bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and biological moderators of response to naltrexone in alcohol dependence: a systematic review of the evidence
Authors: Garbutt James C. , Greenblatt Amy M. , West Suzanne L. , Morgan Laura C. , Kampov‐Polevoy Alexei , Jordan Harmon S. , Bobashev Georgiy V. 
Published: March 2014

AbstractAimThe goal of this systematic review was to identify moderators of naltrexone efficacy in the treatment of alcohol dependence.MethodsWe searched Pubmed, CINHAL, Embase, PsycINFO and the Cochrane Library from 1990 to April 2012 and reference lists of pertinent review articles, which yielded 622 trial, pooled analysis and review articles. Using pre‐established eligibility criteria, two reviewers independently determined whether abstracts contained evidence of demographic or biological characteristics, i.e. moderators, influencing naltrexone response in alcohol dependence. We assessed each publication for risk of bias and evaluated the strength of the body of evidence for each moderator.ResultsTwenty‐eight publications (on 20 studies) met criteria for data synthesis. These included 26 publications from 12 randomized, placebo‐controlled trials, three non‐randomized, non‐placebo studies and one randomized, non‐placebo study. In addition, there were two publications from pooled analyses of four randomized, placebo‐controlled trials. Family history of alcohol problems and the Asn40Asp polymorphism of the μ‐opioid receptor gene showed a positive association with efficacy in four of five and three of five studies, respectively. Other moderators reported to be associated with efficacy included male sex (two of five studies), pre‐treatment drinking (two of two studies) and high craving (two of five studies). However, the overall risk of bias in the published literature is high.ConclusionsThe identification of naltrexone‐responsive alcohol‐dependent patients is still in development. Studies to date point to two potential moderators—family history and presence of the OPRM1 Asn40Asp polymorphism—as having the strongest evidence. However, the data to date is still insufficient to recommend that any moderator be used in determining clinical treatment.
Derivation of Indices of Left Ventricular Contractility in the Setting of Continuous‐Flow Left Ventricular Assist Device Support
Authors: Gupta Sunil , Muthiah Kavitha , Woldendorp Kei , Robson Desiree , Jansz Paul , Hayward Christopher S. 
Published: March 2014

AbstractIt is important to accurately monitor residual cardiac function in patients under long‐term continuous‐flow left ventricular assist device (cfLVAD) support. Two new measures of left ventricular (LV) chamber contractility in the cfLVAD‐unloaded ventricle include IQ, a regression coefficient between maximum flow acceleration and flow pulsatility at different pump speeds; and K, a logarithmic relationship between volumes moved in systole and diastole. We sought to optimize these indices. We also propose RIQ, a ratio between maximum flow acceleration and flow pulsatility at baseline pump speed, as an alternative to IQ. Eleven patients (mean age 49 ± 11 years) were studied. The K index was derived at baseline pump speed by defining systolic and diastolic onset as time points at which maximum and minimum volumes move through the pump. IQ across the full range of pump speeds was markedly different between patients. It was unreliable in three patients with underlying atrial fibrillation (coefficient of determination R2 range: 0.38–0.74) and also when calculated without pump speed manipulation (R2 range: 0.01–0.74). The K index was within physiological ranges, but poorly correlated to both IQ (P = 0.42) and RIQ (P = 0.92). In four patients there was excellent correspondence between RIQ and IQ, while four other patients showed a poor relationship between these indices. As RIQ does not require pump speed changes, it may be a more clinically appropriate measure. Further studies are required to determine the validity of these indices.
Specialist hospital study shows that septic shock and drowsiness predict mortality in children under five with diarrhoea
Authors: Sarmin Monira , Ahmed Tahmeed , Bardhan Pradip K. , Chisti Mohammod J. 
Published: March 2014

AbstractAimTo evaluate the clinical characteristics and outcome in children hospitalised with diarrhoea, comparing those developed septic shock with those who did not.MethodsWe carried out a retrospective chart review on children aged 0–59 months admitted to the Dhaka Hospital, International Centre for Diarrhoeal Diseases Research, Bangladesh, with diarrhoea between October 2010 and September 2011. They were included if they had severe sepsis defined as tachycardia plus hyperthermia or hypothermia or an abnormal white blood cell count plus poor peripheral perfusion in absence of dehydration. Patients unresponsive to fluid and boluses, who required inotropes, were categorised as having septic shock (n = 88). The controls were those without septic shock (n = 116).ResultsDeath was significantly higher among the children with septic shock (67%) than the controls (14%) (p < 0.001). A logistic regression analysis, adjusted for potential confounders, found that children with septic shock were more likely to be drowsy on admission and received blood transfusions and mechanical ventilation (all p < 0.05).ConclusionChildren hospitalised for diarrhoea with septic shock were more likely to die, be drowsy on admission and receive blood transfusions and mechanical ventilation. A randomised clinical trial on inotropes in children with diarrhoea, severe sepsis and drowsiness may expedite their use and prevent mechanical ventilation and deaths.
Circadian rhythm characteristics, poor sleep quality, daytime sleepiness and common psychiatric disorders among Thai college students
Authors: Haregu Alazar , Gelaye Bizu , Pensuksan Wipawan C. , Lohsoonthorn Vitool , Lertmaharit Somrat , Rattananupong Thanapoom , Tadesse Mahlet G. , Williams Michelle A. 
Published: March 2014

AbstractIntroductionTo investigate the relationship between common psychiatric disorders (CPDs) and sleep characteristics (evening chronotype, poor sleep quality and daytime sleepiness) among Thai college students.MethodsA cross‐sectional study was conducted among 2,970 undergraduate students in Thailand. Students were asked to complete a self‐administered questionnaire that collected information about lifestyle and demographic characteristics. The Horne and Ostberg Morningness–Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used to evaluate circadian preference, sleep quality and daytime sleepiness, respectively. The General Health Questionnaire‐12 (GHQ‐12) was used to evaluate presence of CPDs. Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) of CPDs in relation to the covariates of interest.ResultsA total of 337 students were classified as having CPDs (11.2%; 95% CI 10.1–12.3%). Evening chronotype (OR = 3.35; 95% CI 2.09–5.37), poor sleep quality (OR = 4.89; 95% CI 3.66–6.54) and excessive daytime sleepiness (OR = 1.95; 95% CI 1.54–2.47) were statistically significantly associated with CPDs.DiscussionOur study demonstrated that CPDs are common among Thai college students. Further, evening chronotype, poor sleep quality and excessive daytime sleepiness were strongly associated with increased risk of CPDs. These findings highlight the importance of educating students and school administrators about the importance of sleep and their impact on mental health.
The effects of oats on the function of gut microflora in children with coeliac disease
Authors: Tjellström B. , Stenhammar L. , Sundqvist T. , Fälth‐Magnusson K. , Hollén E. , Magnusson K.‐E. , Norin E. , Midtvedt T. , Högberg L. 
Published: March 2014

SummaryBackgroundFaecal short chain fatty acids (SCFAs) are produced by the gut microflora. We have previously reported high faecal SCFA levels in children with coeliac disease (CD), indicating alteration in gut microfloral metabolism. Data accumulated over recent decades by us and others suggest that wheat‐free oats can safely be included in a gluten‐free diet (GFD). However, concerns have been raised with respect to the safety of oats in a subset of coeliacs.AimTo describe faecal SCFA patterns in children with newly diagnosed CD treated for 1 year with a GFD with or without oats.MethodsThis report is part of a randomised, double‐blind study on the effect of a GFD containing oats (GFD‐oats) vs. a standard GFD (GFD‐std). Faecal samples were received from 34 children in the GFD‐oats group and 37 in the GFD‐std group at initial diagnosis and/or after 1 year on a GFD. Faecal SCFAs were analysed.ResultsThe GFD‐std group had a significantly lower total faecal SCFA concentration at 12 months compared with 0 months (P < 0.05). In contrast, total SCFA in the GFD‐oats group remained high after 1 year on the GFD. The children in the GFD‐oats group had significantly higher acetic acid (P < 0.05), n‐butyric acid (P < 0.05) and total SCFA concentration (P < 0.01) after 1‐year diet treatment compared to the GFD‐std group.ConclusionsOur results indicate that oats do affect the gut microflora function, and that some coeliac children receiving oats may develop gut mucosal inflammation, that may present a risk for future complications.
Changes in bedrock channel morphology driven by displacement rate increase during normal fault interaction and linkage
Authors: Hopkins Michael C. , Dawers Nancye H. 
Published: March 2014

AbstractWe attribute changes in the morphology of relay ramp channels (increased slope and decreased width) to variations in displacement rate on ramp‐adjacent normal faults. We map the faults and fluvial channels associated with four sites in different stages of fault interaction and linkage on the Volcanic Tableland, a Late Pleistocene ash‐flow tuff in east‐central California. Because these channels are inactive today, we estimate downstream changes in channel width and depth using HEC‐RAS, a one‐dimensional open channel flow model. Our results show that channel slope must be greater than about 0.05 before there are substantial decreases in width or substantial increases in depth. Displacement rate increases during interaction between en echelon segments results in the increases in channel slope and decreases in channel width. Moreover, our data show that these changes begin to occur during the very early stages of fault interaction, well before the fault geometry would indicate ongoing or imminent linkage.
25‐hydroxy vitamin D levels are associated with childhood asthma in a population‐based study in Peru
Authors: Checkley W. , Robinson C. L. , Baumann L. M. , Hansel N. N. , Romero K. M. , Pollard S. L. , Wise R. A. , Gilman R. H. , Mougey E. , Lima J. J. ,   PURA study investigators
Published: March 2014

SummaryBackgroundVitamin D deficiency may be associated with an increased risk of asthma.ObjectiveWe studied the association between 25‐hydroxy (25‐OH) vitamin D deficiency and asthma prevalence in two Peruvian populations close to the equator but with disparate degrees of urbanization.MethodsWe conducted a population‐based study in 1441 children in two communities in Peru, of which 1134 (79%) provided a blood sample for 25‐OH vitamin D analysis.ResultsIn these 1134 children, mean age was 14.8 years; 52% were boys; asthma and atopy prevalence was 12% in Lima vs. 3% in Tumbes (P < 0.001) and 59% in Lima vs. 41% in Tumbes (P < 0.001), respectively; and, mean 25‐OH vitamin D level was 20.8 ng/mL in Lima vs. 30.1 ng/mL in Tumbes (P < 0.001). Prevalence of 25‐OH vitamin D deficiency (< 20 ng/mL) was 47% in Lima vs. 7% in Tumbes (P < 0.001). In multi‐variable logistic regression, we found that lower 25‐OH vitamin D levels were associated with an increased odds of asthma (OR = 1.7 per each 10 ng/mL decrease in 25‐OH vitamin D levels, 95% CI 1.2–2.6; P < 0.01). In stratified analyses, the association between lower 25‐OH vitamin D levels and asthma was limited to children with atopy (OR = 2.2, 95% CI 1.3–3.6) and not in those without atopy (OR = 0.9, 95% CI 0.5–2.0). We did not find associations between 25‐OH vitamin D levels and other clinical biomarkers for asthma, including exhaled nitric oxide, total serum IgE and pulmonary function.Conclusion and Clinical RelevanceBoth asthma and 25‐OH vitamin D deficiency were common among children living in Lima (latitude = 12.0°S) but not among those in Tumbes (3.6°S). The relationship between 25‐OH vitamin D deficiency and asthma was similar in both sites and was limited among children with atopy. Future supplementation trials may need to consider stratification by atopy at the time of design.
Rapid-onset clinical and mechanistic effects of anti-C5aR treatment in the mouse collagen-induced arthritis model
Authors: Andersson C , Wenander C S , Usher P A , Hebsgaard J B , Sondergaard B-C , Rønø B , Mackay C , Friedrichsen B , Chang C , Tang R , Hornum L 
Published: March 2014

Summary
Preclinical evidence supports targeting the C5a receptor (C5aR) in rheumatoid arthritis (RA). To support ongoing clinical development of an anti-C5aR monoclonal antibody, we have investigated for the first time the mechanism of action and the pharmacodynamics of a blocking anti-murine C5aR (anti-mC5aR) surrogate antibody in mouse collagen-induced arthritis (CIA). First, efficacy was demonstrated in a multiple-dose treatment study. Almost complete inhibition of clinical disease progression was obtained, including reduced bone and cartilage destruction in anti-mC5aR-treated mice. Then, the mechanism of action was examined by looking for early effects of anti-mC5aR treatment in single-dose treatment studies. We found that 48 h after single-dose treatment with anti-mC5aR, the neutrophil and macrophage infiltration into the paws was already reduced. In addition, several inflammatory markers, including tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-17A were reduced locally in the paws, indicating reduction of local inflammation. Furthermore, dose-setting experiments supported a beneficial clinical effect of dosing above the C5aR saturation level. In conclusion, these preclinical data demonstrated rapid onset effects of antibody blockade of C5aR. The data have translational value in supporting the Novo Nordisk clinical trials of an anti-C5aR antibody in rheumatoid arthritis patients, by identifying potential biomarkers of treatment effects as well as by providing information on pharmacodynamics and novel insights into the mechanism of action of monoclonal antibody blockade of C5aR.
Phenotypic and molecular characteristics in eleven Chinese patients with 5α‐reductase Type 2 deficiency
Authors: Zhu Hui , Liu Wei , Han Bing , Fan Mengxia , Zhao Shuangxia , Wang Haining , Lu Yingli , Pan Chunming , Chen Fuguo , Chen Mingdao , Song Huaidong , Cheng Kaixiang , Qiao Jie 
Published: March 2014

SummaryContextSteroid 5α‐reductase type 2 deficiency (5α‐RD2) is a male‐limited, autosomal recessive inherited disease. Affected 46, XY individuals usually present with ambiguous genitalia at birth. An early and precise diagnosis is of great value to the long‐term prognosis of the disease.ObjectiveTo describe the clinical features and molecular determinants in 11 Chinese patients with the SRD5A2 gene mutation and to investigate the functional alteration arising from a novel splicing site mutation identified in one of the patients.Subjects and MethodsEleven subjects born with abnormal external genitalia from 10 unrelated families were recruited. Among them, nine patients who were reared as girls underwent virilization and gender change after puberty. Genotyping analysis of the SRD5A2 gene was performed in each of the patients. Haplotype analysis was performed in five patients with a prevalent mutation of p.G203S to illustrate the founder effect in China. Functional impairment of the new variant was explored by an in vitro splicing study and enzymatic activity assay.ResultsNine mutations in the SRD5A2 gene were detected in the eleven patients. In addition to the previously reported p.G203S, p.R227Q, p.N193S, p.R246Q, p.Q6X, p.A228V, c.655delT and IVS1‐2 A>G, a novel splicing site mutation (IVS4 + 2 T>C) was identified. From an in vitro functional study, this mutation was found to result in a skipping of exon 4 in the course of mRNA splicing, leading to a truncated protein of 205 amino acids that lacks the catalysing activity. Two siblings with the same compound heterozygous mutation (IVS1‐2A>G/p.G203S) exhibited differing phenotypes and opposite patterns of gender rearing. A prevalent variation p.V89L combined with c.655delT was revealed to cause a mild phenotype of 5α‐RD2 with a micropenis.ConclusionThis cohort study describes the phenotypic, biochemical and long‐term outcome in 11 Chinese patients with 5α‐RD2 deficiency and defines the genotypic spectrum of SRD5A2 mutations in China.
Reconciliation of international administrative coding systems for comparison of colorectal surgery outcome
Authors: Munasinghe A. , Chang D. , Mamidanna R. , Middleton S. , Joy M. , Penninckx F. , Darzi A. , Livingston E. , Faiz O. ,   the GI Goal Group Dr Foster Global Comparators (GC) Project, Dr Foster Intelligence in association with the Dr Foster Unit at Imperial College London
Published: March 2014

AbstractAimSignificant variation in colorectal surgery outcomes exists between different countries. Better understanding of the sources of variable outcomes using administrative data requires alignment of differing clinical coding systems. We aimed to map similar diagnoses and procedures across administrative coding systems used in different countries.MethodAdministrative data were collected in a central database as part of the Global Comparators (GC) Project. In order to unify these data, a systematic translation of diagnostic and procedural codes was undertaken. Codes for colorectal diagnoses, resections, operative complications and reoperative interventions were mapped across the respective national healthcare administrative coding systems. Discharge data from January 2006 to June 2011 for patients who had undergone colorectal surgical resections were analysed to generate risk‐adjusted models for mortality, length of stay, readmissions and reoperations.ResultsIn all, 52 544 case records were collated from 31 institutions in five countries. Mapping of all the coding systems was achieved so that diagnosis and procedures from the participant countries could be compared. Using the aligned coding systems to develop risk‐adjusted models, the 30‐day mortality rate for colorectal surgery was 3.95% (95% CI 0.86–7.54), the 30‐day readmission rate was 11.05% (5.67–17.61), the 28‐day reoperation rate was 6.13% (3.68–9.66) and the mean length of stay was 14 (7.65–46.76) days.ConclusionThe linkage of international hospital administrative data that we developed enabled comparison of documented surgical outcomes between countries. This methodology may facilitate international benchmarking.
Biphasic modulation of cancer stem cell‐driven solid tumour dynamics in response to reactivated replicative senescence
Authors: Poleszczuk J. , Hahnfeldt P. , Enderling H. 
Published: March 2014

AbstractObjectivesCell senescence is a physiological programme of irreversible mitotic arrest that is triggered after a variety of intracellular and extracellular events. Its purpose is to protect tissue integrity by disabling mitosis in stressed or damaged cells. The senescence program serves as a tumour suppressor, and cancer cells are believed to bypass senescence to advance to malignancy. Recent studies have shown that senescence can be reactivated in cancer cells through a number of external perturbations, including oncogene activation, tumour suppressor gene withdrawal and irradiation.Materials and methodsWe have developed an agent‐based model of solid tumour growth whose input population composition is based on the cancer stem‐cell hypothesis. It is used to show how cancer stem cells can drive tumour progression, while non‐stem cancer cells (CCs) interfere with this by impeding cancer stem‐cell dynamics.ResultsHere we show that intratumoural competition between the two cell types may arise to modulate tumour progression and ultimately cancer presentation risk. Model simulations reveal that reactivation of the replicative senescence programme in CCs initially increases total tumour burden, as attrition from cell death is partially averted, but evolves to provide tumour control in the long‐term through increasing constraints on stem‐cell compartment kinetics.ConclusionsReactivation of replicative senescence can prolong CC competition with cancer stem cells, thereby ultimately inhibiting malignant progression regardless of tumour size.
Incidence and precipitants of hospitalization for pancreatitis in people with diabetes: the Fremantle Diabetes Study
Authors: Davis T. M. E. , Drinkwater J. , Davis W. A. 
Published: March 2014

AbstractAimsTo determine the relative risk of pancreatitis in diabetes, and to establish whether diabetes‐related as well as recognized risk factors contribute.MethodsWe studied 1426 participants [mean (sd) age 62.1 (13.3) years, 49.6% male, 90.9% Type 2 diabetes, median (interquartile range) diabetes duration 4.0 (1.0–10.0) years] from the community‐based Fremantle Diabetes Study Phase I and 5663 matched residents without diabetes from the same geographical area. Pancreatitis hospitalizations between 1982 and 2010 were ascertained using validated data linkage. For Fremantle Diabetes Study Phase I participants, chart review provided data on the likely causes of pancreatitis.ResultsA total of 21 Fremantle Diabetes Study Phase I participants (1.5%) were hospitalized for pancreatitis before study entry vs 29 (0.5%) of contemporaneous residents without diabetes. During a mean (sd) of 12.1 (5.4) years of follow‐up from entry, 22 (1.6%) Fremantle Diabetes Study Phase I participants were hospitalized for a first‐ever episode of pancreatitis on 37 occasions (1.31/1000 person‐years) compared with 58 (1.0%) residents without diabetes on 81 occasions during a mean (sd) 13.6 (4.8) years (0.75/1000 person‐years). The age‐ and sex‐adjusted hazard ratio (95% CI) for first‐ever pancreatitis hospitalization in Fremantle Diabetes Study Phase I participants was 1.73 (1.06–2.83; P=0.029). Chart review of 17 of the 22 Fremantle Diabetes Study Phase I participants (77%) with incident pancreatitis and available case notes revealed that four (24%) presented without objective evidence of pancreatitis, seven (41%) presented with cholelithiasis, three (18%) with excessive alcohol consumption, two (12%) as a complication of elective endoscopic retrograde cholangiopancreatography, and one (6%) with hypertriglyceridaemia.ConclusionConsistent with previously published data, the risk of pancreatitis was higher in community‐dwelling Fremantle Diabetes Study Phase I participants but conventional precipitants accounted for confirmed cases. These data question whether diabetes‐specific risk factors cause or contribute to pancreatitis.