STIM1 protein link to calcium ions, immune system: a new discovery

Posted on January 28, 2012 by Stone Hearth News

Northwestern University Feinberg School of Medicine researchers have identified a new and unusual role for a key player in the human immune system. A protein initially believed to regulate one routine function within the cell has proven vital for another critical step in the activation of the immune system.

That protein, STIM1, was previously known to sense a change in calcium within immune cells, a process that occurs when the body confronts a pathogen. Upon sensing this change, STIM1 opens a type of pore in the cell membrane, called a CRAC channel, to allow the flow of calcium ions — a vital step in activating the immune system.

The Feinberg team, led by Murali Prakriya, assistant professor of molecular pharmacology and biological chemistry, discovered that STIM1 not only opens these pores but is responsible for determining the exquisite selectivity for calcium ions within the CRAC channels, a critical factor in kick starting the body’s immune system. These findings were recently reported in the journal Nature.

“People have generally thought that selectivity of ion channels is fixed and that selectivity and opening are separate processes; this is a fundamental shift in the way scientists believe ion channels operate,” says Prakriya, referring to the ‘pores’ that STIM1 regulates. “CRAC channels and STIM1 are absolutely vital to activating the immune system. As is observed in some human patients, you can block key parts of the system by blocking these molecules in immune cells. These finding reveal not only a novel mechanism by which CRAC channels operate, but also new ways in which it encodes biological information. This represents exciting new possibilities to develop therapeutics to treat a broad range of conditions.”

To determine that STIM1 is responsible for selectivity and opening, the researchers created a mutated CRAC channel designed to keep the pore open without the assistance of STIM1. When the channel was opened without STIM1, multiple types of ions were passed through the pore, including sodium and potassium. When STIM1 was added back in, the channel became very selective for calcium ions again, like the normal channel. Even at low doses of STIM1, the unmutated channel lost its normally high calcium selectivity, allowing the entry of multiple types of ions.

Conditions that might benefit from immune suppression are likely targets for future CRAC channel targeted therapy, including autoimmune diseases and many types of allergies. Additionally, targeting CRAC channels could provide improvements for existing immune suppression therapies such as those used during transplantation.

“The CRAC channel is emerging to be incredibly important for the immune system,” says Prakriya. “But we have been solely focused on its calcium conducting mode that occurs in response to STIM1. It is certainly possible that there could be other players in the cell that open the CRAC channel pore to permit the flux of other ions to stimulate different cell functions. That’s the next question.”

Also in the Nature article, Prakriya’s team identified the location of the barrier, or gate, within the CRAC channel that controls its opening and closing.

“The identification of the molecular and structural regions of the pore that controls opening and closing is highly valuable for facilitating drug design targeting CRAC channels for the treatment of immune disorders,” he adds.

Source

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How electronic health records may benefit diabetes patients: new study

Posted on January 28, 2012 by Stone Hearth News
Health Serv Res. 2012 Jan 17. doi: 10.1111/j.1475-6773.2011.01370.x. [Epub ahead of print]

The Effectiveness of Implementing an Electronic Health Record on Diabetes Care and Outcomes.

Source

Department of Medicine, Yale University, New Haven, CT; Health Research and Educational Trust, Chicago, IL.

Abstract

OBJECTIVE:

To assess the impact of electronic health record (EHR) implementation on primary care diabetes care.

DATA SOURCES:

Charts were abstracted semi-annually for 14,051 diabetes patients seen in 34 primary care practices in a large, fee-for-service network from January 1, 2005 to December 31, 2010. The study sample was limited to patients aged 40 years or older.

STUDY DESIGN:

A naturalistic experiment in which GE Centricity Physician Office-EMR 2005 was rolled out over a staggered 3-year schedule.

DATA COLLECTION:

Chart audits were conducted using the AMA/Physician Consortium Adult Diabetes Measure set. The primary outcome was the HealthPartners’ “optimal care” measure: HbA1c ≤ 8 percent; LDL cholesterol < 100 mg/dl; blood pressure < 130/80 mmHg; not smoking; and documented aspirin use in patients ≥40 years of age.

PRINCIPAL FINDINGS:

After adjusting for patient age, sex, and insulin use, patients exposed to the EHR were significantly more likely to receive “optimal care” when compared with unexposed patients (p < .001), with an estimated difference of 9.20 percent (95% CI: 6.08, 12.33) in the final year between exposed patients and patients never exposed. Components of the optimal care bundle showing positive improvement after adjustment were systolic blood pressure <80 mmHg, diastolic blood pressure <130 mmHg, aspirin prescription, and smoking cessation. Among patients exposed to EHR, all process and outcome measures except HbA1c and lipid control showed significant improvement.

CONCLUSION:

Implementation of a commercially available EHR in primary care practice may improve diabetes care and clinical outcomes.

© Health Research and Educational Trust.

PMID:
22250953
[PubMed - as supplied by publisher]

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Posted in Diabetes, Health Care, Health Care: Costs, Health Care: Electronic Health Records, Health Care: Health Insurance, Health Care: Home Health Care, Health Care: Literacy, Health Care: Technology | Leave a comment

The cost of pain

Posted on January 28, 2012 by Stone Hearth News

Newswise — Pain is generally under-treated in the U.S., but low-income and minority patients are even less likely to receive guideline-recommended pain treatment in virtually all healthcare settings in the U.S., according to the authors of a new paper from the University of Pennsylvania School of Nursing, even though minority patients often suffer more severe pain and physical impairments than non-minority patients and are more likely to perform potentially harmful physical work.

In “Pain Medicine, the Official Journal of the American Academy of Pain Medicine,” the reviewers recommended:

- Creating public education programs not only for chronic pain but for educating the public about disparities

- Instituting public health marketing campaigns for pain disparities

- Urging pain advocacy groups to unite on issues of common interest, such as disparities in pain care

- Setting quality assurance standards for pain treatment through the Centers for Medicare and Medicaid Services or National Quality Forum

- Including measures of disparities as part of the Pain and Policy Studies Group statewide pain report cards

Poor and minority patients often experience pain for many years before being seen by a specialist in pain treatment, possible because health providers are more likely to under-assess pain in minorities. Further, minority and low-income patients are more likely to live in geographic areas that constrain their access to healthcare. Pharmacies in predominantly minority zip codes are significantly less likely to have sufficient supplies of pain medications than pharmacies in predominantly white zip codes, the reviewers found.

“There is no question that pain treatment disparities matter in many significant ways; the most important are the tremendous burdens placed on patients, health systems, and society when the most effective pain care is not accessible, affordable, and delivered to those in need,” said Penn Nursing professor and lead author Salimah Meghani, PhD, RN. “Until the prevailing issues of inequitable healthcare are realized and confronted through focused and systematic strategies for education, research, and healthcare reform, it is unlikely that progress will occur in reducing and ultimately eliminating pain disparities.”

According to recent estimates, chronic pain affects 116 million American adults and it remains the number one reason people seek medical care. The burden of pain on Americans in direct and indirect costs can reach $635 billion annually. This expenditure includes disability, poor quality of life, relational problems, lost income and productivity, and higher healthcare utilization including longer hospital stays, emergency room visits, and unplanned clinic visits.

The report, “Advancing a National Agenda to Eliminate Disparities in Pain Care: Directions for Health Policy, Education, Practice, and Research,” informs the recent Institute of Medicine Report “Relieving Pain in America” which identifies opportunities for improving pain care in the United States.

While the actual cost of pain treatment disparities in the U.S. has not been quantified, Dr. Meghani and colleagues anticipate this cost to be large given the magnitude of pain under-treatment among minorities and underserved.

Dr. Meghani and colleagues, including Penn Nursing professor Rosemary Polomano, PhD, RN, FAAN, also proposed broad advocacy initiatives such as “Look at the Data Campaigns,” especially targeted at providers to sensitize them to their blind spots that contribute to inequitable pain care, emphasizing the need for targeted education in pain disparities as part of graduate and continuing medical education, as well as in licensure, accreditation, and certification programs for medicine, nursing, and allied health professionals.

While the Patient Protection and Affordable Care Act mandates federally funded programs to consistently collect data to track trends in healthcare disparities, the authors urged the creation of public-private partnerships in promoting standardized reporting of race and ethnicity data to allow researchers to track disparities, monitor efforts to reduce them, and compare findings across studies regardless of the source of funding.

Posted in Health Care: Costs, Pain | Leave a comment

Hard drugs in middle age up death risk: study

Posted on January 28, 2012 by Stone Hearth News

Newswise — Young adults often experiment with hard drugs, such as cocaine, amphetamines and opiates, and all but about 10 percent stop as they assume adult roles and responsibilities. Those still using hard drugs into their 50s are five times more likely to die earlier than those who do not, according to a new study by University of Alabama at Birmingham researchers published online Jan. 27, 2012, in the Journal of General Internal Medicine.

According to the National Survey on Drug Use and Health, 9.4 percent of Americans ages 50-59 and 7 percent of adults ages 35-49 reported use of a drug other than marijuana sometime in the past year. The study’s lead author, Stefan Kertesz, M.D., associate professor in the UAB Division of Preventive Medicine. and colleagues attempted to discover if lifelong hard-drug use shortens lifespan to better enable primary-care doctors to advise patients who use drugs recreationally.

“While government guidelines have not endorsed screening for drugs in primary care, many doctors are challenged when they discover patients continue to dabble with them,” Kertesz says. “In primary-care practice, we often hear from stable patients who report using some cocaine, irregularly, perhaps on weekends. It’s an underappreciated but very common situation. The typical question physicians have to ask is ‘If this patient doesn’t have addiction, what advice can I give other than noting that it’s unwise to break the law?’ After all, we are supposed to be doctors, not law enforcement.”

Kertesz and a research team from other universities looked at data from the Coronary Artery Risk Development in Young Adults Study for their analysis. CARDIA, funded by the National Heart, Lung and Blood Institute, is a long-term research project involving more than 5,000 black and white men and women from Birmingham, Chicago, Minneapolis and Oakland, designed to examine the development and determinants of cardiovascular disease and its risk factors. Participants ages 18-30 were recruited and followed from 1985 to 2006.

The research team looked specifically at the reported use of “hard drugs” by 4,301 of the CARDIA participants. They compared people who stopped drug use early to those who continued and calculated the likelihood of premature death among these groups.

“Fourteen percent of the people in the study reported recent hard-drug use at least once, and of these, half continued using well into middle age,” Kertesz says. “But, most of the drug users in our study were not addicts. They were dabblers who used just a few days a month.”

Kertesz and his colleagues found that older hard-drug users were more likely to report being raised in economically challenged circumstances in a family that was unsupportive, abusive or neglectful. The team also found that those who were heavy drug users into young adulthood and continued at lower levels into middle age were roughly five times more likely to die than persons who didn’t use drugs.

“We can’t assume that drugs caused death, as in an overdose,” he says. “Rather what we found is that middle-age adults who continue to dabble in hard drugs represent a group that is at risk of bad outcomes — which could include death from trauma, heart disease or other causes that are not a direct result of their drug use — at a higher rate than people who stopped using drugs.”

Kertesz added that the team’s findings are a reminder that people who continue to use drugs are potentially quite vulnerable. They often have grown up under economic and psychosocial stress from childhood onward. They continue to smoke and drink and they remain at elevated risk of premature death.

“Based on the data we hope to offer better advice to primary-care doctors struggling with the rising tide of drug-taking by adults who have not left behind many of the bad habits they learned in young adulthood,” he says.

Study co-authors include Yulia Khodneva, M.D., Monika Safford, M.D., and Joseph Schumacher, Ph.D., UAB Division of Preventive Medicine; Jalie Tucker, Ph.D., UAB School of Public Health; Joshua Richman, M.D., Ph.D., UAB Department of Surgery; Bobby Jones, Ph. D., Department of Statistics, Carnegie Mellon University; and Mark J. Pletcher, M.D., departments of Epidemiology & Biostatistics and Medicine, University of California, San Francisco.

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