Tag: 6/7/23

Fluctuating Cholesterol and Triglyceride Levels Linked to Developing Dementia

Photo by Matteo Vistocco on Unsplash

Older people who have fluctuating levels of total cholesterol and triglycerides may have a higher risk of Alzheimer’s disease and related dementias compared to people who have steady levels, according to new research published online in Neurology. Since the study is observational, it cannot establish a causative link.

“Prevention strategies for Alzheimer’s and related dementias are urgently needed,” said study author Suzette J. Bielinski, PhD, of the Mayo Clinic in Rochester, Minnesota. “Routine screenings for cholesterol and triglyceride levels are commonly done as part of standard medical care. Fluctuations in these results over time could potentially help us identify who is at greater risk for dementia, help us understand mechanisms for the development of dementia and ultimately determine whether levelling out these fluctuations could play a role in reducing dementia risk.”

Researchers used health care data to identify 11 571 people age 60 or older without a prior diagnosis of Alzheimer’s disease or dementia. They assessed total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) for the participants on at least three different days in the five years before the start of the study. Then participants were assigned into five equal groups based on the degree of measurement fluctuation, from lowest to highest.

Participants were followed for an average of 13 years. During that time, 2473 of them developed Alzheimer’s disease or another form of dementia. After adjusting for confounding variables, researchers found for total cholesterol, participants in the highest fluctuation group had a 19% increased risk of dementia compared to those in the lowest group. Of the 2311 people in the highest group, 515 developed dementia compared to 483 of the 2311 people in the lowest group. For triglycerides, those in highest group had a 23% increased risk.

No link was found between dementia and variations in LDL and HDL, however.

“It remains unclear why and how fluctuating levels of cholesterol and triglycerides are related to the risk of Alzheimer’s disease,” said Bielinski. “Further studies looking at the changes over time for this relationship are needed in order to confirm our results and potentially consider preventative strategies.”

One study limitation was that researchers looked at Alzheimer’s disease and related dementias as a whole and did not differentiate between the types of dementia.

Source: American Academy of Neurology

Stimulant Drugs for Childhood ADHD not Linked to Later Substance Use

Photo by Annie Spratt on Unsplash

Children prescribed a stimulant to manage symptoms of attention deficit hyperactivity disorder (ADHD) do not have more substance use or substance use disorder (SUD) as adolescents or young adults, according to a new study appearing in JAMA Psychiatry.

The study’s findings may provide some reassurance to parents and clinicians who may be hesitant to prescribe ADHD stimulant medications out of fear that this may result in future substance abuse.

“Stimulants are the first-line treatment recommended for most individuals with ADHD – the drug class is an evidence-based treatment with few side effects,” said Brooke Molina, PhD, professor of psychiatry, psychology and paediatrics at University of Pittsburgh. “Because stimulant medications are classified by the Drug Enforcement Administration as schedule two substances with the potential for misuse, many people fear that harmful substance use could result.”

Marked by chronic patterns of inattention, hyperactivity or impulsivity, ADHD is a chronic condition that must be monitored throughout an individual’s life.

Molina and her colleagues assessed patients with ADHD over a 16-year period from childhood through adolescence to early adulthood to see if there was any association between stimulant treatment and subsequent substance use. The study accounting for dozens of demographic, clinical and psychosocial factors that may predispose an individual to treatment and substance use to address the relationship between childhood use of prescription stimulants and later SUD.

“Our study not only accounted for age, but also used a statistical method that adjusted over time for the many characteristics that may distinguish treated from non-treated individuals,” said study co-author Traci Kennedy, PhD, assistant professor of psychiatry at Pitt. “Considering these factors allowed us to more accurately test the relationship between stimulants and substance use.”

While other studies have sought to uncover and define a possible connection between prescription stimulant use for ADHD and SUD, the association between the two has remained controversial. Some studies suggested a protective effect of prescription stimulant use on the risk of having SUD later in life, while others failed to find an association.

After accounting for a number of factors, the researchers found no evidence that prescription stimulant treatment in childhood provided protection against developing a SUD for adolescents or young adults with ADHD. Nor did they find an association between stimulant use during childhood and increased substance misuse in the future

While some study participants self-reported an increase over time in heavy drinking, marijuana use, daily cigarette smoking and using other substances, an association with age was also found for stimulant treatment, with older participants being less likely to continue taking medication. When these trends were paired with rigorous statistical analysis, results provided no evidence that prolonged stimulant use is associated with reduced or increased risk for SUD.

“We hope the results of this study will help educate providers and patients,” Molina said. “By understanding that stimulant medication initially prescribed in childhood is not linked to harmful levels of substance use, I anticipate that parents’ and patients’ fears will be alleviated.”

Pitt researchers plan to study individuals who were first diagnosed with ADHD and treated with stimulants in adulthood. The study aims to learn if there are differences in the characteristics and outcomes of these adults compared to people who were diagnosed and first treated with stimulants in childhood.

Source: University of Pittsburgh

SA Retirement Home Study Reveals the Mental Health Benefits for Residents Interacting with Children

A small South African study published in the open-access journal PLOS ONE suggests that programmes promoting interaction between retirement home residents and children may provide quality of life improvements and could help manage residents’ anxiety and depression.

Among retirement home residents, previous research has shown that common mental health conditions often go undetected and untreated. These conditions, which include anxiety and depression, are typically treated with a combination of drugs and non-pharmacological interventions.

One intervention is the Eden Alternative, which identifies loneliness, helplessness and boredom as key challenges to overcome provide a higher quality of life. Evidence suggests that programmes that enable older adults to regularly interact with children may improve mental health, but these have mostly been done outside of retirement homes and few have looked at such programmes in South Africa.

To deepen the understanding of potential benefits of intergenerational interactions, Elizabeth Jane Earl and Debbie Marais of Stellenbosch University, South Africa, conducted a study at a retirement home in South Africa. Residents were able to regularly interact with children who attend an onsite preschool. Activities include playing games, doing puzzles, reading, or singing with the children.

Ten female residents were recruited and invited to complete a questionnaire evaluating their anxiety and depression levels, as well as asking them to describe their experiences with the children. Four of the participants were screened as possible having anxiety, depression, or both. The participants all took part in the same interactions, though to varying degrees of participation.

Generally, the participants reported positive experiences with the children. Analysing their responses, the researchers found that the interactions fostered a sense of purpose and belonging, fond reminiscences of their own childhood and a positive influence on mood and emotions. Recollections of childhood also sparked a sense of playfulness and positive self-evaluation. They noted that the participants differed in their preconceptions of children, which might have affected their experiences.

The authors wrote that, “Interactions with children promote a sense of belonging and purpose, evoke reminiscence, and positively influence the mental well-being of older persons.”

Based on their findings, Earl and Marais concluded that intergenerational interaction programmes may help manage the mental health conditions that are common for retirement home residents. They suggest that trained staff facilitate the interaction, preparing the children and residents, and should be voluntary, which helps preserve the residents’ agency. Running the interaction as a regular programme should help build bonds and give the residents something to look forward to. Additionally, there should be an educational aspect for the children, giving the residents a sense of purpose.

Looking to the future, they wrote that larger studies would be able to better outline the benefits of such programmes.

In Osteoarthritis, Molecular Changes Weaken Protective Films

Photo by Towfiqu barbhuiya: https://www.pexels.com/photo/person-feeling-pain-in-the-knee-11349880/

Although osteoarthritis has been extensively studied through a medical perspective, the molecular changes associated with osteoarthritis remain unclear. New research published in Biointerphases suggests that there may be an optimum concentration and size of molecules in the synovial fluid needed to form the protective film in joints.

Osteoarthritis is the most common degenerative joint disease, affecting 22% of adults over 40 globally. The cartilage in the joints, in concert with the synovial fluid, provides a smooth surface to support weight-bearing movements. The fluid contains several molecules, including hyaluronan (HA) and phospholipids. Since the cartilage environment cannot be quickly healed or repaired, researchers have tried to diagnose the early stages of joint disease by monitoring the molecular weight and concentration of HA.

“Although we know that in healthy joints there is very low friction, it is unclear which other molecules are involved and how they change during osteoarthritis,” said Rosa Espinosa-Marzal (EIRH), professor of environmental engineering & science, and materials science & engineering. “During the early stages of osteoarthritis, cartilage starts degrading, and previous research has shown that the molecular composition of the synovial fluid changes. We wanted to see if the two changes are related to each other.”

In a healthy joint, the molecular weight of HA varies between 2–20 MDa with a concentration ranging from 1–4 mg/mL. Studies have shown that in diseased joints, HA is broken down resulting in a lower molecular weight and its concentration is also reduced by 10x. Based on these observations, made by other researchers, the study looked at how the concentration and molecular weight of HA influences the structure of healthy and diseased joints.

To do so, the researchers combined vesicles with high and low molecular weight HA. Using neutron scattering and light scattering, they discovered that the molecular weight of HA can vastly change the structure of the vesicles. Lower molecular weight HA, which mimics osteoarthritis-diseased joints, results in larger vesicle size. Changes in HA’s molecular weight also changed the thickness of the phospholipid layers in the joints.

The researchers also studied how these differences can influence the formation of a protective film; in joints this film is responsible for the very low friction we need for unhindered motion. Once again, they used a combination of techniques, quartz crystal microbalance and atomic force microscopy, to examine how these molecules assemble on gold surfaces.

“The formation of a film is possible only when there is an optimal concentration of HA and phospholipids. Even though the gold surfaces have very little in common with cartilage, our studies indicate that there could also be an optimum concentration under biological conditions,” Espinosa-Marzal said. “This is an important observation because we can use the concentration changes as a diagnostic tool.”

The researchers are now testing this theory using cartilage. They are also interested in studying the other molecular components that are found in joints to build a more comprehensive model of the changes that are associated with osteoarthritis.

Source: Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign

Less than Half of New Drugs add Substantial Benefit over Current Ones

Photo by Marek Studzinski on Unsplash

New drugs are often used not only for one disease (first approved indication) but also for other diseases (supplemental indications). But a study published by The BMJ finds that less than half of approved first indications for new drugs in the US and Europe between 2011 and 2020 add substantial therapeutic value over existing treatments. Only about a third of supplemental approvals add substantial therapeutic value compared with first approvals.

The researchers argue that when first or supplemental indications do not offer added benefit over existing treatments, this information should be clearly communicated to patients and reflected in the price of the drugs.

Previous study findings on the value of new drugs were unclear. To address this, researchers examined all new drugs approved for more than one indication in the US and Europe between 2011 and 2020, and assessed the therapeutic value of supplemental indications compared with first indications.

Using publicly available data, they identified 124 first and 335 supplemental indications approved by the US Food and Drug Administration (FDA) and 88 first and 215 supplemental indications approved by the European Medicines Agency (EMA).

In the US, 48% of drugs had one supplemental indication, 20% had two, 14% had three, and 18% had four or more. In Europe, 48% of drugs had one supplemental indication, 23% had two, 13% had three, and 17% had four or more. Most (58%) of indications approved by the FDA and EMA were for treatment of cancer.

Therapeutic ratings from French and German health technology assessment (HTA) bodies were available for 107 (86%) first and 179 (53%) supplemental indications in the US and for 87 (99%) first and 184 (86%) supplemental indications in Europe.

Among FDA-approved indications with available ratings, 41% (44 of 107) had high therapeutic value ratings for first, compared with 34% (61 of 179) for supplemental indications. In Europe, 47% (41 of 87) of first and 36% (67 of 184) of supplemental indications had high therapeutic value ratings.

Among FDA approvals, when the sample was restricted to the first three approved indications, second indication approvals were 36% less likely to have a high value rating and third indication approvals were 45% less likely when compared to the first indication approval. Similar findings were observed for Europe.

These are observational findings and the researchers acknowledge that therapeutic value ratings were not available for all indications, particularly indications approved in the US but not in Europe. Furthermore, the methods and value assessment system can be influenced by country specific factors and assumptions.

However, they point out that they focused on the highest rating provided by one of the two HTA bodies and did sensitivity analyses with the value scores of each authority separately, which confirmed the initial results.

As such, they conclude: “Fewer than half of approved first indications in the US and Europe were rated as having high therapeutic value, and the proportion of approved supplemental indications rated as having high therapeutic value was substantially lower than for approved first indications.”

“When indications do not offer added therapeutic benefit over other available treatments, that information should be clearly communicated to patients and reflected in the price of the drugs.”

The fact that new does not necessarily mean better needs to be clearly communicated to both patients and clinicians, agrees Beate Wieseler at the German Institute for Quality and Efficiency in Health Care, in a linked editorial.

“The system’s current performance does not meet the expectations of patients and the public, clinicians, or policy makers,” she writes. “Having experienced the potential of a coordinated drug development effort during the covid-19 pandemic, we should seek to align current legislation on drug development more closely with defined public health goals.”

Source: Medical Xpress

iNova Launches New Supplement To Reduce Symptoms Of Osteoarthritis

A new joint health supplement has been launched in South Africa by iNOVA Pharmaceuticals which supports healthy joints and helps reduce the symptoms of osteoarthritis such as joint pain and stiffness1. Unlike other osteoarthritis supplements on the market, POSTEON™ has been shown to start working in as little as five days1.

According to scientifically based research, the ingredients in Posteon™ may help reduce the symptoms of osteoarthritis such as joint pain and stiffness, as well as improving range of motion and mobility1.

Boswellia serrata gum resin extract has traditionally been used to relieve symptoms of osteoarthritis. Taken once a day, Posteon™ contains 100mg of 3-O-Acetyl-11-keto-beta- boswellic acid (AKBA), the most active compound of Boswellia extract which is an inhibitor of 5-lipoxygenase (5-LOX). This is a key enzyme in the biosynthesis of leukotrienes from arachidonic acid in the cellular inflammatory cascade1.

It also contains 300mg of Avocado soy unsaponifiables (ASU), a dietary supplement consisting of one-third avocado oil and two-thirds soybean oil. Studies have found that ASU can reduce the production/action of various joint inflammatory substances which can prevent the destruction of joint cartilage and also help in its repair1.

Osteoarthritis is the most common form of arthritis2 and affects between 55.1% and as many as 82.7% of adults aged over 65 years in South Africa3. Globally, the prevalence of osteoarthritis is increasing, and is expected to continue to escalate4.

POSTEON™, which is now available at leading pharmacies, may reduce these symptoms1 which can significantly impact day-to-day functioning2.

References:

  1. Posteon PI. June 2022
  2. Centers for Disease Control and Prevention (CDC). Osteoarthritis (OA) (2022) at https://www.cdc.gov/arthritis/basics/osteoarthritis.htm# (website accessed on 4 May 2023).
  3. Usenbo, A et al. Prevalence of Arthritis in Africa: A Systematic Review and Meta-Analysis. A Systematic Review of Arthritis Prevalence in Africa (2015) at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524637/ (website accessed on 4 May 2023).
  4. Osteoarthritis Research Society International (OARSI) Osteoarthritis: A Serious Disease, Submitted to the U.S. Food and Drug Administration (2016) at https://oarsi.org/oarsi-white-paper-oa-serious-disease (website accessed on 4 May 2023).

DISCLAIMER: This editorial has been commissioned and brought to you by iNova Pharmaceuticals.

Content in this editorial is for general information only and is not intended to provide medical or other professional advice. For more information on your medical condition and treatment options, speak to your healthcare professional.