bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of an algorithm based on administrative data to detect new onset of atrial fibrillation after cardiac surgery
Authors: Bourgon Labelle Jonathan , Farand Paul , Vincelette Christian , Dumont Myriam , Le Blanc Mathilde , Rochefort Christian M.
Published: April 2020

Introduction

Postoperative atrial fibrillation (POAF) is a frequent complication of cardiac surgery associated with important morbidity, mortality, and costs. To assess the effectiveness of preventive interventions, an important prerequisite is to have access to accurate measures of POAF incidence. The aim of this study was to develop and validate such a measure.

Methods

A validation study was conducted at two large Canadian university health centers. First, a random sample of 976 (10.4%) patients who had cardiac surgery at these sites between 2010 and 2016 was generated. Then, a reference standard assessment of their medical records was performed to determine their true POAF status on discharge (positive/negative). The accuracy of various algorithms combining diagnostic and procedure codes from: 1) the current hospitalization, and 2) hospitalizations up to 6 years before the current hospitalization was assessed in comparison with the reference standard. Overall and site-specific estimates of sensitivity, specificity, positive (PPV), and negative (NPV) predictive values were generated, along with their 95%CIs.

Results

Upon manual review, 324 (33.2%) patients were POAF-positive. Our best-performing algorithm combining data from both sites used a look-back window of 6 years to exclude patients previously known for AF. This algorithm achieved 70.4% sensitivity (95%CI: 65.1–75.3), 86.0% specificity (95%CI: 83.1–88.6), 71.5% PPV (95%CI: 66.2–76.4), and 85.4% NPV (95%CI: 82.5–88.0). However, significant site-specific differences in sensitivity and NPV were observed.

Conclusion

An algorithm based on administrative data can identify POAF patients with moderate accuracy. However, site-specific variations in coding practices have significant impact on accuracy.
Evaluating the impact of the weather conditions on the influenza propagation
Authors: Singh David E. , Marinescu Maria-Cristina , Carretero Jesus , Delgado-Sanz Concepcion , Gomez-Barroso Diana , Larrauri Amparo
Published: April 2020

Background

Predicting the details of how an epidemic evolves is highly valuable as health institutions need to better plan towards limiting the infection propagation effects and optimizing their prediction and response capabilities. Simulation is a cost- and time-effective way of predicting the evolution of the infection as the joint influence of many different factors: interaction patterns, personal characteristics, travel patterns, meteorological conditions, previous vaccination, etc. The work presented in this paper extends EpiGraph, our influenza epidemic simulator, by introducing a meteorological model as a modular component that interacts with the rest of EpiGraph’s modules to refine our previous simulation results. Our goal is to estimate the effects of changes in temperature and relative humidity on the patterns of epidemic influenza based on data provided by the Spanish Influenza Sentinel Surveillance System (SISSS) and the Spanish Meteorological Agency (AEMET).

Methods

Our meteorological model is based on the regression model developed by AB and JS, and it is tuned with influenza surveillance data obtained from SISSS. After pre-processing this data to clean it and reconstruct missing samples, we obtain new values for the reproduction number of each urban region in Spain, every 10 minutes during 2011. We simulate the propagation of the influenza by setting the date of the epidemic onset and the initial influenza-illness rates for each urban region.

Results

We show that the simulation results have the same propagation shape as the weekly influenza rates as recorded by SISSS. We perform experiments for a realistic scenario based on actual meteorological data from 2010-2011, and for synthetic values assumed under simplified predicted climate change conditions. Results show that a diminishing relative humidity of 10% produces an increment of about 1.6% in the final infection rate. The effect of temperature changes on the infection spread is also noticeable, with a decrease of 1.1% per extra degree.Conclusions: Using a tool like ours could help predict the shape of developing epidemics and its peaks, and would permit to quickly run scenarios to determine the evolution of the epidemic under different conditions. We make EpiGraph source code and epidemic data publicly available.
Long-term survival trends in patients with unresectable stage III non-small cell lung cancer receiving chemotherapy and radiation therapy: a SEER cancer registry analysis
Authors: Hansen Ryan N. , Zhang Yiduo , Seal Brian , Ryan Kellie , Yong Candice , Darilay Annie , Ramsey Scott D.
Published: April 2020

Background

To evaluate the value of new therapies for non-small cell lung cancer (NSCLC), it is necessary to understand overall survival (OS) rates associated with previous standard therapies and how these rates have evolved over time.

Methods

We retrospectively analyzed data from patients enrolled in the Surveillance, Epidemiology, and End Results (SEER) cancer registry. Adults with unresectable, stage III NSCLC treated with chemoradiotherapy were grouped by diagnosis year (2000–2002; 2003–2005; 2006–2008; 2009–2011; 2012–2013). The primary endpoint was OS (data cut-off, December 31, 2014), estimated using the Kaplan–Meier estimator. Temporal survival-trend significance was tested using a two-sided log-rank trend test.

Results

Of 12,865 eligible patients, 59.1% were male, 59.9% had stage IIIB disease, and 62.7% had non-squamous histology. Median age at diagnosis was 67 years. Overall, 10,899 (84.7%) patients died and 1966 (15.3%) were censored/lost to follow-up. Median follow-up (95% confidence interval [CI]) was 80 (77–82) months; median OS (95% CI) was 15 (15–16) months; 1- and 3-year survival probabilities (95% CI) were 57.7% (56.9–58.6) and 24.1% (23.3–24.8), respectively. Stratification by diagnosis year showed consistent improvements in survival over time (p < 0.0001 for trend). Median OS was 12, 14, 15, 18, and 19 months in successive cohorts.

Conclusions

OS in patients diagnosed with unresectable, stage III NSCLC between 2003 and 2013 was consistent with that from clinical studies of sequential/concurrent chemoradiotherapy. Despite improvement over time, median OS was < 2 years and mortality remained high during the first year post-diagnosis.
PD-L1 and PD-L2 expression in the tumor microenvironment including peritumoral tissue in primary central nervous system lymphoma
Authors: Furuse Motomasa , Kuwabara Hiroko , Ikeda Naokado , Hattori Yasuhiko , Ichikawa Tomotsugu , Kagawa Naoki , Kikuta Kenichiro , Tamai Sho , Nakada Mitsutoshi , Wakabayashi Toshihiko , Wanibuchi Masahiko , Kuroiwa Toshihiko , Hirose Yoshinobu , Miyatake Shin-Ichi
Published: April 2020

Background

The prevalence of programmed death-ligand 1 (PD-L1) and PD-L2 expression on tumor cells and tumor-infiltrating immune cells in primary central nervous system lymphoma (PCNSL) remains unclear. In the present study, we analyzed needle biopsy and craniotomy specimens of patients with PCNSL to compare the PD-L1 and PD-L2 levels in the tumor and surrounding (peritumoral) tissue. We also assessed the correlation between biological factors and the prognostic significance of PD-L1 and PD-L2 expression.

Methods

We retrospectively analyzed the cases of 70 patients histologically diagnosed with PCNSL (diffuse large B-cell lymphoma). Immunohistochemistry for CD20, CD68, PD-L1, and PD-L2 was performed. In cases with specimens taken by craniotomy, the percentages of PD-L1- and PD-L2-positive macrophages were evaluated in both tumor and peritumoral tissue. The Kaplan-Meier method with log-rank test and Cox proportional hazard model were used for survival analysis.

Results

The tumor cells expressed little or no PD-L1 and PD-L2, but macrophages expressed PD-L1 and PD-L2 in most of the patients. The median percentage of PD-L2-positive cells was significantly higher among peritumoral macrophages (32.5%; 95% CI: 0–94.6) than intratumoral macrophages (27.5%; 95% CI: 0–81.1, p = 0.0014). There was a significant correlation between the percentages of PD-L2-positive intratumoral macrophages and PD-L2-positive peritumoral macrophages (p = 0.0429), with very low coefficient correlation (ρ = 0.098535). PD-L1 expression on macrophages was significantly associated with biological factors (intratumoral macrophages: better KPS, p = 0.0008; better MSKCC score, p = 0.0103; peritumoral macrophages: low proportion of LDH elevation, p = 0.0064) and longer OS (for intratumoral macrophages: high PD-L1 = 60 months, 95% CI = 30–132.6; low PD-L1 = 24 months, 95% CI = 11–48; p = 0.032; for peritumoral macrophages: high PD-L1 = 60 months, 95% CI = 30.7–NR; low PD-L1 = 14 months, 95% CI = 3–26). PD-L1 expression on peritumoral macrophages was strongly predictive of a favorable outcome (HR = 0.30, 95% CI = 0.12–0.77, p = 0.0129).

Conclusions

Macrophages in intratumoral and peritumoral tissue expressed PD-L1 and PD-L2 at a higher rate than tumor cells. PD-L1 expression, especially on peritumoral macrophages, seems to be an important prognostic factor in PCNSL. Future comprehensive analysis of checkpoint molecules in the tumor microenvironment, including the peritumoral tissue, is warranted.
Intraocular pressure changes and corneal biomechanics after hyperopic small-incision lenticule extraction
Authors: Fu Dan , Li Meiyan , Knorz Michael C. , Wei Shengsheng , Shang Jianmin , Zhou Xingtao
Published: April 2020

Background

We aimed to compare the intraocular pressure (IOP) measurements by a dynamic Scheimpflug analyzer (Corvis ST), a non-contact tonometer, and an ocular response analyzer after hyperopic small-incision lenticule extraction (SMILE).

Methods

Thirteen patients who underwent hyperopic SMILE in one eye were enrolled prospectively. IOP and corneal biomechanical parameters were measured preoperatively and at 1 week, 1 month, and 3 months postoperatively with a non-contact tonometer (IOPNCT), Corvis ST (biomechanical corrected IOP [bIOP]), and ocular response analyzer (Goldmann-correlated intraocular pressure [IOPg] and cornea compensated IOP [IOPcc]). A linear mixed model was used to compare the IOPs and biomechanical values among methods at each time point.

Results

IOPNCT, IOPg, and IOPcc dropped significantly after surgery, with the amplitude being 3.15 ± 0.48 mmHg, 5.49 ± 0.94 mmHg, and 4.34 ± 0.97 mmHg, respectively, at the last follow-up visit. IOPNCT decreased by 0.11 ± 0.06 mmHg per μm of excised central corneal thickness. bIOP did not change significantly after surgery. Preoperatively, no difference was found among the four measurements (P > 0.05). Postoperatively, IOPNCT and bIOP were higher than IOPg and IOPcc. bIOP was independent of cornea thickness at last follow-up visit, whereas it correlated significantly with corneal biomechanics similar to the other three IOP values.

Conclusion

bIOP is a relative accurate measure of IOP after hyperopic SMILE.
Efficacy of a self-applied online program to promote resilience and coping skills in university students in four Spanish-speaking countries: study protocol for a randomized controlled trial
Authors: Palma-Gómez Araceli , Herrero Rocío , Baños Rosa , García-Palacios Azucena , Castañeiras Claudia , Fernandez Gabriela Lidia , Llull Dario Martín , Torres Lorena Cudris , Barranco Libia Alvis , Cárdenas-Gómez Leonardo , Botella Cristina
Published: April 2020

Background

There is evidence of a high prevalence of depression and anxiety in university students. Therefore, college time is a key period where prevention of mental disorders through interventions that promote resilience and mental health can be relevant. Currently, there are interventions available, but these are insufficient for those who need them. Online interventions are tools that can facilitate global accessibility and are easy for young people to use. CORE (Cultivating Our Resilience) is a self-administered online program, based on Ryff’s psychological well-being model, to promote resilience and coping skills in university students at risk of developing symptoms of depression or anxiety. The objective is to evaluate the effectiveness of this intervention protocol in comparison with an active control condition targeting healthy lifestyle, and a waiting list control condition. The study will be conducted in four populations of Spanish-speaking university students (Spain, Argentina, Colombia, and Mexico).

Methods

The study design is a randomized controlled trial (RCT). At least 324 university students will be randomly assigned to three conditions: 1) CORE, a 6-week training program to improve resilience; 2) HLP, a 6-week training to promote a healthy lifestyle; and 3) WL, waiting list control condition. The primary outcome measure will be the Connor-Davidson resilience scale. Additionally, measures of anxiety, depression, quality of life and socio-demographic variables (age, sex, incomes, marital status, among others) will be collected. Participants will be evaluated at pre-treatment, after each module, 6 weeks after allocation, and at 3-month follow-up. Intention-to-treat and per-protocol analyses will be performed.

Discussion

The results of this study will contribute to research on Internet-administered interventions and the implementation of a protocol that includes a series of components designed to improve resilience and coping skills, increase psychological well-being, and prevent depression and anxiety disorders in Spanish-speaking university students. In addition, avenues will be opened up for new research on the effectiveness of these interventions focused on the prevention and promotion of mental health in Spanish-speaking countries.

Trial registration

Registered at ClinicalTrials.gov NCT03903978 on April 2, 2019.
Epidemiology of schizophrenia and its management over 8-years period using real-world data in Spain
Authors: Orrico-Sánchez A. , López-Lacort M. , Muñoz-Quiles C. , Sanfélix-Gimeno G. , Díez-Domingo J.
Published: April 2020

Background

Real-World Data (RWD) studies provide important insights in disease epidemiology, in real clinical populations, with long follow-up periods. The aim of the present study was to describe the epidemiology of schizophrenia spectrum disorders (SD) during an 8-year period in Spain.

Methods

A retrospective cohort of subjects aged 15 to 64 years was followed-up using electronic healthcare databases of the Valencia region (2008–2015). SD cases included outpatient and inpatient settings (ICD 9 codes 295.XX). Prevalence of SD was assessed. Incidence rate (IR) in the subpopulation aged between 15 and 34 years was also provided. Healthcare utilization (HCU) rates, including outpatient, specialists, hospitalizations and antipsychotic dispensations were estimated.

Results

The cohort included 3,976,071 subjects; 24,749 of them had a prevalent diagnosis of SD. The overall prevalence for SD was 6.2 per 1000 persons. SD were 76% more prevalent in men than women. IR in the subpopulation aged between 15 and 34 years was 50.25 per 100,000 persons years and was more than 2 times higher for men than for women. 83.4% of the overall outpatient visits from the cohort of patients were related to SD. The 21,095 overall hospitalizations with the SD code resulted in 286,139 days of hospitalization, with a median of 4 days (IQR: 1.6–9.2) per person-year. 93.2% of subjects diagnosed with SD were ever treated with some antipsychotic drug during the study period, and 70% of the patients were ever treated with antipsychotic polypharmacy.

Conclusions

This large population-based study using RWD provides novel and recent information SD in a southern European country. The prevalence and IR of SD showed is greater than previously published and higher in men than in women. The fact of having used a large arsenal of electronic data (including outpatient and inpatient) for 8 years may have influenced. SD represents high burden and healthcare utilization. Contrary to guidelines recommendations the majority of patients were ever treated with antipsychotic polypharmacy.
Association of Serum Uric Acid with cardio-metabolic risk factors and metabolic syndrome in seafarers working on tankers
Authors: Baygi Fereshteh , Herttua Kimmo , Sheidaei Ali , Ahmadvand Alireza , Jensen Olaf Chresten
Published: April 2020

Background

There is still controversy over the clinical interpretation of the association between metabolic syndrome (MetS) and serum uric acid (SUA) levels. Therefore, the aim of this study was to investigate the association of SUA levels with MetS and other cardio-metabolic risk factors (CMRF) in seafarers working on tankers.

Methods

This cross-sectional study was conducted in 2015 and included 234 male seafarers working on tankers. The participants were divided into three groups based on the tertiles of SUA. The report from of the National Committee of Obesity was used to define the MetS. The relationship between SUA, CMRF and MetS adjusted for age, educational level, job history, shift work, smoking and BMI was assessed by logistic regression analysis.

Results

The subjects were aged 36.0 ± 10.3 years (mean ± SD). A notable upward trend was observed in mean weight, body mass index (BMI), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL) and very low-density lipoprotein (VLDL) as tertiles of SUA increased (P < 0.001). In all models of the logistic regression analyses, the odds ratio (OR) of high TG for participants in the 3rd tertile of SUA was four times higher than that for participants in the 1st tertile of SUA (P < 0.001). The odds ratio of high TC and the SUA levels increased, so that the odds ratio of high TC for participants in the 2nd tertile was 2.47 (95% CI: 1.10–5.53) (P < 0.05) as compared with that for participants in the 1st tertile. Significant association was observed between MetS and the levels of SUA; 6.10 (95% CI: 1.77–20.94) (P < 0.05).

Conclusions

Findings revealed that SUA levels were associated with MetS, high TG and high TC. Therefore, it is recommended that clinical attention should be given to symptoms related to elevated SUA - being one of the most important remediable risk factors for MetS - in the annual medical examinations of seafarers.
Prevalence of primary headache disorders among information technology staff in China: the negative effects of computer use and other correlative factors
Authors: Li Chunlin , Zhang Lei , Zhou Jin , Fan Zhiliang , Wang Yan , Wang Xiaolin , Wang Weidong , Yu Shengyuan
Published: April 2020

Background

To date, there have been very few studies that have explored the relationship between headaches and computer use. The chief aim of this study is to investigate the prevalence of primary headache disorders among informational technology staff and identify the potential factors contributing to it.

Methods

This is a cross-sectional study based on annual health checks of employees from the information technology industry. We identified 2216 information technology staff members from Beijing by stratified random sampling who met the inclusion criteria. All participants were initially required to have a physical examination, after which they complete a general situation questionnaire that included a headache screening question. Those who had suffered from headache within the previous year also completed the questionnaire developed by Lifting the Burden. The International Classification of Headache Disorders 3(ICHD-3) criteria was used for the diagnosis of headache.

Results

A total of 2012 valid questionnaires (males, 1544 [76.7%]; females, 468 [23.3%]) were obtained from 2216 participants for a response rate of 90.8%. A total of 619 participants were diagnosed with primary headache, the one-year prevalence of which was 30.8%. Regarding the classification of the primary headache, 152 participants suffered from migraine, with a one-year prevalence of 7.6%; 440 and 27 suffered from tension-type headache and unclassified headaches, with one-year prevalences of 21.9 and 1.3%, respectively. Multivariate regression analysis showed that female gender was a risk factor for migraine and tension-type headache (OR 3.21[95% CI 2.28–4.53] and 1.88[95% CI 1.47–2.40], respectively). Age was also related to migraine and tension-type headache. The 41–50 age group had 2.02 times the probability of migraine, and the 31–40 age group had 1.89 times the probability of tension-type headaches compared to the 18–30 age group. Obesity and excessive computer use (more than 12 h per day) were also factors contributing to tension-type headache (OR: 2.61[95% CI 1.91–3.56] and 1.63[95% CI 1.18–2.25], respectively).

Conclusions

The one-year prevalence of primary headache in this population was 30.8%. The prevalence of tension-type headache in this population was higher than that in the general Chinese population. The occurrence of primary headache is correlated with many factors, among which excessive computer use significantly contributed to the risk of tension-type headache.
The association between BMI and health-related physical fitness among Chinese college students: a cross-sectional study
Authors: Chen Xiaobin , Cui Jie , Zhang Yuyuan , Peng Wenjia
Published: April 2020

Background

Existing studies reporting on the levels of physical fitness among college students used relatively few fitness tests as a reflection of physical fitness, which could not comprehensively evaluate the levels of physical fitness. Thus, the current study aimed to investigate the cross-sectional relationship between body mass index (BMI) and a physical fitness index (PFI) based on six indicators of fitness in Chinese college students.

Method

Anthropometric measurements and six measures of physical fitness (Vital capacity, 50-m sprint, sit and reach, standing long jump, 800/1000-m run, pull-up/bent-leg sit-up) were measured. BMI was calculated to classify individuals into underweight, normal weight, overweight, and obesity groups. Z-scores based on sex-specific mean and standard deviation were calculated, and the sum of z-scores for the six fitness tests was used as a PFI. Three models (a linear regression model, polynomial regression model with a second-order BMI term and a restricted cubic spline regression model) were fitted to discuss the potential relation between BMI and PFI. We compared the models using Akaike Information Criterion (AIC) and R square.

Results

Totally, 8548 freshmen from the years 2014 to 2016 in a medical college completed the physical fitness tests. There was a decreasing trend of physical fitness index from the years 2014 to 2016 (P for trend < 0.01). More male than female students were overweight or obese (23.5% vs. 11.9%), but more female than male students were normal weight (74.7% vs. 64.8%). A restricted cubic spline regression model was superior to linear and polynomial regression model with lower AIC and higher R square.

Conclusions

The relationships between BMI and PFI in college students were non-linear. Underweight, overweight and obese students had poorer performance in physical fitness index than normal weight students. Future prospective, longitudinal cohort studies to identify the causal relations and potential mechanism in a good manner are required.
Household presentation of acute gastroenteritis in a primary care sentinel network: retrospective database studies
Authors: de Lusignan Simon , Sherlock Julian , Ferreira Filipa , O’Brien Sarah , Joy Mark
Published: April 2020

Background

Acute gastroenteritis (AGE) is a highly transmissible condition spreading rapidly between individuals and within households. Rotavirus vaccination was introduced in the UK in 2013. The study objectives were to investigate how acute gastroenteritis incidence changed over 25 years and household incidence of AGE since 2013.

Methods

Repeated cross-sectional study of Royal College of General Practitioners Research and Surveillance Centre network. We used a negative binomial model to report incidence rate ratio (IRR) using the last 5 years data. We also conducted a retrospective cohort analysis, using a shared gamma frailty model (2013–2017). We explored the impact of child under 5- years, household size, socioeconomic status quintile, and rurality.

Results

In the cross-sectional analysis, the IRR of AGE in households with a child of under 5 years was 12.20 (95%CI 11.08–13.45-,p < 0.001) compared with households without; the IRR fell across IMD quintiles, for example there is a 37% decrease in incidence comparing IMD quintile 1 to quintile 5 (95%CI -0.52-0.76,p < 0.001),

The cohort study revealed that the presence of an under 5 in the household was associated with a higher risk of household presentation (HR = 6.29, 95% CI 5.61–7.06,p < 0.001). In addition, we observe a reduction in risk of presentation from the most to the least deprived socioeconomic quintile (second quintile: HR = 0.74 (95%CI 0.59–0.92), to least deprived quintile, HR = 0.55 (95%CI 0.41–0.74). We saw a lower association with male gender, white ethnicity and living outside London, but an increased association with increasing household size.

Conclusions

The incidence of AGE has changed over time: pre-school children, larger households, and living in London were associated with higher rates, and male gender and higher economic status associated with lower rates.
Characterization of visceral leishmaniasis outbreak, Marsabit County, Kenya, 2014
Authors: Kanyina Evalyne Wambui
Published: April 2020

Background

Visceral leishmaniasis (VL) is caused by protozoa of the Leishmania donovani complex. Annually, an estimated 500,000 cases of VL are reported globally posing a public health challenge. The objectives of our study were to confirm and determine the magnitude of VL outbreak, characterize the outbreak clinically and epidemiologically and evaluate the county preparedness and response in Marsabit County, Kenya.

Methods

A retrospective review of laboratory registers and patients’ clinical notes was done at Marsabit County Hospital. Cases were persons with confirmed VL diagnosis either by microscopy, serology or molecular technique coming from Marsabit County from May to October 2014. Cases were interviewed using structured questionnaire to collect clinical and epidemiologic information. Blood samples were collected from cases for laboratory confirmation.

Results

A total of 136 cases were confirmed of which 77% (105) were male with a median age of 17 (IQR: 22) years and 9.6% (13) case fatality rate. All cases were admitted at Marsabit County Referral Hospital, Kenya. Medical records of 133 cases were retrieved. Of the 133 cases, 102 (77%) presented with fever, 43 (32%) with splenomegaly, 26 (20%) with hepatomegaly and 96 (72%) were managed with Sodium stibogluconate (SSG) monotherapy. Thirty-four cases (26%) received Full haemogram (FHG) test and none had more than one Liver Function Tests (LFTs) in a span of 6 months. Presenting with headache (OR: 4.21, 95% CI: 1.10–16.09) and hepatomegaly (OR: 4.2, 95% CI: 1.30–14.11) were associated with VL death. No VL case management training had been conducted nor VL treatment guidelines distributed among health care workers (HCWs) in the last 1 year.

Conclusions

VL cases were confirmed. Inadequate case monitoring and management was evident. VL case management sensitization training was conducted. The County health department should put in place one health VL surveillance and facilitate periodic case management trainings.
Comparative efficacy of statins, metformin, spironolactone and combined oral contraceptives in reducing testosterone levels in women with polycystic ovary syndrome: a network meta-analysis of randomized clinical trials
Authors: Almalki Hussain H. , Alshibani Turki M. , Alhifany Abdullah A. , Almohammed Omar A.
Published: April 2020

Background

Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting about 10% of women in reproductive age and associated with a variety of hormonal abnormalities, including hyperandrogenemia and infertility, all of which could lead to PCOS. Statins were previously introduced as a therapeutic option for reducing testosterone levels in women with PCOS, either alone or in combination. The aim of this study is to evaluate the effectiveness of different statins alone or in combination with metformin in reducing testosterone levels in women with PCOS.

Methods

Medline, Embase, and clinicaltrials.gov were searched for studies that investigated the efficacy of statins, metformin, spironolactone, or combined oral contraceptives (COCs), individually or in combination, in reducing the testosterone level in patients with PCOS. The search was limited to randomized clinical trials and conducted according to the preferred reporting items for systematic reviews and meta-analyses - extension statement for network meta-analyses (PRISMA-NMA). The quality of included studies was assessed using the Cochrane Collaboration risk of bias (RoB) assessment tool. A frequentist network meta-analysis using random-effects models was used to assess the efficacy in reducing testosterone level and were expressed as odds ratios (OR) and 95% credible interval (95%Crl). All statistical analyses were performed using netmeta Version 1.0 on R statistical package.

Result

Nine RCTs involving 613 patients were included. Atorvastatin showed greater reduction in testosterone level compared to COC (MD −2.78, 95%CrI −3.60, −1.97), spironolactone plus metformin (MD −2.83, 95%CrI −3.80, −1.87), simvastatin (MD −2.88, 95%CrI −3.85, −1.92), spironolactone (MD −2.90, 95%CI −3.77, −2.02), simvastatin plus metformin (MD −2.93, 95%CrI −3.79, −2.06), metformin (MD −2.97, 95%CrI −3.69, −2.25), lifestyle modification (MD −3.02, 95%CrI −3.87, −2.18), and placebo (MD −3.04, 95%CrI −3.56, −2.53).

Conclusion

Atorvastatin was found to be more effective than the other management strategies in reducing the total testosterone level for patients with PCOS. Future studies should focus on the optimal dose.
Chronic oral safety study of the aqueous extract of Combretum molle twigs on biochemical, haematological and antioxidant parameters of Wistar rats
Authors: Miaffo David , Wansi Sylvie Léa , Ntchapda Fidèle , Kamanyi Albert
Published: April 2020

Background

Combretum molle R.B/G. Don (Combretaceae) is a graceful deciduous shrub, distributed especially in tropical Africa and used in traditional medicine in the treatment of malaria, diabetes, and bacterial, liver and cardiovascular deseases. To our knowledge, no long-term toxicity studies of C. molle has ever been realized yet.

Methods

The long-term toxicity study was conducted in accordance with OECD 408 guidelines with slight modifications. In fact, rats were divided in groups and treated orally with CMAE at doses of 62.5, 125 and 250 mg/kg for 6 months. The general behavior and signs of toxicity of the rats were daily observed. Body weight, food and water intake were recorded every 2 months for 6 months. At the end of treatment period, urine and blood samples were collected for hematological, biochemical and antioxidant estimations. Immediately, internal organs were collected and weighed.

Results

The results showed that no mortality and visible signs of the toxicity were recorded in all experimental animals. The administration of CMAE had no significant effects on body weight, organ weights, serum electrolyte, and food and water intake. However, all doses of CMAE produced an increase in high density lipoprotein cholesterol, white blood cells, platelets, glutathione, and a decrease in low density lipoprotein cholesterol and malondialdehyde rate. CMAE at doses of 125 and 250 mg/kg decreased in serum proteins and the activity of aspartate amino transferase, and increased the activity of catalase. In addition, CMAE (250 mg/kg) significantly decreased the alanine aminotransferase activity and the level of triglycerides, very low density cholesterol, total proteins and creatinine, and increased in renal clearance, red blood cells, hemoglobin, hematocrit and superoxide dismutase activity.

Conclusions

At the end of this study, no signs of major intoxication was noted during 6 months of treatment. These results suggest that long-term consumption of CMAE at the therapeutic dose (250 mg/kg) presents low risks to human health.
Water extract from processed Polygonum multiflorum modulate gut microbiota and glucose metabolism on insulin resistant rats
Authors: Gu Wen , Yang Min , Bi Qian , Zeng Lin-Xi , Wang Xi , Dong Jin-Cai , Li Feng-Jiao , Yang Xing-Xin , Li Jing-Ping , Yu Jie
Published: April 2020

Background

The incidence of insulin resistance (IR) has rapidly increased worldwide over the last 20 years, no perfect solution has yet been identified. Finding new therapeutic drugs will help improve this situation. As a traditional Chinese medicine, PPM (processed Polygonum multiflorum) has widely been used in the clinic. Recently, other clinical functions of PPM have been widely analyzed.

Results

Administration of the water extract from PPM decreased the level of FBG, TC, and TG, and increased the level of FGC, thereby reducing the IR index and improving IR. Furthermore, Western blot analysis revealed that PPM significantly increased GPR43 and AMPK expression when compared with the MOD group, and GPR43, AMPK were known as glucose metabolism-related proteins. In addition, treatment with PPM can restore the balance of gut microbiota by adjusting the relative abundance of bacteria both at the phylum and genus level, and these changes have been reported to be related to IR.

Methods

Sprague Dawley (SD) rats were fed a high-fat diet and were gavaged daily with either normal saline solution or PPM for 12 weeks. Major biochemical indexes, such as fasting blood glucose (FBG), fasting glucagon (FGC), total cholesterol (TC), and triglyceride (TG) were measured. Then the protein expression of adenosine 5′-monophosphate -activated protein kinase (AMPK) and G protein-coupled receptor 43 (GPR43) was evaluated by using Western blot analysis. Moreover, the composition of gut microbiota was assessed by analyzing 16S rRNA sequences.

Conclusions

Our findings showed that PPM reversed the increasing of FBG and the decreasing of IRI, PPM accelerated the expression of glucose metabolism-related proteins and regulated the intestinal microecological balance. Therefore, we hold the opinion that PPM may be an effective option for treating IR.
Leveraging implementation science to reduce inequities in Children’s mental health care: highlights from a multidisciplinary international colloquium
Authors: Stadnick Nicole A. , Aarons Gregory A. , Blake Lucy , Brookman-Frazee Lauren I. , Dourgnon Paul , Engell Thomas , Jusot Florence , Lau Anna S. , Prieur Constance , Skar Ane-Marthe Solheim , Barnett Miya L.
Published: April 2020

Background and purpose

Access to evidence-based mental health care for children is an international priority. However, there are significant challenges to advancing this public health priority in an efficient and equitable manner. The purpose of this international colloquium was to convene a multidisciplinary group of health researchers to build an agenda for addressing disparities in mental health care access and treatment for children and families through collaboration among scholars from the United States and Europe engaged in innovative implementation science and mental health services research.

Key highlights

Guided by the Exploration, Preparation, Implementation, and Sustainment (EPIS) Framework, presentations related to inner, outer, and bridging context factors that impact the accessibility and quality of mental health evidence-based practices (EBPs) for children and families. Three common topics emerged from the presentations and discussions from colloquium participants, which included: 1) the impact of inner and outer context factors that limit accessibility to EBPs across countries, 2) strategies to adapt EBPs to improve their fit in different settings, 3) the potential for implementation science to address emerging clinical and public health concerns.

Implications

The common topics discussed underscored that disparities in access to evidence-based mental health care are prevalent across countries. Opportunities for cross-country and cross-discipline learnings and collaborations can help drive solutions to address these inequities, which relate to the availability of a trained and culturally appropriate workforce, insurance reimbursement policies, and designing interventions and implementation strategies to support sustained use of evidence-based practices.
Metal air pollution partnership solutions: building an academic-government-community-industry collaboration to improve air quality and health in environmental justice communities in Houston
Authors: Symanski Elaine , An Han Heyreoun , Hopkins Loren , Smith Mary Ann , McCurdy Sheryl , Han Inkyu , Jimenez Maria , Markham Christine , Richner Donald , James Daisy , Flores Juan
Published: April 2020

Background

From 2006 to 2011, the City of Houston received nearly 200 community complaints about air pollution coming from some metal recycling facilities. The investigation by the Houston Health Department (HHD) found that while operating within legal limits, emissions from facilities that use torch cutting, a technique generating metal aerosols, may increase health risks for neighboring residents. Choosing to use collaborative problem solving over legislative rulemaking, HHD reached out to The University of Texas Health Science Center at Houston (UTHealth) to further evaluate and develop plans to mitigate, if necessary, health risks associated with metal emissions from these facilities.

Methods

Utilizing a community-based participatory research approach, we constituted a research team from academia, HHD and an air quality advocacy group and a Community Advisory Board (CAB) to draw diverse stakeholders (i.e., frustrated and concerned residents and wary facility managers acting within their legal rights) into an equitable, trusting and respectful space to work together. Next, we investigated metal air pollution and inhalation health risks of adults living near metal recyclers and ascertained community views about environmental health using key informant interviews, focus groups and surveys. Finally, working collaboratively with the CAB, we developed neighborhood-specific public health action plans to address research findings.

Results

After overcoming challenges, the CAB evolved into an effective partnership with greater trust, goodwill, representation and power among members. Working together to translate and share health risk assessment results increased accessibility of the information. These results, coupled to community survey findings, set the groundwork for developing and implementing a stakeholder-informed action plan, which included a voluntary framework to reduce metal emissions in the scrap yard, improved lines of communication and environmental health leadership training. Tangible outcomes of enhanced capacity of our community and governmental partners included trained residents to conduct door-to-door surveys, adaptation of our field training protocol and survey by our community partner and development of a successful HHD program to engage residents to improve environmental health in their neighborhood.

Conclusions

Academic-government-community-industry partnerships can reduce environmental health disparities in underserved neighborhoods near industrial facilities.
Targeting the spatial context of obesity determinants via multiscale geographically weighted regression
Authors: Oshan Taylor M. , Smith Jordan P. , Fotheringham A. Stewart
Published: April 2020

Background

Obesity rates are recognized to be at epidemic levels throughout much of the world, posing significant threats to both the health and financial security of many nations. The causes of obesity can vary but are often complex and multifactorial, and while many contributing factors can be targeted for intervention, an understanding of where these interventions are needed is necessary in order to implement effective policy. This has prompted an interest in incorporating spatial context into the analysis and modeling of obesity determinants, especially through the use of geographically weighted regression (GWR).

Method

This paper provides a critical review of previous GWR models of obesogenic processes and then presents a novel application of multiscale (M)GWR using the Phoenix metropolitan area as a case study.

Results

Though the MGWR model consumes more degrees of freedom than OLS, it consumes far fewer degrees of freedom than GWR, ultimately resulting in a more nuanced analysis that can incorporate spatial context but does not force every relationship to become local a priori. In addition, MGWR yields a lower AIC and AICc value than GWR and is also less prone to issues of multicollinearity. Consequently, MGWR is able to improve our understanding of the factors that influence obesity rates by providing determinant-specific spatial contexts.

Conclusion

The results show that a mix of global and local processes are able to best model obesity rates and that MGWR provides a richer yet more parsimonious quantitative representation of obesity rate determinants compared to both GWR and ordinary least squares.
The effect of smoking on biological change of recurrent breast cancer
Authors: Takada Koji , Kashiwagi Shinichiro , Asano Yuka , Goto Wataru , Kouhashi Rika , Yabumoto Akimichi , Morisaki Tamami , Fujita Hisakazu , Shibutani Masatsune , Takashima Tsutomu , Hirakawa Kosei , Ohira Masaichi
Published: April 2020

Background

The selection of treatment for a patient with breast cancer largely relies on the cancer subtype. However, this process is complicated by changes in tumor biology at relapse. Smoking has been identified as a risk factor for breast cancer. The direct effect of a tobacco component delivered via blood circulation on the mammary gland tissue and subsequent DNA damage have been proposed to explain the association between cigarette smoking and breast cancer carcinogenesis. This postulation is supported by both tissue culture and animal studies demonstrating that the associated DNA damage further alters breast cancer cells, as indicated by an increased proliferative capacity and malignant transformation. In this study, we aimed to explore the relationship between changes in Estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) each receptor at recurrence, and smoking and the prognosis after recurrence.

Methods

This retrospective study included 989 patients with primary breast cancer who developed relapse after surgery and 50 patients who underwent regenerative biopsy or surgery from December 2007 to March 2018. ER, PgR, and HER2 expression in the primary and recurrent lesions was evaluated using immunohistochemistry, and the correlations of these expression patterns with smoking history (pack-years) were examined.

Results

When ER was evaluated in recurrent tumors, negative and positive conversions were recognized in 3 (6.0%) and 1 patient (2.0%), respectively. When PgR was evaluated, negative conversion was recognized in 15 patients (30.0%). When HER2 was evaluated, positive conversion was recognized in 6 patients (12.0%). Consequently, we observed a change in the intrinsic subtype in in 5 patients with recurrent tumors (10.0%). Although most clinical factors were not correlated with smoking, a positive conversion of HER2 in recurrence was significantly more frequent among smokers than among non-smokers (p = 0.024).

Conclusions

Biological changes during breast cancer recurrence should be given careful clinical consideration because they affect treatment after recurrence. Our results suggest that smoking may induce increased HER2 expression in recurrent breast tumors.
The USP18 cysteine protease promotes HBV production independent of its protease activity
Authors: Li Yujia , Yao Min , Duan Xiaoqiong , Ye Haiyan , Li Shilin , Chen Limin , Yang Chunhui , Chen Yongjun
Published: April 2020

Background

Hepatitis B virus (HBV) infection remains as one of the major public health problems in the world. Type I interferon (IFN) plays an essential role in antiviral defense by induced expression of a few hundred interferon stimulated genes (ISGs), including ubiquitin-specific protease 18 (USP18). The expression level of USP18 was elevated in the pretreatment liver tissues of chronic hepatitis B(CHB) patients who did not respond to IFN treatment. Thus, this study was designed to investigate the effects of USP18 on HBV replication/production.

Methods

The levels of wild type USP18(WT-USP18) and USP18 catalytically inactive form C64S were up-regulated by plasmids transfection in HepAD38 cells, respectively. Real-time PCR and ELISA were used to quantify HBV replication. Type I IFN signaling pathway was monitored at three levels: p-STAT1 (western Blot), interferon stimulated response element (ISRE) activity (dual luciferase assay) and ISGs expression (real time PCR).

Results

Our data demonstrated that overexpression of either WT-USP18 or USP18-C64S inactive mutant increased the intracellular viral pgRNA, total DNA, cccDNA, as well as HBV DNA levels in the culture supernatant, while silencing USP18 led to opposite effect on HBV production. In addition, upregulated WT-USP18 or USP18-C64S suppressed ISRE activity and the expression levels of p-STAT1 and ISGs.

Conclusion

USP18 promoted HBV replication via inhibiting type I IFN signaling pathway, which was independent of its protease activity.
Effectiveness of biological nurturing on early breastfeeding problems: a randomized controlled trial
Authors:   for the Trieste BN (Biological Nurturing) Investigators, Milinco Mariarosa , Travan Laura , Cattaneo Adriano , Knowles Alessandra , Sola Maria Vittoria , Causin Enrica , Cortivo Caterina , Degrassi Maura , Di Tommaso Francesca , Verardi Giuseppa , Dipietro Laura , Piazza Maria , Scolz Sabrina , Rossetto Martina , Ronfani Luca
Published: April 2020

Background

Biological nurturing is a neurobehavioral approach to breastfeeding support that encourages women to breastfed in a relaxed, laidback position. This approach has the potential to reduce breast problems (e.g., sore nipples), making good latch easier and thus facilitating the initiation of exclusive breastfeeding. However, its effects have not been adequately investigated in a real-life situation. The aim of this randomized controlled trial was to assess the effectiveness of biological nurturing, compared to usual hospital practices, on the frequency of breast problems and on the prevalence of exclusive breastfeeding at discharge from the maternity ward, after 1 week, and at one and 4 months.

Methods

Open randomized parallel controlled trial carried out in a third level maternity ward (IRCCS Burlo Garofolo, Trieste, Italy) between March and December 2018. Two-hundred eight women who planned to give birth at the hospital and who expressed the intention to breastfeed were enrolled during pregnancy and randomized to receive breastfeeding support following either the biological nurturing approach or the usual care protocol based on the WHO/UNICEF 20-h course, in use at the hospital. The primary study outcome was the incidence of breast problems during hospital stay, defined as the presence of one or more of the following outcomes, collected separately: sore nipples, cracked nipples, engorgement and mastitis. The primary analysis was performed by intention to treat. The follow up lasted 4 months.

Results

One hundred eighty eight out of 208 women (90.3%) were included in the analysis, 90 allocated to the biological nurturing group and 98 to the usual care group. At discharge from the maternity ward, biological nurturing significantly reduced the risk of breast problems (Relative risk [RR] 0.56, 95% Confidence Interval [CI] 0.40, 0.79), including cracked (RR 0.42, 95% CI 0.24, 0.74) and sore nipples (RR 0.59, 95% CI 0.40, 0.88). No statistically significant difference was observed for exclusive breastfeeding at discharge and up to 4 months. No adverse events occurred.

Conclusions

The biological nurturing approach applied in the real-life situation of a third level hospital was effective in preventing breast problems.

Trial registration

Clinicaltrials.gov NCT03503500. Date of First Submission: 28 March 2018.