"Infants of Inuit race were nearly four times more likely to be admitted for LRTI than mixed or non-Inuit infants," explains Dr. Banerji. "LRTI increases the risk of recurrent infections, chronic lung disease and asthma so there are many potential health complications." According to recent Statistics Canada data, the Aboriginal infant mortality rate in Nunavut is two-to-three times the Canadian average so exploring the effectiveness of immunization could have a major impact on children’s health and mortality rates.
Respiratory infections are the leading cause for admission, medical evacuation and expenditure for Inuit children in the health care system and can result in serious health complications for those affected. Dr. Banerji’s key findings on the risk factors that contribute to LRTIs among Inuit children include:
Infants of mothers who smoked during pregnancy were four times more likely to be admitted for LRTI
Inuit infants were four times more likely to be admitted for LRTI than mixed or non-Inuit infants. It was not determined if this was a result of genetic factors or socio-economic factors
Overcrowded living conditions increased the risk of admission by 2.5 times
Living in a rural community without a hospital increased risk of admission by 2.7 times
Prematurity was not associated with an increased risk of admission
Infants who were not breast-fed were 3.6 times more likely to be admitted for LRTI
Infants who were custom adopted had 4.4 times the risk
Dr. Banerji also conducted a cost analysis by age and location that compared the costs of administering Palivisumab prophylaxis vaccine, an antibody approved for the prevention of respiratory syncytial virus (RSV) – the most common cause of lower respiratory tract infections. The vaccine is used only for prevention and is usually a monthly injection during RSV season.
The results demonstrated that by immunizing rural Inuit infants with the vaccine, the health care system could save money – up to $8,000 per admission avoided. The analysis concludes that preventative measures in infancy can both improve the health of children and result in a significant cost savings for the health-care system.
Dr. Banerji’s research papers were posted online on May 21 in the Published Ahead-Of-Print section of The Pediatric Infectious Disease Journal website.
The research by Dr. Banerji is the second major study on Indigenous children’s health recently released by the Keenan Research Centre at Li Ka Shing Knowledge Institute of St. Michael’s Hospital. Earlier this year, the centre released the Indigenous Children’s Health Report: Health Assessment in Action a project led by Dr. Janet Smylie.
The new treatment reduced disease symptoms and extended the lives of laboratory mice that researchers use to study lupus.
In the study, Philip S. Low and colleagues cite the need for better treatments for lupus, an autoimmune disorder in which the body’s immunological defense system attacks healthy cells, damaging muscles, joints, kidneys and other body parts. Current treatments for lupus — also known as SLE — include high doses of steroids and other medications with serious side effects.
The new approach targets abnormal immune cells in a way that marks the rogue cells for destruction by the body’s immune system without affecting healthy cells. Called folate-hapten-targeted immunotherapy, the treatment greatly reduced damage to the kidneys and other tissues and also prolonged the lives of the mice by 10 months in comparison to untreated animals, the researchers say.
"We suggest that this therapy warrants further evaluation as a possible approach for treatment of SLE in humans," the report states.
This research is described in the September/October issue of ACS’ Molecular Pharmaceutics. The title of the article is "Depletion of Folate-Receptor-Positive Macrophages Leads to Alleviation of Symptoms and Prolonged Survival in Two Murine Models of Systemic Lupus Erythematosus."
The pneumonia was caused when bacteria that normally inhabit the nose and throat invaded the lungs along a pathway created when the virus destroyed the cells that line the bronchial tubes and lungs.
A future influenza pandemic may unfold in a similar manner, say the NIAID authors, whose paper in the Oct. 1 issue of The Journal of Infectious Diseases is now available online. Therefore, the authors conclude, comprehensive pandemic preparations should include not only efforts to produce new or improved influenza vaccines and antiviral drugs but also provisions to stockpile antibiotics and bacterial vaccines as well.
The work presents complementary lines of evidence from the fields of pathology and history of medicine to support this conclusion. "The weight of evidence we examined from both historical and modern analyses of the 1918 influenza pandemic favors a scenario in which viral damage followed by bacterial pneumonia led to the vast majority of deaths," says co-author NIAID Director Anthony S. Fauci, M.D. "In essence, the virus landed the first blow while bacteria delivered the knockout punch."
NIAID co-author and pathologist Jeffery Taubenberger, M.D., Ph.D., examined lung tissue samples from 58 soldiers who died of influenza at various U. S. military bases in 1918 and 1919. The samples, preserved in paraffin blocks, were re-cut and stained to allow microscopic evaluation. Examination revealed a spectrum of tissue damage "ranging from changes characteristic of the primary viral pneumonia and evidence of tissue repair to evidence of severe, acute, secondary bacterial pneumonia," says Dr. Taubenberger. In most cases, he adds, the predominant disease at the time of death appeared to have been bacterial pneumonia. There also was evidence that the virus destroyed the cells lining the bronchial tubes, including cells with protective hair-like projections, or cilia. This loss made other kinds of cells throughout the entire respiratory tract—including cells deep in the lungs—vulnerable to attack by bacteria that migrated down the newly created pathway from the nose and throat.
In a quest to obtain all scientific publications reporting on the pathology and bacteriology of the 1918-1919 influenza pandemic, Dr. Taubenberger and NIAID co-author David Morens, M.D., searched bibliography sources for papers in any language. They also reviewed scientific and medical journals published in English, French and German, and located all papers reporting on autopsies conducted on influenza victims. From a pool of more than 2,000 publications that appeared between 1919 and 1929, the researchers identified 118 key autopsy series reports. In total, the autopsy series they reviewed represented 8,398 individual autopsies conducted in 15 countries.
The published reports "clearly and consistently implicated secondary bacterial pneumonia caused by common upper respiratory flora in most influenza fatalities," says Dr. Morens. Pathologists of the time, he adds, were nearly unanimous in the conviction that deaths were not caused directly by the then-unidentified influenza virus, but rather resulted from severe secondary pneumonia caused by various bacteria. Absent the secondary bacterial infections, many patients might have survived, experts at the time believed. Indeed, the availability of antibiotics during the other influenza pandemics of the 20th century, specifically those of 1957 and 1968, was probably a key factor in the lower number of worldwide deaths during those outbreaks, notes Dr. Morens.
The cause and timing of the next influenza pandemic cannot be predicted with certainty, the authors acknowledge, nor can the virulence of the pandemic influenza virus strain. However, it is possible that—as in 1918—a similar pattern of viral damage followed by bacterial invasion could unfold, say the authors. Preparations for diagnosing, treating and preventing bacterial pneumonia should be among highest priorities in influenza pandemic planning, they write. "We are encouraged by the fact that pandemic planners are already considering and implementing some of these actions," says Dr. Fauci.
A team from the University’s Departments of Health Sciences and Cardiovascular Sciences have put the case for the point at which South Asians should be classed as obese to be redefined. Their study has been published in PLoS One, a journal of the Public Library of Science.
South Asians around the world are at increased risk of developing diabetes and heart disease. They also get these chronic diseases at an earlier age. The study concludes that significantly lower BMI and waist circumference cut points for defining obesity are needed for migrant South Asians.
Dr Laura Gray and Professors Kamlesh Khunti and Melanie Davies led the research utilising data from over 6,000 participants screened for Type 2 Diabetes from Leicester. The research was funded by the Department of Health and the analysis was done as part of the work of the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care (NIHR CLAHRC) in Leicestershire, Northampton and Rutland (LNR).
The NIHR CLAHRC — LNR brings together all the major commissioners and providers of healthcare services in the region in a partnership with the principal academic institution. This unique collaboration between NHS trusts and the University of Leicester is funded by the NIHR and is part of a five year programme to ensure that the lessons learnt from research studies are rapidly and effectively implemented, and develops research capacity and capability within local healthcare organisations.
Professor Khunti who is Professor of Primary Care Diabetes and Vascular Medicine at the University of Leicester said: "Our study shows that the conventional definition of obesity (BMI 30 kg/m2) needs to be lowered in migrant South Asians to detect equivalent levels of cardiovascular risk, based on levels of glucose, blood pressure and cholesterol.
"Our study suggests that migrant South Asians should be classed as obese and therefore at high risk of developing diabetes based on a BMI of between 23-28 kg/m2."
The researchers also define similar lower cut points for waist circumference.
Professor Khunti said: "This is the first study to reassess obesity definitions in a migrant UK south Asian population and could have important clinical implications.
"This research has huge implications globally for screening strategies for south Asians based on BMI and waist circumference cut-points. We need to lower these cut-points when screening for diabetes and cardiovascular disease in these groups."
The results of the Mayo Clinic study are published in the March issue of Nature Genetics.
Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common childhood diseases of the kidneys. ARPKD, also known as infantile PKD, affects one in 20,000 Americans. The disease results in the development of multiple fluid-filled cysts in the kidney, fibrosis in the liver and often poor lung development and neonatal death.
“Identifying the causative gene is a major step forward, as the progression of the disease can now be studied. It improves the prospects for gene-based diagnostics,” says Peter C. Harris, Ph.D., Mayo Clinic nephrologist and the lead researcher in the study.
Improved respiratory treatment has increased newborn survival, but roughly 30 percent of affected babies still die in infancy. Renal disease is usually evident in the neonate. However, when ARPKD appears later in childhood, it is usually associated with less massive renal enlargement and more variability in cyst size. Approximately 50 percent of affected babies who survive the neonatal period progress to end-stage renal disease (ESRD) within 10 years. About 45 percent of infants with ARPKD also have liver disease, which is often a major feature in older children.
Two genes have been identified for the more common, dominant form of PKD. The genetic cause of the recessive type, inherited only when both parents carry an abnormal copy of the disease gene, was more difficult to isolate. In 1994, a German group narrowed the area of the disease gene to a region on chromosome 6. Dr. Harris and colleagues at Mayo Clinic were able to identify the gene by first finding a gene that causes a similar disease in rats. Dr. Harris’ group analyzed a rat with a similar form of PKD that arose in a breeding colony in Japan. Identifying the gene in the rat, and analyzing ARPKD patients, led the researchers to realize that the human equivalent of the rat gene was the one that was abnormal in this disease.
Progress on the Human Genome Project, which sequenced the candidate region on chromosome 6, aided identification of the gene. The gene is very large, covering almost 500,000 DNA bases (an average gene spans about 30,000 bases) and is predicted to encode a large new protein, termed fibrocystin. As yet the normal role of this protein is unknown, but identifying the basic defect in this disorder is a first step to understanding its pathogenesis.
This research was funded in part by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.
"I am still hopeful that the GAD vaccine will work," says Helena Elding Larsson.
Dr Elding Larsson is a paediatrician at Skåne University Hospital in Malmö, Sweden, and a researcher at Lund University’s Diabetes Centre. She is leading the DIAPREV-IT research project. The Juvenile Diabetes Research Foundation (JDRF) in the USA, the world’s largest funder of research on type 1 diabetes, also believes in DIAPREV-IT. It recently awarded the project USD 495 000 (over SEK 3 million) in a three-year grant.
At the beginning of May, the company Diamyd, which manufactures the GAD vaccine, reported that the attempts to halt the destruction of the insulin-producing beta cells in children who have recently fallen ill with type 1 diabetes had not produced any positive results. The European part of the study was therefore ended. The results from a similar study in the US are not expected for another year.
Different conditions for GAD vaccine in DIAPREV-IT
DIAPREV-IT is the first and so far only study in which healthy children at high risk of developing diabetes are vaccinated. The children should have risk genes for type 1 diabetes and at least two antibodies against beta cells, which is a sign that the immune system is starting to attack the cells. "We know that the risk of these children developing diabetes is very high," says Helena Elding Larsson.
It is only once the majority of all the beta cells have been destroyed that the disease breaks out.
"Because we are vaccinating children earlier in the disease process, they have more beta cells left that can be saved. This should mean that there is a greater chance the vaccine will have an effect."
Another difference that could be significant is that some of the children are younger. The lower age limit in DIAPREV-IT is four.
"We will not know for another five years whether it has worked or not, and if it does, a larger study must be carried out to confirm the results," says Helena Elding Larsson. "Because the GAD vaccine doesn’t have any side effects, I think it would be wrong not to pursue DIAPREV-IT to its completion. There is a possibility that it will succeed, and so we cannot pass up this opportunity."
The paper is published in the March 10, 2011 issue of the New England Journal of Medicine.
The drugs, Erlotinib and Gefitinib, which are in a class of highly-specific small molecule tyrosine kinase inhibitors, work by blocking the activation of EGFR which is involved in cell survival and growth, as well as the development of a nourishing blood supply and metastasis.
"Targeting the genetic mutation contributing to the development of the cancer, this class of drugs produced a response rate that exceeded 70% in these patients," notes Dr. Cataldo.
The drugs, taken by mouth, also had fewer side effects. Unlike traditional cytotoxic agents, Erlotinib and Gefitinib do not typically cause myelosuppression, neuropathy, alopecia, or severe nausea.
Lung cancer, the leading cause of cancer-related death worldwide, accounted for an estimated 157,300 deaths in the United States in 2010. Approximately 85 to 90% of all cases of lung cancer are non-small-cell lung cancer (NSCLC) which is also associated with smoking. Advanced-stage NSCLC is currently considered an incurable disease for which standard chemotherapy provides marginal improvement in overall survival at the expense of substantial morbidity and mortality. Furthermore, less than 30% of patients with metastatic NSCLC have a response to platinum-based chemotherapy, the most commonly used initial treatment in this stage of the disease. Even with the addition of newer agents, such as bevacizumab, to chemotherapy, the median overall survival of patients with metastatic NSCLC remains approximately 1 year, and only 3.5% of patients with metastatic NSCLC survive 5 years after diagnosis.
"The EGFR mutation is just one of the mutations associated with non-small-cell lung cancer," says Dr. Cataldo. "These results also provide a model for identifying others, which we are currently pursuing. Treatment targeting the causes of this cancer will not only improve quality of life, but may also improve survival of this devastating disease."
The University of Texas the University of Texas M.D. Anderson Cancer Center, and Montefiore Medical Center, Albert Einstein College of Medicine also participated in the review.
The new report, published in the November issue of the Journal of Internal Medicine, found that neither light-intensity activities nor aerobic fitness level contributed to bone health, contrasting previous studies suggesting that aerobics could play a role. Having a few extra pounds, however, was a help. Among a group of older adults studied, those with greater muscle strength and higher body fat, especially in the abdomen, had higher bone mineral densities.
“Carrying extra body weight increases the forces on bone, strengthening it, though the largest forces come from more vigorous exercise rather than routine low-intensity physical activity,” says lead author Kerry J. Stewart, Ed.D., director of clinical exercise physiology at Hopkins. “In our study of typical older people, who unfortunately do not participate in regular vigorous exercise, daily activities and low-intensity exercise like walking appeared to be relatively ineffective for preventing aging-related bone loss.”
Stewart does not advocate gaining weight to fight osteoporosis.
“Paradoxically, a high percentage of abdominal fat seems to increase bone mineral density,” he says, “but it also increases the risk of heart disease, high blood pressure and diabetes, and worsens the symptoms of chronic conditions such as knee arthritis. Further research is needed to define methods that will reduce obesity while preserving or enhancing bone health.”
Stewart and colleagues studied 84 adults (38 men and 46 women) ages 55 to 75 with higher than normal blood pressure but who were otherwise healthy. They were not exercising regularly, defined as moderate- or high-intensity exercise for 30 minutes a day, three or more times per week.
Researchers used X-rays to measure the participants’ bone mineral density in the total skeleton, lower spine and hip, and magnetic resonance imaging to calculate abdominal fat. They weighed each participant and had each do a treadmill exercise test and a series of weight-training exercises to measure aerobic fitness and muscle strength. In addition, the individuals completed a physical activity questionnaire.
Researchers found that aerobic exercise was not associated with bone mineral density but abdominal fat was. Muscle strength was associated with bone mineral density at some but not all sites.
Thirty percent of the women were taking estrogen and progesterone supplements. While such hormone replacement therapy has been known to positively benefit bone, in this study it contributed only modestly to bone mineral density and only at the lower spine.
###
The study was supported by the National Institutes of Health and the Johns Hopkins Bayview General Clinical Research Center. Co-authors were J.R. DeRegis; K.L. Turner, A.C. Bacher, J. Sung, P.S. Hees, M. Tayback and P. Ouyang.
Stewart, Kerry J., et al, “Fitness, fatness and activity as predictors of bone mineral density in older persons,” Journal of Internal Medicine, Nov. 2002, Vol. 252, No. 5, pp. 1-8.
Related Web Site:
Johns Hopkins Division of Cardiology
cardiology.hopkinsmedicine
But a Stanford University School of Medicine researcher who helped direct the WHI work said the study showed a modest reduction in breast cancer among the women who started with the highest fat intake before cutting back. And it also suggested a health benefit for women who reduced their consumption of saturated and trans fats.
"Just switching to low-fat foods is not likely to yield much health benefit in most women," said Marcia Stefanick, PhD, professor of medicine at the Stanford Prevention Research Center and chair of the WHI steering committee. "Rather than trying to eat ‘low-fat,’ women should focus on reducing saturated fats and trans fats." She also recommended that women eat more vegetables, in particular dark, leafy greens and cruciferous vegetables, though the trial did not specifically study these foods.
The dietary findings are reported in three studies to be published in the Feb. 8 issue of the Journal of the American Medical Association. The studies showed that women on the low-fat diet experienced a 9 percent reduction in the incidence of breast cancer – but this was not statistically significant. (For instance, in a group of 10,000 women, 42 in the low-fat diet group developed breast cancer each year compared with 45 in the group maintaining their regular eating patterns.) The dietary changes made no appreciable difference in the rates for colorectal cancer and cardiovascular disease.
The findings are the latest clinical results from the WHI, a 15-year, broad-based look at the causes and prevention of diseases affecting older women. Previous WHI studies have involved hormone therapy, heart disease and osteoporosis.
The low-fat diet study involved nearly 49,000 postmenopausal women between the ages of 50 and 79 who were tracked over the course of a little more than eight years on average, making it the nation’s largest long-term study of a low-fat diet. The goal was to test a widely held theory that low-fat diets helped reduce the risk of cancer and heart disease.
Forty percent of the participants were assigned to the low-fat diet, in which they were asked to reduce their fat intake to 20 percent of their total calories while eating five or more daily servings of vegetables and fruits and six servings of grains. The remaining 60 percent served as a comparison group and did not change their diet.
Although the primary hypotheses of protective effects of a low-fat diet on breast and colorectal cancer failed the test, the WHI researchers pointed out that the majority of women assigned to the low-fat diet didn’t meet the 20 percent fat goal: On average, the women reduced their fat intake to 24 percent in the first year, but slowly increased their fat intake to 29 percent by the eighth year.
Furthermore, the study showed that women who had the highest fat intake at the study’s outset showed greater evidence for reducing their breast cancer risk on the diet program. There was also a suggestive trend of breast cancer risk reduction for women who initially had the lowest consumption of vegetables and fruits and then increased their intake by one serving per day as part of the diet.
Regarding the heart disease findings, Stefanick noted that the women weren’t asked to differentiate between "good fats" (the unsaturated fats found in fish, nuts and vegetable oils) and "bad fats" (saturated fats and trans fats found in processed foods, meats and some dairy products), which is emphasized in current guidelines for heart disease reduction. "This shows that you can’t rely on using low-fat substitutes to make a difference," Stefanick said. "You really need to think about what kinds of fats you’re eating and the foods that should be part of your diet, such as vegetables, for instance."
For women who want to maintain their health, Stefanick advised them to follow a diet low in saturated and trans fats, and rich in vegetables and fiber – rather than to strive to eat "low-fat" foods. She also advised them to pay attention to total caloric intake regardless of diet composition and to get adequate regular exercise. Women should also get routine mammograms and screenings for colorectal cancer and heart disease risk, including checking their cholesterol profile, blood pressure, blood sugar and body weight.
The low-fat diet study is one of three randomized clinical trials that are part of the WHI. A previous trial on hormone therapy showed that estrogen and a combination of estrogen and progestin increased risks in such diseases as stroke, blood clots and breast cancer among postmenopausal women. The third study on the effects of calcium and Vitamin D on bone fractures and colorectal cancer will be released later this month.
The bacterium Staphyloccus aureus (staph) normally resides on skin and in noses, and typically infects tissues through cuts or rashes. Those infections can remain minor, or lead to illnesses ranging from boils or abscesses to necrotizing skin infections, pneumonia and sometimes blood stream infections. The Centers for Disease Control and Prevention (CDC) reports that staph is one of the leading causes of skin infections in the United States.
Previously, scientists have categorized staph into two main types: antibiotic resistant (MRSA), and methicillin-susceptible Staphyloccus aureus (MSSA), which can be treated by antibiotics in the penicillin or related groups (i.e, beta-lactam antibiotics). Previously, MRSA infections were usually restricted to hospital or healthcare-associated infections. This is clearly no longer the case.
Henry M. Blumberg, MD, is the senior author of the study, and professor of medicine and program director of the Division of Infectious Diseases at Emory University School of Medicine and hospital epidemiologist at Grady Memorial Hospital. He says, "We have seen an explosion of community-acquired MRSA infections among the urban patient populations served by the Grady Health System. Community-acquired MRSA infections are no longer restricted to certain risk groups but appear to be wide spread in the Atlanta community."
The study demonstrated that 72 percent of community-onset Staph skin and soft tissue infections among patients receiving care at the Grady Health System (Grady Memorial Hospital and its affiliated outpatient clinics in Atlanta) are now due to MRSA. The vast majority of these MRSA skin and soft tissue infections are due to a single clone or strain of MRSA called USA300. As noted in the accompanying editorial, MRSA appears to have emerged as a cause of community-acquired skin infections in other U.S. communities as well.
As noted by Dr. Blumberg and other Emory and Grady authors, "Empirical use of antibiotics active against community-acquired MRSA is warranted, especially for patients presenting with serious skin and soft-tissue infections." This represents a major change in prescribing practices for community-onset skin and soft tissue infections.
Dr. Blumberg’s team included first author Mark King, MD, MSc, previously an infectious diseases fellow and faculty member at Emory as well as Dr. Susan Ray, an associate professor of medicine in the Emory Division of Infectious Diseases and Dr. Wayne Wang, a member of the Emory Department of Pathology and Laboratory Medicine and director of the Grady Clinical Microbiology Laboratory.
The Emory scientists began their research in response to observations about increasing number of community-acquired skin and soft tissue infections that were due to MRSA. Dr. Blumberg notes, "In recent years there have been reports of outbreaks of community-acquired infections due to MRSA. Our study now shows that these community-acquired infections are no longer just restricted to certain risk groups but are widespread and now endemic."
The recognition of community-acquired MRSA as a primary cause of skin and soft tissue infections offers implications for prevention and treatment. In the past, Dr. Blumberg says, "skin and soft tissue infections occurring in the community were generally MSSA, and that is how antibiotic therapy was targeted." Currently, many doctors may assume that community-acquired staph infections will not be resistant to antibiotics similar to methicillin and patients may be prescribed ineffective antibiotics.
Implications of the study include that healthcare professionals who diagnose skin or soft tissue infections should prescribe drugs that are active against MRSA. As Dr. Blumberg says, "selection of empiric antibiotics should focus on covering MRSA," and doctors should work toward confirming the diagnosis by obtaining appropriate material for culture in order to achieve a definitive diagnosis and ensure appropriate treatment is given. At Grady Memorial Hospital, where the study took place, Dr. Blumberg reports that his team has already started following up on the findings: "We have worked hard on educating physicians, including those in training, about the need to consider community-acquired MRSA infections," he says. "There have been changes in recommendations for empiric therapy for skin and soft tissue infections."
Dr. Blumberg and his fellow researchers are now conducting follow-up studies at Grady Memorial Hospital and in the community, and hope other scientists might implement clinical trials to definitively determine which antibiotic agents work best for the treatment of community acquired MRSA infections. In the meantime, the CDC’s fact sheet on MRSA suggests that preventing MRSA may be as simple as employing the tried and true cure of soap and water: "Practice good hygiene," is its primary advice.
The study was funded by the Emory Medical Care Foundation, Emory Mentored Clinical Research Scholars Program (supported by a grant from the National Institutes of Health, National Center for Research Resources), and the NIH/National Institute of Allergy and Infectious Diseases.
Healthcare 