Young adults who were prescribed stimulant medications for attention-deficit/hyperactivity disorder (ADHD) were significantly more likely to develop cardiomyopathy compared with those who were not prescribed stimulants, in a study presented at the American College of Cardiology’s Annual Scientific Session.
The study found that people prescribed stimulants such as Adderall and Ritalin were 17% more likely to have cardiomyopathy at one year and 57% more likely to have cardiomyopathy at eight years compared with those who were not taking these medications. Cardiomyopathy involves structural changes in the heart muscle that weaken its pumping ability. It can cause a person to tire easily and limit their ability to perform daily tasks, and it often worsens over time.
However, researchers said that the overall risk of cardiomyopathy remained relatively low even when stimulants were used long-term. They said the findings do not necessarily point to a need for clinicians to change their approach to screening patients or prescribing stimulants.
“The longer you leave patients on these medications, the more likely they are to develop cardiomyopathy, but the risk of that is very low,” said Pauline Gerard, a second-year medical student at the University of Colorado School of Medicine in Aurora, Colorado, and the study’s lead author. “I don’t think this is a reason to stop prescribing these medications. There’s very little increased risk of these medications over the long term; it’s a real risk, but it’s small.”
ADHD is one of the most common neurodevelopmental disorders in children, affecting about 1 out of 10 American children aged 3 to 17, and can continue into adulthood. It is typically treated with behavioural therapy initially, which may be combined with stimulant or non-stimulant medications to help control behaviours that interfere with daily life and relationships. Stimulant medications can elevate blood pressure by causing the heart to beat faster and with greater force.
Most previous studies assessing the safety of stimulant medications have focused on the first year or two of use and found no evidence of harm to the heart. Since many patients are prescribed these medications in early childhood and continue taking them into adulthood, this new study was designed to assess their potential to cause harm over a longer period of time, Gerard said.
Using the TriNetX research database that includes information from about 80 hospitals across the U.S., researchers analysed data from people diagnosed with ADHD between 20–40 years of age. Individuals with the presence or absence of a prescription for stimulant medications along with rates of cardiomyopathy that could potentially be linked to stimulant use were included. Those with heart damage caused by other known factors, such as cancer treatments, were excluded.
For the analysis, the researchers paired each person who had been prescribed stimulants with an individual who had not been prescribed stimulants but was as similar as possible in all other respects, such as age, sex and other health conditions. Overall, 12 759 pairs were created and were followed for at least 10 years. Of these pairs, people prescribed stimulants were found to be significantly more likely to develop cardiomyopathy throughout the 10-year follow-up period, with the gap growing larger each year except the last two, when it narrowed slightly.
Despite the significant gap, the overall prevalence of cardiomyopathy was still quite low in both groups. After being prescribed stimulants for 10 years, 0.72% (less than three-quarters of one percent) of patients developed cardiomyopathy, compared with 0.53% (a little over half of one percent) among those who were not prescribed stimulants.
To put the numbers into context, Gerard said, “You can have almost 2000 patients on these medications for a year and you might only cause one of them to have a cardiomyopathy that they otherwise would not have had, but if you leave them on it for 10 years, 1 in 500 will have that happen.”
At these levels, researchers said the study does not suggest that aggressive testing for cardiovascular risk is warranted before prescribing stimulants, given that the potential benefits of testing must be balanced against the risks and costs. They suggest that further studies could help to identify subgroups of patients at greater risk who may benefit from future screening approaches.
Gerard said that it could also be helpful to study potential differences among different types of ADHD medications and different types of cardiomyopathies.
Condom distribution in South Africa has dropped dramatically over the last five years, finds a Spotlight analysis of data recently published in the Health System Trust’s District Health Barometer.
The South African government distributed 45% fewer male condoms in 2022 than it did in 2018. The total number of male condoms distributed dropped by over 300 million from 728 million in the financial year from March 2018 to February 2019 to 403 million in 2022/2023. Female condom supply also declined over this period, but not as sharply.
The full extent of the actual decline in condom supply across the country over the past five years has not previously been reported. The Democratic Alliance, though, did raise the alarm bells about condom supply challenges in Gauteng in April 2023.
Provincial departments of health have pin-pointed the time required for certification of condoms by the South African Bureau of Standards (SABS) following the start of a new condoms tender in 2022 as a key driver of the decline, yet Health System Trust’s District Health Barometer (DHB) data shows that condom distribution figures have in fact steadily declined over the past five years. Similarly, while COVID-19-related supply chain interruptions were a contributing factor to supply shortages at the height of the pandemic, the decline in government supplied condoms started before the pandemic and continued after COVID-19 supply chain disruptions were resolved (as shown in the below graph).
The large decline in condom distribution in South Africa is alarming in the context of the country’s ongoing fight against HIV. While other biomedical interventions are now available to protect against HIV (such as HIV prevention pills), condoms should remain a cornerstone of countries’ HIV prevention strategies according to the World Health Organization.
Research conducted by the University of Witwatersrand’s Health Economics and Epidemiology Research Office (HE2RO) has found that condoms are not only the most cost-effective intervention available to government to combat HIV, but that provision of condoms is in fact cost saving for the country’s health system.
Where did condom distribution fall the most in 2022?
According to the DHB data, all provinces except for the Free State saw a decline in condom distribution in 2022/2023 compared with 2018/19 levels (as shown in the below graph).
The Eastern Cape distributed 65% fewer condoms in 2022/23 than it did in 2018/19, Gauteng and the Northern Cape distributed around 60% fewer, Limpopo 52% fewer, and the Western Cape around 46% fewer. With a reduction of around 19% over the five years, the decrease was much less pronounced in KwaZulu-Natal than in South Africa’s other provinces with large populations.
Male condoms distributed by province
Province
2018/19
2019/20
2020/21
2021/22
2022/23
Eastern Cape
73 672 416
78 817 157
51 122 509
45 839 588
25 490 700
Free State
50 756 150
53 246 000
52 248 000
55 352 800
52 469 700
Gauteng
172 953 486
135 857 486
146 303 254
129 075 303
69 220 678
KwaZulu-Natal
111 028 599
108 503 920
96 529 200
106 967 000
89 664 600
Limpopo
82 563 322
67 818 200
53 325 900
52 862 900
38 910 442
Mpumalanga
67 150 600
51 749 400
38 316 000
31 364 066
35 627 000
Northern Cape
13 934 960
12 959 400
10 825 929
9 518 000
5 194 000
North West
50 820 283
55 579 921
39 841 971
42 361 097
30 810 803
Western Cape
103 322 800
82 055 960
53 632 226
72 031 600
55 420 700
*This table shows a breakdown of male condoms distributed by province, according to data from the Health Systems Trust’s District Health Barometer.
What caused the decline in condom supply?
Condoms are tendered nationally by the National Department of Health for a three-year period. Condoms procured by government must be tested and certified by the SABS before distribution.
Neither the National Department of Health, nor the Gauteng Department of Health responded to questions from Spotlight about the reasons for the decline in condom distribution. However, Gauteng’s Department of Health has previously pinpointed SABS certification processes as the culprit for condom supply shortages in the province. According to an April 2023 media statement by the Gauteng Department of Health, suppliers that received tenders to supply condoms to the public sector were unable to supply condoms to the province while awaiting SABS certification in 2022 – resulting in low condom stock in the province.
Spokesperson for the Eastern Cape Health Department, Sizwe Kupelo, told Spotlight in response to questions for this article that in 2022/23 “for most of the year there were no condoms to distribute”.
Kupelo said that the decline in condom distribution in the Eastern Cape was due to a combination of lags in supply availability while condom suppliers were awaiting SABS certification and challenges in delivering condoms to distribution sites in the province.
“2022/23 was the end of the condom supply contract and the period to award a new contract effective from 1st April 2022. This transition experienced a delay in availing the condoms due the SABS quality assurance process that could be finalised only around September 2022,” said Kupelo, adding that the province started to receive condoms from October of the same year.
“The second reason were related to suppliers who were not finding it easy to deliver to Eastern Cape areas due to the high cost of transportation to the identified 26 delivery distribution sites across the province. Suppliers are all based in Gauteng,” said Kupelo. This matter he said was now resolved.
Kupelo added that condom supply in the province is now improving. He said that the province had reached 96.7% of its target to distribute 17 million condoms in quarter 3 of 2023/24 (quarter 3 of 2023/24 is September to November 2023).
The SABS’ response
Lungelo Ntobongwana, acting CEO of the SABS, told Spotlight that all condoms that are distributed nationally by the Department of Health are tested at the SABS condom laboratory in Groenkloof, Pretoria. “The laboratory is an accredited and dedicated laboratory for the testing of condoms,” he said.
“Downtime or challenges to operations as a result of unplanned disruptions have been experienced on rare occasions and the SABS has incorporated contingency plans to ensure that the testing processes and deliverables would not be negatively impacted.
“The value chain, from the production of condoms to the distribution and usage of condoms, requires the intervention of various role players. When there is a shortage of condoms, it could be due to several reasons and chinks in the value chain. The SABS can categorically state that there are currently no challenges in its laboratory or deliverables regarding the testing of samples,” said Ntobongwana.
Did clinics run out of condoms in 2022/23?
The National Department of Health insisted in April 2023 that while Gauteng was facing low stocks of condoms, there were no serious condom shortages in the country.
Surveys conducted by community-lead clinic monitoring group Ritshidze also show that condoms remained available in most facilities – but not all – throughout the year, but also indicate a pattern of rationing by health care workers and clinics. In some cases, they say condoms are only available in public clinics on request, and key populations often face stigma and discrimination when seeking to access condoms and lubricant.
Surveys conducted by Ritshidze in 2022, found that only 55% of sex workers could get enough condoms at public facilities. Ritshidze recommends that “condoms and lubricants should be available at all facilities and can easily be placed in the toilets or other areas of the clinic where people could take them without the fear of being seen and judged by others, or being told to put some back”.
Anele Yawa, General Secretary of the Treatment Action Campaign (a member of Ritshidze), told Spotlight that the organisation faced challenges in accessing adequate condoms for its community outreach efforts. He said when TAC undertakes community outreach efforts, its members request condoms from public health facilities for distribution in communities but are sometimes told that there are not enough condoms for this.
Yawa added that people seeking condoms from public clinics are often told they can only take a limited number of condoms because of stock availability and that in some clinics “the condom box is empty, there are no condoms”.
Has the decline in condom availability impacted condom usage?
There are some concerning indicators that condom usage in the country is declining, which may in part be related to the drastic decline in condom supply.
The Human Science Research Council (HSRC), which conducts regular surveys of HIV knowledge and sexual behaviour in South Africa, recently released early data from its 2022 survey. The survey showed that teenagers and young adults between 15 and 24 years old reported lower rates of condom use at last sex than in previous survey years. The data presented did not pin-point a cause for the decline – apart from supply constraints, other factors like a decrease in people’s perceived risk of contracting and dying of HIV may also play a role.
The HSRC will release its full survey results in April 2024, which are expected to provide more insight into why condom use at last sex declined among 15- to 24-year-olds in 2022.
Another concerning indicator of declining condom usage is the reported rise in sexually transmitted infections (STIs) in Gauteng. Spotlight reported in February that the worried resurgence in reported cases of STIs in Gauteng in 2023 is a wake-up call that control and management strategies are not keeping pace with the growing disease burden in South Africa’s most populous province.
In response to the increase in STIs, Gauteng’s Health MEC Nomantu Nkomo-Ralehoko recommended expanded, consistent condom use – noting a number of factors including non-use of condoms, inconsistent use of condoms, and the forgoing of condoms by people using Pre-Exposure Prophylaxis (PrEP) as contributors to the rise in STIs. PrEP refers to antiretrovirals taken to prevent HIV infection.
Dismissing the conclusion of a causal relationship between a higher number of people being initiated on PrEP and the higher recorded number of STIs, Professor Linda-Gail Bekker, director of the Desmond Tutu Health Foundation, told Spotlight that there is no evidence to back up the claim that PrEP is leading to lower rates of condom usage. She added that the increase in STI diagnoses may be attributed to increased rates of testing, which has increased in the PrEP era.
“The notion that sexually transmitted infections have suddenly increased in the era of PrEP does not have evidence to support this,” said Bekker, adding “we have no strong evidence to suggest that people are having more condomless sex than before”.
“The value of condoms as a measure against sexually transmitted infections as well as unwanted pregnancy is not disputed and condoms remain the corner stone of the HIV response” said Bekker. “However, we know that for many people, and particularly young women and young men who have sex with men, the choice to use male condoms is not always a given and negotiating condom use may not be easy and can be dangerous,” she said.
Researchers from Rutgers University in the U.S. believe that they are ahead in a race to find an oral COVID-19 treatment to supplement or replace the antiviral Paxlovid. Their report, published in Science, shows that an alternative medication, a viral papain-like protease inhibitor, inhibits disease progression in animals while also possessing an important advantage over Paxlovid – fewer prescription drug contraindications.
“COVID-19 remains the nation’s third leading cause of death, so there’s already a massive need for additional treatment options,” said Jun Wang, senior author of the study and associate professor at Rutgers. “That need will grow more urgent when, inevitably, COVID-19 mutates in ways that prevent Paxlovid from working.”
The Rutgers team hoped to make a drug that interfered with viral papain-like protease (PLpro), a protein that performs important functions in all known strains of COVID-19.
Creating such a drug required detailed information about PLpro’s structure, which Wang’s team got from the Arnold Lab at Rutgers’ Center for Advanced Biotechnology and Medicine (CABM).
Precise knowledge of PLpro’s structure enabled Wang’s team to design and synthesise 85 drug candidates that would bond to – and interfere with – this vital protein.
“The PLpro crystal structures showed an unexpected arrangement of how the drug candidate molecules bind to its protein target, leading to innovative design ideas implemented by professor Wang’s medicinal chemistry team,” said Eddy Arnold, who is a professor at CABM.
Laboratory testing established that the most effective of those drug candidates, a compound dubbed Jun12682, inhibited several strains of the SARS-CoV-2 virus, including strains that resist treatment with Paxlovid.
Oral treatment with Jun12682 on SARS-CoV-2-infected mice was shown to reduce viral lung loads and lesions while improving survival rates.
“Our treatment was about as effective in mice as Paxlovid was in its initial animal tests,” said Wang, who added the experimental drug appears to have at least one major advantage over the older drug.
“Paxlovid interferes with many prescription medications, and most people who face the highest risk of severe COVID-19 take other prescription medicines, so it’s a real problem,” Wang said.
“We tested our candidate Jun12682 against major drug-metabolising enzymes and saw no evidence that it would interfere with other medications.”
Mycobacterium tuberculosis drug susceptibility test. Photo by CDC on Unsplash
With resistance to chemical antibiotics on the rise, the world needs entirely new forms of antibiotics. A new study published in Microbiology Spectrum, a journal of the American Society for Microbiology, shows that an enzymatic cocktail can kill a variety of mycobacterial species of bacteria, including those that cause tuberculosis. The research was carried out by scientists at Colorado State University and Endolytix Technologies.
“We have a mycobacterial drug that works for Nontuberculous Mycobacteria and M. tuberculosis that is biological, not phage therapy, and not small molecule antibiotics,” said Jason Holder, Ph.D., a study coauthor and Founder and Chief Science Officer at Endolytix Technology.
“Mycobacterial infections are particularly hard to treat due to poor efficacy with standard of care drugs that are used in multidrug regimens resulting in significant toxicities and treatments lasting 6 months to years. This is often followed up by reemergence of the bacterial infection after a year of testing negative.”
In the new proof of principle study, the researchers took a biological approach instead of a chemical one to develop a cocktail of enzymes that attack the cell envelope of mycobacteria.
The cocktail of enzymes contains highly specific biochemical catalysts that target and degrade the mycobacteria cell envelope that is essential for mycobacterial viability.
To increase efficacy, the researchers delivered the enzymatic drug inside of host macrophages where mycobacteria grow. In laboratory experiments, the drug was effective against M. tuberculosis and Nontuberculous Mycobacteria (NTMs), both lethal pulmonary lung diseases (PD). TB kills roughly 1.5 million people per year.
“We characterised the mechanism of bactericide as through shredding of the bacterial cells into fragments,” Holder said.
“We’ve shown we can design and develop biological antibiotics and deliver them to the sites of infection through liposomal encapsulation. By combining drug delivery science with enzymes that lyse bacteria, we hope to open up treatment options in diseases such as NTM pulmonary disease, tuberculosis pulmonary disease and others.”
According to study coauthor Richard Slayden, PhD, a professor in the Department of Microbiology, Immunology and Pathology at Colorado State University, the new therapy complements current standard-of-care drugs and does not have many of the drug-drug interactions that are problematic with many anti-mycobacterial drugs in use. “Endolytix enzymes work powerfully with standard-of-care antibiotics to kill bacteria with lower drug concentrations,” Holder said. “This has the potential to reduce the significant toxicities associated with multi-drug regimens that are the standard for mycobacterial infections and hopefully lead to more rapid cures.”
To improve the efficacy of treating skin blemishes with laser treatment while reducing complications, an Osaka Metropolitan University-led research group has developed an index of the threshold energy density, known as fluence, and the dependent wavelength for picosecond lasers. The use of this indicator, described in Lasers in Surgery and Medicine, is expected to help set irradiation conditions in clinical practice and reduce complications.
Picosecond lasers have in recent years been used to remove pigmented lesions. These lasers deliver energy beams in pulses that last for about a picosecond – a trillionth of a second. The lasers target melanosomes, which produce, store, and transport the melanin responsible for pigment.
Postdoctoral Fellow Yu Shimojo of OMU’s Graduate School of Medicine and Specially Appointed Professor Toshiyuki Ozawa and Professor Daisuke Tsuruta of the school’s Department of Dermatology were among the researchers who developed this first picosecond laser index for each of the wavelengths used in clinical practice in treating pigmented lesions.
Using a mathematical model based on the thresholds, the researchers quantitatively evaluated irradiation parameters for 532-, 730-, 755-, 785-, and 1064-nm picosecond laser treatments.
A suspension of melanosomes extracted from pig eyes was irradiated using picosecond lasers with varying fluence. The mean particle size of the irradiated melanosomes was measured by dynamic light scattering, and their disruption was observed by scanning electron microscopy to determine the disruption thresholds. A mathematical model was developed, combined with the threshold obtained and Monte Carlo light transport to calculate irradiation parameters required to disrupt melanosomes within the skin tissue.
The numerical results quantitatively revealed the relationship between irradiation wavelength, incident fluence, and spot size required to disrupt melanosomes distributed at different depths in the skin tissue. Comparing previously reported clinical studies, the researchers confirmed that clinical results showing low complication rates and high efficacy can be explained based on these wavelength-dependent indicators.
“The use of this indicator is expected to play an important part in setting irradiation conditions in clinical practice,” Postdoc Fellow Shimojo said. “In addition, the implementation of picosecond laser therapy based on scientific evidence, rather than relying solely on physicians’ experience, is expected to improve the safety and effectiveness of the treatment.”
