Injected ‘Hydrogel’ May Be New Option Against Back Pain

Dennis Thompson wrote . . . . . . . . .

Like fixing a flat on the roadside, a new injectable hydrogel is showing promise as a remedy for worn-down spinal discs — pumping them back up and relieving chronic back pain.

The gel, with the brand name Hydrafil, is injected directly into worn discs using X-rays to guide the needle, said lead researcher Dr. Douglas Beall, chief of radiology services at Clinical Radiology of Oklahoma in Edmond. As outlined in a pilot study,. the gel fills in cracks and tears in the spinal disc, adhering to the disc’s center and outer layer.

“It goes in as a heated liquid that cools off and becomes kind of the consistency of a medium hard eraser,” Beall said. “It creates kind of a Fix-a-Flat, filling the disc back up and returning the biomechanical integrity of the disc.”

Twenty patients treated with the gel experienced a 67% reduction in their back pain during a one-year follow-up, Beall said.

The patients also experienced an 85% improvement in disability caused by their back pain. Beall said the gel caused no harmful reactions in any of the patients.

The bones in your spinal column — the vertebrae — are separated by rubbery cushions called spinal discs. These discs act as shock absorbers, preventing the vertebrae from rubbing together and allowing you to move, bend and twist comfortably.

Degenerative disc disease occurs as people age. Spinal discs tend to dry out and wear away over time. They also can be torn or injured as a result of daily activities or sports.

By Beall’s estimates, as many two-thirds of people with back pain caused by degenerative disc disease could be considered candidates for this hydrogel therapy.

He is scheduled to present these findings Sunday in Boston at a meeting of the Society of Interventional Radiology. Findings presented at meetings are considered preliminary until published in a peer-reviewed journal.

Hydrafil was designated as a breakthrough device in 2020 by the U.S. Food and Drug Administration, which allows expedited review when evidence suggests an experimental product could provide more effective treatment for a serious condition compared to current options, researchers said.

Other hydrogels already are being used to treat injured or worn discs, but those products are inserted surgically as a soft solid, “which can pop out of place if you’re not highly skilled in placing it,” Beall said.

“Because this gel is injectable, it requires no incision, and it augments the whole disc, restoring its structural integrity, which nothing we have currently can do,” he said.

Dr. J. David Prologo, an interventional radiologist at Emory University School of Medicine in Atlanta, reacted to the findings.

“The impact of this study I don’t think can be overstated — degenerated disc disease is a condition that affects hundreds of millions of people worldwide, for which there is really no definitive treatment other than a big surgery, with all of the associated costs and risks,” he said.

“Dr. Beall is spearheading the ability to literally inject a liquid replacement to the disc using only a needle and image guidance, removing the needle after the injection and sending the patient home with a replaced disc and Band-Aid over the puncture site,” said Prologo, who chairs the Society for Interventional Radiology’s Pain Management/MSK Clinical Specialty Council.

Dr. Alan Hilibrand, co-director of spinal surgery at the Rothman Orthopaedic Institute in Philadelphia, agreed.

Disc repairs conducted via injection are “almost like the holy grail of treatment for back problems,” he said.

Hilibrand noted that other research groups are trying to repair discs by injecting growth factors or biologic agents intended to promote regrowth of healthy disc material.

These new results come from what Beall characterized as an early feasibility trial, which was conducted among 20 patients ages 22 to 69 in Colombia. All had chronic low back pain due to degenerative disc disease.

A pilot trial involving more patients is underway in Canada, and based on those results a full-scale clinical trial will be conducted in the United States.

The hydrogel therapy is new, but relies on existing techniques and skills regularly used by interventional radiologists, surgeons and other specialists, Beall and Prologo said.

“Interventional radiologists already embody the skillset to perform this procedure,” Prologo said. “Widespread dissemination should follow FDA approval and U.S. studies reproducing its effectiveness. The cost will be many multiples less than an open surgical alternative.”

One major question remains, and should be answered by the full clinical trial: How long will the hydrogel last in a repaired disc?

Beall said Hydrafil has been subjected to a “repetitive stress simulation that simulates 90 years of stress and strain, so hopefully this will be a forever fix.”

But that will need to be demonstrated in actual humans over time, Hilibrand said.

Trials will need to show that the gel “can be maintained in the disc and doesn’t wear out or leak out over time,” he said.

“If something lasts for six months or even 12 months, I don’t think that we as a society can afford to pay for that,” Hilibrand said. “It may not be very cost-effective if it only lasts for a short period of time.”

ReGelTec Inc. is the company that developed Hydrafil, and paid for this early feasibility study, Beall said. Beall is a medical adviser to the company.

Source: HealthDay

Common Prostate Cancer Medications May be Less Safe Than Previously Thought

Men taking either of the two most common oral medications for advanced prostate cancer who had also undergone hormone therapy to treat their disease were at higher risk of serious metabolic or cardiovascular issues than patients who were only receiving hormone therapy, Michigan Medicine researchers found.

Patients taking abiraterone had 1.77 times the risk of being admitted to the emergency room or the hospital due to diabetes, hypertension or heart disease compared to those who were only on hormone therapy. Those receiving enzalutamide were at 1.22 times the risk of these issues.

Compared to patients not receiving abiraterone, those taking abiraterone were also more likely to need an outpatient visit with their physician related to at least one of these health conditions. That was not the case if the man was taking enzalutamide.

Abiraterone and enzalutamide were both found to be relatively safe in clinical trials, but concerns that the population of patients who participated in the trials was different than those in real-life settings prompted the researchers to take another look at the effects of the drugs.

For instance, this research exclusively analyzed patients with Medicare health insurance, and the majority of men studied were significantly older than those in the drugs’ clinical trials.

“Patients enrolled in clinical trials tend to be highly selected and often times do not reflect the patient population in day-to-day practice,” said Lillian Y. Lai, M.D., M.S., a National Institutes of Health T32 Urologic Oncology Research Fellow at Michigan Medicine and the first author of the study. “Trial participants also undergo stringent safety evaluations that some of our patients do not have access to. By studying adverse events in real-life settings, we can better understand the risks of these life-prolonging cancer treatments and help clinicians and patients make informed decisions regarding treatment.”

Since metabolic and cardiovascular conditions tend to be under the purview of primary care providers, Lai and her fellow authors recommend team-based care that involves PCPs for patients with advanced prostate cancer as a way to manage these higher risks.

“With continued expansion of the indications for abiraterone and enzalutamide to earlier stages of the disease, increasing numbers of men will be receiving these therapies for longer periods of time,” Lai said. “This will potentially amplify the scope of men affected and increase the magnitude of the risks of adverse events, making careful attention to management of these issues crucial.”

Source: University of Michigan

Lifestyle Changes, Meds Effective to Prevent or Delay Type 2 Diabetes; No Change in CVD

A lifestyle intervention program of increased physical activity, healthy eating and aiming for weight loss of 7% or more, or taking the medication metformin were effective long-term to delay or prevent Type 2 diabetes in adults with prediabetes. Neither approach, however, reduced the risk of cardiovascular disease for study participants over 21 years of the study, according to the findings of the multicenter Diabetes Prevention Program Outcomes Study (DPPOS), published today in the American Heart Association’s flagship, peer-reviewed journal Circulation.

Type 2 diabetes (T2D) is the most common form of diabetes, affecting more than 34 million people in the U.S., representing nearly 11% of the U.S. population, according to the U.S. Centers for Disease Control and Prevention’s 2020 National Diabetes Statistics Report, and cardiovascular disease (CVD) is the leading cause of death and disability among people with T2D. Type 2 diabetes occurs when the body is unable to efficiently use the insulin it makes and the pancreas is unable to produce sufficient amounts of insulin. Adults with T2D are twice as likely to die from CVD — including heart attack, stroke or heart failure — compared to adults who do not have T2D. People with T2D often have other cardiovascular disease risk factors, including being overweight or having obesity, high blood pressure or high cholesterol.

The DPPOS evaluated 21-years of follow-up (through 2019) for the 3,234 adults who participated in the original, 3-year Diabetes Prevention Program (DPP) trial. This analysis of the DPPOS was focused on determining whether the medication metformin or lifestyle intervention might reduce the risk of cardiovascular disease or the rate of major cardiac events such as heart attack, stroke or death due to cardiovascular disease.

“The risk of cardiovascular disease in people with prediabetes is increased, and CVD risk further increases over time after Type 2 diabetes develops and progresses,” said Ronald B. Goldberg, M.D., chair of the writing group for the DPPOS and a professor of medicine, biochemistry and molecular biology in the division of diabetes, endocrinology and metabolism, and senior faculty member and co-director of the Diabetes Research Institute Clinical Laboratory at the University of Miami’s Miller School of Medicine in Miami, Florida. “We were focused on assessing the impact of lifestyle or metformin interventions for prevention of Type 2 diabetes in people with prediabetes to reduce cardiovascular disease.”

The DPP was a landmark, 27-center randomized trial across the U.S. from 1996-2001 to assess how to prevent or delay the onset of T2D in people with prediabetes. Study participants were screened and accepted in the DPP based upon these criteria: initially, a 2-hour glucose reading of 140-199 mg/dL on an oral glucose tolerance test; fasting glucose levels of 95-125 mg/dL; and body mass index of 24 kg/m2 or higher.

A racially diverse group of 3,234 adults were studied in the original DPP for almost three years. The participants were an average age of 51 years, and nearly 70% of the participants were women. People in the intensive lifestyle intervention group (nutritional improvement and physical activity aimed at achieving a weight loss of 7%) reduced the incidence of developing T2D by 58%, and participants who took twice daily doses of metformin had a reduced incidence of 31% for T2D, when compared to people in the placebo group who received standard care, which included information about effective treatment and management of T2D at the time of diagnosis.

The DPPOS began in 2002 and was open to all participants in the original DPP trial. The DPPOS enrolled almost 90% of the original study participants for up to 25 years of follow-up to assess the long-term impact of the interventions on the development of T2D and its complications. Due to the success of the lifestyle intervention, everyone in the study was offered enrollment in the lifestyle intervention through a group format during a one-year bridge period. The group who took metformin in the original DPP trial were able to continue take the medication during the DPPOS, and they were aware that they were taking metformin not the placebo. (The metformin and placebo groups were blinded in the original DPP, so participants did not know whether they were taking metformin or placebo during that time period.)

“From the beginning of the Diabetes Prevention Program, we were primarily interested in whether prevention of diabetes would lead to a reduction in the development of the complications that are caused by Type 2 diabetes — cardiovascular disease, kidney disease, retinopathy and neuropathy,” said Goldberg. “Managing blood glucose levels is important, and we encourage interventions to prevent the long-term complications of Type 2 diabetes.”

The DPPOS assessed cardiovascular disease outcomes in order to determine the effects of lifestyle and metformin interventions on participants’ risk of having a non-fatal heart attack, stroke or death due to a cardiovascular occurrence, by comparing outcomes of each intervention group to the placebo group. Researchers reported results based on a median follow-up of 21 years, which included the average three-year follow-up period of the original DPP trial. The authors conducted a futility analysis of the cardiovascular outcomes, which resulted in ending the study prior to completing the planned 25-year follow-up.

Throughout the entire study, participants were screened annually with electrocardiogram testing; measures of their cardiovascular disease risk factors, including smoking, cholesterol levels and blood pressure levels; and body mass index measurements. The percentage of all participants taking blood pressure and cholesterol lowering medications increased over the duration of the study and was slightly lower among the participants in the lifestyle group versus the other two groups.

After an average 21 years of follow-up, researchers found no significant differences in the incidence of heart attacks, stroke or cardiovascular death among the three intervention groups. Specifically, the analysis found:

  • There was a continued reduction or delay in the development of T2D for up to 15 years.
  • The number of non-fatal heart attacks across each group was similar: 35 heart attacks occurred in the lifestyle intervention group; 46 in the metformin group; and 43 in the placebo group.
  • Similarities were also found in the number of non-fatal strokes: 39 incidences of stroke in the lifestyle intervention group; 16 in the metformin-only group; and 28 in the placebo group.
  • The number of deaths due to cardiovascular occurrences were low: 37 deaths among the lifestyle intervention participants; 39 in the metformin group; and 27 in the participants who took the placebo during the original DPP trial.

“The fact that neither a lifestyle intervention program nor metformin led to a decrease in cardiovascular disease among people with prediabetes may mean that these interventions have limited or no effectiveness in preventing cardiovascular disease, even though they are highly effective in preventing or delaying the development of Type 2 diabetes,” said Goldberg. “It’s important to note that most study participants also received treatment with cholesterol and blood pressure medications, which are known to reduce CVD risk. Therefore, the low rate of development of cardiovascular disease found overall may have been due to these medications, which would make it difficult to identify a beneficial effect of lifestyle or metformin intervention. Future research to identify higher risk subgroups is needed to develop a more targeted approach to cardiovascular disease prevention in people with prediabetes and Type 2 diabetes.”

There were several limitations to the study. The researchers selected a subgroup of people who met the criteria for prediabetes, however, these results are not generalizable to everyone with prediabetes. Additionally, the intensity of the lifestyle intervention was reduced after the initial DPP phase, and, over the 21-year study period, there was a gradual reduction in medication adherence by participants in the metformin group. There was also out-of-study metformin use in patients who were diagnosed with Type 2 diabetes, which may have diluted differences among the study groups. The high level of blood pressure and cholesterol medications prescribed by the participants’ primary care team, as well as lower use of blood pressure medications in the lifestyle group, may have influenced results. There may have also been some under-estimation of cardiovascular events since some participants did not complete 21 years of follow-up.

”These long-term findings confirm the link between Type 2 diabetes and cardiovascular disease is complex and requires more research to understand it better,” said the American Heart Association’s Chief Medical Officer for Prevention Eduardo Sanchez, M.D., M.P.H., FAHA, FAAFP, and clinical lead for Know Diabetes by Heart, a collaborative initiative between the American Heart Association and the American Diabetes Association addressing the link between diabetes and cardiovascular disease. “However, these important results also tell us that lifestyle intervention is incredibly effective to delay or prevent Type 2 diabetes, which, itself, reduces the risk for cardiovascular disease. The CDC estimates nearly 1 of every 3 adults in the U.S. has prediabetes, therefore, preventing or delaying Type 2 diabetes is a public health imperative to help extend and improve the lives of millions of people.”

Source: American Heart Association

USPSTF: Do Not Start Low-Dose Aspirin to Prevent CVD in 60+

The U.S. Preventive Services Task Force (USPSTF) recommends that the decision to initiate low-dose aspirin for primary prevention of cardiovascular disease (CVD) events should be individualized among those aged 40 to 59 years and is not recommended for those aged 60 years or older. These recommendations form the basis of a final recommendation statement, published in the Journal of the American Medical Association.

Janelle M. Guirguis-Blake, M.D., from the Kaiser Permanente Evidence-based Practice Center in Portland, Oregon, and colleagues conducted a systematic review of the benefits and harms of aspirin in primary prevention of CVD. Data from 11 randomized controlled trials (134,470 participants) and one pilot trial (400 participants) were included in the quantitative synthesis. The researchers found a significant decrease in major CVD events in association with low-dose aspirin (odds ratio, 0.90). For individual CVD outcomes, the results were significant, with a similar magnitude of benefit. No significant reductions in CVD mortality or all-cause mortality were observed. Low-dose aspirin was associated with significant increases in total major bleeding (odds ratio, 1.44) and site-specific bleeding.

Based on these findings, the USPSTF concludes with moderate certainty that for adults aged 40 to 59 years with a 10 percent or greater 10-year CVD risk, aspirin use for primary prevention of CVD events has a small net benefit; consequently, the decision to initiate aspirin should be an individual one (C recommendation). For adults aged 60 years or older, initiating aspirin for primary prevention of CVD events has no net benefit (D recommendation).

“We want to emphasize that these recommendations are focused on starting aspirin to prevent a first heart attack or stroke,” USPSTF member John Wong, M.D., said in a statement.

Source: HealthDay

New USPSTF Guidance: Continue to Take Low-dose Aspirin If You Have a History of Heart Attack, AFib, Stroke or Vascular Stenting

Earlier, the U.S. Preventive Services Task Force (USPSTF) released its final recommendations on low-dose aspirin therapy for the primary prevention of cardiovascular disease in adults: people who have a history of heart attack, atrial fibrillation (AFib), stroke or vascular stenting should continue to take low-dose aspirin, as directed by their doctor. For people who have no history of cardiovascular disease or stroke, low-dose aspirin is not recommended for prevention of heart attack or stroke, particularly for adults with higher risk for bleeding. In consultation with their physician, select middle-aged adults may benefit from low-dose aspirin therapy if they are at high risk for heart attack or stroke due to risk factors such as smoking, hypertension, Type 2 diabetes, high cholesterol or significant family history. The USPTSF is an independent, volunteer panel of medical experts focused on improving the health of people nationwide by making evidence-based recommendations on effective ways to prevent disease and prolong life.

The following statement reflects the views of the American Heart Association/American Stroke Association.

According to the Association’s volunteer President Donald M. Lloyd-Jones, M.D., Sc.M., FAHA, “If you are already taking low-dose aspirin because you have had a heart attack, stroke or stenting or you have a history of AFib, continue to take it as directed by your physician; this new guidance about low-dose aspirin does not apply to your situation. Do not stop taking aspirin without first talking with your doctor.

“The new guidance revising the recommendations on the use of low-dose aspirin strictly applies to adults who have not had a cardiovascular event or any heart disease diagnosis: low-dose aspirin is not appropriate to prevent a first heart attack or stroke in most people. Due to the blood-thinning effects of aspirin, research continues to indicate that for most adults the risk of bleeding may be greater than the number of heart attacks or strokes actually prevented.

“We continue to urge clinicians to be extremely selective when prescribing aspirin for adults without known cardiovascular disease. For example, people with higher risk for gastric or intracerebral bleeding should not take aspirin to prevent a CV event. Aspirin should be limited to only those adults at the highest risk for cardiovascular disease due to the presence and severity of other risk factors, such as smoking, hypertension, Type 2 diabetes, high cholesterol or significant family history, who also have a very low risk of bleeding. Some recent evidence also indicates some people with higher coronary calcium scores, >100 units, indicating higher plaque burden and risk, may also benefit from aspirin therapy if they have no history of prior bleeding.”

Lloyd-Jones, also the chair of the department of preventive medicine and the Eileen M. Foell Professor of Heart Research and professor of preventive medicine, medicine and pediatrics at Northwestern University’s Feinberg School of Medicine in Chicago, stressed the importance of healthy choices for primary prevention of cardiovascular disease, “Various research studies over the past two decades indicate more than 80% of all cardiovascular events may be prevented by healthy lifestyle changes and management of known risk factors (like high blood pressure and adverse cholesterol levels) with medication when needed. Eating healthy foods and beverages, regular physical activity and not smoking are key. The scientific evidence continues to confirm healthy lifestyle habits and effectively managing blood pressure and cholesterol are the top ways to prevent a first heart attack or stroke, not low-dose aspirin. The new USPSTF guidance now aligns with American Heart Association’s 2019 primary prevention guideline. Consult with your doctor and health care team before making any changes in your medications.”

Source: American Heart Association