News Article | February 21, 2017
In less than one year, researchers have developed multiple vaccine platforms that provide robust protection against Zika virus challenge in animal models BOSTON - As public health officials warn that spring's warmer temperatures may herald another increase of Zika virus infections in the Caribbean and North and South America, researchers around the world are racing to develop safe and effective measures to prevent the disease. In a review paper published today in the journal Immunity, a group of leading vaccine scientists -- including Dan H. Barouch, MD, PhD, of Beth Israel Deaconess Medical Center (BIDMC) -- outline advances in the hunt for a Zika vaccine and the challenges that still lie ahead. "The pace of preclinical and early clinical development for Zika vaccines is unprecedented," said Barouch, corresponding author and director of the Center for Virology and Vaccine Research at BIDMC. "In less than a year, our group and others have demonstrated that multiple vaccine platforms can provide robust protection against Zika virus challenge in animal models. However, unique challenges will need to be addressed in the clinical development of a Zika vaccine. " The recent outbreak of the Zika virus in the Americas began in Brazil nearly two years ago. By February 2016, the World Health Organization had declared the epidemic a global public health emergency, based largely on the virus' newly-established link to microcephaly and other major birth defects in babies born to infected mothers. The virus has also been associated with the neurologic disorder Guillain-Barré syndrome in adults. In a previously published paper, Barouch and colleagues, including Colonel Nelson L. Michael, MD, PhD, director of the Military HIV Research Program at the Walter Reed Army Institute of Research (WRAIR) and Stephen Thomas, MD, Upstate Medical University, State University of New York, demonstrated that three different vaccine candidates provided robust protection against Zika virus in both mice and rhesus monkeys. Several human clinical trials began last fall at test sites including BIDMC, WRAIR, and National Institute of Allergy and Infectious Diseases affiliated clinical trial sites. "The rapid advancement of Zika vaccine candidates into clinical trials reflects the uniquely focused and effective collaboration among scientists in the field to address this important global problem," said Barouch. Despite the accelerated pace of research, much remains unknown about the virus, raising unique challenges in developing a vaccine. Safety considerations are especially critical, given that the target population for a Zika vaccine would likely include men and women of childbearing age. Zika is a member of the flavivirus family of viruses, which includes West Nile virus, yellow fever virus, and dengue viruses, for which successful vaccines have been developed. Studies suggest that Zika-induced antibody responses may also cross-react with other flaviviruses, particularly dengue virus. Whether or not this antibody cross-reactivity may have clinical consequences is another consideration for Zika vaccines and requires further study. Co-authors include: Stephen J. Thomas, MD, Upstate Medical University, State University of New York, Syracuse; and Colonel Nelson L. Michael, MD, PhD, director, Military HIV Research Program, at Walter Reed Army Institute of Research (WRAIR). The review's authors acknowledge support from the U.S. Military Research and Material Command and the U.S. Military HIV Research Program; the National Institutes of Health (AI095985, AI096040, AI100663, AI124377); and the Ragon Institute of MGH, MIT, and Harvard. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .
News Article | February 17, 2017
BOSTON - A new study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) has found that lower levels of vitamin D in the blood increase the risk of clinical relapse in patients with Ulcerative Colitis (UC), an inflammatory bowel disease that causes long-lasting inflammation and ulcers in the colon. The study was published in the February issue of the journal Clinical Gastroenterology and Hepatology. Lower vitamin D levels have been associated with active disease in patients with UC, but it has been unknown whether they increase disease relapses. "Prior studies in patients with Crohn's disease and Ulcerative Colitis had linked low vitamin D levels to disease flare-ups," said senior author Alan Moss, MD, a gastroenterologist at the Digestive Disease Center at BIDMC and Associate Professor of Medicine at Harvard Medical School. "However, it has been unclear if the flare-up was lowering vitamin D levels, or if low vitamin D levels were causing the flare-up. We thought that if we looked at vitamin D levels when the disease was inactive and then followed patients moving forward, the impact of baseline vitamin D levels on future events may be clearer." Moss and colleagues collected vitamin D serum levels through a physician-blinded prospective study of 70 patients with UC in clinical remission who were followed up after a surveillance colonoscopy at BIDMC. The study measured vitamin D levels in blood samples and levels of inflammation through blood tests and biopsies. The researchers then followed the patients for 12 months and compared the data from participating patients who remained well and the others who experienced relapses. The investigators found the mean baseline vitamin D level to be lower in patients who later relapsed than those who did not. "Patients who had higher vitamin D levels when their disease was in remission were less likely to experience a relapse in the future," said John Gubatan, MD, a physician at BIDMC and first author of the study. "This suggests that higher vitamin D levels may play some role in preventing the UC relapse." The threshold level of blood vitamin D that was protective was greater than 35ng/ml, which is within the range recommended by the National Institutes of Health for a healthy individual. Ongoing work by Gubatan and Moss is now examining the link between vitamin D and a protein called cathelicidin in the cells lining the colon. The link may have beneficial effects on microbial composition, an important component of a healthy colon. Building on this research, investigators are trying to unravel how vitamin D may protect cells in the colon and the microbial composition of the bacteria, fungi, protozoa and viruses that live on and inside the human body, Moss noted. In addition to Moss and Gubatan, the study was performed at BIDMC by authors Shuji Mitsuhashi, Talia Zenlea, MD, Laura Rosenberg, MD, and Simon Robson, MB, ChB, FRCP, PhD. This work was supported by grants from the National Institutes of Health (K23DK084338) and a Rabb Research Award (ACM). Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .
News Article | February 22, 2017
BOSTON - Sleep remains an enduring biological mystery with major clinical relevance, according to a review by clinician-researcher Thomas Scammell, MD, of Beth Israel Deaconess Medical Center (BIDMC) and colleagues. In recent decades, new technologies have allowed neuroscientists to identify multiple brain circuits that govern the sleep/wake cycle, as well as the factors that can influence it, such as caffeine and light. But the brain's complexity is still a stumbling block in understanding this ubiquitous and necessary animal behavior, the researchers wrote. Their review appeared today in the journal Neuron. "In the last ten years, neuroscientists have had access to new tools with which we can test the roles of very specific neurons in the brain," said lead author Scammell, a professor in the department of neurology at BIDMC. "When we know the specific relevant players in the brain, it allows us to develop therapies to help people get to sleep or help sleepy people be more alert during the day." Specifically, two technologies developed since 2000 allow neurologists to switch specific neurons on or off. In a process called chemogenetics, researchers use drugs that have an effect only in a genetically-defined group of cells to determine the neurons' role. Optogenetics uses laser light to turn on or turn off targeted brain cells. These techniques have revealed which neuronal circuits promote wakefulness and sleep throughout the brain, especially in the brain stem and the hypothalamus. "We can now interrogate neurons in a more precise way," said Scammell. "The techniques are very similar, but optogenetics works over a short time scale, on the order of seconds. With chemogenetics, we can watch over several hours what happens when we turn certain neurons on or off." Sleep researchers have also made important discoveries about the fundamental chemistry of sleepiness in recent years. In a major breakthrough in the late 1990s, scientists discovered a previously unknown chemical, a neurotransmitter called orexin, required for maintaining long periods of wakefulness. The loss of orexin production causes the common sleep disorder narcolepsy, which is characterized by chronic sleepiness and irregular REM sleep. Today, pharmaceutical companies make drugs that intentionally block the orexin system to treat insomnia. Researchers are also trying to develop drugs that mimic orexin to wake people up. "A drug that acts like orexin could be as great for patients with narcolepsy as insulin is for people with diabetes," said Scammell. Neuroscience research has also revealed the brain circuity governing circadian rhythms, the biological clock that synchronizes sleepiness and wakefulness with night and day. Located deep in the hypothalamus, the suprachiasmatic nucleus (SCN) regulates circadian rhythms and is capable of maintaining them for some time even in total darkness. However, the SCN is no match for the social norms surrounding people's sleep habits. "People increasingly use their electronic devices in bed, which tricks the brain into thinking it's being exposed to daylight," said Scammell. "The internal clock gets reset, making it much harder to wake up in the morning." Phones and tablets are just one of the reasons about a third of all American adults are sleep deprived, getting much less than the recommended seven to eight hours of sleep per night. That raises more questions about why some people need more or less than that, and why some people can tolerate a sleep deficit so much better than others. The links among lack of sleep or poor sleep and metabolic disease, cancer risk and mood disorders also require further study. With each of the brain's hundreds of thousands of neurons networked to each other, scientists will need a deeper knowledge of the brain's inner workings to understand how the circuits that regulate sleep interact. "There's tremendous dialog back and forth among these circuits," said Scammell, who notes today's technology allows scientists to monitor dozens of neurons at a time within one region of the brain. "Our ability to record activity in just a handful of neurons simultaneously is still not anything close to understanding the whole brain, but at least it's a step in the right direction." Study co-authors include: Elda Arrigoni, PhD, of BIDMC and Jonathan O. Lipton, MD, PhD, of Boston Children's Hospital. The work was supported by the National Institutes of Health (HL095491, DE022912, NS091126, and HD071026. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .
News Article | December 26, 2016
BOSTON - Scientific research over the past decade has concentrated almost exclusively on the 2 percent of the genome's protein coding regions, virtually ignoring the other 98 percent, a vast universe of non-coding genetic material previously dismissed as nothing more than 'junk.' Now, a team led by investigators at Beth Israel Deaconess Medical Center (BIDMC) reveals that one type -- called long non-coding RNA (lncRNA) -- may be critically important for controlling cellular components in a tissue-specific manner. Published online today in the journal Nature, the new research points to an lncRNA's key role in helping control processes related to muscle regeneration and cancer. Long non-coding RNAs appear to be transcribed from our DNA in a similar manner to coding messenger RNAs but are not translated into proteins. While lncRNA molecules do not produce correspondingly lengthy proteins, researchers have wondered whether some of these molecules may contain segments of sequences that can code for very short proteins, or polypeptides. "Whether such small, hidden polypeptides are actually functional, or represent 'translational noise' within the cell is still relatively unclear," said senior author Pier Paolo Pandolfi, MD, PhD, Director of the Cancer Center and Cancer Research Institute at BIDMC. "Our team set about trying to understand to what extent lncRNA molecules might actually encode functional polypeptides, and how important such peptides might be." The investigators used computational analyses to predict potential polypeptides that could be encoded by known lncRNA molecules, and then they used mass spectrometry to determine if these putative polypeptides were actually expressed. "With this approach we actually identified many expressed hidden polypeptides and went on to characterize one in particular," Pandolfi explained. This specific lncRNA molecule is termed LINC00961 and encodes a 90 amino acid polypeptide. A variety of molecular and biochemical experiments revealed that the LINC00961 encoded polypeptide played an important role in modulating the activity of the mTORC1 protein complex, which is a critical sensor of nutrient availability within cells. The complex also regulates a variety of cellular processes including translation, metabolism, cell growth, and proliferation, and alterations in its function can lead to diseases such as cancer. Because the LINC00961 polypeptide appeared to specifically block mTORC1's ability to sense stimulation with amino acids, the investigators named the peptide encoded by the lncRNA SPAR (Small regulatory Polypeptide of Amino acid Response). Pandolfi and his team found that the SPAR encoding lncRNA is highly expressed in a number of tissue types, including muscle. Experiments conducted in mice demonstrated that through its effects on mTORC1, the SPAR polypeptide helps regulate the muscle's ability to regenerate and repair after injury. Specifically, expression of LINC00961 is blocked following muscle injury in mice, leading to reduced levels of SPAR and maximal mTORC1 activity to promote tissue regeneration. "The experimental approach we used allowed us to eliminate expression of the SPAR polypeptide, while maintaining expression of the host lncRNA," said lead author Akinobu Matsumoto, PhD, research fellow at the Cancer Center at BIDMC and lead author of the study. "We are able to ascribe this function to the coding function of the lncRNA rather than any non-coding function it may also have." The findings suggest that therapeutic strategies that restrict expression of SPAR in injured muscle may promote a more rapid regeneration of tissue. The results suggest that lncRNAs may have diverse roles and functions. Although they may not code for large proteins, lncRNAs may produce small polypeptides that can fine tune the activity of critical cellular components. The findings also expand the repertoire of peptide-coding genes in the human genome that should be studied and annotated. The study also provides insights on how mTORC1 activity may be attuned to meet the distinct needs of a specific tissue. "An ability to target such modulators could be of great advantage from a therapeutic perspective, allowing for control of mTORC1 activity in cells or tissues that express such modulators while not affecting its activity and function in other tissue and cell types," explained co-author John Clohessy, PhD, Instructor in Medicine at BIDMC and a senior member of Pandolfi's research team. Indeed, a key feature of many lncRNAs is that their expression is often highly tissue-specific. Thus, targeting small polypeptides encoded by lncRNA molecules may provide the key to regulating common cellular components in a tissue-specific manner. Because the mTORC1 complex is frequently deregulated in conditions such as cancer, the research team is now seeking to determine if SPAR can influence additional cellular functions of mTORC1 that might be involved in different diseases. "We are very excited about this discovery," said Pandolfi. "It represents a new and startling mechanism by which important sensory pathways can be regulated within cells, and we believe it will have important implications for how we approach the design of therapies and treatments in the future." Study coauthors include BIDMC investigators Akinobu Matsumoto, Alessandra Pasut, Jacqueline Fung, Emanuele Monteleone, and John G. Clohessy. Other co-investigators include Masaki Matsumoto and Keiichi I. Nakayama of Kyushu University, Riu Yamashita of Tohoku University, and Alan Saghatelian of the Salk Institute for Biological Studies. This work was supported in part by the National Institutes of Health grants R01 CA082328 and R35 CA197529. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .
News Article | December 19, 2016
BOSTON - Neuroscientists at Beth Israel Deaconess Medical Center (BIDMC) have mapped the brain injuries - or lesions - that result in delusional misidentification syndromes (DMS), a group of rare disorders that leaves patients convinced people and places aren't really as they seem. In a study published in the journal Brain, Michael D. Fox, MD, PhD, Director of the Laboratory for Brain Network Imaging and Modulation and the Associate Director of the Berenson-Allen Center for Noninvasive Brain Stimulation at BIDMC and colleagues reveal the neuro-anatomy underlying these syndromes for the first time. "How the brain generates complex symptoms like this has long been a mystery," said Fox. "We showed how complex symptoms can emerge based on brain connectivity. With a lesion in exactly the right place, you can disrupt the brain's familiarity detector and reality monitor simultaneously, resulting in bizarre delusions. Understanding where these symptoms come from is an important step toward treating them." Delusional misidentification syndromes are among the most striking and least understood disorders encountered in neurology and psychiatry. First documented nearly a century ago, Capgras syndrome is a rare disorder in which patients recognize a family member while simultaneously experiencing that person as unfamiliar, leading to the conclusion that an imposter is impersonating their loved one. Conversely, the Fregoli delusion is the belief that strangers are actually loved ones in disguise. Misidentification delusions can also apply to pets and places. Fox and colleagues, including lead author R. Ryan Darby, MD, the Sidney R. Baer, Jr. Foundational Fellow in the Clinical Neurosciences at the Berenson-Allen Center at BIDMC, identified 17 patients with delusional misidentification syndromes and mapped them onto a standardized brain atlas. Then, using the lesion network mapping technique they recently developed, Darby and colleagues determined that all 17 lesions were functionally connected to an area of the brain called the retrosplenial cortex - thought to be involved in perceiving familiarity. Sixteen of the 17 lesions were also connected to a region in the right ventral frontal cortex, associated with belief evaluation. The scientists compared the data to 15 control brain injuries that led to delusions other than misidentification delusions. "Lesions causing all types of delusions were connected to belief violation regions, suggesting that these regions are involved in monitoring for delusional beliefs in general," Darby said. "However, only lesions causing delusional misidentifications were connected to familiarity regions, explaining the specific bizarre content - abnormal feelings of familiarity - in these delusions. In other words, lesions had to be connected to both regions to develop delusions like Capgras." The scientists note that their network mapping technique does not involve obtaining functional neuroimaging (fMRI) from the patients studied. Rather, data from normal patients determines which regions of the brain are normally connected to the mapped lesion locations. While this methodology carries several advantages, it does not prove these two regions are dysfunctional in delusional patients following the lesion. Doing so would require recruiting a large number of patients with the rare disorder to a follow up study, noted Darby. However, the new information gleaned from their study may help patients' families cope with a loved one's misidentification delusions -- which sometimes disappear as mysteriously as they come on. "The impact on the patient's family can be heart-breaking," said Darby. "I've seen patients who, thinking their homes were replicas, would pack their bags every night, hoping to return to their 'real' home. Patients who believe a spouse is an imposter often lose intimacy. In these cases, even just knowing that the delusion has a name and is part of a neurological disorder can be helpful for family members." Study coauthors include Simon Laganiere, MD, and Alvaro Pascual-Leone, MD, PhD, of the Berenson-Allen Center for Noninvasive Brain Stimulation at BIDMC; and Sashank Prasad, MD, of the Department of Neurology at Brigham and Women's Hospital. This work was supported by funding from the Sidney R. Baer, Jr. Foundation; grants from the National Institutes of Health (R01HD069776, R01NS073601, R21 NS082870, R21 MH099196, R21 NS085491, R21 HD07616, R25NS065743, K23NS083741); the Football Players Health Study at Harvard University; Harvard Catalyst | The Harvard Clinical and Translational Science Center (NCRR and the NCATS NIH, UL1 RR025758), and the American Brain Foundation. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .
News Article | November 10, 2016
BOSTON - A study led by researchers at Beth Israel Deaconess Medical Center (BIDMC), in collaboration with scientists at Walter Reed Army Institute of Research (WRAIR), Janssen Vaccines & Prevention B.V., one of the Janssen Pharmaceutical Companies of Johnson & Johnson and Gilead Sciences, Inc., has demonstrated that combining an experimental vaccine with an innate immune stimulant may help lead to viral remission in people living with HIV. In animal trials, the combination decreased levels of viral DNA in peripheral blood and lymph nodes, and improved viral suppression and delayed viral rebound following discontinuation of anti-retroviral therapy (ART). The research team's findings appeared online today in the journal Nature. "The objective of our study was to identify a functional cure for HIV - not to eradicate the virus, but to control it without the need for ART," said lead author Dan Barouch, MD, PhD, Director of the Center for Virology and Vaccine Research at BIDMC. "Current antiretroviral drugs, although they're lifesaving, do not cure HIV. They merely hold it in check. We are trying to develop strategies to achieve ART-free, long-term viral suppression." Typically, vaccines "teach" the body to rid itself of viral invaders by provoking an immune response. However, HIV attacks cells of the immune system. The virus kills the majority of infected immune cells but goes dormant in others. This reservoir of dormant, infected cells, where researchers believe HIV remains hidden during antiretroviral therapy, is the primary reason HIV cannot currently be cured. Barouch and colleagues are working on strategies to draw the virus out of hiding with the goal of eradicating it from the body. "We reasoned that if we can activate the immune cells that might harbor the virus, then the vaccine-induced immune responses might perform better seeking them out and destroying them," said Barouch, who is also a Professor of Medicine at Harvard Medical School. "Indeed, we saw the best results when we combined the vaccine together with the innate immune stimulant." In the two-year long study, researchers monitored the viral loads of 36 rhesus monkeys infected with simian immunodeficiency virus (SIV), a virus similar to HIV that infects non-human primates. After taking suppressive ART drugs for six months, the monkeys were given either the experimental vaccines - an adenovirus serotype 26 vector vaccine and an MVA vector vaccine (Ad26/MVA) - alone, the immune stimulant (an experimental drug that works on a protein of the immune system called TLR-7) alone, or the Ad26/MVA and stimulant combination. A control group received no active treatment. "We found the combination of Ad26/MVA vaccination and TLR7 stimulation proved more effective than either component alone," said Col. Nelson Michael, director of MHRP, who helped design the preclinical study. "This was especially striking in viral load set-point, which impacts the future course of the disease." The experimental vaccine induced a robust immune response, both in magnitude (the number of immune cells generated) and breadth (the number of places on the virus the vaccine can targets). To evaluate the efficacy of the vaccine and the immune stimulant, the researchers discontinued ART in all animals and continued to monitor their viral loads. Animals that received only the vaccine demonstrated some reduction of viral load, but the animals that were given the vaccine/immune stimulant combination showed a reduction in plasma viral RNA levels as well as a 2.5-fold delay of viral rebound compared to controls. All nine animals showed decreased viral loads, and the virus was undetectable in a third of the animals. "If all the animals' viral loads had been undetectable, that would have been a home run," said Barouch. "But the fact that all animals showed a reduction in viral load and three out of nine were undetectable, that's a solid base hit. It's definitely something that we can work from." Study coauthors include Erica Borducchi, Crystal Cabral, Kathryn E. Stephenson, Jinyan Liu, Peter Abbink, David Ng'ang'a, Joseph P. Nkolola, Amanda L. Brinkman, Lauren Peter, Benjamin C. Lee, Jessica Jimenez, David Jetton, Jade Modesir, Shanell Mojta, Abishek Chandrashekar and Katherine Molloy all of BIDMC; Galit Alter of the Ragon Institute of MGH, MIT, and Harvard; Jeff M. Gerold and Alison L. Hill of the Program for Evolutionary Dynamics at Harvard University; Mark G. Lewis, of Bioqual; Maria G. Pau, Hanneke Schuitemaker of Janssen Infectious Diseases and Vaccines; Joseph Hesselgesser and Romas Geleziunas of Gilead Sciences; Jerome H. Kim, Merlin L. Robb and Nelson L. Michael of the U.S. Military HIV Reseach Program, Walter Reed Army Institute of Research. This work was supported by the U.S. Army Medical Research and Material Command and the Military HIV Research Program, Walter Reed Army Institute of Research through its cooperative agreement with the Henry M. Jackson Foundation (W81XWH-11-2-0174). Funding was also provided by the National Institutes of Health (AI096040, AI124377, AI1266030) and the Ragon Institute of MGH, MIT, and Harvard. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .
News Article | December 22, 2016
The federal government has cut payments to 769 hospitals with high rates of patient injuries, for the first time counting the spread of antibiotic-resistant germs in assessing penalties. The punishments come in the third year of Medicare penalties for hospitals with patients most frequently suffering from potentially avoidable complications, including various types of infections, blood clots, bed sores and falls. This year the government also examined the prevalence of two types of bacteria resistant to drugs. Based on rates of all these complications, the hospitals identified by federal officials this week will lose 1 percent of all Medicare payments for a year — with that time frame beginning this past October. While the government did not release the dollar amount of the penalties, it will exceed a million dollars for many larger hospitals. In total, hospitals will lose about $430 million, 18 percent more than they lost last year, according to an estimate from the Association of American Medical Colleges. The reductions apply not only to patient stays but also will reduce the amount of money hospitals get to teach medical residents and care for low-income people. Forty percent of the hospitals penalized this year escaped punishment in the first two years of the program, a Kaiser Health News analysis shows. Those 306 hospitals include the University of Miami Hospital in Florida, Cambridge Health Alliance in Massachusetts, the University of Michigan Health System in Ann Arbor and Mount Sinai Hospital in New York City. Nationally, hospital-acquired conditions declined by 21 percent between 2010 and 2015, according to the federal Agency for Healthcare Research and Quality, or AHRQ. The biggest reductions were for bad reactions to medicines, catheter infections and post-surgical blood clots. Still, hospital harm remains a threat. AHRQ estimates there were 3.8 million hospital injuries last year, which translates to 115 injuries during every 1,000 patient hospital stays during that period. Each year, at least 2 million people become infected with bacteria that are resistant to antibiotics, including nearly a quarter-million cases in hospitals. The Centers for Disease Control and Prevention estimates 23,000 people die from them. Between 20 and 50 percent of all antibiotics prescribed in hospitals are either not needed or inappropriate, studies have found. The proliferation of antibiotic use — inside hospitals, among outpatients and in farm animals sold for food — has hastened the spread of stubborn bacterial strains that can be risky for patients. One resistant bacterium that Medicare included into its formula for determining financial penalties for hospitals is methicillin-resistant Staphylococcus aureus, or MRSA, which can cause pneumonia and bloodstream and skin infections. MRSA is prevalent outside of hospitals and sometimes people with it show no signs of disease. But these people can bring the germ into a hospital, where it can be spread by health care providers and be especially dangerous for older or sick patients whose immune system cannot fight the infection. Hospitals have had some success in reducing MRSA infections, which dropped by 13 percent between 2011 and 2014, according to the CDC. AHRQ estimates there were 6,300 cases in hospitals last year. The second bacterium measured for the penalties is Clostridium difficile, known as C. diff, a germ that can multiply in the gut and colon when patients take some antibiotics to kill off other germs. It can also spread through contaminated surfaces or hands. While it can be treated by antibiotics, C. diff can also become so serious that some patients need to have part of their intestines surgically removed. C. diff can cause diarrhea and can be deadly for the elderly and other vulnerable patients. C. diff has challenged infection control efforts. While hospital infections dropped 8 percent from 2008 to 2014, there was a "significant increase" in C. diff that final year, the CDC says. AHRQ estimated there were 100,000 hospital cases last year. "The reality is we don't know how to prevent all these infections," said Dr. Louise Dembry, a professor at the Yale School of Medicine and president of the Society for Healthcare Epidemiology of America. The Hospital-Acquired Condition Reduction Program also factors in rates of infections from hysterectomies, colon surgeries, urinary tract catheters and central line tubes. Those infections carry the most weight in determining penalties, but the formula also takes into account the frequency of bed sores, hip fractures, blood clots and four other complications. Specialized hospitals, such as those that treat psychiatric patients, veterans and children, are exempted from the penalties, as are hospitals with the "critical access" designation for being the only provider in an area. Of the remaining hospitals, the Affordable Care Act requires that Medicare penalize the 25 percent that perform the worst on these measures, even if they have reduced infection rates from previous years. That inflexible quota is one objection the hospital industry has with the penalties. In addition, many hospitals complain that they are penalized because of their vigilance in detecting infections, even ones that do not cause any symptoms in patients. Academic medical centers in particular have been frequently punished. "The HAC penalty payment program is regarded as rather arbitrary, so other than people getting upset when they incur a penalty, it is not in and of itself changing behavior," said Nancy Foster, vice president for quality and patient safety at the American Hospital Association. Federal records show that 347 hospitals penalized last year will not have payments reduced because their performance was better than others. Those include Harbor-UCLA Medical Center in Los Angeles, the Johns Hopkins Hospital in Baltimore and the University of Tennessee Medical Center in Knoxville. Over the lifetime of the penalty program, 241 hospitals have been punished in all three years, including the Cleveland Clinic; Intermountain Medical Center in Murray, Utah; Ronald Reagan UCLA Medical Center in Los Angeles; Grady Memorial Hospital in Atlanta; Northwestern Memorial Hospital in Chicago; and Brigham & Women's Hospital in Boston. The penalties come as the Centers for Medicare & Medicaid Services also launches new requirements for hospitals to ensure that the use of antibiotics is limited to cases where they are necessary and be circumspect in determining which of the drugs are most likely to work for a given infection. Hospitals will have to establish these antibiotic stewardship programs as a condition of receiving Medicare funding under a regulation the government drafted last summer. Lisa McGiffert, who directs Consumers Union's Safe Patient Project, said that as a result of Medicare's penalties and other efforts, "more hospitals are thinking more about appropriate use of antibiotics." However, she said, "I think most hospitals do not have effective antibiotic stewardship programs yet." Kaiser Health News is an editorially independent news service supported by the nonpartisan Kaiser Family Foundation. You can follow Jordan Rau on Twitter: @jordanrau.
News Article | February 15, 2017
Clinical decision-making is a complex process, driven by multiple factors, including social and psychological dynamics, peer pressure and even exposure to drug advertising. Now research from Harvard Medical School shows that when it comes to a physician's choice of insomnia medication, habit may trump all else. The results suggest that many clinicians choose insomnia drugs somewhat reflexively, based on routine, rather than by taking into account a patient's symptoms and medical history. Indeed, the analysis showed that a physician's past prescribing pattern, rather than patient characteristics, was the more potent predictor of what insomnia medication a patient might get. Findings of the research, based on analysis of 1,105 patients' medical records and the accompanying clinical notes, appear Feb. 9 in Scientific Reports. "Our results illuminate the notion that just as everyone else, many physicians are creatures of habit who tend to rely on cognitive shortcuts in their decision-making," said study first author Andrew Beam, a postdoctoral research fellow in the Department of Biomedical Informatics at HMS. "Doctors are not always as rational as we'd like to believe." Insomnia's economic burden is estimated to top $60 billion a year, a number that doesn't account for the physical toll of a condition believed to affect as many as 40 percent of Americans. Yet insomnia remains underdiagnosed and poorly treated. As with any other condition, choosing the optimal medication based on individual patient characteristics is critical to successfully resolving symptoms and to averting the many physiologic, psychological and social consequences of insomnia, Beam added. In their analysis, the researchers focused on the two most commonly prescribed drugs: zolpidem, a newer medication with a great efficacy record but associated with side effects such as next-day drowsiness and dizziness, and trazodone, an older drug typically used for depression that is less effective for insomnia but has a well-established safety profile. How and why physicians choose one drug over another remains unclear so the HMS team set out to untangle the factors that drive clinical choice. Analyzing thousands of patient records and narrative clinical notes and comparing them against each physicians' prescribing records, the researchers found that a doctor who prescribed one medication in the past was three times as likely to continue prescribing the same drug subsequently. Patients who had symptoms of depression in addition to their insomnia were somewhat more likely than those without depression to receive a prescription for trazodone, the analysis showed. The finding, researchers said, suggests that certain patient characteristics do play some, albeit smaller, role in clinical decision-making. In addition to the specific findings of the research, the study underscores how electronic medical records--and the wealth of data they contain--can yield intriguing insights into the interplay between physician decision-making and patient characteristics in treatment choices. "Electronic medical records provide an astounding richness of information at our fingertips that allows us to deconstruct clinical behavior and clinical decision-making in the context of the patient-physician encounter, rather than in isolation," said study senior author Zak Kohane, chair of the department of biomedical informatics at HMS. "This approach can be used in analyzing treatment decisions for other, more complex conditions." The work was supported by the National Institutes of Health Common Fund's BD2K Center for Excellence grant U54 HG007963 with additional funding by Merck. Harvard Medical School has more than 11,000 faculty working in 10 academic departments located at the School's Boston campus or in hospital-based clinical departments at 15 Harvard-affiliated teaching hospitals and research institutes: Beth Israel Deaconess Medical Center, Boston Children's Hospital, Brigham and Women's Hospital, Cambridge Health Alliance, Dana-Farber Cancer Institute, Harvard Pilgrim Health Care Institute, Hebrew SeniorLife, Joslin Diabetes Center, Judge Baker Children's Center, Massachusetts Eye and Ear/Schepens Eye Research Institute, Massachusetts General Hospital, McLean Hospital, Mount Auburn Hospital, Spaulding Rehabilitation Network and VA Boston Healthcare System.
News Article | February 28, 2017
Provides Physical Medicine Rehabilitation Services to Patients in the South Cobb Area including Non-surgical Spine and Functional Medicine OrthoAtlanta is pleased to welcome board-certified physiatrist, Deitrick L. Cox, M.D., to its orthopedic and sports medicine practice in Austell, bringing expertise in physical medicine and rehabilitation (PM&R) to patients in the greater South Cobb area including Austell, Lithia Springs, Mableton, and Smyrna. Dr. Cox provides non-surgical orthopedic care, including non-surgical spine, musculoskeletal medicine and functional medicine to patients suffering muscular, nerve, joint, and tendon injuries. Dr. Cox’s specialty areas of interest include precision-based treatments such as fluoroscopic-guided interventional spinal injections, including, but not limited to, epidural and facet injections, radiofrequency neurotomy, spiral neuromodulation, sacroiliac joint injections, and hip injections. Dr. Cox is also skilled at ultrasound-guided peripheral joint injections, regenerative medicine, electrodiagnostic medicine / electromyography (EMG), and myofascial trigger point injections. Dr. Cox believes in partnering with his patients to develop treatment plans to significantly reduce, if not eliminate, pain and optimize physical function. As expressed by Dr. Cox, “I seek to maintain the perfect balance between teaching and treating when serving patients. My philosophy of care includes listening to the patient, educating the patient, and collaborating with the patient to develop the best treatment plan for them.” Prior to joining OrthoAtlanta, Dr. Cox had his own company providing procedure-based physiatric and pain management procedures and services to orthopedic, physical medicine and pain management practices within the greater Atlanta area. “We are excited to welcome Dr. Deitrick Cox to OrthoAtlanta Austell to provide non-surgical patient care,” stated OrthoAtlanta Medical Director, Dr. Michael Behr. “Dr. Cox combines a passion for orthopedics, physics, and procedure-based treatment plans that help restore patient functionality to return them to the things they love doing.” Dr. Deitrick Cox graduated from Amherst College, Amherst, MA, completing both a Bachelor of Science degree in Religion and pre-medical studies. Awarded a merit-based medical scholarship, Dr. Cox received his Doctor of Medicine degree at Morehouse School of Medicine in Atlanta, GA. He completed his Internship at Harvard Medical School, Cambridge Health Alliance, in Cambridge, MA and medical residency in Physical Medicine and Rehabilitation at Emory University in Atlanta, GA. Medical professionals influencing Dr. Cox’s decision to pursue a medical career and specialty in physiatry include orthopedic surgeon, J. Mandume Kerina of Leesburg, Florida, and PM&R physicians, Dr. Rosalind Bass and Dr. Lisa Merritt. Dr. Cox is a member of the American Academy of Physical Medicine and Rehabilitation, the National Medical Association and the North American Spine Society (NASS). Dr. Cox is a certified provider with the United States Department of Labor (DOL), Office of Federal Workers’ Compensation, and can accept both Federal and non-government occupational and work-related injury cases as well as personal injury cases. Dr. Cox and his wife have a three-year old son and another child on the way. He enjoys travel and sports including football, basketball and track & field. Appointments with Dr. Deitrick Cox may be requested at OrthoAtlanta Austell, 770-944-3303. About OrthoAtlanta OrthoAtlanta is one of the largest orthopaedic and sports medicine practices in the greater Atlanta, Georgia area. With 39 physicians serving in 12 offices, the physician-owned practice is dedicated to providing the highest level of patient care for injury or deformity of muscles, joints, bones and spine. OrthoAtlanta offers convenient accessibility to a full range of musculoskeletal surgeons, specialists and patient services including on-site physical therapy, pain management care, six MRI imaging centers and workers’ compensation coordination. OrthoAtlanta Surgery Centers in Austell and Fayetteville provide cost-effective, same-day surgical procedures in an accredited outpatient center. Comprehensive operative and non-operative musculoskeletal care and expertise includes sports medicine, arthroscopic surgery, hip replacement, knee replacement, neck and spine surgery, elbow and shoulder surgery, foot and ankle surgery, pain management, arthritis treatment, general orthopedics, work related injuries and acute orthopaedic urgent care. Learn more at www.OrthoAtlanta.com. For additional information, please contact Pat Prosser, Public Relations Manager, at OrthoAtlanta, 678-996-7254, or via email pprosser@OrthoAtlanta.com.
News Article | December 13, 2016
StayWell announced today that it will host a webinar for health care providers and health systems administrators on the topic of enhancing patient-physician interactions and optimizing reimbursements under MACRA. Ayesha Khalid, MD, and Jodi Grossfeld, MD, will share insights, patient case examples and participate in a panel discussion during a free webinar on December 19, from 1:00 to 2:00 p.m. EST. The webinar comes on the heels of StayWell’s introduction of the Krames Health Engagement Platform powered by Doctella in November. The platform aims to create patient-provider interactivity at all points throughout the patient’s health care journey and across the continuum of care, to optimize outcomes and improve quality and patient safety. Dr. Khalid is an ENT-otolaryngologist at Cambridge Health Alliance and Massachusetts Eye and Ear Infirmary. Dr. Grossfeld practices medical dermatology and cosmetic procedures at Bruder Medical Group in New York. During this webinar, they will discuss: Space for this webinar is limited. Register today at http://staywell.com/doctella-webinar-registration/ and take advantage of this opportunity to demo this new technology. About StayWell StayWell, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (“Merck”), is a health engagement company that helps its clients engage and educate people to improve health and business results. StayWell brings decades of experience working across the health care industry to design solutions that address its clients’ evolving needs. StayWell fuses expertise in health engagement and the science of behavior change with an integrated portfolio of solutions and robust content assets to effectively engage people to make positive health care decisions. StayWell programs have received numerous top industry honors, including the C. Everett Koop National Health Award and the Web Health Award for health engagement programs. StayWell also has received URAC and NCQA accreditation for several of its programs. StayWell is headquartered in Yardley, Pennsylvania, and also has major locations in Salt Lake City, Utah, and St. Paul, Minn. To learn more, visit http://www.staywell.com.