Scientists have identified a gene which, when missing or impaired, can cause obesity, behavioural problems and, in mothers, postnatal depression. The discovery, reported on 2 July in Cell, may have wider implications for the treatment of postnatal depression, with a study in mice suggesting that oxytocin may alleviate symptoms.
Obesity and postnatal depression are significant global health problems. Postnatal depression affects more than one in 10 women within a year of giving birth and is linked to an increased risk of suicide, which accounts for as many as one in five maternal deaths in high income countries. Meanwhile, obesity has more than doubled in adults since 1990 and quadrupled in adolescents, according to the World Health Organization.
While investigating two boys from different families with severe obesity, anxiety, autism, and behavioural problems triggered by sounds or smells, a team led by scientists at the University of Cambridge, UK, and Baylor College of Medicine, Houston, USA, discovered that the boys were missing a single gene, known as TRPC5, which sits on the X chromosome.
Further investigation revealed that both boys inherited the gene deletion from their mothers, who were missing the gene on one of their X chromosomes. The mothers also had obesity, but in addition had experienced postnatal depression.
To test if it was the TRPC5 gene that was causing the problems in the boys and their mothers, the researchers turned to animal models, genetically-engineering mice with a defective version of the gene (Trpc5 in mice).
Male mice with this defective gene displayed the same problems as the boys, including weight gain, anxiety, a dislike of social interactions, and aggressive behaviour. Female mice displayed the same behaviours, but when they became mothers, they also displayed depressive behaviour and impaired maternal care. Interestingly, male mice and female mice who were not mothers but carried the mutation did not show depression-like behaviour.
Dr Yong Xu, Associate Director for Basic Sciences at the USDA/ARS Children’s Nutrition Research Center at Baylor College of Medicine, said: “What we saw in those mice was quite remarkable. They displayed very similar behaviours to those seen in people missing the TRPC5 gene, which in mothers included signs of depression and a difficulty caring for their babies. This shows us that this gene is causing these behaviours.”
TRPC5 is one of a family of genes that are involved in detecting sensory signals, such as heat, taste and touch. This particular gene acts on a pathway in the hypothalamus region of the brain, where it is known to control appetite.
When the researchers looked in more detail at this brain region, they discovered that TRPC5 acts on oxytocin neurons – nerve cells that produce the hormone oxytocin, often nicknamed the ‘love hormone’ because of its release in response to displays of affection, emotion and bonding.
Deleting the gene from these oxytocin neurons led to otherwise healthy mice showing similar signs of anxiety, overeating and impaired sociability, and, in the case of mothers, postnatal depression. Restoring the gene in these neurons reduced body weight and symptoms of anxiety and postnatal depression.
In addition to acting on oxytocin neurons, the team showed that TRPC5 also acts on so-called POMC neurons, which have been known for some time to play an important role in regulating weight. Children in whom the POMC gene is not working properly often have an insatiable appetite and gain weight from an early age.
Professor Sadaf Farooqi from the Institute of Metabolic Science at the University of Cambridge said: “There’s a reason why people lacking TRPC5 develop all of these conditions. We’ve known for a long time that the hypothalamus plays a key role in regulating ‘instinctive behaviours’ – which enable humans and animals to survive – such as looking for food, social interaction, the flight or fight response, and caring for their infants. Our work shows that TRPC5 acts on oxytocin neurons in the hypothalamus to play a critical role in regulating our instincts.”
While deletions of the TRPC5 gene are rare, an analysis of DNA samples from around 500,000 individuals in UK Biobank revealed 369 people – around three-quarters of whom were women – that carried variants of the gene and had a higher-than-average body mass index.
The researchers say their findings suggests that restoring oxytocin could help treat people with missing or defective TRPC5 genes, and potentially mothers experiencing postnatal depression.
Professor Farooqi said: “While some genetic conditions such as TRPC5 deficiency are very rare, they teach us important lessons about how the body works. In this instance, we have made a breakthrough in understanding postnatal depression, a serious health problem about which very little is known despite many decades of research. And importantly, it may point to oxytocin as a possible treatment for some mothers with this condition.”
There is already evidence in animals that the oxytocin system is involved in both depression and in maternal care and there have been small trials into the use of oxytocin as a treatment. The team say their work provides direct proof of oxytocin’s role, which will be crucial in supporting bigger, multi-centre trials.
Professor Farooqi added: “This research reminds us that many behaviours which we assume are entirely under our control have a strong basis in biology, whether that’s our eating behaviour, anxiety or postnatal depression. We need to be more understanding and sympathetic towards people who suffer with these conditions.”
This work was supported by Wellcome, the National Institute for Health and Care Research (NIHR), NIHR Cambridge Biomedical Research Centre, Botnar Fondation and Bernard Wolfe Health Neuroscience Endowment.
Fish consumption during pregnancy is a complex scientific topic. While fish are rich in nutrients essential to brain development, such as polyunsaturated fatty acids, selenium, iodine, and vitamin D, they also contain methyl mercury, a known neurotoxicant. This has led the US Food and Drug Administration to recommend that expectant mothers limit consumption, inadvertently causing many women to completely stop eating fish during pregnancy.
Fish consumption is an important route of methyl mercury exposure, however, efforts to understand the health risk posed by mercury are further complicated by the fact that the nutritional benefits from fish may modify or reduce the toxicity posed by mercury. A new study appearing in the American Journal of Epidemiology based on data from a cohort of residents of a coastal community in Massachusetts creates a new framework that could untangle these questions, reduce confusion, and produce clearer guidance on fish consumption for pregnant mothers.
“We propose an alternative modelling approach to address limitations of previous models and to contribute thereby to improved evidence-based advice on the risks and benefits of fish consumption,” said the authors. “In fish-eating populations, this can be addressed by separating mercury exposure into fish intake and average mercury content of the consumed fish.”
The new research comes from an analysis of data from the New Bedford Cohort, which was created to assess the health of children born to mothers residing near the New Bedford Harbor Superfund site in Massachusetts. The current study included 361 children from the cohort who were born between 1993 and 1998 and at eight years old, underwent neurodevelopment assessments, including tests for IQ, language, memory, and attention.
The researchers were able to measure mercury exposure during the third trimester of pregnancy through hair sample collected from the mothers after birth. While hair samples have been the traditional method to study maternal mercury exposure, this approach alone cannot distinguish between mothers who frequently consumed low-mercury fish compared to those who consumed a smaller quantity of high-mercury fish.
To overcome this limitation, the researchers instead created a model that includes estimates of mercury exposure per serving of fish. This was possible because mothers in the cohort also completed a food questionnaire and reported the type and frequency of fish and shellfish consumed during pregnancy. The authors estimated the average mercury levels by type of fish, and when combined with the information about the mother’s diet, they were able to create a more precise and detailed method to estimate the joint associations of pregnancy fish intake and fish mercury levels on neurodevelopment.
Using this model, the researchers found that the relation between pregnancy fish consumption and subsequent neurodevelopment varied depending on the estimated average mercury levels in the fish. Specifically, consuming low mercury-containing fish was beneficial, while consuming fish with higher levels of mercury was detrimental.
“Given methodologic limitations to previous analyses, future work expanding our alternative modelling approach to account for both the average mercury and nutritional content of fish could facilitate better estimation of the risk-benefit tradeoffs of fish consumption, a key component of many healthy diets,” said the authors.
The authors are in the process of applying this model to other large studies of maternal fish consumption, including the Seychelles Child Development Study.
Nomantu Nkomo-Ralehoko is sworn in by Judge Lebogang Modiba as the new MEC for Health. (Photo: Gauteng Provincial Government)
By Ufrieda Ho
ANC support in Gauteng dipped below 40% in the recent provincial elections and an ANC-led minority government is now at the helm. Among those in Premier Panyaza Lesufi’s new Cabinet is Nomantu Nkomo-Ralehoko who’s been reappointed as MEC for Health and Wellness.
Nomantu Nkomo-Ralehoko was first appointed Gauteng’s MEC for Health and Wellness in October 2022. A long-time ANC member, she previously served as MEC for Finance and e-Government and has been a member of the provincial legislature since 1999.
She returns to the critical role at a time when the province’s health department, based on extensive reporting by Spotlight and other publications, remains mired in a chronic cycle of administrative and service delivery dysfunction.
At just under R65 billion for the current financial year, the department gets a massive slice of the Gauteng budget. While the National Department of Health leads on health policy, the day-to-day running of public healthcare services is managed by provincial departments of health.
The Gauteng health department has a high number of vacancies. On the administrative side this includes the critical position of a chief financial officer (CFO). The previous CFO, Lerato Madyo, was suspended in August 2022. Her case is still to be concluded. Research conducted last year by community healthcare monitoring group Ritshidze found that the majority of healthcare facility staff and public healthcare users that they surveyed felt that healthcare facilities were understaffed.
Madyo’s case is connected to ongoing investigations into corruption at Tembisa Hospital undertaken by the Special Investigating Unit. This was also the issue that whistle-blower Babita Deokaran was investigating before she was assassinated in August 2021. Deokaran was acting chief finance director before she was killed. Since her death it’s been confirmed that there was corrupt spending to the tune of R1bn at Tembisa Hospital.
When Nkomo-Ralehoko answered 10 questions from Spotlight shortly after her appointment in 2022, she said: “One of my immediate focus areas is to ensure that the department’s systems across delivery areas such as Finance, Human Resources, Monitoring and Evaluation, Risk Management, etc. are strengthened so that processes are not dependent on human vulnerability but there are clear checks and balances. An environment that has no consequence management breeds ill-discipline and a culture of ignoring processes and procedures as prescribed in our legislative framework.”
Gauteng also faces mounting surgery and oncology treatment backlogs. Its clunky supply chains and procurement systems have often left suppliers unpaid and facilities struggling without basic medical consumables as well as not being able to procure large pieces of equipment when it’s been needed. Some hospitals have had periods when patients have had to go without food.
There remains questions about governance capacity in the department. Notable examples from Nkomo-Ralehoko’s tenure so far include inaction over utilising a March 2023 Gauteng Treasury allocation of R784 million for outsourcing radiation oncology services. These ring-fenced funds were secured following sustained pressure and protests by activists and civil society. To date, this money has still not been spent.
The department is also still to implement a June 2022 memorandum of agreement with the University of Witwatersrand. The agreement sets a framework for the department and the university to mutually address many of the health sector challenges in the province, while ensuring the academic training of the next generation of doctors takes place.
Another key challenge for Nkomo-Ralehoko will be how to navigate a changed Gauteng Provincial Legislature in this seventh administration. There is no outright majority and there is no unity government deal that includes the largest opposition party, the Democratic Alliance (DA). This will represent distinct hurdles for passing budgets or garnering enough votes for approvals in the house.
Despite these challenges, the reappointment of 58-year-old Nkomo-Ralehoko is being welcomed by some. They say that she brings stability to a portfolio that has been plagued by shaky, short-lived tenures in the top role. They say she has a flexible leadership style, and that she is open to working with many different stakeholders. But her critics charge that she cannot deliver the overhaul that the department needs and that she has not been tough enough on corruption.
‘More of the same’
Jack Bloom is the DA shadow minister for health in Gauteng. He says: “I don’t think the present MEC deserves to be reappointed, but that’s for the ruling party to determine. What we will get going forward is more of the same. The Gauteng Department of Health needs wholesale change but it’s not going to happen under the present situation.”
Bloom says Nkomo-Ralehoko’s comeback is “cadre deployment and political protection” and he adds: “I’m afraid that the corruption is across the board and the looting is going to continue.”
He says the MEC slow-walked disciplinary action on many suspended senior staffers and has also failed to tighten up on the likes of pre-employment checks on would-be employees, resulting, he says, in weak candidates being appointed.
The EFF is the third largest party in the Gauteng legislature. Nkululeko Dunga was contacted to weigh in on Nkomo-Ralehoko’s reappointment but he declined to take our calls and didn’t respond to written questions.
‘Delays that cost lives’
Speaking briefly to news channel eNCA after she signed her oath of office on 3 July, Nkomo-Ralehoko mentioned oncology and radiation services as one of her priority areas. She referred specifically to the building of bunker-like facilities in order to house specialist cancer treatment equipment procured for Chris Hani Baragwanath Hospital and George Mukhari Hospital.
However, for Salome Meyer of the Cancer Alliance, the fact that equipment has been procured but is sitting in storage amounts to delays that cost lives. She says there are currently 3 000 patients in the province on waiting lists for cancer treatment.
“Our facilities are operational but they aren’t operating at full capacity because the equipment is not in use or we don’t have staff to operate the equipment,” Meyer says.
“What we’re seeing is resignation after resignation of radiation therapists because they aren’t on the correct pay grade. So even when we do get equipment there is not enough people to operate the equipment.
“The MEC has to start looking after her own people – the people who work in our clinics and hospitals,” she says.
‘Ensuring stability’
For the Democratic Nursing Organisation of South Africa (Denosa) in Gauteng though, Nkomo-Ralehoko has used her 20 months in the MEC role so far to start making the right turnarounds for the health department.
Bongani Mazibuko of the nursing association says: “We believe that this welcome appointment of the MEC will go a long way in ensuring that there’s stability in the department and it’s something that Denosa has long been calling for”.
Lack of stability has been a feature of Gauteng health over the last decade or so. When Nkomo-Ralehoko was appointed in 2022, she replaced Nomathemba Mokgethi, who had been in the job for less than two years. Prior to Mokgethi, Bandile Masuku was also in the position for less than two years. Gwen Ramokgopa filled in for a bit more than two years, and before her, Qedani Mahlangu was forced to resign after the Life Esidemeni tragedy.
Denosa in Gauteng also call for the finalisation of CEO appointments and for senior management posts to be filled. They also say fixing of infrastructure is critical “so that the department can be more functional”.
Mazibuko adds: “We need to ensure that appointment of nurses is prioritised as they are the backbone of the system. But we have faith that we can continue working together to ensure that the people of Gauteng get the health that they deserve.”
Right direction, but needs to act on corruption
Treatment Action Campaign Gauteng chairperson Monwabisi Mbasa also supports Nkomo-Ralehoko’s reappointment. He says compared to her predecessors, Nkomo-Ralehoko has so far been someone they feel they can work with.
“We have seen that in the past nearly two years the MEC has been trying to address some issues plaguing public healthcare at provincial, district and clinic level. She is hands-on and flexible, so we have confidence in her still,” Mbasa says.
But Mbasa says she must be held to account on not taking “drastic action against corruption”. He says 26 of Gauteng’s 37 public hospitals have in recent times run out of food but Nkomo-Ralehoko’s intervention included using suppliers and service providers who were not properly registered. He says it is a red flag and they will continue to hold the MEC to account.
Mbasa says to move forward now for health in the province will require alignment of the health department with the departments of infrastructure and development and of finance.
“Infrastructure of our health facilities is an emergency. We are also calling for the improvement of supply chain management and procurement of goods and services and we need to improve human resources.
“There are challenges and weakness in the Cabinet but it’s good that we are not working with completely new people in these portfolios. This is the time to accelerate and to ensure that we use the seventh administration to improve the delivery of public health,” Mbasa says.
After long and tense talks, negotiations with the DA to form part of the provincial executive deadlocked. This resulted in Premier Panyaza Lesufi naming a Cabinet with seven MEC positions for the ANC and one each to the PA, IFP and Rise Mzansi.
A new generation of prosthetic digits is transforming the lives of finger amputees.
Whilst small in size, the role of fingers in our overall body mobility is huge. Our fingers play a critical role in the accomplishment of everyday activities, allowing for tactile sensations and multiple fine movements from the grasping and manipulation of objects through to performing complex tasks.
Unfortunately, a significant number of finger amputations occurs each year. In fact, finger amputations account for well over 90% of all upper limb loss. The impact of this often extends far beyond the immediate area of amputation, having a much greater effect on the individual’s entire mobility. According to the American Medical Association, losing the index and middle fingers mid-metacarpal creates a 40% impairment of the hand, 36% impairment of the upper extremity and 22% impairment of the whole body. The loss of four fingers is equivalent to a leg amputation or the loss of an eye in total impairment.[1]
The role of prosthetics in assisting these amputees to lead a far more mobile and functional life has come a long way. Traditionally, prosthetic fingers were only cosmetic and not functional. However, innovations in prosthetics technology have revolutionised this, enabling partial hand and/ or finger amputees to not only return to work but, as importantly, to a life without limitations. A recent report by the National Library of Medicine, stated that, “Over the past decade, significant advances have been made in 3D-printed prosthetics owing to their light weight, on-site fabrication, and easy customisation.”[2]
“Technology has struggled to provide relevant and fit-for-purpose solutions, leaving a void in the market,” says Ernst van Dyk (Managing Director, Össur South Africa). Össur, a global provider of non-invasive orthopaedics, recently announced its ownership of Naked Prosthetics – a provider of functional devices for partial hand and finger amputees. Making use of traditional machining, injection moulding and 3D printing, Naked Prosthetics develops and makes customised, robust and functional prostheses.
“We offer a fully customisable prosthetic finger design that allows the amputee full finger functionality,” continues van Dyk. These biomechanical prosthetic fingers are designed to replace partial or total loss of the fingers and functions exactly as a finger would. Further, the prosthetic, a non-motorised device, uses the remainder of an amputee’s finger to power the device.
Using sizing rings and photos specific to each amputee, the devices make use of a very high-end 3D printer to create the simple, elegant and fully functional device. Working with physicians, surgeons and prosthetists, each prosthetic finger is customised to the exact needs of each individual patient. Each affected finger receives a custom design to restore digit length, joint spacing and range of motion, accounting for a user’s unique amputation level and joint capability. Beyond the functional design, each has been tested for structural integrity and fatigue life.
Using mass-customisation and novel design, Naked Prosthetics’ fingers restore natural motion, dexterity and strength and are the result of strong collaboration between experienced engineers from aerospace, robotics, prosthetics and product development together with clinicians and patients. A strong focus on engineering design means that the devices are kinematically and structurally optimised to account for both the capabilities of the patient’s driving joints and the conditions under which the devices are used. Each device is designed with a safety factor above and beyond any forces the user will experience and can be used in virtually any environment.
Operated by the user through intuitive movement and driven by remaining intact joints, these prostheses require little acclimation and restore digit dexterity and hand strength without specialised training. Users report that with time these prostheses feel like a part of their bodies.
“Once a customer is fitted with their prosthetic finger, it is only a matter of weeks or months before they are fully functioning,” continues van Dyk. “Although the finger, or a portion of the finger is gone, the vibration of what is left sends a message to the brain allowing it to re-map and bring back function.” These functional, high-quality finger devices aim to restore the user’s ability to perform daily tasks, support job retention and encourage an active lifestyle.
Products such as these were not possible until only a few years ago. Says van Dyk, “Detailed CAD technology and 3-D printing makes it possible to mass-produce mechanical prostheses. It includes our custom body-driven devices (PIPDriver, MCPDriver, and ThumbDriver) that are designed for the unique shape of each patient’s hand and fingers after their amputation as well as the GripLock Finger (a passive, positionable device for those who suffered complete finger amputations or were born with congenital anomalies).” The GripLock Finger weighs in at an industry best of 25 grams and can hold up to 90 kilograms. These prostheses, made from aluminium, stainless steel, and medical-grade nylon (with a conductive tip that works on smart touch screens), are strong and rugged.
“The prevalence of finger and thumb amputations and the impact of this on the lives of these amputees deserves a high level of care,” says van Dyk. “Whilst development of prostheses has been impeded by technical and anatomical challenges, a new generation of practical, durable and body-driven prosthetic digits can enable care teams to address an unmet need and transform the lives of people who have undergone finger amputation.”
Xylazine, only intended for animals, is being added to opioids and cocaine, with deadly effects. Photo by Colin Davis on Unsplash
Xylazine is an FDA-approved sedative and pain reliever for use in animals, but it has severe adverse effects when used in humans. Now, it is now being added illicitly to opioids, like fentanyl and heroin, as well as cocaine – leading to a sharp rise in overdose deaths.
Scripps Research chemical biologists have developed a vaccine to block the effects of xylazine’s toxicity. The vaccine works by training the immune system to attack the drug, which is described in a new paper published in Chemical Communications.
“We demonstrated that a vaccine can reverse the symptoms of a xylazine overdose in rodents,” says study senior author Kim D. Janda, PhD, professor of chemistry at Scripps Research. “There is currently no remedy for xylazine poisoning other than supportive care, thus, we believe our research efforts and the data we have provided will pave the way for an effective treatment in humans.”
The rapid increase in lethal drug overdoses attributed to xylazine combined with fentanyl prompted the White House Office of National Drug Control Policy to declare this combination an emerging threat to the United States. Xylazine intoxication presents similarly to opioid overdose, causing respiratory and central nervous system depression, and it can heighten the effects of opioids. However, naloxone – typically administered to reverse the effects of opioids – does not tackle the impact of xylazine, highlighting the need for effective measures to treat acute toxicity caused by xylazine.
Researchers suspect xylazine works by reducing blood flow to the brain, among other areas of the body. The drug also causes non-healing skin lesions and wounds, often located on the forearms and lower legs, that can require amputation in some cases – giving it the nickname “zombie drug.”
Although no treatment currently exists, targeted vaccines may offer a solution. Antibodies from vaccination can target toxins as well as viruses and bacteria. But sometimes molecules are too small to initiate an immune response, as is the case with xylazine. So, to circumvent this problem, the researchers created a vaccine using a design principle that Janda pioneered, which relies on pairing the drug molecule (called a hapten) with a larger carrier molecule (a protein) and an adjuvant.
In this study, the scientists combined a xylazine hapten with multiple different protein types, to see which combination would create a robust immune response against xylazine. The team tested three vaccine formulations (termed TT, KLH and CRM197, based on the protein involved) to see which vaccine cocktail could help rodents after being challenged with xylazine. One of the three vaccines (TT) significantly increased movement in mice given xylazine after 10 minutes, while two of the three vaccines (TT and KLH) led to an improvement in breathing.
The scientists also examined how these vaccines would limit xylazine blood brain barrier, (BBB) permeation, a filtering mechanism that scrutinizes drug penetration. When xylazine was injected, it immediately crossed into the brain to bind with receptors. Antibodies typically cannot navigate the BBB; however, two of the three vaccines (TT and KLH) showed a strong ability to stop xylazine from reaching its receptors in the brain, limiting its detrimental effects.
A provisional patent has been filed on the research. In the future, his team will build off this work to create a bifunctional antibody that will reverse both fentanyl and xylazine’s toxicity simultaneously, something that naloxone cannot do.
“A monoclonal antibody treatment could be given in tandem with the vaccine to provide both immediate and long-term protection from both opioid substance use disorders as well as opioid-xylazine overdoses,” says Janda. “This strategy could make a significant impact on the opioid epidemic.”
Shin splints are a common complaint among runners, especially if they use treadmills. A randomised controlled trial found that four weeks of gait training outdoors, in addition to home exercises often prescribed for shin splints, led to improved running biomechanics even when the runners were using a treadmill. These improvements included decreasing the time the runners’ feet were in contact with the ground or treadmill, a recently identified contributor to shin splints.
Based on the trial results, the researchers, including UVA Health sports medicine expert David J. Hryvniak, DO, are recommending that clinicians begin including outdoor gait training as part of rehabilitation programs for patients struggling with chronic shin splints.
“This is an important finding for clinicians, as this gives us a tool to use to help these runners,” said Hryvniak, a running medicine specialist who is part of UVA Health’s Runner’s Clinic. “These gait-training cues can be an easy thing to add into a rehab program to help patients improve running mechanics that can underlie many common running injuries.”
Soothing shin splints
Affecting approximately 40% of all runners, shin splints typically begin as tenderness in the lower leg that goes away after exercising. But for regular runners, this pain can worsen and become persistent. In severe cases, shin splints can even lead to stress fractures.
Prior research has found that short courses of outdoor gait training can significantly reduce shin-splint pain for outdoor runners. But experts had been uncertain if these benefits would transfer to the flat, regular surface of treadmill running. That prompted an interdisciplinary team of researchers to launch a randomised trial to find out if outdoor gait training would benefit treadmill users.
The researchers enrolled 17 treadmill runners between ages 18 and 45 who ran at least three times a week and who had been suffering lower leg pain during or after running for at least a month. The volunteers were randomly divided into two groups: One group received four weeks of outdoor gait training and performed commonly prescribed home strengthening exercises, while the other group only performed the home exercises.
During the gait training, participants were provided with “vibrotactile feedback” – meaning they felt a little vibration – when special sensors in their shoes detected their feet were in contact with the ground for too long. This helped them improve their stride and gait to reduce this potential contributor to shin splints.
At the end of the study period, both groups saw strength improvements in their legs. But the gait trainers also had improved running technique, or what the researchers call “favorable adjustments in running gait mechanics.” And, sure enough, these gait improvements were seen during both outdoor runs and treadmill runs.
That suggests outdoor gait training could be an important new tool to help treadmill users work up a sweat pain-free, the researchers say.
“Shin splints are a very common running injury, especially with those who are new to the sport,” Hryvniak said. “These gait cues are something that have been shown to be an effective tool that patients can use literally ‘on the run.’”
A handful of common surgical procedures account for large shares of all opioids dispensed after surgery in children and adults, according to two studies recently published by researchers at the University of Michigan.
The studies, published this week in Pediatrics and JAMA Network Open, report that the top three procedures for children ages 0–11 account for 59% of opioids dispensed after surgery (tonsillectomies and adenoidectomies 50%, upper extremity fractures 5% and removal of deep implants 4%). Among those ages 12–21, the top three procedures account for about a third of post-surgery opioid prescriptions (tonsillectomies and adenoidectomies 13%, knee arthroscopies 13% and caesarean deliveries 8%).
For adults ages 18–44, C-sections account for the highest share of opioids dispensed post-surgery (19%), followed by hysterectomies (7%) and knee arthroscopies (6%). Among those ages 45-64, four of the top five procedures were orthopaedic procedures, collectively accounting for 27% of total opioid prescriptions dispensed after surgery.
“Our findings suggest that surgical opioid prescribing is highly concentrated among a small group of procedures. Efforts to ensure safe and appropriate surgical opioid prescribing should focus on these procedures,” said Kao-Ping Chua, lead author of the study in Pediatrics, assistant professor at the U-M Medical School and School of Public Health, and co-director of the Research and Data Domain at the U-M Opioid Research Institute.
To conduct the study, the researchers developed an algorithm to identify 1082 major surgical procedures using procedure codes, a medical classification tool used to identify specific surgical, medical or diagnostic interventions. The algorithm was then applied to identify privately and publicly insured children and adults undergoing surgery from Dec. 1, 2020 through Nov. 30, 2021.
The information was organized through a novel system developed by the study team, which allowed them to connect different sets of data that had previously been seen as unrelated. This new method allows for improved comparability and contrast, according to lead investigators.
In addition to determining which procedures accounted for the highest shares of opioids, the researchers also examined the size of opioid prescriptions for each procedure. For many procedures, prescriptions were far larger than the amount patients typically need for a particular procedure.
“Our findings suggest that there are important opportunities to reduce surgical opioid prescribing without compromising pain control,” said Dominic Alessio-Bilowus, lead author of the paper focused on adults published in JAMA Network Open and a medical student at Wayne State University who just completed a research year at U-M.
Randomized controlled trials, or RCTs, are believed to be the best way to study the safety and efficacy of new treatments in clinical research. However, a recent study from Michigan State University found that people of colour and white women are significantly underrepresented in RCTs due to systematic biases.
The study, published in the Journal of Ethnicity in Substance Abuse, reviewed 18 RCTs conducted over the last 15 years that tested treatments for post-traumatic stress and alcohol use disorder. The researchers found that despite women having double the rates of post-traumatic stress and alcohol use disorder than men, and people of colour having worse chronicity than white people, most participants were white (59.5%) and male (about 78%).
“Because RCTs are the gold standard for treatment studies and drug trials, we rarely ask the important questions about their limitations and failings,” said Nicole Buchanan, co-author of the study and professor in MSU’s Department of Psychology. “For RCTs to meet their full potential, investigators need to fix barriers to inclusion. Increasing representation in RCTs is not simply an issue for equity, but it is also essential to enhancing the quality of our science and meeting the needs of the public that funds these studies through their hard-earned tax dollars.”
The researchers found that the design and implementation of the randomised controlled trials contributed to the lack of representation of people of colour and women. This happened because trials were conducted in areas where white men were the majority demographic group and study samples almost always reflected the demographic makeup where studies occurred. Additionally, those designing the studies seldom acknowledged race or gender differences, meaning they did not intentionally recruit diverse samples.
Furthermore, the journals publishing these studies did not have regulations requiring sample diversity, equity or inclusion as appropriate to the conditions under investigation.
“Marginalized groups have unique experiences from privileged groups, and when marginalised groups are poorly included in research, we remain in the dark about their experiences, insights, needs and strengths,” said Mallet Reid, co-author of the study and doctoral candidate in MSU’s Department of Psychology. “This means that clinicians and researchers may unknowinglyremain ignorant to how to attend to the trauma and addiction challenges facing marginalised groups and may unwittingly perpetuate microaggressions against marginalised groups in clinical settings or fail to meet their needs.”
A world-first study in animals has found low-dose aspirin may treat flu-induced blood vessel inflammation, creating better blood flow to the placenta during pregnancy. The study, published in Frontiers in Immunology, showed that treatment for preeclampsia could be applied to flu infections – and the results, according to the research team, were very promising.
Lead researcher and RMIT Post-Doctoral Research Fellow, Dr Stella Liong, said flu infections during pregnancy can resemble preeclampsia, a pregnancy complication that causes inflammation to the aorta and blood vessels.
Low-dose aspirin is commonly taken to prevent preeclampsia, as it stops the body from creating chemicals that cause inflammation.
“When the vascular system is inflamed, it leads to poor blood flow and affects the aorta’s function,” she said.
“This is especially a problem during pregnancy where good blood flow to the placenta is crucial to the development of the foetus.”
The research, led by RMIT University in collaboration with Trinity College Dublin, Ireland Professor John O’Leary and University of South Australia Professor Doug Brooks, found foetuses and placenta from mice with influenza A were smaller than those from uninfected mice.
Markers of low oxygen to the blood and poor blood vessel development were also evident in the foetuses.
However, mice treated daily with low-dose aspirin had less inflammation and improved foetal development and offspring survival.
While the research was still awaiting human clinical trials, Liong said low-dose aspirin was already recognised as safe to take during pregnancy.
However, the research team recommended pregnant people seek medical advice before taking new medications.
Brooks said influenza A infections during pregnancy was a big concern as every pregnancy overlaps with part of a flu season.
“There are long term implications for both the mother and the foetus, and aspirin might provide a simple solution for preventing this influenza associated pathology,” Brooks said.
Chemotherapy is known to cause behavioural side effects, including cognitive decline. Notably, the gut microbiome communicates with the brain to affect behaviour, including cognition.
“For the first time ever, our Intelligut Study found that the gut microbiome has been implicated in cognitive side effects of chemotherapy in humans,” said senior author Leah Pyter, associate professor of psychiatry and neuroscience at Ohio State University. “The potential connection between the gut and the brain would allow us to create treatments for the gut to treat the brain.”
This clinical longitudinal observational study explored whether chemotherapy-induced disruption of the gut microbiome relates to cognitive decline and circulating inflammatory signals.
Faecal samples, blood and cognitive measures were collected from 77 patients with breast cancer before, during and after chemotherapy.
“We found that patients treated with chemotherapy who showed decreases in cognitive performance also had reductions in the diversity of their gut microbiome,” said Pyter, also a researcher with Ohio State’s Institute for Behavioral Medicine Research and member of the Cancer Control Research Program at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).
This research builds on Pyter’s prior research in mouse models that found chemotherapy-induced shifts in the gut microbiome cause neurobiological changes and behavioural side effects. The current study indicates that an association between gut microbiome and cognitive performance exists in humans as well.
“Side effects of chemotherapy are common and may reduce quality of life, but these side effects can be dismissed as ‘part of chemotherapy’ and therefore overlooked and under-treated,” Pyter said. “We believe that gut microbiome-focused interventions, such as faecal microbial transplantation, may improve behavioural side effects of chemotherapy.”
OSUCCC—James researchers are also conducting research studies on how the gut microbiome impacts cancer treatment effectiveness and its role in reducing or increasing cancer risk.
“Chemotherapy is a very important tool for stopping many cancers and side effects should not deter patients who would benefit from this type of therapy from pursuing it, but we know the side effects of some treatment regimens can be quite challenging for patients to complete,” said David Cohn, MD, interim chief executive officer of the OSUCCC – James. “It’s a careful tightrope of walking between effective cancer control and side effect management – and our team is working every day, in the hospital clinics and the lab, to develop ways to manage the side effects of disease treatment with an eye toward quality of life.”
