Tag: 4/7/23

Categories : Ageing Surgeries & ProceduresTags : Leave a comment

Surgical Stabilisation of Odontoid Fractures Linked to Better Outcomes

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In a review of patient treatment data, researchers have found that surgical stabilisation of odontoid fractures was associated with better outcomes than nonsurgical approaches. The article will appear in the September issue of Neurosurgery.

Odontoid fractures (C2 vertebra) are common in elderly patients after a low-energy fall. However, whether the initial treatment should be surgical or nonoperative still isn’t known. Previous studies haven’t accounted for differences in injury severity, or the presence or absence of neurologic impairment, which can affect patients’ results.

Michael B. Cloney, MD, MPH, of the Department of Neurological Surgery at Northwestern University in Chicago, and colleagues have published evidence that surgery should be considered as the initial approach for many patients. Compared with nonoperative approaches to treatment, surgical stabilisation of the fracture was associated with less myelopathy (mobility impairment due to spinal cord damage), and lower rates of fracture nonunion, 30-day mortality, and one year mortality.

“Given the increasing incidence of odontoid fractures with the aging population, we believe our findings could assist with neurosurgical decision-making for an increasingly common and complex problem,” the researchers say.

Accounting for nonrandomised patient groups

Dr Cloney and his colleagues reviewed initial treatment data on 296 patients who were cared for at Northwestern Memorial Hospital between January 1, 2010, and December 31, 2020, because of an odontoid fracture. Their average age was 73. During the hospitalisation, 22% had surgery and 78% had nonoperative treatment (5% were immobilised in a halo-vest and 73% received a cervical collar).

Since the patients weren’t randomised to these treatments, the research team used a type of analysis called propensity score adjustment. They calculated “propensity scores” for each individual – the probability that the patient would have been assigned to receive one of the two treatment approaches based on certain characteristics.

For example, to study the effect of surgery on mortality rates, patients were matched on age, sex, Injury Severity Score, Nurick score (a measure of myelopathy), their number of chronic diseases and chronic conditions such as smoking, and whether they had to be admitted to the intensive care unit.

Surgical stabilisation leads to better results

Follow up with patients lasted an average of 45 weeks. On the propensity score–matched analyses, the group that underwent surgery showed significantly better outcomes than the nonoperative group:

  • Lower rate of fracture nonunion – 39.7% vs 57.3%; treatment effect, 15% less risk of nonunion
  • Lower 30-day mortality rate – 1.7% vs 13.8%; treatment effect, 10% less risk of death
  • Lower one year mortality rate – 7.0% vs 23.7%; treatment effect, 10% less risk of death

Other analyses showed patients in the surgery group were 52% less likely than those in the nonoperative group to have poor Nurick scores at the 26-week postoperative follow-up visit and were 41% less likely to die during the overall follow-up period. Both differences were statistically significant.

“The mortality benefit calculated in the existing literature typically represents an unadjusted mortality rate between two potentially different populations, which leaves it liable to confounding,” the authors note. “Our study represents a relatively large institutional series that suggests a benefit from surgical stabilisation in this population while controlling for confounding factors more thoroughly than existing literature.”

Source: EurekAlert!

Categories : CancerTags : Leave a comment

Study Improves Accuracy for Breast Cancer Genetic Markers in Ashkenazi Jewish Women

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Photo by Robert Thiemann on Unsplash

A new study by researchers in the UK and Israel has investigated how to improve breast cancer genetic tests for Ashkenazi Jewish women. By analysing genetic samples from women from Ashkenazi Jewish backgrounds, they were able to correctly adjust the risk estimates from commercially available genetic screening tests, giving a more accurate result. They detail their technique in the journal Genetics in Medicine.

New forms of genetic tests can tell women their personal risk of developing breast cancer. However, previous research has shown they are not accurate for many Black, Asian or Ashkenazi Jewish women, or women with a mixed ethnic background.

The study focuses on tiny genetic variations called Single Nucleotide Polymorphisms (SNPs) – which, depending on the unique combination of them, can increase or decrease the risk of breast cancer.

This information is used to produce a Polygenic Risk Score (PRS), which can inform women whether they are at low, average, or high risk of developing breast cancer in the next 10 years. PRS are becoming more widely available through commercial companies and research studies on the NHS breast screening programme.

Current PRSs were developed from large-scale genome studies which predominantly collected genetic data from mainstream White European populations. As a result, the accuracy of a PRS for an individual will depend on how closely their genetic material resemble those of the people whose data was used to develop the risk score.

This means that while commercially available PRS can accurately predict breast cancer risk for mainstream White European women, they often exaggerate this risk for Black, Asian or Ashkenazi Jewish women, or women with a mixed ethnic background.

In this new study, researchers compared two available PRS based on two SNPs – SNP142 and the commercial SNP78 – and analysed their accuracy for women of Ashkenazi Jewish ancestry.

The findings showed that these PRS tests inaccurately predicted Ashkenazi Jewish women to be at higher risk of developing breast cancer.

After adjusting the test for Ashkenazi Jewish ancestry, the researchers were able to generate a more accurate prediction of breast cancer risk for these women.

The research team used genetic information from Ashkenazi Jewish women in both Manchester and Israel, with data from the Predicting the Risk of Cancer at Screening (PROCAS) study conducted in Greater Manchester, a Manchester regional genetics database, and the Breast Cancer in Northern Israel (BCINIS) study.

This research was led by Professor Gareth Evans, a leading expert in breast cancer genetics and SNPs testing and NIHR Manchester BRC Cancer Prevention and Early Detection Theme Lead.

Professor Evans said: “Polygenic Risk Scores (PRS) are a major component of accurate breast cancer risk prediction and have great potential to improve personalised screening methods. However, it is clear from our findings that you cannot simply apply current PRS developed using genetic data from individuals of white European ancestry to those from Ashkenazi Jewish backgrounds.

“A test result which exaggerates a woman’s risk of the disease could lead to undue stress or concern and unnecessary screening and preventative measures that they don’t need. Future PRS for Ashkenazi Jewish women should be based on their genetic data to provide a more accurate risk prediction.

“This study is an important step forward in our continued research into breast cancer genetic testing for people of different ethnic backgrounds to improve equity. More accurate and personalised PRS are required to avoid further increasing health inequalities and so patients can receive high-quality screening, care, and treatments.”

Source: University of Manchester

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Dr Robot Will See You Now: Medical Chatbots Need to be Regulated

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The Large Language Models (LLM) used in chatbots may appear to offer reliable, persuasive advice in a format which mimics conversation but in they can offer potentially harmful information when prompted with medical questions. Therefore, any LLM-chatbot in a medical setting would require approval as a medical device, argue experts in a paper published in Nature Medicine.

The mistake often made with LLM-chatbots is that they are a true “artificial intelligence” when in fact they are more closely related to the predictive text in a smartphone. They mostly use conversations and text scraped from the internet, and use algorithms to associate words and sentences in a manner that appears meaningful.

“Large Language Models are neural network language models with remarkable conversational skills. They generate human-like responses and engage in interactive conversations. However, they often generate highly convincing statements that are verifiably wrong or provide inappropriate responses. Today there is no way to be certain about the quality, evidence level, or consistency of clinical information or supporting evidence for any response. These chatbots are unsafe tools when it comes to medical advice and it is necessary to develop new frameworks that ensure patient safety,” said Prof Stephen Gilbert at TU Dresden.

Challenges in the regulatory approval of LLMs

Most people research their symptoms online before seeking medical advice. Search engines play a role in decision-making process. The forthcoming integration of LLM-chatbots into search engines may increase users’ confidence in the answers given by a chatbot that mimics conversation. It has been demonstrated that LLMs can provide profoundly dangerous information when prompted with medical questions.

The basis of LLMs do not have any medical “ground truth,” which is inherently dangerous. Chat-interfaced LLMs have already provided harmful medical responses and have already been used unethically in ‘experiments’ on patients without consent. Almost every medical LLM use case requires regulatory control in the EU and US. In the US their lack of explainability disqualifies them from being ‘non devices’. LLMs with explainability, low bias, predictability, correctness, and verifiable outputs do not currently exist and they are not exempted from current (or future) governance approaches.

The authors describe in their paper the limited scenarios in which LLMs could find application under current frameworks. They also describe how developers can seek to create LLM-based tools that could be approved as medical devices, and they explore the development of new frameworks that preserve patient safety. “Current LLM-chatbots do not meet key principles for AI in healthcare, like bias control, explainability, systems of oversight, validation and transparency. To earn their place in medical armamentarium, chatbots must be designed for better accuracy, with safety and clinical efficacy demonstrated and approved by regulators,” concludes Prof Gilbert.

Source: Technische Universität Dresden

Categories : Diet and Nutrition ExerciseTags : Leave a comment

Female Athletes’ Metabolism Drops if They Cut Energy Intake

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Most athletes know that diet and training go hand in hand for the best results, and many of them closely monitor their energy intake and training. However, a new study from Aarhus University shows that the bodies of female athletes are negatively affected when they consume too little energy through their diet in comparison with their training volume, explains PhD student Mikkel Oxfeldt. He and Associate Professor Mette Hansen are behind the study, which is published in the Journal of Physiology.

“We know that both elite female athletes and active women at times, either consciously or unconsciously, don’t have an energy intake that matches their energy expenditure when training. The study shows that insufficient energy intake can negatively affect muscles’ ability to respond to training. After just ten days of low energy intake, we began seeing changes to the hormonal system such as a decrease in the metabolic hormone followed by a decrease in metabolism.”

The study shows that it is important that women are careful not to reduce their energy intake too much. In fact, they should actually be increasing their energy intake if they increase their training volume, says Mikkel Oxfeldt:

“When you don’t get enough energy from your diet, your body will begun to pare down processes that require a lot of energy, just like a mobile phone that goes into battery-saving mode. We know from previous studies that it can cause some women’s periods to stop. However, our results show that other processes in the body, such as building new muscle proteins, are also affected.”

We must confront the unilateral focus on weight

Thirty fit women aged 18–30 participated in the study which is part of the Novo Nordic-funded Team Denmark network called ‘competition preparation and training optimisation’. All the women started the study right after the start of their menstrual period and followed a very controlled training and diet regimen for three weeks.

“Under the supervision of the researchers, the participants carried out individual training programmes aimed at increasing muscle mass, strength and overall fitness. The women’s meals were also provided by us. By controlling their training regimen and their diets, we were able to see how much energy they expended and what they ate during the study,” says Mikkel Oxfeldt and continues:

“This is the first time that such a well-controlled study has been carried out in this area, where both the diet and training of a group of fit women has been regulated to this extent. During the study, all participants drank doubly labelled water, which is enriched with a trace material. When we combine this tracer technique with the retrieval and subsequent analysis of muscle tissue samples, we can gain detailed insight into the muscles’ response to the experimental protocol,” explains Mikkel Oxfeldt.

Mikkel and the research group believe it’s necessary to confront the idea that weight loss leads to medals when in fact weight loss can negatively impact a number of the body’s systems, including muscles.

“In recent years, we’ve heard about public weigh-ins within some elite sports. They are part of promoting a culture in which some women are constantly trying to lose weight. However, our results show that this focus on weight loss can have short and potentially long-term negative consequences for women, both in relation to their health and training results. The study will hopefully provide athletes and coaches with a more nuanced picture of possible side effects.”

In collaboration with colleagues from the University of Copenhagen and University of Southern Denmark, the researchers behind the study are now investigating how physical performance, the immune system and metabolism are affected by an insufficient energy intake. They hope to one day be able to establish whether there is a difference between how women’s and men’s bodies react to inadequate energy intake.

Source: Aarhus University

Categories : Cardiovascular Disease Surgeries & ProceduresTags : Leave a comment

Do not Automatically Bar Stroke Patients on Warfarin from EVT, Study Suggests

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Most ischaemic stroke patients taking the anticoagulant warfarin were no more likely than those not on the medication to experience a brain bleed when undergoing endovascular thrombectomy (EVT), UT Southwestern Medical Center researchers report in a new study. The findings, published in JAMA, could help doctors better gauge the risk of EVT, widening the pool of patients for this intervention.

“Although not very common, patients taking warfarin may still experience a stroke. In clinical practice, it’s very possible that some physicians may withhold an endovascular thrombectomy because patients have been treated with warfarin before their strokes. Our study could increase the number of patients for whom this lifesaving and function-saving surgery would be appropriate,” said study leader Ying Xian, MD, PhD, Associate Professor of Neurology at UT Southwestern.

EVT – a surgery that removes the clot by threading instruments through the blood vessels – is the most common treatment for acute ischaemic stroke. EVTs can sometimes cause potentially fatal symptomatic intracranial haemorrhage (sICH), Dr Xian explained. Although warfarin is a known risk factor for bleeding, it’s been unknown whether the risk of sICH following EVT is higher for stroke patients who have been on the blood thinner.

To help answer this question, Dr Xian worked with Eric Peterson, MD, MPH, Professor of Internal Medicine at UTSW, along with colleagues from other medical institutions across the country. Together, they gathered data on 32 715 stroke patients who underwent EVT within six hours of stroke symptom onset between 2015 and 2020. Data came from the American Heart Association’s Get with the Guidelines-Stroke registry – the world’s largest registry of stroke patients.

The researchers compared a variety of outcomes for the 3087 patients who took warfarin prior to stroke and the 29 628 patients who did not take any blood thinner. They evaluated whether patients experienced sICH within 36 hours of their EVT procedure, whether they had a serious systemic haemorrhage, or whether they had other complications that required additional medical intervention or an extended hospital stay. Researchers also tracked complications from additional therapies that reintroduced blood flow in the brain, in-hospital deaths, and discharges to hospice care.

After adjusting for differences inherent to patients taking or not taking warfarin, the researchers found no difference in overall risk of sICH or other adverse outcomes in patients in these two groups. However, patients with an international normalised ratio (INR) greater than 1.7 – a measure of clotting tendency of blood in patients taking warfarin – the risk of experiencing sICH increased by about 4%.

Whether this effect translates into worse outcomes for patients is unclear, Dr Peterson said. Except for higher risk of bleeding, these patients with INRs greater than 1.7 were no more likely than those not taking warfarin to die or have worse functional outcomes at discharge.

“Physicians must evaluate stroke patients on a case-by-case basis to determine whether EVT is appropriate, but our study suggests that taking warfarin alone should not necessarily be a limiting factor,” he added.

Drs Xian and Peterson said they are planning to study whether other anticoagulants frequently taken by patients at risk of stroke might increase the risk of sICH or other serious complications following EVT for ischaemic stroke.

Source: UT Southwestern Medical Center