Even though HMO are a major component of human milk, present in higher concentration than protein, many of their actions in the infant are not well understood. Furthermore, they’re virtually absent from infant formula. The scientists wanted to find out what formula-fed babies were missing.

“We refer to HMO as the fiber of human milk because we don’t have the enzymes to break down these compounds. They pass into the large intestine where the bacteria digest them.

“We’re curious about the role they play in the development of the breast-fed infant’s gut bacteria because the bacteria found in the guts of formula-fed infants is different,” said Sharon Donovan, the U of I’s Melissa M. Noel Endowed Professor in Nutrition and Health.

With this study, Donovan is gaining insight into the mystery. For the first time, scientists have shown that a complex mixture of HMO and a single HMO component produce patterns of short-chain fatty acids that change as the infant gets older.

A healthy microbiome has both short- and long-term effects on an infant’s health. In the short term, beneficial bacteria protect the infant from infection by harmful bacteria. In the long term, beneficial bacteria strengthen the immune system so that it can fend off chronic health problems like food allergies and asthma, she said.

In the study, breast milk was obtained from mothers of preterm infants at Chicago’s Rush University Medical Center, and the HMO were isolated and analyzed. The scientists tested bacteria from 9- and 17-day-old sow-reared and formula-fed piglets. Because piglets grow so rapidly, these ages reflect approximately three- and six-month-old human infants.

The colon bacteria were added to test tubes containing HMO and two prebiotics commonly used in infant formulas. These mixtures were allowed to ferment and then sampled to see how the bacterial population was changing over time and what products were being produced by the bacteria.

“When the HMOs were introduced, the bacteria produced short-chain fatty acids, at some cases at higher levels than other prebiotics now used in infant formula. The short-chain fatty acids can be used as a fuel source for beneficial bacteria and also affect gastrointestinal development and pH in the gut, which reduces the number of disease-causing pathogens,” she said.

Further, different HMOs produced different patterns of short-chain fatty acids, and the composition of bacteria in the gut changed over time. “It was distinctly different at 9 vs. 17 days, making it likely that the functions of HMO change as the human infant gets older,” she said.

According to Donovan, HMO are critically important in understanding how breastfeeding protects babies.

“Several companies are now able to synthesize HMO, and in the future, we may be able to use them to improve infant formula. There’s evidence that these compounds can bind to receptors on immune cells and, to our knowledge, no current prebiotic ingredient can do that,” she said.

“Exclusive reliance on a drug to prevent HIV or any sexually transmitted disease could actually result in a worse outcome if those at risk don’t understand how their own behavior affects treatment,” said Perry N. Halkitis, PhD, chair of APA’s Committee on Psychology and AIDS. “We know that medical intervention depends on human behavior. The fact that only 28 percent of HIV-positive Americans in care achieve full viral suppression suggests very clearly that any medical intervention depends fully on behavioral as well as social and political factors.”

A Food and Drug Administration panel recommended on May 10 that the FDA approve the drug Truvada to prevent HIV infection. APA has been monitoring the use of this and other drugs to prevent and treat HIV/AIDS. While heartened by the addition of Truvada to the treatment mix, APA believes HIV prevention treatment must include both medical and behavorial approaches in order to succeed. In February, APA passed a resolution emphasizing the need for prevention research that incorporates strategies to deal with mental health, and substance abuse issues, behavior change and adherence. Entitled “Combination Biomedical and Behavioral Approaches to Optimize HIV Prevention,” the resolution calls upon Congress, the executive branch and other governmental and nongovernmental agencies to increase support for further research to identify and disseminate effective strategies to prevent and treat HIV and other sexually transmitted infections.

“Truvada by itself is not a magic bullet,” Halkitis said. “The research to date shows that individuals taking the drug have had challenges adhering to the need to take it every day. It’s also important for anyone taking it as a preventive measure to continue to practice safe sex. These are all behaviors that need to be guided by multidisciplinary health care teams that include psychologists.” APA President Suzanne Bennett Johnson, PhD, agreed, warning. “if people taking the drug are not fully adherent and then contract HIV, that could lead to drug resistance.”

APA’s resolution cites research that shows a combination of behavioral and biomedical approaches work best to prevent HIV and other sexually transmitted infections. It references a 2010 study that tested adherence to Truvada within a group of men at high risk for infection, which found that 91 percent of those who later tested positive for HIV showed no detectable levels of the drug in their bloodstream, meaning they were not taking the drug as prescribed.

The resolution also points out that drugs “may be out of reach for certain populations (e.g., human trafficking victims, sex workers, people living in poverty, children, etc.).” According to news reports, Truvada costs between $11,000 and $14,000 per year, making it inaccessible to many.

The studies show a correlation between readmission rates and how full the hospital was at the time of discharge, suggesting that patients went home before they were healthy enough.

The researchers recommend better planning and other logistical solutions to avoid these problems.

The studies appear in the two most recent issues of the peer-reviewed journal Health Care Management Science:

• “The impact of hospital utilization on patient readmission rate” http://ter.ps/sj
• “Examining the discharge practices of surgeons at a large medical center” http://ter.ps/sk

“Discharge decisions are made with bed-capacity constraints in mind,” says University of Maryland Professor Bruce Golden, the Smith School’s France-Merrick Chair in Management Science, who conducted the research with Ph.D. student David Anderson and other colleagues.

“Patient traffic jams present hospitals and medical teams with major, practical concerns, but they can find better answers than sending the patient home at the earliest possible moment,” Golden adds.

In the studies, Golden and Anderson tracked patient movement at a large, academic medical center located in the United States.

They found that patients discharged when the hospital was busiest were 50 percent more likely to return for treatment within three days. This indicates recovery was incomplete when patients were first released, the researchers say. The study tracks occupancy rates, day of the week, staffing levels and surgical volume.

Surgeons and hospitals are incentive-driven to perform as many surgical procedures as feasible, Golden says.

“The hospital has to maintain revenue levels to meet its financial obligations. Surgeons are working to save lives and earn a livelihood. It’s what they do,” he explains. “If the hospital says ‘sorry there are no beds available,’ there’s a lot of tension and pressure from both sides to keep things moving.”

These problems are much more likely at large hospitals, which tend to provide more advanced, specialized surgeries not accessible at smaller, community institutions,the researchers say. Patients often have to travel a great distance for the procedures, so hospital delays become expensive for both them and the care providers.

The study findings cover surgical discharge data from fiscal year 2007 covering more than 7,800 surgery patients who collectively spent 35,500 nights at the facility.

“This gives us a good snapshot of the pressures at work in a busy non-profit hospital,” Golden adds. “Other institutions may handle the challenges somewhat differently, but the pressures are widespread and these results call for some introspection.”

BETTER LOGISTICS

“Too often, the biggest problem is that hospitals just don’t plan ahead, and this is what gets them in trouble” Golden says. “There are logistical alternatives to sending a patient home too soon.”

He suggests that surgeons use checklists before discharging the patient. “They know better than we do what questions should be asked – questions that would force the surgeon to think about whether they were discharging the patient for the right reason.”

Recently, for example this checklist approach has been used successfully to reduce hospital bacterial infections, Golden points out.

Also, he suggests that hospitals increase the flexibility of where patients go post-surgery. Allowing them to be moved to units with empty beds, for example, could also lessen premature discharges.

Though, this may increase costs in the short run, discharging patients who then quickly return to the hospital offers no long-term savings, and decreases the quality of care, Golden adds.

Each year, seasonal influenza causes serious illnesses in three to five million people and 200,000 to 500,000 deaths. The 2009 H1N1 pandemic killed more than 14,000 people worldwide. Meanwhile, public health and bioterrorism concerns are heightened by new mutations of the H5N1 “bird flu” virus, published last week by the journal Nature, that could facilitate infection among mammals and humans.

Led by Prof. John Schrader, Canada Research Chair in Immunology and director of UBC’s Biomedical Research Centre, the research team found that the 2009 H1N1 “swine flu” vaccine triggers antibodies that protect against many influenza viruses, including the lethal avian H5N1 “bird flu” strain.

Details are published today in the journal Frontiers in Immunology.

“The flu virus has a protein called hemagglutinin, or HA for short. This protein is like a flower with a head and a stem,” says Schrader, a professor in Medicine and Pathology and Laboratory Medicine. “The flu virus binds to human cells via the head of the HA, much like a socket and plug.

“Current flu vaccines target the head of the HA to prevent infections, but because the flu virus mutates very quickly, this part of the HA changes rapidly, hence the need for different vaccines every flu season.”

Vaccines contain bits of weak or dead germs that prompt the human immune system to produce antibodies that circulate in the blood to kill those specific germs. However, the research team found that the 2009 pandemic H1N1 vaccine induced broadly protective antibodies capable of fighting different variants of the flu virus.

“This is because, rather than attacking the variable head of the HA, the antibodies attacked the stem of the HA, neutralizing the flu virus,” says Schrader. “The stem plays such an integral role in penetrating the cell that it cannot change between different variants of the flu virus.”

The new discovery could pave the way to developing universal flu vaccines.

Schrader says the characteristics of the human immune system make it difficult for influenza vaccines to induce broadly protective antibodies against the HA stem. “The pandemic H1N1 swine flu was different, because humans had not been exposed to a similar virus,” he adds.

Schrader has evidence that a vaccine based on a mixture of influenza viruses not circulating in humans but in animals should have the same effect and potentially make influenza pandemics and seasonal influenza a thing of the past.

Nearly 5.3 million individuals in the United States have Alzheimer disease (AD) and the resulting health care costs in 2010 were roughly $172 billion, the authors write as background information in the study. “Prevalence and costs of AD and other dementias are projected to rise dramatically during the next 40 years unless a prevention or a cure can be found. Therefore, it is critical to gain a greater understanding of the key risk factors and etiologic underpinnings of dementia from a population-based perspective,” the authors write.

Deborah E. Barnes, Ph.D., M.P.H., of the University of California, San Francisco and the San Francisco Veterans Affairs Medical Center, and colleagues evaluated data from 13,535 long-term Kaiser Permanente members and examined depressive symptoms assessed in midlife (1964-1973) and in late life (1994-2000) and risks of developing dementia, Alzheimer disease (AD) and vascular dementia (VaD; dementia resulting from brain damage from impaired blood flow to the brain).

Depressive symptoms were present in 14.1 percent of study participants in midlife only, 9.2 percent in late life only and 4.2 percent in both. During six years of follow-up, 22.5 percent of patients were diagnosed with dementia; 5.5 percent with Alzheimer disease and 2.3 percent with VaD.

When examining AD and VaD separately, patients with late-life depressive symptoms had a two-fold increase in AD risk, and patients with midlife and late-life symptoms had more than a three-fold increase in VaD risk.

“Our findings suggest that chronic depression during the life course may be etiologically associated with an increased risk of dementia, particularly VaD, whereas depression that occurs for the first time in late life is likely to reflect a prodromal stage of dementia, in particular AD,” the authors conclude.

According to Etienne Challet, Ph.D., a researcher involved in the work from the Department of Neurobiology of Rhythms at the Institute of Cellular and Integrative Neurosciences at the University of Strasbourg in Pascal, France, “It is now clear that impairment of daily rhythms such as shift-work, exposure to artificial lighting, or jet-lag has multiple adverse effects on human health, every effort should be made to maintain or restore normal temporal organization and to avoid potentially disruptive behaviors such as nocturnal meals or light exposure at night.”

To make this discovery, Challet and colleagues studied two groups of mice. One group was normal and the other group lacked the Rev-Erb alpha gene. In the mice lacking the Rev-Erb alpha gene, it was determined that they became obese and hyperglycaemic even if they ate the same quantity of food at the same time as normal mice. Further scientific investigation showed that when the Rev-Erb alpha-deficient mice were compared to the normal mice, there was a major difference in the way Rev-Erb alpha-deficient mice metabolized the food they ate. The Rev-Erb alpha deficient mice created much more fat than the normal mice, and this occurred specifically during the feeding period. Additionally, the Rev-Erb-alpha deficient mice relied less on carbohydrate stores when at rest.

“The phrase ‘sick and tired’ could never be more true,” said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “This research shows that we evolved to live in synch with the natural light and dark cycles of our planet. Strasbourg has long taught us the finer aspects of cuisine; its scientists now explain how night and day can influence whether we are fat or lean.”

Soo-Jong Um, Ji-Cheon Jeong and colleagues describe previous studies indicating that piperine reduces fat levels in the bloodstream and has other beneficial health effects. Black pepper and the black pepper plant, they note, have been used for centuries in traditional Eastern medicine to treat gastrointestinal distress, pain, inflammation and other disorders. Despite that long medicinal history, scientists know little about how piperine works on the innermost molecular level. The scientists set out to get that information about piperine’s anti-fat effects.

Their laboratory studies and computer models found that piperine interferes with the activity of genes that control the formation of new fat cells. In doing so, piperine may also set off a metabolic chain reaction that helps keep fat in check in other ways. The group suggests that the finding may lead to wider use of piperine or black-pepper extracts in fighting obesity and related diseases.

The tool is based on the latest unbiased research and is intended to jumpstart conversations between women and their doctors about the choices available to them as they approach and experience menopause.

Hormone therapy has been under intense scrutiny since 2002, when a large government study called the Women’s Health Initiative (WHI) reported that hormone therapy—specifically the combination of estrogen and progestin together—increased the risk for blood clots, stroke, breast cancer and heart attacks. The researchers halted the study and concluded that the risks of hormone therapy outweighed the benefits. Although the study was designed to evaluate the role of hormone therapy in the prevention of diseases related to aging, many women and their doctors also abandoned it as therapy for menopausal symptoms.

Over the past 10 years, additional research has found that the level of risk depends on the individual woman, her health history, age, and the number of years since her menopause began. In general, younger women (under 60) who have recently started menopause are at a lower risk than older women when taking low doses of hormone therapy.

“Left with the false impression that hormone therapy isn’t a safe option, far too many women have suffered in silence thinking their options for symptom relief were limited or non-existent,” says Cynthia Stuenkel, MD, a member of The Endocrine Society and an endocrinologist specializing in menopause at the University of California, San Diego. “We know that for some women, hormonal therapy provides the only relief for severe menopausal symptoms. Women deserve some clear answers and helpful tools to engage their doctors in meaningful conversations about the multiple choices available to improve their menopausal symptoms.”

When a woman enters menopause, she stops menstruating and her body produces less of the sex hormones estrogen and progesterone. The process of menopause takes years. During that time, women may experience moderate to severe symptoms, including hot flashes, interrupted sleep, vaginal dryness, and other symptoms that affect her quality of life.

The survey found that 72 percent of women currently experiencing symptoms have not received any treatment for them. Other findings include:

Majorities of menopausal women experiencing symptoms have not talked to their primary health care provider or OB/GYN about hormone therapy (62%) or non-hormone options (61%), and half of them have not talked about lifestyle changes;
Nearly half (49%) of menopausal women experiencing symptoms have a negative impression of hormone therapy; and
While the sample sizes of African Americans and Latinos in the survey are small, only 17 percent of African-American respondents say they have talked to their doctors about hormone therapy, compared to 39 percent of white women and 35 percent of Latinas, suggesting that disparities may exist.
“Unfortunately, as in many health care issues, significant disparities exist. Add to that, many primary care doctors don’t have enough information about the latest research or what to prescribe,” Dr. Stuenkel says. “We want to make health care providers across the nation aware of this tool so that they can facilitate better discussions with their patients.”

The “Menopause Map” is an online interactive tool that guides a woman through the different options available to get relief from her symptoms through a series of prompting questions about those symptoms and her personal health history. The Map also has links to questionnaires that help assess current risk for breast cancer, heart disease, and stroke. The tool weighs hormonal and non-hormonal therapies against the risks based on individual symptoms and medical history.

The Map was not designed to be a self-diagnostic tool. It’s recommended that women print out their results along with a list of provided questions to discuss the best treatment options for them with their provider. Women should revisit this tool to check their symptoms and have a continuous, informed dialogue with their provider.

The important facts to know about hormone therapy are:

Women 60 years and older should not use menopausal hormone therapy.
Women 50-59 years or younger, with no family or personal history of breast cancer, no history of heart disease or stroke, and with moderate to severe menopausal symptoms are the best candidates for hormone therapy.
If considering hormone therapy, women should talk with their health care provider to determine a plan that is right for them.
In addition, lifestyle approach also helps alleviate symptoms and benefit long-term health.
For those who decide on hormone therapy, this is an ongoing process and might require a period of trial and error to find the right fit for each individual woman.
For those who decide on non-hormonal options, there are several proven therapies available that may help with symptoms. It is important women share information about all medications they are using, including over-the-counter drugs and nutritional supplements, to make sure the choice of therapy doesn’t interact with other medications.
The Menopause Map can be found at www.hormone.org/MenopauseMap.

Of the two drugs, Avastin is most frequently used to treat AMD. However, prior to the Comparison of AMD Treatments Trials (CATT), a two-year clinical trial, the two drugs had never been compared head-to-head. Second year results were published today in the journal Ophthalmology. First year results were published in the May 19, 2011 issue of the New England Journal of Medicine.

AMD is the leading cause of vision loss and blindness in older Americans. In its advanced stages, the wet form of AMD spurs the growth of abnormal blood vessels, which leak fluid and blood into the macula and obscure vision. The macula is the central portion of the retina that allows us to look straight ahead and to perceive fine visual detail. Accumulation of fluid and blood damages the macula, causing loss of central vision, which can severely impede mobility and independence. Without treatment, most patients become unable to drive, read, recognize faces or perform tasks that require hand-eye coordination.

“Therapies for AMD require repeated treatment to prevent vision loss. Results of this clinical trial provide evidence that long-term treatment with either drug results in a robust and lasting improvement in vision. Patients and clinicians now have valuable information to base treatment decisions,” said Paul A. Sieving, M.D., Ph.D., director of the NEI.

Avastin and Lucentis block growth of abnormal blood vessels and leakage of fluid from the vessels. Lucentis was approved by the U.S. Food and Drug Administration (FDA) in 2006 for the treatment of AMD. Avastin is very similar to Lucentis but is not approved by the FDA for this purpose. Avastin is approved for other indications. Most clinicians use these drugs on an as-needed basis when there is evidence of active disease, such as fluid leakage. However, in the original clinical trials for AMD, Lucentis was administered monthly. It was unknown if as-needed dosing would produce the same long-term visual improvements achieved with monthly administration.

Thus, CATT was designed to compare Avastin and Lucentis with monthly and as-needed treatment schedules. At enrollment, patients were assigned to four treatment groups defined by drug (Avastin or Lucentis) and dosing regimen (monthly or as-needed). After year one, patients initially assigned to monthly treatment were randomly reassigned to monthly or as-needed treatment without changing their drug assignment.

At two years, visual acuity with monthly treatment was slightly better than with as-needed dosing, regardless of the drug. As measured on an eye chart, monthly treatment resulted in a mean improvement of about half a line better than as-needed dosing. Switching to as-needed treatment after one year of monthly treatment yielded outcomes nearly equal to those obtained with as-needed treatment for the full two years. Changes in retinal anatomy differed by drug and frequency of treatment, but did not have an impact on vision through two years.

“Both drugs were highly effective regardless of the approach to dosing. There was slightly less vision gain with as-needed treatment. Patients seeking the small extra advantage of monthly treatment need to be mindful of the additional burden, risks, and costs of monthly injections. Since as-needed dosing required 10 fewer eye injections over the course of two years and yielded similar visual results, many patients may choose this option.” said Daniel F. Martin, M.D., study chair for CATT and chairman of the Cole Eye Institute at the Cleveland Clinic.

Adverse events indicate development or worsening of a medical condition. They may or may not be causally associated with the clinical trial treatment, but they are always monitored and reported in any clinical trial. The median age of patients in CATT was over 80 years, and a high rate of hospitalizations would be anticipated as a result of chronic or acute medical conditions more common to older populations.

Serious adverse events (SAEs) occurred at a 40 percent rate for patients receiving Avastin and a 32 percent rate for patients receiving Lucentis. Although Avastin had a higher rate of SAEs, they were distributed across many different conditions, most of which were not associated with Avastin when evaluated in cancer clinical trials, in which the drug was administered at 500 times the dose used for AMD. Fewer doses were associated with a higher rate of SAEs, which is not a typical dose-response relationship. The number of deaths, heart attacks, and strokes were low and similar for both drugs during the study. CATT was not capable of determining whether there is an association between a particular adverse event and treatment. Additional data from other clinical trials may provide information on long-term safety profiles of these drugs when used to treat AMD.

“The dramatic and lasting improvement in vision with these two drugs is extraordinary. At two-years, two-thirds of patients had driving vision (20/40 vision or better). With previous treatments, only 15 percent of patients retained similar visual acuity,” said Maureen Maguire, Ph.D., principal investigator, CATT Coordinating Center at the University of Pennsylvania.

A report released today, funded by the Bill & Melinda Gates Foundation and carried out by Results for Development Institute (R4D), identifies strategies necessary to improve the marketplace for LLINs –allowing the global community to improve value for money and hence extend bed net access to hundreds of millions of individuals. The report also argues that market incentives are urgently needed for both improved net performance and innovation to address the mosquito resistance threat. Otherwise, staggering losses in both lives and dollars could occur.

“We cannot allow recent gains in LLIN coverage to make us complacent,” said Kanika Bahl, report author and Managing Director at Results for Development Institute. “By modifying their policies, major donors can dramatically reduce global costs and provide incentives for private enterprises to produce better-performing nets.”

The report is the first of its kind to look comprehensively at LLIN market dynamics, identifying strategies that, when implemented, will drive savings of up to $630 million for the global community over the next five years. This can provide financing to purchase 150 million additional bed nets, protecting up to 300 million individuals.

The report comes at a time when half the world’s population is at alarming risk of malaria. Every day 1,795 people die needlessly from malaria, with annual deaths over 650,000. Meanwhile over 90% of LLINs are donor-funded, with financing precariously concentrated among a small set of major global donors. Aid money has flat-lined as the stability of the global economy remains uncertain.

The study included both an extensive analysis of bed net purchasing data and consultations with over 140 actors across the private and public sector. Private sector consultations included all 10 WHO Pesticide Evaluation Scheme (WHOPES)-recommended LLIN manufacturers. Public sector consultations included five African Ministries of Health in high-malaria burden countries (Nigeria, Kenya, Tanzania, Uganda and Ethiopia) in addition to numerous leading global and in-country institutions.

The report makes six recommendations, proposing specific actions to drive purchasing of the most cost-effective LLINs and generate market incentives for improved net performance – including development of new insecticide resistance management products to address the growing threat of mosquito resistance.

A primary recommendation focuses on ‘product selection’ of the most cost-effective nets. The report shows the benefits of switching from current price-focused policies to ones which value overall cost-effectiveness. Cost-effectiveness policies weight price and performance (chiefly durability, or how long a net lasts). By modifying their policies, donors and countries can save up to $340M while simultaneously creating market incentives for private enterprises to invest in improved net performance and innovation.

The report also argues that ‘rationalization’ of net specifications (e.g. shape, size, color) is another critical opportunity to drive improved value for money. The current net landscape is highly fragmented, with over 200 manufacturer offerings. Certain specifications generate significantly increased costs – for example price premiums of up to 20% for over-sized nets – without evidence of benefits for families using these nets. The report shows that by purchasing the highest value for money net specifications, the global community can save up to $290M while still ensuring a wide choice of over 70 supplier offerings.

Of critical importance, the report also recommends targeted actions to secure future access to insecticide resistance management products. While current LLINs remain effective control tools today, the growing mosquito resistance to current insecticides is concerning. Unless investment are made now to develop insecticide resistance management nets, the global community risks losing ground in recent health gains. The report urges that the global community develop a clear ‘path to market’ for these products, including appropriate donor and regulatory policies.

“We are seeing troubling trends in the bed net market, including major global funding gaps and mosquito resistance to current net insecticides detected across 27 African countries,” said Bahl. “Much more remains to be done to secure vital access to these products.”

The report also makes recommendations targeted at strengthening in-country data to support informed net purchasing decisions, employing strategic procurement practices to maintain a competitive supply base, and ensuring a sustainable private sector marketplace to achieve malaria prevention goals.

“We now have the strategies to drive over $600 million in savings, spur innovation, and address the growing threat of resistance. We must act rapidly to prevent losing ground,” said Bahl.

The report strategies are now being implemented globally by Results for Development Institute, which is collaborating with global institutions including the Global Fund to Fight AIDS, Tuberculosis and Malaria, President’s Malaria Initiative (PMI), the World Health Organization Global Malaria Programme (WHO GMP), African Leaders Malaria Alliance (ALMA), and the Office of the UN Secretary-General’s Special Envoy for Malaria to continue promoting LLIN procurement best practices.