2494 research outputs found
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Exact p-values for pairwise comparison of Friedman rank sums, with application to comparing classifiers
No full textAbstract
Background
The Friedman rank sum test is a widely-used nonparametric method in computational biology. In addition to examining the overall null hypothesis of no significant difference among any of the rank sums, it is typically of interest to conduct pairwise comparison tests. Current approaches to such tests rely on large-sample approximations, due to the numerical complexity of computing the exact distribution. These approximate methods lead to inaccurate estimates in the tail of the distribution, which is most relevant for p -value calculation.
Results
We propose an efficient, combinatorial exact approach for calculating the probability mass distribution of the rank sum difference statistic for pairwise comparison of Friedman rank sums, and compare exact results with recommended asymptotic approximations. Whereas the chi-squared approximation performs inferiorly to exact computation overall, others, particularly the normal, perform well, except for the extreme tail. Hence exact calculation offers an improvement when small p -values occur following multiple testing correction. Exact inference also enhances the identification of significant differences whenever the observed values are close to the approximate critical value. We illustrate the proposed method in the context of biological machine learning, were Friedman rank sum difference tests are commonly used for the comparison of classifiers over multiple datasets.
Conclusions
We provide a computationally fast method to determine the exact p -value of the absolute rank sum difference of a pair of Friedman rank sums, making asymptotic tests obsolete. Calculation of exact p -values is easy to implement in statistical software and the implementation in R is provided in one of the Additional files and is also available at http://www.ru.nl/publish/pages/726696/friedmanrsd.zip
Estimating cardiovascular disease incidence from prevalence: a spreadsheet based model
No full textAbstract
Background
Disease incidence and prevalence are both core indicators of population health. Incidence is generally not as readily accessible as prevalence. Cohort studies and electronic health record systems are two major way to estimate disease incidence. The former is time-consuming and expensive; the latter is not available in most developing countries. Alternatively, mathematical models could be used to estimate disease incidence from prevalence.
Methods
We proposed and validated a method to estimate the age-standardized incidence of cardiovascular disease (CVD), with prevalence data from successive surveys and mortality data from empirical studies. Hallett\u2019s method designed for estimating HIV infections in Africa was modified to estimate the incidence of myocardial infarction (MI) in the U.S. population and incidence of heart disease in the Canadian population.
Results
Model-derived estimates were in close agreement with observed incidence from cohort studies and population surveillance systems. This method correctly captured the trend in incidence given sufficient waves of cross-sectional surveys. The estimated MI declining rate in the U.S. population was in accordance with the literature. This method was superior to closed cohort, in terms of the estimating trend of population cardiovascular disease incidence.
Conclusion
It is possible to estimate CVD incidence accurately at the population level from cross-sectional prevalence data. This method has the potential to be used for age- and sex- specific incidence estimates, or to be expanded to other chronic conditions
A prospective 2-site parallel intervention trial of a research-based film to increase exercise amongst older hemodialysis patients
No full textAbstract
Background
Evidence suggests that exercise training for hemodialysis patients positively improves morbidity and mortality outcomes, yet exercise programs remain rare and are not systematically incorporated into care. We developed a research-based film, Fit for Dialysis, designed to introduce, motivate, and sustain exercise for wellness amongst older hemodialysis patients, and exercise counseling and support by nephrologists, nurses, and family caregivers. The objective of this clinical trial is to determine whether and in what ways Fit for Dialysis improves outcomes and influences knowledge/attitudes regarding the importance of exercise for wellness in the context of end-stage renal disease.
Methods/Design
This 2-site parallel intervention trial will recruit 60 older hemodialysis patients from two urban hospitals. The trial will compare the film\u2009+\u2009a 16-week exercise program in one hospital, with a 16-week exercise-only program in another hospital. Physical fitness and activity measures will be performed at baseline, 8 and 16\ua0weeks, and 12\ua0weeks after the end of the program. These include the 2-min Walk Test, Grip Strength, Duke Activity Status Index, and the Timed Up-and-Go Test, as well as wearing a pedometer for one week. Throughout the 16-week exercise program, and at 12\ua0weeks after, we will record patients\u2019 exercise using the Godin Leisure-time Exercise Questionnaire. Patients will also keep a diary of the exercise that they do at home on non-dialysis days. Qualitative interviews, conducted at baseline, 8, and 16\ua0weeks, will explore the impact of Fit for Dialysis on the knowledge/attitudes of patients, family caregivers, and nephrology staff regarding exercise for wellness, and in what ways the film is effective in educating, motivating, or sustaining patient exercise during dialysis, at home, and in the community.
Discussion
This research will determine for whom Fit for Dialysis is effective, why, and under what conditions. If Fit for Dialysis is proven beneficial to patients, nephrology staff and family caregivers, research-based film as a model to support exercise promotion and adherence could be used to support the National Kidney Foundation\u2019s guideline recommendation (NKF-KDOQI) that exercise be incorporated into the care and treatment of dialysis patients.
Trial registration
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Study protocol of the TIRED study: a randomised controlled trial comparing either graded exercise therapy for severe fatigue or cognitive behaviour therapy with usual care in patients with incurable cancer
No full textAbstract
Background
Fatigue is a common and debilitating symptom for patients with incurable cancer receiving systemic treatment with palliative intent. There is evidence that non-pharmacological interventions such as graded exercise therapy (GET) or cognitive behaviour therapy (CBT) reduce cancer-related fatigue in disease-free cancer patients and in patients receiving treatment with curative intent. These interventions may also result in a reduction of fatigue in patients receiving treatment with palliative intent, by improving physical fitness (GET) or changing fatigue-related cognitions and behaviour (CBT). The primary aim of our study is to assess the efficacy of GET or CBT compared to usual care (UC) in reducing fatigue in patients with incurable cancer.
Methods
The TIRED study is a multicentre three-armed randomised controlled trial (RCT) for incurable cancer patients receiving systemic treatment with palliative intent. Participants will be randomised to GET, CBT, or UC. In addition to UC, the GET group will participate in a 12-week supervised exercise programme. The CBT group will receive a 12-week CBT intervention in addition to UC. Primary and secondary outcome measures will be assessed at baseline, post-intervention (14\ua0weeks), and at follow-up assessments (18 and 26\ua0weeks post-randomisation). The primary outcome measure is fatigue severity (Checklist Individual Strength subscale fatigue severity ). Secondary outcome measures are fatigue (EORTC-QLQ-C30 subscale fatigue ), functional impairments (Sickness Impact Profile total score , EORTC-QLQ-C30 subscale emotional functioning, subscale physical functioning ) and quality of life (EORTC-QLQ-C30 subscale QoL ). Outcomes at 14\ua0weeks (primary endpoint) of either treatment arm will be compared to those of UC participants. In addition, outcomes at 18 and 26\ua0weeks (follow-up assessments) of either treatment arm will be compared to those of UC participants.
Discussion
To our knowledge, the TIRED study is the first RCT investigating the efficacy of GET and CBT on reducing fatigue during treatment with palliative intent in incurable cancer patients. The results of this study will provide information about the possibility and efficacy of GET and CBT for severely fatigued incurable cancer patients.
Trial ..
Participatory design in the development of an early therapy intervention for perinatal stroke
No full textAbstract
Background
Perinatal stroke is the leading cause of unilateral (hemiparetic) cerebral palsy, with life-long personal, social and financial consequences. Translational research findings indicate that early therapy intervention has the potential for significant improvements in long-term outcome in terms of motor function. By involving families and health professionals in the development and design stage, we aimed to produce a therapy intervention which they would engage with.
Methods
Nine parents of children with hemiparesis and fourteen health professionals involved in the care of infants with perinatal stroke took part in peer review and focus groups to discuss evolving therapy materials, with revisions made iteratively. The materials and approach were also discussed at a meeting of the London Child Stroke Research Reference Group. Focus group data were coded using Normalisation Process Theory constructs to explore potential barriers and facilitators to routine uptake of the intervention.
Results
We developed the Early Therapy in Perinatal Stroke (eTIPS) program - a parent-delivered, home-based complex intervention addressing a current gap in practice for infants in the first 6\ua0months of life after unilateral perinatal stroke and with the aim of improving motor outcome. Parents and health professionals saw the intervention as different from usual practice, and valuable (high coherence). They were keen to engage (high cognitive participation). They considered the tasks for parents to be achievable (high collective action). They demonstrated trust in the approach and felt that parents would undertake the recommended activities (high collective action). They saw the approach as flexible and adaptable (high reflexive monitoring). Following suggestions made, we added a section on involving the extended family, and obtained funding for a website and videos to supplement written materials.
Conclusions
Focus groups with parents and health professionals provided meaningful feedback to iteratively improve the intervention materials prior to embarking on a pilot study. The intervention has a high potential to normalize and become a routine part of parents\u2019 interactions with their child following unilateral perinatal stroke
Incidence and medical management of bisphosphonate-associated atypical femoral fractures in a major trauma centre: a retrospective observational study
No full textAbstract
Background
Atypical femoral fractures (AFFs) are rare events associated with increased duration of bisphosphonate exposure. Recommended management of AFFs include cessation of bisphosphonates and imaging of the contralateral femur. The aims of this study were to identify the local incidence of AFFs in bisphosphonate users and to audit the medical management of AFFs against published recommendations.
Methods
A retrospective analysis of the admissions database for a major trauma centre identified all femoral fractures (3150) in a five-year period (July 2009 to June 2014). Electronic health records and radiographs were reviewed using the 2013 American Society for Bone and Mineral Research (ASBMR) diagnostic criteria for AFF to establish the number of cases. To estimate incidence, the total number of bisphosphonate users was derived from primary care prescription and secondary care day-case records. Medical management of cases with AFF on bisphosphonates was audited against guidance from ASBMR and Medicines & Healthcare Products Regulatory Agency.
Results
10 out of 3150 femoral fractures met criteria for AFF; 7 of these patients had a history of exposure to bisphosphonates (6 oral, 1 intravenous). There were 19.1 AFFs per 100,000\ua0years of bisphosphonate use in our region. Bisphosphonates were stopped and the contralateral femur imaged in only 2 of the 7 patients treated with bisphosphonates.
Conclusion
Our local incidence is in line with published figures; however, this is the first published evidence suggesting that medical management and identification of AFF may be suboptimal. Managing these patients remains challenging due to their rarity and possible lack of awareness
A misdiagnosed case of osteoid osteoma of the talus: a case report and literature review
No full textAbstract
Background
Osteoid osteoma (OO) is a common benign bone tumour that is rarely found in the talus. Its nidus is difficult to detect on early imaging. The atypical symptoms of OO and the presence of concurrent trauma or sports injuries may lead to misdiagnosis and delayed treatment. We herein analyse a case of misdiagnosis of OO of the talus and discuss how to improve the early diagnosis of this rare lesion, thereby permitting rapid treatment.
Case presentation
A 23-year-old man with a history of left ankle sprains and chronic pain was diagnosed with another ankle sprain and managed conservatively based on normal X-ray findings. After 1\ua0year of recurring pain, he was diagnosed with ankle traumatic arthritis and underwent arthroscopic surgery. His preoperative ankle X-ray findings were still normal, and magnetic resonance imaging at that time demonstrated bone marrow oedema of the left talus. His symptoms reappeared shortly after surgery and progressively worsened. Magnetic resonance imaging performed 3\ua0months after surgery demonstrated widespread bone marrow oedema of the talus. The patient presented to our hospital for pain assessment and was diagnosed with OO of the talus 3\ua0years after his symptoms began. Preoperative computed tomography (CT) demonstrated a typical nidus of OO of the talus. After a second surgery, the patient\u2019s symptoms completely resolved, and pathologic examination confirmed that the lesion was OO. The patient recovered 3\ua0months later and was able to walk normally.
Conclusions
OO of the ankle joint exhibits a progressive course and is difficult to diagnose at an early stage. Patients with OO of the talus often have atypical imaging findings, no signs of ankle instability, and no anterior talofibular ligament tenderness. CT is valuable for diagnosing OO, although multiple CT scans may be required to detect the nidus. Proper imaging helps doctors to achieve the correct diagnosis early in the disease course, significantly shortening the treatment cycle and improving the patient\u2019s quality of life
Antinociceptive effect of methanol extract of Dalbergia sissoo leaves in mice
No full textAbstract
Background
Dalbergia sissoo DC. (Family: Fabaceae) is a medium to large deciduous tree, is locally called \u201cshishu\u201d in Bangladesh. It is used to treat sore throats, dysentery, syphilis, bronchitis, inflammations, infections, hernia, skin diseases, and gonorrhea. This study evaluated the antinociceptive effect of the methanol extract of D. sissoo leaves (MEDS) in mice.
Methods
The extract was assessed for antinociceptive activity using chemical and heat induced pain models such as hot plate, tail immersion, acetic acid-induced writhing, formalin, glutamate, and cinnamaldehyde test models in mice at the doses of 100, 200, and 400\ua0mg/kg (p.o.) respectively. Morphine sulphate (5\ua0mg/kg, i.p.) and diclofenac sodium (10\ua0mg/kg, i.p.) were used as reference analgesic drugs. To confirm the possible involvement of opioid receptor in the central antinociceptive effect of MEDS, naloxone was used to antagonize the effect.
Results
MEDS demonstrated potent and dose-dependent antinociceptive activity in all the chemical and heat induced mice models ( p \u2009<\u20090.001). The findings of this study indicate that the involvement of both peripheral and central antinociceptive mechanisms. The use of naloxone verified the association of opioid receptors in the central antinociceptive effect.
Conclusions
This study indicated the peripheral and central antinociceptive activity of the leaves of D. sissoo . These results support the traditional use of this plant in different painful conditions
Panaxatriol saponins promotes angiogenesis and enhances cerebral perfusion after ischemic stroke in rats
No full textAbstract
Background
Panaxatriol saponins (PTS), an extract from the traditional Chinese herb Panax notoginseng, which has been used to treat ischemic stroke for many years in China. However, the mechanism underlying the effects of PTS remains unclear. This study aimed to determine whether PTS can protect against ischemic brain injury by promoting angiogenesis and to explore the possible mechanism by which it promotes angiogenesis.
Methods
Middle cerebral artery occlusion (MCAO) was induced in rats, and neurological deficit scores and brain infarct volumes were assessed. Micro-Positron emission tomography (PET) was adopted to assess cerebral perfusion, and real-time PCR and western blotting were used to evaluate vascular growth factor and Sonic hedgehog (Shh) pathway component levels. Immunofluorescence staining was used to determine capillary densities in ischemic penumbrae.
Results
We showed that PTS improved neurological function and reduced infarct volumes in MCAO rats. Micro-PET indicated that PTS can significantly increase
18
F-fluorodeoxyglucose (
18
F-PDG) uptake by ischemic brain tissue and enhance cerebral perfusion after MCAO surgery. Moreover, PTS was able to increase capillary densities and enhance angiogenesis in ischemic boundary zones and up-regulate vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1) expression by activating the Shh signaling pathway.
Conclusion
These findings indicate that PTS exerts protective effects against cerebral ischemic injury by enhancing angiogenesis and improving microperfusion
Protective effects of aucubin on osteoarthritic chondrocyte model induced by hydrogen peroxide and mechanical stimulus
No full textAbstract
Background
During the onset of osteoarthritis (OA), certain biochemical events have been shown to accelerate cartilage degradation, including the dysregulation of cartilage ECM anabolism, abnormal generation of reactive oxygen species (ROS) and overproduction of proteolytic enzymes and inflammatory cytokines. The potency of aucubin in protecting cellular components against oxidative stress, inflammation and apoptosis effects are well documented, which makes it a potential candidate for OA treatment. In this study, we aimed to evaluate the protective benefits of aucubin against OA using H
2
O
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and compression induced OA-like chondrocyte models.
Methods
The effects of aucubin were studied in porcine chondrocytes after 1\ua0mM H
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O
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stimulation for 30\ua0min or sustained compression for 24\ua0h. Effects of aucubin on cell proliferation and cytotoxicity of chondrocytes were measured with WST-1 and LDH assays. ROS production was evaluated by the Total ROS/Superoxide Detection Kit. Caspase-3 activity was evaluated by the CaspACE assay system. The levels of apoptosis were evaluated by the Annexin V-FITC apoptosis detection kit. OA-related gene expression was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Total DNA quantification was evaluated by the DNeasy Blood and Tissue kit. Sulfated-glycosaminoglycans (sGAGs) production and content were evaluated by DMMB assay and Alcian blue staining.
Results
The results showed that the ROS scavenge effects of aucubin appeared after 1\ua0h of pretreatment. Aucubin could reduce the caspase-3 activity induced by H
2
O
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, and reduced the apoptosis cell population in flowcytometry. In RT-qPCR results, aucubin could maintain ACAN and COL2A1 gene expressions, and prevent IL6 and MMP13 gene up-regulation induced by H
2
O
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and compression stimulations. In the DMMB assay and Alcian blue staining, aucubin could maintain the sGAG content and protect chondrocytes against compressive stress, but not oxidative stress from H
2
O
2
.
Conclusions
These results indicated that aucubin has protective effects in an osteoarthritic ..