According to a new paper in Family Practice, medical practice can often be undermined by later research, randomised trials relevant to primary care generally hold up over time.
Medical reversal describes a problem whereby new research causes doctors to stop using a popular medication, procedure or test based on previous evidence. Vinayak Prasad, associate professor at the University of California, San Francisco, had found that up to 46% of original studies on adopted medical practices led to a reversal or shift in evidence of effect.
Evidence-based medicine lets doctors be confident when their decisions are grounded in high quality research. But decisions supported by robust evidence from randomised controlled trials can be reversed. For example, although aspirin is prescribed commonly to prevent cardiovascular disease, new studies indicate this treatment is unlikely to be effective.
Researchers studied the extent to which evidence from randomised control trials relevant to primary care were contradicted in subsequent research. Examining 408 randomised controlled trials from 2002 to 2005 relevant to primary care, the researchers found that over 12-17 years of follow up time, there were just 35 occurrences of evidence reversal, or roughly two a year. About nine in ten of such randomised control trials were not reversed.
“Conclusions from randomised trials relevant to primary care that also meet criteria for validity are stable over time,” said study lead author Christian Ruchon.
New WHO Global Air Quality Guidelines (AQGs) have lowered the acceptable limits of air pollution, providing evidence that even lower concentrations than previously understood have a negative health impact.
Increasing evidence showing how air pollution affects different aspects of health, WHO has adjusted almost all the AQGs levels downwards, warning that exceeding the new air quality guideline levels is associated with significant risks to health.
Air pollution is estimated to cause 7 million premature deaths and the loss of millions more healthy years of life. In children, this could include reduced lung growth and function, respiratory infections and aggravated asthma. In adults, deaths from ischaemic heart disease and stroke are the most common, as well as emerging evidence of diabetes and neurodegenerative conditions. This makes the disease burden from air pollution on par with others such as unhealthy diet and tobacco smoking.
Besides climate change, air pollution is one of the biggest environmental threats to human health. Improving air quality will also help mitigate climate change, thereby reducing the negative health impacts of both. WHO’s new guidelines recommend air quality levels for 6 pollutants, where evidence has advanced the most on health effects from exposure. When action is taken on these so-called classical pollutants – particulate matter (PM), ozone (O₃), nitrogen dioxide (NO₂) sulfur dioxide (SO₂) and carbon monoxide (CO), it also has an impact on other damaging pollutants.
Particulate matterequal or smaller than 10 and 2.5 microns (µm) in diameter (PM₁₀ and PM₂.₅, respectively) is a particular health concern. Both PM₂.₅ and PM₁₀ can penetrate deep into the lungs but PM₂.₅ can even enter the bloodstream, primarily resulting in cardiovascular and respiratory impacts, and also affecting other organs, and were classified as carcinogenic in 2013.
“Air pollution is a threat to health in all countries, but it hits people in low- and middle-income countries the hardest,” said WHO Director-General, Dr Tedros Adhanom Ghebreyesus. “WHO’s new Air Quality Guidelines are an evidence-based and practical tool for improving the quality of the air on which all life depends. I urge all countries and all those fighting to protect our environment to put them to use to reduce suffering and save lives.”
In 2019, over 90% of the world’s population lived in areas where concentrations exceeded the 2005 WHO air quality guideline for long term exposure to PM₂.₅.
Almost 80% of PM₂.₅-related deaths could be avoided if current air pollution levels were reduced to those proposed in the updated guideline. At the same time, reaching interim targets would reduce the burden of disease, of which the greatest benefit would be observed in countries with high concentrations of fine particulates (PM₂.₅) and large populations.
Many young women with breast cancer choose mastectomies but afterwards experience a persistent decline in their sexual and psychosocial well-being, according to new research reported inJAMA Surgery.
In surveys conducted after patients underwent breast cancer surgery, significant quality of life (QoL) impacts were seen with mastectomies, with a greater extent of surgery worsening the QoL outcomes. The findings are important in light of recent trends towards younger women with breast cancer opting for bilateral mastectomies for unilateral breast cancer when breast conserving surgery was also an option.
“Historically, it was felt that 75 percent of breast cancer patients should be eligible for breast conserving surgery. Over time, however, more women, particularly young women, are electing to have a mastectomy,” said study lead author Laura Dominici, MD, a surgeon at Dana-Farber Brigham Cancer Center. “They frequently offer peace of mind as the reason for their decision – even though research shows that unless a woman has a genetic predisposition to breast cancer, she has a very low risk of developing cancer in the healthy breast.”
In this study, 560 participants, 40 and younger with breast cancer, filled in a patient reported outcomes survey known as BREAST-Q, an average 5.8 years after diagnosis.
Compared to those who had breast-sparing surgery, patients who had a mastectomy scored significantly lower in three QoL measures – satisfaction with the appearance of their breasts, psychosocial well-being, and sexual well-being. The results were consistent regardless of whether one or both breasts were removed, and that most had breast reconstruction surgery.
For breast satisfaction, patients who had breast-conserving surgery had an average BREAST-Q score of 65.5, compared with 54.6 in the bilateral mastectomy group.
For psychosocial well-being, patients who had breast-conserving surgery had an average BREAST-Q score of 75.9, compared with 65.1 in the bilateral mastectomy group.
For sexual well-being, patients who had breast-conserving surgery had an average BREAST-Q score of 57.4, compared with 53.4 for the unilateral mastectomy group and 46.2 for the bilateral mastectomy group.
A fourth area examined by the survey, physical function, showed no difference between the groups. Women with financial challenges tended to have lower scores in all four categories.
“The decision of whether to have a mastectomy or breast-conserving surgery should be a shared decision between patients and their doctors,” Dr Dominici added. “Particularly when talking to young women, who are likely to have a long period of survivorship, it’s important that we as clinicians discuss the potential impacts of mastectomy on their quality of life. As our study indicates, those impacts are not insignificant and persist years into the future.”
The study’s main limitation is that it was not randomised, and quality of life was only evaluated at a single time point. Dr Dominici added there was no information about women’s quality of life prior to the study, which could have infuenced their decision making and their quality of life after surgery.
Researchers have found that skeletal muscles play a large part in regulating the liver’s biological clock. The findings were published inScience Advances.
The circadian rhythm is coordinated by the brain at a general level, but each organ or tissue is also subjected to specific regulation, adjusting to time to optimise their processes. However it was not known how the liver “knows” whether it is day or night.
The liver’s main role is digestion, mainly of fats and sugars: the brain is the main consumer of sugar while skeletal muscle is the main consumer of fat.
Scientists at IRB Barcelona discovered a surprising relationship: that it is skeletal muscle which regulates liver function and determines fat metabolism. Skeletal muscle accomplishes this by secreting a that is transported to the liver through serum is responsible for modulating around 35% of the metabolic functions of the liver. The remaining basal functions of this organ and others related to carbohydrate metabolism are independent of muscle activity and are regulated by the basal circadian rhythm from the brain.
“It’s a very nice discovery because it is the first demonstration of the need for communication between the circadian clocks of tissues and organs outside the brain, and we can see that this communication between muscle and liver is altered by aging,” said study leader Dr Salvador Aznar-Benitah at IRB Barcelona. “When we get older, cells stop obeying the biological clock and begin to perform functions in a non-optimal manner, leading to errors that cause tissues to age.”
The researcher’s results show that the liver does not independently regulate the metabolism of fats and that it is muscle that sends the message that it is time to switch on fatty acid metabolism and how it should go about this. “We didn’t expect to find this connection between the liver and muscle because it wasn’t known previously, but, on second thought, it makes complete sense that fat management is coordinated by one of its main consumers,” said Dr Aznar-Benitah. Carbohydrate metabolism meanwhile is dependent on the basal coordination exercised by the brain.
A new discovery about a signalling function in osteoclasts suggests a potential treatment target for osteoporosis and for bone loss from rheumatoid arthritis.
The findings from University of Virginia School of Medicine researchers and their collaborators help us understand why osteoclastsbegin to break down more bone than the body replaces.
“Bone degradation and subsequent repair are fine-tuned through complex interactions between the cells that degrade the bone – osteoclasts – and those that produce new bone matrix. Simple elimination of osteoclasts is, therefore, not always the best approach to treat pathologic bone loss. Instead, we found a ‘signalling node’ in osteoclasts that regulates their function in degrading the bone, but doesn’t reduce osteoclast numbers,” said researcher Sanja Arandjelovic of UVA’s Department of Medicine and UVA’s Carter Immunology Center.
With further research, it may be possible for scientists to one day be able to develop drugs that target the signalling node to prevent or treat bone loss. This discovery also helps explain why some previous attempts to develop osteoporosis treatments produced disappointing results. Researcher Kodi Ravichandran, chair of UVA’s Department of Microbiology, Immunology and Cancer Biology and director of UVA’s Center for Cell Clearance, noted the potential of the findings to inform efforts to develop better treatments for osteoporosis: “In this study,” he said, “we identified previously unappreciated factors that contribute to osteoclast function that are truly exciting and open up new avenues to pursue.”
The researchers have found an important contributor, a cellular protein called ELMO1, which promotes the activity of the bone-removing osteoclasts. Osteoclasts are critical for bone health, as they normally remove just enough to stimulate new bone growth. The problem arises when the osteoclasts become too aggressive and remove more bone than the body makes, resulting in bone mass loss.
This excessive bone degradation is likely influenced by genetic factors, the researchers say. They note that many of the genes and proteins linked to ELMO1 have been previously associated with bone disorders and osteoclast function.
Encouragingly, the researchers were able to prevent bone loss in lab mice by blocking ELMO1, including in two different models of rheumatoid arthritis. That suggests clinicians may be able to target the protein in people as a way to treat or prevent bone loss caused by osteoporosis and rheumatoid arthritis, the researchers say.
They note that prior efforts to treat osteoporosis by targeting osteoclasts have had only mixed success, and they offer a potential explanation for why: Osteoclasts not only remove bone, but play a role in calling in other cells to do bone replacement. As such, targeting ELMO1 may offer a better option than simply waging war on the osteoclasts.
“We used a peptide to target ELMO1 activity and were able to inhibit degradation of the bone matrix in cultured osteoclasts without affecting their numbers,” Ravichandran said. “We hope that these new osteoclast regulators identified in our study can be developed into future treatments for conditions of excessive bone loss such as osteoporosis and arthritis.”
