Month: November 2023

Categories : Environmental Effects NeurologyTags :

Lead Poisoning Part 2: Scientists Find Toxic Metals in Kitchenware

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Photo by Dee @ Copper and Wild on Unsplash

By Jesse Copelyn for Spotlight

A small study published in September found that some ceramic plates and bowls bought from South African chain stores are coated in glaze that contains lead, a toxic heavy metal which can damage multiple organs when consumed. The paper comes in the wake of research that finds that due to its harmful effects on the cardiovascular system, lead exposure is linked to the deaths of somewhere between 2.3 and 8.2 million people a year worldwide (these findings are dissected in part one of this Spotlight special series on lead poisoning).

It is estimated that about 7.8 million children in South Africa (aged 0-14) have lead poisoning, which is about 53% of all young people in that age-range. This means that they have more than five micrograms of lead per 100mL of blood, the clinical threshold for lead poisoning set by the National Institute for Communicable Diseases. Lead increases the risk of health problems at any level, however if a healthcare worker finds that a patient exceeds this threshold then this indicates that the problem is severe enough that they should notify the health department.

But why are children in the country exposed to so much lead?

Scientists from the South African Medical Research Council (SAMRC) have found several sources over the last two decades. These include lead-based paints (which can chip and generate lead dust which people breathe in), certain traditional ayurvedic medicines that contain lead, fishing sinkers (which are sometimes melted down, producing toxic fumes), lead ammunition (which can generate lead dust when fired, and may contaminate hunted game meat), as well as gold mining waste facilities, which can contaminate the surrounding soil.

The recent paper on ceramics adds to a growing body of evidence that cookware and crockery also likely play a role.

Toxic pottery

Research for the new paper was conducted in 2018, when SAMRC scientists purchased 44 randomly selected plates and bowls from six large retail chain stores in Johannesburg. After testing the glaze, they found that almost 60% of the items contained more than the maximum amount of lead recommended by the United Nations – which is 0.009% of total content. Indeed, the average item contained about 47 times this amount.

Glaze is a liquid coating that is applied to ceramic to make it shinier and more durable. Once it’s coated, the ceramic is fired, leaving it with a glossy sheen. Lead is often used in these glazes to add extra colour and increase water-resistance, but if the ceramic isn’t heated at a high enough temperature then the glaze won’t completely solidify. In the case of ceramic crockery, this means that lead may run off into food or water prepared in these dishes, particularly if they are used for cooking or simply holding acidic foods.

Indeed, this is precisely what has happened throughout parts of Mexico. Research in that country finds that children have higher amounts of lead in their blood if they live in households where food is prepared in lead-glazed pottery (a result which researchers have found repeatedly). Recently, health inspectors in the US linked cases of lead poisoning to the use of ceramic cookware bought in Mexico. After the affected individuals stopped using the ceramics, their blood-lead levels went down.

In order to test whether lead is leaching off the South African ceramics, the SAMRC researchers left an acidic solution in the plates and bowls. When they returned 24 hours later, lead was found to have run off one of the 44 items.

Angela Mathee, the head of the SAMRC’s Environment and Health Research Unit and the paper’s lead author, says that while this is comforting, the results may be deceiving: “our speculative concern is that particularly for people who are poor and keep their ceramic ware for a very long time, that with knocks and cracks and wear and tear over the years, it’s possible that the product could start leaching – even if it wasn’t at the time of purchase. Though that is untested”.

A second caveat is that of the 44 bowls and plates, only one was originally made in South Africa, and it’s this item that released lead.

Additionally, even if lead-based ceramics don’t leach, the production of these items may still cause harm. For instance, a study in Brazil found that children who simply lived near artisanal pottery workshops were more likely to have high amounts of lead in their blood. Caregivers of these children did not report having any lead-glazed ceramics or being involved in pottery making. Thus, researchers suspect that children were simply breathing in lead dust generated by the nearby potters.

Lead leaching from cooking pots

Although this is the first time lead has been found in ceramic glazes in South Africa, other kinds of kitchenware products have previously been shown to contain lead. In 2020, researchers published a study in which they purchased 20 cooking pots from informal traders and artisanal manufacturers across South Africa. Each pot was made from recycled aluminium.

Photo by Scott Umstattd on Unsplash

They found lead in every pot, and some also contained dangerous amounts of arsenic (a known carcinogenic). The researchers cut the pots up, and boiled a piece from each one in an acidic solution. They found 11 out of the 20 pieces leached more lead than the maximum permissible limit set by the EU. (The experiment was repeated twice more on the same metal pieces, with similar results).

Thus, the authors conclude that artisanal aluminium pots are a likely source of lead exposure in the country. And the issue may extend past individual households, as the SAMRC has documented the use of artisanal aluminium pots in school feeding programmes.

Not only can lead-based artisanal pots cause lead poisoning by leaching into food, but researchers note that simply manufacturing them likely generates lead dust. As demonstrated in a small follow-up study on informal metal workshops in Kwazulu-Natal and Limpopo which found that workers had a lot more lead dust on their hands by the end of the work day than at the start.

It’s also possible that production facilities like this end up contaminating nearby residential areas. A 2018 study in the Johannesburg suburb of Bertrams found that nearly a third of all garden soil samples contained dangerous amounts of lead (i.e. lead levels that exceeded South Africa’s guidelines for safe soil). The scientists hypothesised that one reason may be that various cottage industries, including scrap metal recyclers, are interspersed among suburban homes.

Are regulations on lead being ignored?

South Africa has already taken legislative steps to deal with lead coatings. In the 2000s, a number of alarming studies found lead-based paints covering homes and playground equipment in public parks across several cities. In response, a law came into effect in 2009 that made it illegal to sell household paint or glaze that is more than 0.06% lead. Draft regulations published in 2021 will further slash this limit to 0.009% in line with recommendations by the UN. These will only become enforceable once the finalised regulations are gazetted.

Though evidence is scant, these laws may have had a positive effect. A study last year found that paints produced by large companies being sold in Botswana, but manufactured in South Africa, were all below the lead-threshold set by the 2009 law (and broadly in line with the new draft regulations as well).

However, the research on ceramics suggests the regulations have not always been adhered to, at least when it comes to glazes. The only South African-made piece of crockery which was tested in the study described earlier had a coating that contained over 100 times the amount of lead legally permissible under the 2009 law (despite the tests being conducted nine years after it was passed).

If additional research finds that the problem is widespread, then Mexico’s experience may offer one path forward. There, a ban on lead glaze has long gone unenforced. NGOs in parts of the country have responded by assisting artisanal potters to switch to lead-free glazes and to develop higher-temperature kilns (which would prevent metals from leaching). This has been coupled with public awareness campaigns about the harms of lead-based pottery and a certification program for potters using lead-free coatings.

But stakeholders say the government needs to play its part as well. The South African Paint Manufacturing Association (SAPMA) has previously urged the government to do more to enforce its regulations. In 2021 they stated that “random samples taken from hardware shelves by the government regularly showed that hazardous levels of paint were still being sold. But no report of any offender being charged by the police appeared in the press”.

The National Department of Health didn’t respond to a request for comment about this at the time of publication.

Speaking to Spotlight for this article however, the executive director of SAPMA, Tara Benn, says “I believe manufacturers are adhering to the current regulation and most if not all have already adopted the new regulation of less than 90 parts per million [i.e. 0.009%], but this regulation has not been published as yet”.

Data and investment needed

Except for a few (mostly wealthy) nations like the United States, very few countries run nationally representative blood-lead surveys. In countries like South Africa, researchers have only been able to make very rough calculations about how many people have lead poisoning by pooling together different studies that have been done in particular communities.

As a result, policy makers lack good data about the extent of the problem. National blood-lead monitoring schemes would also allow health officials to work out which communities are most affected, which in turn, could help them identify the sources of lead exposure.

Bjorn Larsen, an environmental economist who consults for the World Bank, explains: “The first thing that needs to be done is we have to get in place routine blood-lead measurements that are nationally representative…This can be done by adding a [blood-lead] module to existing routine household surveys, for example UNICEF’s Multiple Indicator Cluster Survey…countries also have their own routine household surveys, [blood-lead tests] could be added to those”.

In the United States, all children who are enrolled in Medicaid (the government-run insurance scheme) receive blood-lead tests at ages one and two (these can be done via a simple finger-prick test) . This is in addition to nationally representative surveys which are done by the Centres for Disease Control and Prevention (CDC). Overall, the CDC receives about four million lead test results from across the country each year.

In addition, experts are increasingly calling for greater international health financing for the prevention of lead poisoning in low- and middle-income countries. Last month, a group of experts, including researchers from Stanford and officials from UNICEF, released a joint statement on lead poisoning in developing nations. It argues that “despite the extraordinary health, learning, and economic toll attributable to lead, we find the global lead poisoning crisis remains almost entirely absent from the global health, education, and development agendas”.

The statement argues that $350 million in international aid over the next seven years would be enough to make a significant dent in the problem. They provide a breakdown of these funds, which include international assistance with enforcing anti-lead laws, purchasing lead-testing equipment and assisting companies (such as paint manufacturers) with moving away from lead-based sources.

Note: This is the second in a two-part Spotlight special series on lead poisoning. You can read part one here.

Republished from Spotlight under a Creative Commons Licence.

Source: Spotlight

Categories : Injury & Trauma NeurologyTags :

Scientists Test a Soundwave Treatment for Persistent Concussion Symptoms

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Coup and contrecoup brain injury. Credit: Scientific Animations CC4.0

Recent research has indicated that acoustic stimulation of the brain may ease persistent symptoms in individuals who experienced mild traumatic brain injury in the past.

The study, which appears in Annals of Clinical and Translational Neurology, included 106 military service members, veterans, or their spouses with persistent symptoms after mild traumatic brain injury sustained three months to 10 years ago. Participants were randomised 1:1 to receive either 10 sessions of engineered tones linked to brainwaves (intervention), or random engineered tones not linked to brainwaves (sham control). All participants rested comfortably in the dark in a ‘zero-gravity’ chair, eyes closed and listening to the computer-generated tones via earbud-style headphones. The primary outcome was change in symptom scores, with secondary outcomes of heart rate variability and self-reported measures of sleep, mood, and anxiety.

Among all study participants, symptom scores clinically and statistically improved compared with baseline, with benefits largely sustained at three months and six months; however, there were no significant differences between the intervention and control groups. Similar patterns were observed for secondary outcomes.

The results indicate that although acoustic stimulation is associated with marked improvement in postconcussive symptoms, listening to acoustic stimulation based on brain electrical activity, as it was delivered in this study, may not improve symptoms, brain function, or heart rate variability more than randomly generated, computer engineered acoustic stimulation.

“Postconcussive symptoms have proven very difficult to treat, and the degree of improvement seen in this study is virtually unheard of, though further research is needed to identify what elements are key to its success,” said corresponding author Michael J. Roy, MD, MPH, of Uniformed Services University and the Walter Reed National Military Medical Center, in Bethesda.

Source: Wiley

Categories : Cardiovascular Disease Substance UseTags :

Alcohol Metabolites Play a Complex Role in Cardiovascular Harms and Benefits

On By ModernMedia
Photo by Pavel Danilyuk on Pexels

Although past research has indicated that moderate alcohol consumption can reduce cardiovascular disease (CVD) risk, more recent studies suggest that moderate levels of drinking may be hazardous to heart health. A new analysis now sheds new insight on this complex relationship between alcohol consumption and the progression of CVD, showing that a few particular alcohol metabolites strongly influence its protective effects.

Published in the journal BMC Medicine, the study observed a total of 60 alcohol consumption-related metabolites, identifying seven circulating metabolites that link long-term moderate alcohol consumption with an increased risk of CVD, and three circulating metabolites that link this same drinking pattern with a lower risk of CVD.

The findings from the study led by Boston University School of Public Health and Friedman School of Nutrition Science and Policy at Tufts University (Friedman School) detail the molecular pathway of long-term alcohol consumption and show that further research on these metabolites is needed for targeted prevention and treatment of alcohol-related CVD.

“The study findings demonstrate that alcohol consumption may trigger changes of our metabolomic profiles, potentially yielding both beneficial and harmful outcomes,” says Dr Chunyu Liu, assistant professor of biostatistics at BUSPH and co-corresponding/co-senior author of the study along with Dr.Jiantao Ma, assistant professor in the Division of Nutrition Epidemiology and Data Science at the Friedman School.

“However, rather than definitively settling that debate, this study underscores the intricate effects of alcohol consumption on cardiovascular health and generates a useful hypothesis for future investigations,” Dr Liu says.

The researchers analysed blood samples to measure the association between the cumulative average consumption of beer, wine, and liquor and 211 metabolites among Framingham Heart Study Offspring Study participants, who are the children of participants in the long-running Boston University-based Framingham Heart Study, over 20 years.

Of the 2428 participants, 636 developed CVD over the study period. Among the 60 drinking-related metabolites, 13 metabolites had a stronger association with alcohol consumption in women than in men, perhaps due to higher blood alcohol levels from women’s generally smaller body size versus the same amount of alcohol.

Consuming different types of alcohol was also linked to different metabolomic responses, with beer consumption generating a slightly weaker association overall than wine and liquor.

In roughly two-thirds of the 60 metabolites, higher plasma levels were detected in participants who consumed greater amounts of alcohol. Branched-chain amino acids (BCAAs), were among the metabolites not associated with alcohol consumption.

The researchers then calculated two alcohol consumption-associated metabolite scores, which had opposite associations with the development of CVD.

“While our study presents intriguing findings, validation through state-of-the-art methods and large and diverse study populations is crucial,” Dr Ma says.

“To enhance reliability, we aim to conduct larger-scale research involving a more diverse racial and ethnic background, as the current study participants are all white. In addition, we will expand our study to integrate with other molecular markers such as genetic information to illustrate the complex relationships between alcohol consumption, metabolite features, and cardiovascular risk.”

Source: Boston University School of Public Health

Categories : Cancer NeurologyTags :

The Quest to Repurpose Existing Drugs for Lung Cancer that Metastasised to the Brain

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Lung cancer metastasis. Credit: National Cancer Institute

The largest review of papers for brain metastases of lung cancer has found abnormalities in their genetic mutations and for which licensed drugs could be clinically trialled to find out if they could treat the disease. The research led by the University of Bristol and published in Neuro-Oncology Advances also uncovered differences in those mutations between smokers and non-smokers.

Brain metastases most commonly occur from lung and breast cancer, and in the majority of cases are fatal. The genetic mutations in primary lung cancers have been widely studied, but less is known about the changes in the cancer once it has metastasised to the brain.

The research team wanted to find out the genetic changes in brain metastasis from non-small cell lung cancer (NSCLC) and whether there are drugs already available that could potentially be offered to these patients.

The researchers carried out a review from 72 papers of genetic mutations in brain metastasis of NSCLC from 2346 patients’ data on demographics, smoking status, genomic data, matched primary NSCLC, and PD-L1 – a protein found on cancer cells.

The study found the most commonly mutated genes were EGFR, TP53, KRAS, CDKN2A, and STK11.

Common missense mutations – mutations that lead to a single amino acid change in the protein coded by the gene – included EGFR L858R and KRAS G12C

In certain cases the genetic mutations were different in the brain metastasis from the primary lung cancer.

There were also differences in the genetic mutations in smokers versus patients who had never smoked. Brain metastases of smokers versus non-smokers had different missense mutations in TP53 and EGFR, except for L858R and T790M in EGFR, which were seen in both subgroups.

The research team found from the top ten commonly mutated genes which had primary NSCLC data, 37% of the specific mutations assessed were different between primary NSCLC and brain metastases.

The researchers suggest Medicines and Healthcare products Regulatory Agency-approved drugs already licensed could potentially be tested to treat the disease in clinical trials.

The genetic landscape of the different subtypes of NSCLC is well known. TP53 and LRP1B mutations are common to all NSCLC subtypes, but certain subtypes also have specific alterations.

Lung adenocarcinoma is the most common type of lung cancer and has higher frequencies of KRAS, EGFR, KEAP1, STK11, MET, and BRAF somatic mutations – changes that have accumulated in the cancer genome.

Some studies suggested that the genomic landscape of NSCLC in smokers vs non-smokers differ independent of subtype.

One study found EGFR mutations, ROS1 and ALK fusions to be more prevalent in non-smokers, whereas KRAS, TP53, BRAF, JAK2, JAK3 and mismatch repair gene mutations were more commonly mutated in smokers.

Kathreena Kurian, Professor of Neuropathology and Honorary Consultant at North Bristol NHS Trust, Head of the Brain Tumour Research Centre at the University of Bristol and co-author of the paper, said: “Our research recommends that all patients should have their brain metastasis examined for mutations in addition to their primary lung cancer because they may be different.

“This evidence could form the backbone for new clinical trials for patients with brain metastasis in non-small cell lung cancer using drugs that are already available.”

The team suggest the next steps for the research would be to consider whole genome sequencing on brain metastasis to look for other types of mutations, such as, common insertions/deletions for which drugs are already available.

Source: University of Bristol

Categories : Diseases, Syndromes and Conditions General InterestTags :

International Day of Persons with Disabilities – Inclusivity is Critical to Achieving Health for All

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Photo by Elevate on Unsplash

The United Nations International Day of Persons with Disabilities (IDPD) is celebrated annually on 3 December, aiming to promote an understanding of disability issues and to mobilise support for the dignity, rights and well-being of persons with disabilities. An estimated 1.3 billion people experience significant disability.1a This represents 16% of the world’s population, or 1 in 6 of us.1a In South Africa, that figure is 15%, or 8,9 million.2a

Persons with disabilities face many health inequities, including stigma, discrimination, poverty, and exclusion from education and employment. They also face barriers in all aspects of the health system, such as negative attitudes and discriminatory practices and lack of information or data collection and analysis on disability.1b+c

“Disability inclusion is critical to achieving the Sustainable Development Goals (SDGs) and global health priorities to achieve health for all, as envisioned in the 2030 Agenda for Sustainable Development,” says Prudence Selani, Head of Corporate Affairs at Sanofi South Africa. On this International Day of Persons with Disabilities, Sanofi is celebrating its commitment to the 2023 theme, ‘United in Action to Rescue and Achieve the Sustainable Development Goals (SDGs) For, With, and By Persons with Disabilities,’ through several initiatives.

In collaboration with its implementation partners, Sanofi has launched a unique external training programme for persons with disabilities, especially those from disadvantaged communities. This programme is designed to break barriers to education post-matriculation, offering management training and entrepreneurship skills in areas like financial literacy and marketing. This initiative also supports people with post-matric qualifications striving for employment, enhancing their employability and professional growth.

“As part of our commitment to Broad-Based Black Economic Empowerment (B-BBEE), 10% of learners on our Youth Employment Service “Y.E.S.” programme are persons with disabilities, underlining our commitment to diversity and inclusion,” says Selani.

Sanofi’s Diversity, Equity and Inclusion is bolstered through Employee Resource Groups (ERGs). The Ability+ ERG promotes a safe environment for employees to declare their disabilities, offering support and resources. Sanofi is also offering employees the chance to enrol in South African Sign Language courses, to transform its workplace into a disability-friendly space.

“Our partnerships with local and global organisations that are focused on disabilities will enable us to conduct workshops with leaders and employees, fostering a culture of understanding and empathy.”

“Sanofi also emphasises employee wellness and mental health, offering extensive support and wellness programmes,” says Selani. “These initiatives underscore our dedication to the well-being of all our employees.”

“As we mark IDPD 2023, Sanofi encourages organisations across all sectors to join us in these efforts. Together, we can make significant strides towards a more inclusive society and achieving the SDGs for, with, and by persons with disabilities,” concludes Selani.

Together, we are making a difference. Join us in our journey towards an inclusive future.

References:

1. World Health Organisation (WHO). Disability. [Mar 2023]. Available from: https://www.who.int/news-room/fact-sheets/detail/disability-and-health#:~:text=An%20estimated%201.3%20billion%20people%20%E2%80%93%20or%2016%25%20of%20the%20global,diseases%20and%20people%20living%20longer.
2. National Council of and for Person with Disabilities (NCPD). Available from: https://ncpd.org.za/wp-content/uploads/2023/09/NCPD-Infographic_2023.pdf

Categories : Diseases, Syndromes and Conditions PaediatricsTags :

Antibiotic Slashes Risk of Drug-resistant TB in Kids, Finds Major SA Study

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Tuberculosis bacteria. Credit: CDC

By Elri Voigt for Spotlight

For decades, the standard way to prevent people who were exposed to tuberculosis (TB) from falling ill with the disease was to offer them a medicine called isoniazid, taken daily for six or more months. That changed in the last decade with the development of new preventive therapy regimens that are taken for four, three, or even just one month.

One complexity, however, is that both isoniazid and the new regimens are much better at preventing normal drug-sensitive TB than they are at preventing drug-resistant forms of TB. This is not surprising. As explained by Paediatric Infectious Disease doctor and Professor of Global Child Health at Imperial College London, Dr James Seddon, the two drugs that have mainly been used to prevent drug-susceptible TB are isoniazid and rifampicin (rifampicin’s sister drug rifapentine is also used). Now, by definition, he explains multidrug-resistant (MDR) TB is resistant to both these drugs so it’s unlikely to have any impact.

The situation is particularly tricky when it comes to children. In a 2020 statement the World Health Organization (WHO) says that it estimated that worldwide between 25 000 and 32 000 children develop MDR-TB each year, and mainly acquire it through transmission from close contact with an adult or adolescent who has MDR-TB. According to Seddon, while there is some emerging observational evidence on the use of drugs other than isoniazid and rifampicin to prevent MDR-TB, there has been no clinically tested regimen to give to children following MDR-TB exposure.

Now, much anticipated results from a phase three trial has shown that a single antibiotic pill, given daily for six months, is safe and effective to use in children who have been exposed to MDR-TB.

Results from TB CHAMP

The trial, called TB-CHAMP, looked at the efficacy and safety of using the antibiotic levofloxacin to prevent TB in children exposed to MDR-TB. Top-line findings from the study was presented last week at the Union World Lung Conference held in Paris, France.

“The paediatric population is probably the most neglected of all the populations affected by MDR-TB,” Dr Anneke Hesseling, Director of the Paediatric TB Research Programme at Stellenbosch University, told the conference. “Fewer than 20% who develop MDR-TB disease are actually diagnosed and treated, and so to find more cases and prevent more cases is really, really critical…So prevention is really key, and the TB-CHAMP trial is really a phase three efficacy trial looking at levofloxacin to prevent new cases of TB in children and also looking at the safety of levofloxacin.”

Hesseling, who is the Principal Investigator of the study, says that TB-CHAMP is the first trial to provide clinical data on what drug might be used to prevent TB in children who have been exposed to MDR-TB. It was conducted at five sites across South Africa, all with high MDR-TB burdens. The study was led by Stellenbosch University and the Desmund Tutu TB Centre. The findings have not yet been published in a peer-reviewed journal.

922 children were randomised to receive either levofloxacin or a placebo for six months. 453 children got levofloxacin and 469 got the placebo. The primary efficacy data featured data from 916 of those children, with 451 in the levofloxacin arm and 465 in the placebo arm.

Hesseling says that only children who were exposed to an adult in their household with confirmed MDR-TB were included in the study. At first children below the age of five were recruited, regardless of their TB infection status. Later children between the ages of five and 17 were included, but they had to either have a TB infection or be living with HIV. The majority of the children, 90%, were younger than five years. TB infection was confirmed with a blood test.

By 48 weeks, Hesseling says five children in the levofloxacin arm versus 12 in the placebo arm developed TB, which amounts to an incidence rate of 1.1% in the levofloxacin arm, and 2.6% in the placebo arm.

Implication of results

“While TB preventive therapy (TPT) has long been recommended and available for young child contacts of people with drug-susceptible TB, there has not been sufficient evidence to make strong recommendations for treatment that could prevent DR-TB. Therefore, the TB-CHAMP findings are critically important for a number of reasons,” says Professor Guy Marks, President and Interim Executive Director, International Union Against Tuberculosis and Lung Disease (The Union).

“The study provides the first high-quality evidence that DR-TB can be prevented in children by using six months of daily levofloxacin, and that this is a safe medication. Furthermore, this will encourage more community-based contact screening, which will also lead to early detection of children and contacts of all ages who already have disease, and initiate treatment,” he adds.

“The impact [of the TB-CHAMP results] is potentially tremendous as it would prevent DR TB among child contacts. DR TB is more complex to treat and cure and often children are marginalised, so this study puts the spotlight on an effective way to protect children. This is not just about the life and health of the child but the social, economic and mental health implications for the caregiver and the entire family,” says Dr Priashni Subrayen, Technical Director for TB at The Aurum Institute.

Seddon, who is also one of the Co-PIs for the study, tells Spotlight that it was important to establish the safety of levofloxacin since it belongs to a class of drugs called the fluoroquinolones, which were thought to have terrible side effects when used in children.

Results from TB-CHAMP show that this is not the case.

The side effects were mild, and the regimen was well tolerated, according to Hesseling, with only eight children having a grade one or higher adverse event in the levofloxacin arm compared to four in the placebo arm. Two deaths were reported, one in each study arm, but were unrelated to the study. Overall, six children in the levofloxacin arm discontinued treatment or left the study early.

Researchers from TB-CHAMP collaborated with researchers from the V-QUIN trial – a phase three study that looked at levofloxacin as TB prevention in adults in Vietnam – in order to combine their data which allowed them to show data for levofloxacin across different age groups. Seddon explains: “They’ve applied a novel analytic approach, which uses a Bayesian, or probabilistic, framework, where we take the results of TB-CHAMP and we say well, if we actually use some of the information from V-QUIN to inform the TB-CHAMP results, we can make that a slightly more confident estimate,” he says.

The combined results, according to Hesseling were able to also show that levofloxacin reduced the risk of TB by about 60% across the age spectrum but with a tighter confidence interval, indicating a more precise estimate of the effect.

Seddon tells Spotlight that the combined data showed that there were no serious adverse events, but the adult population experienced more grade one and grade two side effects than the children, but these went away either over time or when the drug was stopped. The side effects included inflammation in the joints and tendons, which is a known side effect of this class of drug.

Not a silver bullet

While the findings could be a game-changer and potentially inform MDR-TB prevention guidelines, particularly in children, the regimen is by no means a silver bullet. Seddon says that while the regimen was safe, when participants were asked whether they liked the medicine, more people said they didn’t like it in the levofloxacin group versus the placebo. Another downside is that the pill was an adult formulation and thus needed to be cut and/or crushed for the kids to swallow.

Seddon explains that the WHO, who have been provided with the data from both studies and expected to meet in early December, would need to consider a variety of factors before deciding what to recommend about the use of levofloxacin for prevention. That includes the fact that you need to treat a lot of children for six months who might not have TB despite being exposed in order to prevent a few cases.

“You have to weigh up the benefits versus the risks and the risks are low, but it is still giving a drug for six months to children and most of them don’t need it. But the consequences of getting MDR-TB are so bad that we really want to prevent that,” he says.

There is also the question around what effect using a broad antibiotic as preventive treatment will have on the microbiome of children and how this might drive resistance to the fluoroquinolones. Seddon says stool samples were collected from the study participants to determine how the drug affected a child’s microbiome and the potential for driving resistance. These data will also be provided to the WHO.

“I think that the evidence base is now very strong on the basis of these two trials. I think you can really say the issue of whether levofloxacin prevents MDR-TB, we’ve put that to bed,” he says. “Are there going to be other studies? Yes. I think that this is not over, levofloxacin is not the perfect drug for preventive therapy.”

Marks adds to this saying: “An important next step for TPT in DR-TB contacts will be studies that evaluate regimens that are shorter than six months – a long time to take medication every day, which can often be challenging. Effective and safe shorter regimens are now being used for child contacts of drug-susceptible TB and we hope the same progress can be made for contacts of DR-TB.”

As Marks has already stated, currently there are no strong recommendations for MDR-TB prevention by the WHO.  In the 2020 TB prevention guidelines, it recommends that the preventative treatment for MDR-TB should be either a fluroquinolone or other second-line agent. It does however caution that these recommendations are based on low-quality evidence. Because of this, it recommends that the preventative treatment for MDR-TB should be individualised, and it be based on the drug resistance profile of the presumed contact. The drugs levofloxacin and moxifloxacin- both fluoroquinolones – may be used unless resistance is suspected. For levofloxacin a dosing schedule for both adults and children are proposed in the document.

Subrayen says that in South Africa the 2019 guidelines for the management of Rifampicin Resistant-TB (RR-TB) does indicate the use of levofloxacin as prevention treatment. The guidelines state that for prevention treatment a fluoroquinolone-based, multidrug regimen is preferred (either levofloxacin and high-dose isoniazid or levofloxacin, high-dose isoniazid and ethambutol). And if exposed to fluoroquinolone-resistant RR-TB, then high-dose isoniazid could be given. Delamanid could be considered as a potential option in very select cases. A training manual published this year by the Department of Health suggests that levofloxacin can be given on its own – but also stresses that the evidence base is weak, something that TB-CHAMP has presumably now changed.

Future of TPT

Seddon says that in a perfect world the ideal TB preventive regimen would be a so-called Pan regimen that could be given for a short period of time, to someone who has been exposed to TB and it works regardless of whether they had been exposed to drug-susceptible or drug-resistant TB.

“There are studies planned to use other drugs for prevention. There’s a study planned to use bedaquiline for a month or two and potentially using injectables that you just have to give once every couple of weeks. So, I think although this [levofloxacin] is a good option now, and it’s probably the best option we have now, this is not perfect,” Seddon says.

The study Seddon is referring to is the BREACH-TB study, a phase three trial that will look at whether a one-month treatment regimen of oral bedaquiline could prevent all forms of tuberculosis. It would be given to people exposed to both drug-resistant and drug-susceptible TB, and in people with HIV infection, including pregnant women and children.

Responding to questions from Spotlight earlier this year when this study was announced in the press, Sonya Krishnan, Assistant Professor of Medicine at Johns Hopkins University and Eric Nuermberger, Professor of Medicine at Johns Hopkins University, said that they anticipate recruiting between 1600 and 2 00 people to take part in the study – they expect around 400 to 500 of these will be people living with HIV. They also said that the control arm will receive the current standard of care in the country rather than placebo.

When asked whether any South African study sites will be included in the clinical trial, they said, “We very much plan to partner with study sites in South Africa. South Africa has a long-standing history of research excellence in TB.”

“A shorter regimen that fights both drug-resistant and drug-susceptible TB would be a game-changer for those living with TB and get us closer to our shared goal of ending the epidemic by 2030,” said Dr. Atul Gawande, USAID assistant administrator for Global Health, in a statement on the study. “This clinical trial will lay the foundation for a remarkable innovation in our fight against TB: a single-dose, long-acting injectable medicine.”

Indeed, if the science and development pans out as Gawande suggests it might, the future of TB preventive therapy might well be an entire course of therapy delivered through a single injection rather than a month or more of pills. As indicated in an article in the journal Clinical Infectious Diseases, work is already underway on the development of bedaquline, isoniazid, and rifapentine long-acting injections – though the research is for now still only in mice.

‘Communities need to be involved’

Hesseling raises the point that when treating or preventing TB, more than just the latest research advancement is needed to improve TB outcomes.

“For me treatment follows diagnosis, actually strengthening healthcare services, making communities more aware and creating demand for kids accessing diagnosis, preventive treatment and appropriate treatment, is actually where it starts,” she says. “So tools are amazing, but we actually need to have strong, effective healthcare services and knowledgeable, empowered communities.”

Seddon adds to this saying that results like those from TB-CHAMP are “a bit irrelevant if it is all kind of top down, paternalistic coming from the researchers, coming from the health system”.

“We really need to generate a community demand for this, where individuals living in communities where this is a problem are calling for this and getting angry about this and demanding it in a way that I think we’ve achieved very well with the HIV community,” he says. “It’s all well and good doing the science and then even better to get it [levofloxacin] into a guideline, but until there’s real demand for from the end user, I think it’s only going to have a certain amount of reach.”

Note: The terms DR-TB and MDR-TB are used somewhat interchangeably – Spotlight uses DR-TB to refer to drug-resistant forms of TB in general and MDR-TB to refer specifically to TB that is resistant to isoniazid and rifampicin.

Republished from Spotlight under a Creative Commons Licence.

Source: Spotlight

Categories : Healthcare Politics and RegulationsTags :

Glaring Voids Threaten SA’s Path to Equitable Healthcare

On By ModernMedia

A coherent, achievable path to universal health coverage now imperative

Glaring voids highlighted in submissions on the National Health Insurance (NHI) Bill threaten South Africa’s path to equitable healthcare access for all, cautions the Health Funders Association (HFA). The organisation has voiced its profound concern, emphasising the disconcerting sway of politics over the bedrock mission of prioritising the well-being of our nation within this critical healthcare deliberation.

“The practical barriers to successfully executing NHI as it is laid out in the Bill are hard to ignore, and yet the numerous concerns and suggestions raised in the consultation process have not been considered or implemented,” says Craig Comrie, chairperson of the National Health Funders Association (HFA).

“The clear shortcomings of the NHI Bill in terms of practical funding mechanisms and lack of collaboration with experienced health funders, among other aspects, have been overlooked for the most part, with only the Western Cape so far rejecting the Bill in its current form.”

The National Council of Provinces (NCOP) Committee on Health’s approval of the NHI Bill with insignificant edits does not address the numerous concerns raised in submissions made by the public and informed stakeholders, including the HFA, on behalf of its members.

The HFA is a professional body representing medical schemes and half of South Africa’s medical aid membership.

“There are constructive solutions to address the problems identified in the NHI Bill effectively, and it is not too late to fix the legislation. While the Bill is rushing towards the President’s pen to be enacted, the HFA respectfully appeals to the President to reconsider the wisdom of signing into law a Bill that has no workable funding mechanism while disregarding solutions proposed by private health funders, leading organisations, businesses and other key constituents,” Comrie says.

“We anticipate considerable resistance to the NHI Bill on Constitutional grounds, and as the HFA, we will continue to advocate for a more achievable approach to fulfilling universal health coverage aims.

“The timing of the recent flurry of activity in moving the Bill through the necessary hoops ahead of next year’s election invites the notion of a blunt instrument, an unrealistic election promise rather than a pragmatic solution for the highly complex health challenges South Africa faces,” he says.

Health Funders Association members, including leading lights in the industry such as Bankmed, CAMAF Medical Scheme, Discovery Health Medical Scheme, Fedhealth, Glencore Medical Scheme, Momentum Medical Scheme, Profmed and PPS Healthcare Administrators, to mention but a few, are ready to work with government to develop evidence-based solutions that will help secure access to quality healthcare for all South Africans.

“There is so much opportunity to make the NHI work. Private public partnerships and collaboration have achieved so much good for the benefit of South Africans in other sectors, and there is much our industry can contribute to help make quality healthcare more accessible and sustainable for all,” Comrie concludes.

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags :

Monitoring for Foetal Heart Condition in Pregnant Women with Autoimmune Antibodies

On By ModernMedia
Photo by Mart Production on Pexels

Some individuals with anti-Ro/SSA antibodies (anti–Sjögren’s-syndrome–related antigen A autoantibodies, also called anti-Ro antibodies) have autoimmune diseases such as lupus or Sjögren’s syndrome, but many have no symptoms. A clinical trial published in Arthritis & Rheumatology found that high levels of these antibodies in pregnant women are associated with foetal atrioventricular block (AVB), which occurs when inflammation and subsequent scarring prevent electric signals from the heart’s atria from reaching the ventricles. The disease is associated with life-long pacing and can be fatal.

In the trial, called Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), the incidence of AVB increased with higher levels of anti-Ro/SSA antibodies, reaching 7.7% for those in the top quartile, which increased to 27.3% in those with a previous child who had AVB, although participant numbers in that category were small.  Antibody titres did not change over time. The trial also revealed that home-based foetal heart rate monitoring reliably detected conduction abnormalities, which may reduce the need for serial echocardiograms.

“Examining the levels of anti-Ro/SSA antibodies is an important advance since for women with low titres, monitoring is probably not necessary and for those with high titres the increased risk supports surveillance,” said corresponding author Jill Buyon, MD, of NYU Langone Health. She added that this study also indicated that titres of antibodies do not change and that additional factors besides antibodies contribute to risk.

“That home monitoring can rapidly and accurately identify early foetal conduction disease is a major step forward that may significantly decrease the need for echocardiograms and hopefully facilitate reversibility,” added senior author and research professor Bettina Cuneo MD, of the University of Arizona-Tucson College of Medicine.

Source: Wiley

Categories : Mental Health Substance UseTags :

Cannabis Users Found to Have Higher Levels of Empathy

On By ModernMedia
Photo by Rodnae Productions on Pexels

A study of regular cannabis users and non-users found that users tend to have a greater understanding of the emotions of others, based on psychological assessments. Brain imaging tests also revealed that cannabis users’ anterior cingulate – a region generally affected by cannabis use and related to empathy – had stronger connectivity with brain regions related to sensing the emotional states of others within one’s own body.

The study, published in the Journal of Neuroscience Research, included 85 regular cannabis users and 51 non-consumers who completed psychometric tests and a subset of 46 users and 34 nonusers who underwent functional magnetic resonance imaging exams.

“Although further research is needed, these results open an exciting new window for exploring the potential effects of cannabis in aiding treatments for conditions involving deficits in social interactions, such as sociopathy, social anxiety, and avoidant personality disorder, among others,” said co-author Víctor Olalde-Mathieu, PhD, of the Universidad Nacional Autónoma de México.

Source: Wiley

Categories : Mental HealthTags :

Stopping Long-term ADHD Meds is Common among Young People

On By ModernMedia
Photo by Inzmam Khan

A pair of new studies has show that many patients stop taking ADHD medications within the first year, while those who take higher doses of ADHD medications long term seem to have a higher risk of some cardiovascular diseases. This is according to two new studies led by researchers from Karolinska Institutet and published in The Lancet Psychiatry and JAMA Psychiatry.

The Lancet Psychiatry study found that more than half of all teenagers, young adults and adults who received ADHD medication had stopped taking it within the first year. The proportion was slightly lower in children, whose decisions are made for them by carers, yet 35% still stopped their medication within a year.

Young adults risk falling between the cracks

The researchers analysed prescription data from over 1.2 million patients who started ADHD medication in Australia, Denmark, Hong Kong, Iceland, the Netherlands, Norway, the UK, Sweden and the USA. The pattern was the same in all countries/regions.

“It’s unlikely that so many people discontinue their treatment because their ADHD symptoms have remitted, meaning that the high rate of early discontinuation may be a major barrier to effective treatment,” says Zheng Chang, senior researcher at Karolinska Institutet who led both studies. “We haven’t been able to analyse the direct causes in this study, but common reasons for discontinuing ADHD medication are adverse reactions and lack of effect.”

The highest rate of medication discontinuation occurred among 18 to 19-year-olds. This is when they leave child and adolescent psychiatry and enter adult psychiatry, a transition where they risk falling between the cracks. This is a shortcoming that the healthcare services must remedy, researchers say.

“We need to improve the transition to adult psychiatry and spread knowledge about the fact that problems associated with ADHD often persist over time,” says Isabell Brikell, research coordinator at Karolinska Institutet, and one of the first authors of the study in The Lancet Psychiatry. “In addition, new digital tools such as simple SMS-based inventions could be used to help people with ADHD manage their medication.”

Denmark sticks out

A country that sticks out in the statistics is Denmark, which had a much lower proportion of children who discontinue their treatment within a year – 18%, as opposed to the mean of 35%. Compared with other Nordic countries like Sweden and Norway, the prescription of ADHD drugs is lower, which could suggest that medication is only prescribed to those with severe ADHD and the greatest need, researchers say.

“Sweden has a relatively high prescription rate of ADHD medication compared with many other European countries, so it is possible that we over-prescribe here,” says Zheng Chang.

In another study conducted with over 275 000 Swedish ADHD patients published in JAMA Psychiatry, Dr Chang and his research group examined ADHD medication use for up to 14 years. They were then able to show that ADHD medication when taken for a longer time and in higher doses than average is associated with a higher risk of some cardiovascular diseases, primarily hypertension and arterial disease. 

The risk of cardiovascular disease increased by approximately 4% per annum. The risk increase was greatest in the first few years of treatment and then levelled off, and it was only statistically significant at doses higher than 1.5 times the average daily dose (the defined daily dose, DDD). This means that those treated with lower doses are not likely to develop cardiovascular disease, according to the researchers.

Follow-up of patients advised

“There is a long list of drugs that have been linked to a comparable increased risk of hypertension when used long-term such as the one found here, so patients should not be alarmed by these findings,” says Le Zhang, postdoc researcher in Dr Chang’s research group and first author of the JAMA Psychiatry study. “However, in clinical practice, the raised risk should be carefully weighed against the recognised benefits of treatment on a case-by-case basis. Doctors should also regularly follow up the ADHD patients to find signs and symptoms of cardiovascular disease while they’re on medication over the long-term.” 

Since this is an observational study, it is not possible to conclude that it is the ADHD medication that leads to an increased risk of cardiovascular disease. As the researchers point out, it could depend on other medications, symptom severity or lifestyle factors.

Source: Karolinska Institutet