bluuebunny/crossref_metadata_2025 huggingface dataset:
A randomized, 29-day, dose-ranging, efficacy and safety study of daprodustat, administered three times weekly in patients with anemia on hemodialysis
Authors: Bailey Christine K. , Caltabiano Stephen , Cobitz Alexander R. , Huang Chun , Mahar Kelly M. , Patel Vickas V.
Published: October 2019

Background

Daprodustat is a hypoxia-inducible factor-prolyl hydroxylase inhibitor currently being investigated as a treatment for anemia of chronic kidney disease (CKD) in both dialysis and nondialysis patients. In clinical studies to date, daprodustat has been administered orally as a once-daily regimen. This randomized, double-blind, placebo-controlled study characterized the initial dose-hemoglobin response as well as the efficacy and safety of three times weekly (TIW) daprodustat in hemodialysis patients switched from stable recombinant human erythropoietin (rhEPO), in accordance with a TIW hemodialysis schedule.

Methods

103 patients on hemodialysis with baseline hemoglobin of 9.0 to 11.5 g/dL and previously receiving a stable dose of rhEPO or its analogs were randomized 1:1:1:1:1 to receive daprodustat 10, 15, 25, or 30 mg or placebo TIW over 29 days.

Results

Mean baseline hemoglobin was 10.6 g/dL for the placebo group and each daprodustat cohort. Daprodustat produced dose-dependent changes in mean hemoglobin from baseline to day 29. Using a Bayesian approach, the estimated dose conversion ratio between once-daily and TIW daprodustat was ~ 2.0 across the evaluated dose range using an Emax model. Daprodustat was generally well tolerated, with an adverse event (AE) profile consistent with the hemodialysis population.

Conclusions

These data help inform the appropriate dose conversion ratio to be applied to daily doses to obtain equivalent daprodustat TIW doses and suggest TIW treatment with daprodustat can treat anemia of CKD safely, supporting future long-term studies for this indication using a TIW dosing regimen.

Trial registration

ClinicalTrials.gov Identifier: NCT02689206; date registered: 02/11/2016.
Clinical outcomes and prognostic factors to predict treatment response in high risk neuroblastoma patients receiving topotecan and cyclophosphamide containing induction regimen: a prospective multicenter study
Authors: Rujkijyanont Piya , Photia Apichat , Traivaree Chanchai , Monsereenusorn Chalinee , Anurathapan Usanarat , Seksarn Panya , Sosothikul Darintr , Techavichit Piti , Sanpakit Kleebsabai , Phuakpet Kamon , Wiangnon Surapon , Chotsampancharoen Thirachit , Chainansamit Su-on , Kanjanapongkul Somjai , Meekaewkunchorn Arunotai , Hongeng Suradej
Published: October 2019

Background

Neuroblastoma is the most common extra-cranial solid tumor among children. Despite intensive treatment, patients with advanced disease mostly experience dismal outcomes. Here, we proposed the use of topotecan and cyclophosphamide containing induction regimen as an upfront therapy to high risk neuroblastoma patients.

Methods

Patients with high risk neuroblastoma undergoing ThaiPOG high risk neuroblastoma protocol from 2016 to 2017 were studied. All patients received 6 cycles of induction regimen consisting of 2 cycles topotecan (1.2 mg/m2/day) and cyclophosphamide (400 mg/m2/day) for 5 days followed by cisplatin (50 mg/m2/day) for 4 days combined with etoposide (200 mg/m2/day) for 3 days on the third and fifth cycles and cyclophosphamide (2100 mg/m2/day) for 2 days combined with doxorubicin (25 mg/m2/day) and vincristine (0.67 mg/m2/day) for 3 days on the fourth and sixth cycles. Treatment response after the 5th cycle before surgery and treatment-related toxicities after each topotecan containing induction cycle were evaluated. Relevant prognostic factors were analyzed to measure the treatment response among those patients.

Results

In all, 107 high risk neuroblastoma patients were enrolled in the study. After the 5th cycle of induction regimen, the patients achieved complete response (N = 2), very good partial response (N = 40), partial response (N = 46) and mixed response (N = 19). None of the patients experienced stable disease or disease progression. The most significant prognostic factor was type of healthcare system. The most common adverse effect was febrile neutropenia followed by mucositis, diarrhea and elevated renal function.

Conclusion

The topotecan and cyclophosphamide containing induction regimen effectively provides favorable treatment response. The regimen is well tolerated with minimal toxicity among patients with high risk neuroblastoma in Thailand.
Ionizing radiation increases the endothelial permeability and the transendothelial migration of tumor cells through ADAM10-activation and subsequent degradation of VE-cadherin
Authors: Kouam Pascaline Nguemgo , Rezniczek Günther A. , Adamietz Irenäus A. , Bühler Helmut
Published: October 2019

Background

We analyzed the changes in permeability of endothelial cell layers after photon irradiation, with a focus on the metalloproteases ADAM10 and ADAM17, and on VE-cadherin, components crucial for the integrity of endothelial intercellular junctions, and their roles in the transmigration of cancer cells through endothelial cell monolayers.

Methods

Primary HUVEC were irradiated with 2 or 4 Gy photons at a dose rate of 5 Gy/min. The permeability of an irradiated endothelial monolayer for macromolecules and tumor cells was analyzed in the presence or absence of the ADAM10/17 inhibitors GI254023X and GW280264X. Expression of ADAM10, ADAM17 and VE-Cadherin in endothelial cells was quantified by immunoblotting and qRT. VE-Cadherin was additionally analyzed by immunofluorescence microscopy and ELISA.

Results

Ionizing radiation increased the permeability of endothelial monolayers and the transendothelial migration of tumor cells. This was effectively blocked by a selective inhibition (GI254023X) of ADAM10. Irradiation increased both, the expression and activity of ADAM10, which led to increased degradation of VE-cadherin, but also led to higher rates of VE-cadherin internalization. Increased degradation of VE-cadherin was also observed when endothelial monolayers were exposed to tumor-cell conditioned medium, similar to when exposed to recombinant VEGF.

Conclusions

Our results suggest a mechanism of irradiation-induced increased permeability and transendothelial migration of tumor cells based on the activation of ADAM10 and the subsequent change of endothelial permeability through the degradation and internalization of VE-cadherin.
Real-world data in retinal diseases treated with anti-vascular endothelial growth factor (anti-VEGF) therapy – a systematic approach to identify and characterize data sources
Authors: Daien Vincent , Eldem Bora M. , Talks James S. , Korobelnik Jean-Francois , Mitchell Paul , Finger Robert P. , Sakamoto Taiji , Wong Tien Yin , Evuarherhe Obaro , Carter Gemma , Carrasco Joao
Published: October 2019

Background

Real-world data (RWD) has been a valuable addition to the scientific literature regarding treatment pathways, clinical outcomes and characteristics of patients with retinal diseases in recent years. Registries, observational studies and patient databases are often used for real-world research. However, there is limited information for each data source on the design, consistency, data captured, limitations and usability for assessing research questions. Using a systematic approach, we identified RWD sources for patients with retinal diseases and assessed them for completeness of data relating to different outcomes.

Methods

A systematic literature review was carried out to identify RWD sources for patients with retinal disease. Potentially relevant articles published between 2006 and 2016 were screened following electronic searches in Embase and MEDLINE. Congress and supplementary searches were undertaken to identify RWD sources that may not be referenced in full publications. For each data source, availability and quantity of data on baseline status, clinical outcomes, treatment and management, safety, and patient-reported and economic burden were assessed using a bespoke completeness assessment tool based on International Consortium for Health Outcomes Measurement guidelines for macular degeneration. Completeness of data for each area of interest in each data source was assessed and rated using a ‘good–moderate–poor’ rating system based on availability and quantity of available data. Each data source was then given an overall score based on its score for each of the 7 areas of interest.

Results

A total of 128 RWD sources from 32 countries were identified. Of the identified sources, 64 sources from 16 countries of interest were analyzed. Most of these sources provided information on baseline status and clinical outcomes and treatment, but few collected data on economic and patient-reported burden. Of the RWD sources analyzed, 10 scored highly in the overall completeness assessment, collecting data on most or all of the areas of interest; these sources are considered to be robust data sources for performing ophthalmology real-world studies.

Conclusions

The study provides a comprehensive list of RWD sources for patients with retinal disease, many of which will be useful for conducting real-world studies in the field of ophthalmology.
The influence of the maternal peer group (partner, friends, mothers’ group, family) on mothers’ attitudes to obesity-related behaviours of their children
Authors: Cameron Adrian J. , Charlton Emma , Walsh Adam , Hesketh Kylie , Campbell Karen
Published: October 2019

Background

Relationships with others can have an impact on the attitudes of new mums to the obesity-related behaviours of their children. The aim of this study was to understand the degree to which other new mums (from their mothers’ group), friends, partners, and other family members have an influence on maternal attitudes to child feeding, physical activity and television viewing behaviours in order to more accurately target obesity prevention interventions.

Methods

In a retrospective cohort study design using data from the InFANT randomized controlled trial, first-time mothers (n = 307) from Melbourne, Australia were asked in 2012–13 how much of an influence their partner, friends, mothers’ group and family were on their attitudes to their pre-school aged child’s feeding, physical activity and television viewing behaviours. The level of influence was examined using chi-square tests, t-tests, and analysis of variance, stratified by maternal education, age and body weight. We also examined associations between the influence of others on maternal attitudes and actual behaviours including breastfeeding duration, age at introduction of solid food and time their child spent outside.

Results

Mothers rated partners as having the strongest influence on their attitudes toward all obesity-related behaviours. The percentage reporting partners as a major influence were 28.7% (95% CI 23.8,34.0), 33.1% (28.0, 38.6) and 24.2% (19.6, 29.3) for child feeding, physical activity and television viewing, respectively. More highly educated mothers rated social connections as more influential than less educated mothers. The influence of partners on attitudes toward child feeding was associated with longer breastfeeding duration.

Conclusions

Mothers rated partners as a powerful influence on their attitudes toward the obesity-related behaviours of their pre-school children, suggesting that partners could be an important target of obesity-prevention initiatives. Since less educated mothers reported peers and family as a much weaker influence on their attitudes to obesity-related behaviours than more educated mothers, equity should be taken into consideration when contemplating obesity-prevention interventions that target mothers’ groups.
Statistical analysis of socioeconomic and demographic correlates of perinatal mortality in Tigray region, Ethiopia: a cross sectional study
Authors: Woldeamanuel Berhanu Teshome , Gelebo Kumachew Kusse
Published: October 2019

Background

Though Ethiopia achieved the fourth Millennium Development Goal, commit to reducing under five child mortalities by the year 2015, but perinatal mortality has remained a major public health problem in Ethiopia, and the Tigray region is experiencing a high perinatal mortality rate. This study aimed to assess the risk factors attributed to perinatal death in the Tigray region.

Methods

A retrospective cross-sectional study was used. The information collected from 2738 children born five years preceding the survey was considered. Variables such as maternal social and demographic characteristics, child demographic characteristics, health and environmental factors were considered as risk factors of perinatal death. The study used descriptive statistics, and logistic regression model to identify significant correlates of perinatal mortality.

Results

The data showed that from total children included in the study, 4.1% are early neonatal deaths, and 2.1% are stillbirth. Overall the prevalence of experiencing perinatal mortality was 6.2% the Tigray region. The logistic analysis revealed, factors small birth interval (less than 15 months) (AOR = 7.902; 95% CI: (4.526–13.795)) and 16–26 months (AOR =2.088; 95% CI: (1.292–3.375)), poor wealth index (AOR = 1.948; 95% CI: (1.011–3.754)), having no toilet facility (AOR =1.649; 95% CI: (1.093–2.488)), child sex (being male) (AOR =1.74; 95% CI: (1.234–2.454)), giving birth at older maternal age (45–49 years) (AOR = 0.293; 95% CI: (0.128–0.668)), rural residence and using the unprotected well water were significantly associated with a higher risk of perinatal death.

Conclusions

The study identified sex of a child, previous birth intervals, availability of toilet facilities, wealth index, birth type, mother’s age, parity, place of residence, mother’s occupation and source of drinking water were the factors significantly associated with perinatal mortality. The prevalence of perinatal mortality shows that Tigray region was experiencing a high perinatal mortality rate than the national.
Simulation as tool for evaluating and improving technical skills in laparoscopic gynecological surgery
Authors: Mannella Paolo , Malacarne Elisa , Giannini Andrea , Russo Eleonora , Caretto Marta , Papini Francesca , Montt Guevara Maria Magdalena , Pancetti Federica , Simoncini Tommaso
Published: October 2019

Background

Simulation in laparoscopic surgery is nowadays recognized as a valid instrument for learning and training surgeons in different procedures. However, its role as evaluation test and self-assessment tool to verify basic surgical skills is still under discussion.

Methods

Thirty-three residents in obstetrics and gynecology at University of Pisa, Italy were recruited, and they received a simulation program consisting of 5 tasks. They had to perform basic laparoscopic surgery maneuvers as creating pneumoperitoneum, positioning trocars under vision, demonstrating the appropriate use of dominant and non-dominant hand and making single stitch and knot. They were evaluated with a modified OSATs scale.

Results

Senior trainees had better score than junior trainees (p value< 0,005) and after different sessions of simulation scores of both groups significantly improved (p < 0,001), especially for the junior group. All the trainees reported self-assessments that matched with the evaluation of external observers demonstrating the importance of simulation also as auto-evaluation test.

Conclusions

In this study, we demonstrated the role of simulation as powerful tool to evaluate and to self-assess surgical technical skills and to improve own capacities, with the use of a modified OSATs scale adapted to specific exercises.
PREVALENCE OF FATIGUE AND IMPACT ON QUALITY OF LIFE IN CASTRATION-RESISTANT PROSTATE CANCER PATIENTS: the VITAL study
Authors: Rodríguez Antolín A. , Martínez-Piñeiro L. , Jiménez Romero M. E. , García Ramos J. B. , López Bellido D. , Muñoz del Toro J. , García García-Porrero A. , Gómez Veiga F.
Published: October 2019

Background

Fatigue is one of the most prevalent symptoms among cancer patients. Specifically, in metastatic castration-resistant prostate cancer (mCRPC) patients, fatigue is the most common adverse event associated with current treatments. The purpose of this study is to describe the prevalence of fatigue and its impact on quality of life (QoL) in patients with CRPC in routine clinical practice.

Methods

This was a cross-sectional, multicentre study. Male chemo-naïve adults with high-risk non-metastatic (M0) CRPC and metastatic (M1) CRPC (mCRPC) were eligible. Fatigue was measured using the Brief Fatigue Inventory (BFI) and QoL was assessed using the Functional Assessment of Cancer Therapy questionnaire for patients with prostate cancer (FACT-P) and the FACT-General (FACT-G) questionnaire. Data were analysed using Mann-Whitney or Kruskal-Wallis tests (non-parametric distribution), a T-test or an ANOVA (parametric distribution) and the Fisher or chi-squared tests (categorical variables).

Results

A total of 235 eligible patients were included in the study (74 [31.5%] with M0; and 161 [68.5%] with M1). Fatigue was present in 74%, with 38.5% of patients reporting moderate-to-severe fatigue. Mean FACT-G and FACT-P overall scores were 77.6 ± 16.3 and 108.7 ± 21.4, respectively, with no differences between the CRPC M0 and CRPC M1 subgroups. Fatigue intensity was associated with decreased FACT-G/P scores, with no differences between groups. Among 151 mCRPC patients with available treatment data, those treated with abiraterone-prednisone ≥3 months showed a significant reduction in fatigue intensity (p = 0.043) and interference (p = 0.04) compared to those on traditional hormone therapy (HT). Patients on abiraterone-prednisone ≥3 months showed significantly better FACT-G/P scores than patients on HT (p = 0.046 and 0.018, respectively).

Conclusion

Our data show a high prevalence and intensity of fatigue and its impact on QoL in chemo-naïve CRPC patients. There is an association between greater fatigue and less QoL, irrespective of the presence or absence of metastasis. Chemo-naïve mCRPC patients receiving more than 3 months of abiraterone acetate plus prednisone showed an improvement of fatigue and QoL when compared to those on traditional HT.

Trial registration

Not applicable since it is not an interventional study.
Association of adiposity with thyroid nodules: a cross-sectional study of a healthy population in Beijing, China
Authors: Yang Hui-xia , Zhong Yu , Lv Wei-hua , Zhang Feng , Yu Hong
Published: October 2019

Background

The relationship between thyroid nodules (TNs) and adiposity is controversial. This paper describes a cross-sectional investigation performed to determine the existence of any such relationship. To assess adiposity, body mass index (BMI) and visceral fat area (VFA) were utilized.

Methods

Between January 1, 2017 and March 3, 2019. Three thousand five hundred thirty four healthy people were examined using thyroid ultrasonography, visceral fat and anthropometric measurements, laboratory tests and questionnaire interview. Binary logistic regression analyses were used.

Results

Of the 3534 healthy subjects, 58.69% (2074/3534) of the subjects had TNs. A total of 55.91% (1976/3534) had BMI ≥ 25 kg/m2 and 39.67% (1402/3534) had VFA ≥ 100 cm2. After adjustment to address confounders, BMI-based overweight and obesity levels only correlated with higher risk TNs when used as a continuous variable (OR = 1.031, 95% CI: 1.008–1.055, P = 0.008), while VFA was both a continuous variable (OR = 1.003, 95% CI: 1.000–1.005, P = 0.034) and a categorical variable (OR = 1.198, 95% CI: 1.014–1.417, P = 0.034) associated with significantly elevated risk of TNs. Analyzing the subgroups, BMI ≥ 25 kg/m2 (OR = 1.500, 95% CI: 1.110–2.026, P = 0.008) was significantly correlated with TN risk in individuals with TG ≥ 1.7 mmol/L. VFA ≥ 100 cm2 correlated with the TN risk irrespective of age (< 50 years: OR = 1.374, 95% CI: 1.109–1.703, P = 0.004; ≥ 50 years: OR = 1.367, 95% CI: 1.063–1.759, P = 0.015) and in the following subgroups: women (OR = 4.575, 95% CI: 2.558–8.181, P = 0.000), FBG ≥ 6.1 mmol/L (OR = 1.522, 95% CI: 1.048–2.209, P = 0.027), and TG ≥ 1.7 mmol/L (OR = 1.414, 95% CI: 1.088–1.838, P = 0.010).

Conclusions

Adiposity correlates with TNs. To assess TN risk in Chinese individuals, VFA is better than BMI.
Patients’ and parents’ perception of care on a paediatric interprofessional training ward
Authors: Straub Christine , Bode Sebastian F. N.
Published: October 2019

Background

Interprofessional training wards (ITWs) have been established in different fields of adult medicine to promote interprofessional learning and interprofessional collaboration of health care profession students. High patient satisfaction rates have been reported for ITWs. No data of parents’ and especially patients’ evaluation of care on a paediatric ITW have been reported so far. This study aims to evaluate parents’ and patients’ perceptions of medical and nursing care on a paediatric ITW.

Methods

In 2017 we established and started an interprofessional training ward in the setting of a general paediatric ward (IPAPAED). Medical students and nurse trainees care for 4–6 patients under supervision of registered nurses and certified physicians. All parents and all patients older than 8 years were invited to evaluate different aspect of their care on the IPAPAED.

Results

Since November 2017 until February 2019 parents (n = 109) rated the overall care of their children on the IPAPAED ward with m = 1.21 (SD ± .43) (1 = “excellent”, 4 = “poor”). Patients (n = 56) rated their overall care with m = 1.29 (SD ± 0.5). Other aspects of care and interprofessional collaboration were rated equally well. Analysis of the (limited) free-text commentaries revealed that perceived quality of care, friendliness and communication were especially valued by patients and parents.

Discussion & conclusion

On a paediatric ITW, in the view of parents and patients in our sample, a high level of care is delivered and satisfaction rates are excellent. An ITW seems, from a patient and parent point of view, feasible, even in paediatrics.
Evaluation of pain knowledge and attitudes and beliefs from a pre-licensure physical therapy curriculum and a stand-alone pain elective
Authors: Bareiss Sonja K. , Nare Lucas , McBee Katie
Published: October 2019

Background

Adequate pain education of health professionals is fundamental in the management of pain. Although an interprofessional consensus of core competencies for health professional pre-licensure education in pain have been established, the degree of their incorporation into physical therapy curriculum varies greatly. The purpose of this study was to 1. Assess students’ pain knowledge and their attitudes and beliefs in a pre-licensure physical therapy curriculum using a cross sectional comparison, and 2. Using a sub-sample of this population, we evaluated if an elective course on pain based on International Association for the Study of Pain (IASP) guidelines had an effect on students’ knowledge and beliefs.

Methods

The Neurophysiology of Pain Questionnaire (NPQ) and the Pain Attitudes and Beliefs Scale for Physiotherapists (PABS-PT) was completed by first semester (n = 72) and final (n = 56) semester doctor of physical therapy (DPT) students. Final semester students completed surveys before and after participation in an elective course of their choosing (pain elective (PE) or other electives (OE)).

Results

Participation rate was > 90% (n = 128/140). We found mean differences in NPQ scores between final semester (3rd year) students (76.9%) compared to first semester students (64%), p < 0.001. Third year students showed a mean difference on PABS-PT subscales, showing decreased biomedical (p < 0.001) and increased biopsychosocial (p = 0.005) scores compared to first semester students. Only final semester students that participated in the PE improved their NPQ scores (from 79 to 86%, p < 0.001) and demonstrated a significant change in the expected direction on PABS-PT subscales with increased biopsychosocial (p = 0.003) and decreased biological scores (p < 0.001).

Conclusions

We suggest that although core pre-licensure DPT education improves students’ pain knowledge and changes their attitudes towards pain, taking a IASP based pain elective continues to improve their pain neurobiology knowledge and also further changes their attitudes and beliefs towards pain. Therefore, a stand-alone course on pain in addition to pain concepts threaded throughout the curriculum may help ensure that entry-level DPT students are better prepared to effectively work with patients with pain.
Customized versus population birth weight charts for identification of newborns at risk of long-term adverse cardio-metabolic and respiratory outcomes: a population-based prospective cohort study
Authors: Erkamp Jan S. , Jaddoe Vincent W. V. , Mulders Annemarie G. M. G. J. , Steegers Eric A. P. , Reiss Irwin K. M. , Duijts Liesbeth , Gaillard Romy
Published: October 2019

Background

Customized birth weight charts take into account physiological maternal characteristics that are known to influence fetal growth to differentiate between physiological and pathological abnormal size at birth. It is unknown whether customized birth weight charts better identify newborns at risk of long-term adverse outcomes than population birth weight charts. We aimed to examine whether birth weight classification according to customized charts is superior to population charts at identification of newborns at risk of adverse cardio-metabolic and respiratory health outcomes.

Methods

In a population-based prospective cohort study among 6052 pregnant women and their children, we measured infant catch-up growth, overweight, high blood pressure, hyperlipidemia, liver steatosis, clustering of cardio-metabolic risk factors, and asthma at age 10. Small size and large size for gestational age at birth was defined as birth weight in the lowest or highest decile, respectively, of population or customized charts. Association with birth weight classification was assessed using logistic regression models.

Results

Of the total of 605 newborns classified as small size for gestational age by population charts, 150 (24.8%) were reclassified as appropriate size for gestational age by customized charts, whereas of the total of 605 newborns classified as large size for gestational age by population charts, 129 (21.3%) cases were reclassified as appropriate size for gestational age by customized charts. Compared to newborns born appropriate size for gestational age, newborns born small size for gestational age according to customized charts had increased risks of infant catch-up growth (odds ratio (OR) 5.15 (95% confidence interval (CI) 4.22 to 6.29)), high blood pressure (OR 2.05 (95% CI 1.55 to 2.72)), and clustering of cardio-metabolic risk factors at 10 years (OR 1.66 (95% CI 1.18 to 2.34)). No associations were observed for overweight, hyperlipidemia, liver steatosis, or asthma. Newborns born large-size for gestational age according to customized charts had higher risk of catch-down-growth only (OR 3.84 (95% CI 3.22 to 4.59)). The direction and strength of the observed associations were largely similar when we used classification according to population charts.

Conclusions

Small-size-for-gestational-age newborns seem to be at risk of long-term adverse cardio-metabolic health outcomes, irrespective of the use of customized or population birth weight charts.
Correction to: Assessment of the efficacy of firocoxib (Previcox®) and grapiprant (Galliprant®) in an induced model of acute arthritis in dogs
Authors: de Salazar Alcalá Andrea García , Gioda Lucile , Dehman Alia , Beugnet Frederic
Published: October 2019

The original article [1] contains two mistaken instances of the molecule ‘fipronil’ in the results. These should instead have stated ‘firocoxib’.
A single-pieced, fully air-driven, cuff-inserted pseudo-blood pressure generator for on-site pre-screening test of non-invasive blood pressure monitor by nurses
Authors: Hwang Young Jun , Kim Gun Ho , Yun Sung Uk , Nam Kyoung Won
Published: October 2019

Background

It is crucial to frequently inspect the proper operation of non-invasive electronic blood pressure monitors in various sites to prevent accidents from inaccurate blood pressure measurements, especially for large-scale hospitals. However, most conventional blood pressure monitor inspection devices are not suitable for such on-site investigation purpose. In this study, we propose a new single-pieced, fully air-driven pseudo blood pressure generator that is suitable for frequent on-site pre-screening tests of the blood pressure monitor by nurses.

Results

The proposed model comprises a rigid cylindrical body, two simulated brachial arteries, two air-pumps, an electronic controller, and a pressure sensor. Control algorithm based on polynomial curve fitting was implemented to generate various user-instructed systolic blood pressure and heart-rate conditions automatically. To evaluate the performance and clinical feasibility of the proposed model, various experiments were performed using ten commercial electronic blood pressure monitors. Experimental results demonstrated that the values of the Pearson coefficient between the reference pseudo-blood pressure waveforms and the actually generated pressure waveforms were 0.983, 0.983 and 0.997 at 60, 70 and 80 beats/min, respectively (p < 0.05). Besides, during the experiments using ten commercial blood pressure monitors, the maximum error in average systolic blood pressure was 2.9 mmHg, the maximum standard deviation in average systolic blood pressure was 3.5 mmHg, and the maximum percentage error in average pumping rate was 3.2%, respectively.

Conclusions

We expect that the proposed model can give an easy and comprehensive way for frequent on-site investigations of the blood pressure monitors by nurses, and improve the safety of patients with abnormal blood pressure, especially in most large-scale hospitals.
Approach and assessment of automated stereotactic radiotherapy planning for early stage non-small-cell lung cancer
Authors: Bai Xue , Shan Guoping , Chen Ming , Wang Binbing
Published: October 2019

Background

Intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) are standard physical technologies of stereotactic body radiotherapy (SBRT) that are used for patients with non-small-cell lung cancer (NSCLC). The treatment plan quality depends on the experience of the planner and is limited by planning time. An automated planning process can save time and ensure a high-quality plan. This study aimed to introduce and demonstrate an automated planning procedure for SBRT for patients with NSCLC based on machine-learning algorithms. The automated planning was conducted in two steps: (1) determining patient-specific optimized beam orientations; (2) calculating the organs at risk (OAR) dose achievable for a given patient and setting these dosimetric parameters as optimization objectives. A model was developed using data of historical expertise plans based on support vector regression. The study cohort comprised patients with NSCLC who were treated using SBRT. A training cohort (N = 125) was used to calculate the beam orientations and dosimetric parameters for the lung as functions of the geometrical feature of each case. These plan–geometry relationships were used in a validation cohort (N = 30) to automatically establish the SBRT plan. The automatically generated plans were compared with clinical plans established by an experienced planner.

Results

All 30 automated plans (100%) fulfilled the dose criteria for OARs and planning target volume (PTV) coverage, and were deemed acceptable according to evaluation by experienced radiation oncologists. An automated plan increased the mean maximum dose for ribs (31.6 ± 19.9 Gy vs. 36.6 ± 18.1 Gy,P < 0.05). The minimum, maximum, and mean dose; homogeneity index; conformation index to PTV; doses to other organs; and the total monitor units showed no significant differences between manual plans established by experts and automated plans (P > 0.05). The hands-on planning time was reduced from 40–60 min to 10–15 min.

Conclusion

An automated planning method using machine learning was proposed for NSCLC SBRT. Validation results showed that the proposed method decreased planning time without compromising plan quality. Plans generated by this method were acceptable for clinical use.
Antidepressant medication use among working age first-generation migrants resident in Finland: an administrative data linkage study
Authors: Bosqui Tania , Väänänen Ari , Buscariolli Andre , Koskinen Aki , O’Reilly Dermot , Airila Auli , Kouvonen Anne
Published: October 2019

Background

A higher risk of common mental health disorders has been found for first-generation migrants in high income countries, but few studies have examined the use of mental health care. This study aimed to identify the level of antidepressant use amongst the largest first generation migrant groups resident in Finland.

Methods

This cohort study used record-based data linkage methodology to examine the hazard of antidepressant use between migrant groups in Finland using Cox proportional hazard models. Data was derived using socio-demographic and prescription data from Statistics Finland and the Finnish Population Registry. The cohort included a random sample of 33% of the working age population in 2007 (N = 1,059,426, 49.8% women, 2.5% migrants) and dispensed antidepressant prescriptions from 2008 to 2014.

Results

After adjustment for socio-demographic characteristics, results show higher antidepressant use for female migrants from North Africa and the Middle East compared to the Finland-born majority, a similar level of use for migrants from Western countries, and lower use for migrants from other non-Western countries.

Conclusions

The gender and country of origin dependent use of antidepressant medication is discussed in terms of socio-political and cultural between-group differences. Recommendations are made to address inequalities in accessing services, particularly for migrants from non-Western countries.
Long noncoding RNA GAS5 inhibits progression of colorectal cancer by interacting with and triggering YAP phosphorylation and degradation and is negatively regulated by the m6A reader YTHDF3
Authors: Ni Wen , Yao Su , Zhou Yunxia , Liu Yuanyuan , Huang Piao , Zhou Aijun , Liu Jingwen , Che Liheng , Li Jianming
Published: October 2019

Background

YAP activation is crucial for cancer development including colorectal cancer (CRC). Nevertheless, it remains unclear whether N6-Methyladenosine (m6A) modified transcripts of long noncoding RNAs (lncRNAs) can regulate YAP activation in cancer progression. We investigated the functional link between lncRNAs and the m6A modification in YAP signaling and CRC progression.

Methods

YAP interacting lncRNAs were screened by RIP-sequencing, RNA FISH and immunofluorescence co-staining assays. Interaction between YAP and lncRNA GAS5 was studied by biochemical methods. MeRIP-sequencing combined with lncRNA-sequencing were used to identify the m6A modified targets of YTHDF3 in CRC. Gain-of-function and Loss-of-function analysis were performed to measure the function of GAS5-YAP-YTHDF3 axis in CRC progression in vitro and in vivo.

Results

GAS5 directly interacts with WW domain of YAP to facilitate translocation of endogenous YAP from the nucleus to the cytoplasm and promotes phosphorylation and subsequently ubiquitin-mediated degradation of YAP to inhibit CRC progression in vitro and in vivo. Notably, we demonstrate the m6A reader YTHDF3 not only a novel target of YAP but also a key player in YAP signaling by facilitating m6A-modified lncRNA GAS5 degradation, which profile a new insight into CRC progression. Clinically, lncRNA GAS5 expressions is negatively correlated with YAP and YTHDF3 protein levels in tumors from CRC patients.

Conclusions

Our study uncovers a negative functional loop of lncRNA GAS5-YAP-YTHDF3 axis, and identifies a new mechanism for m6A-induced decay of GAS5 on YAP signaling in progression of CRC which may offer a promising approach for CRC treatment.
Treatment patterns and economic burden of sickle-cell disease patients prescribed hydroxyurea: a retrospective claims-based study
Authors: Shah Nirmish , Bhor Menaka , Xie Lin , Halloway Rashid , Arcona Steve , Paulose Jincy , Yuce Huseyin
Published: October 2019

Background

This study aimed to evaluate sickle-cell disease (SCD) treatment patterns and economic burden among patients prescribed hydroxyurea (HU) in the US, through claims data.

Methods

SCD patients with pharmacy claims for HU were selected from the Medicaid Analytic Extracts (MAX) from January 1, 2009 - December 31, 2013. The first HU prescription during the identification period was defined as the index date and patients were required to have had continuous medical and pharmacy benefits for ≥6 months baseline and 12 months follow-up periods. Patient demographics, clinical characteristics, treatment patterns, health care utilization, and costs were examined, and variables were analyzed descriptively.

Results

A total of 3999 SCD patients prescribed HU were included; the mean age was 19.24 years, most patients were African American (73.3%), and the mean Charlson comorbidity index (CCI) score was 0.6. Asthma (20.3%), acute chest syndrome (15.6%), and infectious and parasitic diseases (20%) were the most prevalent comorbidities. During the 12-month follow-up period, 58.9% (N = 2357) of patients discontinued HU medication. The mean medication possession ratio (MPR) was 0.52, and 22.3% of patients had MPR ≥80%. The average length of stay (LOS) for SCD-related hospitalization was 13.35 days; 64% of patients had ≥1 SCD-related hospitalization. The mean annual total SCD-related costs per patient were $27,779, mostly inpatient costs ($20,128).

Conclusions

Overall, the study showed the patients had significant unmet needs manifest as poor medication adherence, high treatment discontinuation rates, and high economic burden.
Phloretin attenuates STAT-3 activity and overcomes sorafenib resistance targeting SHP-1–mediated inhibition of STAT3 and Akt/VEGFR2 pathway in hepatocellular carcinoma
Authors: Saraswati Sarita , Alhaider Abdulqader , Abdelgadir Abdelgalil Mohamed , Tanwer Pooja , Korashy Hesham M.
Published: October 2019

Background

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Phloretin (PH) possesses anticancer, antitumor, and hepatoprotective effects, however, the effects and potential mechanisms of phloretin remain elusive.

Methods

Five HCC cells were tested in vitro for sensitivity to PH, Sorafenib (Sor) or both and the apoptosis, signal transduction and phosphatase activity were analyzed. To validate the role of SHP-1, we used PTP inhibitor III and SHP-1 siRNA. Further, we used purified SHP-1 proteins or HCC cells expressing deletion N-SH2 domain or D61A point mutants to study the PH efficacy on SHP-1. The `in vivo studies were conducted using HepG2 and SK-Hep1 and Sor resistant HepG2SRand Huh7SRxenografts. Molecular docking was done with Swiss dock and Auto Dock Vina.

Results

PH inhibited cell growth and induced apoptosis in all HCC cells by upregulating SHP-1 expression and downregulating STAT3 expression and further inhibited pAKT/pERK signaling. PH activated SHP-1 by disruption of autoinhibition of SHP-1, leading to reduced p-STAT3Tyr705level. PH induced apoptosis in two Sor-resistant cell lines and overcome STAT3, AKT, MAPK and VEGFR2 dependent Sor resistance in HCCs. PH potently inhibited tumor growth in both Sor-sensitive and Sor-resistant xenografts in vivo by impairing angiogenesis, cell proliferation and inducing apoptosis via targeting the SHP-1/STAT3 signaling pathway.

Conclusion

Our data suggest that PH inhibits STAT3 activity in Sor-sensitive and -resistant HCCs via SHP-1–mediated inhibition of STAT3 and AKT/mTOR/JAK2/VEGFR2 pathway. Our results clearly indicate that PH may be a potent reagent for hepatocellular carcinoma and a noveltargeted therapy for further clinical investigations.

Graphical abstract
Linoleic acid improves assembly of the CII subunit and CIII2/CIV complex of the mitochondrial oxidative phosphorylation system in heart failure
Authors: Maekawa Satoshi , Takada Shingo , Nambu Hideo , Furihata Takaaki , Kakutani Naoya , Setoyama Daiki , Ueyanagi Yasushi , Kang Dongchon , Sabe Hisataka , Kinugawa Shintaro
Published: October 2019

Background

Linoleic acid is the major fatty acid moiety of cardiolipin, which is central to the assembly of components involved in mitochondrial oxidative phosphorylation (OXPHOS). Although linoleic acid is an essential nutrient, its excess intake is harmful to health. On the other hand, linoleic acid has been shown to prevent the reduction in cardiolipin content and to improve mitochondrial function in aged rats with spontaneous hypertensive heart failure (HF). In this study, we found that lower dietary intake of linoleic acid in HF patients statistically correlates with greater severity of HF, and we investigated the mechanisms therein involved.

Methods

HF patients, who were classified as New York Heart Association (NYHA) functional class I (n = 45), II (n = 93), and III (n = 15), were analyzed regarding their dietary intakes of different fatty acids during the one month prior to the study. Then, using a mouse model of HF, we confirmed reduced cardiolipin levels in their cardiac myocytes, and then analyzed the mechanisms by which dietary supplementation of linoleic acid improves cardiac malfunction of mitochondria.

Results

The dietary intake of linoleic acid was significantly lower in NYHA III patients, as compared to NYHA II patients. In HF model mice, both CI-based and CII-based OXPHOS activities were affected together with reduced cardiolipin levels. Silencing of CRLS1, which encodes cardiolipin synthetase, in cultured cardiomyocytes phenocopied these events. Feeding HF mice with linoleic acid improved both CI-based and CII-based respiration as well as left ventricular function, together with an increase in cardiolipin levels. However, although assembly of the respirasome (i.e., CI/CIII2/CIV complex), as well as assembly of CII subunits and the CIII2/CIV complex statistically correlated with cardiolipin levels in cultured cardiomyocytes, respirasome assembly was not notably restored by dietary linoleic acid in HF mice. Therefore, although linoleic acid may significantly improve both CI-based and CII-based respiration of cardiomyocytes, respirasomes impaired by HF were not easily repaired by the dietary intake of linoleic acid.

Conclusions

Dietary supplement of linoleic acid is beneficial for improving cardiac malfunction in HF, but is unable to completely cure HF.
Combining HPV DNA load with p16/Ki-67 staining to detect cervical precancerous lesions and predict the progression of CIN1–2 lesions
Authors: Li Yuejie , Liu Jie , Gong Li , Sun Xingwang , Long Wenbo
Published: October 2019

Background

Human Papilloma Virus (HPV) DNA tests are highly sensitive and can triage women with mild lesions, improving the prognosis and diagnosis of cervical lesions. However, additional efficient strategies should be developed to improve the specificity of these tests.

Methods

This study aimed to evaluate the clinical value of HPV DNA load in improving the diagnosis and prognosis of cervical lesions by p16/Ki-67 testing. Histological samples were collected from 350 women with HR-HPV genotyping and analyzed by qRT-PCR. Immunohistochemical staining was used to assess p16 and Ki-67 expression and clinical performance characteristics were calculated.

Results

Of the cases, 271 had detectable HR-HPV infection, in which HPV-16 was most prevalent (52.0%), followed by HPV-58 (22.5%). P16/Ki-67-positivity increased with histological severity but not for HR-HPV infection. Amongst the 13 HR-HPV genotypes, only HPV-16 (P = 0.016) and HPV-58 (P = 0.004) viral loads significantly correlated with lesion severity. The P16/Ki-67/HPV DNA load co-test indicated an increased sensitivity for the detection of cervical intraepithelial neoplasia (CIN) lesions compared to p16/Ki-67 staining in HPV-16 and/or 58 positive cases. Viral load did not improve the sensitivity of p16/Ki-67 co-test in non-HPV-16 or 58 positive cases. The clinical performance of the p16/Ki-67/HPV DNA load co-test was limited for the prediction of the outcome of CIN1 lesions. However, amongst the 12 HPV-16 and/or 58 positive CIN2 cases in which return visit results were obtained, the behavior of the lesions could be predicted, with a sensitivity, specificity, positive prediction rate (PPV), and negative prediction rate (NPV) of 0.667, 1, 1 and 0.5, respectively.

Conclusion

Combination of the assessment of HPV DNA load with the intensity of p16 and Ki-67 staining could increase the sensitivity of CIN lesion diagnosis and predict the outcome of CIN2 in patients with a HPV-16 and/or 58 infection.
Experiences of care in the context of payment for performance (P4P) in Tanzania
Authors: Chimhutu Victor , Tjomsland Marit , Mrisho Mwifadhi
Published: October 2019

Background

Tanzania is one of many low income countries committed to universal health coverage and Sustainable Development Goals. Despite these bold goals, there is growing concern that the country could be off-track in meeting these goals. This prompted the Government of Tanzania to look for ways to improve health outcomes in these goals and this led to the introduction of Payment for Performance (P4P) in the health sector. Since the inception of P4P in Tanzania a number of impact, cost-effective and process evaluations have been published with less attention being paid to the experiences of care in this context of P4P, which we argue is important for policy agenda setting. This study therefore explores these experiences from the perspectives of health workers, service users and community health governing committee members.

Methods

A qualitative study design was used to elicit experiences of health workers, health service users and health governing committee members in Rufiji district of the Pwani region in Tanzania. The Payment for Performance pilot was introduced in Pwani region in 2011 and data presented in this article is based on this pilot. A total of 31 in-depth interviews with health workers and 9 focus group discussions with health service users and health governing committee members were conducted. Collected data was analysed through qualitative content analysis.

Results

Study informants reported positive experiences with Payment for Performance and highlighted its potential in improving the availability, accessibility, acceptability and quality of care (AAAQ). However, the study found that persistent barriers for achieving AAAQ still exist in the health system of Tanzania and these contribute to negative experiences of care in the context of P4P.

Conclusion

Our findings suggest that there are a number of positive aspects of care that can be improved by Payment for Performance. However its targeted nature on specific services means that these improvements cannot be generalized at health facility level. Additionally, health workers can go as far as they can in improving health services but some factors that act as barriers as demonstrated in this study are out of their control even in the context of Payment for Performance. In this regard there is need to exercise caution when implementing such initiatives, despite seemingly positive targeted outcomes.