Study investigates genetic variants' role in increasing Parkinson's disease risk

Boston University School of Medicine (BUSM) investigators have led the first genome-wide evaluation of genetic variants associated with Parkinson's disease (PD). The study, which is published online in PLOS ONE, points to the involvement of specific genes and alterations in their expression as influencing the risk for developing PD.

07 oct 2012--Jeanne Latourelle, DSc, assistant professor of neurology at BUSM, served as the study's lead author and Richard H. Myers, PhD, professor of neurology at BUSM, served as the study's principal investigator and senior author.

A recent paper by the PD Genome Wide Association Study Consortium (PDGC) confirmed that an increased risk for PD was seen in individuals with genetic variants in or near the genes SNCA, MAPT, GAK/DGKQ, HLA and RIT2, but the mechanism behind the increased risk was not determined.

"One possible effect of the variants would be to change the manner in which a gene is expressed in the brains, leading to increased risk of PD," said Latourelle.

To investigate the theory, the researchers examined the relationship between PD-associated genetic variants and levels of gene expression in brain samples from the frontal cortex of 26 samples with known PD and 24 neurologically healthy control samples. Gene expression was determined using a microarray that screened effects of genetic variants on the expression of genes located very close to the variant, called cis-effects, and genes that are far from the variant, such as those on a completely different chromosome, called trans-effects.

An analysis of the cis-effects showed that several genetic variants in the MAPT region showed a significant association to the expression of multiple nearby genes, including gene LOC644246, the duplicated genes LRRC37A and LRRC37A2 and the gene DCAKD. Significant cis-effects were also observed between variants in the HLA region on chromosome 6 and two nearby genes HLA-DQA1 and HLA-DQA1. An examination of trans-effects revealed 23 DNA sequence variations that reached statistical significance involving variants from the SNCA, MAPT and RIT2 genes.

"The identification of the specific altered genes in PD opens opportunities to further study them in model organisms or cell lines with the goal of identifying drugs which may rectify the defects as treatment for PD," said Myers.

More information: dx.plos.org/10.137… pone.0046199

Provided by Boston University Medical Center

Aspirin may temper brain power decline in elderly women at risk of heart disease

Daily low dose aspirin could slow the decline in brain power among elderly women at high risk of heart disease, indicates observational research published in the online journal BMJ Open.

06 oct 2012--The researchers base their findings on 681 women between the ages of 70 and 92, 601 of whom were at high risk of heart disease and stroke, defined as a 10% or greater risk on a validated risk scale (Framingham).

All the women were subjected to a battery of tests to measure their physical health and intellectual capacity, including verbal fluency and memory speed, and dementia (mini mental state exam, or MMSE for short) in 2000-1.

Their health was tracked over a period of five years, at the end of which the intellectual capacity of 489 women was assessed again.

Some 129 women were taking low dose aspirin (75 to 160 mg) every day to ward off a heart attack or stroke when the monitoring period started. A further 94 were taking various other non-steroidal anti-inflammatory drugs (NSAIDs).

The MMSE score fell, on average, across the whole group at the end of the five years, but this decline was considerably less in the 66 women who had taken aspirin every day over the entire period.

This held true, even after taking account of age, genetic factors, the use of other NSAIDs, and the cardiovascular risk score.

The researchers then divided up the group into those who had taken aspirin for the entire five years (66); those who had stopped taking it by 2005-6 (18); those who were taking it by 2005-6 (67); and those who hadn't taken the drug at any point (338).

Compared with women who had not taken aspirin at all, those who had done so for all five years, increased their MMSE score, while those who had taken aspirin at some point, registered only insignificant falls in MMSE score.

The test results for verbal fluency and memory speed indicated similar patterns, although the findings weren't statistically significant.

There were no differences, however, in the rate at which the women developed dementia.

The researchers then looked only at the women with a Framingham risk score of more than 10%. Again, similar patterns were evident.

The fall in MMSE score was less among those taking aspirin than those who weren't, and there was no difference between those taking other NSAIDs and those who weren't. The same was true of the verbal and memory tests, although the differences were not statistically significant.

The authors caution that theirs was an observational study, and that the MMSE can't detect subtle changes in cognitive ability. But they suggest their findings indicate that aspirin may protect the brain—at least in women at high risk of a heart attack or stroke.

Provided by British Medical Journal

Limiting the problem of missing data urged for clinical trials

Missing data compromise inferences from clinical trials, and due to the problematic nature of compensation with analysis methods, the importance of avoiding missing data in clinical trials is paramount, according to a special report published in the Oct. 4 issue of the New England Journal of Medicine.

05 oct 2012—Data missing from clinical trials can undermine the credibility of those trials, and little attention has been focused on this issue until recently, experts say.

Even regulatory guidelines that direct how clinical trials should be run offer little advice on dealing with missing information, according to a new report from an expert panel commissioned by the National Research Council.

And, while statisticians may be able to control for the missing data, they can end up making "assumptions about what the outcomes would've been, and when you're doing a phase 3 clinical trial [that could lead to a drug's regulatory approval or denial], people don't want to make assumptions. They want to assure balance, which argues for trying to limit the amount of missing data," said the panel chairman, Rod Little, a biostatistics professor at the University of Michigan School of Public Health in Ann Arbor.

Another panel member, Kay Dickersin, who directs the Center for Clinical Trials and the U.S. Cochrane Center at the John's Hopkins Bloomberg School of Public Health in Baltimore, agreed. "When data are missing from clinical trials, the findings become questionable or of no use. Why are the data missing? Is it because the people with data missing all got better? All got worse? We don't know why the data are missing, and so we cannot even guesstimate what the true findings of the study would be would be if no data were missing," Dickersin said. 
"The main point is that it is far better to prevent missing data than to try to 'fix' the problem in the analysis," she added.

Findings from the panel are published as a special report in the Oct. 4 issue of the New England Journal of Medicine.

In May, a study published in the Journal of the American Medical Association also took clinical trials to task, finding that many are small and of poor quality. That study found that cancer treatment trials often failed to follow the highest standards.

To address the potential problems stemming from missing data in clinical trials, the U.S. Food and Drug Administration requested that the National Research Council convene an expert panel in 2008. The current report focuses primarily on phase 3 clinical trials assessing the safety and efficacy of drugs, biologic products and some medical devices.

Missing data was defined by the panel as information that would have been meaningful to the results of the trial.

The panel found that a major cause of missing data is participants who stop taking their assigned treatment because it's not working, the side effects are troubling or the drug regimen is too inconvenient.

But the panel suggested that researchers should continue to gather follow-up information on them anyway.

"People have the right to discontinue any treatment, but often people don't follow-up. The panel is making the point that in a lot of situations, it's useful to get that information," said Little.

Dickersin said another issue is missing data even when follow-up visits were kept. "Sometimes patients may attend their follow-up visits, but not answer all the questions they were asked. So if, for example, some people in a study about pain fail to fill in their diaries about daily pain, then we may not know that pain relief is only for a short time with the test drug when long-term pain relief is what patients are seeking," she said.

The panelists outlined a number of steps that could be taken to limit the amount of missing data in clinical trials. They include: 

• Conducting a brief run-in period in which all participants are assigned an active drug to see who can tolerate it.
• Allowing the use of rescue medications as part of the treatment regimen, so these drugs are accounted for in the analysis.
• Targeting a group that doesn't have enough current treatment options, because they have more incentive to stay in the trial.
• Shortening the follow-up period.

The panel also recommended changes in the statistical analysis of missing data at the end of the study. Little said some of the current methods used may be too simplistic.

The bottom line, he said, is that "we want to make the best possible decisions about which drugs are effective and safe."

Dickersin added, "Study participants are making an incredibly important contribution to current and future health care by participating in clinical trials. They can contribute to the impact of the findings by ensuring that they follow the protocol as asked. 
"And, even when they have to change treatments or stop the treatment to which they were assigned—say, because of side effects—they still can help the study's success by returning for visits and completing all study forms and questionnaires," she added.

More information: Full Text (subscription or payment may be required)

Beta-blocker use not associated with lower risk of cardiovascular events

Among patients with either coronary artery disease (CAD) risk factors only, known prior heart attack, or known CAD without heart attack, the use of beta-blockers was not associated with a lower risk of a composite of cardiovascular events that included cardiovascular death, nonfatal heart attack or nonfatal stroke, according to a study in the October 3 issue of JAMA.

04 oct 2012--"Treatment with beta-blockers remains the standard of care for patients with coronary artery disease, especially when they have had a myocardial infarction [MI; heart attack]. The evidence is derived from relatively old post-MI studies, most of which antedate modern reperfusion or medical therapy, and from heart failure trials, but has been widely extrapolated to patients with CAD and even to patients at high risk for but without established CAD. It is not known if these extrapolations are justified. Moreover, the long-term efficacy of these agents in patients treated with contemporary medical therapies is not known, even in patients with prior MI," according to background information in the article.

Sripal Bangalore, M.D., M.H.A., of the NYU School of Medicine, New York, and colleagues conducted a study to evaluate the association between beta-blocker use and long-term cardiovascular outcomes. The observational study included data from patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry. From this registry, 44,708 patients met the study inclusion criteria of whom 14,043 patients (31 percent) had prior MI, 12,012 patients (27 percent) had documented CAD but without MI, and 18,653 patients (42 percent) had CAD risk factors only. The last follow-up data collection was April 2009. The primary outcome for this study was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure. The overall median (midpoint) follow-up was 44 months. Among the 44,708 patients in the study, 21,860 were included in the propensity score-matched analysis.

The researchers found that in the prior MI group, the event rates were not significantly different among those with beta-blocker use (489 [16.93 percent]) vs. those without beta-blocker use (532 [18.60 percent]) for the primary outcome, or the secondary outcome (30.96 percent vs. 33.12 percent, respectively). In the CAD without MI cohort, the event rates were not different in those with beta-blocker use (391 [12.94 percent]) vs. those without p-blocker use (405 [13.55 percent]) for the primary outcome, for cardiovascular death, for stroke, and for MI. The event rates were higher in those with beta-blocker use (1,101 [30.59 percent] vs. those without beta-blocker use (1,002 [27.84 percent]) for the secondary outcome and for hospitalization in the propensity score-matched model.

In the risk factors alone group, the event rates were higher in those with beta-blocker use (467 [14.22 percent] vs. those without beta-blocker use (403 [12.11 percent]) for the primary outcome, for the secondary outcome (870 [22.01 percent] vs. 797 [20.17 percent], respectively) but not for MI or stroke. In the propensity score-matched model, there were similar event rates for cardiovascular death and for hospitalization.

The researchers also found that among patients with recent MI (one year or less), beta-blocker use was associated with a lower incidence of the secondary outcome.

"Among patients enrolled in the international REACH registry, beta-blocker use was not associated with a lower event rate of cardiovascular events at 44-month follow-up, even among patients with prior history of MI. Further research is warranted to identify subgroups that benefit from beta-blocker therapy and the optimal duration of beta-blocker therapy," the authors conclude.

More information: JAMA. 2012;308[13]:1340-1349. 

Provided by JAMA and Archives Journals

Study finds direct correlation between hospital bedsores, patient mortality

3 oct 2012—A new clinical study spearheaded by the dean of UCLA's School of Nursing has found a direct correlation between pressure ulcers—commonly known as bedsores—and patient mortality and increased hospitalization. 
  
The research is believed to be the first of its kind to use data directly from medical records to assess the impact of hospital-acquired pressure ulcers on Medicare patients at national and state levels. 
  
According to the study, featured as the lead article in the current issue of the Journal of the American Geriatrics Society, seniors who developed pressure ulcers were more likely to die during their hospital stay, to have longer stays in the hospital, and to be readmitted to the hospital within 30 days of their discharge.

To arrive at their findings, the researchers tracked more than 51,000 randomly selected Medicare beneficiaries hospitalized across the United States in 2006 and 2007. 
  
"Hospital-acquired pressure ulcers were shown to be an important risk factor associated with mortality," said Dr. Courtney Lyder, lead investigator on the study and dean of the UCLA School of Nursing. "It is incumbent upon hospitals to identify individuals at high risk for these ulcers and implement preventive interventions immediately upon admission." 
  
According to Lyder and his research team, individuals at the highest risk are those with existing chronic conditions, such as congestive heart failure, pulmonary disease, cardiovascular disease, diabetes and obesity, as well as those on steroids. 
  
In conducting the study, the researchers were challenged by the fact that there is no large single database to help determine the incidence of pressure ulcers among hospitalized Medicare patients. They therefore culled their data from Medicare's claim history, a national surveillance system designed to identify adverse events—or "unintended harm"—within the hospitalized Medicare population. The researchers looked at this data to determine the cause and patterns of hospital-acquired pressure ulcers. 
  
The study found that 4.5 percent of the patients tracked acquired a pressure ulcer during their stay in the hospital. The majority of these bedsores were found on the tailbone or sacrum, followed by the hip, buttocks and heels. The study also revealed that of the nearly 3,000 individuals who entered the hospital with a pressure ulcer, 16.7 percent developed at least one new bedsore on a different part of their body during their hospitalization. 
  
"This is a serious issue, and now we have data that can help the health care system address this ongoing problem," Lyder said. "When individuals enter the hospital with the risk conditions that we've identified, it should send up an immediate warning signal that appropriate steps should be taken to minimize the chance of pressure ulcers occurring."

Provided by University of California, Los Angeles

Misconduct, not error, accounts for most scientific paper retractions, new study finds

In sharp contrast to previous studies suggesting that errors account for the majority of retracted scientific papers, a new analysis—the most comprehensive of its kind—has found that misconduct is responsible for two-thirds of all retractions. In the paper, misconduct included fraud or suspected fraud, duplicate publication and plagiarism. The paper's findings show as a percentage of all scientific articles published, retractions for fraud or suspected fraud have increased 10-fold since 1975. The study, from a collaboration between three scientists including one at Albert Einstein College of Medicine of Yeshiva University, published online today in the Proceedings of the National Academy of Sciences (PNAS).

02 oct 2012--"Biomedical research has become a winner-take-all game—one with perverse incentives that entice scientists to cut corners and, in some instances, falsify data or commit other acts of misconduct," said senior author Arturo Casadevall, M.D., Ph.D. , the Leo and Julia Forchheimer Chair and professor of microbiology & immunology and professor of medicine at Einstein. Dr. Casadevall is also editor-in-chief of the journal mBio.

The study reviewed 2,047 papers retracted from the biomedical literature through May 2012. To determine the reasons for the retractions, the researchers consulted several secondary sources, such as the National Institutes of Health (NIH) Office of Research Integrity and Retractionwatch.com, which investigate scientific misconduct.

The researchers found that about 21 percent of the retractions were attributable to error, while 67 percent were due to misconduct, including fraud or suspected fraud (43 percent), duplicate publication (14 percent), and plagiarism (10 percent). Miscellaneous or unknown reasons accounted for the remaining 12 percent.

"What's troubling is that the more skillful the fraud, the less likely that it will be discovered, so there likely are more fraudulent papers out there that haven't yet been detected and retracted," said Dr. Casadevall.

Earlier studies that underestimated the extent of scientific misconduct relied solely on the journals' retraction notices, which are written by the papers' authors, according to Dr. Casadevall. "Many of those notices are wrong," he said. "Authors commonly write, 'We regret we have to retract our paper because the work is not reproducible,' which is not exactly a lie. The work indeed was not reproducible—because it was fraudulent. Researchers try to protect their labs and their reputations, and these retractions are written in such a way that you often don't know what really happened."

The PNAS study also found that journals with higher impact factors (a measure of a publication's influence in scientific circles) had especially high rates of retractions. Dr. Casadevall attributes the growing number of retracted papers to the prevailing culture in science, which disproportionately rewards scientists for publishing large numbers of papers and getting them published in prestigious journals.

"Particularly if you get your papers accepted in certain journals, you're much more likely to get recognition, grants, prizes and better jobs or promotions," he said. "Scientists are human, and some of them will succumb to this pressure, especially when there's so much competition for funding. Perhaps our most telling finding is what happened after 2005, which is when the number of retractions began to skyrocket. That's exactly when NIH funding began to get very tight."

In a recent article in Infection and Immunity, Dr. Casadevall proposed various solutions to the problem of scientific misconduct, including: 

• more emphasis on the quality of publications rather than quantity
• less emphasis on impact measures when rating journals
• fostering a cooperative and collaborative culture in the research community
• developing more stable and sustainable sources of research funding.
• creating more flexible career pathways to prevent the ongoing loss of capable scientists due to inadequate funding

The retraction study's findings weren't all gloom and doom. "There is a very optimistic piece of data in the paper," noted Dr. Casadevall: 43 percent of all retractions came from just 38 of the thousands of labs worldwide. "So while we're not looking at a systemic disease, so to speak, in the scientific community, our findings do indicate a significant problem that needs to be addressed."

More information: The PNAS paper is titled, "Misconduct accounts for the majority of retracted scientific publications."

Provided by Albert Einstein College of Medicine

Alzheimer's disease in men linked to low levels of hormone, IGF-1

Low serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) are associated with Alzheimer's Disease in men, but not women, according to a recent study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM).

02 oct 2012--IGF-1 and IGFBP-3 are involved in longevity and could be beneficial to cognition, especially in Alzheimer's disease where experimental studies have shown that IGF-1 opposes the main pathological processes of Alzheimer's disease. The current study investigated the relationship between IGF-1 and IGFBP-3 serum levels and cognitive impairment, including Alzheimer's disease.

"At this time, no curative treatment is available for Alzheimer's disease so focus on modifiable associated factors is of major importance," said Emmanuelle Duron, MD, PhD, of Broca Hospital in Paris, France and lead author of the study. "Our research shows a possible usefulness of IGF-1 in Alzheimer's disease treatment, especially in early stages."

In this multicentric cross-sectional study, researchers measured IGF-1 and IGFBP-3 serum levels in 694 elderly subjects (218 men and 476 women). Of the study participants, 481 had memory complaints and were diagnosed with Alzheimer's disease or mild cognitive impairment. Duron and her colleagues found that IGF-1 and IGFBP-3 serum levels were significantly associated with cognitive status in men, but not in women.

"Our cross-sectional association does not mean a causal relationship," notes Duron. "Our results justify a longitudinal study to evaluate whether circulating IGF-1/IGFBP-3 are predictive of cognitive decline according to gender."

More information: The article, "Insulin-like Growth Factor-I and Insulin-like Growth Factor Binding Protein-3 in Alzheimer's Disease," appears in the December 2012 issue of JCEM.

Provided by The Endocrine Society

Study discovers first real indicator of longevity in mammals

A team of researchers from the Spanish National Cancer Research Centre (CNIO), headed by CNIO Director María Blasco, has demonstrated in a pioneering study on mammals that longevity is defined at a molecular level by the length of telomeres. The work—which is published today in the online edition of the journal Cell Reports—opens the door to further study of these cellular components in order to calculate the rate at which cells age and thus be able to determine life expectancy for a particular organism.

01 oct 2012--Chromosomes—the cellular containers holding the genetic information in living creatures—have repetitive sequences of DNA at their extremities called telomeres. These sequences act as hoods that protect the genetic material in the face of any external agent which might damage it and compromise the function of the cells.

Several transversal population studies—measuring telomere length once over time in a large group of individuals—show a relationship between the length of the telomeres and the risk of suffering illnesses—cardiovascular disease or cancer, for example.

Until now, however, the use of telomeric measurements to predict real life expectancy in mammals had not been evaluated.

"In the transversal studies, it appears that individuals with short telomeres have a significantly increased probability of developing illnesses, including cancer. But this information is not applicable to a specific individual", says Blasco.

To determine a real ageing prediction method, the authors of the present study have carried out longitudinal studies of telomere length in mice, in which a single individual is followed over a period of time.

After taking periodic blood samples from the same individual, from which cells were extracted for study, they found that those mice which managed to live longer were not the ones that had longer telomeres at any given age but those in which showed less telomeric shortening over time.

"The important thing is not so much the long telomeres at any given time as the tendency or the evolution of the length of the telomeres over time", says Elsa Vera, lead author of the study.

NEW OPTIONS FOR STUDYING AGEING AND ITS CAUSES

With this study, Blasco's team suggests using mice as an animal model in longitudinal studies that allow for health prognoses in humans. Blasco says that: "while telomere length in normal mice is much greater than in humans, we have found, surprisingly, that the telomere shortening rate in mice is 100 times faster than in humans, so the old dogma of normal mice not getting old due to the shortening of their telomeres is wrong".

This study further opens the possibility of studying, via the longitudinal examination of these genetic guardians, the real effect of lifestyle choices such as diet, smoking or exercise on individual ageing rates.

These studies might therefore be crucial in preventing illnesses or in developing new medicines to treat them.

More information: The rate of increase of short telomeres predicts longevity in mammals. Elsa Vera, Bruno Bernades de Jesus, Miguel Foronda, Juana M. Flores, and Maria A. Blasco. Cell Reports (2012). doi: 10.1016/j.celrep.2012.08.023

Provided by Centro Nacional de Investigaciones Oncologicas (CNIO)

Landmark guidelines for optimal quality care of geriatric surgical patients just released

New comprehensive guidelines for the pre- operative care of the nation's elderly patients have been issued by the American College of Surgeons (ACS) and the American Geriatrics Society (AGS). The joint guidelines—published in the October issue of the Journal of the American College of Surgeons—apply to every patient who is 65 years and older as defined by Medicare regulations. The guidelines are the culmination of two years of research and analysis by a multidisciplinary expert panel representing the ACS and AGS, as well as by expert representatives from a range of medical specialties.

30 sept 2012--"The major objective of these guidelines is to help surgeons and the entire perioperative care team improve the quality of surgical care for elderly patients," said Clifford Y. Ko, MD, FACS, Director of the ACS National Surgical Quality Improvement Program (ACS NSQIP®) and the ACS Division of Research and Optimal Patient Care in Chicago, professor of surgery at University of California, Los Angeles (UCLA) and director of UCLA's Center for Surgical Outcomes and Quality.

One of the driving forces behind the guidelines is America's expanding geriatric popu- lation, Dr. Ko explained. The U.S. Census Bureau projects the percentage of men and women 65 years and older will more than double between 2010 and 2050 and will increase by 20 per-cent of the total population by 2030.* In 2006, elderly patients underwent 35 percent of inpatient surgical procedures and 32 percent of outpatient procedures according to study authors.

"For elderly patients undergoing surgical procedures, we want to ensure we are optimiz-ing each patient's medical condition," Dr. Ko said. "This population is growing in numbers and we want to emphasize the depth and breadth of care required for them. These evidence-based guidelines will enhance surgical practice by setting higher standards and performance measures for surgeons and the entire perioperative care team," he said. This is the first time ACS has worked with AGS to develop guidelines for geriatric patients according to Dr. Ko.

The guidelines recommend and specify 13 key issues of preoperative care for the elderly: cognitive impairment and dementia; decision-making capacity; postoperative delirium; alcohol and substance abuse; cardiac evaluation; pulmonary evaluation; functional status, mobility, and fall risk; frailty; nutritional status; medication management; patient counseling; preoperative testing; and patient-family and social support system.

"There is no single magic bullet for rendering this level of surgical care," Dr. Ko said. "Each of the 13 issues covered by the guidelines is very important, comprehensive, and difficult to prioritize. For example, surgeons and perioperative team members may do perfectly well when analyzing a patient's cognitive functioning , but not so well on the polypharmacy issue. So then suddenly, polypharmacy becomes the number-one issue for the surgical team to address during the preoperative care phase," he explained.

Furthermore, the expert panel said there are complex problems specific to the elderly, including use of multiple medications, functional status, frailty, risk of malnutrition, cognitive impairment, and comorbidities. "When surgeons evaluate elderly patients before they undergo operations, they want to know how many and what specific medications their patients are taking. This step will enable them to identify potential medication issues before operations and before the surgeons start adding pain medication to the patient's medication list," Dr. Ko explained.

As the guidelines state: "consider minimizing the patient's risk for adverse drug reac-tions by identifying what should be discontinued before surgery or should be avoided and dose reducing or substituting potentially inappropriate medications."

Additionally, the number and severity of underlying medical problems call for special strategies by the entire surgical team, according to Dr. Ko.

"Patients who are 90 years old tend to have more comorbidities than those who are 65 years," he said. "There may be something wrong with the heart, the lungs, the kidneys, the liver. Surgeons have to plan and deal with these comorbidities simultaneously while the patient is undergoing a surgical procedure."

The guidelines state that evaluating patients for developing heart disease and heart attack is critical to identify patients at higher risk. All patients should be evaluated for perioperative cardiac risk.

"Caring for the elderly generally requires a team approach," said Dr. Ko. "The surgeon knows how to perform surgery and the cardiologist knows how to take care of the heart. It's best for everyone to work together to take care of the patient. We want everyone on the same page of providing good quality care."

These guidelines have been developed in response to a performance measure that the ACS has developed with the Centers for Medicare & Medicaid Services (CMS), according to Dr. Ko. The performance measure evaluates the quality of care in patients eligible for Medicare.

ACS NSQIP has worked with CMS to develop "The Elderly Surgery Measure." This is a hospital-based measure that assesses the outcome of elderly patients undergoing surgical procedures. The ACS and CMS will launch a pilot program in October that gives hospitals the opportunity to publicly and voluntarily report the outcome results.

More information: * Source: U.S. Census Bureau Statistical Brief. Sixty-five Plus in the United States. Available at www.census.gov/pop… gebrief.html. Accessed September 26, 2012.

Provided by American College of Surgeons

Ageing and the city: Chronic diseases more prevalent in city-dwellers than country counterparts

Ageing Australian city-dwellers are more likely to suffer from non-infectious chronic diseases such as type 2 diabetes, arthritis, cancer and asthma than their rural counterparts, according to new research from the University of Sydney.

29 sept 2012--The research, conducted by academics from the University's Faculty of Health Sciences and published in this month's edition of the Australasian Journal of Ageing, tracked seven years of longitudinal data for 1256 over-45s who had lived in the same area for at least 20 years.

Results showed people living in urban areas had greater odds of having from a non-infectious chronic disease than people in rural and remote areas.

Every year of age increased the odds of having a long-term health condition by 1.05, or five percent compared with the previous year, while living in the lowest socioeconomic area increased the odds of having a long-term health condition by 90 percent.

"In the city you're exposed to a range of environmental stressors, such as poor air quality, aircraft and road noise, high density housing, lack of adequate transport, poor urban design, a lack of green spaces and shade trees, and so on," says lead author Professor Deborah Black, from the University's Ageing, Work and Health Research Unit.

Lower socioeconomic status was associated with a higher prevalence of non-infectious chronic disease because cheaper housing was generally located in areas with high levels of environmental stressors, such as industrial areas, airports or busy roads.

"As people get older, their bodies are less able to cope physiologically with environmental stressors, and exposure can accelerate the ageing process and trigger or exacerbate disease," Professor Black says.

"With 85 percent of Australians living in the city and 22 percent of Australians estimated to be 65 or older by 2026, it's crucial that we update policy, urban design and primary care in line with the realities of our population."

The research responds to a pressing need to better understand the problems faced by Australia's increasingly urban, ageing population. While the link between urbanisation and population health is well established, until now there has been very little research on the interaction between age and urban living.

According to Professor Black, climate change is one of the most critical issues for the health of ageing Australians.

"In cities, the lack of trees and green spaces create what's called the heat island effect, wherein the sun heats exposed urban surfaces such as roads, roofs, and pavements to temperatures up to 50 degrees Celsius hotter than the air temperature," she says.

"Because older people are less able to cope with high temperatures, they are more at risk of climate change-related health problems than the rest of the population. Effective thermoregulation and hydration are particularly difficult for older people in hot weather, which can lead to problems with heart and kidney function, medication management and falls.

"We also find that because an ageing population is not as mobile, they don't have the opportunity to get away from the environmental stressors around their home and community."

Provided by University of Sydney

Over 65s at increased risk of developing dementia with benzodiazepine

Patients over the age of 65 who begin taking benzodiazepine (a popular drug used to treat anxiety and insomnia) are at an approximately 50% increased risk of developing dementia within 15 years compared to never-users, a study published today on BMJ website suggests.

28 sept 2012--The authors say that "considering the extent to which benzodiazepines are prescribed and the number of potential adverse effects indiscriminate widespread use should be cautioned against".

Benzodiazepine is a widely prescribed drug for the over 65s in many countries: 30% of this age group in France, 20% in Canada and Spain, 15% in Australia. Although less widespread in the UK and US it is still very widely used and many individuals take this drug for years despite guidelines suggesting it should be limited to a few weeks. Previous studies have found an increased risk of dementia, but others have been non-conclusive.

Researchers from France therefore carried out a study on 1063 men and women (average age 78) in France who were all free of dementia at the start. The study started in 1987 and follow-up was 20 years. The researchers used the first 5 years to identifying the factors leading to benzodiazepine initiation and evaluated then the association between new use of this drug and the development of dementia. They also assessed the association between further benzodiazepine initiation during the follow-up period and risk of subsequent dementia. Rates were adjusted for many factors potentially affecting dementia, such as age, gender, educational level, marital status, wine consumption, diabetes, high blood pressure, cognitive decline, and depressive symptoms.

95 out of the 1063 patients started taking benzodiazepine during the study. 253 (23.8%) cases of dementia were confirmed, 30 in benzodiazepine users and 223 in non-users. New initiation of the drug was associated with shorter dementia-free survival.

In absolute numbers, the chance of dementia occurring was 4.8 per 100 person years in the exposed group compared to 3.2 per 100 person years in the non-exposed group. A "person year" is a statistical measure representing one person at risk of development of a disease during a period of one year.

The authors say that although benzodiazepine remains useful for treating anxiety and insomnia, there is increasing evidence that its use may induce adverse outcomes in the elderly such as serious falls and fall-related fractures and this study may add dementia to the list. They say that their data add to the accumulating evidence that the use of benzodiazepines is associated with increased risk of dementia and, if true, that this "would constitute a substantial public health concern". Therefore, taken the evidence of potential adverse effects into account, physicians should assess expected benefits, limit prescriptions to a few weeks, and uncontrolled use should be cautioned against. They conclude that further research should "explore whether use of benzodiazepine in those under 65 is also associated with increased risk of dementia and that mechanisms need to be explored explaining the association"

Provided by British Medical Journal

Surfing the net helps the elderly stay connected

Seniors in rural areas are embracing new technology, according to a University of Adelaide study. 

The internet is giving older people in rural areas a new lease on life, according to a report released today by the University of Adelaide.

27 sept 2012--Surfing the net, using Skype, email and social networking sites is literally keeping older people "connected" with their communities, says lead report author Dr Helen Feist.

Dr Feist, the Deputy Director of the Australian Population and Migration Research Centre at the University of Adelaide, has spent the past three years investigating how technology can be used in remote and rural areas of Australia to improve the lives of older people.

The project, which was funded by the Australian Government Department of Health and Ageing, looked at the best ways of encouraging older people to adopt new technology in a non-threatening way.

A survey in the Murray Lands region of South Australia found that nearly 25% of people aged 80 years and over and more than a third of those in the 65-79 year age bracket were open to learning new technologies.

"In order for people to remain integrated within a world that increasingly relies on new technology, it is important that older people are offered opportunities to adopt and use these new technologies such as computers, smart phones, personal tablets and the Internet," says Dr Feist.

Study participants introduced to iPads and laptop computers quickly embraced the new technology, reporting a 30% increase in comfort levels with computers and the internet after using them over a 12-month period.

"Older adults who adopt new skills as they age improve their confidence, health, enjoy richer levels of social and civic engagement and are more resilient to life stressors and crises," Dr Feist says.

"New technology is enabling older people to keep connected regardless of location, distance or mobility."

Dr Feist says the most important motivator among the elderly for taking up new technologies is to stay connected to family and friends.

"Their willingness to learn suggests there is indeed an untapped market for information and communication technology training in rural areas.

"Given the right device, along with personalised training and support, older people of all ages will take up and continue to use new technology," Dr Feist says.

The report makes a number of recommendations, including better financial support for seniors for learning new technologies; subsidies for Internet connections; and the introduction of `come and try' programs in local community centres.

Provided by University of Adelaide

Population aging will have long-term implications for economy

The aging of the U.S. population will have broad economic consequences for the country, particularly for federal programs that support the elderly, and its long-term effects on all generations will be mediated by how—and how quickly—the nation responds, says a new congressionally mandated report from the National Research Council. The unprecedented demographic shift in which people over age 65 make up an increasingly large percentage of the population is not a temporary phenomenon associated with the aging of the baby boom generation, but a pervasive trend that is here to stay.

26 sept 2012--"The bottom line is that the nation has many good options for responding to population aging," said Roger Ferguson, CEO of TIAA-CREF and co-chair of the committee that wrote the report. "Nonetheless, there is little doubt that there will need to be major changes in the structure of federal programs, particularly those for health. The transition to sustainable policies will be smoother and less costly if steps are taken sooner rather than later."

Social Security, Medicare, and Medicaid are on unsustainable paths, and the failure to remedy the situation raises a number of economic risks, the report says. Together, the cost of the three programs currently amounts to roughly 40 percent of all federal spending and 10 percent of the nation's gross domestic product. Because of overall longer life expectancy and lower birth rates, these programs will have more beneficiaries with relatively fewer workers contributing to support them in the coming decades. Combined with soaring health care costs, population aging will drive up public health care expenditures and demand an ever-larger fraction of national resources.

Population aging is also occurring in other industrialized nations, so any consequences for the U.S. must be considered in the broader context of a global economy. Adapting to this new economic landscape entails costs and policy options with different implications for which generations will bear the costs or receive the benefits. Recent policy actions have attempted to address health care costs, but their effects are as yet unclear. According to the report, the ultimate national response will likely be some combination of major structural changes to public support programs, more savings during people's working years, and longer working lives.

"The nation needs to rethink its outlook and policies on working and retirement," said Ronald Lee, professor of demography and economics at the University of California, Berkeley, and committee co-chair. "Although 65 has conventionally been considered a normal retirement age, it is an increasingly obsolete threshold for defining old age and for setting benefits for the elderly." The committee found that there is substantial potential for increased labor force participation at older ages, which would boost national output, slow the draw-down on retirement savings, and allow workers to save longer. The report adds that longer working lives would have little effect on employment opportunities for younger workers, productivity, or innovation.

In addition, workers can better prepare for retirement by planning ahead and adapting their saving and spending habits, the report suggests. Improved financial literacy will be critical, since between one-fifth and two-thirds of today's older population have not saved enough for retirement and therefore rely heavily on Social Security and Medicare.

More research in areas such as health measurement and projections, capacity to work, and changes in consumption and saving will help to inform decision making, but the report emphasizes the need to act now in order to craft a balanced response.

"Population aging does not pose an insurmountable challenge provided that sensible policies are implemented with enough lead time to allow people, companies, and other institutions to respond," Ferguson said.

A follow-up study from the National Research Council will look more in-depth at the long-term macroeconomic effects of population aging and provide quantitative assessments of specific policy choices.

Provided by National Academy of Sciences

For a health reform model, try Brazil

During the Harvard-Brazil Symposium, Luciana Mendes Santos Servo (pictured), health coordinator at the Institute for Applied Economic Research in Brazil, traced the changes in that country to Brazil’s 1988 constitution, which recognized health as a right for citizens and created a government obligation to improve it. 

With the 2015 deadline to meet the United Nations' Millennium Development Goals (MDG) approaching, scholars and government officials gathered at the Harvard School of Public Health (HSPH) on Tuesday to search for lessons in the dramatic progress that Brazil has made in recent decades.

25 sept 2012--The eight Millennium Development Goals, adopted in 2000, set targets to attain international development objectives, including reducing extreme poverty and hunger; reducing child mortality; improving maternal health; achieving universal primary education; increasing equality for women; fighting AIDS, malaria, and other diseases; ensuring environmental sustainability; and fostering global partnerships for development.

The Harvard-Brazil Symposium, held in HSPH's Kresge Building, featured discussions of the health-related goals and of Brazil's progress in meeting them. It was sponsored by the Department of Global Health and Population, which is marking its 50th anniversary, as well as the Harvard Global Health Institute and Fundação Maria Cecilia Souto Vidigal.

Harvard School of Public Health Dean Julio Frenk, who sits on UN Secretary General Ban Ki-Moon's MDG Advocacy Group, introduced the event, saying that the goals' adoption marked the first time the world's nations agreed on common development objectives and on indicators to measure progress.

The result, he said, has been an unprecedented level of funding for the needs outlined, as well as progress that has been, in some cases, spectacular. Yet much remains to be done, making the search for examples that might be adapted to other situations an important strategy.

"The challenges that remain are enormous," Frenk said.

Luciana Mendes Santos Servo, health coordinator at the Institute for Applied Economic Research in Brazil, traced the changes in that country to Brazil's 1988 constitution, which recognized health as a right for citizens and created a government obligation to improve it.

That sparked the creation of several social welfare programs and reform of the health care system from one that was centered on hospitals and financed by private insurance, held mainly by those in the formal labor pool, to one that emphasized primary care and was open to all.

Brazil has already achieved the goals for reducing poverty and hunger and is on track to achieve the goals involving child mortality and universal education. Maternal health in the nation has improved, but the goal appears out of reach by 2015. Mendes credited three programs with the bulk of the change: a social security benefit for the elderly, a cash-transfer program for poor families, and a family health program that focuses on primary care.

The programs have provided additional benefits beyond health. The cash-transfer program for poor families, called Bolsa Familia, requires children to attend school, which has boosted school attendance, helping the nation to achieve universal primary school education.

While those programs appear to have been effective, some audience members questioned whether the cost burdens they put on government, particularly in an economic downturn, are sustainable. Mendes said that future financing will be a challenge, because she believes the government can't raise taxes further.

Eduardo Rios Neto, a professor at Brazil's Federal University of Minas Gerais, said the government programs were helped along by a period of economic growth and improvement of the labor market, and that, despite recent progress, social and income inequality in Brazil remain a major problem.

Brazil's progress doesn't mean its health challenges are over either, Mendes said. The rise of noncommunicable diseases, like heart disease, diabetes, and cancer, is a growing challenge.

"We have progressed, but we have some challenges," Mendes said.

Provided by Harvard University

Reduced physical activity reduces life span

24 sept 2012— A regular exercise regimen will increase life expectancy in the elderly, new research has found.

The Monash University-led study examined the significance of weight and physical function and the interaction on mortality in 1435 men and women aged 65 to 97 years, living in the community and representative of the Taiwanese population.

The results of the eight-year study were recently published in the Journal of Nutrition, Health and Aging. The study also included researchers from the National Health Research Institutes, Taiwan and the National Defense Medical Centre, Taiwan.

Lead author, Emeritus Professor Mark Wahlqvist from Monash University's Department of Epidemiology and Preventive Medicine and the Monash Asia Institute, said being frail or losing weight was generally regarded as a major risk for reduced survival among the elderly.

"We found thin, elderly Taiwanese with sarcopenia – a condition of age-related loss of muscle mass and strength - and less skeleton are at the most risk of death, especially if physical function is limited. Those within the normal weight range or even overweight and active had a longer life expectancy with fewer health problems," Emeritus Professor Wahlqvist.

Survival was assessed in relation to weight and body composition, along with physical function such as walking, climbing, performing daily chores and personal care.

The researchers found weight in relation to height (body mass index (BMI) = weight/height2) was twice as likely to shorten the survival of the elderly when low (BMI < 18.5) than high (above 24.0). This increased to nine times more likely when combined with limited physical function. The findings took into account factors such as age, gender, socio-economics and personal behaviours that could have explained the association.

Emeritus Professor Wahlqvist said although this was not an intervention study, it raised the possibility that if physical function could be maintained, then mortality could be markedly reduced in this older age group.

"In light of these figures, both those in public health and clinicians need to look at preventive approaches or intervention strategies that might achieve better survival in older people in regard to thinness and physical dysfunction," Emeritus Professor Wahlqvist said.

"Even small changes involving modest regular physical aerobic and strengthening activities for several days a week could make a substantial difference in health outcomes for the elderly."

More information: DOI: 10.1007/s12603-012-0379-3

Physiotherapy beneficial for people with Parkinson's disease in the short term

23 sept 2012—Results from a systematic review and meta-analysis led by the University of Birmingham in the UK suggest that physiotherapy benefits people with Parkinson's disease in the short term (< 3 months).

The management of Parkinson's disease has traditionally centred on drug treatment, however, there has been increasing support for the inclusion of rehabilitation therapies, such as physiotherapy, to supplement pharmacological and neurosurgical treatment.

Dr Claire Tomlinson, from the University of Birmingham Clinical Trials Unit, and colleagues selected 39 randomised controlled trials including 1827 participants for review.  The review included trials assessing a variety of different physiotherapy methods used to treat participants including general physiotherapy, exercise, treadmill training and dance. 

Of the 18 potential physiotherapy outcomes assessed, physiotherapy resulted in improvements in nine areas.  For three outcomes (gait speed, the Berg balance scale and a clinician-rated disability scale) there is existing evidence to suggest that these improvements may be clinically meaningful to people with Parkinson's disease.  For example, participants demonstrated that with physiotherapy intervention they were able to walk faster or maintain their balance better compared to no intervention.

Dr Tomlinson, said: "This study indicates that physiotherapy could provide clinically meaningful benefits in the short term for people with Parkinson's disease. Further improved studies are needed; these will shed more light on how beneficial physiotherapy can be for patients in the longer term.  Once a larger and better quality of evidence is achieved, there might be scope for a recommendation for change in practice to be made."

More information: Physiotherapy intervention in Parkinson's disease: systematic review and meta-analysis, published by the British Medical Journal (BMJ) 2012;345(7872).

Provided by University of Birmingham

New strategies needed to combat disease in developing countries

So-called lifestyle diseases are gaining ground with epidemic speed in low-income countries. The traditional health focus in these countries has been to combat communicable diseases such as malaria, HIV and tuberculosis. However, research from the University of Copenhagen suggests that dividing campaigns into combating either non-communicable or communicable diseases is ineffective and expensive. A new article by Danish scientists published in the well-reputed journal Science provides an overview.

22 sept 2012--A prognosis from WHO in 2002 indicates that by 2030, we can expect the relationship between non-communicable and communicable diseases to have shifted so that non-communicable diseases are the most common cause of death in the world's poorest countries. The shift is anticipated due to longer lifespan as well as increased urbanisation in low-income countries:

"This development means that 57% of the world's deaths in 2030 will be due to the major non-communicable killers we know from the developed world: cardiovascular diseases, chronic lung diseases, diabetes and many types of cancer," explains Professor Ib Bygbjergfrom the Department of International Health, Immunology and Microbiology at the University of Copenhagen. In an article recently published in the well-reputed journal Science, he explains the need for new strategies to combat disease globally.

Ignoring new research

In 2011 the UN member countries drew up a political declaration on the prevention and control of non-communicable diseases. And even though it was a large step forward for the UN to put non-communicable disease on the agenda, the situation is still problematic, according to Professor Bygbjerg:

"The declaration continued an unfortunate tradition of dividing campaigns into communicable and non-communicable diseases. This practice ignores many new research results showing, among other things, that many types of cancer are caused by viral infections, while communicable diseases such as tuberculosis, for example, can only be fought effectively by also looking at tobacco and alcohol consumption," states Ib Bygbjerg.

In the article published in Science, Professor Bygbjerg gives several examples of the necessity of having a joint campaign against communicable and non-communicable diseases. The simplest example is probably that since we know that diabetes increases the risk of tuberculosis – just as tuberculosis can bring on or exacerbate diabetes – why do we try to combat them separately?

"Naturally the main idea is that since we know that patients often suffer from several diseases, and that various diseases and their treatments influence each other, it is pointless to continue to develop large health programmes that only focus on fighting one single disease," continues Ib Bygbjerg.

Integrated health programmes are the key

We can kill several birds with one stone by focusing on known common risk factors, such as poor nutrition, and developing strategies that integrate efforts to combat diabetes and tuberculosis, for example.

Stimulated by Danish support, China, India and other countries with major diabetes and tuberculosis problems have begun developing integrated health programmes with double-screening for these diseases. However, in many other cases, structural problems have prevented this type of integration.

"Researchers, healthcare workers and politicians are often forced to meet short-term results contracts as part of 'new public management'. This practice can easily turn efforts to deal with current and impending health problems into a battlefield over money needed to combat one disease or another, instead of addressing the actual double burden of communicable and non-communicable disease that will be borne by the large populations in developing countries, now and in future," concludes Professor Ib Bygbjerg.

Provided by University of Copenhagen

Non-communicable diseases prevention 'more important than life or death'

Proposals designed to prevent non-communicable diseases (NCDs) such as "fat taxes" will have wide-ranging effects on the economy and health but wider research is needed to avoid wasting resources on ineffective measures, according to an economist from the London School of Hygiene & Tropical Medicine.

21 sept 2012--Writing in Science, Professor Richard Smith says that effective prevention of the increasing problem of NCDs will require changes in how we live our lives, which will in turn lead to significant economic changes across populations, industries and countries. But unless evidence is provided about who and what is positively or negatively affected, it is impossible to know which policies will benefit both economies and health.

He calls for global studies concerning the whole economy and suggests lessons should be learned from infectious diseases such as AIDS where clear demonstration of the overall economic impact played a key role in securing funding initiatives at the highest level.

With increasing numbers of people in the developed and developing world suffering from ill health associated with both genetic and lifestyle factors, the problem is more than just a medical concern. NCDs affect the economy "profoundly and pervasively" and using the example of Liverpool Football Club manager Bill Shankly who said football was "not just a matter of life and death, it's more important than that", Professor Smith claims that for economists so are NCDs.

The target set at the 65th World Health Assembly to reduce premature deaths from NCDs by 25% by 2025 adds to the urgency and there is a growing swell of opinion about the importance of tackling the problem. The School's Centre for Global Non-Communicable Diseases is just one example of a high-level response to the worldwide call for action.

Purely micro-economic approaches will not work, however, Prof Smith argues. Prices are "pivotal" for economics and this concept provides the logic for the current enthusiasm for the introduction (already implemented in Denmark and Hungary) of a "fat tax" to reduce consumption of foods high in saturated fat by increasing their price through tax.

But Prof Smith sets out the various potential effects of such a mechanism which have not been analysed such as the alternative products consumers might turn to instead and changes in farming practices. According to the paper, there is a major gap in knowledge about the "macro-economic" big picture perspective which needs to be filled before society-wide NCD prevention can move forward.

He writes: "A food tax will affect the risk of NCDs in an unpredictable manner as it begins to indirectly influence other sectors in the national economy and interface with the rest of the world," he writes. "If the net effect is to increase health, then this should feed positively into theeconomy itself, by reducing healthcare costs and by improving workforce productivity. However, we do not know that this will be the effect, because we do not consider the broader macro-economic picture."

More information: "Can Noncommunicable Diseases Be Prevented? Lessons from Studies of Populations and Individuals," by M. Ezzati et al., Science, 2012.

Provided by London School of Hygiene & Tropical Medicine

Diseases of aging map to a few 'hotspots' on the human genome

20 sept 2012—Researchers have long known that individual diseases are associated with genes in specific locations of the genome. Genetics researchers at the University of North Carolina at Chapel Hill now have shown definitively that a small number of places in the human genome are associated with a large number and variety of diseases. In particular, several diseases of aging are associated with a locus which is more famous for its role in preventing cancer.

For this analysis, researchers at UNC Lineberger Comprehensive Cancer Center catalogued results from several hundred human Genome-Wide Association Studies (GWAS) from the National Human Genome Research Institute. These results provided an unbiased means to determine if varied different diseases mapped to common 'hotspot' regions of the human genome. This analysis showed that two different genomic locations are associated with two major subcategories of human disease.

"Our team is interested in understanding genetic susceptibility to diseases associated with aging, including cancer," said PhD student William Jeck, who was first author on the study, published in the journal Aging Cell.

The team examined the large NHGRI dataset and first eliminated hereditable traits such as eye or hair color and other non-disease traits like drug metabolism. The group then focused on variants identified from GWAS that contributed to actual diseases. Combining results from all of these studies, there was enough data to arrive at statistically valid conclusions. The team then mapped the disease associations to the appropriate locations of the genome, counting the number of unique diseases mapping to specific genomic regions, in order to see if disparate diseases mapped randomly throughout the genome, or clustered in hotspots.

"What we ended up with is a very interesting distribution of disease risk across the genome. More than 90 percent of the genome lacked any disease loci. Surprisingly, however, lots of diseases mapped to two specific loci, which soared above all of the others in terms of multi-disease risk. The first locus at chromosome 6p21, is where the major histocompatibility (MHC) locus resides. The MHC is critical for tissue typing for organ and bone marrow transplantation, and was known to be an important disease risk locus before genome-wide studies were available. Genes at this locus determine susceptibility to a wide variety of autoimmune diseases such as arthritis, celiac disease, Type I diabetes, asthma, psoriasis, and lupus," said Jeck.

"The second place where disease associations clustered is the INK4/ARF (or CDKN2a) tumor suppressor locus. This area, in particular, was the location for diseases associated with aging: atherosclerosis, heart attacks, stroke, Type II diabetes, glaucoma and various cancers." he added.

"The finding that INK4/ARF is associated with lots of cancer, and MHC is associated with lots of diseases of immunity is not surprising—these associations were known. What is surprising is the diversity of diseases mapping to just two small places: 30 percent of all tested human diseases mapped to one of these two places. This means that genotypes at these loci determine a substantial fraction of a person's resistance or susceptibility to multiple independent diseases," said Ned Sharpless, MD, Wellcome Distinguished Professor of Cancer Research and Associate Director of Translational Research at UNC Lineberger.

Another interesting finding was the apparent role of two biological processes in multi-disease association. In addition to the MHC and INK4/ARF loci, five less significant hotspot loci were also identified. Of the seven total hotspot loci, however, all contained genes associated with either immunity or cellular senescence. Cellular senescence is a permanent form of cellular growth arrest, and it is an important means whereby normal cells are prevented from becoming cancerous. It has been long known that senescent cells accumulate with aging, and may cause aspects of aging. This new analysis provides evidence that genetic differences in an individual's ability to regulate the immune response and activate cellular senescence determine their susceptibility to many seemingly disparate diseases.

"We call the absence of disease 'wellness', and our results suggest the genetics of wellness may be much more simple than previously suspected. Put another way, these unbiased data from about two million people suggest that your eccentric Uncle Joe, who drank and smoked, but who also lived to be 110 and was never sick a day in his life—well Uncle Joe may have just been genetically fortunate at a couple of loci," said Sharpless.

More information: www.wiley.com/Wile… Cd-ACEL.html

Provided by University of North Carolina Health Care