.72 to -29.79; P=0.04) on day 7. Conclusion: This pilot trial showed that HDIVC might show a potential signal of benefit for critically ill patients with COVID-19, improving oxygenation even though it failed to improve IMVFD28. Clinicaltrial.gov identifer and date: NCT04264533. Registered February 14 2020.
Clinical differences between toric intraocular lens (IOL) and monofocal intraocular lens (IOL) implantation when myopia is determined as target refraction
Authors: Shin Da young , Hwang Ho Sik , Kim Hyun Seung , Kim Man Soo , Kim Eun Chul
Published: September 2020

Background: The aim of this study is to analyze and compare the clinical results of toric intraocular lens (IOL) and monofocal IOL implantation when the target refraction value is determined -3 diopter (D) in cataract patients with corneal astigmatism >1.5 diopters (D).Methods: We performed a retrospective chart review for patients with corneal astigmatism >1.5D who underwent cataract surgery and their target refraction is determined -3D. 100 eyes (100 patients; monofocal IOL, 60; toric IOL, 40) were enrolled in the current study. Near and distant uncorrected visual acuity (UCVA), corrected VA, spherical equivalent and refractive, corneal astigmatism were evaluated before and after surgery.Results: The near UCVA of the toric IOL group (0.26±0.33) after cataract surgery was significantly better than that of the monofocal IOL group (0.48±0.32) (p=0.030). The distant UCVA of the toric IOL group (0.38 ± 0.14) was also significantly better than that of the monofocal IOL group (0.55 ± 0.22) (p = 0.026). There were no significant intergroup differences in postoperative best-corrected visual acuity (p = 0.710) and mean spherical equivalent (p = 0.465). In the toric IOL group, postoperative refractive astigmatism was -0.80 ± 0.46D and postoperative corneal astigmatism was -1.50 ± 0.62D, whereas the corresponding values in the monofocal IOL group were -1.65 ± 0.77D and -1.45 ± 0.64D; residual refractive astigmatism was significantly lower with toric IOL implantation compared with monofocal IOL implantation (p = 0.001). There were no postoperative complications and no adverse events were reported.Conclusions: When myopic refraction such as -3D was determined as the target power in patients with corneal astigmatism, toric IOL implantation led to excellent improvement in both near and distant UCVA.
A Load Sharing Principle in Abdominal Wall Reconstruction. Communication and Collaboration Among Plastic & Reconstructive Surgeons, Oncologic Surgeons, and General Surgeons.
Authors: Dickinson Brian P , Vu Monica , Vu-Huynh Nikkie , Shadid Alexander , Harris Todd S , Selby Robert , Perl Larry , Mori Kristina , Wang Peter , Beanes Steven , Mendivil Alberto , Hurwitz Michael
Published: September 2020

Background: Abdominal wall reconstruction of ventral hernias can be challenging. Patients have undergone successful treatment of cancer or other intra-abdominal processes and have worked hard to get back to a “normal” life. Successful repair of abdominal wall hernias can be difficult as many comorbidities persist. Previous radiation, ongoing smoking, or overall protein malnutrition may affect wound healing and overall outcome. Surgical teams need to communicate to maximize repair success and decrease recurrence. Purpose: To create a systematic approach from our current method of abdominal wall reconstruction that facilitates communication between general surgeons and plastic and reconstructive surgeons for optimizing hernia repair outcomes. Methods: A retrospective chart review was done on patients who underwent abdominal wall reconstruction of ventral hernias and recurrent hernias with component separation and placement of strattice acellular dermal matrix or synthetic mesh over a 10 year period. Pre-op imaging consisted of an abdominal/pelvic CT-scan. A surgical flight plan was created to determine a plane of Strattice insertion and abdominal wall exposure. Pre/post-operative CT-scans were compared as well as before and after photographs. Patient satisfaction was assessed subjectively in follow-up appointments. Results: The most commonly encountered clinical scenarios were placed into a pictorial essay and a step by step approach to abdominal wall reconstruction was then created. Strattice or synthetic mesh were placed using a “load-sharing” principle and restoration of a dynamic abdominal wall was associated with high patient satisfaction, a more functional repair, and a lower incidence of recurrence. Conclusions: Successful repair of primary and recurrent abdominal wall hernias requires communication between general surgeons and plastic & reconstructive surgeons. Incision placement is important for adequate exposure and the ability to place transfascial sutures. T-junction skin breakdown and seroma formation can be minimized by maintaining blood supply and minimizing dead space. High protein nutritional stores are important for expeditious healing.
Arabic Translation, Cultural Adaptation, and Validation of Australian Pelvic Floor Questionnaire in a Saudi Population
Authors: Malaekah Haifaa , Almedbal Haifaa Saud , Almuwallad Sameerah , asiri Zahra Al , Albadrani Alhanouf , Abduallah Hussam
Published: September 2020

Introduction and hypothesis: The aims of the study were the translation, cultural adaptation, and validation of self-administered Australian Pelvic Floor Questionnaire (APFQ) on a Saudi population. Methods: The translation and cultural adaptation was performed in 854 women over 18 and not pregnant who agreed to answer the Arabic version of the questionnaire. The content/face validity, internal consistency (reliability), and construct validity (factor analysis) were assessed. Statistical analysis was carried out using SPSS 24.0 statistical software.Results: The Cronbach’s alpha results were above 0.8 for the questionnaire’s overall reliability (bladder function: 0.877, bowel function: 0.834, prolapse symptoms: 0.784, sexual function: 0.762) showing adequate internal consistency reliability and high statistical significance. A statistically significant correlation was observed among the 40 items of the questionnaire. The issue of multicollinearity was not found, and the determinant of the correlation matrix was 0.001. A value of >0.5 was achieved when the Kaiser–Meyer–Olkin (KMO) and Bartlett’s tests measured 0.806 and the Bartlett’s test of sphericity was statistically significant χ2 (780)=4150.46 (P<0.001). The values of loading indicate that all 4 factors (bladder function, bowel function, prolapse symptoms, sexual function) contributed to each of their items.Conclusions: This study provides the Arabic version of the self-administered APFQ as a reliable and valid instrument for evaluating symptom severity and impact of pelvic floor dysfunction on the quality of life (QOL) of Arabic women. It also will enable the researchers from Arab countries to use this instrument to assess pelvic floor dysfunction (PFD) prevalence in their settings.
Small-Molecule Antagonist of VLA-4 (GW559090) Attenuated Neuro-Inflammation by Targeting Th17 Cell Trafficking across the Blood-Retinal Barrier in Experimental Autoimmune Uveitis
Authors: Chen Yi-Hsing , Eskandarpour Malihe , Zhang Xiaozhe , Galatowicz Grazyna , John Greenwood , Lightman Sue , Calder Virginia
Published: September 2020

Background: The integrin VLA-4 (α4β1) plays an important role in leukocyte trafficking. This study investigated the efficacy of a novel topical α4β1 integrin inhibitor (GW559090, GW) in a mouse model for non-infectious posterior uveitis (experimental autoimmune uveitis; EAU) and its effect on intraocular leukocyte subsets.Methods: Mice (female; B10.RIII or C57Bl/6; aged 6-8 weeks) were immunized with specific interphotoreceptor retinoid-binding protein (IRBP) peptides to induce EAU. Topically administered GW (3, 10, and 30 mg/ml) were given twice daily either therapeutically once disease was evident, or prophylactically, and compared with vehicle-treated (Veh) and 0.1% dexamethasone-treated (Dex) controls. Mice were sacrificed at peak disease. The retinal T cell subsets were investigated by immunohistochemistry and immunofluorescence staining. The immune cells within the retina, blood and draining lymph nodes (dLNs) were phenotyped by flow cytometry. The effect of GW559090 on non-adherent, adherent and migrated CD4+ T cell subsets across a central nervous system (CNS) endothelium was further assayed in vitro and quantitated by flow cytometry.Results: There was a significant reduction in clinical and histological scores in GW10 and Dex treated groups as compared to controls either administered therapeutically or prophylactically. There were fewer CD45+ leukocytes infiltrating the retinae and vitreous fluids in the treated GW10 group (P < 0.05). Immunofluorescence staining and flow cytometry data identified decreased levels of retinal Th17 cells (P ≤ 0.001) in the GW10 treated eyes, leaving systemic T cell subsets unaffected. In addition, fewer Ly6C+ inflammatory monocyte/macrophages (P = 0.002) and dendritic cells (P = 0.017) crossed the BRB following GW10 treatment. In vitro migration assays confirmed that Th17 cells were selectively suppressed by GW559090 by adhering to endothelial monolayers.Conclusions: This α4β1 integrin inhibitor may exert a modulatory effect in EAU progression by selectively blocking Th17 cell migration across the blood-retinal barrier without affecting systemic CD4+ T cell subsets. Local α4β1 integrin-directed inhibition could be clinically relevant in treating a Th17-dominant form of uveitis.