Sydney Local Health District

Researchers have found a new way to supply the body with insulin. The medication that can be taken orally has already been tested on baboons, in which it was found to lower the blood sugar levels without causing hypoglycemia. The new insulin is ready to be tested on humans in 2025. If all goes well, diabetics are facing an easier life without injections. There are approximately 425 million people worldwide with diabetes. Approximately 75 million of these inject themselves with insulin daily. Now they may soon have a new alternative to syringes or insulin pumps. Scientists have found a new way to supply the body with smart insulin. The new insulin can be eaten by taking a capsule or even better, within a piece chocolate. Inside these we find tiny nano-carriers to which the insulin is encapsulated. The particles are 1/10,000th the width of a human hair and so small that you cannot even see them under a normal microscope. "This way of taking insulin is more precise because it delivers the insulin rapidly to the areas of the body that need it most. When you take insulin with a syringe, it is spread throughout the body where it can cause unwanted side effects," explains Professor Peter McCourt at UiT Norway's Arctic University. He is one of the researchers behind the study. The research was recently published in Nature Nanotechnology. Delivered to the liver It was researchers at the University of Sydney and Sydney Local Health District who, in collaboration with UiT, discovered many years ago that it was possible to deliver medicines via nano-carriers to the liver. The method has then been further developed in Australia and in Europe. Many medicines can be taken by mouth, but until now people have had to inject insulin into the body. McCourt explains that the problem with insulin with a nano-carrier is that it breaks down in the stomach and thus does not get to where it is needed in the body. This has been a major challenge for developing a diabetes medicine that can be taken orally. But now the researchers have solved this challenge. "We have created a coating to protect the insulin from being broken down by stomach acid and digestive enzymes on its way through the digestive system, keeping it safe until it reaches its destination, namely the liver," says McCourt, who is a liver biologist. The coating is then broken down in the liver by enzymes that are active only when the blood sugar levels are high, releasing the insulin where it can then act in the liver, muscle, and fat to remove sugar from the blood. "This means that when blood sugar is high, there is a rapid release of insulin, and even more importantly, when blood sugar is low, no insulin is released," says Nicholas J. Hunt at the University of Sydney who, together with Victoria Cogger, leads the project. He explains that this is a more practical and patient-friendly method of managing diabetes because it greatly reduces the risk of a low blood sugar event occurring, namely hypoglycemia and allows for the controlled released of insulin depending on the patient's needs, unlike injections where all the insulin is released in one shot. Fewer side effects The new method works similarly to how insulin works in healthy people. The pancreas produces insulin which first passes through the liver where a large portion of it is absorbed and maintains stable blood sugar levels. In the new insulin method, the nano-carrier releases insulin in the liver, where it can be taken up or enter the blood to circulate in the body. "When you inject insulin under the skin with a syringe, far more of it goes to the muscles and to adipose tissues that would normally happen if it was released from the pancreas, which can lead to the accumulation of fats. It can also lead to hypoglycemia, which can potentially be dangerous for people with diabetes. With the new method, there will be fewer such side effects. In addition, you do not need to stab yourself with a needle and you can take the medicine you need in a slightly more discreet way. Also, this form of insulin does not need to be refrigerated. Tested on baboons The oral insulin has been tested on nematodes, on mice and rats. And lastly, the medicine has now been tested on baboons in the National Baboon Colony in Australia. "In order to make the oral insulin palatable we incorporated it into sugar-free chocolate, this approach was well received" says Hunt. He says that 20 baboons have taken part in this study. When they received the medicine, their blood sugar was lowered. The baboons were normal, healthy baboons, but the oral insulin have also been tested on mice and rats that actually have diabetes. The mice and rats did not have low blood sugar events (hypoglycemia), gain weight or fat accumulation in the liver overcoming current challenges with injectable and other oral insulins. What remains now is to test the new method on humans. Ready for use in 2-3 years "Trials on humans will start in 2025 led by the spin out company Endo Axiom Pty Ltd. Clinical trials are performed in 3 phases; in the phase I trial we will investigate the safety of the oral insulin and critically look at the incidence of hypoglycemia in healthy and type 1 diabetic patients. Our team is very excited to see if we can reproduce the absent hypoglycemia results seen in baboons in humans as this would be a huge step forward. The experiments follow strict quality requirements and must be carried out in collaboration with physicians to ensure that they are safe for the test subjects" says Hunt. "After this phase I we will know that it is safe for humans and will investigate how it can replace injections for diabetic patients in phase 2 trials," says the researcher. The researchers hope that the new medicine can be ready for use by everyone in 2-3 years.

Opioid pain-relieving medicines are not more effective than a placebo in relieving acute back and neck pain and may even cause harm, according to a recent trial. Opioid pain-relieving medicines are not more effective than a placebo in relieving acute back and neck pain and may even cause harm, according to a world-first trial led by the University of Sydney. The researchers say this is proof that treatment guidelines should be updated to advise against the use of opioids for this purpose. Over 577 million people worldwide experience low back and neck pain at any one time. Despite a global push to reduce the use of opioids, in Australia approximately 40 to 70 percent of those who present with neck and back complaints are prescribed opioids for their pain. The OPAL trial recruited close to 350 participants from 157 primary care and emergency department sites. Participants with acute-meaning sudden and generally short-term-back or neck pain were randomly allocated to a six-week course of a commonly prescribed opioid or a placebo. Both groups also received standard care including advice to avoid bed rest and stay active. Participants were followed for 52 weeks. The results of the trial are published in The Lancet today. What did the study find? The research team says that according to current back and neck pain guidelines opioids can be considered as a last resort if all other pharmacological options have failed, however, this study is evidence that opioids should not be recommended at all. "We have clearly shown there is no benefit to prescribing an opioid for pain management in people with acute back or neck pain, and in fact, it could cause harm in the long-term even with only a short course of treatment," said lead investigator Professor Christine Lin from Sydney Musculoskeletal Health, an initiative of the University of Sydney, Sydney Local Health District and Northern Sydney Local Health District "Opioids should not be recommended for acute back and neck pain full stop. "Not even when other drug treatments are not able to be prescribed or have not been effective for a patient." The study complements previous research into opioid use for chronic (long-term) low back pain which found a small treatment benefit, but increased risk of harm. Global push to reduce opioid use Reducing the overuse of opioids is a global health priority. Medical authorities around the world have cautioned that due to the significant risk of harm to individuals and society, opioids should only be used where there is evidence that the benefits outweigh the harms. Co-author Professor Chris Maher said in recent years there has been a shift in focus from opioid to non-opioid treatments for low back pain, with a focus on physical and psychological therapies and simple analgesics such as anti-inflammatory medicines (called NSAIDs). "This study is further evidence that the first line management of acute low back pain and neck pain should rely on reassurance and advice to stay active, and simple analgesics like non-steroidal anti-inflammatory drugs if necessary," said Professor Maher, also of Sydney Musculoskeletal Health. Harm caused by opioid use Professor Andrew McLachlan, Dean of Sydney Pharmacy School and co-investigator, said the Lancet study is important and should influence prescribing and dispensing of these medicines as Australia faces rising rates of opioid use. According to Australia's Therapeutic Goods Administration, every day in Australia nearly 150 hospitalisations and 14 emergency department admissions involve issues relating to opioid use, and three people die from the harm that results from prescription opioid use. "The possible harmful effects of opioids are well known. They range from minor harms such as constipation and drowsiness to major harms such as dependence, addiction, overdose, and even unintentional death," said Professor McLachlan. "The findings from the OPAL trial further reinforce the need to reassess the use of opioid pain-relieving medicines as there is limited evidence of benefit and known significant risk of harm." The authors note some study limitations including data gaps due to participant attrition and issues with medication adherence consistent with other back pain drug trials. They suggest neither are likely to have impacted the main outcomes of the study. The trial is a collaboration between the University of Sydney, The George Institute for Global Health, UNSW, St Vincent's Hospital Sydney, Sydney Local Health District and Erasmus University Medical Center in the Netherlands.

Study estimates there will be over 800 million cases of low back pain in 2050, a 36 percent increase from 2020. With an aging population, researchers say we must 'put the brakes' on low back pain cases before the burden becomes too great for our healthcare system. Analysis of over 30 years of data has shown the number of cases of low back pain is growing, with modelling suggesting by 2050, 843 million people will be affected by the condition largely due to population increases and ageing of populations. The continued lack of a consistent approach on back pain treatment, and limited treatment options have researchers concerned that this will lead to a healthcare crisis, as low back pain is the leading cause of disability in the world. In Australia, there will be a nearly 50 percent increase in cases by 2050. The landscape of back pain cases is set to shift, with the biggest increases in back pain cases to be in Asia and Africa. The findings are published in Lancet Rheumatology today, and is the new Global Burden of Disease (GBD) 2021 study. "Our analysis paints a picture of growing low back pain cases globally, putting enormous pressure on our healthcare system. We need to establish a national, consistent approach to managing low back pain that is informed by research," says lead author, Professor Manuela Ferreira from Sydney Musculoskeletal Health, an initiative of the University of Sydney, Sydney Local Health District and Northern Sydney Local Health District. "Currently, how we have been responding to back pain has been reactive. Australia is a global leader in back pain research; we can be proactive and lead by example on back pain prevention," said Professor Ferreira who is based at Sydney's Kolling Institute. The study reveals several milestones in back pain cases. Since 2017, the number of low back pain cases has ticked over to more than half a billion people. In 2020, there were approximately 619 million cases of back pain. At least one third of the disability burden associated with backpain was attributable to occupational factors, smoking and being overweight. A widespread misconception is that low back pain mostly affects adults of working age. But researchers say this study has confirmed that low back pain is more common among older people. Low back pain cases were also higher among females compared to males. This is the most comprehensive and up-to-date available data that includes for the first time global projections and the contribution of GBD risk factors to low back pain. The work was made possible by the joint efforts of The University of Sydney, the Institute for Health Metrics and Evaluation (IHME) at the University of Washington's School of Medicine, IHME's international collaborators, and the Global Alliance for Musculoskeletal Health. "We also know that most available data come from high-income countries, making it sometimes hard to interpret these results for low to mid-income countries. We urgently need more population-based back pain and musculoskeletal data from countries of low to mid-income," said senior author Professor Lyn March from Sydney Musculoskeletal Health and the Kolling Institute. The study analysed GBD data from 1990 to 2020 from over 204 countries and territories to map the landscape of back pain cases over time. The GBD is the most comprehensive picture of mortality and disability across countries, time, age, and It is also the first study to be used for modelling the future prevalence of back pain cases. "Health systems need to respond to this enormous and rising burden of low back pain that is affecting people globally. Much more needs to be done to prevent low back pain and ensure timely access to care, as there are effective ways of helping people in pain" said Prof Anthony Woolf, co-chair of the Global Alliance for Musculoskeletal Health which is calling for priority to be given to addressing the growing burden of musculoskeletal conditions. "Ministries of health cannot continue ignoring the high prevalence of musculoskeletal conditions including low back pain. These conditions have important social and economic consequences, especially considering the cost of care. Now is the time to learn about effective strategies to address the high burden and to act" said Dr Alarcos Cieza, Unit Head, World Health Organization, Headquarters, Geneva. National guidelines will form basis of back pain prevention In 2018, experts (independent to this study) voiced their concerns in The Lancet and gave recommendations, especially regarding exercise and education, about the need for a change in global policy on the best way to prevent and manage low back pain to stop the rise of inappropriate treatments. However, since then, there has been little change. Common treatments recommended for low back pain have been found to have unknown effectiveness or to be ineffective -- this includes some surgeries and opioids. Professor Ferreira says there is a lack of consistency in how health professionals manage back pain cases and how the healthcare system needs to adapt. "It may come as a surprise to some that current clinical guidelines for back pain treatment and management do not provide specific recommendations for older people." "Older people have more complex medical histories and are more likely to be prescribed strong medication, including opioids for back pain management, compared to younger adults. But this is not ideal and can have a negative impact on their function and quality of life, especially as these analgesics may interfere with their other existing medications. This is just one example of why we need to update clinical guidelines to support our health professionals." Co-author Dr Katie de Luca, from CQUniversity, said if the right action is not taken, low back pain can become a precursor to chronic health conditions such as diabetes, cardiovascular disease and mental health conditions, invasive medical procedures, and significant disability. "Low back pain continues to be the greatest cause of disability burden worldwide. There are substantial socio-economic consequences of this condition, and the physical and personal impact directly threatens healthy ageing."