2,714 research outputs found
Functional gastrointestinal disorders in inflammatory bowel disease: Time for a paradigm shift?
Recent advances in biological therapies have revolutionalised and redefined treatment targets in inflammatory bowel disease (IBD). There is now a stronger emphasis on achieving the more stringent therapeutic goals of mucosal and histological healing, rather than clinical remission alone. Consequently, the treatment of refractory âfunctionalâ gastrointestinal symptoms, often attributed as the aftermath of previous inflammation, has recently become more prominent in quiescent disease. With further expected advances in anti-inflammatory treatments on the horizon, the burden of such symptoms in quiescent disease, which have been relatively neglected, is set to become an even bigger problem. In this article, we highlight the current state of research and understanding in this field, including recent developments and clinical practice guidelines on the diagnosis and management of functional gastrointestinal symptoms, such as irritable bowel syndrome and functional anorectal and pelvic floor disorders, in patients with quiescent IBD. These disorders are not only highly prevalent in these patients, they are often misdiagnosed, and are difficult to treat, with very few evidence-based therapies. Moreover, they are associated with substantial impairment in quality-of-life, considerable morbidity, and psychological distress. There is therefore an urgent need for a change in emphasis towards earlier recognition, positive diagnosis, and targeted treatment for patients with ongoing functional gastrointestinal symptoms in the absence of active IBD. This article also highlights the need for further research to develop much needed evidence-based therapies
Optimising use of electronic health records to describe the presentation of rheumatoid arthritis in primary care: a strategy for developing code lists
Background
Research using electronic health records (EHRs) relies heavily on coded clinical data. Due to variation in coding practices, it can be difficult to aggregate the codes for a condition in order to define cases. This paper describes a methodology to develop âindicator markersâ found in patients with early rheumatoid arthritis (RA); these are a broader range of codes which may allow a probabilistic case definition to use in cases where no diagnostic code is yet recorded.
Methods
We examined EHRs of 5,843 patients in the General Practice Research Database, aged âĽ30y, with a first coded diagnosis of RA between 2005 and 2008. Lists of indicator markers for RA were developed initially by panels of clinicians drawing up code-lists and then modified based on scrutiny of available data. The prevalence of indicator markers, and their temporal relationship to RA codes, was examined in patients from 3y before to 14d after recorded RA diagnosis.
Findings
Indicator markers were common throughout EHRs of RA patients, with 83.5% having 2 or more markers. 34% of patients received a disease-specific prescription before RA was coded; 42% had a referral to rheumatology, and 63% had a test for rheumatoid factor. 65% had at least one joint symptom or sign recorded and in 44% this was at least 6-months before recorded RA diagnosis.
Conclusion
Indicator markers of RA may be valuable for case definition in cases which do not yet have a diagnostic code. The clinical diagnosis of RA is likely to occur some months before it is coded, shown by markers frequently occurring âĽ6 months before recorded diagnosis. It is difficult to differentiate delay in diagnosis from delay in recording. Information concealed in free text may be required for the accurate identification of patients and to assess the quality of care in general practice
Measurement of the antineutrino neutral-current elastic differential cross section
arXiv:1309.7257v1 [hep-ex
Transactivation of EGFR by LPS induces COX-2 expression in enterocytes
Necrotizing enterocolitis (NEC) is the leading cause of gastrointestinal morbidity and mortality in preterm infants. NEC is characterized by an exaggerated inflammatory response to bacterial flora leading to bowel necrosis. Bacterial lipopolysaccharide (LPS) mediates inflammation through TLR4 activation and is a key molecule in the pathogenesis of NEC. However, LPS also induces cyclooxygenase-2 (COX-2), which promotes intestinal barrier restitution through stimulation of intestinal cell survival, proliferation, and migration. Epidermal growth factor receptor (EGFR) activation prevents experimental NEC and may play a critical role in LPS-stimulated COX-2 production. We hypothesized that EGFR is required for LPS induction of COX-2 expression. Our data show that inhibiting EGFR kinase activity blocks LPS-induced COX-2 expression in small intestinal epithelial cells. LPS induction of COX-2 requires Src-family kinase signaling while LPS transactivation of EGFR requires matrix metalloprotease (MMP) activity. EGFR tyrosine kinase inhibitors block LPS stimulation of mitogen-activated protein kinase ERK, suggesting an important role of the MAPK/ERK pathway in EGFR-mediated COX-2 expression. LPS stimulates proliferation of IEC-6 cells, but this stimulation is inhibited with either the EGFR kinase inhibitor AG1478, or the selective COX-2 inhibitor Celecoxib. Taken together, these data show that EGFR plays an important role in LPS-induction of COX-2 expression in enterocytes, which may be one mechanism for EGF in inhibition of NEC
Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases
PURPOSE: Bone metastases secondary to solid tumors increase the risk of skeletal-related events (SREs), including the occurrence of pathological fracture (PF), radiation to bone (RB), surgery to bone (SB), and spinal cord compression (SCC). The aim of this study was to evaluate the impact of SREs on patients' pain, analgesic use, and pain interference with daily functioning.
METHODS: Data were combined from patients with solid tumors and bone metastases who received denosumab or zoledronic acid across three identically designed phase 3 trials (N = 5543). Pain severity (worst pain) and pain interference were assessed using the Brief Pain Inventory at baseline and each monthly visit. Analgesic use was quantified using the Analgesic Quantification Algorithm.
RESULTS: The proportion of patients with moderate/severe pain and strong opioid use generally increased in the 6 months preceding an SRE and remained elevated, while they remained relatively consistent over time in patients without an SRE. Regression analysis indicated that all SRE types were significantly associated with an increased risk of progression to moderate/severe pain and strong opioid use. PF, RB, and SCC were associated with significantly greater risk of pain interference overall. Results were similar for pain interference with emotional well-being. All SRE types were associated with significantly greater risk of pain interference with physical function.
CONCLUSIONS: SREs are associated with increased pain and analgesic use in patients with bone metastases. Treatments that prevent SREs may decrease pain and the need for opioid analgesics and reduce the impact of pain on daily functioning
Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases
PURPOSE: Bone metastases secondary to solid tumors increase the risk of skeletal-related events (SREs), including the occurrence of pathological fracture (PF), radiation to bone (RB), surgery to bone (SB), and spinal cord compression (SCC). The aim of this study was to evaluate the impact of SREs on patients' pain, analgesic use, and pain interference with daily functioning.
METHODS: Data were combined from patients with solid tumors and bone metastases who received denosumab or zoledronic acid across three identically designed phase 3 trials (N = 5543). Pain severity (worst pain) and pain interference were assessed using the Brief Pain Inventory at baseline and each monthly visit. Analgesic use was quantified using the Analgesic Quantification Algorithm.
RESULTS: The proportion of patients with moderate/severe pain and strong opioid use generally increased in the 6 months preceding an SRE and remained elevated, while they remained relatively consistent over time in patients without an SRE. Regression analysis indicated that all SRE types were significantly associated with an increased risk of progression to moderate/severe pain and strong opioid use. PF, RB, and SCC were associated with significantly greater risk of pain interference overall. Results were similar for pain interference with emotional well-being. All SRE types were associated with significantly greater risk of pain interference with physical function.
CONCLUSIONS: SREs are associated with increased pain and analgesic use in patients with bone metastases. Treatments that prevent SREs may decrease pain and the need for opioid analgesics and reduce the impact of pain on daily functioning
Scaling properties of protein family phylogenies
One of the classical questions in evolutionary biology is how evolutionary
processes are coupled at the gene and species level. With this motivation, we
compare the topological properties (mainly the depth scaling, as a
characterization of balance) of a large set of protein phylogenies with a set
of species phylogenies. The comparative analysis shows that both sets of
phylogenies share remarkably similar scaling behavior, suggesting the
universality of branching rules and of the evolutionary processes that drive
biological diversification from gene to species level. In order to explain such
generality, we propose a simple model which allows us to estimate the
proportion of evolvability/robustness needed to approximate the scaling
behavior observed in the phylogenies, highlighting the relevance of the
robustness of a biological system (species or protein) in the scaling
properties of the phylogenetic trees. Thus, the rules that govern the
incapability of a biological system to diversify are equally relevant both at
the gene and at the species level.Comment: Replaced with final published versio
Prevalence of neck pain in subjects with metabolic syndrome - a cross-sectional population-based study
<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) is increasingly common. Obesity has been suggested to associate with neck pain but prevalence of neck pain in subjects with MetS has not been studied. Aim of this study was to analyse the association between MetS and neck pain.</p> <p>Methods</p> <p>The study population consisted of 1294 middle-aged subjects in Pieksämäki, Finland. A total of 399 males and 500 females participated (69%). The mean age of both males and females was 46 years. Clinical and biochemical measurements were taken. The participants filled out a standard questionnaire. Psychological distress was assessed with the 12-item General Health Questionnaire (GHQ-12). Neck pain was defined as neck pain perceived daily. MetS was defined using National Cholesterol Education Program (NCEP) criteria. Statistical comparisons between the groups were performed using a bootstrap-type t-test or Chi-Square test. Risk ratios of having neck pain were calculated using generalised linear models with age, smoking, alcohol use, exercise and GHQ-12 score as covariates.</p> <p>Results</p> <p>The prevalence of MetS was 33% in males and 29% in females. Neck pain was present in 11% (N = 42) of males and 19% (N = 93) of females (P < 0.001). The prevalence of neck pain was 7.9% (95% CI, 4.9% to 12%) among male subjects without MetS and 16% (95% CI, 10% to 23%) among those with MetS. The respective proportions among females were 16% (95% CI, 12% to 20%) and 25% (95% CI, 18% to 33%). The multivariate analysis showed an increased risk of neck pain in males with MetS (RR 2.1, 95% CI, 1.2 to 3.7, P = 0.010) and in females with MetS (RR 1.5, 95% CI, 1.0 to 2.1, P = 0.040).</p> <p>Conclusions</p> <p>MetS was associated with neck pain. This association was stronger in males, but the prevalence of neck pain was higher in females. Prospective studies should explore the potential causal association between neck pain and MetS and the potential common background factors of neck pain and MetS.</p
Changing eating behaviours to treat childhood obesity in the community using Mandolean: the Community Mandolean randomised controlled trial (ComMando) â a pilot study
Background
Around one in five children in England is obese when they leave primary school. Thus far, it has not been demonstrated that primary care interventions to manage childhood obesity can achieve significant weight reduction. Training obese children to eat more slowly as an adjunct to other healthy lifestyle behaviour change has been shown to increase weight reduction in a hospital setting.
Objectives
This pilot study aimed to test recruitment strategies, treatment adherence, clinic attendance and participantsâ experiences of using a device [MandoleanÂŽ (previously MandometerÂŽ, Mikrodidakt AB, Lund, Sweden)] to slow down speed of eating as an adjunct to dietary and activity advice in treating obesity in primary school-aged children.
Design
A two-arm, parallel, randomised controlled trial with a qualitative study embedded within the pilot. Randomisation occurred after informed consent and baseline measures were collected. Participants were randomised by the Bristol Randomised Trials Collaboration randomisation service with allocation stratified by hub and minimised by age of the child, gender, and baseline body mass index (BMI) standard deviation score (BMI z-value) of the child, and by BMI of the study parent (obese/not obese).
Setting
General practices across Bristol, North Somerset and South Gloucestershire primary care trusts.
Participants
Children (BMI âĽâ95th percentile) aged 5â11 years and their families.
Intervention
Standard care comprised dietary and activity advice by trained practice nurses. Adjunctive Mandolean training (the intervention) educated participants to eat meals more slowly and to rate levels of fullness (satiety). Mandolean is a small computer device attached to a weighing scale that provides visual and oral feedback during meals while generating a visual representation of levels of satiety during the meal. Participants were encouraged to eat their main meal each day from the Mandolean. One parent was also given a Mandolean to use when eating with the child.
Outcome measures
Outcomes for the pilot were recruitment of 36 families to the trial in the 9-month pilot phase, that meals would be eaten at least five times a week off a Mandolean by 90% of patients randomised to the intervention arm, that 80% of patients in both arms would attend the weight management clinic appointment 3 months post randomisation and that >â60% of children using Mandolean would demonstrate a reduction in speed of eating from baseline within 3 months of randomisation.
Results
None of the criteria for progression to the main trial were reached. Despite numerous pathways being available for referral, only 21 (13 to standard care, eight to intervention arm; 58%) of the target 36 families were recruited in the pilot phase. Less than 20% of those randomised to Mandolean used the device at least five times a week. The >â60% target for slowing down of eating speed by 3 months was unmet. Attendance at the weight management clinic in general practice hubs for both arms of the study at 3 months was 44% against a target of 80%.
Conclusions
This pilot trial failed to meet its objectives in terms of recruitment, treatment adherence, demonstration of a reduction in speed of eating in sufficient numbers of children, and attendance at followâup appointments. Despite a high prevalence of childhood obesity in the geographical area and practices signing up for the trial, this study, like many others, demonstrates a failure of families to engage with and respond to primary care weight management interventions. We need to understand why the target population seems inured to the health message that childhood obesity is a significant health-care issue and identify the barriers to seeking help and then acting on positive health behaviour retraining. Only when we have fully understood the general publicâs perceptions of childhood obesity and have identified ways of engaging target populations can we hope to develop interventions that can work in a primary or community-based setting
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