In a clinical trial, two new antibody treatments for Crohn’s disease were approximately similar in effectiveness, according to findings published in The Lancet.
This allows clinicians and patients to make treatment choices based on tolerance, according to Stephen Hanauer, MD, the Clifford Joseph Barborka Professor and a co-author of the study.
“The safety and efficacy of two agents with different mechanisms of action appears to be quite comparable over one year,” said Prof Hanauer.
Crohn’s disease (CD) is a chronic, progressive inflammatory bowel disease, causing abdominal pain, weight loss and fatigue. Treatment has usually focused on alleviating symptoms to achieve clinical remission using corticosteroids or immunomodulators, but more effective treatment is still needed, according to Prof Hanauer.
‘While there are numerous therapies and mechanisms of action for drugs approved for moderate-severe Crohn’s disease there has been a therapeutic ceiling as far as outcomes are concerned, with usually less than 50% of patients in long-term remission,” Prof Hanauer explained.
Recently, several biologic agents have been approved for use. Adalimumab is a monoclonal antibody that reduces inflammatory cytokines by inhibiting tumor necrosis factor alpha. Ustekinumab is another monoclonal antibody, though the drug targets a different set of proteins: interleukin (IL) 12 and IL-23.
Researchers recruited with Crohn’s disease, randomising 191 to receive ustekinumab and 195 to adalimumab. Patients reaching clinical remission were similar between both groups: 65% of 191 patients in the ustekinumab group versus 61% of 195 in the adalimumab group. There were no deaths through one year of study, though slightly more patients in the ustekinumab group discontinued study treatment. Disease severity measures decreased similarly over the study.
Both treatment regimens resulted in clinical remission with similar toxicity profiles.
“There are numerous options for patients with moderate-severe disease. However, the key is to treat patients with an effective regimen and treat to targets as early in the course as possible since we do not have any drugs that impact on fibrosis once it occurs,” Prof Hanauer said.
US States that legalised recreational marijuana saw a subsequent increase in traffic crashes and fatalities, researchers reported in the Journal of Studies on Alcohol and Drugs.
“The legalisation of marijuana doesn’t come without cost,” stated lead researcher Charles M. Farmer, PhD, of the Insurance Institute for Highway Safety.
Dr Farmer and colleagues’ analysis of five states that allow the recreational use of marijuana for adults age 21 and older revealed a 5.8% increase in the rate of traffic crash injuries and a 4.1% increase in fatal crash rates after legalisation and the onset of retail sales. At the same time, there was no increase in a comparison group of states which did not legalise marijuana.
The injury crash rate jumped after legalisation but before retail sales began. Traffic crash injuries rose 6.5% after legalisation but decreased slightly (-0.7%) after retail sales commenced. However, fatal crash rates increased both after legalisation (+2.3%) and after retail sales were authorised (+1.8%).
“Legalisation removes the stigma of marijuana use, while the onset of retail sales merely increases access,” explained Dr Farmer. “But access to marijuana isn’t difficult, even in places without retail sales. Users who previously avoided driving high may feel that it’s okay after legalisation.”
Marijuana legalisation’s stronger relationship with traffic crash injuries, rather than fatalities, may be due to how some drivers compensate when impaired by marijuana. Often, drivers under the influence of marijuana slow down and maintain a larger distance between themselves and other vehicles. A crash may be harder to avoid while impaired, but the lower-speed crashes that occur may be less likely to be fatal.
The authors note that earlier studies involving driving simulators have shown marijuana use to affect reaction time, road tracking, lane keeping and attention. However, Farmer notes that the current study is correlational, and increased marijuana use itself is likely not the sole cause of the increases seen.
“Studies looking for a direct causal link between marijuana use and crash risk have been inconclusive,” he says. “Unlike alcohol, there is no good objective measure of just how impaired a marijuana user has become. Until we can accurately measure marijuana impairment, we won’t be able to link it to crash risk.”
The researchers collected data on traffic crashes and traffic volume for 2009–2019 from 11 states and from the Federal Highway Administration. During the study period, five states had legalised recreational marijuana while a comparison group of six states did not. The authors statistically adjusted for factors known to contribute to crashes and fatalities, including seat belt use and unemployment rate.
In the states that legalised cannabis, changes in injury crash rates varied: Colorado had the biggest jump (+17.8%) and California the smallest (+5.7%) after both legalisation and the onset of retail sales. Nevada’s rate decreased (-6.7%). For fatal crashes, increases occurred in Colorado (+1.4%) and Oregon (3.8%), but decreases were found in Washington (-1.9%), California (-7.6%) and Nevada (-9.8%).
Farmer points out that states considering marijuana legalisation should consider a few steps to help forestall a potential increase in crashes. “First, convince everyone that driving under the influence of marijuana is not okay,” he says. “Then, enact laws and sanctions penalising those who ignore the message. Finally, make sure you have the resources (ie, staffing and training) to enforce these laws and sanctions.”
Salt restriction has long been held to be a key component of heart failure treatment, but cutting back too much may actually worsen the outcomes for people with preserved ejection fraction, suggests research published in Heart.
The findings indicate that younger people and those of black and other ethnicities seem to be most at risk.
Salt restriction is frequently recommended in heart failure guidelines, but the optimal restriction range (from less than 1.5g to less than 3g daily) and its effect on patients with heart failure with preserved ejection fraction (HFpEF) is less clear as they have often been excluded from relevant studies.
HFpEF, which accounts for half of all heart failure cases, occurs when the lower left chamber of the heart (left ventricle) isn’t able to fill properly with blood (diastolic phase), so reducing the amount of blood pumped out into the body.
In a bid to explore the association with salt intake further, the researchers drew on secondary analysis of data from 1713 people aged 50 and above with heart failure with preserved ejection fraction who were part of the TOPCAT trial.
A phase III, randomised, double-blind, placebo-controlled study, this trial was designed to find out if the drug spironolactone could effectively treat symptomatic heart failure with preserved ejection fraction.
Participants were asked how much salt they routinely added to the cooking of staples, such as rice, pasta, and potatoes; soup; meat; and vegetables, and this was scored as: 0 points (none); 1 (⅛tsp); 2 (¼tsp); and 3 (½+tsp).
They were followed up for an average of three years for the primary endpoint, a composite of death from cardiovascular disease or admission to hospital for heart failure plus aborted cardiac arrest. Secondary outcomes were all cause mortality and cardiovascular disease mortality plus hospitalisation for heart failure.
Around half the participants (816) had a cooking salt score of zero: more than half of them were men (56%) and most were of white ethnicity (81%). They weighed significantly more and had a lower diastolic blood pressure (70 mm Hg) than those with a cooking salt score above zero (897).
They had also been admitted to hospital more often for heart failure, were more likely to have type 2 diabetes, poorer kidney function, to be taking meds to control their heart failure, and to have a reduced left ventricular ejection fraction (lower cardiac output).
Participants with a cooking salt score above zero were at significantly lower risk of the primary endpoint than those whose score was zero, mainly driven by the fact that they were less likely to be hospitalised for heart failure. But all-cause mortality or CVD mortality was no higher than those whose cooking salt score was zero.
Those aged 70 or younger were significantly more likely to benefit from adding salt to their cooking than were those older than 70 in terms of the primary endpoint and admission to hospital for heart failure.
Similarly, those of black and other ethnicities seemed to benefit more from adding salt compared with white participants, although the numbers were small.
Gender, previous hospitalisation for heart failure, and the use of heart failure meds weren’t associated with heightened risks of the measured outcomes and cooking salt score.
This is an observational study, and as such, can’t establish cause. Not all relevant data from the TOPCAT trial were available, while the cooking salt score was self-reported, acknowledge the researchers. And reverse causation, whereby people with poorer health might have been advised to further restrict their salt intake, can’t be ruled out.
Lower sodium intake is usually associated with lower blood pressure and a reduced risk of cardiovascular disease in the general public and in those with high blood pressure. It is thought that it reduces fluid retention and the triggering of the hormones involved in blood pressure regulation.
But restricting salt intake to control heart failure is less straightforward, say the researchers. It may prompt intravascular volume contraction, which could, in turn, reduce congestion and the requirement for water tablets to ease fluid retention.
But the researchers pointed out that the that the volume of plasma in the blood, an indicator of congestion, wasn’t significantly associated with cooking salt score – suggesting that low sodium intake didn’t ease fluid retention in people with heart failure with preserved ejection fraction.
“Overstrict dietary salt intake restriction could harm patients with [heart failure with preserved ejection fraction] and is associated with worse prognosis. Physicians should reconsider giving this advice to patients,” they conclude.
New research published in Clinical and Experimental Allergy reveals that prescriptions of specialised infant formula have increased in recent years in England, Norway, and Australia, with rates over 10 times what would normally be expected for the number of children with milk allergies.
Increasing specialised formula use has been interpreted as evidence for milk allergy overdiagnosis, leading to the use of specialised formula for managing common infant symptoms. This is because there is little evidence in high-income countries for a change in milk allergy incidence to explain rises in specialised formula prescription. While specialised formula is reasonably well tolerated by most infants, and supports infant nutrition and growth, there are significant differences from standard cow’s milk-based infant formula or human breastmilk. In specialised formula products, the lactose found in breastmilk or cow’s milk is partially or completely replaced by alternative carbohydrate sources, often free sugars such as glucose or sucrose.
Soya milk alternatives were prevalent in the 1990s, but in the 2000s were displaced by amino-acid formulations after health concerns emerged over soya milk use in infants. Prescribed amounts of specialised formula for infants rose 2.8-fold in England from 2007–2018, with similar trends in other regions of the United Kingdom. Amounts rose 2.2-fold in Norway from 2009–2020 and 3.2-fold in Australia from 2001–2012.
In addition to added expense (specialised formula costs an average of US117 extra per birth in England), these findings are of particular concern due to their higher levels of sugar, which may promote tooth decay and obesity in young children.
“These data suggest high levels of milk allergy over-diagnosis and mark an important shift in early child nutrition,” the authors wrote.
As many men age, they lose their Y chromosome, which causes heart muscle to scar and can lead to deadly heart failure, new research from the shows. The finding, which appears in Science, may help explain why men die, on average, several years younger than women.
University of Virginia School of Medicine researcher Kenneth Walsh, PhD, says the new discovery suggests that men who suffer Y chromosome loss – estimated to include 40% of 70-year-olds – may particularly benefit from an existing drug that targets dangerous tissue scarring. The drug, he suspects, may help counteract the harmful effects of the chromosome loss – effects that may manifest not just in the heart but in other parts of the body as well.
On average, women live five years longer than men in the United States. The new finding, Prof Walsh estimates, may explain nearly four of the five-year difference.
“Particularly past age 60, men die more rapidly than women. It’s as if they biologically age more quickly,” said Prof Walsh. “There are more than 160 million males in the United States alone. The years of life lost due to the survival disadvantage of maleness is staggering. This new research provides clues as to why men have shorter lifespans than women.”
Many men begin to lose their Y chromosome in a fraction of their cells as they age, especially in smokers. The loss occurs predominantly in cells that undergo rapid turnover, such as blood cells. However, Y chromosome loss does not occur in male reproductive cells, so it is not inherited by the children of men who exhibit Y chromosome loss. It has been observed that men who suffer Y chromosome loss are more likely to die at a younger age and suffer age-associated maladies such as Alzheimer’s disease. This new research however is believed to be the first hard evidence that the chromosome loss harms men’s health.
Walsh and his team used CRISPR gene-editing technology to develop a special mouse model to better understand the effects of Y chromosome loss in the blood. The loss accelerated age-related diseases, made the mice more prone to heart scarring, leading to earlier death. But more than just the results of inflammation, there was complex series of responses in the immune system, leading to fibrosis throughout the body. This tug-of-war within the immune system, the researchers believe, may accelerate disease development.
The scientists also looked at the effects of Y chromosome loss in human men. They conducted three analyses of data compiled from the UK Biobank, a massive biomedical database, and found that Y chromosome loss was associated with cardiovascular disease and heart failure. As chromosome loss increased, the scientists found, so did the risk of death.
The findings suggest that targeting the effects of Y chromosome loss could help men live longer, healthier lives. One treatment option might be a drug, pirfenidone, approved in the US for the treatment of idiopathic pulmonary fibrosis. The drug is also being tested for the treatment of heart failure and chronic kidney disease, two conditions for which tissue scarring is a hallmark. Based on his research, Walsh believes that men with Y chromosome loss could respond particularly well to this drug, and other classes of antifibrotic drugs that are being developed, though more research will be needed to determine that.
At the moment, doctors have no easy way to determine which men suffer Y chromosome loss. Prof Walsh’s collaborator Lars A. Forsberg, of Uppsala University in Sweden, has developed an inexpensive polymerase chain reaction (PCR) test that can detect Y chromosome loss, but the test is largely confined to his and Prof Walsh’s labs. Prof Walsh, however, can foresee that changing: “If interest in this continues and it’s shown to have utility in terms of being prognostic for men’s disease and can lead to personalised therapy, maybe this becomes a routine diagnostic test,” he said.
“The DNA of all our cells inevitably accumulate mutations as we age. This includes the loss of the entire Y chromosome within a subset of cells within men. Understanding that the body is a mosaic of acquired mutations provides clues about age-related diseases and the aging process itself,” said Walsh, a member of UVA’s Department of Biochemistry and Molecular Genetics. “Studies that examine Y chromosome loss and other acquired mutations have great promise for the development of personalised medicines that are tailored to these specific mutations.”
