bluuebunny/crossref_metadata_2025 huggingface dataset:
Pazopanib versus sunitinib in Chinese patients with locally advanced or metastatic renal cell carcinoma: pooled subgroup analysis from the randomized, COMPARZ studies
Authors: Sheng Xinan , Jin Jie , He Zhisong , Huang Yiran , Zhou Aiping , Wang Jinwan , Ren Xiubao , Ye Dingwei , Zhang Xu , Qin Shukui , Zhou Fangjian , Wang Binhui , Guo Jun
Published: March 2020

Background

We performed a pooled analysis of the COMPARZ study assessing efficacy and safety of pazopanib versus sunitinib in treatment-naïve Chinese patients with locally advanced and/or metastatic renal cell carcinoma (a/mRCC).

Methods

In the COMPARZ study, patients were randomized (1:1) to receive pazopanib 800 mg once daily (QD) continuously or sunitinib 50 mg QD in 6-week cycles (4 weeks on, 2 weeks off). The primary endpoint was progression-free survival (PFS); secondary endpoints included overall response rate (ORR), overall survival (OS), and safety. PFS and ORR were assessed by independent review committee (IRC) and local investigators.

Results

Of the 209 Chinese patients (pazopanib, [n = 109] and sunitinib, [n = 100]), 155 (74%) were males and median age was 57 years (range, 18–79). Median PFS was 13.9 months for pazopanib versus 14.3 months for sunitinib per investigator assessment and 8.3 months in both arms per IRC assessment; PFS hazard ratio was 1.17 (investigator) and 0.99 (IRC). Median OS was not reached in pazopanib arm and was 29.5 months in sunitinib arm. ORR was significantly higher in pazopanib arm versus sunitinib arm (investigator: 41% versus 23% [P = 0.0052]; IRC: 35% versus 20% [P = 0.0203]). Pazopanib was generally well tolerated in Chinese patients with a/mRCC. Most frequent AEs in the pazopanib arm were diarrhea and hair color changes whereas the most frequent AEs in the sunitinib arm were decreased platelets, decreased neutrophil count, and thrombocytopenia.

Conclusion

The results of the pooled analysis were consistent with the overall population in the COMPARZ study, and confirmed similar PFS and OS of pazopanib and sunitinib in the Chinese patients.

Trial registration

clinical trials.gov,NCT00720941(August 14, 2008) andNCT01147822(May 19, 2010).
Pseudoduplication of the optic disc initially resembling a bifurcated optic nerve in a strabismus child: a case report
Authors: Huang Liuhui , Zhang Qi , Jin Haiying , Zhao Peiquan
Published: March 2020

Background

Pseudoduplication of the optic disc is a rare clinical condition that is characterized by a circumscribed, disc-like lesion with radiating vessels but only one normal optic nerve. We report a rare case that initially resembled a bifurcated optic nerve in a strabismus child.

Case presentation

A 6-year-old female child was initially referred to our hospital due to perceptual exotropia of 15 degrees with poor fixation of the left eye. The visual acuity of the left eye was 3/100 with a refraction of + 1.75/− 1.25 × 175. Fundus images of her left eye revealed a circumscribed and disc-like lesion located one disc diameter (DD) below the true optic disc that showed profound central cupping resembling a second optic disc with a vascular supply. B scan ultrasonography showed an optic nerve with a bifurcated weak-echo region, suggesting that two strands originated from the optic nerve. Optic coherence tomography (OCT) demonstrated a large crater-like depression of the lesion, indicating a colobomatous defect covered by a mysterious membranous structure, a disturbed nerve fibre layer and the absence of regular outer retinal layers. A perimetric examination revealed a relatively superior defect. Magnetic resonance imaging (MRI) revealed the left eye globe showed an abnormal morphology and that the optic nerve was abnormally shaped and shifted nasally in the left eye. Fundus fluorescein angiography (FFA) of the left eye revealed the absence of independent vascular vessels in the disc-like lesion. Hyperfluorescence with patchy fluorescence was evident in the inferotemporal area of the disc. Vascular loops surrounding the temporal region were evident in both eyes. Her right eye was normal except for the vascular loop. We proposed that this represented a case of pseudoduplication of the optic disc. The patient did not undergo any treatment, and her visual acuity remained stable during the follow-up period.

Conclusions

Our patient presented with a deep and ectatic coloboma below the optic disc that communicated with the true optic nerve and was originally thought to indicate a bifurcated optic nerve. This case suggests that atypical ectatic colobomas should be considered before diagnosing malformations related to the optic nerve in double optic disc cases.
Analysis of the dietary factors associated with suspected pediatric nonalcoholic fatty liver disease and potential liver fibrosis: Korean National Health and Nutrition Examination Survey 2014-2017
Authors: Kim Mi Jin , Lee Kyung Jae
Published: March 2020

Background

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased as the obese pediatric population has increased. NAFLD causes progressive liver injury and the only effective treatment is lifestyle modifications. However, few studies have examined the dietary risk factors for pediatric NAFLD or liver fibrosis. Here, we evaluated the dietary factors associated with suspected NAFLD and potential liver fibrosis in Korean children.

Methods

Data collected from 1674 children and adolescents aged 10–18 years during the 2014–2017 Korean National Health and Nutrition Examination Surveys analyzed. The 24-h recall method measured the food consumed 1 day before the survey. The “suspected NAFLD” group included excessive body mass index (BMI) subjects ≥ 85th percentile) with alanine aminotransferase (ALT) levels exceeding the upper normal limit (24.1 U/L for boys and 17.7 U/L for girls); the “healthy control” group included subjects with a BMI and ALT level below these thresholds. Sodium intake was assessed by the urinary sodium-to-urinary specific gravity unit ratio (U-Na-to-SGU ratio). A pediatric NAFLD index (PNFI) higher than 3 indicated potential liver fibrosis.

Results

The overall prevalence of suspected NAFLD and potential liver fibrosis was 8.2 and 4.5%, respectively. The suspected NAFLD group had a larger proportion of males and subject with a greater height, BMI standard deviation score (BMI-SDS), systolic and diastolic blood pressure SDS, waist circumference, hemoglobin A1c, and levels of total cholesterol, triglycerides, aspartate aminotransferase (AST) and ALT than the control group. The suspected NAFLD group presented significantly higher U-Na-to-SGU ratios and cholesterol intake. The PNFI > 3 subgroup included a significantly larger proportion of males and subjects with higher BMI-SDS, AST and ALT values, and intake of water, carbohydrate, protein, calcium, phosphorus, iron and vitamin B2. After adjusting for confounders, male, BMI-SDS, AST, and protein and carbohydrate intake were independent risk factors for potential liver fibrosis. Niacin intake was an independent protective factor for potential liver fibrosis.

Conclusions

Children with suspected NAFLD had higher urinary sodium level and cholesterol intake than healthy controls. Protein and carbohydrate intake were independent risk factors for potential liver fibrosis; niacin was an independent protective factor.
Effectiveness of a school-based intervention on knowledge, attitude and practice on healthy lifestyle and body composition in Malaysian adolescents
Authors: Sharif Ishak Sharifah Intan Zainun , Chin Yit Siew , Mohd. Taib Mohd. Nasir , Chan Yoke Mun , Mohd. Shariff Zalilah
Published: March 2020

Background

The ‘Eat Right, Be Positive About Your Body and Live Actively’ (EPaL) intervention programme was developed to prevent overweight and disordered eating in Malaysian adolescents. This study aimed to evaluate the effectiveness of the EPaL programme on knowledge, attitudes and practices on healthy lifestyle and body composition (body mass index z-score [zBMI], waist circumference [WC] and body fat percentage [BF%]) among adolescents.

Methods

All measures were taken at three time points: before intervention (Pre), after intervention (Post I) and 3 months after intervention (Post II). The intervention group (IG) participated in the EPaL programme for 16 weeks, whereas the comparison group (CG) received no intervention. Seventy-six adolescents (IG: n = 34; CG: n = 42) aged 13–14 years were included in the final analysis. Repeated measures analysis of covariance (ANCOVA) was used to assess the impact of the EPaL intervention programme on the measures between groups (IG and CG) at Post I and Post II.

Results

The IG reported significantly higher knowledge scores at both Post I (adjusted mean difference = 3.34; 95% confidence interval [CI] = 0.99, 5.69; p = 0.006) and Post II (adjusted mean difference = 2.82; 95% CI = 0.86, 4.78; p = 0.005) compared with the CG. No significant differences between the IG and CG were found at either Post I or Post II in attitudes, practices, zBMI, WC and BF%. The proportion of participants who were overweight or obese was consistent from Pre to Post II in the IG (35.3%) and increased from 26.2% at Pre to 28.5% at Post II in the CG, but the difference was not statistically significant. The proportion of participants who had abdominal obesity in the IG decreased from 17.6% at Pre to 14.7% at Post II and increased from 16.7% at Pre to 21.4% at Post II in the CG, but the differences were not statistically significant.

Conclusion

Despite no significant reduction of body composition, this programme shows the positive effect on the adolescents’ knowledge regarding healthy lifestyle. This study contributes to the evidence on the effectiveness of school-based health interventions in Malaysian adolescents.

Trial registration

UMIN Clinical Trial Registration UMIN000024349. Registered 11 October 2016.
Spatio-temporal dynamics of EEG features during sleep in major depressive disorder after treatment with escitalopram: a pilot study
Authors: Wu Li , Wang Xue-Qin , Yang Yong , Dong Teng-Fei , Lei Ling , Cheng Qi-Qi , Li Su-Xia
Published: March 2020

Background

Previous studies have shown escitalopram is related to sleep quality. However, effects of escitalopram on dynamics of electroencephalogram (EEG) features especially during different sleep stages have not been reported. This study may help to reveal pharmacological mechanism underlying escitalopram treatment.

Methods

The spatial and temporal responses of patients with major depressive disorder (MDD) to escitalopram treatment were analyzed in this study. Eleven MDD patients and eleven healthy control subjects who completed eight weeks’ treatment of escitalopram were included in the final statistics. Six-channel sleep EEG signals were acquired during sleep. Power spectrum and nonlinear dynamics were used to analyze the spatio-temporal dynamics features of the sleep EEG after escitalopram treatment.

Results

For temporal dynamics: after treatment, there was a significant increase in the relative energy (RE) of δ1 band (0.5 - 2 Hz), accompanied by a significant decrease in the RE of β2 band (20 - 30 Hz). Lempel-Ziv complexity and Co - complexity values were significantly lower. EEG changes at different sleep stages also showed the same regulation as throughout the night sleep. For spatio dynamics: after treatment, the EEG response of the left and right hemisphere showed asymmetry. Regarding band-specific EEG complexity estimations, δ1 and β2 in stage-1 and δ1 in stage-2 sleep stage in frontal cortex is found to be much more sensitive to escitalopram treatment in comparison to central and occipital cortices.

Conclusions

The sleep quality of MDD patients improved, EEG response occurred asymmetry in left and right hemispheres due to escitalopram treatment, and frontal cortex is found to be much more sensitive to escitalopram treatment. These findings may contribute to a comprehensive understanding of the pharmacological mechanism of escitalopram in the treatment of depression.
Attitudes of European physicians towards the use of long-acting injectable antipsychotics
Authors: Patel Maxine X. , Bent-Ennakhil Nawal , Sapin Christophe , di Nicola Sylvie , Loze Jean-Yves , Nylander Anna-Greta , Heres Stephan
Published: March 2020

Background

Prescription rates for long-acting injectable (LAI) antipsychotic formulations remain relatively low in Europe despite improved adherence over alternative oral antipsychotic treatments. This apparent under-prescription of LAI antipsychotics may have multiple contributing factors, including negative mental health practitioner attitudes towards the use of LAIs.

Methods

The Antipsychotic Long acTing injection in schizOphrenia (ALTO) non-interventional study (NIS), conducted across several European countries, utilised a questionnaire that was specifically designed to address physicians’ attitudes and beliefs towards the treatment of schizophrenia with LAI antipsychotics. Exploratory principal component analysis (PCA) of feedback from the questionnaire aimed to identify and characterize the factors that best explained the physicians’ attitudes towards prescription of LAIs.

Results

Overall, 136/234 solicited physicians returned fully completed questionnaires. Physicians’ mean age was 48.5 years, with mean psychiatric experience of 20.0 years; 69.9% were male, 84.6% held a consultant position, and 91.9% had a clinical specialty in general adult care. Most physicians considered themselves to have a high level of clinical experience with LAI antipsychotics (77.2%), with an increased rate of LAI antipsychotics prescription over the last 5 years (59.6%). Although the majority of physicians (69.9%) declared feeling no difference in stress levels when offering LAI compared to oral antipsychotics, feelings of ‘no/more stress’ versus ‘less stress’ was found to influence prescription patterns. PCA identified six factors which collectively explained 66.1% of the variance in physician feedback. Multivariate analysis identified a positive correlation between physicians willing to accept usage of LAI antipsychotics and the positive attitude of colleagues (co-efficient 3.67; p = 0.016).

Conclusions

The physician questionnaire in the ALTO study is the first to evaluate the attitudes around LAI antipsychotics across several European countries, on a larger scale. Findings from this study offer an important insight into how physician attitudes can influence the acceptance and usage of LAI antipsychotics to treat patients with schizophrenia.
Breastfeeding reduces ultra-processed foods and sweetened beverages consumption among children under two years old
Authors: Spaniol Ana Maria , da Costa Teresa Helena Macedo , Bortolini Gisele Ane , Gubert Muriel Bauermann
Published: March 2020

Background

Breastfeeding and adequate complementary feeding are associated with healthy eating habits, prevention of nutritional deficiencies, obesity and non-communicable diseases. Our aim was to identify feeding practices and to evaluate the association between breastmilk intake and complementary feeding, focusing on ultra-processed foods (UPF) and sweetened beverages, among children under 2 years old.

Methods

We conducted a cross-sectional study including 847 children from 20 Primary Health Units. We evaluated children’s food consumption using a food intake markers questionnaire. We conducted a logistic regression to evaluate the effect of breastmilk intake on feeding practices.

Results

The breastmilk intake was associated with lower odds of consuming non-recommended foods, such as cookies or crackers (OR: 0.29; IC 95%: 0.20–0.41) for children under 6 months, yogurt (OR: 0.33; CI 95%: 0.12–0.88) for children between 6 and 12 months and soft drinks (OR: 0.36; CI 95%: 0.17–0.75) for children between 12 and 24 months. Moreover, the breastmilk intake was associated with lower odds of consuming UPF (OR: 0.26; CI 95%: 0.09–0.74) and sweetened beverages (OR: 0.13; CI 95%: 0.05–0.33) for children under 6 months. For children between 12 and 24 months, breastmilk intake was associated with lower odds of consuming sweetened beverages (OR: 0.40; CI 95%: 0.24–0.65).

Conclusion

Breastmilk intake was associated with a reduced consumption of UPF and sweetened beverages. Investment in actions to scale up breastfeeding can generate benefits, besides those of breastmilk itself, translating into better feeding habits and preventing health problems in childhood.
Factors associated with 36-month loss to follow-up and mortality outcomes among HIV-infected adults on antiretroviral therapy in Central Kenya
Authors: Wekesa Paul , McLigeyo Angela , Owuor Kevin , Mwangi Jonathan , Nganga Evelyne , Masamaro Kenneth
Published: March 2020

Background

The scale-up of HIV treatment programs has resulted in a reduction in HIV-related morbidity and mortality. However, retention of patients in these programs remains a challenge in sub-Saharan Africa. Understanding factors associated with loss to follow-up (LTFU) and mortality outcomes is therefore important to inform targeted program interventions.

Methods

A retrospective multi-cohort analysis of 23,890 adult patients on ART over 36 months of follow-up in Kenya was done. Multivariate logistic regression analysis was done to assess for factors associated with LTFU and mortality at 6, 12, 24, and 36 months of follow-up.

Results

Majority, 67.7%, were female. At 36 months, 27.2% were LTFU and 13.5% had died. Factors associated with mortality at 36 months included older age (51 years and above) using 20–35 years as reference [(adjusted odds ratio [aOR], 1.51, 95% confidence interval (CI) 1.23–1.86, p < 0.001], being male (aOR, 1.59, 95% CI 1.39–1.83, p < 0.001), divorced using married as reference (aOR, 1.86, 95% CI 1.56–2.22, p < 0.001), having a body mass index (BMI) score of less than 18.5 kg/m2 using 18.5–24.9 kg/m2 as reference (aOR = 1.79, 95% CI 1.52–2.11, p < 0.001), and, World Health Organization stage III and IV using stage I as the reference (aOR, 1.94, 95% CI 1.43–2.63 and aOR, 4.24, 95% CI 3.06–5.87, p < 0.001 respectively). Factors associated with LTFU at 36 months included being young between 20 and 35 years (aOR, 1.49, 95% CI 1.40–1.59, p < 0.001) using 36–50 years as reference, being male (aOR, 1.19, 95% CI 1.12–1.27, p < 0.001), and being single or divorced using married as reference (aOR, 1.34, 95% CI 1.23–1.45 and aOR, 1.25, 95% CI 1.15–1.36, p < 0.001 respectively). Patients with baseline BMI of less than 18.5 kg/m2 using normal BMI as reference (aOR, 1.68, 95% CI 1.39–2.02, p < 0.001) were also likely to be LTFU.

Conclusions

Factors associated with LTFU and mortality were generally similar over time. Implementation of programs in similar settings should be tailored to gender, age profiles, nutritional, and, marital status of patients to address LTFU. In addition, programs should focus on the care of older patients to reduce the risk of mortality.
Assertive outreach treatment versus care as usual for the treatment of high-need, high-cost alcohol related frequent attenders: study protocol for a randomised controlled trial
Authors: Blackwood R. , Wolstenholme A. , Kimergård A. , Fincham-Campbell S. , Khadjesari Z. , Coulton S. , Byford S. , Deluca P. , Jennings S. , Currell E. , Dunne J. , O’Toole J. , Winnington J. , Finch E. , Drummond C.
Published: March 2020

Background

Alcohol-related hospital admissions have doubled in the last ten years to > 1.2 m per year in England. High-need, high-cost (HNHC) alcohol-related frequent attenders (ARFA) are a relatively small subgroup of patients, having multiple admissions or attendances from alcohol during a short time period. This trial aims to test the effectiveness of an assertive outreach treatment (AOT) approach in improving clinical outcomes for ARFA, and reducing resource use in the acute setting.

Methods

One hundred and sixty ARFA patients will be recruited and following baseline assessment, randomly assigned to AOT plus care as usual (CAU) or CAU alone in equal numbers. Baseline assessment includes alcohol consumption and related problems, physical and mental health comorbidity and health and social care service use in the previous 6 months using standard validated tools, plus a measure of resource use. Follow-up assessments at 6 and 12 months after randomization includes the same tools as baseline plus standard measure of patient satisfaction. Outcomes for CAU + AOT and CAU at 6 and 12 months will be compared, controlling for pre-specified baseline measures. Primary outcome will be percentage of days abstinent at 12 months. Secondary outcomes include emergency department (ED) attendance, number and length of hospital admissions, alcohol consumption, alcohol-related problems, other health service use, mental and physical comorbidity 6 and 12 months post intervention. Health economic analysis will estimate the economic impact of AOT from health, social care and societal perspectives and explore cost-effectiveness in terms of quality adjusted life years and alcohol consumption at 12-month follow-up.

Discussion

AOT models piloted with alcohol dependent patients have demonstrated significant reductions in alcohol consumption and use of unplanned National Health Service (NHS) care, with increased engagement with alcohol treatment services, compared with patients receiving CAU. While AOT interventions are costlier per case than current standard care in the UK, the rationale for targeting HNHC ARFAs is because of their disproportionate contribution to overall alcohol burden on the NHS. No previous studies have evaluated the clinical and cost-effectiveness of AOT for HNHC ARFAs: this randomized controlled trial (RCT) targeting ARFAs across five South London NHS Trusts is the first.

Trial registration

International standard randomized controlled trial number (ISRCTN) registry:ISRCTN67000214, retrospectively registered 26/11/2016.
Circulating matrix metalloproteinases and tissue metalloproteinase inhibitors in patients with idiopathic pulmonary fibrosis in the multicenter IPF-PRO Registry cohort
Authors:   on behalf of the IPF-PRO Registry investigators, Todd Jamie L. , Vinisko Richard , Liu Yi , Neely Megan L. , Overton Robert , Flaherty Kevin R. , Noth Imre , Newby L. Kristin , Lasky Joseph A. , Olman Mitchell A. , Hesslinger Christian , Leonard Thomas B. , Palmer Scott M. , Belperio John A.
Published: March 2020

Background

Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) play important roles in the turnover of extracellular matrix and in the pathogenesis of idiopathic pulmonary fibrosis (IPF). This study aimed to determine the utility of circulating MMPs and TIMPs in distinguishing patients with IPF from controls and to explore associations between MMPs/TIMPs and measures of disease severity in patients with IPF.

Methods

The IPF cohort (n = 300) came from the IPF-PRO Registry, an observational multicenter registry of patients with IPF that was diagnosed or confirmed at the enrolling center in the past 6 months. Controls (n = 100) without known lung disease came from a population-based registry. Generalized linear models were used to compare circulating concentrations of MMPs 1, 2, 3, 7, 8, 9, 12, and 13 and TIMPs 1, 2, and 4 between patients with IPF and controls, and to investigate associations between circulating levels of these proteins and measures of IPF severity. Multivariable models were fit to identify the MMP/TIMPs that best distinguished patients with IPF from controls.

Results

All the MMP/TIMPs analyzed were present at significantly higher levels in patients with IPF compared with controls except for TIMP2. Multivariable analyses selected MMP8, MMP9 and TIMP1 as top candidates for distinguishing patients with IPF from controls. Higher concentrations of MMP7, MMP12, MMP13 and TIMP4 were significantly associated with lower diffusion capacity of the lung for carbon monoxide (DLCO) % predicted and higher composite physiologic index (worse disease). MMP9 was associated with the composite physiologic index. No MMP/TIMPs were associated with forced vital capacity % predicted.

Conclusions

Circulating MMPs and TIMPs were broadly elevated among patients with IPF. Select MMP/TIMPs strongly associated with measures of disease severity. Our results identify potential MMP/TIMP targets for further development as disease-related biomarkers.
TKA in the treatment of bilateral dysplasia epiphysealis hemimelica (Trevor’s Disease) of the knee in a 50-year-old man: a case report
Authors: Gao Fei , Chen Guo , Wang Ruoyu , Huang Pan , Wang Jing , Xu Weihua
Published: March 2020

Background

Dysplasia epiphysealis hemimelica (DEH), also known as Trevor’s disease, is a rare skeletal developmental disorder affecting the epiphyses in pediatric patients. DEH is characterized by an asymmetric osteochondral overgrowth arising from either the medial or lateral portion of an epiphysis and usually occurs in the joints of lower limbs, most commonly in the knees and ankles. However, bilateral involvement in an adult is extremely rare, and total knee arthroplasty (TKA) for a patient with DEH has been reported only once before.

Case presentation

Here, we present a case of bilateral DEH of the knees that caused varus deformity and dysfunction of the lower limbs in a 50-year-old man. TKA was performed for treatment, and the patient had satisfactory function with no angular knee deformity and a normal range of motion after 1 year of follow-up.

Conclusions

The patient in this case exhibited its specific clinical and radiological features of late-term DEH and TKA was proved to be an appropriate procedure for treating the severe deformity caused by this rare disease.
Accuracy of pedicle screw insertion for unilateral open transforaminal lumbar interbody fusion: a side-by-side comparison of percutaneous and conventional open techniques in the same patients
Authors: Sumiya Satoshi , Numano Fujiki , Ogawa Takahisa , Yoshii Toshitaka , Okawa Atsushi , Komori Hiromichi
Published: March 2020

Background

The aim of the study was to compare the accuracy of percutaneous pedicle screw (PPS) insertion (P-side) with that of conventional open screw insertion (O-side) during unilateral open transforaminal lumbar interbody fusion (TLIF) in the same patients. We also sought to determine the incidence of pedicle screw misplacement and to identify relevant risk factors.

Methods

The study was a retrospective analysis of prospectively collected data for 766 pedicle screws placed in 181 consecutive patients who underwent a unilateral open-TLIF procedure in the lumbosacral spine. Our minimally invasive TLIF was performed by unilateral open freehand insertion of pedicle screws for decompression on one side and PPS on the opposite side. Using this approach, we were able to compare the accuracy of PPS insertion with that of conventional open screw insertion in the same patients. There were 383 PPSs and 383 screws inserted by the open method. The accuracy of screw placement was evaluated on reconstructed computed tomography images obtained postoperatively, and screw misplacement was classified. Potential risk factors for screw misplacement were investigated in three-level mixed-effects logistic regression analysis.

Results

Thirty-four screws (8.9%) were misplaced on the P-side and 37 (9.5%) were misplaced on the O-side; the difference was not statistically significant (P = 0.803). Subclassification analysis revealed minor perforation of 28 screws (7.3%) on the P-side and 32 (8.4%) on the O-side, moderate perforation of 5 screws (1.3%) on the P-side and 4 (1.0%) on the O-side, and severe perforation of 1 screw (0.3%) on each side. Three-level mixed-effects logistic regression analysis identified body mass index as a significant risk factor for screw misplacement on the P-side (odds ratio 1.194, 95% confidence interval 1.066–1.338).

Conclusions

Accuracy of pedicle screw insertion was not significantly different between PPS insertion and conventional open screw insertion in the same patients. Body mass index had a significant influence on the risk of screw misplacement in PPS insertion.
A novel family of expression vectors with multiple affinity tags for wheat germ cell-free protein expression
Authors: Nagy Szilvia Krisztina , Kállai Brigitta Margit , András Judit , Mészáros Tamás
Published: March 2020

Background

Cell-free protein expression has become a widely used alternative of in vivo, cell-based systems in functional and structural studies of proteins. The wheat germ-based method outstands from the commercially available eukaryotic in vitro translation systems by its flexibility, high translation efficiency and success rate of properly folded eukaryotic protein synthesis. The original T7 promoter containing pEU3-NII vector was improved previously by addition of a ligation-independent cloning site, His6- and GST-tags, and a TEV protease cleavage site to facilitate the creation of recombinant plasmids, permit affinity purification, and enable production of purified, tag-free target proteins, respectively.

Results

Here, we describe a further development of pEU3-NII vector by inserting the rare-cutting, NotI restriction enzyme cleavage site to simplify vector linearization step prior to in vitro transcription. Additionally, His12, FLAG, and Halo affinity tag coding vectors have been created to increase detection sensitivity, specificity of interaction studies, and provide covalently linkable ligands for pull-down assays, respectively. Finally, the presented GST-His6, and GST-biotin double-tagging vectors could broaden the range of possibilities of protein-protein interaction studies.

Conclusions

The new generation of pEU3-NII vector family allows a more rapid production of translationally active mRNA and wheat germ cell-free expression of target proteins with a wide variety of affinity tags thus enables designing flexible and diverse experimental arrangement for in vitro studies of proteins.
Cyclooxygenase enzyme and PGE2 expression in patients with functional and non-functional pituitary adenomas
Authors: Akbari Nasrin , Ghorbani Mohammad , Salimi Vahid , Alimohammadi Alimohammad , Khamseh Mohammad E. , Akbari Hamideh , Nourbakhsh Mitra , Sheikhi Alireza , Taghavi S. Fahimeh , Tavakoli-Yaraki Masoumeh
Published: March 2020

Background

Pituitary adenomas as multifactorial intracranial neoplasms impose a massive burden of morbidity on patients and characterizing the molecular mechanism underlying their pathogenesis has received considerable attention. Despite the appealing role of cyclooxygenase enzymes and their bioactive lipid products in cancer pathogenesis, their relevance to pituitary adenoma pathogenesis is debated and yet to be determined. Thus, the current study perused this relevance.

Methods

The expression level of the isoforms of cyclooxygenase (COX-1 and COX-2) was evaluated in hormone-secreting and in-active pituitary adenoma tumors and normal pituitary tissues through Real-Time PCR. The level of PGE2, as the main product of enzymes, was assessed using enzyme immunoassay kits in patients and healthy subjects.

Results

The results of the current study demonstrated that COX-1 and COX-2 expression levels were increased in pituitary tumors including non-functional pituitary adenoma (NFPA), acromegaly, Cushing’s disease and prolactinoma compared with normal pituitary tissues. A significant expression level of COX-2 was observed in NFPA compared with the other pituitary tumors. Furthermore, the COX-2 expression level was significantly increased in macroadenoma and invasive tumors. The level of PGE2 was consistent with COX enzymes enhanced in pituitary adenoma tumors compared with healthy pituitary tissue. A significant elevation in the PGE2 level was detected in NFPA compared with hormone-secreting pituitary tumors. Additionally, the PGE2 level was increased in macroadenoma compared with microadenoma and in invasive compared with non-invasive pituitary tumors. The diagnostic values of cyclooxygenase isoforms and PGE2 were considerable between patients and healthy groups; however, COX-2 revealed more value in distinguishing endocrinologically active and non-active pituitary tumors.

Conclusions

Data from the current study provides expression patterns of COX-1, COX-2 and PGE2 in prevalent pituitary tumors and their association with patients’ clinical features which may open up new molecular targets for early diagnosis/follow up of pituitary tumor growth.
A pilot study: a possible implication of Candida as an etiologically endogenous pathogen for oral lichen planus
Authors: He Hong , Xia Xinyu , Yang Haiping , Peng Qiao , Zheng Jiaoer
Published: March 2020

Background

The aim of this study was to investigate the prevalence and genotypic profiles of Candida albicans in patients with oral lichen planus (OLP).

Materials and methods

Positive rates and genotypic profiles of Candida albicans strains from OLP patients and healthy controls were analyzed. Random amplified polymorphic DNA and internal transcribed spacer of ribosome DNA polymerase chain reactions were used to sequence the DNA of these strains, and then their genetic similarity was measured using BLAST, UIV Band, and Vector NTI Suite Sequence Analyses Software.

Results

The prevalence of C. albicans strains detected from erosive-OLP, non-erosive OLP, and normal individuals was 18.87, 18.75, and 7.92%, respectively. Four different genotypes were revealed by the two methods. To be specific, type I was found only in the healthy subjects; type II a and II b were found in non-erosive OLP, and type III was identified in erosive OLP. Intragroup similarity coefficients, i.e. SAB were 100%, and inter-groups similarity coefficients, i.e. SAB were less than 30%.

Conclusions

The genotypic results of C. albicans in OLP revealed an endogenous rather than exogenous infection of C. albicans. In addition, a possible pathogenic role of C. albicans in OLP, with the etiologic sense contributing to a more proper recognition on the pathogenesis, development, and progression of OLP, as well as some strategies for its diagnosis and treatment were identified.
Incidence trend of breast Cancer in women of eastern Mediterranean region countries from 1998 to 2019: A systematic review and meta-analysis
Authors: Zahedi Razieh , Molavi Vardanjani Hossein , Baneshi Mohammad Reza , Haghdoost Ali Akbar , Malekpour Afshar Reza , Ershad Sarabi Roghayeh , Tavakoli Fatemeh , Zolala Farzaneh
Published: March 2020

Background

This study was conducted to provide evidence on the current status of breast cancer and its incidence trend in Eastern Mediterranean Region during 1998–2019. Also, this study aimed to investigate the association between the incidence of breast cancer and Human Development Index and some factors related to this index, including total fertility rate, and obesity, using a meta-analysis.

Method

Data on incidence of breast cancer were collected from various sources, including PubMed, Embase, Web of Science, and WHO, from 1998 to 2019 using systematic review and meta-analysis. Pooled age standardized rate was calculated based on study duration and quality of data using a subgroup analysis and random effect meta-analysis.

Results

A total of 80 studies (545 data points) were analyzed. Pooled age standardized rate of breast cancer for Eastern Mediterranean Region was 37.1 per 100,000 person-year (95% confidence interval [CI], 34.5, 39.8) during 2011–2019. age standardized rate of breast cancer had an upward trend in Eastern Mediterranean Region from 2005 to 2019. However, the increasing trend was found to be slightly different in various regions based on quality of data. Moreover, pooled age standardized rate had a significant association with Human Development Index [− 89.2 (95% CI, − 119.8, − 58.7)] and obesity [1.2 (95% CI, 0.9, 1.5)].

Conclusion

Pooled age standardized rate of breast cancer in Eastern Mediterranean Region was lower than the global average. Also, the age standardized rate value and its incremental trend have been higher in countries with high-quality data than in other countries of this region in recent years. Data quality or physiological factors, such as increase in obesity rates, could be the reasons for this incremental trend.
Attitudes of Israeli medical students towards the medical treatment of uninsured migrants
Authors: Mor Zohar , Cadesky Adam , Halleluyan Ran , Sheffer Rivka
Published: March 2020

Background

Undocumented migration to developed countries poses practical concerns, as migrants are not medically insured. This cross-sectional study aims to appraise the attitudes of Israeli medical students towards the uninsured migrant population.

Methods

Participants from five medical schools in Israel completed anonymous questionnaires in Hebrew, based on the “Medical Students’ Attitudes Toward the Underserved” (MSATU), which assessed students’ attitudes regarding the professional responsibility and societal expectations towards the migrants. It also evaluated students’ views of the migrants as eligible for expensive medical procedures.

Results

A total of 891 students completed the survey with a median age of 28 years. The majority were Jews (N = 816, 91.6%) and singles (N = 681, 68.5%). Participants in the pre-clinical years were likely to be female and unmarried compared to those in clinical training. They also demonstrated higher scores on professional responsibilities and societal expectations than students in clinical training, but no significant differences were found in their views on expensive medical services. Students of minorities (non-Jews and migrants) scored higher on professional responsibilities and societal expectations.

The scores for professional responsibilities and societal expectations decreased as students progressed in their medical training (Spearman coefficient p = 0.04 and p = 0.01, respectively). This trend was more apparent in males rather than females.

Conclusion

MSATU scores declined as students progressed through medical school, with females maintaining more favorable attitudes than males. Medical schools should attempt to maintain the enthusiasm and idealism that students possess as they enter medical training and provide clinical experience with migrant populations that allows for cross-cultural communication.
Disease awareness or subtle product placement? Orphan diseases featured in the television series “House, M.D.” - a cross-sectional analysis
Authors: Mechler Konstantin , Rausch Juliane , Mountford William K. , Ries Markus
Published: March 2020

Background

Approximately 7% of the general population is affected by an orphan disease, which, in the United States, is defined as affecting fewer than 1 in 1500 people. Disease awareness is often low and time-to-diagnosis delayed. Different legislations worldwide have created incentives for pharmaceutical companies to develop drugs for orphan diseases. A journalistic article in Bloomberg Businessweek has claimed that pharmaceutical companies have tried marketing orphan drugs by placing a specific disease into the popular television series “House, M.D.” which features diagnostic journeys and was produced between 2004 and 2012. This study aimed to describe the presentation of orphan diseases in the television series “House, M.D.”, to test in an exploratory fashion the hypothesis that treatable orphan conditions are overrepresented in “House, M.D.” and to discuss whether such marketing practices may or may not be ethical.

Methods

A list of all medical cases depicted in the television series “House, M.D.” was obtained and classified as orphan or non-orphan according to the Orphanet database. The ratios of orphan diseases among all diseases, such with an orphan drug designation and such with an orphan drug approval by the FDA were then compared with conservative approximations of real world conditions (chi-squared tests for equality of proportions). STROBE criteria were respected.

Results

Out of a total of n = 181 different medical diagnoses, n = 42 (23.2%) were orphan diseases. The difference in percentages in between “House, M.D.” and reality was not statistically significant for orphan diseases overall (p = 0.96), yet was statistically significantly higher for both orphan diseases with one or more orphan drug designations (p = 0.0192) and such with one or more approved orphan drugs (p < 0.0001).

Conclusions

Orphan diseases with a designated and/or approved orphan drug were overrepresented in the television series “House, M.D.” with statistical significance while orphan diseases overall were not. This may be explained by (so far) undocumented efforts of pharmaceutical companies to place their orphan drugs in the television series, as described in the article in Bloomberg Businessweek. Further research is needed into marketing practices in popular and emerging media formats.
Methods to improve the quality of smoking records in a primary care EMR database: exploring multiple imputation and pattern-matching algorithms
Authors: Garies Stephanie , Cummings Michael , Quan Hude , McBrien Kerry , Drummond Neil , Manca Donna , Williamson Tyler
Published: March 2020

Background

Primary care electronic medical record (EMR) data are emerging as a useful source for secondary uses, such as disease surveillance, health outcomes research, and practice improvement. These data capture clinical details about patients’ health status, as well as behavioural risk factors, such as smoking. While the importance of documenting smoking status in a healthcare setting is recognized, the quality of smoking data captured in EMRs is variable. This study was designed to test methods aimed at improving the quality of patient smoking information in a primary care EMR database.

Methods

EMR data from community primary care settings extracted by two regional practice-based research networks in Alberta, Canada were used. Patients with at least one encounter in the previous 2 years (2016–2018) and having hypertension according to a validated definition were included (n = 48,377). Multiple imputation was tested under two different assumptions for missing data (smoking status is missing at random and missing not-at-random). A third method tested a novel pattern matching algorithm developed to augment smoking information in the primary care EMR database. External validity was examined by comparing the proportions of smoking categories generated in each method with a general population survey.

Results

Among those with hypertension, 40.8% (n = 19,743) had either no smoking information recorded or it was not interpretable and considered missing. Those with missing smoking data differed statistically by demographics, clinical features, and type of EMR system used in the clinic. Both multiple imputation methods produced fully complete smoking status information, with the proportion of current smokers estimated at 25.3% (data missing at random) and 12.5% (data missing not-at-random). The pattern-matching algorithm classified 18.2% of patients as current smokers, similar to the population-based survey (18.9%), but still resulted in missing smoking information for 23.6% of patients. The algorithm was estimated to be 93.8% accurate overall, but varied by smoking status category.

Conclusion

Multiple imputation and algorithmic pattern-matching can be used to improve EMR data post-extraction but the recommended method depends on the purpose of secondary use (e.g. practice improvement or epidemiological analyses).
Multi-level strategies to tailor patient-centred care for women: qualitative interviews with clinicians
Authors: Filler Tali , Dunn Sheila , Grace Sherry L. , Straus Sharon E. , Stewart Donna E. , Gagliardi Anna R.
Published: March 2020

Background

Patient-centered care (PCC) is one approach for ameliorating persistent gendered disparities in health care quality, yet no prior research has studied how to achieve patient-centred care for women (PCCW). The purpose of this study was to explore how clinicians deliver PCCW, challenges they face, and the strategies they suggest are needed to support PCCW.

Methods

We conducted semi-structured qualitative interviews (25–60 min) with clinicians. Thirty-seven clinicians representing 7 specialties (family physicians, cardiologists, cardiac surgeons, obstetricians/gynecologist, psychiatrists, nurses, social workers) who manage depression (n = 16), cardiovascular disease (n = 11) and contraceptive counseling (n = 10), conditions that affect women across the lifespan. We used constant comparative analysis to inductively analyze transcripts, mapped themes to a 6-domain PCC conceptual framework to interpret findings, and complied with qualitative research reporting standards.

Results

Clinicians said that women don’t always communicate their health concerns and physicians sometimes disregard women’s health concerns, warranting unique PCC approaches.. Clinicians described 39 approaches they used to tailor PCC for women across 6 PCC domains: foster a healing relationship, exchange information, address emotions/concerns, manage uncertainty, make decisions, and enable self-management. Additional conditions that facilitated PCCW were: privacy, access to female clinicians, accommodating children through onsite facilities, and flexible appointment formats and schedules. Clinicians suggested 7 strategies needed to address barriers of PCCW they identified at the: patient-level (online appointments, transport to health services, use of patient partners to plan and/or deliver services), clinician-level (medical training and continuing professional development in PCC and women’s health), and system-level (funding models for longer appointment times, multidisciplinary teamwork to address all PCC domains).

Conclusions

Our research revealed numerous strategies that clinicians can use to optimize PCCW, and health care managers and policy-makers can use to support PCCW through programs and policies. Identified strategies addressed all domains of an established PCC conceptual framework. Future research should evaluate the implementation and impact of these strategies on relevant outcomes such as perceived PCC among women and associated clinical outcomes to prepare for broad scale-up.
Functional complexity of hair follicle stem cell niche and therapeutic targeting of niche dysfunction for hair regeneration
Authors: Chen Chih-Lung , Huang Wen-Yen , Wang Eddy Hsi Chun , Tai Kang-Yu , Lin Sung-Jan
Published: March 2020

Stem cell activity is subject to non-cell-autonomous regulation from the local microenvironment, or niche. In adaption to varying physiological conditions and the ever-changing external environment, the stem cell niche has evolved with multifunctionality that enables stem cells to detect these changes and to communicate with remote cells/tissues to tailor their activity for organismal needs. The cyclic growth of hair follicles is powered by hair follicle stem cells (HFSCs). Using HFSCs as a model, we categorize niche cells into 3 functional modules, including signaling, sensing and message-relaying. Signaling modules, such as dermal papilla cells, immune cells and adipocytes, regulate HFSC activity through short-range cell-cell contact or paracrine effects. Macrophages capacitate the HFSC niche to sense tissue injury and mechanical cues and adipocytes seem to modulate HFSC activity in response to systemic nutritional states. Sympathetic nerves implement the message-relaying function by transmitting external light signals through an ipRGC-SCN-sympathetic circuit to facilitate hair regeneration. Hair growth can be disrupted by niche pathology, e.g. dysfunction of dermal papilla cells in androgenetic alopecia and influx of auto-reacting T cells in alopecia areata and lichen planopilaris. Understanding the functions and pathological changes of the HFSC niche can provide new insight for the treatment of hair loss.