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Global Health, Infectious Disease, Stanford News

Stanford physician shares his story of treating Ebola patients in Liberia

Stanford physician shares his story of treating Ebola patients in Liberia

P1030655For a month, emergency physician Colin Bucks, MD, found himself in the remote, dense jungle of northeast Liberia in the heat of the battle against Ebola. A clinical assistant professor of surgery at Stanford, Bucks was a volunteer with the International Medical Corps at a new tent-like unit hastily built to accept the continuing stream of Ebola patients in the hard-hit West African country.

The facility, a series of low, tin-roofed, concrete buildings, were primitive in design but had very effective methods for controlling infection, including spigots everywhere that dispensed virus-killing doses of chlorine and protective gear for covering the body head to toe. Aside from providing basic care, such as fluid and electrolyte replacement, Bucks said much of his time was spent comforting patients, who were physically isolated from family members because of the threat of infection.

P1030673“In this setting (in West Africa), there is an additional barrier because you have one physical degree of separation, as your head, your hands, your face are completely covered. But that doesn’t preclude the same level of connection to the patient and the same sense of responsibility and care,” said Bucks, who left Liberia Oct. 22 and is now isolated at his home in Redwood City, Calif. “There is maybe a higher percentage of sad cases because Ebola has a high-case fatality rate, so there is an added burden there. But there is a similarity to working a tough case in rural Liberia to working a tough case in a U.S. critical care unit.”

He said the unit received patients from a nearby hospital, as well as those brought in by makeshift ambulances that might travel as much as eight hours to retrieve ailing victims. “We would get these reports everyday from the ambulance – we have four cases and three flat tires. The roads would be blocked with trees. They would have to drive through dense jungles. The ambulance stories were by far the most riveting.”

Colin Trish PPEBucks said the caregivers at the unit, which included 125 Liberians, were able to save just under half the patients who came in, with each survivor serving as an important ambassador to the community.

“The public health message was blanketing the country, but there was still a lot of fear and misunderstanding,” he said. “People are scared to come to the hospital. People are scared to undergo treatment. It helped every time we had patients discharged as cured.”

Bucks, who is now following recommendations and Stanford requirements to remain in isolation for 21 days, says there is a desperate need for other U.S. volunteers like himself to help contain the spread of the virus. “There needs to be a rational policy that facilitates health-care workers going to and from the U.S. Policy should help this – not impede this. But you need an organized response on West Africa. Otherwise we will be fighting a much bigger battle in the U.S. and around the globe.”

Previously: How to keep safe while operating on Ebola patients, Experience from the trenches in the first Ebola outbreak, Ebola: A look at what happened and what can be done and Dr. Paul Farmer: We should be saving Ebola patients
Photos courtesy of Colin Bucks

Cancer, In the News, Nutrition, Patient Care, Surgery

“Prehab” routines before cancer surgery help patients bounce back faster

Surgery_flickr_thinkpanamaIf you’ve ever had surgery, especially an orthopedic one, you’ve probably had rehabilitation therapy. In recent years, orthopedic surgery plans have begun to include a period of “prehabilitation” exercise to help prepare patients for their procedure. Now, researchers have demonstrated that a pre-surgery work-out routine combined with some dietary changes may be able to help cancer patients regain their baseline strength levels sooner. A story on NPR’s Shots blog described the recent study:

Researchers from McGill University in Montreal studied 77 patients scheduled for colorectal cancer surgery. A kinesiologist gave the patients aerobic exercises and strength training to do at home. A registered dietitian gave them nutritional counseling and prescribed a whey supplement to make up any protein deficits, and a psychologist provided anxiety-reducing relaxation exercises.

Half of the patients were told to start the program before surgery – an average of about 25 days before – and to continue afterward for eight weeks. The other group was told to start right after surgery.

Not surprisingly, the group assigned to prehabilitation did better on a presurgery test that measured how far they could walk in 6 minutes. And it paid off.

Two months after surgery, the prehabilitation group walked an average of 23.7 meters farther than when they started the study. Rehab-only patients walked an average of 21.8 meters less than when they started. (A change of 20 meters is considered clinically significant.) And a greater proportion of the prehabilitation group was back to baseline exercise capacity by then.

Because of the methology the researchers used, it’s not clear how the diet or the exercise prescribed in the pre-surgery regimen affected the outcome. Previous studies that looked at exercise-only regimens did not show post-surgery improvements. A larger study with a more varied pool of patients is likely needed for definitive answers.

Previously: Wellness after cancer: Stanford opens clinic to address survivors’ needs and A call for rehab services for cancer survivors
Photo by thinkpanama

Genetics, Pediatrics, Research, Science, Stanford News

Move over CRISPR, there’s a new editor in town: Stanford-devised approach cures hemphilia in mice

Move over CRISPR, there's a new editor in town: Stanford-devised approach cures hemphilia in mice

A lot of attention has been paid lately to the idea of genome editing. This technique allows researchers to precisely modify an animal’s DNA to replace one version of a gene with another, or to add a working copy for a mutated gene. An approach called CRISPR/Cas9 in particular has garnered interest with its ease of use, ability to modify multiple genes, and relatively quick turnaround time when making specific strains of laboratory animals like mice for study.

Now pediatrician and geneticist Mark Kay, MD, PhD, has published  in Nature a new way to conduct genome editing that could give CRISPR a run for its money because it could be both safer and longer-lasting than other methods. As described in our press release:

The approach differs from that of other hailed techniques because it doesn’t require the co-delivery of an enzyme called an endonuclease to clip the recipient’s DNA at specific locations. It also doesn’t rely on the co-insertion of genetic “on” switches called promoters to activate the new gene’s expression.

Inclusion of endonucleases and promoters run the risk of a gamut of adverse effects in the recipient, from cancers if the promoter turns on the wrong gene in the genome to an unwanted immune response geared toward the foreign proteins. The researchers in Kay’s lab, including postdoctoral scholar and study lead author Adi Barzel, PhD, found a way around their use, and showed that it worked to enable mice with hemophilia to produce a missing blood clotting factor:

The technique devised by the researchers uses neither nucleases to cut the DNA nor a promoter to drive expression of the clotting factor gene. Instead, the researchers hitch the expression of the new gene to that of a highly expressed gene in the liver called albumin. The albumin gene makes the albumin protein, which is the most abundant protein in blood. It helps to regulate blood volume and to allow molecules that don’t easily dissolve in water to be transported in the blood.

The researchers used a modified version of a virus commonly used in gene therapy called adeno-associated virus, or AAV. In the modified version, called a viral vector, all viral genes are removed and only the therapeutic genes remain. They also relied on a biological phenomenon known as homologous recombination to insert the clotting factor gene near the albumin gene. By using a special DNA linker between the genes, the researchers were able to ensure that the clotting factor protein was made hand-in-hand with the highly expressed albumin protein.

As Kay, who is also a member of the Stanford Cancer Institute, the Stanford Child Health Research Institute and Stanford Bio X, explained, the integration of the clotting factor gene is key to the successful treatment (other clinical trials involving gene therapy for hemophilia rely on the expression of a free floating, unintegrated gene in the nucleus):

The real issue with AAV is that it’s unclear how long gene expression will last when the gene is not integrated into the genome. Infants and children, who would benefit most from treatment, are still growing, and an unintegrated gene could lose its effectiveness because it’s not copied from cell to cell. Furthermore, it’s not possible to re-administer the treatment because patients develop an immune response to AAV. But with integration we could get lifelong expression without fear of cancers or other DNA damage.

Previously: Gene “editing” could correct a host of genetic disorders, Policing the editor: Stanford scientists devise way to monitor CRISPR effectiveness and Both a doctor and a patient: Stanford physician talks about his hemophilia

Ask Stanford Med, Neuroscience, Surgery

A Stanford neurosurgeon discusses advances in treating brain tumors

A Stanford neurosurgeon discusses advances in treating brain tumors

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Last year, an estimated 70,000 people were diagnosed with a primary brain tumor, which originates and remains in the brain, and far more will develop metastatic brain tumors, those that begin as cancer elsewhere in the body and spread to the brain. Although physicians face a number of challenges in treating these tumors, the encouraging news is that advances in technology and new therapies are improving patient outcomes.

During a Stanford Health Library event on Thursday, Steven Chang, MD, director of the Stanford Neurogenetics Program and the Stanford Neuromolecular Innovation Program, will deliver an update on the latest in surgical and non-surgical treatments of brain tumors. (The lecture will also be webcasted for those unable to attend.) In anticipation of the talk, Chang answered some questions related to the topics he’ll be addressing.

Why has a greater understanding of genetics and the biology of tumors improved physicians’ understanding of how patients will respond to certain therapies?

Having a greater understanding of the genetics and biology of brain tumors helps neurosurgeons to tailor treatments for each patient. In essence, we are able to deliver personalized medicine if we understand which subsets of brain tumors respond to specific treatments. For example, we now understand that gliomas with certain genetic makers are more likely to respond to chemotherapy treatments. The presence or absence of these genetic markers will also help guide patients in determining which clinical trials it may be most appropriate for them to enroll in.

How have advances in brain-mapping technologies made a difference in treating low-grade gliomas, which are slow growing and often affect younger patients?

Low-grade gliomas don’t typically contrast enhance on brain MRI scans. Furthermore, low-grade gliomas are more likely than higher-grade gliomas to have appearances similar to normal brain tissue, with no obvious color or consistency distinction between tumor and normal brain. These factors make resection of low-grade gliomas potentially more complex than high-grade gliomas, which often have distinct appearances from normal brain tissue. Advances in brain-mapping technologies include both image guided navigation and electrophysiologic mapping. Image-guided navigation consists of the use of MR imaging to provide real-time guidance during tumor resections. High-speed computer workstations provide images that show neurosurgeons exactly where they are with respect to brain anatomy during tumor resections. Electrophysiologic mapping is the use of specific electrical simulations of the brain tissue to identify eloquent brain cortex. By mapping out these critical brain regions, the neurosurgeon can safely avoid them when performing tumor resection.

In what ways have improvements in imaging technology over the last decade changed the treatment approach for both surgical and non-surgical treatment of brain tumors?

Improvements in imaging technology over the last several years have provided valuable tools for neurosurgeons in the treatment of brain tumors. A significant advance in surgical treatment of brain tumors has been the development of intraoperative MRI scanners. This allows a surgeon to perform a tumor resection, and then, post resection, perform a set of MR imaging directly in the operating room. If this MR imaging shows residual tumor, the surgeon has an opportunity to perform a further resection prior to completing the surgical operation. Additional imaging advances include functional MR imaging. This provides a graphic representation of critical functions such as speech or motor function. This is useful in determining both whether a patient is inoperative candidate and in assessing risk of the surgical resection.

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Addiction, Emergency Medicine, Health Policy, Research, Stanford News

Assessing the opioid overdose epidemic

Assessing the opioid overdose epidemic

Vicodin bottle Flickr Sharyn MorrowIn recent years, doctors and policy-makers have become aware of the dangers of prescription opioid medications like methadone, oxycodone and hydrocodone (which is sold as OxyContin or Vicodin). In a study published in this month’s JAMA Internal Medicine, Stanford medical student Michael Yokell and Stanford surgeon Nancy Wang, MD, took a new approach to quantifying those dangers.

Many previous studies of the toll of opioids looked at death certificate data and examined trends among deaths due to opioid overdoses, including street drugs like heroin and prescription painkillers. The new study looked at emergency department admissions and found that more than two thirds of ER visits due to overdoses were related to prescription opioids, while heroin overdoses accounted for 16 percent. Moreover, only about 2 percent of cases that made it to the ER died, but more than half the patients needed further hospitalization.

The study also found that those admitted to the emergency room because of opioid overdoses are more likely to have conditions such as chronic breathing problems, heart problems or mental health issues. Yokell explained that it’s important for doctors to be aware of the possibility of overdose and consider prescribing alternatives or discuss the risk of overdose with patients.

Beyond providing better access to emergency medical care and treatments for patients, an important next step to resolving the problem of opioid misuse is to establish or improve statewide prescription monitoring programs. For example, California has a prescription drug-monitoring database called CURES, but not all doctors actively use the program. “We can do a better job of making that database more widely used by physicians in the state.  We need more doctors to sign up and use it. It’s a valuable resource,” said Yokell.

Additionally, many people get access to prescription opioids via fraudulent prescriptions or from dealers that have illegally obtained the drugs – sometimes from breaking into and raiding pharmacies. “It’s important to keep in mind that good prescribing practices are one component of an effective strategy. There are many other ways for people to get their hands on [prescription opioids] and use them inappropriately.”

Although fixing things on the prescription side is important for managing the opioid overdose epidemic, Yokell notes that it’s not enough. Cases that make it to the ER are likely to survive, but Yokell noted that the fear of criminal charges often results in people avoiding medical care for overdoses caused by opioids and that getting this group better access to emergency services and treatment could improve outcomes. Paramedics and doctors have access to the drug naxolone, marketed as Narcan, which is safe and effective treatment for opioid overdose. But “people don’t call 911, so they are dying,” Yokell told me.

Previously: Stanford addiction expert: It’s often a “subtle journey” from prescription-drug use to abuse, Increasing access to an anti-overdose drug and A focus on addiction, the country’s leading cause of accidental death
Photo by Sharyn Morrow

Medical Education, SMS Unplugged

“It’s tough feeling like you’re always in a position to be judged” and other thoughts on medical school

SMS (“Stanford Medical School”) Unplugged was recently launched as a forum for students to chronicle their experiences in medical school. The student-penned entries appear on Scope once a week; the entire blog series can be found in the SMS Unplugged category.

One of the hardest parts about medical school for me has been the constant pursuit of approval. Having a pass/fail system during pre-clinical years helped ease things some, but there remains a personal desire to prove myself. In front of attendings, all I can focus on is performing my physical exam just right, presenting in the perfect manner, and nailing the assessment and plan. Unfortunately, my strong desire to look good in my evaluators’ eyes has led to missing learning opportunities at times. For example, I often passed up offers to do a procedure I really wanted to do, for fear that I would look bad if I messed up.

It’s tough feeling like you’re always in a position to be judged.

As I find myself in the middle of residency applications, I realize that this feeling of scrutiny has been elevated to a whole new level. And from this point, I’ll be judged on what is already done and how I’ve been evaluated on my rotations over the last few years. I can’t do anything more to change the “me” that those who review my application see. Part of the process is an interview, but it seems as if the interview has been taking place since I began medical school.

I’m extremely grateful for the training and preparation that Stanford has provided me, and I’m confident in my application – but the uncertainty is real. And the way I see it, my success with residency applications isn’t just reflective of me: I want to make my family and the Stanford faculty and mentors who have supported me along the journey proud.

As stressful as this process and the worry about judgment are, though, I’ve been trying to re-focus myself and “check my privilege.” To even be in the position of applying and interviewing for residency is huge. I’m months away from being able to put MD behind my name. As much as I could complain about how hard medical school has been, I’ve been blessed with a wonderful opportunity to be in a position to care for people when they most need it. And, in fact, of all the evaluations that we’re required to seek during a rotation, the ones I value most are from patients and their families.

For me, medicine comes easiest when my patients and their health outcomes are front and center in my mind -  not whether I stand out to my team or answer a tough question correctly. And so with my future patients in mind, it’s time to suit up (tie-clip and all). The work’s been done.

Moises Gallegos is a fourth-year medical student. He’ll be going into emergency medicine, and he’s interested in public-health topics such as health education, health promotion and global health.

Photo in featured-entry box by Yuya Tamai

Imaging, Immunology, Infectious Disease, Neuroscience, Research, Stanford News

Some headway on chronic fatigue syndrome: Brain abnormalities pinpointed

Some headway on chronic fatigue syndrome: Brain abnormalities pinpointed

patchbrainHow can you treat a disease when you don’t know what causes it? Such a mystery disease is chronic fatigue syndrome, which not so long ago was written off by many physicians as a psychiatric phenomenon because they just couldn’t figure out what else might be behind it. No one was even able to identify an anatomical or physiological “signature” of the disorder that could distinguish it from any number of medical lookalikes.

“If you don’t understand the disease, you’re throwing darts blindfolded,” Stanford neuroradiologist Mike Zeineh, MD, PhD, told me about a week ago. Zeineh is working to rip that blindfold from CFS researchers’ eyes.

From a release I wrote about some breaking CFS research by Zeineh and his colleagues:

CFS affects between 1 million and 4 million individuals in the United States and millions more worldwide. Coming up with a more precise number of cases is tough because it’s difficult to actually diagnose the disease. While all CFS patients share a common symptom — crushing, unremitting fatigue that persists for six months or longer — the additional symptoms can vary from one patient to the next, and they often overlap with those of other conditions.

A study just published in Radiology may help to resolve those ambiguities. Comparing brain images of 15 CFS patients with those from 14 age- and sex-matched healthy volunteers with no history of fatigue or other conditions causing similar symptoms, Zeineh and his colleagues found distinct differences between the brains of patients with CFS and those of healthy people.

The 15 patients were chosen from a group of 200 people with CFS whom Stanford infectious-disease expert Jose Montoya, MD, has been following for several years in an effort to identify the syndrome’s underlying mechanisms and speed the search for treatments. (Montoya is a co-author of the new study.)

In particular, the CFS patients’ brains had less overall white matter (cable-like brain infrastructure devoted to carrying signals rather than processing information), aberrant structure in a portion of a white-matter tract called the right arcuate fasciculus, and thickened gray matter (that’s the data-crunching apparatus of the brain) in the two places where the right arcuate fasciculus originates and terminates.

Exactly what all this means is not clear yet, but it’s unlikely to be spurious. Montoya is excited about the discovery. “In addition to potentially providing the CFS-specific diagnostic biomarker we’ve been desperately seeking for decades, these findings hold the promise of identifying the area or areas of the brain where the disease has hijacked the central nervous system,” he told me.

No, not a cure yet. But a well-aimed ray of light that can guide long-befuddled CFS dart-throwers in their quest to score a bullseye.

Previously: Unbroken: A chronic-fatigue patient’s long road to recovery, Deciphering the puzzle of chronic-fatigue syndrome and Unraveling the mystery of chronic-fatigue syndrome
Photo by Kai Schreiber

Aging, Mental Health, Parenting, Research

Girls at high risk for developing depression show signs of stress and premature aging

Girls at high risk for developing depression show signs of stress and premature aging

14465-telomeres_newsAs we age and our cells divide, caps at the ends of our chromosomes called telomeres shorten. When a telomere grows too short, it will die or lose its ability to divide, which causes our skin to wrinkle or sag, as well as damage to our organs. Previous research has shown that depression, chronic stress and inflammation can accelerate this process, causing premature aging and making our bodies more susceptible to infections and disease.

In an effort to better understand the connection between stress, depression and changes in the body, Stanford psychologist Ian Gotlib, PhD, and colleagues studied healthy girls with a family history of depression and compared them to a group of their peers without that medical background. During the experiment, researchers measured participants’ stress response through a series of tests and analyzed their DNA samples for telomere length. According to a Stanford Report story:

Before this study, “No one had examined telomere length in young children who are at risk for developing depression,” Gotlib said.

Healthy but high-risk 12-year-old girls had significantly shorter telomeres, a sign of premature aging.

“It’s the equivalent in adults of six years of biological aging,” Gotlib said, but “it’s not at all clear that that makes them 18, because no one has done this measurement in children.”

The researchers are continuing to monitor the girls from the original study. “It’s looking like telomere length is predicting who’s going to become depressed and who’s not,” Gotlib said.

Based on these findings, researchers recommended that girls at high-risk for depression learn stress reduction techniques.

Previously: How meditation can influence gene activity, Shrinking chromosome caps spell aging cells, sniffles, sneezes… and cognitive decline?, Study finds phobias may speed biological aging and Study suggests anticipation of stress may accelerate cellular aging
Photo by Paulius Brazauskas/Shutterstock

Medical Education, Medicine and Literature

The book that made me go to medical school – and other good reads

The book that made me go to medical school - and other good reads

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Editor’s note: Over the last several months, numerous young Scope readers have inquired about which books they should be reading to prepare for a potential future in medicine. We asked medical student (and SMS-Unplugged contributor) Natalia Birgisson to offer some suggestions.

“In my business, you can lose big, but sometimes you win big, too.” So begins page 87 of the book that made me go to medical school. It was the summer after my freshman year of college and I was volunteering in an outpatient pediatric ward. In the span of a week, I had seen two babies die. A newborn died of complications from seizures right in front of me, and a two week old baby died of malnutrition as we watched him wither away in an incubator.

I couldn’t stand the feeling of being a part of a system that was cumbersome and ineffective, I couldn’t stand my heart breaking, and I wanted to want to be anything other than a doctor. I lay in bed the next day and looked around my rented tropical room for distraction. On the night table was a book left by the last guest, The Soul of Medicine: Tales from the Bedside by Sherwin Nuland, MD, and what I found in his collection of stories was solace, companionship, and hope. It is a compilation of stories, each chapter written by a doctor in a different specialty discussing his or her most memorable patient. If you’re interested in medicine, the reality of it, then I suggest taking Nuland up on his offer to glimpse the mark that medicine leaves on a doctor’s soul. I keep it next to my couch in case a lost friend ever happens upon it the way I did.

Mountains Beyond Mountains by Tracy Kidder was the next book that strongly influenced me. A detailed glimpse into the life story and accomplishments of Paul Farmer, MD, PhD, who not only serves as a role model for anyone interested in global health, but who has changed the world for the better in a tangible way. What I remember from this book is a short scene in which we learn that, at least during the time the journalist was shadowing him, Farmer saw his daughter only once a month. They say that part of a teenager’s angst is realizing that her parents are not perfect and being angry at them for their flaws. Well, Dr. Farmer, I’m still angry with you for missing out on your daughter’s childhood the way my dad did. And for the rest of my life, when I think about changing the world by saving peoples lives, it will be with the caveat of improving on the model that he lived by. Because to me, there’s no point in helping strangers if I’m hurting the ones I love.

Blue Collar, Blue Scrubs and Hot Lights, Cold Steel by Michael J. Collins, MD, were two medical memoirs that resonated strongly with me. I read these the summer that I was writing my medical school applications. Somehow, the application process has a way of making everyone feel incompetent or mediocre at best. And here was a guy who decided to take post-bachelor classes as a construction worker, carpool to medical school, and marry the love of his life before starting residency at the Mayo Clinic. Almost every page of his books had me laughing or crying as I rooted for him.

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Behavioral Science, Cardiovascular Medicine, Medicine and Society, Research, Stanford News

The lonely are more likely to die. But why?

The lonely are more likely to die. But why?

11317715623_e27537b3f3_zLoneliness isn’t healthy — most everyone knows that. But why exactly does isolation lead to disease, or even death? Stanford researcher Sylvia Kreibig, PhD, set out to answer that question by digging through data from the Heart and Soul Study, an inquiry that followed more than 1,000 coronary heart disease patients for about 10 years, starting in 2000.

Turns out that socially isolated patients are 61 percent more likely to die in any given year than other patients, Kreibig and her team found. Yet you don’t need many friends to stave off the ill effects of solitude. Those with at least one to three regular contacts fared no better than the most-social butterfly. Even tossing in factors that affect mortality such as age and weight didn’t affect general conclusion: friendless folks die sooner. But why?

Kreibig’s team, which included Stanford psychologist James Gross, PhD, delved deeper to figure it out.

It isn’t depression. Depression is independently related to mortality, but it couldn’t explain the link between solitude and risk of death. Instead, Kreibig and colleagues found a strong link between several behavior factors such as smoking, omega-3 concentration (a representative of diet quality), and medication adherence and isolation.

“If you are more integrated, you have people around that look after you and care for you, making sure you’re eating healthy foods, not smoking and taking medications as directed,” Kreibig told me. “You yourself as a patient actually have a lot of control over factors that affect your health… Just by integrating some salmon into your diet, you have a better chance of survival.”

The team classified 1,019 patients into four categories of social integration (low, medium, medium-high and high), based on whether or not they had a partner, strength of linkages with family and friends and membership in religious congregations and community groups. Patients in the low category were more likely to smoke, eat unhealthy foods and skip their medications, the study found.

She cautioned that the study, which appears in this month’s issue of Psychosomatic Medicine, demonstrated correlation, not causation. In addition, the patients were primary male and, as they suffered from heart disease, could be affected differently than healthy, or younger, patients.

Next, Kreibig said she plans to examine the emotions related to social isolation and their effect on health.

Previously: The importance of human connection as part of the patient experience, How social media and online communities can improve clinical care for elderly patients and How loneliness can impact the immune system
Photo by Alex Krasavtsev 

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