bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age, sex, disease severity, and disease duration difference in placebo response: implications from a meta-analysis of diabetes mellitus
Authors: Lin Chu , Cai Xiaoling , Yang Wenjia , Lv Fang , Nie Lin , Ji Linong 
Published: November 2020

AbstractBackgroundThe placebo response in patients with diabetes mellitus is very common. A systematic evaluation needs to be updated with the current evidence about the placebo response in diabetes mellitus and the associated factors in clinical trials of anti-diabetic medicine.MethodsLiterature research was conducted in Medline, Embase, the Cochrane Central Register of Controlled Trials, andClinicalTrials.govfor studies published between the date of inception and June 2019. Randomized placebo-controlled trials conducted in type 1and type 2 diabetes mellitus (T1DM/T2DM) were included. Random-effects model and meta-regression analysis were accordingly used. This meta-analysis was registered in PROSPERO as CRD42014009373.ResultsSignificantly weight elevation (effect size (ES) = 0.33 kg, 95% CI, 0.03 to 0.61 kg) was observed in patients with placebo treatments in T1DM subgroup while significantly HbA1c reduction (ES = − 0.12%, 95% CI, − 0.16 to − 0.07%) and weight reduction (ES = − 0.40 kg, 95% CI, − 0.50 to − 0.29 kg) were observed in patients with placebo treatments in T2DM subgroup. Greater HbA1c reduction was observed in patients with injectable placebo treatments (ES = − 0.22%, 95% CI, − 0.32 to − 0.11%) versus oral types (ES = − 0.09%, 95% CI, − 0.14 to − 0.04%) in T2DM (P = 0.03). Older age (β = − 0.01, 95% CI, − 0.02 to − 0.01,P < 0.01) and longer diabetes duration (β = − 0.02, 95% CI, − 0.03 to − 0.21 × 10−2,P = 0.03) was significantly associated with more HbA1c reduction by placebo in T1DM. However, younger age (β = 0.02, 95% CI, 0.01 to 0.03,P = 0.01), lower male percentage (β = 0.01, 95% CI, 0.22 × 10−2, 0.01,P < 0.01), higher baseline BMI (β = − 0.02, 95% CI, − 0.04 to − 0.26 × 10−2,P = 0.02), and higher baseline HbA1c (β = − 0.09, 95% CI, − 0.16 to − 0.01,P = 0.02) were significantly associated with more HbA1c reduction by placebo in T2DM. Shorter diabetes duration (β = 0.06, 95% CI, 0.06 to 0.10,P < 0.01) was significantly associated with more weight reduction by placebo in T2DM. However, the associations between baseline BMI, baseline HbA1c, and placebo response were insignificant after the adjusted analyses.ConclusionThe placebo response in diabetes mellitus was systematically outlined. Age, sex, disease severity (indirectly reflected by baseline BMI and baseline HbA1c), and disease duration were associated with placebo response in diabetes mellitus. The association between baseline BMI, baseline HbA1c, and placebo response may be the result of regression to the mean.
Use of electronic cigarettes and secondhand exposure to their aerosols are associated with asthma symptoms among adolescents: a cross-sectional study
Authors: Alnajem Abdullah , Redha Abdullah , Alroumi Dalal , Alshammasi Ahmed , Ali Mohamad , Alhussaini Maram , Almutairi Waad , Esmaeil Ali , Ziyab Ali H. 
Published: November 2020

Abstract
Background
Globally, a surge in electronic cigarette (e-cigarette) use has been observed in recent years, with youth being the most susceptible group. Given their recent emergence, studies assessing the health consequences of using e-cigarettes and exposure to their secondhand aerosols (SHA) are limited. Hence, this study sought to assess associations between e-cigarette use and household exposure to SHA from e-cigarettes with asthma symptoms among adolescents.

Methods
A school-based cross-sectional study was conducted by enrolling high school students (n = 1565; aged 16–19 years) in Kuwait. Participants self-completed a questionnaire on tobacco products use (e-cigarettes and cigarettes) and asthma symptoms. Current e-cigarette use and cigarette smoking were defined as any use in the past 30 days. Household exposure to SHA from e-cigarettes in the past 7 days was reported as none (0 days), infrequent (1–2 days), and frequent (≥ 3 days). Asthma symptoms included current (past 12 months) wheeze, current asthma (history of clinical diagnosis and current wheeze and/or medication use), and current symptoms of uncontrolled asthma (≥ 4 attacks of wheeze, ≥ 1 night per week sleep disturbance from wheeze, and/or wheeze affecting speech). Associations were assessed using Poisson regression with robust variance estimation, and adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were estimated.

Results
Among the analytical study sample (n = 1345), current e-cigarette use and cigarette smoking was reported by 369 (27.4%) and 358 (26.6%) participants, respectively. Compared to never e-cigarette users and never cigarette smokers, current e-cigarette users with no history of cigarette smoking had increased prevalence of current wheeze (aPR = 1.54, 95% CI 1.01–2.45) and current asthma (aPR = 1.85, 95% CI 1.03–3.41). Moreover, the frequency of exposure to household SHA from e-cigarettes was associated with asthma symptoms. For example, compared to those with no exposure to household SHA, frequent exposure to household SHA was associated with current wheeze (aPR = 1.30, 95% CI 1.04–1.59), current asthma (aPR = 1.56, 95% CI 1.13–2.16), and current uncontrolled asthma symptoms (aPR = 1.88, 95% CI 1.35–2.62).

Conclusions
E-cigarette use and their household SHA exposure were independently associated with asthma symptoms among adolescents. Hence, such observations indicate that e-cigarette use and passive exposure to their aerosols negatively impact respiratory health among adolescents.
Study design and operational framework for a community-based Malaria Elimination Demonstration Project (MEDP) in 1233 villages of district Mandla, Madhya Pradesh
Authors: Rajvanshi Harsh , Bharti Praveen K. , Nisar Sekh , Jain Yashpal , Jayswar Himanshu , Mishra Ashok K. , Sharma Ravendra K. , Saha Kalyan B. , Shukla Man Mohan , Das Aparup , Kaur Harpreet , Wattal Suman L. , Singh Neeru , Lal Altaf A. 
Published: November 2020

Abstract
Background
In the past decade substantial reduction in malaria morbidity and mortality has been observed through well-implemented case management and vector control strategies. India has also achieved a significant reduction in malaria burden in 2018 and has committed to eliminate malaria by 2030. The Mandla Malaria Elimination Demonstration Project (MEDP) was started in 2017 in 1233 villages of District Mandla to demonstrate malaria elimination in a tribal district with hard-to-reach areas was possible using active and passive surveillance, case management, vector control, and targeted information, education and communication campaigns. An operational plan was developed to strengthen the existing surveillance and malaria elimination systems, through fortnightly active case detection to ensure that all cases including those that are introduced into the communities are rapidly identified and treated promptly. The plan also focused on the reduction of human-mosquito contact through the use of Long-Lasting Insecticial Nets (LLINs) and Indoor Residual Spray (IRS). The operational plan was modified in view of the present COVID-19 pandemic by creating systems of assistance for the local administration for COVID-related work while ensuring the operational integrity of malaria elimination efforts.

Results
The use of MEDP study design and operational plan, with its built-in management control systems, has yielded significant (91%) reduction of indigenous cases of malaria during the period from June 2017 to May 2020. The malaria positivity rate was 0.33% in 2017–18, 0.13% in 2018–19, and 0.06% in 2019–20. Mass screening revealed 0.18% malaria positivity in September–October 2018, followed by 0.06% in June 2019, and 0.03% in December 2019, and these were mostly asymptomatic cases in the community. The project has been able to sustain the gains of the past three years during the ongoing COVID-19 pandemic.

Conclusion
This paper provides the study design and the operational plan for malaria elimination in a high-burden district of Central India, which presented difficulties of hard to reach areas, forest malaria, and complex epidemiology of urban and rural malaria. The lessons learned could be used for malaria elimination efforts in rest of the country and other parts of South Asia with comparable demography and epidemiology.
Investigation of safety for electrochemotherapy and irreversible electroporation ablation therapies in patients with cardiac pacemakers
Authors: Jarm Tomaz , Krmac Tadej , Magjarevic Ratko , Kos Bor , Cindric Helena , Miklavcic Damijan 
Published: November 2020

Abstract
Background
The effectiveness of electrochemotherapy of tumors (ECT) and of irreversible electroporation ablation (IRE) depends on different mechanisms and delivery protocols. Both therapies exploit the phenomenon of electroporation of the cell membrane achieved by the exposure of the cells to a series of high-voltage electric pulses. Electroporation can be fine-tuned to be either reversible or irreversible, causing the cells to either survive the exposure (in ECT) or not (in IRE), respectively. For treatment of tissues located close to the heart (e.g., in the liver), the safety of electroporation-based therapies is ensured by synchronizing the electric pulses with the electrocardiogram. However, the use of ECT and IRE remains contraindicated for patients with implanted cardiac pacemakers if the treated tissues are located close to the heart or the pacemaker. In this study, two questions are addressed: can the electroporation pulses interfere with the pacemaker; and, can the metallic housing of the pacemaker modify the distribution of electric field in the tissue sufficiently to affect the effectiveness and safety of the therapy?

Results
The electroporation pulses induced significant changes in the pacemaker ventricular pacing pulse only for the electroporation pulses delivered during the pacing pulse itself. No residual effects were observed on the pacing pulses following the electroporation pulses for all tested experimental conditions. The results of numerical modeling indicate that the presence of metal-encased pacemaker in immediate vicinity of the treatment zone should not impair the intended effectiveness of ECT or IRE even when the casing is in direct contact with one of the active electrodes. Nevertheless, the contact between the casing and the active electrode should be avoided due to significant tissue heating at the site of the other active electrode for the IRE protocol and may cause the pulse generator to fail to deliver the pulses due to excessive current draw.

Conclusions
The observed effects of electroporation pulses delivered in close vicinity of the pacemaker or its electrodes do not indicate adverse consequences for either the function of the pacemaker or the treatment outcome. These findings should contribute to making electroporation-based treatments accessible also to patients with implanted cardiac pacemakers.
Social inequalities in heat-attributable mortality in the city of Turin, northwest of Italy: a time series analysis from 1982 to 2018
Authors: Ellena Marta , Ballester Joan , Mercogliano Paola , Ferracin Elisa , Barbato Giuliana , Costa Giuseppe , Ingole Vijendra 
Published: November 2020

AbstractBackgroundUnderstanding context specific heat-health risks in urban areas is important, especially given anticipated severe increases in summer temperatures due to climate change effects. We investigate social inequalities in the association between daily temperatures and mortality in summer in the city of Turin for the period 1982–2018 among different social and demographic groups such as sex, age, educational level, marital status and household occupants.MethodsMortality data are represented by individual all-cause mortality counts for the summer months between 1982 and 2018. Socioeconomic level and daily mean temperature were assigned to each deceased. A time series Poisson regression with distributed lag non-linear models was fitted to capture the complex nonlinear dependency between daily mortality and temperature in summer. The mortality risk due to heat is represented by the Relative Risk (RR) at the 99th percentile of daily summer temperatures for each population subgroup.ResultsAll-cause mortality risk is higher among women (1.88; 95% CI = 1.77, 2.00) and the elderly (2.13; 95% CI = 1.94, 2.33). With regard to education, the highest significant effects for men is observed among higher education levels (1.66; 95% CI = 1.38, 1.99), while risks for women is higher for the lower educational level (1.93; 95% CI = 1.79, 2.08). Results on marital status highlighted a stronger association for widower in men (1.66; 95% CI = 1.38, 2.00) and for separated and divorced in women (2.11; 95% CI = 1.51, 2.94). The risk ratio of household occupants reveals a stronger association for men who lived alone (1.61; 95% CI = 1.39, 1.86), while for women results are almost equivalent between alone and not alone groups.ConclusionsThe associations between heat and mortality is unequal across different aspects of social vulnerability, and, inter alia, factors influencing the population vulnerability to temperatures can be related to demographic, social, and economic aspects. A number of issues are identified and recommendations for the prioritisation of further research are provided. A better knowledge of these effect modifiers is needed to identify the axes of social inequality across the most vulnerable population sub-groups.
Retinol-binding protein 4 (RBP4) and high sensitivity C-reactive protein (hs-CRP) levels in patients with diminished ovarian reserve (DOR): a cross-sectional study
Authors: Zou Wen , Wang Zehao , Xia Jing , Yang Jing 
Published: November 2020

AbstractBackgroundAntioxidant/oxidant imbalance has been reported to be related to diminished ovarian reserve (DOR). Vitamin A (retinol), a kind of antioxidant, plays a role in restoring ovarian oxidative damage, while C-reactive protein (CRP) is the classical marker of oxidative stress and has recently been identified as an independent variable that is associated with low anti-Mullerian hormone (AMH) levels in young women with DOR. Additionally, retinol binding protein 4 (RBP4) can be considered a substitute for retinol in healthy, nonobese women. The study aim was to determine the relationship between serum RBP4, high sensitivity C-reactive protein (hs-CRP) concentrations and ovarian reserve in nonobese DOR patients.MethodsThis study included 24 DOR women and 48 normal ovarian reserve (NOR) women from the reproductive medical center of Renmin Hospital of Wuhan University. The serum RBP4 and high-sensitivity CRP (hs-CRP) levels were measured with ELISA kits.ResultsRBP4 levels (20,648.36 ± 5475.16 ng/ml vs 23,986.48 ± 5995.64 ng/ml,p = 0.025) were decreased, and hs-CRP levels (695.08 ± 1090.19 ng/ml vs 364.32 ± 786.29 ng/ml,p = 0.012) were increased in the DOR group. Serum RBP4 was positively related to AMH (Pearsonr = 0.518,p = 0.000), while hs-CRP was negatively correlated with AMH (Spearmanr = − 0.345,p = 0.005). after adjustments were made for the covariables, multiple line regression analysis showed that positive association between RBP4 and AMH still existed (β = 0.450,p< 0.001).ConclusionDecreased serum RBP4 levels and increased serum hs-CRP were observed in DOR patients in our study, and the strong correlation between RBP4 and AMH supports the notion that oxidative stress plays a role in DOR, and that appropriate levels of antioxidant vitamin A may be protective against ovarian reserve dysfunction.
Impact of changes in the methodology of external price referencing on medicine prices: discrete-event simulation
Authors: Vogler Sabine , Schneider Peter , Lepuschütz Lena 
Published: November 2020

Abstract
Background
Several governments apply the policy of external price referencing (EPR), which considers the prices of a medicine in one or more other countries for the purpose of setting the price in the own country. Different methodological choices can be taken to design EPR. The study aimed to analyse whether, or not, and how changes in the methodology of EPR can impact medicine prices.

Methods
The real-life EPR methodology as of Q1/2015 was surveyed in all European Union Member States (where applicable), Iceland, Norway and Switzerland through a questionnaire responded by national pricing authorities. Different scenarios were developed related to the parameters of the EPR methodology. Discrete-event simulations of fictitious prices in the 28 countries of the study that had EPR were run over 10 years. The continuation of the real-life EPR methodology in the countries as surveyed in 2015, without any change, served as base case.

Results
In most scenarios, after 10 years, medicine prices in all or most surveyed countries were—sometimes considerably—lower than in the base case scenario. But in a few scenarios medicine prices increased in some countries. Consideration of discounts (an assumed 20% discount in five large economies and the mandatory discount in Germany, Greece and Ireland) and determining the reference price based on the lowest price in the country basket would result in higher price reductions (on average − 47.2% and − 34.2% compared to the base case). An adjustment of medicine price data of the reference countries by purchasing power parities would lead to higher prices in some more affluent countries (e.g. Switzerland, Norway) and lower prices in lower-income economies (Bulgaria, Romania, Hungary, Poland). Regular price revisions and changes in the basket of reference countries would also impact medicine prices, however to a lesser extent.

Conclusions
EPR has some potential for cost-containment. Medicine prices could be decreased if certain parameters of the EPR methodology were changed. If public payers aim to apply EPR to keep medicine prices at more affordable levels, they are encouraged to explore the cost-containment potential of this policy by taking appropriate methodological choices in the EPR design.
Pelvic Ewing sarcoma: a retrospective outcome analysis of 104 patients who underwent pelvic tumor resection at a single supra-regional center
Authors: Guder Wiebke K. , Hardes Jendrik , Nottrott Markus , Steffen Anne Juliane , Dirksen Uta , Streitbürger Arne 
Published: November 2020

Abstract
Background
Local treatment in pelvic Ewing sarcoma (ES) consists of operation, radiation therapy, or a combination of both. Reported outcomes vary depending on the treatment modality performed. It is the objective of this study to analyze surgical outcome and complications as well as oncological outcome and complications of chemo- and radiation therapy in this patient cohort and evaluate prognostic factors.

Methods
Retrospective review of 104 patients who underwent tumor resection for pelvic ES from 1988 to 2014.

Results
All patients underwent pelvic resection and radiation therapy was administered in 77.9%. Margins were clear in 94.2%. The response to chemotherapy was good in 78.8%. Local recurrence occurred in 7.7%. The presence of distant metastases at the time of operation was the most important negative predictor for overall survival (p = 0.003). The cumulative 5- and 10-year survival rates were 82.7% and 80.1% for non-metastasized and 61.4% and 41.6% for metastasized pelvic ES at operation. In the presence of a single-distant metastatic site at operation compared to multiple metastatic sites, the cumulative survival rates were 64.3% versus 50% at five and 50.7% versus 16.7% at 10 years.

Conclusions
A combined treatment approach of tumor resection and radiation therapy leads to a local control and overall survival rates comparable with those of extremity locations in this study’s patient cohort with localized pelvic ES. Therefore, surgical tumor resection (combined with (neo-)adjuvant radiation therapy) in non-metastatic pelvic ES seems feasible. In metastatic patients, however, the significance of tumor resection as a part of local treatment remains less certain and improved outcomes of combined local treatment approaches need to be weighed against these patients’ prognosis and quality of life.
Tricuspid valve repair in isolated tricuspid pathology: a 12-year single center experience
Authors: Zubarevich Alina , Szczechowicz Marcin , Brcic Andreas , Osswald Anja , Tsagakis Konstantinos , Wendt Daniel , Schmack Bastian , Sá Michel Pompeu B. O. , Van den Eynde Jef , Ruhparwar Arjang , Zhigalov Konstantin 
Published: November 2020

Abstract
Objectives
Long-term data on isolated surgical tricuspid valve procedures is limited. Current guidelines on heart valve disease recommend valve repair over valve replacement. In this study we report our 12-year single-center experience with isolated surgical tricuspid valve repair in patients with various tricuspid valve pathologies.

Methods
Between May 2007 and December 2019, 26 consecutive patients underwent isolated tricuspid valve annuloplasty/repair for various indications. In 18 patients (69.2%) an open ring or band annuloplasty (26.9 and 42.3%, respectively) was performed, 5 patients (19.2%) underwent a tightening of the annulus using the DeVega technique, 5 patients (19.2%) had a leaflet reconstruction with patch or bicuspidalization and in 3 patients (11.5%) a leaflet debridement was performed. In 15.4% of the cohort a combination of the techniques was utilized.

Results
The mean follow-up time was 2.1 (0.3–5.0) years. Early survival at 30 days after surgery was 84.6%. Mean hospital stay was 11 (6.7–16) days. One-year survival was 73%. No patient required a redo procedure on the tricuspid valve during follow-up.

Conclusion
Tricuspid valve repair is suggested as a treatment of choice according to recent guidelines on heart valve disease. If chosen correctly, various repair techniques provide good long-term results. Tricuspid valve repair may be safely applied in patients undergoing surgical isolated tricuspid valve procedures.
Reproduction of contagious bovine pleuropneumonia via aerosol-based challenge with Mycoplasma mycoides subsp. mycoides
Authors: Sacchini Flavio , Liljander Anne Mariana , Heller Martin , Poole Elizabeth Jane , Posthaus Horst , Schieck Elise , Jores Joerg 
Published: November 2020

AbstractContagious bovine pleuropneumonia (CBPP) is a respiratory disease caused by Mycoplasma mycoides subsp. mycoides. Infection occurs via Mycoplasma-containing droplets and therefore requires close contact between animals. The current infection models are suboptimal and based on intratracheal installation of mycoplasmas or in-contact infection. This work tested the infection of adult cattle via aerosols containing live mycoplasmas mimicking the infection of cattle in the field. Therefore, we infected six cattle with aerosolized Mycoplasma mycoides subsp. mycoides strain Afadé over seven consecutive days with altogether 109 colony forming units. All animals seroconverted between 11–24 days post infection and five out of six animals showed typical CBPP lesions. One animal did not show any lung lesions at necropsy, while another animal had to be euthanized at 25 days post infection because it reached endpoint criteria. Seroconversion confirmed successful infection and the spectrum of clinical and lesions observed mirrors epidemiological models and the field situation, in which only a fraction of animals suffers from acute clinical disease post infection.