Tag: 8/4/21

Ambivalent Results for ‘SlowMo’ Digital Psychosis Therapy

A digital cognitive behavioral therapy for psychosis called SlowMo did not result in significant improvements for those suffering from paranoia, although it had other benefits.

“The therapy was engaging, and over 80% of participants completed all therapy sessions,” Philippa Garety, PhD, of King’s College London, wrote in an email to MedPage Today. “It is at least as effective as longer, more complex psychological treatments for paranoia, which are generally more challenging to deliver and frequently not available in clinical services.”

Garety herself was surprised by some of the study’s results, specifically the lack of improvements in some areas at the 24-week follow-up point. She said her team was also surprised — and pleased — to see that SlowMo was “equally effective across our wide demographic, of differing ages, gender, and ethnicities,” she wrote.

Some of the trial’s results surprised her, specifically the lack of improvements in some areas at the 24-week follow-up point. But her team was also pleased to see that it was equally effective across a wide demographic.

The study recruited 361 eligible adult participants from three UK community mental health services, and were randomised 1:1 to usual care only or to usual care plus SlowMo, which consisted of eight digitally supported face-to-face sessions and a mobile app .

The researchers saw improvements at the halfway point for both aspects of the 32-item Green et al. Paranoid Thoughts Scale (GPTS), which includes social reference (Part A) and persecution  (Part B). At the end of the trial, SlowMo did have a significant effect on Part B of the GPTS, but not on Part A.

Positive secondary outcomes were seen in observer-rated measurements, at a 12-week follow-up in Psychotic Symptom Rating Scales (PSYRATS) Delusion subscale and belief flexibility, as well as at 24 weeks. SlowMo did significantly affect the rate at which patients jumped to conclusions.

Dr Garety and co-authors noted that limitations including not controlling for time spent with therapists, as well as treatment as usual being used as the comparator.

Katherine Newman-Taylor, of University of Southampton in England, a psychologist focussing on patients with psychosis, said that the initial results are hopeful.

“This study shows that belief flexibility and worry are key therapeutic targets when working with people struggling with distressing paranoia,” Newman-Taylor told MedPage Today in an email. “As psychological therapists, we need to consider how people think, as well as what they think, when seeking to understand distressing psychosis and support individuals’ recovery.”

“In this trial, we have demonstrated, for the first time in a large randomized controlled trial, that helping people to slow down their thinking reduces paranoia in everyday life, and improves quality of life and wellbeing,” Dr Garety told MedPage Today.

Source: MedPage Tooday

Journal information: Garety P, et al “Effects of SlowMo, a blended digital therapy targeting reasoning, on paranoia among people with psychosis” JAMA Psychiatry 2021; DOI: 10.1001/jamapsychiatry.2021.0326.

Smartphone Tracking in COVID Shows Movement Linked to Case Rise

According to a new study which used mobility tracking of cell phone data, a greater movement of people is a strong predictor of increased COVID cases rates.

Until people are widely vaccinated against SARS-CoV-2, the array of nonpharmaceutical public health interventions such as physical distancing and limiting travel and social contacts will remain the most effective means of controlling COVID. Capturing the interrelationship between human behaviour and infectious diseases is one of the hardest problems in epidemiology.

“Mobility measures capturing human activity through anonymized tracking of smartphones are believed to be reasonable proxies of contact rates outside of one’s own home; these measures can provide more timely and reliable sources of information on contact rates compared with time-use surveys or contact tracing,” the authors wrote.

Researchers looked at anonymised smartphone mobility data from nearly 12 months from March 2020 to March 2021, both at a national and provincial level, while controlling for date and temperature. A 10% increase in the mobility of Canadians outside their homes was found to be associated with a 25% increase in subsequent SARS-CoV-2 weekly growth rates. They investigated at the mobility threshold (the level needed to control the virus) and the mobility gap (the difference between the threshold and actual movement).

“The mobility threshold and mobility gap can be used by public health officials and governments to estimate the level of restrictions needed to control the spread of SARS-CoV-2 and guide, in real-time, the implementation and intensity of nonpharmaceutical public health interventions to control the COVID-19 pandemic,” wrote the authors.

Source: News-Medical.Net

Journal information: Brown, K. A., et al. (2021) The mobility gap: estimating mobility thresholds required to control SARS-CoV-2 in Canada. Canadian Medical Association Journal. doi.org/10.1503/cmaj.210132.

‘Absolutely Revolutionary’ Kaftrio Drug Betters Lives of Cystic Fibrosis Patients

In an article by the BBC, one woman with cystic fibrosis recounts how the “absolute revolutionary” Kaftrio drug has improved her life.

Jody Lewis, 31, is an avid rider and one of around 80 people in Wales to have had Kaftrio, a “revolutionary” drug treatment for cystic fibrosis, at Liverpool Heart and Chest Hospital.

Cystic fibrosis is a genetic condition resulting in faulty cystic fibrosis transmembrane conductance regulator (CFTR) proteins which regulate the transfer of chloride ions into and out of the cells. The condition causes thick, sticky mucus to build up in the lungs, gastrointentinal system and other organs.

The treatment is suitable for around 90% of CF patients aged 12 and over and has been approved for use in the UK. Kaftrio is a triple combination of elexacaftor, tezacaftor which corrects the faulty CFTR protein, and  ivacaftor, which potentiates CFTR. 

Ms Lewis, said since taking it she had “a whole future and life” ahead of her.
Her condition worsened about two and a half years ago, when she was put on continuous oxygen supply, needing four or five oxygen bottles a day, almost placed on a ventilator and considered for a lung transplant. This meant stopping riding and changing how she cared for her four dogs.

“I’d have to change my complete lifestyle just to survive. I get that I’d have a second chance at life but it wouldn’t be me, it wouldn’t be true to who I am,” she said. At her worst, she said she could barely cope with simple tasks such as making tea.

This all changed when she started taking Kaftrio last year.

“Within a week, my [oxygen saturation] was going up and up to 94, 96 and I wasn’t even on oxygen and I can’t remember the last time I saw those numbers, it was mad.

“I’m now as good as I was back when I was 25, so I’ve like regained six years of my life,” she said.

“When I was 25 I was fine, I was in work, living a normal life, so it’s given me all that back really,” she said, adding that it was “really emotional” and “fantastic” to be able to ride her horse again after two and a half years..

“I’ve got a whole future and life in front of me that I’ve never had to think about.”

Consultant Martin Ledson, clinical lead for respiratory medicine at Liverpool Heart and Chest Hospital, described the drug treatment as “absolutely revolutionary”, saying that it had changed the lives of 222 of the hospital’s patients.

He said that when his patients were born, they could expect to live to their 30s, so they have “lived all their lives with the knowledge that their life expectation could be 30 or even less”.

“What this drug does is extend that life expectancy who knows how long?

“Not only that, the patients immediately – within 24 hours – feel amazingly better. Their breathing tests improve, they get less chest infections, their digestion improves, they put on weight and in many cases need to take less treatment,” he said.

Source: BBC News

Most Glucose Consumption in Non-cancer Cells, Upending Century-old View

A study has found that cancer cells are not the main consumers of glucose in tumours, challenging an observation held for over a century.

“The field of cancer metabolism has really exploded over the last 20 years, but it has been based on this observation that Otto Warburg published in 1922—that cancer cells can consume glucose at a very high rate,” said Jeffrey Rathmell, PhD, Cornelius Vanderbilt Professor of Immunobiology and director of the Vanderbilt Center for Immunobiology. “We now know that tumors include many types of cells, and it’s surprising that non-cancer cells are actually the major glucose consumers in the tumor.”

One application of the Warburg effect is where cancer cells are picked out based on their glucose metabolism in positron emission tomography (PET), a radioactive tracer of glucose (FDG). However, this doesn’t always yield the results expected by clinicians.

“I had been curious about why PET scans are ‘hot’ or ‘not hot’ for many years because the kidney cancer type that I study, from what we understand about the biology, should light up hot on PET and often doesn’t,” said W. Kimryn Rathmell, MD, PhD, Hugh J Morgan Professor and Chair of the Department of Medicine. “Jeff and I have had many conversations about which cells are using the glucose: is it the cancer cells; is it the immune cells; how does it all fit together? You can just imagine our dinner table.”

A pair of MD-PhD students from their labs, Bradley Reinfeld and Matthew Madden, decided to resolve this conundrum. They administered two different PET tracers (one for glucose, one for glutamine) to mice with tumours, isolated the tumors and separated them into various cell types and then measure the radioactivity in the cells. Six different tumour models were used, including colorectal, kidney and breast cancer. The results showed that, in each case, myeloid immune cells (primarily macrophages) had the highest uptake of glucose, followed by T cells and cancer cells. Cancer cells, in contrast, had the highest glutamine uptake.

“We think this is a general phenomenon that extends across cancer types,” Madden said.

The researchers showed that, instead of limiting nutrients, certain cellular signaling pathways drove the differences in glucose and glutamine uptake. The prevailing view is rather of metabolic competition taking place in the tumour microenvironment, where the cancer cells “win” to deplete nutrients and suppress immune cells.

“The idea has been that the cancer cells are gobbling up all of the glucose, and consequently, immune cells can’t get enough glucose and can’t do their job,” Madden said. “Our data suggest that nutrients aren’t limiting. Instead, cells are programmed to consume certain nutrients, and there is partitioning of nutrients between cells: cancer cells pick up glutamine and fatty acids; immune cells pick up glucose.”

Knowing that cells in the tumour microenvironment use different nutrients “may allow for specifically targeting particular cell types—for new therapies or for imaging people’s tumors,” Reinfeld said.

Kimryn Rathmell added, “We’re in a good place now to be able to have more sophisticated PET radiotracers. It’s time to think about testing fluoridated glutamine or other nutrient probes in patients.”

The study’s findings also have implications for interpreting FDG-PET imaging results, she said. “We order FDG-PET scans all the time, and we need to have a good sense of what that information is providing us. We use it to judge tumor response, but it may be telling us about inflammatory response and not tumor response.”

Source: Medical Xpress

Journal information: Cell-programmed nutrient partitioning in the tumour microenvironment, Nature (2021). DOI: 10.1038/s41586-021-03442-1

New Clinical Practice Review for Diabetes Drugs

A new clinical practice review article in The New England Journal of Medicine (NEJM) collates the latest trial results and guidelines into a systematic approach for the treatment of patients with diabetes and a risk of cardiovascular disease. It is the journal’s first such review by the journal in nearly a decade.

Clinical practice reviews differ from research studies in that they present a common clinical problem along with the evidence supporting various treatment strategies and review the guidelines. Finally, the author offers clinical recommendations for optimising patient care.

Compared to those without the disease, people with type 2 diabetes have over double the risk of developing atherosclerotic cardiovascular disease and heart failure. In South Africa, 10.1% of the population over 15 is believed to have type 2 diabetes, and is expected to cost the health sector R35.1 billion by 2030. 

The NEJM article by Johns Hopkins Medicine endocrinologist and associate professor Rita Rastogi Kalyani, MD, presents an up-to-date approach for health care providers when choosing among glucose-lowering therapies for their patients with diabetes, particularly to reduce the risk of cardiovascular disease. Dr Kalyani reviews the cardiovascular benefits and risks of the most common diabetes drugs currently available on the US market.

“We’ve seen a major shift in diabetes care over the past few years,” said Dr Kalyani. “We now have tools to better understand how to reduce both microvascular and macrovascular complications in people with type 2 diabetes.”

Dr Kalyani highlighted specific agents in two newer drug classes, which she showed are beneficial for patients with diabetes who already show signs of heart or blood vessel disease.

The glucagon-like peptide 1 (GLP-1) receptor agonists liraglutide, injectable semaglutide and dulaglutide increase insulin production from the body, particularly after meals.

Sodium glucose cotransporter 2 (SGLT2) inhibitors empagliflozin and canagliflozin reduce the amount of glucose the body re-absorbs through urine. 

All of these are effective in risk reduction for major cardiovascular events, such as heart attack or stroke. The SGLT2 inhibitor dapagliflozin is effective in reducing the risk of hospitalisation for heart failure.

“After metformin, which is widely considered the initial drug treatment for type 2 diabetes, specific drugs in the GLP-1 receptor agonist and SGLT2 inhibitor classes with demonstrated cardiovascular benefit should be considered as additional medications for patients who already have cardiovascular disease. This should be done irrespective of whether their A1C level is at target to reduce the risk of future cardiovascular events,” advised Kalyani.

The A1C test measures the average percentage of glucose in a person’s haemoglobin over the span of several months. Healthy A1C levels are below 5.7%, and typically, A1C levels over 6.5% indicate diabetes.

Newer drugs tend to be costlier, and long-term effects are unknown. Also, prior to 2008, the US Food and Drug Administration did not require large outcome trials for drugs after they were released onto the market, meaning that older drugs have less certain cardiovascular outcomes, said Dr Kalyani.
The NEJM article details specific drugs that offer additional benefits for patients with diabetes who have conditions such as multiple cardiovascular disease risk factors, heart failure and chronic kidney disease.

“Some agents such as dulaglutide and dapagliflozin also have demonstrated cardiovascular benefit in patients with multiple cardiovascular risk factors,” said Dr Kalyani.

Further, specific SGLT2 inhibitors can be beneficial for patients who have heart failure with reduced ejection fraction, as well for patients with chronic kidney disease.

Comprehensive drug tables in the article take into account factors for consideration in clinical practice when choosing a glucose-lowering drug for patients with type 2 diabetes, including A1C-lowering efficacy, route and frequency of administration, cost, impacts weight, hypoglycaemia risk, side effects and clinical benefits.

“Health care providers in primary care, endocrinology, cardiology and nephrology are now prescribing these newer glucose-lowering drugs for their patients,” Dr Kalyani said. “Diabetes care will need to be increasingly collaborative in the future and, at its core, remain patient-centered.”

Source: Medical Xpress

Journal information: Rita R. Kalyani et al. Glucose-Lowering Drugs to Reduce Cardiovascular Risk in Type 2 Diabetes, New England Journal of Medicine (2021). DOI: 10.1056/NEJMcp2000280