Cardiologists at Washington University School of Medicine in St. Louis have developed a non-invasive imaging technique that may help determine whether children who have had heart transplants are showing early signs of rejection. The technique could reduce the need for these patients to undergo invasive imaging tests every one to two years.
The invasive imaging test, a coronary angiogram, involves inserting a catheter into a blood vessel and injecting a dye to look for dangerous plaque on the walls of arteries feeding blood to the heart. This plaque build-up indicates coronary artery disease and is a sign that the body may be rejecting the new heart. Since pediatric heart transplant patients are at high risk of developing coronary artery disease, doctors monitor their arteries on a regular basis. But recurring angiograms become problematic.
‘Many of these children have undergone so many operations, we have lost access to their big blood vessels,’ says Charles E. Canter, MD, professor of pediatrics. ‘Sometimes it
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A new study by Weill Cornell Medical College researchers provides compelling evidence that electronic health records (EHRs) enhance the quality of patient care in a community-based setting with multiple players, which is representative of how medicine is generally practiced across the United States.
The use of EHRs is on the rise, in part because the federal government has invested up to $29 billion in incentives promoting the meaningful use of these systems, with the aim of tracking and improving patient outcomes. Previous studies have provided conflicting evidence about the impact of EHRs, and until now it had been not clear whether they improved the quality of patient care, particularly in typical communities that use commercially available systems.
‘The previous studies on the effects of electronic health records in the outpatient setting have been mixed,’ says the study’s lead investigator, Dr. Lisa M. Kern, associate professor of public health and medicine at Weill Cornell Medical College. ‘This is one of the first studies to find a positive association between the use of EHRs and quality of care in a typical community-based setting, using an off-the-shelf electronic health record that has not been extensively tailored and refined. This increases the generalisability of these findings.’
‘This study starts to grow the evidence that the use of these systems can systematically improve the quality of care, although their maximum value likely lies in their ability to support new health care delivery models,’ says the study’s senior investigator Dr. Rainu Kaushal, director of the Center for Healthcare Informatics and Policy and the Frances and John L. Loeb Professor of Medical Informatics at Weill Cornell Medical College. ‘The findings of this study lend support to the very significant investments in health information technology that are being made by the federal government, states, and health care providers.’
This study was conducted with the Health Information Technology Evaluation Collaborative (HITEC)
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UCSF researchers found that poor HIV-infected individuals living in San Francisco are significantly more likely to visit emergency rooms and to have hospital stays if they lack access to food of sufficient quality and quantity for a healthy life.
‘In the prior three months, a quarter of participants in the study reported an ER visit, and just over a tenth reported a hospitalisation, which shows that we are dealing with a population with high levels of illness. But the food insecure people were even sicker than the food secure, which is consistent with their experiencing higher rates of chronic diseases,’ said the study’s primary investigator, Sheri Weiser, MD, assistant professor of medicine in the UCSF HIV/AIDS Division at San Francisco General Hospital and Trauma Center.
The study recruited 347 HIV-infected urban poor participants living in substandard housing in San Francisco. To determine levels of food insecurity, the participants were questioned about their anxiety and uncertainty about their food supply, whether they were able to access sufficient quality and variety of food, and their experience of insufficient food intake and the physical consequences. Just over half of the group, 56 percent, was classified as food insecure. The entire cohort of food secure and food insecure individuals was followed for two years, looking at healthcare utilisation as a primary outcome.
‘Compared to food secure participants, the odds were approximately two times higher that a food insecure participant was hospitalised or that a food insecure participant had visited the ER over the study’s time period,’ said Weiser. ‘For a long time we have known that adequate nutrition is crucial for HIV-positive patients to live long healthy lives. Our findings that food insecure individuals are also more likely to use costly services from hospitals and emergency rooms build on our previous work showing that food insecure individuals experience poorer HIV treatment outcomes.’
Food insecurity among HIV-infected homeless and marginally housed individuals in the City is higher than the rate of food insecurity seen nationally in non HIV-infected homeless persons, with about a quarter to a third experiencing food insecurity. For the general population, about one in seven Americans is food insecure.
‘Roughly three quarters of our participants are accessing some form of food aid. Project Open Hand, Glide, and other programs providing food assistance to San Francisco’s urban poor do a phenomenal job, but with falling levels of funding and increasing client loads, their efforts have not been enough to take people out of food insecurity,’ said the study’s senior investigator, Margot B. Kushel, MD, associate professor in the UCSF Division of Internal Medicine at San Francisco General Hospital and Trauma Center.
‘One part of the problem lies in housing,’ she said. ‘While about a tenth of participants had a recent experience of homelessness, most of the rest were housed in single-room occupancy hotels, many of which do not include kitchen facilities. Providing secure housing with functional kitchens is an important part of addressing the problem.’
Surprisingly, said Weiser, less than a fifth of the participants had received federal food assistance through the Supplemental Nutrition Assistance Programs (SNAP) over the previous year and only about a tenth had received SNAP over the previous month. ‘We were alarmed to see such low numbers accessing SNAP, since presumably this program is intended to serve urban poor who experience food insecurity. But many of our food insecure participants have a monthly income that is slightly above the $1,080 a month SNAP cut-off.’ In other words, SNAP does not seem to be reaching the majority of HIV-infected persons in need of food assistance.
EurekAlert
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Researchers from the University of Cambridge, the Wellcome Trust Sanger Institute, and Cambridge University Hospitals used advanced DNA sequencing technologies to confirm the presence of an ongoing outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in a Special Care Baby Unit in real time. This assisted in stopping the outbreak earlier, saving possible harm to patients. This approach is much more accurate than current methods used to detect hospital outbreaks.
Using this technology, the team revealed that the outbreak had extended into the wider community, a conclusion that could not be reached with available methods. They also used sequencing to link the outbreak to an unsuspecting carrier, who was treated to eradicate MRSA.
‘We are always seeking ways to improve our patient care and wanted to explore the role that the latest sequencing technologies could play in the control of infections in hospitals,’ says Dr Nick Brown, author, consultant microbiologist at the Health Protection Agency and infection control doctor at Addenbrooke‟s Hospital Cambridge. ‘Our aim is to prevent outbreaks, and in the event that they occur to identify these rapidly and accurately and bring them under control.
‘What we have glimpsed through this pioneering study is a future in which new sequencing methods will help us to identify, manage and stop hospital outbreaks and deliver even better patient care.’
Over a six month period, the hospital infection control team used standard protocols to identify 12 patients who were carrying MRSA. However, this standard approach alone could not give enough information to confirm or refute whether or not an ongoing outbreak was actually taking place.
In this study, the researchers analysed MRSA isolates from these 12 patients with DNA sequencing technology and demonstrated clearly that all the MRSA bacteria were closely related and that this was an outbreak. They also revealed that the outbreak was more extensive than previously realised, finding that over twice as many people were carrying or were infected with the same outbreak strain. Many of these additional cases were people who had recent links to the hospital but were otherwise healthy and living in the community when they developed a MRSA infection.
While this sequencing study was underway, the infection control team identified a new case of MRSA carriage in the Special Care Baby Unit, which occurred 64 days after the last MRSA-positive patient had left the same unit. The team used advanced DNA sequencing to show in real time that this strain was also part of the outbreak, despite the lack of apparent links between this case and previous patients. This raised the possibility that an individual was unknowingly carrying and transmitting the outbreak MRSA strain.
The infection control team screened 154 healthcare workers for MRSA and found that one staff member was carrying MRSA. Using DNA sequencing, they confirmed that this MRSA strain was linked to the outbreak. This healthcare worker was quickly treated to eradicate their MRSA carriage and thus remove the risk of further spread.
‘Our study highlights the power of advanced DNA sequencing used in real time to directly influence infection control procedures,’ says Dr Julian Parkhill, lead author from the Wellcome Trust Sanger Institute. ‘There is a real health and cost burden from hospital outbreaks and significant benefits to be gained from their prevention and swift containment. This technology holds great promise for the quick and accurate identification of bacterial transmissions in our hospitals and could lead to a paradigm shift in how we manage infection control and practice.’
In this instance, DNA sequencing was a key step in bringing the outbreak to a close, saving possible harm to patients and potentially saving the hospital money.
Cambridge University
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UC Davis cancer researchers have discovered significant differences in radiation-therapy response among patients with oropharyngeal cancer depending on whether they carry the human papillomavirus (HPV), a common sexually transmitted virus. The findings could lead to more individualised radiation treatment regimens, which for many patients with HPV could be shorter and potentially less toxic.
HPV-related cancers of the oropharynx (the region of the throat between the soft palate and the epiglottis, including the tonsils, base of tongue and uvula) have steadily increased in recent years, according to the National Cancer Institute, especially among men. At the same time, the incidence of oropharyngeal cancers related to other causes, such as smoking or alcohol consumption, is declining. HPV is the most common sexually transmitted infection in the United States; it can spread through direct skin-to-skin contact during vaginal, anal and oral sex.
The UC Davis study, conducted by Allen Chen, associate professor in the UC Davis Department of Radiation Oncology, examined patterns of tumour reduction during radiation treatment in two otherwise similar groups of patients with oropharyngeal cancer: those who tested positive for HPV and those who tested negative for the virus. None of the HPV patients in the study was a smoker, a leading risk factor for the disease.
Chen used CT scans acquired during image-guided radiation therapy (IGRT) and endoscopy (a tube with a small camera) to capture 3D images of the patients’ tumours and monitor their treatment progress. He found that within the first two weeks after starting radiation, the gross tumour volume decreased by 33 percent in HPV-positive patients, while the volume decreased by only 10 percent in HPV-negative patients.
Chen said the results demonstrate that HPV-positive patients have a more rapid and robust response to radiation treatments, confirming what clinicians have suspected for years.
‘These HPV-related tumours literally melt before your eyes,’ he said. ‘It is very gratifying to tell patients early on during treatment that their tumours are responding so quickly. Most of them are pleasantly relieved to hear such news.’
The rapid rate of tumour regression did not continue, however, after the second week of radiation treatment, and by the end of the seven-week regimen, the total tumour shrinkage in both groups of patients was nearly the same.
However, ‘the dramatic early response observed in the HPV-positive patients strongly implies that these tumours behave distinctly from a biological standpoint and could be approached as a separate disease process,’ Chen said.
For example, the findings suggest that treatment for HPV-positive cancer may not need to be as intensive for it to be effective, Chen said, adding that a shorter, abbreviated treatment regimen would potentially lessen the side effects from radiation, which include sore throat, dry mouth, taste loss and swallowing difficulties.
‘It is likely that treatment in the future will be individualised based on biomarkers present in the tumour, and HPV has the potential to do just that,’ said Chen.
Chen said there is increasing evidence that HPV-positive patients who receive radiation treatments live longer and have higher cure rates. According to the NCI, 88 percent of the HPV-positive patients are still alive two years after their treatments, compared with 66 percent of the HPV-negative patients.
‘Given the impressive outcomes for patients with HPV-positive cancer using currently aggressive treatments, how to de-intensify therapy while maintaining cure rates is definitely a hot topic right now,’ said Chen.
UC Davis Comprehensive Cancer Center
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Researchers have used computational analysis to identify a new Achilles heel for the treatment of drug-resistant breast cancer. The results reveal that the disruption of glucose metabolism is an effective therapeutic strategy for the treatment of tumours that have acquired resistance to front-line cancer drugs such as Lapatinib.
‘The growth and survival of cancer cells can often be impaired by treatment with drugs that interfere with the actions of one or more oncogenes,’ said Prahlad Ram, the senior author of the study and Professor at the University of Texas MD Anderson Cancer Center, Houston, Texas. ‘However, the clinical benefits to patients are often short lived due to acquired drug resistance. Finding alternative intervention points or so-called new addictions for cancer cells is of critical importance for designing novel therapeutic strategies against tumours. Our results reveal specific new targets for drug intervention in the metabolic pathways of cancer cells and identify existing drugs that can be used to treat drug-resistant cancer.’
Lapatinib is used for the treatment of patients with advanced or metastatic breast cancer in cases where tumours over-express the ErbB2 gene. The ErbB2 gene provides instructions for making a specific growth factor receptor. If too much of this ErbB2 growth factor receptor is made, it can lead to cells that grow and divide continuously, one of the defining characteristics of breast cancer.
The scientists used microarrays to measure gene expression in breast cancer cells with and without treatment with Lapatinib. Computational analysis of more than 15000 gene interactions revealed four major populations of genes that were regulated in a significant way. Three of these groups were the regular suspects related to drug resistance, such as genes involved in oxidation and reduction reactions or cell cycle processes. A fourth group comprised a network of reactions linked to the deprivation of glucose.
Analysis of the gene expression networks of ErbB2-positive breast cancer patients revealed that the glucose deprivation network is linked to low survival rates of the patients. Computational screening of a library of existing drugs for therapeutics that target the glucose deprivation response identified several drugs that could be effective in treating drug-resistant breast cancer.
‘By developing novel gene expression analysis algorithms and integrating diverse data, we have been able to look beyond changes in the immediate molecular signaling pathways of breast cancer cells and to consider the wider system of molecular networks within the cell,’ remarked Ram. ‘Our approach predicts new uses for existing drugs that impact the metabolism of breast cancer cells and may offer an expedient route to improved treatments for breast cancer patients.’
The glucose-deprivation response network counteracts EGFR signalling in lapatinib resistant cells
EMBO
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Scientists have identified a group of small molecules that interfere with the activity of a compound that initiates multiple steps in blood clotting, including those that lead to the obstruction of veins or arteries, a condition called thrombosis. Blocking the activity of this compound, polyphosphate, could treat thrombosis with fewer bleeding side effects than the drugs that are currently on the market.
Blood clots are formed at the site of an injured blood vessel to prevent blood loss. Sometimes, however, blood clots completely clog an artery or vein and the surrounding tissues are damaged. The U.S. Centers for Disease Control and Prevention reports that annually, 300,000 to 600,000 Americans are afflicted with deep vein thrombosis or pulmonary embolism, a blocked lung artery that often results from thrombosis, and 60,000 to 100,000 people die each year as a result of these conditions.
There are two pathways that trigger blood clotting. The tissue factor pathway helps stop bleeding if a person is injured. If any of the proteins of this pathway are missing, a bleeding problem will develop. In contrast, the contact pathway is activated when blood comes into contact with some artificial substances. Although this pathway can cause pathological blood clots, humans who lack proteins in this pathway do not have bleeding problems. These two pathways eventually converge to form a common pathway.
In 2006, the researchers found that compounds called polyphosphates can, when released from cell fragments called platelets, activate the contact pathway, said University of Illinois biochemistry professor James H. Morrissey, who led that study and the new analysis.
Because the contact pathway is not essential for normal blood clotting after an injury, interrupting polyphosphate ‘wouldn
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Post-stroke depression is a major issue affecting approximately 33% of stroke survivors. A new study reports that the level to which survivors are uncertain about the outcome of their illness is strongly linked to depression. The relationship is more pronounced for men than for women.
‘Male stroke survivors in the US who subscribe to traditional health-related beliefs may be accustomed to, and value highly, being in control of their health,’ says lead investigator Michael J. McCarthy, PhD, of the University of Cincinnati College of Health Sciences School of Social Work. ‘For these individuals, loss of control due to infirmity caused by stroke could be perceived as a loss of power and prestige. These losses, in turn, may result in more distress and greater depressive syndromes.’
Thirty-six survivors (16 female, 20 male) who had experienced their first stroke within the preceding 36 months participated in the study. Survivors’ depressive symptoms and ability to perform activities of daily living, such as bathing and cutting food with a knife and fork, were measured. The degree to which survivors were experiencing health ambiguity, or uncertainty about the outcomes of their illness, was evaluated by their agreement with statements such as ‘I don’t know what’s wrong with me,’ and ‘I have a lot of questions without answers.’
Investigators found health ambiguity was significantly associated with greater depression for both sexes, and the association was stronger for male survivors than for females. ‘These findings suggest that reducing health ambiguity through proactive communication with patients and family members may be an effective approach for reducing survivor distress and, ultimately, for improving rehabilitation outcomes, Dr. McCarthy says. ‘The also reinforce the importance of rehabilitation professionals acknowledging that health-related beliefs can have a tangible impact on patient outcomes.’
Dr. McCarthy notes that there was a wide variability in time since diagnosis in the study, and patients were likely at different points in recovery with respect to health ambiguity and depressive syndromes. The small sample size and lack of sample diversity may limit the generalisability of the findings to the broader stroke population. ‘Future research, with more socio-economically diverse samples, should examine how gender-based health-related beliefs affect survivor outcomes, and explore the factors that protect female stroke survivors from the harmful effects of health ambiguity,’ he concludes.
EurekAlert
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