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A study comparing life expectancy of people with inflammatory bowel disease (IBD) and without found that, while life expectancy increased for both groups, people with IBD generally died sooner. The study is published in CMAJ (Canadian Medical Association Journal).

"The good news is life expectancy has increased in people with IBD, but there is still a gap between people with and without the disease," says Dr. Eric Benchimol, a senior core scientist at ICES, and a pediatric gastroenterologist who works at The Hospital for Sick Children (SickKids). "However, people with IBD suffer from pain, which can negatively affect daily functioning and contribute to decreased health-adjusted life expectancy."

The study included 32 818 people living with IBD in 1996 (matched to 163 284 people without IBD), increasing to 83 672 in 2011 (matched to 418 360 people without IBD). In women with IBD, life expectancy increased by almost 3 years between 1996 (75.5 years) and 2011 (78.4 years). Life expectancy among men with IBD increased by 3.2 years between 1996 and 2011, from 72.2 years to 75.5 years.

However, people with IBD had a consistently shorter life expectancy than those without IBD. Women with IBD can expect to live between 6.6 years and 8.1 years less than women without IBD. Men with IBD can expect to live between 5.0 years and 6.1 years less than men without IBD. When measuring health-adjusted life expectancy, a measure of how health-related symptoms and functioning affects both quality of life and life expectancy, the gap between those with and without IBD was even greater. Women with IBD have a health-adjusted life expectancy that is 9.5 to 13.5 years shorter than women without IBD. Men with IBD have a health-adjusted life expectancy that is 2.6 to 6.7 years shorter than men without IBD.

Patients with IBD often experience inflammation beyond the intestinal tract and are more likely to be diagnosed with cancer, heart disease, arthritis and other conditions.

"In light of the increasing prevalence of IBD in Canada, and the frequency of pain in patients with IBD and its impact on health-related quality of life, we need to develop better pain-management strategies," says Dr. Ellen Kuenzig, the study's lead author and a postdoctoral fellow at ICES and the CHEO Research Institute in Ottawa.

"Life expectancy and health-adjusted life expectancy in people with inflammatory bowel disease" is published November 9, 2020.

Disparities in unilateral knee replacement surgery have been well-documented, with lower utilization and higher complication rates among African American patients. While previous studies have focused on single knee replacement surgery, researchers at Hospital for Special Surgery (HSS) set out to determine if racial variations exist for same-day bilateral knee replacement, as well.

"In our retrospective analysis, we found the utilization rate of bilateral knee replacement was much lower in African American patients compared to white patients," said Bella Mehta, MBBS, a rheumatologist at HSS. "On the other hand, although African Americans having unilateral knee replacement have been shown to have higher in-hospital complication rates compared to white patients, this pattern was not consistent for bilateral knee replacement during the time period we studied." She presented the findings on November 9 at the American College of Rheumatology annual meeting, which took place virtually.

Dr. Mehta and colleagues compiled information from the National Inpatient Sample (NIS) - Healthcare Cost and Utilization Project (HCUP) database from 2007 to 2016. They looked at trends in utilization and major in-hospital complication rates of unilateral versus bilateral knee replacement nationwide in patients age 50 and older.

Investigators assessed racial differences over time, adjusting for age, sex and comorbidities; hospital variables, including hospital volume, number of beds, region and teaching status; and community level factors, such as median household income.

From 2007 to 2016, 5.5 million unilateral and 276,000 bilateral knee replacements were performed in the United States. The percentage of bilateral knee replacements declined from 5.53% in 2007-08 to 4.03% in 2015-16.

The researchers found that African Americans were much less likely to undergo a double knee replacement compared to white patients during the years analyzed. In-hospital complication rates varied throughout the study period, with no significant difference between African American and white patients.

To explain the study findings concerning complication rates, Dr. Mehta said there could be a more rigorous patient selection process when considering candidates for same-day bilateral knee replacement. Regarding the lower number of African Americans having the bilateral procedure, she said physicians may be offering it less often to African American patients or they may be choosing not to have the procedure.

"Since the complication rate for bilateral knee replacement is not higher for African American patients, health providers should work to provide access to all appropriate patients," Dr. Mehta said. She noted that future studies could take a closer look at the patient selection process or assess the role of an individual's health insurance plan in utilization of the bilateral procedure.

"As we seek to achieve health equity for our patients, we must understand the challenges they face in accessing care, as well as variance in their outcomes," said Michael Parks, MD, an orthopedic surgeon at HSS and study author. "Our ultimate goal is to provide the same quality of care to everyone."

Embargoed until 4 a.m. CT/ 5 a.m. ET Monday, Nov. 9, 2020

DALLAS, Nov. 9, 2019 - Using neighborhood and local data in combination with existing information sources creates a more accurate prediction on a patient's recovery prospects after an out-of-hospital cardiac arrest (OHCA), according to preliminary research to be presented at the American Heart Association's Resuscitation Science Symposium 2020. The 2020 meeting will be held virtually, November 14-16, and will feature the most recent advances related to treating cardiopulmonary arrest and life-threatening traumatic injury.

The machine learning algorithms were developed and tested on nearly 10,000 cases of OHCA that happened in Chicago's 77 neighborhoods between 2014 and 2019. Researchers used OHCA information from the existing Cardiac Arrest Registry to Enhance Survival (CARES) database to identify incidents that happened outside of a health care system or a nursing home facility around the Chicago area. Information about individual communities from the Chicago Health Atlas (CHA), including crime rates, access to health care and education, was then added.

Researchers merged the CARES and CHA information to train a machine learning model to predict OHCA survival. The addition of the CHA data increased the average recall of OHCA survival predictions from 84.5 to nearly 87%.

"This is exciting," says the study's lead author, Samuel Harford, M.S., a Ph.D. candidate in the department of mechanical and industrial engineering at the University of Illinois at Chicago. "We were able to provide a machine learning model with information from publicly available, real-world sources that helped us find patterns that might be otherwise unseen, therefore, yielding better results. This strategy has the potential to be helpful in more accurately predicting other clinical outcomes in future studies."

The study had limitations based on the quality of data, and more information that could impact the results such as weather, traffic, EMS routes and socioeconomic status still need to be examined.

**Strictly embargoed until 10:00 (GMT) Friday 6 November 2020**

Scientists and students publish blueprints for a cheaper single-molecule microscope to make the specialist technique more widely available

A team of scientists and students from the University of Sheffield has published the blueprints for a specialist single-molecule microscope they built for a tenth of the cost of commercially available equipment

Their paper in Nature Communications provides labs with the build instructions and software needed to run the microscope

The single-molecule method this microscope is capable of is currently only available in a few specialist labs throughout the world

A team of scientists and students from the University of Sheffield has designed and built a specialist microscope, and shared the build instructions to help make this equipment available to many labs across the world.

The microscope, called the smfBox, is capable of single-molecule measurements allowing scientists to look at one molecule at a time rather than generating an average result from bulk samples and works just as well as commercially available instruments.

This single-molecule method is currently only available at a few specialist labs throughout the world due to the cost of commercially available microscopes.

Today (6 November 2020), the team has published a paper in the journal Nature Communications which provides all the build instructions and software needed to run the microscope, to help make this single-molecule method accessible to labs across the world.

The interdisciplinary team spanning the University of Sheffield's Departments of Chemistry and Physics, and the Central Laser Facility at the Rutherford Appleton Laboratory, spent a relatively modest £40,000 to build a piece of kit that would normally cost around £400,000 to buy.

The microscope was built with simplicity in mind so that researchers interested in biological problems can use it with little training, and the lasers have been shielded in such a way that it can be used in normal lighting conditions, and is no more dangerous than a CD player.

Dr Tim Craggs, the lead academic on the project from the University of Sheffield, said: "We wanted to democratise single-use molecule measurements to make this method available for many labs, not just a few labs throughout the world. This work takes what was a very expensive, specialist piece of kit, and gives every lab the blueprint and software to build it for themselves, at a fraction of the cost.

"Many medical diagnostics are moving towards increased sensitivity, and there is nothing more sensitive than detecting single molecules. In fact, many new COVID tests currently under development work at this level. This instrument is a good starting point for further development towards new medical diagnostics."

The original smfBox was built by a team of academics and undergraduate students at the University of Sheffield.

Ben Ambrose, the PhD lead on the project, said: "This project was an excellent opportunity to work with researchers at all levels, from undergraduates to scientists in national facilities. Between biophysicists and engineers, we have created a new and accessible platform to do some cutting edge science without breaking the bank. We are already starting to do some great work with this microscope ourselves, but I am excited to see what it will do in the hands of other labs who have already begun to build their own."

The Craggs Lab at the University of Sheffield has already used the smfBox in its research to investigate fundamental biological processes, such as DNA damage detection, where improved understanding in this field could lead to better therapies for diseases including cancer.

ATLANTA -- New research presented at ACR Convergence, the American College of Rheumatology's annual meeting, shows that use of warfarin, a vitamin K drug widely prescribed to prevent blood clots, is associated with a significantly greater risk of knee and hip replacements in patients with osteoarthritis (ABSTRACT #0934).

Osteoarthritis (OA) is a common joint disease that most often affects middle-age to elderly people. It used to be commonly referred to as "wear and tear" of the joints, but we now know that OA is a disease of the entire joint, involving the cartilage, joint lining, ligaments, and bone.

Vitamin K deficiency has been associated with OA, and recent research shows that vitamin K supplementation may reduce OA progression. However, no studies to date have evaluated whether vitamin K antagonism with the use of warfarin, an anticoagulant drug, can be detrimental to OA. This new study evaluated the relationship of warfarin, a medication commonly prescribed for atrial fibrillation--which is the management of quivering or irregular heartbeats--to the risk of knee and hip replacements in end-stage OA.

"We hypothesized that disruption of the functioning of vitamin K-dependent bone and cartilage proteins through vitamin K antagonism may lead to abnormalities in chondrocyte functioning with adverse effects on cartilage health, which in turn can increase the risk of developing or worsening of OA," says study co-author Priyanka Ballal, MD, rheumatology fellow at Boston University Medical Center. "Because direct oral anti-coagulants are alternate options for anticoagulation that do not inhibit vitamin K's functioning, clarifying this risk of warfarin would give providers and patients valuable information when they consider their choice of anticoagulation in patients with atrial fibrillation."

The nested, case-control study used data from the Health Improvement Network, a general practitioner-based electronic medical records database from the United Kingdom (UK) that is representative of the general population. The study sample was limited to adults ages 40-89 with atrial fibrillation since this diagnosis warrants anticoagulation therapy. They compared warfarin, which is a vitamin K antagonist, with direct oral anticoagulants which do not inhibit vitamin K and were first marketed in the UK in 2008. Among other exclusions, they excluded anyone who had a knee or hip replacement before 2014, anyone with severe comorbidities that would limit surgery, those who took warfarin or direct oral anticoagulants within one year prior to the study period, and anyone who used both drugs in the study period. They identified cases as anyone who had a knee or hip replacement between 2014 and 2018. Each case was matched with up to four controls for age and gender. Warfarin and direct oral anticoagulant use were defined as having one or more prescriptions after the study entry and within one year before the index date.

The researchers assessed how warfarin compared with direct oral anticoagulants for the risk of knee or hip replacements. The study included 913 patients who had either knee or hip replacement, age- and gender-matched four-to-one with 3,652 controls. Their mean age was 74 and 46% were female. Of the 913 surgery cases, 64.9% were warfarin users and 35.1% were direct oral anticoagulant users.

After adjusting for potential confounders, they found that warfarin users had 1.57 times higher odds of having a knee replacement or hip replacement than direct oral anticoagulant users. They also found an increasing risk of knee or hip replacement surgery with the duration of warfarin use compared to direct oral anticoagulants use.

The researchers stress that their data supports the importance of adequate vitamin K in limiting the progression of OA in patients and raises the consideration of using direct oral anticoagulants instead of warfarin when indicated in people with OA or at risk for the disease.

"Our research supports the importance of adequate Vitamin K and dependent proteins for limiting progression of OA," says Dr. Ballal. "Given these potential adverse effects of warfarin on joint health, our study suggests that direct oral anticoagulants could be considered for managing atrial fibrillation among patients who have OA. The next steps for our group's research are the design and launch of an adequately powered randomized trial to test the efficacy of vitamin K supplementation for OA outcomes."

ATLANTA -- New research shows that adults with lupus who take the antimalarial drug, hydroxychloroquine, do not have any differences in their corrected QT (QTc) intervals, an electrocardiogram (EKG) measurement of the heart's electrical signals, even if they have chronic kidney disease (CKD), a complication of lupus that can be associated with increased levels of the medication. The study was presented at ACR Convergence, the American College Rheumatology's annual meeting (ABSTRACT #1844).

Systemic lupus erythematosus (SLE or lupus) is a chronic (long-term) disease that causes systemic inflammation which affects multiple organs. In addition to affecting the skin and joints, it can affect other organs in the body such as the kidneys, the tissue lining the lungs, heart, and brain. Many patients experience fatigue, weight loss, and fever.

Current lupus treatment recommendations include hydroxychloroquine for all patients. It is well tolerated and considered low risk for side effects. The drug can produce a delay in the heart's electrical conduction system, but prior studies found no association with symptoms or a serious risk of abnormal heart rhythm. However, one concern is that in lupus patients with decreased kidney function, higher levels of hydroxychloroquine may be more likely to affect the heart.

One way to assess the heart's electrical signaling is the QTc interval measurement on an EKG. It measures how long it takes the heart to contract and relax on each heartbeat. People with prolonged QT intervals are at higher risk for heart arrhythmias, which are irregular heartbeats, that could be life-threatening. This new study compared QTc intervals in adults with lupus based on their use of hydroxychloroquine, and if they did or did not have chronic kidney disease.

"Hydroxychloroquine use increased during the COVID-19 pandemic, with some contradictory reports regarding its cardiac safety," says the study's co-author, H. Michael Belmont, MD, professor of medicine, NYU Grossman School of Medicine and co-director of NYU Langone Health's Lupus Center. "It is important to provide reassurance to lupus patients who need to take this medication regularly and for long periods that it is generally safe and without consequential risk for serious heart toxicity."

There were 194 patients with lupus included in the study, which used retrospective data from the electronic medical records database at NYU Langone Health from March 2012 through May 2020. The researchers collected data on patients' EKG results, including the QTc intervals from their first and last EKGs. Prolonged QTc intervals are more than 450 milliseconds for males and more than 470 milliseconds for females. Severe prolongation is more than 500 milliseconds. The researchers also looked at patients' creatinine levels and demographics, and whether or not they had CKD.

Only 90 people in the study had taken at least one EKG during this period, and of these, 91% were female, 32.2% were African American, 6.6% were Asian, 28.8% were white, 20% were Hispanic, and 2.2% were of other races. Seventy-five were taking hydroxychloroquine, while 15 were not on the drug. Eight out of 75 patients who were on hydroxychloroquine had prolonged QTc intervals, and only one of the 15 people not taking the drug had a prolonged interval. There was no significant difference in mean QTc intervals based on hydroxychloroquine treatment.

What about lupus patients with CKD? The 23 patients with chronic kidney disease in the study did not have any significant differences in their mean QTc intervals either, whether or not they were taking hydroxychloroquine. None of these patients had any documented tachyarrythmia, or more rapid than normal heart rate, or Torsades de pointes (Tdp), a potentially life-threatening arrhythmia.

"The findings of this study can provide some comfort to lupus patients including those with CKD that hydroxychloroquine is not likely to produce serious heart arrhythmias," says Dr. Belmont. "Future studies could investigate these observations in even larger numbers of patients and include a prospective examination of QTc intervals in patients before and after starting the medication to provide even further assurance of drug safety."

ATLANTA -- A new study shows that women with interstitial lung disease (ILD) related to autoimmune disease may not need to terminate their pregnancies--despite the increased risk of adverse outcomes--provided they have close monitoring from their team of multidisciplinary physicians before, during and after pregnancy. Results of the research was presented at ACR Convergence, the American College of Rheumatology's annual meeting (ABSTRACT #1446).

Interstitial lung disease is a condition that involves inflammation and scarring of tissue inside the lungs. Patients may experience severe breathing difficulties as their lung tissue stiffens and scars. ILD may be seen in people who also have other autoimmune diseases, including scleroderma, lupus, and sarcoidosis.

Patients with ILD are often advised to avoid or even terminate pregnancy based on very limited published data on potential outcomes or complications of pregnancy with the disease. For this study, researchers at Duke University School of Medicine in Durham, North Carolina collected retrospective data on pregnancy outcomes of patients with ILD secondary to autoimmune disease, creating the largest cohort to date. Their goal was to provide physicians with the data to better counsel ILD patients on pregnancy risks.

"Our goal was to allow healthcare providers and patients to make more informed decisions on whether to conceive or continue pregnancies," says the study's co-author, Megan Clowse, MD, MPH, Associate Professor of Medicine, Division of Rheumatology and Immunology at Duke. "Our hope is that patients with ILD and their providers can have more open and honest conversations on pregnancy risks, likely allowing more women living with ILD to safely create the families they desire."

The researchers reviewed medical records on pregnancies in patients diagnosed with ILD secondary to autoimmune disease at Duke University Health System from January 1996 to July 2019. They classified the pregnancies according to the severity of ILD based on two standard breathing tests for the disease: forced vital capacity and diffusion capacity for carbon monoxide, with cut-off values that were normal, mild, moderate or severe. They also defined adverse pregnancy outcomes, including pre-eclampsia, preterm delivery, infants small for their gestational age, fetal death and neonatal death, according to two standard scores: PROMISSE-APO and PROMISSE-APO SEVERE.

Sixty-seven patients who had 94 pregnancies, including five twin pregnancies, were included in the study. Their average maternal age was 32.1 and 83% identified as Black. Overall, 69% of the pregnant patients were diagnosed with sarcoidosis, and 31% had a connective tissue disease-associated ILD. Of the 64 pregnancies with available data to classify their ILD severity, 11% were severe ILD, 25% were moderate ILD, 50% were mild ILD and 14% were normal. All the pregnancies in the severe group had connective tissue disease-associated ILD, and 89% of the normal pregnancies had sarcoidosis. Seven of the pregnancies were conceived when the woman was taking mycophenolate, a medication known to cause pregnancy loss and major birth defects.

The study's results showed that 70% of the pregnancies resulted in a live birth. Ten percent were terminated. The results also showed a 15% rate of pre-eclampsia. None of the women died, though patients with severe ILD had more adverse pregnancy outcomes. Only 2.1% required care in an ICU during or soon after delivery. In 4.2% ILD patients experienced significant shortness of breath due to increased fluid volume around the time of delivery, and in one case, the patient developed postpartum heart failure. In eight pregnancies, the patient required oxygen during delivery and one patient was intubated mid-pregnancy for asthma.

The study's findings suggest that women with stable ILD do not necessarily have to avoid conception or terminate pregnancy, says Dr. Clowse.

"Women with ILD who are considering pregnancy should discuss their individual risks for pregnancy and disease-related complications with their rheumatologist, pulmonologist, high-risk obstetrician and/or other specialists prior to stopping contraceptive measures," she says. "Furthermore, patients on teratogenic immunosuppressives should to be switched over to pregnancy-compatible medications prior to pregnancy to decrease the risk of pregnancy loss and birth defects. By planning pregnancy, we hope that women with stable ILD can have safer and healthier outcomes. In the future, work needs to be done to confirm these findings in other centers. Additionally, developing best practices in the clinical setting will likely increase the ability of women living with ILD to have safe pregnancies and healthy babies."

ATLANTA -- A new study reveals that many older men who experience a fracture are still underdiagnosed with and undertreated for osteoporosis. Details of the study was presented at ACR Convergence, the American College Rheumatology's annual meeting (ABSTRACT #0533).

Osteoporosis is a common condition that results from a loss of bone mass, measured as bone density, and from a change in bone structure. Bone is living tissue that is in a constant state of regeneration. By their mid-30s, most people begin to slowly lose more bone than can be replaced. As a result, bones become thinner and weaker in structure. This accelerates in women at the time of the menopause. In men, bone loss usually becomes more of an issue around age 70.

Osteoporosis can cause significant burden upon patients, including physical symptoms, increased cost of healthcare and mortality. Approximately one quarter of patients with fractures are male, and emerging evidence suggests that men with osteoporotic fractures have worse outcomes than women. This new study looked at the baseline characteristics of male Medicare patients who have had an osteoporosis-related fracture. Addressing the absence or gap in undergoing bone density screening was the major reason for the study.

"Men are typically not part of routinely recommended screening with DXA and so they are both underdiagnosed and undertreated. While many comorbidities (i.e., cardiovascular disease) are commonly recognized and treated in men, sometimes even more than women, osteoporosis is not one of them. Even post fracture for major fractures like a hip, rates of treatment are disappointingly low, leaving men at risk for yet another fracture," says the study's co-author, Jeffrey Curtis, MD, MS, MPH, Professor of Medicine, Division of Clinical Immunology and Rheumatology at the University of Alabama at Birmingham. "There is also a lack of consistent guidelines for osteoporosis screening recommendations for men. Among women, the World Health Organization, American Association of Clinical Endocrinologists, United States Preventive Services Task Force, National Osteoporosis Foundation (NOF) and the American Academy of Family Physicians all recommend screening women over 65 years of age. However, among men, these groups do not make any recommendation at all, except for the NOF which recommends that all men over 70, and those between the ages of 50 to 69 who have risk factors, must be screened."

The researchers studied Medicare fee-for-service (FFS) beneficiaries who had a closed-fragility, or osteoporosis-related, fracture between January 2010 and September 2014. The inclusion criteria for the study included age 65 or older at the time of the index date, and continuous enrollment in Medicare FFS with medical and pharmacy benefits for a minimum of one year before the index date through at least one month after. Medicare beneficiaries were excluded if they died within 30 days of the index date. They also excluded patients with either Paget's disease or any malignancy, except non-melanoma skin cancer, at baseline. Patients were divided into four groups based on their diagnoses and/or treatment of osteoporosis at baseline. Osteoporosis diagnoses could be listed in any position on any medical claim.

The study included 9,876 Medicare beneficiaries. Sixty one percent were 75 or older and 90% were white. Fewer than 6% had a bone mineral density test with DXA, the standard test, in the two years before their fracture. Researchers also found that two-thirds (62.8%) of the patients had a history of musculoskeletal pain and nearly half (48.5%) had a history of opioid use one year prior to their fracture. The most common sites of fractures were the spine, hip and ankle. Of all patients with a qualifying fracture, about 92% did not have any claim for a DXA test or prescription claim for osteoporosis treatment in the two years prior to their index fracture. At baseline, 2.8% had been tested and not treated, 2.3% were treated but not tested, and only 2.1% were both tested and treated. The decline in the DXA scans in 2012 to 2014 was particularly high among men 75 years and older who are more likely to be at risk of fracture.

Based on the study's conclusions, earlier identification of high-risk male patients who might benefit from targeted osteoporosis screening and therapies would be of great value, the researchers say.

"There is a need for consistent osteoporosis screening recommendation in men," says Dr. Curtis. "Incorporation of these recommendations in quality-of-care measures for osteoporosis management and post-fracture care are warranted to improve health outcomes in this population. As for the next steps for research in this area, there is a need for better characterization of high-risk patients including existing comorbidities that may have shared etiology or risk factors that may enable earlier identification and treatment."

ATLANTA -- New research reveals that, in the U.S., Black patients with lupus have a threefold higher risk of stroke and a 24-fold higher risk of ischemic heart disease. The study also found several lupus-specific symptoms that predict stroke and IHD in these patients. Details of the study was presented at ACR Convergence, the American College Rheumatology's annual meeting (ABSTRACT #0433).

Systemic lupus erythematosus, also called lupus or SLE, is a chronic disease that causes systemic inflammation affecting multiple organs, such as the skin, joints, kidneys, the tissue lining the lungs (pleura), heart (pericardium) and brain. Many patients experience fatigue, weight loss and fever. The disease is more common among Black, Asian, and Native American people and tends to be worse in these groups.

Black people with lupus have a 19-fold higher occurrence of cardiovascular disease compared to other groups and have a disproportionately higher number of stroke-related events around the time of lupus diagnosis. Researchers wanted to know more about the specific risks and predictors of stroke and ischemic heart disease in Black people with lupus.

"The risk for developing cardiovascular disease is up to 52 times higher in patients with lupus, compared to patients without lupus. Black populations have three times higher risk to develop lupus, develop it at a significantly younger age and have more severe disease. However, most prior lupus and cardiovascular disease (CVD) studies were conducted in predominantly white cohorts, limiting the generalizability of the findings," says the study's co-author, Shivani Garg, MD, MS, Assistant Professor of Medicine at the University of Wisconsin School of Medicine and Public Health. "It's important to quantify the risk, predictors and timing of stroke and ischemic heart disease in Black people with lupus in order to guide early CVD diagnosis and preventive interventions in this at-risk population." The study highlights the need for aggressive heart disease preventive care to reduce these racial disparities and improve lupus outcomes, particularly in recently diagnosed patients, she adds.

The researchers collected data from the Georgia Lupus Registry of lupus patients from Atlanta. They identified patients from 2002 to 2004 who met four or more of the ACR's SLE criteria or three criteria with a final lupus diagnosis by their own rheumatologist. They matched the patients to the Georgia Hospital Discharge Database and National Death Index from 2000 to 2013. Stroke and ischemic heart disease-related hospitalizations and deaths were based on hospital admission and death medical codes. Transient ischemic attacks were included in the stroke data, and myocardial infarction (heart attack) and angina were included in ischemic heart disease data. The researchers also examined symptoms that predicted strokes and ischemic heart disease. Of the 336 lupus patients included in the final study, 87% were female, 75% were Black, and the mean age at diagnosis was 40.

They found 38 stroke-related and 25 ischemic heart disease -related health events or deaths that occurred from two years before to 14 years after a lupus diagnosis. In the 11% of patients who had strokes, the mean age at first stroke was 48, and 78% of the strokes occurred in females. Ninety percent of the strokes occurred in Black patients. The peak number of strokes happened in the second year after lupus diagnosis. The study also showed that 8% of the patients had ischemic heart disease, and their mean age at diagnosis was 52. All the ischemic heart disease cases occurred in females, 96% occurred in Black patients and the peak number of cases occurred in the 14th year after diagnosis with lupus. All in all, the data showed that Black patients with lupus have a threefold higher stroke risk and a 24-fold higher ischemic heart disease risk than other groups.

What about potential predictors of stroke or ischemic heart disease? Discoid rash at the time of lupus diagnosis predicted a five-fold higher risk of stroke, while renal disorder at the time of lupus diagnosis predicted a two-fold higher stroke risk. Neither discoid rash nor renal disorder predicted ischemic heart disease, however. Strong predictors of ischemic heart disease were neurologic disorders (prior psychosis or seizure) and immunologic disorders (anti-DNA, anti-Sm, or antiphospholipid antibodies), but these did not predict strokes.

These findings highlight significant racial disparities in both stroke and ischemic heart disease among patients with lupus, says Dr. Garg.

"Our study increases awareness of higher risk, the timing of accelerated risk and disease presentations that contribute to higher risk of stroke and ischemic heart disease among Black patients with lupus. Such knowledge can help patients and providers look for and diagnose CVD events earlier and discuss starting preventive care to reduce their risk," says Dr. Garg. "Timely interventions could help reduce cardiovascular disparities in lupus and reduce CVD-related morbidity and mortality in young lupus patients, who are at relatively higher risk of premature CVD."

ATLANTA -- New research presented at ACR Convergence, the American College of Rheumatology's annual meeting, discovers that use of hydroxychloroquine, a generic drug, does not cause any significant differences in QTc length or prolonged QTc, key measures of heart rate, in people with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) (ABSTRACT #0431).

Rheumatoid arthritis is the most common type of autoimmune arthritis. It is caused when the immune system (the body's defense system) is not working properly. RA causes pain and swelling in the wrist and small joints of the hand and feet. SLE is a chronic disease that causes systemic inflammation which affects multiple organs.

Hydroxychloroquine is a cornerstone treatment for SLE, and patients with RA may also take the drug either alone or in combination with other treatments. However, there are concerns about its possible heart-related side effects: the prolongation of QTc, or the time span the heart takes to contract and relax, and the development of arrhythmia (irregular heartbeats). This new study assessed QTc lengths in patients with RA and SLE and its association with hydroxychloroquine use.

"Hydroxychloroquine remains the foundation of disease-modifying antirheumatic drug therapy in rheumatic disease patients. Given recent concerns surrounding hydroxychloroquine's use in COVID-19 patients and subsequent arrhythmic events, we wanted to examine the associations between its use and the QTc length on electrocardiograms in a large, asymptomatic cohort of RA and SLE patients," says study co-author Elizabeth Park, MD, Rheumatology Fellow at Columbia University Irving Medical Center.

The study analyzed data on 681 RA and SLE patients without clinical cardiovascular disease, including two prospective RA cohorts of 307 patients and a retrospective SLE cohort of 374patients, that included electrocardiogram (EKG) results. The researchers explored the association between QTc length and hydroxychloroquine use by these patients, and they adjusted the data for disease-specific characteristics and cardiovascular disease (CVD) risk factors. Of the whole study group (RA and SLE), 54% used hydroxychloroquine and 44% had QTc lengths of more than 440 milliseconds. They found that the adjusted QTc length among hydroxychloroquine users was comparable to those who did not use the drug.

Their results also showed that hydroxychloroquine use did not significantly predict prolonged QTc for either the whole cohort or the RA and SLE patient cohorts. However, nine out of 11 of the SLE patients who did have a prolonged QTc were taking hydroxychloroquine. Yet these observations were too small to detect statistically significant differences between the hydroxychloroquine groups.

Prolonged QTc, or more than 500 milliseconds, was not associated with arrhythmias or deaths among these patients. The study also did not find any significant interactions between hydroxychloroquine and other QTc-prolonging medications in the patients. Hydroxychloroquine use combined with other QTc-prolonging medications resulted in a comparable QTc interval to hydroxychloroquine alone. In the SLE group, hydroxychloroquine combined with anti-psychotic drugs did result in longer QTc compared to using hydroxychloroquine alone, however.

"Overall, the use of hydroxychloroquine did not predict QTc length, even while adjusting for critical confounding factors, namely the use of other QTc-prolonging medications," says Dr. Park. "Our findings reinforce the fact that hydroxychloroquine remains a safe, effective long-term disease-modifying drug for our rheumatic disease patients. It's important to remember that COVID-19 patients who received hydroxychloroquine were likely critically ill. Therefore, the effect of COVID-19 itself on the heart and subsequent arrhythmia must be considered. They also likely concurrently received azithromycin, another QTc-prolonging medication. Our next steps are to stratify data by length and cumulative dose of hydroxychloroquine therapy and analyze the associations with QTc length."

This research was supported by funding from the Rheumatology Research Foundation.

ATLANTA -- A new study presented at ACR Convergence, the American College of Rheumatology's annual meeting, shows that after three months of treatment with oral methotrexate, adults with primary knee osteoarthritis (OA) with inflammation had significant improvements in physical function and inflammation, a sign that this inexpensive, generic pill may be an important intervention for knee OA (ABSTRACT #1648).

OA is a common joint disease that most often affects middle age to older people. It is commonly referred to as "wear and tear" of the joints, but it is now known that OA is a disease of the entire joint, involving the cartilage, joint lining, ligaments, and bone.

Many people with knee OA show clinical signs of joint inflammation, including swelling, warmth and pain. Although inflammation may play a major role in pain and loss of function and progressive damage in joints with OA, there are no current, accepted drug therapies to address the condition in these patients. This study, which was conducted by researchers at SSKM Hospital in Kolkata, India, compared oral methotrexate to placebo treatment with glucosamine, a common supplement for arthritis pain relief, in adults with primary knee OA.

"Almost all patients with primary knee OA experience periods of warmth and swelling in the joint, with increases in pain and reduction of function," says the study's co-author, Biswadip Ghosh, MD, associate professor, Department of Rheumatology, at Institute of Post Graduate Medical Education and Research in Kolkata, India. "Those episodes are inflammation, and every episode damages the structures of the knees a little more. After some time, swelling subsides partly due to burning out of materials. That leaves the knee in a hopeless state of function loss where physiotherapy helps minimally with enlistment for knee replacement. It will be helpful for patients if we can decrease the inflammation and rescue the joint," says Dr. Ghosh.

Male and female patients with primary knee OA who had swelling and pain in both knee joints for at least six months, and also had evidence of OA on their X-rays, were recruited for the study. Researchers excluded anyone with advanced OA or secondary OA; anyone who had undergone arthroscopy (a procedure for diagnosing and treating joint problems) ; intra-articular steroid injection in the previous three months; or patients who had uncontrolled diabetes, renal or hepatic diseases, or gout.

Patients with signs of local inflammation, such as pain and swelling of the whole knee with warmth, were checked for erythrocyte sedimentation rate and C-reactive protein blood levels. Any patient with increases in both inflammatory markers on one exam or either on two exams held one month apart was placed in an inflammatory group in the study. Other patients were placed in a non-inflammatory group.

Blood samples collected from all the patients and healthy controls were tested for selected biomarkers of osteoarthritis. Patients in the inflammatory group of primary knee OA were screened for other inflammatory arthritis with a clinical exam, blood tests, musculoskeletal ultrasound and X-ray, as well as MRI scans of their knees. Patients in the inflammatory group were then randomly allocated to take 15-20 mg/week of oral methotrexate or 1,500 mg/day of glucosamine as a placebo, then checked once a month for three months. Patients were allowed to take acetaminophen or tramadol for pain if needed and were also given NSAIDs for 7-10 days at the beginning of the study to improve compliance.

A total of 344 people with primary knee OA were included and examined from July 2016 to June 2019. The researchers found that 249 patients had local inflammation, or swelling with pain and warmth in both knees, and 172 of those 249 had elevated erythrocyte sedimentation rate and/or C-reactive protein, both markers at one exam or either marker at two exams held at one month apart. The study's results showed that patients with primary knee OA with evidence of inflammation had significant improvements on their WOMAC scores, a widely used measurement of physical function, and erythrocyte sedimentation rate and C-reactive protein after three months of taking oral methotrexate. Patients who took glucosamine had no significant improvement in these measures of function and inflammation. This new data suggests that methotrexate can be an effective intervention for people with knee OA who experience pain and inflammation.

"Treatments offered to patients with primary knee OA are usually physical support and knee replacement, which are basically directed to manage the effect of the disease. Our study provides hope to patients not only from this inexpensive molecule, methotrexate, but other therapies directed towards one cause of the disease: inflammation," says Dr. Ghosh. "We should think of using methotrexate if we find signs of both local and systemic inflammation in patients with primary knee OA when conventional therapies are not helpful. Additionally, more research should be directed towards the inflammatory pathways of the disease in the future."

ATLANTA -- A new study shows that the COVID-19 infection incidence has been low in people with rheumatic diseases, and most of those infected experience a mild course of illness. Additionally, fatalities have been low among rheumatic disease patients infected with COVID-19. Details of this research was presented at ACR Convergence, the American College of Rheumatology's annual meeting (ABSTRACT #0008).

COVID-19 is the infectious disease caused by the novel coronavirus SARS-CoV-2. As the COVID-19 pandemic surged worldwide in early 2020, the risk of serious infection, complications or fatality was unknown for people with rheumatic disease. Many patients with rheumatic disease are treated with immunosuppressant medications that leave them more susceptible to infection.

As the pandemic began, it was unclear how people with rheumatic diseases, on immunosuppressant therapy, were affected by a COVID-19 infection. Some early studies even suggested that these drugs could have a protective effect, but concerns remained about the vulnerability of this patient population. To learn more, researchers conducted a systematic review of studies that reported outcomes of COVID-19 infection among patients with rheumatic diseases who were taking biologic and targeted therapies.

"When the pandemic started, there was concern on whether to continue or hold immune therapies among patients with rheumatic diseases because they are at increased risk for infection," says the study's co-author, Akhil Sood, MD, an internal medicine resident in rheumatology at the University of Texas Medical Branch in Galveston. "We were interested to see if these patients are at an increased risk for COVID-19 infection. If they were to become infected, we wanted to know the severity of their clinical course. This can help us to determine whether it is safe to continue or hold immune therapies in setting of COVID-19 infection."

The researchers systematically searched PubMed/Medline and Scopus to identify relevant studies from January to June 2020 that reported the outcomes of COVID-19 among patients with rheumatic disease. They extracted demographic information and patients' use of biologics or targeted therapy with Janus kinase (JAK) inhibitors. They measured the following COVID-19 outcomes: hospitalization, admission to an ICU and death. Based on their clinical symptoms, patients were split into two groups: severe, or having increased risk of respiratory failure or life-threatening complications or non-severe.

The final review included 6,095 patients with rheumatic diseases from eight observational cohort studies, with 28% having rheumatoid arthritis (RA) and 7% having psoriatic arthritis (PsA). Of the 6,095 patients, only 123 or 2% were positive or highly suspicious for COVID-19. Across all the studies used for the review, 68% of COVID-19 patients were taking biologics, with 31% taking anti-TNF drugs and 6% taking JAK inhibitors. Among those patients who were infected with the coronavirus, 91 or 73% were never hospitalized. Thirteen patients who were hospitalized required admission to an ICU and four patients died.

"In our analysis, there was a small number of patients on biologic and targeted therapies to make definite conclusions on whether to continue or hold therapies," says Dr. Sood. "We are waiting for additional extensive studies that include more patients with rheumatic disease on biologic and targeted therapies. Another area of interest for us is examining risk factors for severe COVID-19 infection in patients with rheumatic disease. We hope this can help us identify which patients to closely monitor and possibly develop precautions to mitigate their risk."

ATLANTA -- New research presented at ACR Convergence, the American College Rheumatology's annual meeting, showed that patients with rheumatic diseases whose infliximab treatment was individually assessed and adjusted with a new strategy called therapeutic drug monitoring did not achieve remission at higher rates compared to those who received standard care. (ABSTRACT #2029)

Tumor necrosis factor inhibitors (TNFi) are drugs approved for treatment of rheumatoid arthritis, psoriatic arthritis and other inflammatory conditions. They are part of a class of drugs called biologic disease-modifying anti-rheumatic drugs, or biologics. TNFi drugs may help patients lower their disease activity, relieve debilitating symptoms, and manage their condition long term.

Some patients experience a lack or loss of response to TNFi, possibly due to low serum drug levels and or the formation of anti-drug antibodies. Therapeutic drug monitoring is one proposed strategy to prevent loss of response and to optimize TNFi effectiveness. It is an individualized strategy that includes regular assessments of a patient's serum drug levels. This personalized monitoring can be time-consuming and costly, and it is unclear whether it actually improves clinical outcomes. To learn more, researchers in Norway launched the first open-label, multi-center, randomized, controlled trial to assess its effectiveness in achieving remission in patients with several inflammatory diseases.

"Based on observational data showing associations between serum drug levels and effectiveness, we believed that individual treatment, with optimizing drug levels and early identification of anti-drug antibodies, would optimize the efficacy, safety and cost effectiveness of TNFi therapy," says the study's principal author, Silje Watterdal Syversen, MD, PhD, a rheumatologist at Diakonhjemmet Hospital in Oslo, Norway.

Adults with rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, ulcerative colitis, Crohn's disease and psoriasis who were starting infliximab therapy were recruited for the study. Patients were randomly assigned to receive infliximab either with or without therapeutic drug monitoring. They were examined at each infusion visit. The study's primary endpoint was remission at week 30. The study included 411 patients from 21 medical centers between January 2017 and December 2018: 80 with rheumatoid arthritis, 42 with psoriatic arthritis, 117 with spondyloarthritis, 80 with ulcerative colitis, 57 with Crohn's, and 22 with psoriasis. The researchers included 198 patients in the therapeutic drug monitoring arm and 200 patients were included in the control group. Researchers also recorded any adverse events the patients experienced, such as infections or infusion reactions.

According to their results, therapeutic drug monitoring was not superior to standard treatment for achieving disease remission at 30 weeks in people with a range of rheumatic diseases. In the study's therapeutic drug monitoring arm, 100 or 53% of patients achieved remission, while 106 or 54% of the patients in the standard treatment group also achieved remission. The study also found that 10% of patients who had therapeutic drug monitoring and 15% of patients receiving standard treatment developed significant levels of anti-drug antibodies. Adverse events were similar for both treatment groups as well, but infusion reactions were less frequent in patients who received therapeutic drug monitoring.

"Our study does not support therapeutic drug monitoring be applied as a general treatment strategy during induction of infliximab. Despite a lack of clinical trial data and diverging guidelines, proactive therapeutic drug monitoring has already been adopted in clinical practice across different specialities. This study highlights the need for thorough evaluation of monitoring tools and treatment strategies before their implementation in clinical care," says Dr. Syversen. "We feel that our results put to rest a long-standing debate on the merits of using therapeutic drug monitoring in all patients starting TNFi."

Future research should explore if more targeted applications of therapeutic drug monitoring, such as assessment of serum drug levels in treatment failures, could be a useful clinical tool, she adds.

ATLANTA -- New research presented at ACR Convergence, the American College of Rheumatology's annual meeting, identified key clinical features of chronic nonbacterial osteomyelitis (CNO), which leads to an important step toward the development of much-needed classification criteria for a disease that affects children and young adults worldwide (ABSTRACT #1162).

Chronic nonbacterial osteomyelitis (CNO), also called chronic recurrent multifocal osteomyelitis (CRMO), is a disease that mostly affects children and young adults. Hallmark symptoms include painful swelling of the bones, especially the long bones, but also the pelvis, clavicle and spine.

Currently, there are no classification criteria for CNO. That means rheumatologists, pediatricians and other physicians lack widely accepted sets of defining features of the disease to identify patients for clinical trials and research studies. There are also no validated diagnostic criteria for CNO, which are sets of key disease features used to diagnose these young patients. In this new study, researchers set out to refine the potential items that could be part of classification criteria for pediatric patients with CNO. To do that, they conducted a study that compared clinical, laboratory and imaging features of CNO to features of other diseases that mimic it.

"There is no specific confirmatory test for CNO, and many children need a bone biopsy to exclude cancer and infection," says study co-author Yongdong Zhao, MD, PhD, RhMSUS, Assistant Professor and Director of Ultrasound at Seattle Children's Hospital and its Center for Clinical and Translational Research. "A sensitive and specific classification criteria set will enable researchers to identify appropriate patients to carry out high-quality clinical trials, which physicians with less experience in this potentially debilitating disease need to determine effective treatments."

For this international study, researchers collected clinical and investigational features of CNO from 450 patient cases from 20 medical centers across four continents and seven countries. They also gathered cases of patients who had likely "mimickers" of CNO. All patients included in the study had at least 12 months of medical follow-up unless pathology or labs in mimicker cases confirmed the diagnosis.

They reviewed each patient's case to determine how confident they were that the patient either had CNO or one of its mimicker diseases. The confidence levels used in the study had a cut-off measurement of +/- 2 for "moderately confident." They used 264 CNO and 145 mimicker control cases for the analysis.

When comparing to patients with mimicker conditions, they found a higher percentage of female patients with CNO. They also found that patients with CNO often have intermittent versus continued pain, especially in the neck, back and upper torso, and less commonly have fevers. Another common feature of CNO was swelling of the clavicle, while active arthritis was a less common feature. CNO patients also commonly undergo whole body imaging tests, usually MRIs. Imaging helps to identify other common features of CNO, the study showed.

CNO patients commonly have symmetric patterns of bone lesions, and their disease frequently involves these bones: the thoracic spine, clavicle, pelvis, bilateral femur, bilateral tibia, unilateral fibula and feet. Imaging data collected in the study also showed that signs of malignancy and infection, such as cortical bone disruption, disorganized bone formation, mass structure, marrow infiltrates, and abscess or geographic appearances, are less common in patients with CNO. The study also found that completed and sustained responses to antibiotics are less frequent in young people with CNO.

Using actual patient cases, the study successfully identified key features of CNO that could support the development of the much-needed classification criteria for this disease, the researchers said.

"These results confirmed important features that physicians can look for to distinguish CNO from its mimicker diseases in daily practice using a large international database," says Dr. Zhao. "The next step is to determine the appropriate weight of each criterion by an expert panel using 1000MINDs. A threshold will be set for the new criteria, and another cohort of patients will be used to validate the set. We welcome more collaborators to join us for the collection of a validation cohort."

Nearly half of pregnancies in the U.S. are unplanned, and there's a wide gap between the most affluent women who are likely to have access to the most reliable forms of birth control and those from lower income households.

But removing out-of-pocket costs for contraception may help reduce the income-related disparities that play such a significant role in unintended pregnancies, a new Michigan Medicine-led study suggests.

The Affordable Care Act's elimination of cost-sharing for birth control was associated with more consistent contraceptive use and a decrease in birth rates among all income groups, according to the research in JAMA Network Open.

But the most prominent decline was seen among people from the lowest income group, which saw a 22 % drop in births from before and after the law's implementation.

"Our findings suggest that expanded coverage of prescription contraception may be associated with a reduction in income-related disparities in unintended pregnancy rates," says lead author Vanessa Dalton, M.D., M.P.H., obstetrician gynecologist at Michigan Medicine Von Voigtlander Women's Hospital and researcher with the University of Michigan Institute for Healthcare Policy and Innovation.

"Reducing unintended pregnancies improves the health of women, families and society."

The ACA included contraception on its list of preventative services that most employer-sponsored insurance plans were required to provide without cost-sharing. This meant that many women had access to birth control, including the most reliable long-acting forms like intrauterine devices, without out-of-pocket costs like copayments or deductible payments.

Michigan researchers examined birth rates by income among 4.6 million women ages 15-45 covered by employer-sponsored health plans before the ACA's elimination of cost sharing (2008-2013) and after (2014-2018).

In addition to lower birth rates, authors also reported a decrease in annual rates of women not filling a prescription method of contraception after 2014. The two lowest household income groups experienced a more rapid decrease than the higher income group.

The findings are consistent with previous studies showing that removing out-of-pocket costs for contraception is associated with increased consistent use of the most effective methods to prevent unplanned pregnancies, Dalton says.

"Contraception is a clinically efficient and cost effective strategy for reducing unintended pregnancy and helping individuals meet their reproductive life goals," says Dalton, who is also the director of the U-M Program on Women's Healthcare Effectiveness Research (PWHER.)

"Policies that eliminate cost sharing for contraception will help us achieve our clinical goals of ensuring that all families can decide whether and when to have children.

This policy particularly benefits people with low incomes who may be more deterred by birth control prices and may have also had less comprehensive insurance coverage before the ACA."

Unplanned pregnancies are associated with delayed prenatal care, reduced likelihood of breastfeeding, maternal depression, and higher maternal and infant mortality rates, Dalton notes.

"Mistimed births have serious, long term, life opportunity consequences for women and children," Dalton says.

They have a societal cost too, including an estimated $5 billion per year in direct and indirect costs for the U.S. health care system. In 2011, 42 % of unintended pregnancies (excluding miscarriages) ended in abortion and two thirds of unplanned births were funded by public insurance programs such as Medicaid.

Authors note that recent court decision, including the 2020 Supreme Court decision upholding rules that expand exceptions from the contraceptive requirement could roll back improvement in access for some women.

"Removing cost related barriers for birth control may not eliminate unintended pregnancies, but it's a critical part of the strategy to address this important public health concern in the U.S.," Dalton says.