B cells are thought to play a critical role in innate and adaptive immunity, but their exact role in anti-tumour immunity remains unknown. Looking at B cells with a technique called single-cell profiling, which looks at all the genes in the cell, researchers found a protein that – when deleted – reduced tumour growth. The researchers write in Nature that this regulator could be a target for new cancer treatments.
The team, consisting of immunologists at Brigham and Women’s Hospital and dermatologists from Massachusetts General Hospital, identified a subset of B cells that expands specifically in the draining lymph node over time in mice with melanoma tumours.
They found a cell surface receptor called TIM-1 expressed on these B cells during melanoma growth. They also characterised multiple accompanying cell surface proteins that were involved in the B cell’s immune function. Interestingly, they found that deleting a molecule TIM-1, but not any of the other accompanying proteins, dramatically decreased tumour growth. The researchers concluded that TIM-1 controls B cell activation and immune response that combats cancer, including activating another type of the killer tumour-specific T cells for inhibiting tumour growth.
“The collaboration across institutions was extremely fruitful as we combined our immunology expertise at the Brigham with work at David Fisher’s MGH laboratory where seminal discoveries in skin malignancies have been made,” said lead author Lloyd Bod, PhD, of the Department of Neurology at the Brigham, who conducted this work while completing his postdoctoral fellowship at the Brigham. “The collaboration allowed us to test and demonstrate the therapeutic potential of targeting TIM-1 in melanoma models.”
New research published in Nature Communications has found that in a mouse model mimicking Alzheimer’s Disease (AD) pain signals are not processed in the same way as in healthy mice. The research, from King’s College London, suggests that the perception of pain in people with Alzheimer’s Disease may be altered, and asks whether changes in management of pain in people with AD could improve their quality of life.
While chronic musculoskeletal pain is common in individuals with AD, it remains largely untreated as it can go unreported due to the cognitive deficits attached to the disease.
In this study, the researchers sought to explore whether there is also an alteration in the body’s response to pain by the nervous system in people with AD.
In healthy mice, pain signals are transmitted from the point of origin to the central nervous system to initiate an immune response. The protein Galectin-3 has been demonstrated to be responsible for pain signal transmission to the spinal cord. Upon reaching the spinal cord, it binds to another protein, TLR4, to initiate the immune response.
In this study, researchers used an AD mice model and gave them rheumatoid arthritis, a type of chronic inflammatory disease, through blood transfer. They observed an increase in allodynia, pain caused by a stimulus that doesn’t normally provoke pain, as a response to the inflammation. They also saw increased activation of a microglia in the spinal cord. They determined that these effects were regulated by TLR4.
Researchers found that the mice with AD lacked TLR4 in the immune cells of their central nervous system and were therefore unable to respond to pain in the typical way as the signals were not being perceived.
This resulted in the mice with AD developing less joint inflammation related pain, and a less powerful immune cell response to the pain signals received by the central nervous system.
Professor Marzia Malcangio, Professor of Neuropharmacology at King’s IoPPN and the study’s senior author said, “Nociceptive pain – pain which is the result of tissue damage – is the second most prevalent comorbidity in individuals with Alzheimer’s disease. Our study has shown that, in mice with Alzheimer’s, the body’s ability to process that pain is altered due to the lack of TLR4; a protein vital to the immune response process in the central nervous system.
“These are important findings, as untreated pain can contribute to the psychiatric symptoms of the disease. Increasing our understanding of this area could, with more research, lead to more effective treatments and ultimately improve people’s quality of life.”
George Sideris-Lampretsas, a PhD student at King’s IoPPN and the study’s first author said, “The results of this study have the potential to make an impact, not only by identifying Galectin-3/TLR4 as a potential therapeutic target for chronic pain, but most importantly by raising awareness around the underreported and untreated pain experienced by patients with AD.”
In spite of burgeoning studies, the biological roots of autism remain elusive. Microbial approaches however have shown some promise, and now a study published in Nature Neuroscience has uncovered a microbial signature associated with autism, which clearly overlaps with metabolic pathways.
The study re-analysed of dozens of previously published datasets and found that they align with a recent, long-term study of autistic individuals that used a microbiome-focused intervention. These findings also underscore the importance of longitudinal studies in elucidating the interplay between the microbiome and complex conditions such as autism.
“We were able to harmonise seemingly disparate data from different studies and find a common language with which to unite them. With this, we were able to identify a microbial signature that distinguishes autistic from neurotypical individuals across many studies,” says Jamie Morton, one of the study’s corresponding authors. “But the bigger point is that going forward, we need robust long-term studies that look at as many datasets as possible and understand how they change when there is a [therapeutic] intervention.”
With 43 authors, this study brought together leaders in computational biology, engineering, medicine, autism and the microbiome who hailed from institutions in North America, South America, Europe and Asia. “The sheer number of fields and areas of expertise in this large-scale collaboration is noteworthy and necessary to get a new and consistent picture of autism,” says Rob Knight, the director of the Center for Microbiome Innovation at the University of California San Diego and a study co-author.
Autism is inherently complex, and studies that attempt to pinpoint specific gut microbes involved in the condition have been confounded by this complexity. First, autism presents in heterogeneous ways – autistic individuals differ from each other genetically, physiologically and behaviourally. Second, the microbiome presents unique difficulties. Microbiome studies typically report simply the relative proportions of specific microbes, requiring sophisticated statistics to understand which microbial population changes are relevant to a condition of interest.
This makes it challenging to find the signal amongst the noise. Making matters more complicated, most studies to date have been one-time snapshots of the microbial populations present in autistic individuals. “A single time point is only so powerful; it could be very different tomorrow or next week,” says study co-author Brittany Needham, assistant professor of anatomy, cell biology and physiology at the Indiana University School of Medicine.
“We wanted to address the constantly evolving question of how the microbiome is associated with autism, and thought, ‘let’s go back to existing datasets and see how much information we may be able to get out of them,'” says co-corresponding author Gaspar Taroncher-Oldenburg, director of Therapeutics Alliances at New York University, who initiated the work with Morton while he was a consultant-in-residence for SFARI.
In the new study, the research team developed an algorithm to re-analyse 25 previously published datasets containing microbiome and other “omic” information, such as gene expression, immune system response and diet, from both autistic and neurotypical cohorts. Within each dataset, the algorithm found the best matched pairs of autistic and neurotypical individuals in terms of age and sex, two factors that can typically confound autism studies.
Novel computational methodologies
“Rather than comparing average cohort results within studies, we treated each pair as a single data point, and thus were able to simultaneously analyse over 600 ASD-control pairs corresponding to a de facto cohort of over 1200 children,” says Taroncher-Oldenburg. “From a technical standpoint, this required the development of novel computational methodologies altogether,” he adds. Their new computational approach enabled them to reliably identify microbes that have differing abundances between ASD and neurotypical individuals.
The analysis identified autism-specific metabolic pathways associated with particular human gut microbes. Importantly, these pathways were also seen elsewhere in autistic individuals, from their brain-associated gene expression profiles to their diets. “We hadn’t seen this kind of clear overlap between gut microbial and human metabolic pathways in autism before,” says Morton.
Even more striking was an overlap between microbes associated with autism, and those identified in a recent long-term faecal microbiota transplant study led by James Adams and Rosa Krajmalnik-Brown at Arizona State University. “Another set of eyes looked at this, from a different lens, and they validated our findings,” says Krajmalnik-Brown, who was not involved in this study.
“What’s significant about this work is not only the identification of major signatures, but also the computational analysis that identified the need for future studies to include longitudinal, carefully designed measurements and controls to enable robust interpretation,” says Kelsey Martin, executive vice president of SFARI and the Simons Foundation Neuroscience Collaborations, who was not involved in the study.
“Going forward, we need more long-term studies that involve interventions, so we can get at cause-and-effect,” says Morton. Taroncher-Oldenburg, who cites the compliance issues often faced by traditional long-term studies, suggests that study designs could more effectively take into account the realities of long-term microbiome sampling of autistic individuals. “Practical, clinical restrictions must inform the statistics, and that will inform the study design,” he says. Further, he points out that long-term studies can reveal insights about both the group and the individual, as well as how that individual responds to specific interventions over time.
Importantly, researchers say these findings go beyond autism. The approach set forth here could also be employed across other areas of biomedicine that have long proved challenging. “Before this, we had smoke indicating the microbiome was involved in autism, and now we have fire. We can apply this approach to many other areas, from depression to Parkinson’s to cancer, where we think the microbiome plays a role, but where we don’t yet know exactly what the role is,” says Knight.
In a new study, scientists at Stanford Medicine have described a new category of depression, the cognitive biotype, which accounts for 27% of depressed patients and is not effectively treated by commonly prescribed antidepressants. The findings were reported in JAMA Network.
For these patients, cognitive tasks showed difficulty in planning ahead, self-control, sustaining focus despite distractions and suppressing inappropriate behaviour; imaging showed decreased activity in two brain regions responsible for those tasks.
Because depression has traditionally been defined as a mood disorder, doctors commonly prescribe selective serotonin reuptake inhibitors (SSRIs), but these are less effective for patients with cognitive dysfunction. Researchers said that targeting these cognitive dysfunctions with less commonly used antidepressants or other treatments may alleviate symptoms and help restore social and occupational abilities.
The study is part of a broader effort by neuroscientists to find treatments that target depression biotypes, according to the study’s senior author, Leanne Williams, PhD, professor of psychiatry and behavioural sciences.
“One of the big challenges is to find a new way to address what is currently a trial-and-error process so that more people can get better sooner,” Williams said. “Bringing in these objective cognitive measures like imaging will make sure we’re not using the same treatment on every patient.”
Finding the biotype
In the study, 1008 adults with previously unmedicated major depressive disorder were randomly given one of three widely prescribed typical antidepressants: escitalopram (Lexapro) or sertraline (Zoloft), which act on serotonin, or venlafaxine-XR (Effexor), which acts on both serotonin and norepinephrine. Seven hundred and twelve of the participants completed the eight-week regimen.
Before and after treatment with the antidepressants, the participants’ depressive symptoms were measured using two surveys – one, clinician-administered, and the other, a self-assessment, which included questions related to changes in sleep and eating. Measures on social and occupational functioning, as well as quality of life, were tracked as well.
The participants also completed a series of cognitive tests, before and after treatment, measuring verbal memory, working memory, decision speed and sustained attention, among other tasks.
Before treatment, scientists scanned 96 of the participants using functional magnetic resonance imaging as they engaged in a task called the “GoNoGo” that requires participants to press a button as quickly as possible when they see “Go” in green and to not press when they see “NoGo” in red. The fMRI tracked neuronal activity by measuring changes in blood oxygen levels, which showed levels of activity in different brain regions corresponding to Go or NoGo responses. Researchers then compared the participants’ images with those of individuals without depression.
The researchers found that 27% of the participants had more prominent symptoms of cognitive slowing and insomnia, impaired cognitive function on behavioural tests, as well as reduced activity in certain frontal brain regions – a profile they labelled the ‘cognitive biotype’.
“This study is crucial because psychiatrists have few measurement tools for depression to help make treatment decisions,” said Laura Hack, MD, PhD, the lead author of the study and an assistant professor of psychiatry and behavioural sciences. “It’s mostly making observations and self-report measures. Imaging while performing cognitive tasks is rather novel in depression treatment studies.”
Pre-treatment fMRI showed those with the cognitive biotype had significantly reduced activity in the dorsolateral prefrontal cortex and dorsal anterior cingulate regions during the GoNoGo task compared with the activity levels in participants who did not have the cognitive biotype. Together, the two regions form the cognitive control circuit, which is responsible for limiting unwanted or irrelevant thoughts and responses and improving goal selection, among other tasks.
After treatment, the researchers found that for the three antidepressants administered, the overall remission rates were 38.8% for participants with the newly discovered biotype and 47.7% for those without it. This difference was most prominent for sertraline, for which the remission rates were 35.9% and 50% for those with the biotype and those without, respectively.
“Depression presents in different ways in different people, but finding commonalities – like similar profiles of brain function – helps medical professionals effectively treat participants by individualising care,” Williams said.
Depression isn’t one size fits all
Williams and Hack propose that behaviour measurement and imaging could help diagnose depression biotypes and lead to better treatment. A patient could complete a survey on their own computer or in the doctor’s office, and if they are found to display a certain biotype, they might be referred to imaging for confirmation before undergoing treatment.
Researchers under Williams and Hack are studying another drug, guanfacine, that specifically targets the dorsolateral prefrontal cortex region. They believe this treatment could be more effective for patients with the cognitive subtype.
Williams and Hack hope to conduct studies with participants who have the cognitive biotype, comparing different types of medication with treatments such as transcranial magnetic stimulation (TMS) and cognitive behavioural therapy.
“I regularly witness the suffering, the loss of hope and the increase in suicidality that occurs when people are going through our trial-and-error process,” Hack said. “And it’s because we start with medications that have the same mechanism of action for everyone with depression, even though depression is quite heterogeneous. I think this study could help change that.”
As reported in the journal Science Advances, researchers at Baylor College of Medicine have come across a drug that, in laboratory cultures and animal models, significantly slows the development of antibiotic resistance in bacteira. The drug, called dequalinium chloride (DEQ), is a proof-of-concept for evolution-slowing drugs.
In this study, corresponding author Dr Susan M. Rosenberg and her colleagues looked for drugs that could prevent or slow down E. coli bacteria from developing resistance to two antibiotics when exposed to a third antibiotic, ciprofloxacin (cipro), the second most prescribed antibiotic in the US and one associated with high bacterial resistance rates.
The resistance is caused by new gene mutations that occur in the bacteria during infection. The drug DEQ reduces the speed at which new mutations are formed in bacteria, the team finds.
Previous work from the Rosenberg lab had shown that bacterial cultures in the lab exposed to cipro turn up mutation rate. They found a mutational “program” that is switched on by bacterial stress responses. Stress responses are genetic programs that instruct cells to increase production of protective molecules during stress, including stress from low concentrations of cipro. Low concentrations occur at the beginning and end of antibiotic therapies and if doses are missed.
The same stress responses also increase the ability to make genetic mutations, the Rosenberg group, then many other labs, have shown. Some of the mutations can confer resistance to cipro, while other mutations can allow resistance to antibiotics not yet encountered. Mutation-generating processes that are turned on by stress responses are called stress-induced mutation mechanisms.
Bacteria with antibiotic resistance mutations can then sustain an infection in the presence of cipro. This study is the first to show that in animal infections treated with cipro, the bacteria activate a known stress-induced genetic mutational process. Cipro resistance occurs mostly by the bacteria developing new mutations, both clinically and in the laboratory, rather than by acquiring genes that confer antibiotic resistance from other bacteria.
Looking to prevent the development of antibiotic resistance, the researchers screened 1120 drugs approved for human use for their ability to dial down the master bacterial stress response, which they showed counters the emergence of resistance mutations. In addition, and counterintuitively, they wanted “stealth” drugs that would not slow bacterial proliferation, which would confer a growth advantage to any bacterial mutants that resist the mutation-slowing drug itself. That is, drugs that are not antibiotics themselves.
“We found that DEQ fulfilled both requirements. Given together with cipro, DEQ reduced the development of mutations that confer antibiotic resistance, both in laboratory cultures and in animal models of infection, and bacteria did not develop resistance to DEQ,” said first author Yin Zhai, a postdoctoral associate in the Rosenberg lab. “In addition, we achieved this mutation-slowing effect at low DEQ concentrations, which is promising for patients. Future clinical trials are needed to evaluate the ability of DEQ to decelerate bacterial antibiotic resistance in patients.”
The rate at which women eliminate alcohol from their bloodstream is largely predicted by their lean body mass, although age plays a role, too, scientists found in a new study published in the journal Alcohol Clinical and Experimental Research. Since women with obesity also have more lean body mass, older women with obesity clear alcohol from their systems 52% faster than younger women of healthy weights, the study found.
“We believe the strong relationship we found between participants’ lean body mass and their alcohol elimination rate is due to the association that exists between lean body mass and lean liver tissue – the part of the liver responsible for metabolising alcohol,” said research group leader M. Yanina Pepino, a professor of food science and human nutrition at the University of Illinois Urbana-Champaign.
To explore links between body composition and alcohol elimination rates, the team conducted a secondary analysis of data from a study performed at and another at Indiana University, Indianapolis. Both projects used similar methods to estimate the rate at which alcohol is broken down in the body.
The combined sample from the studies used in the analysis included 143 women who ranged in age from 21 to 64 and represented a wide range of body mass indices – from healthy weights to severe obesity. Among these were 19 women who had undergone different types of bariatric surgery. Lean body mass is total body weight minus fat.
In a subsample of 102 of these women, the researchers had measured the proportions of lean and fat tissue in their bodies and calculated their body mass indices. Based on their BMI, those in the subsample were divided into three groups: normal weight (BMI of 18.5–24.9), overweight BMI (25–29.9) and obese (BMI 30+).
As the researchers expected, women with higher BMI had not only more fat mass than women of healthy weights, they also had more lean mass. On average, the group with obesity had 52.3 kg of lean mass, compared with 47.5 kg for the normal weight group.
The two studies both used an alcohol clamp technique, where participants received an intravenous infusion of alcohol at a rate controlled by a computer-assisted system. The system calculated personalised infusion rates based upon each participant’s age, height, weight and gender and was programmed so they would reach a target blood alcohol concentration of .06% within 15 minutes and maintain that level for about two hours
Using a breathalyser, breath samples were collected at regular intervals throughout the experiments to estimate participants’ blood alcohol concentration and provide feedback to the system.
“We found that having a higher fat-free body mass was associated with a faster alcohol elimination rate, particularly in women in the oldest subgroups,” said Neda Seyedsadjadi, a postdoctoral fellow at the university and the first author of the study.
“The average alcohol elimination rates were 6 grams per hour for the healthy weight group, 7 grams for the overweight group, and 9 grams for the group with obesity,” she said. “To put this in perspective, one standard drink is 14 grams of pure alcohol, which is found in 12 ounces of beer, 5 ounces of table wine or 1.5 ounces shot of distilled spirits.”
The interaction between participants’ age and lean body mass accounted for 72% of the variance in the time required to eliminate the alcohol from their system, the team found.
Pepino, who also holds an appointment as a health innovation professor at Carle Illinois College of Medicine, has conducted several studies on alcohol response in bariatric surgery patients.
The findings also shed light on alcohol metabolism and body composition in women who have undergone weight loss surgery. Researchers have long known that bariatric surgery alters women’s response to alcohol but were uncertain if it affected how quickly they cleared alcohol from their systems.
Some prior studies found that these patients metabolised alcohol more slowly after they had weight loss surgery. The new study’s findings indicate that these participants’ slower alcohol elimination rates can be explained by surgery-induced reductions in their lean body mass. Weight loss surgery itself had no independent effects on patients’ alcohol elimination rates, the team found.
In apparent resistant hypertension (aRH), more medication and medical management is needed than for normal hypertension. Novel research published in Hypertension found that aRH prevalence was lower in a real-world sample than previously reported, but still relatively frequent – affecting nearly 1 in 10 hypertensive patients. The researchers stressed the need for clinicians to be on the lookout for the condition.
In their analysis, the Cedars-Sinai investigators also learned that patients with well-managed aRH were more likely to be treated with mineralocorticoid receptor antagonist (MRA). These MRA treatments were used in 34% of patients with controlled aRH, but only 11% of patients with uncontrolled aRH.
“Apparent resistant hypertension is more common than many would anticipate,” said Joseph Ebinger, MD, assistant professor of Cardiology in the Smidt Heart Institute and corresponding author of the study. “We also learned that within this high-risk population, there are large differences in how providers treat high blood pressure, exemplifying a need to standardise care.”
Study findings were based on a unique design, which used clinically generated data from the electronic health records of three large, geographically diverse healthcare organisations. Of the 2 420 468 patients analysed in the study, 55% were hypertensive. Of these hypertension patients, 8.5%, or 113 992 individuals, met criteria for aRH.
According to Ebinger, treating aRH can be just as tricky as diagnosing it.
In fact, the “apparent” in apparent resistant hypertension stems from the fact that before diagnosis, medical professionals must first rule out other potential reasons for a patient’s blood pressure to be high.
These reasons might include medication non-adherence, inappropriate medication selection, or white coat hypertension from measurement in the doctor’s office.
“Large amounts of data tell us that patients with aRH, compared to those with non-resistant forms of hypertension, are at greatest risk for adverse cardiovascular events,” said Ebinger, director of Clinical Analytics in the Smidt Heart Institute. “Identifying these patients and possible causes for their elevated blood pressure is increasingly important.”
The takeaway, Ebinger says, is awareness – for both medical professionals and patients. He says providers should be mindful that if it’s taking four or more antihypertensive medications to control a patient’s blood pressure, they should consider evaluation for alternative causes of hypertension, or refer patients to a specialist.
Similarly, patients should press their healthcare providers to help them navigate the complex disease, including talking about strategies for remembering to take their medication and addressing possible treatment side effects.
Significant advances in breast cancer treatment have improved care to the point where most women with an early invasive breast cancer diagnosis can expect to be survivors. A new study involved half a million women in England has found that in England, the cumulative mortality within five years of an early invasive breast cancer diagnosis has fallen from roughly 14% in the 1990s to just under 5% for women diagnosed in 2010–2015. The findings, published in The BMJ, also serve to identify the cases with the greatest risks, and point to the need for progressively larger study sizes for new treatments.
Annually, more than 2 million patients receive a diagnosis of invasive breast cancer around the world. For most, it is their first cancer. Most have early stage disease and receive surgery as their first treatment. Post-treatment outcomes vary widely across patient characteristics and countries. In order to inform treatment, follow-up and likely outcomes, more detailed mortality estimates were needed.
To address this, the researchers conducted a retrospective population based cohort study of 512 447 women, looking at diagnoses made within four time periods: 1993–99, 2000–04, 2005–09, and 2010–15. They examined annual breast cancer mortality rates and cumulative risks by time since diagnosis, calendar period of diagnosis, and nine characteristics of patients and tumours.
Across all time periods, the crude annual breast cancer mortality rate was highest during the five years after diagnosis and then declined. For any given time since diagnosis, crude annual breast cancer mortality rates and risks decreased with increasing calendar period. Crude five year breast cancer mortality risk was 14.4% for women with a diagnosis made during 1993-99 and 4.9% for women with a diagnosis made during 2010-15.
Adjusted annual breast cancer mortality rates also decreased with increasing calendar period in nearly every patient group, by a factor of about three in oestrogen receptor positive disease and about two in oestrogen receptor negative disease. Mortality rates were highest during the five years after diagnosis before declining with each following five-year period.
There was still significant difference in mortality according to individual characteristics: <3% for 62.8% of women but taking into account age, oestrogen receptor type, and the number of lymph nodes involved, among other factors, for 4.6% the risk was ≥20%.
“[O]ur findings can be used to reassure most women treated for early breast cancer that they are likely to become long term survivors” as well as to identify cases with high mortality risk, the researchers wrote in The BMJ. They also note that the reduced mortality means that future randomised controlled trials, such as for new interventions, will need to be larger in order to have sufficient statistical power.
Patients with implanted cardiac devices are more likely to stop taking their heart medications if they are feeling depressed or anxious, according to research presented at ACNAP 2023, a scientific congress of the European Society of Cardiology (ESC).
The study author, psychologist Ole Skov at the University of Southern Denmark, said: “Medications help to control symptoms and prevent further heart problems so adherence is important. Patients with an implantable cardioverter defibrillator (ICD) who feel depressed or anxious should be encouraged to express their concerns, thoughts, and feelings and contact a health care professional who can screen them for distress to explore the best course of action. This could be referral to a psychologist or other measures.”
An ICD implantation is recommended for people at high risk of a life-threatening arrhythmia and for those who have had a sudden cardiac arrest. It is estimated that one in five patients with an ICD are affected by depression or anxiety, something which has been linked to increased mortality risk for those patients. Most patients with an ICD are prescribed medication to manage their heart disease. It is therefore crucial to identify patients at risk of stopping their medication so that support measures can be initiated.
This study examined whether anxiety and depression at the time of ICD implantation are associated with medication adherence one year after receiving the device. The study was a secondary analysis of the ACQUIRE-ICD randomised controlled trial of an eHealth intervention. Of 478 patients in the trial with an ICD or an ICD with cardiac resynchronisation therapy (CRT-D), 433 (91%) were taking at least one heart medication when their device was implanted. These included beta-blockers, ACE inhibitors, statins and diuretics. Of the 433 patients, 322 patients (74%) completed assessments of medication adherence at both baseline (implantation) and 12 months after implantation and were included in the current analyses.
Medication adherence was measured by self-report using the Morisky Medication Adherence Scale (MMAS) which is scored from 0 to 8. Low, medium and high adherence were defined as scores below 6, 6 to <8, and 8, respectively. Depression and anxiety were assessed at baseline with the Patient Health Questionnaire 9 (PHQ-9; scores 0–27) and the Generalised Anxiety Disorder (GAD-7; scores 0–21) scale, with higher scores indicating more symptoms. Both were used as continuous measures, and patients were not categorized as depressed/not depressed or anxious/not anxious.
The average age of participants was 60 years and 84% were men. Medication adherence was generally medium to high at baseline (6.8% low adherence, 40.1% medium adherence, 53.1% high adherence; average MMAS score 7.31) and at 12 months (8.1% low adherence, 37.3% medium adherence, 54.6% high adherence; average MMAS score 7.33).
The researchers analysed the association between mental health scores and medication adherence after adjusting for baseline MMAS score, sex, trial intervention group, heart failure severity and implantation centre. Depression scores at baseline were negatively associated with medication adherence at 12 months (p=0.02). The association with anxiety was not statistically significant.
Mr. Skov said: “Patients with higher levels of depressive symptoms at the time of ICD implantation were less likely to be taking their heart medications one year later. The effect of depression was statistically significant but small, which is not surprising given the complexity and multitude of factors involved in medication adherence.”
He concluded: “These results highlight the importance of considering the psychological status of people receiving an ICD. Those with symptoms of depression at the time of implantation could be at risk of discontinuing their heart medications, even if they are taking them initially, and may need extra support.”
Patients who had heart attacks during the first COVID lockdown in the UK and Spain are predicted to live 1.5 and 2 years less, respectively, than their pre-COVID counterparts. That’s the finding of a study just published in European Heart Journal – Quality of Care and Clinical Outcomes.
“Restrictions to treatment of life-threatening conditions have immediate and long-term negative consequences for individuals and society as a whole,” said study author Professor William Wijns of the Lambe Institute for Translational Medicine, University of Galway, Ireland. “Back-up plans must be in place so that emergency services can be retained even during natural or health catastrophes.”
Research has shown that during the first wave of the pandemic, about 40% fewer heart attack patients went to hospital as governments told people to stay at home, fear of catching the virus, and the stopping of some routine emergency care. Compared to receiving timely treatment, heart attack patients who stayed at home were more than twice as likely to die, while those who delayed going to the hospital were nearly twice as likely to have serious complications that could have been avoided.
Heart attacks require urgent treatment with stents (called percutaneous coronary intervention or PCI) to open the blocked artery and restore blood flow. Delays, and the resulting lack of oxygen, lead to irreversible damage of the heart muscle and can cause heart failure or other complications. When a large amount of heart tissue is damaged, potentially fatal cardiac arrest results.
This study estimated the long-term clinical and economic implications of reduced heart attack treatment during the pandemic in the UK and Spain. The researchers compared the predicted life expectancy of patients who had a heart attack during the first lockdown with those who had a heart attack at the same time in the previous year. The study focused on ST-elevation myocardial infarction (STEMI), where a coronary artery is completely blocked. The researchers also compared the cost of STEMIs during lockdown with the equivalent period the year before.
A model was developed to estimate long-term survival, quality of life and costs related to STEMI. The UK analysis compared the period 23 March (when lockdown began) to 22 April 2020 with the equivalent time in 2019. The Spanish analysis compared March 2019 with March 2020 (lockdown began on 14 March 2020). Survival projections considered age, hospitalisation status and time to treatment using published data for each country. For example, using published data, it was estimated that 77% of STEMI patients in the UK were hospitalised prior to the pandemic compared with 44% during lockdown. The equivalent rates for Spain were 74% and 57%. The researchers also compared how many years in perfect health were lost for patients with a STEMI before versus during the pandemic.
The analysis predicted that patients who had a STEMI during the first UK lockdown would lose an average of 1.55 years of life compared to patients presenting with a STEMI before the pandemic. In addition, while alive, those with a STEMI during lockdown were predicted to lose approximately one year and two months of life in perfect health. The equivalent figures for Spain were 2.03 years of life lost and around one year and seven months of life in perfect health lost.
The cost analysis focused on initial hospitalisation and treatment, follow-up treatment, management of heart failure and productivity loss in patients unable to return to work. For example, the cost applied to a STEMI admission with PCI was £2837 in the UK and €8780 in Spain. Heart failure costs were estimated at £6086 in year one and £3882 in all subsequent years for the UK. The equivalent figures for Spain were €3815 (year one) and €2930 (each subsequent year).
Professor Wijns said: “The findings illustrate the repercussions of delayed or missed care. Patients and societies will pay the price of reduced heart attack treatment during just one month of lockdown for years to come. Health services need a list of lifesaving therapies that should always be delivered, and resilient healthcare systems must be established that can switch to emergency plans without delay. Public awareness campaigns should emphasise the benefits of timely care, even during a pandemic or other crisis.”
