391 research outputs found
The endorsement of cognitive distortions: comparing child pornography offenders and contact sex offenders
This study examined the endorsement of cognitive distortions in child pornography
offenders (CPOs), using an established assessment tool, the Abel and Becker
Cognition Scale. The scale was expanded to include cognitions specific to child
pornography offending, extracted from Howitt and Sheldon’s Children and Sexual
Activities Inventory (C&SA). Three samples of CPOs, child sex offenders and
offenders with both offence types responded to the cognition items. An exploratory
Principal Component Analysis suggested six main components of the scale. CPOs
were significantly less likely to endorse these statements in general, and this was more
pronounced on items that project blame onto the child or other people, describe a need
for power and consider children as sexually active. The statements extracted from
C&SA did not differentiate between the groups. These findings are discussed under
consideration of the relationship between cognitive distortions and contact sex
offending, and in reference to the general criticism concerning the definition and
appropriate measurement of cognitive distortion
Implantable cardioverter defibrillators for the treatment of arrhythmias and cardiac resynchronisation therapy for the treatment of heart failure: systematic review and economic evaluation
Background
This assessment updates and expands on two previous technology assessments that evaluated implantable cardioverter defibrillators (ICDs) for arrhythmias and cardiac resynchronisation therapy (CRT) for heart failure (HF).
Objectives
To assess the clinical effectiveness and cost-effectiveness of ICDs in addition to optimal pharmacological therapy (OPT) for people at increased risk of sudden cardiac death (SCD) as a result of ventricular arrhythmias despite receiving OPT; to assess CRT with or without a defibrillator (CRT-D or CRT-P) in addition to OPT for people with HF as a result of left ventricular systolic dysfunction (LVSD) and cardiac dyssynchrony despite receiving OPT; and to assess CRT-D in addition to OPT for people with both conditions.
Data sources
Electronic resources including MEDLINE, EMBASE and The Cochrane Library were searched from inception to November 2012. Additional studies were sought from reference lists, clinical experts and manufacturers’ submissions to the National Institute for Health and Care Excellence.
Review methods
Inclusion criteria were applied by two reviewers independently. Data extraction and quality assessment were undertaken by one reviewer and checked by a second. Data were synthesised through narrative review and meta-analyses. For the three populations above, randomised controlled trials (RCTs) comparing (1) ICD with standard therapy, (2) CRT-P or CRT-D with each other or with OPT and (3) CRT-D with OPT, CRT-P or ICD were eligible. Outcomes included mortality, adverse events and quality of life. A previously developed Markov model was adapted to estimate the cost-effectiveness of OPT, ICDs, CRT-P and CRT-D in the three populations by simulating disease progression calculated at 4-weekly cycles over a lifetime horizon.
Results
A total of 4556 references were identified, of which 26 RCTs were included in the review: 13 compared ICD with medical therapy, four compared CRT-P/CRT-D with OPT and nine compared CRT-D with ICD. ICDs reduced all-cause mortality in people at increased risk of SCD, defined in trials as those with previous ventricular arrhythmias/cardiac arrest, myocardial infarction (MI) > 3 weeks previously, non-ischaemic cardiomyopathy (depending on data included) or ischaemic/non-ischaemic HF and left ventricular ejection fraction ≤ 35%. There was no benefit in people scheduled for coronary artery bypass graft. A reduction in SCD but not all-cause mortality was found in people with recent MI. Incremental cost-effectiveness ratios (ICERs) ranged from £14,231 per quality-adjusted life-year (QALY) to £29,756 per QALY for the scenarios modelled. CRT-P and CRT-D reduced mortality and HF hospitalisations, and improved other outcomes, in people with HF as a result of LVSD and cardiac dyssynchrony when compared with OPT. The rate of SCD was lower with CRT-D than with CRT-P but other outcomes were similar. CRT-P and CRT-D compared with OPT produced ICERs of £27,584 per QALY and £27,899 per QALY respectively. The ICER for CRT-D compared with CRT-P was £28,420 per QALY. In people with both conditions, CRT-D reduced the risk of all-cause mortality and HF hospitalisation, and improved other outcomes, compared with ICDs. Complications were more common with CRT-D. Initial management with OPT alone was most cost-effective (ICER £2824 per QALY compared with ICD) when health-related quality of life was kept constant over time. Costs and QALYs for CRT-D and CRT-P were similar. The ICER for CRT-D compared with ICD was £27,195 per QALY and that for CRT-D compared with OPT was £35,193 per QALY.
Limitations
Limitations of the model include the structural assumptions made about disease progression and treatment provision, the extrapolation of trial survival estimates over time and the assumptions made around parameter values when evidence was not available for specific patient groups.
Conclusions
In people at risk of SCD as a result of ventricular arrhythmias and in those with HF as a result of LVSD and cardiac dyssynchrony, the interventions modelled produced ICERs of < £30,000 per QALY gained. In people with both conditions, the ICER for CRT-D compared with ICD, but not CRT-D compared with OPT, was < £30,000 per QALY, and the costs and QALYs for CRT-D and CRT-P were similar. A RCT comparing CRT-D and CRT-P in people with HF as a result of LVSD and cardiac dyssynchrony is required, for both those with and those without an ICD indication. A RCT is also needed into the benefits of ICD in non-ischaemic cardiomyopathy in the absence of dyssynchrony.
Study registration
This study is registered as PROSPERO number CRD42012002062.
Funding
The National Institute for Health Research Health Technology Assessment programme
The three dimensions of online child pornography offending
The internet has opened up opportunities for non-contact sex offending, such as the viewing of child pornography. This paper proposes a model for the classification of child pornography offenders as an aid for their assessment and treatment, deducted from empirical studies and existing
typologies for child pornography offenders. Different subgroups of child pornography offenders may be described according to three dimensions: (1) type of offending, (2) the motivation behind child pornography offending and (3) the situational and social engagement in the offending behaviour. Distinct pathways of child pornography offending can be identified, related to differing criminogenic
needs, severity of offending, and appropriate assessment and treatment strategies for the offenders
Transforming Community Health Services for Children and Young People who are Ill : A quasi-experimental evaluation
Background: Children’s community nursing (CCN) services support children with acute, chronic, complex and end-of-life care needs in the community. Objectives: This research examined the impact of introducing and expanding CCN services on quality, acute care and costs. Methods: A longitudinal, mixed-methods, case study design in three parts. The case studies were in five localities introducing or expanding services. Part 1: an interrupted time series (ITS) analysis of Hospital Episode Statistics on acute hospital admission for common childhood illness, and bed-days and length of stay for all conditions, including a subset for complex conditions. The ITS used between 60 and 84 time points (monthly data) depending on the case site. Part 2: a cost–consequence analysis using activity data from CCN services and resource-use data from a subset of families (n = 32). Part 3: in-depth interviews with 31 parents of children with complex conditions using services in the case sites and a process evaluation of service change with 41 NHS commissioners, managers and practitioners, using longitudinal in-depth interviews, focus groups and documentary data. Findings: Part 1: the ITS analysis showed a mixed pattern of impact on acute activity, with the greatest reductions in areas that had rates above the national average before CCN services were introduced and significant reductions in some teams in acute activity for children with complex conditions. Some models of CCN appear to have more potential for impact than others. Part 2: the cost–consequence analysis covered only part of the CCN teams’ activity. It showed some potential savings from reduced admissions and bed-days, but none that was greater than the total cost of the services. Part 3: three localities implemented services as planned, one achieved partial service change and one was not able to achieve any service change. Organisational stability, finance, medical stakeholder support, competition, integration with primary care and visibility influenced the planning and implementation of new and expanded CCN services. Feeling supported to manage their ill child at home was a key outcome of using services for parents. Various service features contributed to this and were important in different ways at different times. Other outcomes included being able to avoid hospital care, enabling the child to stay in school, and getting respite. Although parents judged that care was of high quality when teams enabled them to feel supported, reassured and secure in managing their ill child at home, this did not depend on a constant level of contact from teams. Limitations: Delays in service reconfigurations required adaptation of research activity across sites. Use of administrative data, such as Hospital Episode Statistics, for research purposes is technically difficult and imposed some limitations on both the ITS and the cost–consequence analyses. Conclusions: Large, generic CCN teams that integrate acute admission avoidance for all children with support for children with complex conditions and highly targeted teams for children with complex conditions offer the possibility of supporting children more appropriately at home while also making some difference to acute activity. This possibility remains to be tested further. Future work: Further work should refine the evidence on outcomes of services by looking at outcomes in promising models, value for money and measuring quality-based outcomes. Funding: The National Institute for Health Research Health Services and Delivery Research Programme
Preventing postpartum uterine disease in dairy cattle depends on avoiding, tolerating and resisting pathogenic bacteria
Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function
Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes
New Antibiotics for Staphylococcus aureus Infection : An Update from the World Association of Infectious Diseases and Immunological Disorders (WAidid) and the Italian Society of Anti-Infective Therapy (SITA)
Altres ajuts: World Association for Infectious Diseases and Immunological Disorders (WAidid; WAidid-2022-01).Staphylococcus aureus is an extremely virulent pathogen that is capable of quickly evolving and developing antibiotic resistance. To overcome this problem, new antibiotics have been developed. Some of these have been licenced for use in clinical practice, mainly for the treatment of adults with acute skin and soft tissue infections, in addition to both community-acquired pneumonia (CAP) and nosocomial pneumonia (hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia). In this paper, the main characteristics and clinical use of new licenced anti-staphylococcal drugs have been discussed. In vitro studies have demonstrated that some new anti-staphylococcal antibiotics have better antimicrobial activity and, at least in certain cases, more favourable pharmacokinetic properties and higher safety and tolerability than the presently available anti-staphylococcal drugs. This suggests that they may have a potential use in reducing the risk of failure of S. aureus therapy. However, an in-depth analysis of microbiological and clinical studies carried out with these new drugs seems to indicate that further studies need to be conducted before the problem of resistance of S. aureus to the antibiotics available today can be completely solved. Considering the overall available research, the drugs that are active against S. aureus appear to present a great therapeutic opportunity for overcoming resistance to traditional therapy. There are advantages in the pharmacokinetic characteristics of some of these drugs and they have the potential to reduce hospital stays and economic costs associated with their use
Black liquor and the hangover effect: fish assemblage recovery dynamics following a pulse disturbance
Anthropogenic perturbations impact aquatic systems causing wide-ranging responses, from assemblage restructuring to assemblage recovery. Previous studies indicate the duration and intensity of disturbances play a role in the dynamics of assemblage recovery. In August 2011, the Pearl River, United States, was subjected to a weak black liquor spill from a paper mill which resulted in substantial loss of fish in a large stretch of the main channel. We quantified resilience and recovery of fish assemblage structure in the impacted area following the event. We compared downstream (impacted) assemblages to upstream (unimpacted) assemblages to determine initial impacts on structure. Additionally, we incorporated historic fish collections (1988–2011) to examine impacts on assemblage structure across broad temporal scales. Based on NMDS, upstream and downstream sites generally showed similar assemblage structure across sample periods with the exception of the 2 months postdischarge, where upstream and downstream sites visually differed. Multivariate analysis of variance (PERMANOVA) indicated significant seasonal variation among samples, but found no significant interaction between impacted and unimpacted assemblages following the discharge event. However, multivariate dispersion (MVDISP) showed greater variance among assemblage structure following the discharge event. These results suggest that 2 months following the disturbance represent a time period of stochasticity in regard to assemblage structure dynamics, and this was followed by rapid recovery. We term this dynamic the “hangover effect” as it represents the time frame from the cessation of the perturbation to the assemblage's return to predisturbance conditions. The availability and proximity of tributaries and upstream refugia, which were not affected by the disturbance, as well as the rapid recovery of abiotic parameters likely played a substantial role in assemblage recovery. This study not only demonstrates rapid recovery in an aquatic system, but further demonstrates the value of continuous, long-term, data collections which enhance our understanding of assemblage dynamics.Ye
Ablation of PGC-1β Results in Defective Mitochondrial Activity, Thermogenesis, Hepatic Function, and Cardiac Performance
The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1β (PGC-1β) has been implicated in important metabolic processes. A mouse lacking PGC-1β (PGC1βKO) was generated and phenotyped using physiological, molecular, and bioinformatic approaches. PGC1βKO mice are generally viable and metabolically healthy. Using systems biology, we identified a general defect in the expression of genes involved in mitochondrial function and, specifically, the electron transport chain. This defect correlated with reduced mitochondrial volume fraction in soleus muscle and heart, but not brown adipose tissue (BAT). Under ambient temperature conditions, PGC-1β ablation was partially compensated by up-regulation of PGC-1α in BAT and white adipose tissue (WAT) that lead to increased thermogenesis, reduced body weight, and reduced fat mass. Despite their decreased fat mass, PGC1βKO mice had hypertrophic adipocytes in WAT. The thermogenic role of PGC-1β was identified in thermoneutral and cold-adapted conditions by inadequate responses to norepinephrine injection. Furthermore, PGC1βKO hearts showed a blunted chronotropic response to dobutamine stimulation, and isolated soleus muscle fibres from PGC1βKO mice have impaired mitochondrial function. Lack of PGC-1β also impaired hepatic lipid metabolism in response to acute high fat dietary loads, resulting in hepatic steatosis and reduced lipoprotein-associated triglyceride and cholesterol content. Altogether, our data suggest that PGC-1β plays a general role in controlling basal mitochondrial function and also participates in tissue-specific adaptive responses during metabolic stress
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