Posted on Rheumatoid arthritis

Hydroxychloroquine Not Linked to Longer Heart Rhythm Intervals in Rheumatoid Arthritis or Lupus Patients

Heart attack

 

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.”

Posted on Patient Talk

New insights into pregnancy and early signs of MS

Autism and Pregnancy
MS and Pregnancy

Women with MS often report fewer symptoms during pregnancy. But studies exploring whether becoming pregnant or having children affects whether or when someone develops MS have so far been inconclusive. Now, the biggest study yet suggests pregnancy may be linked to a delay in experiencing one of the early signs of MS.

MS and clinically-isolated syndrome (CIS)

The new study, from Australia and the Czech Republic, suggests pregnancy is associated with a 3 year delay to the onset of clinically-isolated syndrome (CIS). 

CIS is a first episode of neurological conditions that lasts at least 24 hours. It’s caused by the loss of the myelin coat that surround nerves. It is often the first stage in a diagnosis of MS, but some people never go on to experience further symptoms or develop MS.

What happened in the study?

The researchers analysed data from 2557 women who were all signed up to MS Base – a large database with information from people with MS and MS clinics. All the women in this study had MS and had previously been diagnosed with CIS. The researchers then looked back at when they developed CIS and whether they had ever been pregnant.

They found women who had been pregnant were diagnosed with CIS, on average, just over three years later than women who had never been pregnant. The researchers didn’t find a link between the number of times women had been pregnant and the time of CIS onset.

What does this mean for people with MS who are thinking about having children?

MS affects over 130,000 of us in the UK, with women ‘of reproductive age’ almost three times more likely to be diagnosed. So there are often lots of questions around family planning.

The authors are clear they aren’t claiming that being pregnant actually causes a delay in the onset of CIS. The study shows only an association between the two.

What’s more, the study looked at the link between pregnancy and onset of CIS, not MS itself. The researchers specifically chose to look at CIS so they could be more confident that the onset of symptoms was linked to pregnancy and not to other factors. For example we know that some people may change their behaviour after being diagnosed with CIS, for example by starting to take a DMT.

MS is different for everyone. And women with and without MS choose not to become pregnant for many reasons.

New avenues for MS treatments

Dr Emma Gray, our Assistant Director of Research, says: “The reasons for pregnancy’s positive effect are not fully understood, but it’s thought the answer lies in our immune system – which misbehaves in MS, but is dampened during pregnancy.

“We want to slow, stop and eventually prevent MS, and these findings could help us with that goal. If we can figure out the mechanisms underlying this apparent protective effect of pregnancy, it could lead to new avenues for treatment.”

More research is needed

We don’t fully understand why pregnancy seems to play a protective role in MS but researchers think it could be to do with the hormones oestrogen and progesterone. During pregnancy, the levels of these hormones change dramatically, which may impact the immune system.

We now need further research to understand the link between MS, pregnancy and hormone levels. Large registry studies involving data from thousands of people with MS – like MS Base and the UK’s MS Register – are one way to help us build this picture.

Posted on Diabetes

Research takes early step towards drug to treat common diabetes complication hypoglycaemia

Diabetes hypos | What does hypoglycaemia Feel Like? | Diabetes UK - YouTube

New research has taken an important step towards the goal for a treatment for the common diabetes complication hypoglycaemia, or low blood sugar.

In all forms of diabetes, blood sugars become too high as the body is either unable to produce insulin, or cannot make enough of it, or the insulin it produces is not effective. This means people with diabetes have to manage their blood sugar levels themselves, and these levels can commonly become dangerously high (hyperglycaemia) or low (hypoglycaemia).

Episodes of hypoglycaemia, also known as “hypos” often occur at night, disrupting sleep and sometimes causing seizures. Hypoglycaemia cause unpleasant symptoms such as anxiety, palpitations, sweating and hunger. If extreme, they can also cause dizziness, confusion, loss of consciousness and, if untreated, coma and even death.

Now, research published in Frontiers in Endocrinology led by the University of Exeter, working with Rigel Pharmaceuticals, found a way help to defend against hypoglycaemia by boosting hormonal defence systems. The team believes they have identified a promising target in the brain could be useful for future drug development to create an anti-hypoglycaemia drug.

The researchers, funded by JDRF and supported by Diabetes UK, conducted laboratory experiments using a pre-clinical test compound (R481), that acts a little like metformin, a widely used type 2 diabetes drug. However, R481 works differently because it enters the brain and switches on an important brain fuel gauge called AMPK (AMP-activated protein kinase).

Lead study author Dr Ana Cruz, of the University of Exeter, said: “Our work highlights the importance of better understanding the brain-pancreas communication to boost the body’s defences against hypoglycaemia. I see the daily emotional and physical impact hypoglycaemia can have and believe that these findings have taken us one step closer to finding targets within this brain-pancreas network to attenuate the impact of hypoglycaemia.” 

The researchers conducted experiments on specialised brain glucose-sensing neurons (GT1-7 cells) in petri dishes, and found that the compound works by activating this brain fuel gauge.

They then found that in healthy rats, the drug boosts the hormonal defence against hypoglycaemia, by increasing the release of a hormone called glucagon from the pancreas. The drug switched on a brain-pancreas link to defend against hypoglycaemia, yet did not change fasting blood sugar levels.

Senior study author Dr Craig Beall, of the University of Exeter, said: “Our findings suggest that switching on the brain fuel gauge we’ve identified could be useful for preventing hypoglycaemia. In the long term, our aim is to create a pill that could be swallowed before bed, to prevent night time hypos. This is just the first step in a long road, and we hope one day we may be able to give some peace of mind to people with diabetes and parents of children with diabetes that they won’t have a bad night time hypo.”

Dr Lucy Chambers, Head of Research Communications at Diabetes UK, which supported the study, said: “This early stage research, funded by Diabetes UK has uncovered important links between the brain and the pancreas, that could in future lead to new treatments to help people with diabetes avoid hypos, or bring back their ability to recognise signs of low blood sugars.

“Hypos and hypo unawareness can be dangerous and debilitating, and can have a huge impact on the daily lives of people living with all types of diabetes. New treatments for treating hypos, or hypo unawareness would make living with diabetes much easier – reducing anxieties and crucially protecting people from the serious consequences that hypos can have.”

Conor McKeever, Research Communications Manager at type 1 diabetes charity JDRF, said: “Hypoglycaemia is one of the things people with type 1 report fearing most about their condition, so a treatment to prevent hypos would go a long way to relieving some of the burden that comes with living with type 1.

“It could also help reduce the worry felt by family members, who tell us they regularly lose sleep for fear that their loved one will have a hypo in the night.

“We’re proud to have funded this research and are keen to see how it develops on the road towards a new treatment for the 400,000 people living with type 1 in the UK.”

Evidence suggests the 400,000 people with type 1 diabetes in the UK experience an average of two episodes of hypoglycaemia per week and one severe episode per year.  People with type 2 diabetes experience up to five episodes of hypoglycaemia per year. Although the frequency is lower in type 2 diabetes, the overall rate is higher, because the condition affects well over 4 million people in the UK.

The researchers have published the structure of the compounds in their paper, entitled ‘Brain permeable AMP-activated protein kinase activator R481 raises glycaemia by autonomic nervous system activation and amplifies the counter regulatory response to hypoglycaemia in rats’ It is published in Frontiers in Endocrinology.

Posted on Multiple Sclerosis

Pilot study of exercise and cognition in progressive multiple sclerosis highlights need to assess outcomes of randomized controlled trials

Brian M. Sandroff, PhD


Dr. Sandroff is senior research scientist in the Center for Neuropsychology and Neuroscience at Kessler Foundation, and director of the Exercise Neurorehabilitation Research Laboratory. CREDIT Kessler Foundation

An international team ofmultiple sclerosis (MS) experts reported lack of association between cognition and physical activity and cardiorespiratory fitness in a large sample of individuals with progressive MS. These findings have important implications for studies involving exercise interventions aimed at treating the cognitive effects of MS. The article, titled, “Cardiorespiratory fitness and free-living physical activity are not associated with cognition in persons with progressive multiple sclerosis: Baseline analyses from the CogEx study,” was published in Multiple Sclerosis Journal on October 1, 2021, doi: 10.1177/13524585211048397. The authors represent Canada, the United States, Italy, the UK, Denmark, and Belgium.

Article link: https://pubmed.ncbi.nlm.nih.gov/34595972/

The effects of exercise interventions on cognition are a focus of rehabilitation research in conditions associated with deficits and decline in cognition. Cognitive benefits of aerobic exercise have been reported in relapsing-remitting (non-progressive) MS and in age-related cognitive decline. One small pilot study conducted in progressive MS found an association between aerobic ergometer exercise and cardiovascular fitness, alertness, and verbal memory.

To examine these associations, the authors analyzed baseline data from the CogEx study, a multi-national, multi-arm, randomized, blinded, sham-controlled trial looking at the effects of cognitive rehabilitation and aerobic exercise training on cognition and neuroimaging findings in 240 individuals with progressive MS. They measured cardiorespiratory fitness, free-living moderate-to-vigorous physical activity, and cognitive performance.

“Neither cardiorespiratory fitness nor free living physical activity correlated with cognitive performance in this study sample,” said lead author Brian Sandroff, PhD, senior research scientist in the Center for Neuropsychology and Neuroscience Research at Kessler Foundation. “This suggests that other mechanisms of action may mediate the potential effects of aerobic training on cognition in this population. The neuroimaging data collected in this trial may help clarify these underlying mechanisms.”  

The findings have important implications for randomized controlled trials in progressive MS. “It’s clear that we need to carefully assess the outcome measures for studies of exercise and cognition in this population,” added co-author John DeLuca, PhD, Senior Vice President for Research and Training at Kessler Foundation. “Improving cognition and brain health is essential to maintaining quality of life for people with progressive MS. To achieve that, we need to expand our investigation of how exercise affects brain function.”

Posted on Autism

Study finds few pediatric providers discuss transportation with their autistic patients Is this true for you?

BUS ART | Colourful Beautiful Bus | Indian Pakistani Decorated Bus - YouTube


A collaborative study from the Center for Injury Research and Prevention (CIRP) and the Center for Autism Research (CAR) at Children’s Hospital of Philadelphia (CHOP) found that only 8% of pediatric healthcare and behavioral service providers feel prepared to assess whether their autistic patients are ready to drive. These findings, recently published in the Journal of Autism and Developmental Disorders, suggest a critical need to develop resources that prepare providers and others who work with autistic youth to effectively facilitate independence and mobility as their patients become adults.

This study is part of a body of research that aims to understand the transportation needs of autistic adolescents. Prior studies have examined how individualized training, parental support, and driving patterns contribute to safe driving. Other studies have found that, whether autistic adolescents decide to drive or not, being able to get where they want to go on their own improves psychosocial, health and employment outcomes. While making decisions about transportation, families of both autistic and non-autistic youth seek guidance from their child’s pediatric healthcare and behavioral service providers. However, little is known about these conversations or how providers approach these topics with patients.

The researchers surveyed a total of 78 providers who care for both autistic and non-autistic patients in March and April of 2019. Most providers were attending pediatric physicians and psychologists located in Pennsylvania and New Jersey. Half reported they had general transportation-related discussions with their non-autistic patients, while only 1 in 5 had these conversations with their autistic patients. When discussing driving, 33% of providers believed they could assess if their non-autistic patients were ready to drive, while only 8% believed they could do so for their autistic patients.

“It was also surprising to learn that only 1 in 4 providers refer their patients, autistic or not, to other providers for driving-related issues,” says Emma Sartin, PhD, MPH, lead author and a postdoctoral fellow at CIRP. “Our next steps will be to start developing resources and tools so that families, and the professionals who support them, are not left largely on their own to make or guide important decisions about driving.”

A lack of guidance for families on how to navigate transportation decisions could be critical, as previous CHOP research found that two-thirds of 15- to 18-year-old autistic adolescents without intellectual disability are currently driving or planning to drive, and 1 in 3 autistic individuals without intellectual disability get licensed by age 21. Other recent research conducted at CHOP found that newly licensed young autistic drivers have similar to lower crash rates than their non-autistic peers, suggesting those who do become licensed are generally safe drivers. Additionally, young autistic drivers are much less likely to have their license suspended or to receive a traffic violation than their non-autistic peers.

“One important way that providers can help autistic teens and their families is to start talking about driving and transportation before they get to high school,” says Benjamin E. Yerys, PhD, study author and a clinical psychologist at CAR. “We know this seems early, but it provides more time for them to benefit from supports, including those services that come from outside of healthcare, including tailored instruction from a driving rehabilitation specialist.”

Resources for families to help their autistic teens transition to adulthood are available at the Center for Autism Research at CHOP and TeenDriverSource.org.

This research was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the National Institutes of Health Awards R01HD079398 and R01HD096221.

Sartin et al, “Brief Report: Healthcare Providers’ Discussions Regarding Transportation and Driving with Autistic and Non-autistic Patients.” J Autism Dev Disord. Online December 1, 2021.DOI: 10.1007/s10803-021-05372-3