bluuebunny/crossref_metadata_2025_split huggingface dataset:
What is the influence of parents' myopia on their children's myopic progression? A 22‐year follow‐up study
Authors: Pärssinen Olavi , Kauppinen Markku 
Published: April 2016

AbstractPurposeTo study the connection between parental myopia and their children's myopia from school age to adulthood.MethodsTwo hundred and forty myopic schoolchildren (119 boys, 121 girls, mean age 10.9 years) with no previous spectacles for myopia were recruited to a 3‐year treatment trial with different use of spectacles. Follow‐ups were performed at mean ages of 13.9, 23.7 and 33.2 years for 238, 176 and 170 subjects respectively. Subjective refraction was calibrated to the spherical equivalent at corneal level (SEcor). Corneal refractive power (CR) and axial length (AL) were measured. Parental myopia was assessed with a questionnaire and the children assigned accordingly to one of three hereditary groups: both parents myopic H++, one myopic parent = H+− and no myopic parents = H−.ResultsAt baseline, no significant gender differences in age or SEcor were found in the different hereditary groups. Among girls, CR was significantly higher in hereditary group H++ (45.20 ± 1.08 D) than in group H+− (44.19 ± 1.28 D; p = 0.006) or H– (43.84 ± 1.18 D; p < 0.001). Among boys, the differences in CR between the hereditary groups were smaller and significant at follow‐up 2 only. At follow‐up end, among males, no significant differences between the hereditary groups were found in SEcor, CR, AL or myopic progression. Among females, myopic progression was 4.21 ± 1.81 D if one or both parents were myopic and −3.19 ± 1.36 D if neither parent was myopic (p = 0.035), but no significant difference was observed in AL.ConclusionsThe main difference between the hereditary groups was higher CR and myopic progression among females with myopic parents than non‐myopic parents, but with no significant difference in AL with respect to parental myopia at study end.
Chronic nonbacterial osteomyelitis may be associated with renal disease and bisphosphonates are a good option for the majority of patients
Authors: Pastore Serena , Ferrara Giovanna , Monasta Lorenzo , Meini Antonella , Cattalini Marco , Martino Silvana , Alessio Maria , Torre Francesco La , Teruzzi Barbara , Gerloni Valeria , Breda Luciana , Taddio Andrea , Lepore Loredana 
Published: April 2016

AbstractAimThe aim of this Italian study was to describe the clinical features, treatment options and outcomes of a cohort of patients with chronic nonbacterial osteomyelitis (CNO).MethodsThis was a retrospective cohort study. Laboratory data, diagnostic imaging, histological features and clinical course are reported.ResultsWe enrolled 47 patients diagnosed with CNO. Bone pain was the leading symptom, and multifocal disease was present in 87% of the patients. The majority of the bone lesions were located in the appendicular skeleton (58%). Extraosseous manifestations were present in 34% of the patients, and renal involvement was detected in four patients. Inflammatory indices were increased in 80%, and bone x‐rays were negative in 15% of the patients. Nonsteroidal anti‐inflammatory drugs (NSAIDs) were the first therapy for all patients, achieving clinical remission in 27%. A good response to NSAIDs was significantly associated with a better prognosis. Bisphosphonates were used in 26 patients, with remission in 73%. Only six patients (13%), all with spine involvement, developed sequelae.ConclusionWe found a possible association between CNO and renal disease. Bisphosphonates were more likely to lead to clinical remission when NSAIDs and corticosteroids had failed. Vertebral localisation was the only risk factor for potential sequelae.
Hepatic venous outflow tract obstruction: treatment outcomes and development of a new prognostic score
Authors: Shalimar  , Kumar A. , Kedia S. , Sharma H. , Gamanagatti S. R. , Gulati G. S. , Nayak B. , Thakur B. , Acharya S. K. 
Published: April 2016

SummaryBackgroundResults of endovascular interventions in hepatic venous outflow tract obstruction (HVOTO) have been reported from limited studies. Treatment outcomes and prognostic scores need further validation.AimTo evaluate treatment outcomes and prognostic scores for hepatic venous outflow tract obstruction in an Indian population.MethodsConsecutive patients with hepatic venous outflow tract obstruction diagnosed at a tertiary centre were included. Technical success and clinical response after endovascular interventional therapy were documented. Predictors of survival were assessed with Cox‐proportional model. A new score was derived from the factors significant on multivariate analysis and compared with Child–Turcotte–Pugh, model for end‐stage liver disease (MELD), Rotterdam prognostic index (PI) and Budd‐Chiari syndrome‐transjugular intrahepatic portosystemic shunt ( BCS‐TIPSS) PI.ResultsThree hundred and thirty‐four patients (56.6% males), median age 24 (3–62) years were included. Hepatic vein was the commonest site of block‐isolated hepatic vonous block in 48%, combined hepatic venous‐inferior vena cava block in 46%. Endovascular interventional therapy was performed in 233/334 (70%) with 90% technical success. Clinical response was complete in 166 (71.2%), partial in 58 (24.9%) and no response in nine (3.9%). Majority of cases with HV block did not require TIPSS and could be treated with angioplasty (with/without stenting). On Cox‐proportional multivariate analysis, Child class C and response to intervention were independent predictors of outcome and used to derive the All India Institute of Medical Sciences (AIIMS) hepatic venous outflow tract obstruction score. The 5‐year survival was 92% (95% CI, 81–97%) for score ≤3, 79% (95%CI, 63–88%) for score >3 and ≤4, and 39% (95% CI, 21–57%) for score >4. The performance of AIIMS hepatic venous outflow obstruction score was superior to other prognostic indices.ConclusionsAdvanced Child class and no response to intervention are associated with poor outcomes. The All India Institute of Medical Sciences hepatic venous outflow tract obstruction score predicts survival better than other prognostic scores.
Review article: emerging anti‐fibrotic therapies in the treatment of non‐alcoholic steatohepatitis
Authors: Noureddin M. , Anstee Q. M. , Loomba R. 
Published: April 2016

SummaryBackgroundNon‐alcoholic fatty liver disease (NAFLD) can lead to non‐alcoholic steatohepatitis (NASH) and cirrhosis. Fibrosis predicts worse outcomes and mortality. New treatments targeting fibrosis are being investigated to reverse disease progression.AimTo review the new pipeline therapeutic agents targeting fibrosis in NASH patients, with particular focus on clinical trials in which reversing fibrosis and portal hypertension are the primary outcomes.MethodsThe literature was searched in PubMed between January 2000 and January 2016 using search terms non‐alcoholic fatty liver disease and NASH, with filters of ‘English language’. We focused on fibrosis improvement as the key outcome. We also searched the ClinicalTrials.gov for promising agents that target fibrosis in NASH patients.ResultsSignificant advances have been made on approaches targeting fibrosis in NASH patients. Many therapeutic agents are already in development, some of which have shown promising results in preclinical and phase I studies. Novel therapies have entered phase II and III studies targeting fibrosis reversal and/or improvement in portal hypertension. Innovative studies have also started looking into combining these agents, aiming at different mechanisms to maximise therapeutic outcomes. We found five clinical trials in phase II and one in phase III focusing on fibrosis in NASH patients as key outcomes. One of the phase II trials is using combination therapy to target fibrosis.ConclusionsOngoing research studies are already investigating new pathways aimed at reversing fibrosis in NASH patients. Novel therapeutic agents are in development and are expected to offer unique options to NASH patients with advanced fibrosis.
Nested case–control study: hepatocellular carcinoma risk after hepatitis B surface antigen seroclearance
Authors: Gounder P. P. , Bulkow L. R. , Snowball M. , Negus S. , Spradling P. R. , Simons B. C. , McMahon B. J. 
Published: April 2016

SummaryBackgroundHepatocellular carcinoma (HCC) risk after resolving chronic hepatitis B virus (HBV) infection is unclear.AimTo compare HCC risk between Alaska Native (AN) patients with and without hepatitis B surface antigen (HBsAg) seroclearance.MethodsWe selected persons with (case‐patients) and without (control‐patients) HBsAg seroclearance from a cohort of 1346 chronically HBV‐infected AN patients followed during 1982‒2013. We attempted to match two control‐patients/case‐patient on sex, HBV genotype, and age. Person‐years of follow‐up for case‐patients began on the date of HBsAg resolution and for control‐patients began on the date equivalent to the cohort entry date plus the years of HBsAg duration for their corresponding case‐patient. We compared HCC risk using a Cox proportional hazards model.ResultsThe 238 case‐patients (4 with HCC) and 435 control‐patients (9 with HCC) were similar in age [P‐value (P) = 0.30], sex (P = 0.53) and HBV genotype (P = 0.99). Case‐patients had longer person‐years of follow‐up than control‐patients (11.7 vs. 10.1 years; P = 0.04). The HCC rate/100 000 persons was similar between case‐ (132) and control‐patients (178; P = 0.65). The adjusted hazard ratio comparing case‐ and control‐patients was similar for HCC [0.7; 95% confidence interval (CI): 0.2–2.4], increased for each 1‐year increment for age (1.1; CI: 1.0–1.1; P < 0.01), and was greater if the initial HBeAg was positive (3.5; CI: 1.1–11.0; P = 0.03).ConclusionsHepatitis B surface antigen seroclearance was not associated with reduced HCC risk; the HCC risk estimates are limited by wide 95% confidence intervals. Persons meeting HCC surveillance indications prior to HBsAg seroclearance could benefit from continued surveillance after seroclearance.
Prescribing pattern of antipsychotic drugs during the years 1996–2010: a population‐based database study in Europe with a focus on torsadogenic drugs
Authors: Oteri Alessandro , Mazzaglia Giampiero , Pecchioli Serena , Molokhia Mariam , Ulrichsen Sinna Pilgaard , Pedersen Lars , Poluzzi Elisabetta , De Ponti Fabrizio , Garbe Edeltraut , Schink Tania , Herings Ron , Bezemer Irene D. , Sturkenboom Miriam C. J. M. , Trifirò Gianluca 
Published: April 2016

IntroductionAntipsychotic drugs (APDs) are used to treat several mental illnesses. Some APDs have long been known to be associated with QT prolongation, potentially leading to torsades de pointes (TdP) and sudden cardiac death (SCD). In 2005, thioridazine was withdrawn because of the risk of SCD, bringing further attention to the arrhythmogenic potential of APDs.AimThe aim of the current study was to evaluate the use of APDs in five European countries during the years 1996–2010.MethodsA cohort study was conducted using prescription/dispensing data from seven healthcare databases [the AARHUS University Hospital Database (Denmark), the German Pharmacoepidemiological Research Database (GePaRD) (Germany), Health Search Database/Thales (HSD) and Emilia Romagna Regional Database (ERD) (Italy), PHARMO Database Network and Integrated Primary Care Information (IPCI) (the Netherlands) and The Health Improvement Network (THIN) (the UK), covering a population of 27 million individuals.The annual prescription rate of APDs was measured overall and for individual medications. APDs were classified as torsadogenic according to the Arizona‐CERT list. All analyses were stratified by age, gender and calendar year.ResultsA total of 559 276 person‐years (PYs) of exposure to APDs was captured. The crude annual prescription rate of APD use ranged from 3.0/1000 PYs in ERD to 7.7/1000 PYs in AARHUS. Among APDs with established torsadogenic potential, thioridazine was the most frequently used medication in the UK. Haloperidol was commonly prescribed in Italy and the Netherlands. The use of APDs with torsadogenic potential was much higher in elderly patients.ConclusionsSubstantial use of APDs with torsadogenic potential has been reported in Europe in recent years, in spite of increasing concerns about their arrhythmogenic potential. This use was even greater in elderly patients, who are at higher risk of SCD.
Ventricular tachyarrhythmia and sudden cardiac death with domperidone use in Parkinson's disease
Authors: Renoux Christel , Dell'Aniello Sophie , Khairy Paul , Marras Connie , Bugden Shawn , Turin Tanvir Chowdhury , Blais Lucie , Tamim Hala , Evans Charity , Steele Russell , Dormuth Colin , Ernst Pierre ,   the Canadian Network for Observational Drug Effect Studies (CNODES) investigators
Published: April 2016

AimDomperidone is preferentially used over other antiemetic agents to treat digestive symptoms in Parkinson's disease (PD). Concerns have been raised regarding an increased risk of ventricular tachyarrhythmia and sudden cardiac death (VT/SCD) associated with domperidone in the general population. However, the risk in PD is unknown.MethodsWe conducted a multicentre retrospective cohort study using administrative databases from seven Canadian provinces and the UK Clinical Practice Research Datalink. Using a nested case–control analysis, we estimated the rate ratios (RRs) of VT/SCD associated with domperidone use compared to no use in patients newly‐diagnosed with PD. VT/SCD events were identified using administrative medical records and vital statistics with a manual review of all potential cases. Meta‐analytic methods were used to estimate overall effects across sites.ResultsAmong 214 962 patients with PD, 2907 cases of VT/SCD were identified during 886 581 person‐years of follow‐up (incidence rate 3.28 per 1000 persons per year). Current use of domperidone was associated with a non‐statistically significant 22% increased risk of VT/SCD (RR 1.22; 95% CI 0.99–1.50) compared with no use. The risk was significantly elevated in those with a history of cardiovascular disease (RR 1.38; 95% CI 1.07–1.78), but not in those without (RR 1.21; 95% CI 0.81–1.81). Dose and duration of use did not affect the magnitude of the risk.ConclusionDomperidone use may increase the risk of VT/SCD in patients with PD, particularly those with a history of cardiovascular disease. This risk may be underestimated because of imprecision in identifying VT/SCD events.
COMPARE: Pharmacokinetic profiles of subcutaneous peginterferon beta‐1a and subcutaneous interferon beta‐1a over 2 weeks in healthy subjects
Authors: Hu Xiao , Shang Shulian , Nestorov Ivan , Hasan Jawad , Seddighzadeh Ali , Dawson Katherine , Sperling Bjørn , Werneburg Brian 
Published: April 2016

AimSubcutaneous (s.c.) peginterferon beta‐1a injected once every 2 weeks and s.c. interferon beta‐1a injected three times per week (Rebif®) have demonstrated efficacy in relapsing–remitting multiple sclerosis, but direct comparisons of pharmacological activity and tolerability between the two products are lacking. COMPARE was an open label, crossover, pharmacokinetic (PK) study evaluating drug exposure and the safety and tolerability of s.c. peginterferon beta‐1a and s.c. interferon beta‐1a, over 2 weeks in healthy subjects.MethodsThirty healthy subjects received one dose of peginterferon beta‐1a (125 μg s.c.) or six doses of interferon beta‐1a (44 μg s.c.) over 2 weeks, followed by the alternate treatment after a 2 week washout period. Drug concentrations were measured using an enzyme‐linked immunosorbent assay (ELISA) and PK parameters including cumulative area under the concentration–time curve (AUC0‐336h) over 2 weeks and maximum observed serum concentrations (Cmax) were estimated using a non‐compartmental analysis.ResultsThe PK analysis population comprised 26 subjects for each treatment. Drug exposure (AUC0‐336h) was 60% higher with s.c. peginterferon than with s.c. interferon beta‐1a (117.4 ng ml−1h, 95% confidence interval 95.6, 144.3 vs. 73.1 ng ml−1 h, 95% confidence interval 61.2, 87.3, respectively; P < 0.0001). Injection‐site reactions (ISRs) were the most common adverse events (AEs) observed with both treatments. Numerically lower frequencies and incidence rates of ISRs, headache, myalgia and chills were observed with s.c. peginterferon beta‐1a.ConclusionsOne dose of s.c. peginterferon delivered significantly greater drug exposure than s.c. interferon beta‐1a three times a week over 2 weeks, and a lower frequency of AEs.
High prevalence of risk factors in elderly patients using drugs associated with acquired torsades de pointes chronically in Colombia
Authors: Moreno‐Gutiérrez Paula Andrea , Gaviria‐Mendoza Andrés , Cañón Mauricio Montoya , Machado‐Alba Jorge Enrique 
Published: April 2016

AimsMedication is one of the main causes of long QT syndrome (LQTS) and torsades de pointes (TdP), and the older adult population is at particularly high risk. The aim of the present study was to describe the prescription patterns of drugs with a risk of TdP in the Colombian older adult population.MethodsPatients older than 65 years who received medication with a risk of TdP during three consecutive months were selected. The medication was obtained and classified according to the QT Drug List from Crediblemeds.org. The data were analysed using SPSS‐22.ResultsA total of 55 932 patients were chronically receiving QT‐prolonging drugs; 61.9% (n = 34 ,632) were women and the mean age of the sample was 75.6 years. Drugs with a conditional risk were consumed by 95.2% of patients, 5.3% received drugs with a known risk and 2.9% received drugs with a possible risk. Two or more QT‐prolonging drugs were consumed by 10.3% of the patients (n = 5786). Most of the sample (96.8%, n = 54 170) had at least one additional risk factor for LQTS, with a mean of 3.1 ± 0.9 risk factors. Patients receiving QT‐prolonging drugs for psychiatric and neurological disease were at a higher risk of major polypharmacy [odds ratio (OR) 3.0; 95% confidence interval (CI) 2.80, 3.22) and of receiving high doses of QT‐prolonging drugs (OR 3.8; 95% CI 3.52, 4.05).ConclusionsThe widespread use of medication that causes TdP and the high prevalence of additional risks in the older adult population raise the need for accurate prediction of risk and constant patient monitoring. Patients taking psychiatric drugs are at a higher risk of TdP.
Measurement of Rhodamine 123 in Three‐Dimensional Organoids: A Novel Model for P‐Glycoprotein Inhibitor Screening
Authors: Zhang Yuanjin , Zeng Zhiyang , Zhao Junfang , Li Dali , Liu Mingyao , Wang Xin 
Published: April 2016

AbstractP‐glycoprotein (P‐gp), as the most important efflux transporter in intestines, plays the key role to determine the bioavailability of many drugs. The three‐dimensional (3D) organoid model is suitable to imitate small intestinal epithelium. In this study, a rapid, sensitive and efficient method to measure rhodamine 123 (Rh123, P‐gp substrate) in 3D organoids was developed to analyse P‐gp‐mediated drug transport. Ultrasonic cell disruptor was used to smash the organoid, and automatic microplate reader was used for detecting the concentration of Rh123 (λex/λem= 485/520 nm). Moreover, verapamil, quinidine and mitotane were used to make validation about this newly developed approach. All three P‐gp inhibitors significantly inhibited the transport of Rh123 into 3D organoids. Therefore, the above‐mentioned method could serve as a new model for P‐gp inhibitor screening in a high‐throughput way.
Agmatine Reverses Sub‐chronic Stress induced Nod‐like Receptor Protein 3 (NLRP3) Activation and Cytokine Response in Rats
Authors: Sahin Ceren , Albayrak Ozgur , Akdeniz Tuğba F. , Akbulut Zeynep , Yanikkaya Demirel Gulderen , Aricioglu Feyza 
Published: April 2016

AbstractThe activation of Nod‐like receptor protein 3 (NLRP3) has lately been implicated in stress and depression as an initiator mechanism required for the production of interleukin (IL)‐1β and IL‐18. Agmatine, an endogenous polyamine widely distributed in mammalian brain, is a novel neurotransmitter/neuromodulator, with antistress, anxiolytic and antidepressant‐like effects. In this study, we examined the effect of exogenously administered agmatine on NLRP3 inflammasome pathway/cytokine responses in rats exposed to restraint stress for 7 days. The rats were divided into three groups: stress, stress+agmatine (40 mg/kg; i.p.) and control groups. Agmatine significantly down‐regulated the gene expressions of all stress‐induced NLRP3 inflammasome components (NLRP3, NF‐κB, PYCARD, caspase‐1, IL‐1β and IL‐18) in the hippocampus and prefrontal cortex (PFC) and reduced pro‐inflammatory cytokine levels not only in both brain regions, but also in serum. Stress‐reduced levels of IL‐4 and IL‐10, two major anti‐inflammatory cytokines, were restored back to normal by agmatine treatment in the PFC. The findings of the present study suggest that stress‐activated NLRP3 inflammasome and cytokine responses are reversed by an acute administration of agmatine. Whether antidepressant‐like effect of agmatine can somehow, at least partially, be mediated by the inhibition of NLRP3 inflammasome cascade and relevant inflammatory responses requires further studies in animal models of depression.
Interplay between the kinin B1 receptor and inducible nitric oxide synthase in insulin resistance
Authors: Haddad Youssef , Couture Réjean 
Published: April 2016

Background and PurposeKinins are vasoactive and pro‐inflammatory peptides whose biological effects are mediated by two GPCRs, named B1 and B2 receptors. While the B2 receptor plays a protective role in the cardiovascular system via the activation of endothelial NOS, the B1 receptor is associated with vascular inflammation, insulin resistance and diabetic complications. Because the B1 receptor is a potent activator of the inducible form of NOS (iNOS), this study has addressed the role of iNOS in the deleterious effects of B1 receptors in insulin resistance.Experimental ApproachMale Sprague–Dawley rats (50–75 g) had free access to a drinking solution containing 10% d‐glucose or tap water (control) for 9 weeks. During the last week, a selective iNOS inhibitor (1400W, 1 mg·kg−1 twice daily) or its vehicle was administered s.c.Key ResultsProlonged glucose treatment caused insulin resistance and several hallmarks of type 2 diabetes. Whereas the treatment with 1400W had no impact on the elevated systolic blood pressure and leptin levels in glucose‐fed rats, it significantly reversed or attenuated hyperglycaemia, hyperinsulinaemia, insulin resistance (HOMA index), body weight gain, peroxynitrite formation (nitrotyrosine expression) and the up‐regulation of biomarkers of inflammation (B1 receptor, carboxypeptidase M, iNOS and IL‐1β) in renal cortex and aorta and to some extent in the liver.Conclusions and ImplicationsPharmacological blockade of iNOS prevents the formation of peroxynitrite, which amplifies the pro‐inflammatory effects of B1 receptors through a positive feedback mechanism. Hence, targeting iNOS can prevent the deleterious effects of B1 receptors in insulin resistance and peripheral inflammation.