bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discontinuing statins or not in the elderly? Study protocol for a randomized controlled trial
Authors: Bonnet Fabrice , Bénard Antoine , Poulizac Pierre , Afonso Mélanie , Maillard Aline , Salvo Francesco , Berdaï Driss , Salles Nathalie , Rousselot Nicolas , Marchi Sébastien , Hayes Nathalie , Joseph Jean-Philippe 
Published: March 2020

Abstract
Background

The risk/benefit ratio of using statins for cardiovascular (CV) primary prevention in elderly people has not been established. The main objectives of the present study are to assess the cost-effectiveness of statin cessation and to examine the non-inferiority of statin cessation in terms of mortality in patients aged 75 and over treated with statins for primary prevention.

Methods

The Statins In The Elderly (SITE) Study is an ongoing 3-year follow-up, open-label comparative multi-centre randomised clinical trial that is being conducted in two parallel groups in outpatient primary care offices.

Participants meeting the following criteria are being included: people aged 75 years and older being treated with statins as primary prevention for CV events who provide informed consent. After randomisation, patients in the statin-cessation strategy are instructed to withdraw their treatment. In the comparison strategy, patients continue their statin treatment at the usual dosage.

The cost-effectiveness of the statin-cessation strategy compared to continuing statins will be estimated through the incremental cost per quality-adjusted life years (QALY) gained at 36 months based on the perspective of the French healthcare system. Overall mortality will be the primary clinical endpoint.

We assumed that the mortality rate at 3 years will be 15%. The sample size was computed to achieve 90% power in showing the non-inferiority of statin cessation, assuming a non-inferiority margin of 5% of the between-group difference in overall mortality. In total, the SITE study will include 2,430 individuals.

Discussion

There is some debate regarding the value of statins in people over 75 years old, especially for primary prevention, due to a lack of evidence of their efficacy in this population, potential compliance-related events, drug-drug interactions and side effects that could impair quality of life. Data from clinical trials guide the initiation of medication therapy for primary or secondary prevention of CV disease but do not define the timing, safety, or risks of discontinuing the agents.

The SITE study is one of the first to examine whether treatment cessation is a cost-effective strategy that has no adverse effects on the prognosis of people over 75 years old formerly treated with statins.

Trial registration

This research has been registered at clinicaltrials.gov under number NCT02547883, 11 September 2015, https://clinicaltrials.gov/ct2/show/NCT02547883
Dispensation of attention deficit hyperactivity disorder (ADHD) medications in patients receiving opioid agonist therapy; a national prospective cohort study in Norway from 2015 to 2017
Authors: Vold Jørn Henrik , Aas Christer , Skurtveit Svetlana , Odsbu Ingvild , Chalabianloo Fatemeh , Halmøy Anne , Johansson Kjell Arne , Fadnes Lars Thore 
Published: March 2020

Abstract
Background
It is estimated that up to a third of patients on opioid agonist therapy (OAT) have attention deficit hyperactivity disorder (ADHD). Treatment by ADHD medication, including a centrally acting stimulant (CAS) or atomoxetine is one of the essential approaches. This study evaluates the use of dispensed ADHD medications in the Norwegian OAT population in the period from 2015 to 2017. Types and doses of ADHD medications, co-dispensations of other potentially addictive drugs like benzodiazepines, z-hypnotics, gabapentinoids, and non-OAT opioids, as well as direct-acting antivirals (DAA) against hepatitis C infection, are investigated.

Methods
Information about all dispensed ADHD medication, OAT opioids, and the defined potentially addictive drugs were recorded from the Norwegian Prescription Database. Dispensation rates, the types, and the doses of dispensed ADHD medications were estimated by summarizing the number of dispensations, and the dispensed doses. Logistic regression analyses were employed to assess the associations between ADHD medication, and OAT opioid use, and dispensations of other potentially addictive drugs and DAAs against hepatitis C infection.

Results
A total of 9,235 OAT patients were included. The proportion of patients who were dispensed ADHD medication increased from 3.5% to 4.6% throughout the study period. The three most dispensed CAS were short- and intermediate-acting methylphenidate (55%), lisdexamphetamine (24%), and dexamphetamine (17%) in 2017. Buprenorphine, rather than methadone, as OAT opioid (adjusted odds ratio: 1.6, CI: 1.2-2.1) was associated with being dispensed ADHD medication. Among patients who received CAS and OAT opioids each calendar year, the dispensed doses of methylphenidate increased from 63 mg/day in 2015 to 76 mg/day in 2017 (p = 0.01). Eighty-five of 142 patients receiving ADHD medications were also dispensed other addictive drugs concomitantly in 2017. Similar results were found in 2015 and 2016.

Conclusion
Co-prescription of ADHD medications was low among patients on OAT in Norway, considering a high prevalence of ADHD in this patient group. On the other hand, concurrent dispensations of multiple addictive drugs were common in this population. Understanding the underlying reasons for such prescribing is essential, and research on how to optimize ADHD medication of patients with ADHD receiving OAT is needed.
Risk factor analysis for predicting kyphosis reoccurrence of thoracolumbar burst fracture patients treated with posterior short-segment fixation
Authors: Sun Xiangyao , Chen Zhaoxiong , Sun Siyuan , Zhang Tongtong , Zhang Xinuo , Hai Yong , Lu Shibao 
Published: March 2020

Abstract
Background: The thresholds of risk factors of kyphosis recurrence in thoracolumbar burst fracture patients were still controversial. The aim of this multi-center study was to identify these thresholds. Methods: 169 patients were included in this study. Upper intervertebral angle (UIVA), lower intervertebral angle (LIVA), Cobb angle (CA), anterior vertebral height ratio (AVH%), regional angle (RA), posterior vertebral height ratio (PVH%), vertebral wedge angle (VWA), anteroposterior ratio (A/P%), Clinical assessment included Load Sharing Classification (LSC) score, Thoracolumbar Injury Classification and Severity (TLICS) score, Visual Analogue Scale (VAS), and Body mass index (BMI) were perioperatively evaluated. Patients were divided into KR group and none KR (NKR) group according to whether the loss of CA correction was less than 5˚ or not. The risk factors of KR before or after implant removal were analyzed, respectively. Results: There were significant improvements in postoperative parameters compared with preoperative parameters, such as AVH%, A/P%, VAS, CA, VWA, PVH% ( P < 0.001, respectively), and UIVA ( P = 0.02). Age (AUC = 0.828) and BMI (AUC = 0.846) were good predictors of KR before implant removal. BMI (AUC = 0.871) was a good predictor of KR after implant removal. Conclusions: There were significant differences in risk factors of KR at different postoperative follow-up stages: age > 49 years, BMI > 24 were risk factors of KR before implant removal; BMI > 25.17 was a risk factor of KR after implant removal.
Comparison of simultaneous bilateral versus unilateral total knee replacement on pain levels and functional recovery
Authors: Alghadir Ahmad H , Iqbal Zaheen A , Anwer Shahnawaz , Anwar Dilshad 
Published: March 2020

Abstract
Background

Total knee replacement is a common operative procedure to improve pain, function, and quality of life in patients with end stage knee osteoarthritis. The current study aimed to compare simultaneous bilateral versus unilateral total knee replacement on pain intensity and recovery of function.

Methods

A total of 80 patients (bilateral 50, unilateral 30) aged 63.28 (9.4) years undergone total knee replacement participated in the current study. The participants were admitted for 5-7 days in the hospital. Participants in both the group received similar inpatient and outpatient physiotherapy sessions. Pain intensity and function capacity were assessed at baseline, day 7, and day 30 post-operatively using visual analogue scale and lower extremity functional scale, respectively. Repeated measures analysis of variance was used to analyze the data.

Results

Both groups showed a significant reduction of pain intensity (Day 0, mean 8.9, SD 1.0; Day 30, mean 2.2, SD 1.3 in bilateral total knee replacement; Day 0, mean 8.8, SD 1.1; Day 30, mean 2.0, SD 1.5 in unilateral total knee replacement; p<0.001) and improvement in the functional capacity (Day 0, mean 16.2, SD 10.1; Day 30, mean 55.6, SD 14.6 in bilateral total knee replacement; Day 0, mean 19.1, SD 9.1; Day 30, mean 56.7, SD 15.8 in unilateral total knee replacement; p<0.001) following total knee replacement at 30 days post-operatively. However, there was a non-significant difference noted between bilateral versus unilateral total knee replacement on the reduction of pain intensity (mean changes, 6.9 versus 6.8) and improvement in the functional capacity (mean changes, 39.4 versus 37.6) at 30 days post-operatively (p>0.05).

Conclusion

Simultaneous bilateral total knee replacement was associated with a similar reduction of pain intensity and recovery of function compared to unilateral total knee replacement, suggesting the use of simultaneous bilateral total knee replacement in patients with bilateral knee osteoarthritis since its costs and rehabilitation process could be reduced compared to staged bilateral total knee replacement.
Ubiquitin-specific protease-44 inhibits the proliferation and migration of cells via inhibition of JNK pathway in clear cell renal cell carcinoma
Authors: Zhou Jiangqiao , Wang Tianyu , Qiu Tao , Chen Zhongbao , Ma Xiaoxiong , Zhang Long , Zou Jilin 
Published: March 2020

Abstract
Background: Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer. Ubiquitin-specific protease (USP)44 has been reported to be involved in various cancers. We investigated the function, role and molecular mechanism of USP44 in ccRCC. Methods: Data obtained from the Cancer Genome Atlas Data Portal and Gene Expression Omnibus database were analyzed to uncover the clinical relevance of USP44 expression and tumor development. USP44 function in the proliferation and migration of tumor cells was assessed by cellular and molecular analyses using ccRCC lines (786-O cells and Caki-1 cells).Results: USP44 showed low expression in ccRCC cancer tissues compared with that in normal tissue. USP44 expression was negatively correlated with tumor stage, tumor grade, and patient survival . USP44 overexpression inhibited the proliferation and migration of 786-O cells and Caki-1 cells significantly. USP44 overexpression also prohibited cell proliferation by upregulating expression of P21, downregulating cyclin-D1 expression, and inhibiting cell migration by upregulating expression of matrix metalloproteinase (MMP)2 and MMP9. USP44 knockdown enhanced the proliferation and migration of 786-O cells and Caki-1 cells. USP44 function in inhibiting the proliferation and migration of 786-O cells and Caki-1 cells was associated with phosphorylation of Jun N-terminal kinase (JNK). Conclusion: USP44 may be a marker in predicting ccRCC progression. Inhibition by USP44 of the proliferation and migration of 786-O cells and Caki-1 cells is dependent upon the JNK pathway.
Height predict incident non-alcoholic fatty liver disease among general adult population in Tianjin, China, independent of body mass index, waist circumference, waist-to-height ratio, and metabolic syndrome
Authors: Kumari Shubham , Wang Xuena , Liu Yunyun , Gu Yeqing , Huang Yuhan , Zhang Qing , Liu Li , Meng Ge , Wu Hongmei , Sun Shaomei , Wang Xing , Zhou Ming , Jia Qiyu , Wang Guolin , Song Kun , Niu Kaijun 
Published: March 2020

Abstract
Background : Early-life hormonal and nutritional factors can greatly influence the risk of non-alcoholic fatty liver disease (NAFLD). Adult height is a simple marker for these factors. This study aimed to investigate the association between adult height and NAFLD.
Methods : We performed a prospective cohort study of 35,994 participants aged 25 years or over with measured height at baseline. NAFLD was diagnosed by abdominal ultrasound and self-reported history of alcohol intake. Multivariable Cox proportional hazards regression models were conducted to assess the gender-specific association between height and the risk of NAFLD.
Results: During a follow-up period of 5.5 years, 6 ,245 of 35,994 subjects developed NAFLD. The adjusted hazard ratios (95% confidence interval) of NAFLD for increasing quintiles of height were 1.00 (reference), 0.82 (0.73, 0.92), 0.84 (0.73, 0.97), 0.72 (0.61, 0.85) and 0.63 (0.50, 0.79) ( P for trend < 0.0001) in males, and 1.00 (reference), 1.00 (reference), 0.80 (0.69, 0.91), 0.72 (0.61, 0.85), 0.60 (0.49, 0.74) and 0.45 (0.35, 0.59) ( P for trend <0.0001) in females, respectively.
Conclusions: A higher adult height was associated with lower risk of NAFLD among males and females in Tianjin, China.
Meta-analytic evaluation of the correlation between event-free survival and overall survival in randomized controlled trials of newly diagnosed Ewing sarcoma.
Authors: Tanaka Kazuhiro , Kawano Masanori , Iwasaki Tatsuya , Itonaga Ichiro , Tsumura Hiroshi 
Published: March 2020

Abstract
Background

In randomized controlled trials (RCTs) of adjuvant treatment for malignant tumors, event-free survival (EFS) is considered the most acceptable surrogate for overall survival (OS). However, even though EFS has repeatedly been selected as a primary endpoint in RCTs of Ewing sarcoma (ES), the surrogacy of EFS for OS has not been investigated. This study aimed to evaluate the surrogacy of EFS for OS in RCTs of chemotherapy for newly diagnosed ES using a meta-analytic approach.

Methods

We identified seven RCTs of newly diagnosed ES through a systematic review, and a meta-analysis was performed to evaluate the efficacy and adverse events associated with chemotherapy for previously untreated ES. The correlation between EFS and OS was investigated using weighted linear regression analysis and Spearman rank correlation coefficients (ρ). The strength of the correlation was evaluated using the coefficient of determination (R2).

Results

A total of 3,612 patients were randomly assigned to 17 treatment arms in the eligible RCTs. The meta-analysis revealed that the hazard ratios for OS and EFS showed significantly better results in the experimental treatment groups with increasing toxicities. The correlation between the hazard ratios for EFS and OS was good (R2 = 0.747, ρ = 0.683), and the correlation tended to be more favorable in cases of localized ES (R2 = 0.818, ρ = 0.929).

Conclusions

Overall, the trial-level correlation between EFS and OS was good for newly diagnosed ES and was very good in cases of localized disease. EFS may be useful as a surrogate endpoint in RCTs of ES, and the surrogacy of EFS is worth verifying using individual data.
Long Term Outcomes of Cataract Surgery in Severe and End Stage Glaucoma with Controlled IOP:A Retrospective Study
Authors: Fu Lin , Chan Yau Kei , Li Junhua , Nie Li , Li Na , Pan Weihua 
Published: March 2020

Abstract
Background: To investigate the long term surgical outcomes of cataract surgery in severe and end stage glaucoma patients with preoperative intraocular pressure less than 21mmHg, and to detect the associated factors.Methods: A retrospective study of primary angle closure glaucoma patients was conducted on who underwent cataract surgery or combined with goniosynechialysis from March 2015 to April 2018. Main outcome measures were visual acuity, intraocular pressure, number of glaucoma medications and complications. Results: Sixteen patients (19 eyes) were included. The mean age was 64.89 ± 11.68 years and the mean followed up duration was 21.89 ± 7.85 months. The final visual acuity was significantly improved from 0.69 ± 0.55 to 0.46 ± 0.52 logMAR , within 12 (63.2%) eyes improved, 4 (21.1%) eyes kept unchanged, and 3 (15.8%) eyes reduced. Linear regression analysis indicated that higher mean deviation, higher visual field index and lower glaucoma stage associated with better final visual acuity (r = -0.511, r = -0.493, r = 0.537 respectively). Moreover, the final number of medications were reduced from 1.26 ± 0.99 to 0.26 ± 0.56 (p < 0.01). The mean intraocular pressure was not significantly reduced with the final IOP of 14.48 ± 3.74 mmHg (p = 0.97). While the eyes with intraocular pressure above 15 mmHg was decreased to 6 (31.6%) eyes compared to 10 (52.6%) eyes at baseline. Moreover, the number of eyes free of medications was increased from 4 (21.1%) preoperatively to 15 (78.9%) eyes postoperatively.Conclusions: Final visual acuity was significantly improved in the severe and end stage primary angle closure glaucoma patients and the number of eyes came off medications increased by 57.8% after cataract surgery. Preoperatively, the glaucoma stage, mean deviation and visual field index are important parameters to predict the final visual acuity after cataract surgery.
Knowledge, attitudes and practices towards viral haemorrhagic fevers amongst healthcare workers in urban and rural public healthcare facilities in the N’zérékoré prefecture, Guinea: a cross-sectional study
Authors: Raab Manuel , Pfadenhauer Lisa M. , Millimouno Tamba Jacques , Hoelscher Michael , Froeschl Guenter 
Published: March 2020

Abstract
Introduction: The 2013-2016 Ebola epidemic in West Africa began in Guinea’s Forest region, a region now considered to be at high risk for future epidemics of viral haemorrhagic fevers (VHF). Good knowledge, attitudes and practices towards VHF amongst healthcare workers in such regions are a central pillar of infection prevention and control (IPC). To inform future training in IPC, this study assesses the knowledge, attitudes and practices (KAP) towards VHF amongst healthcare workers in public healthcare facilities in the most populated prefecture in Forest Guinea, and compares results from urban and rural areas.
Methods: In June and July 2019, we interviewed 102 healthcare workers in the main urban and rural public healthcare facilities in the N’zérékoré prefecture in Forest Guinea. We used an interviewer-administered questionnaire adapted from validated KAP surveys.
Results: The great majority of respondents demonstrated good knowledge and favourable attitudes towards VHF. However, respondents reported some gaps in preventive practices such as VHF suspect case detection. They also reported a shortage of protective medical equipment used in everyday clinical work in both urban and rural healthcare facilities and a lack of training in IPC, especially in rural healthcare facilities. However, whether or not healthcare workers had been trained in IPC did not seem to influence their level of KAP towards VHF.
Conclusions: Three years after the end of the Ebola epidemic, our findings suggest that public healthcare facilities in the N’zérékoré prefecture in Forest Guinea still lack essential protective equipment and some practical training in VHF suspect case detection. To minimize the risk of future VHF epidemics and improve management of outbreaks of infectious diseases in the region, current efforts to strengthen the public healthcare system in Guinea should encompass questions of supply and IPC training.
Short-chain fatty acid-Butyrate ameliorates hypoxia-induced pulmonary hypertension in rat
Authors: He Shixin , Zhu Tengteng , Zhu Zhaowei , Huang Yiyuan , Tai Shi , Tang Liang , Fang Zhenfei 
Published: March 2020

Abstract
Background: Gut Microbiome can produce numerous metabolites which may be absorbed into the circulation and play a critical role in the development of diseases. Our study wants to find out the roles of faecal microbiota and its metabolite in the development of pulmonary hypertension. Methods: SD rats were expose to either normoxia (Control, n=8) or chronic hypoxia (10% O 2 ) (n=16). Rats in chronic hypoxia were randomly received sodium butyrate (500 mg/kg) (n=8) or volume-matched saline (n=8) once a day. Rats in normoxia condition also received volume-matched saline once a day. RVSP and lung vascular features were assessed after 3 week’s treatment. Rats’ fecal samples were collected and analyzed by GCMS and 6S/18S Amplicon Sequencing. Activation of HIF-1α, HMGB2, TLR4, TNF-α, HDAC5 and PCNA was assessed using Western blot analysis. The effect of sodium butyrate on proliferation of pulmonary artery smooth muscle cell, induced by PDGF or hypoxia (1% O 2 ), was evaluated by CCK-8, EDU assay and wound healing assay. Results: Hypoxia significantly increased RVSP and induced a significant decrease in butyrate-producing bacteria, but a slight decrease of SCFAs without statistic difference. Administration of sodium butyrate remarkably attenuated the RVSP and improved lung vascular features. Decreased expression of HDAC5, PCNA, HIF-1α, HMGB2, TLR4, TNF-α and inhibited proliferation of PASMC were found in rats or cells with sodium butyrate. Conclusions: Decreased butyrate-producing bacteria may contribute to the development of PH, and sodium butyrate supplement can effectively attenuate hypoxia-induced PH in rats probably by inhibiting the proliferation and migration of PASMC.
Interpretation and content validity of the items of the numeric rating version Short-WORC to evaluate outcomes in management of rotator cuff pathology: A cognitive interview approach.
Authors: Furtado Rochelle , MacDermid Joy C , Bryant Dianne , Faber Kenneth J , Athwal George S 
Published: March 2020

Abstract
Background: The shortened version of the Western Ontario Rotator Cuff Index (Short-WORC) is a patient reported outcome measure that evaluates quality of life (QoL) of patients with rotator cuff pathology. However, formal content validation of the full or Short-WORC has not been reported. This study aims to understand how 1) people interpret and calibrate responses to items on the Short-WORC and 2) compensatory strategies that might enhance function and thereby affect responses.

Methods: This study uses cognitive interviewing, a qualitative methodology that focuses on the interpretation of questionnaire items. Patients with rotator cuff disorders (n=10), clinicians (n=6) and measurement researchers (n=10) were interviewed using a talk aloud structured interview that evaluated each of the 7 items of the Short-WORC. All interviews were recorded and transcribed verbatim by one researcher (R.F). Analysis was done through an open coding scheme using a previously established framework.

Results: Overall, the items on the Short-WORC were well received by participants. Through the interviews, the 6 themes of: Comprehension, Inadequate response definition, Reference Point, Relevance, Perspective Modifiers and Calibration Across Items emerged. The items of working above the shoulder (90%), compensating with the unaffected arm (88%) and lifting heavy objects (92%) were the most relevant to participants. Participants calibrated their scores on the items of sleeping and styling (19%) the most. Perspective modifiers of gender, influenced the calibrations of items of styling your hair (30%) and dressing or undressing (19%). Compensatory strategies of task-re allocation and using assistive devices/resources were frequently mentioned by participants. Overall, participants had minor comprehension issues, but found the 7- items of the Short-WORC to be relevant to QoL.

Conclusions: Therefore, the findings demonstrate that the Short-WORC is not cognitively complex, but varies with patient perspectives. Overall, the Short-WORC provides evidence of demonstrating strong content validity when used for rotator cuff disorder patients.