bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the alcohol harm paradox: an analysis of sex‐ and condition‐specific hospital admissions by socio‐economic group for alcohol‐associated conditions in England
Authors: Sadler Susannah , Angus Colin , Gavens Lucy , Gillespie Duncan , Holmes John , Hamilton Jean , Brennan Alan , Meier Petra 
Published: December 2016

AbstractBackground and AimsIn many countries, conflicting gradients in alcohol consumption and alcohol‐associated mortality have been observed. To understand this ‘alcohol harm paradox’ we analysed the socio‐economic gradient in alcohol‐associated hospital admissions to test whether it was greater in conditions which were: (1) chronic (associated with long‐term drinking) and partially alcohol‐attributable, (2) chronic and wholly alcohol‐attributable, (3) acute (associated with intoxication) and partially alcohol‐attributable and (4) acute and wholly alcohol‐attributable. Our aim was to clarify how (1) drinking patterns (e.g. intoxication linked to acute admissions or dependence linked to chronic conditions) and (2) non‐alcohol causes (e.g. smoking and poor diet which are risks for partially alcohol‐attributable conditions) contribute to the paradox.DesignRegression analysis testing the modifying effects of condition‐group (1–4 above) and sex on the relationship between area‐based deprivation and admissions.SettingEngland, April 2010–March 2013.ParticipantsA total of 9 239 629 English hospital admissions where a primary or secondary cause was one of 36 alcohol‐associated conditions.MeasurementsAdmissions by condition and deciles of Index of Multiple Deprivation (IMD). Socio‐economic gradient measured as the relative index of inequality (RII, the slope of a linear regression of IMD on admissions adjusted for overall admission rate). Conditions were categorized by ICD‐10 code.FindingsA socio‐economic gradient in hospitalizations was seen for all conditions, except partially attributable chronic conditions. The gradient was significantly steeper for conditions which were wholly attributable to alcohol and for acute conditions than for conditions partially alcohol‐attributable and for chronic conditions. Gradients were steeper for men than for women in cases of wholly alcohol attributable conditions.ConclusionsThere is a socio‐economic gradient in English hospital admission for most alcohol‐associated conditions. The greatest inequalities are in conditions associated with alcohol dependence, such as liver disease and mental and behavioural conditions, and in acute conditions, such as alcohol poisoning and assault. Socio‐economic differences in harmful drinking patterns (dependence and intoxication) may contribute to the ‘alcohol harm paradox’.
The costs of crime during and after publicly funded treatment for opioid use disorders: a population‐level study for the state of California
Authors: Krebs Emanuel , Urada Darren , Evans Elizabeth , Huang David , Hser Yih‐Ing , Nosyk Bohdan 
Published: December 2016

AbstractBackground and aimsTreatment for opioid use disorders (OUD) reduces the risk of mortality and infectious disease transmission; however, opportunities to quantify the potential economic benefits of associated decreases in drug‐related crime are scarce. This paper aimed to estimate the costs of crime during and after periods of engagement in publicly funded treatment for OUD to compare total costs of crime during a hypothetical 6‐month period following initiation of opioid agonist treatment (OAT) versus detoxification.DesignRetrospective, administrative data‐based cohort study with comprehensive information on drug treatment and criminal justice systems interactions.SettingPublicly funded drug treatment facilities in California, USA (2006–10).ParticipantsA total of 31 659 individuals admitted for the first time to treatment for OUD, and who were linked with criminal justice and mortality data, were followed during a median 2.3 years. Median age at first treatment admission was 32, 35.8% were women and 37.1% primarily used prescription opioids.MeasurementsDaily costs of crime (US$2014) were calculated from a societal perspective and were composed of the costs of policing, court, corrections and criminal victimization. We estimated the average marginal effect of treatment engagement in OAT or detoxification adjusting for potential fixed and time‐varying confounders, including drug use and criminal justice system involvement prior to treatment initiation.FindingsDaily costs of crime during treatment compared with after treatment were $126 lower for OAT [95% confidence interval (CI) = $116, $136] and $144 lower for detoxification (95% CI = $135, $154). Summing the costs of crime during and after treatment over a hypothetical 6‐month period using the observed median durations of OAT (161 days) and detoxification (19 days), we estimated that enrolling an individual in OAT as opposed to detoxification would save $17 550 ($16 840, $18 383).ConclusionsIn publicly funded drug treatment facilities in California, USA, engagement in treatment for opioid use disorders is associated with lower costs of crime in the 6 months following initiation of treatment, and the economic benefits were far greater for individuals receiving time‐unlimited treatment.
Infliximab for ipilimumab‐induced colitis: A series of 13 patients
Authors: Hillock Nadine T , Heard Sharryn , Kichenadasse Ganessan , Hill Catherine L , Andrews Jane 
Published: December 2016

AbstractObjectiveTo review the outcomes of metastatic melanoma patients treated with infliximab for severe steroid‐refractory colitis secondary to ipilimumab therapy.BackgroundImmune‐related colitis is a known potential adverse effect of ipilimumab, that causes significant morbidity and extended hospital stays. There are limited outcome data for patients treated with infliximab for ipilimumab‐induced colitis refractory to corticosteroids. Management guidelines have been developed based on case study evidence only.Design and settingA retrospective review of all patients administered infliximab for ipilimumab‐induced colitis at South Australian public hospitals between October 2011 and April 2015.Main outcome measuresResolution of colitis/diarrhea, duration of hospital stay, dosage regimen of infliximab used (single dose vs multiple dose) and surgical intervention if required.ResultsBetween October 2011 and April 2015, 106 patients were dispensed ipilimumab from South Australian public hospitals for the treatment of metastatic melanoma. Thirteen were administered infliximab for severe, steroid‐refractory colitis secondary to ipilimumab. Sixty‐two percent received a single dose of infliximab only. Four patients achieved resolution of colitis symptoms at 1 month postinfliximab. Thirty‐three percent required surgical intervention despite treatment with infliximab. One patient declined surgery and subsequently died due to bowel perforation. The average number of overnight bed days due to colitis was 27.ConclusionThis series of patients with severe ipilimumab‐induced colitis suggests that despite treatment with infliximab a high proportion of patients do not achieve resolution of symptoms. Review of these cases has highlighted the absence of evidence‐based guidelines to treat severe, steroid refractory colitis secondary to ipilimumab. Further prospective studies may clarify the role of infliximab for the treatment of ipilimumab‐induced colitis.
Longitudinal study shows that addictive Internet use during adolescence was associated with heavy drinking and smoking cigarettes in early adulthood
Authors: Lee Bo Hye , Lee Hae Kook 
Published: December 2016

AbstractAimExisting studies showing an association between substance use disorders and Internet addiction have been limited due their cross‐sectional design. This longitudinal study investigated the association between addictive Internet use during adolescence and heavy drinking and cigarette smoking in early adulthood.MethodsWe focused on middle school students from the Korea Youth Panel Study who were 15 in 2003:1804 who did not drink alcohol and 2277 who did not smoke. Multivariate logistic analysis investigated the relationships between Internet use at the age of 15, with regard to location, time spent and reason for use, and drinking and smoking at the age of 20.ResultsUsing the Internet for chatting, games and adult websites at the age of 15 had a significant association with heavy drinking at the age of 20. The Internet café as the location for Internet use at the age of 15 was associated with smoking behaviour at the age of 20.ConclusionThis study confirmed significant associations between addictive use of the Internet at the age of 15 and heavy drinking and cigarette smoking at the age of 20. The findings demonstrated the negative effects of addictive Internet use, one of the biggest problems with adolescents.
Touchscreen generation: children's current media use, parental supervision methods and attitudes towards contemporary media
Authors: Kostyrka‐Allchorne Katarzyna , Cooper Nicholas R. , Simpson Andrew 
Published: December 2016

AbstractAimTo explore media preferences and use among young children, as well as to obtain information about parental supervision methods and beliefs about media.MethodNinety parents of three‐ to six‐year‐olds, recruited from a relatively economically advantaged area in the United Kingdom, completed a media opinion survey.ResultsAlthough traditional television remains the favourite type of media platform among young children, touchscreen devices are gaining in popularity, and may promote simultaneous multi‐screen use. Moreover, parents believe that the effects of media on developmental outcomes are generally positive. However, they do monitor the content of traditional and new media their children are exposed to.ConclusionThis study shows an emerging evidence of concurrent multi‐screen use among very young children. More detailed examination of early media multitasking, and its relationship to cognitive and behavioural outcomes, is necessary.
New mothers’ experiences of the urban environment with their preterm infants involve complex social, emotional and psychological processes
Authors: Gullino Silvia , Kaiser Anthony , Khan Hammad , Phillips Aisling , Elwin Alice , Edwards AD 
Published: December 2016

AbstractAimStudies have explored how mothers and premature babies make the transition from a neonatal unit (NNU) to home, but little is known about how mothers cope with urban life with a vulnerable baby. This controlled trial investigated how first‐time mothers with singleton preterm babies handled that experience in the first few months after discharge from a NNU, compared to the first‐time mothers of healthy, singleton term‐born infants.MethodsThis parent‐led, qualitative study was carried out in London, UK, from 2013 to 2015 and used diaries and walking interviews with researchers. Thematic network analysis was performed to provide insights into the experiences of these 19 mothers.ResultsThe two groups had similar experiences and needs in the urban environment, and these common experiences of city life shaped their new identities as mothers. However, the mothers of preterm babies had difficulties developing supportive relationships and seeking affirming social environments.ConclusionThis study highlights what the mothers of preterm babies experienced in the first few months after their infant was discharged from hospital. It stresses the need to understand the complexity of the mothers’ social, emotional and psychological processes when they make the transition from home to visit the city with a vulnerable baby.
Neuromuscular changes and the rapid adaptation following a bout of damaging eccentric exercise
Authors: Goodall S. , Thomas K. , Barwood M. , Keane K. , Gonzalez J. T. , St Clair Gibson A. , Howatson G. 
Published: December 2016

AbstractIntroductionAn initial bout of eccentric exercise is known to protect against muscle damage following a repeated bout of the same exercise; however, the neuromuscular adaptations owing to this phenomenon are unknown.AimTo determine whether neuromuscular disturbances are modulated following a repeated bout of eccentric exercise.MethodsFollowing eccentric exercise performed with the elbow flexors, we measured maximal voluntary force, resting twitch force, muscle soreness, creatine kinase (CK) and voluntary activation (VA) using motor point and motor cortex stimulation at baseline, immediately post‐exercise and at 1, 2, 3, 4 and 7 days post‐exercise on two occasions, separated by 3 weeks.ResultsSignificant muscle damage and fatigue were evident following the first exercise bout; maximal voluntary contraction (MVC) was reduced immediately by 35% and remained depressed at 7 days post‐exercise. Soreness and CK release peaked at 3 and 4 days post‐exercise respectively. Resting twitch force remained significantly reduced at 7 days (−48%), whilst VA measured with motor point and motor cortex stimulation was reduced until 2 and 3 days respectively. A repeated bout effect (RBE) was observed with attenuated soreness and CK release and a quicker recovery of MVC and resting twitch force. A similar decrement in VA was observed following both bouts; however, following the repeated bout there was a significantly smaller reduction in, and a faster recovery of, VA measured using motor cortical stimulation.ConclusionOur data suggest that the RBE may be explained, partly, by a modification in motor corticospinal drive.
Carnitine and γ‐Butyrobetaine Stimulate Elimination of Meldonium due to Competition for OCTN2‐mediated Transport
Authors: Liepinsh Edgars , Makarova Elina , Sevostjanovs Eduards , Hartmane Dace , Cirule Helena , Zharkova‐Malkova Olga , Grinberga Solveiga , Dambrova Maija 
Published: December 2016

AbstractMeldonium (3‐(2,2,2‐trimethylhydrazinium)propionate) is the most potent clinically used inhibitor of organic cation transporter 2 (OCTN2). Inhibition of OCTN2 leads to a decrease in carnitine and acylcarnitine contents in tissues and energy metabolism optimization‐related cardioprotective effects. The recent inclusion of meldonium in the World Anti‐Doping Agency List of Prohibited Substances and Methods has raised questions about the pharmacokinetics of meldonium and its unusually long elimination time. Therefore, in this study, the rate of meldonium washout after the end of the treatment was tested with and without administration of carnitine, γ‐butyrobetaine (GBB) and furosemide to evaluate the importance of competition for OCTN2 transport in mice. Here, we show that carnitine and GBB administration during the washout period effectively stimulated the elimination of meldonium. GBB induced a more pronounced effect on meldonium elimination than carnitine due to the higher affinity of GBB for OCTN2. The diuretic effect of furosemide did not significantly affect the elimination of meldonium, carnitine and GBB. In conclusion, the competition of meldonium, carnitine and GBB for OCTN2‐mediated transport determines the pharmacokinetic properties of meldonium. Thus, due to their affinity for OCTN2, GBB and carnitine but not furosemide stimulated meldonium elimination. During long‐term treatment, OCTN2‐mediated transport ensures a high muscle content of meldonium, while tissue clearance depends on relatively slow diffusion, thus resulting in the unusually long complete elimination period of meldonium.
Synergistic Combination for Chemoprevention of Hepatocellular Carcinoma: An In Silico and In Vitro Approach
Authors: Mishra Savita , Katare Deepshikha Pande 
Published: December 2016

AbstractCombination therapy is one of the best methods to manage the fatality rate in hepatocellular carcinoma (HCC). This study aimed to formulate a synergistic combination of synthetic and herbal compounds for the treatment of HCC as well as to elucidate a possible signalling mechanism. MTT and enzymatic assay were performed to determine the synergistic effect of drug combination (sorafenib, vitamin K1 and trans‐chalcone) on HepG2 cell lines after intoxication with H2O2. Protein–protein interaction and docking studies were performed using Pathwaylinker2.0 and Schrödinger's software application to find out the mechanism of action and major targets for drug combination. The overall in vitro result showed that combination of trans‐chalcone, vitamin K1 and sorafenib (10, 5 and 5 μM concentration, respectively) enhanced the resistance against oxidative stress generated by H2O2. The interaction studies helped in identification of few targets for docking of ligands (trans‐chalcone, vitamin K1 and sorafenib). The study reports the synergistic effects of the formulation that can protect the cells from oxidative stress and restore normal levels of cellular enzymes in HepG2 cell line. We were able to determine the mechanism of action of herbal and synthetic formulation through in silico studies. Finally, docking studies confirmed potential targets for inhibition of hepatocarcinogenesis.
Approach to patients with essential thrombocythaemia and very high platelet counts: what is the evidence for treatment?
Authors: Falchi Lorenzo , Bose Prithviraj , Newberry Kate J. , Verstovsek Srdan 
Published: December 2016

SummaryTreatment of essential thrombocythaemia (ET) is directed at decreasing the risk of complications of the disease, including arterial and venous thrombosis and bleeding episodes. Established risk factors for vascular events in patients with ET include advanced age (>60 years) and prior history of thrombosis or haemorrhage. The role, if any, of other potential risk factors, including cardiovascular risk factors, leucocytosis, high haematocrit, and JAK2 V617F has been analysed in multiple studies. The impact of thrombocytosis on the risk of vascular events has also been investigated. Many clinicians consider an elevated platelet count to be a risk factor for thrombosis or, when extreme, bleeding and utilize this as a criterion to start cytoreductive therapy. However, the relationship between thrombocytosis and vascular events is controversial and solid evidence to support the use of cytoreductive therapy in ET patients who have no other risk factors is lacking. In this review, we discuss current treatment recommendations for patients with ET, the biology underlying vascular events and risk factors thereof. We then review the evidence on the management of patients with ET and extreme thrombocytosis.
Knowledge insufficient: the management of haemoglobin SC disease
Authors: Pecker Lydia H. , Schaefer Beverly A. , Luchtman‐Jones Lori 
Published: December 2016

SummaryAlthough haemoglobin SC (HbSC) accounts for 30% of sickle cell disease (SCD) in the United States and United Kingdom, evidence‐based guidelines for genotype specific management are lacking. The unique pathology of HbSC disease is complex, characterized by erythrocyte dehydration, intracellular sickling and increased blood viscosity. The evaluation and treatment of patients with HbSC is largely inferred from studies of SCD consisting mostly of haemoglobin SS (HbSS) patients. These studies are underpowered to allow definitive conclusions about HbSC. We review the pathophysiology of HbSC disease, including known and potential differences between HbSS and HbSC, and highlight knowledge gaps in HbSC disease management. Clinical and translational research is needed to develop targeted treatments and to validate management recommendations for efficacy, safety and impact on quality of life for people with HbSC.
Exacerbation of oxidative stress during sickle vaso‐occlusive crisis is associated with decreased anti‐band 3 autoantibodies rate and increased red blood cell‐derived microparticle level: a prospective study
Authors: Hierso Régine , Lemonne Nathalie , Villaescusa Rinaldo , Lalanne‐Mistrih Marie‐Laure , Charlot Keyne , Etienne‐Julan Maryse , Tressières Benoit , Lamarre Yann , Tarer Vanessa , Garnier Yohann , Hernandez Ada Arce , Ferracci Serge , Connes Philippe , Romana Marc , Hardy‐Dessources Marie‐Dominique 
Published: December 2016

SummaryPainful vaso‐occlusive crisis, a hallmark of sickle cell anaemia, results from complex, incompletely understood mechanisms. Red blood cell (RBC) damage caused by continuous endogenous and exogenous oxidative stress may precipitate the occurrence of vaso‐occlusive crises. In order to gain insight into the relevance of oxidative stress in vaso‐occlusive crisis occurrence, we prospectively compared the expression levels of various oxidative markers in 32 adults with sickle cell anaemia during vaso‐occlusive crisis and steady‐state conditions. Compared to steady‐state condition, plasma levels of free haem, advanced oxidation protein products and myeloperoxidase,RBCcaspase‐3 activity, as well as the concentrations of total, neutrophil‐ andRBC‐derived microparticles were increased during vaso‐occlusive crises, whereas the reduced glutathione content was decreased inRBCs. In addition, natural anti‐band 3 autoantibodies levels decreased during crisis and were negatively correlated with the rise in plasma advanced oxidation protein products andRBCcaspase‐3 activity. These data showed an exacerbation of the oxidative stress during vaso‐occlusive crises in sickle cell anaemia patients and strongly suggest that the higher concentration of harmful circulatingRBC‐derived microparticles and the reduced anti‐band 3 autoantibodies levels may be both related to the recruitment of oxidized band 3 into membrane aggregates.
How do we approach thrombocytopenia in critically ill patients?
Authors: Thachil Jecko , Warkentin Theodore E. 
Published: December 2016

SummaryA low platelet count is a frequently encountered haematological abnormality in patients treated in intensive treatment units (ITUs). Although severe thrombocytopenia (platelet count <20 × 109/l) can be associated with bleeding, even moderate‐degree thrombocytopenia is associated with organ failure and adverse prognosis. The aetiology for thrombocytopenia in ITU is often multifactorial and correcting one aetiology may not normalise the low platelet count. The classical view for thrombocytopenia in this setting is consumption associated with thrombin‐mediated platelet activation, but other concepts, including platelet adhesion to endothelial cells and leucocytes, platelet aggregation by increased von Willebrand factor release, red cell damage and histone release, and platelet destruction by the complement system, have recently been described. The management of severe thrombocytopenia is platelet transfusion in the presence of active bleeding or invasive procedure, but the risk‐benefit of prophylactic platelet transfusions in this setting is uncertain. In this review, the incidence and mechanisms of thrombocytopenia in patients with ITU, its prognostic significance and the impact on organ function is discussed. A practical approach based on the authors' experience is described to guide management of a critically ill patient who develops thrombocytopenia.